Sample records for papillary mucinous carcinoma
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Sung, Ji-Youn; Jung, Yoon Yang; Kim, Hyun-Soo
2018-05-01
Mucinous metaplasia of the endometrium occurs as a spectrum of epithelial alterations ranging from the formation of simple, tubular glands to architecturally complex glandular proliferation with intraglandular papillary projection and cellular tufts. Endometrial mucinous metaplasia often presents a diagnostic challenge in endometrial curettage. We analyzed the clinicopathological characteristics and the mutation status for V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) of 11 cases of endometrial mucinous metaplasia. Electronic medical record review and histopathological examination were performed. KRAS mutation status was analyzed using a pyrosequencing technique. Cases were classified histopathologically into simple (5/11) or papillary (6/11) mucinous metaplasias. All (6/6) papillary mucinous metaplasias were associated with atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN; 1/6) or carcinoma (5/6), whereas in a single patient with simple mucinous metaplasia, grade 1 endometrioid carcinoma was incidentally detected. The difference in frequency of association of the metaplasia with AH/EIN or carcinoma was significant (p=0.015). KRAS mutations were identified in five out of six cases of papillary mucinous metaplasias, comprising three cases with G12D and two with G12V mutations; the frequency of KRAS mutation was significantly higher (p=0.015) than in cases of simple mucinous metaplasia (0/5). Papillary mucinous metaplasia is frequently associated with endometrial neoplastic lesions. The high incidence of KRAS mutations in papillary mucinous metaplasia suggests that papillary mucinous metaplasia may be a precancerous lesion of a certain subset of mucinous carcinomas of the endometrium. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Swartz, Michael J.; Hsu, Charles C.; Pawlik, Timothy M.
2010-03-01
Purpose: Intraductal papillary mucinous neoplasms are mucin-producing cystic neoplasms of the pancreas. One-third are associated with invasive carcinoma. We examined the benefit of adjuvant chemoradiotherapy (CRT) for this cohort. Methods and Materials: Patients who had undergone pancreatic resection at Johns Hopkins Hospital between 1999 and 2004 were reviewed. Of these patients, 83 with a resected pancreatic mass were found to have an intraductal papillary mucinous neoplasm with invasive carcinoma, 70 of whom met inclusion criteria for the present analysis. Results: The median age at surgery was 68 years. The median tumor size was 3.3 cm, and invasive carcinoma was presentmore » at the margin in 16% of the patients. Of the 70 patients, 50% had metastases to the lymph nodes and 64% had Stage II disease. The median survival was 28.0 months, and 2- and 5-year survival rate was 57% and 45%, respectively. Of the 70 patients, 40 had undergone adjuvant CRT. Those receiving CRT were more likely to have lymph node metastases, perineural invasion, and Stage II-III disease. The 2-year survival rate after surgery with vs. without CRT was 55.8% vs. 59.3%, respectively (p = NS). Patients with lymph node metastases or positive surgical margins benefited significantly from CRT (p = .047 and p = .042, respectively). On multivariate analysis, adjuvant CRT was associated with improved survival, with a relative risk of 0.43 (95% confidence interval, 0.19-0.95; p = .044) after adjusting for major confounders. Conclusion: Adjuvant CRT conferred a 57% decrease in the relative risk of mortality after pancreaticoduodenectomy for intraductal papillary mucinous neoplasms with an associated invasive component after adjusting for major confounders. Patients with lymph node metastases or positive margins appeared to particularly benefit from CRT after definitive surgery.« less
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Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions.
Terris, Benoît; Dubois, Sylvie; Buisine, Marie-Pierre; Sauvanet, Alain; Ruszniewski, Philippe; Aubert, Jean-Pierre; Porchet, Nicole; Couvelard, Anne; Degott, Claude; Fléjou, Jean-Francois
2002-08-01
Intraductal papillary-mucinous tumours (IPMTs) of the pancreas are heterogeneous proliferations characterized by a malignant potential. The molecular mechanisms underlying the tumourigenesis process are not well understood. Recently, it has been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis, but the complete pattern of MUC gene expression has not yet been established. The aims of this study were to evaluate the mucin gene expression in 57 IPMTs and eight related lesions surgically resected and to relate MUC gene expression to the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90 conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2 (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric glandular adenomas exhibited little or no expression of MUC2. The mucin expression profile supports the existence of two types of invasive tumour associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain of MUC1 and has a greater tendency to metastasize. In conclusion, the altered expression of mucin, characteristic of IPMT of adenoma type and of colloid carcinomas, may contribute to the better clinical outcome of these neoplasms, compared to conventional pancreatic ductal adenocarcinomas. Copyright 2002 John Wiley & Sons, Ltd.
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Komo, Toshiaki; Oishi, Koichi; Kohashi, Toshihiko; Hihara, Jun; Kanou, Mikihiro; Nakashima, Akira; Kaneko, Mayumi; Mukaida, Hidenori; Hirabayashi, Naoki
2018-06-04
Intraductal papillary mucinous neoplasms (IPMNs) occasionally involve formation of fistulas with other adjacent organs. Pancreatobiliary fistulas associated with IPMNs are rare, but affected patients often develop obstructive jaundice and cholangitis. A 79-year-old man was referred to our hospital for evaluation of abnormal biliary enzymes. Contrast-enhanced computed tomography and endoscopic retrograde cholangiopancreatography demonstrated multiple cystic lesions with septa in the pancreatic head and fistulas between the cystic lesions and common bile duct. The clinical diagnosis was pancreatobiliary fistula associated with a mixed-type IPMN and accompanying obstructive jaundice. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy. The resected specimen showed fistulas between the cystic lesions and common bile duct. Histopathological examination showed that the main and branch ducts of the pancreatic head were dilated and filled with mucus. The epithelia of the pancreatic ducts revealed papillary proliferation and an invasive adenocarcinoma arising from an intraductal neoplasm. Immunohistochemistry examination showed CDX2- and MUC2-positive reactions. The final diagnosis was an intraductal papillary mucinous carcinoma of the intestinal-type. The patient remained disease-free for 9 months postoperatively. The causes of death in patients who have pancreatobiliary fistulas associated with IPMNs without resection are cholangitis or hepatic insufficiency. Nonoperative treatment is limited for cases with obstructive jaundice. It is necessary to prevent obstructive jaundice and cholangitis due to a large quantity of mucinous material. Surgical resection should be considered, if possible, in patients with pancreatobiliary fistulas associated with IPMNs. A better prognosis is expected with prevention of obstructive jaundice or cholangitis. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Basturk, Olca; Tan, Marcus; Bhanot, Umesh; Allen, Peter; Adsay, Volkan; Scott, Sasinya N; Shah, Ronak; Berger, Michael F; Askan, Gokce; Dikoglu, Esra; Jobanputra, Vaidehi; Wrzeszczynski, Kazimierz O; Sigel, Carlie; Iacobuzio-Donahue, Christine; Klimstra, David S
2017-01-01
In 2010, the World Health Organization reclassified the entity originally described as intraductal oncocytic papillary neoplasm as the ‘oncocytic subtype’ of intraductal papillary mucinous neoplasm. Although several key molecular alterations of other intraductal papillary mucinous neoplasm subtypes have been discovered, including common mutations in KRAS, GNAS, and RNF3, those of oncocytic subtype have not been well characterized. We analyzed 11 pancreatic ‘oncocytic subtype’ of intraductal papillary mucinous neoplasms. Nine pancreatic ‘oncocytic subtype’ of intraductal papillary mucinous neoplasms uniformly exhibited typical entity-defining morphology of arborizing papillae lined by layers of cells with oncocytic cytoplasm, prominent, nucleoli, and intraepithelial lumina. The remaining two were atypical. One lacked the arborizing papilla and had flat oncocytic epithelium only; the other one had focal oncocytic epithelium in a background of predominantly intestinal subtype intraductal papillary mucinous neoplasm. Different components of this case were analyzed separately. Formalin-fixed, paraffin-embedded specimens of all cases were microdissected and subjected to high-depth-targeted next-generation sequencing for a panel of 300 key cancer-associated genes in a platform that enabled the identification of sequence mutations, copy number alterations, and select structural rearrangements involving all targeted genes. Fresh frozen specimens of two cases were also subjected to whole-genome sequencing. For the nine typical pancreatic ‘oncocytic subtype’ of intraductal papillary mucinous neoplasms, the number of mutations per case, identified by next-generation sequencing, ranged from 1 to 10 (median = 4). None of these cases had KRAS or GNAS mutations and only one had both RNF43 and PIK3R1 mutations. ARHGAP26, ASXL1, EPHA8, and ERBB4 genes were somatically altered in more than one of these typical ‘oncocytic subtype’ of intraductal papillary mucinous
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Biliary papillary neoplasm of the liver.
Nakanuma, Y; Sasaki, M; Ishikawa, A; Tsui, W; Chen, T C; Huang, S F
2002-01-01
Biliary papillary neoplasia of the liver characterized by intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk has been sporadically reported, and includes intraductal growing cholangiocarcinoma and biliary papillomatosis. In addition, biliary papillary dysplasia and in situ and microinvasive carcinoma with papillary configuration reported in hepatolithiasis and in other chronic biliary diseases, could be included in this category. Usually, they arise in the intrahepatic large bile ducts, and the neoplastic and non-neoplastic parts of the intrahepatic biliary tree show saccular and segmental dilatation with mucin hypersecretion. This neoplasia frequently shows intraductal spreading and peribiliary glandular involvement. Acute repeated episodes of cholangitis or obstructive jaundice are a frequent clinical manifestation. Gastroenteric metaplasia with aberrant expression of cytokeratin 20, MUC2, MUC5AC, and/or MUC6, is frequent in the neoplastic parts, and biliary epithelial dysplasia with such metaplasia may give rise to in situ and then invasive carcinoma in hepatolithiasis. Interestingly, this type tends to contain foci of mucinous carcinoma elements, and this element may be predominant (mucinous carcinoma). Some may progress to "mucinous biliary cystadenocarcinoma" without ovarian mesenchymal stroma and with intraluminal continuous growth into the neighboring bile duct lumens. Interestingly, the biliary papillary neoplasm resembles histologically, phenotypically and clinically intraductal papillary mucinous neoplasm of the pancreas which is now being established as an infrequent, slow-growing pancreatic neoplasm. Recognition of such biliary papillary neoplasm with respect to the pancreatic equivalent may lead to a better understanding and further studies of the intrahepatic biliary neoplasm.
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Fine-needle aspiration cytology of intraductal papillary-mucinous tumors: a retrospective analysis.
Layfield, Lester J; Cramer, Harvey
2005-01-01
Intraductal papillary-mucinous tumor (IPMT) of the pancreas has become the accepted terminology for a group of mucin-producing epithelial proliferations lying within ectatic segments of the main pancreatic duct or its large branches. These neoplasms generally are associated with an indolent course, characteristic endoscopic ultrasonographic (EUS) findings, and a variable histo- and cytomorphology ranging from hyperplasia to carcinoma. Cytological specimens obtained by endoscopic ultrasound-guided or percutaneous fine-needle aspiration (FNA) are characterized by a background containing abundant mucin in which are entrapped single or loosely cohesive clusters of neoplastic cells characteristically showing a goblet-cell morphology. The degree of nuclear atypia, cell crowding, and cell shape varies between smears within a single case and between cases. Cytomorphological examination, when coupled with EUS features, is accurate for the diagnosis of these lesions but often it underdiagnoses the grade of the neoplasm. (c) 2005 Wiley-Liss, Inc.
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Nam, Kee-Hyun; Noh, Tae-Woong; Chung, So-Hyang; Lee, So Hee; Lee, Mi Kyung; Hong, Soon Won; Chung, Woong Youn; Lee, Eun Jig; Park, Cheong Soo
2011-07-01
Papillary thyroid carcinoma (PTC) is the most frequent carcinoma of the thyroid gland and has a relatively good prognosis. However, it is important to identify PTC characteristics that indicate high risk for recurrence and metastasis. To date, overexpression of the membrane mucin, MUC1, has been investigated as a key molecular event in the pathogenesis of aggressive PTC. However, other membrane-associated mucins, matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-13 (TIMP-3), have not been studied yet. The aim of this study was to evaluate the expression levels of MUC4, MUC15, MMP-13, and TIMP-3 and their prognostic significance in PTC. We analyzed MUC4, MUC15, MMP-13, and TIMP-3 expression in 10 PTC and 10 normal thyroid tissue samples using real-time reverse transcription-polymerase chain reaction. Tissue array blocks were obtained from 98 PTC cases. Tumor regions and nontumor regions were analyzed in tissue array blocks and immunohistochemistry studies were conducted using sectioned slides. Semiquantitative scores were correlated with clinicopathological factors of 98 PTC patients. MUC4- and MUC15-specific mRNA was increased by 78-fold and 4.75-fold, respectively, in PTC samples compared with normal thyroid tissues. MMP-13 and TIMP-3 gene expression levels were decreased by approximately 0.39-fold and 0.53-fold, respectively. By immunohistochemistry, MUC4 and MUC15 expression levels were increased in PTC samples compared with normal thyroid tissues (p < 0.001). MMP-13 and TIMP-3 expression levels were decreased in PTC samples compared with normal thyroid tissues (p < 0.001). High MUC4 scores were significantly correlated with small tumor size and papillary thyroid microcarcinoma subtype. High MUC15 scores were significantly correlated with age (≥45 years), distant metastasis, and multifocality. MUC4 and MUC15 were overexpressed in PTC, and high MUC15 expression was associated with high malignant potential. MUC15 may serve as a
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Scholten, Lianne; van Huijgevoort, Nadine C M; Bruno, Marco J; Fernandez-Del Castillo, Carlos; Satoi, Sohei; Sauvanet, Alain; Wolfgang, Christopher; Fockens, Paul; Chari, Suresh T; Del Chiaro, Marco; van Hooft, Jeanin E; Besselink, Marc G
2018-05-16
The risk of invasive cancer in resected intraductal papillary mucinous neoplasm with main pancreatic duct involvement is 33%-60%. Most guidelines, therefore, advise resection of main duct intraductal papillary mucinous neoplasm and mixed type intraductal papillary mucinous neoplasm in surgically fit patients, although advice on the surgical strategy (partial or total pancreatectomy) differs. We performed a survey amongst international experts to guide the design of future studies and help to prepare for a single international set of guidelines. An online survey including case vignettes was sent to 221 international experts who had published on main duct/mixed type intraductal papillary mucinous neoplasm in the previous decade and to all surgeon and gastroenterologist members of the pancreatic cyst guideline committees of the European Study Group and the International Association of Pancreatology. Overall, 97 experts (67 surgeons, 30 gastroenterologists) from 19 countries replied (44% response rate). Most (93%) worked in an academic hospital, with a median of 15 years' experience with intraductal papillary mucinous neoplasm treatment. In main duct/mixed type intraductal papillary mucinous neoplasm patients with pancreatic duct dilation (>5 mm) in the entire pancreas, 41% (n = 37) advised nonoperative surveillance every 3-6 months, whereas 59% (n = 54) advised operative intervention. Of those who advised operative intervention, 46% (n = 25) would perform a total pancreatectomy and 31% (n = 17) pancreatoduodenectomy with follow-up. No structural differences in advice were seen between surgeons and gastroenterologists, between continents where the respondents lived, and based on years of experience. This international survey identified a clinically relevant lack of consensus in the treatment strategy in main duct/mixed type intraductal papillary mucinous neoplasm among experts. Studies with long-term follow-up including quality of life after partial and
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Intraductal papillary mucinous tumors of the pancreas: biology, diagnosis, and treatment.
Grützmann, Robert; Niedergethmann, Marco; Pilarsky, Christian; Klöppel, Günter; Saeger, Hans D
2010-01-01
Pancreatic intraductal papillary mucinous neoplasms (IPMNs) rank among the most common cystic tumors of the pancreas. For a long time they were misdiagnosed as mucinous cystadenocarcinoma, ductal adenocarcinoma in situ, or chronic pancreatitis. Only in recent years have IPMNs been fully recognized as clinical and pathological entities, although their origin and molecular pathogenesis remain poorly understood. IPMNs are precursors of invasive carcinomas. When resected in a preinvasive state patient prognosis is excellent, and even when they are already invasive, patient prognosis is more favorable than with ductal adenocarcinomas. Subdivision into macroscopic and microscopic subtypes facilitates further patient risk stratification and directly impacts treatment. There are main duct and branch duct IPMNs, with the main duct type including the intestinal, pancreatobiliary, and oncocytic types and the branch duct type solely harboring the gastric type. Whereas main duct IPMNs have a high risk for malignant progression, demanding their resection, branch duct IPMNs have a much lower risk for harboring malignancy. Patients with small branch duct/gastric-type IPMNs (<2 cm) without symptoms or mural nodules can be managed by periodic surveillance.
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Mucinous breast carcinoma with tall columnar cells.
Tsoukalas, N; Kiakou, M; Tolia, M; Kostakis, I D; Galanopoulos, M; Nakos, G; Tryfonopoulos, D; Kyrgias, G; Koumakis, G
2018-05-01
Mucinous carcinoma of the breast represents 1%-4% of all breast cancers. The World Health Organization classification divides this type of tumour into three different subtypes: mucinous carcinoma, mucinous carcinoma with tall columnar cells (mucinous cystadenocarcinoma and columnar cell mucinous carcinoma) and signet ring cell carcinoma. A 74-year-old woman presented a tumour with inflammatory features in the upper outer quadrant of her left breast, 7 cm in diameter. The core biopsy showed infiltrating ductal carcinoma of no specific type. The tumour-node-metastasis clinical staging was T4cN3M0 (Stage IIIC). She received neoadjuvant chemotherapy, underwent left mastectomy with radical axillary resection and subsequently received radiotherapy and chemotherapy. The histological examination of the surgical specimen revealed two solid tumors in the tail of Spence, which corresponded to adenocarcinoma with high columnar cells. The patient died 16 months after the diagnosis, suffering from pulmonary metastases and anterior chest wall infiltration. A review of the literature revealed only 21 reports of mucinous carcinoma of the breast with tall columnar cells, including our case. This is only the third time that the specific histological type of columnar cell mucinous carcinoma has been reported in the literature.
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Targeting Src in Mucinous Ovarian Carcinoma
Matsuo, Koji; Nishimura, Masato; Bottsford-Miller, Justin N.; Huang1, Jie; Komurov, Kakajan; Armaiz-Pena, Guillermo N.; Shahzad, Mian M. K.; Stone, Rebecca L.; Roh, Ju Won; Sanguino, Angela M.; Lu, Chunhua; Im, Dwight D.; Rosenshien, Neil B.; Sakakibara, Atsuko; Nagano, Tadayoshi; Yamasaki, Masato; Enomoto, Takayuki; Kimura, Tadashi; Ram, Prahlad T.; Schmeler, Kathleen M.; Gallick, Gary E.; Wong, Kwong K.; Frumovitz, Michael; Sood, Anil K.
2014-01-01
PURPOSE Mucinous ovarian carcinomas have a distinct clinical pattern compared to other subtypes of ovarian carcinoma. Here, we evaluated (i) stage-specific clinical significance of mucinous ovarian carcinomas in a large cohort and (ii) the functional role of src kinase in pre-clinical models of mucinous ovarian carcinoma. EXPERIMENTAL DESIGN 1302 ovarian cancer patients including 122 (9.4%) cases of mucinous carcinoma were evaluated for survival analyses. Biological effects of src kinase inhibition were tested in a novel orthotopic mucinous ovarian cancer model (RMUG-S-ip2) using dasatinib-based therapy. RESULTS Patients with advanced-stage mucinous ovarian cancer had significantly worse survival compared to those with serous histology: median overall survival, 1.67 versus 3.41 years, p=0.002; and median survival time after recurrence of 0.53 versus 1.66 years, p<0.0001. Among multiple ovarian cancer cell lines, RMUG-S-ip2 mucinous ovarian cancer cells showed the highest src kinase activity. Moreover, oxaliplatin treatment induced phosphorylation of src kinase. This induced activity by oxaliplatin therapy was inhibited by concurrent administration of dasatinib. Targeting src with dasatinib in vivo showed significant anti-tumor effects in the RMUG-S-ip2 model, but not in the serous ovarian carcinoma (SKOV3-TR) model. Combination therapy of oxaliplatin with dasatinib further demonstrated significant effects on reducing cell viability, increasing apoptosis, and in vivo anti-tumor effects in the RMUG-S-ip2 model. CONCLUSIONS Our results suggest that poor survival of women with mucinous ovarian carcinoma is associated with resistance to cytotoxic therapy. Targeting src kinase with combination of dasatinib and oxaliplatin may be an attractive approach in this disease. PMID:21737505
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Primary Papillary Mucinous Adenocarcinoma of the Ureter Mimicking Genitourinary Tuberculosis
Gulwani, Hanni; Jain, Aruna
2010-01-01
Primary adenocarcinomas of the renal pelvis and ureter are rare and account for less than 1% of all malignancies at this site. We report a case of primary papillary mucinous adenocarcinoma of the ureter that clinically mimicked genitourinary tuberculosis. Early diagnosis is important for the better outcome. PMID:21151719
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Thyroid cancer - papillary carcinoma
... this page: //medlineplus.gov/ency/article/000331.htm Thyroid cancer - papillary carcinoma To use the sharing features on ... the lower neck. Causes About 80% of all thyroid cancers diagnosed in the United States are the papillary ...
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Erickson, L A; Yousef, O M; Jin, L; Lohse, C M; Pankratz, V S; Lloyd, R V
2000-09-01
In most cases, the histopathologic and cytologic distinction between Graves' disease and papillary thyroid carcinoma is relatively easy, but on occasion Graves' disease may simulate a thyroid papillary carcinoma. For example, papillary fronds with fibrovascular cores may be present in both Graves' disease and papillary carcinoma. p27kip1 (p27) is a cyclin-dependent kinase inhibitory protein that has been shown to be an independent prognostic factor in a variety of human tumors. Our previous studies of p27 expression in hyperplastic and neoplastic endocrine lesions showed that the level of p27 was quite different in these two conditions. To determine if this distinction could also be made between Graves' disease and papillary carcinoma, we analyzed expression of p27 and other cell cycle proteins in a series of cases of Graves' disease with papillary hyperplasia and a series of papillary thyroid carcinomas. Formalin-fixed paraffin-embedded tissues from 61 randomly selected patients with thyroid disease, including 29 cases of Graves' disease with papillary architectural features and 32 cases of papillary carcinoma, were analyzed for expression of p27, Ki-67, and DNA topoisomerase II alpha (topo II alpha) by immunostaining. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI) plus or minus the standard error of the mean. The papillary hyperplasia of Graves' disease had a p27 LI of 68.2 +/- 3.1 (range, 24 to 88), whereas papillary carcinomas had a LI of 25.6 +/- 2.5 (range, 12 to 70) (P < .0001). No significant differences in Ki-67 or topo II alpha expression were identified between papillary hyperplasia in Graves' disease and papillary carcinoma. These results indicate that p27 protein expression is significantly higher in papillary hyperplasia of Graves' disease compared to papillary carcinoma, which may be diagnostically useful in difficult cases.
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Yoshida, Yukinari; Endo, Takao; Tanaka, Eiichi; Kikuchi, Takefumi; Akino, Kimishige; Mita, Hiroaki; Adachi, Yasuyo; Nakamura, Masahiro; Adachi, Yasushi; Ishii, Yoshifumi; Matsumoto, Joe; Hirano, Satoshi; Nitta, Takeo; Mitsuhashi, Tomoko; Kato, Yasuo
2017-01-01
We herein report the case of a 78-year-old woman with an intraductal tumor with scant mucin production in a moderately dilated main pancreatic duct that resembled an intraductal tubulopapillary neoplasm (ITPN) on imaging. An endoscopic transpapillary forceps biopsy enabled an accurate preoperative diagnosis of the tumor as an oncocytic type intraductal papillary mucinous neoplasm (IPMN) of the pancreas microscopically showing papillary growth consisting of oncocytic cells with a typical mucin expression profile, although with few intraepithelial lumina containing mucin. This is the first case of an oncocytic type IPMN mimicking an ITPN that was able to be diagnosed preoperatively. PMID:29021473
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Budzynska, Agnieszka; Hartleb, Marek; Nowakowska-Dulawa, Ewa; Krol, Robert; Remiszewski, Piotr; Mazurkiewicz, Michal
2014-04-14
Cystic hepatic neoplasms are rare tumors, and are classified into two separate entities: mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor. Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B. This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.
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Stein, Louis H.; Witkiewicz, Agnieszka K.; Kennedy, Eugene P.; Yeo, Charles J.
2012-01-01
Background Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized pancreatic neoplasm characterized by excessive mucin secretion by ductal epithelial cells resulting in a cystic dilation of the pancreatic duct. Aim The objective of this study was to review Thomas Jefferson University’s experience and the literature to determine the significance of extra-pancreatic mucin when associated with an IPMN. Results A retrospective analysis at our institution revealed only two cases of IPMN associated with extra-pancreatic mucin, which were classic IPMNs with rupture of the pancreatic duct and peritoneal mucin spillage. This specific finding is not previously described, although is assumed as five cases were reported in the literature with IPMN and mucin extension demonstrated by pseudomyxoma peritonei (PMP). We propose IPMN of the pancreas may be grossly compared to a mucocele of the appendix, as both are characterized by excessive secretion of mucin by ductal epithelial cells. A morbid complication of a mucocele is PMP. The presence of extra-pancreatic mucin with an IPMN could present a rare but important marker of the eventual seeding of tumor outside the primary IPMN. This has been documented with cases of iatrogenic spilling of pancreatic mucin, as well as multiple cases of IPMN associated with pseudomyxoma peritonei. Conclusions At this time, there is scant reporting and consensus for the treatment of IPMN with extra-pancreatic mucin. PMID:22258877
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Magro, Gaetano; Schiappacassi, Monica; Perissinotto, Daniela; Corsaro, Antonella; Borghese, Cinzia; Belfiore, Antonino; Colombatti, Alfonso; Grasso, Sebastiano; Botti, Carlo; Bombardieri, Emilio; Perris, Roberto
2003-07-01
Mucins are primary glycoproteins of epithelia that are known to undergo major changes in their post-translational processing during neoplastic transformation. This study has examined the expression pattern of seven primary mucins, ie mucin (MUC) 1, 2, 3, 4, 5AC, 5B and 6, in normal, hyperplastic, benign neoplastic, and papillary-type carcinoma (PTC) tissues of the thyroid. MUC1 and MUC5B were the only mucins to be widely transcribed in both benign and malignant tissues. In contrast, MUC4 transcripts were undetectable in normal thyroids, and were present in only 40% of the hyperplastic and malignant thyroid tissues. In PTC, MUC1 was identified as a single mRNA transcript, rejecting the idea that this mucin may undergo transformation-dependent alternative splicing in thyroid tumours. The tissue distribution of MUC1 and MUC4 proteins was highly heterogeneous: this largely paralleled their mRNA expression profiles and supported the conclusion that whereas MUC1 was ubiquitously expressed in PTC, MUC4 was detectable in less than 20% of the cases analysed. In order to determine whether post-translational modifications of MUC1, putatively associated with malignancy, also occurred in the mucin produced by PTC, immunohistochemistry was performed with a panel of well-characterized anti-MUC1 antibodies in conjunction with digestion of the tissue sections with deglycosylating enzymes. These experiments, which were supported by immunochemical analyses of the MUC1 and MUC4 glycoforms extracted from tissues, collectively demonstrated markedly divergent MUC1 glycosylation profiles in normal and benign thyroid tissues when compared with PTC. Characteristically, these latter neoplastic cells produced mucin molecules carrying complex poly-N-lactosamine-type glycans capped with fucose and neuraminic acid residues. The present study also found evidence in PTC for the potential presence of proteolytically processed MUC1 isoforms which differ in their post-translational traits depending
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The many faces and mimics of papillary thyroid carcinoma.
Albores-Saavedra, Jorge; Wu, Jianhua
2006-01-01
This article provides an overview of the 15 histologic variants of papillary thyroid carcinoma listed by the 2004 World Health Organization (WHO) monograph on endocrine tumors. The histologic features, differential diagnosis, and clinical course of each variant are discussed in some detail. The follicular variants (conventional and macrofollicular) constitute a morphologic challenge because the majority of these tumors are encapsulated and, also, because, in many tumors, not all neoplastic cells show the nuclear features considered to be diagnostic of papillary carcinoma. As a result, most of these tumors are missed even by experienced pathologists. Moreover, hyperplastic thyroid lesions, follicular adenomas, and Hashimoto's thyroiditis may contain cells with clear nuclei resembling those of papillary carcinoma. Papillary carcinomas composed entirely of hyperchromatic cells have been overlooked. The WHO monograph defines papillary carcinoma with focal spindle and giant cell carcinoma components but its clinical behavior is unknown. Papillary carcinoma with an insular pattern that does not show the artifactual separation of the cell nests has been misinterpreted as the solid variant of papillary carcinoma. Papillary microcarcinomas include not only the conventional type and the follicular variants but also the tall cell and columnar cell variants.
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Molecular genetics of intraductal papillary-mucinous neoplasms of the pancreas.
Furukawa, Toru
2007-01-01
Intraductal papillary-mucinous neoplasms of the pancreas show characteristic clinicopathological and molecular pathobiological features which are distinct from those of conventional ductal adenocarcinomas. Alterations of KRAS, AKT/PKB, CDKN2A, TP53, SMAD4, STK11/LKB1, and DUSP6, and other molecular alterations, including global expression studies as well as their clinical implications, are discussed.
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Shibata, Wataru; Kinoshita, Hiroto; Hikiba, Yohko; Sato, Takeshi; Ishii, Yasuaki; Sue, Soichiro; Sugimori, Makoto; Suzuki, Nobumi; Sakitani, Kosuke; Ijichi, Hideaki; Mori, Ryutaro; Endo, Itaru; Maeda, Shin
2018-04-18
Pancreatic ductal adenocarcinoma (PDA) has a 5-year survival rate of less than 5% and is the sixth leading cause of cancer death. Although KRAS mutations are one of the major driver mutations in PDA, KRAS mutation alone is not sufficient to induce invasive pancreatic cancer in mice model. HER2, also known as ERBB2, is a receptor tyrosine kinase, and overexpression of HER2 is associated with poor clinical outcomes in pancreatic cancer. However, no report has shown whether HER2 and its downstream signaling contributes to the pancreatic cancer development. By immunohistochemical analysis in human cases, HER2 protein expression was detected in 40% of PDAs and 29% of intraductal papillary mucinous carcinomas, another type of pancreatic cancer. In a mouse model, we showed overexpression of activated HER2 (HER2 NT ) in the pancreas, in which cystic neoplastic lesions resembling intraductal papillary mucinous neoplasm-like lesions in humans had developed. We also found that HER2 NT cooperated with oncogenic Kras to accelerate the development of pancreatic intraepithelial neoplasms. In addition, using pancreatic organoids in 3D cultures, we found that organoids cultured from HER2 NT /Kras double transgenic mice showed proliferative potential and tumorigenic ability cooperatively. HER2-signaling inhibition was suggested to be an new therapeutic target in some types of PDAs.
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Management of intraductal papillary mucinous neoplasms.
Crippa, Stefano; Fernández-del Castillo, Carlos
2008-04-01
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are being diagnosed with increasing frequency, probably due to the widespread use of cross-sectional imaging. The natural history of these tumors is still largely unknown. Several studies have shown topographical as well as biological differences between main duct and branch duct IPMNs. In the past few years, diagnostic work-up and, in particular, management of these tumors have evolved significantly. Data support the need for resection of main duct IPMNs and the possibility of nonoperative management in selected cases of branch duct tumors. In this systematic review, we analyze the most recent publications related to IPMNs, with particular emphasis on problems related to managing this challenging disease.
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[A case of mucinous noncystic carcinoma of the pancreas].
Jung, Jun Young; Song, Moon Hee; Park, Young Sook; Jo, Yun Ju; Kim, Seong Hwan; Jun, Dae-Won; Kim, Dong Hee; Lee, Won Mi
2008-03-01
Mucinous (colloid) carcinoma is defined as pools of stromal extracellular mucin containing scanty, floating carcinoma cells. It is a well-defined entity in breast or large bowel. However, mucinous noncystic carcinoma of the pancreas (MNCC) is uncommon, comprising between 1% and 3% of all carcinomas of the pancreas. In the past, MNCC generally had been categorized together with ordinary ductal adenocarcinoma or misdiagnosed as mucinous cystadenocarcinoma or signet-ring cell carcinoma. The new WHO classification lists MNCC as a variant of ductal adenocarcinoma. Herein, we report a 32-year-old woman with incidentally found pancreatic body mass who underwent subtotal pancreatectomy. She was diagnosed as MNCC histologically.
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Yorita, Kenji; Kuroda, Naoto; Naroda, Takushi; Tamura, Masato; Ohe, Chisato; Divatia, Mukul; Amin, Mahul B; Cubilla, Antonio L; Kazakov, Dimitry V; Hes, Ondrej; Michal, Michael; Michal, Michal
2018-04-01
Stratified mucin-producing intra-epithelial lesion (SMILE) and invasive stratified mucin-producing carcinoma (ISMC) are recently described cervical and penile lesions. We report an unusual case of mixed variant of penile squamous cell carcinomas with warty, usual and mucoepidermoid SMILE/ISMC features. A 62-year-old Japanese man had a glans penis lesion of one-and-a-half years' duration, suggesting malignancy. Partial penectomy and left inguinal lymphadenectomy were performed. Pathological evaluation revealed a mixed squamous cell carcinoma with warty, mucinous and usual features. The mucinous component resembled mucoepidermoid carcinoma (MEC) and SMILE/ISMC. Glandular differentiation was absent. All the diverse tumour components were negative for p16, which was confirmed by negative human papillomavirus (HPV) genotyping. The mucinous component was diffusely positive for cytokeratin 7 and largely negative for cytokeratin 5 and p63. Fluorescence in-situ hybridisation did not detect rearrangement in the MAML2 or EWSR1 genes. The tumour was pathological stage pT2, pN1 (AJCC prognostic stage group IIIA) and was disease-free 26 months after surgery. The lack of glands in the mucinous areas suggested that MEC should be separated from adenosquamous carcinoma (ASC). Penile SMILE/ISMC may occur without dependence upon HPV status. Further studies will be necessary to determine the pathogenesis and definition of penile SMILE/ISMC, the presence of true MEC arising from the glans penis and the clinicopathological differences of penile ASC, MEC and SMILE/ISMC. Herein, we refer to the SMILE-like penile lesion as 'mucinous penile intra-epithelial neoplasia'. © 2017 John Wiley & Sons Ltd.
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Tsukagoshi, Mariko; Araki, Kenichiro; Saito, Fumiyoshi; Kubo, Norio; Watanabe, Akira; Igarashi, Takamichi; Ishii, Norihiro; Yamanaka, Takahiro; Shirabe, Ken; Kuwano, Hiroyuki
2018-04-01
International consensus guidelines for intraductal papillary mucinous neoplasms (IPMNs) were revised in 2012. We aimed to evaluate the clinical utility of each predictor in the 2006 and 2012 guidelines and validate the diagnostic value and surgical indications. Forty-two patients with surgically resected IPMNs were included. Each predictor was applied to evaluate its diagnostic value. The 2012 guidelines had greater accuracy for invasive carcinoma than the 2006 guidelines (64.3 vs. 31.0%). Moreover, the accuracy for high-grade dysplasia was also increased (48.6 vs. 77.1%). When the main pancreatic duct (MPD) size ≥8 mm was substituted for MPD size ≥10 mm in the 2012 guidelines, the accuracy for high-grade dysplasia was 80.0%. The 2012 guidelines exhibited increased diagnostic accuracy for invasive IPMN. It is important to consider surgical resection prior to invasive carcinoma, and high-risk stigmata might be a useful diagnostic criterion. Furthermore, MPD size ≥8 mm may be predictive of high-grade dysplasia.
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Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma
Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary
2016-01-01
Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169
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Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.
Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary
2016-01-14
Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).
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Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas
Paini, Marina; Crippa, Stefano; Partelli, Stefano; Scopelliti, Filippo; Tamburrino, Domenico; Baldoni, Andrea; Falconi, Massimo
2014-01-01
Since the first description of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in the eighties, their identification has dramatically increased in the last decades, hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases. However, the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions. The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed. We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms, identifying some genes, molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy. The knowledge of molecular biology of IPMNs has impressively developed over the last few years. A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified, in pancreatic juice or in blood or in the samples from the pancreatic resections, but further researches are required to use these informations for clinical intent, in order to better define the natural history of these diseases and to improve their management. PMID:25110429
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Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas.
Paini, Marina; Crippa, Stefano; Partelli, Stefano; Scopelliti, Filippo; Tamburrino, Domenico; Baldoni, Andrea; Falconi, Massimo
2014-08-07
Since the first description of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in the eighties, their identification has dramatically increased in the last decades, hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases. However, the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions. The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed. We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms, identifying some genes, molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy. The knowledge of molecular biology of IPMNs has impressively developed over the last few years. A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified, in pancreatic juice or in blood or in the samples from the pancreatic resections, but further researches are required to use these informations for clinical intent, in order to better define the natural history of these diseases and to improve their management.
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Aggressive Variants of Papillary Thyroid Carcinoma: Hobnail, Tall Cell, Columnar, and Solid.
Nath, Meryl C; Erickson, Lori A
2018-05-01
Papillary thyroid carcinomas are the most common endocrine cancer and are usually associated with good survival. However, some variants of papillary thyroid carcinomas may behave more aggressively than classic papillary thyroid carcinomas. The tall cell variant of papillary thyroid carcinoma is the most common aggressive variant of papillary thyroid carcinoma. The aggressive behavior has been ascribed to the histologic subtype and/or to the clinicopathologic features, an issue that remains controversial. The columnar variant of papillary thyroid carcinoma can be aggressive, particularly in older patients, with larger tumors showing a diffusely infiltrative growth pattern and extrathyroidal extension. A papillary thyroid carcinoma is designated as solid/trabecular variant when all or nearly all of a tumor not belonging to any of the other variants has a solid, trabecular, or nested (insular) appearance. This tumor must be distinguished from poorly differentiated thyroid carcinoma which has the same growth pattern but lacks nuclear features of papillary thyroid carcinoma and may show tumor necrosis and high mitotic activity. New to the fourth edition of the WHO Classification of Tumours of Endocrine Organs, the hobnail variant of papillary thyroid carcinoma is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. All of these variants are histologically unique and important to recognize due to their aggressive behavior.
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WT1 immunoreactivity in breast carcinoma: selective expression in pure and mixed mucinous subtypes.
Domfeh, Akosua B; Carley, AnnaMarie L; Striebel, Joan M; Karabakhtsian, Rouzan G; Florea, Anca V; McManus, Kim; Beriwal, Sushil; Bhargava, Rohit
2008-10-01
Current literature suggests that strong WT1 expression in a carcinoma of unknown origin virtually excludes a breast primary. Our previous pilot study on WT1 expression in breast carcinomas has shown WT1 expression in approximately 10% of carcinomas that show mixed micropapillary and mucinous morphology (Mod Pathol 2007;20(Suppl 2):38A). To definitively assess as to what subtype of breast carcinoma might express WT1 protein, we examined 153 cases of invasive breast carcinomas. These consisted of 63 consecutive carcinomas (contained 1 mucinous tumor), 20 cases with micropapillary morphology (12 pure and 8 mixed), 6 micropapillary 'mimics' (ductal no special type carcinomas with retraction artifacts), 33 pure mucinous carcinomas and 31 mixed mucinous carcinomas (mucinous mixed with other morphologic types). Overall, WT1 expression was identified in 33 carcinomas, that is, 22 of 34 (65%) pure mucinous carcinomas and in 11 of 33 (33%) mixed mucinous carcinomas. The non-mucinous component in these 11 mixed mucinous carcinomas was either a ductal no special type carcinoma (8 cases) or a micropapillary component (3 cases). WT1 expression level was similar in both the mucinous and the non-mucinous components. The degree of WT1 expression was generally weak to moderate (>90% cases) and rarely strong (<10% cases). None of the breast carcinoma subtype unassociated with mucinous component showed WT1 expression.
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Mucinous breast carcinoma with myoepithelial-like spindle cells.
Miyake, Yasuyuki; Hirokawa, Mitsuyoshi; Norimatsu, Yoshiaki; Kanahara, Takuo; Monobe, Yasumasa; Ohno, Setsuyo; Miyamoto, Tomoyuki; Yakushiji, Hiromasa; Sakaguchi, Takuya; Aratake, Yatsuki; Ohno, Eiji
2009-06-01
Appearance of spindle cells has been believed as a benign index of breast cytology. But, we have frequently observed the spindle cells in smears from mucinous carcinoma of the breast. Here, we characterized the biochemical nature of the spindle cells, so as to clarify their identity in cytology. Nineteen cases of breast mucinous carcinoma were used for cytological examination. The spindle cells were located at edges of tumor cell nests and in the backgrounds of cytological specimens. Immunohistological examination revealed that the spindle cells exhibited both immunoreactivity against carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Immunoreactivity against vimentin, cytokeratin, or alpha-smooth muscle actin was, however, not observed. The mode of distribution of biochemical markers suggests that the positive cells for anti-CEA antibody and anti-EMA antibody are tumor cells compressed by mucin, while the vimentin-positive cells are fibroblasts. We assert that the presence of spindle cells can be a characteristic feature of mucinous carcinoma of the breast. Discrimination of the spindle cells in mucinous carcinoma from myoepithelial cells and naked bipolar nuclei in benign lesions was established here. It should facilitate precise diagnosis of breast cancer. (c) 2009 Wiley-Liss, Inc.
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Guo, Zhenying; Ge, Minghua; Chu, Ying-Hsia; Asioli, Sofia; Lloyd, Ricardo V
2018-07-01
Papillary thyroid carcinomas account for ∼80% of well-differentiated thyroid tumors. During the past decade, several new variants of papillary-like thyroid neoplasms and papillary thyroid carcinomas have been recognized. Some of these neoplasms that were previously classified as malignant have been reclassified as low-grade neoplasms, as the diagnostic criteria have evolved. Similarly, some of the papillary thyroid carcinomas that were previously classified as conventional or classic papillary thyroid carcinomas have now been recognized as more aggressive variants of papillary thyroid carcinomas. Recognizing these differences becomes more important for the proper medical, surgical, and radiotherapeutic management of patients with these neoplasms.
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Mucinous cystadenocarcinoma of the breast coexisting with infiltrating ductal carcinoma.
Chen, Wei-Yu; Chen, Ching-Shyang; Chen, Hsin-Chi; Hung, Yi-Ju; Chu, Jan-Show
2004-10-01
A recently described and rare variant of breast carcinoma, mucinous cystadenocarcinoma (MCA), is reported in a 65-year-old post-menopausal woman. She presented with a gradually enlarged breast tumor. A well-circumscribed tumor measuring about 3 cm in diameter was noted in the mammographic and ultrasonographic examinations. The mammographic and ultrasonographic findings were indistinguishable from more common mucinous carcinoma (colloid carcinoma) of the breast. The gross appearance of the tumor was well-defined and cystic, consisting of abundant transparent to bloody mucin, as well as whitish solid parts. Microscopically, the tumor was characterized by abundant extracellular and intracellular mucin. It looked like a mucinous cystic neoplasm of the ovary and pancreas. Particularly, few microscopic foci of ordinary intermediate-grade infiltrating ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) were observed around the main lesion in this case. A transition from ordinary DCIS to MCA in situ was found. It might indicate MCA derives from a metaplasia process of ordinary DCIS. MCA can be easily differentiated from mucinous carcinoma by quite different histologic and immunohistochemical findings. According to the previously reported and present cases, MCA of the breast more commonly affects elderly women and has a relatively favorable prognosis.
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Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza
2013-08-01
Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.
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Tamura, Koji; Ohtsuka, Takao; Date, Kenjiro; Fujimoto, Takaaki; Matsunaga, Taketo; Kimura, Hideyo; Watanabe, Yusuke; Miyazaki, Tetsuyuki; Ohuchida, Kenoki; Takahata, Shunichi; Ishigami, Kousei; Oda, Yoshinao; Mizumoto, Kazuhiro; Nakamura, Masafumi; Tanaka, Masao
2016-07-01
To clarify the usefulness of molecular biomarkers for distinguishing invasive carcinoma derived from intraductal papillary mucinous neoplasms (IPMNs [Inv-IPMN]) from concomitant pancreatic ductal adenocarcinoma (PDAC). Data from 19 patients with resected concomitant PDAC were retrospectively reviewed. KRAS/GNAS mutations and immunohistochemical (IHC) expression of p53 and p16/CDKN2A were assessed in both IPMN and distinct PDAC. As controls, KRAS/GNAS mutations and IHC labeling were assessed between invasive and noninvasive components in 1 lesion of 22 independent patients. KRAS/GNAS mutation status of invasive and noninvasive components in Inv-IPMN was consistent in 18 (86%) of 21 patients. Conversely, mutational patterns in IPMN and distinct PDAC in the same pancreas differed from each other in 17 (89%) of 19. There were 10 (53%) and 8 (42%) of 19 patients who showed the same p53 and p16/CDKN2A staining between concomitant PDAC and distinct IPMN. In the Inv-IPMN cohort, 19 (86%) of 22 patients showed the same IHC expression pattern between the noninvasive and invasive components. It may be possible to distinguish Inv-IPMN from concomitant PDAC by assessing these molecular biomarkers. More precise distinction of Inv-IPMN and concomitant PDAC will lead to adequate recognition of the natural history of IPMNs and hence optimal management.
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Casey, Mary B; Lohse, Christine M; Lloyd, Ricardo V
2003-01-01
The histopathology of papillary thyroid hyperplasia and papillary thyroid carcinoma is similar enough to cause a diagnostic dilemma in a few cases. Both lesions may have papillary fronds with fibrovascular cores, nuclear crowding, and nuclear anisocytosis. Formalin- fixed paraffin-embedded tissues from 30 randomly selected patients with papillary thyroid hyperplasia and an equal number from patients with papillary thyroid carcinoma were analyzed for expression of cytokeratin 19 (CK19), galectin-3, and HBME-1. Cases of papillary thyroid carcinoma had moderate to strong CK19, galectin-3, and HBME-1 reactivity although both CK19 and galectin-3 showed positive staining in a significant number of nonneoplastic thyroid cases. HBME-1 was uncommon in the nonneoplastic cases. These results indicate that HBME-1 may be useful in helping to distinguish papillary thyroid carcinoma from hyperplasia in diagnostically difficult cases.
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Pheochromocytoma, papillary thyroid carcinoma.
Nasser, Tariq; Qari, Faiza
2009-08-01
A 53-year-old woman presented with labile and difficult to control hypertension on 3 different anti-hypertensive medications. Abdominal computed tomography and ultrasonography of the thyroid gland showed a 1.8 cm thyroid nodule. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum thyroid stimulating hormone and free thyroxine, calcitonin, carcinoembryonic antigen, intact parathyroid hormone, and calcium levels were within normal limits. A 24-hour urine metanephrine showed significant elevation in urine metanephrine of approximately 3 times the upper limit of normal, and the result of 131I-metaiodobenzyleguanjdjne (131I-MIBG) scintigraphy confirmed that the adrenal mass was pheochromocytoma. Right adrenalectomy and total thyroidectomy were performed. The final pathology was pheochromocytoma and papillary thyroid carcinoma. An analysis of c-ret porto-oncogene mutation yielded a negative result. This unusual association of 2 tumors represents a new entity.
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Shao, Tiffany; Yousef, Peter; Shipilova, Irina; Saleeb, Rola; Lee, Jason Y; Krizova, Adriana
2016-03-01
Multifocal renal cell carcinoma of different histological subtypes within a single kidney is rare. We report a recently classified clear cell (tubulo) papillary renal cell carcinoma as part of an unusual case of multifocal renal cell carcinoma of discordant histological subtypes. A 57 year-old-man was found to have multiple renal tumors and cysts on imaging and underwent a laparoscopic left radical nephrectomy. Pathological review showed multifocal renal cell carcinoma (clear cell (tubulo) papillary, clear cell and papillary renal cell carcinomas and papillary adenomas). Morphology of clear cell papillary renal cell carcinoma was supported by immunohistochemical profile (CK7+, HMWK+, CAIX+, AMACR-, CD10-, TFE3-). This is the first report of clear cell papillary renal cell carcinoma as part of multifocal renal cell carcinoma of different histological subtypes. Related lineage of clear cell renal cell carcinoma and papillary renal cell carcinoma is supported by the highest prevalence of their combination within multifocal renal cell carcinoma of different histological subtypes along with their molecular interconnection. Clear cell papillary renal cell carcinoma may be uniquely placed between clear cell and papillary renal cell carcinomas since it shows morphological features intermediate between clear cell and papillary renal cell carcinoma along with overlapping but unique immunohistochemical profile. Clear cell papillary renal cell carcinoma may be molecularly related to clear cell and papillary renal cell carcinomas since the tumors overexpress markers of HIF pathway activation with normal/elevated VHL mRNA expression and some tumors show losses of chromosome 3. Due to the overlapping morphology, it is possible that cases of clear cell papillary renal cell carcinoma may have been misclassified as papillary or clear cell renal cell carcinoma in the literature, incorrectly increasing their reported prevalence. Identification of multifocal RCCs may be related to the
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Mucin profiles in signet-ring cell carcinoma.
Nguyen, Minh D; Plasil, Brian; Wen, Ping; Frankel, Wendy L
2006-06-01
Signet-ring cell carcinoma (SRCC) is a poorly differentiated mucin-producing adenocarcinoma that may arise from many different organs, but all SRCCs share identical morphology. It is not possible to differentiate sites of origin for metastatic SRCC based on morphology alone. Mucins are high-molecular-weight glycoproteins differentially expressed in glandular epithelia and in adenocarcinomas. To identify mucin profiles of primary and metastatic SRCCs using immunohistochemistry to determine whether mucin staining could help distinguish sites of origin. Forty-seven SRCCs, including 38 primary (21 stomach, 11 colorectum, and 6 breast) and 9 metastases from these primary sites were retrieved from archival files. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC (MUC5), and MUC6 on separate slides. Cytoplasmic staining was scored based on proportion of positive tumor cells as follows: 0+ (<5%), 1+ (5%-25%), 2+ (26%-50%), and 3+ (>50%). Mucin profiles were recorded as MUC+, MUCv, and MUC- for consistent, variable, and negative expression, respectively. The mucin profiles for gastric, colorectum, and breast SRCCs are MUC1.2.4.5.6v, MUC2.4+/MUC5v/ MUC1.6-, and MUC1+/MUC2.5.6v/MUC4-, respectively. Mucin profiles of metastatic cases shared profiles with their respective primaries. Signet-ring cell carcinomas of the stomach, colorectum, and breast have distinct mucin expression patterns that are maintained in metastases. Mucin profiling may be useful to identify the origin of a metastatic SRCC of unknown primary.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Oberholzer, Katja, E-mail: oberholz@radiologie.klinik.uni-mainz.de; Menig, Matthias; Kreft, Andreas
2012-02-01
Purpose: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). Methods and Materials: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgicalmore » specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). Results: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p {<=} 0.001). Positive resection margins (ypCRM {<=} 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p {<=} 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). Conclusion: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.« less
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Primary mucinous carcinoma with rhabdoid cells of the thyroid gland: a case report.
Matsuo, Mioko; Tuneyoshi, Masazumi; Mine, Mari
2016-06-10
Primary mucinous carcinoma of the thyroid gland is a rare disease; only 6 cases of primary mucinous carcinoma of the thyroid have been previously reported. Primary mucinous carcinoma of the thyroid gland with incomplete tumor resection tends to be associated with a poor prognosis, resulting in death within a few months. An early and appropriate diagnosis may contribute to improvement in patient prognosis; however, it is extremely difficult to diagnose primary mucinous carcinoma of the thyroid. We present the seventh reported case of primary mucinous carcinoma in the thyroid gland; moreover, rhabdoid cells were detected, which, to our knowledge, is a novel finding. An 81-year-old Japanese woman was initially diagnosed with a poorly differentiated thyroid carcinoma, and she underwent a hemithyroidectomy. Pathological examination revealed the presence of abundant mucus and agglomeration of large atypical cells. Rhabdoid cells were also seen scattered among the tumor cells. Immunostaining was performed for various markers, and on the basis of these results, we diagnosed the lesion as primary mucinous carcinoma with rhabdoid cells in the thyroid gland. Ten months after surgery, recurrence was noted in the paratracheal lymph nodes; therefore, total resection of the residual thyroid gland and paratracheal lymphadenectomy with thyroid-stimulating hormone suppression were performed. The patient is currently alive and disease-free. The current case is of interest not only because of the rare histological findings, but also because the patient achieved long-term survival following diagnosis of a mucinous carcinoma. We believe this report will be helpful for diagnosing future cases of mucinous carcinoma of the thyroid.
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Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas.
Saito, T; Endo, T; Kawaguchi, A; Ikeda, M; Katoh, R; Kawaoi, A; Muramatsu, A; Onaya, T
1998-01-01
Iodide is concentrated to a much lesser extent by papillary thyroid carcinoma as compared with the normal gland. The Na+/I- symporter (NIS) is primarily responsible for the uptake of iodide into thyroid cells. Our objective was to compare NIS mRNA and protein expression in papillary carcinomas with those in specimens with normal thyroid. Northern blot analysis revealed a 2.8-fold increase in the level of NIS mRNA in specimens with papillary carcinoma versus specimens with normal thyroid. Immunoblot analysis using anti-human NIS antibody that was produced with a glutathione S-transferase fusion protein containing NIS protein (amino acids 466-522) showed the NIS protein at 77 kD. The NIS protein level was elevated in 7 of 17 cases of papillary carcinoma but was not elevated in the normal thyroid. Immunohistochemical staining revealed abundant NIS in 8 of 12 carcinomas, whereas NIS protein was barely detected in specimens with normal thyroid. Although considerable patient-to-patient variation was observed, our results indicate that NIS mRNA is elevated, and its protein tends to be more abundant, in a subset of papillary thyroid carcinomas than in normal thyroid tissue. PMID:9525971
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Intraductal papillary-mucinous neoplasia of the pancreas: Histopathology and molecular biology.
Verbeke, Caroline S
2010-10-27
Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a clinically and morphologically distinctive precursor lesion of pancreatic cancer, characterized by gradual progression through a sequence of neoplastic changes. Based on the nature of the constituting neoplastic epithelium, degree of dysplasia and location within the pancreatic duct system, IPMNs are divided in several types which differ in their biological properties and clinical outcome. Molecular analysis and recent animal studies suggest that IPMNs develop in the context of a field-defect and reveal their possible relationship with other neoplastic precursor lesions of pancreatic cancer.
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Geisler, J P; Sorosky, J I; Duong, H L; Buekers, T E; Geisler, M J; Sood, A K; Anderson, B; Buller, R E
2001-12-01
Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and chi(2) tests. Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC (P < 0.001). Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus. (c)2001 Elsevier Science.
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Marine-Lenhart syndrome with papillary thyroid carcinoma.
Atmaca, Hulusi; Çolak, Ramis; Yazici, Zihni Acar; Kefeli, Mehmet; Tosun, Fevziye Canbaz
2015-04-01
Graves' disease with accompanying functioning nodules is known as Marine-Lenhart syndrome. Autonomously functioning thyroid nodules (AFTNs) also within Graves' thyroid tissue are almost always bening in nature. A 45-year-old man developed hyperthyroidism due to the coexistence of Graves' disease and AFTN. Total thyroidectomy was performed. The hyperfunctioning nodule with centrally hypoactive foci detected by technetium-99m thyroid scanning was histologically diagnosed as papillary thyroid carcinoma that was 2.5 cm in diameter. We report the presence of papillary thyroid carcinoma within AFTN in patients with Marine-Lenhart syndrome, which has not been reported so far.
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Papillary Carcinoma in Median Aberrant Thyroid (Ectopic) - Case Report
K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi
2014-01-01
Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed. PMID:25121039
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Papillary carcinoma in median aberrant thyroid (ectopic) - case report.
Hebbar K, Ashwin; K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi
2014-06-01
Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed.
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Lee, Sheng-Huang; Chaung, Chen-Rong
2008-09-01
Mammary mucinous cystadenocarcinoma (MCA) is a rare, invasive ductal carcinoma (IDC) of the breast that is virtually identical morphologically to MCA of the ovary, pancreas or appendix. Synchronous bilateral breast tumors, not uncommonly encountered in fibroadenoma and lobular carcinoma, are unusual in IDC. Reported herein is a primary MCA of the right breast coexisting with a bilateral ordinary IDC in a 55-year-old Taiwanese woman who underwent modified radical mastectomy of both breasts with bilateral axillary level I and II lymph node dissection. In the right breast a 2.5 cm unilocular mucus-filled cyst was found. It had complex papillae, some of which were supported by delicate fibrovascular stroma, lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin and an abundance of intracystic extracellular mucin, coexisting with a low-grade ordinary IDC. In the left breast a high-grade ordinary IDC was discovered. The patient had undergone simple abdominal total hysterectomy for myoma uteri along with bilateral salpingo-oophorectomy 10 years previously. Based on pathological studies and a literature review, it is suggested that mammary MCA arises from mucinous metaplasia and macrocystic transformation of ordinary breast carcinoma. A brief discussion of bilateral breast cancers is also given.
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Mucinous cystadenocarcinoma of the breast.
Koenig, C; Tavassoli, F A
1998-06-01
Four unusual cases of primary mammary mucinous cystadenocarcinoma composed predominantly of tall columnar cells with abundant intracytoplasmic mucin are reported; they were multicystic and appeared virtually identical to mucinous cystadenocarcinomas of the ovary and pancreas. Three of the women were white and one was black, they ranged in age from 49 to 67 years (average 58), and they had tumors that ranged from 0.8 to 19 cm in diameter. Microscopically, the tumors were characterized by cystic spaces lined by predominantly bland-appearing columnar mucinous cells with stratification, tufting, and papillary formations. Varying degrees of cytologic atypia were focally evident, with gradual loss of the intracytoplasmic mucin and transformation to an eosinophilic squamoid cell population. Multifocal invasion generally emanated from these eosinophilic, squamoid areas in all cases. All four tumors displayed immunoreactivity for MIB-1 (Ki-67) in a relatively high percentage of cells and failed to show immunoreactivity for estrogen receptors and progesterone receptors. All four stained positively with cytokeratin 7 (CK7) but were negative with cytokeratin 20 (CK20). Mastectomy and axillary lymph node dissection were performed in three cases and lumpectomy with lymph node dissection in the remaining case. Lymph node metastases, identified in only one patient, retained the distinctive morphology. Three of the patients are alive without evidence of disease 11, 22, and 24 months after the diagnosis; the fourth is a recent case. These tumors are a rare, clinicopathologically distinct type of primary breast carcinoma that should be distinguished from typical mucinous (colloid) carcinomas of the breast and, more importantly, metastases from other sites.
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Morrison, Carl; Merati, Kambiz; Marsh, William L; De Lott, Lindsey; Cohn, David E; Young, Gregory; Frankel, Wendy L
2007-12-01
Mucin expression patterns have been studied in tumors from various sites. Previous studies have shown an association of MUC1 with poor prognosis and MUC2 and MUC5AC with a mucinous phenotype. The pattern of mucin expression in endometrial carcinomas has not been documented in a large series. We determined the mucin expression profile in endometrial carcinomas and evaluated the relationship between mucin expression and clinical-pathologic parameters. A tissue microarray of 310 cases of endometrial carcinoma with known clinical outcome was constructed from formalin-fixed, paraffin-embedded donor blocks using two 0.6 mm cores from each tumor. Sections were stained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC, and MUC6. Staining was considered positive if greater than or equal to 5% of cells stained positively in either core. Mucin expression was correlated with tumor type, histologic grade, International Federation Gynecology and Obstetrics stage, lymph node involvement, depth of myometrial invasion, patient age, ethnicity, and clinical outcome. MUC1 was expressed in 267/310 (86.1%) of endometrial carcinomas, MUC2 in 2/310 (0.6%), MUC4 in 73/310 (23.5%), MUC5AC in 1/310 (0.3%), and MUC6 in 4/310 (1.2%). Endometrioid endometrial carcinoma showed a higher rate of MUC1 expression than nonendometrioid endometrial carcinoma (227/258, 88.0% vs. 39/52, 75.0%, P=0.01). No significant differences in any of the mucins were noted among the other end points evaluated. Mucin expression did not correlate with tumor grade, stage, or patient outcome.
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Management of the Patient with Aggressive and Resistant Papillary Thyroid Carcinoma
Miftari, Rame; Topçiu, Valdete; Nura, Adem; Haxhibeqiri, Valdete
2016-01-01
Purpose: Papillary carcinoma is the most frequent type of thyroid cancer and was considered the most benign of all thyroid carcinomas, with a low risk of distant metastases. However, there are some variants of papillary thyroid carcinoma that have affinity to spread in many organs, such as: lymph nodes, lungs and bones. Aim: The aim of this study was presentation of a case with papillary carcinoma of the thyroid gland, very persistent and resistant in treatment with I 131. Material and results: A man 56 years old were diagnosed with papillary carcinoma of thyroid gland. He underwent a surgical removal of the tumor and right lobe of thyroid gland. With histopathology examination, were confirmed follicular variant of papillary carcinoma pT4. Two weeks later he underwent total thyroidectomy and was treated with 100 mCi of J 131. Six months later, the value of thyroglobulin was found elevated above upper measured limits (more than 500 ng/ml). Patient underwent surgical removal of 10 metastatic lymph nodes in the left side of the neck and has been treated with 145 mCi of radioiodine I 131. The examination after 5 months shows elevation of thyroglobulin, more than 20000 ng/ml and focally uptake of J 131 in the left lung. Patient was treated once again with 150 mCi radioiodine J 131. Whole body scintigraphy was registered focal uptake of radioiodine in the middle of the left collarbone. After a month, patient refers the enlargement of the lymph node in the right side of the neck. Currently patient is being treated with kinase inhibitor drug sorafenib and ibandronate. We have identified first positive response in treatment. Enlarged lymph node in the neck was reduced and the patient began feeling better. Conclusion: This study suggests that some subtypes of papillary thyroid carcinoma appear to have more aggressive biological course. Subtypes of papillary thyroid carcinoma such as diffuse sclerosing carcinoma, tall cell or columnar cell and insular variants, appears to
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Kumar, Mayank; Pottipati, Bhaswanth; Arakeri, Surekha U; Javalgi, Anita P
2017-06-01
Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast.
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Pottipati, Bhaswanth; Arakeri, Surekha U.; Javalgi, Anita P.
2017-01-01
Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast. PMID:28764176
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Park, Cheol Keun; Yoon, Gun; Cho, Yoon Ah; Kim, Hyun-Soo
2016-06-28
Papillary proliferation of the endometrium is an unusual lesion that is composed of papillae with fibrovascular stromal cores covered with benign-appearing glandular epithelium. We studied the clinicopathological and immunohistochemical features of four cases of endometrial papillary proliferations. All patients were postmenopausal. Two lesions were incidental findings in hysterectomy specimens, and two lesions were detected in endometrial curettage specimens. Based on the degree of architectural complexity and extent of proliferation, we classified papillary proliferations histopathologically into "simple" or "complex" growth patterns. Three cases were classified as simple papillary proliferation, and one case was classified as complex papillary proliferation. Simple papillary proliferations were characterized by slender papillae with delicate stromal cores. In contrast, complex papillary proliferations had intracystic papillary projections and cellular clusters with frequent branching and occasional cytological atypia. All cases showed coexistent metaplastic epithelial changes, including mucinous metaplasia, eosinophilic cell change, and ciliated cell metaplasia. One patient with simple papillary proliferations had coexistent well-differentiated endometrioid carcinoma. One patient had subsequent hyperplasia without atypia, and another patient had subsequent atypical hyperplasia/endometrioid intraepithelial neoplasia; both patients underwent total hysterectomy within four months. Our observations are consistent with previous data demonstrating that endometrial papillary proliferations coexist with or develop into atypical hyperplasia/endometrioid intraepithelial neoplasia or endometrioid carcinoma. It is very important for pathologists to discriminate papillary proliferations from neoplastic lesions (including atypical hyperplasia/endometrioid intraepithelial neoplasia and well-differentiated endometrioid carcinoma) and benign mimickers (including papillary
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Park, Cheol Keun; Yoon, Gun; Cho, Yoon Ah; Kim, Hyun-Soo
2016-01-01
Papillary proliferation of the endometrium is an unusual lesion that is composed of papillae with fibrovascular stromal cores covered with benign-appearing glandular epithelium. We studied the clinicopathological and immunohistochemical features of four cases of endometrial papillary proliferations. All patients were postmenopausal. Two lesions were incidental findings in hysterectomy specimens, and two lesions were detected in endometrial curettage specimens. Based on the degree of architectural complexity and extent of proliferation, we classified papillary proliferations histopathologically into “simple” or “complex” growth patterns. Three cases were classified as simple papillary proliferation, and one case was classified as complex papillary proliferation. Simple papillary proliferations were characterized by slender papillae with delicate stromal cores. In contrast, complex papillary proliferations had intracystic papillary projections and cellular clusters with frequent branching and occasional cytological atypia. All cases showed coexistent metaplastic epithelial changes, including mucinous metaplasia, eosinophilic cell change, and ciliated cell metaplasia. One patient with simple papillary proliferations had coexistent well-differentiated endometrioid carcinoma. One patient had subsequent hyperplasia without atypia, and another patient had subsequent atypical hyperplasia/endometrioid intraepithelial neoplasia; both patients underwent total hysterectomy within four months. Our observations are consistent with previous data demonstrating that endometrial papillary proliferations coexist with or develop into atypical hyperplasia/endometrioid intraepithelial neoplasia or endometrioid carcinoma. It is very important for pathologists to discriminate papillary proliferations from neoplastic lesions (including atypical hyperplasia/endometrioid intraepithelial neoplasia and well-differentiated endometrioid carcinoma) and benign mimickers (including
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Papillary carcinoma in ectopic thyroid detected by Tl-201 scintigraphy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Michigishi, T.; Mizukami, Y.; Mura, T.
1991-05-01
A 37-year-old man with papillary carcinoma in an ectopic thyroid is presented. Excisional biopsy revealed the cervical mass to be a metastasis from thyroid cancer. X-ray, ultrasonography, and computed tomography, however, failed to identify the primary tumor in the thyroid. Incidental TI-201 uptake was noted in the midline of the anterior neck, and a palpable nodule was discovered in this area. Fine needle aspiration cytology demonstrated Class V papillary adenocarcinoma, and subsequent surgery confirmed a papillary carcinoma in the ectopic thyroid. This case suggests the usefulness of TI-201 scintigraphy for the detection of ectopic thyroid malignancy.
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Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients
2012-01-01
Background Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15–3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival. Methods Patients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15–3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0. Results Serum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15–3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p< 0.001) than in patients with benign disease. Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression. Conclusions This study found
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Hanski, C; Hofmeier, M; Schmitt-Gräff, A; Riede, E; Hanski, M L; Borchard, F; Sieber, E; Niedobitek, F; Foss, H D; Stein, H; Riecken, E O
1997-08-01
Mucinous carcinomas of the colorectum have been reported to overexpress the intestinal mucin MUC2. The purpose of this study was to determine whether this alteration is shared by mucinous tumours of the ovary, breast, and pancreas. A total of 40 breast carcinomas (22 of mucinous and 18 of ductal invasive type), 39 ovarian adenocarcinomas (16 mucinous, 23 serous), 47 colorectal carcinomas (25 mucinous and 22 non-mucinous), and 41 pancreatic adenocarcinomas (14 mucinous, 27 non-mucinous) were investigated by immunohistochemistry with the anti-MUC2 monoclonal antibody 4F1 and the expression pattern was ranked. MUC2 mucin is expressed in the normal colonic epithelium; in the normal epithelium of the breast, ovary, and pancreas, it was not detectable by immunohistochemistry or by reverse transcriptase-polymerase chain reaction (RT-PCR). In agreement with previous reports, the colonic mucinous carcinomas differed significantly from the non-mucinous carcinomas by strong MUC2 expression. In all mucinous carcinomas of the ovary, breast, and pancreas, de novo expression of the MUC2 gene was observed, which differentiated mucinous and non-mucinous carcinomas of these tissues (P < 0.001). The overexpression or ectopic expression of the MUC2 gene exhibited by mucinous carcinomas of four organs indicates a common genetic lesion associated with the mucinous tumour phenotype.
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Lee, Nam Kyung; Kim, Suk; Kim, Hyun Sung; Jeon, Tae Yong; Kim, Gwang Ha; Kim, Dong Uk; Park, Do Youn; Kim, Tae Un; Kang, Dae Hwan
2011-01-01
Various mucin-producing neoplasms originate in different abdominal and pelvic organs. Mucinous neoplasms differ from non-mucinous neoplasms because of the differences in clinical outcome and imaging appearance. Mucinous carcinoma, in which at least 50% of the tumor is composed of large pools of extracellular mucin and columns of malignant cells, is associated with a worse prognosis. Signet ring cell carcinoma is characterized by large intracytoplasmic mucin vacuoles that expand in the malignant cells with the nucleus displaced to the periphery. Its prognosis is also generally poor. In contrast, intraductal papillary mucinous neoplasm of the bile duct and pancreas, which is characterized by proliferation of ductal epithelium and variable mucin production, has a better prognosis than other malignancies in the pancreaticobiliary tree. Imaging modalities play a critical role in differentiating mucinous from non-mucinous neoplasms. Due to high water content, mucin has a similar appearance to water on ultrasound (US), computed tomography (CT), and magnetic resonance imaging, except when thick and proteinaceous, and then it tends to be hypoechoic with fine internal echoes or have complex echogenicity on US, hyperdense on CT, and hyperintense on T1- and hypointense on T2-weighted images, compared to water. Therefore, knowledge of characteristic mucin imaging features is helpful to diagnose various mucin-producing neoplastic conditions and to facilitate appropriate treatment. PMID:22147976
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Ying, Shi-Hong; Teng, Xiao-Dong; Wang, Zhao-Ming; Wang, Qi-Dong; Zhao, Yi-Lei; Chen, Feng; Xiao, Wen-Bo
2015-01-01
AIM: To investigate gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) of intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). METHODS: The imaging findings of five cases of IPMN-B which were pathologically confirmed at our hospital between March 2012 and May 2013 were retrospectively analyzed. Three of these cases were diagnosed by duodenal endoscopy and biopsy pathology, and two cases were diagnosed by surgical pathology. All five patients underwent enhanced and non-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography, and Gd-EOB-DTPA-enhanced MRI; one case underwent both Gd-EOB-DTPA-enhanced MRI and positron emission tomography-CT. The clinical data and imaging results for these cases were compared and are presented. RESULTS: Conventional imaging showed diffuse dilatation of bile ducts and multiple intraductal polypoid and papillary neoplasms or serrated changes along the bile ducts. In two cases, Gd-EOB-DTPA-enhanced MRI revealed dilated biliary ducts and intraductal tumors, as well as filling defects caused by mucin in the dilated bile ducts in the hepatobiliary phase. Gd-EOB-DTPA-enhanced MRI in one case clearly showed a low-signal tumor in the hepatobiliary phase, similar to what was seen by positron emission tomography-CT. In two patients, routine inspection was unable to discern whether the lesions were inflammation or tumors. However, Gd-EOB-DTPA-enhanced MRI revealed a pattern of gradual enhancement during the hepatobiliary phase, and the signal intensity of the lesions was lower than the surrounding liver parenchyma, suggesting tissue inflammation in both cases, which were confirmed by surgical pathology. CONCLUSION: Gd-EOB-DTPA-enhanced MRI reveals the intraductal mucin component of IPMN-B in some cases and the extent of tumor infiltration beyond the bile ducts in invasive cases. PMID:26167082
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Ying, Shi-Hong; Teng, Xiao-Dong; Wang, Zhao-Ming; Wang, Qi-Dong; Zhao, Yi-Lei; Chen, Feng; Xiao, Wen-Bo
2015-07-07
To investigate gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) of intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). The imaging findings of five cases of IPMN-B which were pathologically confirmed at our hospital between March 2012 and May 2013 were retrospectively analyzed. Three of these cases were diagnosed by duodenal endoscopy and biopsy pathology, and two cases were diagnosed by surgical pathology. All five patients underwent enhanced and non-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography, and Gd-EOB-DTPA-enhanced MRI; one case underwent both Gd-EOB-DTPA-enhanced MRI and positron emission tomography-CT. The clinical data and imaging results for these cases were compared and are presented. Conventional imaging showed diffuse dilatation of bile ducts and multiple intraductal polypoid and papillary neoplasms or serrated changes along the bile ducts. In two cases, Gd-EOB-DTPA-enhanced MRI revealed dilated biliary ducts and intraductal tumors, as well as filling defects caused by mucin in the dilated bile ducts in the hepatobiliary phase. Gd-EOB-DTPA-enhanced MRI in one case clearly showed a low-signal tumor in the hepatobiliary phase, similar to what was seen by positron emission tomography-CT. In two patients, routine inspection was unable to discern whether the lesions were inflammation or tumors. However, Gd-EOB-DTPA-enhanced MRI revealed a pattern of gradual enhancement during the hepatobiliary phase, and the signal intensity of the lesions was lower than the surrounding liver parenchyma, suggesting tissue inflammation in both cases, which were confirmed by surgical pathology. Gd-EOB-DTPA-enhanced MRI reveals the intraductal mucin component of IPMN-B in some cases and the extent of tumor infiltration beyond the bile ducts in invasive cases.
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Kim, Sung Eun; Park, Ji Hye; Hong, SoonWon; Koo, Ja Seung; Jeong, Joon
2012-01-01
Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA. PMID:23323116
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Kim, Sung Eun; Park, Ji Hye; Hong, Soonwon; Koo, Ja Seung; Jeong, Joon; Jung, Woo-Hee
2012-12-01
Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA.
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Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma.
Kim, Jisup; Lim, Beom Jin; Hong, Soon Won; Pyo, Ju Yeon
2018-03-01
Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation. Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.
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Amico, Paolo; Lanzafame, Salvatore; Li Destri, Giovanni; Greco, Paolo; Caltabiano, Rosario; Vecchio, Giada Maria; Magro, Gaetano
2010-01-01
Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course.
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Amico, Paolo; Lanzafame, Salvatore; Li Destri, Giovanni; Greco, Paolo; Caltabiano, Rosario; Vecchio, Giada Maria; Magro, Gaetano
2010-01-01
Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course. PMID:20593036
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Cassol, Clarissa A; Guo, Miao; Ezzat, Shereen; Asa, Sylvia L
2010-12-01
Activating mutations of GNAq protein in a hotspot at codon 209 have been recently described in uveal melanomas. Since these neoplasms share with thyroid carcinomas a high frequency of MAP kinase pathway-activating mutations, we hypothesized whether GNAq mutations could also play a role in the development of thyroid carcinomas. Additionally, activating mutations of another subtype of G protein (GNAS1) are frequently found in hyperfunctioning thyroid adenomas, making it plausible that GNAq-activating mutations could also be found in some of these nodules. To investigate thyroid papillary carcinomas and thyroid hyperfunctioning nodules for GNAq mutations in exon 5, codon 209, a total of 32 RET/PTC, BRAF, and RAS negative thyroid papillary carcinomas and 13 hyperfunctioning thyroid nodules were evaluated. No mutations were identified. Although plausible, GNAq mutations seem not to play an important role in the development of thyroid follicular neoplasms, either benign hyperfunctioning nodules or malignant papillary carcinomas. Our results are in accordance with the literature, in which no GNAq hotspot mutations were found in thyroid papillary carcinomas, as well as in an extensive panel of other tumors. The molecular basis for MAP-kinase pathway activation in RET-PTC/BRAF/RAS negative thyroid carcinomas remains to be determined.
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Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma
Kim, Jisup; Lim, Beom Jin; Hong, Soon Won; Pyo, Ju Yeon
2018-01-01
Background Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation. Methods Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. Results WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. Conclusions The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA. PMID:29429327
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Targeting Src and tubulin in mucinous ovarian carcinoma
Liu, Tao; Hu, Wei; Dalton, Heather J.; Choi, Hyun Jin; Huang, Jie; Kang, Yu; Pradeep, Sunila; Miyake, Takahito; Song, Jian H.; Wen, Yunfei; Lu, Chunhua; Pecot, Chad V.; Bottsford-Miller, Justin; Zand, Behrouz; Jennings, Nicholas B; Ivan, Cristina; Gallick, Gary E.; Baggerly, Keith A; Hangauer, David G.; Coleman, Robert L.; Frumovitz, Michael; Sood, Anil K.
2013-01-01
Purpose To investigate the antitumor effects of targeting Src and tubulin in mucinous ovarian carcinoma. Experimental design The in vitro and in vivo effects and molecular mechanisms of KX-01, which inhibits Src pathway and tubulin polymerization, were examined in mucinous ovarian cancer models. Results In vitro studies using RMUG-S and RMUG-L cell lines showed that KX-01 inhibited cell proliferation, induced apoptosis, arrested the cell cycle at the G2/M phase, and enhanced the cytotoxicity of oxaliplatin in the KX-01-sensitive cell line, RMUG-S. In vivo studies showed that KX-01 significantly decreased tumor burden in RMUG-S and RMUG-L mouse models relative to untreated controls, and the effects were greater when KX-01 was combined with oxaliplatin. KX-01 alone and in combination with oxaliplatin significantly inhibited tumor growth by reducing cell proliferation and inducing apoptosis in vivo. PTEN knock-in experiments in RMUG-L cells showed improved response to KX-01. Reverse phase protein array analysis showed that in addition to blocking downstream molecules of Src family kinases, KX-01 also activated acute stress-inducing molecules. Conclusion Our results showed that targeting both the Src pathway and tubulin with KX-01 significantly inhibited tumor growth in preclinical mucinous ovarian cancer models, suggesting that this may be a promising therapeutic approach for patients with mucinous ovarian carcinoma. PMID:24100628
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Ocular melanoma and mammary mucinous carcinoma in an African lion.
Cagnini, Didier Q; Salgado, Breno S; Linardi, Juliana L; Grandi, Fabrizio; Rocha, Rafael M; Rocha, Noeme S; Teixeira, Carlos R; Del Piero, Fabio; Sequeira, Julio L
2012-09-25
Reports of neoplasms in Panthera species are increasing, but they are still an uncommon cause of disease and death in captive wild felids. The presence of two or more primary tumor in large felids is rarely reported, and there are no documented cases of ocular melanoma and mammary mucinous carcinoma in African lions. An ocular melanoma and a mammary mucinous carcinoma are described in an African lion (Panthera leo). The first tumour was histologically characterized by the presence of epithelioid and fusiform melanocytes, while the latter was composed of mucus-producing cells with an epithelial phenotype that contained periodic acid-Schiff (PAS) and Alcian blue staining mucins. Metastases of both tumor were identified in various organs and indirect immunohistochemistry was used to characterize them. Peribiliary cysts were observed in the liver. This is the first description of these tumor in African lions.
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Homayouni, Maryam; Mohammad Arabzadeh, Seyed Ali; Nili, Fatemeh; Razi, Farideh; Amoli, Mahsa Mohammad
2017-07-01
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. EBV is one of the most important viruses related to different types of malignancies. This study investigated the relationship between EBV and papillary thyroid carcinoma. In this study the presence of Epstein-Barr Nuclear Antigen 1 (EBNA1) gene in papillary thyroid carcinoma tissues were examined by nested-PCR method. Paraffin-embedded tissues (N=41) blocks of thyroid cancer were used. DNA was extracted from all samples and then samples were evaluated for the presence of EBV gene. In 41 samples, EBNA1 was detected in 65.8% of patients with papillary thyroid carcinoma which was significantly higher in younger ages. The significant presence of EBV genome in papillary thyroid carcinoma suggests that this virus may play a role in this cancer especially in younger ages. As a result, monitoring of patients with EBV latent infection for PTC can be very important. Copyright © 2017 Elsevier GmbH. All rights reserved.
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[A Case of Metachronous Multiple Thyroid Papillary Carcinoma with FAP].
Tajima, Yusuke; Kumamoto, Kensuke; Yamamoto, Azusa; Chika, Noriyasu; Watanabe, Yuichiro; Matsuzawa, Takeaki; Ishibashi, Keiichiro; Mochiki, Erito; Iwama, Takeo; Akagi, Kiwamu; Ishida, Hideyuki
2015-11-01
Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, the result of a germ line mutation in the adenomatous polyposis coli (APC) gene. FAP can be associated with various extracolonic lesions, including thyroid cancer, which frequently occurs in women. We report the case of a 36-year-old woman diagnosed as having FAP with multiple metachronous thyroid papillary carcinomas. She underwent left thyroidectomy at the age of 19 years without a diagnosis of FAP. Multiple polyps in her stomach were detected by medical examination and more than 100 polyps in the colon were found by colonoscopy. She was referred to our hospital after a diagnosis of non-profuse FAP. Multiple tumors with a maximum diameter of 10mm were detected in the right lobe of the thyroid gland during the preoperative examination. Papillary carcinoma was suspected based on fine-needle aspiration cytology. We performed a right thyroidectomy after prophylactic colectomy. Pathological findings revealed a cribriform-morula variant of papillary thyroid carcinoma. The patient remains well after 2 year 6 months with no recurrence.
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Vysetti, Suneetha; Sridhar, Preethi; Theckedath, Boby; Gilden, Janice L; Morawiecki, Peter
2012-10-01
The occurrence of a papillary thyroid carcinoma in a patient with primary hyperparathyroidism is rare. Awareness of this condition will enable clinicians to evaluate for possible thyroid pathology in patients with primary hyperparathyroidism. Both of these endocrine conditions could then be managed with a single surgery involving concomitant resection of the thyroid and parathyroid glands. We report a case of a 53-year-old woman with a parathyroid adenoma and a unilateral papillary thyroid carcinoma, and detail the clinical features, diagnosis, and management.
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Warthin-like papillary carcinoma of the thyroid: a case series and review of the literature.
Erşen, Ayça; Durak, Merih Güray; Canda, Tülay; Sevınç, Ali Ibrahim; Saydam, Serdar; Koçdor, Mehmet Ali
2013-01-01
Warthin-like tumor of the thyroid is a recently described rare variant of thyroid papillary carcinoma. The distinguishing histological feature of this variant is papillary foldings lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. Its prognosis has been reported to be almost similar to conventional papillary carcinoma. In this case series, we report four cases with Warthin-like papillary carcinoma of the thyroid, diagnosed at Dokuz Eylul University Faculty of Medicine Department of Pathology in 2008 and 2009. Three patients were female. The mean patient age was 39 years (range, 20-56) and the mean tumor size was 1.7 cm (range, 0.9-2.0 cm). All of the cases had lymphocytic thyroiditis in the background. None of the tumors showed lymphovascular invasion. The patients are free of any recurrence and/or distant metastasis with a mean follow-up of 25 months. This rare variant of thyroid papillary carcinoma with distinct histopathological features should be indicated in pathology reports. Further studies and long-term follow-up of patients are needed to highlight the biological behavior of this variant.
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Shimizu, Yasuhiro; Yamaue, Hiroki; Maguchi, Hiroyuki; Yamao, Kenji; Hirono, Seiko; Osanai, Manabu; Hijioka, Susumu; Hosoda, Waki; Nakamura, Yasushi; Shinohara, Toshiya; Yanagisawa, Akio
2013-07-01
The present study was a retrospective investigation of predictors of malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The subjects were 310 patients who underwent pancreatic resection at 3 high-volume centers. Preoperative laboratory and imaging findings were analyzed in logistic regression analyses. Endoscopic ultrasonography measurements were essential for the size of mural nodules, and a central review was conducted for pathological diagnosis. Pathological diagnosis was benign IPMN in 150 cases and malignant in 160 (noninvasive carcinoma, n = 100; invasive, n = 60). In multivariate analysis, size of mural nodules, diameter of main pancreatic duct, and cyst size of branch pancreatic duct were independent predictors of malignancy, and areas under the receiver operating characteristic curve for these 3 factors were 0.798, 0.643, and 0.601, respectively. With 7 mm taken as the cutoff value for the size of mural nodules, the diagnosis of malignant IPMN had sensitivity of 74.3% and specificity of 72.7%. Carcinoma without nodules was present in 15 patients (15/160 [9.4%]). The size of mural nodules measured with endoscopic ultrasonography showed high predictive ability. However, about 10% of carcinoma patients did not have nodules, and the handling of the diagnosis in such cases is a problem for the future.
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Anaplastic carcinoma occurring in association with a mucinous cystic neoplasm of the pancreas.
Lane, R B; Sangüeza, O P
1997-05-01
Anaplastic carcinomas of the pancreas are considered variants of ductal adenocarcinoma. They typically occur in elderly men. They have rarely been reported to occur in association with mucinous cystic neoplasms of the pancreas. We report a case of anaplastic carcinoma occurring in association with a pancreatic mucinous cystic neoplasm, borderline-type, in a 25-year-old woman who presented with lymph node and hepatic metastases.
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Aimoto, Takayuki; Mizutani, Satoshi; Kawano, Youichi; Suzuki, Hideyuki; Uchida, Eiji
2013-01-01
We investigated the clinicopathological features of borderline resectable invasive carcinomas (BRICs) derived from intraductal papillary mucinous neoplasms (IPMNs) and examined the significance of the aggressive "surgery first" approach compared with the treatment of conventional borderline resectable pancreatic ductal adenocarcinomas (BRPDAs). We retrospectively studied 7 patients with BRICs derived from IPMNs and 14 patients with conventional BRPDAs. Several factors were reviewed: initial symptoms, preoperative imaging, serum level of CA19-9, perioperative factors, pathological findings, adjuvant chemotherapy, and outcome. All BRICs derived from IPMN were huge tumors (more than 3 cm in diameter) suspected to involve <180° of the circumference of the vessel. Five patients (71%) underwent a modified Whipple procedure, and 2 (29%) underwent distal pancreatectomy. Only 3 patients (43%) required vascular resection. Curative resection was achieved in all 7 patients, who are alive with no evidence of recurrence. There were no severe postoperative complications. With regards to the pathological IPMN subtype, 2 tumors (29%) were gastric and 5 (71%) were intestinal. Only 2 patients (29%) had lymph node metastasis. The final stage was II in 4 (57%) cases and IVa in 3 cases (43%). The 3-year survival rate was 100%. Tumors of BRICs derived from IPMNs were larger than those of conventional BRPDAs (p<0.05). The BRICs derived from IPMN less frequently metastasized to lymph nodes (p<0.05) and were of an earlier stage (p<0.05) than were conventional BRPDAs. The 3-year survival rate was significantly higher for BRICs derived from IPMNs (100%) than for conventional BRPDAs (19%, p<0.001). The BRICs derived from an intestinal or gastric IPMN are less aggressive than conventional BRPDAs and have a more favorable prognosis. In addition, aggressive "surgery first" approach may contribute to this better prognosis.
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Yang, L M; Li, Q; Zhao, B W; Lyu, J G; Xu, H S; Xu, L L; Li, S Y; Gao, L; Zhu, J
2017-04-07
Objective: To investigate the occurrence of occult carcinoma in contralateral lobes based on the ultrasonic features of unilateral papillary thyroid carcinoma. Methods: The study included 202 consecutives cases of unilateral papillary thyroid carcinoma with benign nodules in the contralateral lobe identified by preoperative ultrasound or fine-needle aspiration from June 2014 to December 2015. All patients received total thyroidectomies, and with postoperative pathological examination they were divided into two groups, one including 60 cases with positive occult cancer and another one consisting of 142 cases with negative occult cancer. Univariate and multivariate analyses were performed to analyze the sonographic features of unilateral papillary thyroid carcinoma relevant to the occurrence of occult carcinoma in the contralateral nodules. Results: Univariate analysis indicated occult carcinoma in the contralateral lobes was associated with Hashimoto's thyroiditis(χ(2)=3.955, P =0.047), unclear border (χ(2)=4.375, P =0.036)and multifocality in the ipsilateral(χ(2)=7.375, P =0.007), but not with tumors maximum size, location, A/T, shape, internal structure, internal echo, acoustic halo, calcification, capsular invasion and blood flow signal in the lobe with carcinoma on another side. Multivariate analysis showed unclear border ( OR =2.727, P =0.010) and multifocality in the ipsilateral( OR =2.807, P =0.005)of carcinoma were independent predictive factor for contralateral occult PTC. Conclusions: Unclear border and multifocality of PTC in the ipsilateral were closely relevant to the occurrence of occult carcinoma in the contralateral nodules.
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Kitazono, Iwao; Higashi, Michiyo; Kitamoto, Sho; Yokoyama, Seiya; Horinouchi, Michiko; Osako, Masahiko; Shimizu, Takeshi; Tabata, Mineo; Batra, Surinder K; Goto, Masamichi; Yonezawa, Suguru
2013-10-01
This study aimed to examine expression profile of MUC4 in intraductal papillary mucinous neoplasm of the pancreas (IPMN). We performed immunohistochemistry (IHC) of MUC4 in 142 IPMNs, with evaluation of the specificity of 2 anti-MUC4 monoclonal antibodies, 8G7 and 1G8, in cancer cell lines. Monoclonal antibody 8G7 showed a clear immunoreactivity, whereas MAb 1G8 did not show any immunoreactivity, in the Western blotting and IHC for human pancreatic carcinoma cell lines expressing MUC4 messenger RNA. However, IHC signals detected by both monoclonal antibodies were observed in the tissue specimens. The expression rates of MUC4/8G7 detected by MAb 8G7 and MUC4/1G8 detected by MAb 1G8 in the intestinal-type IPMNs were significantly higher than those in the gastric-type IPMNs. In the intestinal-type IPMNs, MUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells, whereas MUC4/1G8 was expressed mainly at the cell apexes. Even in the gastric-type IPMNs with rare MUC4 expression in the low-grade dysplasia, both MUC4 expression rates increased when dysplasia advanced. A significantly higher expression of MUC4 in intestinal-type IPMNs than in gastric-type IPMNs will be one of the biomarkers to discriminate between the intestinal-type IPMNs with high malignancy potential from gastric-type IPMNs with low malignancy potential.
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Xiong, Jinjun; He, Mai; Jackson, Cynthia; Ou, Joyce J; Sung, C James; Breese, Virgina; Steinhoff, Margaret M; Quddus, M Ruhul; Tejada-Berges, Trevor; Lawrence, W Dwayne
2013-09-01
K-ras gene product in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway is critical in the development of certain types of malignancies. K-ras mutation-associated pancreatic and ovarian carcinomas often display mucinous differentiation. Previous studies have shown that k-ras mutation is found in 10% to 30% of endometrial carcinomas. We investigated k-ras mutations in several morphologic subtypes of endometrial carcinomas with particular emphasis on various degrees of mucinous differentiation. Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections. Polymerase chain reaction amplification for k-ras codons 12 and 13 were performed, followed by sequencing using capillary electrophoresis. The Fisher exact test is used to compare the prevalent difference of k-ras mutation among the groups. P < 0.05 was considered significant. K-ras mutations were detected in 8 (80%) of 10 mucinous carcinomas, 12 (67%) of 18 endometrioid carcinomas (ECs) with significant mucinous differentiation (ECMD), 4 (25%) of 16 ECs, and 1 (9%) of 11 serous carcinomas. The differences were statistically significant between mucinous carcinomas versus EC (P < 0.01) and ECMD versus EC (P < 0.05). The findings suggest that mucinous carcinoma and endometrioid carcinoma with significant mucinous component are more likely to be associated with k-ras mutation. Potential clinical implications of k-ras mutation lies in the management of recurrent or higher-stage endometrial mucinous tumors, which would not be responsive to treatment protocols containing epidermal growth factor receptor inhibitors.
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Guo, Shuangping; Wang, Yingmei; Rohr, Joseph; Fan, Chaoliang; Li, Qinglong; Li, Xia; Wang, Zhe
2016-04-01
Solid papillary carcinoma of the breast, a newly-defined entity, is poorly recognized, and its nature and management is still debated. Eleven cases of pure solid papillary breast carcinoma in our archive and 253 cases reported in previous literature were retrospectively analyzed for their clinicopathological features and outcomes. The eleven cases occurred in elderly females. Grossly, all tumors were well-circumscribed and typically composed of solid papillary nodules. The tumor cells were bland-looking with low-grade atypia and mitoses < 5/10HPF. Immunophenotypically, all eleven cases showed positivity for ER and PR, negativity for CK5/6 and HER2, and a low proliferative index of Ki67. Five cases showed scattered positivity for myoepithelial marker p63, and four cases were positive for CK5/6 and CD10 around the nodules, whereas the other cases were completely negative for all myoepithelial markers. Five cases expressed the neuroendocrine marker synaptophysin, and six cases expressed chromogranin. In nine cases, mastectomy and axillary lymph nodes excision were performed, and only one showed micrometastasis in an axillary lymph node. There was no local recurrence or distant metastasis or breast carcinoma related-death during the follow-up periods of 50 months. Out of 253 solid papillary breast carcinomas reported in literature, the percentage of axillary lymph node metastasis was 4/136 (3%), with rare local recurrences and distant metastasis; only three patients died of breast carcinoma. Solid papillary carcinoma of the breast is a rare entity with distinctive clinicopathological features and excellent prognosis and should be distinguished from conventional breast carcinoma to avoid over-treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Not all occult papillary carcinomas are minimal
DOE Office of Scientific and Technical Information (OSTI.GOV)
Allo, M.D.; Christianson, W.; Koivunen, D.
1988-12-01
Occult papillary carcinomas are characterized as small papillary tumors of less than 1.5 cm in maximum diameter, with or without bulky metastatic deposits in cervical nodes. The primary lesion is usually not palpable, and although the clinical behavior usually follows a benign course, tumors with unfavorable histologic features (invasiveness, multifocality) or extrathyroidal disease or a combination of both may not do so. In this report six cases are presented to illustrate this entity. No patient had a history of irradiation to the head or neck. All had primary lesions smaller than 1.5 cm. None had a palpable nodule or abnormalmore » thyroid scan results, and the diagnosis of thyroid cancer was based on cervical lymph node or lung biopsy specimens, which revealed papillary thyroid cancer. All of the patients underwent total or near-total thyroidectomies and were found to have small, invasive papillary lesions with additional metastases to cervical nodes noted at the time of thyroidectomy. Adjunctive treatment consisted of a 5 mCi iodine-131 scan, ablative iodine-131 therapy, and suppression with L-thyroxine. Although distant metastasis to lung or other organs is uncommon and the mortality rate is low (as in larger papillary cancers), these invasive lesions--despite their small size--have a high propensity for recurrence and should be considered to behave more like encapsulated papillary tumors with extrathyroidal extension than like their small, unencapsulated intrathyroidal counterparts.« less
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Genetic drivers of papillary renal cell carcinoma - TCGA
A comprehensive genomic analysis of 161 tumors from people with papillary renal cell carcinoma (PRCC) – the second most common form of kidney cancer –provided insights into the molecular basis of this cancer and may inform its classification and treatment.
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Struma Ovarii with Papillary Thyroid Carcinoma
Alvarez, Daniel M.; Lee, Victor; Bhatt, Shweta; Dogra, Vikram S.
2011-01-01
Struma ovarii is an uncommon condition, in which thyroid tissue is the predominant or exclusive element in an ovarian teratoma. Thyroid tissue may demonstrate the same spectrum of pathological features as in the normal thyroid including benign and malignant changes. We present a case of papillary thyroid carcinoma arising in a struma ovarii of the left ovary in a 21-year-old female. PMID:22315711
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Kaushal, Seema; Sharma, Mehar Chand; Mathur, Sandeep R; Rastogi, Shishir; Bal, Chander Shekhar; Chumber, Sunil
2011-01-01
A 52-year-old woman presented with fracture upper end of the left humerus after trivial trauma and aspiration cytology from the lytic lesion in the upper humerus seen on X-ray revealed a metastatic papillary carcinoma from the thyroid. Total thyroidectomy confirmed the papillary carcinoma thyroid. Post-operatively, she was given radioactive iodine (I-131) ablation therapy for 8 years and was asymptomatic during this period; however, for the last 1 year, she has been complaining of swelling in the shoulder, which did not respond to palliative radiotherapy and rapidly increased in size. Disarticulation of the shoulder joint was performed, which showed anaplastic carcinoma on histopathological examination. Anaplastic transformation of papillary carcinoma at the metastatic sites is well documented in the literature and is rare. However, the same has not been reported at the shoulder and from India before. Although soft tissue sarcomas are most common at this site, however, the possibility of anaplastic transformation should be kept in the differential diagnosis of rapidly enlarging painful mass in a known case of metastatic thyroid carcinoma to prevent misdiagnosis.
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Warthin-Like Papillary Carcinoma of the Thyroid Gland: Case Report and Review of the Literature
Paliogiannis, Panagiotis; Attene, Federico; Trogu, Federica; Trignano, Mario
2012-01-01
We present a case of Warthin-like papillary thyroid carcinoma in a 22-year-old woman and a review of the literature on the topic. The patient had the occasional discovery of a hypoechoic thyroid nodule of approximately 18 mm, characterized by irregular margins, hyperechoic spots, rich intra- and perilesional vascularization, and a suspicious enlarged right laterocervical lymph node. Fine-needle aspiration was performed for both lesions and the diagnosis of papillary thyroid carcinoma without lymph node involvement was made. The patient underwent thyroidectomy and central neck lymphadenectomy without complications. Histopathological examination suggested a Warthin-like papillary carcinoma of the thyroid gland, with all the removed lymph nodes being free of disease. The patient subsequently underwent iodine ablative therapy and she remains free of disease one year after surgery. Warthin-like papillary thyroid carcinoma is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. Morphologically, it resembles Warthin tumors of the salivary glands, with T and B lymphocytes infiltrating the stalks of papillae lined with oncocytic cells. Surgical and postoperative management is identical to that of classic differentiated thyroid cancer, while prognosis seems to be favourable. PMID:23243533
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Warthin-like papillary carcinoma of the thyroid gland: case report and review of the literature.
Paliogiannis, Panagiotis; Attene, Federico; Trogu, Federica; Trignano, Mario
2012-01-01
We present a case of Warthin-like papillary thyroid carcinoma in a 22-year-old woman and a review of the literature on the topic. The patient had the occasional discovery of a hypoechoic thyroid nodule of approximately 18 mm, characterized by irregular margins, hyperechoic spots, rich intra- and perilesional vascularization, and a suspicious enlarged right laterocervical lymph node. Fine-needle aspiration was performed for both lesions and the diagnosis of papillary thyroid carcinoma without lymph node involvement was made. The patient underwent thyroidectomy and central neck lymphadenectomy without complications. Histopathological examination suggested a Warthin-like papillary carcinoma of the thyroid gland, with all the removed lymph nodes being free of disease. The patient subsequently underwent iodine ablative therapy and she remains free of disease one year after surgery. Warthin-like papillary thyroid carcinoma is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. Morphologically, it resembles Warthin tumors of the salivary glands, with T and B lymphocytes infiltrating the stalks of papillae lined with oncocytic cells. Surgical and postoperative management is identical to that of classic differentiated thyroid cancer, while prognosis seems to be favourable.
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Mixed papillary-sarcomatoid carcinoma of the penis: report of an aggressive subtype.
Bovolim, Graziele; da Costa, Walter Henriques; Guimaraes, Gustavo Cardoso; Soares, Fernando Augusto; da Cunha, Isabela Werneck
2017-12-01
Several different histological subtypes of penile carcinoma had been described in the last decades, many with different biological behavior and prognosis. The association of two histological subtypes (mixed tumors) can be observed in one third of the cases. The most common association is of warty and basaloid tumors, two HPV-related carcinomas. Here, we described a mixed papillary-sarcomatoid carcinoma, never reported before. Although it is a clinical aspect of a low-grade verruciform tumor, its prognosis showed it to be very aggressive due to the sarcomatoid component hidden above the papillary component. The two components showed opposite cadherin/vimentin expression pointed to epithelial-mesenchymal transition between them.
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An unusual metastasis of a papillary thyroidian carcinoma with follicular pattern.
Coconu, M; Berdan, G; Roşculescu, I; Herlea, V
1998-01-01
The case of a 67-year-old man is presented. He was admitted for the presence of a left parietal tumour with progressive growing, without any other objective or subjective symptomatology. CT-scan detects a left parietal osteolytic area. The histopathological aspect suggested an adenocarcinomatous metastasis with papillary pattern, moderately differentiated. With the purpose of diagnosing the original tumour, immunnohistochemical techniques were performed, which led to a diagnosis of a thyroidian carcinoma. At the histological examination of the surgical extirpated thyroid, it was proved to be a papillary carcinoma (Chan, 1990, Hay, 1990), the follicular pattern.
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Kanno, Atsushi; Satoh, Kennichi; Kimura, Kenji; Hirota, Morihisa; Umino, Jun; Masamune, Atsushi; Satoh, Akihiko; Asakura, Tohru; Egawa, Shinichi; Sunamura, Makoto; Endoh, Mareyuki; Shimosegawa, Tooru
2006-11-01
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas show heterogeneous proliferations with latent malignancy. Mucins (MUC) are high-molecular-weight glycoproteins, with an aberrant expression profile in various malignancies. Recently, MUC4 and MUC5AC expressions have been demonstrated to correlate with the unfavorable and the favorable prognosis of pancreatic duct cell carcinoma, respectively. However, little is known about these mucin expressions in IPMNs. To clarify the role of MUC4 and MUC5AC expressions in IPMNs, the expression profiles of MUC4 and MUC5AC were investigated in 50 lesions from 17 specimens with 16 IPMNs by immunohistochemistry, using each of their specific antibodies. The expression of MUC4 was found in the lesions ranging from adenoma to cancer lesions of IPMNs, whereas it was undetectable in normal and hyperplastic lesions. Frequent expression of MUC4 is found in the higher grade of IPMNs (borderline and cancer lesions; 16/18 lesions, 94%). The differences were independently significant (P < 0.001) when the cutoff point was set between adenoma and borderline IPMNs. Similarly, frequent expression of MUC5AC was detected in the lesions from adenoma to cancer of IPMNs (32/34, 94%), whereas no intense expression was detected in normal or hyperplastic lesions. The significant difference was found when the cutoff point was set between hyperplasia and adenoma of IPMNs (P < 0.001). These results indicated that the expressions of MUC4 and MUC5AC are potential markers to distinguish adenoma or above malignant lesions of IPMNs from lesser malignant ones, respectively.
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Alsadoun, Nadjla; MacGrogan, Gaëtan; Truntzer, Caroline; Lacroix-Triki, Magali; Bedgedjian, Isabelle; Koeb, Marie-Hélène; El Alam, Elsy; Medioni, Dan; Parent, Michel; Wuithier, Pascal; Robert, Isabelle; Boidot, Romain; Arnould, Laurent
2018-05-21
Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above. We found that solid papillary carcinoma with reverse polarity harbor specific morphologic features as cuboid or tall cells with abundant eosinophilic cytoplasms located at the basal pole giving the impression of reverse nuclear polarity. Nuclei were sometimes grooved. Immunohistochemistry demonstrated the lack of myoepithelial cells, as in encapsulated papillary carcinoma and solid papillary carcinoma, questioning their invasive nature. Seven of nine solid papillary carcinoma with reverse polarity showed a low Ki67 proliferative index (Ki67 <5%). They showed expression of CK5/6 as in intraductal papilloma with usual ductal hyperplasia. They showed expression of calretinin and a low or lack of hormonal receptor (HR) expression that were not observed in other breast tumors studied. By whole-exome analysis, seven of nine solid papillary carcinomas with reverse polarity (78%) harbored a hotspot mutation in IDH2 (R172) that was totally absent in other groups. Six of nine tumors (67%) also harbored PRUNE2 mutation, including the two IDH2 wild-type cases. We also demonstrated for the first time in this breast tumor, immunostaining with a specific antibody IDH1/2 mutant R132/R172 (7/9) that can highlight IDH2 mutation. Moreover, transcriptomic analysis showed that proteoglycan pathway was significantly enriched. Our findings support the fact that solid papillary carcinoma with
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Heinzelmann‐Schwarz, Viola A; Scolyer, Richard A; Scurry, James P; Smith, Alison N; Gardiner‐Garden, Margaret; Biankin, Andrew V; Baron‐Hay, Sally; Scott, Carolyn; Ward, Robyn L; Fink, Daniel; Hacker, Neville F; Sutherland, Robert L; O'Brien, Philippa M
2007-01-01
Background Currently, no specific immunohistochemical markers are available to differentiate primary mucinous epithelial ovarian cancer (MOC) from adenocarcinomas originating at other sites that have metastasised to the ovary, which may have an impact on patient management and prognosis. Aim To investigate the expression of two intestinal markers, galectin 4 and meprin α, in mucinous carcinomas of the ovary and gastrointestinal tract. Methods Using immunohistochemical analysis, the expression of galectin 4 and meprin α was investigated in 10 MOCs and in 38 mucinous adenocarcinomas of colon, pancreas, stomach and appendix, the most common sites of origin of ovarian metastases. Results Total cytoplasmic galectin 4 expression was relatively consistent between the different carcinomas. Membranous meprin α expression was significantly lower in MOCs compared with gastrointestinal carcinomas. Moreover, meprin α expression showed greater discrimination between the ovarian and gastrointestinal carcinomas than the cytokeratins CK7 and CK20, the current standard immunohistochemical markers used to determine the tissue origin of mucinous carcinomas involving the ovaries. Conclusions Meprin α is a useful additional marker in differentiating primary from secondary mucinous adenocarcinomas of the ovary. PMID:16822880
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Kitazono, Iwao; Higashi, Michiyo; Kitamoto, Sho; Yokoyama, Seiya; Horinouchi, Michiko; Osako, Masahiko; Shimizu, Takeshi; Tabata, Mineo; Batra, Surinder K.; Goto, Masamichi; Yonezawa, Suguru
2013-01-01
Objectives This study aimed to examine expression profile of MUC4 in intraductal papillary mucinous neoplasm of the pancreas (IPMN). Methods We performed immonohistochemistry (IHC) of MUC4 in 142 IPMNs, with evaluation of the specificity of two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, in cancer cell lines. Results MAb 8G7 showed a clear immunoreactivity, whereas MAb 1G8 did not show any immunoreactivity, in the Western blotting and IHC for human pancreatic carcinoma cell lines expressing MUC4 mRNA. However, IHC signals detected by both MAbs were observed in the tissue specimens. The expression rates of MUC4/8G7 detected by MAb 8G7 and MUC4/1G8 detected by MAb 1G8 in the intestinal-type IPMNs were significantly higher than those in the gastric-type IPMNs. In the intestinal-type IPMNs, MUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells, whereas MUC4/1G8 was expressed mainly at the cell apexes. Even in the gastric-type IPMNs with rare MUC4 expression in the low-grade dysplasia, both MUC4 expression rates increased when dysplasia advanced. Conclusions A significantly higher expression of MUC4 in intestinal-type IPMNs than in gastric-type IPMNs will be one of the biomarkers to discriminate between the intestinal-type IPMNs with high malignancy potential from gastric-type IPMNs with low malignancy potential. PMID:23921963
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Papillary thyroid carcinoma formation in a thyroglossal cyst. A case report.
Ali, Ma; Abussa, A; Hashmi, H
2007-09-01
Thyroglossal cyst rarely presents with carcinoma formation in the remnants of the thyroid gland. We report a 40 year old male with papillary thyroid carcinoma formation in a thyroglossal cyst. The patient underwent surgical intervention for the cyst. His pathology was positive for thyroid carcinoma and he underwent complete thyroidectomy with postoperative radioactive iodine treatment. His follow up revealed no evidence of recurrence.
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Woodhams, Reiko; Kakita, Satoko; Hata, Hirofumi; Iwabuchi, Keiichi; Umeoka, Shigeaki; Mountford, Carolyn E; Hatabu, Hiroto
2009-07-01
The purposes of this study were to compare the apparent diffusion coefficient (ADC) of mucinous carcinoma of the breast with that of other breast tumors and to analyze correlations between signal intensity on diffusion-weighted images and the histologic features of mucinous carcinoma. Two hundred seventy-six patients with 277 lesions, including 15 mucinous carcinomas (13 pure type, two mixed type), 204 other malignant tumors, and 58 benign lesions, were examined with 1.5-T MRI at b values of 0 and 1,500 s/mm(2). The correlations between cellularity and ADC, homogeneity of signal intensity on diffusion-weighted images, and histopathologic findings were analyzed. The difference was statistically significant (p < 0.05). The mean ADC of mucinous carcinoma (1.8 +/- 0.4 x 10(-3) mm(2)/s) was statistically higher than that of benign lesions (1.3+/- 0.3 x 10(-3) mm(2)/s) and other malignant tumors (0.9 +/- 0.2 x 10(-3) mm(2)/s) (p < 0.001). The ADC of pure type mucinous carcinoma (1.8 +/- 0.3 x 10(-3) mm(2)/s) was higher than that of mixed type mucinous carcinoma (1.2 +/- 0.2 x 10(-3) mm(2)/s) (p < 0.001) and other histologic types (p > 0.05). The correlation between mean cellularity and the ADC of mucinous carcinoma was significant (rho(s) = -0.754; p = 0.001). The homogeneity of signal intensity on diffusion-weighted images correlated with the homogeneity of histologic structures of mucinous carcinoma (p < 0.001; kappa = 0.826). Mucinous carcinoma can be clearly differentiated from other breast tumors on the basis of ADC. The low signal intensity of mucinous carcinoma on diffusion-weighted images appears to reflect the presence of mucin and low cellularity. High signal intensity on diffusion-weighted images may reflect the presence of fibrovascular bundles, increased cell density, or a combination of these features.
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[The expression and clinical significance of EphA2 and E-cadherin in papillary thyroid carcinoma].
Liu, Yan; Miao, Yuhua; Li, Xiaoming
2015-06-01
To investigate the expression and clinical significance of EphA2 and E cadherin proteins in papillary thyroid carcinoma tissues, and to explore the relationship between them. Using immunohistochemical SP/PV method, we detected the expression of EphA2 and E cadherin in tumors of 43 papillary thyroid carcinomas, 11 thyroid adenoma and 10 normal thyroid tissues, then studied their relationships with clinic pathological factors. The total positive rates of EphA2 and E cadherin expression were 58. 14% and 32. 56% in papillary thyroid carcinoma tissues, 18. 18% and 81. 81% in thyroid adenoma.tissues and they were 10. 00% and 100. 00% in normal thyroid tissues respectively. The positive expression of EphA2 in carcinoma tissues was higher than in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05) and the positive expression of E cadherin in carcinoma tissues was lower than that in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05). The positive expression of EphA2 and E cadherin was associated with lymph node metastasis and histological grade (P<0. 05), but it was not associated with all the clinic-pathological factors including age, sex and the tumor size (P>0. 05). In papillary thyroid carcinoma tissues, the expression of EphA2 was negatively correlated with the expression of E cadherin protein (r= -0. 416, P<0. 01). EphA2 and E cadherin may be involved in carcinogenesis and development of papillary thyroid carcinoma.
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Kato, Hiroki; Kanematsu, Masayuki; Yokoi, Shigeaki; Miwa, Kousei; Horie, Kengo; Deguchi, Takashi; Hirose, Yoshinobu
2011-01-01
The authors describe the computed tomography (CT) and magnetic resonance imaging (MRI) findings of an 18-year-old man with renal cell carcinoma (RCC) associated with the Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion (Xp11 translocation carcinoma). The lesion was hyperdense on unenhanced CT, hypovascular on contrast-enhanced studies, hypointense on T2-weighted MR images, and hemosiderin deposition was suspected on phase-shift gradient-echo MR images. Histopathological specimens revealed pathological findings resembling papillary RCC predominantly and exhibited immunoreactivity for TFE3. Because there is often considerable morphological overlap between this carcinoma and papillary RCC, the imaging findings of Xp11 translocation carcinoma may be similar to those of the papillary subtype. Therefore, Xp11 translocation carcinoma should be considered, particularly in young patients when radiologic images demonstrate a renal tumor mimicking the papillary subtype. Copyright © 2010 Wiley-Liss, Inc.
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Wang, X Q; Wei, W; Wei, X; Xu, Y; Wang, H L; Xing, X J; Zhang, S
2018-03-23
Objective: To investigate the correlation between ultrasonographic features of papillary thyroid carcinoma and central cervical lymph node metastasis. Methods: We retrospectively analyzed 486 patients with papillary thyroid carcinoma(PTC), pathologically confirmed after surgery in Tianjin Medical University Cancer Institute & Hospital. All patients were divided into central cervical lymph node metastasis group and non-metastasis group. No lateral cervical lymph node metastasis was found in preoperative ultrasonography and postoperative pathology. The characteristics of the ultrasound was observed and analyzed. Results: 297 out of 486 patients with papillary thyroid carcinomahad central metastasis, and the other 189 cases did not. Take pathology results as a standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of preoperative ultrasound diagnosis in PTC patients with central cervical lymph node metastasis were 35.3%, 88.6%, 83.2%, 47.4%, 56.6%, respectively. Univariate analysis showed that multi-focus, taller-than-wide, diameter>1 cm, located in the lower pole, ill-defined margin, hypoechogenicity, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma were significantly associated with central cervical lymph node metastasis (all P <0.05). Multivariate analysis showed that diameter>1 cm, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma became independent risk factors of central cervical neck lymph node metastasis (all P <0.05). Conclusions: Preoperative description of ultrasonographical features has important value to assess central cervical lymph node metastasis in patients with papillary thyroid carcinoma. More information could be provided for clinical treatment. When the papillary thyroid carcinoma presented as diameter>1 cm, micro-calcification, and capsule invasion more than 1/4 perimeter of, there will be a greater risk
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Shiono, Saori; Saito, Tsuyoshi; Fujii, Hiroaki; Arakawa, Atsushi; Nakamura, Takanori; Yao, Takashi
2014-01-01
We report a case of a 44-year-old woman with bilateral ovarian carcinoma that had metastasized from the colon and mimicked primary mucinous cystadenocarcinoma. Macroscopically, both ovarian tumors were large, multiloculated cystic masses with abundant mucinous content. Histologically, they were lined with mucinous epithelium with mild to moderate nuclear atypia and showed stromal invasion and surface involvement. At first, the tumors were diagnosed as bilateral primary ovarian mucinous cystadenocarcinomas. However, three months after surgery, a large villous tumor was discovered in the ascending colon by colonoscopic examination and was surgically resected. Histologically, the colonic tumor was a villous adenomatous tumor with invasive components of mucinous adenocarcinoma composed of well-differentiated adenocarcinoma and exhibited abundant extracellular mucin production. As a villous adenomatous component was present in the mucosal area, the colonic tumor was considered a primary tumor. Therefore, the original diagnosis of bilateral ovarian tumors was revised for consistent with metastasis from the colon carcinoma, in line with the findings of immunohistochemistry and loss of heterozygosity analysis. This case highlights the importance of considering the possibility of metastatic tumors from the gastrointestinal tract in the diagnosis of mucinous ovarian tumors. PMID:24427362
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Mueller, Jennifer J; Schlappe, Brooke A; Kumar, Rahul; Olvera, Narciso; Dao, Fanny; Abu-Rustum, Nadeem; Aghajanian, Carol; DeLair, Deborah; Hussein, Yaser R; Soslow, Robert A; Levine, Douglas A; Weigelt, Britta
2018-05-21
Mucinous ovarian cancer (MOC) is a rare type of epithelial ovarian cancer resistant to standard chemotherapy regimens. We sought to characterize the repertoire of somatic mutations in MOCs and to define the contribution of massively parallel sequencing to the classification of tumors diagnosed as primary MOCs. Following gynecologic pathology and chart review, DNA samples obtained from primary MOCs and matched normal tissues/blood were subjected to whole-exome (n = 9) or massively parallel sequencing targeting 341 cancer genes (n = 15). Immunohistochemical analysis of estrogen receptor, progesterone receptor, PTEN, ARID1A/BAF250a, and the DNA mismatch (MMR) proteins MSH6 and PMS2 was performed for all cases. Mutational frequencies of MOCs were compared to those of high-grade serous ovarian cancers (HGSOCs) and mucinous tumors from other sites. MOCs were heterogeneous at the genetic level, frequently harboring TP53 (75%) mutations, KRAS (71%) mutations and/or CDKN2A/B homozygous deletions/mutations (33%). Although established criteria for diagnosis were employed, four cases harbored mutational and immunohistochemical profiles similar to those of endometrioid carcinomas, and one case for colorectal or endometrioid carcinoma. Significant differences in the frequencies of KRAS, TP53, CDKN2A, FBXW7, PIK3CA and/or APC mutations between the confirmed primary MOCs (n = 19) and HGSOCs, mucinous gastric and/or mucinous colorectal carcinomas were found, whereas no differences in the 341 genes studied between MOCs and mucinous pancreatic carcinomas were identified. Our findings suggest that the assessment of mutations affecting TP53, KRAS, PIK3CA, ARID1A and POLE, and DNA MMR protein expression may be used to further aid the diagnosis and treatment decision-making of primary MOC. Copyright © 2018 Elsevier Inc. All rights reserved.
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Tajima, Naoshi; Utano, Kenichi; Kijima, Shigeyoshi; Kawai, Akira; Fujita, Akifumi; Sakuma, Kazuya; Sugimoto, Hideharu; Fujii, Hirofumi
2013-07-01
A 65-year-old man was referred to our hospital due to epigastric pain. Abdominal enhanced computed tomography (CT) demonstrated marked dilatation of the main pancreatic duct (MPD) and communication to the gastric and duodenal lumen was suspected. Esophagogastroduodenoscopy (EGD) showed a villous tumor with white mucous discharge in the posterior wall of the gastric corpus and duodenal bulb. Pathological specimens showed mucin-producing epithelium with nuclear atypia that had developed in a papillary form. Based on these findings, we diagnosed intraductal papillary mucinous neoplasm (IPMN) arising in the MPD with penetration into the gastric and duodenal lumen. Magnetic resonance cholangiopancreatography (MRCP) with an oral negative contrast agent (manganese chloride tetrahydrate) showed a fistulous tract not only to the stomach and duodenum, but also to the jejunum. MRCP demonstrated mucous streaming with remarkably high intensity. In this case, an oral negative contrast agent was useful to distinguish mucous discharge from gastric fluid, facilitating the diagnosis of penetration to the jejunum. This finding was unobtainable by CT or EGD. When IPMN penetrating to other organs is suspected, MRCP with an oral negative contrast agent may provide important information. Copyright © 2012 Wiley Periodicals, Inc.
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Kunovsky, Lumir; Kala, Zdenek; Svaton, Roman; Moravcik, Petr; Mazanec, Jan; Husty, Jakub; Prochazka, Vladimir
2018-01-01
Mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) are diagnoses that were classified by the World Health Organization in 2010 as mucin-producing bile duct tumors of the hepatobiliary system. The preoperative differential diagnosis between these two entities is difficult; the presence of a communication with the bile duct is usually considered as a typical sign of IPMN-B. However, the presence of an ovarian-like stroma (OLS) has been established to define the diagnosis of MCN-L. We present the case of a 33-year-old woman with a rapid progression of a cystic tumor of the liver. In 2 years, the lesion increased from 27 to 64 mm and a dilation of the left hepatic duct appeared. Percutaneous transhepatic drainage with a biopsy was performed. No malignant cells were found on biopsy. Because of the rapid progression of the cystic tumor and unclear malignant potential, left hemihepatectomy was performed. Even though tumor masses were present in the biliary duct, on the basis of the presence of OLS, histology finally confirmed MCN-L with intermediate-grade intraepithelial dysplasia to high-grade intraepithelial dysplasia. The patient is currently under oncologic follow-up with no signs of recurrence of the disease. We present a rare case where MCN-L caused a dilation of the left hepatic duct, a sign that is usually a characteristic of IPMN-B.
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The radiologist's role in the management of papillary renal cell carcinoma.
Corral de la Calle, M Á; Encinas de la Iglesia, J; Martín López, M R; Fernández Pérez, G C; Águeda Del Bas, D S
Papillary carcinoma is the second most common renal cell carcinoma. It has a better prognosis than the more frequent clear cell carcinoma, although this does not hold true for advanced cases, because no specific treatment exists. It presents as a circumscribed peripheral tumor (small and homogeneously solid or larger and cystic/hemorrhagic) or as an infiltrating lesion that invades the veins, which has a worse prognosis. Due to their low vascular density, papillary renal cell carcinomas enhance less than other renal tumors, and this facilitates their characterization. On computed tomography, they might not enhance conclusively, and in these cases they are impossible to distinguish from hyperattenuating cysts. Contrast-enhanced ultrasonography and magnetic resonance imaging are more sensitive for detecting vascularization. Other characteristics include a specific vascular pattern, hypointensity on T2-weighted images, restricted water diffusion, and increased signal intensity in opposed phase images. We discuss the genetic, histologic, clinical, and radiological aspects of these tumors in which radiologists play a fundamental role in management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.
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Surface topography and ultrastructural changes of mucinous carcinoma breast cells.
Voloudakis, G E; Baltatzis, G E; Agnantis, N J; Arnogianaki, N; Misitzis, J; Voloudakis-Baltatzis, I
2007-01-01
Mucinous carcinoma of the breast (MCB) is histologically classified into 2 groups: (1) pure MCB and (2) mixed MCB. Pure MCB carries a better diagnosis than mixed MCB. This research relates to the cell surface topography and ultrastructure of the cells in the above cases and aims to find the differences between them, by means of two methods: scanning electron microscopy (SEM) and transmission electron microscopy (TEM). For the SEM examination, it was necessary to initially culture the MCB tissues and then proceed with the usual SEM method. In contrast, for the TEM technique, MCB tissues were initially fixed followed by the classic TEM method. The authors found the topography of pure MCB cases to be without nodes. The cell membrane was smooth, with numerous pores and small ruffles that covered the entire cell. The ultrastructural appearance of the same cases was with a normal cell membrane containing abundant collagen fibers. They also had many small vesicles containing mucin as well as secretory droplets. In contrast the mixed MCB had a number of lymph nodes and their cell surface topography showed stronger changes such as microvilli, numerous blebs, ruffles and many long projections. Their ultrastructure showed very long microvilli with large cytoplasmic inclusions and extracellular mucin collections, electron-dense material vacuoles, and many important cytoplasmic organelles. An important fact is that mixed MCB also contains areas of infiltrating ductal carcinoma. These cells of the cytoplasmic organelles are clearly responsible for the synthesis, storage, and secretion of the characteristic mucin of this tumor type. Evidently, this abnormal mucin production and the abundance of secretory granules along with the long projections observed in the topographical structure might be responsible for transferring tumor cells to neighboring organs, thus being responsible for metastatic disease.
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Van der Kwast, Theodorus H; Zlotta, Alexandre R; Fleshner, Neil; Jewett, Michael; Lopez-Beltran, Antonio; Montironi, Roldolfo
2008-12-01
Since the introduction of the World Health Organization (WHO) 1973 terminology for bladder cancer, noninvasive epithelial bladder tumors have consistently been labeled bladder carcinomas. In the WHO 2004 classification the removal of the "carcinoma" label from a small subset of noninvasive bladder carcinomas with indolent behavior created the entity of papillary urothelial neoplasms of low malignant potential, but the remaining noninvasive carcinomas of the urothelial tract retained this label. In this overview, we analyze clinical, pathologic and molecular-genomic findings to support a more evidence-based nomenclature of papillary neoplastic lesions of the urinary tract. In line with the tendency during the last few decades to label flat precancerous lesions of various organs intraepithelial neoplasms, we may now also refer to dysplasia and carcinoma in situ of the urinary tract as low and high grade intraurothelial neoplasia, respectively. To harmonize nomenclature, we now propose that the terms low and high grade papillary urothelial carcinoma be replaced by low and high grade papillary intraurothelial neoplasiafor all noninvasive urothelial cancers.
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Adrenal Metastasis from Uterine Papillary Serous Carcinoma.
Singh Lubana, Sandeep; Singh, Navdeep; Tuli, Sandeep S; Seligman, Barbara
2016-04-27
Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case.
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Expanding the histologic spectrum of mucinous tubular and spindle cell carcinoma of the kidney.
Fine, Samson W; Argani, Pedram; DeMarzo, Angelo M; Delahunt, Brett; Sebo, Thomas J; Reuter, Victor E; Epstein, Jonathan I
2006-12-01
Mucinous tubular and spindle cell carcinomas (MTSCs) are polymorphic neoplasms characterized by small, elongated tubules lined by cuboidal cells and/or cords of spindled cells separated by pale mucinous stroma. Nonclassic morphologic variants and features of MTSC have not been well studied. We identified 17 previously unreported MTSCs from Surgical Pathology and consultative files of the authors and their respective institutions and studied their morphologic features. A total of 10/17 cases were considered "classic," as described above, with 5/10 showing at least focal (20% to 50%) tubular predominance without apparent mucinous matrix. Alcian blue staining revealed abundant (>50%) mucin in all classic cases. Seven of 17 MTSCs were classified as "mucin-poor," with little to no extracellular mucin appreciable by hematoxylin and eosin. Four of these cases showed equal tubular and spindled morphology, 2 cases showed spindle cell predominance (70%; 95%), and 1 case showed tubular predominance (90%). In 5/7 mucin-poor cases, staining for Alcian blue revealed scant (<10%) mucin in cellular areas with the other 2 cases having 30% mucin. Unusual histologic features identified in the 17 cases were: foamy macrophages (n=8), papillations/well formed papillae (n=6/n=1), focal clear cells in tubules (n=3), necrosis (n=3), oncocytic tubules (n=2; 40%, 5%), numerous small vacuoles (n=2), heterotopic bone (n=1), psammomatous calcification (n=1), and nodular growth with lymphocytic cuffing (n=1). An exceptional case contained a well-circumscribed, HMB45-positive angiomyolipoma within the MTSC. MTSCs may be "mucin-poor" and show a marked predominance of either of its principal morphologic components, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, and necrosis, may mimic other forms of renal cell carcinoma. Pathologists must be aware of the spectrum of histologic findings within MTSCs to ensure their accurate diagnosis.
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Holschbach, A; Kriete, A; Schäffer, R
1990-01-01
Papillae with fibrovascular cores are characteristic of papillary carcinoma of the thyroid. Papillae may be found in diffuse hyperplasia, nodular hyperplasia, Hashimoto's disease and follicular adenoma. Tissues from ten benign hyperplasias and ten papillary carcinomas were reconstructed from serial sections with three dimensional reconstruction programs. Significant qualitative and quantitative differences were found between the hyperplasia and the carcinoma. The principal differences between papillae of papillary carcinoma and hyperplasia were more clearly seen in the three dimensional reconstruction, than by means of morphometric methods. Certain criteria, e.g. the volume of papillae, were useful only with regard to the third dimension. Nevertheless, three dimensional reconstruction of biological tissue is a time consuming procedure which is not yet suitable for routine examination.
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Kondo, Tetsuo; Nakazawa, Tadao; Terada, Nobuo; Nakazawa, Kumiko; Kawasaki, Tomonori; Mochizuki, Kunio; Yamane, Tetsu; Ohno, Shinichi; Katoh, Ryohei
2012-06-01
We present an unusual case of papillary thyroid carcinoma in a 47-year-old Japanese woman. The tumor, 0.8 cm in diameter, was located in the upper left lobe of the thyroid. Histologically, we observed a microfollicular-like and trabecular arrangement of the tumor cells with marked hyalinized stroma and hyaline globules. Immunohistochemically, tumor cells were positive for thyroglobulin and thyroid transcription factor 1. Hyaline stroma and globular bodies were immunopositive for laminin and type IV collagen. MIB-1 index was approximately 1% without membranous immunoreactivity. Under the electron microscope, hyaline stroma and globules showed electron-dense, complex meshwork structures composed of granular and fibrous elements similar to the structure of the lamina densa. Genetic analysis demonstrated a BRAF(V600E) mutation. Based on these findings, we diagnosed the present tumor as a rare morphological variation of papillary thyroid carcinoma with excessive hyaline globules consisting of basal membrane materials. Copyright © 2012 Elsevier Inc. All rights reserved.
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A unique case of spontaneous regression of metastatic papillary renal cell carcinoma: a case report
Lim, Rebecca; Tan, Puay Hoon; Cheng, Christopher; Agasthian, Thirugnanam; Tan, Hwei Ling; Teh, Bin Tean
2009-01-01
Spontaneous regression of cancer is a rare, but well documented, phenomenon. We present a unique case of an 82 year old Chinese male who experienced spontaneous regression of histologically-verified metastatic type II papillary renal cell carcinoma in the absence of intervening systemic therapy or surgery. This is the first reported case of spontaneous regression of papillary renal cell carcinoma. The mechanism of spontaneous regression remains unknown, and represents a challenge for existing oncology paradigms. PMID:19918481
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Association of a renal papillary carcinoma with a low grade tumour of the collecting ducts
Daniel, L; Zattara-Cannoni, H; Lechevallier, E; Pellissier, J
2001-01-01
This case report describes a 75 year old man who had a renal papillary carcinoma associated with a low grade tumour of the collecting ducts. These tumours showed different immunohistochemical patterns for epithelial membrane antigen, cytokeratin 19, and Ulex europaeus lectin expression. In addition, cytogenetic findings were 47, XY, +7 <7> and 45, XY, -8, add(12)(q–ter)<10> for the papillary renal carcinoma and the low grade tumour of the collecting ducts, respectively. This is the first report where these two types of tumour are associated and cytogenetically distinguished. Key Words: renal cell carcinoma • low grade tumour of the collecting ducts PMID:11477121
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Yang, Jeong Hoon; Bae, Sung Jin; Park, Sanghui; Park, Hyun-Kyung; Jung, Hye Seung; Chung, Jae Hoon; Min, Yong-Ki; Lee, Myung-Shik; Kim, Kwang-Won; Lee, Moon-Kyu
2007-04-01
A 42-year old woman presented with headache, palpitation and facial flushing. Ultrasonograms and computed tomograms revealed tumors in both of the adrenal glands, anterior aspect of the inferior vena cava, and the right lobe of the thyroid gland. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum calcitonin, CEA, intact PTH and calcium levels were within normal limits. Markedly elevated levels of urinary normetanephrine and vanillylmandelic acid, and the result of 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy indicated that both adrenal masses were pheochromocytoma. Bilateral adrenalectomy, paracaval mass removal and total thyroidectomy together with central lymph node dissection were performed. The final pathological diagnosis was bilateral adrenal pheochromocytoma, paraganglioma, papillary thyroid carcinoma and either parathyroid adenoma or hyperplasia. Analysis of the RET proto-oncogene mutation, von Hippel Lindau mutation, succinate dehydrogenase subunit B mutation, and succinate dehydrogenase subunit D mutation yielded negative results. The relationship of these lesions could not be determined. This is the first report of a combination of bilateral pheochromocytoma, abdominal paraganglioma, papillary thyroid carcinoma and either parathyroid adenoma or hyperplasia without hyperparathyroidism.
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Sisson, James C; Giordano, Thomas J; Avram, Anca M
2012-04-01
Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid-occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and (131)I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.
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Zhang, Hui-mao; Yao, Fang; Liu, Gui-feng; Wang, Xiao-bin; Xiu, Dian-hui; Gen, Iinuma
2011-12-01
To investigate the difference in the radiological features of malignant and benign branch duct type of IPMT (Intraductal Papillary Mucinous Tumor) of the pancreas. Thirty-six patients who were referred for operation with branch duct type of IPMT of the pancreas were included in this study. All cases underwent both CT and MRI with contrast enhancement. The size of the cystic lesions, the presence and size of mural nodules, and the amount of dilatation of the MPD were assessed by two independent radiologists, and the results were compared with pathological findings. Histological examination revealed adenoma in 8 cases, AH (atypical hyperplasia) in 8 cases, CIS (carcinoma in situ) in 8 cases and invasive carcinoma in 12 cases. Patients of the malignant group were older than those in the benign group (mean age: 67 yrs vs 60 yrs, respectively), but no statistically significant (p=0.05). Males (16/4 vs 10/6) more often complained weight loss and jaundice. The malignant tumor was more frequently located in the head-body and body. Compared with the benign group, the mean sizes of the cyst, mural nodules, MPD of the malignant group were 44 mm, 13 mm, 7.5 mm and benign group were 31 mm, 5 mm, 3.5 mm respectively. All these difference are statistically significant (p<0.05). In 4 cases of the 20 in the malignant group, soft tissue suggesting spread of disease into the adjacent viscera and peritoneum was detected. Cyst size over 30 mm and mural nodule over 8 mm, irregular thick septa, dilatation of the MPD, and accompany with soft tissue mass may be helpful factors in determining malignancy. Copyright © 2011. Published by Elsevier Ireland Ltd.
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Zidan, Jamal; Karen, Drumea; Stein, Moshe; Rosenblatt, Edward; Basher, Walid; Kuten, Abraham
2003-03-01
The follicular variant of papillary thyroid carcinoma (FVPTC) is a common subtype of papillary thyroid carcinoma. Few studies have compared the clinical behavior and treatment outcome of patients with FVPTC with the outcome of patients with pure papillary carcinoma (PTC). A retrospective study was performed to identify the influence of FVPTC compared with PTC on therapeutic variables, prognostic variables, and survival. A clinicopathologic analysis of 243 patients with papillary carcinoma was performed. One hundred forty-three tumors were PTC, and 100 tumors were FVPTC. The following variables were evaluated: age at diagnosis, tumor size, stage of tumor, treatment, capsular invasion, and survival. The median follow-up was 11.5 years. The median age was 43 years in the PTC group and 44 years in the FVPTC group. The median tumor size, disease stage, and type of initial surgery and iodine 131 ablation were similar. More patients had capsular invasion by the tumor and less metastases to cervical lymph nodes in the FVPTC group. The actuarial survival of patients age < 40 years was higher compared with the survival of patients age > 50 years in both groups. The 21-year overall actuarial survival was 82% in patients with PTC and 86% in patients with FVPTC (P value not significant). The pathologic and clinical behaviors of PTC and FVPTC were comparable. Prognostic factors, treatment, and survival also were similar. Patients in both groups must be treated identically. Copyright 2003 American Cancer Society.
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CT differentiation of mucin-producing cystic neoplasms of the liver from solitary bile duct cysts.
Kim, Hyoung Jung; Yu, Eun Sil; Byun, Jae Ho; Hong, Seung-Mo; Kim, Kyoung Won; Lee, Jong Seok; Kim, So Yeon
2014-01-01
The purpose of this study was to identify the CT features required for differentiating mucin-producing cystic neoplasms of the liver (mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct) from solitary bile duct cysts. CT images of pathologically confirmed mucinous cystic neoplasms (n = 15), cyst-forming intraductal papillary neoplasms of the bile duct (n = 16), and solitary bile duct cysts (n = 31) were reviewed. Analysis of the CT findings included shape, presence of septa, location of septa (peripheral vs central), thickness of septa (thin vs thick), mosaic pattern, mural nodules, intracystic debris, calcification, upstream bile duct dilatation, downstream bile duct dilatation, and communication between a cystic lesion and the bile duct. The maximum size of a cystic lesion and the maximum size of the largest mural nodule were measured. The presence of septa, central septa, mural nodules, upstream bile duct dilatation, and downstream bile duct dilatation were found to be significant CT findings for differentiating mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct from solitary bile duct cysts (p < 0.05 for each finding). When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucin-producing cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively. When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively [corrected]. With the use of specific CT criteria, mucin-producing cystic neoplasms of the liver can be differentiated from solitary bile duct cysts with a high degree of accuracy.
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Cubilla, Antonio L; Lloveras, Belén; Alemany, Laia; Alejo, María; Vidal, August; Kasamatsu, Elena; Clavero, Omar; Alvarado-Cabrero, Isabel; Lynch, Charles; Velasco-Alonso, Julio; Ferrera, Annabelle; Chaux, Alcides; Klaustermeier, Joellen; Quint, Wim; de Sanjosé, Silvia; Muñoz, Nubia; Bosch, Francisco Xavier
2012-06-01
There are 3 distinct variants of penile squamous cell carcinoma frequently associated with human papillomavirus (HPV): basaloid, warty-basaloid, and warty carcinomas. Considering the high incidence rates of penile cancer in some countries, a large international study was designed to evaluate the presence of HPV, its genotype distribution, and its association with histologic types of penile cancer. In this international review of >900 cases, we found a group of highly distinct papillary neoplasms composed of basophilic cells resembling urothelial tumors but frequently associated with HPV. Macroscopically, tumors were exophytic or exoendophytic. Microscopically, there was a papillomatous pattern of growth with a central fibrovascular core and small basophilic cells lining the papillae. Positivity for HPV was present in 11 of 12 tumors (92%). Single genotypes found were HPV-16 in 9 tumors and HPV-51 in 1 tumor. Multiple genotypes (HPV-16 and HPV-45) were present in another case. Overexpression of p16 was observed in all cases. Uroplakin-III was negative in all cases. The differential diagnosis was with basaloid, warty-basaloid, warty, and papillary squamous cell carcinoma and with urothelial carcinomas. Local excision (4 cases), circumcision (3 cases), or partial penectomy (5 cases) were preferred treatment choices. Tumor thickness ranged from 1 to 15 mm (average, 7 mm). Two patients with tumors invading 11 and 15 mm into the corpus spongiosum developed inguinal nodal metastasis. Of 11 patients followed up (median 48 mo), 7 were alive with no evidence of metastatic disease, 3 died from causes other than penile cancer, and another died postoperatively. This morphologically distinct tumor probably represents a papillary variant of basaloid carcinomas (papillary-basaloid carcinomas). Unlike typical basaloid carcinomas, the overall prognosis was excellent. However, deeply invasive tumors were associated with regional nodal metastasis indicating a potential for tumor
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Prognostic significance of atypical papillary urothelial hyperplasia.
Swierczynski, Sharon L; Epstein, Jonathan I
2002-05-01
Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis
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BRAF mutation status in papillary thyroid carcinoma: significance for surgical strategy.
Miccoli, P; Basolo, F
2014-02-01
BRAF mutation is probably the only molecular marker acting as a risk factor that is available before surgery: for this reason, soon after it became quite widespread, it seemed an important tool as a guide towards an individualized surgical therapy in papillary thyroid carcinoma. Capsule invasion, multifocality, and lymph node involvement are the most important parameters influencing the choice of surgical strategy in front of small papillary cancers and, in more detail, of micro papillary carcinomas. The relationship between these parameters and the BRAF mutation are closely examined through the more recent literature. Capsular invasion seems to show the strongest correlation with the mutation and this has important correlations, thus suggesting that a more aggressive local surgery might be advisable, whereas the correlation between the mutation and lymph node involvement would be weaker, at least according to the most recent studies. The personalization of surgical therapy, today, seems easier to achieve thanks to molecular testing. In particular, an important result could be in the short term reduction in the number of completion thyroidectomies following simple lobectomies. Also, post operative radioactivated iodine therapies should be more carefully evaluated and tailored according to BRAF status. A possible flow chart for the decision of the therapeutic approach is proposed in accordance to the results of the literature.
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Ip, Philip Pun-Ching
2018-02-14
Benign proliferations that mimic malignancies are commonly encountered during the course of assessment of small and fragmented endometrial samples. Although benign, endometrial epithelial metaplasias often coexist with premalignant or malignant lesions causing diagnostic confusion. The difficulty with mucinous metaplasia lies in its distinction from atypical mucinous glandular proliferations and mucinous carcinomas, which are associated with significant interobserver variability. Papillary proliferation of the endometrium is commonly associated with hormonal drugs and endometrial polyps and is characterised by papillae with fibrovascular cores covered by epithelial cells without cytologic atypia. They are classified into simple or complex papillary proliferations depending on the architectural complexity and extent of proliferation. Complex papillary proliferations are associated with a high risk of concurrent or subsequent hyperplasia with atypia/carcinoma. Papillary proliferations may have coexisting epithelial metaplasias and, most commonly, mucinous metaplasia and syncytial papillary change. Those with striking mucinous metaplasia overlap morphologically with papillary mucinous metaplasia. The latter has been proposed as a precursor of endometrial mucinous carcinoma. Misinterpreting the Arias-Stella reaction as a malignant or premalignant lesion is more likely to occur if the pathologist is unaware that the patient is pregnant or on hormonal drugs. Endometrial hyperplasia with secretory changes may occasionally be difficult to distinguish from the torturous and crowded glands of a late secretory endometrium. Endometrial polyps may have abnormal features that can be misinterpreted as endometrial hyperplasia or Mullerian adenosarcoma. Awareness of these benign endometrial proliferations and their common association with hormonal medication or altered endogenous hormonal levels will help prevent the over-diagnosis of premalignant and malignant lesions.
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Moris, Demetrios; Damaskos, Christos; Spartalis, Eleftherios; Papalampros, Alexandros; Vernadakis, Spyridon; Dimitroulis, Dimitrios; Griniatsos, John; Felekouras, Evangelos; Nikiteas, Nikolaos
2017-05-01
Intraductal papillary mucinous neoplasms (IPMNs) are presumed to evolve from low-grade dysplasia to high-grade dysplasia to invasive carcinoma. Resection of lesions before the development of pancreatic cancer may prevent the development of an incurable process as, once IPMNs progress to invasive cancer, the prognosis may be as poor as resected conventional pancreatic ductal adenocarcinoma. Resection of IPMNs, particularly in the setting of high-grade dysplasia, is presumed to provide a survival benefit. IPMNs also present many challenges as the identification of high-grade dysplasia and early invasive carcinoma and the timing and frequency of malignant progression are not yet established. The limited predictive accuracy presents a challenge as pancreatic resection is associated with a risk of substantial morbidity and mortality; 20-30% and 2-4%, respectively. Diagnostic armamentarium contains pancreas-protocol computed tomography (CT) scan, gadolinium-enhanced magnetic resonance imaging (MRI) with or without magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS). The most promising method is endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as this technique allows analysis of cyst fluid using biomarkers. Until now, in clinical practice, we utilize two biomarkers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9); however, DNA analysis of pancreatic cystic fluid and genomic analysis could offer new tools to the diagnosis and administration of IPMNs. Novel genomic and serum biomarkers could play an important future role to identify those individuals who will benefit from an early operation and those who will benefit from watchful waiting approach. More prospective studies are needed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Mito, Kumiko; Saito, Michihiro; Morita, Kohei; Maetani, Iruru; Sata, Naohiro; Mieno, Makiko; Fukushima, Noriyoshi
2018-06-01
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a primary pancreatic ductal epithelial neoplasm with the potential to develop into an invasive adenocarcinoma. This study aimed to investigate the clinicopathologic and prognostic significance of four potential biomarkers for the preoperative evaluation of patients with IPMN. Clinicopathologic materials from 104 patients with IPMN who underwent surgical resection at Jichi Medical University Hospital were analyzed. IPMNs (110 lesions in total) were histologically classified into low-grade IPMN (Group 1; n = 68), high-grade IPMN (Group 2; n = 16), or IPMN with an associated invasive carcinoma (Group 3; n = 26). We evaluated the immunohistochemical expression of MUC13, AGR2, FUT8, and FXYD3, which were previously reported to be overexpressed in pancreatic ductal adenocarcinoma. The expression of MUC13 was more common in Group 3 compared with groups 1 and 2 (p < 0.001) and was associated with poor prognosis (p = 0.004). The expression of MUC13 was not associated with age, sex, tumor location, histological subtype, lymphatic or vascular invasion, or neural invasion. In most cases of IPMN, the loss of expression of AGR2 appeared to show an association with tumor recurrence and poorly differentiated histology of invasive carcinoma; however, this association was not statistically significant. The expressions of FUT8 and FXYD3were not associated with the clinicopathological features of IPMNs. The results suggest that MUC13 overexpression and loss of expression of AGR2 may predict the progression of IPMN and an unfavorable prognosis in patients with IPMN. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.
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Fonseca, Elsa; Castanhas, Salome; Sobrinho-Simoes, Manuel
1996-01-01
In order to characterize the pattern of expression of carbohydrate structures in several types of thyroid tissues and to evaluate the putative usefulness of the detection of such antigens in diagnostic surgical pathology, we undertook the immunohistochemical study of simple mucin type antigens (T, Tn, and sialyl Tn), Lewis type I antigens (Lewis a, sialyl Lewis a, and Lewis b), and Lewis type 2 related antigens (precursor type 2, H type 2, Lewis x, sialyl Lewis x, and Lewis y) in thyroid samples obtained from 65 patients. The material consisted on paraffin sections of normal thyroid (n = 43), benign lesions (13 goiters/hyperplastic lesions and 15 adenomas), and malignant tumors (12 follicular carcinomas and 27 papillary carcinomas, 5 of which had lymph node metastases) of the thyroid follicular epithelium. Tn, T, and precursor type 2 antigens were the only antigens that were detected and very rarely in normal thyroid. Benign lesions were similar to normal thyroid despite displaying a higher prevalence of immunoreactivity for several antigens of the three groups. Thyroid carcinomas presented a significantly higher level of expression of all types of simple mucin, Lewis type 1, and Lewis type 2 antigens than the normal thyroid and benign lesions. The expression of sialyl Tn was restricted to malignant tumors, and the expression of sialyl Lewis x was closely associated, though not exclusively, to papillary carcinomas. The immunoreactivity was stronger and the number of positive cases was higher in papillary than in follicular carcinomas. No differences were found between primary tumors and the respective metastases. The existence of distinct patterns of expression of carbohydrate antigens in different types of thyroid lesions points to the usefulness of the detection of some of these antigens in thyroid surgical pathology. The putative role of such antigens in the peculiar metastatic properties of thyroid carcinomas remains unsettled.
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Wang, Liang; Xia, Yu; Jiang, Yu-Xin; Dai, Qing; Li, Xiao-Yi
2012-11-01
To assess the efficacy of sonography for discriminating nodular Hashimoto thyroiditis from papillary thyroid carcinoma in patients with sonographically evident diffuse Hashimoto thyroiditis. This study included 20 patients with 24 surgically confirmed Hashimoto thyroiditis nodules and 40 patients with 40 papillary thyroid carcinoma nodules; all had sonographically evident diffuse Hashimoto thyroiditis. A retrospective review of the sonograms was performed, and significant benign and malignant sonographic features were selected by univariate and multivariate analyses. The combined likelihood ratio was calculated as the product of each feature's likelihood ratio for papillary thyroid carcinoma. We compared the abilities of the original sonographic features and combined likelihood ratios in diagnosing nodular Hashimoto thyroiditis and papillary thyroid carcinoma by their sensitivity, specificity, and Youden index. The diagnostic capabilities of the sonographic features varied greatly, with Youden indices ranging from 0.175 to 0.700. Compared with single features, combinations of features were unable to improve the Youden indices effectively because the sensitivity and specificity usually changed in opposite directions. For combined likelihood ratios, however, the sensitivity improved greatly without an obvious reduction in specificity, which resulted in the maximum Youden index (0.825). With a combined likelihood ratio greater than 7.00 as the diagnostic criterion for papillary thyroid carcinoma, sensitivity reached 82.5%, whereas specificity remained at 100.0%. With a combined likelihood ratio less than 1.00 for nodular Hashimoto thyroiditis, sensitivity and specificity were 90.0% and 92.5%, respectively. Several sonographic features of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in a background of diffuse Hashimoto thyroiditis were significantly different. The combined likelihood ratio may be superior to original sonographic features for
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Hereditary Papillary Renal Cell Carcinoma
... of papillary cancer called type 1 papillary renal cell cancer. Individuals with HPRC have an increased risk of ... that the risk for type 1 papillary renal cell cancer can be passed from generation to generation in ...
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Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga; Arun, B R
2015-01-01
Warthin-like Papillary thyroid carcinoma (WPTC) is a rare variant of papillary carcinoma of thyroid, PTC which derives its name by closely resembling Warthin's tumor of salivary gland. Hallmark histological feature of this variant is papillary folding lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. It is thought to be one of those differentiated thyroid cancers with favorable prognosis. We report a case of Graves' disease with a cold nodule harboring WPTC with initial presentation of lymph nodal metastases. It is important to identify this peculiar variant of PTC as 5 to 10% of them undergo dedifferentiation and 30% have the lymph nodal metastases and extra thyroidal extension.
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Adsay, Volkan; Jang, Kee-Taek; Roa, Juan Carlos; Dursun, Nevra; Ohike, Nobuyuki; Bagci, Pelin; Basturk, Olca; Bandyopadhyay, Sudeshna; Cheng, Jeanette D; Sarmiento, Juan M; Escalona, Oscar Tapia; Goodman, Michael; Kong, So Yeon; Terry, Paul
2012-09-01
displayed some foci of low-grade dysplasia, and 15/47 (32%) had no identifiable invasion. (4) Overall, 55% of the cases had an associated invasive carcinoma (pancreatobiliary type, 58; others, 10). Factors associated significantly with invasion were the extent of high-grade dysplasia, cell type (biliary or foveolar), and papilla formation. Among systematically analyzed invasive carcinomas, tumoral intraepithelial neoplasia was detected in 6.4% (39/606). (5) The 3-year actuarial survival was 90% for cases without invasion and 60% for those associated with invasion. In contrast, those associated with invasion had a far better clinical outcome compared with pancreatobiliary-type GB carcinomas (3-yr survival, 27%), and this survival advantage persisted even with stage-matched comparison. Death occurred in long-term follow-up even in a few noninvasive cases (4/55; median 73.5 mo) emphasizing the importance of long-term follow-up. In conclusion, tumoral preinvasive neoplasms (≥1 cm) in the GB are analogous to their pancreatic and biliary counterparts (biliary intraductal papillary neoplasms, pancreatic intraductal papillary mucinous neoplasms, and intraductal tubulopapillary neoplasms). They show variable cellular lineages, a spectrum of dysplasia, and a mixture of papillary or tubular growth patterns, often with significant overlap, warranting their classification under 1 unified parallel category, intracholecystic papillary-tubular neoplasm. Intracholecystic papillary-tubular neoplasms are relatively indolent neoplasia with significantly better prognosis compared with pancreatobiliary-type GB carcinomas. In contrast, even seemingly innocuous examples such as those referred to as "pyloric gland adenomas" can progress to carcinoma and be associated with invasion and fatal outcome.
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Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David L
2015-10-20
Aberrant expression of membrane-associated and secreted mucins, as evident in epithelial tumors, is known to facilitate tumor growth, progression and metastasis, and to provide protection against adverse growth conditions, chemotherapy and immune surveillance. Emerging evidence provides support for the oncogenic role of MUC1 in gastrointestinal carcinomas and relates its expression to an invasive phenotype. Similarly, mucinous differentiation of gastrointestinal tumors, in particular increased or de novo expression of MUC2 and/or MUC5AC, is widely believed to imply an adverse clinicopathological feature. Through formation of viscous gels, too, MUC2 and MUC5AC significantly contribute to the biology and pathogenesis of mucin-secreting gastrointestinal tumors. Here, we investigated the mucin-depleting effects of bromelain (BR) and N-acetylcysteine (NAC), in nine different regimens as single or combination therapy, in in vitro (MKN45, KATOIII and LS174T cell lines) and in vivo (female nude mice bearing intraperitoneal MKN45 and LS174T) settings. The inhibitory effects of the treatment on cancer cell growth and proliferation were also evaluated in vivo. Our results suggest that a combination of BR and NAC with dual effects on growth and mucin products of mucin-expressing tumor cells is a promising candidate towards the development of novel approaches to gastrointestinal malignancies with the involvement of mucin pathology. This capability supports the use of this combination formulation in locoregional approaches for reducing the adverse effects of the aberrantly secreted gel-forming mucins, as in pseudomyxoma peritonei and similar pathologies with ectopic production of mucin.
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Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David L.
2015-01-01
Aberrant expression of membrane-associated and secreted mucins, as evident in epithelial tumors, is known to facilitate tumor growth, progression and metastasis, and to provide protection against adverse growth conditions, chemotherapy and immune surveillance. Emerging evidence provides support for the oncogenic role of MUC1 in gastrointestinal carcinomas and relates its expression to an invasive phenotype. Similarly, mucinous differentiation of gastrointestinal tumors, in particular increased or de novo expression of MUC2 and/or MUC5AC, is widely believed to imply an adverse clinicopathological feature. Through formation of viscous gels, too, MUC2 and MUC5AC significantly contribute to the biology and pathogenesis of mucin-secreting gastrointestinal tumors. Here, we investigated the mucin-depleting effects of bromelain (BR) and N-acetylcysteine (NAC), in nine different regimens as single or combination therapy, in in vitro (MKN45, KATOIII and LS174T cell lines) and in vivo (female nude mice bearing intraperitoneal MKN45 and LS174T) settings. The inhibitory effects of the treatment on cancer cell growth and proliferation were also evaluated in vivo. Our results suggest that a combination of BR and NAC with dual effects on growth and mucin products of mucin-expressing tumor cells is a promising candidate towards the development of novel approaches to gastrointestinal malignancies with the involvement of mucin pathology. This capability supports the use of this combination formulation in locoregional approaches for reducing the adverse effects of the aberrantly secreted gel-forming mucins, as in pseudomyxoma peritonei and similar pathologies with ectopic production of mucin. PMID:26436698
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Kalinichenko, O V; Myshunina, T M; Tron'ko, M D
2013-01-01
To clarify possible role of cysteine cathepsin H, B and L in the proteolytic processes that contribute to the progression of tumor growth in the thyroid, we studied their activity in lysosomes isolated from the tissue of papillary carcinomas. It was shown that for these enzymes there is a dependence of the changes in their activity on a number of biological characteristics of the tumors. Thus, the sharp increase in the activity ofcathepsin H observed in lysosomes of tissue carcinomas category T2 and T3, with intra-and ekstrathyroid and lymphatic invasion of tumor cells. An increase in the activity of cathepsin B is set in the lysosomes of tissue heterogeneous follicular structure, especially in the presence of solid areas, in comparison with typical papillary tumors and in the lysosomes of tissue carcinomas in intrathyroid and cathepsin L-at extrathyroid invasion. A common feature of the enzymes is to increase the activity of cathepsins in lysosomes of tissue nonencapsulated papillary carcinomas. These enzymes probably do not take part in the invasion of tumor cells into blood vessels and in the mechanisms of tumor metastasis to regional lymph nodes. The latter shows no changes in the activity of cathepsins in lysosomes of tissue carcinomas category N1. The results indicate the different role of cathepsin H, B and L in thyroid carcinogenesis, where each enzyme has its specific function.
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Chakrabarti, Suvadip; Desai, Sanjay M.; Mehta, Dharmendra Y.; Somanath, Shreyas
2016-01-01
Dual malignancy is rare in adolescents. Dual malignancy with the second malignancy of thyroid is rare. No association has been reported between dysgerminoma of ovary and carcinoma thyroid in medical literature. Despite a thorough PubMed search (key words — Papillary carcinoma of thyroid, metachronous, dysgerminoma ovary), we were unable to find a previous reported case of metachronous papillary carcinoma of thyroid (PTC) following dysgerminoma of the ovary. After surgery, the patient is being regularly followed up for recurrence/development of new primary. We report this unusual and rare case in a 17-year-old female patient. PMID:27904567
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Cherian, Mathew Pynumootil; Nair, Balakrishnan; Thomas, Shaji; Somanathan, Thara; Sebastian, Paul
2009-10-01
We report a rare case of synchronous occurrence of thyroglossal duct cyst carcinoma and thyroid carcinoma and discuss its management in detail. A 59-year-old woman was clinically diagnosed to have a thyroglossal duct cyst and a solitary nodule. Fine-needle aspiration cytology revealed a papillary carcinoma in the thyroglossal duct cyst and a colloid in the thyroid nodule. Sistrunk's procedure along with a total thyroidectomy was performed followed by postoperative radioiodine ablation. Histopathologic examination revealed thyroglossal duct cyst carcinoma and bilateral foci of papillary carcinoma in the thyroid gland. She has remained free of disease on follow-up. Most cancers arising in thyroglossal duct cysts are of low risk, and Sistrunk's procedure is an adequate treatment for such cancers. However, for synchronously occurring cancers of the thyroglossal duct cyst and thyroid gland, or high-risk thyroglossal duct cyst cancers, more aggressive treatment comprising total thyroidectomy, Sistrunk's procedure, and radioiodine therapy is indicated. (c) 2009 Wiley Periodicals, Inc.
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Vaquero, Eva C; Salcedo, Maria T; Cuatrecasas, Míriam; De León, Hannah; Merino, Xavier; Navarro, Salvador; Ginès, Angels; Abu-Suboh, Monder; Balsells, Joaquim; Fernández-Cruz, Laureano; Molero, Xavier
2014-01-01
Chronic pancreatitis lesions usually embrace both intraduct papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC). Patients at genetically-determined high risk of PDAC often harbor IPMN and/or chronic pancreatitis, suggesting IPMN, chronic pancreatitis and PDAC may share pathogenetic mechanisms. Chronic autoimmune pancreatitis (AIP) may also herald PDAC. Concurrent IPMN and AIP have been reported in few patients. Here we describe two patients with IPMN who developed type-1 AIP fulfilling the Honolulu and Boston diagnostic criteria. AIP diffusively affected the whole pancreas, as well as peripancreatic lymph nodes and the gallbladder. Previous pancreatic resection of focal IPMN did not show features of AIP. One of the patients carried a CFTR class-I mutation. Of notice, serum IgG4 levels gradually decreased to normal values after IPMN excision. Common risk factors to IPMN and AIP may facilitate its coincidental generation. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.
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Taşli, Funda; Ozkök, Güliz; Argon, Asuman; Ersöz, Didem; Yağci, Ayşe; Uslu, Adam; Erkan, Nazif; Salman, Tarik; Vardar, Enver
2014-12-01
Hashimoto's thyroiditis (HT) is considered to be a risk factor for the formation of papillary carcinoma. The association of IgG4-related sclerosing disease with tumor is reported to be as sporadic cases in many organs. In this study, it was intended to re-classify the HT diagnosed cases on the basis of the existence of IgG4 (+) plasma cells; to investigate the clinicopathologic and histopathologic features of the both groups; and in addition, to evaluate the papillary carcinoma prevalence in IgG4 (+) and IgG4 (-) HT cases as well as the prognostic parameters between these groups. Totally 59 cases between the years 2008-2013, 29 of which contain Hashimoto thyroiditis diagnosis in total thyroidectomy materials, and 30 of which contain the diagnosis of HT+papillary carcinoma, were included in the study. The materials were immunohistochemically applied IgG and IgG4; and the cases were classified in two groups as IgG4-positive HT and IgG4-negative HT containing cases, on the basis of IgG4/IgG rate. All histopathologic and clinicopathologic parameters between these two groups, as well as their association with papillary carcinoma were investigated. Thirty eight (64.4%) of total 59 cases were NonIgG4 thyroiditis, and 21 (35.5%) were IgG4 thyroiditis. Tumors were detected in 14 (36.8%) of the NonIgG4 thyroiditis cases, and in 16 (76.1%) of the IgG4 thyroiditis cases. The association of IgG4 thyroiditis with tumor is statistically significant (p < 0.004). Multifocality was found to be at a higher rate in IgG4 thyroiditis cases. Perithyroidal extension was detected in six of the cases with tumor, and five of the six cases were IgG4 thyroiditis cases. The association of IgG4 (+) HT cases with increased papillary carcinoma prevalence is suggestive of that IgG4 (+) plasma cells can play a role in carcinogenesis in papillary carcinomas developed in HTs, without a chronic sclerosing ground. In addition, although the number of cases is limited, the high-association of IgG4
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Hyperfunctioning papillary thyroid carcinoma: A case report with literature review.
Salih, Abdulwahid M; Kakamad, F H; Nihad, Han
2016-01-01
Thyroid malignant tumors are rarely associated with hyperfunctioning thyroid. The incidence of this co-incidence is highly variable. Here we report a rare case of papillary thyroid cancer associated with hyperthyroidism with brief literature review. A 40-year-old male, presented with palpitation, excess sweating and weight loss for one month duration. There was asymmetrical swelling of the neck, more on right side, mobile. Free T3: 11.09pmol/L, free T4: 34.41pmol/L, TFT: less than 0.005mIU/ml, Neck ultrasound showed features of background thyroiditis. Left lobe contained 9×7×5mm nodule with irregular outline and multiple dots of calcification, other nodules are of the same features. Under ultrasound guide, fine needle aspiration cytology showed features of papillary carcinoma. After preparation, total thyrodectomy done and the result of histopathological examination confirmed papillary thyroid carcinoma. The patient was put on 0.2mg thyroxine daily. Literature review has showed an increasing number of papers reporting the association of high level of thyroid function tests and thyroid malignancy. The cause of high level of TH in thyroid malignancy is thought to be due to an active mutation of the gene of TH receptor. Niepomniszcze and colleagues found that a combination of TSH receptor mutations and Ki-RAS was the main etiological factor for hyperfunction of the thyroid malignancy. Although the coexistence of them is rare, thyroid malignancy should be put in the differential diagnosis of hyperthyroid goiter. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
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2016-12-02
Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma
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Vitiazeva, Varvara; Kattla, Jayesh J.; Flowers, Sarah A.; Lindén, Sara K.; Premaratne, Pushpa; Weijdegård, Birgitta; Sundfeldt, Karin; Karlsson, Niclas G.
2015-01-01
Background Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer. Methods In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes. Results The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC). Conclusion Mucinous benign and LMPs along with mucinous low-grade carcinomas
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Unbalanced 5;16 translocation in a boy with papillary thyroid carcinoma
DOE Office of Scientific and Technical Information (OSTI.GOV)
McDonald, M.; Maynard, S.; Sheldon, S.
This is the first reported case of an unbalanced chromosome rearrangement resulting in trisomy 5q35.5{r_arrow}qter and monosomy 16p 13.3{r_arrow}pter, in a boy with mental and growth retardation, minor anomalies, and a history of bilateral papillary thyroid carcinoma. This was the result of a familial balanced translocation. The clinical and cytogenetic manifestations of the case are presented and the possible role of the chromosomal rearrangement in the etiology of the thyroid carcinoma is discussed. 25 refs., 5 figs., 1 tab.
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Jang, Jin-Young; Park, Taesung; Lee, Selyeong; Kim, Yongkang; Lee, Seung Yeoun; Kim, Sun-Whe; Kim, Song-Cheol; Song, Ki-Byung; Yamamoto, Masakazu; Hatori, Takashi; Hirono, Seiko; Satoi, Sohei; Fujii, Tsutomu; Hirano, Satoshi; Hashimoto, Yasushi; Shimizu, Yashuhiro; Choi, Dong Wook; Choi, Seong Ho; Heo, Jin Seok; Motoi, Fuyuhiko; Matsumoto, Ippei; Lee, Woo Jung; Kang, Chang Moo; Han, Ho-Seong; Yoon, Yoo-Seok; Sho, Masayuki; Nagano, Hiroaki; Honda, Goro; Kim, Sang Geol; Yu, Hee Chul; Chung, Jun Chul; Nagakawa, Yuichi; Seo, Hyung Il; Yamaue, Hiroki
2017-12-01
This study evaluated individual risks of malignancy and proposed a nomogram for predicting malignancy of branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) using the large database for IPMN. Although consensus guidelines list several malignancy predicting factors in patients with BD-IPMN, those variables have different predictability and individual quantitative prediction of malignancy risk is limited. Clinicopathological factors predictive of malignancy were retrospectively analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in Korea and Japan. The patients with main duct dilatation >10 mm and inaccurate information were excluded. The study cohort consisted of 2258 patients. Malignant IPMNs were defined as those with high grade dysplasia and associated invasive carcinoma. Of 2258 patients, 986 (43.7%) had low, 443 (19.6%) had intermediate, 398 (17.6%) had high grade dysplasia, and 431 (19.1%) had invasive carcinoma. To construct and validate the nomogram, patients were randomly allocated into training and validation sets, with fixed ratios of benign and malignant lesions. Multiple logistic regression analysis resulted in five variables (cyst size, duct dilatation, mural nodule, serum CA19-9, and CEA) being selected to construct the nomogram. In the validation set, this nomogram showed excellent discrimination power through a 1000 times bootstrapped calibration test. A nomogram predicting malignancy in patients with BD-IPMN was constructed using a logistic regression model. This nomogram may be useful in identifying patients at risk of malignancy and for selecting optimal treatment methods. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.
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Orellana, María José; Fulle, Angelo; Carrillo, Diego; Escobar, Lucía; Ebensperger, Alicia; Martínez, Raúl; Rumié Carmi, Hana
Papillary thyroid carcinoma (PTC) is a rare childhood disease. The development of PTC in dyshormonogenetic congenital hypothyroidism (CH) is infrequent, with very few case reports in literature. To report a case of PTC in a boy with dyshormonogenetic CH without goitre and exposed to ionising radiation. To evaluate relationships between these factors and development of PTC. We present a boy with dyshormonogenetic CH since birth. Early hormonal substitution was initiated, with subsequent normal levels of thyrotropin and thyroid hormones. He has also congenital cardiomyopathy, exposed to interventional treatment with 10 heart catheterisations, and approximately 26 chest X-rays at paediatric doses. A thyroid nodule was found in thyroid echography at the age of 6 years old. Fine needle aspiration biopsy confirmed high probability of thyroid carcinoma (Bethesda 5). The pre-surgical thorax and cerebral scan showed no evidence of metastasis. The patient underwent total thyroidectomy. Pathological examination revealed a 0.5cm papillary thyroid micro-carcinoma in the right lobe, with no evidence of dissemination. Genetic mutations and radiation exposure may play an important role in the development of PTC. There may be common pathways between dyshormonogenetic CH and thyroid carcinoma that need further investigation. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
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Sejben, István; Szabó, Zoltán; Lukács, Nándor; Loránd, Márta; Sükösd, Farkas; Cserni, Gábor
2013-01-01
An asymptomatic 1-cm large papillary renal cell carcinoma (RCC) embedded in a 3.5-cm large oncocytoma was diagnosed and removed by right nephrectomy in a 68-year-old male investigated for the abdominal symptoms associated with cholelithiasis. The papillary RCC displayed positive immunohistochemical stainings with cytokeratin 7, alpha-methylacyl-CoA racemase and vimentin and was negative for the E-cadherin and CD117 immunostains, whereas the oncocytoma part showed opposite staining patterns. No gains of chromosomes 7 and 17 or loss of chromosome Y was detected in the papillary carcinoma by fluorescent in situ hybridization with centromeric enumeration probes. This finding is in keeping with the morphologic diagnosis of type 2 papillary RCC reported to have lower rates of these characteristic chromosomal changes. The combination of papillary RCC and oncocytoma, two tumours of different postulated origin, is extremely rare. It may represent a simple coincidence, but 2 previous cases and our current one share a few features, including the intimate embedment of the papillary RCC in the oncocytoma, the small size of the RCC and the old age of the patients. This case raises the point that renal oncocytomas can contain a hidden malignant tumour. PMID:23914273
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Fine-needle aspiration study of cystic papillary thyroid carcinoma: Rare cytological findings
Mokhtari, Maral; Kumar, Perikala Vijayananda; Hayati, Kamran
2016-01-01
Background: Cystic papillary thyroid carcinoma (CPTC) is a variant of papillary carcinoma that has many mimickers in cytological grounds. Aim: To study the cytomorphologic features of CPTC and compare them to those of other cystic thyroid lesions using fine-needle aspiration cytology (FNAC). We also aimed to identify the cytomorphologic features that distinguish CPTC from other cystic thyroid lesions. Materials and Methods: Seventy-three cases of CPTC were included in the study. The cytomorphologic features of these cases were analyzed. The FNA smears of other thyroid lesions with cystic changes (300 colloid goiters, 290 adenomatoid nodules, 11 follicular neoplasms, and 9 hurtle cell neoplasm) were also studied. Results: The smears in CPTC revealed isolated follicular cells, small groups of cells with scalloped margins, cell swirls, small clusters with a cartwheel pattern, papillary clusters, intranuclear inclusions, nuclear grooves, sticky colloid, intracellular colloids, psammoma bodies, multinucleated giant cells, and foamy and hemosiderin laden macrophages. Small groups of cells with scalloped borders, cellular swirls, and small clusters with a cartwheel pattern were seen in CPTC, but not in other cystic lesions. Interestingly, mesothelial-like cells and hemophagocytic cells were seen in five and three cases of CPTC, respectively, but not in other cystic lesions. Conclusion: Mesothelial-like cells and hemophagocytic cells were observed in five and three cases of CPTC, respectively. Similar finding have not been previously reported in the literature. PMID:27756982
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Rossi, E D; Raffaelli, M; Mule', A; Miraglia, A; Lombardi, C P; Vecchio, F M; Fadda, G
2006-06-01
The histological diagnosis is critical for the postsurgical management and follow-up of thyroid malignancies. The differential diagnosis between papillary carcinoma and hyperfunctioning lesions, either with papillary hyperplasia or with a follicular architecture, can create real diagnostic difficulty. The aim of this study was to evaluate the expression of several antibodies considered to be markers of malignancy in malignant and hyperfunctioning thyroid neoplasms and to include the most effective of them in a diagnostic panel. One hundred resected thyroid nodules--58 hyperfunctioning benign lesions and 42 papillary carcinomas (14 follicular variant, 14 macrofollicular variant and 14 classic type)--were immunohistochemically studied for HBME-1, galectin-3, cytokeratin (CK) 19 and RET-proto-oncogene. HBME-1 and galectin-3 showed 92.8% and 89% sensitivity, respectively, and their coexpression was present in 36 out of 42 papillary carcinomas (85.7%) and absent in non-malignant lesions. Their association increased sensitivity to 94.7% and the diagnostic accuracy to 97.9% and involved the highest number of cases (95%) in comparison with two other panels including, respectively, three (HBME-1, galectin-3, CK19) and all four antibodies. An immunohistochemical panel consisting of HBME-1 and galectin-3 can make a correct distinction between malignant and hyperfunctioning thyroid neoplasms with high diagnostic accuracy.
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Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.
Wreesmann, Volkert B; Ghossein, Ronald A; Hezel, Michael; Banerjee, Debenranrath; Shaha, Ashok R; Tuttle, R Michael; Shah, Jatin P; Rao, Pulivarthi H; Singh, Bhuvanesh
2004-08-01
The majority of thyroid tumors are classified as papillary (papillary thyroid carcinomas; PTCs) or follicular neoplasms (follicular thyroid adenomas and carcinomas; FTA/FTC) based on nuclear features and the cellular growth pattern. However, classification of the follicular variant of papillary thyroid carcinoma (FVPTC) remains an issue of debate. These tumors contain a predominantly follicular growth pattern but display nuclear features and overall clinical behavior consistent with PTC. In this study, we used comparative genomic hybridization (CGH) to compare the global chromosomal aberrations in FVPTC to the PTC of classical variant (classical PTC) and FTA/FTC. In addition, we assessed the presence of peroxisome proliferator-activated receptor-gamma (PPARG) alteration, a genetic event specific to FTA/FTC, using Southern blot and immunohistochemistry analyses. In sharp contrast to the findings in classical PTC (4% of cases), CGH analysis demonstrated that both FVPTC (59% of cases) and FTA/FTC (36% of cases) were commonly characterized by aneuploidy (P = 0.0002). Moreover, the pattern of chromosomal aberrations (gains at chromosome arms 2q, 4q, 5q, 6q, 8q, and 13q and deletions at 1p, 9q, 16q, 17q, 19q, and 22q) in the follicular variant of PTC closely resembled that of FTA/FTC. Aberrations in PPARG were uniquely detected in FVPTC and FTA/FTC. Our findings suggest a stronger relationship between the FVPTC and FTA/FTC than previously appreciated and support further consideration of the current classification of thyroid neoplasms. Copyright 2004 Wiley-Liss, Inc.
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Chaux, Alcides; Soares, Fernando; Rodríguez, Ingrid; Barreto, José; Lezcano, Cecilia; Torres, José; Velazquez, Elsa F; Cubilla, Antonio L
2010-02-01
There is a group of low-grade papillomatous squamous cell carcinomas (SCC) of the penis, collectively designated as "verruciform," that are difficult to classify. A proposal of classification grouped these tumors in warty (condylomatous), verrucous, and papillary carcinomas. Papillary SCC, not otherwise specified is the third distinctive type of penile low-grade verruciform neoplasms. We are presenting clinicopathologic features of 35 cases from 2 institutions. All specimens were penectomies or circumcisions. Mean age was 57 years. Sites of involvement were glans alone in 18 cases (51%), glans, coronal sulcus and foreskin in 13 cases (37%), glans and sulcus in 3 cases (9%), and foreskin in 1 case (3%). Papillary carcinomas were large (mean 5.6 cm) exophytic low-grade squamous neoplasms with hyperkeratosis and papillomatosis. Papillae were variable in length and shape. The tip was straight, undulated, spiky, or blunt. There was no koilocytosis. The interface between tumor and stroma was characteristically jagged and a moderate stromal reaction was evident in most cases. The majority of the tumors (94%) showed a low-grade histology with focally present poorly differentiated areas in 6% of the cases. The mean thickness of the tumor was 9.4 mm. The most commonly invaded anatomic levels were the corpus spongiosum and/or dartos (77% cases). Corpus cavernosum was invaded in 8 cases (23%). Vascular and perineural invasion were unusual. Frequent associated lesions were squamous hyperplasia, differentiated penile intraepithelial neoplasia, and lichen sclerosus (74%, 46%, and 34%, respectively). Nodal metastases were identified in 3 of 12 patients with bilateral groin dissections. Of the 20 patients followed, 18 were either with no evidence of disease (15 cases) or died from unrelated causes (3 cases). One patient was alive with evidence of systemic metastases and 1 died from disseminated penile cancer 32 months after original penectomy. In conclusion, papillary carcinomas
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[Cellular architecture of papillary and nonpapillary transitional cell carcinoma].
Moriyama, M
1989-07-01
To characterize the cellular architecture of papillary and nonpapillary transitional cell carcinoma. 2 normal ureters, 6 papillary bladder cancers and 5 nonpapillary bladder cancers were subjected to light and electron microscopic study as well as three dimensional reconstruction by 0.5 microns thick serial sections. Normal urothelium consisted of three cell layers of the basal, intermediate and superficial cells, each of which was morphologically characterized in terms of cell shape and development of cell organelles. Over 90% of the epithelial cells were proved to be connected to the uniform basement membrane directly or with long, fine cytoplasmic processes, forming hemidesmosomes at the junctional portion. Papillary tumors had, as a rule, the same cellular architecture as that of normal epithelium in terms of the regularity of cellular polarity, arrangement and differentiation, and the connection to the basement membrane. But, in G2 tumors, the connection between the intermediate and superficial cells and the basement membrane failed to be confirmed in 7 to 44% of the cells, suggesting the heterogeneity of the tumors. In contrast, nonpapillary tumors showed a high irregularity of the cellular architecture in both lesions of stromal and intra-epithelial invasion. The development of the basement membrane was indefinite, often showing thinning or disruption where occasional cytoplasmic protrusion of the tumor cells into the lamina propria was found. Nearly all of the intermediate and superficial cells in the intraepithelial lesions proved not to communicate with the basement membrane. The present results indicate distinct differences of cellular architecture between the papillary and nonpapillary urothelial tumors, which may reflect not only the growth pattern but also the biological behaviour of the individual tumors.
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Vallonthaiel, Archana George; Agarwal, Shipra; Jain, Deepali; Yadav, Rajni; Damle, Nishikant A
2017-09-01
Warthin-like papillary thyroid carcinoma (WLPTC) is a rare morphological variant of papillary thyroid carcinoma which mimics various benign and malignant lesions on thyroid aspiration cytology. As correct cytological diagnosis is the cornerstone for appropriate patient management, awareness of the salient cytomorphological characteristics of this tumor is essential. Here, we present cytological features of a case of WLPTC along with discussion of the common differential diagnoses and a brief review of the literature to ascertain the most consistent cytological findings of WLPTC. The present case also harboured BRAFV600E mutation which is the commonest molecular alteration seen in WLPTC. © 2017 Wiley Periodicals, Inc.
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Murtezaoglu, Afsin Rahman; Gucer, Hasan
In this study, we compared the diagnostic value of TROP-2 expression in distinguishing between benign and malignant thyroid lesions to those of HBME-1, CK19 and galectin-3. We selected 102 cases from our archive including 20 normal thyroid tissues, 23 follicular nodular diseases, 17 follicular adenomas, 20 follicular variant papillary carcinomas and 22 classical variant papillary carcinomas. Tissue microarrays constructed from these cases were immunohistochemically analyzed with HBME-1, CK19, galectin-3 and TROP-2. Respectively 73.8%, 83.3%, 69% and 50% of all papillary carcinomas were positive with HBME-1, CK19, galectin-3 and TROP-2. CK19 was positive respectively by 100%, 43.5% and 35.3% in cases of normal thyroid, follicular nodular diseases and follicular adenoma, while the other markers were negative. In distinguishing benign and malignant lesions, which constitutes this study, HBME-1, CK19, galectin-3 and TROP-2 were statistically significant (p < 0.001). In distinguishing cases of follicular variant papillary carcinoma from follicular nodular diseases and follicular adenoma, HBME-1 and galectin-3 were statistically significant (p < 0.001). Consequently, in this study, we found that all immunohistochemical markers were effective in distinguishing benign and malignant thyroid lesions. In determining malignancy, HBME-1 had the highest diagnostic accuracy, while CK19 was the most sensitive marker. The sensitivity increased when the markers were used together.
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Skin metastasis on the neck: an unusual presentation of recurrence of papillary thyroid carcinoma
Soylu, Selen; Teksoz, Serkan; Ozcan, Murat; Bukey, Yusuf
2017-01-01
Skin metastasis of papillary thyroid carcinoma (PTC) is rare. Here, two cases of skin metastases of PTC are presented. Both of the patients were females, one is 83 and the other is 65 years old. The patients were admitted to the hospital with a movable skin lesion on anterior neck region. Free T3 and T4 levels were in normal levels and TSH levels were low in both patients. The 83-year-old patient underwent total thyroidectomy due to papillary thyroid cancer and received 131I ablation therapy and then thyroid suppression therapy. After the surgery, the patient lived without evidence of disease for 3 years and then skin metastasis occurred. The 65-year-old patient had a total thyroidectomy 5 years ago due to PTC then neck dissection due to metastasis 3 years later and then received 131I ablation therapy. Thyroid ultrasonography of both patients showed hypoechoic nodules with central vascularization. In the histological examination of both patients, cystic lesions filled with papillary structures were seen. Fine needle aspiration biopsy (FNAB) taken from both patients were papillary carcinoma with solid trabecular pattern. PTC tends to metastasize to regional lymph nodes but distant metastasis is rare. When distant metastasis develops, prognosis of the disease is poor. Therefore, skin metastasis of papillary thyroid cancer is a poor prognostic factor. If the patient does not have a thyroid malignancy history, diagnosis of PTC metastatic to the skin may be difficult since primary skin tumors such as apocrine tumors have similar histopathological features. However, in the presented cases since there was a PTC history, the diagnosis was easier with the help of histopathological examination. Skin metastasis of PTC should be kept in mind when differential diagnosis of atypical skin lesions are made especially in the patients with thyroid malignancy history. PMID:29142854
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Janus, Dominika; Wojcik, Malgorzata; Kalicka-Kasperczyk, Anna; Drabik, Grazyna; Wyrobek, Lukasz; Wedrychowicz, Anna; Starzyk, Jerzy B
2017-10-01
The coincidence of autoimmune thyroiditis (AIT) in patients with papillary thyroid carcinoma (PTC) is ranging between 10 and 58% in the general population. In the present study retrospective ultrasound, clinical and autoimmune assessment of 24 patients diagnosed with papillary thyroid carcinoma between 2000-2016 was performed. The coexistence of PTC and AIT was found in 50% of patients with PTC. Patients were divided into two groups. PTC AIT (+) group involved 12 children at the mean age 14.9 years (range 11-20 years, 9 girls) and PTC AIT (-) 12 children at the mean age 12.9 years (range 7-18 years, 5 girls). Papillary thyroid microcarcinoma (PTMC) was diagnosed in 6 patients (in 5 with AIT). US characteristics of PTC was heterogenous: hypoechogenic with/without increased vascularisation, normoechogenic with halo, with/without microcalcifications. In 70% PTC AIT (+) and in all PTC AIT (-) patients ultrasound analysis revealed that the thyroid tissue of the whole gland was normoechogenic. Local metastases in lymph nodes were found in 40% of PTMC AIT (+). Lack of increased vascularization and microcalcifications and presence of``halo`in the nodule does not exclude malignancy. Due to the presence of lymph node involvement in PTMC in all children with PTC total thyroidectomy should be performed with lymph nodes verification.
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Bardosi, Sebastian; Bardosi, Attila; Nagy, Zsuzsanna; Reglodi, Dora
2016-10-01
Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PACAP and its specific PAC1 receptor in human thyroid gland pathologies have not yet been investigated. Therefore, the aim of the present study was to investigate expression of PACAP and its PAC1 receptor in human thyroid papillary carcinoma, the most common endocrine malignant tumor. PACAP and PAC1 receptor expressions were investigated from thyroid gland samples of patients with papillary carcinomas. The staining intensity of follicular epithelial cells and thyroid colloid of tumor tissue was compared to that of tumor-free tissue in the same thyroid glands in a semi-quantitative way. Our results reveal that both PACAP(-like) and PAC1 receptor(-like) immunoreactivities are altered in papillary carcinoma. Stronger PACAP immunoreactivity was observed in active follicles. Colloidal PACAP immunostaining was either lacking or very weak, and more tumorous cells displayed strong apical immunoreactivity. Regarding PAC1 receptor, cells of the normal thyroid tissue showed strong granular expression, which was lacking in the tumor cells. The cytoplasm of tumor cells displayed weak, minimal staining, while in a few tumor cells we observed strong PAC1 receptor expression. This pattern was similar to that observed in the PACAP expression, but fewer in number. In summary, we showed alteration of PACAP and PAC1 receptor expression in human thyroid papillary carcinoma, indicating that PACAP regulation is disturbed in tumorous tissue of the thyroid gland. The exact role of PACAP in thyroid tumor growth should be further explored.
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Terada, Tadashi
2013-01-01
Various tumors can arise in the urinary bladder (UB); most common is urothelial carcinoma (UC). UC of the UB have many variants. Other types of carcinomas such as adenocarcinoma (AC) and small cell carcinoma (SmCC) can occur in UB carcinomas. Expression of KIT and PDGFRA has not been reported. A 66-year-old man admitted to our hospital because of hematuria. Cystoscopy revealed papillary invasive tumor and a transurethral bladder tumorectomy (TUR-BT) was performed. The TUR-BT showed UC, AC, SmCC, large cell carcinoma (LCC), and pleomorphic carcinoma (PC). The UC component showed plasmacytoid, spindle, nested, clear cell, acantholytic variants. The AC element showed tubular adenocarcinoma and signet-ring cell carcinoma (Sig). Immunohistochemically, all of these subtypes were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK34BE12, CK5, CK6, CK7, CK8, CK18, CK19, CK20, EMA, CEA, p63, CA19-9, p53 (positive 45%), MUC1, NSE, NCAM, KIT, PDGFRA, and Ki-67 (87%). They were negative for vimentin, chromogranin, synaptophysin, S100 protein, CD34, CD14, α-smooth muscle actin, CD31, caldesmon, CD138, CD45, κ-chain, λ-chain, MUC2, MUC5AC and MUC6. Mucin histochemistry revealed mucins in AC element including Sig. A molecular genetic analysis using PCR-direct sequencing method identified no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The carcinoma was highly aggressive and invaded into muscular layer. The nuclear grade was very high, and there were numerous lymphovascular permeations were seen. The surface showed carcinoma in situ involving von-Brunn's nests. This case shows that carcinoma of UB can show diverse differentiations into numerous histological types and variants, and can express KIT and PDGFRA. The both genes showed no mutations in the present case.
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Moriya, Toshiyuki; Kimura, Wataru; Semba, Shuho; Sakurai, Fumiaki; Hirai, Ichiro; Ma, Jinfeng; Fuse, Akira; Maeda, Kunihiko; Yamakawa, Mitsunori
2005-01-01
Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail. PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two. A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2. Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015). In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began
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González-Colunga, Karla Judith; Loya-Solis, Abelardo; Ceceñas-Falcón, Luis Ángel; Barboza-Quintana, Oralia; Rodríguez-Gutiérrez, René
2015-01-01
Defining the histologic variant of thyroid carcinoma is an important clinical implication as their progression, recurrence, aggressiveness, and prognosis differ. Warthin-like variant is one of the rarest histologic variants of papillary thyroid cancer. A 36-year-old female sought consult for assessment of a painless right neck tumor. High-resolution neck ultrasound revealed a right hypoechoic, 1.71 × 1.05 cm thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy report was a Bethesda grade III. Thyroid function tests showed Hashimoto's thyroiditis. The patient underwent right hemithyroidectomy. Microscopically, the tumor was composed of papillae lined by cells with eosinophilic cytoplasm, nuclear chromatin clearing, grooves, and pseudoinclusions and a characteristic lymphoplasmacytic infiltrate of the papillae cores. Extension into the perithyroidal soft tissue and 3 ipsilateral lymph nodes was found to be positive for cancer. Warthin-like variant is an uncommon and relatively unknown variant of papillary thyroid carcinoma that has been usually associated with an excellent prognosis. Interestingly, BRAF mutations have been reported to be present in up to 75% of the patients. It is frequently associated with Hashimoto's thyroiditis and presents unique morphological features that make it recognizable on histologic examination. The cytological diagnosis is difficult to assess due to the overlap in its findings with the classical variant and Hashimoto's thyroiditis.
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Molecular biomarkers for progression of intraductal papillary mucinous neoplasm of the pancreas.
Kuboki, Yuko; Shimizu, Kyoko; Hatori, Takashi; Yamamoto, Masakazu; Shibata, Noriyuki; Shiratori, Keiko; Furukawa, Toru
2015-03-01
We aimed to identify molecular biomarkers for assessing the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN). We retrospectively investigated molecular aberrations and their associations with clinicopathological features in 172 IPMNs. GNAS and KRAS mutations were detected in 48% and 56% of IPMNs, respectively. No mutations of EGFR, PIK3CA GNAO1, GNAQ, or GNAI2 were observed. Significant associations were observed between IPMN morphological types and GNAS mutations, KRAS mutations, the expression of phosphorylated MAPK (pMAPK), AKT, and phosphorylated AKT (pAKT), nuclear accumulation of β-catenin, SMAD4 loss, and TP53 overexpression; histological grades and the expression of EGFR, pMAPK, AKT, and pAKT, the nuclear β-catenin, SMAD4 loss, and TP53 overexpression; invasive phenotypes and KRAS mutations, the nuclear β-catenin, and SMAD4 loss; and prognosis and SMAD4 loss and TP53 overexpression. Multivariate analysis to compare prognostic impacts of multiple molecular features revealed that TP53 overexpression was an independent prognostic factor (P = 0.030; hazard ratio, 5.533). These results indicate that mutations in GNAS and KRAS, the expression of EGFR and pMAPK, the nuclear β-catenin, SMAD4 loss, and TP53 overexpression may be relevant for assessing the clinical course of IPMN, including its progression into different morphological types, invasion, and prognosis.
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Guma, Sergei; Maglantay, Remegio; Lau, Ryan; Wieczorek, Rosemary; Melamed, Jonathan; Deng, Fang-Ming; Zhou, Ming; Makarov, Danil; Lee, Peng; Pincus, Matthew R; Pei, Zhi-Heng
2016-01-01
The human papilloma virus (HPV) is a carcinogen known for its strong association with cervical cancers and cervical lesions. It is also known to be associated with a variety of squamous cell carcinomas in other areas, such as the penis, vulva, anus and head and neck. However, the association with urothelial carcinoma remains controversial. Here, we report a case of urothelial carcinoma with squamous differentiation associated with HPV-6/HPV-11. This is a case of a 70 year old man who presented with nocturia and pressure during urination. During the TURP procedure for what was clinically thought to be benign prostate hyperplasia with pathologic diagnosis as prostate carcinoma, a 2 cm papillary mass was found in the distal penile urethra. The papillary mass was found to be a high grade urothelial carcinoma positive for GATA 3 expression, with focal areas of squamous differentiation. The areas with squamous differentiation demonstrated koilocytic differentiation, which were positive for strong p16 expression. The tumor was found to harbor low risk HPV 6/11 by in situ hybridization. This study case demonstrates HPV infection with a low risk subtype (HPV 6/11) associated with an urothelial carcinoma with squamous differentiation and condylomatous features.
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Kadour-Peero, Einav; Sagi-Dain, Lena; Cohen, Gil; Korobochka, Roman; Agbarya, Abed; Bejar, Jacob; Sagi, Shlomi
2018-05-07
BACKGROUND There is now evidence to support that some cases of high-grade serous papillary carcinoma arise from the fallopian tubes rather than the ovaries. Common symptoms at presentation include abdominal pain and swelling, vomiting, altered bowel habit and urinary symptoms. To our knowledge, this is the first case of serous papillary carcinoma presenting as a vaginal mass lesion. CASE REPORT A 41-year-old woman was referred to the Bnai-Zion Medical Center with the main complaint of irregular vaginal bleeding, vaginal mucous discharge, and suspected pelvic mass. Physical examination showed a soft, painless mass, measuring about 10 cm in diameter located mainly in the recto-vaginal septum, but not involving the uterus. Ultrasound examination showed no abnormal ovarian or uterine findings. Transvaginal biopsies of the mass showed a poorly differentiated serous papillary carcinoma of ovarian, tubal, or peritoneal origin. The physical examination and imaging findings strongly indicated an inoperable tumor, and the patient was treated with neoadjuvant (pre-surgical) chemotherapy. Pre-operative computed tomography (CT) imaging showed the partial involvement of the colon, and so surgical treatment included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, partial vaginectomy, anterior rectal resection, and lymph node dissection. Histopathology of the surgical specimens showed a poorly differentiated serous carcinoma originating from the fimbria of the right fallopian tube. CONCLUSIONS To the best of our knowledge, this is the first report to describe primary fallopian tube papillary serous carcinoma presenting as a vaginal mass. Therefore, physicians should be aware of this possible diagnosis.
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Yılmaz, Ravza; Cömert, Rana Günöz; Aliyev, Samil; Toktaş, Yücel; Önder, Semen; Emirikçi, Selman; Özmen, Vahit
2018-04-01
Male breast cancer is an uncommon disease that constitutes 1% of all breast cancers and encapsulated papillary carcinoma (EPC) is a rare subtype of malignant male diseases. Gynecomastia is the most common disease of the male breast. We report a 63-year-old male patient with EPC accompanied by gynecomastia that was diagnosed and treated at our breast center. Mammography showed an oval-shaped dense mass with circumscribed margins on the ground of nodular gynecomastia. On ultrasonographic exam, we saw a well-circumscribed complex mass with a solid component which was vascular on Doppler ultrasonography. Magnetic resonance imaging revealed a complex cystic mass containing solid components. Dynamic images showed enhancement of the cystic mass wall and mural components. Tumor stage was evaluated as T2N0. The lesion's histologic examination and immunohistochemical analysis by showing no myoepithelial layer revealed an encapsulated papillary carcinoma. To our knowledge, this is the first case report which describes MR imaging findings of male breast encapsulated papillary cancer.
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Kim, Yikwon; Kang, MeeJoo; Han, Dohyun; Kim, Hyunsoo; Lee, KyoungBun; Kim, Sun-Whe; Kim, Yongkang; Park, Taesung; Jang, Jin-Young; Kim, Youngsoo
2016-01-04
Intraductal papillary mucinous neoplasm (IPMN) is a common precursor of pancreatic cancer (PC). Much clinical attention has been directed toward IPMNs due to the increase in the prevalence of PC. The diagnosis of IPMN depends primarily on a radiological examination, but the diagnostic accuracy of this tool is not satisfactory, necessitating the development of accurate diagnostic biomarkers for IPMN to prevent PC. Recently, high-throughput targeted proteomic quantification methods have accelerated the discovery of biomarkers, rendering them powerful platforms for the evolution of IPMN diagnostic biomarkers. In this study, a robust multiple reaction monitoring (MRM) pipeline was applied to discovery and verify IPMN biomarker candidates in a large cohort of plasma samples. Through highly reproducible MRM assays and a stringent statistical analysis, 11 proteins were selected as IPMN marker candidates with high confidence in 184 plasma samples, comprising a training (n = 84) and test set (n = 100). To improve the discriminatory power, we constructed a six-protein panel by combining marker candidates. The multimarker panel had high discriminatory power in distinguishing between IPMN and controls, including other benign diseases. Consequently, the diagnostic accuracy of IPMN can be improved dramatically with this novel plasma-based panel in combination with a radiological examination.
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Mucinous Breast Cancer: a Review Study of 5 Year Experience from a Hospital-Based Series of Cases.
Dumitru, Adrian; Procop, Alexandru; Iliesiu, Andreea; Tampa, Mircea; Mitrache, Luminita; Costache, Mariana; Sajin, Maria; Lazaroiu, Anca; Cirstoiu, Monica
2015-03-01
Mucinous carcinoma (also known as colloid carcinoma) is a particular type of breast cancer characterized by the presence of extracellular mucin and is linked with a more favorable prognosis than invasive breast carcinoma of no special type. Mucinous carcinoma of the breast is an uncommon form of breast tumor, often presenting as a lobulated, moderately well circumscribed mass on mammography, sonography, and MRI imaging. It accounts for 1 to 7% of all breast cancers. Pure mucinous breast carcinomas are rare and account for about 2% of all primary breast carcinomas. Metastatic disease happens at a lower rate than in other types of invasive carcinoma. We present our 5 year experience with this particular pathology in a retrospective review study. We identified 25 patients with mixed and pure mucinous breast cancer, the tumor size varied greatly from 2 to 19 cm in diameter. A subset of mixed mucinous carcinomas (8 cases) showed neuroendocrine differentiation or other associated premalignant lessions. Mucinous carcinoma of the breast is a rare entity with a favorable prognosis due to low incidence of lymph node metastases. Pure mucinous breast carcinoma has an even rare.
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Mucinous Breast Cancer: a Review Study of 5 Year Experience from a Hospital-Based Series of Cases
DUMITRU, Adrian; PROCOP, Alexandru; ILIESIU, Andreea; TAMPA, Mircea; MITRACHE, Luminita; COSTACHE, Mariana; SAJIN, Maria; LAZAROIU, Anca; CIRSTOIU, Monica
2015-01-01
Background: Mucinous carcinoma (also known as colloid carcinoma) is a particular type of breast cancer characterized by the presence of extracellular mucin and is linked with a more favorable prognosis than invasive breast carcinoma of no special type. Mucinous carcinoma of the breast is an uncommon form of breast tumor, often presenting as a lobulated, moderately well circumscribed mass on mammography, sonography, and MRI imaging. It accounts for 1 to 7% of all breast cancers. Pure mucinous breast carcinomas are rare and account for about 2% of all primary breast carcinomas. Metastatic disease happens at a lower rate than in other types of invasive carcinoma. Methods: We present our 5 year experience with this particular pathology in a retrospective review study. Results: We identified 25 patients with mixed and pure mucinous breast cancer, the tumor size varied greatly from 2 to 19 cm in diameter. A subset of mixed mucinous carcinomas (8 cases) showed neuroendocrine differentiation or other associated premalignant lessions. Conclusion: Mucinous carcinoma of the breast is a rare entity with a favorable prognosis due to low incidence of lymph node metastases. Pure mucinous breast carcinoma has an even rare. PMID:26225144
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Synchronous Papillary Carcinoma and Hemangiopericytoma with Lung Metastases
Malagutti, Nicola; Iannini, Valeria; Rocchi, Andrea; Stomeo, Francesco; Frassoldati, Antonio; Borin, Michela; Pelucchi, Stefano
2013-01-01
Hemangiopericytomas (HPC) are uncommon tumors that originate from perivascular cells of capillary vessels. HPC are about 1% of all vascular tumors and can be found in the head-neck region with an incidence between 16% and 33%. HPC is a neoplasm of uncertain malignant potential; it can behave as an aggressive tumor with metastases and increased mitotic activity or as a relatively benign neoplasm with only local development. In this paper we describe a case of hemangiopericytoma with uncertain malignant potential with cervical location associated with a concomitant papillary thyroid carcinoma and lung metastasis of unknown origin; this case led us to follow a specific and uncommon diagnostic and therapeutic strategy. PMID:24368958
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Tfayli, Hala M; Teot, Lisa A; Indyk, Justin A; Witchel, Selma Feldman
2010-09-01
Whereas thyroid nodules are less common among children than among adults, the anxiety generated by the finding of a thyroid nodule is high because 20% of nodules found in children contain thyroid cancer. Discovery of a nodule in the context of hyperthyroidism is usually comforting due to the presumption that the nodule represents a benign toxic adenoma. An 11-year-old girl presented with heavy menses, fatigue, and a right thyroid mass. Laboratory evaluation revealed elevated triiodothyronine and undetectable thyroid-stimulating hormone. Thyroid ultrasonography revealed a 3.5 cm nonhomogenous nodule, and scintigraphy was consistent with an autonomous hyper-functioning nodule. Fine-needle aspiration biopsy could not rule out malignancy, and patient underwent right hemithyroidectomy and isthmusectomy. Pathology was consistent with papillary thyroid carcinoma. We report the discovery of papillary thyroid carcinoma in an autonomously hyperfunctioning nodule in an 11-year-old girl. Detection of an autonomously functioning thyroid nodule in children and adolescents does not exclude the possibility of thyroid carcinoma and warrants careful evaluation and appropriate therapy.
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Tfayli, Hala M.; Teot, Lisa A.; Indyk, Justin A.
2010-01-01
Background Whereas thyroid nodules are less common among children than among adults, the anxiety generated by the finding of a thyroid nodule is high because 20% of nodules found in children contain thyroid cancer. Discovery of a nodule in the context of hyperthyroidism is usually comforting due to the presumption that the nodule represents a benign toxic adenoma. Summary An 11-year-old girl presented with heavy menses, fatigue, and a right thyroid mass. Laboratory evaluation revealed elevated triiodothyronine and undetectable thyroid-stimulating hormone. Thyroid ultrasonography revealed a 3.5 cm nonhomogenous nodule, and scintigraphy was consistent with an autonomous hyper-functioning nodule. Fine-needle aspiration biopsy could not rule out malignancy, and patient underwent right hemithyroidectomy and isthmusectomy. Pathology was consistent with papillary thyroid carcinoma. Conclusions We report the discovery of papillary thyroid carcinoma in an autonomously hyperfunctioning nodule in an 11-year-old girl. Detection of an autonomously functioning thyroid nodule in children and adolescents does not exclude the possibility of thyroid carcinoma and warrants careful evaluation and appropriate therapy. PMID:20718686
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Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer
2017-11-15
Inflammatory Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Tubular Ductal Breast Carcinoma
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Warthin-Like Papillary Thyroid Carcinoma Associated with Lymphadenopathy and Hashimoto's Thyroiditis
González-Colunga, Karla Judith; Loya-Solis, Abelardo; Ceceñas-Falcón, Luis Ángel; Barboza-Quintana, Oralia; Rodríguez-Gutiérrez, René
2015-01-01
Defining the histologic variant of thyroid carcinoma is an important clinical implication as their progression, recurrence, aggressiveness, and prognosis differ. Warthin-like variant is one of the rarest histologic variants of papillary thyroid cancer. A 36-year-old female sought consult for assessment of a painless right neck tumor. High-resolution neck ultrasound revealed a right hypoechoic, 1.71 × 1.05 cm thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy report was a Bethesda grade III. Thyroid function tests showed Hashimoto's thyroiditis. The patient underwent right hemithyroidectomy. Microscopically, the tumor was composed of papillae lined by cells with eosinophilic cytoplasm, nuclear chromatin clearing, grooves, and pseudoinclusions and a characteristic lymphoplasmacytic infiltrate of the papillae cores. Extension into the perithyroidal soft tissue and 3 ipsilateral lymph nodes was found to be positive for cancer. Warthin-like variant is an uncommon and relatively unknown variant of papillary thyroid carcinoma that has been usually associated with an excellent prognosis. Interestingly, BRAF mutations have been reported to be present in up to 75% of the patients. It is frequently associated with Hashimoto's thyroiditis and presents unique morphological features that make it recognizable on histologic examination. The cytological diagnosis is difficult to assess due to the overlap in its findings with the classical variant and Hashimoto's thyroiditis. PMID:25821606
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PIK3CA Mutations in Mucinous Cystic Neoplasms of the Pancreas
Garcia-Carracedo, Dario; Chen, Zong-Ming; Qiu, Wanglong; Huang, Alicia S.; Tang, Sophia M.; Hruban, Ralph H.; Su, Gloria H.
2014-01-01
Objectives Mucinous cystic neoplasms (MCNs) are rare, potentially curable, mucin-producing neoplasms of the pancreas. We have previously reported PIK3CA (phosphoinositide-3-kinase catalytic subunit, p110α) mutations in intraductal papillary mucinous neoplasms, another mucin-producing neoplasm of the pancreas. In this study, we analyzed the presence of PIK3CA and AKT1/PKB (V-akt murine thymoma viral oncogene homolog 1) hot-spot mutations in MCN specimens. Methods Using the genomic DNA sequencing of tumor tissues isolated by laser capture microdissection, we evaluated 15 well-characterized MCNs for the E542K, E545K(exon 9), and H1047R (exon 20) hot-spotmutations in the PIK3CA gene and the E17K mutation in the AKT1 gene. Results A hot-spotmutation (E545K) of the PIK3CA gene was detected in 1 of the 15 MCNs and further confirmed by a mutant-enriched method. Interestingly, this mutation was found to be present only in the high-grade but not in low-grade dysplastic epithelium obtained from this neoplasm and coexisted with a KRASG12D mutation. No mutations were identified in the AKT1 gene. Conclusions Our data, when combined with previous reports on intraductal papillary mucinous neoplasms, indicate that oncogenic activation of the PI3K pathway involving PIK3CA gene mutations can contribute to the progression of mucin-producing neoplasms but not pancreatic intraepithelial neoplasia. PIK3CA status could be useful for understanding their progression to malignancy. PMID:24518503
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Han, Fei; Zhang, Long; Zhang, Suxia; Zhou, Hong; Yi, Xianghua
2015-01-01
Warthin-Like tumor of the thyroid is a recently described rare variant of papillary thyroid cancer. The distinct histological feature of this variant is papillary architecture lining oncocytic epithelial cells with nuclear characteristics of papillary carcinoma, accompanied by prominent lymphocytic infiltration in the papillary stalks. Here, we present a case of occult Warthin-like papillary thyroid carcinoma, 0.5-cm in maximum dimension, underwent left thyroid lobectomy in a 65 years old Chinese woman. In this case, there was no extrathyroid extension, vascular invasion and lymphatic metastasis, as well as no complication of lymphocytic thyroiditis. Immunohistochemistry staining revealed that the tumor cells were positive for Leu-M1, HBME-1, 34βE12, and MIB-1 labeling index was low. RET/PTC expression was absent in tumor cells. Furthermore, activated point mutations of BRAF V600E and V600K were concurrently detected by DNA sequencing. Further studies are needed to elucidate the prevalence and role of BRAF(V600K) mutation in papillary thyroid carcinoma, and long-term follow-up for the patient is needed to clarify the biological behavior of this variant with dual BRAF mutations.
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Han, Fei; Zhang, Long; Zhang, Suxia; Zhou, Hong; Yi, Xianghua
2015-01-01
Warthin-Like tumor of the thyroid is a recently described rare variant of papillary thyroid cancer. The distinct histological feature of this variant is papillary architecture lining oncocytic epithelial cells with nuclear characteristics of papillary carcinoma, accompanied by prominent lymphocytic infiltration in the papillary stalks. Here, we present a case of occult Warthin-like papillary thyroid carcinoma, 0.5-cm in maximum dimension, underwent left thyroid lobectomy in a 65 years old Chinese woman. In this case, there was no extrathyroid extension, vascular invasion and lymphatic metastasis, as well as no complication of lymphocytic thyroiditis. Immunohistochemistry staining revealed that the tumor cells were positive for Leu-M1, HBME-1, 34βE12, and MIB-1 labeling index was low. RET/PTC expression was absent in tumor cells. Furthermore, activated point mutations of BRAF V600E and V600K were concurrently detected by DNA sequencing. Further studies are needed to elucidate the prevalence and role of BRAFV600K mutation in papillary thyroid carcinoma, and long-term follow-up for the patient is needed to clarify the biological behavior of this variant with dual BRAF mutations. PMID:26191315
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2018-06-04
Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma
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Onishi, Junji; Sato, Yuichiro; Sawaguchi, Akira; Yamashita, Atsushi; Maekawa, Kazunari; Sameshima, Hiroshi; Asada, Yujiro
2016-09-01
Stratified mucin-producing intraepithelial lesion (SMILE) is considered to be a variant of adenocarcinoma in situ (defined as intraepithelial malignant glandular epithelium without invasion) or adenosquamous carcinoma in situ of the uterine cervix. However, recent study suggested that SMILE is more similar to high-grade squamous epithelial lesion by their immunohistochemical findings. An invasive form of SMILE "invasive stratified mucin-producing carcinoma (ISMC)" has been also proposed, but immunohistochemical features are not well documented. Therefore, this study aimed to clarify the immunohistochemical characteristics of SMILE and ISMC. Twelve cases of SMILE were found among 445 patients (2.7%) with high-grade intraepithelial lesions or invasive carcinomas, 3 of whom had solely intraepithelial disease with SMILE component (mean age, 37 years; range, 30-48 years) and 9 with invasive carcinomas (mean age, 47 years; range, 37-66 years; including ISMC). Immunohistochemically, SMILE and ISMC were diffusely positive for p16 and CAM5.2, focally for IMP3, and almost negative or only focally positive for p63. Nuclear signals in SMILE and invasive carcinomas were detected by human papillomavirus (HPV) in situ hybridization; 5 cases showed HPV16 and/or HPV18 polymerase chain reaction products. The ultrastructural study of 1 case showed surface microvilli and small vacuolar structure in SMILE; ISMC had mucous-like vacuoles, many mitochondria and intracytoplasmic lumen but lacked tonofilament. These findings were more similar to adenocarcinoma in situ or adenocarcinoma than squamous intraepithelial lesion or squamous cell carcinoma. We suggest that SMILE is an intraepithelial neoplasm and ISMC is an invasive form of SMILE. Copyright © 2016 Elsevier Inc. All rights reserved.
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Decision making for pancreatic resection in patients with intraductal papillary mucinous neoplasms.
Xu, Bin; Ding, Wei-Xing; Jin, Da-Yong; Wang, Dan-Song; Lou, Wen-Hui
2013-03-07
To identify a practical approach for preoperative decision-making in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Between March 1999 and November 2006, the clinical characteristics, pathological data and computed tomography/magnetic resonance imaging (CT/MRI) of 54 IPMNs cases were retrieved and analyzed. The relationships between the above data and decision-making for pancreatic resection were analyzed using SPSS 13.0 software. Univariate analysis of risk factors for malignant or invasive IPMNs was performed with regard to the following variables: carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and the characteristics from CT/MRI images. Receiver operating characteristic (ROC) curve analysis for pancreatic resection was performed using significant factors from the univariate analysis. CT/MRI images, including main and mixed duct IPMNs, tumor size > 30 mm or a solid component appearance in the lesion, and preoperative serum CA19-9 > 37 U/mL had good predictive value for determining pancreatic resection (P < 0.05), but with limitations. Combining the above factors (CT/MRI images and CA19-9) improved the accuracy and sensitivity for determining pancreatic resection in IPMNs. Using ROC analysis, the area under the curve reached 0.893 (P < 0.01, 95%CI: 0.763-1.023), with a sensitivity, specificity, positive predictive value and negative predictive value of 95.2%, 83.3%, 95.2% and 83.3%, respectively. Combining preoperative CT/MRI images and CA19-9 level may provide useful information for surgical decision-making in IPMNs.
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Krukenberg carcinoma metastasized from stomach resembling mucinous cystadenocarcinoma of the ovary.
Doğanay, Melike; Topçu, Hasan Onur; Kokanalı, Mahmut Kuntay; Güzel, Ali I Rfan; Oskovi, Aslı; Akbay, Serap; Cavkaytar, Sabri
2017-09-01
The ovaries are common site of metastasis in a variety of primary neoplasms. Multiple tumors such as breast, lung, and pancreas have been reported to metastasize to the ovary, however; the colon and stomach are the most common primary cancer sites that of ovarian metastasis. An ovarian mass mostly originates from its self-tissue, but sometimes it can be a metastasis of a gastrointestinal system tumor. Such cases are often misdiagnosed as primary ovarian cancers. A 42-year-old woman was admitted to our hospital with pelvic pain. She had a history of her complaints for two months. Bilateral large ovarian mass was detected in transvaginal ultrasound. Laparotomy was performed, the pathologist suggested inspection of the stomach after the frozen section analysis; therefore, an irregular mass on the stomach was detected. The general surgeon was attended to the operation, and an inoperative stomach tumor was reported by the general surgeon. After that due to the partial obstruction of jejunum, a gastrojejunostomy was performed. It is in fact difficult to distinguish between metastatic mucinous carcinomas and primary mucinous carcinomas of the ovary, due to the similar appearance of as cystic tumors on gross examination. The clinicians should be aware of the likely concomitant gastrointestinal system tumor when a large and bilaterally mass was detected on physical examination. This case also reminds that a systemic examination is necessary even if the large ovarian tumors suspicious of primary malignancy were noticed.
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Krukenberg carcinoma metastasized from stomach resembling mucinous cystadenocarcinoma of the ovary.
Doğanay, Melike; Topçu, Hasan Onur; Kokanali, Mahmut Kuntay; Güzel, Ali Irfan; Oskovi, Asli; Akbay, Serap; Cavkaytar, Sabri
2015-01-01
The ovaries are common site of metastasis in a variety of primary neoplasms. Multiple tumors such as breast, lung, and pancreas have been reported to metastasize to the ovary, however; the colon and stomach are the most common primary cancer sites that of ovarian metastasis. An ovarian mass mostly originates from its self-tissue, but sometimes it can be a metastasis of a gastrointestinal system tumor. Such cases are often misdiagnosed as primary ovarian cancers. A 42-year-old woman was admitted to our hospital with pelvic pain. She had a history of her complaints for two months. Bilateral large ovarian mass was detected in transvaginal ultrasound. Laparotomy was performed, the pathologist suggested inspection of the stomach after the frozen section analysis; therefore, an irregular mass on the stomach was detected. The general surgeon was attended to the operation, and an inoperative stomach tumor was reported by the general surgeon. After that due to the partial obstruction of jejunum, a gastrojejunostomy was performed. It is in fact difficult to distinguish between metastatic mucinous carcinomas and primary mucinous carcinomas of the ovary, due to the similar appearance of as cystic tumors on gross examination. The clinicians should be aware of the likely concomitant gastrointestinal system tumor when a large and bilaterally mass was detected on physical examination. This case also reminds that a systemic examination is necessary even if the large ovarian tumors suspicious of primary malignancy were noticed.
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Xu, Jiajie; Chen, Chao; Zheng, Chuanming; Wang, Kejing; Shang, Jinbiao; Fang, Xianhua; Ge, Minghua; Tan, Zhuo
2016-04-01
The present study aimed to discuss the advantage of the application of a cervical low incision for functional neck dissection in patients with thyroid papillary carcinoma. The study was a retrospective analysis of 87 thyroid papillary carcinoma patients; cervical low incision in the functional neck dissection was applied for 47 cases and the classic 'L' incision was applied for 40 cases. The different integrity, surgical time, blood loss and the aesthetic property of the incision were compared between the cervical low incision and the classic 'L' incision for lateral neck dissection of thyroid cancer. The postoperative pathological diagnosis was that the average total amount and the region II lymph nodes of the unilateral neck dissection were 33 and 10 for the cervical low incision group, and 32 and 11 for the classic 'L' incision group, respectively (P>0.05). The average unilateral neck dissection times were 87 and 58 min for the cervical low incision group and the classic 'L' incision group, respectively (P<0.05). The blood loss of the cervical low incision group was 67 ml, while the loss for the classic 'L' incision group was 61 ml (P>0.05). The postoperative incision of the cervical low incision group was smaller and more concealing. Additionally, the cosmetic deformities were milder for an inconspicuous cervical scar, and the sensation was improved for the patients in comparison with the classic 'L' incision group. These results suggest that the application of cervical low incision for functional neck dissection in thyroid papillary carcinoma patients aids in reducing postoperative complications, without increasing recurrence rates. Therefore, the classic 'L' incision can be replaced by the cervical low incision.
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Ito, Yasuhiro; Miyauchi, Akira; Jikuzono, Tomoo; Higashiyama, Takuya; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Matsuzuka, Fumio; Ichihara, Kiyoshi; Kuma, Kanji
2007-04-01
In 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients. We examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995. Clinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b. Clinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors.
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Transoral videolaryngoscopic surgery for papillary carcinoma arising in lingual thyroid.
Mogi, Chisato; Shinomiya, Hirotaka; Fujii, Natsumi; Tsuruta, Tomoyuki; Morita, Naruhiko; Furukawa, Tatsuya; Teshima, Masanori; Kanzawa, Maki; Hirokawa, Mitsuyoshi; Otsuki, Naoki; Nibu, Ken-Ichi
2018-05-15
Carcinoma arising in lingual thyroid is an extremely rare entity accounting for only 1% of all reported ectopic thyroids. Here, we report a case of carcinoma arising in lingual thyroid, which has been successfully managed by transoral resection and bilateral neck dissections. A lingual mass 4-cm in diameter with calcification was incidentally detected by computed tomography at medical check-up. No thyroid tissue was observed in normal position. Ultrasound examination showed bilateral multiple lymphadenopathies. Fine needle aspiration biopsy from lymph node in his right neck was diagnosed as Class III and thyroglobulin level of the specimen was 459ng/ml. Due to the difficulty in performing FNA of the lingual masses, right neck dissection was performed in advance for diagnostic purpose. Pathological examination showed existence of large and small follicular thyroid tissues in several lymph nodes, suggesting lymph node metastasis from thyroid carcinoma. Two months after the initial surgery, video-assisted transoral resection of lingual thyroid with simultaneous left neck dissection was performed. Postoperative course was uneventful. Papillary carcinoma was found in the lingual thyroid and thyroid tissues were also found in left cervical lymph nodes. Video-assisted transoral resection was useful for the treatment of thyroid cancer arising in lingual thyroid. Copyright © 2018 Elsevier B.V. All rights reserved.
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Genome-wide significant risk associations for mucinous ovarian carcinoma.
Kelemen, Linda E; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; Lee, Janet M; Seo, Ji-Heui; Phelan, Catherine M; Beesley, Jonathan; Chen, Xiaoqing; Spindler, Tassja J; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia
2015-08-01
Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10(-8)), rs711830 at 2q31.1 (P = 7.5 × 10(-12)) and rs688187 at 19q13.2 (P = 6.8 × 10(-13)). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10(-4), false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.
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Mahajan, S; Agarwal, S; Kocheri, N; Jain, D; Mathur, S R; Iyer, V K
2018-06-01
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently described, indolent thyroid tumor, with well-defined histopathological diagnostic criteria. Cytology features are not well documented. We reviewed cytology of histologically proven cases of NIFTP and some of its common differentials to look for salient diagnostic features. Cases reported on histopathology as follicular variant of papillary thyroid carcinoma (FVPTC), or NIFTP between July 2015 and April 2017 having available cytology smears were retrieved and reclassified as NIFTP, FVPTC, and classical papillary thyroid carcinoma with predominant follicular pattern (PTC-FP). Cytological features were assessed, classified as per The Bethesda System for Reporting Cytopathology and compared. There were 23 NIFTP cases, 18 FVPTC and 8 PTC-FP. A microfollicle-predominant pattern was seen in all. Nuclear score was 2 in most NIFTP cases (61%). Pseudoinclusions were absent. NIFTP showed features of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (III) in 61%, follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) (IV) in 35% and suspicious for malignancy (SFM) (V) in 4%. Most of the FVPTCs were also called FN/SFN (IV) (56%) or AUS/FLUS (III) (22%). Nuclear features did not statistically differ from NIFTP. PTC-FP showed high-grade cytology in 75%, and higher nuclear score (3 in 75%) in contrast to NIFTP (P = .003). NIFTP and FVPTC show a similar distribution among the Bethesda categories hence precluding conclusive distinction on cytology. PTC-FP, in contrast, was found to have a statistically significant higher nuclear score and more commonly showed malignant cytology. © 2018 John Wiley & Sons Ltd.
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Yamaguchi, Rin; Tanaka, Maki; Tse, Gary M; Yamaguchi, Miki; Terasaki, Hiroshi; Nomura, Yoriko; Takenaka, Miki; Naito, Yoshiki; Akiba, Jun; Yano, Hirohisa
2014-03-01
A prominent fibrovascular stromal core is one of the widely accepted histological features of breast papillomas, but some papillary carcinomas also show such broad fibrovascular cores, leading to confusion in diagnosis, particularly in needle biopsy specimens. We investigated the histological characteristics of papillary lesions, focusing on broad fibrovascular cores and their relationship with the architectural patterns. Among 185 cases of needle biopsies of papillomas and papillary carcinomas, the number of cases with broad fibrovascular cores in each group was compared. The broad fibrovascular core density in the subsequently resected specimens was evaluated and compared between papillary predominant pattern (papillary structures >80% of tumours) and mixed pattern (papillary, solid, cribriform and others) within the lesions. Significantly more papillary carcinomas than papillomas and B3 atypical papillary lesions had broad fibrovascular cores (p=0.0091 and p=0.0164, respectively). The papillary predominant pattern was more prominent in carcinomas than in papillomas in the needle biopsies (p=0.048) and showed the same tendency in the resections (p=0.058). The broad fibrovascular core density was significantly lower in the 18 papillomas than in the 37 papillary carcinomas (p=0.0079) and was not significantly different between the papillary predominant and mixed patterns in carcinomas and papillomas. Broad fibrovascular cores in mammary papillary lesions are not specific for papillomas, as they are also present focally in papillary carcinomas. As the frequency of papillary carcinoma with broad fibrovascular cores is relatively high, caution in diagnosis has to be exercised, especially in needle biopsy specimens.
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Intraductal papillary neoplasm originating from an anomalous bile duct.
Maki, Harufumi; Aoki, Taku; Ishizawa, Takeaki; Tanaka, Mariko; Sakatani, Takashi; Beck, Yoshifumi; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Kokudo, Norihiro
2017-04-01
An 82-year-old woman who had been suffering from repeated obstructive jaundice for 7 years was referred to our hospital. Although endoscopic aspiration of the mucin in the common bile duct had been temporally effective, origin of the mucin production had not been detectable. The patient thus had been forced to be on long-term follow-up without curative resection. Endoscopic retrograde cholangioscopy on admission revealed massive mucin in the common bile duct. In addition, an anomalous bile duct located proximal to the gallbladder was identified. Since the lumen of the anomalous duct was irregular and the rest of biliary tree was completely free of suspicious lesions, the anomalous duct was judged to be the primary site. Surgical resection of the segment 4 and 5 of the liver combined with the extrahepatic biliary tract was performed. Pathological diagnosis was compatible to intraductal papillary neoplasm with high-grade intraepithelial dysplasia of the anomalous bile duct. The patient has been free from the disease for 6.5 years after resection. This is the first case of intraductal papillary neoplasm derived from an anomalous bile duct, which was resected after long-term conservative treatment. The present case suggested the slow growing character of natural history of the neoplasm.
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Fridman, Mikhail; Lam, Alfred King-Yin; Krasko, Olga
2016-12-01
Studies of thyroid cancer related to the Chernobyl accident have focused on children as they are the most vulnerable group with the highest risk of developing radiation-associated cancer. In contrast, our research aimed to look at the clinical and pathological features of patients with post-Chernobyl papillary thyroid carcinoma that were 2 years old or less at the time of the Chernobyl accident. The study subjects were patients (n = 359) aged 0 to 2 at the time of the Chernobyl accident and aged ≥19 years at presentation/surgery who were treated in Belarus for papillary thyroid carcinoma during the period 2003-2013. In conventional or oncocytic variant of papillary thyroid carcinoma, the prevalence of extra-thyroidal extension, nodal disease, infiltrative growth or lymphatic vessel invasion was above 50%. These features were less pronounced when compared to tall cell or diffuse sclerosing variants of papillary thyroid carcinoma. The highest frequency of central lymph node metastases was found in patients aged 1-2 years at exposure (P = 0·004). Subjects exposed in utero were characterized by absent/insignificant lymphocytic infiltration around the carcinoma (P = 0·025), predominance of conventional papillary architecture and an association with lymphocytic thyroiditis. A number of features were associated with this group of patients that were very young at the time of radiation exposure. In addition, the incidence and basic characteristics of adult papillary thyroid carcinoma varied depending on the types of exposure conditions. © 2016 John Wiley & Sons Ltd.
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XU, JIAJIE; CHEN, CHAO; ZHENG, CHUANMING; WANG, KEJING; SHANG, JINBIAO; FANG, XIANHUA; GE, MINGHUA; TAN, ZHUO
2016-01-01
The present study aimed to discuss the advantage of the application of a cervical low incision for functional neck dissection in patients with thyroid papillary carcinoma. The study was a retrospective analysis of 87 thyroid papillary carcinoma patients; cervical low incision in the functional neck dissection was applied for 47 cases and the classic ‘L’ incision was applied for 40 cases. The different integrity, surgical time, blood loss and the aesthetic property of the incision were compared between the cervical low incision and the classic ‘L’ incision for lateral neck dissection of thyroid cancer. The postoperative pathological diagnosis was that the average total amount and the region II lymph nodes of the unilateral neck dissection were 33 and 10 for the cervical low incision group, and 32 and 11 for the classic ‘L’ incision group, respectively (P>0.05). The average unilateral neck dissection times were 87 and 58 min for the cervical low incision group and the classic ‘L’ incision group, respectively (P<0.05). The blood loss of the cervical low incision group was 67 ml, while the loss for the classic ‘L’ incision group was 61 ml (P>0.05). The postoperative incision of the cervical low incision group was smaller and more concealing. Additionally, the cosmetic deformities were milder for an inconspicuous cervical scar, and the sensation was improved for the patients in comparison with the classic ‘L’ incision group. These results suggest that the application of cervical low incision for functional neck dissection in thyroid papillary carcinoma patients aids in reducing postoperative complications, without increasing recurrence rates. Therefore, the classic ‘L’ incision can be replaced by the cervical low incision. PMID:27073645
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Ferreira, Luciana Bueno; Tavares, Catarina; Pestana, Ana; Pereira, Catarina Leite; Eloy, Catarina; Pinto, Marta Teixeira; Castro, Patricia; Batista, Rui; Rios, Elisabete; Sobrinho-Simões, Manuel; Pereira Gimba, Etel Rodrigues; Soares, Paula
2016-01-01
Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches. PMID:27409830
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Ferreira, Luciana Bueno; Tavares, Catarina; Pestana, Ana; Pereira, Catarina Leite; Eloy, Catarina; Pinto, Marta Teixeira; Castro, Patricia; Batista, Rui; Rios, Elisabete; Sobrinho-Simões, Manuel; Gimba, Etel Rodrigues Pereira; Soares, Paula
2016-08-09
Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches.
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Raju, U B; Lee, M W; Zarbo, R J; Crissman, J D
1989-11-01
The presence or absence of myoepithelial cells (ME) has been considered as an important feature in the differential diagnosis of benign and malignant papillary lesions of the breast. We evaluated the distribution of myoepithelial cells in formalin-fixed paraffin-embedded tissue sections of 25 papillomas and 18 papillary carcinomas by ABC immunoperoxidase technique with antibodies to muscle actin (HHF-35) and high molecular weight (HMW) keratin (clone 34BE12, cytokeratins 1, 5, 10, and 14; reacting preferentially with ME cells) and an antiserum to S-100 protein. Also included in the study were eight cases of micropapillary ductal carcinoma in situ (DCIS) having a few fibrovascular cores and five peripheral papillomas with accompanying ductal carcinoma in situ or atypical hyperplasia. The antibodies to muscle actin were sensitive and relatively specific for ME cells of the breast and uniformly labeled ME cells in all 25 papillomas. ME cells were absent or extremely sparse in papillary carcinomas. They were present focally in some of the fibrovascular cores of the micropapillary DCIS, and a mixed pattern was observed in peripheral papillomas with areas of carcinoma. HMW keratin was variably expressed in ME cells in most cases with positive internal controls and was present in several normal ductal and papilloma epithelial cells but not in epithelial cells of papillary carcinomas. HMW keratin, although less specific for ME cells, was a useful adjunct because of its reactivity with ME cells as well as hyperplastic epithelial cells in papillomas, which resulted in a combined positive reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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Cystic mucinous adenocarcinoma of the lung: a case report
2011-01-01
Mucinous cystic tumors of the lung are uncommon, the preoperative pathologic diagnosis is difficult and their biological behavior is still controversial. We report the case of a patient with a clinically benign cystic lesion that post-operatively showed to be consistent with an invasive adenocarcinoma arising in a mucinous cystadenoma of the lung, We underline the difficulty of the clinical pre-operative diagnosis of this cystic neoplasia radiologically mimicking a hydatid cyst, and we report the negative TTF1 immunostaining potentially misleading in the differential diagnosis with metastatic mucinous carcinomas. Finallly, we evidence the presence of a pre-existing mucinous benign lesion suggesting early and complete resection of benign appearing lung cysts because they can undergo malignant transformation if left untreated or they can already harbor foci of invasive carcinoma at the time of the presentation. Even if a good prognosis, better than in other lung carcinomas, with no recurrrence or metastasis after complete surgical exicision, has been reported for cystic mucinous cystoadenocarcinomas, the follow-up showed an aggressive biological behaviour, with the early onset of metastasis, in keeping with P53 positive immunostaining and high Ki-67 proliferation index. PMID:21970610
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Li, Xiucan; Wang, Yiguo; Zhao, Yongfei; Liu, Jianheng; Xiao, Songhua; Mao, Keya
2017-11-15
MINI: A 3D printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma. The personalized porous implant printed in Ti6AL4V provided excellent physicochemical properties and biological performance, including biocompatibility, osteogenic activity, and bone ingrowth effect. A unique case report. A three-dimensional (3D) printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma in a middle-age female patient. Papillary thyroid carcinoma is a malignant neoplasm with a relatively favorable prognosis. A metastatic lesion in multilevel cervical spine (C2-C4) destroys neurological functions and causes local instability. Radical excision of the metastasis and reconstruction of the cervical vertebrae sequence conforms with therapeutic principles, whereas the special-shaped multilevel upper-cervical spine requires personalized implants. 3D printing is an additive manufacturing technology that produces personalized products by accurately layering material under digital model control via a computer. Reporting of this recent technology for reconstructing multilevel cervical spine (C2-C4) is rare in the literature. Anterior-posterior surgery was performed in one stage. Radical resection of the metastatic lesion (C2-C4) and thyroid gland, along with insertion of a personalized implant manufactured by 3D printing technology, were performed to rebuild the cervical spine sequences. The porous implant was printed in Ti6AL4V with perfect physicochemical properties and biological performance, such as biocompatibility and osteogenic activity. Finally, lateral mass screw fixation was performed via a posterior approach. Patient neurological function gradually improved after the surgery. The patient received 11/17 on the Japanese Orthopedic Association scale and ambulated with a personalized skull-neck-thorax orthosis on
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Fridman, Mikhail; Krasko, Olga; Lam, Alfred King-Yin
2018-06-01
There is lack of data to predict lymph node metastases in pediatric thyroid cancer. The aims are to study (1) the factors affecting the lymph node metastases in children and adolescence with papillary thyroid carcinoma in region exposed to radiation and (2) to evaluate the predictive significance of these factors for lateral compartment lymphadenectomy. Five hundred and nine patients with papillary thyroid carcinoma underwent total thyroidectomy and lymph nodes resection (central and lateral compartments of the neck) surgery during the period of 1991-2010 in Belarus were recruited. The factors related to lymph node metastases were studied in these patients. In the patients with papillary thyroid carcinoma, increase number of cancer-positive lymph nodes in the central neck compartment were associated with a risk to develop lateral nodal disease as well as bilateral nodal disease. Futhermore, positive lateral compartment nodal metastases are associated with age and gender of the patients, tumour size, minimal extra-thyroidal extension, solid architectonic, extensive desmoplasia in carcinoma, presence of psammoma bodies, extensive involvement of the thyroid and metastatic ratio index revealed after examination of the central cervical chain lymph nodes. The presence of nodal disease, degree of lymph node involvement and the distribution of lymph node metastases significantly increase the recurrence rates of patients with papillary thyroid carcinoma. To conclude, the lymph nodes metastases in young patients with papillary thyroid carcinoma in post-Chernobyl exposed region are common and the pattern could be predicted by many clinical and pathological factors. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
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[Biological characteristics and management of familial papillary thyroid carcinoma].
Zhao, Jing; Yu, Yang; Xia, Ting-ting; Liu, You-zhong; Wei, Song-feng; Zheng, Xiang-qian; Gao, Ming
2011-11-01
To analyze the clinical biological characteristics and investigate the managements of familial papillary thyroid carcinoma (FPTC). Clinical data of 36 patients with PTC from 15 families were retrospectively analyzed compared with 95 control cases taken randomly from the patients with sporadic PTC diagnosed and treated in Tianjin Cancer Hospital between January 2010 and August 2011. Of the 36 patients with FPTC, 15 (41.7%) were ≥45 years old, 12 (33.3%) had bilateral carcinoma, 20 (55.6%) were multifocality, 27 (75.0%) had neck lymph node metastases, 17 (47.2%) coexisted thyroid benign tumors. Of the 95 patients with SPTC, 60 (63.2%) were ≥45 years old, 12(12.6%)had bilateral carcinomas, 21 (22.1%) were multifocality, 51 (53.7%) had neck lymph node metastases, and 26(27.4%)coexisted thyroid benign tumors. Of the 36 patients with FPTC, 22 (61.1%) underwent total thyroidectomy and 14 (38.9%) with unilateral thyroidectomy plus isthmusectomy, 3 (8.3%) received unilateral or bilateral lateral neck dissection and central compartment neck dissection (CND), 7 (19.4%) received unilateral or bilateral posterolateral neck dissection and CND, 6 (16.6%) received posterolateral neck dissection and bilateral CND, and 20 (55.6%) received unilateral or bilateral CND. Age at disease presentation of FPTC was younger than that of SPTC. FPTC has higher rates of multifocality and bilateral carcinoma coexisting with thyroid benign tumor than those of SPTC. It necessary to take family history in detail and to evaluate diseases before operation.
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Comprehensive mutation profiling of mucinous gastric carcinoma.
Rokutan, Hirofumi; Hosoda, Fumie; Hama, Natsuko; Nakamura, Hiromi; Totoki, Yasushi; Furukawa, Eisaku; Arakawa, Erika; Ohashi, Shoko; Urushidate, Tomoko; Satoh, Hironori; Shimizu, Hiroko; Igarashi, Keiko; Yachida, Shinichi; Katai, Hitoshi; Taniguchi, Hirokazu; Fukayama, Masashi; Shibata, Tatsuhiro
2016-10-01
Mucinous gastric carcinoma (MGC) is a unique subtype of gastric cancer with a poor survival outcome. Comprehensive molecular profiles and putative therapeutic targets of MGC remain undetermined. We subjected 16 tumour-normal tissue pairs to whole-exome sequencing (WES) and an expanded set of 52 tumour-normal tissue pairs to subsequent targeted sequencing. The latter focused on 114 genes identified by WES. Twenty-two histologically differentiated MGCs (D-MGCs) and 46 undifferentiated MGCs (U-MGCs) were analysed. Chromatin modifier genes, including ARID1A (21%), MLL2 (19%), MLL3 (15%), and KDM6A (7%), were frequently mutated (47%) in MGC. We also identified mutations in potential therapeutic target genes, including MTOR (9%), BRCA2 (9%), BRCA1 (7%), and ERBB3 (6%). RHOA mutation was detected only in 4% of U-MGCs and in no D-MGCs. MYH9 was recurrently (13%) mutated in MGC, with all these being of the U-MGC subtype (p = 0.023). Three U-MGCs harboured MYH9 nonsense mutations. MYH9 knockdown enhanced cell migration and induced intracytoplasmic mucin and cellular elongation. BCOR mutation was associated with improved survival. In U-MGCs, the MLH1 expression status and combined mutation status (TP53/BCL11B or TP53/MLL2) were prognostic factors. A comparative analysis of driver genes revealed that the mutation profile of D-MGC was similar to that of intestinal-type gastric cancer, whereas U-MGC was a distinct entity, harbouring a different mutational profile to intestinal- and diffuse-type gastric cancers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Analysis of papillary renal adenocarcinoma.
Mydlo, J H; Bard, R H
1987-12-01
A retrospective review was conducted comparing the angiographic findings, tumor volumes, staging, and survival of patients with papillary renal adenocarcinoma as compared with the more common clear and granular cell renal adenocarcinoma. The data suggest that the papillary histopathologic organization confers an improved prognosis, which concurs with previous findings. We speculate on why this tumor behaves differently from clear cell carcinoma.
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Follicular variant of papillary carcinoma presenting as a hyperfunctioning thyroid nodule.
Gabalec, Filip; Svilias, Ioannis; Plasilova, Ivana; Hovorkova, Eva; Ryska, Aler; Horacek, Jiri
2014-03-01
In this study, we describe a case of papillary carcinoma in a 15-year-old girl who presented with a hyperfunctioning (hot) thyroid nodule and discuss it in the context of current management guidelines for patients with thyroid nodules. In adults, hot nodules rarely require cytologic or histologic evaluation, and hyperthyroidism is often treated with radioiodine (131I). However, in children and adolescents, the malignancy rate for nodules (both cold and hot) is higher and surgery is often necessary. Surgery may serve as a therapy, as well as a diagnostic tool, to treat hot nodules in children and adolescents.
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Vincent, Jeremy G; Chan, May P
2015-10-01
Increased dermal mucin is a feature of lupus erythematosus (LE); however, its amount and distribution have not been well characterized. The differentiation of LE from other forms of dermatitis can be challenging when other features of LE are subtle or equivocal. One hundred and thirty-five skin specimens showing LE, graft vs. host disease, erythema multiforme/fixed drug eruption, lichen planus, polymorphous light eruption (PMLE), urticaria, eczematous dermatitis and psoriasis and normal skin with and without photodamage were collected. The amounts of mucin in the papillary, superficial reticular and deep reticular dermis were scored from 0 to 3 on hematoxylin-eosin (H&E) and alcian blue (AB) stains, and compared between groups. The mean scores in the reticular dermis were significantly higher in LE than in other categories except PMLE and eczematous dermatitis. A combined H&E + AB score of ≥5 in the superficial reticular dermis gave an overall specificity of 85.7% for LE. Mucin in the papillary dermis failed to distinguish among entities. Normal photodamaged skin showed significantly more mucin in the superficial reticular dermis compared to non-photodamaged skin. While LE is associated with increased mucin deposition, scant to moderate amount of mucin alone has limited specificity and is common in other dermatitides or photodamaged skin. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Hayes, Malcolm; Peckova, Kvetoslava; Martinek, Petr; Hora, Milan; Kalusova, Kristyna; Straka, Lubomir; Daum, Ondrej; Kokoskova, Bohuslava; Rotterova, Pavla; Pivovarčikova, Kristyna; Branzovsky, Jindrich; Dubova, Magdalena; Vesela, Pavla; Michal, Michal; Hes, Ondrej
2015-03-01
Xp11.2-translocation renal carcinoma (TRCC) is suspected when a renal carcinoma occurs in young patients, patients with a prior history of exposure to chemotherapy and when the neoplasm has morphological features suggestive of that entity. We retrieved 20 renal tumours (from 17,500 archival cases) of which morphology arose suspicion for TRCC. In nine cases, TFE3 translocation was confirmed by fluorescence in situ hybridisation analysis. In 9 of the remaining 11 TRCC-like cases (7 male, 4 female, aged 22-84 years), material was available for further study. The morphological spectrum was diverse. Six tumours showed a mixture of cells with eosinophilic or clear cytoplasm in tubular, acinar and papillary architecture. One case was high grade with epithelioid, spindle cell and sarcomatoid areas. Another showed tubular, solid, and papillary areas and foci containing spindle cells reminiscent of mucinous tubular and spindle cell carcinoma. The third showed dyscohesive nests of large epithelioid and histiocytoid cells in a background of dense lymphoplasmacytic infiltrate. By immunohistochemistry, keratin AE1/AE3 was diffusely positive in three tumours, while CK7 strongly stained one tumour and another focally and weakly. CD10 and Pax8 were expressed by eight, AMACR and vimentin by seven, CA-IX by four and TFE3 and cathepsin K by two tumours. Of the two TFE3-positive tumours, one showed polysomy of chromosome 7 and the other of 17; they were VHL normal and diagnosed as unclassifiable RCC. Of the seven TFE3-negative tumours, three showed polysomy of 7/17 and VHL abnormality and were diagnosed as combined clear cell RCC/papillary RCC. One TFE3-negative tumour with normal 7/17 but LOH 3p (VHL abnormality) was diagnosed as clear cell RCC. One TFE3-negative tumour with polysomy 7/17 but normal VHL was diagnosed as papillary RCC, and two with normal chromosomes 7/17 and VHL gene were considered unclassifiable. As morphological features and IHC are heterogeneous, TRCC-like renal
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Woo, Sungmin; Kim, Sang Youn; Lee, Myoung Seok; Moon, Kyung Chul; Kim, See Hyung; Cho, Jeong Yeon; Kim, Seung Hyup
2015-03-01
OBJECTIVE. The purpose of this study was to compare the MDCT features of renal cell carcinoma (RCC) associated with Xp11.2 translocation and TFE3 gene fusion (Xp11 RCC) and papillary RCC. MATERIALS AND METHODS. The study included 19 and 39 patients with histologically proven Xp11 RCC and papillary RCC, respectively, who underwent multiphase renal MDCT before nephrectomy. CT findings were compared between Xp11 RCC and papillary RCC using the Student t test and chi-square test. Subgroup analyses of small (< 4 cm) renal masses for these features were performed. RESULTS. Patients with Xp11 RCC were younger (p < 0.001), and it was more prevalent in women (p = 0.007). Tumor size was greater in Xp11 RCC (p = 0.004) and more common in cystic change (p < 0.001). Calcification and unenhanced high-attenuating areas were more frequent in Xp11 RCC (p = 0.001 and 0.026, respectively). Xp11 RCCs were more prevalent in lymph node and distant metastasis (p < 0.001 and p = 0.031, respectively). Xp11 RCC and papillary RCC showed no significant difference in epicenter, margin, and venous and collecting duct invasion (p = 0.403-1.000). Although Xp11 RCC and papillary RCC had lower attenuation than the renal cortex on corticomedullary and early excretory phases (p < 0.001), only Xp11 RCCs were hyperattenuating to the cortex on the unenhanced phase (p < 0.001). Xp11 RCCs had significantly higher attenuation compared with papillary RCCs on all phases (p ≤ 0.02). Regarding small masses, cystic change, calcification, and lymph node metastasis were still more frequent in Xp11 RCCs (p ≤ 0.016). CONCLUSION. Greater size, more cystic change, calcification, high-attenuating areas on unenhanced imaging, and lymph node and distant metastasis were helpful for differentiating Xp11 RCC from papillary RCC.
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Intraductal papillary mucinous neoplasms: does a family history of pancreatic cancer matter?
Nehra, Deepika; Oyarvide, Vicente Morales; Mino-Kenudson, Mari; Thayer, Sarah P; Ferrone, Cristina R; Wargo, Jennifer A; Muzikansky, Alona; Finkelstein, Dianne; Warshaw, Andrew L; Castillo, Carlos Fernández-del
2012-01-01
The purpose of this study is to compare surgically resected intraductal papillary mucinous neoplasms (IPMNs) in patients with and without a family history of pancreatic cancer to gain insight into differences that may suggest the need for differential management. A retrospective review of patients who underwent resection of an IPMN at the Massachusetts General Hospital (1990-2011) was conducted. Three hundred and twenty-four patients of whom 45 (13.9%) had a family history of pancreatic cancer were identified. Patients with (PFH) and without (NFH) a family history of pancreatic cancer were compared. There were no differences in demographic characteristics between groups. Extra-pancreatic malignancies diagnosed prior to the IPMN were more common in those with a PFH (35.6% vs 20.1%, p = 0.03). There were no differences in IPMN characteristics between groups including no difference in the presence of invasive disease (p = 0.55). Concurrent pancreatic ductal adenocarcinomas were more common in those with a PFH (11.1% vs 2.9%, p = 0.02). The survival in the PFH group was marginally lower than the NFH group, a difference found to be attributable to the higher prevalence of extra-pancreatic malignancies. Characteristics of surgically resected IPMNs are not different between patients with and without a family history of pancreatic cancer. Most importantly, the incidence of invasive disease is not different, suggesting that these lesions may not be more aggressive when they occur in the presence of a family history of pancreatic cancer. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.
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Fazeli, Roghayeh; VandenBussche, Christopher J; Bishop, Justin A; Ali, Syed Z
2016-01-01
The follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common subtype of papillary carcinoma after the classical variant. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been introduced to standardize the practice of thyroid fine needle aspiration (FNA) reporting. We evaluated the impact of TBSRTC on the FNA interpretation of histologically proven FVPTCs. Cytology reports of 455 histologically proven FVPTCs were reviewed. The rate of each TBSRTC category was compared between pre- and post-TBSRTC eras. The distribution of FNA diagnoses for pre-TBSRTC cases included suspicious for follicular neoplasm (SFN; n = 51, 28.7%), papillary thyroid carcinoma (PTC; n = 47, 26.4%), suspicious for malignancy (SFM; n = 32, 18%), atypia of undetermined significance (AUS; n = 23, 13%), benign (n = 18, 10.1%), and nondiagnostic (ND; n = 7, 4%). Post-TBSRTC diagnoses were: AUS (n = 68, 24.6%), PTC (n = 64, 23.1%), SFM (n = 50, 18%), SFN and benign (n = 42, 15.2%) and ND (n = 11, 4%). SFN rate decreased significantly from 28.7 to 15.2% (p = 0.001) and AUS increased from 12.9 to 24.5% (p = 0.003). Following implementation of TBSRTC, the frequency of AUS diagnoses on FNA prior to surgical resection increased. Given that the rate of FVPTC diagnoses on thyroidectomy increased over the same period, this suggests that the use of AUS has resulted in greater surgical resection of FVPTC. © 2016 S. Karger AG, Basel.
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Sargent, Rachel; LiVolsi, Virginia; Murphy, Justin; Mantha, Geeta; Hunt, Jennifer L
2006-01-01
Chronic lymphocytic thyroiditis (CLT) has an epidemiological relationship to papillary thyroid carcinoma (PTC). The follicular epithelium in CLT can be markedly atypical, with cytologic changes ranging from oncocytic morphology to clearing and overlapping. At the molecular level, the association between CLT and PTC is more controversial. In order to further characterize the molecular changes in CLT, this study examined the BRAF gene in 27 patient samples with CLT and without carcinoma and 28 samples with CLT and carcinoma (12 conventional papillary carcinomas, 13 follicular variants, and 3 tall cell variants). Microdissection, PCR, and sequencing of exon 15 of the BRAF gene were performed. BRAF mutations were uncommon in the cases studied with only two microscopic and two clinically sized PTCs had BRAF mutations (14%). There was no evidence of BRAF mutation in any of the areas with atypical follicular epithelium in CLT. These data suggest that BRAF is a less frequent mechanism of tumorigenesis in a background of CLT and that BRAF mutation is not present in the atypical follicular epithelium of CLT.
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Mohammed, Rabab A A; Makboul, Rania; Elsers, Dalia A H; Elsaba, Tarek M A M; Thalab, Abeer M A B; Shaaban, Omar M
2017-01-01
Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant tumors (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur.
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2017-06-07
Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Invasive Cribriform Breast Carcinoma; Invasive Ductal Carcinoma, Not Otherwise Specified; Lobular Breast Carcinoma In Situ; Mucinous Breast Carcinoma; Papillary Breast Carcinoma; Progesterone Receptor Positive; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Tubular Breast Carcinoma
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Kubota, Keiichi; Nakanuma, Yasuni; Kondo, Fukuo; Hachiya, Hiroyuki; Miyazaki, Masaru; Nagino, Masato; Yamamoto, Masakazu; Isayama, Hiroyuki; Tabata, Masami; Kinoshita, Hisafumi; Kamisawa, Terumi; Inui, Kazuo
2014-03-01
The aim of this study was to determine the clinicopathological features and surgical outcomes of mucinous cystic neoplasm of the liver (MCN) and mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB). We performed a multi-institutional, retrospective study of patients with MCN or M-IPNB pathologically defined by the presence or absence of an ovarian-like stroma. The M-IPNB and MCN were diagnosed in 119 and nine patients, respectively. MCN was observed in female patients, while M-IPNB produced symptoms of cholangitis. M-IPNBs were classed as low or intermediate grade in 53 cases, high grade in 23 and invasive carcinoma in 43. Fifty-one of the M-IPNBs were the pancreatobiliary type (PT), 33 were the intestinal type (IT), 23 were the oncocytic type (OT), and 12 were the gastric type (GT). The 1-, 5- and 10-year survival rates for the 105 patients with M-IPNB were 96%, 84% and 81%, respectively, while the 5-year survival rate for patients with MCN was 100%. OT and GT M-IPNB had better 10-year survival rates than PT and IT M-IPNB. Although MCN has different features from M-IPNB, both diseases have a good prognosis after resection. The cellular type of M-IPNB appears to predict outcome. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
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2017-10-25
Acinar Cell Carcinoma; Ampulla of Vater Adenocarcinoma; Cholangiocarcinoma; Duodenal Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary Mucinous Neoplasm, Pancreatobiliary-Type; Periampullary Adenocarcinoma
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Sauvanet, Alain; Gaujoux, Sébastien; Blanc, Benjamin; Couvelard, Anne; Dokmak, Safi; Vullierme, Marie-Pierre; Ruszniewski, Philippe; Belghiti, Jacques; Lévy, Philippe
2014-08-01
To assess the feasibility and outcomes of parenchyma-sparing pancreatectomy (PSP), including enucleation (EN), resection of uncinate process (RUP), and central pancreatectomy (CP), as an alternative to standard pancreatectomy for presumed noninvasive intraductal papillary and mucinous neoplasms (IPMNs). Pancreaticoduodenectomy and distal pancreatectomy are associated with significant perioperative morbidity, a substantial risk of pancreatic insufficiency, and may overtreat noninvasive IPMNs. From 1999 to 2011, PSP was attempted in 91 patients with presumed noninvasive IPMNs, after complete preoperative work-up including computed tomography, magnetic resonance imaging, and endoscopic ultrasonography. Intraoperative frozen section examination was routinely performed to assess surgical margins and rule out invasive malignancy. Follow-up included clinical, biochemical, and radiological assessments. Overall PSP was achieved with a feasibility rate of 89% (n = 81), including 44 ENs, 5 RUPs, and 32 CPs. Postoperative mortality rate was 1.3% (n = 1), and overall morbidity was noteworthy (61%; n = 47). Definitive pathological examination confirmed IPMN diagnosis in 95% of patients (n = 77), all except 2 (3%), without invasive component. After a median follow-up of 50 months, both pancreatic endocrine/exocrine functions were preserved in 92% of patients. Ten-year progression-free survival was 76%, and reoperation for recurrence was required in 4% of patients (n = 3). In selected patients, PSP for presumed noninvasive IPMN in experienced hands is highly feasible and avoids inappropriate standard resections for IPMN-mimicking lesions. Early morbidity is greater than that after standard resections but counterbalanced by preservation of pancreatic endocrine/exocrine functions and a low rate of reoperation for tumor recurrence.
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Mucinous cystadenocarcinoma of the breast with a basal-like immunophenotype.
Deng, Yunte; Xue, Debin; Wang, Xiaoyan; Xu, Sanpeng; Ao, Qilin; Hu, Zhiyong; Wang, Guoping
2012-06-01
Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41-year-old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well-circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal-like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal-like immunophenotype. © 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
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Genome-wide significant risk associations for mucinous ovarian carcinoma
Kelemen, Linda E.; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; M. Lee, Janet; Seo, Ji-Heui; Phelan, Catherine M.; Beesley, Jonathan; Chen, Xiaoqin; Spindler, Tassja J.; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Chen, Y. Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T.; Edwards, Robert P.; Eilber, Ursula; Ekici, Arif B.; Engelholm, Svend Aage; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Moes-Sosnowska, Joanna; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston, Lara; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wlodzimierz, Sawicki; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Freedman, Matthew L.; Chenevix-Trench, Georgia; Pharoah, Paul D.; Gayther, Simon A.; Berchuck, Andrew
2015-01-01
Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10−8), rs711830 at 2q31.1 (P = 7.5 × 10−12) and rs688187 at 19q13.2 (P = 6.8 × 10−13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10−4, FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. PMID:26075790
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Rübenthaler, J; Reimann, R; Hristova, P; Staehler, M; Reiser, M; Clevert, D A
2015-10-16
The aim of this study was to analyse clear cell and papillary renal cell carcinoma (RCC) examined with contrast-enhanced ultrasound (CEUS) and a second generation blood pool agent (SonoVue®, Bracco, Milan, Italy) before clinical intervention. A total of 41 patients with histologically proven subtypes of RCC were examined. 29 patients had a clear cell RCC and 12 patients showed a papillary RCC. Average size in the clear cell RCC group was 6.07 cm and 1.88 cm in the papillary RCC group. An experienced radiologist examined all patients with CEUS. The following parameters were analysed: maximum signal intensity (PEAK), time elapsed until PEAK is reached (MTT), local blood flow (RBF), area under the time intensity curve (AUC) and the signal intensity (SI) during the course of time. For both groups all comparisons were made based on healthy renal parenchyma. In the clear cell RCC significant differences (significance level p < 0.05) between cancerous tissue and the healthy renal parenchyma were noticed in all four parameters. The clear cell RCC showed a significant reduced blood volume. It reached the PEAK reading relatively rapidly and its signal intensity was always lower than that of the healthy renal parenchyma. In the arterial phase retarded absorption of the contrast agent was observed, followed by fast washing out of the contrast agent bubbles.In the papillary RCC group, significant findings as to PEAK and RBF as well as a slightly significant difference as to AUC were recorded. The papillary RCC had a lower blood supply and reached its PEAK reading later. Its signal intensity was also reduced. The signal intensity of papillary NCC was significantly lower compared with clear cell RCC; absorption and washing out of the contrast agent was delayed. CEUS seems to be an useful additional method to clinically differentiate between clear cell and papillary RCC. In daily clinical use, patients with contraindication for other imaging methods, especially the
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[Role of intraosteal administration of antibiotics in treatment of local oral mucinous carcinoma].
Ivanov, V M; Ivanova, O V; Sheĭkin, M V
2013-01-01
The problems of prophylaxis of infectious complications in the treatment of oral local mucinous carcinoma are considered relevant to 204 respective cases. More favourable results of the combined and complex treatment of the patients were shown when a multidisciplinary approach was used with obligatory participation of stomatologists. Special stomatologic prophylactic and therapeutic procedures with using reamberin orally and intravenously in the chemo- and radiotherapy and adequate antibiotic therapy during the surgical operation resulted in less frequent infectious complications, that was in favour of the patients life quality. Intraosteal administration of antibiotics was shown preferable.
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Stenner, Markus; Müller, Klaus-Michael; Koopmann, Mario; Rudack, Claudia
2014-01-01
Abstract We report on a rare case of a laryngeal carcinoma arising in a multifocal pharyngolaryngeal oncocytic papillary cystadenoma (OPC). The disease of a 63-year-old man is well documented by computed and positron emission tomography, histology, and electron microscopy. We could show that an OPC can even develop in the pharynx. The coexistence of both tumors makes this a challenging diagnosis for pathologists. Treated by surgery and radiotherapy, both lesions dissolved. Based on the literature available, we discuss the theory that the laryngeal carcinoma might be the result of a true metaplasia facilitated by chronic irritation and recommend a regular follow-up for OPC too. As in benign oncocytic lesions, we could show that the detection of numerous mitochondria is a diagnostic indicator for malignant variants as well. PMID:25211046
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Wu, Gang; Guo, Jing-Jing; Ma, Zhen-Yu; Wang, Jie; Zhou, Zhong-Wen; Wang, Yi
2015-01-01
The correlation between calcification and papillary thyroid carcinoma has received increasing attention. We investigated the ability of bone sialoprotein (BSP) and osteopontin (OPN) protein levels to diagnose papillary thyroid carcinoma (PTC), and explored the correlation between BSP and OPN protein levels and calcification in PTC. Archival PTC specimens from patients with PTC with calcification and lateral cervical lymph node metastasis (LNM) were included in this retrospective immunohistochemical study. The protein levels of BSP and OPN were analysed immunohistochemically using routinely prepared tissue sections. PTC specimens from 66 patients with PTC were reviewed retrospectively (25 patients with histological calcification seen in paraffin sections, 41 patients without calcification; 35 patients with lateral cervical LNM, 31 patients without LNM). The percentage of samples that had cells that demonstrated positive protein staining differed significantly between PTC specimens, benign thyroid nodules, and adjacent normal follicular epithelium (BSP: 87.88%, 55.00%, and 42.50%, respectively; OPN: 83.33%, 70.00% and 50.00%, respectively). There was a significant difference in the immunohistochemical score (IHS) for BSP and OPN protein staining between PTC specimens with and without calcification (P < 0.05). The level of BSP protein staining was found to be significantly correlated with the level of OPN protein staining in PTC specimens. We conclude that the strong correlation between BSP and OPN and PTC suggests a role for BSP and OPN in calcification and tumor progression of PTC. BSP and OPN might be useful tumour markers for the diagnosis of PTC with limited value, because both of them had low specificity.
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Berger, Andreas W; Schwerdel, Daniel; Costa, Ivan G; Hackert, Thilo; Strobel, Oliver; Lam, Sandra; Barth, Thomas F; Schröppel, Bernd; Meining, Alexander; Büchler, Markus W; Zenke, Martin; Hermann, Patrick C; Seufferlein, Thomas; Kleger, Alexander
2016-08-01
Intraductal papillary mucinous neoplasms (IPMNs) are the most frequent cystic pancreatic tumors. Little is known about their molecular alterations, but mutations in GNAS have been reported to promote IPMN formation. A tumor-derived fraction of circulating cell-free DNA (cfDNA), isolated from blood samples, contains many of the same mutations as the primary tumor, and could be a tool for noninvasive disease monitoring. We found that the total amount of cfDNA can discriminate between individuals without pancreatic lesions (controls) and patients with Fukuoka-negative branch-duct IPMN or pancreatic cancer. Furthermore, we detected GNAS mutations in cfDNA from patients with IPMN, but not in patients with serous cystadenoma or controls. Analyses of cfDNA might therefore be used in the diagnosis of patients with IPMN or in monitoring disease progression. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.
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Zaino, Richard J.; Brady, Mark F.; Lele, Subodh M.; Michael, Helen; Greer, Benjamin; Bookman, Michael A.
2010-01-01
Background Primary mucinous adenocarcinomas of the ovary are uncommon and their biologic behavior uncertain. Retrospective studies suggest that many mucinous carcinomas diagnosed as primary to the ovary were actually metastatic from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. Methods A phase III trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were re-classified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared with each other and with that of patients with serous carcinomas. Results Forty-four cases were classified as mucinous adenocarcinoma at review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high with unanimity of opinion in 30 of the 44 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, p<0.001). Conclusion Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. PMID:20862744
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Mapping fundamental life elements in papillary thyroid carcinoma tissue
NASA Astrophysics Data System (ADS)
Merolle, L.; Ragazzi, M.; Gianoncelli, A.; Altissimo, M.; Ciarrocchi, A.; Bedolla, D. E.; Marraccini, C.; Baricchi, R.; Pertinhez, T. A.
2018-05-01
Well-differentiated papillary thyroid carcinomas (PTCs) are the most common type of thyroid cancer. Thyroid function depends on the presence of certain trace elements necessary for both the synthesis and the metabolism of thyroid hormones. We conducted an observational translational study on formalin fixed paraffin embedded thyroid tissue slices collected from five patients who underwent surgical resection of thyroid gland after thyroid cancer diagnosis. A synchrotron-based XRF set up was used to map the distribution of oxygen, sodium, aluminum, selenium and magnesium in PTC sections. These experiments were performed at the TwinMic beamline (Elettra—Sincrotrone Trieste, Trieste, Italy). Our results show that Mg levels in PTC tissues are significantly higher than in the control ones. The results seem to provide highly valuable information suggesting that Mg may play a role in the development and metabolic process of PTC.
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Fayek, Ihab Samy
2015-01-01
Prognostic value of prophylactic level VII nodal dissection in papillary thyroid carcinoma has been highlighted. A total of 27 patients with papillary thyroid carcinoma with N0 neck underwent total thyroidectomy with level VI and VII nodal dissection through same collar neck incision. Multicentricity, bilaterality, extrathyroidal extension, level VI and VII lymph nodes were studied as separate and independent prognostic factors for DFS at 24 months. 21 females and 6 males with a mean age of 34.6 years old, tumor size was 5-24 mm. (mean 12.4 mm.), multicentricity in 11 patients 2-4 foci (mean 2.7), bilaterality in 8 patients and extrathyroidal extension in 8 patients. Dissected level VI LNs 2-8 (mean 5 LNs) and level VII LNs 1-4 (mean 1.9). Metastatic level VI LNs 0-3 (mean 1) and level VII LNs 0-2 (mean 0.5). Follow-up from 6-51 months (mean 25.6) with 7 patients showed recurrence (3 local and 4 distant). Cumulative DFS at 24 months was 87.8% and was significantly affected in relation to bilaterality (p-value<0.001), extrathyroidal extension (p-value<0.001), level VI positive ((p-value<0.001) and level VII positive ((p-value<0.001) LNs. No recurrences were detected during the follow-up period in the absence of level VI and level VII nodal involvement. Level VII prophylactic nodal dissection is an important and integral prognostic factor in papillary thyroid carcinoma. A larger multicenter study is crucial to reach a satisfactory conclusion about the necessity and safety of this approach.
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de Kretser, T A; Thorne, H J; Jacobs, D J; Jose, D G
1985-09-01
A monoclonal antibody, designated OM-1, was raised against ovarian serous papillary cystadenocarcinoma (stage IV) cells. This antibody was found to react strongly with primary and metastatic ovarian serous cystadenocarcinomas and endometrioid carcinomas but the antigen detected was either absent or at very low levels in ovarian mucinous adenocarcinomas, clear cell carcinomas, benign serous and mucinous cystadenomas and Brenner tumours. The OM-1 antibody gave no detectable reaction with 93 other human tumours, including examples of breast and colon adenocarcinomas. In normal tissues the OM-1 antibody reacted with normal sebaceous gland cells, lung type II pneumocytes and placental syncytial trophoblasts. In the normal ovary OM-1 reactivity was confined to extremely weak staining of the surface epithelium. No reaction with any other ovarian cell type could be detected. No evidence of reaction with other normal cell populations present in 24 adult and seven foetal tissues was found. The antigen detected is compared with other ovarian tumour-associated antigens. The OM-1 antibody is likely to prove of value in the detection and diagnosis of ovarian carcinoma.
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Juxtaglomerular cell tumor of the kidney: report of two cases with a papillary pattern.
Têtu, B; Vaillancourt, L; Camilleri, J P; Bruneval, P; Bernier, L; Tourigny, R
1993-11-01
We report the clinicopathologic, immunohistochemical, and electron microscopic study of two cases of juxtaglomerular cell tumor of the kidney with a hitherto unreported dominant papillary pattern. Both tumors were associated with high blood pressure that did not respond to medical therapy, but that returned to normal after removal of the kidney. They were well delineated, tan, and had no necrosis. The cores of the papillary structures consisted of polygonal cells found to express renin by immunohistochemistry and to contain renin protogranules by electron microscopy. The papillary fronds were covered by one layer of cuboidal epithelial cells that did not stain for renin and had ultrastructural features reminiscent of the collecting duct epithelium. These tumors must be differentiated from malignant papillary tumors of the kidney, such as papillary clear cell carcinoma, transitional cell carcinoma, and collecting duct carcinoma.
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Papillary Architecture and Functional Characterization of Mucosubstances in the Sheep Tongue.
Erdoğan, Serkan; Sağsöz, Hakan
2018-04-30
This research aimed to reveal the general morphology and topographic distribution of lingual papillae, epithelial characteristics, mucosal structure, and glands with their mucin content in the sheep tongue, with consideration of species-specific characteristics. The tongues of ten sheep were analyzed for this purpose. Filiform and fungiform papillae existed within the borders of the ventral surface of the lingual apex. The majority of the filiform papillae had multiple secondary projections. Fungiform papillae were also seen on the lingual torus among lenticular papillae, as well as 6 to 10 circumvallate papillae arranged on its caudal border. The species-specific details of the general anatomical structure of the tongue were determined and, in general, the papillary organization in the sheep was similar to goats, while the papillary organization also was similar to features with deer species, specifically the filiform papilla from the mechanical papillae and fungiform papilla from the gustatory papillae. Neutral and weak sulfated mucins and N-acetyl sialomucins were located in seromucous glands, salivary duct epithelium and von Ebner's glands. Carboxylated acid mucins and N-acetyl sialomucins were not present in seromucous and von Ebner's glands. In seromucous glands, MUC1, MUC5AC and MUC6 localized only in epithelial cells of ducts, whereas MUC2 localized in both glandular and ductal epithelial cells. All MUCs were present in both von Ebner's glands and salivary ducts. We showed that this mucin composition, may serve as a physical barrier in the initial section of the digestive system. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.
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Cell culture of the mucinous variant of human colorectal carcinoma.
Tibbetts, L M; Chu, M Y; Vezeridis, M P; Miller, P G; Tibbetts, L L; Poisson, M H; Camara, P D; Calabresi, P
1988-07-01
Two cell lines, RW-2982 and RW-7213, have been established for the first time from the mucinous variant of human colorectal carcinoma, which is a distinctive and important subtype that has a worse prognosis than the more common nonmucogenic large bowel carcinoma. Methods of establishment and observations made during 7 and 3 years, respectively, of continuous culture are described. These cell lines required 4-9 months of adaptation to tissue culture conditions before noticeable growth occurred. Both cell lines have the following unique properties: (a) growth in vitro as delicate branching three-dimensional tumor particles within a wide gel of insoluble, often translucent mucus (proteoglycan); (b) production of large quantities of carcinoembryonic antigen; (c) ability to survive or adapt to growth in media free of serum, hormones, growth factors, and all protein; and (d) tumorigenicity in multiple sites in nude mice, including liver, with especially rapid growth in the peritoneal cavity as gelatinous material that is nonadherent and noninvasive and thus resembles pseudomyxoma peritonei. Unlike other reported colorectal cell lines, these mucus-coated particulate cell lines will not readily grow as monolayers and grow much more slowly with a doubling time of 2 weeks or more. A serially transplantable tumor from the RW-7213 surgical specimen has also been maintained in nude mice since August 8, 1984. This tumor retains properties of the original specimen. Observations made on the tumor biology of mucogenic colorectal carcinoma using these cell lines are discussed.
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Lehman, M B; Hart, W R
2001-11-01
The clinicopathologic features of nine cases of papillary proliferation of the endometrium devoid of malignant nuclear features were studied. The patients ranged in age from 33 to 71 years (median 57 years). All were postmenopausal, except the youngest. The most common symptom was postmenopausal bleeding. Two patients were receiving hormonal replacement therapy and two were taking megestrol acetate. Two lesions were incidental findings in a hysterectomy specimen. Seven were diagnosed in endometrial biopsy or curettage specimens. In six cases (67%) the lesion involved an endometrial polyp. In all cases the papillae had fibrovascular stromal cores and variable degrees of branching. Two architectural patterns were found. A simple papillary pattern with involvement of only a few glands and little epithelial proliferation occurred in five cases, including three that were entirely intracystic. A complex papillary pattern with more extensive involvement of endometrial glands, a greater degree of branching of the papillae, and cellular tufting occurred in four cases. One or more metaplastic epithelial changes occurred in all cases, including endocervical-type mucinous metaplasia in nine cases (90%), eosinophilic cell change in eight (89%), ciliated cell change in seven (70%), focal squamous metaplasia in two cases (22%), and hobnail cell change in two (22%). Mitotic figures were found in three cases. In four lesions (44%), all with a complex papillary pattern, the proliferating cells had mild nuclear atypia. Three of these patients underwent hysterectomy within 5 months. Simple nonpapillary hyperplasia and two endometrial polyps were found in one patient, complex nonpapillary hyperplasia in one, and atrophic endometrium in the other. Two patients had additional endometrial samplings within 4 months that contained small residual simple papillary lesions. One of these had another biopsy at 16 months that showed only atrophy. One patient had no subsequent diagnostic or
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Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin
2017-04-01
Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT. Copyright © 2017 Elsevier GmbH. All rights reserved.
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Yu, Marc Gregory; Atun, Jenny Maureen
2016-01-01
Tuberculous (TB) lymphadenitis can mimic cervical node metastasis from papillary thyroid carcinoma (PTC) since the distribution and appearance of affected lymph nodes are similar. We present the case of an asymptomatic 50-year-old Filipino who sought consult for a gradually enlarging anterior neck mass and a single palpable cervical lymph node. Preoperative workup suggested a thyroid malignancy with nodal metastasis. He underwent total thyroidectomy with node dissection where histopathology confirmed follicular variant- (FV-) PTC. Lymph node examination, however, revealed TB lymphadenitis, and the patient was given standard antimycobacterial therapy. This is the first documented case in Southeast Asia, a high TB burden region. This is also the first report involving FV-PTC, which has features between those of conventional PTC and follicular thyroid carcinoma. The case suggests that, in endemic areas, TB should be a differential in the etiology of cervical lymphadenopathy in PTC patients. In developed countries, this differential diagnosis is also valuable because of the increasing incidence of HIV and TB coinfection. Proper preoperative evaluation is important and needs to be highlighted in the formulation of local guidelines.
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Atun, Jenny Maureen
2016-01-01
Tuberculous (TB) lymphadenitis can mimic cervical node metastasis from papillary thyroid carcinoma (PTC) since the distribution and appearance of affected lymph nodes are similar. We present the case of an asymptomatic 50-year-old Filipino who sought consult for a gradually enlarging anterior neck mass and a single palpable cervical lymph node. Preoperative workup suggested a thyroid malignancy with nodal metastasis. He underwent total thyroidectomy with node dissection where histopathology confirmed follicular variant- (FV-) PTC. Lymph node examination, however, revealed TB lymphadenitis, and the patient was given standard antimycobacterial therapy. This is the first documented case in Southeast Asia, a high TB burden region. This is also the first report involving FV-PTC, which has features between those of conventional PTC and follicular thyroid carcinoma. The case suggests that, in endemic areas, TB should be a differential in the etiology of cervical lymphadenopathy in PTC patients. In developed countries, this differential diagnosis is also valuable because of the increasing incidence of HIV and TB coinfection. Proper preoperative evaluation is important and needs to be highlighted in the formulation of local guidelines. PMID:27746818
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Choi, Byung Se; Kim, Ah Young; Kim, Kyoung Won; Park, Sung Won; Kim, Pyo Nyun; Ha, Hyun Kwon; Lee, Moon-Gyu; Kim, Song Cheol
2003-01-01
Objective To compare the usefulness of magnetic resonance cholangiopancreatography (MRCP) and MR angiography (MRA) in differentiating malignant from benign intraductal papillary mucinous tumors of the pancreas (IPMTs), and to determine the findings which suggest malignancy. Materials and Methods During a 6-year period, 46 patients with IPMT underwent MRCP. Morphologically, tumor type was classified as main duct, branch duct, or combined. The diameter of the main pancreatic duct (MPD), the extent of the dilated MPD, and the location and size of the cystic lesion, septum, and communicating channel were assessed. For all types of IPMTs, enhanced mural nodules and portal vein narrowing were evaluated at MRA. Results Combined-type IPMTs were more frequently malignant (78%) than benign (42%) (p < 0.05). Compared with benign lesions, malignant lesions were larger, and the caliber of the communicating channel was also larger (p < 0.05). Their dilated MPD was more extensive and of greater diameter (p < 0.05), and the presence of mural nodules was more frequent (p < 0.001). Conclusion Combined MRCP and MRA might be useful for the differential diagnosis of malignant and benign IPMTs of the pancreas. PMID:14530644
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Liszewski, Walter; Sittig, Mark; Kandil, Emad; Van Sickels, Nicholas; Safah, Hana
2015-01-01
Primary Hodgkin's lymphoma of the colon is a rare phenomenon previously only reported in patients with chronic diverticulitis or inflammatory bowel disease. Herein we report a case of primary Hodgkin's lymphoma of the sigmoid colon in an HIV-positive patient without a history of inflammatory bowel disease or chronic diverticulitis that was later complicated by the discovery of concurrent papillary thyroid carcinoma.
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Mahomed, Farzana
2011-09-01
This review focuses on the immunohistochemical expression of members of the MUC-type mucin family in salivary gland tumors and head and neck squamous cell carcinomas (HNSCC). Information is available on changes in the expression levels and distribution profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6 and MUC7 in tumors of the salivary glands; and of MUC1, MUC2 and MUC4 in HNSCC. In salivary gland tumors the expression patterns of MUC2, MUC3, MUC5AC and MUC6 appear to be very closely correlated with the histopathological tumor type indicating their potential use to improve diagnostic accuracy in salivary gland neoplasia. Some MUC-type mucins have emerged as valuable prognostic indicators in pleomorphic adenoma, mucoepidermoid carcinoma and HNSCC. Nine antibodies directed against different MUC1 antigens have thus far been examined in HNSCC of which monoclonal antibodies DF3, HMFG-1 and Ma695 have shown significant correlations with disease outcome. The importance of taking the specific anti-MUC antibody into consideration when comparing the results of different studies on MUC expression in salivary gland tumors and HNSCC is also highlighted in this review. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Kiatpanabhikul, Phatharaporn; Shuangshoti, Shanop; Chantra, Kraisri; Navicharern, Patpong; Kingpetch, Kanaungnit; Houngngam, Natnicha; Snabboon, Thiti
2017-07-01
Co-existence of thyrotropin/growth hormone-secreting pituitary adenoma with differentiated thyroid carcinoma is exceedingly rare, with less than 15 cases having been reported. Its clinical presentation and treatment strategy are challenging. We report a case of pituitary macroadenoma, with clinical syndromes of acromegaly and hyperthyroidism, and a thyroid nodule, with cytologically confirmed to be a papillary thyroid carcinoma. Clinical implications, focusing on the strategy for proper management, and possible pathogenesis were discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Coexistence of papillary thyroid cancer and Hashimoto thyroiditis in children: report of 3 cases.
Koibuchi, Harumi; Omoto, Kiyoka; Fukushima, Noriyoshi; Toyotsuji, Tomonori; Taniguchi, Nobuyuki; Kawano, Mikihiko
2014-07-01
This report documents 3 pediatric papillary thyroid carcinoma cases with associated Hashimoto thyroiditis. In all 3 cases, hypoechoic nodules accompanied by multiple echogenic spots were noted on sonography of the thyroid. Hashimoto thyroiditis was suspected on the basis of positive thyroid autoantibody test results and pathologic examinations of thyroidectomy specimens, which revealed chronic thyroiditis with lymphocytic infiltration as the background of papillary thyroid carcinoma development. The potential for papillary carcinoma development warrants close follow-up, and meticulous sonographic examinations must be performed in children with Hashimoto thyroiditis. © 2014 by the American Institute of Ultrasound in Medicine.
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Gál, János; Csikó, György; Pásztor, István; Bölcskey-Molnár, Antal; Albert, Mihály
2010-03-01
Postmortem examination of the carcass of an approximately 10-year-old male Red-eared slider ( Trachemys scripta elegans ) was performed. The thyroid gland was enlarged, showed follicular structure, and shifted the base of the heart caudally. Histology revealed differently shaped and sized follicles in the thyroid gland. Based on the macroscopic appearance and histopathological changes of the thyroid gland, the pathological process was established as a papillary-cystic carcinoma. Neoplasia of the endocrine organs, especially of the thyroid gland, is rare in reptiles. The current case seems to be the first report of thyroid carcinoma in a Red-eared slider.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Anne, E-mail: akim2@health-quest.org; Schreiber, David; Rineer, Justin
2011-11-15
Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: Wemore » identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) Conclusion: In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.« less
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Ribeiro-Silva, Alfredo
2007-01-01
An 84-year-old woman underwent hysterectomy due to a friable endometrial mass infiltrating almost half way through the myometrial wall. The tumor consisted of papillary structures with thin fibrovascular cores covered by several layers of pleomorphic cells. The deeply located neoplastic cells were ovoid with a pale eosinophilic cytoplasm resembling urothelial cells. A diagnosis of papillary squamous cell carcinoma of the endometrium with transitional cell differentiation was made. Although she recovered well after surgery, she died one year later because of disseminated disease. In an attempt to obtain new insights into the physiopathology of this very rare tumor, an immunohistochemical panel with 32 markers was performed. The neoplastic cells were positive for cytokeratin 5, vimentin, p63, p21, VEGF, Ki67, BAG1, and bcl-2. The expression of BAG-1 and bcl-2 may suggest that anti-apoptotic stimuli are preponderant in this neoplasm. PMID:17645802
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Watanabe, Yusuke; Niina, Yusuke; Nishihara, Kazuyoshi; Okayama, Takafumi; Tamiya, Sadafumi; Nakano, Toru
2018-01-15
Accurate preoperative prediction for malignant IPMN is still challenging. The aim of this study was to investigate the validity of neutrophil-to-lymphocyte ratio (NLR) and mural nodule height (MNH) for predicting malignant intraductal papillary mucinous neoplasm (IPMN). The medical records of 60 patients who underwent pancreatectomy for IPMN were retrospectively reviewed. NLR tended to be higher in malignant IPMN (median: 2.23) than in benign IPMN (median: 2.04; p = .14). MNH was significantly greater in malignant IPMN (median: 16 mm) than in benign IPMN (median: 8 mm; p < .01). The optimal cutoff values for the NLR and MNH were 3.60 and 11 mm, respectively. The sensitivity and specificity of NLR ≥3.60 for predicting malignant IPMN were 40% and 93%, and those of MNH ≥11 mm were 73% and 77%, respectively. Univariate analysis revealed that NLR ≥3.60 (p < .01) and MNH ≥11 mm (p < .01) were significant predictive factors. On multivariate analysis, enhanced solid component was identified as an independent factor, but NLR ≥3.60 and MNH ≥11 mm were not. NLR and MNH are suboptimal tests in predicting malignant IPMN; however, they can be useful to assist in clinical decision-making.
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MIB-1 labeling index, Ki-67, is an indicator of invasive intraductal papillary mucinous neoplasm.
Shimura, Tatsuo; Kofunato, Yasuhide; Okada, Ryo; Yashima, Rei; Okada, Koji; Araki, Kenichiro; Hosouchi, Yasuo; Kuwano, Hiroyuki; Takenoshita, Seiichi
2016-08-01
Despite strict criteria for the observation of intraductal papillary mucinous neoplasm (IPMN), it remains difficult to distinguish invasive IPMN from non-invasive IPMN. The aim of the present study was to identify an indicator of invasive IPMN. The present study retrospectively evaluated 53 patients (28 with non-invasive and 25 with invasive IPMN) who underwent resection of IPMN, and examined the usefulness of the MIB-1 labeling index as an indicator of invasive IPMN. The MIB-1 labeling indexes in patients with invasive IPMN were significantly higher compared with those with non-invasive IPMN (P<0.001). A receiver operating characteristic curve revealed that the area under the curve was 0.822. These results suggested that a cut-off level for the MIB-1 labeling index should be set to 15.5% to distinguish invasive from non-invasive IPMN. A multivariate analysis using a logistic regression model revealed the MIB-1 labeling index (hazard ratio, 18.692; 95% confidential interval, 4.171-83.760; P<0.001) and the existence of mural nodules (hazard ratio, 6.187, 95% confidential interval, 1.039-36.861; P=0.045) were predictive factors for invasive IPMN. However, no statistically significant differences were observed between patients with a lower MIB-1 labeling index and patients with a higher MIB-1 labeling index (P=0.798). The MIB-1 labeling index must be considered as a candidate for the classification of IPMN.
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Park, Jiyoung; Lee, Hae-Beom; Jeong, Seong Mok
2017-01-01
To report the surgical treatment of a pulmonary emphysematous cyst concurrent with primary pulmonary bronchoalveolar papillary carcinoma in a dog. Clinical case report. 12-year-old 6.4 kg spayed female Shih Tzu dog. The dog presented for surgical treatment of pulmonary emphysema. Radiography revealed that more than half of the left caudal lung lobe was enlarged and hyperlucent and computed tomography (CT) confirmed the presence of an emphysematous space. Thoracoscopic lung lobectomy was attempted but was converted to an intercostal thoracotomy due to poor visualization and pleural adhesions. A left caudal total lung lobectomy was performed using a self-cutting endoscopic stapler. The dog recovered uneventfully and a postoperative histopathologic diagnosis of pulmonary cystic bronchoalveolar papillary carcinoma was made. Re-evaluation using a CT scan with contrast study on postoperative days 27 and 177 revealed no evidence of residual, metastatic, or recurrent lesions. The dog has been doing well since surgery during the 11 month follow-up period. This case report suggests a potential relationship between pulmonary emphysematous diseases and primary lung tumors in dogs. © 2016 The American College of Veterinary Surgeons.
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Moerman, Philippe; Amant, Frederic; Vergote, Ignace
2016-10-01
This article describes the case of a 70-year-old woman with an adnexal cystadenocarcinoma located in the right broad ligament and displaying a striking resemblance to a well-differentiated endometrioid adenocarcinoma. The uniqueness of this pseudoendometrioid carcinoma lies in the fact that its mesonephric nature is revealed by the origin from a papillary cystadenoma of the broad ligament, where remnants of the mesonephric duct are seated, and the immunohistochemical profile, particularly a uniform negativity for estrogen and progesterone receptors, apical-luminal positivity for CD10, and strong nuclear positivity for GATA3. © The Author(s) 2016.
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Zhang, Lina; Zhuang, Ling; Shi, Chang; Miao, Yanwei; Zhang, Weisheng; Song, Qingwei; Kang, Jianyun; Lang, Zhijin; Xin, Xuegang; Liu, Ailian; Hu, Jiani
2017-08-07
Solid papillary carcinoma (SPC) is a rare variant of breast papillary carcinoma with unique pathological morphology and biological behavior. There is only one case report on T 1 -MRI of SPC. In this study, we report our findings on this new category of papillary carcinoma to fill the gap in MRI characterization of SPC. This retrospective study included four pathology-confirmed in situ SPC patients. Conventional MRI, diffusion weighted imaging (DWI), and magnetic resonance spectroscopy (MRS) were performed with a 1.5 T whole-body MR scanner before surgical operation. The following characteristics of each lesion were recorded: signal intensity on T 2 WI/STIR and T 1 FSPGR, morphology, maximum lesion size, and time intensity curve (TIC) on dynamic contrast enhancement MRI (DCE-MRI), apparent diffusion coefficient (ADC) value from DWI, and Cho peak from MRS. Signal intensities of all lesions were heterogenous on T 2 WI/STIR and T 1 FSPGR. Mass enhancements were observed for all lesions with either oval or irregular shapes on DCE-MRI. The maximum lesion size ranged from 0.8 cm to 3.2 cm. All lesion margins were circumscribed, and internal enhancements were homogeneous or heterogeneous from DCE-MRI. TIC appeared with a rapid increase in initial contrast phases of all lesions. All lesions on DWI (b = 1000s/mm 2 ) were slightly hyperintense with an ADC value range of 1.3 × 10 -3 mm 2 /s to 1.9 × 10 -3 mm 2 /s. Cho peak was absent at 3.2 ppm for all lesions. MRI characteristics of SPC include heterogeneous signal intensity within the lesion on T 2 WI/STIR and T 1 FSPGR, mass enhancement with circumscribed margins, either oval or irregular shapes, and a rapid initial enhancement of TIC on DCE-MRI. ADC values and the absence of Cho peak may provide valuable information to distinguish SPC from other invasive breast carcinomas.
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Schröder, S; Marthaler, B
1996-09-01
Data in the literature communicated in 63 publications were evaluated in which scintigraphically warm or hot nodules were described as identical to a follicular or papillary carcinoma diagnosed based on histology of the resection specimen, thus suggesting autonomous hyperfunction of a malignant thyroid neoplasia. In the majority of cases, this assumption could not be accepted, or only within strict limits. In these patients, it appeared more likely that the carcinoma was located adjacent to or within a benign hyperfunctioning thyroid area or that large masses of a thyroid carcinoma had only simulated the picture of a hyperfunctioning nodule by suppression of endogenous TSH and thus of the residual parenchyma's function. In other cases, the diagnosis of a hyperfunctioning thyroid carcinoma had to be doubted or rejected owing to the lack of plausibility of the documented morphological findings. At the end of the literature survey, only 10 case descriptions unequivocally verified that, though very rarely, a papillary or follicular thyroid carcinoma may manifest itself as a solitary warm or hot thyroid nodule. Such a scintigraphical finding thus cannot be regarded as proof of benignancy of a given thyroid tumour.
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Ilies, Maria; Sappa, Praveen Kumar; Iuga, Cristina Adela; Loghin, Felicia; Gesell Salazar, Manuela; Weiss, Frank Ulrich; Beyer, Georg; Lerch, Markus M; Völker, Uwe; Mayerle, Julia; Hammer, Elke
2018-02-01
Efforts for the early diagnosis of the pancreatic ductal adenocarcinoma (PDAC) have recently been driven to one of the precursor lesions, namely intraductal papillary mucinous neoplasm of the pancreas (IPMN). Only a few studies have focused on IPMN molecular biology and its overall progression to cancer. Therefore, IPMN lacks comprehensive characterization which makes its clinical management controversial. In this study, we characterized plasma proteins in the presence of IPMNs in comparison to healthy controls, chronic pancreatitis, and PDAC by a proteomics approach using data-independent acquisition based mass spectrometry. We describe several protein sets that could aid IPMN diagnosis, but also differentiation of IPMN from healthy controls, as well as from benign and malignant diseases. Among all, high levels of carbonic anhydrases and hemoglobins were characteristic for the IPMN group. By employing ELISA based quantification we validated our results for human tissue inhibitor of metalloproteinase inhibitor 1 (TIMP-1). We consider IPMN management directed towards an early potential cancer development a crucial opportunity before PDAC initiation and thus its early detection and cure. Copyright © 2017 Elsevier B.V. All rights reserved.
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Pathological criteria and practical issues in papillary lesions of the breast - a review.
Ni, Yun-Bi; Tse, Gary M
2016-01-01
Papillary lesions of the breast include a broad spectrum of lesions, ranging from benign papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS) to papillary carcinoma. The accurate diagnosis of mammary papillary lesions is a challenge for pathologists, owing to the overlapping features among these lesions. In this review, some of the diagnostic criteria of papillary lesions are discussed, with special emphasis on some key morphological features, namely fibrovascular cores, epithelial proliferation in a solid pattern, intraductal papilloma complicated by ADH or DCIS, and invasion and its mimics. The roles of immunohistochemistry, and the interpretation of myoepithelial cell markers, hormone receptors, and high molecular weight cytokeratin, are addressed. Finally, novel biomarkers and genetic aberrations in papillary lesions are summarized. © 2015 John Wiley & Sons Ltd.
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Shibata, Hideki; Ohike, Nobuyuki; Norose, Tomoko; Isobe, Tomohide; Suzuki, Reika; Imai, Hideyuki; Shiokawa, Akira; Aoki, Takeshi; Murakami, Masahiko; Mizukami, Hiroki; Tanaka, Jun-Ichi; Takimoto, Masafumi
2017-12-01
Pancreatic and hepatic mucinous cyst neoplasms (MCNs) have a malignant potential, but indolent MCNs are not uncommon. The pathological and genetic characteristics of resected MCNs (n=15) categorized by the amount of mucin of the lining epithelium were investigated. MCNs were divided into two groups: (i) a rich (r)-MCN group (n=6), in which more than half of the epithelium was lined by abundant mucinous epithelium; and (ii) a poor (p)-MCN group (n=9), which consisted of the remaining cases. Three patients in the r-MCN group showed invasive carcinoma or high-grade dysplasia, whereas all patients in the p-MCN group showed low-grade dysplasia. Mutations of Kirsten rat sarcoma viral oncogene homolog (KRAS) were more frequent in the r-MCN group (83%) (p-MCN; 11%, p<0.05). Mucinous MCNs more frequently have KRAS mutations and higher risk of malignant progression. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Liyanapathirana, Nishantha; Seneviratne, Sanjeewa Anuruddha; Samarasekera, Dharmabandhu Nandadeva
2015-12-17
Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited intestinal polyposis syndrome with an incidence of about 1/8300 births and accounts for about 1% of all colorectal cancers. It has a spectrum of extra-intestinal manifestations including thyroid carcinoma which occur in 1-2% of affected. The cribriform morular variant (CMV) is a rare but distinct histological subtype of papillary thyroid carcinoma (PTC) associated with FAP. Most of the reported cases describe the above entity in the background of well-established FAP. We report a case where both entities presenting simultaneously in a previously undiagnosed patient with FAP without a family history of polyposis. A 24 year old Asian female presented to the surgical clinic with a goitre of eight months duration and recent onset of altered bowel habits with features of anaemia. She was previously healthy and there was no family history of adenomatous polyposis, colorectal carcinoma or thyroid neoplasms. Colonoscopy revealed large bowel polyposis and fine needle aspiration of thyroid revealed a smear suspicious for malignancy. She underwent total thyroidectomy which revealed CMV PTC. Histology was characterized by a prominent cribriform pattern of growth with interspersed cell clusters arranged as morules along with papillary structures which are the key features of this subtype. Diagnosis of CMV warrants ruling out of underlying FAP, irrespective of family history or gastrointestinal symptoms.
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Mucinous expression in benign and neoplastic glandular lesions of the uterine cervix.
Baker, Allyson C; Eltoum, Isam; Curry, Rebecca O; Stockard, Cecil R; Manne, Upender; Grizzle, William E; Chhieng, David
2006-10-01
Mucins are glycoproteins produced by both normal and neoplastic glandular epithelial cells including endocervix. To determine the expression of mucins in uterine cervical glandular lesions and whether mucin expression correlates with the nature and origin of the glandular lesions. Antibodies to MUC1, MUC2, MUC4, and MUC5AC were applied on 52 cases including 14 endocervical adenocarcinomas (including 4 adenosquamous carcinomas), 9 endometrial carcinomas (8 endometrioid adenocarcinomas and 1 adenosquamous carcinoma), 8 adenocarcinoma in situ (AIS), 2 glandular dysplasias, 6 tubal metaplasias, 10 microglandular hyperplasias, and 3 normal endocervix. The presence of any staining was considered positive. All benign endocervical epithelia, including tubal metaplasia and microglandular hyperplasia, expressed MUC1, MUC4, and MUC5AC but not MUC2. Almost all endocervical AIS and carcinomas and all endometrial adenocarcinomas expressed MUC1; the exceptions were 2 cases of endocervical adenocarcinoma and 1 case of adenosquamous carcinoma of the endocervix. MUC2 staining was noted in 25%, 40%, and 22% of AIS, endocervical adenocarcinomas, and endometrial adenocarcinomas, respectively. About 38% of AIS, 75% of endocervical adenocarcinomas, and 44% of endometrial adenocarcinomas expressed MUC4. Half of AIS, most of endocervical adenocarcinomas, and 22% of endometrial adenocarcinomas expressed MUC5AC. The difference in MUC4 and MUC5AC expression between benign endocervical lesions and AIS and the difference in MUC5AC expression between endocervical and endometrial neoplasms were statistically significant. Mucin expressions differed among benign endocervical lesions and AIS and among endocervical and endometrial malignancies. These results suggest that mucin staining may potentially be helpful in differentiating various uterine cervical glandular lesions.
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Jeong, Gui-Ae; Kim, Hyung-Chul; Kim, Hee-Kyung; Cho, Gyu-Seok
2014-09-01
Distant metastasis from papillary thyroid carcinoma (PTC), particularly from papillary thyroid microcarcinoma, is rare. We present a case of perigastric lymph node metastasis from PTC in a patient with early gastric cancer and breast cancer. During post-surgical follow-up for breast cancer, a 56-year-old woman was diagnosed incidentally with early gastric cancer and synchronous left thyroid cancer. Therefore, laparoscopic distal gastrectomy with lymph node dissection and left thyroidectomy were performed. On the basis of the pathologic findings of the surgical specimens, the patient was diagnosed to have papillary thyroid microcarcinoma with perigastric lymph node metastasis and early gastric cancer with mucosal invasion. Finally, on the basis of immunohistochemical staining with galectin-3, the diagnosis of perigastric lymph node metastasis from PTC was made. When a patient has multiple primary malignancies with lymph node metastasis, careful pathologic examination of the surgical specimen is necessary; immunohistochemical staining may be helpful in determining the primary origin of lymph node metastasis.
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Liu, Wen; Cheng, Ruochuan; Ma, Yunhai; Wang, Dan; Su, Yanjun; Diao, Chang; Zhang, Jianming; Qian, Jun; Liu, Jin
2018-05-03
Early preoperative diagnosis of central lymph node metastasis (CNM) is crucial to improve survival rates among patients with papillary thyroid carcinoma (PTC). Here, we analyzed clinical data from 2862 PTC patients and developed a scoring system using multivariable logistic regression and testified by the validation group. The predictive diagnostic effectiveness of the scoring system was evaluated based on consistency, discrimination ability, and accuracy. The scoring system considered seven variables: gender, age, tumor size, microcalcification, resistance index >0.7, multiple nodular lesions, and extrathyroid extension. The area under the receiver operating characteristic curve (AUC) was 0.742, indicating a good discrimination. Using 5 points as a diagnostic threshold, the validation results for validation group had an AUC of 0.758, indicating good discrimination and consistency in the scoring system. The sensitivity of this predictive model for preoperative diagnosis of CNM was 4 times higher than a direct ultrasound diagnosis. These data indicate that the CNM prediction model would improve preoperative diagnostic sensitivity for CNM in patients with papillary thyroid carcinoma.
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Pea, Antonio; Yu, Jun; Rezaee, Neda; Luchini, Claudio; He, Jin; Molin, Marco Dal; Griffin, James F.; Fedor, Helen; Fesharakizadeh, Shahriar; Salvia, Roberto; Weiss, Matthew J.; Bassi, Claudio; Cameron, John L.; Zheng, Lei; Scarpa, Aldo; Hruban, Ralph H.; Lennon, Anne Marie; Goggins, Michael
2016-01-01
Objective The aim of this study was to characterize patterns of local progression following resection for pancreatic intraductal papillary mucinous neoplasms (IPMN) using targeted next-generation sequencing (NGS). Background Progression of neoplastic disease in the remnant pancreas following resection of IPMN may include development of a new IPMN or ductal adenocarcinoma (PDAC). However, it is not clear whether this progression represents recurrence of the same neoplasm or an independent second neoplasm. Methods Targeted-NGS on genes commonly mutated in IPMN and PDAC was performed on tumors from (1) 13 patients who developed disease progression in the remnant pancreas following resection of IPMN; and (2) 10 patients who underwent a resection for PDAC and had a concomitant IPMN. Mutations in the tumors were compared in order to determine the relationship between neoplasms. In parallel, clinical and pathological characteristics of 260 patients who underwent resection of noninvasive IPMN were reviewed to identify risk factors associated with local progression. Results We identified 3 mechanisms underlying local progression in the remnant pancreas: (1) residual microscopic disease at the resection margin, (2) intraparenchymal spread of neoplastic cells, leading to an anatomically separate but genetically related recurrence, and (3) multifocal disease with genetically distinct lesions. Analysis of the 260 patients with noninvasive IPMNs showed that family history of pancreatic cancer (P = 0.027) and high-grade dysplasia (HGD) (P = 0.003) were independent risk factors for the development of an IPMN with HGD or an invasive carcinoma in the remnant pancreas. Conclusions Using NGS, we identify distinct mechanisms for development of metachronous or synchronous neoplasms in patients with IPMN. Patients with a primary IPMN with HGD or with positive family history are at an increased risk to develop subsequent high-risk neoplasms in the remnant pancreas. PMID:27433916
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Lininger, R A; Park, W S; Man, Y G; Pham, T; MacGrogan, G; Zhuang, Z; Tavassoli, F A
1998-10-01
Papillary carcinoma of the breast is a variant of predominantly intraductal carcinoma characterized by a papillary growth pattern with fibrovascular support. Loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci (including loci reported to show frequent genetic alterations in breast cancer) to determine the frequency of genetic mutations in these tumors and their precursors. Thirty-three papillary lesions of the breast (6 papillary carcinomas, 12 carcinomas arising in a papilloma, and 15 intraductal papillomas with florid epithelial hyperplasia) were retrieved from the files of the Armed Forces Institute of Pathology (AFIP). Tumor cells and normal tissue were microdissected in each case and screened for LOH at INT-2 and p53 as well as several loci on chromosome 16p13 in the TSC2/PKD1 gene region (D16S423, D16S663, D16S665). LOH on chromosome 16p13 was present in 10 of 16 (63%) informative cases of either papillary carcinoma or carcinoma arising in a papilloma as well as in 6 of 10 (60%) informative cases of intraductal papilloma with florid epithelial hyperplasia (IDH). One case showed simultaneous LOH in both the florid IDH and carcinoma components of a papilloma. LOH was not observed at either INT-2 or p53 in any of the papillary carcinomas or papillomas with florid IDH. In conclusion, a high frequency of LOH at chromosome 16p13 (the TSC2/PKD1 gene region) is in both papillary carcinomas of the breast as well as in papillomas with florid IDH, including a case with LOH present simultaneously in both components. These findings suggest that chromosome 16p contains a tumor suppressor gene that frequently is mutated early in papillary neoplasia.
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Intraductal papillary neoplasm of the bile duct: a case report.
Peeters, Karen; Delvaux, Peter; Huysentruyt, Frederik
2017-08-01
Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors, characterized by papillary growth within the bile duct lumen and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. IPNBs are mainly found in patients from Far Eastern areas, where hepatolithiasis and clonorchiasis are endemic. The Western experience, however, remains limited. In this article, we report a 56-year-old man, referred to our hospital because of deranged liver function tests. Further imaging modalities showed a cystic lesion of 9 cm diameter, arising from the left hepatic duct. Inlying was a heterogeneous, lobulated mass. The patient underwent a left hemihepatectomy and adjuvant chemotherapy. Despite recent advanced technologies, diagnosis of IPNB is still challenging, especially in western countries due to its rarity. Early identification and resection of lesions, even in asymptomatic or minimally symptomatic patients, are however important prognostic factors.
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The Role of Fragile Sites in Sporadic Papillary Thyroid Carcinoma
Dillon, Laura W.; Lehman, Christine E.; Wang, Yuh-Hwa
2012-01-01
The incidence of thyroid cancer is increasing, especially papillary thyroid carcinoma (PTC), making it currently the fastest-growing cancer among women. Reasons for this increase remain unclear, but several risk factors including radiation exposure and improved detection techniques have been suggested. Recently, the induction of chromosomal fragile site breakage was found to result in the formation of RET/PTC1 rearrangements, a common cause of PTC. Chromosomal fragile sites are regions of the genome with a high susceptibility to forming DNA breaks and are often associated with cancer. Exposure to a variety of external agents can induce fragile site breakage, which may account for some of the observed increase in PTC. This paper discusses the role of fragile site breakage in PTC development, external fragile site-inducing agents that may be potential risk factors for PTC, and how these factors are especially targeting women. PMID:22762011
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Yasuoka, Hironao; Kodama, Rieko; Hirokawa, Mitsuyoshi; Takamura, Yuuki; Miyauchi, Akira; Sanke, Tokio; Nakamura, Yasushi
2008-09-30
Metastasis to regional lymph nodes is a common step in the progression of cancer. Recent evidence suggests that tumor production of CXCR4 promotes lymph node metastasis. Nitric oxide (NO) may also increase metastatic ability in human cancers. Nitrite/nitrate levels and functional CXCR4 expression were assessed in K1 and B-CPAP papillary thyroid carcinoma (PTC) cells after induction and/or inhibition of NO synthesis. CXCR4 expression was also analyzed in primary human PTC. The relationship between nitrotyrosine levels, which are a biomarker for peroxynitrate formation from NO in vivo, CXCR4 expression, and lymph node status was also analyzed. Production of nitrite/nitrate and functional CXCR4 expression in both cell lines was increased by treatment with the NO donor DETA NONOate. The NOS inhibitor L-NAME eliminated this increase. Positive CXCR4 immunostaining was observed in 60.7% (34/56) of PTCs. CXCR4 expression was significantly correlated with nitrotyrosine levels and lymph node metastasis in human PTC. Our data indicate that NO stimulates CXCR4 expression in vitro. Formation of the NO biomarker nitrotyrosine was also correlated with CXCR4 expression and lymph node metastasis in human PTC. NO may induce lymph node metastasis via CXCR4 induction in papillary thyroid carcinoma.
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Yasuoka, Hironao; Kodama, Rieko; Hirokawa, Mitsuyoshi; Takamura, Yuuki; Miyauchi, Akira; Sanke, Tokio; Nakamura, Yasushi
2008-01-01
Background Metastasis to regional lymph nodes is a common step in the progression of cancer. Recent evidence suggests that tumor production of CXCR4 promotes lymph node metastasis. Nitric oxide (NO) may also increase metastatic ability in human cancers. Methods Nitrite/nitrate levels and functional CXCR4 expression were assessed in K1 and B-CPAP papillary thyroid carcinoma (PTC) cells after induction and/or inhibition of NO synthesis. CXCR4 expression was also analyzed in primary human PTC. The relationship between nitrotyrosine levels, which are a biomarker for peroxynitrate formation from NO in vivo, CXCR4 expression, and lymph node status was also analyzed. Results Production of nitrite/nitrate and functional CXCR4 expression in both cell lines was increased by treatment with the NO donor DETA NONOate. The NOS inhibitor L-NAME eliminated this increase. Positive CXCR4 immunostaining was observed in 60.7% (34/56) of PTCs. CXCR4 expression was significantly correlated with nitrotyrosine levels and lymph node metastasis in human PTC. Conclusion Our data indicate that NO stimulates CXCR4 expression in vitro. Formation of the NO biomarker nitrotyrosine was also correlated with CXCR4 expression and lymph node metastasis in human PTC. NO may induce lymph node metastasis via CXCR4 induction in papillary thyroid carcinoma. PMID:18826577
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Furge, Kyle A; Dykema, Karl; Petillo, David; Westphal, Michael; Zhang, Zhongfa; Kort, Eric J; Teh, Bin Tean
2007-01-01
Using high-throughput gene-expression profiling technology, we can now gain a better understanding of the complex biology that is taking place in cancer cells. This complexity is largely dictated by the abnormal genetic makeup of the cancer cells. This abnormal genetic makeup can have profound effects on cellular activities such as cell growth, cell survival and other regulatory processes. Based on the pattern of gene expression, or molecular signatures of the tumours, we can distinguish or subclassify different types of cancers according to their cell of origin, behaviour, and the way they respond to therapeutic agents and radiation. These approaches will lead to better molecular subclassification of tumours, the basis of personalized medicine. We have, to date, done whole-genome microarray gene-expression profiling on several hundreds of kidney tumours. We adopt a combined bioinformatic approach, based on an integrative analysis of the gene-expression data. These data are used to identify both cytogenetic abnormalities and molecular pathways that are deregulated in renal cell carcinoma (RCC). For example, we have identified the deregulation of the VHL-hypoxia pathway in clear-cell RCC, as previously known, and the c-Myc pathway in aggressive papillary RCC. Besides the more common clear-cell, papillary and chromophobe RCCs, we are currently characterizing the molecular signatures of rarer forms of renal neoplasia such as carcinoma of the collecting ducts, mixed epithelial and stromal tumours, chromosome Xp11 translocations associated with papillary RCC, renal medullary carcinoma, mucinous tubular and spindle-cell carcinoma, and a group of unclassified tumours. Continued development and improvement in the field of molecular profiling will better characterize cancer and provide more accurate diagnosis, prognosis and prediction of drug response. PMID:18542781
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2011-12-07
Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Tubular Ductal Breast Carcinoma
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Song, Eyun; Jeon, Min Ji; Oh, Hye-Seon; Han, Minkyu; Lee, Yu-Mi; Kim, Tae Yong; Chung, Ki-Wook; Kim, Won Bae; Shong, Young-Kee; Song, Dong Eun; Kim, Won Gu
2018-06-06
Evidence for unfavorable outcomes of each type of aggressive variant papillary thyroid carcinoma (AV-PTC) is not clear because most previous studies are focused on tall cell variant (TCV) and did not control for other major confounding factors contributing to clinical outcomes. Retrospective cohort study. This study included 763 patients with classical PTC (cPTC) and 144 with AV-PTC, including TCV, columnar cell variant (CCV), and hobnail variants. Disease-free survival (DFS) and dynamic risk stratification (DRS) were compared after two-to-one propensity score matching by age, sex, tumor size, lymph node metastasis, and extrathyroidal extension. The AV-PTC group had significantly lower DFS rates than its matched cPTC group (HR=2.16, 95% CI 1.12-4.16, p=0.018). When TCV and CCV were evaluated separately, there was no significant differences in DFS and DRS between patients with TCV (n=121) and matched cPTC. However, CCV group (n=18) had significantly poorer DFS than matched cPTC group (HR=12.19, 95% CI 2.11-70.33, p=0.005). In DRS, there were significantly more patients with structural incomplete responses in CCV group compared by matched cPTC group (p=0.047). CCV was an independent risk factor for structural persistent/recurrent disease in multivariate analysis (HR, 4.28; 95% CI, 1.66-11.00, p=0.001). When other clinicopathological factors were similar, patients with TCV did not exhibit unfavorable clinical outcome whereas those with CCV had significantly poorer clinical outcome. Individualized therapeutic approach might be necessary for each type of AV-PTCs.
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Trpkov, Kiril; Athanazio, Daniel; Magi-Galluzzi, Cristina; Yilmaz, Helene; Clouston, David; Agaimy, Abbas; Williamson, Sean R; Brimo, Fadi; Lopez, Jose I; Ulamec, Monika; Rioux-Leclercq, Nathalie; Kassem, Maysoun; Gupta, Nilesh; Hartmann, Arndt; Leroy, Xavier; Bashir, Samir Al; Yilmaz, Asli; Hes, Ondřej
2018-04-01
To further characterise biphasic squamoid renal cell carcinoma (RCC), a recently proposed variant of papillary RCC. We identified 28 tumours from multiple institutions. They typically showed two cell populations-larger cells with eosinophilic cytoplasm and higher-grade nuclei, surrounded by smaller, amphophilic cells with scanty cytoplasm. The dual morphology was variable (median 72.5% of tumour, range 5-100%); emperipolesis was found in all cases. The male/female ratio was 2:1, and the median age was 55 years (range 39-86 years). The median tumour size was 20 mm (range 9-65 mm). Pathological stage pT1a was found in 21 cases, pT1b in three, and pT3a and pT3b in one each (two not available). Multifocality was found in 32%: multifocal biphasic RCC in one case, biphasic + papillary RCC in two cases, biphasic + clear cell RCC in three cases, biphasic + low-grade urothelial carcinoma of the renal pelvis in one case, and biphasic + Birt-Hogg-Dubé syndrome in one case. Positive immunostains included: PAX8, cytokeratin (CK) 7, α-methylacyl-CoA racemase, epithelial membrane antigen, and vimentin. Cyclin D1 was expressed only in the larger cells. The Ki67 index was higher in the larger cells (median 5% versus ≤1%). Negative stains included: carbonic anhydrase 9, CD117, GATA-3, WT1, CK5/6, and CK20; CD10 and 34βE12 were variably expressed. Gains of chromosomes 7 and 17 were found in two evaluated cases. Follow-up was available for 23 patients (median 24 months, range 1-244 months): 19 were alive without disease, one was alive with recurrence, and one had died of disease (two had died of other causes). Biphasic papillary RCC is a rare variant of papillary RCC, and is often multifocal. © 2017 John Wiley & Sons Ltd.
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Jiang, Zhong; Lohse, Christine M.; Chu, Peigou G.; Wu, Chin-Lee; Woda, Bruce A.; Rock, Kenneth L.; Kwon, Eugene D.
2009-01-01
BACKGROUND Whether an oncofetal protein, IMP3, can serve as a prognostic biomarker to predict metastasis for patients with localized papillary and chromophobe subtypes of renal cell carcinomas (RCCs) was investigated. METHODS The expression of IMP3 in 334 patients with primary papillary and chromophobe RCC from multiple medical centers was evaluated by immunohistochemistry. The 317 patients with localized papillary and chromophobe RCCs were further evaluated for outcome analyses. RESULTS IMP3 was significantly increased in a subset of localized papillary and chromophobe RCCs that subsequently metastasized. Patients with localized IMP3-positive tumors (n = 33; 10%) were over 10 times more likely to metastasize (risk ratio [RR], 11.38; 95% confidence interval [CI], 5.40–23.96; P <.001) and were nearly twice as likely to die (RR, 1.91; 95% CI, 1.13–3.22; P =.016) compared with patients with localized IMP3 negative tumors. The 5-year metastasis-free and overall survival rates were 64% and 58% for patients with IMP3-positive localized papillary and chromophobe RCCs compared with 98% and 85% for patients with IMP3 negative tumors, respectively. In multivariable analysis adjusting for the TNM stage and nuclear grade, patients with IMP3-positive tumors were still over 10 times more likely to progress to distant metastasis (RR, 13.45; 95% CI, 6.00–30.14; P <.001) and were still nearly twice as likely die (RR, 1.95; 95% CI, 1.15–3.31; P =.013) compared with patients with IMP3-negative tumors. CONCLUSIONS IMP3 is an independent prognostic biomarker that can be used to identify a subgroup of patients with localized papillary and chromophobe RCC who are at high risk for developing distant metastasis. PMID:18412154
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Jain, Tarun Kumar; Karunanithi, Sellam; Sharma, Punit; Vijay, Maneesh Kumar; Ballal, Sanjana; Bal, Chandrasekhar
2014-11-01
Isolated asymptomatic brain metastasis in papillary carcinoma thyroid (PCT) is extremely rare. We here present such a case of a 48-year-old woman with PCT. SPECT/CT localized the 131I radiotracer concentration seen on whole-body scan in this patient to the right posterior parietal cortex, suggesting brain metastasis. Contrast-enhanced MRI and 18F-FDG PET/CT confirmed the diagnosis and the patient was taken for gamma-knife radiosurgery. 131I SPECT/CT in this case accurately restaged the patient by detecting asymptomatic isolated brain metastasis and correctly directed the management strategy.
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Paja Fano, Miguel; Ugalde Olano, Aitziber; Fuertes Thomas, Elena; Oleaga Alday, Amelia
2017-02-01
The BRAF V600E mutation is the most common genetic change in papillary thyroid carcinoma and is associated with a poorer clinical course. Usual methods for its study (DNA sequencing or molecular test based on PCR) are expensive and time-consuming. Recently, immunohistochemistry (IHC) for BRAF mutation has been introduced. To compare the results of IHC and real time PCR (RT-PCR) in the detection of BRAF V600E mutation in papillary thyroid carcinoma. Analysis of clinical and pathological differences depending on RT-PCR results is included. A prospective study was performed in 82 consecutive samples, 54 of them taken through a core needle biopsy. IHC was performed on tissue fixed for 24hours with 10% neutral formalin using the anti-BRAF V600E (VE-1) mouse monoclonal primary antibody and was rated as positive or negative. DNA was extracted from formalin-fixed, paraffin-embedded tissues by manual microdissection, and BRAF mutation was detected by RT-PCR using the Cobas® 4800 BRAF V600 mutation test (Roche). Both techniques were concordant in 81 cases, and BRAF was positive in 49. Discordance appeared in a follicular variant showing positive IHC and negative RT-PCR, attributed to histological heterogeneity. Cost of materials for IHC was less than half of the cost for RT-PCR. IHC appears to be a reliable, economical and easily available alternative to molecular biology techniques for routine detection of the BRAF V600E mutation in papillary thyroid carcinoma patients, provided optimal fixation conditions are used. It may be a useful technique in hospitals with no access to molecular biology techniques. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.
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Basavaiah, Sridevi Hanaganahalli; Sreeram, Saraswathy; Suresh, Pooja Kundapur; Kini, Hema; Adiga, Deepa; Sahu, Kausalya Kumari; Pai, Radha R
2016-01-01
Introduction Papillary neoplasms are a group of lesions that are characterized by presence of papillae supported by fibrovascular cores lined by epithelial cells with or without myoepithelial cell layer. These neoplasms may be benign, atypical or malignant. Aims This study was conducted to analyse the clinicopathological characteristics of papillary lesions of the breast. Materials and Methods A retrospective and prospective analysis of 34 cases of papillary lesions received over a period of 7 years from 2009 to 2015 was done. The patient’s clinical details were collected from medical archives and the histopathological findings were reviewed. The lesions were classified into benign, atypical and malignant categories. Results During the study period, there were 34 cases of papillary lesions of breast. The mean age was 58 years. The central quadrant was the most common location (66.6%). The most common presenting complaint was lump (76.5% cases). Papillary lesions presented more commonly as solitary lump (82.4%) rather than multifocal disease. Benign papillary lesions were more common than the atypical and malignant lesions. The most common papillary lesion accounting for 43% of the cases was intraductal papilloma. Malignant lesions accounted for 41.2% cases with intraductal papillary carcinoma and invasive papillary carcinoma constituting 14.7% cases each. Conclusion Diagnosis of papillary carcinoma is challenging and its classification includes different entities that have specific diagnostic criteria. Due to their heterozygosity in morphology with benign, atypical and malignant subtypes, morphological features such as type of fibrovascular core and continuity of myoepithelial layer along with immunohistochemical stains for myoepithelial cells should be considered for proper and accurate diagnosis. PMID:27656446
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Pagetoid spread of bladder urothelial carcinoma to the vagina and vulva.
Lu, Bingjian; Liang, Yun
2015-01-01
To study the clinicopathologic features of a rare disease of pagetoid urothelial intraepithelial neoplasia (PUIN) in the vulva. We reviewed a case of PUIN in a Chinese woman with a long history of bladder urothelial carcinoma. The patient presented with vulvar pruritus for more than 1 month. Gynecologic examination showed a red, thickened, eczematoid lesion in the bilateral labia minora and a palpable 4-cm mass between the middle part of the vagina and the urethral meatus. Microscopically, the neoplastic cells with clear or pale eosinophilic cytoplasm were distributed throughout the squamous epithelium, with a predilection for the middle and basal portion in the vulva. Acantholysis-related papillary formation and pagetoid spread pattern to the normal squamous epithelium were also present. Invasive carcinoma was found underneath the unremarkable squamous epithelium in the vaginal biopsy. Immunohistochemistry demonstrated that these cells were negative for mucin stain, carcinoembryonic antigen, and 34βE12 and were strongly positive for cytokeratins 5/6, 7, 18, 19, and 20. This rare entity of PUIN was associated with metastatic urothelial carcinoma and should be discriminated from vulvar Paget disease and pagetoid squamous cell carcinoma in situ.
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McCluggage, W Glenn; McBride, Hilary A
2012-05-01
Uterine serous carcinoma (USC) is an aggressive variant of Type 2 endometrial carcinoma, which in most cases exhibits, at least focally, a papillary architecture. Occasionally, especially in small biopsy specimens, it may be difficult to distinguish between USC and a variety of metaplastic or reactive processes. In particular, papillary syncytial metaplasia (PSM), as a result of endometrial breakdown, may be confused with USC or its precursor serous endometrial intraepithelial carcinoma. In such cases, immunohistochemistry is often undertaken, the panel of markers usually including estrogen receptor (ER), p53, p16, and MIB1. The expected immunoprofile of USC is ER negative, p53 and p16 positive, and a high MIB1 proliferation index, although studies have shown that significant numbers of cases deviate from this immunophenotype. With regard to the aforementioned markers, PSM has not been studied extensively, but intuitively, the expected immunophenotype would be ER positive, p53 and p16 negative, and a low MIB1 proliferation index. After 2 index cases in which breaking down menstrual endometrium with florid PSM was misdiagnosed on an endometrial biopsy as USC or suspected USC, in part due to the observed immunophenotype, we studied the expression of ER, p53, p16, MIB1, and HMGA2 (a recently described useful marker of USC) in 10 further cases of PSM associated with endometrial breakdown. We illustrate that compared with a nonbreaking down endometrium, PSM is characterized by a decreased expression of ER and an increased expression of p53 (although still wild-type staining) and p16, the latter marker typically being diffusely positive. HMGA2 is negative, and there is a low MIB1 proliferation index. In cases of PSM, which are morphologically problematic, the immunophenotype may further heighten the suspicion of serous malignancy and potentially result in a misdiagnosis.
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Wasif, Nabil; Bentrem, David J.; Farrell, James J.; Ko, Clifford Y.; Hines, Oscar J.; Reber, Howard A.; Tomlinson, James S.
2010-01-01
Introduction Although invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. We compare survival and identify prognostic factors following resection for invasive IPMN vs. stage-matched PAC. Methods The Surveillance, Epidemiology, and End Results (SEER) database (1991-2005) was utilized to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection. Results Patients with resected invasive IPMN experienced improved overall survival when compared to resected PAC (median survival 21mos vs. 14mos, p<0.001). Stratification by nodal status demonstrated no difference in survival among node positive patients, however, median survival of resected, node negative, invasive IPMN was significantly improved compared to node negative PAC (34mos vs. 18mos, p <0.001). On multivariate analysis PAC histology was an adverse predictor of overall survival (HR 1.31, 95% CI 1.15-1.50) compared to invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR 1.98, 95% CI 1.50- 2.60), high tumor grade (HR 1.74, 95% CI 1.31- 2.31), tumor size >2cm (HR 1.50, 95% CI 1.04- 2.19), and age >66 years (HR 1.33, 95% CI 1.03- 1.73) were adverse predictors of survival. Conclusions Although node negative invasive IPMN shows improved survival following resection compared to node negative PAC, the natural history of node positive invasive IPMN mimics that of node positive PAC. We also identify adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis following resection of invasive IPMN. PMID:20564064
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Djenic, Brano; Duick, Daniel; Newell, James O.; Demeure, Michael J.
2014-01-01
Introduction Papillary (PTC) and follicular (FTC) thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Sites of metastases from FTC are usually osseous and those from PTC are in regional nodal basins and the lungs. Visceral metastases are rare and when they do occur, they tend do so in multiple sites. We present the case of a patient with a follicular variant of PTC and a solitary metastasis to the liver then review the relevant literature. Presentation of case An otherwise healthy 68-year-old woman was diagnosed with follicular variant papillary thyroid cancer in 2003 and subsequently underwent thyroidectomy. The patient’s endocrinologist conducted surveillance of her thyroid cancer. In 2012, due to rise in thyroglobulin, a whole body radioiodine scan was obtained which revealed an iodine-avid left liver lobe mass. Three cycles of radioiodine ablation therapy were unsuccessful and eventually the patient was referred for surgical resection. Metastatic evaluation including a PET scan was negative with the exception of an isolated enhancing 4 cm mass in segment 4B of the liver. Anatomic segmental resection of liver was performed without complications. Intraoperative ultrasonography was used to guide resection of the liver mass. Pathology reports confirmed metastatic follicular variant of PTC. Surgical margins were free of tumor. Patient was discharged home and is doing well one year after surgery. The latest thyroglobulin level was undetectable. Discussion Post-operative surveillance by PCP, endocrinologist or surgeon for patients with thyroid carcinoma should be performed routinely. If identified, a solitary liver metastasis from primary thyroid carcinoma should be considered for surgical resection. Due to sparse data available in literature, collecting more data to establish algorithms for treatment of such rare metastatic cancers may be able to aid physicians to achieve better outcomes. Conclusion
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Alexiev, Borislav A; Zou, Ying S
2014-12-01
Chromosomal microarray analysis using novel Molecular Inversion Probe (MIP) technology demonstrated 2,570 kb copy neutral LOH of 10q11.22 in two clear cell papillary renal cell carcinomas. In addition, one of the tumors had a big 29,784 kb deletion of 13q11-q14.2. There were two variants of unknown significance, a 2,509 kb gain of Xp22.33 and a 257 kb homozygous deletion of 8p11.22. The somatic mutation panel containing 74 mutations in nine genes did not reveal any mutations. Besides identification of submicroscopic duplications or deletions, SNP microarrays can reveal abnormal allelic imbalances including LOH and copy neutral LOH, which cannot be recognized by chromosome, FISH, and non-SNP microarray arrays. To the best of our knowledge, this is the first study demonstrating copy neutral LOH of 10q11.22 in clear cell papillary renal cell carcinomas using the new MIP SNP OncoScan FFPE Assay Kit on formalin-fixed paraffin-embedded tumor samples. Copyright © 2014 Elsevier GmbH. All rights reserved.
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Ultrasonographic Features of Papillary Thyroid Carcinoma in Patients with Graves' Disease
Chung, Jin Ook; Cho, Dong Hyeok; Chung, Dong Jin
2010-01-01
Background/Aims To characterize ultrasonographic findings in papillary thyroid carcinoma (PTC) combined with Graves' disease. Methods Medical records and ultrasonographic findings of 1,013 patients with Graves' disease and 3,380 patients without Graves' disease were analyzed retrospectively. A diagnosis of PTC was based on a pathologic examination. Results The frequency of hypoechogenicity was lower in patients with PTC and Graves' disease than in patients with PTC alone (p < 0.05). The frequency of perinodular blood flow in patients with PTC and Graves' disease was significantly higher than in those with PTC alone (p < 0.05). PTC combined with Graves' disease was characterized by more ill-defined borders and less frequency of overall calcification, punctate calcification, and heterogeneous echogenicity, although the difference was not statistically significant. Conclusions Our results suggest that patients with Graves' disease more frequently have atypical PTC findings on ultrasonography. PMID:20195406
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Mucinous cystadenocarcinoma of the breast: a case report and review of the literature.
Honma, Naoko; Sakamoto, Goi; Ikenaga, Motoko; Kuroiwa, Kojiro; Younes, Mamoun; Takubo, Kaiyo
2003-08-01
We report a case of mucinous cystadenocarcinoma (MCA) of the breast in a 96-year-old woman. This is an extremely rare variant of primary breast carcinoma that bears a striking resemblance to MCAs of the ovary and pancreas. The macroscopic appearance and secretion pattern (cytologic findings) resembled cystic hypersecretory carcinoma. However, microscopically, the epithelial cells were quite different from those of cystic hypersecretory carcinoma. In the present study as well as in the literature, MCAs tend to occur more frequently in elderly women. Immunohistochemical findings suggest that they may develop independently of estrogenic stimulation. Although MCAs show high proliferative activity, the prognosis was favorable in the present case as well as in the reported cases. Because MCAs appear to have a distinct pathogenesis and biologic behavior, they should be distinguished from ordinary mucinous carcinomas, cystic hypersecretory carcinomas, and carcinomas of other histologic subtypes.
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Papillary carcinoma occurring within an adenomatous goiter of the thyroid gland in Cowden's disease.
Kameyama, K; Takami, H; Miyajima, K; Mimura, T; Hosoda, Y; Ito, K; Ito, K
2001-01-01
Cowden's disease is an autosomal dominant disorder characterized by multiple benign and malignant neoplastic lesions involving many organs. The presence of characteristic cutaneous lesions is crucial for the diagnosis. Thyroid disease is a major extracutaneous manifestation of this disease; however, the histologic characteristics have not been described in detail. We report a case of thyroid tumor associated with Cowden's disease. Grossly, the tumor showed a multinodular appearance, like an adenomatous goiter. Microscopically, it consisted of follicular adenomas with a trabecular pattern. Some of the nodules had a second component resembling papillary carcinoma. This was thought to be a unique histological feature not described previously, and might be specific to thyroid tumor associated with Cowden's disease.
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Honjo, Kie; Hiraki, Tsubasa; Higashi, Michiyo; Noguchi, Hirotsugu; Nomoto, Mitsuharu; Yoshimura, Takuya; Batra, Surinder K; Yonezawa, Suguru; Semba, Ichiro; Nakamura, Norifumi; Tanimoto, Akihide; Yamada, Sohsuke
2018-02-01
In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.
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Semba, Shuho; Moriya, Toshiyuki; Kimura, Wataru; Yamakawa, Mitsunori
2003-04-01
Akt/PKB promotes cell proliferation and rescues cells from apoptosis. To evaluate the role of Akt/PKB, a key molecule in phosphatidylinositol 3-OH kinase (PI3K) signaling, during the development of pancreatic duct neoplasias such as intraductal papillary-mucinous tumor (IPMT) and invasive ductal adenocarcinoma (IDAC) of the pancreas. In PK-45H pancreatic cancer cells, the growth-inhibitory and apoptosis-inducing effects of LY294002, a PI3K inhibitor, were detected in a concentration-dependent manner, followed by the reduction of phosphorylated Akt levels. Immunohistochemical analyses revealed that frequent overexpression of phosphorylated Akt (Ser473) was detected in 10 (63%) of 16 IPMTs and 14 (70%) of 20 IDACs. It is interesting that the incidence of Akt phosphorylation closely correlated with Ki-67 immunoreactivity and had an inverse association with the number of cases of apoptotic bodies in both IPMT and IDAC. Although there was no good correlation with other clinicopathologic parameters, the two patients with recurrent IPMT had high levels of phosphorylated Akt. Our findings suggest that activation of Akt plays an important role during the progression of these pancreatic duct neoplasias at the early stage. Furthermore, inhibition of the PI3K-Akt/PKB pathway may have therapeutic potential in the treatment of pancreatic duct tumors.
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Fukushima, N; Sakamoto, M; Mukai, K; Kanai, Y; Shimada, K; Kosuge, T; Hirohashi, S
2001-08-01
Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in certain cases, 5-year survival can be achieved after surgical resection. Analysis of the pathologic findings associated with good survival rates will assist in identifying the optimum treatment. The clinicopathologic features of 67 patients who underwent surgical resection of ductal adenocarcinoma of the pancreas between 1990 and 1996 were reviewed and correlated with survival rates. There were 42 men and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5 years after surgical resection. The intraductal papillary component (IDPC) of the carcinoma was the main focus of the pathologic observations. IDPC was defined as intraductal papillary proliferative lesions seen in the tumor nodule with proliferative cells consistent with carcinomatous cellular atypia. IDPC was clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using the Mantel-Cox test, a statistically significant correlation was found between the presence of IDPC (either + or ++) and postoperative patient survival (P =.002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression.
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Nam, Yoon Jeong; Kim, Bo Hyun; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju
2013-12-01
Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies.
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Wasif, Nabil; Bentrem, David J; Farrell, James J; Ko, Clifford Y; Hines, Oscar J; Reber, Howard A; Tomlinson, James S
2010-07-15
Although invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. The authors compared survival and identify prognostic factors after resection for invasive IPMN versus stage-matched PAC. The Surveillance, Epidemiology, and End Results database (1991-2005) was used to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection. Patients with resected invasive IPMN experienced improved overall survival when compared with resected PAC (median survival, 21 vs 14 months; P<.001). Stratification by nodal status demonstrated no difference in survival among lymph node-positive patients; however, median survival of resected, lymph node-negative, invasive IPMN was significantly improved compared with lymph node-negative PAC (34 vs 18 months; P<.001). On multivariate analysis, PAC histology was an adverse predictor of overall survival (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.50) compared with invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR, 1.98; 95% CI, 1.50-2.60), high tumor grade (HR, 1.74; 95% CI, 1.31-2.31), tumor size>2 cm (HR, 1.50; 95% CI, 1.04-2.19), and age>66 years (HR, 1.33; 95% CI, 1.03-1.73) were adverse predictors of survival. Although lymph node-negative invasive IPMN showed improved survival after resection compared with lymph node-negative PAC, the natural history of lymph node-positive invasive IPMN mimicked that of lymph node-positive PAC. The authors also identified adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis after resection of invasive IPMN. Copyright (c) 2010 American Cancer Society.
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Gatalica, Zoran; Foster, Jason M.; Loggie, Brian W.
2008-01-01
Pseudomyxoma peritonei is a clinical syndrome characterized by peritoneal dissemination of a mucinous tumor with mucinous ascites. The vast majority of the pseudomyxoma peritoneis are associated with mucinous neoplasms of the appendix. We describe a case of pseudomyxoma peritonei associated with mucinous adenocarcinoma of the cervix in a 60-year-old woman. The patient developed low grade mucinous peritoneal carcinomatosis 8 years after hysterectomy for cervical adenocarcinoma. No other primary mucinous tumor was identified and peritoneal carcinomatosis tested positive for high-risk human papilloma virus (HPV), showing both integrated and episomal pattern. HPV has been previously associated with development of cervical carcinomas (both squamous and mucinous) but neither has cervical adenocarcinoma nor HPV been implicated in development of pseudomyxoma peritonei. To the best of our knowledge, this is the first description of HPV-associated malignancy presenting as pseudomyxoma peritonei. PMID:18925701
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Jang, Dong Kee; Ryu, Ji Kon; Chung, Kwang Hyun; Lee, Ban Seok; Park, Joo Kyung; Lee, Sang Hyub; Kim, Yong-Tae
2016-08-01
The 2012 international guidelines state that surgery should be considered for all surgically fit patients with pancreatic main-duct (MD)/mixed intraductal papillary mucinous neoplasms (IPMNs). This study evaluated the follow-up results of MD/mixed IPMNs and risk factors for progression or malignancy. Patients with MD/mixed IPMNs were retrospectively enrolled and divided into surgical and nonsurgical groups. These 2 groups were compared and further categorized as progression/malignancy or not. In the nonsurgical group, disease progression was defined as radiologic tumor growth or adjacent organ invasion. Data from 101 patients (73 males; mean [SD] age, 66.3 [9.1] years), including 27 and 74 in the nonsurgical and surgical groups, respectively, were analyzed. Mural nodules were more frequently detected in the surgical group (7.4% vs 31.1%, P = 0.018), whereas more multifocal cysts were observed in the nonsurgical group (40.7% vs 20.3%, P = 0.037). Forty-one patients (40.6%) showed progression or malignancy. Multivariate analysis showed that main pancreatic duct of 10 mm or greater (odds ratio, 4.368; P = 0.024) and pre-existing diabetes (odds ratio, 3.077; P = 0.046) were independent risk factors for progression or malignancy. A watchful waiting strategy could be feasible for some patients with MD/mixed IPMNs, particularly those with a main pancreatic duct of less than 10 mm and without diabetes.
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[Solitary hyperfunctioning thyroid gland carcinomas].
Zivaljevic, V; Zivic, R; Diklic, A; Krgovic, K; Kalezic, N; Vekic, B; Stevanovic, D; Paunovic, I
2011-08-01
Thyroid gland carcinomas usually appear as afunctional and hypofunctional lesions on thyroid scintigrams, but some rare cases of thyroid carcinoma with scintigraphic hyperfunctional lesions have also been reported. The aim of our retrospective study was to elucidate the frequency of carcinomas in patients operated for solitary hyperfunctional thyroid nodules and to represent their demographic and clinical features. During one decade (1997/2006), 308 patients were operated for solitary hyperfunctional thyroid nodules in the Centre for Endocrine Surgery in Belgrade. Malignancy was revealed in 9 cases (about 3 %) by histopathological examination. In 6 cases papillary microcarcinomas were found adjacent to dominant hyperfunctional adenomas, while in 3 cases (about 1 %) real hyperfunctional carcinomas were confirmed. Follicular carcinoma was diagnosed in 2 cases and papillary carcinoma in one. All 3 patients were preoperatively hyperthyroid. In both patients with follicular carcinoma we performed lobectomies. In the third case we carried out a total thyroidectomy considering the intraoperative frozen section finding of a papillary carcinoma. According to our results the frequency of solitary hyperfunctioning thyroid carcinomas is about 1 %, so that the possibility that a hyperfunctional nodule is malignant should be considered in the treatment of such lesions. © Georg Thieme Verlag KG Stuttgart ˙ New York.
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Ok, Kyung-Sun; Kim, Gwang Ha; Park, Do Youn; Lee, Hyun Jeong; Jeon, Hye Kyung; Baek, Dong Hoon; Lee, Bong Eun; Song, Geun Am
2016-01-01
Background/Aims Magnifying endoscopy with narrow band imaging (ME-NBI) is a useful modality for the detailed visualization of microsurface (MS) and microvascular (MV) structures in the gastrointestinal tract. This study aimed to determine whether the MS and MV patterns in ME-NBI differ according to the histologic type, invasion depth, and mucin phenotype of early gastric cancers (EGCs). Methods The MS and MV patterns of 160 lesions in 160 patients with EGC who underwent ME-NBI before endoscopic or surgical resection were prospectively collected and analyzed. EGCs were categorized as either differentiated or undifferentiated and as either mucosal or submucosal, and their mucin phenotypes were determined via immunohistochemistry of the tumor specimens. Results Differentiated tumors mainly displayed an oval and/or tubular MS pattern and a fine network or loop MV pattern, whereas undifferentiated tumors mainly displayed an absent MS pattern and a corkscrew MV pattern. The destructive MS pattern was associated with submucosal invasion, and this association was more prominent in the differentiated tumors than in the undifferentiated tumors. MUC5AC expression was increased in lesions with either a papillary or absent MS pattern and a corkscrew MV pattern, whereas MUC6 expression was increased in lesions with a papillary MS pattern and a loop MV pattern. CD10 expression was more frequent in lesions with a fine network MV pattern. Conclusions ME-NBI can be useful for predicting the histopathology and mucin phenotype of EGCs. PMID:27021504
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Nam, Yoon Jeong; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju
2013-01-01
Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies. PMID:24396701
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Studies on the mucin derived from human colloid breast carcinoma
Adams, J. B.
1965-01-01
1. A non-diffusible mucoid, showing a single peak in the ultracentrifuge, was isolated from human colloid breast carcinoma by treatment with trypsin and pepsin. The material contained threonine, leucine (isoleucine), valine, proline, glycine and glutamic acid in the approximate molar proportions 5:1:1:2:1:1. Smaller amounts of aspartic acid and serine were also found. For each 5 threonine residues, 6 N-acetylgalactosamine and 3–4 galactose residues were present. 2. The mucoid possessed reducing properties by the Park & Johnson (1949) procedure; these were attributable to the action of mild alkali, as employed in this procedure. Mild alkaline treatment by the Aminoff, Morgan & Watkins (1952) procedure gave rise to a diffusible N-acetylgalactosamine chromophore that gave an enhanced colour with Ehrlich's reagent. That galactosyl-(1→3)-N-acetylgalactosamine residues were liberated was supported by periodate studies. 3. Alkaline liberation of hexosamine residues was accompanied by a specific destruction of threonine. After 40 min. at 100° in 0·18 n-lithium hydroxide, both moieties had almost completely disappeared from the ninhydrin-positive components formed on subsequent acid hydrolysis. Glycine and α-oxobutyric acid were present in the acid hydrolysate, showing that both possible pathways of a β-elimination reaction were involved. Formation of diffusible peptide on very mild alkaline treatment was attributable to the rupture of the original peptide core, necessitated by the second of these two pathways. 4. Hydroxamate formation on treatment with hydroxylamine showed the presence of carbohydrate linkage to glutamic acid or aspartic acid residues or both. This could account for the single N-acetylgalactosamine residue not linked to threonine. 5. The native mucin contained sialic acid, which was cleaved by the acid environment used in the treatment with pepsin. A statistical model of the mucin would require each prosthetic group to be linked, via N
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The endometrium in breast cancer patients on tamoxifen.
Dallenbach-Hellweg, G; Schmidt, D; Hellberg, P; Bourne, T; Kreuzwieser, E; Dören, M; Rydh, W; Rudenstam, G; Granberg, S
2000-04-01
We restudied histologically and immunohistochemically 17 endometrial carcinomas, 2 malignant mixed tumors and 180 endometria with benign changes during or after tamoxifen therapy. The carcinomas were subtyped according to the 1994 WHO-classification. Endometrial biopsies were taken only if the endometrial thickness was > 8 mm sonographically, when a polyp was seen, or for postmenopausal bleeding. About half of the endometrial specimens showed simple or cystic atrophy, 55-76% had cystic-atrophic polyps or regressive hyperplasia. Depending upon the dose of tamoxifen, 7-19% (30 mg) to 27-36% (20 mg) showed moderate glandular proliferation. 20-33% had foci of mucinous, clear cell or serous-papillary metaplasia. 68-70% revealed diffuse extensive fibrosis of the endometrial stroma. None of 11 patients biopsied before starting tamoxifen therapy had advanced endometrial glandular proliferation in the second endometrial biopsy after tamoxifen treatment. None of the 19 endometrial neoplasms after tamoxifen therapy was of the endometrioid type: 11 were mucinous adenocarcinomas, 4 clear cell carcinomas, 2 serous-papillary carcinomas, one carcinosarcoma and one malignant Mullerian mixed tumor. The reasons for discrepancies between suspicious sonograms and endometrial atrophy are discussed.
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Progress in the study of pancreatic cancer and its pathology.
Yanagisawa, A
1998-01-01
Recent advances in diagnostic techniques allow detection of relatively small ductal cancers and mucinous cystic neoplasms of the human pancreas. The histopathological characteristics of a series of such small pancreatic carcinomas encountered in our hospital were: 1) all were invasive ductal carcinomas accompanied by fibrosis, 2) four of seven carcinomas were thought to originate in the branch ducts, 3) no precancerous lesions were found, and 4) lymph node metastasis was detected in only one patient. Mucinous cystic neoplasms were of two types: megacystic and ductectatic. The megacystic type is the classical mucinous cystic neoplasm. The ductectatic type is characterized by the presence of multilocular cysts (reminiscent of bronchiectasia of the lung), and papillary proliferation of the lining epithelium-differing from typical ductal carcinomas as well as from megacystic lesions in terms of morphological features, intrapancreatic location, patient age, and sex. The ductectatic type occurs exclusively in the head and body of the pancreas, and is found predominantly in aging males.
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Primary mammary mucinous cystadenocarcinoma: cytological and histological findings.
Sentani, Kazuhiro; Tashiro, Takashi; Uraoka, Naohiro; Aosaki, Yoriyuki; Yano, Satomi; Takaeko, Fumio; Yasui, Wataru
2012-07-01
Mucinous cystadenocarcinoma (MCA), commonly encountered in the ovary or pancreas, is rare in the breast and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. Only 11 cases of primary mammary MCA have been reported. In this article, we report a case of primary mammary MCA with focus on cytological and histological findings. A 65-year-old female noticed right palpable breast mass. Sonography showed an irregularly shaped 2.8 × 2.4 cm lesion in the upper outer quadrant of the right breast. Fine-needle aspiration cytology was performed on the right breast nodule, and cytopathologic examination suggested an adenocarcinoma composed of tall columnar cells with mucin. A partial mastectomy of the right breast and the axillary lymph nodes dissection was performed. The gross examination revealed a well-demarcated and mucus-filled tumor. Histologically, it had complex papillae, some of which were supported by delicate fibrovascular stroma lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin, coexisting with MCA in situ and ordinary intraductal carcinoma component (ICC). Immunohistochemically, ICC was HER2-negative and estrogen receptor/progesterone receptor-positive, while MCA was triple negative. MCA might be derived from a metaplasia of ordinary ICC, but its pathogenesis and biologic behavior remains unclear. Despite the invasive nature of mammary MCA, these carcinomas appear to be associated with a good prognosis. The patient has remained well and disease-free for 6 months after the operation. Copyright © 2011 Wiley Periodicals, Inc.
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[Papillary cystadenoma of the epididymis. 2 case reports].
Raimoldi, A; Berti, G L; Canclini, L; Giola, V; Leidi, G L; Maccaroni, A; Sironi, M; Veneroni, L; Bacchioni, A M; Assi, A
1997-12-01
Tumors of the epididymis are very rare. They are benign tumors in 75 per cent of the cases. Papillary cystadenoma represents 4-9 per cent of epididymal benign tumors. Often associated with the syndrome of von Hippel Lindau and infertility, histologically it can be confused with metastatic renal cell carcinoma. We report two cases of papillary cystadenoma located in the head of the right epididymis, with no concomitance with the syndrome of von Hippel Lindau, cured by the removal of the neoplastic nodule. There was no recidivation, in confirmation of the neoplastic benignity.
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Kosmas, Konstantinos; Tsonou, Anna; Mitropoulou, Georgia; Salemi, Eufrosyni; Kazi, Danai; Theofanopoulou, Ageliki
2018-02-01
Papillary thyroid carcinoma (PTC) is by far the most common thyroid malignancy (over 85%) of all the thyroid cancers. It has excellent prognosis and 10-year survival rate in most of the cases (95%). Most of the tumors are indolent and do not recur or metastasize after removal. However, widespread metastases to lung, skeleton, central nervous system and, occasionally, other organs may be observed. In rare instances, this disease may metastasize to the pleura and manifest as a malignant pleural effusion (MPE) and portend poor prognosis. This article reports the cytomorphologic and immunocytochemical findings of a female patient with a symptomatic pleural effusion resulting from PTC metastatic to the pleura. Pleural fluid cytology revealed abundant papillary clusters with relatively nuclear pleomorphism, intranuclear cytoplasmic inclusions and nuclear grooves, small and distinct nucleoli as well as small discrete vacuoles. Psammoma bodies were not seen. Immunocytochemical staining was positive for TGB, EMA, Ber-EP4, CK19, and negative for TTF-1. Metastasis of PTC to pleural fluid is extremely rare and diagnosing the disease by cytology is challenging and requires medical expertise as well as knowledge of clinical context and immunocytochemical staining. Additionally, a cytologic diagnosis of MPE due to PTC provides important treatment information and plays an important role in prognosis. © 2017 Wiley Periodicals, Inc.
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2018-03-20
Bladder Cancer; Bladder Neoplasm; Bladder Tumors; Cancer of Bladder; Cancer of the Bladder; Malignant Tumor of Urinary Bladder; Neoplasms, Bladder; Urinary Bladder Cancer; Carcinoma in Situ of Bladder; Papillary Carcinoma of Bladder (Diagnosis); BCG-Unresponsive Bladder Cancer
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Mucinous cystadenocarcinoma of the breast: the challenge of diagnosing a rare entity.
Koufopoulos, Nektarios; Goudeli, Christina; Syrios, John; Filopoulos, Evangelos; Khaldi, Lubna
2017-10-03
Mucinous cystadenocarcinoma is an extremely rare variant of primary breast tumor which is histologically similar to mucinous cystadenocarcinoma of the ovary and pancreas. Herein we report a case of a 63 years old woman diagnosed with diverse histological types of non-synchronous rare primary breast tumors, a medullary carcinoma of the right breast and a mucinous cystadenocarcinoma of the left breast. Macroscopically the neoplasm appeared multilocular filled with mucoid material. Under light microscopy the cystic areas were lined by columnar cells with abundant intracellular and extracellular mucin. Solid areas were composed of tall columnar cells with intracellular mucin. Moderate to marked atypia was noticed and tumor cells stained positive for cytokeratin 7 and negative for cytokeratin 20. Moreover tumor cells displayed a basal like immunophenotype expressed as followed: ER negative, PR negative, HER-2 negative, cytokeratin (CK5/6) positive and EGFR positive.
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Yu, Songfeng; Takasu, Naoki; Watanabe, Toshihiro; Fukumoto, Tsuyoshi; Okazaki, Shinji; Tezuka, Koji; Sugawara, Shuichiro; Hirai, Ichiro; Kimura, Wataru
2017-08-01
The 2012 Fukuoka consensus guideline has stratified the risks of malignant intraductal papillary mucinous neoplasm (IPMN) of the pancreas into "high-risk stigmata" (HRS) and "worrisome feature" (WF). This study aimed to evaluate its clinical validity based on a single institution experience. Eighty-nine patients who underwent surgical resection with pathological diagnosis of IPMN were retrospectively studied. High-risk stigmata was significantly correlated with the prevalence of malignant IPMN as compared with WF. The positive predictive values of HRS and WF were 66.7% and 35.7% for branch duct IPMN and 80% and 38.1% for main duct IPMN, respectively. Univariate analysis indicated that all the factors in HRS and WF had statistical significance. Whereas multivariate analysis revealed only enhanced solid component (odds ratio [OR], 50.01; P = 0.008), presence of mural nodule (OR, 73.83; P < 0.001) and lymphadenopathy (OR, 20.85; P = 0.03) were independent predictors. Scoring HRS and WF by different numbers of positive factors resulted in improved predictive value. The area under the curve of HRS score was significantly lower than that of WF or HRS + WF score (0.680 vs 0.900 or 0.902, respectively; P < 0.001). As supplementary to the 2012 Fukuoka guideline, we suggest that calculating scores of WF and HRS may have superior diagnostic accuracy in predicting malignant IPMN.
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Wang, Jian; Guli, Qie-Re; Ming, Xiao-Cui; Zhou, Hai-Tao; Cui, Yong-Jie; Jiang, Yue-Feng; Zhang, Di; Liu, Yang
2018-01-01
This study reports a case of primary mucinous carcinoma of the thyroid gland with signet-ring-cell differentiation, and reviews the literature to evaluate its real incidence and the prognosis of these patients. A 74-year-old Chinese woman, presenting with a mass in the right lobe of thyroid gland, came to the hospital. Computed tomography revealed a mass in the right lobe of the thyroid gland, accompanied with right neck lymphadenectasis and airway deviation caused by tumor compression. Thyroid imaging suggested a thyroid malignant tumor and suspicious lymph node metastasis. Histologically, the tumor was characterized by the tumor cells arranged in small nests or trabeculae with an abundant extracellular mucoid matrix. The tumor cells formed diffuse invasion among thyroid follicles. In the peripheral regions, prominent signet-ring-cells formed a sheet-like structure and extended into the extrathyroidal fat tissue. The tumor cells were diffusely positive for thyroid transcription factor-1 (TTF-1) and PAX8, while they were focally positive for pan-cytokeratin (AE1/AE3) and weakly expressed thyroglobulin. Based on the histological features and immunohistochemical profile, a diagnosis of primary mucinous carcinoma of the thyroid gland with signet-ring-cell differentiation was rendered. Using a panel of immunohistochemical markers may be helpful for differential diagnosis and for determining whether the tumor is primary or not.
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Deregulation of E2-EPF Ubiquitin Carrier Protein in Papillary Renal Cell Carcinoma
Roos, Frederik C.; Evans, Andrew J.; Brenner, Walburgis; Wondergem, Bill; Klomp, Jeffery; Heir, Pardeep; Roche, Olga; Thomas, Christian; Schimmel, Heiko; Furge, Kyle A.; Teh, Bin T.; Thüroff, Joachim W.; Hampel, Christian; Ohh, Michael
2011-01-01
Molecular pathways associated with pathogenesis of sporadic papillary renal cell carcinoma (PRCC), the second most common form of kidney cancer, are poorly understood. We analyzed primary tumor specimens from 35 PRCC patients treated by nephrectomy via gene expression analysis and tissue microarrays constructed from an additional 57 paraffin-embedded PRCC samples via immunohistochemistry. Gene products were validated and further studied by Western blot analyses using primary PRCC tumor samples and established renal cell carcinoma cell lines, and potential associations with pathologic variables and survival in 27 patients with follow-up information were determined. We show that the expression of E2-EPF ubiquitin carrier protein, which targets the principal negative regulator of hypoxia-inducible factor (HIF), von Hippel-Lindau protein, for proteasome-dependent degradation, is markedly elevated in the majority of PRCC tumors exhibiting increased HIF1α expression, and is associated with poor prognosis. In addition, we identified multiple hypoxia-responsive elements within the E2-EPF promoter, and for the first time we demonstrated that E2-EPF is a hypoxia-inducible gene directly regulated via HIF1. These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC. PMID:21281817
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Goh, Brian K P; Tan, Damien M Y; Ho, Mac M F; Lim, Tony K H; Chung, Alexander Y F; Ooi, London L P J
2014-07-01
The Sendai Consensus Guidelines (SCG) was formulated in 2006 to guide the management of intraductal papillary mucinous neoplasms (IPMN). The main area of controversy is the criteria for selection of branch duct (BD)-IPMN for resection. Although these guidelines have gained widespread acceptance, there is limited data to date supporting its use. This systematic review is performed to evaluate the utility of the Sendai Consensus Guidelines (SCG) for BD-IPMN. Studies evaluating the clinical utility of the SCG in surgically resected neoplasms were identified. The SCG were retrospectively applied to all resected neoplasms in these studies. BD-IPMNs which met the criteria for resection were termed SCG+ve and those for surveillance were termed SCG-ve. Twelve studies were included, of which, 9 were suitable for pooled analysis. There were 690 surgically resected BD-IPMNs, of which, 24% were malignant. Five hundred one BD-IPMNs were classified as SCG+ve and 189 were SCG-ve. The positive predictive value (PPV) of SCG+ve neoplasms ranged from 11 to 52% and the NPV of SCG-ve neoplasms ranged from 90 to 100%. Overall, there were 150/501 (29.9%) of malignant BD-IPMNs in the SCG+ve group and 171/189 (90%) of benign BD-IPMNs in the SCG-ve group. Of the 18 reported malignant (11 invasive) BD-IPMNs in the SCG-ve group, 17 (including all 11 invasive) were from a single study. When the results from this single study were excluded, 170/171 (99%) of SCG-ve BD-IPMNs were benign. The results of this review confirm the limitations of the SCG for BD-IPMN. The PPV of the SCG in predicting a malignant BD-IPMN was low and some malignant lesions may be missed based on these guidelines.
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Kim, Seok-Mo; Jun, Hak Hoon; Chang, Ho-Jin; Chun, Ki Won; Kim, Bup-Woo; Lee, Yong Sang; Chang, Hang-Seok; Park, Cheong Soo
2016-06-01
Tuberculosis (TB) lymphadenitis is a frequent cause of lymphadenopathy in areas in which TB is endemic. Cervical lymphadenopathy in TB can mimic lateral neck metastasis (LNM) from papillary thyroid carcinoma (PTC). This study evaluated the clinicopathological features of patients with PTC and TB lateral neck lymphadenopathy. Of the 9098 thyroid cancer patients who underwent thyroid cancer surgery at the Thyroid Cancer Center of Gangnam Severance Hospital between January 2009 and April 2013, 28 had PTC and showed TB lymphadenopathy of the lateral neck node. The clinicopathological features of these 28 patients were evaluated. Preoperatively, all 28 patients were diagnosed with PTC and showed cervical lymphadenopathy. All had radiological characteristics suspicious of metastasis in lateral neck nodes. Based upon the results from intraoperative frozen sections, lymph node dissection (LND) was not performed on 19 patients. Seven of eight patients who underwent LND had metastasis combined with tuberculous lymphadenopathy, with the remaining patient negative for LNM. Intraoperative sampling and frozen sectioning of lymph nodes suspicious of metastasis can help avoid unnecessary LND for tuberculous lymphadenopathy. © 2014 Royal Australasian College of Surgeons.
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Zeh, Nina; Wild, Peter J; Bode, Peter K; Kristiansen, Glen; Moch, Holger; Sulser, Tullio; Hermanns, Thomas
2013-02-12
Malignant transformation describes the phenomenon in which a somatic component of a germ cell teratoma undergoes malignant differentiation. A variety of different types of sarcoma and carcinoma, all non-germ cell, have been described as a result of malignant transformation. A 33-year-old man presented with a left testicular mass and elevated tumour markers. Staging investigations revealed retroperitoneal lymphadenopathy with obstruction of the left ureter and distant metastases. Histopathology from the left radical orchiectomy showed a mixed germ cell tumour (Stage III, poor prognosis). The ureter was stented and four cycles of cisplatin, etoposide and bleomycin chemotherapy administered. After initial remission, the patient recurred four years later with a large retroperitoneal mass involving the renal vessels and the left ureter. Left retroperitoneal lymph node dissection with en-bloc resection of the left kidney was performed.Histopathology revealed a germ cell tumour metastasis consisting mainly of mature teratoma. Additionally, within the teratoma a papillary renal cell carcinoma was found. The diagnosis was supported by immunohistochemistry showing positivity for AMACR, CD10 and focal expression of RCC and CK7. There was no radiological or histo-pathological evidence of a primary renal cell cancer. To the best of our knowledge, malignant transformation into a papillary renal cell carcinoma has not been reported in a testicular germ cell tumour metastasis following platinum-based chemotherapy. This histological diagnosis might have implications for potential future therapies. In the case of disease recurrence, renal cell cancer as origin of the recurrent tumour has to be excluded because renal cell carcinoma metastases would not respond well to the classical germ cell tumour chemotherapy regimens.
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Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
2018-06-27
Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastrointestinal Stromal Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma
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Kitamura, Y; Shimizu, K; Tanaka, S; Ito, K; Emi, M
2000-05-01
Papillary thyroid carcinomas, most of which are characterized by slow growth and good prognosis, account for the majority of thyroid carcinomas. To provide appropriate postoperative management, it is important to classify them by prediction of their prognosis. To find genetic markers associated with poor prognosis, allelic loss at all 39 nonacrocentric chromosome arms was compared in 24 deceased cases and 45 age-, sex-, stage-, and type-matched survived cases. Allelic loss was examined in primary tumors from both groups using highly polymorphic microsatellite markers on 39 nonacrocentric autosomal arms. Age at diagnosis, sex, stage, and types of tumors were matched between the two groups. No recurrent tumor was used for DNA analysis. Mean fractional allelic loss in the deceased and survived cases was 0.10+/-0.08 and 0.03+/-0.05 (P < 0.001). The survived cases showed marginal frequencies of allelic loss throughout all chromosome arms except 22q. The deceased cases showed frequent allelic losses on chromosomes 1q (37%), 4p (21%), 7q (20%), 9p (36%), 9q (31%), and 16q (29%), with significant difference (P < 0.05). These chromosome regions may include tumor suppressor genes whose inactivation is associated with aggressive phenotypes of papillary thyroid carcinoma.
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Weindel, Michael; Zulfiqar, Muhammad; Bhalla, Amarpreet; Shidham, Vinod B
2013-12-01
Pancreatic neoplasms, including ductal adenocarcinoma, intraductal papillary mucinous neoplasm, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and ampullary carcinoma, are associated with different genetic abnormalities. Liver neoplasms, including hepatic adenomas, hepatocellular carcinomas, and cholangiocarcinomas, are associated with identifiable risk factors and genetic changes. Gall bladder adenomas and adenocarcinomas arise from distinct molecular pathways. The molecular abnormalities seen in these tumors are not used routinely in the molecular diagnostic laboratory. Copyright © 2013 Elsevier Inc. All rights reserved.
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Papillary bile duct dysplasia in primary sclerosing cholangitis.
Ludwig, J; Wahlstrom, H E; Batts, K P; Wiesner, R H
1992-06-01
A 62-year-old man with a 20-year history of chronic ulcerative colitis and a 9-year history of primary sclerosing cholangitis (PSC) underwent orthotopic liver transplantation because of symptoms related to PSC and cholangiographic features compatible with a biliary neoplasm. Study of the excised liver revealed papillary mucosal lesions in the common hepatic duct and the right and left hepatic ducts as well as cholangiectases and other features typically associated with PSC. The papillary lesions consisted of abundant fibrovascular stroma covered by biliary epithelium with low-grade and high-grade dysplasia. Some periductal glands were also dysplastic. These features distinguished papillary dysplasia from classic biliary papillomatosis. Only one focus of microinvasion was found; there were no metastases. Among 60 cases of PSC in whom the entire liver could be studied after orthotopic liver transplantation, this was the only instance of unequivocal dysplasia. However, in one specimen, papillary hyperplasia was found. Detailed macroscopic and microscopic rereview of 23 livers from our patients with the longest history of PSC (range, 5-24 years) failed to reveal any additional cases with dysplasia. It is concluded that (a) papillary mucosal lesions in PSC may represent papillary dysplasia without invasion; (b) these lesions may evolve from papillary hyperplasia; (c) the process may be largely, if not entirely, in situ; and (d) the prevalence of dysplasia and carcinoma of bile ducts may be less than the 7%-9% reported in the literature for malignancies associated with PSC.
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Mucinous cystadenocarcinoma of the breast: the challenge of diagnosing a rare entity
Koufopoulos, Nektarios; Goudeli, Christina; Syrios, John; Filopoulos, Evangelos; Khaldi, Lubna
2017-01-01
Mucinous cystadenocarcinoma is an extremely rare variant of primary breast tumor which is histologically similar to mucinous cystadenocarcinoma of the ovary and pancreas. Herein we report a case of a 63 years old woman diagnosed with diverse histological types of non-synchronous rare primary breast tumors, a medullary carcinoma of the right breast and a mucinous cystadenocarcinoma of the left breast. Macroscopically the neoplasm appeared multilocular filled with mucoid material. Under light microscopy the cystic areas were lined by columnar cells with abundant intracellular and extracellular mucin. Solid areas were composed of tall columnar cells with intracellular mucin. Moderate to marked atypia was noticed and tumor cells stained positive for cytokeratin 7 and negative for cytokeratin 20. Moreover tumor cells displayed a basal like immunophenotype expressed as followed: ER negative, PR negative, HER-2 negative, cytokeratin (CK5/6) positive and EGFR positive. PMID:29081926
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Scharpf, Joseph; Kamani, Dipti; Sadow, Peter M; Randolph, Gregory W
2017-01-01
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a new terminology proposed for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Recently, thyroid cancer incidence has increased dramatically, without affecting related mortality rate. This increase is widely attributed to the intensified surveillance leading to a substantial increase in the diagnosis of small classic papillary thyroid cancers and EFVPTCs. Recent studies emphasize the indolent behavior of the EFVPTC. Recently, there has been a reclassification of EFVPTC as NIFTP, a benign entity. The financial and emotional burden of 'cancer' diagnosis and treatment can be significant. This review recapitulates the literature supporting the reclassification of EFVPTC as NIFTP, a benign entity, and reviews standardized diagnostic criteria for EFVPTC. The information highlighted in this review will affect surgical decision making and may promote the offering of hemithyroidectomy over a total thyroidectomy to some patients with 'indeterminate' cytopathological category; postoperative radioiodine ablation will not be required for NIFTP patients.
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Gangopadhyay, A; Bhattacharya, M; Chatterjee, S K; Barlow, J J; Tsukada, Y
1985-04-01
The distribution of an antigen recognized by murine monoclonal antibody 1D3 (Bhattacharya, M., Chatterjee, S.K., Barlow, J. J., and Fuji, H. Cancer Res., 42: 1650-1654, 1982) was investigated in various types of human malignant and normal adult tissues by indirect immunoperoxidase assay in fixed paraffin-embedded sections. One hundred percent of ovarian mucinous cystadenocarcinomas expressed high levels of the antigen with intense staining of 80 to 100% of the tumoral area, thus confirming our previous finding with radioimmunoassay and absorption analyses. About 51% of colonic carcinomas, 33% of gastric carcinomas, and 22% of pancreatic carcinomas were also positive for this high-molecular-weight mucoprotein antigen. All other ovarian and nonovarian carcinomas tested including carcinoma of lung, breast, endometrium, cervix, and prostate were not stained by 1D3. In addition, sarcomas, melanomas, and lymphomas also did not express any detectable level of the antigen. When surveyed against various normal adult tissues, 1D3 had reactivity limited to the colon. Normal colon, however, exhibited reduced staining intensities compared to tumors or to the apparently normal colon adjacent to tumors. The antigen thus appears to be a colorectal tissue-specific antigen showing increased levels in ovarian mucinous cystadenocarcinomas and in some gastrointestinal tumors. 1D3 antigen is a potential tumor marker for mucinous ovarian and colonic tumors.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Mauri, Giovanni, E-mail: vanni.mauri@gmail.com; Cova, Luca; Ierace, Tiziana
2016-07-15
PurposeTo assess the effectiveness of percutaneous laser ablation (PLA) of cervical lymph node metastases from papillary thyroid carcinoma.Materials and Methods24 patients (62.3 ± 13.2 year; range 32–80) previously treated with thyroidectomy, neck dissection, and radioiodine ablation underwent ultrasound-guided PLA of 46 {sup 18}FDG-PET/CT—positive metachronous nodal metastases. All patients were at high surgical risk or refused surgery and were unsuitable for additional radioiodine ablation. A 300 µm quartz fiber and a continuous-wave Nd-YAG laser operating at 1.064 mm were used. Technical success, rate of complications, rate of serological conversion, and local control at follow-up were derived. Fisher’s exact test and Mann–Whitney U test were used andmore » Kaplan–Meier curve calculated.ResultsTechnical success was obtained in all 46 lymph nodes (100 %). There were no major complications. Thyroglobulin levels decreased from 8.40 ± 9.25 ng/ml before treatment to 2.73 ± 4.0 ng/ml after treatment (p = 0.011), with serological conversion in 11/24 (45.8 %) patients. Overall, local control was obtained in 40/46 (86.9 %) lymph nodes over 30 ± 11 month follow-up, with no residual disease seen at imaging in 19/24 (79.1 %) patients. Local control was achieved in 40/46 (86.9 %) lymph nodes at 1 year and in all of the 25 nodes (100 %) followed for 3 years. Estimated mean time to progression was 38.6 ± 2.7 m.ConclusionUltrasound-guided PLA is a feasible, safe, and effective therapy for the treatment of cervical lymph node metastases from papillary thyroid carcinoma.« less
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[Pleural metastases of renal carcinoma].
Giigoruk, O G; Lazarev, A F; Doroshenko, V S
2007-01-01
Metastases in renal carcinoma are diagnosed at initial diagnosis in 25% examinees. Traditional renal carcinoma has higher metastatic potential, is associated with worse survival of the patients compared to papillary cancer. We studied cytological characteristics of renal carcinoma metastases to the pleura in comparison with histological studies of the primary lesion using immunohistochemical findings. We examined cytologically pleural liquid in renal carcinoma metastases to the pleura in 6 patients (2.3% of carcinomatous pleuricies). High efficacy was shown by a cytocentrifuge CYTOSPIN-4. In 3 cases initial cancer was renal cell carcinoma, pleural exudation developed 2 years later, clear cell carcinoma appeared 6 years later and papillary cancer--10 years later. In the other 3 cases malignant cells were detected in new-onset cases. Renal carcinoma was diagnosed in one case. Cytological preparations were studied with identification of cytological signs typical for classic clear cell, granulocell and papillary renal cancer. Immunohistochemical examination of primary tumor lesion in the kidney discovered high proliferative activity of tumor cells by Ki-67 index to 5.28%. The tumors had solitary Bcl-2 positive cells. Expression of mutant p-53 took place in 0.93%. Her-2/neu hyperexpression was not found in the tumors of the above patients. Such immunohistochemical parameters point to poor prognosis. This is confirmed by renal carcinoma metastases to the pleura.
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Amita, Krishnappa; Vijayshankar, Shivshankar; Sanjay, Manchaiah
2015-09-01
Tuberculosis (TB) and cancer are two lethal diseases causing significant morbidity and mortality in developing countries like India. Co-existence of these two disease lead to diagnostic dielemma among the clinicians. Overlapping clinical manifestations lead to delay in diagnosis. We report a case of acinic cell carcinoma -papillary cystic variant of the salivary gland and extra pulmonary tuberculosis in a young female. We emphasize the importance of the awareness of the co-existence of these two diseases and the role of fine needle aspiration cytology in the initial diagnosis.
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Pulmonary giant cell carcinoma associated with pseudomyxoma peritonei.
Goldin, Mark; Li, Jinghong; Amirrezvani, Ali; Riker, David
2012-01-01
Pulmonary giant cell carcinoma is a rare subtype of sarcomatoid carcinoma. Pseudomyxoma peritonei (PMP) is a rare condition in which gelatinous material accumulates within the peritoneal cavity. It is believed PMP arises from a primary appendiceal mucinous neoplasm that perforates the gut, causing mucinous ascites. There are sporadic reports of PMP associated with neoplasms of other organs, rarely the lung. Here, we report on a 60-year-old woman with pulmonary giant cell carcinoma associated with PMP. She presented with progressive dyspnea and abdominal distention. Abdominal computed tomography revealed moderately dense ascites without an obvious mass. Chest computed tomography revealed a large, solitary right lower-lobe lung mass. She underwent transbronchial fine-needle aspiration of the mass, and was diagnosed with pulmonary giant cell carcinoma. The ascites showed scattered malignant cells in a background of mucin, confirming PMP. To our knowledge, this is the first report of pulmonary giant cell carcinoma associated with PMP.
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A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas
Sinha, Jessica; Cao, Zheng; Dai, Jianliang; Tang, Huiyuan; Partyka, Katie; Hostetter, Galen; Simeone, Diane M.; Feng, Ziding; Allen, Peter J.; Brand, Randall E.; Haab, Brian B.
2016-01-01
Molecular indicators to specify the risk posed by a pancreatic cyst would benefit patients. Previously we showed that most cancer-precursor cysts, termed mucinous cysts, produce abnormal glycoforms of the proteins MUC5AC and endorepellin. Here we sought to validate the glycoforms as a biomarker of mucinous cysts and to specify the oligosaccharide linkages that characterize MUC5AC. We hypothesized that mucinous cysts secrete MUC5AC displaying terminal N-acetylglucosamine (GlcNAc) in either alpha or beta linkage. We used antibody-lectin sandwich assays to detect glycoforms of MUC5AC and endorepellin in cyst fluid samples from three independent cohorts of 49, 32, and 66 patients, and we used monoclonal antibodies to test for terminal, alpha-linked GlcNAc and the enzyme that produces it. A biomarker panel comprising the previously-identified glycoforms of MUC5AC and endorepellin gave 96%, 96%, and 87% accuracy for identifying mucinous cysts in the three cohorts with an average sensitivity of 92% and an average specificity of 94%. Glycan analysis showed that MUC5AC produced by a subset of mucinous cysts displays terminal alpha-GlcNAc, a motif expressed in stomach glands. The alpha-linked glycoform of MUC5AC was unique to intraductal papillary mucinous neoplasms (IPMN), whereas terminal beta-linked GlcNAc was increased in both IPMNs and mucinous cystic neoplasms (MCN). The enzyme that synthesizes alpha-GlcNAc, A4GNT, was expressed in the epithelia of mucinous cysts that expressed alpha-GlcNAc, especially in regions with high-grade dysplasia. Thus IPMNs secrete a gastric glycoform of MUC5AC that displays terminal alpha-GlcNAc, and the combined alpha-GlcNAc and beta-GlcNAc glycoforms form an accurate biomarker of mucinous cysts. PMID:27992432
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Deregulation of E2-EPF ubiquitin carrier protein in papillary renal cell carcinoma.
Roos, Frederik C; Evans, Andrew J; Brenner, Walburgis; Wondergem, Bill; Klomp, Jeffery; Heir, Pardeep; Roche, Olga; Thomas, Christian; Schimmel, Heiko; Furge, Kyle A; Teh, Bin T; Thüroff, Joachim W; Hampel, Christian; Ohh, Michael
2011-02-01
Molecular pathways associated with pathogenesis of sporadic papillary renal cell carcinoma (PRCC), the second most common form of kidney cancer, are poorly understood. We analyzed primary tumor specimens from 35 PRCC patients treated by nephrectomy via gene expression analysis and tissue microarrays constructed from an additional 57 paraffin-embedded PRCC samples via immunohistochemistry. Gene products were validated and further studied by Western blot analyses using primary PRCC tumor samples and established renal cell carcinoma cell lines, and potential associations with pathologic variables and survival in 27 patients with follow-up information were determined. We show that the expression of E2-EPF ubiquitin carrier protein, which targets the principal negative regulator of hypoxia-inducible factor (HIF), von Hippel-Lindau protein, for proteasome-dependent degradation, is markedly elevated in the majority of PRCC tumors exhibiting increased HIF1α expression, and is associated with poor prognosis. In addition, we identified multiple hypoxia-responsive elements within the E2-EPF promoter, and for the first time we demonstrated that E2-EPF is a hypoxia-inducible gene directly regulated via HIF1. These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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RAMAN spectroscopy imaging improves the diagnosis of papillary thyroid carcinoma
NASA Astrophysics Data System (ADS)
Rau, Julietta V.; Graziani, Valerio; Fosca, Marco; Taffon, Chiara; Rocchia, Massimiliano; Crucitti, Pierfilippo; Pozzilli, Paolo; Onetti Muda, Andrea; Caricato, Marco; Crescenzi, Anna
2016-10-01
Recent investigations strongly suggest that Raman spectroscopy (RS) can be used as a clinical tool in cancer diagnosis to improve diagnostic accuracy. In this study, we evaluated the efficiency of Raman imaging microscopy to discriminate between healthy and neoplastic thyroid tissue, by analyzing main variants of Papillary Thyroid Carcinoma (PTC), the most common type of thyroid cancer. We performed Raman imaging of large tissue areas (from 100 × 100 μm2 up to 1 × 1 mm2), collecting 38 maps containing about 9000 Raman spectra. Multivariate statistical methods, including Linear Discriminant Analysis (LDA), were applied to translate Raman spectra differences between healthy and PTC tissues into diagnostically useful information for a reliable tissue classification. Our study is the first demonstration of specific biochemical features of the PTC profile, characterized by significant presence of carotenoids with respect to the healthy tissue. Moreover, this is the first evidence of Raman spectra differentiation between classical and follicular variant of PTC, discriminated by LDA with high efficiency. The combined histological and Raman microscopy analyses allow clear-cut integration of morphological and biochemical observations, with dramatic improvement of efficiency and reliability in the differential diagnosis of neoplastic thyroid nodules, paving the way to integrative findings for tumorigenesis and novel therapeutic strategies.
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Gunalp, Bengul; Okuyucu, Kursat; Ince, Semra; Ayan, Aslı; Alagoz, Engin
2017-01-01
There has been much discussion recently about the risk category of tall cell variant (TVC) histology and its effects on the management of papillary thyroid carcinoma (PTC). We, therefore, undertook a retrospective study to compare stage-matched risk factors and recurrence rates between classical PTC (cPTC) patients and patients with TCV histology. A total of 3128 well-differentiated thyroid carcinoma patients who were treated and followed-up for more than 5 years in our clinic from 1995 to 2016 were included in this study. There were 2783 PTC (89%) patients, 1113 (40%) of them were cPTC and 56 (2%) of them were TCV patients. In all stages, the stage-matched incidence of extrathyroidal extension (ETE), lymphovascular invasion and initial lymph node metastases were significantly higher in TCV patients than in cPTC patients (P<0.001). Recurrence was in 10 of 27 patients (37%) with TCV and in 91 of 890 (10%) patients with cPTC diagnosed in stage I (odds ratio (OR)=5.16); in 4 of 6 patients with TCV and 18 of 84 (21%) patients with cPTC in stage II (OR=7.33); in 5 of 6 patients with TCV and 11 of 46 (23%) patients with cPTC in stage III (OR=15.90); and in 13 of 17 patients with TCV and 31 of 93 (33%) patients with cPTC in stage IV (OR=6.50). Stage-matched recurrence rates were found significantly higher in all stages of TCV patients than in cPTC patients (OR=8.49, P<0.001). Recurrence with distant metastases was seen more frequently in TCV patients than in cPTC patients (P<0.001) and treatment of metastatic disease was more difficult in TCV patients. Tall cell variant was an independent poor prognostic factor in papillary thyroid carcinoma patients even if they were diagnosed at early stages of the disease. Patients with tall cell variant histology required more aggressive therapeutic approach and closer follow-up than classical patients.
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Diffuse lipomatosis of the thyroid gland with papillary microcarcinoma: Report of a rare entity.
Nandyala, Hariharanadha Sarma; Madapuram, Srinivasulu; Yadav, Megha; Katamala, Sudheer Kumar
2015-01-01
Presence of lobules of adipose tissue either focally or diffusely is very rare in the thyroid gland. Fat accumulation can be macroscopic or microscopic. Focal infiltrates of fat have been reported in conditions such as adenolipoma, intrathyroid lipoma, and encapsulated papillary carcinoma. Diffuse lipomatosis has been reported in conditions such as amyloid goitre, heterotopic fat nests, thyrolipoma and liposarcoma. The exact mechanism of fat accumulation is not known although there are many theories postulated. Investigations such as ultrasound, computed tomography scan, and magnetic resonance imaging can detect the presence of macroscopic fat in the thyroid gland. Accurate diagnosis of the type of fat accumulation is necessary because tumorous and nontumorous conditions fall into the differential diagnosis. Only nine cases of papillary carcinoma associated with lipomatosis of thyroid are reported so far. We report possibly the first case of diffuse lipomatosis of the thyroid gland with a focus of papillary microcarcinoma.
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Delogu, Daniele; Pisano, Ilia Patrizia; Pala, Carlo; Pulighe, Fabio; Denti, Salvatore; Cossu, Antonio; Trignano, Mario
2014-01-01
The aim of this study was to evaluate the role of prophylactic central neck lymph node dissection in high risk patients with T1 or T2 papillary thyroid cancer. Seventy-three patients who had undergone total thyroidectomy for papillary thyroid cancer smaller than 4cm, without cervical lymphadenopathy and prophylactic central neck lymph node dissection were included. Patients were divided in two groups: low risk patients (group A) and high risk patients (group B). High risk patients were considered those with at least one of the followings: male sex, age ≥ 45 years, and extracapsular or extrathyroid disease. Statistical significant differences in persistent disease, recurrence and complications rates between the two groups were studied. Persistence of the disease was observed in one case in group A (5.9%) and in three cases in group B (5.4%), while thyroid cancer recurrence was registered in zero and two (3.6%) cases respectively. One single case (5.9%) of transitory recurrent laryngeal nerve damage was reported in group A and none in group B, while transitory hypoparathyroidism was observed in 2 (3.6%) patients in group A, and 1 (1.8%) patient in group B. Permanent recurrent laryngeal nerve damage was observed in one patient in group A, while permanent hypoparathyroidism was registered in one case in group B. Logistic regression evidenced that multifocality was the only risk factor significantly related to persistence of disease and recurrence. Our results suggests that prophylactic central neck lymph node dissection can be safely avoided in patients with T1 or T2 papillary thyroid cancer, except in those with multifocal disease. Cancer, Central neck, Cervical, Lymphadenectomy, Lymph nodes, Papillary carcinoma, Thyroid.
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Long-term survival in a patient with brain metastases of papillary thyroid carcinoma
Guelho, Daniela; Ribeiro, Cristina; Melo, Miguel; Carrilho, Francisco
2016-01-01
We present the case of a 43-year-old woman who underwent total thyroidectomy with bilateral lymphadenectomy for a papillary thyroid carcinoma (PTC), solid variant (T4bN1bMx), with V600E BRAF mutation. After ablative therapy, she presented undetectable thyroglobulin (Tg) but progressively increasing anti-Tg antibodies (TgAbs). During follow-up, nodal, lung and brain metastases were identified. She was submitted to surgical excision of lung lesions, radiosurgery of brain metastases and five radioiodine treatments. The latest brain MRI showed no lesions, pulmonary CT showed stable micronodules and there was progressive reduction in TgAbs. This is a peculiar case of a PTC with lung and brain metastatic lesions detected through TgAbs. Initial histological and molecular study suggested a more aggressive clinical behaviour, which was eventually confirmed. Although PTC brain metastases are extremely rare and present poor prognosis, our patient presented a good response to treatment and longer survival than usually reported for similar cases. PMID:26961557
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NASA Astrophysics Data System (ADS)
Kim, Edward; Baloch, Zubair; Kim, Caroline
2015-03-01
The number of new cases of thyroid cancer are dramatically increasing as incidences of this cancer have more than doubled since the early 1970s. Tall cell variant (TCV-PTC) papillary thyroid carcinoma is one type of thyroid cancer that is more aggressive and usually associated with higher local recurrence and distant metastasis. This variant can be identified through visual characteristics of cells in histological images. Thus, we created a fully automatic algorithm that is able to segment cells using a multi-stage approach. Our method learns the statistical characteristics of nuclei and cells during the segmentation process and utilizes this information for a more accurate result. Furthermore, we are able to analyze the detected regions and extract characteristic cell data that can be used to assist in clinical diagnosis.
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Structural alterations in tumor-draining lymph nodes before papillary thyroid carcinoma metastasis.
Hinson, Andrew M; Massoll, Nicole A; Jolly, Lee Ann; Stack, Brendan C; Bodenner, Donald L; Franco, Aime T
2017-08-01
The purpose of this study was to define and characterize the thyroid tumor-draining lymph nodes in genetically engineered mice harboring thyroid-specific expression of oncogenic Braf V600E with and without Pten insufficiency. After intratumoral injection of methylene blue, the lymphatic drainage of the thyroid gland was visualized in real time. The thyroid gland/tumor was resected en bloc with the respiratory system for histological analysis. Although mice harboring Braf V600E mutations were smaller in body size compared with their wild-type (WT) littermates, the size of their thyroid glands and deep cervical lymph nodes were significantly larger. Additionally, the tumor-draining lymph nodes showed increased and enlarged lymphatic sinuses that were distributed throughout the cortex and medulla. Tumor-reactive lymphadenopathy and histiocytosis, but no frank metastases, were observed in all mice harboring Braf V600E mutations. The tumor-draining lymph nodes undergo significant structural alterations in immunocompetent mice, and this may represent a primer for papillary thyroid carcinoma (PTC) metastasis. © 2017 Wiley Periodicals, Inc.
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ENHANCED BETA-CATENIN EXPRESSION IS ASSOCIATED WITH THE RECURRENCE OF PAPILLARY THYROID CARCINOMA.
Kordestani, Zeinab; Sanjari, Mojgan; Safavi, Moeinadin; Mashrouteh, Mahdieh; Asadikaram, Gholamreza; FekriSoofiAbadi, Maryam; Mirzazadeh, Ali
2018-03-02
A direct role of Catenin beta-1(βcat) in the proliferation of human thyroid tumor cells has been identified. This study aimed to determine if there is an association between βcat gene expression and the staging, recurrence, metastasis, and disease free survival of papillary thyroid cancer. A retrospective cohort study was conducted using data from available information in the medical records and paraffin blocks of 81 of 400 patients referred to the endocrine clinic over a 10-year period. Real-time polymerase chain reaction (PCR) was used to evaluate βcat gene expression. Disease-free survival was assessed using Kaplan-Meier method. The ten-year survival rate in these patients was 98.25% and disease-free survival was 48.1%. Cumulative dose of radioactive iodine that patients received was significantly and positively correlated with βcat gene expression (r = -0.2, p value=0.03).Also, in patients with recurrence, βcat gene expression was higher and statistically significant (5 fold increase p=0.002). Patients in more advanced stage and those with recurrence /distant metastasis had higher βcat gene expression .We found that the patients had a better survival (lower recurrence) if they had a lower βcat gene expression. (SD = 0.142-0.052) (Mantel-Cox test, P =0.002). We concluded that βcat gene expression was positively correlated with recurrence, distant metastasis and TNM stage. PTC = Papillary thyroid carcinoma; βcat = Catenin beta-1; FTC = Follicular thyroid cancer; TCF/LEF-1 = T-cell factor / lymphoid enhancer factor1; IHC = immunohistochemical; TG = Thyroglobulin; AUC = Area under the ROC curve; APC = Adenomatosis polyposis coli.
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Huang, Hui; Xu, Zhengang; Wang, Xiaolei; Wu, Yuehuang; Liu, Shaoyan
2015-10-01
To retrospectively analyze the long-term results of prophylactic central lymph node dissection in cN0 papillary thyroid carcinoma (PTC), and investigate the treatment method of the cervical lymph nodes for cN0 PTC. One hundred and thirty-six patients with cN0 PTC were treated by surgery at the Cancer Hospital of Chinese Academy of Medical Sciences from 2000 to 2006. Their clinicopathological characteristics, surgical procedures and survival outcomes were collected and analyzed. The occult lymph node metastasis rate in central compartment was 61.0%. The average number of positive lymph nodes was 2.47 (1-13), in which 54 patients had 1-2 and 29 patients had ≥ 3 positive lymph nodes. Multiple logistic regression analysis showed that age less than 45 (P=0.001, OR 3.571, 95% CI 1.681-7.587)and extracapsular spread (ECS) (P=0.015, OR 2.99, 95% CI 1.241-7.202)were independent risk factors for lymph node metastasis in the central compartment. The ten-year cumulative overall survival rate was 98.3% and cumulative lateral neck metastasis rate was 25.2%. Multivariate analysis with Cox regression model showed that ECS (P=0.001, OR 5.211, 95% CI1.884-14.411) and positive lymph nodes in the central compartment ≥ 3 (P=0.009, OR 4.005, 95% CI 1.419-11.307) were independent risk factors for lymph node recurrence in the lateral neck region. The distribution of recurrent lymph nodes: level IV (82.4%), level III (64.7%), level II (29.4%) and level V (11.8%). Routine central lymph node dissection, at least unilateral, should be conducted for cN0 papillary thyroid carcinoma. Attention should be paid to the treatment of lateral neck region in patients with cN0 papillary thyroid carcinoma. Selective neck dissection is suggested for cN0 PTC with ECS or positive central lymph nodes ≥ 3, or both. The range of dissection should include level III and IV at least.
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Foda, Abd Al-Rahman Mohammad; Mohamed, Mie Ali
2015-10-01
c-KIT and DOG-1 are 2 highly expressed proteins in gastrointestinal stromal tumors. Few studies had investigated c-KIT, but not DOG-1, expression in colorectal carcinoma (CRC). This study aims to investigate expressions of c-KIT and DOG-1 in colorectal mucinous carcinoma and nonmucinous carcinoma using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique, and immunohistochemistry for c-KIT and DOG-1 was done. We found that aberrant c-KIT expression was detected in 12 cases (8%); 6 cases (4%) showed strong expression. Aberrant DOG-1 expression was detected in 15 cases (10%); among them, only 4 cases (2.7%) showed strong expression. Nonmucinous adenocarcinoma showed a significantly high expression of c-KIT, but not DOG-1, than MA. Aberrant c-KIT and DOG-1 expressions were significantly unrelated but were associated with excessive microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. In conclusion, aberrant c-KIT and DOG-1 expressions in CRC are rare events, either in NMA or MA. Nonmucinous adenocarcinoma showed a significantly higher expression of c-KIT, but not DOG-1, than MA. The expressions of both in CRC are significantly unrelated but are associated with microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. So, c-KIT and DOG-1 immunostaining is not a cost-effective method of identifying patients with CRC who may benefit from treatment with tyrosine kinase inhibitors. Copyright © 2015 Elsevier Inc. All rights reserved.
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2018-06-25
Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma
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Stenner, Markus; Müller, Klaus-Michael; Koopmann, Mario; Rudack, Claudia
2014-09-01
We report on a rare case of a laryngeal carcinoma arising in a multifocal pharyngolaryngeal oncocytic papillary cystadenoma (OPC). The disease of a 63-year-old man is well documented by computed and positron emission tomography, histology, and electron microscopy. We could show that an OPC can even develop in the pharynx. The coexistence of both tumors makes this a challenging diagnosis for pathologists. Treated by surgery and radiotherapy, both lesions dissolved. Based on the literature available, we discuss the theory that the laryngeal carcinoma might be the result of a true metaplasia facilitated by chronic irritation and recommend a regular follow-up for OPC too. As in benign oncocytic lesions, we could show that the detection of numerous mitochondria is a diagnostic indicator for malignant variants as well.
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Role of chronic lymphocytic thyroiditis in central node metastasis of papillary thyroid carcinoma.
Paulson, Lorien M; Shindo, Maisie L; Schuff, Kathryn G
2012-09-01
(1) To investigate the role of chronic lymphocytic thyroiditis (CLT) in central node metastasis of papillary thyroid carcinoma (PTC) and (2) to evaluate the presence of chronic lymphocytic thyroiditis according to PTC-specific molecular markers. Historical cohort study. Academic medical center. All patients who underwent total thyroidectomy with central neck dissection for PTC at Oregon Health & Science University between 2005 and 2010 were screened for the presence of CLT and reviewed for clinical prognostic factors. Patients with inadequate central neck dissections were excluded. Molecular markers for PTC were analyzed on archived tumor samples. A total of 139 patients met selection criteria. The rate of CLT was 43.8%. The rate of central node positivity was 63%. Presence of CLT was associated with a significantly lower proportion of central node metastases (49% vs 74%, P = .003) and angiolymphatic invasion (31% vs 15%, P = .03). There was no significant difference in mean age, tumor size, and extracapsular extension. Molecular genotyping did not reveal a significant difference in the types of mutations found in both groups. The data indicate a lower incidence of central compartment lymph node metastasis in those with CLT in this patient population, suggesting a potential protective role in tumor spread. The equal distribution of tumor mutations between the carcinomas with and without evidence of CLT argues against a mutation-specific antigen as the immunologic stimulus. Further research is needed to characterize the role of autoimmunity in thyroid cancer.
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Gene expression and the biological phenotype of papillary thyroid carcinomas.
Delys, L; Detours, V; Franc, B; Thomas, G; Bogdanova, T; Tronko, M; Libert, F; Dumont, J E; Maenhaut, C
2007-12-13
The purpose of this paper is to correlate the molecular phenotype of papillary thyroid carcinoma (PTC) to their biological pathology. We hybridized 26 PTC on microarrays and showed that nearly 44% of the transcriptome was regulated in these tumors. We then combined our data set with two published PTC microarray studies to produce a platform- and study-independent list of PTC-associated genes. We further confirmed the mRNA regulation of 15 genes from this list by quantitative reverse transcription-PCR. Analysis of this list with statistical tools led to several conclusions: (1) there is a change in cell population with an increased expression of genes involved in the immune response, reflecting lymphocyte infiltration in the tumor compared to the normal tissue. (2) The c-jun N-terminal kinase pathway is activated by overexpression of its components. (3) The activation of ERKK1/2 by genetic alterations is supplemented by activation of the epidermal growth factor but not of the insulin-like growth factor signaling pathway. (4) There is a downregulation of immediate early genes. (5) We observed an overexpression of many proteases in accordance with tumor remodeling, and suggested a probable role of S100 proteins and annexin A2 in this process. (6) Numerous overexpressed genes favor the hypothesis of a collective migration mode of tumor cells.
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Septin 7 immunoexpression in papillary thyroid carcinoma: a preliminary study.
Igci, Yusuf Ziya; Erkilic, Suna; Arslan, Ahmet
2014-07-01
Papillary thyroid carcinoma (PTC) is the most common type among thyroid cancers. The diagnosis of PTC may be challenging when follicular variant (FVPTC) of this disease is present due to the resemblance of nuclear properties of the classical type (CVPTC). However, making use of ancillary molecular markers in the diagnosis of PTC may help. In our study, we aimed to evaluate the SEPT7 protein expression in PTC. A total of 55 paraffin block tissue samples comprising encapsulated FVPTC (FVPTC(e), n=25), and CVPTC (n=15), and benign hyperfunctioning thyroid nodules (HypN, n=15) were used in this study. Nuclear, cytoplasmic, and overall (total) SEPT7 protein expression levels were determined by using immunohistochemistry. Nuclear, cytoplasmic, and overall SEPT7 expressions (p=0.02, p=0.001, p=0.002, respectively) were significantly lower in FVPTC(e) tissues when compared to HypN. In CVPTC group, nuclear expression was significantly lower (p=0.004) while overall and cytoplasmic expressions were not changed (p>0.05). In HypN group, highest nuclear (mean=2.73), cytoplasmic (mean=2.86), and overall (mean=2.86) expression scores were detected. Significantly lower SEPT7 expression in all expressional categories in FVPTC(e) group may be a sign of different molecular signature in this type of tissue. Copyright © 2014 Elsevier GmbH. All rights reserved.
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Gonzalo, Irene T Gaw; Itti, Emmanuel; Mlikotic, Anton; Pham, Le H; Cesar, Romeo B; Meignan, Michel; Mishkin, Fred S
2003-01-01
To evaluate the feasibility of using [(18)F]fluorodeoxyglucose ((18)FDG) triple-head coincidence imaging as a potential cost-effective alternative to positron emission tomography in the setting of suspected recurrence of papillary thyroid carcinoma. We retrospectively studied 10 patients with suspected recurrence of papillary carcinoma of the thyroid, who underwent (18)FDG coincidence imaging,(131)I scanning, and a reference anatomic scan (computed tomography, magnetic resonance imaging, or both) within 1 year in most cases. The (131)I scan detected the recurrence in five patients (62.5%) and failed to reveal recurrent cancer in three patients (37.5%); in contrast,(18)FDG imaging detected the recurrence in eight patients (100%) and was true negative in two patients in whom the scans were performed more than 1 year after effective therapy for the recurrence. The sensitivity of detection was unrelated to lesion size. The (18)FDG imaging results led to additional radiotherapy in all (131)I-negative patients, two of whom had high thyroglobulin levels and one of whom had a low thyroglobulin concentration but the presence of antithy-roglobulin antibodies. We conclude that (18)FDG triple-head coincidence imaging is useful for routine management of patients with thyroid cancer who have no abnormalities detected on (131)I scans but have high serum thyroglobulin levels. This technique, however, may not be as sensitive as a dedicated positron emission tomographic device, particularly for the assessment of small tumors.
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Sezer, Atakan; Celik, Mehmet; Bulbul, Buket Yilmaz; Can, Nuray; Tastekin, Ebru; Ayturk, Semra; Ustun, Funda; Guldiken, Sibel; Sut, Necdet
2017-01-01
Lymphovascular invasion (LVI) is an important prognostic factor in various solid tumors, however, data on the association between LVI and thyroid carcinomas are limited. In this study, we evaluated the relationship between LVI and clinicopathological features of papillary thyroid carcinoma (PTC). Six hundred seventy-eight patients diagnosed with PTC between 2012 and 2015 were included into the study. Patients were classified based on the presence or absence of LVI. Gender, age, ultrasonography (US), tumor size and multifocality, BRAFV600E mutation, perineural and capsular invasion, extrathyroid extension (ETE), nodal metastasis, and recurrences were evaluated, and risk analysis was performed for each parameter. The number of patients with LVI [LVI (+)] was 63, while the number of patients without LVI [LVI (-)] was 615. The female/male ratio was 564/114. LVI was present in 18.4% of male patients and in 7.4 % of female patients. In the age group between 17-25 years LVI was detected in 6/13 patients, and this result was statistically significant compared to other age groups (p = 0.004). Suspicious lymph nodes upon US, perineural or capsular invasion, ETE, tumor size, and nodal metastasis were significantly more frequent in LVI (+) group (p < 0.001). The frequency of BRAFV600E mutation was also significantly higher in LVI (+) group (p < 0.001). Overall, the presence of LVI was associated with gender, tumor size, age, lymph node metastasis, pathological lymph nodes, perineural and capsular invasion, ETE, and BRAFV600E mutation. These results suggest that in PTC patients undergoing thyroidectomy, the presence of LVI should be considered as an indicator of aggressive clinicopathological features and those patients should be followed up carefully for recurrences and metastasis. PMID:28284178
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Histopathologically proven mucinous cystadenocarcinoma metastatic to the choroid.
Henderson, Robert H; Cohen, Victoria M; Rath, Pamela P; Luthert, Philip; Hungerford, John L
2010-01-01
To report the first case of conventional transcleral choroidal biopsy in the diagnosis of ovarian carcinoma metastatic to the choroid and to summarize the published cases of ovarian carcinoma metastatic to the choroid. Case report and Medline literature review. This is the tenth case reported in the literature and the only case that underwent conventional transcleral choroidal biopsy. Transcleral choroidal biopsy allowed the diagnosis of metastatic mucinous cystadenocarcinoma of the ovary. Choroidal metastases are not associated with central nervous system involvement; however, investigations may reveal distal boney or pulmonary metastases. Ovarian carcinoma rarely metastases to the choroid and unlike breast carcinoma, concurrent central nervous system disease has not been reported. When systemic investigations fail to reveal active intraperitoneal disease or distal metastases, the clinician should consider referral to an ocular oncology center for a choroidal biopsy.
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Primary mucinous adenocarcinoma of the vulva, intestinal type
Lee, In Ho; Kim, Mi Kyung; Lee, Yoo Kyung; Hong, Sung Ran
2017-01-01
Primary vulva malignancy is a rare gynecologic malignancy. Most of them are squamous cell carcinomas and adenocarcinomas are much less common. Intestinal type is a rare variant of primary adenocarcinoma of the vulva. It histologically resembles mucinous colonic carcinomas. Origin from cloacal remnants has been suggested but remains speculative. A 64-year-old woman was referred to our clinic with a 1-month history of an itching vulva mass. An incisional biopsy was performed at other hospital and disclosed adenocarcinoma of intestinal type. Extensive workups were performed to detect other underlying carcinomas but revealed nothing abnormal. She underwent wide local excision without lymph node dissection for a primary vulva carcinoma. She received no adjuvant therapy and has been free from recurrent disease for 12 months after surgery. The authors report a rare case and review the relevant literature. PMID:28791269
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Fritz, Stefan; Fernandez-del Castillo, Carlos; Mino-Kenudson, Mari; Crippa, Stefano; Deshpande, Vikram; Lauwers, Gregory Y; Warshaw, Andrew L; Thayer, Sarah P; Iafrate, A John
2009-03-01
To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis.
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Lennon, Anne Marie; Victor, David; Zaheer, Atif; Ostovaneh, Mohammad Reza; Jeh, Jessica; Law, Joanna K.; Rezaee, Neda; Molin, Marco Dal; Ahn, Young Joon; Wu, Wenchuan; Khashab, Mouen A.; Girotra, Mohit; Ahuja, Nita; Makary, Martin A.; Weiss, Matthew J.; Hirose, Kenzo; Goggins, Michael; Hruban, Ralph H.; Cameron, Andrew; Wolfgang, Christopher L.; Singh, Vikesh K.; Gurakar, Ahmet
2015-01-01
Background Intraductal papillary mucinous neoplasms (IPMNs) have malignant potential, and can progress from low- to high-grade dysplasia to invasive adenocarcinoma. The management of patients with IPMNs is dependent on their risk of malignant progression, with surgical resection recommended for patients with branch duct-IPMN (BD-IPMN) who develop high-risk features. There is increasing evidence that liver transplant patients are at increased risk of extra-hepatic malignancy. However there are few data regarding the risk of progression of BD-IPMNs in liver transplant recipients. The aim of this study was to determine if liver transplant recipients with BD-IPMNs are at higher risk of developing high-risk features than patients with BD-IPMNs who did not receive a transplant. Methods Consecutive patients who underwent a liver transplant with BD-IPMNs were included. Patients with BD-IPMNs with no history of immunosuppression were used as controls. Progression of the BD-IPMNs was defined as development of a high-risk feature (jaundice, dilated main pancreatic duct, mural nodule, cytology suspicious or diagnostic for malignancy, cyst diameter ≥3cm). Results Twenty three liver transplant patients with BD-IPMN were compared with 274 control patients. The median length of follow-up was 53.7 and 24 months in liver transplant and control groups respectively. Four (17.4%) liver transplant patients and 45 (16.4%) controls developed high-risk features (p=0.99). In multivariate analysis, progression of BD-IPMNs was associated with age at diagnosis but not with liver transplantation. Conclusion There was no statistically significant difference in the risk of developing high-risk features between the liver transplant and control groups. PMID:25155689
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Kolb, Jennifer M; Argiriadi, Pamela; Lee, Karen; Liu, Xiaoyu; Bagiella, Emilia; Lucas, Aimee L; Kim, Michelle Kang; Kumta, Nikhil A; Nagula, Satish; Sarpel, Umut; DiMaio, Christopher J
2018-03-11
For patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs, cysts), it is a challenge to identify those at high risk for malignant lesions. We sought to identify factors associated with development of pancreatic cancer, focusing on neoplasm growth rate. We performed a retrospective study of 189 patients with BD-IPMNs who underwent at least 2 contrast-enhanced cross-sectional imaging studies, 1 year or more apart, at a tertiary referral center from January 2003 through 2013. Patients with cysts that had Fukuoka worrisome or high-risk features were excluded. Two radiologists reviewed all images. Cyst size was recorded at the initial and final imaging studies and growth rate was calculated. We collected patient demographic data, cyst characteristics, and clinical outcomes; univariate logistic regression models were used to determine the odds of developing worrisome features. The primary outcomes were to determine growth rate of low-risk BD-IPMNs and to assess whether cyst growth rate correlates high-risk features of IPMNs. Based on image analyses, cysts were initially a median 11 mm (range, 3-31 mm) and their final size was 12.5 mm (range, 3-42 mm). After a median follow-up time of 56 months (range, 12-163 months), the median cyst growth rate was 0.29 mm/year. Twelve patients developed worrisome features, no patients developed high-risk features, 4 patients had surgical resection, and no cancers developed. The rate of BD-IPMN growth was greater in patients who developed worrisome features than those who did not (2.84 mm/year vs 0.23 mm/year; P < .001). The odds of developing worrisome features increased for each unit (mm) increase in cyst size (odds ratio, 1.149; 95% CI, 1.035-1.276, P = .009). In a retrospective analysis of images from patients with BD-IPMN, we found low-risk BD-IPMNs to grow at an extremely low rate (less than 0.3 mm/year). BD-IPMNs in only about 6% of patients developed worrisome features, and none developed high-risk features
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Lee, Sohee; Kim, Ha Yan; Lee, Cho Rok; Park, Seulkee; Son, Haiyoung; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo
2014-07-01
Body image is associated with self-esteem and identity and has a close relationship with quality of life (QoL). We compared the impact of surgical scars on the patient's perception of body image between conventional open thyroidectomy (OT) and robotic thyroidectomy (RT) in female papillary thyroid carcinoma patients. From October 2009 to December 2010, we enrolled prospectively 116 papillary thyroid carcinoma patients who underwent total thyroidectomy at the Yonsei University Health System (Seoul, Korea). Of these 116 patients, 56 had OT and 60 RT. Their scars were assessed using the Vancouver Scar Scale (VSS), and psychometric properties were evaluated using the Body Image Scale (BIS) questionnaire postoperatively. Both groups were compared using cross-sectional and time-series methods. Mean age was significantly younger in the RT group. Regarding scar quality, the OT group showed superiority in scar pigmentation and the total VSS score during the early postoperative period, but the VSS score improved over time and was similar between both groups at 9 months. The RT group had better scores regarding most of the BIS items, a trend that remained relatively constant over time. In patients with noticeable scars (VSS ≥ 2) at 9 months, the RT group had better BIS scores regarding almost all items, including "self-conscious," "physical attractiveness," "feeling of less feminine," "sexual attractiveness," "dissatisfaction with body, scar and appearance when dressed," and "avoidance of people due to appearance." RT provides a better self-body image and improves QoL compared with conventional OT by avoiding a noticeable cervical scar. Copyright © 2014 Mosby, Inc. All rights reserved.
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Tulla, Kiara A; Maker, Ajay V
2018-03-01
Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging characteristics to determine appropriate surgical candidates. However, the majority of resected cysts remain low-risk lesions, many of which may be feasible to have under surveillance. We herein characterize the most promising and up-to-date molecular diagnostics in order to identify optimal components of a molecular signature to distinguish levels of IPMN dysplasia. A comprehensive systematic review of pertinent literature, including our own experience, was conducted based on the PRISMA guidelines. Molecular diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and serum were evaluated and organized into the following categories: oncogenes, tumor suppressor genes, glycoproteins, markers of the immune response, proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific targets in each of these categories, and in aggregate, were identified by their ability to both characterize a cyst as an IPMN and determine the level of cyst dysplasia. Combining molecular signatures with clinical and imaging features in this era of next-generation sequencing and advanced computational analysis will enable enhanced sensitivity and specificity of current models to predict the biologic behavior of IPMN.
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Thyroid carcinoma at King Edward VIII Hospital, Durban, South Africa.
Mulaudzi, T V; Ramdial, P K; Madiba, T E; Callaghan, R A
2001-05-01
Western literature depicts papillary carcinoma as the most common thyroid malignancy followed by follicular carcinoma. To assess the clinical pattern of thyroid carcinoma among African and Indian patients. King Edward VIII Hospital, Durban, South Africa. A retrospective study. One hundred patients with thyroid carcinoma treated at a tertiary teaching hospital between 1990 and 1997. Seventy seven patients were Africans and 23 were Indians. The male to female ratio was 1:6. Ninety eight patients presented with goitre with or without regional lymph node involvement or distant disease. The duration of symptoms ranged from one to 360 months. The mean age at presentation was 48.6 +/- 16.0 years. Follicular carcinoma was the most common malignancy among African patients (68%), followed by papillary carcinoma (16%), anaplastic carcinoma (13%) and medullary carcinoma (2.6%). Papillary carcinoma was the most common malignancy among Indian patients (57%) followed by follicular carcinoma and medullary carcinoma. There was no anaplastic carcinoma among Indian patients. Fifty five patients underwent lobectomy with 32 undergoing subsequent completion thyroidectomy. Nine patients had near total thyroidectomy, 27 were offered total thyroidectomy as primary surgery and eight had biopsy only. The in-hospital mortality was 8%. Recurrence rate was 8%. Most patients present long after the development of symptoms. Follicular carcinoma is the most common thyroid malignancy among Africans. Further studies are required to explain this phenomenon.
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Recurrent mucinous adenocarcinoma of the ovary presenting as an inguino-labial hernia.
Ben-Hur, H; Schachter, M; Mashiah, A; Lifschitz-Mercer, B; Pfeffermann, R
1996-01-01
We report a case of a 65-year-old woman who nine years previously had undergone total abdominal hysterectomy and bilateral salpingoophorectomy for a large ovarian cyst. During surgery the cyst had ruptured and some mucinous material had been spilled intraabdominally. Histopathological studies demonstrated the cyst to be a mucinous adenocarcinoma of low malignant potential. Appendectomy had also been performed due to an enlarged appendix, which proved to be a mucocoele. The patient had been lost to subsequent follow-up. Her current presenting symptom was a giant inguino-labial hernia of 25 cm diameter with two small skin perforations leaking a gelatinous discharge. Subsequent laparotomy and inguinal exploration have disclosed herniated small intestine with an attached metastatic multicystic mucinous adenocarcinoma. This case represents a case of borderline mucinous adeno-carcinoma-pseudomyxoma peritonei recurring in a unique pattern as a huge inguino-labial hernia, and serves to emphasize the possible consequences of spillage of ovarian cyst contents during surgery.
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Mean platelet volume could be a possible biomarker for papillary thyroid carcinomas.
Baldane, Suleyman; Ipekci, Suleyman H; Sozen, Mehmet; Kebapcilar, Levent
2015-01-01
Thyroid cancer is the most prevalent endocrine cancer and is evident in nearly 5% of thyroid nodules. The correlation between mean platelet volume (MPV) and many other cancer types has been investigated previously. However, the correlation between papillary thyroid carcinoma (PTC) and MPV has not yet been studied in detail. The aim of this study was to examine whether MPV would be a useful inflammatory marker to differentiate PTC patients from cases of benign goiter and healthy controls. Preoperative MPV levels in patients with PTC were found to be significantly higher when compared with benign goiter patients and healthy controls ((respectively, 8.05 femtoliter (fl), 7.57 fl, 7.36 fl, p=0.001). After surgical treatment of PTC patients, a significant decrease in MPV levels was seen (8.05 fl versus 7.60 fl, p=0.005). ROC analysis suggested 7.81 as the cut-off value for MPV (AUC=0.729, sensitivity 60%, specificity 80%). In conclusion, maybe changes in MPV levels can be used as an easily available biomarker for monitoring the risk of PTC in patients with thyroid nodules, enabling early diagnosis of PTC.
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Woodford, Randall Lyndon; Nikiforov, Yuri E; Hunt, Jennifer L; Bellizzi, Andrew M; Zhang, Xiaotang; Mills, Stacey E; Stelow, Edward B
2010-11-01
Encapsulated papillary oncocytic neoplasms (EPONs) of the thyroid are rare tumors, whose relationship to other thyroid tumors has not been thoroughly elucidated. Earlier, they have been regarded as variants of papillary thyroid carcinoma (PTC), hyperplastic lesions, and follicular neoplasms. Eighteen EPONs were retrieved from our surgical pathology files and reviewed for defining morphologic features. Cases having the typical nuclear features of PTC were excluded. Immunohistochemistry (IHC) for CK19, HBME1, and CD56 was carried out. Microdissection, polymerase chain reaction, and sequencing of exon 15 of the BRAF gene were completed. Cases were evaluated for rearranged in transformation/papillary thyroid carcinoma RET/PTC rearrangement by fluorescent in situ hybridization (FISH). The majority of the tumors exhibited a distinctive histologic appearance. They were composed of true papillae lined by a single layer of predominantly cuboidal cells with oncocytic cytoplasm; hobnailing was typically prominent. Three tumors showed taller cells with uniformly apical nuclei and no hobnailing. Ten of 18 cases showed vascular and/or capsular invasion; hence, if the diagnostic criteria used to evaluate follicular neoplasms are applied, more than half of the tumors would be considered minimally invasive carcinomas. No cases were immunoreactive with antibodies to HBME1, whereas only 1 of 13 was immunoreactive for CK19. Six of 7 interpretable cases were immunoreactive for CD56. No BRAF point mutations or RET/PTC rearrangements were identified in the examined cases. All patients were alive at the time of last follow-up and no locally recurrent disease had been reported; however, 1 case was remarkable for a lymph node metastasis. Our results confirm that EPONs are histologically, immunohistochemically, and molecularly distinct from papillary thyroid carcinoma and seem to be most related to follicular neoplasms.
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Akhter, Javed; Pillai, Krishna; Chua, Terence C; Alzarin, Naeef; Morris, David Lawson
2014-01-01
Compared to current treatment for pseudomyxoma peritonei (PMP), the extraction of solubilised mucin through peritoneal catheter can be minimally invasive. However, mucin has variable appearance that may influence mucolysis. Hence, we investigated the mucolysis of 36 mucin samples with a novel agent. Using visual inspection and hardness index, PMP mucin was classified into three grades. The mucin pathological category was identified from patient record. Subsequently, the dissolution of the samples was tested. For in vitro, 1 g of mucin was treated to the mucolytic agent in 10 ml TRIS buffer at 37 deg. Celsius for 3 hours, with weighing of residual mucin. Control treatment was similar but received TRIS buffer. For in vivo, 2 g of implanted intra-peritoneal mucin in nude rats was treated to mucolytic (2 X 500 ul/24 hr, over 48 hours, plus another treatment before sacrifice at 56 hours, with weighing of residual mucin. Controls were treated but only with TRIS buffer. Six animals were used for each mucin grade (3 mucolytic treated & and 3 controls). Grades of mucin were soft mucin (62%), semi hard (20%) and hard mucin (18%). Diffuse peritoneal adenomucinosis had 50% of soft mucin and peritoneal mucinous carcinoma had 11% (P = 0.0382). In vitro and in vivo absolute disintegration was 100% for soft, 57.38% and 48.67% for semi hard, 50% and 28.67% for hard mucin. Majority of mucin were soft with complete disintegration, the rest showed variable disintegration, suggesting that the mucolytic has potential for treating PMP. PMID:25232491
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Nguyen, Andrew H; Toste, Paul A; Farrell, James J; Clerkin, Barbara M; Williams, Jennifer; Muthusamy, V Raman; Watson, Rabindra R; Tomlinson, James S; Hines, O Joe; Reber, Howard A; Donahue, Timothy R
2015-02-01
The 2012 Sendai Criteria recommend that patients with 3 cm or larger branch duct intraductal papillary mucinous neoplasms (BD-IPMN) without any additional "worrisome features" or "high-risk stigmata" may undergo close observation. Furthermore, endoscopic ultrasound (EUS) is not recommended for BD-IPMN <2 cm. These changes have generated concern among physicians treating patients with pancreatic diseases. The purposes of this study were to (i) apply the new Sendai guidelines to our institution's surgically resected BD-IPMN and (ii) reevaluate cyst size cutoffs in identifying patients with lesions harboring high-grade dysplasia or invasive cancer. We retrospectively reviewed 150 patients at a university medical center with preoperatively diagnosed and pathologically confirmed IPMNs. Sixty-six patients had BD-IPMN. Pathologic grade was dichotomized into low-grade (low or intermediate grade dysplasia) or high-grade/invasive (high-grade dysplasia or invasive cancers). Fisher's exact test, chi-square test, student's t test, linear regression, and receiver operating characteristic (ROC) analyses were performed. The median BD-IPMN size on imaging was 2.4 cm (interquartile range 1.5-3.0). Fifty-one (77 %) low-grade and 15 (23 %) high-grade/invasive BD-IPMN were identified. ROC analysis demonstrated that cyst size on preoperative imaging is a reasonable predictor of grade with an area under the curve of 0.691. Two-thirds of high-grade/invasive BD-IPMN were <3 cm (n = 10). Compared to a cutoff of 3, 2 cm was associated with higher sensitivity (73.3 vs. 33.3 %) and negative predictive value (83.3 vs. 80 %, NPV) for high-grade/invasive BD-IPMN. Mural nodules on endoscopic ultrasound (EUS) or atypical cells on endoscopic ultrasound-fine needle aspiration (EUS-FNA) were identified in all cysts <2 and only 50 % of those <3 cm. Forty percent of cysts >3 cm were removed based on size alone. Our results suggest that "larger" size on noninvasive imaging can indicate high
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Wan, Han-Feng; Zhang, Bin; Yan, Dan-Gui; Xu, Zhen-Gang
2015-01-01
The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the BRAFT1799A mutation is associated with aggressive PTMC, the relationship between BRAFT1799A mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including BRAFT1799A mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. From January 2011 to December 2013,we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection. BRAFT1799A mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or BRAFT1799A mutation. A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was 0.33±0.21 cm. The BRAFT1799A mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or BRAFT1799A mutation. Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.
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Danilovic, Debora Lucia Seguro; de Mello, Evandro Sobroza; Frazzato, Eliana Salgado Turri; Wakamatsu, Alda; de Lima Jorge, Alexander Augusto; Hoff, Ana Oliveira; Marui, Suemi
2018-06-01
Nuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2, transcription factor of antioxidative genes. In the presence of reactive oxygen species, Keap1 (Kelch-ECH-associating protein-1) inhibitor complex undergoes conformational changes disrupting Keap1-Nrf2 binding and Nrf2 translocates into nucleus. We evaluated the presence of mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs) and correlated them with clinical presentation. Coding regions of NFE2L2 and KEAP1 were sequenced in 131 patients with PTC. Clinical and histopathological features were analyzed. Immunohistochemical analysis of Nrf2 expression was performed in mutated carcinomas. Although no mutations were found in NFE2L2, missense mutations in KEAP1 were observed in 6 patients with PTC (4.6%). Immunohistochemistry showed increased Nrf2 expression in nuclei of all mutated carcinomas, which presented poor prognostic features in histopathology. We identified mutations in KEAP1 associated with Nrf2 overexpression in PTC. Mutations favored disruption of inhibitory interaction Nrf2-Keap1 to enable increased antioxidant Nrf2 activity, possibly with prognostic consequences. © 2018 Wiley Periodicals, Inc.
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Expression and clinical significance of connective tissue growth factor in thyroid carcinomas.
Wang, Guimin; Zhang, Wei; Meng, Wei; Liu, Jia; Wang, Peisong; Lin, Shan; Xu, Liyan; Li, Enmin; Chen, Guang
2013-08-01
To examine expression of the connective tissue growth factor (CTGF) gene in human thyroid cancer and establish whether a correlation exists between the presence of CTGF protein and clinicopathological parameters of the disease. CTGF protein expression was investigated retrospectively by immunohistochemical analysis of CTGF protein levels in thyroid tumour tissue. Associations between immunohistochemical score and several clinicopathological parameters were examined. In total, 131 thyroid tissue specimens were included. High levels of CTGF protein were observed in papillary thyroid carcinoma tissue; benign thyroid tumour tissue scored negatively for CTGF protein. In papillary thyroid carcinoma, there was a significant relationship between high CTGF protein levels and Union for International Cancer Control disease stage III-IV, and presence of lymph node metastasis. In papillary thyroid carcinomas, CTGF protein levels were not significantly associated with sex or age. These findings suggest that the CTGF protein level is increased in papillary thyroid carcinoma cells compared with benign thyroid tumours. CTGF expression might play a role in the development of malignant tumours in the thyroid.
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Warthin-like variant of papillary thyroid carcinoma: single institution experience.
Jun, Hak Hoon; Kim, Seok-Mo; Hong, Soon Won; Lee, Yong Sang; Chang, Hang-Seok; Park, Cheong Soo
2016-06-01
Correct diagnosis of the variants of papillary thyroid carcinoma (PTC) is important because these variants differ in clinical course. The Warthin-like variant (WLV) is relatively uncommon and is recognized as not different from conventional PTC. We therefore assessed the clinicopathological features of patients with WLV of PTC who were diagnosed and treated at our institution. Of the 8179 patients treated for PTC at the Thyroid Cancer Center, Gangnam Severance Hospital, Yonsei University College of Medicine, between January 2007 and December 2012, 16 patients (0.2%) were pathologically diagnosed with WLV of PTC. Their clinicopathological features and post-operative follow-up for local recurrence and distant metastasis were retrospectively investigated. Mean patient age was 44.9 years (range: 23-61 years), with seven (44%) being younger than 45 years. Only one of the 16 patients was male (6%). Mean tumour size was 8.9 mm (range: 3-22 mm). Extrathyroidal extension was observed in seven patients (44%), associated thyroiditis in 11 (69%) and lymph node metastasis in six (38%). The mean follow-up period was 37 months (range: 13-78 months), during which none of the 16 patients experienced recurrence or metastasis. Fifteen patients (94%) had MACIS score <6, with the remaining patient having a MACIS score of 6.33. WLV of PTC is rare, with favourable prognosis. Nevertheless, it is important to determine the histopathological features of these tumours. © 2014 Royal Australasian College of Surgeons.
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Biankin, Andrew V; Kench, James G; Biankin, Sandra A; Lee, C-Soon; Morey, Adrienne L; Dijkman, Floriaan P; Coleman, Maxwell J; Sutherland, Robert L; Henshall, Susan M
2004-09-01
The development of pancreatic cancer (PC) several years after curative resection for noninvasive intraductal papillary mucinous neoplasm (IPMN) and the presence of PC distant from IPMN suggest that PC may develop independently of the IPMN. Here, we identified pancreatic intraepithelial neoplasia (PanIN) lesions, the putative precursors of PC, in the ducts of pancreata resected for IPMN and assessed the frequency of molecular aberrations common to PanIN and PC, within these lesions. The protein expression of p53, p21(WAF1/CIP1), cyclin D1, p16(INK4A) and DPC4/Smad4 were examined by immunohistochemistry in 267 PanIN lesions from a cohort of 23 patients with IPMN. Overexpression of p21(WAF1/CIP1) was present in PanIN-1A and -1B lesions and increased in frequency in PanIN-2 and PanIN-3. Overexpression of p53 and cyclin D1, and loss of p16(INK4A) expression were detected in PanIN-2 and PanIN-3 lesions. Loss of DPC4/Smad4 expression occurred only in the PanIN-3 lesions. PanIN lesions that were more dysplastic than the coincident IPMN were identified in 5 of 12 patients, and 2 of these contained a greater number of aberrations in protein expression than the IPMN. PanIN lesions seen in association with IPMN demonstrate molecular and histologic changes identical to PanIN lesions found in association with PC and, in some cases, are more advanced than the associated IPMN. These data suggest that PanIN lesions found in the ducts of a pancreas with IPMN may be relevant to the development of PC either coincident with IPMN or in the remnant pancreas after curative resection of IPMN.
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NONINVASIVE FOLLICULAR TUMOR WITH PAPILLARY-LIKE NUCLEAR FEATURES: NOT A TEMPEST IN A TEAPOT.
Agrawal, Nidhi; Abbott, Collette E; Liu, Cheng; Kang, Stella; Tipton, Laura; Patel, Kepal; Persky, Mark; King, Lizabeth; Deng, Fang-Ming; Bannan, Michael; Ogilvie, Jennifer B; Heller, Keith; Hodak, Steven P
2017-04-02
Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been retermed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative treatment since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radio-active iodine (RAI) therapy. This was a retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The conservative management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the aggressive management (AM) group received either completion thyroidectomy or RAI or both. From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 40 (16%) also received postsurgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17,629 ± 2,865, nearly twice the $8,637 ± 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer," the clinical indolence of these tumors will be better appreciated, and cost savings will result from more conservative and appropriate clinical management. AM = aggressive management CM = conservative management ENIFVPTC = encapsulated noninvasive form of FVPTC FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI
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Chakraborty, Subhankar; Swanson, Benjamin J; Bonthu, Neelima; Batra, Surinder K
2010-07-01
Mucins comprise a family of high-molecular-weight glycoproteins. MUC4, a large transmembrane mucin, has recently emerged as a novel marker for diagnosis, prognosis and therapy in several malignancies. However, its role in skin pathologies remains unknown. The aim of this study was to analyse the expression of MUC4 in cutaneous pathologies by immunohistochemistry for potential diagnostic, prognostic and therapeutic applications. A total of 330 tissue spots representing the normal skin, and benign and malignant cutaneous diseases, were analysed after staining with the monoclonal antibody to human MUC4 (clone 8G7). While the normal epidermis showed a negative to weak-positive expression of MUC4, its expression was significantly upregulated in squamous cell carcinomas (SCCs) where the intensity of staining correlated negatively with tumour grade and positively with age. A moderately strong MUC4 expression was also noted in 2/20 cancer adjacent normal skin and 2/21 chronically inflamed skin tissues, while 10/19 cases of vulval condyloma acuminate, 3/12 of vulval hyperplasia and 2 cases of verruca vulgaris also showed strong MUC4 positivity. Malignant melanoma, basal cell carcinoma and cutaneous cysts were negative. The results indicate that MUC4 expression is aberrantly upregulated in cutaneous SCCs, vulval condylomas and verruca vulgaris. Further, it appears that MUC4 expression in the skin may be modulated by chronic inflammation and the presence of an adjacent cutaneous malignancy in certain cases. These observations suggest a novel role for MUC4 mucin in the pathogenesis of cutaneous SCC and a possible application as a diagnostic and/or prognostic marker in cutaneous pathologies.
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Preoperative subclinical hypothyroidism in patients with papillary thyroid carcinoma.
Ahn, Dongbin; Sohn, Jin Ho; Kim, Jae Hyug; Shin, Chang Min; Jeon, Jae Han; Park, Ji Young
2013-01-01
To assess the effect of preoperative subclinical hypothyroidism on prognosis and on the tumour's clinicopathological features at initial diagnosis of papillary thyroid carcinoma (PTC). 328 patients who underwent surgery for PTC between January 2001 and December 2006 were enrolled in this study. Of these, we compared 35 patients with preoperative subclinical hypothyroidism with 257 patients who were euthyroid before the operation, with respect to clinicopathological characteristics and prognosis. No significant differences were observed in tumour size, extrathyroidal extension, and multifocality between subclinical hypothyroidism and euthyroid patients. Patients with subclinical hypothyroidism had a considerably lower percentage of lymph node metastasis than did euthyroid patients (8.6% vs. 21.8%, p=0.068). Although preoperative subclinical hypothyroidism decreased the risk of lymph node metastasis at 0.313 of odds ratio in the multivariate analysis, its significance was not verified (95% confidence internal, 0.089-1.092; p=0.068). Patients with preoperative subclinical hypothyroidism tended to have a better prognosis than did preoperative euthyroid patients, for both recurrence (2.9% vs. 14.0%, p=0.099) and 7-year disease-free survival (97.1% vs. 87.8%, p=0.079), during the 82-month mean follow-up period. However, even as thyroid-stimulating hormone (TSH) concentration increased, there were no consistent relationships observed between the TSH levels and the prognostic parameters. We could find neither a consistent positive nor a negative linear relationship between TSH levels and several prognostic parameters, indicating that subclinical hypothyroidism with elevated TSH is not an independent predictor of tumour aggressiveness and poor prognosis in PTC. Copyright © 2013 Elsevier Inc. All rights reserved.
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Mandai, Koichiro; Uno, Koji; Yasuda, Kenjiro
2014-08-01
This study aimed to evaluate the relationship between pancreatic ductal adenocarcinoma (PDAC) family history and PDAC development in patients followed up for intraductal papillary mucinous neoplasms (IPMNs) and to assess the cyst size relevance in determining follow-up strategies. We analyzed 300 patients with branch duct and mixed-type IPMN who were followed up at our facility. Among the patients aged 70 years or older, the frequency of PDAC did not differ significantly between those with 1 first-degree relative with PDAC and those without a family history. Although patients with IPMNs of greater than or equal to 30 mm were followed up for a significantly shorter duration than those patients with IPMNs of less than 30 mm, the frequency of IPMN progression and malignant IPMN was significantly greater in the former. The frequency of IPMN progression and pancreatic cancer did not differ significantly according to IPMN size (<10, 10-20, and 20-30 mm) in cases without mural nodules. Patients with 1 first-degree relative with PDAC can be followed up using the same criteria for patients without a family history. Special attention should be paid to IPMN progression and malignant transformation in patients with IPMNs of greater than or equal to 30 mm, but cyst size need not be considered when determining follow-up strategies for patients with IPMNs of less than 30 mm without mural nodules.
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Inhibition of the Growth of Papillary Thyroid Carcinoma Cells by CI-1040
Henderson, Ying C.; Ahn, Soon-Hyun; Clayman, Gary L.
2015-01-01
Background Papillary thyroid carcinoma (PTC), the most common type of thyroid malignancy, usually possesses mutations, either RET/PTC rearrangement or BRAF mutation. Both mutations can activate the mitogen-activated protein kinase kinase/extracellular signal–related kinase signaling transduction pathway, which results in activation of transcription factors that regulate cellular proliferation, differentiation, and apoptosis. Objective To test the effects of CI-1040 (PD184352), a specific MEK1/2 inhibitor, on PTC cells carrying either an RET/PTC1 rearrangement or a BRAF mutation. Design The effects of CI-1040 on PTC cells were evaluated in vitro and in vivo. Main Outcome Measures The effects of CI-1040 on PTC cells were evaluated in vitro using a cell proliferation assay, cell cycle analysis, and immunoblotting. The antitumor effects of CI-1040 in vivo were evaluated in an orthotopic mouse model. Results The concentrations of CI-1040 needed to inhibit 50% cell growth were 0.052μM for PTC cells with a BRAF mutation and 1.1μM for PTC cells with the RET/PTC1 rearrangement. After 3 weeks of oral administration of CI-1040 (300 mg/kg/d) to mice with orthotopic tumor implants of PTC cells, the mean tumor volume of implants bearing the RET/PTC1 rearrangement (n=5) was reduced 47.5% compared with untreated mice (from 701.9 to 368.5 mm3), and the mean volume of implants with a BRAF mutation (n=8) was reduced 31.3% (from 297.3 to 204.2 mm3). Conclusions CI-1040 inhibits PTC cell growth in vitro and in vivo. Because RET/PTC rearrangements are unique to thyroid carcinomas and a high percentage of PTCs possess either mutation, these findings support the clinical evaluation of CI-1040 for patients with PTC. PMID:19380355
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Nguyen, P L; Niehans, G A; Cherwitz, D L; Kim, Y S; Ho, S B
1996-01-01
Abnormalities of mucin-type glycoproteins have been described in lung cancers, but their molecular basis is unknown. In this study, mucin-core-peptide-specific antibodies and cDNA probes were used to determine the relative expression of mucin genes corresponding to one membrane-bound mucin (MUC1), two intestinal mucins (MUC2 and MUC3), and one tracheobronchial mucin (MUC4) in normal (nonneoplastic) lung, and in lung neoplasms. Normal lung tissues exhibited a distinct pattern of mucin gene expression, with high levels of MUC1 and MUC4 mRNA and low to absent levels of MUC2 and MUC3 mucin immunoreactivity and mRNA. In contrast, lung adenocarcinomas, especially well-differentiated cancers, exhibited increased MUC1, MUC3, and MUC4 mRNA levels. Lung squamous-cell, adenosquamous, and large-cell carcinomas were characterized by increased levels of MUC4 mucin only. We conclude that the expression of one membrane-bound and several secretory-type mucins is independently regulated and markedly altered in lung neoplasms. The frequent occurrence of increased MUC4 transcripts in a variety of non-small-cell lung cancers indicates the potential importance of this type of mucin in lung cancer biology.
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Dobrinja, C; Makovac, P; Pastoricchio, M; Cipolat Mis, T; Bernardi, S; Fabris, B; Piscopello, L; de Manzini, N
2016-04-01
The association between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) has been investigated for several years from different perspectives. In spite of that, there were only few attempts to design a common frame of references to understand the complex mutual interactions between the various pathways of inflammatory response and of thyroid tumor induction and progression. This study compares two independent groups of patients aiming to determine the frequency and the prognostic significance of CLT in patients with PTC. From January 2005 to September 2013, we conducted a retrospective study on 160 patients with PTC who underwent thyroidectomy. CLT was diagnosed histopathologically. Age, sex, tumor features (dimensions, angioinvasion, capsular infiltration, mono/multifocality and lymph node metastases) pathologic findings and outcome were considered. Mean follow-up (metastasis, completeness-of-resection, serum thyroglobulin levels, tumor recurrence) period was 61 months (ranged from 18 to 132 months). A p < 0.05 was considered statistically significant. Patients were divided in 2 groups. In group A there were 90 patients affected by PTC alone, and in group B there were 70 patients affected with PTC associated with CLT. Our data showed that the presence of CLT correlate with a lower grade of PTC (p < 0.05). Considering the sex of the patients there were a statistically significant correlation (p < 0.02) and the presence of CLT associated with PTC was most representative in female patients. The presence of CLT in patients with PTC correlated with a lower grade of PTC, but it does not affect the overall survival of papillary thyroid cancers. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.
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Multifocality and Bilaterality of Papillary Thyroid Microcarcinoma
So, Yoon Kyoung; Kim, Myung Woo
2015-01-01
Objectives Papillary thyroid carcinomas frequently occur as two or more separate foci within the thyroid gland (18%-87%). However, those multifocal tumors are easy to be undetected by preoperative radiologic evaluations, which lead to remnant disease after initial surgery. We aimed to study the incidence of multifocal papillary thyroid microcarcinomas (PTMCs), diagnostic accuracy of preoperative radiologic evaluation, predictive factors, and the chance of bilateral tumors. Methods Two hundred and seventy-seven patients with PTMC were included in this study. All patients underwent total thyroidectomy as an initial treatment. Medical records, pathologic reports, and radiological reports were reviewed for analysis. Results Multifocal PTMCs were detected in 100 of 277 patients (36.1%). The mean number of tumors in each patient was 1.6±1.1, ranging from 1 to 10. The additional tumor foci were significantly smaller (0.32±0.18 cm) than the primary tumors (0.63±0.22 cm) (P<0.001). There was no significant relationship between primary tumor size and the presence of contralateral tumors. With more tumors detected in one lobe, there was greater chance of contralateral tumors; 18.8% with single tumor focus, 30.2% with 2 tumor foci, and 46.2% with 3 or more tumor foci in one lobe. Sensitivity of preoperative sonography was 42.7% for multifocal tumors and 49.0% for bilateral tumors. With multivariate analysis, nodular hyperplasia was the only significant factor for multifocal tumors. Conclusion In cases of PTMCs, the incidence of multifocal tumors is high. However, additional tumor foci are too small to be diagnosed preoperatively, especially under the recent guidelines on radiologic screening tests for papillary thyroid carcinoma. Multifocal PTMCs have high risk of bilateral tumors, necessitating more extensive surgery or more thorough follow-up. PMID:26045918
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Mucinous cystic neoplasms of the pancreas: update on the surgical pathology and molecular genetics.
Fukushima, Noriyoshi; Zamboni, Giuseppe
2014-11-01
Mucinous cystic neoplasms (MCNs) of the pancreas are primary pancreatic cyst-forming neoplasms that can be a precursor to invasive adenocarcinoma of the pancreas. MCNs occur almost exclusively in the distal pancreas of middle-aged women. MCNs typically show a "cyst-in-cyst" pattern of growth and are well encapsulated by a thick fibrous wall. MCNs are composed of mucin-producing neoplastic epithelial cells and "ovarian-type" subepithelial stroma. The epithelium is dysplastic and the grade can range from low to high grade; some MCNs have an associated invasive carcinoma. It is this associated invasive carcinoma that determines prognosis. MCNs harbor several characteristic genetic and epigenetic alterations, some of which are shared with conventional invasive pancreatic ductal adenocarcinoma. Furthermore, several studies reveal characteristic patterns of gene expression in the ovarian-type stroma that suggest steroidogenesis in the ovarian-type stroma. Better knowledge of the molecular alterations could help in the management of patients with this type of precursor of invasive carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.
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Thyroid carcinoma in Graves' disease: A meta-analysis.
Staniforth, Joy U L; Erdirimanne, Senarath; Eslick, Guy D
2016-03-01
The incidence of thyroid carcinoma is increasing worldwide. Graves' disease is the most common hyperthyroid disease. Studies have suggested an increased risk of thyroid malignancy in Graves' disease: there has not yet been a meta-analysis to allow quantitative comparison. The purpose of this study was to determine the risk of thyroid carcinoma in Graves' disease, and to gather information on the histological subtypes of carcinoma and the co-existence of thyroid nodules. Several databases and article reference lists were searched. Inclusion criteria included appropriate diagnostic criteria for thyroid conditions and a diagnoses of carcinoma based on histology. 33 studies were selected, all reporting on surgically-resected specimens. The event rate of thyroid carcinoma in Graves' disease was 0.07 (95% CI 0.04 to 0.12). There was no data to allow comparison with patients without hyperthyroid diseases. There was no increase in the odds of developing carcinoma in Graves' disease compared to toxic multinodular goitre and toxic uninodular goitre. 88% of thyroid carcinomas in Graves' disease were papillary, with solitary papillary micro-carcinoma (diameter 10 mm or less) comprising 23% of all detected thyroid carcinomas. Patients with Graves' disease and co-existing thyroid nodules were almost 5 times more likely to be diagnosed with thyroid carcinoma than those without nodules. Thyroid malignancy in Graves' disease requiring surgical treatment should be considered as likely as in other hyperthyroid diseases needing surgical treatment. Clinicians should consider screening selected patients with Graves' disease for nodules whilst being aware of potentially over-diagnosing papillary micro-carcinoma. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.
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[GST genes expression as prognostic factor in papillary thyroid cancer].
Gonçalves, Antonio Jose; Monte, Osmar; Morari, Eliane Cristina; Ward, Laura Sterian; Nakasako, Diana Shimoda; Nieto, Juliana; Nakai, Marianne Yumi
2009-01-01
Analyze the relationship between the AMES classification and molecular factors from Glutation-S-Transferase System, specifically the GSTT1 and GSTM1 in patients with well differentiated thyroid cancer. Samples of thyroid tissue of 66 patients with papillary thyroid carcinoma were obtained (53 women and 13 men). Patients were divided in two groups (high and low risk) according to the AMES classification. In each group, presence of the null genotype of both GST enzymes system was studied. These results were compared with the AMES classification. Samples were obtained in the operating room immediately after thyroidectomy, placed in cryotubes, immersed in liquid nitrogen and stored in a freezer at -80 masculineC. DNA of this enzymes was extracted by the fenol-cloroformium method. There were 17 high risk patients and 49 low risk patients. The null genotype of the high risk group was 5.8% and in the other group was 6.1%. There was no relationship between absence of genes GSTT1 and GSTM1 and prognosis of the papillary thyroid carcinoma when compared to the AMES classifications.
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MicroRNA-mediated networks underlie immune response regulation in papillary thyroid carcinoma
NASA Astrophysics Data System (ADS)
Huang, Chen-Tsung; Oyang, Yen-Jen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen
2014-09-01
Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with low death rate but increased incidence and recurrence in recent years. MicroRNAs (miRNAs) are small non-coding RNAs with diverse regulatory capacities in eukaryotes and have been frequently implied in human cancer. Despite current progress, however, a panoramic overview concerning miRNA regulatory networks in PTC is still lacking. Here, we analyzed the expression datasets of PTC from The Cancer Genome Atlas (TCGA) Data Portal and demonstrate for the first time that immune responses are significantly enriched and under specific regulation in the direct miRNA-target network among distinctive PTC variants to different extents. Additionally, considering the unconventional properties of miRNAs, we explore the protein-coding competing endogenous RNA (ceRNA) and the modulatory networks in PTC and unexpectedly disclose concerted regulation of immune responses from these networks. Interestingly, miRNAs from these conventional and unconventional networks share general similarities and differences but tend to be disparate as regulatory activities increase, coordinately tuning the immune responses that in part account for PTC tumor biology. Together, our systematic results uncover the intensive regulation of immune responses underlain by miRNA-mediated networks in PTC, opening up new avenues in the management of thyroid cancer.
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Ruggeri, Rosaria Maddalena; Campennì, Alfredo; Giovinazzo, Salvatore; Saraceno, Giovanna; Vicchio, Teresa Manuela; Carlotta, Dario; Cucinotta, Maria Paola; Micali, Carmelo; Trimarchi, Francesco; Tuccari, Giovanni; Baldari, Sergio; Benvenga, Salvatore
2013-02-01
Autonomously functioning, "hot", thyroid nodules are not common in children and adolescents. Such nodules are not considered alarming because they are assumed to be benign adenomas. Herein, we present a 15-year-old girl with a papillary thyroid carcinoma of 3.5 cm in diameter, which was functionally autonomous and scintigraphically hot. The patient, initially referred to our Endocrine Unit because of a thyroid nodule, returned 6 months later for symptoms of hyperthyroidism. Hyperthyroidism was confirmed biochemically. Radioactive iodine ((131)I) thyroid scintigraphy was consistent with an autonomous thyroid nodule. As per guidelines, the patient underwent surgery and a pathological examination revealed papillary carcinoma, follicular variant. The excised nodule was examined for activating mutations of the thyrotropin receptor (TSHR), Gsα (GNAS1), H-RAS, N-RAS, K-RAS, and BRAF genes by direct sequencing. No mutations were found. Nevertheless, two combined nonfunctioning mutations were detected: a single-nucleotide polymorphism (SNP) of the TSHR gene, in exon 7, at codon 187 (AAT→AAC, both encoding asparagine), and a SNP within exon 8 of the Gsα gene at codon 185 (ATC→ATT, both encoding isoleucine). Both SNPs were also identified in the germline DNA of the patient. The same SNPs were sought in the parents and brother of our patient. Her father was heterozygous for the TSHR SNP, her mother heterozygous for the Gsα SNP, and her brother was wild type. This case demonstrates that the presence of hyperfunctioning thyroid nodule(s) does not rule out cancer and warrants careful evaluation, especially in childhood and adolescence to overlook malignancy.
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Gunawan, Bastian; von Heydebreck, Anja; Fritsch, Thekla; Huber, Wolfgang; Ringert, Rolf-Hermann; Jakse, Gerhard; Füzesi, László
2003-10-01
We evaluated clinical characteristics, patient outcome (mean follow-up, 47 months), and cytogenetic abnormalities in the largest as yet reported cytogenetic series of 47 primary and 11 secondary papillary renal cell carcinomas for differences between the recently proposed type 1 and type 2 subtypes. Secondary tumors were more often of type 2 morphology (P = 0.02), whereas primary type 2 tumors were associated with higher clinical stage (P = 0.001) and worse patient outcome (P = 0.02). Although both subtypes had at least one of the primary chromosomal gains at 17q, 7, and 16q, type 2 tumors had moderately lower frequencies of primary gains at 17p (61 versus 94%; P = 0.007) and 17q (72 versus 97%; P = 0.02). On the other hand, type 2 tumors overall had more chromosomal alterations than type 1 tumors (P = 0.01), particularly gains of 1q (28 versus 3%; P = 0.02) and losses of 8p (33 versus 0%; P = 0.001), 11 (28 versus 3%; P = 0.02), and 18 (44 versus 9%; P = 0.01). Hierarchical clustering suggested cytogenetic patterns common but not restricted to type 2 morphology, one characterized by multiple additional gains, and another predominantly showing additional losses. These findings provide genetic evidence that type 1 and type 2 tumors arise from common cytogenetic pathways and that type 2 tumors evolve from type 1 tumors. Independently of type, losses of 9p were statistically correlated with advanced disease (P = 0.0008) and may serve as a potential adverse prognostic marker in papillary renal cell carcinomas.
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Poorly Differentiated Thyroid Carcinoma.
Setia, Namrata; Barletta, Justine A
2014-12-01
Poorly differentiated thyroid carcinoma (PDTC) has been recognized for the past 30 years as an entity showing intermediate differentiation and clinical behavior between well-differentiated thyroid carcinomas (ie, papillary thyroid carcinoma and follicular thyroid carcinoma) and anaplastic thyroid carcinoma; however, there has been considerable controversy around the definition of PDTC. In this review, the evolution in the definition of PDTC, current diagnostic criteria, differential diagnoses, potentially helpful immunohistochemical studies, and molecular alterations are discussed with the aim of highlighting where the diagnosis of PDTC currently stands. Published by Elsevier Inc.
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Lawson, Robert D; Hunt, Gordon C; Giap, Andrew Q; Krinsky, Mary L; Slezak, Jeff; Tang, Raymond S; Gonzalez, Ingrid; Kwong, Wilson T; Fehmi, Syed A; Savides, Thomas J
2015-01-01
The risk of developing pancreatic cancer is uncertain in patients with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD-IPMN) based on the "high-risk stigmata" or "worrisome features" criteria proposed in the 2012 international consensus guidelines ("Fukuoka criteria"). Retrospective case series involving patients referred for endoscopic ultrasound (EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent with BD-IPMN. Rates of pancreatic cancer occurring at any location in the pancreas were compared between groups of patients with one or more Fukuoka criteria ("Highest-Risk Group", HRG) and those without these criteria ("Lowest-Risk Group", LRG). After exclusions, 661 patients comprised the final cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001). This study supports using Fukuoka criteria to stratify the immediate and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of pancreatic cancer was highest during the first year and occurred exclusively in those with "high-risk stigmata" or "worrisome features" criteria. After the first year all BD-IPMN continued to have a low but persistent cancer risk.
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Association of human papilloma virus with atypical and malignant oral papillary lesions.
McCord, Christina; Xu, Jing; Xu, Wei; Qiu, Xin; Muhanna, Nidal; Irish, Jonathan; Leong, Iona; McComb, Richard John; Perez-Ordonez, Bayardo; Bradley, Grace
2014-06-01
This study aimed to examine atypical and malignant papillary oral lesions for low- and high-risk human papillomavirus (HPV) infection and to correlate HPV infection with clinical and pathologic features. Sections of 28 atypical papillary lesions (APLs) and 14 malignant papillary lesions (MPLs) were examined for HPV by in situ hybridization and for p16 and MIB-1 by immunohistochemistry; 24 conventional papillomas were studied for comparison. Low-risk HPV was found in 10 of 66 cases, including 9 APLs and 1 papilloma. All low-risk HPV-positive cases showed suprabasilar MIB-1 staining, and the agreement was statistically significant (P < .0001). Diffuse p16 staining combined with high-risk HPV was not seen in any of the cases. A subset of HPV(-) APLs progressed to carcinoma. Oral papillary lesions are a heterogeneous group. Low-risk HPV infection is associated with a subset of APLs with a benign clinical course. Potentially malignant APLs and MPLs are not associated with low- or high-risk HPV. Copyright © 2014 Elsevier Inc. All rights reserved.
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Mohammad, A; Makaju, R
2006-01-01
To find out the spectrum of various histopathological types of primary neoplasms of different parts/organs of the female reproductive system seen at the Kathmandu University Teaching Hospital (KUTH) as there exists a worldwide wide variation in the distribution of various neoplasms, which appears largely due to exogenous factors rather than due to inherent differences between populations. This was a retrospective study. It was carried out at KUTH. All neoplasms of the female reproductive system seen at the KUTH during the period of 20 months from 1st January 2004 to 31st August 2005 were included in this study and examined by light microscope (LM). A total number of 60 cases of neoplasms of the female reproductive system were seen. Out of these, 1 (1.7%) was of the vagina (squamous cell carcinoma, papillary variant); 16 (26.7%) were of the cervix of the uterus (all squamous cell carcinoma in advanced stage); none were of the endometrium; 20 (33.3%) were of the body of the uterus/uterine muscle (all liomyomas); 16 (26.7%) were of the ovary, (11 benign, consisting of nine mature cystic tertoma, also known as dermoid cyst, one serous papillary cystdenoma and one mucinous cystadenoma; and, five malignant, consisting of two serous cystadenocarcinoma, two mucinous cystadenocarcinoma and one mixed mucinous and serous cystadenocarcinoma); and, 7 (11.6%) were of the breast (two benign, consisting of fibroadenoma and five malignant, all consisting of infiltrating ductal carcinoma in advanced stage). There were relatively a large number of cases of advanced stage of cancer of uterine cervix. All breast cancers seen were also in advanced stage. Endometrial carcinoma was conspicuously absent in our this small series of cases.
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Muller, Marie; Guillaud-Bataille, Marine; Salleron, Julia; Genestie, Catherine; Deveaux, Sophie; Slama, Abdelhamid; de Paillerets, Brigitte Bressac; Richard, Stéphane; Benusiglio, Patrick R; Ferlicot, Sophie
2018-02-06
Hereditary leiomyomatosis and renal cell carcinoma syndrome is characterized by an increased risk of agressive renal cell carcinoma, often of type 2 papillary histology, and is caused by FH germline mutations. A prominent eosinophilic macronucleolus with a perinucleolar clear halo is distinctive of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma according to the 2012 ISUP and 2016 WHO kidney tumor classification. From an immunohistochemistry perspective, tumors are often FH-negative and S-(2-succino)-cysteine (2SC) positive. We performed a pathology review of 24 renal tumors in 23 FH mutation carriers, and compared them to 12 type 2 papillary renal cell carcinomas from FH wild-type patients. Prominent eosinophilic nucleoli with perinucleolar halos were present in almost all FH-deficient renal cell carcinomas (23/24). Unexpectedly, they were also present in 58% of type 2 papillary renal cell carcinomas from wild-type patients. Renal cell carcinoma in mutation carriers displayed a complex architecture with multiple patterns, typically papillary, tubulopapillary, and tubulocystic, but also sarcomatoid and rhabdoid. Such pattern diversity was not seen in non-carriers. FH/2SC immunohistochemistry was informative as all hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas were either FH- or 2SC+. For FH and 2SC immunohistochemistries taken separately, sensitivity of negative anti-FH immunohistochemistry was 87.5% and specificity was 100%. For positive anti-2SC immunohistochemistry, sensitivity, and specificity were 91.7% and 91.7%, respectively. All FH wild-type renal cell carcinoma were FH-positive, and all but one were 2SC-negative. In conclusion, multiplicity of architectural patterns, rhabdoid/sarcomatoid components and combined FH/2SC staining, but not prominent eosinophilic nucleoli with perinucleolar halos, differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal
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Evans, Juanita J; Crist, Henry S; Durvesh, Saima; Bruggeman, Richard D; Goldenberg, David
2012-07-01
Anaplastic thyroid carcinoma (ATC) is an extremely aggressive and rapidly fatal neoplasm. The aim of this study was to identify a limited cell cycle associated protein expression pattern unique to ATC and to correlate that pattern with clinical outcome. This represents one of the largest tissue micro-array projects comparing the cell cycle protein expression data of ATC to other well-differentiated tumors in the literature. Tissue microarrays were created from 21 patients with ATC and an age and gender matched cohort of patients with papillary thyroid carcinoma (PTC). Expression of epidermal growth factor receptor, cyclin D1, cyclin E, p53, p21, p16, aurora kinase A, opioid growth factor (OGF), OGF-receptor, thyroglobulin and Ki-67 was evaluated in a semi-quantitative fashion. Differences in protein expression between the cohorts were evaluated using chi-square tests with Bonferroni adjustments. Survival time and presence of metastasis at presentation were collected. The ATC cohort showed a statistically significant decrease (p < 0.05) in thyroglobulin expression and statistically significant increases (p < 0.05) in Ki-67 and p53 expression as compared with the PTC cohort. A trend toward loss of p16 and p21 expression was noted in the ATC cohort. A trend toward decreased survival was noted with p21 expression. These data indicate disruption of the normal cell cycle with aberrant expression of multiple protein markers suggesting increased proliferative activity and loss of control of cell cycle progression to G₁ phase. These findings support the assertion that ATC may represent the furthest end of a continuum of thyroid carcinoma dedifferentiation.
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Yeo, Min-Kyung; Bae, Ja Seong; Lee, Sohee; Kim, Min-Hee; Lim, Dong-Jun; Lee, Youn Soo; Jung, Chan Kwon
2015-01-01
Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the salivary glands. Due to its rarity, the clinicopathologic and molecular features of WLPTC remain unclear. Methods. Of the 2,139 patients who underwent surgical treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and compared to 200 consecutive patients with classic PTC. BRAF mutation was tested with pyrosequencing. Results. There were no significant differences in age, predilection for women, multifocality, extrathyroidal extension, or lymph node metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly associated with Hashimoto's thyroiditis than classic PTCs (93% versus 36%, resp., P < 0.001) and showed significantly lower rate of BRAF mutation when compared to classic PTCs (65% versus 84%, resp., P = 0.007). In classic PTC, the frequency of BRAF mutations was negatively correlated with coexisting Hashimoto's thyroiditis. When we compared WLPTC and classic PTC in the patients with coexisting Hashimoto's thyroiditis, there were no significant differences in clinicopathologic characteristics or the BRAF mutational rate between the two groups. Conclusions. Patients with WLPTC have similar demographic, clinical, pathologic, and molecular characteristics to those with classic PTC coexisting with Hashimoto's thyroiditis.
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Yeo, Min-kyung; Bae, Ja Seong; Lim, Dong-Jun; Lee, Youn Soo
2015-01-01
Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the salivary glands. Due to its rarity, the clinicopathologic and molecular features of WLPTC remain unclear. Methods. Of the 2,139 patients who underwent surgical treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and compared to 200 consecutive patients with classic PTC. BRAF mutation was tested with pyrosequencing. Results. There were no significant differences in age, predilection for women, multifocality, extrathyroidal extension, or lymph node metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly associated with Hashimoto's thyroiditis than classic PTCs (93% versus 36%, resp., P < 0.001) and showed significantly lower rate of BRAF mutation when compared to classic PTCs (65% versus 84%, resp., P = 0.007). In classic PTC, the frequency of BRAF mutations was negatively correlated with coexisting Hashimoto's thyroiditis. When we compared WLPTC and classic PTC in the patients with coexisting Hashimoto's thyroiditis, there were no significant differences in clinicopathologic characteristics or the BRAF mutational rate between the two groups. Conclusions. Patients with WLPTC have similar demographic, clinical, pathologic, and molecular characteristics to those with classic PTC coexisting with Hashimoto's thyroiditis. PMID:25983754
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Painless thyroiditis associated to thyroid carcinoma: role of initial ultrasonography evaluation.
Valentini, Raisa Bressan; Macedo, Bruno Mussoi de; Izquierdo, Rogério Friedrich; Meyer, Erika Laurini Souza
2016-04-01
Even though it is a rare event, most associations of thyroid carcinoma with subacute thyroiditis described in the literature are related to its granulomatous form (Quervain's thyroiditis). We present a patient with subacute lymphocytic thyroiditis (painless thyroiditis) and papillary thyroid cancer that was first suspected in an initial ultrasound evaluation. A 30-year old female patient who was referred to the emergency room due to hyperthyroidism symptoms was diagnosed with painless thyroiditis established by physical examination and laboratory findings. With the presence of a palpable painless thyroid nodule an ultrasound was prescribed and the images revealed a suspicious thyroid nodule, microcalcification focus in the heterogeneous thyroid parenquima and cervical lymphadenopathy. Fine needle aspiration biopsy was taken from this nodule; cytology was assessed for compatibility with papillary thyroid carcinoma. Postsurgical pathology evaluation showed a multicentric papillary carcinoma and lymphocytic infiltration. Subacute thyroiditis, regardless of type, may produce transitory ultrasound changes that obscure the coexistence of papillary carcinoma. Due to this, initial thyroid ultrasound evaluation should be delayed until clinical recovery. We recommended a thyroid ultrasound exam for initial evaluation of painless thyroiditis, particularly in patients with palpable thyroid nodule. Further cytological examination is recommended in cases presenting with suspect thyroid nodule and/or non-nodular hypoechoic (> 1 cm) or heterogeneous areas with microcalcification focus.
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Chao, Kuan-Chong; Chen, Yi-Jen; Juang, Chi-Mou; Lau, Hei-Yu; Wen, Kuo-Chang; Sung, Pi-Lin; Fang, Feng-Ying; Twu, Nae-Fang; Yen, Ming-Shyen
2013-03-01
To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3-16.7] and PSOC groups (median 16.7 months, 95% CI 12.9-20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6-104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7-85.2; p = 0.006, log-rank statistic). PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ. Copyright © 2013. Published by Elsevier B.V.
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Diffuse sclerosing variant of thyroid carcinoma presenting as Hashimoto thyroiditis: a case report.
Vukasović, Anamarija; Kuna, Sanja Kusacić; Ostović, Karmen Trutin; Prgomet, Drago; Banek, Tomislav
2012-11-01
The aim of report is to present a case of a rare diffuse sclerosing variant of a papillary thyroid carcinoma. A 15-year old girl referred for ultrasound examination because of painless thyroid swelling lasting 10 days before. An ultrasound of the neck showed diffusely changed thyroid parenchyma, without nodes, looking as lymphocytic thyroiditis Hashimoto at first, but with snow-storm appearance, predominantly in the right lobe. Positive thyroid peroxidase antibodies (TPO-AT) also suggested Hashimoto thyroiditis. Repeated US-FNAB (fine needle-aspiration biopsy) of the right lobe revealed diffuse sclerosing variant of papillary thyroid carcinoma and patient underwent total thyreoidectomy. Patohistologic finding confirmed diffuse sclerosing variant of a papillary thyroid carcinoma in the both thyroid lobes and several metastatic lymph nodes. Two months later patient recived radioablative therapy with 3700 MBq (100 mCi) of 1-131 followed by levothyroxine replacement. At the moment, patient is without evidence of local or distant metastases and next regular control is scheduled in 6 months. In conclusion, a diffuse sclerosing variant is rare form of papillary thyroid carcinoma that echographically looks similar to Hashimoto thyroiditis and sometimes could be easily overlooked.
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Aspiration cytology of mammary analogue secretory carcinoma of the salivary gland.
Jung, Min Jung; Kim, Sang Yoon; Nam, Soon Yuhl; Roh, Jong-Lyel; Choi, Seung-Ho; Lee, Jeong Hyun; Baek, Jung Hwan; Cho, Kyung-Ja
2015-04-01
Aspiration cytologic findings of mammary analogue secretory carcinoma (MASC), a newly established salivary gland neoplasm defined by a t(12;15)(p13;q25) ETV6-NTRK3 translocation, are not fully characterized to date. We report cytologic descriptions of nine cases of molecularly confirmed MASC, including two with unusual findings. Aspiration smears from nine MASCs of the salivary glands were retrospectively reviewed and analyzed according to the cellular and structural features of the corresponding surgical specimens. Aspiration smears of MASC generally reflected the histologic diversity of the tumors. Among usual histologic findings, a micropapillary pattern was associated with a predominance of vacuolated individual cells on aspiration smears, a papillary-cystic pattern with a predominance of thin branching papillary structures, and a microcystic pattern with a predominance of irregular sheets of eosinophilic cells. There were two unusual cases, one with three-dimensional groups of high-grade atypical cells, and one with epithelial clusters floating in a notably mucinous background. These cases represented MASC with high-grade transformation and MASC with cystadenocarcinoma-like features, respectively. The secretory activity of MASC was not prominent in the aspiration specimens. Although unusual cases were present, most MASC cases showed characteristic cytologic findings, which could aid the cytologic diagnosis of MASC. And knowledge of the histologic spectrum of MASC, including high-grade transformation, could be valuable for cytological differential diagnoses of salivary gland tumors, and the management of patients with MASC. © 2014 Wiley Periodicals, Inc.
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Differentiated thyroid carcinoma with functional autonomy.
Yaturu, Subhashini; Fowler, Marjorie R
2002-01-01
To present a case of papillary carcinoma in an autonomously hyperfunctioning thyroid nodule. We chronicle the clinical and laboratory findings in a patient with a painless neck mass, with a particular focus on the pathologic findings after surgical removal of the right thyroid lobe. A 39-year-old woman had an enlarging nodule of the right thyroid lobe. Results of thyroid function tests suggested subclinical hyperthyroidism. Two months later, the patient complained of increasing swelling in the neck (but still had no symptoms suggestive of hyperthyroidism). Thus, resection of the right thyroid lobe was performed. Pathologic analysis disclosed low-grade papillary thyroid carcinoma within the nodule, with a small rim of compressed inactive-appearing thyroid tissue surrounding the nodule. Subsequently, she underwent total thyroidectomy and follow-up care for thyroid carcinoma. Although solitary hyperfunctioning nodules of the thyroid gland are usually considered benign, the current case suggests that the diagnosis of autonomous thyroid nodules does not preclude thyroid carcinoma in a functioning nodule.
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Haake, Scott M.; Li, Jiannong; Bai, Yun; Kinose, Fumi; Fang, Bin; Welsh, Eric; Zent, Roy; Dhillon, Jasreman; Pow-Sang, Julio; Chen, Yian Ann; Koomen, John; Rathmell, W. Kimryn; Fishman, Mayer; Haura, Eric B.
2016-01-01
Purpose Targeted therapies in renal cell carcinoma (RCC) are limited by acquired resistance. Novel therapeutic targets are needed to combat resistance and, ideally, target the unique biology of RCC subtypes. Experimental Design Tyrosine kinases provide critical oncogenic signaling and their inhibition has significantly impacted cancer care. In order to describe a landscape of tyrosine kinase activity in RCC that could inform novel therapeutic strategies, we performed a mass spectrometry-based system-wide survey of tyrosine phosphorylation in 10 RCC cell lines as well as 15 clear cell and 15 papillary RCC human tumors. To prioritize identified tyrosine kinases for further analysis, a 63 tyrosine kinase inhibitor (TKI) drug screen was performed. Results Among the cell lines, 28 unique tyrosine phosphosites were identified across 19 kinases and phosphatases including EGFR, MET, JAK2, and FAK in nearly all samples. Multiple FAK TKIs decreased cell viability by at least 50% and inhibited RCC cell line adhesion, invasion, and proliferation. Among the tumors, 49 unique tyrosine phosphosites were identified across 44 kinases and phosphatases. FAK pY576/7 was found in all tumors and many cell lines, while DDR1 pY792/6 was preferentially enriched in the papillary RCC tumors. Both tyrosine kinases are capable of transmitting signals from the extracellular matrix and emerged as novel RCC therapeutic targets. Conclusions Tyrosine kinase profiling informs novel therapeutic strategies in RCC and highlights the unique biology amongst kidney cancer subtypes. PMID:27220961
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Subcentimeter noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).
Rosario, Pedro Weslley
2018-05-23
Recently, it was proposed that the noninvasive encapsulated follicular variant of papillary thyroid carcinoma (noninvasive E-FVPTC) start to be called "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). 1 As the original cohort of 109 patients with NIFTP studied by the consensus conference included only tumors which were equal or more than 1 cm in size, the consensus diagnostic criteria of NIFTP did not explicitly address subcentimeter lesions. 1,2 In fact, in a recent review published in this journal, Hung & Barletta recognize that there are a few published subcentimetre NIFTP in the literature. 3 This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Primary mucinous cystadenocarcinoma of the breast with endocervical-like mucinous epithelium.
Lin, Dong-Liang; Hu, Ji-Lin; Shao, Shi-Hong; Sun, Dong-Mei; Wang, Ji-Gang
2013-12-01
Primary mucinous cystadenocarcinoma of the breast is an extremely rare entity. To the best of our knowledge, only 17 patients have been described in the PubMed database. Here, we report a primary breast mucinous cystadenocarcinoma with endocervical-like mucinous epithelium in a 62-year-old woman. The patient was followed for 5 months without any adjuvant treatment and she continues to be disease free. Primary breast mucinous cystadenocarcinoma usually displays unique pathologic and immunohistochemical characteristics simulating its ovarian counterparts; it seems to have a good prognosis after complete resection.
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Frank, Renee; Baloch, Zubair W; Gentile, Caren; Watt, Christopher D; LiVolsi, Virginia A
2014-09-01
Multifocal fibrosing thyroiditis (MFT) is characterized by numerous foci of fibrosis in a stellate configuration with fibroelastotic and fibroblastic centers entrapping epithelial structures. MFT has been proposed as a risk factor for papillary thyroid carcinoma (PTC) development. We attempted to identify whether MFT showed such molecular changes and could possibly be related to PTC. We identified seven cases of PTC with MFT in our institutional pathology database and personal consult service of one of the authors (VAL) for the years 1999 to 2012. Areas of PTC, MFT, and normal tissue were selected for BRAF analysis. Macro-dissection, DNA extraction and PCR amplification, and pyrosequencing were performed to detect BRAF mutations in codon 600. All of the MFT lesions and normal thyroid tissue were negative for BRAF mutations. Of the seven PTCs analyzed, five (71 %) were negative for BRAF mutations, while two cases were positive. In our study, none of the MFT lesions harbored BRAF mutations, whereas 29 % (two of seven) PTCs in the same gland were positive. Hence, in this small study, we found no evidence that the MFT lesion is a direct precursor to PTC. It is likely an incidental bystander in the process and a reflection of the background thyroiditis.
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Qiu, Wei-Hai; Chen, Gui-Yan; Cui, Lu; Zhang, Ting-Ming; Wei, Feng; Yang, Yong
2016-01-01
To identify differential pathways between papillary thyroid carcinoma (PTC) patients and normal controls utilizing a novel method which combined pathway with co-expression network. The proposed method included three steps. In the first step, we conducted pretreatments for background pathways and gained representative pathways in PTC. Subsequently, a co-expression network for representative pathways was constructed using empirical Bayes (EB) approach to assign a weight value for each pathway. Finally, random model was extracted to set the thresholds of identifying differential pathways. We obtained 1267 representative pathways and their weight values based on the co-expressed pathway network, and then by meeting the criterion (Weight > 0.0296), 87 differential pathways in total across PTC patients and normal controls were identified. The top three ranked differential pathways were CREB phosphorylation, attachment of GPI anchor to urokinase plasminogen activator receptor (uPAR) and loss of function of SMAD2/3 in cancer. In conclusion, we successfully identified differential pathways (such as CREB phosphorylation, attachment of GPI anchor to uPAR and post-translational modification: synthesis of GPI-anchored proteins) for PTC using the proposed pathway co-expression method, and these pathways might be potential biomarkers for target therapy and detection of PTC.
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Sai, Jin Kan; Suyama, Masafumi; Kubokawa, Yoshihiro; Watanabe, Sumio; Maehara, Tadayuki
2009-03-01
The International Consensus Guidelines are helpful for the management of branch-duct intraductal papillary mucinous neoplasms (IPMNs), because they allow us to exclude malignancy. However, it is not possible to predict malignancy with certainty, and further preoperative differentiation between benign and malignant IPMNs is required to avoid the false-positive results. To examine the usefulness of pancreatic-duct-lavage cytology by using an originally designed double-lumen catheter for discriminating benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines. Pancreatic-duct-lavage cytology was investigated in 24 patients with branch-duct IPMNs who underwent surgical resection based on the International Consensus Guidelines, namely, they either had intramural nodules or the ectatic branch duct was >30 mm in diameter. Single-center retrospective study. Academic medical center. The sensitivity and specificity of pancreatic-duct-lavage cytology for discriminating benign from malignant IPMNs. More than 30 mL of pancreatic-duct-lavage fluid was obtained from each patient, and there were no patients with noninformative results. The sensitivity, specificity, positive predictive value, and negative predictive value of the cytologic diagnosis were 78%, 93%, 88%, and 88%, respectively. Single-center and small number of patients. Pancreatic-duct-lavage cytology can improve differentiation between benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines.
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Srinivasan, Nandhini; Teo, Jin-Yao; Chin, Yung-Ka; Hennedige, Tiffany; Tan, Damien M; Low, Albert S; Thng, Choon Hua; Goh, Brian K P
2018-02-24
This systematic review was performed to assess the clinical utility of the Sendai Consensus Guidelines (SCG) and Fukuoka Consensus Guidelines (FCG) for intraductal papillary mucinous neoplasm (IPMN). A computerized search of PubMed was performed to identify all the studies which evaluated the SCG and FCG in surgically resected, histologically confirmed IPMNs. Ten studies evaluating the FCG, 8 evaluating the SCG and 4 evaluating both guidelines were included. In 14 studies evaluating the FCG, out of a total of 2498 neoplasms, 849 were malignant and 1649 were benign neoplasms. Pooled analysis showed that 751 of 1801 (42%) FCG+ve neoplasms were malignant and 599 neoplasms of 697 (86%) FCG-ve neoplasms were benign. PPV of the high risk and worrisome risk groups were 465/986 (47%) and 239/520 (46%) respectively. In 12 studies evaluating the SCG, 1234 neoplasms were analyzed of which 388 (31%) were malignant and 846 (69%) were benign. Pooled analysis demonstrated that 265 of 802 (33%) SCG+ve neoplasms were malignant and 238 of 266 SCG-ve (90%) neoplasms were benign. The FCG had a higher PPV compared to the SCG. However, the NPV of the FCG was slightly lower than that of the SCG. Malignant and even invasive IPMN may be missed according to both guidelines. Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Cytomorphologic features of papillary lesions of the male breast: a study of 11 cases.
Reid-Nicholson, Michelle D; Tong, Guoxia; Cangiarella, Joan F; Moreira, Andre L
2006-08-25
Breast masses occur in men far less commonly than women and are infrequently subjected to fine-needle aspiration (FNA) biopsy. Papillary lesions of the male breast are rare and are comprised of a spectrum of lesions ranging from papillary hyperplasia in gynecomastia to invasive papillary carcinoma. The following study describes the cytomorphology of papillary breast lesions in 11 men. The patients ranged in age from 23 to 78 years old and each presented with an unilateral subareolar or periareolar breast mass that varied in size from 0.5 to 3 cm. Two patients presented with bloody nipple discharge. Archival material (8-year period) from FNA biopsies of papillary lesions of the male breast was reviewed. The reviewed cases were correlated with appropriate clinicopathologic follow-up. The smears had variable cellularity but all showed papillary clusters of mammary epithelial cells with and without fibrovascular cores. Single epithelial cells with a high nuclear-to-cytoplasmic ratio and eccentric nuclei were seen in all smears; however, these were more numerous in cases of adenocarcinoma. Hemosiderin-laden macrophages were present in all cases. Nipple discharge was seen only in the 2 benign lesions. All adenocarcinomas occurred in older men. The only cytologic criteria that differentiated benign from malignant papillary lesions were marked cellularity and the presence of abundant 3-dimensional clusters. To the best of the authors' knowledge, the current series is the largest in the English literature to date that examines the cytomorphologic features of papillary breast lesions in men. Copyright 2006 American Cancer Society.
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Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma
Fu, Hangcheng; Liu, Yidong; Xu, Le; Chang, Yuan; Zhou, Lin; Zhang, Weijuan; Yang, Yuanfeng; Xu, Jiejie
2016-01-01
Abstract Mucin-4 (MUC4), a member of membrane-bound mucins, has been reported to exert a large variety of distinctive roles in tumorigenesis of different cancers. MUC4 is aberrantly expressed in clear-cell renal cell carcinoma (ccRCC) but its prognostic value is still unveiled. This study aims to assess the clinical significance of MUC4 expression in patients with ccRCC. The expression of MUC4 was assessed by immunohistochemistry in 198 patients with ccRCC who underwent nephrectomy retrospectively in 2003 and 2004. Sixty-seven patients died before the last follow-up in the cohort. Kaplan–Meier method with log-rank test was applied to compare survival curves. Univariate and multivariate Cox regression models were applied to evaluate the prognostic value of MUC4 expression in overall survival (OS). The predictive nomogram was constructed based on the independent prognostic factors. The calibration was built to evaluate the predictive accuracy of nomogram. In patients with ccRCC, MUC4 expression, which was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 3.891; P < 0.001), was negatively associated with tumor size (P = 0.036), Fuhrman grade (P = 0.044), and OS (P < 0.001). The prognostic accuracy of TNM stage, UCLA Integrated Scoring System (UISS), and Mayo clinic stage, size, grade, and necrosis score (SSIGN) prognostic models was improved when MUC4 expression was added. The independent prognostic factors, pT stage, distant metastases, Fuhrman grade, sarcomatoid, and MUC4 expression were integrated to establish a predictive nomogram with high predictive accuracy. MUC4 expression is an independent prognostic factor for OS in patients with ccRCC. PMID:27124015
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Zhu, Feng; Shen, Yi Bin; Li, Fu Qiang; Fang, Yun; Hu, Liang; Wu, Yi Jun
2016-01-01
Abstract The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT). A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases. Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC-associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126–0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with
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Lawson, Robert D.; Hunt, Gordon C.; Giap, Andrew Q.; Krinsky, Mary L.; Slezak, Jeff; Tang, Raymond S.; Gonzalez, Ingrid; Kwong, Wilson T.; Fehmi, Syed A.; Savides, Thomas J.
2015-01-01
Background The risk of developing pancreatic cancer is uncertain in patients with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD-IPMN) based on the “high-risk stigmata” or “worrisome features” criteria proposed in the 2012 international consensus guidelines (“Fukuoka criteria”). Methods Retrospective case series involving patients referred for endoscopic ultrasound (EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent with BD-IPMN. Rates of pancreatic cancer occurring at any location in the pancreas were compared between groups of patients with one or more Fukuoka criteria (“Highest-Risk Group”, HRG) and those without these criteria (“Lowest-Risk Group”, LRG). Results After exclusions, 661 patients comprised the final cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001). Conclusions This study supports using Fukuoka criteria to stratify the immediate and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of pancreatic cancer was highest during the first year and occurred exclusively in those with “high-risk stigmata” or “worrisome features” criteria. After the first year all BD-IPMN continued to have a low but persistent cancer risk. PMID:26423829
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Primary Mucinous Cystadenocarcinoma of the Breast with Endocervical-Like Mucinous Epithelium
Lin, Dong-Liang; Hu, Ji-Lin; Shao, Shi-Hong; Sun, Dong-Mei; Wang, Ji-Gang
2013-01-01
Summary Background Primary mucinous cystadenocarcinoma of the breast is an extremely rare entity. To the best of our knowledge, only 17 patients have been described in the PubMed database. Case Report Here, we report a primary breast mucinous cystadenocarcinoma with endocervical-like mucinous epithelium in a 62-year-old woman. The patient was followed for 5 months without any adjuvant treatment and she continues to be disease free. Conclusions Primary breast mucinous cystadenocarcinoma usually displays unique pathologic and immunohistochemical characteristics simulating its ovarian counterparts; it seems to have a good prognosis after complete resection. PMID:24550753
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McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler
2014-01-01
Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431
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Hu, Wei; Shi, Jun-Yi; Sheng, Yuan; Ll, Li
2008-03-01
The treatment for papillary thyroid carcinoma (PTC) without cervical lymph node metastasis (cN0) is controversial. This study was to explore a suitable method to dissect cervical lymph nodes for stage cN0 PTC patients. Eighty-four stage cN0 PTC patients, diagnosed by B ultrasound or cervical MRI from 2005--2006, were randomly divided into two groups. Thyroidectomy and ipsilateral central lymph node dissection were performed in Group A, while only thyroidectomy was performed in Group B. Each group contained 42 patients. Both groups took thyroxin tablets after operation. An average of 3 lymph nodes were found in each case of Group A, and the lymph node metastasis rate was 47.62%. The occurrence rates of complications were not significantly different between the two groups (P<0.05). Thyroidectomy plus ipsilateral central lymph node dissection is recommended for the treatment of stage cN0 PTC. It can also avoid damage of recurrent laryngeal nerve in re-dissection.
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Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung
2016-01-01
Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385
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Lee, Seung Eun; Hwang, Tae Sook; Choi, Yoon-La; Kim, Wook Youn; Han, Hye Seung; Lim, So Dug; Kim, Wan-Seop; Yoo, Young Bum; Kim, Suk Kyeong
2017-06-01
The BRAF V600E mutation in papillary thyroid carcinoma (PTC) is particularly prevalent in Korea, and a considerable number of wild-type BRAF PTCs harbor RAS mutations. In addition, subsets of other genetic alterations clearly exist, but their prevalence in the Korean population has not been well studied. Recent increased insight into noninvasive encapsulated follicular variant PTC has prompted endocrine pathologists to reclassify this entity as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). This study analyzed the genetic alterations among the histologic variants of PTC, including NIFTP. Mutations of the BRAF and RAS genes and rearrangement of the RET/PTC1, NTRK1, and ALK genes using 769 preoperative fine-needle aspiration specimens and resected PTCs were analyzed. Molecular alterations were found in 687 (89.3%) of 769 PTCs. BRAF V600E mutation (80.8%) was the most frequent alteration, followed by RAS mutation and RET/PTC1, NTRK1, and ALK rearrangements (5.6%, 2.1%, 0.4%, and 0%, respectively). The low prevalence of NTRK1 fusions and the absence of an ALK fusion detected in Korea may also be attributed to the higher prevalence of the BRAF V600E mutation. There were significant differences in the frequency of the genetic alterations among the histologic variants of PTC. The prevalence of NIFTP in PTC was 2.7%, and among the NIFTPs, 28.6% and 57.1% harbored BRAF and RAS mutations, respectively. Clinicopathologic factors and mutational profiles between NIFTP and encapsulated follicular variant PTC with capsular invasion group were not significantly different. Genetic alterations in PTC vary among its different histologic variants and seem to be different in each ethnic group.
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Haake, Scott M; Li, Jiannong; Bai, Yun; Kinose, Fumi; Fang, Bin; Welsh, Eric A; Zent, Roy; Dhillon, Jasreman; Pow-Sang, Julio M; Chen, Y Ann; Koomen, John M; Rathmell, W Kimryn; Fishman, Mayer; Haura, Eric B
2016-11-15
Targeted therapies in renal cell carcinoma (RCC) are limited by acquired resistance. Novel therapeutic targets are needed to combat resistance and, ideally, target the unique biology of RCC subtypes. Tyrosine kinases provide critical oncogenic signaling and their inhibition has significantly impacted cancer care. To describe a landscape of tyrosine kinase activity in RCC that could inform novel therapeutic strategies, we performed a mass spectrometry-based system-wide survey of tyrosine phosphorylation in 10 RCC cell lines as well as 15 clear cell and 15 papillary RCC human tumors. To prioritize identified tyrosine kinases for further analysis, a 63 tyrosine kinase inhibitor (TKI) drug screen was performed. Among the cell lines, 28 unique tyrosine phosphosites were identified across 19 kinases and phosphatases including EGFR, MET, JAK2, and FAK in nearly all samples. Multiple FAK TKIs decreased cell viability by at least 50% and inhibited RCC cell line adhesion, invasion, and proliferation. Among the tumors, 49 unique tyrosine phosphosites were identified across 44 kinases and phosphatases. FAK pY576/7 was found in all tumors and many cell lines, whereas DDR1 pY792/6 was preferentially enriched in the papillary RCC tumors. Both tyrosine kinases are capable of transmitting signals from the extracellular matrix and emerged as novel RCC therapeutic targets. Tyrosine kinase profiling informs novel therapeutic strategies in RCC and highlights the unique biology among kidney cancer subtypes. Clin Cancer Res; 22(22); 5605-16. ©2016 AACR. ©2016 American Association for Cancer Research.
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Esophageal adenosquamous carcinoma mimicking acantholytic squamous cell carcinoma
Matsukuma, Susumu; Takahashi, Oh; Utsumi, Yoshitaka; Tsuda, Masaki; Miyai, Kosuke; Okada, Kenji; Takeo, Hiroaki
2017-01-01
Herein is described a unique case of esophageal cancer mimicking acantholytic squamous cell carcinoma (SCC). The patient succumbed to the disease within one month of diagnosis. Autopsy revealed a 10-cm esophageal tumor, characterized by prominent acantholysis-like areas composed of discohesive cancer cells, along with nested growth of SCC. These discohesive cancer cells focally exhibited pagetoid extension into adjacent esophageal epithelium, comprised ~60% of the esophageal tumor volume and had widely metastasized to the lungs, chest wall, liver, spleen, right adrenal gland, bones and lymph nodes. No metastases of SCC were observed. SCC cells were immunohistochemically positive for keratin 5/6 and E-cadherin and were negative for mucin and carcinoembryonic antigen (CEA). However, the discohesive cancer cells exhibited negativity for keratin 5/6, positivity for mucin and CEA, and diminished or no immunostaining for E-cadherin. Thus, these discohesive cells represented true adenocarcinomatous differentiation rather than acantholytic SCC cells. It was concluded that this tumor was an esophageal adenosquamous carcinoma with ‘pseudo’-acantholytic adenocarcinoma components, which should be considered as a rare but distinctive type of aggressive cancer. PMID:29085501
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Pathology of carcinoma in situ of the urinary bladder and related lesions.
Farrow, G M
1992-01-01
In the United States, nearly all cases of bladder cancer are of the transitional cell type, and epidemiological evidence indicates that among these, approximately 80% present initially as more or less well-differentiated, superficial papillary neoplasms with a tendency for multifocal or diffuse involvement of the urothelial surface and/or recurrent tumor episodes, but with limited potential for invasive growth or a lethal outcome. Bladder tumors with lethal potential generally begin as poorly differentiated, sessile growths that are usually invasive at first diagnosis. Carcinoma in situ is a change that must be elicited among intact surface cells before progressive proliferation results in a tumor mass. Evidence for such an association is both temporal and spatial. Since most transitional cell carcinomas begin as well-differentiated tumors, i.e., resembling normal urothelium, recognition of early neoplastic alteration before a papillary structure forms is unlikely and most of the evidence is spatial based upon urothelial changes adjacent to papillary tumors. The morphologic definition of carcinoma in situ is arbitrary and generally defined as a total replacement of the urothelial surface by cells which bear morphologic features of carcinoma, but which lack architectural alteration other than an increase in the number of cell layers, i.e., a flat lesion. The Union Internationále Contra Cancer/American Joint Committee on Cancer (UICC/AJCC) staging scheme for bladder cancer distinguishes non-invasive papillary growths as Ta and carcinoma in situ as Tis. Because detection of carcinoma in situ, either by cytology or biopsy, depends upon recognizable malignant morphologic characteristics, studies of the lesion tend to be limited to the higher grade or more anaplastic examples.(ABSTRACT TRUNCATED AT 250 WORDS)
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Competing endogenous RNA regulatory network in papillary thyroid carcinoma.
Chen, Shouhua; Fan, Xiaobin; Gu, He; Zhang, Lili; Zhao, Wenhua
2018-05-11
The present study aimed to screen all types of RNAs involved in the development of papillary thyroid carcinoma (PTC). RNA‑sequencing data of PTC and normal samples were used for screening differentially expressed (DE) microRNAs (DE‑miRNAs), long non‑coding RNAs (DE‑lncRNAs) and genes (DEGs). Subsequently, lncRNA‑miRNA, miRNA‑gene (that is, miRNA‑mRNA) and gene‑gene interaction pairs were extracted and used to construct regulatory networks. Feature genes in the miRNA‑mRNA network were identified by topological analysis and recursive feature elimination analysis. A support vector machine (SVM) classifier was built using 15 feature genes, and its classification effect was validated using two microarray data sets that were downloaded from the Gene Expression Omnibus (GEO) database. In addition, Gene Ontology function and Kyoto Encyclopedia Genes and Genomes pathway enrichment analyses were conducted for genes identified in the ceRNA network. A total of 506 samples, including 447 tumor samples and 59 normal samples, were obtained from The Cancer Genome Atlas (TCGA); 16 DE‑lncRNAs, 917 DEGs and 30 DE‑miRNAs were screened. The miRNA‑mRNA regulatory network comprised 353 nodes and 577 interactions. From these data, 15 feature genes with high predictive precision (>95%) were extracted from the network and were used to form an SVM classifier with an accuracy of 96.05% (486/506) for PTC samples downloaded from TCGA, and accuracies of 96.81 and 98.46% for GEO downloaded data sets. The ceRNA regulatory network comprised 596 lines (or interactions) and 365 nodes. Genes in the ceRNA network were significantly enriched in 'neuron development', 'differentiation', 'neuroactive ligand‑receptor interaction', 'metabolism of xenobiotics by cytochrome P450', 'drug metabolism' and 'cytokine‑cytokine receptor interaction' pathways. Hox transcript antisense RNA, miRNA‑206 and kallikrein‑related peptidase 10 were nodes in the ceRNA regulatory network
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Functional significance of CD105-positive cells in papillary renal cell carcinoma.
Matak, Damian; Brodaczewska, Klaudia K; Szczylik, Cezary; Koch, Irena; Myszczyszyn, Adam; Lipiec, Monika; Lewicki, Slawomir; Szymanski, Lukasz; Zdanowski, Robert; Czarnecka, Anna M
2017-01-05
CD105 was postulated as a renal cell carcinoma (RCC) stem cell marker, and CD133 as a putative RCC progenitor. Hypoxia, a natural microenvironment that prevails in tumors, was also incorporated into the study, especially in terms of the promotion of hypothetical stem-like cell properties. Within this study, we verify the existence of CD105+ and CD133+ populations in selected papillary subtype RCC (pRCC) cell lines. Both populations were analyzed for correlation with stem-like cell properties, such as stemness gene expression, and sphere and colony formation. For the preliminary analysis, several RCC cell lines were chosen (786-O, SMKT-R2, Caki-2, 796-P, ACHN, RCC6) and the control was human kidney cancer stem cells (HKCSC) and renal cells of embryonic origin (ASE-5063). Four cell lines were chosen for further investigation: Caki-2 (one of the highest numbers of CD105+ cells; primary origin), ACHN (a low number of CD105+ cells; metastatic origin), HKCSC (putative positive control), and ASE-5063 (additional control). In 769-P and RCC6, we could not detect a CD105+ population. Hypoxia variously affects pRCC cell growth, and mainly diminishes the stem-like properties of cells. Furthermore, we could not observe the correlation of CD105 and/or CD133 expression with the enhancement of stem-like properties. Based on this analysis, CD105/CD133 cannot be validated as cancer stem cell markers of pRCC cell lines.
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Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma.
Kim, Seo Ki; Woo, Jung-Woo; Lee, Jun Ho; Park, Inhye; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo
2016-01-01
It has been reported that papillary thyroid carcinoma (PTC) with chronic lymphocytic thyroiditis (CLT) is less associated with extrathyroidal extension (ETE), advanced tumor stage and lymph node (LN) metastasis. Other studies have suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients. Since the clinical significance of the BRAF mutation has been particularly associated with conventional PTC, the purpose of this study was to determine the clinical significance of CLT according to BRAF mutation status in conventional PTC patients. We retrospectively reviewed the medical records of 3332 conventional PTC patients who underwent total thyroidectomy with bilateral central neck dissection at the Thyroid Cancer Center of Samsung Medical Center between January 2008 and June 2015. In this study, the prevalence of BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%). CLT was an independent predictor for low prevalence of ETE in both BRAF-negative (OR=0.662, P=0.023) and BRAF-positive (OR=0.817, P=0.027) conventional PTC patients. In addition, CLT was an independent predictor for low prevalence of CLNM in both BRAF-negative (OR=0.675, P=0.044) and BRAF-positive (OR=0.817, P=0.030) conventional PTC patients. In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT. However, CLT was an independent predictor for less aggressiveness in conventional PTC patients regardless of BRAF mutation status. © 2016 Society for Endocrinology.
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Kihara, Atsushi; Yoshida, Hiroshi; Watanabe, Reiko; Takahashi, Kenta; Kato, Tomoyasu; Ino, Yoshinori; Kitagawa, Masanobu; Hiraoka, Nobuyoshi
2017-07-01
Microcystic, elongated, and fragmented (MELF) pattern is seen in the invasive front of some endometrial endometrioid carcinomas. Although MELF pattern can be expected as an indicator of patient outcomes, its prognostic significance remains unclear. This study was conducted to elucidate clinicopathologic features and the prognostic impact of MELF pattern in patients with endometrial endometrioid carcinoma. We retrospectively analyzed data of 479 consecutive patients with endometrial endometrioid carcinoma that had been surgically resected. In 45 of 427 patients (11%) with low-grade endometrioid carcinoma, MELF pattern was found, but it was found in none of the 52 patients with high-grade endometrioid carcinoma. Among the patients with low-grade endometrioid carcinoma, MELF pattern was associated significantly with larger tumor size, myometrial invasion of more than 50%, advanced International Federation of Gynecology and Obstetrics stages, lymphovascular space invasion, lymph node metastasis, papillary architecture, and mucinous differentiation. However, survival analysis revealed that the patients with MELF pattern showed no significantly worse prognosis than those without MELF pattern either in disease-specific survival or in recurrence-free survival. MELF was not a significant prognosticator after adjustment for International Federation of Gynecology and Obstetrics stage (disease-specific survival [hazard ratio, 1.47; 95% confidence interval, 0.28-7.67; P=0.64], recurrence-free survival [hazard ratio, 0.98, 95% confidence interval, 0.32-2.99, P=0.98]). Immunohistochemical analysis revealed that MELF pattern was positive for p16 and p21 and almost negative for Ki-67 labeling, which suggested that tumor cells in MELF pattern were involved in growth arrest or cellular senescence. We conclude that MELF pattern could have little impact on outcomes of patients with low-grade endometrial endometrioid carcinoma.
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Abrosimov, Alexander; Saenko, Vladimir; Meirmanov, Serik; Nakashima, Masahiro; Rogounovitch, Tatiana; Shkurko, Olesya; Lushnikov, Eugeny; Mitsutake, Norisato; Namba, Hiroyuki; Yamashita, Shunichi
2007-01-01
This study addressed the immunohistochemical expression of MUC1 in papillary thyroid carcinoma (PTC) of different histotypes, sizes, and morphological features of aggressiveness, and its correlation with the overexpression of cyclin D1, a target molecule of the Wnt pathway. MUC1 expression was examined in a total of 209 PTCs. Cytoplasmic MUC1 expression was elevated in the tall, columnar cell and oncocytic variants (100%), Warthin-like (78%), and conventional PTCs (61%), and in papillary microcarcinoma (PMC) with the conventional growth pattern (52%). On the contrary, it was low in the follicular variant (27%) of PTC and PMCs with follicular architecture (13%). Cytoplasmic MUC1 accumulation did not associate with any clinicopathological features except peritumoral lymphoid infiltration in PTCs and in PMCs with the conventional growth pattern. MUC1 staining correlated with cyclin D1 overexpression in conventional PTCs and PMCs and PMCs with follicular architecture. The results demonstrate that MUC1 expression varies broadly in different histological variants of PTC, being the lowest in tumors with follicular structure. In general, it does not prove to be a prognosticator of PTC aggressiveness. A high correlation between MUC1 and cyclin D1 implies MUC1 involvement in the Wnt cascade functioning in a large subset of human PTCs and PMCs.
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2018-06-22
Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary-Mucinous Neoplasm; Stage I Pancreatic Cancer AJCC v6 and v7; Stage IA Pancreatic Cancer AJCC v6 and v7; Stage IB Pancreatic Cancer AJCC v6 and v7; Stage II Pancreatic Cancer AJCC v6 and v7; Stage IIA Pancreatic Cancer AJCC v6 and v7; Stage IIB Pancreatic Cancer AJCC v6 and v7
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Chi, Angela C; Neville, Brad W
2015-06-01
The purpose of this study is to evaluate surface papillary epithelial hyperplasia, a microscopic finding that corresponds to the clinical finding of rough or stippled mucosa, as a predictor of polymorphous low-grade adenocarcinoma (PLGA). We conducted a retrospective review of minor salivary gland neoplasms submitted to our biopsy service from 1991 to 2013. Our review was limited to lesions involving the oral cavity/soft palate with the following diagnoses: PLGA, pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC). A total of 202 minor salivary gland neoplasms were included in the study. Among cases in which surface epithelium was present for evaluation (n = 112), surface papillary epithelial hyperplasia was evident in 30 % of PLGA and 1 % of non-PLGA (i.e., MEC, ACC, PA). The greater frequency of surface papillary epithelial hyperplasia in the PLGA versus non-PLGA cases and in the benign versus malignant cases was significant (p = .0001 and p = .041, respectively). The sensitivity and specificity of papillary epithelial hyperplasia for PLGA were 30 % (95 % confidence interval (CI) 11.97-54.27 %) and 99 % (95 % CI 94-99.82 %), respectively. The clinical presentation of PLGA appeared relatively nonspecific, with all analyzed tumor types exhibiting a predilection for females, middle-aged to older adults, palatal location, pink/tan/normal color, and firm consistency. In conclusion, papillary epithelial hyperplasia was evident in only a minority of PLGA. However, when present within the context of a palatal salivary gland neoplasm, it appears to indicate a high probability of PLGA. Accordingly, rough mucosa may be a useful clinical pearl for identification of PLGA.
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Haugen, Bryan R; Sawka, Anna M; Alexander, Erik K; Bible, Keith C; Caturegli, Patrizio; Doherty, Gerard M; Mandel, Susan J; Morris, John C; Nassar, Aziza; Pacini, Furio; Schlumberger, Martin; Schuff, Kathryn; Sherman, Steven I; Somerset, Hilary; Sosa, Julie Ann; Steward, David L; Wartofsky, Leonard; Williams, Michelle D
2017-04-01
American Thyroid Association (ATA) leadership asked the ATA Thyroid Nodules and Differentiated Thyroid Cancer Guidelines Task Force to review, comment on, and make recommendations related to the suggested new classification of encapsulated follicular variant papillary thyroid carcinoma (eFVPTC) without capsular or vascular invasion to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The task force consists of members from the 2015 guidelines task force with the recusal of three members who were authors on the paper under review. Four pathologists and one endocrinologist were added for this specific review. The manuscript proposing the new classification and related literature were assessed. It is recommended that the histopathologic nomenclature for eFVPTC without invasion be reclassified as a NIFTP, given the excellent prognosis of this neoplastic variant. This is a weak recommendation based on moderate-quality evidence. It is also noted that prospective studies are needed to validate the observed patient outcomes (and test performance in predicting thyroid cancer outcomes), as well as implications on patients' psychosocial health and economics.
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Wang, Chung-Chieh; Huang, Chao-Yuan; Jhuang, Yu-Lin; Chen, Chih-Chi; Jeng, Yung-Ming
2018-04-01
Mutations in FGFR3 and the promoter region of the telomerase reverse transcriptase (TERT) gene have been found frequently in urothelial carcinoma of the urinary bladder. However, related data for papillary urothelial neoplasm of low malignant potential (PUNLMP) are limited. In this study, we investigated the mutation status of the TERT promoter, FGFR3 and HRAS in low-grade papillary urothelial neoplasms and evaluated their prognostic significance. The cases included in this study comprised 21 inverted papillomas, 30 PUNLMPs and 34 low-grade non-invasive papillary urothelial carcinomas (NIPUCs). TERT promoter mutations were observed in 10 (33%) PUNLMPs and 17 (50%) low-grade NIPUCs, but not in any inverted papilloma. FGFR3 mutations were observed more frequently in PUNLMP and low-grade NIPUC than in inverted papillomas (P = 0.009), whereas the opposite trend was noted for HRAS mutations (P < 0.001). Regarding the clinical outcome, TERT promoter mutation was associated with a higher recurrence rate in PUNLMP (P = 0.024) but not in low-grade NIPUC (P = 0.530). Notably, PUNLMP cases with TERT promoter mutations had a similar recurrence rate to that in low-grade NIPUC cases (P = 0.487). Our results suggest that the status of the TERT promoter mutation may serve as a biomarker of prognostic stratification in patients with PUNLMP. © 2017 John Wiley & Sons Ltd.
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The pros and cons of prophylactic central neck dissection in papillary thyroid carcinoma.
Glover, Anthony R; Gundara, Justin S; Norlén, Olov; Lee, James C; Sidhu, Stan B
2013-11-01
Prophylactic central neck dissection (pCND) for management of papillary thyroid carcinoma (PTC) is controversial. Compared to many malignancies, PTC has a high overall survival but local recurrence due to lymph node metastases continue to present management challenges. Unlike lateral cervical nodal metastasis metastasis, central neck nodal metastasis are unable to be reliably detected clinically or radiologically at pre-operative assessment. Residual disease (recurrent or persistent) typically requires re-operative surgery in the central compartment, which carries a heightened risk of significant morbidity. These nodal groups can be accessed during the index thyroidectomy for PTC. Thus, pCND offers potential to reduce the rates of recurrence and the need for re-operative surgery in the central neck. This benefit needs to be balanced with the potential morbidity risk from pCND itself at the index resection. This review will discuss the advantages and disadvantages of pCND with regard to long-term outcomes and potential morbidity. The rationale of pCND will be discussed, along with the indications for ipsilateral and contralateral pCND, the role of re-operative surgery for recurrence and the use of selective versus routine pCND. Strategies to select higher risk patients for pCND with the use of molecular markers will be addressed, along with a discussion of quality of life (QoL) research in PTC.
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Ma, Yuqin; Zhang, Xia; Wang, Yutao
2017-01-01
This study investigated the effect of thyroid stimulating hormone (TSH) on the proliferation of papillary thyroid carcinoma (PTC) cells and the therapeutic effect of levothyroxine sodium (TH). PTC cells (TPC-1) were cultured using 0.1, 1.0 and 10 U/l TSH and 10−2, 10−4 and 10−6 mol/l TH. After the appropriate concentration was screened, TPC-1 cells were further divided into control group, TSH group, TH group and TSH+TH group. The cell proliferation was detected via methyl thiazolyl tetrazolium (MTT) method, TPC-1 cell cycle was detected via flow cytometer, and the mRNA and protein expression of cyclin D1 were detected via real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Compared with control group, TSH significantly promoted the proliferation of TPC-1 cells (P<0.05 or P<0.01), obviously promoted the transition of TPC-1 cells from G1 phase to S phase (P<0.01) and remarkably increased the mRNA and protein expression of cyclin D1 (P<0.01); but TH had a significant inhibitory effect on these results of TSH (P<0.05 or P<0.01). TSH can promote the proliferation of PTC cells, and the appropriate complement of TH can inhibit its proliferation. PMID:29250166
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Koca, E; Sokmensuer, C; Yildiz, B O; Engin, H; Bozkurt, M F; Aras, T; Barista, I; Gurlek, A
2004-06-01
A 61-yr-old woman presented with complaints of weakness and pain in her legs. A magnetic resonance imaging showed a 3 x 5.6 x 7.8 cm mass lesion destructing the T1 and T2 vertebral bodies and compressing the spinal cord. The mass was excised surgically. It was follicular carcinoma metastasis of the cervicodorsal region. Then, she underwent a total thyroidectomy. Pathological examination showed two different types of carcinomas in two different focuses; follicular carcinoma in the left lobe and follicular variant papillary carcinoma in the isthmic lobe. After the operation she was given 100 mCi 131I. This is the first report of a patient who had both metastatic follicular carcinoma and follicular variant papillary carcinoma together.
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Jeong, Jun Soo; Kim, Hyun Ki; Lee, Cho-Rok; Park, Seulkee; Park, Jae Hyun; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo
2012-08-01
The study aimed to identify the clinical characteristics of coexisting chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to evaluate the influence on prognosis. A total of 1,357 patients who underwent thyroid surgery for PTC were included. The clinicopathological characteristics were identified. Patients who underwent total thyroidectomy (n = 597) were studied to evaluate the influence of coexistent CLT on prognosis. Among the total 1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence of females was higher than in the control group without CLT (P < 0.001). Mean tumor size and mean age in the patients with CLT were smaller than without CLT (P = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597 patients, disease-free survival rate in the patients with CLT was significantly higher than without CLT (P = 0.042). However, the multivariate analysis did not reveal a negative association between CLT coexistence and recurrence. Patients with CLT display a greater female preponderance, smaller size, younger and lower extrathyroidal extension. CLT is not a significant independent negative predictive factor for recurrence, although presence of CLT indicates a reduced risk of recurrence.
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Jeong, Jun Soo; Kim, Hyun Ki; Lee, Cho-Rok; Park, Seulkee; Park, Jae Hyun; Kang, Sang-Wook; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo
2012-01-01
The study aimed to identify the clinical characteristics of coexisting chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to evaluate the influence on prognosis. A total of 1,357 patients who underwent thyroid surgery for PTC were included. The clinicopathological characteristics were identified. Patients who underwent total thyroidectomy (n = 597) were studied to evaluate the influence of coexistent CLT on prognosis. Among the total 1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence of females was higher than in the control group without CLT (P < 0.001). Mean tumor size and mean age in the patients with CLT were smaller than without CLT (P = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597 patients, disease-free survival rate in the patients with CLT was significantly higher than without CLT (P = 0.042). However, the multivariate analysis did not reveal a negative association between CLT coexistence and recurrence. Patients with CLT display a greater female preponderance, smaller size, younger and lower extrathyroidal extension. CLT is not a significant independent negative predictive factor for recurrence, although presence of CLT indicates a reduced risk of recurrence. PMID:22876054
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Sterle, Igor; Zupančič, Daša; Romih, Rok
2014-01-01
Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5) and transient receptor potential vanilloid channels (TRPV1, and TRPV4). Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns. PMID:24868547
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Sterle, Igor; Zupančič, Daša; Romih, Rok
2014-01-01
Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5) and transient receptor potential vanilloid channels (TRPV1, and TRPV4). Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.
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Machairas, Nikolaos; Kostakis, Ioannis D; Prodromidou, Anastasia; Stamopoulos, Paraskevas; Feretis, Themistoklis; Garoufalia, Zoe; Damaskos, Christos; Tsourouflis, Gerasimos; Kouraklis, Gregory
2017-11-01
Carcinogenesis has been related to systematic inflammatory response. Our aim was to study white blood cell and platelet indices as markers of this inflammatory response in thyroid cancer and to associate them with various clinicopathological parameters. We included 228 patients who underwent thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma and 139 with multinodular hyperplasia. We examined potential links between white blood cell and platelet indices on the one hand and the type thyroid pathology and various clinicopathological parameters on the other. No significant differences were detected between thyroid cancer and multinodular hyperplasia and no significant associations were detected with regard to lymphovascular invasion and tumor size. However, the mean platelet volume was higher in multifocal tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio were increased in cases with extrathyroidal extension and in T3 tumors. Additionally, T3 tumors had lower platelet distribution width. These associations demonstrated low accuracy in predicting these pathological features, but they were found to provide a satisfying negative predictive value, with the exception of the mean platelet volume. White blood cell and platelet indices cannot assist in distinguishing benign goiter from thyroid cancer. However, they can provide information about tumor multifocality, extrathyroidal extension, and presence of a T3 tumor, and they may be used as a means to exclude these pathological characteristics, especially the last two, in papillary thyroid carcinoma.
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[Primary carcinoma of the thyroid growing in thyroglossal duct cyst: presentation of two cases].
Godlewska, Paulina; Bruszewska, Elzbieta; Kozłowicz-Gudzińska, Izabella; Prokurat, Andrzej I; Chrupek, Małgorzata; Zegadło-Mylik, Maria A; Kluge, Przemysław
2007-01-01
Thyroglossal duct remnants (TGDR), most often cysts, are the most common type of developmental abnormalities of the thyroid gland. In about 1 to 2% of TGDR neoplastic transformation occurs. Papillary carcinoma of the thyroid may be encountered in over 90% of such cases. Two cases of primary papillary carcinoma of the thyroid in TGDR in young girls are presented. The diagnostic and therapeutic problems are shared, and up-to-date management guidelines in similar cases are discussed.
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Laco, J; Ryska, A; Cáp, J; Celakovský, P
2008-10-01
The immunohistochemical expression of galectin-3 (Gal3), cytokeratin 19 (CK19), neural cell adhesion molecule (NCAM), and E-cadherin (Ecad) was evaluated to assess their use in diagnostics of papillary thyroid carcinoma (PTC). A total of 84 PTCs - 36 classical variants (cPTCs), 26 follicular variants (fPTCs), and 22 papillary microcarcinomas (mPTCs) were studied. Expression of Gal3 was found in 36/36 (100%) cPTCs, 24/26 (92%) fPTCs, and 19/22 (86%) mPTCs. CK19 expression was detected in 34/36 (94%) cPTCs, 17/26 (65%) fPTCs, and 13/22 (59%) mPTCs. Expression of NCAM was seen in 5/36 (14%) cPTCs, 7/26 (27%) fPTCs, and 9/22 (41%) mPTCs. Ecad expression was found in 23/36 (64%) cPTCs, 17/26 (65%) fPTCs, and 18/22 (82%) mPTCs. A significant difference in CK19 expression was observed between cPTC and both fPTC and mPTC (p < 0.001). Furthermore, extrathyroid tumor spread significantly correlated with both level of CK19 expression and loss of Ecad expression (p = 0.001, p = 0.04). Our findings suggest that Gal3 and CK19 are useful markers for PTC, although decreased CK19 expression in mPTC and fPTC must be considered. Furthermore, CK19 and Ecad may play a role in extrathyroid tumor spread.
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Díaz Del Arco, Cristina; Fernández Aceñero, M Jesús
2018-06-01
To assess the cytological findings of noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), conventional papillary thyroid carcinomas (C-PTC), and invasive follicular variants of papillary thyroid carcinomas (IFV-PTC) to determine if there are cytological differences between groups. We have reviewed all thyroid fine-needle aspiration cytology samples diagnosed between 2000 and 2017. We have included all NIFTP cases (n = 6) and randomly selected cases of C-PTC (n = 14) and IFV-PTC (n = 8). Comparing NIFTP and C-PTC cases, NIFTP cases showed significantly less papillary or pseudopapillary architecture, more bidimensional groups and microfollicles, and less tridimensionality, giant cells, and nuclear folds. We observed a trend towards significance for smear cellularity and amount of cytoplasm. Presence of nuclear folds was the only significant difference between NIFTP and IFV-PTC cases. The differences between groups in percent papillary or pseudopapillary architecture, cellularity, and tridimensionality showed a trend towards significance. Amount of colloid, dirty background, pleomorphism or atypia, nuclear pseudoinclusions, type of chromatin, and nucleolus were not significant. No cytopathological feature can differentiate between invasive and encapsulated IFV-PTC. In accordance with the recently accepted category, PTC smears with cells arranged in a predominantly follicular architecture should be reported as Bethesda IV category with descriptive terms to avoid false-positive cases. © 2018 S. Karger AG, Basel.
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Chen, Xiancheng; Gan, Weidong; Ye, Qing; Yang, Jun; Guo, Hongqian; Li, Dongmei
2014-12-16
To explore the value of self-designed fluorescent in situ hybridization (FISH) polyclonal break-apart probes specific for TFE3 gene in the diagnosis of Xp11.2 translocation renal cell carcinoma. All tissue samples were collected from 2006 to 2013, including Xp11.2 translocation renal cell carcinoma (n = 10), renal clear cell carcinoma (n = 10) and renal papillary cell carcinoma (n = 10). FISH was conducted for paraffin-embedded tumor tissue sections with probes. The types of fluorescence were observed by fluorescent microscopy to determine the existence or non-existence of translocated TFE3 gene. All sections were successfully probed. The split red and green signals within a single nucleus were detected simultaneously in 9 cases of Xp11.2 translocation renal cell carcinoma as diagnosed by traditional pathological and immunohistochemical methods. And it was consistent with the initial diagnosis. Detection of fusion signal in 1/10 and negative FISH result did not conform to the initial diagnosis. The fluorescent types of renal clear cell carcinoma and renal papillary cell carcinoma were all fusion signals. FISH tests were negative for renal clear and papillary cell carcinomas. Xp11.2 translocation renal cell carcinomas diagnosed by traditional pathological and immunohistochemical methods are sometimes misdiagnosed. Detecting the translocation of TFE3 gene with FISH polyclonal break-apart probes is both accurate and reliable for diagnosing Xp11.2 translocation renal cell carcinoma.
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Zhu, Qingqiang; Zhu, Wenrong; Wu, Jingtao; Fu, Jianxiong; Chen, Wenxin; Wang, Zhongqiu
2014-05-20
To comparative study of CT and MRI appearances in renal cell carcinoma associated with XP11.2 translocation/TFE gene fusion (XP11.2 RCC) and papillary renal cell carcinoma (PRCC). 12 patients with XP11.2 RCC and 18 patients with PRCC were retrospectively studied, and the data was analyzed by AVONA and chi-square text. 12 patients with XP11.2 RCC and 18 patients with PRCC, cystic components (2 vs 11, P < 0.05), calcification (0 vs 6, P < 0.05), hemorrhage (9 vs 5, P < 0.05), homogeneous enhancement (10 vs 7, P < 0.05) and had lymph node (3 vs 0) or hepatic metastasis (1vs 0) (P < 0.05). On unenhanced CT, the density of XP11.2 RCC was greater than PRCC, normal renal cortex or medulla (P < 0.05). Their degree of enhancement were less than normal renal cortex on all enhanced phases (P < 0.05). The enhancement degree of XP11.2 RCC was higher than PRCC (on all phases) and renal medulla (on cortical and medullary phase) (P < 0.05), but less than normal renal medulla on the delayed phase (P < 0.05). The enhancement degree of PRCC was lower than renal medulla on all phases (P < 0.05). The XP11.2 RCC was isointense on T1-weighted imaging, hypointense on T2-weighted imaging. The PRCC was isointense or hypointense on T1-weighted imaging, isointense on T2-weighted imaging. The CT and MRI could show imagings features of XP11.2 RCC and PRCC, and these features were helpful in predicting a specific subtype of renal cell carcinoma.
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Haddad, Mustafa M; Schmit, Grant D; Kurup, A Nicholas; Schmitz, John J; Boorjian, Stephen A; Geske, Jennifer; Thompson, R Houston; Callstrom, Matthew R; Atwell, Thomas D
2018-06-07
To evaluate treatment outcomes with percutaneous cryoablation (PCA) based on renal cell carcinoma (RCC) histology. Patients treated with PCA for a solitary, sporadic stage T1a RCC from 2003 to 2016 were identified from a single institution's renal ablation registry. Patients with multiple tumors, history of RCC, or genetic syndromes associated with RCC (n = 60); no specific RCC subtype determined from core biopsy (n = 66); RCC subtype other than clear-cell or papillary (n = 7); or less than 3 mo of follow-up imaging (n = 5) were excluded. In total, 173 patients met study inclusion criteria. Oncologic outcomes, clinical outcomes, and complications were evaluated based on tumor subtype. Of the 173 patients who underwent PCA for a stage T1a RCC, 130 (75%) had clear-cell RCC (ccRCC) and 43 (25%) had papillary RCC (pRCC). Median tumor size was 2.9 cm (range, 1.3-4.0 cm). Technically successful cryoablation was achieved in all 173 patients. Local tumor recurrence developed in 6 patients with ccRCC (4.6%), new renal tumors developed in 1 patient (0.8%), and metastatic RCC developed in 1 patient (0.8%) who also had local tumor recurrence. No patients with pRCC showed local tumor recurrence, new renal tumors, or metastatic disease. The 5-year disease-free survival rate in patients with ccRCC was 88%, compared with 100% in patients with pRCC (P = .48). Nine patients (5.2%), all with ccRCC, experienced major complications (P = .11). Percutaneous ablation is a viable treatment option for patients with clinical stage T1a pRCC and ccRCC. Percutaneous ablation may be a very favorable treatment strategy particularly for pRCC. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.
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Cuneo, Kyle C; Dash, Rajesh C; Wilke, Lee G; Horton, Janet K; Koontz, Bridget F
2012-09-01
Benign papillary lesions of the breast include papilloma and papillomatosis. A retrospective analysis of patients with a papillary breast lesion diagnosed between October 1992 and December 2009 was performed. Patients were excluded if they had a previous or concurrent diagnosis of invasive or in situ cancer or less than 6 months of follow-up. The Kaplan-Meier method was used to determine the risk of developing subsequent malignancy. The log rank test was used to compare groups of patients. Median follow-up for the 167 patients included in the study was 4.6 years. Fifty-one patients had a papillary lesion with atypia and 116 patients had a papillary lesion without atypia. Patients with a papillary lesion with atypia were more likely to develop invasive or in situ breast cancer with a 5 year risk of 13.0% versus 4.6% in patients with no atypia (p = 0.03). © 2012 Wiley Periodicals, Inc.
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Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer.
Tobiás, Bálint; Halászlaki, Csaba; Balla, Bernadett; Kósa, János P; Árvai, Kristóf; Horváth, Péter; Takács, István; Nagy, Zsolt; Horváth, Evelin; Horányi, János; Járay, Balázs; Székely, Eszter; Székely, Tamás; Győri, Gabriella; Putz, Zsuzsanna; Dank, Magdolna; Valkusz, Zsuzsanna; Vasas, Béla; Iványi, Béla; Lakatos, Péter
2016-01-01
The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature.
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Jung, Mi Sook; Visovatti, Moira
2017-03-01
The purpose of the study is to assess cognitive function in papillary thyroid cancer, one type of differentiated thyroid cancer, and to identify factors associated with cognitive dysfunction. Korean women treated with papillary thyroid cancer post thyroidectomy (n = 90) and healthy women similar in age and educational level (n = 90) performed attention and working memory tests and completed self-report questionnaires on cognitive complaints, psychological distress, symptom distress, and cultural characteristics. Comparative and multivariable regression analyses were performed to determine differences in cognitive function and possible predictors of neurocognitive performance and cognitive complaints. Thyroid cancer survivors performed and perceived their function to be significantly worse on tests of attention and working memory compared to individuals without thyroid cancer. Regression analyses found that having thyroid cancer, older age, and lower educational level were associated with worse neurocognitive performance, while greater fatigue, more sleep problems, and higher levels of childrearing burden but not having thyroid cancer were associated with lower perceived effectiveness in cognitive functioning. Findings suggest that women receiving thyroid hormone replacement therapy after thyroidectomy for papillary thyroid cancer are at risk for attention and working memory problems. Coexisting symptoms and culture-related women's burden affected perceived cognitive dysfunction. Health care providers should assess for cognitive problems in women with thyroid cancer and intervene to reduce distress and improve quality of life.
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Fascin and EMMPRIN expression in primary mucinous tumors of ovary: a tissue microarray study.
Alici, Omer; Kefeli, Mehmet; Yildiz, Levent; Baris, Sancar; Karagoz, Filiz; Kandemir, Bedri
2014-12-01
The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors. Copyright © 2014 Elsevier GmbH. All rights reserved.
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Spectrum of the Breast Lesions With Increased 18F-FDG Uptake on PET/CT
Dong, Aisheng; Wang, Yang; Lu, Jianping; Zuo, Changjing
2016-01-01
Abstract Interpretation of 18F-FDG PET/CT studies in breast is challenging owing to nonspecific FDG uptake in various benign and malignant conditions. Benign conditions include breast changes in pregnancy and lactation, gynecomastia, mastitis, fat necrosis, fibroadenoma, intraductal papilloma, and atypical ductal hyperplasia. Among malignancies, invasive ductal carcinoma and invasive lobular carcinoma are common histological types of breast carcinoma. Rarely, other unusual histological types of breast carcinomas (eg, intraductal papillary carcinoma, invasive micropapillary carcinoma, medullary carcinoma, mucinous carcinoma, and metaplastic carcinoma), lymphoma, and metastasis can be the causes. Knowledge of a wide spectrum of hypermetabolic breast lesions on FDG PET/CT is essential in accurate reading of FDG PET/CT. The purpose of this atlas article is to demonstrate features of various breast lesions encountered at our institution, both benign and malignant, which can result in hypermetabolism on FDG PET/CT imaging. PMID:26975010
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NASA Astrophysics Data System (ADS)
Martirosyan, A.; Olesen, M. J.; Fenton, R. A.; Kjems, J.; Howard, K. A.
2016-06-01
This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal loops. The findings present a mucosal design-based system tailored for local delivery of oligonucleotides that may maximize the effectiveness of gene silencing therapeutics within tumours at mucosal sites.This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal
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Vavinskaya, Vera; Baumgartner, Joel M; Ko, Albert; Saenz, Cheryl C; Valasek, Mark A
2016-01-01
Primary appendiceal mucinous lesions are uncommon and represent a spectrum from nonneoplastic mucous retention cysts to invasive adenocarcinoma. Low-grade appendiceal mucinous neoplasms (LAMNs) represent an intermediate category on this spectrum and can be classified according to whether or not they are confined to the appendix. Although LAMNs are frequently confined to the appendix, they can also spread to the peritoneum and clinically progress as pseudomyxoma peritonei (i.e., mucinous ascites). Thus, the appropriate classification of appendiceal primary neoplasia is essential for prognosis and influences clinical management. In addition, the precise classification, management, and clinical outcome of patients with disseminated peritoneal disease remain controversial. Here, we report an unusual case of LAMN with pseudomyxoma peritonei that initially presented with mucinous and bloody vaginal discharge. Pathological evaluation revealed low-grade appendiceal mucinous neoplasm with secondary involvement of the peritoneum, ovaries, and endometrial surface. Therefore, LAMN should be considered in the differential diagnosis of mucinous vaginal discharge.
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Jeon, Min Ji; Song, Dong Eun; Jung, Chan Kwon; Kim, Won Gu; Kwon, Hyemi; Lee, Yu-Mi; Sung, Tae-Yon; Yoon, Jong Ho; Chung, Ki-Wook; Hong, Suck Joon; Baek, Jung Hwan; Lee, Jeong Hyun; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae
2016-01-01
Background The follicular variant of papillary thyroid cancer (FVPTC), especially the encapsulated non-invasive subtype, is a controversial entity. Recent study suggested using ‘non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)’ for these indolent carcinomas. We evaluated the impact of reclassification from non-invasive encapsulated FVPTCs (EFVPTCs) to NIFTPs in the diagnosis of thyroid nodules with architectural atypia. Methods We reviewed 1301 thyroid nodules with architectural atypia in core needle biopsy (CNB) specimens obtained from March 2012 to February 2013. Nodules were classified into atypia of undetermined significance with architectural atypia (AUS-A, 984, 76%) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN, 317, 24%). Among them, diagnostic surgery was performed in 384 nodules (30%). Results In total, 160 nodules (42%) presented final malignant diagnoses including 39 non-invasive encapsulated FVPTCs (10%). The malignancy rate was estimated to be 7–35% in AUS-A nodules and 28–49% in FN/SFN nodules. After reclassification, the malignancy rate was much decreased and estimated to be 5–24% in AUS-A nodules, and 23–39% in FN/SFN nodules. Thyroid nodules with final malignant diagnoses were significantly more likely to have a FN/SFN CNB diagnosis, malignant US features and concomitant nuclear atypia in CNB specimens. However, these factors could not differentiate NIFTPs from other malignancies. Conclusions After reclassification of non-invasive EFVPTCs to NIFTPs, the malignancy rate of thyroid nodules with architectural atypia in CNB specimens was decreased. However, there were no preoperative factors differentiating other malignancies from NIFTPs. The presence of malignant US features or concomitant nuclear atypia might help clinicians deciding diagnostic surgery but, these features also might indicate NIFTPs. PMID:27936121
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Hoffman, David H; Ream, Justin M; Hajdu, Christina H; Rosenkrantz, Andrew B
2017-04-01
To evaluate whole-lesion ADC histogram metrics for assessing the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs), including in comparison with conventional MRI features. Eighteen branch-duct IPMNs underwent MRI with DWI prior to resection (n = 16) or FNA (n = 2). A blinded radiologist placed 3D volumes-of-interest on the entire IPMN on the ADC map, from which whole-lesion histogram metrics were generated. The reader also assessed IPMN size, mural nodularity, and adjacent main-duct dilation. Benign (low-to-intermediate grade dysplasia; n = 10) and malignant (high-grade dysplasia or invasive adenocarcinoma; n = 8) IPMNs were compared. Whole-lesion ADC histogram metrics demonstrating significant differences between benign and malignant IPMNs were: entropy (5.1 ± 0.2 vs. 5.4 ± 0.2; p = 0.01, AUC = 86%); mean of the bottom 10th percentile (2.2 ± 0.4 vs. 1.6 ± 0.7; p = 0.03; AUC = 81%); and mean of the 10-25th percentile (2.8 ± 0.4 vs. 2.3 ± 0.6; p = 0.04; AUC = 79%). The overall mean ADC, skewness, and kurtosis were not significantly different between groups (p ≥ 0.06; AUC = 50-78%). For entropy (highest performing histogram metric), an optimal threshold of >5.3 achieved a sensitivity of 100%, a specificity of 70%, and an accuracy of 83% for predicting malignancy. No significant difference (p = 0.18-0.64) was observed between benign and malignant IPMNs for cyst size ≥3 cm, adjacent main-duct dilatation, or mural nodule. At multivariable analysis of entropy in combination with all other ADC histogram and conventional MRI features, entropy was the only significant independent predictor of malignancy (p = 0.004). Although requiring larger studies, ADC entropy obtained from 3D whole-lesion histogram analysis may serve as a biomarker for identifying the malignant potential of IPMNs, independent of conventional MRI features.
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2014-01-01
As rare condition, mucoepidermoid carcinoma may occur in liver although its etiology and pathogenesis is still unclear. We report here a case of intrahepatic mucoepidermoid carcinoma misdiagnosed as cholangiocarcinoma and squamous cell carcinoma by preoperative radiologic and intraoperative histological examinations, respectively. A 60-year-old woman presented with a 1-month history of progressive jaundice, epigastric discomfort, and weight loss with slightly increased carbohydrate antigen 19-9 (CA19-9). Computed tomography (CT) showed a large tumor, 8.0 cm in diameter, in the left lobe of the liver. A preliminary diagnosis of a cholangiocarcinoma of the liver was made. In the intraoperative histological examination, a diagnosis of squamous cell carcinoma was made based on predominantly invasive epidermoid cells with abundant keratinization and absence of mucin-producing cell component. However, postoperative histological diagnosis of the lesion was mucoepidermiod carcinoma of liver by thoroughly microscopical inspection and the presence of mucin-producing cells confirmed by Alcian blue staining. Despite surgical excision and chemotherapy, the tumor showed very aggressive malignancy with tumor recurrence. The patient died shortly afterward, surviving 6 months after surgery. Due to its rarity and distinct morphological features, mucoepidermoid carcinoma might be erroneously interpreted as squamous cell carcinoma by those who were not familiar with this condition in unusual locations. Therefore, removal of sufficient tissue from different portions of the lesion is essential for the surgeons and pathologists to make a precise diagnosis in the intraoperative histological examination. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4956311271136060 PMID:24475740
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Mehra, Rohit; Vats, Pankaj; Cieslik, Marcin; Cao, Xuhong; Su, Fengyun; Shukla, Sudhanshu; Udager, Aaron M; Wang, Rui; Pan, Jincheng; Kasaian, Katayoon; Lonigro, Robert; Siddiqui, Javed; Premkumar, Kumpati; Palapattu, Ganesh; Weizer, Alon; Hafez, Khaled S; Wolf, J Stuart; Sangoi, Ankur R; Trpkov, Kiril; Osunkoya, Adeboye O; Zhou, Ming; Giannico, Giovanna; McKenney, Jesse K; Dhanasekaran, Saravana M; Chinnaiyan, Arul M
2016-11-01
Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma (RCC) with distinctive morphologic and cytogenetic features. Here, we carry out whole-exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n = 22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSG) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes, whereas other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to biallelic alterations in these TSGs. As a readout of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. Taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation. MTSCC is a rare and relatively recently described subtype of RCC. Next-generation sequencing of a multi-institutional MTSCC cohort revealed recurrent chromosomal losses and somatic mutations in the Hippo signaling pathway genes leading to potential YAP1 activation. In virtually all cases of MTSCC, there was evidence of Hippo pathway dysregulation, suggesting a common mechanistic basis for this disease. Cancer Discov; 6(11); 1258-66. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1197. ©2016 American Association for Cancer Research.
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Dong, Chao; Wang, Xiao-li; Ma, Bin-lin
2015-01-01
Aim. Spindle and kinetochore-associated protein 1 (SKA1) is one subtype of SKA, whose protein can make spindle microtubules attach steadily to the kinetochore in the middle of mitosis. At present, there are fewer researches on the relationship between SKA1 expression and tumor development. Methods. In this study, immunohistochemical analysis was used to determine the expression of SKA1 in papillary thyroid carcinoma (PTC) and adjacent tissues. We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis to further verify the results. Results. We found that SKA1 expression was significantly higher in PTC tissues than normal adjacent tissues (P < 0.05). There existed a significant correlation among a higher SKA1 expression, including lymphoid node (P = 0.005), clinical stage (P = 0.015), and extrathyroid invasion (P = 0.004). Survival analysis showed high SKA1 expression in PTC patients more likely to relapse after surgery. Conclusion. High SKA1 expression is predictive of poor prognosis of PTC, implying that SKA1 may be a promising new target for targeted therapies for PTC. PMID:26063960
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Multifocal hyperfunctioning thyroid carcinoma without metastases.
Nishida, Akiko T; Hirano, Shigeru; Asato, Ryo; Tanaka, Shinzo; Kitani, Yoshiharu; Honda, Nobumitsu; Fujiki, Nobuya; Miyata, Kouji; Fukushima, Hideyuki; Ito, Juichi
2008-09-01
Hyperthyroidism due to thyroid carcinoma is rare, and most cases are caused by hyperfunctioning metastatic thyroid carcinoma rather than primary carcinoma. Among primary hyperfunctioning thyroid carcinoma, multifocal thyroid carcinoma is exceedingly rare, with the only one case being reported in the literature. Here, we describe the case of a 62-year-old woman with multifocal functioning thyroid carcinoma. Technetium-99m (99m Tc) scintigraphic imaging showed four hot areas in the thyroid gland. Histopathological examination of all four nodules revealed papillary carcinoma, corresponding to hot areas in the 99m Tc scintigram. DNA sequencing of the thyrotropin receptor (TSH-R) gene from all nodules revealed no mutation, indicating that activation of TSH-R was unlikely in the pathophysiogenesis of hyperfunctioning thyroid carcinoma in the present case.
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Transmembrane mucins as novel therapeutic targets.
Constantinou, Pamela E; Danysh, Brian P; Dharmaraj, Neeraja; Carson, Daniel D
2011-11-01
Membrane-tethered mucin glycoproteins are abundantly expressed at the apical surfaces of simple epithelia, where they play important roles in lubricating and protecting tissues from pathogens and enzymatic attack. Notable examples of these mucins are MUC1, MUC4 and MUC16 (also known as cancer antigen 125). In adenocarcinomas, apical mucin restriction is lost and overall expression is often highly increased. High-level mucin expression protects tumors from killing by the host immune system, as well as by chemotherapeutic agents, and affords protection from apoptosis. Mucin expression can increase as the result of gene duplication and/or in response to hormones, cytokines and growth factors prevalent in the tumor milieu. Rises in the normally low levels of mucin fragments in serum have been used as markers of disease, such as tumor burden, for many years. Currently, several approaches are being examined that target mucins for immunization or nanomedicine using mucin-specific antibodies.
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Na, Kiyong; Lee, Jung-Yun; Sung, Ji-Youn; Kim, Gun Min; Koo, Ja Seung; Kim, Hyun-Soo
2018-06-20
Causes of peritoneal carcinomatosis (PC) in patients with a history of breast carcinoma include both metastatic breast carcinoma (MBC) and primary peritoneal/ovarian carcinoma (PPOC). The origin of PC is important to determine the appropriate treatment strategy. Cytological examination of the peritoneal fluid (PF), which may be the first diagnostic approach to PC, is of distinct value in confirming the presence of malignant cells and determining the origin of PC. We analyzed the clinicopathological and cytomorphological characteristics of 33 patients with a history of breast carcinoma whose PF cytology contained malignant cells. Cases showing positive immunoreactivity for PAX8 and a lack of GATA3 expression were considered as PPOC. Sixteen patients developed PC caused by PPOC. PPOC patients were characterized by early-stage primary breast carcinoma, absence of non-peritoneal MBC before PC, and normal serum levels of CEA and CA15-3. Fourteen PPOC patients had pathogenic germline BRCA mutations. Cytological examination revealed that most of the PPOC cases had a dominant papillary arrangement of the tumor cells with severe nuclear pleomorphism, occasional bizarre nuclei, and atypical mitotic figures. Patients with PPOC who underwent cytoreductive surgery had a significantly longer survival time compared to those who did not, or MBC patients. In patients with a history of breast carcinoma presenting with PC, the presence of early-stage primary breast carcinoma, no prior non-peritoneal MBC, and a dominant papillary cellular arrangement pattern in the PF cytology were independent predictors of PPOC. Cytoreductive surgery significantly improved survival for patients with PPOC.
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Surgical perspective of T1799A BRAF mutation diagnostic value in papillary thyroid carcinoma.
Brahma, Bayu; Yulian, Erwin Danil; Ramli, Muchlis; Setianingsih, Iswari; Gautama, Walta; Brahma, Putri; Sastroasmoro, Sudigdo; Harimurti, Kuntjoro
2013-01-01
Throughout Indonesia, thyroid cancer is one of the ten commonest malignancies, with papillary thyroid carcinoma (PTC) in our hospital accounting for about 60% of all thyroid nodules. Although fine needle aspiration biopsy (FNAB) is the most reliable diagnostic tool, some nodules are diagnosed as indeterminate and second surgery is common for PTC. The aim of this study was to establish the diagnostic value and feasibility of testing the BRAF T1799A mutation on FNA specimens for improving PTC diagnosis. This prospective study enrolled 95 patients with thyroid nodules and future surgery planned. Results of mutational status were compared with surgical pathology diagnosis. Of the 70 cases included in the final analysis, 62.8% were PTC and the prevalence of BRAF mutation was 38.6%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for BRAF mutation analysis were 36%, 100%, 100% and 48%, respectively. With other data findings, nodules with "onset less than 5 year" and "hard consistency" were proven as diagnostic determinants for BRAF mutation with a probability of 62.5%. This mutation was also a significant risk factor for extra-capsular extension. Molecular analysis of the BRAF T1799A mutation in FNAB specimens has high specificity and positive predictive value for PTC. It could be used in the selective patients with clinical characteristics to facilitate PTC diagnosis and for guidance regarding extent of thyroidectomy.
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Kim, Woon Won; Ha, Tae Kwun; Bae, Sung Kwon
2018-01-09
The purpose of this study was to examine the possible prognostics and clinicopathologic characteristics underlying the BRAFV600E mutation and papillary thyroid carcinoma (PTC) coexisting or in absence of chronic lymphocytic thyroiditis (CLT). This study was conducted on 172 patients who had undergone total thyroidectomy or unilateral total thyroidectomy for PTC; the patients were then examined for the BRAFV600E mutation using specimens obtained after their surgery from January 2013 to August 2015. BRAF mutations were found in 130 of 172 patients (75.6%). CLT was present in 27.9% of patients (48/172). The incidence of the BRAFV600E mutation was significantly increased in the group with no CLT (P = 0.001). The findings of the multivariate analysis pertaining to the coexistence of CLT and PTC showed no significant correlation other than the BRAFV600E mutation. No significant difference was noted in the clinicopathologic factors between the two groups based on the coexistence of CLT in univariate and multivariate analyses. The BRAFV600E mutation is less frequent in PTC coexisting with CLT presumably because CLT and the BRAFV600E mutation operate independently in the formation and progression of thyroid cancer.
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Moll, R.; Wu, X. R.; Lin, J. H.; Sun, T. T.
1995-01-01
Uroplakins (UPs) Ia, Ib, II, and III, transmembrane proteins constituting the asymmetrical unit membrane of urothelial umbrella cells, are the first specific urothelial differentiation markers described. We investigated the presence and localization patterns of UPs in various human carcinomas by applying immunohistochemistry (avidin-biotin-peroxidase complex method), using rabbit antibodies against UPs II and III, to paraffin sections. Positive reactions for UP III (sometimes very focal) were noted in 14 of the 16 papillary noninvasive transitional cell carcinomas (TCCs) (88%), 29 of the 55 invasive TCCs (53%), and 23 of the 35 TCC metastases (66%). Different localization patterns of UPs could be distinguished, including superficial membrane staining like that found in normal umbrella cells (in papillary carcinoma), luminal (microluminal) membrane staining (in papillary and invasive carcinoma), and, against expectations, peripheral membrane staining (in invasive carcinoma). Non-TCC carcinomas of various origins (n = 177) were consistently negative for UPs. The presence of UPs in metastatic TCCs represents a prime example of even advanced tumor progression being compatible with the (focal) expression of highly specialized differentiation repertoires. Although of only medium-grade sensitivity, UPs do seem to be highly specific urothelial lineage markers, thus operating up interesting histodiagnostic possibilities in cases of carcinoma metastases of uncertain origin. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7485401
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Mucin Binding Reduces Colistin Antimicrobial Activity.
Huang, Johnny X; Blaskovich, Mark A T; Pelingon, Ruby; Ramu, Soumya; Kavanagh, Angela; Elliott, Alysha G; Butler, Mark S; Montgomery, A Bruce; Cooper, Matthew A
2015-10-01
Colistin has found increasing use in treating drug-resistant bacterial lung infections, but potential interactions with pulmonary biomolecules have not been investigated. We postulated that colistin, like aminoglycoside antibiotics, may bind to secretory mucin in sputum or epithelial mucin that lines airways, reducing free drug levels. To test this hypothesis, we measured binding of colistin and other antibiotics to porcine mucin, a family of densely glycosylated proteins used as a surrogate for human sputum and airway mucin. Antibiotics were incubated in dialysis tubing with or without mucin, and concentrations of unbound antibiotics able to penetrate the dialysis tubing were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The percentage of antibiotic measured in the dialysate after 4 h in the presence of mucin, relative to the amount without mucin, was 15% for colistin, 16% for polymyxin B, 19% for tobramycin, 52% for ciprofloxacin, and 78% for daptomycin. Antibiotics with the strongest mucin binding had an overall polybasic positive charge, whereas those with comparatively little binding were less basic. When comparing MICs measured with or without added mucin, colistin and polymyxin B showed >100-fold increases in MICs for multiple Gram-negative bacteria. Preclinical evaluation of mucin binding should become a standard procedure when considering the potential pulmonary use of new or existing antibiotics, particularly those with a polybasic overall charge. In the airways, mucin binding may reduce the antibacterial efficacy of inhaled or intravenously administered colistin, and the presence of sub-MIC effective antibiotic concentrations could result in the development of antibiotic resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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Papillary renal cell carcinoma: a clinicopathological and whole-genome exon sequencing study
Liu, Kunpeng; Ren, Yuan; Pang, Lijuan; Qi, Yan; Jia, Wei; Tao, Lin; Hu, Zhengyan; Zhao, Jin; Zhang, Haijun; Li, Li; Yue, Haifeng; Han, Juan; Liang, Weihua; Hu, Jianming; Zou, Hong; Yuan, Xianglin; Li, Feng
2015-01-01
Papillary renal cell carcinoma (PRCC) represents the second most common histological subtype of RCC, and comprises 2 subtypes. Prognosis for type 1 PRCC is relatively good, whereas type 2 PRCC is associated with poor clinical outcomes. The aim of the present study was to evaluate the clinicopathological and mutations characteristics of PRCC. Hence, we reported on 13 cases of PRCC analyzed using whole-exome sequencing. Histologically, type 2 PRCC showed a higher nuclear grade and lymphovascular invasion rate versus type 1 PRCC (P < 0.05). Immunostaining revealed type 1 PRCC had higher CK7 and lower Top IIα expression rates (P < 0.05). Whole-exome sequencing data analysis revealed that the mutational statuses of 373 genes (287 missense, 69 silent, 6 nonsense, and 11 synonymous mutations) differed significantly between PRCC and normal renal tissues (P < 0.05). Functional enrichment analysis was used to classify the 287 missense-mutated genes into 11 biological process clusters (comprised of 61 biological processes) and 5 pathways, involved in cell adhesion, microtubule-based movement, the cell cycle, polysaccharide biosynthesis, muscle cell development and differentiation, cell death, and negative regulation. Associated pathways included the ATP-binding cassette transporter, extracellular matrix-receptor interaction, lysosome, complement and coagulation cascades, and glyoxylate and dicarboxylate metabolism pathways. The missense mutation status of 19 genes differed significantly between the groups (P < 0.05), and alterations in the EEF1D, RFNG, GPR142, and RAB37 genes were located in different chromosomal regions in type 1 and 2 PRCC. These mutations may contribute to future studies on pathogenic mechanisms and targeted therapy of PRCC. PMID:26339402
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Uncommon BRAF mutations in the follicular variant of thyroid papillary carcinoma: New insights.
Rossi, Esther Diana; Martini, Maurizio; Bizzarro, Tommaso; Capodimonti, Sara; Cenci, Tonia; Lombardi, Celestino Pio; Pontecorvi, Alfredo; Fadda, Guido; Larocca, Luigi Maria
2015-10-01
Mutational analysis is reshaping the practice of fine-needle aspiration cytology for the diagnosis of thyroid nodules. The v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) valine (V) to glutamic acid (E) substitution at codon 600 (BRAF(V600E)) is the most effective diagnostic/prognostic marker and is used mainly for papillary thyroid carcinomas (PTCs). Although BRAF(V600E) represents 95% of all BRAF mutations, uncommon BRAF mutations have been identified in thyroid carcinomas. For the current study, the authors evaluated morphologic (plump pink cells and sickle-shaped nuclei) anti-BRAF(V600E) antibody (VE1) immunocytochemical and molecular findings of BRAF mutations in PTCs and in the follicular variant of PTC (FVPC). Between January 2013 and June 2014, there were 150 cytologic samples with surgical follow-up at the authors' institution. BRAF mutations, which were identified using liquid-based cytology, were classified into wild-type BRAF, BRAF(V600E), and uncommon BRAF mutations. All clinicopathologic correlations between BRAF and FVPCs were analyzed. Forty-four of 150 samples were identified as benign histologic lesions, and the authors focused on the 106 cytologic samples from patients who had malignant outcomes (60 PTCs and 46 FVPCs). The series included 16 follicular neoplasms, 36 samples diagnosed as suspicious of malignancy, and 54 samples diagnosed as positive for malignancy. The BRAF(V600E) mutation was detected in 17.4% of FVPCs and in 66.6% of PTCs, whereas uncommon BRAF mutations were detected only in FVPCs. Plump pink cells and VE1 expression were not identified in samples that had uncommon BRAF mutations. VE1 immunocytochemistry yielded positive results in all 36 samples that had the BRAF(V600E) mutation. Uncommon BRAF mutations were observed only in FVPCs and were linked to less aggressive behavior. Negative/weak VE1 expression was observed in both wild-type and uncommon BRAF mutations. The current investigation did not reveal any plump cells or
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Hahn, Soo Yeon; Shin, Jung Hee; Oh, Young Lyun; Kim, Tae Hyuk; Lim, Yaeji; Choi, Ji Soo
2017-09-01
Follicular variant of papillary thyroid carcinoma (FVPTC) is traditionally divided into infiltrative and encapsulated types. Adding to this classification, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a reclassification of a subset of cases (encapsulated tumors without lymphovascular or capsular invasion). The purpose of this study was to assess the role of ultrasound (US) in predicting tumor invasiveness in FVPTC. From January 2014 to May 2016, preoperative US examinations were performed on 151 patients with 152 FVPTCs who underwent surgery. Based on a pathologic analysis, the FVPTCs were categorized into three groups: NIFTP, invasive encapsulated FVPTC (iE-FVPTC), or infiltrative FVPTC (I-FVPTC). Each nodule was categorized based on the US pattern according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American Thyroid Association (ATA) guidelines. The correlation between tumor invasiveness and the K-TIRADS or ATA category was investigated using Spearman's rank correlation coefficient. Among the 152 FVPTCs, there were 48 (31.6%) NIFTPs, 60 (39.5%) iE-FVPTCs, and 44 (28.9%) I-FVPTCs. US characteristics of the FVPTCs differed significantly according to tumor invasiveness (p ≤ 0.030). Tumor invasiveness showed a significant positive correlation with K-TIRADS (tumors of all sizes: r = 0.591, p < 0.001; tumors ≥1.0 cm: r = 0.427, p < 0.001) and ATA categories (tumors of all sizes: r = 0.532, p < 0.001; tumors ≥1.0 cm: r = 0.466, p < 0.001). According to both K-TIRADS and ATA guidelines for all-sized tumors, the most common subtype was NIFTP in low-suspicion nodules (52.6% and 51.6%), iE-FVPTC in intermediate-suspicion nodules (52.7% and 54.2%), and I-FVPTC in high-suspicion nodules (82.5% and 69.4%). After surgery, lymph node metastases were confirmed in two (4.2%) NIFTP cases, three (5.0%) iE-FVPTC cases, and eight (18.2%) I-FVPTC cases (p
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RET/PTC Translocations and Clinico-Pathological Features in Human Papillary Thyroid Carcinoma
Romei, Cristina; Elisei, Rossella
2012-01-01
Thyroid carcinoma is the most frequent endocrine cancer accounting for 5–10% of thyroid nodules. Papillary histotype (PTC) is the most prevalent form accounting for 80% of all thyroid carcinoma. Although much is known about its epidemiology, pathogenesis, clinical, and biological behavior, the only documented risk factor for PTC is the ionizing radiation exposure. Rearrangements of the Rearranged during Transfection (RET) proto-oncogene are found in PTC and have been shown to play a pathogenic role. The first RET rearrangement, named RET/PTC, was discovered in 1987. This rearrangement constitutively activates the transcription of the RET tyrosine-kinase domain in follicular cell, thus triggering the signaling along the MAPK pathway and an uncontrolled proliferation. Up to now, 13 different types of RET/PTC rearrangements have been reported but the two most common are RET/PTC1 and RET/PTC3. Ionizing radiations are responsible for the generation of RET/PTC rearrangements, as supported by in vitro studies and by the evidence that RET/PTC, and particularly RET/PTC3, are highly prevalent in radiation induced PTC. However, many thyroid tumors without any history of radiation exposure harbor similar RET rearrangements. The overall prevalence of RET/PTC rearrangements varies from 20 to 70% of PTCs and they are more frequent in childhood than in adulthood thyroid cancer. Controversial data have been reported on the relationship between RET/PTC rearrangements and the PTC prognosis. RET/PTC3 is usually associated with a more aggressive phenotype and in particular with a greater tumor size, the solid variant, and a more advanced stage at diagnosis which are all poor prognostic factors. In contrast, RET/PTC1 rearrangement does not correlate with any clinical–pathological characteristics of PTC. Moreover, the RET protein and mRNA expression level did not show any correlation with the outcome of patients with PTC and no correlation between RET/PTC rearrangements and the
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Ohnishi, Takamitsu; Takizawa, Hajime; Watanabe, Shinichi
2002-01-01
Mucinous carcinoma of the skin (MCS) is a rare epithelial tumor which arises primarily in the skin. Metastatic MC from extracutaneous sites, especially breast or colon, mimics MCS and cannot be differentiated from MCS by routine histology alone. Nine cases of MCS were analyzed immunohistochemically using monoclonal antibodies against cytokeratins (CKs) and human milk fat globulin 1 (HMFG) in order to clarify their nature and compare the immunophenotypes with those of other MCs studied in the literature. Expression of simple epithelial CKs in most of the tumor cells of all cases studied and co-expression of simple and stratified epithelial CKs in some tumor cells of two cases were recognized. CK 20 expression could not detected in any tumor cells. Focal HMFG expression in the luminal or outer surface of the nests was observed in three cases. From CKs expression, MCS was speculated to differentiated mainly toward the secretory cells of the sweat glands, and some tumor cells toward the transient portion between the dermal duct and the secretory portion. Focal HMFG expression suggested either a consequence of malignant transformation or apocrine differentiation. No expression of CK 20 in MCS suggests that we may exclude the diagnosis of metastatic colorectal MC which expressed CK 20.
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Kuroda, Naoto; Furuya, Mitsuko; Nagashima, Yoji; Gotohda, Hiroko; Moritani, Suzuko; Kawakami, Fumi; Imamura, Yoshiaki; Bando, Yoshimi; Takahashi, Masayuki; Kanayama, Hiro-omi; Ota, Satoshi; Michal, Michal; Hes, Ondrej; Nakatani, Yukio
2014-06-01
In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors. Copyright © 2014 Elsevier Inc. All rights reserved.
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2013-01-01
Background BRAF mutation is an important diagnostic and prognostic marker in patients with papillary thyroid carcinoma (PTC). To be applicable in clinical laboratories with limited equipment, diverse testing methods are required to detect BRAF mutation. Methods A shifted termination assay (STA) fragment analysis was used to detect common V600 BRAF mutations in 159 PTCs with DNAs extracted from formalin-fixed paraffin-embedded tumor tissue. The results of STA fragment analysis were compared to those of direct sequencing. Serial dilutions of BRAF mutant cell line (SNU-790) were used to calculate limit of detection (LOD). Results BRAF mutations were detected in 119 (74.8%) PTCs by STA fragment analysis. In direct sequencing, BRAF mutations were observed in 118 (74.2%) cases. The results of STA fragment analysis had high correlation with those of direct sequencing (p < 0.00001, κ = 0.98). The LOD of STA fragment analysis and direct sequencing was 6% and 12.5%, respectively. In PTCs with pT3/T4 stages, BRAF mutation was observed in 83.8% of cases. In pT1/T2 carcinomas, BRAF mutation was detected in 65.9% and this difference was statistically significant (p = 0.007). Moreover, BRAF mutation was more frequent in PTCs with extrathyroidal invasion than tumors without extrathyroidal invasion (84.7% versus 62.2%, p = 0.001). To prepare and run the reactions, direct sequencing required 450 minutes while STA fragment analysis needed 290 minutes. Conclusions STA fragment analysis is a simple and sensitive method to detect BRAF V600 mutations in formalin-fixed paraffin-embedded clinical samples. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5684057089135749 PMID:23883275
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The tear film and ocular mucins.
Davidson, Harriet J; Kuonen, Vanessa J
2004-01-01
Abstract The trilaminar tear film, composed of the lipid, aqueous and mucin layers, has many functions including defending the ocular surface. The aqueous layer has several soluble antimicrobial factors that protect the ocular surface. Ocular mucins have recently been studied with regard to their role in the defense of the eye as well as in dry eye syndromes. To date, 15 mucin genes have been identified, and six of these mucin genes are localized to or secreted by ocular glands or epithelia. Understanding the production, secretion and function of ocular mucins will aid in the treatment of dry eye syndromes and ocular surface microbial infections.
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Should Level V Be Routinely Dissected in N1b Papillary Thyroid Carcinoma?
Kim, Seo Ki; Park, Inhye; Hur, Nayoon; Lee, Jun Ho; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo
2017-02-01
For N1b papillary thyroid carcinoma (PTC) patients, modified radical neck dissection (MRND) encompassing levels II-V is generally recommended. However, routine level V dissection is controversial because of the low incidence of metastasis/recurrence in level V and the increased morbidities associated with level V dissection. This study retrospectively reviewed 646 N1b PTC patients who underwent unilateral MRND between January 1997 and June 2015. Specifically, to assess surgery-related outcomes of level V dissection, outcomes from N1b PTC patients who underwent unilateral MRND (levels II-V) were compared with those who underwent unilateral selective neck dissection (SND; levels II-IV) using propensity score matching. Overall and occult level V metastases were observed in 13.9% and 8.6% of patients, respectively. Level V recurrences were observed in only 2.26 (7.7%) recurred N1b PTC patients who underwent unilateral MRND. In multivariate analysis, three-level (II, III, and IV) simultaneous metastasis (adjusted odds ratio = 3.079, p = 0.003) was an independent predictor for level V metastasis. Under a matched condition, "shoulder syndrome" encompassing shoulder dysfunction and pain (9.1% vs. 2.7%, p = 0.002) was significantly more frequent in the MRND group than it was in the SND group. Because of the low incidence of metastasis/recurrence in level V and the clear evidence of increased morbidities, level V dissection in N1b PTC patients may be reserved for those with three-level simultaneous metastasis or clinically/radiologically evident level V metastasis.
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Roch, Alexandra M; Parikh, Janak A; Al-Haddad, Mohammad A; DeWitt, John M; Ceppa, Eugene P; House, Michael G; Nakeeb, Attila; Schmidt, C Max
2014-10-01
Pancreatitis is associated with intraductal papillary mucinous neoplasm (IPMN). This association is in part due to inflammation from pancreatic ductal obstruction. Although the correlation between pancreatitis and the malignant potential of IPMN is unclear, the 2012 International Consensus Guidelines (ICG) consider pancreatitis a "worrisome feature." We hypothesized that serum pancreatic enzymes, markers of inflammation, are a better predictor of malignancy than pancreatitis in patients with IPMN. Between 1992 and 2012, 364 patients underwent resection for IPMN at a single university hospital. In the past decade, serum amylase and lipase were collected prospectively as an inflammatory marker in 203 patients with IPMN at initial surveillance and "cyst clinic" visits. The latest serum pancreatic enzyme values within 3 months preoperatively were studied. Pancreatitis was defined according to the 2012 revision of the Atlanta Consensus. Of the 203 eligible patients, there were 76 with pancreatitis. Pancreatitis was not associated with an increased rate of malignancy (P = .51) or invasiveness (P = .08). Serum pancreatic enzymes categorically outside of normal range (high or low) were also not associated with malignancy or invasiveness. In contrast, as a continuous variable, the higher the serum pancreatic enzymes were, the greater the rate of invasive IPMN. Of the 127 remaining patients without pancreatitis, serum pancreatic enzymes outside of normal range (low and high) were each associated with a greater rate of malignancy (P < .0001 and P = .0009, respectively). Serum pancreatic enzyme levels above normal range (high) were associated with a greater rate of invasiveness (P = .02). In patients with IPMN without a history of pancreatitis, serum pancreatic enzymes outside of the normal range are associated with a greater risk of malignancy. In patients with a history of pancreatitis, there is a positive correlation between the levels of serum pancreatic enzymes
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Prognostic significance of muc4 expression in gallbladder carcinoma.
Lee, Hyeon Kook; Cho, Min-Sun; Kim, Tae Hun
2012-10-27
Mucins are high molecular glycoproteins and play protective and lubricating roles in various epithelial tissues. Deregulated expression of mucins is involved in carcinogenesis and tumor invasion. MUC4 expression has been identified as a poor prognostic factor in pancreatobiliary carcinomas. To date, the relation between MUC4 expression and prognosis in gallbladder carcinoma remains to be determined. Authors examined MUC4 expression in gallbladder carcinoma and investigated its impact on prognosis. The expression profiles of MUC4, MUC1, MUC2 mucins in gallbladder carcinoma tissues from 63 patients were investigated using immunohistochemical staining. For gallbladder carcinoma, positive staining of MUC4, MUC1, and MUC2 was 55.6%, 81.0%, 28.6%, respectively. There was a significant correlation between the expression of MUC4 and the expression of MUC1 or MUC2 (p = 0.004, p = 0.009, respectively). Univariate analysis showed that MUC4 expression (p = 0.047), differentiation (p < 0.05), T-stage (p < 0.05) and lymph node metastasis (p < 0.001) were significantly associated with poor survival. Expression of MUC1 and MUC2 was not correlated to survival. The backward stepwise multivariate analysis showed that MUC4 expression (p = 0.039) and lymph node metastasis (p = 0.001) were significant independent risk factors. In combined assessment of MUC4 and MUC2 expression, MUC4 positive and MUC2 negative group showed a significantly worse outcome than MUC4 negative groups(MUC4-/MUC2+ and MUC4-/MUC2-) and MUC4/MUC2 co-expression group(MUC4+/MUC2+) (p < 0.05). MUC4 expression in gallbladder carcinoma is an independent poor prognostic factor. Therefore, MUC4 expression may be a useful marker to predict the outcome of patients with surgically resected gallbladder carcinoma. MUC2 expression may have prognostic value when combined with MUC4 expression.
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Prognostic significance of muc4 expression in gallbladder carcinoma
2012-01-01
Background Mucins are high molecular glycoproteins and play protective and lubricating roles in various epithelial tissues. Deregulated expression of mucins is involved in carcinogenesis and tumor invasion. MUC4 expression has been identified as a poor prognostic factor in pancreatobiliary carcinomas. To date, the relation between MUC4 expression and prognosis in gallbladder carcinoma remains to be determined. Authors examined MUC4 expression in gallbladder carcinoma and investigated its impact on prognosis. Methods The expression profiles of MUC4, MUC1, MUC2 mucins in gallbladder carcinoma tissues from 63 patients were investigated using immunohistochemical staining. Results For gallbladder carcinoma, positive staining of MUC4, MUC1, and MUC2 was 55.6%, 81.0%, 28.6%, respectively. There was a significant correlation between the expression of MUC4 and the expression of MUC1 or MUC2 (p = 0.004, p = 0.009, respectively). Univariate analysis showed that MUC4 expression (p = 0.047), differentiation (p < 0.05), T-stage (p < 0.05) and lymph node metastasis (p < 0.001) were significantly associated with poor survival. Expression of MUC1 and MUC2 was not correlated to survival. The backward stepwise multivariate analysis showed that MUC4 expression (p = 0.039) and lymph node metastasis (p = 0.001) were significant independent risk factors. In combined assessment of MUC4 and MUC2 expression, MUC4 positive and MUC2 negative group showed a significantly worse outcome than MUC4 negative groups(MUC4-/MUC2+ and MUC4-/MUC2-) and MUC4/MUC2 co-expression group(MUC4+/MUC2+) (p < 0.05). Conclusions MUC4 expression in gallbladder carcinoma is an independent poor prognostic factor. Therefore, MUC4 expression may be a useful marker to predict the outcome of patients with surgically resected gallbladder carcinoma. MUC2 expression may have prognostic value when combined with MUC4 expression. PMID:23101681
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He, Jian; Zhou, Kefeng; Zhu, Bin; Zhang, Gutian; Li, Xiaogong; Guo, Hongqian; Gan, Weidong; Zhou, Zhengyang; Liu, Tian
2015-01-01
To compare the differences of CT characteristics between renal cell carcinomas (RCCs) associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 RCCs) and papillary cell renal cell carcinomas (PRCCs). CT images and clinical records of 64 patients (25 Xp11.2 RCCs, 15 type 1 and 24 type 2 PRCCs) were analyzed and compared retrospectively. Xp11.2 RCC more frequently affected young (30.7 ± 8.7 years) women (16/25, 64%) with gross hematuria (12/25, 48%), while PRCC more frequently involved middle-aged (54.8 ± 11.1 years) men (28/39, 71.8%) asymptomatically. Xp11.2 RCC tended to be heterogeneous density with some showing circular calcification. Lesion sizes of Xp11.2 RCC (5.4 ± 2.2 cm) and type 2 PRCC (5.7 ± 2.5 cm) were significantly larger than that of type 1 PRCC (3.8 ± 1.8 cm). Xp11.2 RCC contained more cystic components (22/25, 88%) than type 1 PRCC (all solid) and type 2 PRCC (9/24, 36.0%). Type 1 PRCC (13/15, 86.7%) and Xp11.2 RCC (21/25, 84.0%) showed more clear boundary than type 2 PRCC (12/24, 50.0%). CT features including diameter, boundary, attenuation, nature, and circular calcification of the tumor, combined with demographic information and symptoms, may be useful to differentiate Xp11.2 RCC from different subtypes of PRCC.
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Foda, Abd Al-Rahman Mohammad; Mohammad, Mie Ali; Abdel-Aziz, Azza; El-Hawary, Amira Kamal
2015-06-01
Glypican-3 (GPC3) is a member of the membrane-bound heparin sulfate proteoglycans. E-cadherin is an adhesive receptor that is believed to act as a tumor suppressor gene. Many studies had investigated E-cadherin expressions in colorectal carcinoma (CRC) while only one study had investigated GPC3 expression in CRC. This study aims to investigate expression of GCP3 and E-cadherin in colorectal mucinous carcinoma (MA) and non-mucinous adenocarcinoma (NMA) using manual tissue microarray technique. Tumor tissue specimens are collected from 75 cases of MC and 75 cases of NMA who underwent radical surgery from Jan 2007 to Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their clinicopathological parameters and survival data were revised and analyzed using established statistical methodologies. High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique and immunohistochemistry for GPC3 and E-cadherin was done. NMA showed higher expression of GPC3 than MA with no statistically significant relation. NMA showed a significantly higher E-cadherin expression than MA. GPC3 and E-cadherin positivity rates were significantly interrelated in NMA, but not in MA, group. In NMA group, there was no significant relation between either GPC3 or E-cadherin expression and the clinicopathological features. In a univariate analysis, neither GPC3 nor E-cadherin expression showed a significant impact on disease-free survival (DFS) or overall survival (OS). GPC3 and E-cadherin expressions are not independent prognostic factors in CRC. However, expressions of both are significantly interrelated in NMA patients, suggesting an excellent interplay between both, in contrast to MA. Further molecular studies are needed to further explore the relationship between GCP3 and E-cadherin in colorectal carcinogenesis.
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Gou, Qiheng; Gao, Linbo; Nie, Xinwen; Pu, Wenchen; Zhu, Jingqiang; Wang, Yichao; Liu, Xuesha; Tan, Shuangyan; Zhou, Jian-Kang; Gong, Yanqiu; He, Juan; Wu, Ke; Xie, Yuxin; Zhao, Wanjun; Dai, Lunzhi; Liu, Lunxu; Xiang, Rong; Wei, Yu-Quan; Zhang, Lin; Peng, Yong
2018-05-07
Long noncoding RNAs (lncRNAs) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell cycle arrest and tumor growth inhibition in vitro and in vivo, whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis. Copyright ©2018, American Association for Cancer Research.
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He, Zhongshi; Sun, Min; Ke, Yuan; Lin, Rongjie; Xiao, Youde; Zhou, Shuliang; Zhao, Hong; Wang, Yan; Zhou, Fuxiang; Zhou, Yunfeng
2017-04-25
Although papillary renal cell carcinoma (PRCC) accounts for 10%-15% of renal cell carcinoma (RCC), no predictive molecular biomarker is currently applicable to guiding disease stage of PRCC patients. The mRNASeq data of PRCC and adjacent normal tissue in The Cancer Genome Atlas was analyzed to identify 1148 differentially expressed genes, on which weighted gene co-expression network analysis was performed. Then 11 co-expressed gene modules were identified. The highest association was found between blue module and pathological stage (r = 0.45) by Pearson's correlation analysis. Functional enrichment analysis revealed that biological processes of blue module focused on nuclear division, cell cycle phase, and spindle (all P < 1e-10). All 40 hub genes in blue module can distinguish localized (pathological stage I, II) from non-localized (pathological stage III, IV) PRCC (P < 0.01). A good molecular biomarker for pathological stage of RCC must be a prognostic gene in clinical practice. Survival analysis was performed to reversely validate if hub genes were associated with pathological stage. Survival analysis unveiled that all hub genes were associated with patient prognosis (P < 0.01).The validation cohort GSE2748 verified that 30 hub genes can differentiate localized from non-localized PRCC (P < 0.01), and 18 hub genes are prognosis-associated (P < 0.01).ROC curve indicated that the 17 hub genes exhibited excellent diagnostic efficiency for localized and non-localized PRCC (AUC > 0.7). These hub genes may serve as a biomarker and help to distinguish different pathological stages for PRCC patients.
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Significance of mucin on the ocular surface.
Watanabe, Hitoshi
2002-03-01
To review the significance of mucin in the tear film and the ocular surface epithelium. Summary of the information on how mucin derived from the corneal and conjunctival epithelia and from goblet cells plays a role in the stability of the tear film over the ocular surface. The change in mucin expression derived from the ocular surface epithelium is also discussed with reference to ocular surface disease. The corneal and conjunctival epithelia produce transmembrane mucins such as MUC1, MUC2, and MUC4. In contrast, goblet cells produce the gel-forming secretory mucin, MUC5AC. The lacrimal gland produces MUC7. On the ocular surface, cooperation between transmembrane mucin and secretory mucin is necessary for the stability of the tear film. The expression of mucin from the ocular surface epithelium is coordinated from the time of eyelid opening and is altered in conditions such as squamous metaplasia and dry eye. This alteration may result in instability of the tear film. CONCLU SION: The induction of mucin from the ocular surface may facilitate the stability of the tear film, and increased knowledge may lead to the development of a new modality for the treatment of dry eye.
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Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza
2014-06-01
Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.
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Selmansberger, Martin; Braselmann, Herbert; Hess, Julia; Bogdanova, Tetiana; Abend, Michael; Tronko, Mykola; Brenner, Alina; Zitzelsberger, Horst; Unger, Kristian
2015-01-01
One of the major consequences of the 1986 Chernobyl reactor accident was a dramatic increase in papillary thyroid carcinoma (PTC) incidence, predominantly in patients exposed to the radioiodine fallout at young age. The present study is the first on genomic copy number alterations (CNAs) of PTCs of the Ukrainian–American cohort (UkrAm) generated by array comparative genomic hybridization (aCGH). Unsupervised hierarchical clustering of CNA profiles revealed a significant enrichment of a subgroup of patients with female gender, long latency (>17 years) and negative lymph node status. Further, we identified single CNAs that were significantly associated with latency, gender, radiation dose and BRAF V600E mutation status. Multivariate analysis revealed no interactions but additive effects of parameters gender, latency and dose on CNAs. The previously identified radiation-associated gain of the chromosomal bands 7q11.22-11.23 was present in 29% of cases. Moreover, comparison of our radiation-associated PTC data set with the TCGA data set on sporadic PTCs revealed altered copy numbers of the tumor driver genes NF2 and CHEK2. Further, we integrated the CNA data with transcriptomic data that were available on a subset of the herein analyzed cohort and did not find statistically significant associations between the two molecular layers. However, applying hierarchical clustering on a ‘BRAF-like/RAS-like’ transcriptome signature split the cases into four groups, one of which containing all BRAF-positive cases validating the signature in an independent data set. PMID:26320103
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Membrane-associated mucins in normal human conjunctiva.
Berry, M; Ellingham, R B; Corfield, A P
2000-02-01
To examine the presence of specific membrane-associated mucins in normal human conjunctiva. Glycoconjugates were extracted from membranes with two detergents: octylglucoside and Triton X114. Mucins were separated by cesium chloride density gradient centrifugation. Size was assessed by gel filtration on Sepharose CL2B and charge by ion-exchange chromatography on MonoQ. Cross reaction with antibodies against mucin gene products was assessed in blots of electrophoresis gels. Extraction of total tissue membranes yielded material with a buoyant density typical of mucins. Gel filtration showed material reacting with antimucin antibodies in a range of molecular sizes. Agarose electrophoresis confirmed the presence of MUC1 and MUC4 and the absence of MUC2 or MUC5AC. Isolation of membrane mucins by sequential, exhaustive extraction with octylglucoside followed by Triton X114 suggested the existence of mucins in different membrane environments. Reagents to carbohydrate epitopes revealed high mobility material, comigrating with MUC1 and MUC4. Low mobility membrane-bound mucins did not cross-react with any antibodies to mucin genes known to be expressed in human conjunctiva. Membrane-associated mucins are distinct from secreted mucins in normal human conjunctiva. MUC1 and MUC4 mature products decorate the membranes of conjunctival epithelial cells. Their segregation between octyl glucoside and the detergent and aqueous phases of Triton X114 suggests a variety of membrane anchoring modes.
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Pignata, Sandro; Ferrandina, Gabriella; Scarfone, Giovanna; Scollo, Paolo; Odicino, Franco; Cormio, Gennaro; Katsaros, Dionyssios; Villa, Antonella; Mereu, Liliana; Ghezzi, Fabio; Manzione, Luigi; Lauria, Rossella; Breda, Enrico; Alletti, Desiderio Gueli; Ballardini, Michela; Lombardi, Alessandra Vernaglia; Sorio, Roberto; Mangili, Giorgia; Priolo, Domenico; Magni, Giovanna; Morabito, Alessandro
2008-01-01
Background Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer. Methods The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000–2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible. Results Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056) and less advanced FIGO stage (p = 0.025). At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024). About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03). Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026), with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04). Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023). Conclusion This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed. PMID:18761742
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miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhu, Hongling; Fang, Jin; Zhang, Jichen
2014-07-18
Highlights: • miR-182 and CHL1 expression patterns are negatively correlated. • CHL1 is a direct target of miR-182 in PTC cells. • miR-182 suppression inhibits PTC cell growth and invasion. • CHL1 is involved in miR-182-mediated cell behavior. - Abstract: In this study, we investigated the role and underlying mechanism of action of miR-182 in papillary thyroid carcinoma (PTC). Bioinformatics analysis revealed close homolog of LI (CHL1) as a potential target of miR-182. Upregulation of miR-182 was significantly correlated with CHL1 downregulation in human PTC tissues and cell lines. miR-182 suppressed the expression of CHL1 mRNA through direct targeting ofmore » the 3′-untranslated region (3′-UTR). Downregulation of miR-182 suppressed growth and invasion of PTC cells. Silencing of CHL1 counteracted the effects of miR-182 suppression, while its overexpression mimicked these effects. Our data collectively indicate that miR-182 in PTC promotes cell proliferation and invasion through direct suppression of CHL1, supporting the potential utility of miR-182 inhibition as a novel therapeutic strategy against PTC.« less
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Meng, Xiaomei; Zhu, Peng; Li, Ning; Hu, Jinchen; Wang, Shaoguang; Pang, Shuguang; Wang, Jiahui
2017-04-01
Bone morphogenetic protein 4 (BMP-4) is a member of the BMP protein family. BMP-4 was reported to induce epithelial-mesenchymal transition (EMT) and promote tumor cell immigration and invasion. This study aimed to investigate the expression of BMP-4 in papillary thyroid carcinoma (PTC) and its correlation with the patients' clinicophathological features and with tumor invasion and metastasis. Surgically resected PTC specimens from 82 patients admitted to the Department of Thyroid Surgery of Yantai Yuhuangding Hospital between Feb 1st and May 31st, 2016 were collected. The expression level of BMP-4 in PTC tissues was examined by immunohistochemical staining. The full clinical records of all patients were collected to analyze the relevance between BMP-4 expression and the clinical pathological features of PTC. Our result showed that BMP-4-positive cell rate and staining intensity were positively correlated with the patient's age (P=0.031, 0.037), tumor size (P=0.033, 0.019), capsular invasion (P=0.001, 0.002) and TNM stage (P=0.001, 0.004), while not correlated with gender, multicentricity of tumor or lymphatic metastasis. In conclusion, this study identified BMP-4 as a potential molecular marker for predicting the invasion and progression of PTC. Copyright © 2017 Elsevier GmbH. All rights reserved.
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Li, Hui; Li, Xiang; Liu, Jie; Jin, Langping; Yang, Fan; Wang, Junbo; Wang, Ouchen; Gao, Ying
2017-10-01
Studies have showed that lead was associated with human health. However, the effects of lead on thyroid functions are inconsistent, and studies based on Chinese population are fragmentary. To evaluate the correlation between lead and thyroid functions of Chinese with different thyroid diseases, we conducted a hospital-based study. Ninety-six papillary thyroid carcinoma (PTC), 10 nodular goiter (NG), and 7 thyroid adenoma (TA) patients were recruited from the First Affiliated Hospital of Wenzhou Medical University, China. Serum triiodothyronine (T3), free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone (TSH) were evaluated with chemiluminescent microparticle immunoassay. Serum lead was assessed with ICP-MASS. Partial correlation was used to explore the correlations of serum lead and thyroid diseases. Compared to PTC, the level of lead was significantly higher in TA, and lower in NG (p < 0.05). This difference remained significant in females when stratified by sex. Serum lead was negatively correlated with TSH (r s = - 0.27, p < 0.05) in PTC group. T3 was positively related to lead at quartile4 (r s = 0.61, p < 0.05) in PTC group. No significant correlations were observed between lead and FT3 or FT4 in any group. The results suggested that lead might have different etiological roles in these three thyroid diseases.
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Kaur, Sukhwinder; Momi, Navneet; Chakraborty, Subhankar; Wagner, David G; Horn, Adam J; Lele, Subodh M; Theodorescu, Dan; Batra, Surinder K
2014-01-01
Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p≤0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma.
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Kaur, Sukhwinder; Momi, Navneet; Chakraborty, Subhankar; Wagner, David G.; Horn, Adam J.; Lele, Subodh M.; Theodorescu, Dan; Batra, Surinder K.
2014-01-01
Purpose Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. Material and Methods Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. Results MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p≤0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). Conclusion The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma. PMID:24671186
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Yoo, Yeon Hwa; Kim, Jeong-Ah; Son, Eun Ju; Youk, Ji Hyun; Kwak, Jin Young; Kim, Eun-Kyung; Park, Cheong Soo
2013-12-01
To analyze sonographic findings suggesting central lymph node metastasis of papillary thyroid carcinoma and to evaluate the influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography for predicting central lymph node metastasis. A total of 124 patients (101 female and 23 male; mean age, 47.5 years; range, 21-74 years) underwent sonographically guided fine-needle aspiration in central lymph nodes from January 2008 to July 2011. Sonographic features of size, shape, margin, thickening of the cortex, cortical echogenicity, presence of a hilum, cystic changes, calcification, and vascularity of enlarged lymph nodes were analyzed before fine-needle aspiration and classified into 2 categories (probably benign and suspicious). Sonographic findings were correlated with the pathologic diagnosis and associated chronic lymphocytic thyroiditis. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance of sonography for predicting central lymph node metastasis according to the associated thyroiditis. Fifty-one lymph nodes (39.5%) were malignant, and 73 (60.5%) were benign. On univariate analysis, size, shape, margin, cortical thickening, cortical echogenicity, cystic changes, calcification, and vascularity were significantly different between the benign and metastatic nodes (P < .05). On multivariate analysis, eccentric cortical thickening (odds ratio, 26.59; 95% confidence interval [CI], 3.26-216.66) and hyper echogenicity of the cortex (odds ratio, 18.46; 95% CI, 2.44-139.64) were significantly associated with malignant nodes (P < .05). The area under the curve values for sonography for predicting metastasis were 0.756 (95% CI, 0.618-0.894) in chronic lymphocytic thyroiditis-positive patients and 0.971 (95% CI, 0.938-1.000) in negative patients. Eccentric cortical thickening and cortical hyperechogenicity were the sonographic findings predictive of central lymph node metastasis from papillary
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Tsilchorozidou, Tasoula; Vafiadou, Eleni; Yovos, John G; Romeo, Giovani; McKay, James; Lesueur, Fabienne; Bonora, Elena
2005-12-01
The familial form of nonmedullary thyroid carcinoma (FNMTC) has been recognized as a distinct clinical entity and is characterized by multifocality and a more severe phenotype than its sporadic counterpart. The majority of FNMTC pedigrees are small in size, show variable modes of inheritance, and may present with a variety of additional benign thyroid disorders. The existence of marked phenotypic differences between FNMTC families suggests that there is genetic heterogeneity. Recent studies have mapped a susceptibility locus for FNMTC at 2q21. This locus appears particular relevant to families with at least one case of the follicular variant of papillary thyroid cancer (fvPTC). We describe the clinical and pathologic characteristics of a large three-generation fPTC kindred, with two of the four PTC patients presented with the follicular variant of PTC. It is of interest the occurrence of PTC in three siblings within a period of 3 years. In addition, multinodular goiter (MNG) was diagnosed in seven individuals, lymphocytic thyroiditis in four, while one diagnosed with a benign adenoma. From the PTC patients, one had MNG and fvPTC, one MNG, lymphocytic thyroiditis and papillary pattern of PTC, one lymphocytic thyroiditis and fvPTC, and one MNG and papillary pattern of PTC. The inheritance pattern was autosomal dominant with incomplete penetrance and women were affected more frequently than men. Considering all PTC-affected individuals, the limit of detection (LOD) score we got for this family on 2q21 was 0.5. The low LOD score is caused by a PTC patient who does not share the affected haplotype, suggesting that maybe a new locus for PTC predisposition is present in this kindred. Linkage analysis also excluded TCO, MNG, and fPTC/PRN as susceptibility loci to FNMTC in this family.
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Ciliated muconodular papillary tumour of the lung: a newly defined low-grade malignant tumour.
Sato, Shuichi; Koike, Teruaki; Homma, Keiichi; Yokoyama, Akira
2010-11-01
We present two cases of ciliated muconodular papillary tumour (CMPT) in this report. CMPT is a newly defined low-grade malignant tumour with ciliated columnar epithelial cells, occurring in the peripheral lung. Both patients underwent pulmonary resection due to an enlarged solitary pulmonary nodule. Pathological findings in both cases confirmed a papillary tumour with a mixture of ciliated columnar and goblet cells. The tumours were rich in mucous and had spread along the alveolar walls, as observed in bronchioloalveolar carcinoma. Nuclear atypia was mild, and no mitotic activity was observed. Immunohistochemically, tumour cells stained positive for carcinoembryonic antigen, thyroid transcription factor-1 and cytokeratin 7 but not for cytokeratin 20. The immunohistochemical staining patterns were almost identical to those of pulmonary adenocarcinoma. We definitively diagnosed as CMPT. Both patients remained relapse-free.
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Skenderi, Faruk; Ulamec, Monika; Vanecek, Tomas; Martinek, Petr; Alaghehbandan, Reza; Foix, Maria Pane; Babankova, Iva; Montiel, Delia Perez; Alvarado-Cabrero, Isabel; Svajdler, Marian; Dubinský, Pavol; Cempirkova, Dana; Pavlovsky, Michal; Vranic, Semir; Daum, Ondrej; Ondic, Ondrej; Pivovarcikova, Kristyna; Michalova, Kvetoslava; Hora, Milan; Rotterova, Pavla; Stehlikova, Adela; Dusek, Martin; Michal, Michal; Hes, Ondrej
2017-04-01
Oncocytic papillary renal cell carcinoma (PRCC) is a distinct subtype of PRCC, listed as a possible new variant of PRCC in the 2016 WHO classification. It is composed of papillae aligned by large single-layered eosinophilic cells showing linearly arranged oncocytoma-like nuclei. We analyzed clinicopathologic, morphologic, immunohistochemical and molecular-genetic characteristics of 11 oncocytic PRCCs with prominent tumor lymphocytic infiltrate, morphologically resembling Warthin's tumor. The patients were predominantly males (8/11, 73%), with an average age of 59years (range 14-76), and a mean tumor size of 7cm (range 1-22cm). Tumors had the features of oncocytic PRCCs with focal pseudostratification in 8/11 cases and showed dense stromal inflammatory infiltration in all cases. Papillary growth pattern was predominant, comprising more than 60% of tumor volume. Tubular and solid components were present in 5 and 3 cases, respectively. Uniform immunohistochemical positivity was found for AMACR, PAX-8, MIA, vimentin, and OSCAR. Tumors were mostly negative for carboanhydrase 9, CD117, CK20, and TTF-1. Immunohistochemical stains for DNA mismatch repair proteins MLH1 and PMS2 were retained in all cases, while MSH2 and MSH6 were negative in 1 case. Tumor infiltrating lymphocytes (TILs) consisted of both B and T cells. Chromosomal copy number variation analysis showed great variability in 5 cases, ranging from a loss of one single chromosome to complex genome rearrangements. Only one case showed gains of chromosomes 7 and 17, among other aberrations. In 4 cases no numerical imbalance was found. Follow up data was available for 9 patients (median 47.6months, range 1-132). In 6 patients no lethal progression was noted, while 3 died of disease. In conclusion, Warthin-like PRCC is morphologically very close to oncocytic PRCC, from which it differs by the presence of dense lymphoid stroma. Chromosomal numerical aberration pattern of these tumors is variable; only one case showed
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Yıldırım, Ayhan; Kösem, Mustafa; Sayar, İlyas; Gelincik, İbrahim; Yavuz, Alparslan; Bozkurt, Aliseydi; Erkorkmaz, Ünal; Bayram, İrfan
2014-01-01
In the present study, the intention was to reveal the relationship of histological grade and stage with c-erbB2, CD44s, and PCNA immunoreactivity in bladder urothelial carcinomas (UC). In our study, we evaluated 46 items of transurethral resection material of patients submitted by YYU Faculty of Medicine, Main Department of Pathology, with a mass revealed in their bladder after clinical and radiological studies at our laboratories and who were diagnosed with urothelial carcinomas. PCNA, c-erbB2, and CD44s were applied in an immunohistochemical manner comprised from nine low-malignant potential papillary urothelial neoplasia, 23 low-grade papillary urothelial carcinoma, and 14 high-grade papillary urothelial carcinoma. Immunostaining was scored according to the percentage of positive cells. The immunohistochemical study demonstrated that the c-erbB2 and PCNA staining ratio increased when an increase occurred in stage and grade. The CD44s staining ratio decreased. C-erbB2, PCNA, and CD44s appear to be a useful marker in the assessment of the prognosis and treatment options in urothelial carcinomas. PMID:25035774
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Mucin gene expression in human male urogenital tract epithelia
Russo, Cindy Leigh; Spurr-Michaud, Sandra; Tisdale, Ann; Pudney, Jeffrey; Anderson, Deborah; Gipson, Ilene K.
2010-01-01
BACKGROUND Mucins are large, hydrophilic glycoproteins that protect wet-surfaced epithelia from pathogen invasion as well as provide lubrication. At least 17 mucin genes have been cloned to date. This study sought to determine the mucin gene expression profile of the human male urogenital tract epithelia, to determine if mucins are present in seminal fluid, and to assess the effect of androgens on mucin expression. METHODS AND RESULTS Testis, epididymis, vas deferens, seminal vesicle, prostate, bladder, urethra and foreskin were assessed for mucin expression by RT-PCR and immunohistochemistry. Epithelia of the vas deferens, prostate and urethra expressed the greatest number of mucins, each expressing 5–8 mucins. Messenger RNA of MUC1 and MUC20, both membrane-associated mucins, were detected in most tissues analyzed. Conversely, MUC6 was predominantly detected in seminal vesicle. MUC1, MUC5B and MUC6 were detected in seminal fluid samples by immunoblot analysis. Androgens had no effect on mucin expression by cultured human prostatic epithelial cells. CONCLUSIONS Each region of urogenital tract epithelium expressed a unique mucin gene repertoire. Secretory mucins are present in seminal fluid, and androgens do not appear to regulate mucin gene expression. PMID:16997931
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Carretta, A; Canneto, B; Calori, G; Ceresoli, G L; Campagnoli, E; Arrigoni, G; Vagani, A; Zannini, P
2001-08-01
The incidence of adenocarcinoma and bronchoalveolar carcinoma has increased in recent years. The aim of this study was to retrospectively evaluate radiological and pathological factors affecting survival in patients with bronchoalveolar carcinoma (BAC) or BAC associated with adenocarcinoma who underwent surgical treatment. From May 1988 to September 1999, 49 patients with BAC or BAC and adenocarcinoma underwent surgical treatment. Complete resection was performed in 42 patients. In these patients the impact of the following factors on survival was evaluated: stage, TNM status, radiological and pathological findings (percentage of bronchoalveolar carcinoma in the tumour, presence or absence of sclerosing and mucinous patterns, vascular invasion and lymphocytic infiltration). Twenty-nine patients were male and 20 female. Mean age was 63 years. Five-year survival was 54%. Univariate analysis of the patients who underwent complete resection demonstrated a favourable impact on survival in stages Ia and Ib (P = 0.01) and in the absence of nodal involvement (P = 0.02) and mucinous patterns (P = 0.02). Mucinous pattern was also prognostically relevant at multivariate analysis (P = 0.02). In the 27 patients with stage Ia and Ib disease, univariate analysis demonstrated that the absence of mucinous pattern (P = 0.006) and a higher percentage of BAC (P = 0.01) favourably influenced survival. The latter data were also confirmed by multivariate analysis (P = 0.01). Surgical treatment of early-stage BAC and combined BAC and adenocarcinoma is associated with favourable results. However, the definition of prognostic factors is of utmost importance to improve the results of the treatment. In our series tumours of the mucinous subtype and with a lower percentage of BAC had a worse prognosis.
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Lubiprostone stimulates small intestinal mucin release
2012-01-01
Background Lubiprostone is a synthetic bicyclic fatty acid derivative of prostaglandin E1 (PGE1) used for chronic constipation. The best known action of lubiprostone is simulation of Cl- dependent fluid secretion. In a mouse model of the genetic disease cystic fibrosis, we previously showed that in vivo administration of lubiprostone resulted in greater mucus accumulation in the small intestine. The aim of this study was to directly test whether lubiprostone stimulates intestinal mucin release. Methods Mucin release was measured by mounting segments (4-5 cm) of mouse proximal-mid small intestine in an organ bath, allowing access to the perfusate (luminal) and the bath (serosal) solutions. Nifedipine (10-6 M) and indomethacin (10-5 M) were included in all solutions to inhibit smooth muscle activity and endogenous prostaglandin production, respectively. The tissue was equilibrated under flow for 30 min, using the perfusate collected during the final 10 min of the equilibration period to measure unstimulated release rate. Stimulus was then added to either the perfusate or the bath and the perfusate was collected for another 30 min to measure the stimulated mucin release rate. Mucin in perfusates was quantified by periodic acid-Schiff's base dot-blot assay, using purified pig gastric mucin as a standard. Results When applied luminally at 1 μM lubiprostone was ineffective at stimulating mucin release. When added to the serosal solution, 1 μM lubiprostone stimulated mucin release to ~300% of the unstimulated rate. As a positive control, serosal 1 μM prostaglandin E2 increased mucin release to ~400% of the unstimulated rate. Conclusions These results support the idea that lubiprostone has prostaglandin-like actions on the intestine, which includes stimulation of mucin release. Stimulation of mucin release by lubiprostone may be protective in gastrointestinal conditions where loss of mucus is believed to contribute to pathogenesis. Thus, in addition to chronic
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Lubiprostone stimulates small intestinal mucin release.
De Lisle, Robert C
2012-11-06
Lubiprostone is a synthetic bicyclic fatty acid derivative of prostaglandin E1 (PGE1) used for chronic constipation. The best known action of lubiprostone is simulation of Cl- dependent fluid secretion. In a mouse model of the genetic disease cystic fibrosis, we previously showed that in vivo administration of lubiprostone resulted in greater mucus accumulation in the small intestine. The aim of this study was to directly test whether lubiprostone stimulates intestinal mucin release. Mucin release was measured by mounting segments (4-5 cm) of mouse proximal-mid small intestine in an organ bath, allowing access to the perfusate (luminal) and the bath (serosal) solutions. Nifedipine (10-6 M) and indomethacin (10-5 M) were included in all solutions to inhibit smooth muscle activity and endogenous prostaglandin production, respectively. The tissue was equilibrated under flow for 30 min, using the perfusate collected during the final 10 min of the equilibration period to measure unstimulated release rate. Stimulus was then added to either the perfusate or the bath and the perfusate was collected for another 30 min to measure the stimulated mucin release rate. Mucin in perfusates was quantified by periodic acid-Schiff's base dot-blot assay, using purified pig gastric mucin as a standard. When applied luminally at 1 μM lubiprostone was ineffective at stimulating mucin release. When added to the serosal solution, 1 μM lubiprostone stimulated mucin release to ~300% of the unstimulated rate. As a positive control, serosal 1 μM prostaglandin E2 increased mucin release to ~400% of the unstimulated rate. These results support the idea that lubiprostone has prostaglandin-like actions on the intestine, which includes stimulation of mucin release. Stimulation of mucin release by lubiprostone may be protective in gastrointestinal conditions where loss of mucus is believed to contribute to pathogenesis. Thus, in addition to chronic constipation, there is greater potential for the
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[Hyperthyroidism and carcinoma of the thyroid gland].
Ardito, G; Mantovani, M; Vincenzoni, C; Guidi, M L; Corsello, S; Rabitti, C; Fadda, G; Di Giovanni, V
1997-01-01
The incidence of thyroid carcinoma in hyperthyroidism varies considerably from as low as 0.3% to as high as 16.6% with a higher rate in toxic nodular goiters. Occult thyroid carcinoma (< 1.5 cm or microscopic foci) is the rule and only a few tumors are suspected preoperatively with ultrasonography or fine needle aspiration or 131 I scan. In 408 patients who underwent surgery for hyperthyroidism in our Surgery Department from January 1967 through December 1994 the incidence of thyroid carcinoma was 5.6% (23 cases). In detail, a neoplasm occurred in 5 cases of Graves' disease (specific incidence: 3.8%), in 13 cases of toxic nodular goiter (12.5%) and in 5 cases of hyperfunctioning adenomas (2.8%). 19 cancers were papillary (12 in toxic nodular goiter, 3 in Graves' disease, 4 in hyperfunctioning adenomas), three were follicular (1 in Graves' disease, 1 in toxic nodular goiter, 1 in hyperfunctioning adenomas) and 1 medullary in Graves' disease. A papillary carcinoma was diagnosed preoperatively on fine needle aspiration with ultrasonography in only two patients with Graves' disease and confirmed by postoperative histological examination on permanent section. We do not believe in the frozen-section examination intraoperatively because it's not diagnostical for follicular lesions and evaluates rarely capsular invasion. Twenty patients received total thyroidectomy and four of them also lymphoadenectomy. Three patients received emithyroidectomy: in two cases for occult papillary carcinoma and in the last case for local cancer invasion (T4N0M0). Twenty patients are alive and with no evidence of cancer recurrence. Mean follow-up is 59.6 months. Our retrospective study shows a progressive increase of the incidence of coexisting thyroid malignancy and hyperthyroidism especially in toxic nodular goiter, probably related to extended surgical indications. Our findings do confirm that, even in the presence of hyperthyroidism, all thyroid nodules require careful diagnostics for
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Sams, Sharon B; Rosser, Julie A
2017-09-01
Urothelial carcinoma (UC) rarely metastasizes to the gynecologic tract, occurring in descending order of frequency, within the vagina, uterus, ovaries, and cervix. Significant morphologic overlap exists between primary gynecologic squamous lesions (both benign and malignant) and metastatic UC, thus potentially hindering a timely and accurate diagnosis. We present a case of UC metastatic to the uterine cervix in a 69-year-old female initially found to have noninvasive high-grade papillary UC of the bladder. Complaints of vaginal spotting lead to identification and biopsy of a mass in the uterine cervix. Histologic evaluation of the cervical mass showed a neoplastic proliferation of atypical epithelioid cells arranged in a papillary architecture. The differential in this case included primary uterine cervical tumors such as condyloma acuminatum, immature condyloma, verrucous carcinoma, warty/condylomatous carcinoma, and papillary squamotransitional cell carcinoma, as well as metastatic UC. A careful evaluation of histologic variances and a selective immunohistochemical panel allows differentiation of these tumors. We herein review the subtle, albeit significant, histologic and immunohistochemical differences of the aforementioned lesions.
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Mapping the protein domain structures of the respiratory mucins: a mucin proteome coverage study.
Cao, Rui; Wang, T Tiffany; DeMaria, Genevieve; Sheehan, John K; Kesimer, Mehmet
2012-08-03
Mucin genes encode a family of the largest expressed proteins in the human genome. The proteins are highly substituted with O-linked oligosaccharides that greatly restrict access to the peptide backbones. The genomic organization of the N-terminal, O-glycosylated, and C-terminal regions of most of the mucins has been established and is available in the sequence databases. However, much less is known about the fate of their exposed protein regions after translation and secretion, and to date, detailed proteomic studies complementary to the genomic studies are rather limited. Using mucins isolated from cultured human airway epithelial cell secretions, trypsin digestion, and mass spectrometry, we investigated the proteome coverage of the mucins responsible for the maintenance and protection of the airway epithelia. Excluding the heavily glycosylated mucin domains, up to 85% coverage of the N-terminal region of the gel-forming mucins MUC5B and MUC5AC was achieved, and up to 60% of the C-terminal regions were covered, suggesting that more N- and sparsely O-glycosylated regions as well as possible other modifications are available at the C-terminus. All possible peptides from the cysteine-rich regions that interrupt the heavily glycosylated mucin domains were identified. Interestingly, 43 cleavage sites from 10 different domains of MUC5B and MUC5AC were identified, which possessed a non-tryptic cleavage site on the N-terminal end of the peptide, indicating potential exposure to proteolytic and/or "spontaneous cleavages". Some of these non-tryptic cleavages may be important for proper maturation of the molecule, before and/or after secretion. Most of the peptides identified from MUC16 were from the SEA region. Surprisingly, three peptides were clearly identified from its heavily glycosylated regions. Up to 25% coverage of MUC4 was achieved covering seven different domains of the molecule. All peptides from the MUC1 cytoplasmic domain were detected along with the three non
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Latent childhood thyroid carcinoma in diffuse lymphocytic thyroiditis.
Siegal, A; Mimouni, M; Kovalivker, M; Griffel, B
1983-07-01
Diffuse thyroid enlargement in a child is a rare presenting symptom of thyroid carcinoma. A papillary carcinoma may be hidden in a diffuse lymphocytic thyroiditis and should be carefully searched for during surgery. Furthermore, the finding, in frozen sections, of psammoma bodies in a lymphocytic thyroiditis should raise the suspicion of an occult malignant neoplasm. A case illustrating these diagnostic difficulties in a 5-year-old child is presented.
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Structure and interactions of human respiratory mucin
NASA Astrophysics Data System (ADS)
Purdy, Kirstin; Sheehan, John; Rubinstein, Michael; Wong, Gerard
2006-03-01
Human respiratory mucin plays a crucial role in the pathology of Cystic Fibrosis lung infections. Mucin is a flexible, linear polyelectrolyte, characterized by its many charged oligo-carbohydrate side chains that give it its bottle-brush structure. The macroscopic properties of a mucin suspension are known to change drastically with changes in ion concentration and solution pH, but little is known about the effect of these variables on individual mucin structure. We present preliminary results on the structural response of individual human respiratory mucin molecules to variations in concentration of ions of different valences via small angle x-ray diffraction.
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Rego-Iraeta, Antonia; Pérez-Méndez, Luisa F; Mantinan, Beatriz; Garcia-Mayor, Ricardo V
2009-04-01
Thyroid cancer incidence is increasing throughout the world. Most studies attribute this rise entirely to the increase in papillary carcinoma, the most common thyroid malignancy in iodine-sufficient areas. A variety of nonetiological factors such as changes in clinical practice may affect the incidence of thyroid cancer and some researchers have suggested that this rise is only apparent due to an increase in diagnostic activity. Since data on the epidemiology of thyroid cancer in Spain are scarce, the main goal of this study was to analyze changes in thyroid cancer presentation, incidence, and prevalence in Vigo (northwestern Spain) between 1978 and 2001, and to investigate the relationship between the incidence rates and trends in tumor size and thyroid surgery. In this descriptive epidemiologic study, an analysis was carried out on new thyroid cancer cases obtained from the Pathology Registry of the University Hospital of Vigo (500,000 inhabitants). Trends in age, sex, thyroid surgery, histological type, tumor size, and incidence rates were calculated. The prevalence of thyroid cancer was determined in three cross-sectional surveys. The rate of population undergoing thyroid surgery significantly increased over time. Out of 322 new primary thyroid cancers, papillary thyroid cancer (PTC) was the predominant type (76%). The age-standardized incidence rate shows a significant increase in females: 1.56 per 100,000 year (1978 to 1985) to 3.83 (1986 to 1993) and 8.23 (1994 to 2001); and in males: 0.33, 1.19, and 2.65, respectively. PTC was mainly responsible for this pattern and was the result of both the increase in micropapillary thyroid carcinoma (MPTC) incidence and in PTC measuring more than 1 cm. Besides MPTC cases, no significant variations were observed in tumor size over time. In northwestern Spain, the incidence of thyroid cancer is increasing. These data should be taken into account when planning health resources for these patients. Our results may reflect
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Kim, Ga Ram; Shin, Jung Hee; Hahn, Soo Yeon; Ko, Eun Young; Oh, Young Lyun
2016-04-25
Warthin-like variant of papillary thyroid carcinoma (WVPTC) is a rare entity recently characterized. We evaluated ultrasonographic (US) features and clinical characteristics of WVPTC. Nine patients were diagnosed with WVPTC through surgery in our institution from May 2005 to January 2015. Eight of nine patients had available preoperative US images. A retrospective review of the US and clinical characteristics was performed. WVPTC compromised of 0.06% of 14,071 PTCs surgically confirmed. A mean age of nine patients was 53.2 years (range, 32-75 years). The mean nodule size of nine WVPTCs was 0.9 cm (range, 0.5-1.5 cm). Two patients showed central nodal metastasis and one patient with conventional PTC as an index tumor underwent central and lateral neck dissection. No one showed recurrence or distant metastasis during the follow-up period (mean, 4.6 years; range, 0.6-10 years). The most common US features of WVPTCs were solid composition (62.5%), hypoechogenicity (75%), and wider-than-tall shape (100%), respectively. Four (50%) of eight nodules showed well-defined margin and three (37.5%) of them had cystic component. One of eight resembled focal thyroiditis. Three nodules were considered as probably benign with US. All nine cases demonstrated underlying heterogeneous parenchymal echogenicity and accompanied chronic lymphocytic thyroiditis in permanent sections. Thyroid function tests in all patients were normal except for one with subclinical hypothyroidism. WVPTC is an uncommon subtype of PTC and has favorable prognosis, which can be misdiagnosed as a probably benign nodule or focal thyroiditis with US. All cases are associated with heterogeneous parenchyma in the background.
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Identification of occult tumors by whole-specimen mapping in solitary papillary thyroid carcinoma.
Park, Seog Yun; Jung, Yuh-S; Ryu, Chang Hwan; Lee, Chang Yoon; Lee, You Jin; Lee, Eun Kyung; Kim, Seok-Ki; Kim, Tae Sung; Kim, Tae Hyun; Jang, Jeyun; Park, Daeyoon; Dong, Seung Myung; Kang, Jae-Goo; Lee, Jin Soo; Ryu, Junsun
2015-08-01
We undertook this study to estimate an accurate incidence and spread patterns of occult papillary thyroid carcinoma (PTC) in patients with a preoperative diagnosis of solitary PTC by using whole-specimen mapping of all specimens after a total thyroidectomy. Enrolled prospectively in this whole-thyroid mapping study are 82 consecutive patients who underwent a total thyroidectomy under a preoperative diagnosis of solitary PTC. All thyroidectomy specimens were serially sectioned in 2 mm thickness and whole-thyroid mapping was carried out for additional foci of occult PTC. The frequencies of occult lesions detected in the whole and contralateral lobe were determined, and clinicopathologic factors associated with multifocality were assessed. Whole-thyroid mapping revealed 66 occult PTC lesions missed by preoperative ultrasound in 37 (45.1%) of the 82 patients. The great majority (92.5%) of the occult PTC was smaller than 3 mm in size and 25 patients (30.5%) had contralateral lesions. We found that the male sex was an independent predictor of multifocality (odds ratio (OR), 3.00; 95% CI, 1.11-8.14), adjusting for preoperative findings. Analysis with pathologic parameters showed that the male sex (OR, 5.03; 95% CI, 1.68-15.08) and extrathyroidal extensions (OR, 3.03; 95% CI, 1.03-8.95) were associated with multifocal PTC. However, none of the clinicopathologic factors evaluated predicted contralateral PTC. Our study demonstrates the diagnostic limitations of ultrasound for the detection of multifocal PTC and the need to consider the possibility of occult lesions in the management of solitary PTC, especially in male patients. © 2015 Society for Endocrinology.
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He, Yayi; Liu, Shu; Guo, Hui; Shi, Bingyin
2014-01-01
The simultaneous occurrence of hyperthyroidism and hyperparathyroidism was previously reported to be rare, but it was recognised more and more clearly by effective evaluations. Recent studies also mentioned the coexistence of parathyroid adenoma and papillary thyroid carcinoma (PTC). The potential mechanism is still unknown. We report a case of a 46-year-old man coexisted with primary hyperparathyroidism, Graves’ hyperthyroidism and occult PTC. The patient had a 6-month history of polyphagia and irritability. Blood examinations showed elevated serum calcium and parathyroid hormone levels. Serum phosphate was lower. Thyroid function evaluation indicted Graves’ hyperthyroidism. Ultrasound showed a solitary hyperchoic thyroid nodule in the right gland. Parathyroid radioisotope scanning found a mild enhancement of 99mTc absorption in the lower part of the right parathyroid gland. A surgical exploration was carried out and the parathyroid adenoma resection was performed. An occult micro-PTC with BRAFV600E mutation was also detected. PMID:24879726
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Zhang, Jianbin; Lv, Yan; Wang, Bing; Zhao, Shan; Tan, Mingqian; Lv, Guojun; Ma, Xiaojun
2015-03-02
Mucus layer, a selective diffusion barrier, has an important effect on the fate of drug delivery systems in the gastrointestinal tract. To study the fate of microemulsions in the mucus layer, four microemulsion formulations with different particle sizes and lipid compositions were prepared. The microemulsion-mucin interaction was demonstrated by the fluorescence resonance energy transfer (FRET) method. Moreover, the microemulsions were observed aggregated into micron-sized emulsions by laser confocal microscopy. We concluded the microemulsion-mucin interaction not only led to microemulsions closely adhered to mucins but also destroyed the structure of microemulsions. At last, the diffusion of blank microemulsions and microemulsion-carried drugs (resveratrol and hymecromone) through mucin solutions was determined by the fluorescence recovery after photobleaching (FRAP) method and the Franz diffusion cell method. The results demonstrated the diffusion of microemulsions was significantly hindered by mucin solutions. The particle size of microemulsions had a negligible effect on the diffusion coefficients. However, the type of lipid played an important role, which could form hydrophobic interactions with mucins. Interestingly, microemulsion-carried drugs with different core/shell locations seemed to suffer different fates in the mucin solutions. The drug incorporated in the oil core of microemulsions, resveratrol, was transported through the mucus layer by the carriers, while the drug incorporated in the surfactant shell of microemulsions, hymecromone, was separated from the carriers and diffused toward the epithelium in the form of free molecules.
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Ahmed, Omar I; Salih, Ziyan T
2017-09-01
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Simultaneous involvement of the thyroid gland by multiple malignancies, is a rare occurrence. Similarly, primary thyroid lymphomas are also rare. We are reporting a rare case of a dual thyroid malignancy; PTC with secondary thyroid involvement by chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diagnosed on cytology and confirmed with flow cytometry, histology and immunohistochemistry. Imaging showed two hypermetabolic nodules, one in left parotid gland, and the other in the thyroid isthmus. Cytology smears showed features of PTC along with an atypical lymphocytic infiltrate, which co-expressed CD5, CD19, and CD23 on flowcytometry analysis. Subsequent thyroidectomy showed the atypical lymphocytic infiltrate involving the PTC papillae themselves. The diagnosis of dual malignancies on thyroid FNA is extremely rare and often unexpected, but is possible using appropriate ancillary studies. © 2017 Wiley Periodicals, Inc.
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Wong, Joyce; Weber, Jill; Centeno, Barbara A; Vignesh, Shivakumar; Harris, Cynthia L; Klapman, Jason B; Hodul, Pamela
2013-01-01
Surgical resection for intraductal papillary mucinous neoplasm (IPMN) of the pancreas has increased over the last decade. While IPMN with main duct communication are generally recommended for resection, indications for resection of side-branch IPMN (SDIPMN) have been less clear. We reviewed our single institutional experience with SDIPMN and indications for resection. Patients who underwent resection for IPMN were identified from a prospectively maintained IRB-approved database. Patients with main pancreatic duct communication were excluded. Outcome, clinical and pathologic characteristics were correlated with endoscopic ultrasound (EUS) findings. From 2000 to 2010, 105 patients who underwent preoperative EUS evaluation and resection for SDIPMN were identified. The mean age was within the sixth decade of life, and there was a slight female predominance (55 vs. 45 %). The most common presenting symptom was abdominal pain (N = 47, 45 %), followed by jaundice (N = 24, 23 %) and weight loss (N = 24, 23 %). Only ten patients (10 %) were asymptomatic at presentation; seven (70 %) had suspicious features on EUS. Of the total cohort, few patients had intracystic septations (N = 27, 26 %) or presence of mural nodules (N = 2, 2 %) on EUS. Of 39 patients who had invasive pancreatic ductal adenocarcinoma (PDAC) on final pathology, EUS-fine needle aspiration (EUS-FNA) demonstrated malignancy in only 21 (54 %). An additional seven (18 %) had EUS-FNA findings of atypia or concern for mucinous neoplasm. EUS evaluation of cyst size was correlated with final pathology. Of 70 patients with EUS cyst size <3 cm, 12 (17 %) had a preoperative EUS diagnosis of malignancy. Final pathology revealed 24 (34 %) to have PDAC: 1 of 7 (14 %) patients with cyst size <1 cm, 2 of 19 (11 %) with cyst size 1-2 cm, and 21of 44 (48 %) with cyst size 2-3 cm. Fifteen of 35 (43 %) patients with cyst size >3 cm had PDAC on final pathology. Of the patients with cyst
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Papillary endothelial hyperplasia in angiokeratoma.
Mehta, Anurag; Sayal, Satish Kumar; Raman, Deep Kumar; Sood, Aradhana
2003-01-01
Papillary endothelial hyperplasia (Masson's tumour) is a reactive proliferation of endothelium producing papillary structures with fibrovascular cores. Dilatation, stasis and accompanying inflammation have been incriminated as the inciting events, evident by the presence of this lesion in haemorrhoids, urethral caruncles and laryngeal polyps. We present here a case of papillary endothelial hyperplasia in angiokeratoma hitherto undescribed despite sharing common etiopathogenetic features of dilatation and stasis with other aforementioned lesions.
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Two cases of matrix-producing carcinoma showing chondromyxoid matrix in cytological specimens.
Tajima, Shogo; Koda, Kenji
2015-01-01
Matrix-producing carcinoma (MPC) is extremely rare. Limited reports have described the cytological aspects of MPC. Herein, we present 2 cases of MPC, both of which showed ring-enhancement on magnetic resonance imaging (MRI) and chondromyxoid matrix on cytological specimens. In these cases, the diagnosis of MPC was preoperatively suspected. Recognizing extracellular matrix as chondromyxoid matrix on the cytological specimen is important in making a distinction between MPC and mucinous carcinoma. They share some features on cytology and MRI (ring-enhancement) but have different prognoses and involve different approaches for obtaining histological specimens for neoadjuvant therapy. The reason for the different approaches for obtaining the histological specimens is that tumor cells usually distribute peripherally in MPC in contrast to the relatively uniform distribution of mucinous carcinoma. Therefore, it would be helpful if the diagnosis of MPC can be suspected by examination of the cytological specimen.
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He, Jian; Zhou, Kefeng; Zhu, Bin; Zhang, Gutian; Li, Xiaogong; Guo, Hongqian; Gan, Weidong; Zhou, Zhengyang; Liu, Tian
2015-01-01
Purpose. To compare the differences of CT characteristics between renal cell carcinomas (RCCs) associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 RCCs) and papillary cell renal cell carcinomas (PRCCs). Methods. CT images and clinical records of 64 patients (25 Xp11.2 RCCs, 15 type 1 and 24 type 2 PRCCs) were analyzed and compared retrospectively. Results. Xp11.2 RCC more frequently affected young (30.7 ± 8.7 years) women (16/25, 64%) with gross hematuria (12/25, 48%), while PRCC more frequently involved middle-aged (54.8 ± 11.1 years) men (28/39, 71.8%) asymptomatically. Xp11.2 RCC tended to be heterogeneous density with some showing circular calcification. Lesion sizes of Xp11.2 RCC (5.4 ± 2.2 cm) and type 2 PRCC (5.7 ± 2.5 cm) were significantly larger than that of type 1 PRCC (3.8 ± 1.8 cm). Xp11.2 RCC contained more cystic components (22/25, 88%) than type 1 PRCC (all solid) and type 2 PRCC (9/24, 36.0%). Type 1 PRCC (13/15, 86.7%) and Xp11.2 RCC (21/25, 84.0%) showed more clear boundary than type 2 PRCC (12/24, 50.0%). Conclusion. CT features including diameter, boundary, attenuation, nature, and circular calcification of the tumor, combined with demographic information and symptoms, may be useful to differentiate Xp11.2 RCC from different subtypes of PRCC. PMID:26636097
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Mitogen-activated protein kinase inhibition reduces mucin 2 production and mucinous tumor growth.
Dilly, Ashok K; Song, Xinxin; Zeh, Herbert J; Guo, Zong S; Lee, Yong J; Bartlett, David L; Choudry, Haroon A
2015-10-01
Excessive accumulation of mucin 2 (MUC2) protein (a gel-forming secreted mucin) within the peritoneal cavity is the major cause of morbidity and mortality in pseudomyxoma peritonei (PMP), a unique mucinous malignancy of the appendix. Mitogen-activated protein kinase (MAPK) signaling pathway is upregulated in PMP and has been shown to modulate MUC2 promoter activity. We hypothesized that targeted inhibition of the MAPK pathway would be a novel, effective, and safe therapeutic strategy to reduce MUC2 production and mucinous tumor growth. We tested RDEA119, a specific MEK1/2 (MAPK extracellular signal-regulated kinase [ERK] kinase) inhibitor, in MUC2-secreting LS174T cells, human PMP explant tissue, and in a unique intraperitoneal murine xenograft model of PMP. RDEA119 reduced ERK1/2 phosphorylation and inhibited MUC2 messenger RNA and protein expression in vitro. In the xenograft model, chronic oral therapy with RDEA119 inhibited mucinous tumor growth in an MAPK pathway-dependent manner and this translated into a significant improvement in survival. RDEA119 downregulated phosphorylated ERK1/2 and nuclear factor κB p65 protein signaling and reduced activating protein 1 (AP1) transcription factor binding to the MUC2 promoter in LS174T cells. This study provides a preclinical rationale for the use of MEK inhibitors to treat patients with PMP. Copyright © 2015 Elsevier Inc. All rights reserved.
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Yanagibashi, T; Gorai, I; Nakazawa, T; Miyagi, E; Hirahara, F; Kitamura, H; Minaguchi, H
1997-01-01
Six permanent human ovarian carcinoma cell lines (OVISE, OVTOKO, OVMANA and OVSAYO from clear cell adenocarcinoma, and OVSAHO and OVKATE from serous papillary adenocarcinoma) were established from solid tumours. The cell lines have been in culture for 5-8 years, the passage number varying from 62 to 246. Immunohistochemical analysis has shown that five of the six cell lines express at least six cytokeratin (CK) polypeptides. OVISE and OVSAYO expressed CKs 6, 7, 8, 18, 19 and 15 and/or 16. OVTOKO was positive for CKs 7, 8, 18, 19 and 15 and/or 16. OVSAHO expressed CKs 6, 7, 8, 14, 18, 19 and 15 and/or 16. OVMANA expressed CKs 6, 7, 8, 18, 19, 20 and 15 and/or 16. OVKATE expressed CKs 6, 7, 8, 13, 17, 18, 19, 20 and 15 and/or 16. The expression of CK7, additional expression of vimentin, and clinical and histopathological findings enabled us to confirm that six cell lines had been established from primary ovarian cancers. Two of the six cell lines were positive for CK20, although CK20 was not expressed in the original tumours. The heterotransplanted tumours produced by CK20-positive cells also expressed CK20. This is the first report of ovarian carcinoma cell lines that express CK20 irrespective of their histological type. CK20 has been found in all colon carcinoma cell lines, but only in the mucinous type of ovarian tumours. These new ovarian carcinoma cell lines will therefore provide a relevant experimental system for elucidating the regulatory control mechanisms of intermediate filament expression.
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Paulsen, Friedrich; Langer, Gesa; Hoffmann, Werner; Berry, Monica
2004-05-01
The objective of this study was to determine whether the lacrimal gland synthesizes mucins and whether they are changed with age or in cases of dry eye. Expression of mucins in human lacrimal glands was monitored by reverse transcription-polymerase chain reaction analysis. Furthermore, the presence and distribution of MUC1, -2, -4, -5AC, -5B, -6 and -7 in epithelia of the human lacrimal gland and its excretory duct system were assessed with antisera to mucin peptide cores. Thirty normal tissues from cadavers of different ages were tested, plus four with dry eye treated with artificial tears. Expression studies detected mRNAs for mucins MUC1, -4, -5AC, -5B, -6 and -7; whereas the MUC2 message was absent. The message for MUC4 was present in all four cases of dry eye, but only in six out of the 30 normal glands from individuals who did not receive artificial tears. MUC6 mRNA was detected only in about half of the investigated samples. Immunohistochemistry revealed membrane-bound MUC1 at the apical surface of acinar cells, absence of MUC2, MUC5AC associated with goblet cells of excretory ducts, MUC5B and -7 in the cytoplasm of acinar cells, and MUC7 also in epithelial cells of excretory ducts. MUC4 mucin was detected only in those individuals in which message was identified. In dry eyes, MUC5AC and -5B were localized in the same acinar cells; whereas MUC2 and MUC6 were not detectable. Dot-blot analysis clearly revealed increased amounts of MUC4, -5AC, and -5B in the glands of elderly women who received treatment for dry eyes. These results confirm that the human lacrimal gland synthesizes a spectrum of mucins; part of them might be correlated with age. Copyright 2004 Springer-Verlag
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Incidental cervical metastases from thyroid carcinoma during neck dissection.
Périé, S; Torti, F; Lefevre, M; Chabbert-Buffet, N; Jafari, A; Lacau St Guily, J
2016-12-01
To quantify and discuss the prevalence of unsuspected thyroid lymph node metastases discovered in specimens from neck dissection for head and neck squamous cell carcinoma (HNSCC) and discuss the impact on patient management. Retrospective study between May 2004 and January 2007. University hospital. Pathological analysis of cervical lymph node dissection performed during surgery for HNSCC in a total of 349 neck dissections in 266 consecutive patients. Twenty-one patients showed metastatic lymph nodes from thyroid cancer (prevalence 7.9%): 13 cases were metastatic from a papillary thyroid carcinoma and 8 cases from a follicular carcinoma. In 5 of the 21 patients, classical dissection was associated to recurrent nerve dissection and unilateral lobectomy; no thyroid carcinoma was found. Thirteen patients received radiotherapy for HNSCC. Follow-up comprised annual ultrasonographic examination of the neck and thyroid in these 21 patients. Total thyroidectomy was decided on in 5, with discovery of 3 micro-papillary thyroid carcinomas, in a single patient (complementary 131 I treatment). No thyroid carcinomas were found for the other 4 patients. No patients died from thyroid carcinoma during follow-up (mean: 41 months). The prevalence of lymph node metastasis from thyroid carcinoma in cervical lymph node dissection during treatment of HNSCC seems higher (7.9%) than rates reported in the literature (0.3 to 1.6%). This may be due to the histopathological methods employed. Management of patients should be discussed in the light of thyroid ultrasonography and prognosis of HNSCC. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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Ryu, Ji Kon; Matthaei, Hanno; dal Molin, Marco; Hong, Seung-Mo; Canto, Marcia I.; Schulick, Richard D.; Wolfgang, Christopher; Goggins, Michael G.; Hruban, Ralph H.; Cope, Leslie; Maitra, Anirban
2011-01-01
Background Biomarkers for the diagnostic classification of pancreatic cysts are urgently needed. Deregulated microRNA (miRNAs) expression is widespread in pancreatic cancer. We assessed whether aberrant miRNAs in pancreatic cyst fluid could be used as potential biomarkers for cystic precursor lesions of pancreatic cancer. Methods Cyst fluid specimens were prospectively collected from 40 surgically resected pancreatic cysts, and small RNAs were extracted. The ‘mucinous’ cohort included 14 intraductal papillary mucinous neoplasms (including 3 with an associated adenocarcinoma) and 10 mucinous cystic neoplasms; the ‘nonmucinous’ cohort included 11 serous cystadenomas and 5 other benign cysts. Quantitative reverse transcription PCR was performed for five miRNAs (miR-21, miR-155, miR-221, miR-17-3p, miR-191), which were previously reported as overexpressed in pancreatic adenocarcinomas. Results Significantly higher expression of miR-21, miR-221, and miR-17-3p was observed in the mucinous versus nonmucinous cysts (p < 0.01), with the mean relative fold differences being 7.0-, 7.9-, and 5.4-fold, respectively. Receiver operating characteristic curves demonstrated the highest median area under the curve for miR-21, with a median specificity of 76%, at a sensitivity of 80%. Conclusion This pilot study demonstrates that profiling miRNAs in pancreatic cyst fluid samples is feasible and can yield potential biomarkers for the classification of cystic lesions of the pancreas. PMID:21757972
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Essential role of gastric gland mucin in preventing gastric cancer in mice
Karasawa, Fumitoshi; Shiota, Akira; Goso, Yukinobu; Kobayashi, Motohiro; Sato, Yoshiko; Masumoto, Junya; Fujiwara, Maiko; Yokosawa, Shuichi; Muraki, Takashi; Miyagawa, Shinichi; Ueda, Masatsugu; Fukuda, Michiko N.; Fukuda, Minoru; Ishihara, Kazuhiko; Nakayama, Jun
2012-01-01
Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Previously, we identified human α1,4-N-acetylglucosaminyltransferase (α4GnT), which is responsible for the O-glycan biosynthesis and characterized αGlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt–/– mice to better understand its role in vivo. A4gnt–/– mice showed complete lack of αGlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence in the absence of H. pylori infection. Microarray and quantitative RT-PCR analysis revealed upregulation of genes encoding inflammatory chemokine ligands, proinflammatory cytokines, and growth factors, such as Ccl2, Il-11, and Hgf in the gastric mucosa of A4gnt–/– mice. Further supporting an important role for this O-glycan in cancer progression, we also observed significantly reduced αGlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of αGlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, αGlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation. PMID:22307328
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Patyra, Konrad; Jaeschke, Holger; Löf, Christoffer; Jännäri, Meeri; Ruohonen, Suvi T; Undeutsch, Henriette; Khalil, Moosa; Kero, Andreina; Poutanen, Matti; Toppari, Jorma; Chen, Min; Weinstein, Lee S; Paschke, Ralf; Kero, Jukka
2018-05-25
Thyroid function is controlled by thyroid-stimulating hormone (TSH), which binds to its G protein-coupled receptor [thyroid-stimulating hormone receptor (TSHR)] on thyrocytes. TSHR can potentially couple to all G protein families, but it mainly activates the G s - and G q/11 -mediated signaling cascades. To date, there is a knowledge gap concerning the role of the individual G protein cascades in thyroid pathophysiology. Here, we demonstrate that the thyrocyte-specific deletion of G s -protein α subunit (Gα s ) in adult mice [tamoxifen-inducible G s protein α subunit deficient (iTGα s KO) mice] rapidly impairs thyrocyte function and leads to hypothyroidism. Consequently, iTGα s KO mice show reduced food intake and activity. However, body weight and the amount of white adipose tissue were decreased only in male iTGα s KO mice. Unexpectedly, hyperplastic follicles and papillary thyroid cancer-like tumor lesions with increased proliferation and slightly increased phospho-ERK1/2 staining were found in iTGα s KO mice at an older age. These tumors developed from nonrecombined thyrocytes still expressing Gα s in the presence of highly elevated serum TSH. In summary, we report that partial thyrocyte-specific Gα s deletion leads to hypothyroidism but also to tumor development in thyrocytes with remaining Gα s expression. Thus, these mice are a novel model to elucidate the pathophysiological consequences of hypothyroidism and TSHR/G s /cAMP-mediated tumorigenesis.-Patyra, K., Jaeschke, H., Löf, C., Jännäri, M., Ruohonen, S. T., Undeutsch, H., Khalil, M., Kero, A., Poutanen, M., Toppari, J., Chen, M., Weinstein, L. S., Paschke, R., Kero, J. Partial thyrocyte-specific Gα s deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice.
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Akaishi, Junko; Kondo, Tetsuo; Sugino, Kiminori; Ogimi, Yuna; Masaki, Chie; Hames, Kiyomi Y; Yabuta, Tomonori; Tomoda, Chisato; Suzuki, Akifumi; Matsuzu, Kenichi; Uruno, Takashi; Ohkuwa, Keiko; Kitagawa, Wataru; Nagahama, Mitsuji; Katoh, Ryohei; Ito, Koichi
2018-04-25
Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is rare; it may occur in cases of familial adenomatous polyposis (FAP) or be sporadic. To clarify the clinicopathological features of CMV-PTC, the medical records of these patients were investigated retrospectively. Between 1979 and 2016, a total of 17,062 cases with PTC underwent initial surgery at Ito Hospital. Of these, 30 (0.2%) cases histologically diagnosed with CMV-PTC were reviewed. The patients were all women, with a mean age at the time of surgery of 24 years. Seven (23%) cases were thought to have FAP because they had colonic polyposis or a family history of FAP or APC gene mutation. The remaining 23 (77%) were thought to be sporadic. Multiple tumors were detected in 6 cases, with a solitary tumor in 24. One patient had lung metastasis at diagnosis. Eleven patients underwent total thyroidectomy or subtotal thyroidectomy, and 19 underwent lobectomy. Twenty-six (87%) patients underwent neck lymph node dissection. Three patients had tumor metastasis in central lymph nodes, but these were incidentally detected metastatic classical PTC (cPTC) based on histological examination. In this series, there were no cases of LN metastases of CMV-PTC. During a mean follow-up of 15 years, one patient had new cPTC in the remnant thyroid after initial surgery, and the other patients showed no signs of recurrence. CMV-PTC occurred in young women, their long-term prognosis was excellent. Total thyroidectomy is recommended for FAP-associated CMV-PTC, but modified neck lymph node dissection is not necessary.
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Pyo, J-S; Sohn, J H; Kang, G
2017-03-01
The aim of this study was to elucidate the cytological characteristics and the diagnostic usefulness of intraoperative cytology (IOC) for papillary thyroid carcinoma (PTC). In addition, using decision tree analysis, effective features for accurate cytological diagnosis were sought. We investigated cellularity, cytological features and diagnosis based on the Bethesda System for Reporting Thyroid Cytopathology in IOC of 240 conventional PTCs. The cytological features were evaluated in terms of nuclear score with nuclear features, and additional figures such as presence of swirling sheets, psammoma bodies, and multinucleated giant cells. The nuclear score (range 0-7) was made via seven nuclear features, including (1) enlarged, (2) oval or irregularly shaped nuclei, (3) longitudinal nuclear grooves, (4) intranuclear cytoplasmic pseudoinclusion, (5) pale nuclei with powdery chromatin, (6) nuclear membrane thickening, and (7) marginally placed micronucleoli. Nuclear scores in PTC, suspicious for malignancy, and atypia of undetermined significance cases were 6.18 ± 0.80, 4.48 ± 0.82, and 3.15 ± 0.67, respectively. Additional figures more frequent in PTC than in other diagnostic categories were identified. Cellularity of IOC significantly correlated with tumor size, nuclear score, and presence of additional figures. Also, IOCs with higher nuclear scores (4-7) significantly correlated with larger tumor size and presence of additional figures. In decision tree analysis, IOCs with nuclear score >5 and swirling sheets could be considered diagnostic for PTCs. Our study suggests that IOCs using nuclear features and additional figures could be useful with decreasing the likelihood of inconclusive results.
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Rambau, Peter F; McIntyre, John B; Taylor, Jennifer; Lee, Sandra; Ogilvie, Travis; Sienko, Anna; Morris, Don; Duggan, Máire A; McCluggage, W Glenn; Köbel, Martin
2017-05-01
The 2014 World Health Organization Classification of Tumors of Female Reproductive Organs endorsed the new category of seromucinous carcinoma, a neoplasm that exhibits morphologic and immunophenotypic overlap with other histotypes of ovarian carcinoma. The goal of this study was to determine whether seromucinous carcinoma was a distinct histotype by assessing its diagnostic reproducibility and comparing its molecular composition to the 5 major histotypes of ovarian carcinoma. Thirty-two tumors diagnosed as seromucinous carcinomas from 2 centers were studied. Eighteen cases were randomly selected for a review set comprising a total of 50 ovarian carcinomas of various histotypes. Morphologic histotype was independently assessed by 4 pathologists. For the 32 seromucinous carcinomas, a histotype-specific immunophenotype was assigned using a diagnostic immunohistochemical panel. Histotype-specific genotype was assigned using a combination of immunohistochemistry and targeted next-generation sequencing for somatic mutations, including genes recurrently mutated in ovarian carcinomas. There was low to modest agreement between pathologists with the reference diagnosis of seromucinous carcinoma, ranging from 39% to 56% for the 4 observers. The immunophenotype was not unique but overlapped predominantly with endometrioid and to a lesser extent with mucinous and low-grade serous carcinoma. Genomic and immunohistochemical alterations were detected in a number of target genes, including KRAS (70%), PIK3CA (37%), PTEN (19%), and ARID1A (16%); no CTNNB1 mutations were identified. Nine cases (30%) harbored concurrent KRAS/PIK3CA mutations. An endometrioid genotype was assigned to 19 cases, a low-grade serous genotype to 9, and a mucinous genotype to 1 and 3 cases were uninformative. Integrating morphology, immunophenotype, and genotyping resulted in reclassifying the seromucinous carcinomas to endometrioid 23/32 (72%), low-grade serous 8/32 (25%), and mucinous 1/32 (3%). The
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[Evaluation of central lymph node dissection for papillary thyroid carcinoma in cN0 T1/T2].
Zhao, S Y; Ma, Y H; Yin, Z; Zhan, X X; Cheng, R C; Qian, J
2018-02-07
Objective: To evaluate the application of the central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC) in cN0 T1/T2. Methods: Retrospective analysis of 532 cases with PTC in cN0 T1/T2 who underwent CLND between October 2014 and September 2016 in the Department of Thyroid Surgery, the First Affiliated Hospital of the Kunming Medical University. The incidence of central lymph node (CLN) metastasis and risk factors were analyzed. Results: CLN metastasis rates: 41.2% (42/102) in males vs 34.9% (150/430) in females, P =0.252; 33.9% (116/342) in single focal carcinoma vs 40.4% (74/183) in multifocal carcinoma, P =0.157; 44.0% (125/284) in patients with 45 years old or less vs 27.0% (67/248) in patients more than 45 years old, P =0.000; 30.3% (113/373) in microcarcinoma vs 50.9% (81/159) in non-microcarcinoma, P =0.000.In unilateral lesions, ipsilateral CLN metastasis was correlated with the tumor diameter ( P =0.012), but not with the number of lesions ( P =0.653). also contralateral CLN metastasis was correlated with the tumor diameter ( P =0.000), but not with the number of lesions ( P =0.815). For the left or right unilateral single focal lesion, the tumor diameter was not correlated with the metastasis of the posterior to right recurrent laryngeal nerve central lymph nodes (LN-prRLN-CLN) ( P =0.652, P =0.088). But in bilateral multifocal carcinoma the tumor diameter was correlated with metastasis of LN-prRLN-CLN ( P =0.039). Conclusions: Prophylactic CLND is reasonable for PTC in cN0 T1/T2. A bilateral CLND should be conducted for patients with bilateral multi-focus cancer and unilateral or bilateral non-microcarcinoma, especially in patients more than 45 years old. For unilateral single focal microcarcinoma on the right, the content of CLND should be from laryngeal nerve on right center to posterior branche; for unilateral single focal microcarcinoma on the left side, the left CLND should be conducted. An ipsilateral CLND can be considered in
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Hartman, Douglas J; Binion, David G; Regueiro, Miguel D; Miller, Caitlyn; Herbst, Cameron; Pai, Reetesh K
2018-05-17
Chronic idiopathic inflammatory bowel disease (IBD) is a significant risk factor for the development of intestinal adenocarcinoma. The underlying molecular alterations in IBD-associated intestinal adenocarcinoma remain largely unknown. We compared the clinicopathologic and molecular features of 35 patients with 47 IBD-associated intestinal adenocarcinomas with a consecutive series of 451 patients with sporadic colorectal carcinoma identified at our institution and published data on sporadic colorectal carcinoma. c-MYC amplification was the most frequent molecular alteration identified in 33% of IBD-associated intestinal adenocarcinoma that is a significantly higher frequency than in sporadic colorectal carcinoma (8%) (P = 0.0001). Compared to sporadic colorectal carcinoma, IBD-associated intestinal adenocarcinomas more frequently demonstrated mucinous differentiation (60% vs 25%, P < 0.001) and signet ring cell differentiation (28% vs 4%, P < 0.001). Mucinous and signet ring cell differentiation were significantly associated with the presence of c-MYC amplification (both with P < 0.05). HER2 positivity (11%), KRAS exon 2 or 3 mutation (10%), and IDH1 mutation (7%) were less commonly observed in IBD-associated intestinal adenocarcinoma. There was an association between poor survival and HER2 status with 3 of 4 patients having HER2-positive adenocarcinoma dead of disease at last clinical follow-up; however, no statistically significant survival effect was identified for any of the molecular alterations identified. We demonstrate that IBD-associated intestinal adenocarcinomas have a high frequency of c-MYC amplification that is associated with mucinous and signet ring cell differentiation. Many of the identified molecular alterations have potential therapeutic relevance, including HER2 amplification, IDH1 mutation, and low frequency KRAS mutation.
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Bagué, Sílvia; Rodríguez, Ingrid M; Prat, Jaime
2002-11-01
Ten mucinous cystic ovarian tumors that contained sarcoma-like mural nodules are described. The nodules were studied by conventional and immunohistochemical methods. The sarcoma-like mural nodules occurred predominantly in middle-aged women, were multiple and sharply demarcated from the adjacent mucinous tumor, had small size, and exhibited a heterogeneous cell population. Distinction of these lesions from true sarcomatous nodules and foci of anaplastic carcinoma is important because of the worse prognosis of the two latter tumors compared with the favorable behavior of the sarcoma-like mural nodules. Six of the eight patients with follow-up information were alive and clinically free of recurrence at a mean follow-up interval of 12 years. Two patients died of other causes (thyroid and breast carcinomas). The nature of the nodules is not clear. Sarcoma-like mural nodules probably represent a reactive and self-limited phenomenon within a neoplasia. Their coexpression of vimentin and cytokeratins is consistent with an origin from submesothelial mesenchymal cells, which undergo partial transformation into epithelial cells.
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Doshi, Ankur M; Ream, Justin M; Kierans, Andrea S; Bilbily, Matthew; Rusinek, Henry; Huang, William C; Chandarana, Hersh
2016-03-01
The purpose of this study was to determine whether qualitative and quantitative MRI feature analysis is useful for differentiating type 1 from type 2 papillary renal cell carcinoma (PRCC). This retrospective study included 21 type 1 and 17 type 2 PRCCs evaluated with preoperative MRI. Two radiologists independently evaluated various qualitative features, including signal intensity, heterogeneity, and margin. For the quantitative analysis, a radiology fellow and a medical student independently drew 3D volumes of interest over the entire tumor on T2-weighted HASTE images, apparent diffusion coefficient parametric maps, and nephrographic phase contrast-enhanced MR images to derive first-order texture metrics. Qualitative and quantitative features were compared between the groups. For both readers, qualitative features with greater frequency in type 2 PRCC included heterogeneous enhancement, indistinct margin, and T2 heterogeneity (all, p < 0.035). Indistinct margins and heterogeneous enhancement were independent predictors (AUC, 0.822). Quantitative analysis revealed that apparent diffusion coefficient, HASTE, and contrast-enhanced entropy were greater in type 2 PRCC (p < 0.05; AUC, 0.682-0.716). A combined quantitative and qualitative model had an AUC of 0.859. Qualitative features within the model had interreader concordance of 84-95%, and the quantitative data had intraclass coefficients of 0.873-0.961. Qualitative and quantitative features can help discriminate between type 1 and type 2 PRCC. Quantitative analysis may capture useful information that complements the qualitative appearance while benefiting from high interobserver agreement.
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Yoon, Yeo-Hoon; Kim, Hak Joon; Lee, Jin Woo; Kim, Jin Man; Koo, Bon Seok
2012-03-01
The goal of this study is to determine the clinicopathologic differences in patients with papillary thyroid carcinoma (PTC) with or without chronic lymphocytic thyroiditis (CLT). We reviewed the medical records of 195 consecutive PTC patients who underwent total thyroidectomy and bilateral central lymph node dissection from April 2008 to March 2010. The differences in clinicopathologic factors, such as age, gender, size of primary tumor, perithyroidal invasion, lymphovascular invasion, capsular invasion, and central lymph node (CLN) metastasis, were analyzed in PTC patients with or without CLT. Among 195 patients, 56 (28.7%) had co-existing CLT. Patients with CLT had the following characteristics as compared to patients without CLT: significantly younger, female predominance, smaller tumor size, and lower incidence of capsular invasion (p = 0.038, 0.006, 0.037, and 0.026, respectively). Also, patients with CLT (12.5%) had a significantly lower incidence of CLN metastases than patients without CLT (28.1%; p = 0.025) based on univariate analysis. Moreover, multivariate analysis showed that younger age (p = 0.042, odds ratio = 1.033) and female gender (p = 0.012, odds ratio = 6.865) are independent clinical factors in patients with CLT compared to patients without CLT. CLT was shown to be commonly associated with PTC. Compared to patients with PTC without CLT, patients with CLT were younger with a female predominance, which are the most important and well-known prognostic variables for thyroid cancer mortality.
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miR-204-5p suppresses cell proliferation by inhibiting IGFBP5 in papillary thyroid carcinoma
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Lianyong; Wang, Jingnan; Li, Xiangqi
2015-02-20
microRNAs (miRNAs) are frequently dysregulated in human malignancies. It was recently shown that miR-204-5p is downregulated in papillary thyroid carcinoma (PTC); however, the functional significance of this observation is not known. This study investigated the role of miR-204-5p in PTC. Overexpressing miR-204-5p suppressed PTC cell proliferation and induced cell cycle arrest and apoptosis. The results of a luciferase reporter assay showed that miR-204-5p can directly bind to the 3′ untranslated region (UTR) of insulin-like growth factor-binding protein 5 (IGFBP5) mRNA, and IGFBP5 overexpression partially reversed the growth-inhibitory effects of miR-204-5p. These results indicate that miR-204-5p acts as a tumor suppressormore » in PTC by regulating IGFBP5 expression and that miR-204-5p can potentially serve as an antitumorigenic agent in the treatment of PTC. - Highlights: • miR-204-5p expression is downregulated in PTC tissues and cell lines. • miR-204-5p suppresses proliferation and promotes apoptosis in PTC cells. • miR-204-5p suppresses IGFBP5 expression by direct binding to the 3′-UTR. • IGFBP5 overexpression reverses the effects of miR-204-5p.« less
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Xue, Nianyu; Xu, Youfeng; Huang, Pintong; Zhang, Shengmin; Wang, Hongwei; Yu, Fei
2016-08-01
The present study aimed to report the shear wave elastography (SWE) findings in a patient with the diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC). Since patients with DSVPTC may present with typical clinicopathological features and initially appear to have Hashimoto's thyroiditis, a thorough clinical evaluation and an early diagnosis are important. A 20-year-old female patient presented with a 1-month history of a neck mass and sore throat. Conventional ultrasound and SWE were performed using an AIXPLORER system with 14-5 MHz linear transducer. The patient had undergone total thyroidectomy and bilateral neck lymph node dissection, and an intraoperative pathology consultation to confirm the malignancy of lymph node metastasis. Pathological diagnosis was DSVPTC in both lobes, with lymph node metastases in the bilateral neck. The clinical presentation and serological findings were all indicative of Hashimoto's thyroiditis. Thyroid ultrasonography revealed diffuse enlargement of the both lobes, heterogenous echogenicity without mass formation, diffuse scattered microcalcifications and poor vascularization. SWE revealed stiff values of the thyroid: The mean stiffness was 99.7 kpa, the minimum stiffness was 59.1 kpa and the maximum stiffness was 180.1 kpa. The maximum stiffness of the DSVPTC (180.1 kpa) was higher compared with the diagnostic criteria of malignant thyroid nodules (65 kPa). SWE may be considered as a novel and valuable method to diagnose DSVPC.
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Xue, Nianyu; Xu, Youfeng; Huang, Pintong; Zhang, Shengmin; Wang, Hongwei; Yu, Fei
2016-01-01
The present study aimed to report the shear wave elastography (SWE) findings in a patient with the diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC). Since patients with DSVPTC may present with typical clinicopathological features and initially appear to have Hashimoto's thyroiditis, a thorough clinical evaluation and an early diagnosis are important. A 20-year-old female patient presented with a 1-month history of a neck mass and sore throat. Conventional ultrasound and SWE were performed using an AIXPLORER system with 14-5 MHz linear transducer. The patient had undergone total thyroidectomy and bilateral neck lymph node dissection, and an intraoperative pathology consultation to confirm the malignancy of lymph node metastasis. Pathological diagnosis was DSVPTC in both lobes, with lymph node metastases in the bilateral neck. The clinical presentation and serological findings were all indicative of Hashimoto's thyroiditis. Thyroid ultrasonography revealed diffuse enlargement of the both lobes, heterogenous echogenicity without mass formation, diffuse scattered microcalcifications and poor vascularization. SWE revealed stiff values of the thyroid: The mean stiffness was 99.7 kpa, the minimum stiffness was 59.1 kpa and the maximum stiffness was 180.1 kpa. The maximum stiffness of the DSVPTC (180.1 kpa) was higher compared with the diagnostic criteria of malignant thyroid nodules (65 kPa). SWE may be considered as a novel and valuable method to diagnose DSVPC. PMID:27446574
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Nilsson, Linda N; Keane, Margaret G; Shamali, Awad; Millastre Bocos, Judith; Marijinissen van Zanten, Monica; Antila, Anne; Verdejo Gil, Cristina; Del Chiaro, Marco; Laukkarinen, Johanna
The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management. A systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015. MCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93-95%). They are usually found incidentally at the age of 40-60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0-34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%. Compared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs
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Yu, Jun; Sadakari, Yoshihiko; Shindo, Koji; Suenaga, Masaya; Brant, Aaron; Almario, Jose Alejandro Navarro; Borges, Michael; Barkley, Thomas; Fesharakizadeh, Shahriar; Ford, Madeline; Hruban, Ralph H; Shin, Eun Ji; Lennon, Anne Marie; Canto, Marcia Irene; Goggins, Michael
2017-01-01
Objective Secretin-stimulated pancreatic juice contains DNA shed from cells lining the pancreatic ducts. Genetic analysis of this fluid may form a test to detect pancreatic ductal neoplasia. Design We employed digital next-generation sequencing (‘digital NGS’) to detect low-abundance mutations in secretin-stimulated juice samples collected from the duodenum of subjects enrolled in Cancer of the Pancreas Screening studies at Johns Hopkins Hospital. For each juice sample, digital NGS necessitated 96 NGS reactions sequencing nine genes. The study population included 115 subjects (53 discovery, 62 validation) (1) with pancreatic ductal adenocarcinoma (PDAC), (2) intraductal papillary mucinous neoplasm (IPMN), (3) controls with non-suspicious pancreata. Results Cases with PDAC and IPMN were more likely to have mutant DNA detected in pancreatic juice than controls (both p<0.0001); mutant DNA concentrations were higher in patients with PDAC than IPMN (p=0.003) or controls (p<0.001). TP53 and/or SMAD4 mutations were commonly detected in juice samples from patients with PDAC and were not detected in controls (p<0.0001); mutant TP53/SMAD4 concentrations could distinguish PDAC from IPMN cases with 32.4% sensitivity, 100% specificity (area under the curve, AUC 0.73, p=0.0002) and controls (AUC 0.82, p<0.0001). Two of four patients who developed pancreatic cancer despite close surveillance had SMAD4/TP53 mutations from their cancer detected in juice samples collected over 1 year prior to their pancreatic cancer diagnosis when no suspicious pancreatic lesions were detected by imaging. Conclusions The detection in pancreatic juice of mutations important for the progression of low-grade dysplasia to high-grade dysplasia and invasive pancreatic cancer may improve the management of patients undergoing pancreatic screening and surveillance. PMID:27432539
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Zhu, Feng; Shen, Yi Bin; Li, Fu Qiang; Fang, Yun; Hu, Liang; Wu, Yi Jun
2016-02-01
The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT).A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases.Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC-associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126-0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under
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Molecular Pathways: Mucins and Drug Delivery in Cancer.
Rao, Chinthalapally V; Janakiram, Naveena B; Mohammed, Altaf
2017-03-15
Over the past few decades, clinical and preclinical studies have clearly demonstrated the role of mucins in tumor development. It is well established that mucins form a barrier impeding drug access to target sites, leading to cancer chemoresistance. Recently gained knowledge regarding core enzyme synthesis has opened avenues to explore the possibility of disrupting mucin synthesis to improve drug efficacy. Cancer cells exploit aberrant mucin synthesis to efficiently mask the epithelial cells and ensure survival under hostile tumor microenvironment conditions. However, O-glycan synthesis enzyme core 2 beta 1,6 N-acetylglucosaminyltransferase (GCNT3/C2GnT-2) is overexpressed in Kras-driven mouse and human cancer, and inhibition of GCNT3 has been shown to disrupt mucin synthesis. This previously unrecognized developmental pathway might be responsible for aberrant mucin biosynthesis and chemoresistance. In this Molecular Pathways article, we briefly discuss the potential role of mucin synthesis in cancers, ways to improve drug delivery and disrupt mucin mesh to overcome chemoresistance by targeting mucin synthesis, and the unique opportunity to target the GCNT3 pathway for the prevention and treatment of cancers. Clin Cancer Res; 23(6); 1373-8. ©2016 AACR . ©2016 American Association for Cancer Research.
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Mucin-based targeted pancreatic cancer therapy.
Torres, Maria P; Chakraborty, Subhankar; Souchek, Joshua; Batra, Surinder K
2012-01-01
The prognosis of pancreatic cancer (PC) patients is very poor with a five-year survival of less than 5%. One of the major challenges in developing new therapies for PC is the lack of expression of specific markers by pancreatic tumor cells. Mucins are heavily Oglycosylated proteins characterized by the presence of short stretches of amino acid sequences repeated several times in tandem. The expression of several mucins including MUC1, MUC4, MUC5AC, and MUC16 is strongly upregulated in PC. Recent studies have also demonstrated a link between the aberrant expression and differential overexpression of mucin glycoproteins to the initiation, progression, and poor prognosis of the disease. These studies have led to increasing recognition of mucins as potential diagnostic markers and therapeutic targets in PC. In this focused review we present an overview of the therapies targeting mucins in PC, including immunotherapy (i.e. vaccines, antibodies, and radioimmunoconjugates), gene therapy, and other novel therapeutic strategies.