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Sample records for papillary mucinous carcinoma

  1. "Mucin"-secreting papillary renal cell carcinoma: clinicopathological, immunohistochemical, and molecular genetic analysis of seven cases.

    PubMed

    Pivovarcikova, Kristyna; Peckova, Kvetoslava; Martinek, Petr; Montiel, Delia Perez; Kalusova, Kristyna; Pitra, Tomas; Hora, Milan; Skenderi, Faruk; Ulamec, Monika; Daum, Ondrej; Rotterova, Pavla; Ondic, Ondrej; Dubova, Magdalena; Curik, Romuald; Dunatov, Ana; Svoboda, Tomas; Michal, Michal; Hes, Ondrej

    2016-07-01

    Mucin and mucin-like material are features of mucinous tubular and spindle renal cell carcinoma (MTS RCC) but are rarely seen in papillary renal cell carcinoma (PRCC). We reviewed 1311 PRCC and identified 7 tumors containing extracellular and/or intracellular mucinous/mucin-like material (labeled as PRCCM). We analyzed these using morphological, histochemical, immunohistochemical, and molecular genetic methods (arrayCGH, FISH). Clinical data were available for six of the seven patients (five males and one female, age range 61-78 years). Follow-up was available for four patients (2-4 years); one patient died of widespread metastases. Tumor size ranged from 3 to 5 cm (mean 3.8). Of all cases, histological architecture showed a predominantly papillary pattern. Mucin or mucin-like was extracellular in one, intracellular in three, and both intra/extracellular in three cases. All tumors were positive for AMACR, vimentin, and OSCAR, while CK7 was positive in four. Mucicarmine stain was positive in all cases, PAS in six and Alcian blue in three cases. Five tumors were positive for MUC 1, but none were positive for MUC 2, MUC 4, or MUC 6. In only four cases, genetic analysis could be performed. Gain of chromosomes 7 and 17 was found in two cases; gain of 17 only was found in one case. Loss of heterozygosity of 3p was found in one case together with polysomy of chromosomes 7 and 17. No abnormalities of VHL, fumarate dehydrogenase, and TFE3 genes were detected. We conclude that PRCCM is a rare but challenging subtype of RCC that deserves to be further studied. In all the tumors, the mucin-like material was found in those stained with mucicarmin, but other conventional and immunohistochemical stains did not reveal consistent features of a single mucin. The molecular-genetic profile of these tumors was most consistent with that of typical papillary RCC, although one case had mixed genetic features of papillary and clear RCC. PRCCM has metastatic potential, as evidenced by

  2. Rare condition of needle tract seeding after EUS-guided FNA for intraductal papillary mucinous carcinoma

    PubMed Central

    Yamabe, Akane; Irisawa, Atsushi; Shibukawa, Goro; Hoshi, Koki; Fujisawa, Mariko; Igarashi, Ryo; Sato, Ai; Maki, Takumi; Hojo, Hiroshi

    2016-01-01

    Background and study aims: We report on a 75-year-old man who was admitted due to pancreatic cystic lesion accompanied by a solid mass with liver metastasis. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed on the solid mass, and pathological findings revealed the lesion to be an adenocarcinoma diagnosed as intraductal papillary mucinous carcinoma (IPMC). Approximately 3 months after, a cystic subepithelial lesion appeared in the posterior gastric wall where the EUS-FNA had been performed. We performed EUS-FNA again, which revealed that the cystic mass was IPMC with pathology similar to the original lesion. This is a rare case demonstrating needle tract seeding of EUS-FNA for IPMC.

  3. A case of undifferentiated carcinoma of the pancreas mimicking main-duct intraductal papillary mucinous neoplasm (IPMN).

    PubMed

    Kawai, Yuichi; Nakamichi, Rei; Kamata, Noriko; Miyake, Hideo; Fujino, Masahiko; Itoh, Shigeki

    2015-03-01

    We report here a rare case of undifferentiated carcinoma of the pancreas mimicking main-duct intraductal papillary mucinous neoplasm. In an 80-year-old woman, an approximately 8-mm papillary mass was incidentally detected at the downstream edge of a dilatated main pancreatic duct lumen on CT and MRI. Main pancreatic duct dilatation in the pancreatic body and tail and parenchymal atrophy were observed in the upstream of the mass. Histopathologically, the tumor protruded into the downstream edge of the dilatated main pancreatic duct lumen in the pancreatic body. The tumor cells had highly atypical nuclei and abundant polymorphic structures, and showed positive staining for granulocyte colony-stimulating factor, which led to the diagnosis of undifferentiated carcinoma. A total of 13 cases of undifferentiated carcinoma with intraductal tumor growth have been reported to date. The case report by Bergmann et al. has been the smallest in histopathological specimen, and the present case is the smallest in size detected by radiological images. Since early undifferentiated carcinoma of the pancreas can resemble those of main-duct intraductal papillary mucinous neoplasm in cross-sectional images, we have to consider undifferentiated carcinoma in the differential diagnosis of the solitary and papillary mass with low contrast enhancement in early phase in the main pancreatic duct. PMID:25526684

  4. Adjuvant Chemoradiotherapy After Pancreatic Resection for Invasive Carcinoma Associated With Intraductal Papillary Mucinous Neoplasm of the Pancreas

    SciTech Connect

    Swartz, Michael J.; Hsu, Charles C.; Pawlik, Timothy M.; Winter, Jordan; Hruban, Ralph H.; Guler, Mehmet; Schulick, Richard D.; Cameron, John L.; Laheru, Daniel A.; Wolfgang, Christopher L.; Herman, Joseph 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 present 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.

  5. Subcellular localization of KL-6 mucin in intraductal papillary mucinous neoplasm of the pancreas.

    PubMed

    Inagaki, Yoshinori; Seyama, Yasuji; Hasegawa, Kiyoshi; Tang, Wei; Kokudo, Norihiro

    2014-08-01

    This study aimed to clarify the expression profile of KL-6 mucin in intraductal papillary mucinous neoplasm (IPMN) and its relation to tumor malignancy. Expression of KL-6 mucin in 38 IPMNs (intraductal papillary mucinous adenoma (IPMA), 24 cases; minimally invasive intraductal papillary mucinous carcinoma (MI-IPMC), 8 cases; invasive carcinoma originating from IPMC (IC-IPMC), 6 cases) and 66 pancreatic ductal adenocarcinomas (PDACs) was evaluated immunohistochemically. IC-IPMCs and MI-IPMCs had positive staining of KL-6 mucin whereas 58% of IPMAs tested negative. Subcellular localization of KL-6 mucin varied among IPMNs whereas all of the PDAC had positive expression in the circumferential membrane and cytoplasm of cancer cells. IC-IPMCs and MI-IPMCs had a higher frequency of circumferential membrane and cytoplasmic localization of KL-6 mucin than did IPMAs. These results suggest that localization of KL-6 mucin could be used to predict the malignancy of IPMN. PMID:25047009

  6. Usefulness of KL-6 in the subtyping of intraductal papillary mucinous neoplasia of the pancreas, including carcinoma, dysplasia, and hyperplasia.

    PubMed

    Ohtsuki, Yuji; Watanabe, Ryohei; Kimura, Masashi; Nomura, Katsuyoshi; Maeda, Tomoharu; Kito, Katsumi; Takeji, Miyuki; Lee, Gang-Hong; Furihata, Mutsuo

    2015-06-01

    KL-6 is known as a useful serum biomarker of the disease activity in interstitial pneumonias. We investigated its usefulness as a biomarker for subtyping intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. IPMNs are generally divided into 4 subtypes, namely pancreatobiliary (PB), intestinal (INT), gastric (GS), and oncocytic (ONC). Aside from the KL-6 antibody, the MUC1, MUC2, MUC5AC, MUC6, and MIB-1 antibodies were also examined. Eighteen IPMN cases were examined, including 12 cases of intraductal papillary mucinous carcinomas (IPMCs) simultaneously associated with dysplasia (IPMDs) and hyperplasia (IPMHs) and 6 IPMD cases with IPMH. KL-6 antibody was positive in the 8 IPMC cases, corresponding to a MUC2-negative PB subtype, but negative in 4 IPMC cases, corresponding to the INT subtype, which is positive for MUC2. IPMD of moderate-to-severe degree positively stained for the KL-6 antibody in the IPMC cases of the PB subtype but not in those of the INT subtype. The IPMH cases were mostly negative for KL-6, similar to the mild IPMD cases. In the 6 cases of mild IPMD and/or IPMH, KL-6 and MUC2 expressions were mostly negative. In conclusion, the KL-6 antibody is immunohistochemically a good biomarker of the PB subtype of IPMC, but not the INT subtype. Identifying IPMN subtypes based on KL-6 stainability would be useful. Clinicopathological studies with more IPMC cases might be needed for further progress in this field of study. PMID:24908068

  7. Tracking the Clonal Evolution of Adenosquamous Carcinoma, a Rare Variant of Intraductal Papillary Mucinous Neoplasm of the Pancreas.

    PubMed

    Matsuzaka, Suguru; Karasaki, Hidenori; Ono, Yusuke; Ogata, Munehiko; Oikawa, Kensuke; Tamakawa, Susumu; Chiba, Shin-Ichi; Muraki, Miho; Yokochi, Tomoki; Funakoshi, Hiroshi; Kono, Toru; Nagashima, Kazuo; Mizukami, Yusuke

    2016-07-01

    Adenosquamous carcinoma (ASC) is an uncommon variant of pancreatic neoplasm. We sought to trace the mode of tumor progression using specimens of ASC associated with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. A resected specimen of the primary pancreatic ASC, developed in a 72-year-old man, was subjected to mutation profiling using amplicon-targeted sequencing and digital polymerase chain reaction. DNA was isolated from each histological compartment including noninvasive IPMN, squamous cell carcinoma (SCC), and adenocarcinoma (AC). Histologically, an IPMN with a large mural nodule was identified. The invasive tumor predominantly consisted of SCC, and a smaller AC was found around the lesion. Squamous metaplasias were sporadically distributed within benign IPMNs. Mutation alleles KRAS and GNAS were identified in all specimens of IPMN including the areas of squamous metaplasia. In addition, these mutations were found in SCC and AC. Clear transition from flat/low-papillary IPMN to SCC indicated a potent invasion front, and the SCC compartment was genetically unique, because the area has a higher frequency of mutation KRAS. The invasive tumors with distinct histological appearances shared the form of noninvasive IPMN as a common precursor, rather than de novo cancer, suggesting the significance of a genetic profiling scheme of tumors associated with IPMN. PMID:27295533

  8. A case of pancreatic heterotopy of duodenal wall, intraductal papillary mucinous tumor and intraepithelial neoplasm of pancreas, papillary carcinoma of kidney in a single patient.

    PubMed

    Nobili, Cinzia; Franciosi, Claudio; Degrate, Luca; Caprotti, Roberto; Romano, Fabrizio; Perego, Elisa; Trezzi, Rosangela; Leone, Biagio Eugenio; Uggeri, Franco

    2006-01-01

    We report a case of the contemporaneous presence of two histologically different pancreatic neoplasms, one renal cancer and one embryogenic duodenal anomaly in a single patient. A 66-year-old man underwent ultrasound examination because of urinary disorders; a solid neoformation within the inferior pole of the left kidney was observed. Computed tomography confirmed the renal lesion, but also a heterogeneous mass within the pancreatic head appeared without bile ducts dilatation. Abdominal magnetic resonance revealed a multiloculated cystic component of the pancreatic mass. A second CT scan confirmed the renal and biliary findings, but it revealed a modest enlargement of the pancreatic asymptomatic mass. A resection of the left kidney inferior pole and a pylorus-preserving pancreaticoduodenectomy were performed. Histopathologic analysis of the surgical specimen revealed mild differentiated papillary renal carcinoma, intraductal papillary mucinous adenoma of the pancreatic head, foci of intraepithelial pancreatic neoplasm and pancreatic heterotopy of duodenal muscular and submucosal layers. The coexistence of several primaries and anomalies in one patient led us to suppose a genetic predisposition to different lesions, even in the absence of known familial genetic syndromes. The study of such cases may help to improve the investigation of molecular correlations and etiological factors of different solid tumors. Nowadays, surgery is the only effective cure. PMID:17168444

  9. Mucinous tubular and spindle cell carcinoma of the kidney with prominent papillary component, a non-classic morphologic variant. A histologic, immunohistochemical, electron microscopic and fluorescence in situ hybridization study.

    PubMed

    Alexiev, Borislav A; Burke, Allen P; Drachenberg, Cinthia B; Richards, Stephanie M; Zou, Ying S

    2014-07-01

    Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor with relatively indolent behavior. Non-classic morphological variants have not been well studied and rarely been reported. We report a challenging case MTSCC with a peculiar morphology in a 42-year-old man, arising in a background of end-stage renal disease (ESRD). Predominant areas with extensive papillary architecture, psammoma bodies and stromal macrophageal aggregates, reminiscent of a papillary renal cell carcinoma (papillary RCC), were intermixed with foci that transitioned into a MTSCC-like morphology exhibiting elongated tubules and a low grade spindle cell component in a background of mucinous stroma. Immunohistochemistry demonstrated diffuse positivity for P504s/AMACR and vimentin in tumor cells. Focal positivity for RCC, CD10 and CK7 was also noted. Kidney-specific cadherin, cytokeratin 34betaE12 and TFE3 stains were negative in the tumor. The major differential diagnostic considerations were papillary RCC, clear cell papillary RCC, and Xp11.2 translocation carcinoma. Negative FISH studies for trisomy 7 and 17 in both papillary and spindled components supported the diagnosis of MTSCC. The ultrastructural profile was not entirely indicative of the cellular origin of the tumor. Cytogenetic analysis should be performed in atypical cases of MTSCC for precise diagnosis. PMID:24702883

  10. Intraductal Papillary Mucinous Neoplasm of Pancreas

    PubMed Central

    Machado, Norman Oneil; al Qadhi, Hani; al Wahibi, Khalifa

    2015-01-01

    Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are neoplasms that are characterized by ductal dilation, intraductal papillary growth, and thick mucus secretion. This relatively recently defined pathology is evolving in terms of its etiopathogenesis, clinical features, diagnosis, management, and treatment guidelines. A PubMed database search was performed. All the relevant abstracts in English language were reviewed and the articles in which cases of IPMN could be identified were further scrutinized. Information of IPMN was derived, and duplication of information in several articles and those with areas of persisting uncertainties were excluded. The recent consensus guidelines were examined. The reported incidence of malignancy varies from 57% to 92% in the main duct-IPMN (MD-IPMN) and from 6% to 46% in the branch duct-IPMN (BD-IPMN). The features of high-risk malignant lesions that raise concern include obstructive jaundice in a patient with a cystic lesion in the pancreatic head, the findings on radiological imaging of a mass lesion of >30 mm, enhanced solid component, and the main pancreatic duct (MPD) of size ≥10 mm; while duct size 5-9 mm and cyst size <3 mm are considered as “worrisome features.” Magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are primary investigations in diagnosing and following up on these patients. The role of pancreatoscopy and the analysis of aspirated cystic fluid for cytology and DNA analysis is still to be established. In general, resection is recommended for most MD-IPMN, mixed variant, and symptomatic BD-IPMN. The 5-year survival of patients after surgical resection for noninvasive IPMN is reported to be at 77-100%, while for those with invasive carcinoma, it is significantly lower at 27-60%. The follow-up of these patients could vary from 6 months to 1 year and would depend on the risk stratification for invasive malignancy and the pathology of the resected specimen. The understanding of

  11. Intraductal Papillary Mucinous Neoplasm of the Pancreas: An Update

    PubMed Central

    Xiao, Shu-Yuan

    2012-01-01

    Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas. The etiology is unknown, but increasing evidence suggests the involvement of several tumorigenesis pathways, including an association with hereditary syndromes. IPMN occurs more commonly in men, with the mean age at diagnosis between 64 and 67 years old. At the time of diagnosis, it may be benign, with or without dysplasia, or frankly malignant with an invasive carcinoma. Tumors arising from the main pancreatic duct are termed main-duct IPMNs, those involving the branch ducts, branch-duct IPMNs. In general, small branch-duct IPMNs are benign, particularly in asymptomatic patients, and can be safely followed. In contrast, main-duct tumors should be surgically resected and examined carefully for an invasive component. In the absence of invasion, patient's survival is excellent, from 94 to 100%. For patients with an IPMN-associated invasive carcinoma, the prognosis overall is better than those with a de novo pancreatic ductal adenocarcinoma, with a 5-year survival of 40% to 60% in some series. However, no survival advantage can be demonstrated if the invasive component in an IPMN patient is that of the conventional tubular type (versus mucinous carcinoma). Several histomorphologic variants are recognized, although the clinical significance of this “subtyping” is not well defined. PMID:24278753

  12. Uterine papillary serous carcinoma.

    PubMed

    Moore, Kathleen N; Fader, Amanda Nickles

    2011-06-01

    Uterine papillary serous carcinoma (UPSC) is a histologic variant of endometrial cancer that accounts for only 10% of new cases of uterine cancer but is responsible for 40% of deaths from the disease. UPSC is an aggressive tumor with a predilection for early spread beyond the uterus. Treatment for UPSC typically entails surgery and in most women is followed by multimodality adjuvant therapy. In this review, we describe the epidemiology, natural history, treatment, and outcome of UPSC. PMID:21508697

  13. Pancreatic lipoma with a solid nodule mimicking invasion from adjoining intraductal papillary mucinous neoplasm.

    PubMed

    Namiki, Yoko; Maeda, Eriko; Gonoi, Wataru; Akamatsu, Nobuhisa; Ikemura, Masako; Ohtomo, Kuni

    2016-06-01

    A 74-year-old man was referred to our hospital for a mass in the pancreatic head found during screening chest computed tomography. Contrast computed tomography showed a 5-cm multicystic mass with an irregular border containing a solid component showing contrast enhancement. Caudal to this mass, a 5-cm solid mass of fat density with a nodular soft-tissue component was found. Cytology of the aspirated pancreatic fluid revealed malignant cells, and surgery was performed for suspected intraductal papillary mucinous carcinoma. Pathologic analysis of the resected specimen revealed a collision tumor of intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia and pancreatic lipoma. The soft-tissue component within the lipoma was a nodule consisting of pancreatic tissue with inflammatory infiltration and hyalinization and was not associated with IPMN invasion. PMID:27257448

  14. Composite encapsulated papillary carcinoma and solid papillary carcinoma.

    PubMed

    Cui, Xiaoyan; Wei, Shi

    2015-03-01

    Encapsulated papillary carcinoma (EPC) and solid papillary carcinoma (SPC) are distinctive variants of intraductal papillary carcinomas, each accounting for <1% of breast carcinomas. Here we report a composite carcinoma consisting of EPC and SPC. A 73-year-old woman was found to have a high density mass in the left breast on mammogram. A biopsy showed intermediate to high grade ductal carcinoma in situ (DCIS). Gross examination of the lumpectomy specimen revealed a solid, multinodular mass. Microscopic examination demonstrated two morphologically distinct intraductal carcinomas intermingled with each other. One had delicate papillae in multi-cystic spaces surrounded by thick fibrous capsule, consistent with EPC. The other had solid tumor nests with delicate fibrovascular cores. The cells were monotonous with round nuclei and salt and pepper-like chromatin, characteristic of SPC. The lack of myoepithelial cells within the papillae and at the periphery of the lesion was confirmed by immunostaining for p63 and CK5/6. Neuroendocrine differentiation of SPC was demonstrated by neuron specific enolase staining. To our knowledge, this is the first reported case of composite EPC and SPC. It raises an interesting question as to a possible common pathway of carcinogenesis of these two rare variants. PMID:25545718

  15. Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

    PubMed Central

    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

  16. [Intraductal papillary mucinous neoplasia: which findings support observation?].

    PubMed

    Mayerle, J; Kraft, M; Menges, P; Simon, P; Ringel, J; Partecke, L I; Heidecke, C D; Lerch, M M

    2012-02-01

    On abdominal CT scans asymptomatic cystic lesions of the pancreas are accidentally detected in 1-2% of patients. Congenital cysts and pancreatic pseudocysts account for two thirds of these lesions. Pancreatic pseudocysts are a frequent complication of acute and chronic pancreatitis. Among resected cystic neoplasms serous cystic adenoma accounts for 30%, mucinous cystic neoplasms for 45% and intraductal papillary mucinous neoplasms for 25%. The diagnosis of a cystic pancreatic lesion is usually made by diagnostic imaging. Symptomatic lesions require definitive therapeutic treatment after appropriate diagnostic work-up. In the diagnosis of asymptomatic cystic lesions several factors are important, among them whether the cyst is connected to the pancreatic duct (as in IPMN and pseudocysts), the size of lesion (for treatment indications) and whether nodules form in the wall of the cyst (a sign of potential malignancy). EUS-guided fine needle aspiration of the cyst fluid adds to the discrimination between benign, premalignant and malignant cystic lesions. Measuring lipase activity, CEA, viscosity and mucin as well as cytology can help in differentiating cystic lesions. An algorithm is discussed for the differential diagnosis and for selection of the appropriate treatment for pancreatic cystic lesions, most of which never require surgery. PMID:22271054

  17. MRI findings of intraductal papillary mucinous neoplasms (IPMNs).

    PubMed

    Lana, Silvia; Vallara, Manuela; Bono, Nicola Emanuele; Russo, Giuseppe; Artioli, Giulia; Capretti, Giovanni; Paladini, Ilaria; Pesce, Antonella; Ruggirello, Margherita; Barbalace, Sandro; Mostardi, Maurizio

    2016-01-01

    Cystic lesions of the pancreas are relatively frequent imaging findings due to the improvement of imaging technologies. They may be secondary to both benign and malignant disease processes and their prevalence increases with age. In most cases, these lesions are detected incidentally by computed tomography and magnetic resonance imaging (MRI) performed for other reasons. Intraductal papillary mucinous neoplasms (IPMNs) represent 25% of the cystic neoplasms, morphologically classified into "main pancreatic duct IPMN" (MPD-IPMN), "side branches IPMN" (SB-IPMN) and mixed forms. Magnetic Resonance Cholangiopancreatography (MRCP) is a multiparametricity not invasive radiological technique that doesn't use ionizing radiation or organ iodinized contrast agents; it allows an accurate characterization of the lesions (number and size of cystic lesions, internal features of a cyst, ducts dilation, communication with main pancreatic duct) that is important to guide the differential diagnosis and establish a correct follow-up. International guidelines consider IPMN of MPD and mixed forms to be an indication for surgery, while clinical and radiological follow-up is indicated in asymptomatic patients with SB-IPMN, especially when lesions are < 2,5-3 cm in diameter and there are no mural nodules or dilation of MPD. PMID:27467864

  18. Mucinous Urothelial Carcinoma of the Renal Pelvis

    PubMed Central

    Behzatğlu, Kemal; Boyaci, Ceren; Okçu, Oğuzhan; Hacihasanoğlu, Ezgi; Çakir, Yasemin; Darakçi, Seher

    2014-01-01

    Urothelial carcinoma with abundant myxoid stroma is a newly-described and extremely rare entity. Since only very few cases have been reported, there is no consensus on its nomenclature. Microscopic examination revealed invasive urothelial carcinoma with widespread low-grade noninvasive areas. There were focal invasive areas in the neighborhood of the renal parenchyma. Malignant urothelial tumor/cell groups localized in the stroma had abundant myxoid/mucinous background in the invasive areas. The cytoplasm of the tumoral cells was more eosinophilic in these areas and the cells formed small groups and cords. Histochemically, PAS and Alcian Blue were positive in the cytoplasm of the tumoral cells and in the stroma while negative in the non-mucinous areas. Immunohistochemically, the tumoral cells of the mucinous invasive areas diffusely expressed MUC1 and MUC2. We discuss the origin of the mucinous/myxoid stroma, the tumor’s nature and its nomenclature with histochemical and immunohistochemical features. PMID:25568745

  19. Cyst infection of intraductal papillary mucinous neoplasms of the pancreas: management of a rare complication: report of 2 cases.

    PubMed

    Watanabe, Kenji; Karasaki, Hidenori; Mizukami, Yusuke; Kawamoto, Toru; Kono, Toru; Imai, Koji; Einama, Takahiro; Taniguchi, Masahiko; Kohgo, Yutaka; Furukawa, Hiroyuki

    2014-04-01

    The purpose of this study was to describe the cyst infection of intraductal papillary mucinous neoplasm in 2 patients. The patients were 62- and 74-year-old men. The initial symptom was acute febrile abdominal pain. Laboratory tests revealed severe infection (C-reactive protein concentrations were 23.3 µg/mL in patient 1 and 22.3 µg/mL in patient 2) and multilocular cystic masses (the diameters were 70 mm in patient 1 and 50 mm in patient 2) at the pancreatic head that involved peripancreatic vessels were demonstrated by computed tomography. Laboratory and radiographic findings were markedly improved by endoscopic transpapillary drainage. The enteric bacteria were detected in the drainage specimens. Curative resection was achieved, and histological findings indicated a carcinoma in situ in patient 1 and an invasive carcinoma in patient 2. Neither hyperamylasemia nor histological fat necrosis, frequently observed in acute pancreatitis, was evident. Both patients were free from recurrence after surgery (17 months in patient 1, and 18 months in patient 2). Cyst infection is an unknown complication of intraductal papillary mucinous neoplasm. Transpapillary drainage is highly recommended as an initial intervention. It is difficult to distinguish between cyst infection and unresectable invasive carcinoma with imaging modalities; however, surgical intervention after drainage may contribute to long-term survival. PMID:24622083

  20. Refractory Jaundice From Intraductal Papillary Mucinous Neoplasm Treated With Cholangioscopy-Guided Radiofrequency Ablation.

    PubMed

    Brown, Nicholas G; Camilo, Joel; McCarter, Martin; Shah, Raj J

    2016-04-01

    Intraductal papillary mucinous neoplasms (IPMNs) are epithelial neoplasms treated with surgical resection when appropriate. We present a 79-year-old man with jandice refractory to endoscopic stenting. Biliary radiofrequency ablation (RFA) with cholangioscopy was used as palliation of obstructive jaundice due to a mucin-producing pancreatic IPMN with fistulous biliary communication. Clinical improvement permitted surgery, and he returned to pre-illness status at 17 months. The use of cholangioscopy in the setting of mucinous filling defects can guide over-the-wire RFA for palliation and may be a bridge to surgery. PMID:27144205

  1. Refractory Jaundice From Intraductal Papillary Mucinous Neoplasm Treated With Cholangioscopy-Guided Radiofrequency Ablation

    PubMed Central

    Brown, Nicholas G.; Camilo, Joel; McCarter, Martin

    2016-01-01

    Intraductal papillary mucinous neoplasms (IPMNs) are epithelial neoplasms treated with surgical resection when appropriate. We present a 79-year-old man with jandice refractory to endoscopic stenting. Biliary radiofrequency ablation (RFA) with cholangioscopy was used as palliation of obstructive jaundice due to a mucin-producing pancreatic IPMN with fistulous biliary communication. Clinical improvement permitted surgery, and he returned to pre-illness status at 17 months. The use of cholangioscopy in the setting of mucinous filling defects can guide over-the-wire RFA for palliation and may be a bridge to surgery. PMID:27144205

  2. Validation of international consensus guideline 2012 for intraductal papillary mucinous neoplasm of pancreas

    PubMed Central

    Han, Dong Hyeon; Lee, Huisong; Park, Jin Young; Kwon, Wooil; Heo, Jin Seok; Choi, Seong Ho

    2016-01-01

    Purpose Intraductal papillary mucinous neoplasm (IPMN) has variable malignant potential ranging from premalignant intraductal lesions to malignant neoplasms with invasive carcinoma. To help physicians managing patients with IPMN, International consensus guidelines was made in 2006 and revised in 2012. This study was designed to evaluate the clinical usefulness of guidelines and to validate. Methods From October 1996 to December 2011, we retrospectively reviewed the data of 230 patients who underwent pancreatic resection for IPMN. Univariate and multivariable analyses were used to identify significant predictors of malignancy in IPMN. Results Of the 230 patients, 62 patients (27%) were diagnosed with invasive carcinoma. Jaundice (P < 0.001; 95% confidence interval [CI], 3.086–40.010) main pancreatic duct diameter equal to or greater than 10 mm (P < 0.001; 95% CI, 1.723–6.673) and also abdominal pain (P < 0.001; 95% CI, 4.363–22.600) show statistical significance in univariate and multivariate analysis. "High-risk stigmata" was statistical powerful predictors of malignancy than "worrisome features". International consensus guidelines 2012 had improvement on specificity but deterioration of sensitivity. Conclusion Revised guidelines seemed to bring about an improvement of weak side of Sendai criteria. Abdominal pain, jaundice, main pancreas duct greater than 10 mm can be clinical variables to predict malignancy. PMID:26942155

  3. Not all occult papillary carcinomas are minimal

    SciTech Connect

    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 abnormal 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.

  4. Intraductal Papillary Mucinous Neoplasm of the Pancreas: Current State of the Art and Ongoing Controversies.

    PubMed

    Fong, Zhi Ven; Ferrone, Cristina R; Lillemoe, Keith D; Fernández-Del Castillo, Carlos

    2016-05-01

    With the widespread use and advances in radiographic imaging, Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are identified with increasing frequency. Although many studies have addressed its biology and treatment, true understanding of its natural history continues to elude us. Its malignant potential places careproviders in a clinical dilemma of balancing the morbidity of pancreatectomy against the risk of malignant transformation while under continuous surveillance. Recently, there have been conflicting data published in the literature, generating more uncertainty in the field. In this article, we critically analyze the contrasting consensus guidelines from the International Association of Pancreatology and the American Gastroenterology Association, and address lingering questions and controversies. We also synthesize newly published data in the context of current standard of care, and provide a comprehensive review and recommendations for the clinical diagnosis, treatment, and follow-up strategy in the management of patients with Intraductal Papillary Mucinous Neoplasms. PMID:26727096

  5. Characterization of intraductal papillary neoplasm of bile duct with respect to histopathologic similarities to pancreatic intraductal papillary mucinous neoplasm.

    PubMed

    Nakanuma, Yasuni; Kakuda, Yuko; Uesaka, Katsuhiko; Miyata, Takashi; Yamamoto, Yusuke; Fukumura, Yuki; Sato, Yasunori; Sasaki, Motoko; Harada, Kenichi; Takase, Masaru

    2016-05-01

    Intraductal papillary neoplasm of bile duct (IPNB) is a papillary tumor covered by well-differentiated neoplastic epithelium with fine fibrovascular cores in the dilated bile ducts. It reportedly shows similarities to intraductal papillary mucinous neoplasm of pancreas (IPMN), to various degrees. Herein, IPNB was pathologically analyzed by classifying 52 cases into 4 groups based on the histopathologic similarities to IPMN: group A (identical to IPMN, 19 cases), group B (similar to but slightly different from IPMN, 18 cases), group C (vaguely similar to IPMN, 5 cases), and group D (different from IPMN, 10 cases). In group A, intrahepatic and perihilar regions were mainly affected, most cases were of low/intermediate or high grade without invasion, and gastric type was the most common phenotype, followed by oncocytic and intestinal types. In groups C and D, perihilar and distal bile ducts were affected, almost all cases were of high grade with invasion, and most of them were of intestinal and pancreatobiliary phenotypes. Most group B cases were of intestinal phenotype, and all were of high grade with or without invasion. In conclusion, these 4 groups of IPNB showed unique pathologic features and behaviors. Group A cases were less aggressive and shared many features with IPMN, whereas group C and D cases were more aggressive and mainly found in perihilar and distal bile ducts. Group B resembling IPMN was intermediate between them. This classification may be useful in clinical practice and holds promise for a novel approach to analyze IPNB tumorigenesis. PMID:27067788

  6. Clinical management of uterine papillary serous carcinoma.

    PubMed

    Roelofsen, Thijs; van Ham, Maaike A; de Hullu, Joanne A; Massuger, Leon F

    2011-01-01

    Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer. Owing to its rarity, most clinicians are unfamiliar with the clinical aspects and management of UPSC. Furthermore, little prospective evidence exists regarding how best to treat this subset of patients. In anticipation of prospective clinical trials, this article summarizes the latest results of various clinical management options in the different substages of UPSC, with a special focus on the effects of cytoreductive surgery, comprehensive surgical staging and different adjuvant treatment options in relation to recurrence rate and survival outcome. PMID:21166512

  7. Cytopathologic Diagnosis of Oncocytic Type Intraductal Papillary Mucinous Neoplasm: Criteria and Clinical Implications of Accurate Diagnosis

    PubMed Central

    Reid, Michelle D.; Stallworth, Christina R.; Lewis, Melinda M.; Akkas, Gizem; Memis, Bahar; Basturk, Olca; Adsay, Volkan

    2016-01-01

    BACKGROUND Cytologic findings of pancreatic oncocytic-type intraductal papillary mucinous neoplasms (IPMNs)/intraductal oncocytic papillary neoplasms (IOPNs) are largely unknown. METHODS Five IOPNs encountered by the authors were analyzed. RESULTS Four IOPNs were located in the pancreatic head, and 1 was located in the pancreatic body/tail in 2 men and 3 women ages 56 to 84 years (mean age, 66 years). Radiologic diagnoses included pancreatic ductal adenocarcinoma (PDAC) in 2 patients, invasive cancer associated with IPMN in 1 patient, IPMN versus mucinous cystic neoplasm in 1 patient, and cystic mass in 1 patient. Cytologic findings included: hypercellular smears (4 of 5 cases) containing well formed clusters of oncocytic cells (5 of 5 cases) with prominent, slightly eccentric nucleoli (4 of 5 cases), predominantly arranged in sheets/papillary units (5 of 5 cases), with punched-out intercytoplasmic spaces (4 of 5 cases), and with occasional 3-dimensional groups and focal necrosis (3 of 5 cases). The intracytoplasmic mucin and thick extracellular mucin typical of other IPMNs were observed only in 2 cases and were very limited. The mean size on resection was 4.5 cm. Invasion was observed in 3 cases (0.1, 0.3, and 2.0 cm) of tubular-type IPMN. Initial cytologic evaluation was performed by the authors in 4 of 5 cases, which were diagnosed as IOPN (n = 3) and IPMN versus cystic PDAC (n = 1). One case was initially misdiagnosed as PDAC and, on resection, proved to be noninvasive IOPN. CONCLUSIONS Cytologic features of IOPNs are classical, similar to their histologic counterparts, and differ significantly from other IPMN subtypes. Because of their highly complex appearance, they are often radiologically misdiagnosed as PDAC; thus, failure to recognize their characteristic features on fine-needle aspiration may lead to inappropriate treatment. Patients with IOPN have an incomparably better prognosis than patients with ordinary PDAC, even when their neoplasms are invasive

  8. Immunophenotypic and genomic characterisation of papillary carcinomas of the breast

    PubMed Central

    Lacroix-Triki, Magali; Lambros, Maryou B; MacKay, Alan; A’Hern, Roger; Gauthier, Arnaud; Pawar, Vidya; Colombo, Pierre-Emanuel; Daley, Frances; Natrajan, Rachael; Ward, Eric; MacGrogan, Gaëtan; Arbion, Flavie; Michenet, Patrick; Weigelt, Britta; Vincent-Salomon, Anne; Reis-Filho, Jorge S

    2016-01-01

    Papillary carcinomas are a special histological type of breast cancer, and have a relatively good outcome. We characterised the genomic and phenotypic characteristics of papillary carcinomas, and to determine whether they would constitute an entity distinct from grade- and oestrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs). The phenotype of 63 papillary carcinomas of the breast and grade- and ER-matched IDC-NSTs was determined by immunohistochemistry. DNA of sufficient quality was extracted from 49 microdissected papillary carcinomas and 49 microdissected grade- and ER-matched IDC-NSTs. These samples were subjected to high-resolution microarray-based comparative genomic hybridisation (aCGH) and MassARRAY Sequenom sequencing analysis of 19 known oncogenes. Papillary carcinomas were predominantly of low histological grade, expressed immunohistochemical markers consistent with a luminal phenotype, and a lower rate of lymph node metastasis and p53 expression than grade- and ER-matched IDC-NSTs. Papillary carcinomas displayed less genomic aberrations than grade- and ER-matched IDC-NSTs; however the patterns of gene copy number aberrations found in papillary carcinomas were similar to those of ER- and grade-matched IDC-NSTs, including 16q losses. Furthermore, PIK3CA mutations were found in 43% and 29% of papillary carcinomas and grade- and ER-matched IDC-NSTs respectively. The genomic profiles of encapsulated, solid and invasive papillary carcinomas, the three morphological subtypes, were remarkably similar. Our results demonstrate that papillary carcinomas are a homogeneous special histological type of breast cancer. The similarities in the genomic profiles of papillary carcinomas and grade- and ER-matched IDC-NSTs suggest that papillary carcinomas may be best positioned as part of the spectrum of ER-positive breast cancers rather than as a distinct entity. Furthermore, the good prognosis of papillary carcinomas may stem from the

  9. Mucinous Variant of Follicular Carcinoma of the Thyroid Gland: Case Report and Review of the Literature.

    PubMed

    Squillaci, Salvatore; Pitino, Antonio; Spairani, Cinzia; Ferrari, Mauro; Carlon, Eugenio; Cosimi, Maria Fabia

    2016-04-01

    The rare reports of mucinous variant of follicular carcinoma of the thyroid gland have not provided enough evidence to support the recognition of these tumors as a distinct clinicopathologic entity or to understand their etiopathogenesis. We report the fourth case of mucinous variant of follicular carcinoma displaying a minimally invasive tumor with diffuse expression of thyroglobulin, TTF-1, CD56, PAX-8, cytokeratins 7 and 19, in the absence of monoclonal carcinoembryonic antigen (CEA), cytokeratin 20, chromogranin, HBME-1, P63 expression, and BRAF gene mutation, in a 51-year-old woman who is alive without signs of disease 13 months after total thyroidectomy, bilateral neck dissection, and radioactive iodine. Herein, fine-needle aspiration cytology disclosed "worrisome" cytologic features consisting of large epithelial cells arranged in clusters or singularly, with high nucleocytoplasmic ratio, nuclear grooves and evident nucleoli which were shared by those of mucin-producing papillary thyroid carcinoma. Therefore, knowledge of the cytological and histopathological spectrum of this lesion is important to avoid misdiagnosis. The morphologic clues leading to the correct diagnosis of mucinous variant of follicular neoplasm have been correlated with the data of the literature, and the differential diagnosis is briefly discussed. PMID:26582770

  10. Penile mucinous carcinoma: A case report

    PubMed Central

    ÖZTÜRK, HAKAN

    2015-01-01

    Penile cancer is an extremely rare form of urological cancer that usually originates in the epithelium of the inner preputium or glans. Major etiological factors include phimosis, poor penile hygiene and smoking. Nearly 95% of penile cancers are squamous cell carcinomas and usually occur in the sixth decade of life. The disease exhibits two variants, namely metastatic and atypical disease. Squamous differentiation may also present with mucinous metaplasia. An extremely limited number of case reports on penile cancer are available in the literature. The present study reports the case of a 39-year-old patient with penile mucinous adenocarcinoma who was admitted with the complaint of perineal discharge, which is, to the best of our knowledge, the first case in the literature. The patient underwent total penectomy and inguinal lymph node dissection. The tumor was staged as T4N1M0, according to the European Association of Urology’s tumor-node-metastasis classification system. The patient was treated with pelvic radiotherapy and six cycles of systemic neoadjuvant chemotherapy with cisplatin and paclitaxel simultaneously, over a period of four months. After nine months of follow-up the patient succumbed to the disease due to widespread metastases. PMID:25663900

  11. Adrenal Metastasis from Uterine Papillary Serous Carcinoma

    PubMed Central

    Lubana, Sandeep Singh; Singh, Navdeep; Tuli, Sandeep S.; Seligman, Barbara

    2016-01-01

    Patient: Female, 60 Final Diagnosis: UPSC with adrenal metastasis Symptoms: Post menopausal bleeding Medication: — Clinical Procedure: Adrenalectomy Specialty: Oncology Objective: Rare disease Background: 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. Case Report: 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. Conclusions: 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. PMID:27117594

  12. Adrenal Metastasis from Uterine Papillary Serous Carcinoma.

    PubMed

    Singh Lubana, Sandeep; Singh, Navdeep; Tuli, Sandeep S; Seligman, Barbara

    2016-01-01

    BACKGROUND 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. CASE REPORT 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. CONCLUSIONS 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. PMID:27117594

  13. Intracystic Papillary Carcinoma of the Breast in a Male Patient

    PubMed Central

    Hu, Zishuo Ian; Liu, Chengbao; Fisher, Paul R.; Cohen, Jules A.

    2016-01-01

    We report a case of intracystic papillary carcinoma of the right breast in a 59-year old man presenting with bloody nipple discharge for 1 week prior to presentation. Mammography, ultrasonography, and core needle aspiration were consistent with intracystic papillary carcinoma. The patient underwent right simple mastectomy. Pathology was also consistent with low grade intracystic papillary carcinoma. The 21-gene assay revealed a recurrence score of 0, corresponding to a 3% risk of distant recurrence at 10 years. A patient did not receive chemotherapy or post-mastectomy radiotherapy. The patient was placed on tamoxifen and has been free of disease to date. PMID:27134706

  14. Intraductal papillary mucinous neoplasm of the bile duct with gastric and duodenal fistulas

    PubMed Central

    Hong, Man Yong; Yu, Dong Wook; Hong, Seung Goun

    2014-01-01

    Intraductal papillary mucinous neoplasm (IPMN) of the bile duct is still rare and not yet understood despite of its increased incidence and similar clinicopathologic characteristics compared with IPMN of the pancreas. The fistula formation into other organs can occur in IPMN, especially the pancreatic type. To our knowledge, only two cases of IPMN of the bile duct with a choledochoduodenal fistula were reported and we have recently experienced a case of IPMN of the bile duct penetrating into two neighboring organs of the stomach and duodenum presenting with abdominal pain and jaundice. Endoscopy showed thick mucin extruding from two openings of the fistulas. Endoscopic suction of thick mucin using direct peroral cholangioscopy with ultra-slim endoscope through choledochoduodenal fistula was very difficult and ineffective because of very thick mucin and next endoscopic suction through the stent after prior insertion of biliary metal stent into choledochogastric fistula also failed. Pathologic specimen obtained from the proximal portion of the choledochogastric fistula near left intrahepatic bile duct through the metal stent showed a low grade adenoma. The patient declined the surgical treatment due to her old age and her abdominal pain with jaundice was improved after percutaneous transhepatic biliary drainage with the irrigation of N-acetylcysteine three times daily for 10 d. PMID:25031793

  15. Proteomic Profiling of Thyroid Papillary Carcinoma

    PubMed Central

    Ban, Yoshiyuki; Yamamoto, Gou; Takada, Michiya; Hayashi, Shigeo; Ban, Yoshio; Shimizu, Kazuo; Akasu, Haruki; Igarashi, Takehito; Bando, Yasuhiko; Tachikawa, Tetsuhiko; Hirano, Tsutomu

    2012-01-01

    Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. We performed shotgun liquid chromatography (LC)/tandem mass spectrometry (MS/MS) analysis on pooled protein extracts from patients with PTC and compared the results with those from normal thyroid tissue validated by real-time (RT) PCR and immunohistochemistry (IHC). We detected 524 types of protein in PTC and 432 in normal thyroid gland. Among these proteins, 145 were specific to PTC and 53 were specific to normal thyroid gland. We have also identified two important new markers, nephronectin (NPNT) and malectin (MLEC). Reproducibility was confirmed with several known markers, but the one of two new candidate markers such as MLEC did not show large variations in expression levels. Furthermore, IHC confirmed the overexpression of both those markers in PTCs compared with normal surrounding tissues. Our protein data suggest that NPNT and MLEC could be a characteristic marker for PTC. PMID:22518348

  16. Distinct patterns of peritumoral histological findings in subtypes of intraductal papillary mucinous neoplasms of the pancreas.

    PubMed

    Saito, Michihiro; Imada, Hiroki; Suzuki, Tsukasa; Sata, Naohiro; Yasuda, Yoshikazu; Maetani, Iruru; Fukushima, Noriyoshi

    2015-10-01

    Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are primary pancreatic neoplasms that can act as precursors to invasive adenocarcinoma of the pancreas. The peritumoral stroma has been increasingly recognized to play an important role in many types of tumors. Therefore, to investigate the clinicopathological significance of the peritumoral stroma in IPMNs, we examined the histological features of the peritumoral stroma in each subtype and histological grade of IPMNs. Eighty-two patients with IPMN, who underwent surgical resection, were reviewed clinicopathologically. Intraductal papillary mucinous neoplasms (86 lesions in total) were histologically subclassified into gastric (n = 51), intestinal (n = 22), pancreatobiliary (n = 11), and oncocytic (n = 2) subtypes. Peritumoral histological features between the gastric and intestinal subtypes were evaluated by each histological grade. The results showed that subepithelial edema and inflammatory cell infiltration were more commonly observed in the gastric subtype (74% and 79%, respectively) than in the intestinal subtype (12% and 25%, respectively) of low-grade IPMNs. On the other hand, mucus lakes were more commonly observed in the intestinal subtype (100%) than in the gastric subtype (0%) of high-grade IPMNs. In addition, pancreatobiliary subtype IPMNs tended to exhibit acute inflammation such as neutrophil predominance. This study showed that peritumoral histological features differed among subtypes of IPMNs from low-grade tumors. These differences suggest the possibility that each subtype of IPMNs has a distinct mechanism from an early stage of tumor progression, which is reflected in the properties of the peritumoral stroma. PMID:26265194

  17. Current roles of endoscopy in the management of intraductal papillary mucinous neoplasm of the pancreas.

    PubMed

    Tanaka, Masao

    2015-05-01

    Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized by intraductal papillary proliferation of mucin-producing epithelial cells that exhibit various degrees of dysplasia. IPMN is classified into four histological subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) according to its histomorphological and immunohistochemical characteristics. Endoscopic retrograde cholangiopancreatography plays a crucial role in the evaluation of these features of IPMN. Endoscopic ultrasonography (EUS) has proven to be more sensitive than computed tomography or magnetic resonance imaging for early detection of malignancy. The present review addresses the current roles of endoscopy and related techniques in the management of IPMN. The particular focus is on diagnosing IPMN and malignancy within IPMN, detecting pancreatic cancer concomitant with IPMN, differentiating the epithelial subtypes of IPMN, determining the optimal strategy for the management of branch duct IPMN, and discussing innovative endoscopic technology related to IPMN. The disadvantages of endoscopic examinations of IPMN and different attitudes toward EUS-guided fine-needle aspiration for IPMN between Japan (negative) and other countries (active) are also discussed. PMID:25588761

  18. Synchronous Nesidioblastosis, Endocrine Microadenoma, and Intraductal Papillary Mucinous Neoplasia in a Man Presenting With Hyperinsulinemic Hypoglycemia.

    PubMed

    De Sousa, Sunita M C; Haghighi, Koroush S; Qiu, Min Ru; Greenfield, Jerry R; Chen, Daniel L T

    2016-01-01

    Herein, we report the first case of concomitant nesidioblastosis, pancreatic neuroendocrine tumor, and intraductal papillary mucinous neoplasia. The combination is significant as each of these pathological entities is independently very rare. The patient was a 33-year-old man who presented with symptomatic hyperinsulinemic hypoglycemia and no risk factors for pancreatic disease. Abdominal imaging showed an isolated 12 mm pancreatic lesion, whilst selective arterial calcium stimulation testing demonstrated multiple territories of insulin excess. He proceeded to subtotal pancreatectomy. Histopathology revealed an endocrine microadenoma, α and β cell nesidioblastosis, and multifocal intraductal papillary mucinous neoplasia. The endocrine microadenoma and nesidioblastosis stained for insulin, suggesting both likely contributed to hypoglycemia. Glucagon immunohistochemistry was also positive, though there were no clinical features of glucagon excess. Hypoglycemia resolved postoperatively. This case and other evidence from the literature suggest that hyperplasia and neoplasia may occur sequentially in the pancreas, and that endocrine and exocrine tumorigenesis may be linked in some individuals. Further study is required to identify a unifying mechanism, and to elucidate potential ramifications in the management of patients with pancreatic neoplasms. PMID:26658039

  19. Papillary serous carcinoma of the peritoneal surface: matched-case comparison with papillary serous ovarian carcinoma.

    PubMed

    Killackey, M A; Davis, A R

    1993-11-01

    Between 1984 and 1991, 199 patients underwent laparotomy for epithelial "ovarian" malignancy. In 29 cases (15%) normal-sized ovaries (< 4 cm in diameter) with minimal invasion by papillary serous carcinoma were found. This entity in the setting of peritoneal carcinomatosis has been previously described and is reported here as papillary serous cancer of the peritoneal surface (PSPS). The clinical, surgical, and pathologic features of PSPS are compared with a group of age-, grade-, and stage-matched cases with papillary serous ovarian carcinomas (PSOC). PSPS was also characterized by ascites (mean = 3036 cc), malignant washings (91%), and omental involvement with bulky infiltration and/or multiple tumor nodules (96%). Mean cytoreduction in the PSPS group was 65.5% compared to 79% in the PSOC group (P = 0.049). Patients received combination chemotherapy with platinum-based regimens. In general, there was a poor response to treatment with a disease-free interval of 3.4 and median survival time of 19 months in PSPS compared to 11.7 and 31 months in the PSOC patients. Patients with PSPS have more limited cytoreduction, shorter disease-free interval, and shorter overall survival time. Such differences prompt re-evaluation of treatment modalities for PSPS and recognition that this is a condition distinct from PSOC. PMID:8276289

  20. [A case of mucinous tubular and spindle cell carcinoma of the kidney].

    PubMed

    Saito, Katsuyuki; Shimada, Makoto; Inoue, Katsuki; Shiiki, Kazuhiko; Nagata, Masakazu; Ogawa, Yuichiro; Matsubara, Eiji; Maeda, Tomoko; Matsumoto, Yuki; Kunimura, Toshiaki; Mikogami, Tetsuya

    2013-02-01

    Mucinous tubular and spindle cell carcinoma (MTSCC) is a distinct entity in the World Health Organization classification of kidney tumors since 2004. Herein, we report a case of a patient with MTSCC of the kidney. A 48-year-man visited our hospital with a chief complaint of occult blood in his urine, confirmed by urine occult blood reaction. Computed tomography revealed a solid tumor in the right kidney. The tumor was 40×38 mm in length and was slightly enhanced (cT1aN0M0). Therefore, we performed radical nephrectomy. On analysis of the resected specimen, we found that the number of comparatively small malignant cells had increased markedly, forming branched tubular cuboidal cells. Further more, positive results were obtained on staining the stroma with both PAS and alcian blue stains characteristic of papillary renal cell carcinoma ; however, extracellular mucinous material was found to be depleted. Therefore, we needed to differentiate between papillary renal cell carcinoma and MTSCC. Finally, on the basis of the immunohistochemical staining results-vimentin (+), CK34βE12 (-), and CD10 (-)-MTSCC was confirmed. PMID:23552753

  1. Papillary carcinoma in ectopic thyroid detected by Tl-201 scintigraphy

    SciTech Connect

    Michigishi, T.; Mizukami, Y.; Mura, T.; Nomura, T.; Watanabe, K.; Tonami, N.; Hisada, K. )

    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.

  2. Gd-EOB-DTPA-enhanced magnetic resonance imaging for bile duct intraductal papillary mucinous neoplasms

    PubMed Central

    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

  3. Integrated genomic characterization of papillary thyroid carcinoma.

    PubMed

    2014-10-23

    Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D, and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors, and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease. PMID:25417114

  4. Integrated Genomic Characterization of Papillary Thyroid Carcinoma

    PubMed Central

    Agrawal, Nishant; Akbani, Rehan; Aksoy, B. Arman; Ally, Adrian; Arachchi, Harindra; Asa, Sylvia L.; Auman, J. Todd; Balasundaram, Miruna; Balu, Saianand; Baylin, Stephen B.; Behera, Madhusmita; Bernard, Brady; Beroukhim, Rameen; Bishop, Justin A.; Black, Aaron D.; Bodenheimer, Tom; Boice, Lori; Bootwalla, Moiz S.; Bowen, Jay; Bowlby, Reanne; Bristow, Christopher A.; Brookens, Robin; Brooks, Denise; Bryant, Robert; Buda, Elizabeth; Butterfield, Yaron S.N.; Carling, Tobias; Carlsen, Rebecca; Carter, Scott L.; Carty, Sally E.; Chan, Timothy A.; Chen, Amy Y.; Cherniack, Andrew D.; Cheung, Dorothy; Chin, Lynda; Cho, Juok; Chu, Andy; Chuah, Eric; Cibulskis, Kristian; Ciriello, Giovanni; Clarke, Amanda; Clayman, Gary L.; Cope, Leslie; Copland, John; Covington, Kyle; Danilova, Ludmila; Davidsen, Tanja; Demchok, John A.; DiCara, Daniel; Dhalla, Noreen; Dhir, Rajiv; Dookran, Sheliann S.; Dresdner, Gideon; Eldridge, Jonathan; Eley, Greg; El-Naggar, Adel K.; Eng, Stephanie; Fagin, James A.; Fennell, Timothy; Ferris, Robert L.; Fisher, Sheila; Frazer, Scott; Frick, Jessica; Gabriel, Stacey B.; Ganly, Ian; Gao, Jianjiong; Garraway, Levi A.; Gastier-Foster, Julie M.; Getz, Gad; Gehlenborg, Nils; Ghossein, Ronald; Gibbs, Richard A.; Giordano, Thomas J.; Gomez-Hernandez, Karen; Grimsby, Jonna; Gross, Benjamin; Guin, Ranabir; Hadjipanayis, Angela; Harper, Hollie A.; Hayes, D. Neil; Heiman, David I.; Herman, James G.; Hoadley, Katherine A.; Hofree, Matan; Holt, Robert A.; Hoyle, Alan P.; Huang, Franklin W.; Huang, Mei; Hutter, Carolyn M.; Ideker, Trey; Iype, Lisa; Jacobsen, Anders; Jefferys, Stuart R.; Jones, Corbin D.; Jones, Steven J.M.; Kasaian, Katayoon; Kebebew, Electron; Khuri, Fadlo R.; Kim, Jaegil; Kramer, Roger; Kreisberg, Richard; Kucherlapati, Raju; Kwiatkowski, David J.; Ladanyi, Marc; Lai, Phillip H.; Laird, Peter W.; Lander, Eric; Lawrence, Michael S.; Lee, Darlene; Lee, Eunjung; Lee, Semin; Lee, William; Leraas, Kristen M.; Lichtenberg, Tara M.; Lichtenstein, Lee; Lin, Pei; Ling, Shiyun; Liu, Jinze; Liu, Wenbin; Liu, Yingchun; LiVolsi, Virginia A.; Lu, Yiling; Ma, Yussanne; Mahadeshwar, Harshad S.; Marra, Marco A.; Mayo, Michael; McFadden, David G.; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Miller, Michael; Mills, Gordon; Moore, Richard A.; Mose, Lisle E.; Mungall, Andrew J.; Murray, Bradley A.; Nikiforov, Yuri E.; Noble, Michael S.; Ojesina, Akinyemi I.; Owonikoko, Taofeek K.; Ozenberger, Bradley A.; Pantazi, Angeliki; Parfenov, Michael; Park, Peter J.; Parker, Joel S.; Paull, Evan O.; Pedamallu, Chandra Sekhar; Perou, Charles M.; Prins, Jan F.; Protopopov, Alexei; Ramalingam, Suresh S.; Ramirez, Nilsa C.; Ramirez, Ricardo; Raphael, Benjamin J.; Rathmell, W. Kimryn; Ren, Xiaojia; Reynolds, Sheila M.; Rheinbay, Esther; Ringel, Matthew D.; Rivera, Michael; Roach, Jeffrey; Robertson, A. Gordon; Rosenberg, Mara W.; Rosenthall, Matthew; Sadeghi, Sara; Saksena, Gordon; Sander, Chris; Santoso, Netty; Schein, Jacqueline E.; Schultz, Nikolaus; Schumacher, Steven E.; Seethala, Raja R.; Seidman, Jonathan; Senbabaoglu, Yasin; Seth, Sahil; Sharpe, Samantha; Mills Shaw, Kenna R.; Shen, John P.; Shen, Ronglai; Sherman, Steven; Sheth, Margi; Shi, Yan; Shmulevich, Ilya; Sica, Gabriel L.; Simons, Janae V.; Sipahimalani, Payal; Smallridge, Robert C.; Sofia, Heidi J.; Soloway, Matthew G.; Song, Xingzhi; Sougnez, Carrie; Stewart, Chip; Stojanov, Petar; Stuart, Joshua M.; Tabak, Barbara; Tam, Angela; Tan, Donghui; Tang, Jiabin; Tarnuzzer, Roy; Taylor, Barry S.; Thiessen, Nina; Thorne, Leigh; Thorsson, Vésteinn; Tuttle, R. Michael; Umbricht, Christopher B.; Van Den Berg, David J.; Vandin, Fabio; Veluvolu, Umadevi; Verhaak, Roel G.W.; Vinco, Michelle; Voet, Doug; Walter, Vonn; Wang, Zhining; Waring, Scot; Weinberger, Paul M.; Weinstein, John N.; Weisenberger, Daniel J.; Wheeler, David; Wilkerson, Matthew D.; Wilson, Jocelyn; Williams, Michelle; Winer, Daniel A.; Wise, Lisa; Wu, Junyuan; Xi, Liu; Xu, Andrew W.; Yang, Liming; Yang, Lixing; Zack, Travis I.; Zeiger, Martha A.; Zeng, Dong; Zenklusen, Jean Claude; Zhao, Ni; Zhang, Hailei; Zhang, Jianhua; Zhang, Jiashan (Julia); Zhang, Wei; Zmuda, Erik; Zou., Lihua

    2014-01-01

    Summary Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease. PMID:25417114

  5. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    PubMed Central

    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

  6. A case of mixed adenoneuroendocrine carcinoma of the gallbladder arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction.

    PubMed

    Meguro, Yoshiyuki; Fukushima, Noriyoshi; Koizumi, Masaru; Kasahara, Naoya; Hydo, Masanobu; Morishima, Kazue; Sata, Naohiro; Lefor, Alan T; Yasuda, Yoshikazu

    2014-09-01

    A 54-year-old Japanese woman was referred with a gallbladder tumor. Based on the results of the computed tomography scan, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography, a mucin-producing neoplasm of the gallbladder associated with pancreaticobiliary maljunction was diagnosed. Extended cholecystectomy, extrahepatic bile duct resection, and choledochojejunostomy were performed, and she remains free of recurrence 24 months after resection. Histopathological examination revealed that the papillary component of the lesion was an intracystic papillary neoplasm with diverse characteristics of pancreaticobiliary epithelium and intestinal epithelium including mucin. In this component, most of the papillary lesion was a high-grade intraepithelial neoplasm, but also showed slight invasion into the muscular layer. The nodular component consisted of both poorly differentiated biliary type adenocarcinoma and large cell neuroendocrine carcinoma. We report a rare case of a mixed adenoneuroendocrine carcinoma arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction. As for the histogenesis of this tumor, based on the histopathologic appearance, transdifferentiation from poorly differentiated biliary type adenocarcinoma to large cell neuroendocrine carcinoma is considered the most possible histogenesis of this tumor. PMID:25146100

  7. BRAF Testing in Multifocal Papillary Thyroid Carcinoma

    PubMed Central

    Kimbrell, Hillary Z.; Sholl, Andrew B.; Ratnayaka, Swarnamala; Japa, Shanker; Lacey, Michelle; Carpio, Gandahari; Bhatia, Parisha; Kandil, Emad

    2015-01-01

    Background. BRAF V600E mutation is associated with poor prognosis in patients with papillary thyroid carcinoma (PTC). PTC is often multifocal, and there are no guidelines on how many tumors to test for BRAF mutation in multifocal PTC. Methods. Fifty-seven separate formalin-fixed and paraffin-embedded PTCs from twenty-seven patients were manually macrodissected and tested for BRAF mutation using a commercial allele-specific real-time polymerase chain reaction-based assay (Entrogen, Woodland Hills, CA). Data related to histologic characteristics, patient demographics, and clinical outcomes were collected. Results. All mutations detected were BRAF V600E. Seventeen patients (63%) had concordant mutation status in the largest and second-largest tumors (i.e., both were positive or both were negative). The remaining ten patients (37%) had discordant mutation status. Six of the patients with discordant tumors (22% overall) had a BRAF-negative largest tumor and a BRAF-positive second-largest tumor. No histologic feature was found to help predict which cases would be discordant. Conclusions. Patients with multifocal PTC whose largest tumor is BRAF-negative can have smaller tumors that are BRAF-positive. Therefore, molecular testing of more than just the dominant tumor should be considered. Future studies are warranted to establish whether finding a BRAF mutation in a smaller tumor has clinical significance. PMID:26448939

  8. The RET oncogene in papillary thyroid carcinoma.

    PubMed

    Prescott, Jason D; Zeiger, Martha A

    2015-07-01

    Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, accounting for greater than 80% of cases. Surgical resection, with or without postoperative radioiodine therapy, remains the standard of care for patients with PTC, and the prognosis is generally excellent with appropriate treatment. Despite this, significant numbers of patients will not respond to maximal surgical and medical therapy and ultimately will die from the disease. This mortality reflects an incomplete understanding of the oncogenic mechanisms that initiate, drive, and promote PTC. Nonetheless, significant insights into the pathologic subcellular events underlying PTC have been discovered over the last 2 decades, and this remains an area of significant research interest. Chromosomal rearrangements resulting in the expression of fusion proteins that involve the rearranged during transfection (RET) proto-oncogene were the first oncogenic events to be identified in PTC. Members of this fusion protein family (the RET/PTC family) appear to play an oncogenic role in approximately 20% of PTCs. Herein, the authors review the current understanding of the clinicopathologic role of RET/PTC fusion proteins in PTC development and progression and the molecular mechanisms by which RET/PTCs exert their oncogenic effects on the thyroid epithelium. PMID:25731779

  9. Synchronous invasive ductal carcinoma in encapsulated papillary ductal carcinoma

    PubMed Central

    Regan, J.P.; Casaubon, J.T.; Genelus-Dominique, E.

    2016-01-01

    Encapsulated papillary ductal carcinoma (EPC) of the breast is a rare form of cancer with defining histopathology of encapsulation. These lesions are typically indolent but may rarely have concomitant, synchronous invasive lesions. This report details a 56-year-old black female who presented with a palpable left breast mass. Adenosis with focal fibrous and ductal hyperplasia characteristics were found on core needle biopsy. Excisional biopsy showed EPC with invasive components. A simple mastectomy was performed and a second lesion was identified as invasive ductal carcinoma. EPC typically has good prognosis and a low incidence of invasion. The risk increases in the presence of a second, synchronous lesion as in our case. Management is typically performed with breast conserving methods; however, missing a second lesion is possible. This report provides an overview of the literature and discussion of the role of MRI in preoperative workup. PMID:27562577

  10. Soft tissue invasion of papillary thyroid carcinoma.

    PubMed

    Lin, Jen-Der; Hsueh, Chuen; Chao, Tzu-Chieh

    2016-08-01

    Extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) is common and clinical presentation can vary from minimal to extensive locoregional involvement. Although PTC is generally considered the most benign among all thyroid carcinomas, it may present with local invasion with poor prognosis. Our retrospective study involved 3267 PTC patients undergoing regular follow-up at Chang Gung Medical Center in Linkou, Taiwan. Among them, 269 were PTC cases with ETE, having tumors greater than 1 cm in size and treated with total or complete thyroidectomy with or without lymph node dissection for which the follow-up period was over 10 years. The mean age of 269 cases was 46.8 ± 15.1 (range 11-83 years) years. The number of females was 204 (75.8 %). Patients were categorized into minimal ETE (175 cases) and extensive ETE (94 cases) groups according to surgical findings and pathological reports. Mean follow-up period was 13.3 ± 5.5 (range 0.2-29.3) years, during which 28 (10.4 %) patients died of thyroid cancer; and 63 (23.4 %) of all-cause mortality. Multivariate analysis showed that age, gender, extensive ETE, and lymph node metastasis had a statistically significant effect on thyroid cancer mortality. Survival rates were significantly different between minimal ETE and extensive ETE groups (p < 0.0001). In conclusion, perithyroidal soft tissue involvement by PTC is an important factor that determines patient prognosis and a closer follow-up and more aggressive treatment is necessary for patients who are old, male, extensive ETE, and with lymph node involvement. PMID:27154220

  11. Current roles of endoscopy in the management of intraductal papillary mucinous neoplasm of the pancreas

    PubMed Central

    2015-01-01

    Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized by intraductal papillary proliferation of mucin‐producing epithelial cells that exhibit various degrees of dysplasia. IPMN is classified into four histological subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) according to its histomorphological and immunohistochemical characteristics. Endoscopic retrograde cholangiopancreatography plays a crucial role in the evaluation of these features of IPMN. Endoscopic ultrasonography (EUS) has proven to be more sensitive than computed tomography or magnetic resonance imaging for early detection of malignancy. The present review addresses the current roles of endoscopy and related techniques in the management of IPMN. The particular focus is on diagnosing IPMN and malignancy within IPMN, detecting pancreatic cancer concomitant with IPMN, differentiating the epithelial subtypes of IPMN, determining the optimal strategy for the management of branch duct IPMN, and discussing innovative endoscopic technology related to IPMN. The disadvantages of endoscopic examinations of IPMN and different attitudes toward EUS‐guided fine‐needle aspiration for IPMN between Japan (negative) and other countries (active) are also discussed. PMID:25588761

  12. Quantitative microscopic evaluation of mucin areas and its percentage in mucinous carcinoma of the breast using tissue histological images.

    PubMed

    Saha, Monjoy; Arun, Indu; Basak, Bijan; Agarwal, Sanjit; Ahmed, Rosina; Chatterjee, Sanjoy; Bhargava, Rohit; Chakraborty, Chandan

    2016-06-01

    Mucinous carcinoma (MC) of the breast is very rare (∼1-7% of all breast cancers), invasive ductal carcinoma. Presence of pools of extracellular mucin is one of the most important histological features for MC. This paper aims at developing a quantitative computer-aided methodology for automated identification of mucin areas and its percentage using tissue histological images. The proposed method includes pre-processing (i.e., colour space transformation and colour normalization), mucin regions segmentation, post-processing, and performance evaluation. The proposed algorithm achieved 97.74% segmentation accuracy in comparison to ground truths. In addition, the percentage of mucin present in the tissue regions is calculated by the mucin index (MI) for grading MC (pure, moderately, minimally mucinous). PMID:26971129

  13. Intracystic papillary breast carcinoma with areas of infiltration

    PubMed Central

    Martín Gutiérrez, Silvia; Nieto Gallo, María Antonia; Noguero Meseguera, Rosario; Rodríguez Prieto, Ignacio

    2012-01-01

    Intracystic papillary carcinoma of the breast associated with areas of infiltration is rare in that it constitutes less than 1% of breast cancers. After initial radiological study, these tumors show lesions with little likelihood of malignancy in a high proportion of cases. Two cases of intracystic papillary carcinoma associated with infiltration were diagnosed at the Breast Unit of Hospital Infanta Cristina. In both cases, the reason for consultation arose after palpation of a nodule and the initial radiographic analyses showed lesions with little likelihood of malignancy. PMID:24893058

  14. Intracystic papillary carcinoma associated with ductal carcinoma in situ in a male breast: a case report

    PubMed Central

    El M’rabet, Fatema Zahra; Akesbi, Yusra; Benbrahim, Zineb; El Hind, fatemi; Znati, Kawtar; Benlemlih, Amal; Tbaili, Naima; Maaroufi, Mustapha; Tizniti, Siham; Amarti, Afaf; El Mesbahi, Omar

    2009-01-01

    Introduction Intracystic papillary carcinoma represents a small distinctive subgroup of noninvasive breast cancer, accounts for <0.5% of breast malignancies and is extremely rare in men, it was originally reported as a localized non-invasive carcinoma, but is usually associated with ductal carcinoma in situ around the main tumor or invasive carcinoma. Case presentation We report a case of 50-year-old man with intracystic papillary carcinoma in man with ductal carcinoma in situ who underwent a tumorectomy following by a radical Patey intervention (Halsted). Conclusion Nowadays, there is still no clear consensus regarding optimal treatment of intracystic papillary carcinoma. Most papers reinforce the importance of an adequate surgical margin in conservative treatment. Surgeons must pay much attention to the potential for ductal carcinoma in situ around the tumor when selecting the operative procedure. PMID:19829939

  15. Thyroglossal Duct Papillary Thyroid Carcinoma and Synchronous Lingual Thyroid Atypia

    PubMed Central

    Yoo, Timothy; Kim, Yohanan; Simental, Alfred; Inman, Jared C.

    2016-01-01

    Thyroglossal duct and lingual thyroid ectopic lesions are exceedingly rare synchronous findings. Papillary thyroid carcinoma of these ectopic thyroid sites is well understood but still a rare finding. This case points to some management nuances in regard to ectopic thyroid screening with imaging and also shows the effectiveness of minimally invasive transoral robotic surgery for lingual thyroid. PMID:27119036

  16. Systemic paraneoplastic vasculitis secondary to papillary carcinoma of the thyroid.

    PubMed

    Guerouaz, N; Alaoui, M; Raiss, M; Hassam, B; Senouci, K

    2016-08-01

    Systemic vasculitis secondary to thyroid carcinomas is exceptional. We report the case of a 55-year-old woman who presented with systemic vasculitis involving leucocytoclastic cutaneous vasculitis and renal disorders secondary to papillary thyroid carcinoma (PTC). Her symptoms resolved completely after total thyroidectomy. Other causes of vasculitis were excluded. To our knowledge, this is only the second case reported of systemic vasculitis associated with PTC in a paraneoplastic manner. PMID:27416971

  17. The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma

    PubMed Central

    von Figura, Guido; Fukuda, Akihisa; Roy, Nilotpal; Liku, Muluye E.; Morris, John P.; Kim, Grace E.; Russ, Holger A.; Firpo, Matthew A.; Mulvihill, Sean J.; Dawson, David W.; Ferrer, Jorge; Mueller, William F.; Busch, Anke; Hertel, Klemens J.; Hebrok, Matthias

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDA) develops through distinct precursor lesions, including pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). However, genetic features resulting in IPMN-associated PDA (IPMN–PDA) versus PanIN-associated PDA (PanIN-PDA) are largely unknown. Here we find that loss of Brg1, a core subunit of SWI/SNF chromatin remodelling complexes, cooperates with oncogenic Kras to form cystic neoplastic lesions that resemble human IPMN and progress to PDA. Although Brg1-null IPMN–PDA develops rapidly, it possesses a distinct transcriptional profile compared with PanIN-PDA driven by mutant Kras and hemizygous p53 deletion. IPMN–PDA also is less lethal, mirroring prognostic trends in PDA patients. In addition, Brg1 deletion inhibits Kras-dependent PanIN development from adult acinar cells, but promotes Kras-driven preneoplastic transformation in adult duct cells. Therefore, this study implicates Brg1 as a determinant of context-dependent Kras-driven pancreatic tumorigenesis and suggests that chromatin remodelling may underlie the development of distinct PDA subsets. PMID:24561622

  18. Immunobiology and immunosurveillance in patients with intraductal papillary mucinous neoplasms (IPMNs), premalignant precursors of pancreatic adenocarcinomas.

    PubMed

    Beatty, Pamela L; van der Geest, Rick; Hashash, Jana G; Kimura, Takashi; Gutkin, Dmitriy; Brand, Randall E; Finn, Olivera J

    2016-07-01

    Premalignant lesions for many cancers have been identified, and efforts are currently directed toward identification of antigens expressed on these lesions that would provide suitable targets for vaccines for cancer prevention. Intraductal papillary mucinous neoplasms (IPMNs) are premalignant pancreatic cysts of which a subset has the potential to progress to cancer. Currently, there are no validated predictive markers for progression to malignancy. We hypothesized that the presence or absence of immune surveillance of these lesions would be one such factor. Here we show that the tumor antigen MUC1, which is abnormally expressed on pancreatic cancer and is a target for cancer immunosurveillance, is also abnormally expressed on premalignant IPMN. We show that some IPMN patients make MUC1-specific IgG. Moreover, we show evidence of CD4 and CD8 T cell infiltration into IPMN areas of high dysplasia suggesting an ongoing immune response within the lesions. We also found, however, increased levels of circulating myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in some IPMN patients as well as evidence of T cell exhaustion. Further studies correlating immunosurveillance or immunosuppression with IPMN progression to malignancy will help define the immune response as a biomarker of risk, leading potentially to a vaccine to boost spontaneous immunity and prevent progression to cancer. PMID:27106024

  19. Trends in malignant intraductal papillary mucinous neoplasm in US adults from 1990 to 2010: a SEER database analysis

    PubMed Central

    McCarty, Thomas R.; Njei, Basile

    2016-01-01

    Background: Intraductal papillary mucinous neoplasms (IPMNs) are precancerous lesions with a well-described adenoma-carcinoma sequence. Although the risk of malignant transformation has been well studied, data on trends in long-term survival and important prognostic factors associated with survival in malignant IPMN are lacking. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with confirmed malignant IPMN based upon pathologic diagnosis or radiographic evidence concerning for malignant potential. Median survival and age-adjusted incidence were calculated. Cox proportional hazard regression was used to determine independent mortality factors. Results: Based upon the SEER database query, 2651 patients were diagnosed with malignant IPMN between 1990 and 2010. The age-adjusted incidence of IPMN in 1990 was 0.361 per 100 000 persons (95% confidence interval [CI]: 0.285–0.451) with a steady decline observed through 2010 (0.135 per 100 000 persons, 95% CI: 0.098–0.186). A total of 564 patients (21.3%) underwent a surgical procedure, though the number of patients who underwent surgery from 1990 to 2010 also decreased (1990–1995, n = 132 to 2006–2010, n = 96, respectively). The overall median survival was 4 months and remained relatively stable from 1990 to 2010. Performance of surgery (HR: 0.45, 95% CI: 0.40–0.53, P < 0.001) was associated with a decreased risk of death. Conclusion: A significant decrease in the incidence of malignant IPMN was seen from 1990 to 2010. There was also no improvement observed in long-term survival. The small percentage of eligible cases receiving surgical treatment suggests that there is room for further improvement in survival, with increased utilization of surgery. PMID:26818977

  20. Stromal Fibrosis and Expression of Matricellular Proteins Correlate With Histological Grade of Intraductal Papillary Mucinous Neoplasm of the Pancreas

    PubMed Central

    Kakizaki, Yasuharu; Makino, Naohiko; Tozawa, Tomohiro; Honda, Teiichiro; Matsuda, Akiko; Ikeda, Yushi; Ito, Miho; Saito, Yoshihiko; Kimura, Wataru; Ueno, Yoshiyuki

    2016-01-01

    Objective The aim of the study was to clarify the correlation between the microenvironmental factors and histological grade in intraductal papillary mucinous neoplasm (IPMN). Methods We investigated 65 IPMNs resected at Yamagata University Hospital between 2000 and 2011, and all cases were categorized to low-inter (including low- and intermediate-grade dysplasia) and high-inv (including high-grade dysplasia and IPMN with an associated invasive carcinoma) groups. We compared between the 2 groups pathologically with regard to fibrosis and the expression of alpha-smooth muscle actin (α-SMA), periostin, and galectin-1 in the periductal stroma of IPMN. Results There were 41 low-inter and 24 high-inv. The subtype was categorized as 22 main duct type (MD-IPMN) and 43 branch duct type (BD-IPMN). The degree of fibrosis and the expression of α-SMA, periostin, and galectin-1 were significantly higher in high-inv than in low-inter within BD-IPMNs. Multivariate logistic regression analysis indicated that high expression of α-SMA (odds ratio, 13.802; 95% confidence interval, 1.108–171.893; P = 0.0414) was a significant independent related factor of high-inv in BD-IPMN. Conclusions Stromal fibrosis and expression of α-SMA, periostin, and galectin-1 are more marked in high-inv than in low-inter within BD-IPMNs, and they could become new markers for determining the indications for surgery in BD-IPMN. PMID:26967452

  1. [A case of peritoneal serous papillary carcinoma].

    PubMed

    Takeuchi, Nobuhiro; Sakata, Yoshio; Nishida, Yu; Nomura, Yusuke; Makino, Tetsuya; Maeda, Tetsuo; Tada, Hidetoshi; Kimoto, Takeo; Ueno, Sayaka; Fujiwara, Kiyoshi

    2011-08-01

    A 65-year-old female was admitted to our hospital with abdominal distension. Abdominal CT and MRI revealed massive ascites and an omental cake, but the ovaries were of normal size. After an omentum biopsy was performed during open abdominal surgery, she was diagnosed as peritoneal serous papillary adenocarcinoma. After 6 courses of chemotherapy with paclitaxel and carboplatin, the massive ascites totally disappeared, and a second look operation could be performed. She is still alive with no sign of recurrence. PMID:21829076

  2. Clear cell papillary renal cell carcinoma: a review.

    PubMed

    Kuroda, Naoto; Ohe, Chisato; Kawakami, Fumi; Mikami, Shuji; Furuya, Mitsuko; Matsuura, Keiko; Moriyama, Masatsugu; Nagashima, Yoji; Zhou, Ming; Petersson, Fredrik; López, José I; Hes, Ondrej; Michal, Michal; Amin, Mahul B

    2014-01-01

    The disease concept of clear cell (tubulo) papillary renal cell carcinoma (CCP-RCC) as a distinct subtype of renal cell carcinoma has been recently established. First described in the setting of end stage renal disease, this tumor type is more frequently recognized and encountered in a sporadic setting. In this article, we provide an overview of the recent understanding of this tumor. Macroscopically, tumors are well circumscribed with well-developed tumor capsule. Histologically, the tumor cells are cuboidal to low columnar cell with clear cytoplasm and papillary and tubulo-papillary configuration. Immunohistochemically, tumor cells generally show diffuse expression for cytokeratin 7, CA9 (cup-shaped pattern), HIF-1, GLUT-1 and high molecular weight cytokeratin, but negative for AMACR, RCC Ma and TFE3. CD10 is negative or focally positive in most tumors. Genetically, this tumor has no characteristics of clear cell RCC or papillary RCC. Prognostically, patients with CCP-RCC behave in an indolent fashion in all previously reported cases. In conclusion, although this tumor has been integrated into recent International Society of Urologic Pathology Classification of renal neoplasia, both aspects of disease concept and clinical behavior are yet to be fully elucidated. Further publications of large cohorts of patients will truly help understand the biologic potential and the molecular underpinnings of this tumor type. PMID:25550767

  3. Clinicopathologic Characteristics of 29 Invasive Carcinomas Arising in 178 Pancreatic Mucinous Cystic Neoplasms With Ovarian-type Stroma

    PubMed Central

    Jang, Kee-Taek; Park, Sang Mo; Basturk, Olca; Bagci, Pelin; Bandyopadhyay, Sudeshna; Stelow, Edward B.; Walters, Dustin M.; Choi, Dong Wook; Choi, Seoung Ho; Heo, Jin Seok; Sarmiento, Juan M.; Reid, Michelle D.; Adsay, Volkan

    2015-01-01

    Information on the clinicopathologic characteristics of invasive carcinomas arising from mucinous cystic neoplasms (MCNs) is limited, because in many early studies they were lumped and analyzed together with noninvasive MCNs. Even more importantly, many of the largest prior studies did not require ovarian-type stroma (OTS) for diagnosis. We analyzed 178 MCNs, all strictly defined by the presence of OTS, 98% of which occurred in perimenopausal women (mean age, 47 y) and arose in the distal pancreas. Twenty-nine (16%) patients had associated invasive carcinoma, and all were female with a mean age of 53. Invasion was far more common in tumors with grossly visible intracystic papillary nodule formation ≥ 1.0 cm (79.3% vs. 8.7%, P = 0.000) as well as in larger tumors (mean cyst size: 9.4 vs. 5.4 cm, P = 0.006); only 4/29 (14%) invasive carcinomas occurred in tumors that were < 5 cm; however, none were < 3 cm. Increased serum CA19-9 level (> 37 U/L) was also more common in the invasive tumors (64% vs. 23%, P = 0.011). Most invasive carcinomas (79%) were of tubular type, and the remainder (5 cases) were mostly undifferentiated carcinoma (2, with osteoclast-like giant cells), except for 1 with papillary features. Interestingly, there were no colloid carcinomas; 2 patients had nodal metastasis at the time of diagnosis, and both died of disease at 10 and 35 months, respectively. While noninvasive MCNs had an excellent prognosis (100% at 5 y), tumors with invasion often had an aggressive clinical course with 3- and 5-year survival rates of 44% and 26%, respectively (P = 0.000). The pT2 (> 2 cm) invasive tumors had a worse prognosis than pTl (≤ 2 cm) tumors (P = 0.000), albeit 3 patients with T1a (< 0.5 cm) disease also died of disease. In conclusion, invasive carcinomas are seen in 16% of MCNs and are mostly of tubular (pancreatobiliary) type; colloid carcinoma is not seen in MCNs. Serum CA19-9 is often higher in invasive carcinomas, and invasion is typically seen in OTS

  4. Metastatic gastrinoma in the breast mimicking primary solid papillary carcinoma.

    PubMed

    Burt, Michael; Madan, Rashna; Fan, Fang

    2016-10-01

    We report a case of metastatic gastrinoma to the breast morphologically mimicking solid papillary carcinoma of the breast. A 59-year-old woman presented with a hypoechoic right breast mass that histologically revealed solid nests of small monotonous tumor cells, fibrovascular cores, and round to oval nuclei with fine chromatin and small nucleoli. Immunohistochemistry demonstrated chromogranin and synaptophysin positivity. Tumor prognostic markers showed weak positivity for estrogen receptor and negativity for progesterone receptor. Although an initial diagnosis of solid papillary carcinoma was rendered, subsequent identification of the patient's clinical history of pancreatic gastrinoma and an additional immunohistochemical stain for gastrin supported a diagnosis of metastatic gastrinoma. We report this rare case to increase awareness of metastatic neuroendocrine tumors in the breast. Multiple breast lesions and lack of expression of estrogen/progesterone hormone receptors should prompt careful review of the patient's clinical history to rule out metastatic neuroendocrine disease. PMID:27342908

  5. Three cases of macrofollicular variant of papillary thyroid carcinoma

    PubMed Central

    Emad, Raddaoui; Maha, Arafah; Kfoury, Hala K.; Al-Sheikh, Abdul Malik; Zaidi, Shaesta N.

    2011-01-01

    The macrofollicular variant of papillary thyroid carcinoma (MFPTC) is a well-established entity with characteristic large follicles containing pale colloid and lined by cells with nuclear features of papillary thyroid carcinoma (PTC). In this study, we present three cases of MFPTC, along with a brief review of the literature. For all three of our cases, the histology of the resected specimen showed predominantly macrofollicular structures lined by cells with nuclear characteristics of PTC. Immunohistochemically, the three cases show positivity for galactin-3, cytokeratin-19, and HBME-1. These cases will help us in understanding the distinction from other benign and malignant follicular lesions of the thyroid, which is of utmost importance. The key to diagnosis is a high-power examination of any macrofollicular lesion of the thyroid. PMID:22048513

  6. Pigmented papillary carcinoma: a rare tumor of the male breast.

    PubMed

    Farkas, Andrea; Istók, Roland; Székely, Eszter; Glasz, Tibor; Kulka, Janina

    2008-09-01

    Primary melanin pigment containing tumors of the breast are rare. We report a pigmented papillary carcinoma of a 60-year-old male patient who presented a firm mass 1.7 cm in diameter with an ill defined border on ultrasonography behind the mamilla. To the best of our knowledge this is the third case report of this type of tumor in male breast. PMID:18575825

  7. Value of apparent diffusion coefficient for predicting malignancy of intraductal papillary mucinous neoplasms of the pancreas

    PubMed Central

    Zhang, Lei; Rao, Sheng-Xiang; Xu, Xue-Feng; Wang, Dan-Song; Jin, Da-Yong; Zeng, Meng-Su

    2016-01-01

    PURPOSE We aimed to explore the potential value of the whole tumor apparent diffusion coefficient (ADC) for discriminating between benign and malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS Forty-two patients underwent 1.5 T magnetic resonance imaging that included diffusion-weighted imaging (DWI, b=0.500 s/mm2). The mean, minimum, and maximum ADC values were measured for the whole tumor. The differences between benign and malignant IPMNs were calculated for the mean ADC, ADC-min, and ADC-max values. Receiver operating characteristics (ROC) analysis was conducted to evaluate their potential diagnostic performance. RESULTS Fifteen of 25 benign IPMNs demonstrated low or iso-signal intensity on DWI with a b value of 500 s/mm2 compared with normal pancreatic parenchyma, whereas all malignant IPMNs demonstrated high signal intensity. The mean value of ADC was significantly higher in benign IPMNs compared with malignant IPMNs (3.39×10−3 mm2/s vs. 2.39×10−3 mm2/s, P < 0.001), with an area under the ROC curve (AUC) of 0.92 (95% confidence interval [CI], 0.79–0.98). The ADC-min value of malignant IPMNs was also significantly lower than that of benign IPMNs (1.24×10−3 mm2/s vs. 2.58×10−3 mm2/s, P < 0.001), with an AUC of 0.94 (95% CI, 0.82–0.99). No marked difference was found between benign and malignant IPMNs for the ADC-max value (3.89×10−3 mm2/s vs. 3.78×10−3 mm2/s, P = 0.299). CONCLUSION Lower mean and minimum ADC values of the whole tumor might be potential predictors of malignant IPMNs of the pancreas. PMID:27283593

  8. MIB-1 labeling index, Ki-67, is an indicator of invasive intraductal papillary mucinous neoplasm

    PubMed Central

    Shimura, Tatsuo; Kofunato, Yasuhide; Okada, Ryo; Yashima, Rei; Okada, Koji; Araki, Kenichiro; Hosouchi, Yasuo; Kuwano, Hiroyuki; Takenoshita, Seiichi

    2016-01-01

    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. PMID:27446570

  9. AXIN2 is Associated With Papillary Thyroid Carcinoma

    PubMed Central

    Liu, Xin; Li, Shuang; Lin, Xuejun; Yan, Kangkang; Zhao, Longyu; Yu, Qiong; Liu, Xiaodong

    2016-01-01

    Background: Findings of recent studies have demonstrated a rapid increase of the incidence of papillary thyroid carcinoma (PTC), which accounts for nearly 80% of thyroid cancers. Objectives: The aim of this study was to explore the association between AXIN2 gene polymorphism and papillary thyroid carcinoma (PTC). Patients and Methods: 106 blood samples (56 PTC patients and 50 healthy controls) were drawn from China-Japan Union Hospital in Jilin province, China, during October 2010 to March 2011. A case-control study was designed to examine the association between AXIN2 and PTC. Seven tag single nucleotide polymorphisms (tag SNPs) in AXIN2 were selected and genotyped. Frequencies of different genotypes and alleles were analyzed between the patients and the controls, using the R × C column contingency table χ2 test. The possible association of haplotypes constructed by the combined effects of two or more loci with PTC was analyzed through the UNPHASED 3.1.4 program. Results: Rs11655966, rs3923086 and rs7591 of AXIN2 showed significant associations with PTC (P < 0.05). The result of haplotypes analysis showed that rs11655966-rs3923086-rs4791169 had statistically significant differences between the two groups (P < 0.05). Conclusions: Together with the functions of the target genes, we further elucidated that AXIN2 is associated with papillary thyroid carcinoma in the Chinese Han population. PMID:27168945

  10. Sub-branch and mixed-type intraductal papillary mucinous neoplasms of the pancreas: 2 case reports.

    PubMed

    Ozmen, Zafer; Aktas, Fatma; Okan, İsmail; Özsoy, Zeki; Arıcı, Akgül

    2016-03-01

    Intraductal papillary mucinous neoplasia (IPMN) is one of the cystic neoplasias of the pancreas. The imaging findings provide that these tumors are differentiated from the other cystic lesions of the pancreas, especially from the chronic pancreatitis, where the treatment protocol is completely different. Therefore, the correct diagnosis and classification of the IPMN ensures that the patient receives the correct approach and the appropriate surgery, if necessary. The purpose of this study is to emphasize the imaging findings of the different types of the IPMN and the changes in the management protocol of the patients according to these radiological findings. PMID:26973726

  11. Intracystic papillary neoplasm with an associated mucinous adenocarcinoma arising in Rokitansky-Aschoff sinus of the gallbladder.

    PubMed

    Sato, Ryuichiro; Ando, Toshinori; Tateno, Hiroo; Rikiyama, Toshiki; Furukawa, Toru; Ebina, Nobuo

    2016-12-01

    Intraepithelial neoplasias are preinvasive neoplastic lesions found throughout in the digestive system, and when such lesions are discovered in the gallbladder, they are referred to as intracystic papillary neoplasm (ICPN). In the gallbladder, mucinous adenocarcinoma is a rare histologic phenotype, and adenocarcinomas involving Rokitansky-Aschoff (RA) sinuses are uncommon, which were indeed found in a case reported here. A 64-year-old male presenting with upper abdominal pain demonstrated a spherical mass protruding outward from the gallbladder fundus in imaging studies. Laparoscopic cholecystectomy was performed, and the resected specimen revealed a subserosal cystic mass with a small communication with the gallbladder lumen. The cystic mass contained a gelatinous material without solid component. Histologically, the mass was consisted of subserosal cysts lined by atypical columnar mucinous epithelium with micropapillary growth and nuclear stratification. The neoplastic transformation was more pronounced toward the serosal side of the lesion where disruption of the cyst wall, intrastromal mucin lakes, and invasion of the neoplastic cells into surrounding stroma were observed. The epithelium was of intestinal lineage, which was supported by the positive immunoreactivity against CDX2 and MUC2. The cystic spaces were communicated with surrounding RA sinuses, which indicated that the tumor arose in the sinus. The pathological diagnosis was ICPN, intestinal type, with an associated mucinous adenocarcinoma arising in RA sinus. PMID:27316722

  12. [Extraovarian peritoneal serous papillary carcinoma: an unusual surgical case].

    PubMed

    Meier, C; Seifert, M; Wehrli, H

    1999-01-01

    The extraovarian peritoneal serous papillary carcinoma (EPSPC) is a multicentric peritoneal tumor with minimal or absent involvement of the ovaries. The actual treatment regimen consists of a cytoreductive surgery followed by a combination chemotherapy. Few studies have compared outcome of EPSPC to papillary serous ovarian cancer (PSOC). Several authors have documented similar clinical behavior between EPSPC and PSOC, but this finding has not been universal. A 64-year-old female patient with symptomatic gall stone disease underwent elective laparoscopic cholecystectomy. Unexpectedly we found some uncommon small nodular structures on the serosa of the right colon. The histological findings suggested a poorly differentiated peritoneal serous papillary carcinoma. Biopsies of both ovaries showed no signs of tumor infiltration and the diagnosis of EPSPC was established. After surgery, a combination chemotherapeutic regimen with carboplatin and cyclophosphamid was given. Laparoscopic reassessment 7 months after the first procedure showed no tumor. 3 identical cycles completed chemotherapy. Normal ovaries and no other tumor sites were found in a final laparoscopic look after 11 months. PMID:10073126

  13. Human papillomavirus-related squamous cell carcinoma of the anal canal with papillary features

    PubMed Central

    Leon, Marino E; Shamekh, Rania; Coppola, Domenico

    2015-01-01

    Human papillomavirus (HPV) related squamous cell carcinoma (SCC) involving the anal canal is a well-known carcinoma associated with high-risk types of HPV. HPV-related SCC with papillary morphology (papillary SCC) has been described in the oropharynx. We describe, for the first time, a case of anal HPV-related squamous carcinoma with papillary morphology. The tumor arose from the anal mucosa. The biopsies revealed a superficially invasive SCC with prominent papillary features and associated in situ carcinoma. The tumor cells were positive for p16 and were also positive for high-risk types of HPV using chromogenic in situ hybridization. The findings are consistent with a HPV-related SCC of the anal canal with papillary features. This tumor shows histologic features similar to a papillary HPV-related SCC of the oropharynx. Additional studies are needed to characterize these lesions. PMID:25717259

  14. AZD6244 in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

    ClinicalTrials.gov

    2016-09-02

    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

  15. Composite Mucoepidermoid Carcinoma and Columnar Cell Variant of Papillary Carcinoma of the Thyroid: A Case Report and Review of the Literature.

    PubMed

    Taconet, Sarah; Bosq, Jacques; Hartl, Dana; Schlumberger, Martin; Leboulleux, Sophie; Scoazec, Jean-Yves; Al-Ghuzlan, Abir

    2016-06-01

    Primary mucoepidermoid carcinoma (MEC) of the thyroid and columnar cell variant of papillary carcinoma of the thyroid (PCT) are uncommon neoplasms. We report the first case of composite MEC and columnar cell variant of PCT. An 86-year-old man consulted for a 47-mm thyroid nodule, cytologically compatible with PCT. Total thyroidectomy was performed. Histological diagnosis, with support of histochemistry and immunohistochemistry, was mixed primary carcinoma of the thyroid, associating an MEC component with predominantly columnar cell variant of PCT. Sixteen months after surgery and external beam radiation therapy, the patient was free of recurrence or distant metastasis. This case report offers an opportunity to highlight the potential pitfalls concerning the interpretation of mucin histochemistry in thyroid tumors. PMID:26755714

  16. Rectal Cancer: Mucinous Carcinoma on Magnetic Resonance Imaging Indicates Poor Response to Neoadjuvant Chemoradiation

    SciTech Connect

    Oberholzer, Katja; Menig, Matthias; Kreft, Andreas; Schneider, Astrid; Junginger, Theodor; Heintz, Achim; Kreitner, Karl-Friedrich; Hoetker, Andreas M.; Hansen, Torsten; Dueber, Christoph; Schmidberger, Heinz

    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 surgical 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.

  17. Association of urothelial carcinoma of the renal pelvis with papillary and medullary thyroid carcinomas. A new sporadic neoplastic syndrome?

    PubMed

    Albores-Saavedra, Jorge; Dorantes-Heredia, Rita; Chablé-Montero, Fredy; Córdova-Ramón, Juan Carlos; Henson, Donald E

    2014-10-01

    We describe 2 adult women (72 and 54 years), 1 with a low-grade noninvasive papillary urothelial carcinoma of the renal pelvis, who 14 years later developed a papillary carcinoma in 1 thyroid lobe and a medullary carcinoma in the contralateral lobe. Both neoplasms were similar in size and appeared symmetrical. Despite its small size, the medullary carcinoma metastasized in multiple cervical lymph nodes. The second patient had a high-grade invasive papillary urothelial carcinoma of the renal pelvis that infiltrated the renal parenchyma and metastasized in one of the lungs. Five months later, a papillary carcinoma was discovered in the thyroid gland. The 2 papillary thyroid carcinomas were of the follicular variant. Adjacent to 1 papillary carcinoma, there was a dominant nodule of a colloid and adenomatous goiter. The medullary carcinoma contained stromal amyloid and was immunoreactive for calcitonin and carcinoembryonic antigen. There was no C-cell hyperplasia (medullary carcinoma in situ). The 2 patients are alive, 1 is living with pulmonary metastasis from the high-grade urothelial carcinoma. Twelve cases of this neoplastic association were registered in the Survey, Epidemiology, and End Results Program from 1980 to 2009. We believe that the combination of these unusual neoplasms in the same patient may represent a new sporadic neoplastic syndrome. PMID:25175810

  18. Malignant Transformation of a Mature Cystic Ovarian Teratoma into Thyroid Carcinoma, Mucinous Adenocarcinoma, and Strumal Carcinoid: A Case Report and Literature Review

    PubMed Central

    Hinshaw, Hilary D.; Smith, Ashlee L.; Desouki, Mohamed Mokhtar; Olawaiye, Alexander B.

    2012-01-01

    Malignant transformation of a mature cystic teratoma (MCT) is an infrequent, often asymptomatic event. We report the first example of a struma ovarii with a focus of follicular variant of papillary thyroid carcinoma (a), mucinous adenocarcinoma (b), and strumal carcinoid tumor (c)—all three arising in one mature cystic teratoma of the ovary. From our reviews, we found limited data to guide management when these malignant foci occur within an MCT. Consideration should be given to thyroidectomy followed by total-body scanning and serum studies for foci of thyroid carcinoma and adjuvant therapy with thyroidectomy and radioablation if residual disease is identified (a). Additionally, extrapolating from data for mucinous adenocarcinomas, consideration could be given to adjuvant chemotherapy after appropriate staging (b). Strumal carcinoid tumors should be treated as tumors of low malignant potential. Observation is appropriate if after complete staging, no invasive implants are noted (c). PMID:23029627

  19. Molecular analysis of ovarian mucinous carcinoma reveals different cell of origins.

    PubMed

    Wang, Yihong; Shwartz, Lauren Ende; Anderson, Derek; Lin, Ming-Tseh; Haley, Lisa; Wu, Ren-Chin; Vang, Russell; Shih, Ie-Ming; Kurman, Robert J

    2015-09-01

    It is believed that a subset of primary ovarian mucinous tumors is derived from mature teratomas [1-5]. To confirm this, we performed microsatellite genotyping using a variety of short tandem repeat makers and analyzed allelotypes of 8 mucinous tumors (4 mucinous carcinomas, 3 atypical proliferative mucinous tumors and 1 mucinous cystadenoma) associated with a teratoma to determine whether they were clonally related. 7 of the 8 mucinous tumors showed complete or a high degree of homozygosity. Among the 6 pairs of tumors with teratoma tissue available for comparison, 5 of 6 showed a high or complete degree of allelotypes matching, which differed from the somatic allelotypes of the normal control tissue. A discrepancy was detected between carcinoma and teratoma in one pair at several loci, with different X-chromosome inactivation patterns revealed by the HUMARA clonality assay. We also investigated the allelotypes of 16 ovarian mucinous carcinomas without a teratoma in young patients (range 13-30) and in 6 older patients (range 40-67) using the same method. None of these tumors showed pure homozygosity. The number of homozygous loci in this cohort was significantly lower than that in the first. Our results suggest first, that most mucinous tumors associated with a teratoma are derived from the teratoma but occasionally they could be collision tumors and second that the majority of pure mucinous tumors in young women in whom a teratoma is not present are not derived from a teratoma. PMID:26355245

  20. Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas.

    PubMed

    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. PMID:23665089

  1. K-Ras and cyclooxygenase-2 coactivation augments intraductal papillary mucinous neoplasm and Notch1 mimicking human pancreas lesions

    PubMed Central

    Chiblak, Sara; Steinbauer, Brigitte; Pohl-Arnold, Andrea; Kucher, Dagmar; Abdollahi, Amir; Schwager, Christian; Höft, Birgit; Esposito, Irene; Müller-Decker, Karin

    2016-01-01

    Mutational activation of K-Ras is an initiating event of pancreatic ductal adenocarcinomas (PDAC) that may develop either from pancreatic intraepithelial neoplasia (PanIN) or intraductal papillary mucinous neoplasms (IPMN). Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) is causally related to pancreatic carcinogenesis. Here, we deciphered the impact of COX-2, a key modulator of inflammation, in concert with active mutant K-RasG12D on tumor burden and gene expression signature using compound mutant mouse lines. Concomitant activation of COX-2 and K-RasG12D accelerated the progression of pancreatic intraepithelial lesions predominantly with a cystic papillary phenotype resembling human IPMN. Transcriptomes derived from laser capture microdissected preneoplastic lesions of single and compound mutants revealed a signature that was significantly enriched in Notch1 signaling components. In vitro, Notch1 signaling was COX-2-dependent. In line with these findings, human IPMN stratified into intestinal, gastric and pancreatobillary types displayed Notch1 immunosignals with high prevalence, especially in the gastric lesions. In conclusion, a yet unknown link between activated Ras, protumorigenic COX-2 and Notch1 in IPMN onset was unraveled. PMID:27381829

  2. K-Ras and cyclooxygenase-2 coactivation augments intraductal papillary mucinous neoplasm and Notch1 mimicking human pancreas lesions.

    PubMed

    Chiblak, Sara; Steinbauer, Brigitte; Pohl-Arnold, Andrea; Kucher, Dagmar; Abdollahi, Amir; Schwager, Christian; Höft, Birgit; Esposito, Irene; Müller-Decker, Karin

    2016-01-01

    Mutational activation of K-Ras is an initiating event of pancreatic ductal adenocarcinomas (PDAC) that may develop either from pancreatic intraepithelial neoplasia (PanIN) or intraductal papillary mucinous neoplasms (IPMN). Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) is causally related to pancreatic carcinogenesis. Here, we deciphered the impact of COX-2, a key modulator of inflammation, in concert with active mutant K-Ras(G12D) on tumor burden and gene expression signature using compound mutant mouse lines. Concomitant activation of COX-2 and K-Ras(G12D) accelerated the progression of pancreatic intraepithelial lesions predominantly with a cystic papillary phenotype resembling human IPMN. Transcriptomes derived from laser capture microdissected preneoplastic lesions of single and compound mutants revealed a signature that was significantly enriched in Notch1 signaling components. In vitro, Notch1 signaling was COX-2-dependent. In line with these findings, human IPMN stratified into intestinal, gastric and pancreatobillary types displayed Notch1 immunosignals with high prevalence, especially in the gastric lesions. In conclusion, a yet unknown link between activated Ras, protumorigenic COX-2 and Notch1 in IPMN onset was unraveled. PMID:27381829

  3. Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients

    PubMed Central

    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

  4. The Role of Fragile Sites in Sporadic Papillary Thyroid Carcinoma

    PubMed Central

    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

  5. Extensive laryngeal infiltration from a neglected papillary thyroid carcinoma: A case report

    PubMed Central

    Georgiades, Fanourios; Vasiliou, George; Kyrodimos, Efthimios; Thrasyvoulou, Giannis

    2016-01-01

    Papillary carcinoma of the thyroid is the commonest type of thyroid cancer. Laryngeal infiltration from papillary thyroid carcinoma is extremely rare, with only a few cases of partial invasion described in the literature. We present a very unusual case of complete infiltration of both thyroid and cricoid cartilages from a neglected papillary thyroid carcinoma in a 59-year-old male. This sequel resulted from refusal of the patient to undergo treatment when initially diagnosed. An invasion to such an extent has not been described in the literature before, and in this case warranted a total laryngectomy followed by radioactive iodine. Prompt management of papillary carcinomas is crucial for avoiding such complications. Future guidelines should include management options for the patients who deny treatment initially. PMID:27458595

  6. Choroidal Metastasis of Papillary Thyroid Carcinoma Demonstrated on SPECT-CT.

    PubMed

    Torun, Nese; Reyhan, Mehmet; Yapar, Ali Fuat; Karatas, Muge

    2016-05-01

    We report a 68-year-old woman with papillary thyroid carcinoma metastasizing to choroid. The choroid metastasis was diagnosed with SPECT-CT and then was treated with high-dose radioactive iodine therapy. PMID:26825205

  7. Quiz. Correct answer to the quiz. Check your diagnosis. Clear cell papillary renal cell carcinoma.

    PubMed

    Joseph, Keva; Liu, Kai-Wen; Chang, I-Wei

    2015-06-01

    We incidentally observed a case of clear cell papillary renal cell carcinoma of an 81-year-old woman, presenting with intermittent left flank pain. It is a recently described rare renal parenchymal tumor. PMID:26328282

  8. Genome-wide significant risk associations for mucinous ovarian carcinoma

    PubMed Central

    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

  9. Genome-wide significant risk associations for mucinous ovarian carcinoma.

    PubMed

    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. PMID:26075790

  10. Mouse models of papillary thyroid carcinoma - short review.

    PubMed

    Rusinek, Dagmara; Krajewska, Jolanta; Jarząb, Michał

    2016-01-01

    Thyroid carcinoma (TC) is the most common endocrine malignancy, and its frequency is still rising. Papillary thyroid carcinoma (PTC) accounts for 80% of all TCs and usually is related to a very good prognosis. However, the standard therapeutic approaches are not always sufficient and disease progression is sometimes observed. These data highlight the limitation of our understanding of molecular mechanisms underlying tumorigenesis and how they vary between individual patients. Over the last 19 years mouse models of thyroid cancers have been developed in order to give answers to questions about their genetic background, relations of key molecular events with pathways fundamental for cancer, and many others. Among these models genetically engineered mice were of utmost importance regarding the input of knowledge about human tumorigenesis. In the present review the most significant mouse models of PTC are described with particular emphasis on BRAFV600E-induced ones, for the sake of its frequency in PTC, relation to factors of poor prognosis, and the fact that, since its identification, it became an attractive target in novel therapies. For the presented mouse models phenotype consequences of particular genetic alterations are described as well as the limitations of the used methods. (Endokrynol Pol 2016; 67 (2): 212-223). PMID:27082155

  11. MicroRNA profiles classify papillary renal cell carcinoma subtypes

    PubMed Central

    Wach, S; Nolte, E; Theil, A; Stöhr, C; T Rau, T; Hartmann, A; Ekici, A; Keck, B; Taubert, H; Wullich, B

    2013-01-01

    Background: Besides the conventional clear-cell renal cell carcinoma (ccRCC), papillary RCC (pRCC) is the second most common renal malignancy. Papillary RCCs can further be subdivided into two distinct subtypes. Although a clinical relevance of pRCC subtyping has been shown, little is known about the molecular characteristics of both pRCC subtypes. Methods: We performed microarray-based microRNA (miRNA) expression profiling of primary ccRCC and pRCC cases. A subset of miRNAs was identified and used to establish a classification model for ccRCC, pRCC types 1 and 2 and normal tissue. Furthermore, we performed gene set enrichment analysis with the predicted miRNA target genes. Results: Only five miRNAs (miR-145, -200c, -210, -502-3p and let-7c) were sufficient to identify the samples with high accuracy. In a collection of 111 tissue samples, 73.9% were classified correctly. An enrichment of miRNA target genes in the family of multidrug-resistance proteins was noted in all tumours. Several components of the Jak-STAT signalling pathway might be targets for miRNAs that define pRCC tumour subtypes. Conclusion: MicroRNAs are able to accurately classify RCC samples. Deregulated miRNAs might contribute to the high chemotherapy resistance of RCC. Furthermore, our results indicate that pRCC type 2 tumours could be dependent on oncogenic MYC signalling. PMID:23799849

  12. Laparoscopic Anatomical Left Hepatectomy for Intrahepatic Bile Duct Papillary Mucinous Cystadenoma With Intraoperative Vascular Repair: A Case Report.

    PubMed

    Li, Hongyu; Peng, Bing

    2016-02-01

    Laparoscopic hepatectomy has been widely performed for patients with benign liver tumors such as hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma.We here present a case of a 78-year-old female patient who was initially admitted to our department due to fever and jaundice for 2 days. Abdominal enhanced computed tomography scan showed intrahepatic and extrahepatic bile duct dilatation with liver atrophy of left lobe. Unenhanced nodules were seen within the left intrahepatic bile duct. Ultrasonography revealed intrahepatic and extrahepatic bile duct dilatation with viscous fluid, tubular adenoma? Tumor markers including alpha fetoprotein, carcinoembryonic antigen, and CA19-9 were normal. Preoperative total bilirubin was 64.4 mmol/L.Laparoscopic anatomical left hepatectomy and common bile duct exploration were performed. In this procedure, a lot of mucus was seen within the common bile duct and left intrahepatic bile duct. No bile duct stones were found after the exploration. During parenchymal transection, intraoperative hemorrhage from middle hepatic vein was met, and we repaired middle hepatic vein by laparoscopic suture (5-0 Prolene). No air embolism and hypotension were met. This operation took 232 minutes and estimated blood loss was 300 mL. Postoperative ultrasonography indicated a normal outflow of middle hepatic vein and there was no stricture. The patient's postoperative course was uneventful and was discharged on the 6th day after surgery. Postoperative pathological diagnosis was intrahepatic bile duct papillary mucinous cystadenoma. PMID:26871845

  13. What is the Minimal Surgery for Papillary Thyroid Carcinoma?

    PubMed Central

    Fridman, Eran; Gil, Ziv

    2016-01-01

    Although thyroid surgery for treatment of papillary thyroid carcinoma (PTC) has been practiced for more than 100 years, there is still controversy regarding the minimal surgery needed for cure. The main reason for this controversy is lack of prospective randomized trials. The data accumulated in the last four decades indicate that hemithyroidectomy can be sufficient and safely practiced in low-risk patients with PTC. Patients <45 years of age with a single tumor less than 2 cm, with no lymphatic spread, and in the absence of other risk factors, can be equally managed by hemithyroidectomy or total thyroidectomy. A slight increase in the risk of vocal cord paralysis and hypocalcemia after total thyroidectomy suggests that hemithyroidectomy is appropriate for the management of patients with stage T1 disease. Any choice regarding the extent of surgery should be made with the patient and his family and in a multidisciplinary setup, which has been shown to improve decision-making procedures before the operation and during follow-up. PMID:26886960

  14. A case of Krukenberg carcinoma metastasized from colon cancer resembling mucinous cystadenocarcinoma of the ovary.

    PubMed

    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

  15. Papillary Carcinoma Within a Thyroglossal Duct Cyst in a 17-Year-Old Child.

    PubMed

    Cheon, Nam Ju; Lee, Young Man; Lee, Jun Ho; Han, Jong Kyu; Lee, Ji Hye

    2016-05-01

    Thyroglossal duct cyst is a frequent event; however, papillary carcinoma within a thyroglossal duct cyst is rare, particularly in children. A 17-year-old girl presented with an asymptomatic mid-submental mass for the last 2 months. The diagnosis of thyroglossal duct cyst was made based on physical examination and computed tomography finding. After performance of Sistrunk procedure, an incidental papillary carcinoma within the thyroglossal duct cyst was observed on pathology. We reviewed the pediatric cases of thyroglossal duct carcinoma, and then decided not to perform a concurrent thyroidectomy. We will continue close follow-up for future thyroid involvement. PMID:27054418

  16. Surgical treatment of mucin-producing cholangiocarcinoma arising from intraductal papillary neoplasm of the intrahepatic bile duct: a report of 2 cases

    PubMed Central

    Baterdene, Namsrai; Lee, Jong-Wook; Jung, Min-Jae; Shin, Heeji; Seo, Hye Kyoung; Kim, Myeong-Hwan; Lee, Sung-Koo

    2016-01-01

    Intraductal papillary neoplasms of the bile duct (IPNB) leads to malignant transformation and mucin production. Herein, we presented two cases of mucin-producing IPNB with obstructive jaundice who underwent resection of the intrahepatic lesions and bypass hepaticojejunostomy. The first case was a 69 year-old male patient with 5-year follow up for gallstone disease. Imaging studies showed mucin-secreting IPNB mainly in the hepatic segment III bile duct (B3) and multiple intrahepatic duct stones for which, segment III resection, intrahepatic stone removal, end-to-side choledochojejunostomy and B3 hepaticojejunostomy were conducted. The second case was a 74 year-old female patient with 11-year follow up for gallstone disease. Imaging studies showed mucin-producing IPNB with dilatation of the segment IV duct (B4) and mural nodules for which, segment IV resection, partial resection of the diaphragm and central hepaticojejunostomy were conducted. Both patients recovered uneventfully from surgery. These cases highlight that in patients with IPNB, abundant production of highly viscous mucin inducing obstructive jaundice may be associated with malignant transformation. PMID:27621752

  17. Coexistence of resistance to thyroid hormone and papillary thyroid carcinoma

    PubMed Central

    Igata, Motoyuki; Tsuruzoe, Kaku; Kawashima, Junji; Kukidome, Daisuke; Kondo, Tatsuya; Motoshima, Hiroyuki; Shimoda, Seiya; Furukawa, Noboru; Nishikawa, Takeshi; Miyamura, Nobuhiro

    2016-01-01

    Summary Resistance to thyroid hormone (RTH) is a syndrome of reduced tissue responsiveness to thyroid hormones. RTH is majorly caused by mutations in the thyroid hormone receptor beta (THRB) gene. Recent studies indicated a close association of THRB mutations with human cancers, but the role of THRB mutation in carcinogenesis is still unclear. Here, we report a rare case of RTH with a papillary thyroid carcinoma (PTC). A 26-year-old woman was referred to our hospital due to a thyroid tumor and hormonal abnormality. She had elevated serum thyroid hormones and non-suppressed TSH levels. Genetic analysis of THRB identified a missense mutation, P452L, leading to a diagnosis of RTH. Ultrasound-guided fine-needle aspiration biopsy of the tumor and lymph nodes enabled the cytological diagnosis of PTC with lymph node metastases. Total thyroidectomy and neck lymph nodes dissection were performed. Following surgery, thyroxine replacement (≥500 μg) was necessary to avoid the symptoms of hypothyroidism and to maintain her TSH levels within the same range as before the operation. During the follow-up, basal thyroglobulin (Tg) levels were around 6 ng/ml and TSH-stimulated Tg levels were between 12 and 20 ng/ml. Up to present, the patient has had no recurrence of PTC. This indicates that these Tg values are consistent with a biochemical incomplete response or an indeterminate response. There is no consensus regarding the management of thyroid carcinoma in patients with RTH, but aggressive treatments such as total thyroidectomy followed by radioiodine (RAI) and TSH suppression therapy are recommended. Learning points There are only a few cases reporting the coexistence of RTH and thyroid carcinoma. Moreover, our case would be the first case presenting one with lymph node metastases. Recent studies indicated a close association of THRB mutations with human cancers, but the role of THRB mutation in carcinogenesis is still unclear. When total thyroidectomy is performed in

  18. Afamin promotes glucose metabolism in papillary thyroid carcinoma.

    PubMed

    Shen, Chen-Tian; Wei, Wei-Jun; Qiu, Zhong-Ling; Song, Hong-Jun; Luo, Quan-Yong

    2016-10-15

    Circulating afamin (AFM) concentrations have been investigated as a tumor biomarker in various types of carcinomas. However, suitable cell lines expressing human afamin have not yet been reported and current knowledge of the functions of afamin, particularly at the mechanistic molecular level, is very limited. In the current study, thyroid cancer cell lines 8505c and K1 were used to investigate the potential functions of afamin. AFM over-expression models and vector controls of 8505c (8505c + AFM and 8505c + NC) and K1 (K1 + AFM and K1 + NC) were successfully established by Lenti-LV5-AFM and Lenti-LV5-NC transfection. The change of gene expression was detected by qRT-PCR and western blotting analysis. (18)F-FDG imaging in xenografts model was performed using a micro PET/CT. We found that protein level of GAPDH, GLUT1, HK2, p-AKT, AKT, p-mTOR and PARP1 were up-regulated in K1 + AFM cells when compared to K1 and K1 + NC. While in 8505c, 8505c + NC and 8505c cells, the expression level of these genes were not significantly changed. (18)F-FDG uptake was much higher in K1 + AFM cells when compared to K1 and K1 + NC in vitro and in vivo. In conclusion, afamin could promote glycometabolism by up-regulating the glucose metabolism key enzymes in papillary thyroid carcinoma. These findings reveal new clues of the molecular function of AFM. PMID:27329154

  19. Clear cell papillary renal cell carcinoma: a potential mimic of conventional clear cell renal carcinoma on core biopsy.

    PubMed

    Liddell, Heath; Mare, Anton; Heywood, Sean; Bennett, Genevieve; Chan, Hin Fan

    2015-01-01

    Clear cell papillary renal cell carcinoma (CCP-RCC) is a recently described, relatively uncommon variant of renal cell carcinoma (RCC) with a reported incidence of 4.1%. Thought to only arise in those with end stage renal disease, CCP-RCC is increasingly identified in those without renal impairment. CCP-RCCs have unique morphologic, genetic, and immunohistochemical features distinguishing them from both conventional clear cell renal cell carcinomas and papillary renal cell carcinomas. Immunohistochemically, these tumors are positive for CK7 and negative for CD10 and racemase. This is in contrast to conventional cell renal cell carcinomas (CK7 negative, CD10 positive) and papillary cell carcinomas (CK7, CD10, and racemase positive). These tumours appear to be indolent in nature, with no current documented cases of metastatic spread. We present the case of a 42-year-old female who presented with an incidental finding of a renal mass that on a core biopsy was reported as clear cell carcinoma, Fuhrman grade 1. She subsequently underwent a radical nephrectomy and further histological examination revealed the tumor to be a clear cell papillary renal cell carcinoma, Fuhrman grade 1. PMID:25709850

  20. Do Clear Cell Papillary Renal Cell Carcinomas Have Malignant Potential?

    PubMed

    Diolombi, Mairo L; Cheng, Liang; Argani, Pedram; Epstein, Jonathan I

    2015-12-01

    There have been no recurrences or metastases of clear cell papillary renal cell carcinoma (CCPRCC) in 268 reported cases with follow-up in the English-language literature. We identified all our cases of CCPRCC (1990 to 2013), reviewing all cases that preceded the formal designation of the entity. Immunohistochemical stains were performed on 32 cases during their initial workup. In addition, stains for carbonic anhydrase IX and cytokeratin 7 were performed on 2 cases, one with atypical follow-up and the other with a more compact morphology, although not performed initially. An extended panel with AMACR, CD10, and renal cell carcinoma (RCC) was added to the case with atypical follow-up. Fluorescence in situ hybridization for chromosomes 3p, 7, and 17 was performed on the latter case and on another clinically presumed metastatic tumor. In classic cases, immunohistochemical staining was not performed. Fifty-eight patients (31 women; 27 men) with follow-up data were included in our study; 39 cases were from our consult service. The patients' ages ranged from 36 to 83 years. Thirty-five patients had cystic or partially cystic lesions; 6 tumors were multifocal, 3 of which were bilateral. The majority (53 patients; 91.4%) presented with stage pT1 disease (size range, 0.2 to 8 cm), 2 patients presented with pT2 disease (8.5 and 10.3 cm), 1 patient presented with pT3 disease (6.5 cm sarcomatoid RCC focally extending out of the kidney), and pathologic stage was unavailable in 2 cases. Treatment consisted of 29 partial nephrectomies, 26 radical nephrectomies, 2 cryoablations, and 1 cyst ablation. The resection margins were negative in all but one case, with this case disease free after a 26-month period. Two patients had intraoperative tumor disruption and were disease free at 9 and 34 months. Five patients had synchronous ipsilateral renal cell carcinomas (non-CCPRCC). Mean follow-up time was 21 months (range, 1 to 175 mo), with all but 3 patients having no evidence of

  1. Extraovarian peritoneal serous papillary carcinoma: a case-control retrospective comparison to papillary adenocarcinoma of the ovary.

    PubMed

    Bloss, J D; Liao, S Y; Buller, R E; Manetta, A; Berman, M L; McMeekin, S; Bloss, L P; DiSaia, P J

    1993-09-01

    Since the establishment of extraovarian peritoneal serous papillary carcinoma (EPSPC) as a clinical entity in 1959, less than 250 cases have been described and its clinicopathologic features remain obscure. The present series is a retrospective, case-controlled study comparing the response and survival to cytoreductive surgery followed by cisplatin-based multiagent chemotherapy of 33 women with confirmed EPSPC versus 33 cases with papillary serous ovarian cancer (PSOC). Each EPSPC case was matched to a PSOC control for extent and distribution of disease prior to and following cytoreductive surgery, tumor grade, patient age, and treatment. Additionally, the new Gynecologic Oncology Group criteria for the diagnosis for EPSPC are discussed. There were no significant differences in tumor response to therapy, disease-free interval, and actuarial survival between cases and controls. These data suggest that EPSPC is clinically similar to PSOC and support the need for a prospective clinical trial to compare these two entities further. PMID:8406199

  2. Gynecologic Cancer InterGroup (GCIG) consensus review for mucinous ovarian carcinoma.

    PubMed

    Ledermann, Jonathan A; Luvero, Daniela; Shafer, Aaron; O'Connor, Dennis; Mangili, Giorgia; Friedlander, Michael; Pfisterer, Jacobus; Mirza, Mansoor R; Kim, Jae-Weon; Alexandre, Jerome; Oza, Amit; Brown, Jubilee

    2014-11-01

    Mucinous carcinomas of the ovary can be primary or metastatic in origin. Improvements in the pathological diagnosis have increased the ability to distinguish between primary and metastatic ovarian cancers and shown that primary mucinous carcinomas are a rare subtype of ovarian cancer. Most tumors are diagnosed at an early stage, and the prognosis after surgery is good. Advanced or recurrent mucinous carcinoma of the ovary responds poorly to current cytotoxic treatments, and the prognosis is poor. Here, we review the guidelines for surgery and the results of treatment of advanced and recurrent disease. Chemotherapy with platinum and paclitaxel is currently used to treat advanced disease, but the effect of these drugs is modest, and new treatments are needed. PMID:25341574

  3. Renal metastasis from papillary carcinoma thyroid detected by whole body iodine scan: A case report and review of the literature

    PubMed Central

    Nair, Lekha M.; Anila, K. R.; Sreekumar, A.; Pradeep, V. M.

    2016-01-01

    Papillary carcinoma is the most common thyroid malignancy. Usual sites of metastasis include lungs and bone, but renal metastasis is very rare. Here we present a case of a follicular variant of papillary carcinoma with renal and lung metastasis at presentation. PMID:27385900

  4. A case of minocycline-induced black thyroid associated with papillary carcinoma.

    PubMed

    Nishimoto, Kohei; Kumai, Yoshihiko; Murakami, Daizo; Yumoto, Eiji

    2016-03-01

    We report a rare case of black thyroid accompanied by papillary carcinoma in a patient with an extended history of minocycline treatment. A 78-year-old man was referred to our outpatient clinic with swelling in his neck. He had been taking minocycline for the previous 2 years and 7 months to treat chronic perianal pyoderma. Neck ultrasonography and computed tomography demonstrated a 3.5 × 3.7 × 5.0-cm nodule in the left thyroid lobe, and fine-needle aspiration cytology identified it as a papillary carcinoma. The patient underwent a total thyroidectomy and neck dissection. During the procedure, a distinct black discoloration of the thyroid parenchyma was observed. Histopathology confirmed both the black thyroid and the papillary carcinoma. Based on the thyroid gland's discoloration and the history of minocycline use, the patient was diagnosed with minocycline-induced black thyroid. He was symptom-free 20 months after surgery. PMID:26991226

  5. Global Genomic Analysis of Intraductal Papillary Mucinous Neoplasms of the Pancreas Reveals Significant Molecular Differences Compared to Ductal Adenocarcinoma

    PubMed Central

    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

    2013-01-01

    Objective To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). Summary Background Data 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. Methods 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. Results 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. Conclusions 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. PMID:19247032

  6. HABP2 G534E Variant in Papillary Thyroid Carcinoma

    PubMed Central

    Tomsic, Jerneja; Fultz, Rebecca; Liyanarachchi, Sandya; He, Huiling; Senter, Leigha; de la Chapelle, Albert

    2016-01-01

    The main nonmedullary form of thyroid cancer is papillary thyroid carcinoma (PTC) that accounts for 80–90% of all thyroid malignancies. Only 3–10% of PTC patients have a positive family history of PTC yet the familiality is one of the highest of all cancers as measured by case control studies. A handful of genes have been implicated accounting for a small fraction of this genetic predisposition. It was therefore of considerable interest that a mutation in the HABP2 gene was recently implicated in familial PTC. The present work was undertaken to examine the extent of HABP2 variant involvement in PTC. The HABP2 G534E variant (rs7080536) was genotyped in blood DNA from 179 PTC families (one affected individual per family), 1160 sporadic PTC cases and 1395 controls. RNA expression of HABP2 was tested by qPCR in RNA extracted from tumor and normal thyroid tissue from individuals that are homozygous wild-type or heterozygous for the variant. The variant was found to be present in 6.1% familial cases, 8.0% sporadic cases (2 individuals were homozygous for the variant) and 8.7% controls. The variant did not segregate with PTC in one large and 6 smaller families in which it occurred. In keeping with data from the literature and databases the expression of HABP2 was highest in the liver, much lower in 3 other tested tissues (breast, kidney, brain) but not found in thyroid. Given these results showing lack of any involvement we suggest that the putative role of variant HABP2 in PTC should be carefully scrutinized. PMID:26745718

  7. Somatic amplifications and deletions in genome of papillary thyroid carcinomas.

    PubMed

    Passon, Nadia; Bregant, Elisa; Sponziello, Marialuisa; Dima, Maria; Rosignolo, Francesca; Durante, Cosimo; Celano, Marilena; Russo, Diego; Filetti, Sebastiano; Damante, Giuseppe

    2015-11-01

    Somatic gene copy number variation contributes to tumor progression. Using comparative genomic hybridization (CGH) array, the presence of genomic imbalances was evaluated in a series of 27 papillary thyroid carcinomas (PTCs). To detect only somatic imbalances, for each sample, the reference DNA was from normal thyroid tissue of the same patient. The presence of the BRAF V600E mutation was also evaluated. Both amplifications and deletions showed an uneven distribution along the entire PTC cohort; amplifications were more frequent than deletions (mean values of 17.5 and 7.2, respectively). Number of aberration events was not even among samples, the majority of them occurring only in a small fraction of PTCs. Most frequent amplifications were detected at regions 2q35, 4q26, and 4q34.1, containing FN1, PDE5A, and GALNTL6 genes, respectively. Most frequent deletions occurred at regions 6q25.2, containing OPMR1 and IPCEF1 genes and 7q14.2, containing AOAH and ELMO1 genes. Amplification of FN1 and PDE5A genomic regions was confirmed by quantitative PCR. Frequency of amplifications and deletions was in relationship with clinical features and BRAF mutation status of tumor. In fact, according to the American Joint Committee on Cancer stage and American Thyroid Association (ATA) risk classification, amplifications are more frequent in higher risk samples, while deletions tend to prevail in the lower risk tumors. Analysis of single aberrations according to the ATA risk grouping shows that amplifications containing PDE5A, GALNTL6, DHRS3, and DOCK9 genes are significantly more frequent in the intermediate/high risk group than in the low risk group. Thus, our data would indicate that analysis of somatic genome aberrations by CGH array can be useful to identify additional prognostic variables. PMID:25863487

  8. Tumor-associated macrophages are involved in tumor progression in papillary renal cell carcinoma.

    PubMed

    Behnes, Carl Ludwig; Bremmer, Felix; Hemmerlein, Bernhard; Strauss, Arne; Ströbel, Philipp; Radzun, Heinz-Joachim

    2014-02-01

    Tumor-associated macrophages (TAMs) play a key role in cancer development. Especially, the immunosuppressive M2 phenotype is associated with increased tumor growth, invasiveness and metastasis. The differentiation of macrophages to the alternative phenotype M2 is mediated, inter alia, by macrophage colony-stimulating factor (M-CSF). Papillary renal cell carcinoma (RCC) represents a rare tumor type which, based upon histological criteria, can be subdivided into two subtypes (I and II), of which type II is associated with poor prognosis. In both subtypes, typically, a dense infiltrate of macrophages is found. In the present study, the expression of CD68, CD163, M-CSF, Ki-67, and CD31 was examined in 30 type I and 30 type II papillary RCCs (n = 60). Both types of papillary RCCs contained an equally dense infiltrate of CD68-positive macrophages. Nearly all macrophages in papillary RCC type II expressed CD163, a characteristic for M2 macrophages. In type I papillary RCC, less than 30 % of macrophages expressed CD163. Furthermore, tumor cells in type II papillary RCC expressed significantly more M-CSF and showed increased (Ki-67 expression defined) proliferative activity in comparison with type I papillary RCC. In addition, the (CD31 defined) capillary density was higher in type II than in type I papillary RCC. A dense infiltrate of M2 phenotype TAM and high M-CSF expression in tumor cells are key features of type II papillary RCC. These findings might explain why the prognosis of papillary RCC type II is worse than that of type I. PMID:24327306

  9. Malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously: A case report.

    PubMed

    Ozgun, Alpaslan; Tuncel, Tolga; Emirzeoglu, Levent; Celik, Serkan; Bilgi, Oguz; Haholu, Abdullah; Urhan, Muammer; Karagoz, Bulent

    2015-01-01

    Malignant melanoma can be successfully treated when it is identified in its early stages, but the disease is associated with a poor prognosis when it is detected in an advanced stage. Papillary thyroid carcinoma is a thyroid cancer that has a good prognosis. The present study reports a rare case of malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously. The present patient was a 37-year-old male, in whom examination of a skin biopsy that was obtained from a lesion in the right retroauricular region revealed the lesion to be consistent with malignant melanoma. The patient underwent radical neck dissection upon the detection of malignant melanoma metastasis to the sentinel lymph node. Metastases of papillary thyroid carcinoma were detected in four out of 38 lymph nodes. The patient was then diagnosed with papillary thyroid carcinoma and underwent total thyroidectomy. The patient was administered with high-dose followed by moderate-dose interferon-α therapy for the treatment of malignant melanoma. The patient also received concurrent radioactive iodine therapy for the treatment of papillary thyroid carcinoma, at the same time as the interferon therapy. The two primary tumors of the patient were treated successfully. During therapy, no serious side-effects were observed, with the exception of fever caused by high-dose interferon therapy. Malignant melanoma and papillary thyroid carcinoma may occur concurrently, although this is rarely observed. The present study reports a rare case that demonstrates that the two tumors can be successfully treated simultaneously. PMID:25436010

  10. Long-term survival in uterine clear cell carcinoma and uterine papillary serous carcinoma.

    PubMed

    Lindahl, Bengt; Persson, Jan; Ranstam, Jonas; Willén, Roger

    2010-09-01

    Uterine clear cell carcinoma (UCC) and uterine papillary serous carcinoma (UPSC) are rare entities that differ in clinical behavior from endometrial adenocarcinoma. Compared with endometrioid adenocarcinoma, they more often metastasize early and more commonly in the upper abdomen including the omentum. Treatment programs of UCC and UPSC at different stages vary and range from no adjuvant therapy in stage Ia to a wide variety of chemotherapies and radiotherapies in more advanced stages. This study presents the outcome of 109 patients with UCC or UPSC treated according to essentially the same treatment program from May 1993 to December 2004. Most patients were treated with a simple hysterectomy with no further adjuvant treatment. In stage Ia, 2/46 patients died of their disease and amongst all the stages, 30/109 patients died of their disease. These survival outcomes are comparable to or better than those presented previously. PMID:20944161

  11. Biphasic papillary and lobular breast carcinoma with PIK3CA and IDH1 mutations.

    PubMed

    Ang, Daphne; VanSandt, Amanda M; Beadling, Carol; Warrick, Andrea; West, Robert B; Corless, Christopher L; Troxell, Megan L

    2012-12-01

    Morphologic "special types" of breast carcinomas have been recognized for many years, and their molecular and genetic properties have not been specifically studied until recently. Lobular carcinoma lacks functional E-cadherin expression but shares molecular similarities with low-grade invasive ductal carcinomas. Papillary carcinoma is relatively rare, and molecular features are just being elucidated. We report a case of concurrent invasive lobular and papillary carcinoma, the latter with extensive nodal involvement. Multiplex screening for activating point mutations identified different point mutations in the distinct morphologic components: lobular PIK3CA H1047R, papillary; PIK3CA Q546P, and IDH1 R132H. These molecular data favor coincidental "collision tumors" over clonal evolution. The IDH1 R132H point mutation is common in gliomas and acute myelogenous leukemia, but this has not been previously reported in breast carcinoma. The characterization of activating point mutations in morphologic special types of breast carcinoma may suggest avenues amenable to targeted therapy. PMID:23111200

  12. CLIP2 as radiation biomarker in papillary thyroid carcinoma.

    PubMed

    Selmansberger, M; Feuchtinger, A; Zurnadzhy, L; Michna, A; Kaiser, J C; Abend, M; Brenner, A; Bogdanova, T; Walch, A; Unger, K; Zitzelsberger, H; Hess, J

    2015-07-23

    A substantial increase in papillary thyroid carcinoma (PTC) among children exposed to the radioiodine fallout has been one of the main consequences of the Chernobyl reactor accident. Recently, the investigation of PTCs from a cohort of young patients exposed to the post-Chernobyl radioiodine fallout at very young age and a matched nonexposed control group revealed a radiation-specific DNA copy number gain on chromosomal band 7q11.23 and the radiation-associated mRNA overexpression of CLIP2. In this study, we investigated the potential role of CLIP2 as a radiation marker to be used for the individual classification of PTCs into CLIP2-positive and -negative cases-a prerequisite for the integration of CLIP2 into epidemiological modelling of the risk of radiation-induced PTC. We were able to validate the radiation-associated CLIP2 overexpression at the protein level by immunohistochemistry (IHC) followed by relative quantification using digital image analysis software (P=0.0149). Furthermore, we developed a standardized workflow for the determination of CLIP2-positive and -negative cases that combines visual CLIP2 IHC scoring and CLIP2 genomic copy number status. In addition to the discovery cohort (n=33), two independent validation cohorts of PTCs (n=115) were investigated. High sensitivity and specificity rates for all three investigated cohorts were obtained, demonstrating robustness of the developed workflow. To analyse the function of CLIP2 in radiation-associated PTC, the CLIP2 gene regulatory network was reconstructed using global mRNA expression data from PTC patient samples. The genes comprising the first neighbourhood of CLIP2 (BAG2, CHST3, KIF3C, NEURL1, PPIL3 and RGS4) suggest the involvement of CLIP2 in the fundamental carcinogenic processes including apoptosis, mitogen-activated protein kinase signalling and genomic instability. In our study, we successfully developed and independently validated a workflow for the typing of PTC clinical samples into CLIP2

  13. Metastatic papillary carcinoma of the thyroid in a patient previously treated for Graves' disease.

    PubMed

    Yunusa, Garba H; Kotze, Tessa; Brink, Anita

    2014-01-01

    Incidental papillary carcinoma of the thyroid in patients treated surgically for benign thyroid diseases including Graves' disease is a known phenomenon. However, the management of these patients remains an issue of concern and controversy for those who care for them. We report a case of metastatic papillary carcinoma of the thyroid in a patient previously treated for Graves' disease. The subject of this presentation is a 50-year-old lady who was diagnosed with Graves' disease at the age of 29, for which she had a subtotal thyroidectomy following failure of medical and radioactive iodine treatment. Three years later, the patient was referred to our nuclear medicine department with a clinical diagnosis of suspected metastatic lymph nodes presumably from a thyroid malignancy.She had an 123I diagnostic whole body scan that showed 123I avid areas in the thyroid bed as well as left cervical lymph nodes, which later turned out to be metastatic papillary carcinoma of the thyroid on histology. She was treated with therapeutic doses of 131I. Follow-up radioactive iodine scans and serum thyroglobulin assays showed no evidence of malignant thyroid tissue. The occurrence of papillary carcinoma of the thyroid after a subtotal thyroidectomy for Graves' disease is hereby reported. The need for vigilance and regular follow-up in patients who receive all forms of treatment for benign thyroid diseases is emphasized. PMID:24705115

  14. Accuracy of 2012 International Consensus Guidelines for the prediction of malignancy of branch-duct intraductal papillary mucinous neoplasms of the pancreas

    PubMed Central

    Robles, Enrique Pérez-Cuadrado; Cros, Jérôme; Vullierme, Marie-Pierre; Rebours, Vinciane; Sauvanet, Alain; Aubert, Alain; Dokmak, Safi; Lévy, Philippe; Ruszniewski, Philippe

    2016-01-01

    Objective To determine accuracy of 2012 International Consensus Guidelines (ICG) predicting malignancy in a surgical cohort of branch-duct intraductal papillary mucinous neoplasms (BD-IPMN). Methods This study included all consecutive patients with final pathological diagnosis of pure BD-IPMN resected between 2006 and 2014 at Beaujon Hospital. Neoplasms were classified as malignant in presence of high-grade dysplasia (HGD) or invasive carcinoma. Medical, pathological, and radiological data were retrospectively recorded. Results One hundred and twenty patients (65 males, mean age: 57.9 ± 10.8 years) were included. Malignant BD-IPMN accounted for 30% (HGD: 18%, invasive: 12%). Thickened cyst walls (odds ratio (OR): 3.058, 95% confidence interval (CI 95%): 1.102–8.484, p = 0.032), main duct diameter 5–9 mm (OR: 3.395, CI 95%: 1.349–8.543, p = 0.007), and mural nodule (OR: 3.802, CI 95%: 1.156–12.511, p = 0.028) were independently associated with malignancy in multivariate analysis. Among the 89 patients (74%) who underwent surgical resection with ICG criteria, the malignancy rate was 38%, compared with 6% in the 31 ICG-negative group. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for malignancy of having at least one ICG criteria were 94%, 34%, 38%, 94%, and 53%, respectively. Patients with malignant tumors had more ICG criteria than those with benign lesions (2.06 ± 0.98 vs. 0.99 ± 0.95, p < 0.001). Conclusions 2012 ICG criteria are useful to manage BD-IPMN permitting not to miss a malignant form (NPV of 94%), but frequently point out unnecessary surgery (PPV of 38%). Malignancy rate increases with the number of ICG criteria. In patients with only one criterion, additional criteria would be necessary.

  15. Metastatic Collision Tumour (Papillary Thyroid Carcinoma and Squamous Cell Carcinoma) in Cervical Lymph Nodes: An Immunohistochemical Analysis.

    PubMed

    Alhanafy, Alshimaa Mahmoud; Al-Sharaky, Dalia; Abdou, Asmaa Gaber; Abdallah, Rania Abdallah

    2016-02-01

    Collision tumours are a rare entity, in this report, we describe a case of 73-year-old woman presented with a rapid enlargement of left upper cervical lymph node (LN) associated with right thyroid nodular goiter. The histopathological examination of the excised LN showed definite areas of papillary thyroid carcinoma admixed with moderately differentiated squamous cell carcinoma (SCC). Thyroglobulin immunostaining was positive in papillary carcinomatous areas confirming thyroid gland as a source of metastasis. Then the patient underwent total thyroidectomy and neck dissection, which revealed multicentric classic papillary thyroid carcinoma with an absence of squamous differentiation on extensive sampling. The patient received adjuvant radioactive iodine, but the neck swelling was rapidly progressing, ulcerated and infected. Computed tomography (CT) revealed left large cervical amalgamated LN and two metastatic lung nodules, the patient received 2 cycles of chemotherapy and was planned for external beam radiotherapy but she died within 7 months of first presentation. Collision tumours pose a diagnostic as well as therapeutic challenge and carry a rapidly progressive course and a fatal outcome. SCC is considered as a dedifferentiation of papillary thyroid carcinoma, which may appear in metastatic site rather than the primary site. PMID:27042475

  16. Mucin production by human colonic carcinoma cells correlates with their metastatic potential in animal models of colon cancer metastasis.

    PubMed Central

    Bresalier, R S; Niv, Y; Byrd, J C; Duh, Q Y; Toribara, N W; Rockwell, R W; Dahiya, R; Kim, Y S

    1991-01-01

    Patients with mucinous colorectal cancers characteristically present with advanced disease, however, the relationship between mucin production by colon cancer cells and their metastatic potential remains unclear. We therefore sought to define the relationship between mucin production by human colon cancer cells and metastatic ability by employing animal models of colon cancer metastasis. LS LiM 6, a colon carcinoma cell line with high liver metastasizing ability during cecal growth in nude mice produced twofold more metabolically labeled intracellular mucin and secreted four- to fivefold more mucin into the culture medium compared to poorly metastatic parental line LS174T. This was accompanied by a similar elevation in poly(A)+ RNA detected by blot hybridization with a human intestinal mucin cDNA probe, and increases in mucin core carbohydrate antigens determined immunohistochemically. Variants of LS174T selected for high (HM 7) or low (LM 12) mucin synthesizing capacity also yielded metastases after cecal growth and colonized the liver after splenic-portal injection in proportion to their ability to produce mucin. Inhibition of mucin glycosylation by the arylglycoside benzyl-alpha-N-acetyl-galactosamine greatly reduced liver colonization after splenic-portal injection of the tumor cells. These data suggest that mucin production by human colon cancer cells correlates with their metastatic potential and affects their ability to colonize the liver in experimental model systems. Images PMID:1999484

  17. Biphasic Squamoid Alveolar Renal Cell Carcinoma: A Distinctive Subtype of Papillary Renal Cell Carcinoma?

    PubMed

    Hes, Ondrej; Condom Mundo, Enric; Peckova, Kvetoslava; Lopez, Jose I; Martinek, Petr; Vanecek, Tomas; Falconieri, Giovanni; Agaimy, Abbas; Davidson, Whitney; Petersson, Fredrik; Bulimbasic, Stela; Damjanov, Ivan; Jimeno, Mireya; Ulamec, Monika; Podhola, Miroslav; Sperga, Maris; Pane Foix, Maria; Shelekhova, Ksenya; Kalusova, Kristyna; Hora, Milan; Rotterova, Pavla; Daum, Ondrej; Pivovarcikova, Kristyna; Michal, Michal

    2016-05-01

    Biphasic squamoid alveolar renal cell carcinoma (BSARCC) has been recently described as a distinct neoplasm. Twenty-one cases from 12 institutions were analyzed using routine histology, immunohistochemistry, array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization. Tumors were removed from 11 male and 10 female patients, whose age ranged from 53 to 79 years. The size of tumors ranged from 1.5 to 16 cm. Follow-up information was available for 14 patients (range, 1 to 96 mo), and metastatic spread was found in 5 cases. All tumors comprised 2 cell populations arranged in organoid structures: small, low-grade neoplastic cells with scant cytoplasm usually lining the inside of alveolar structures, and larger squamoid cells with more prominent cytoplasm and larger vesicular nuclei arranged in compact nests. In 9/21 tumors there was a visible transition from such solid and alveolar areas into papillary components. Areas composed of large squamoid cells comprised 10% to 80% of total tumor volume. Emperipolesis was present in all (21/21) tumors. Immunohistochemically, all cases were positive for cytokeratin 7, EMA, vimentin, and cyclin D1. aCGH (confirmed by fluorescence in situ hybridization) in 5 analyzable cases revealed multiple numerical chromosomal changes including gains of chromosomes 7 and 17 in all cases. These changes were further disclosed in 6 additional cases, which were unsuitable for aCGH. We conclude that tumors show a morphologic spectrum ranging from RCC with papillary architecture and large squamoid cells to fully developed BSARCC. Emperipolesis in squamoid cells was a constant finding. All BSARCCs expressed CK7, EMA, vimentin, and cyclin D1. Antibody to cyclin D1 showed a unique and previously not recognized pattern of immunohistochemical staining. Multiple chromosomal aberrations were identified in all analyzable cases including gains of chromosomes 7 and 17, indicating that they are akin to papillary RCC. Some BSARCCs were

  18. Clear cell papillary renal cell carcinoma-like tumors in patients with von Hippel-Lindau disease are unrelated to sporadic clear cell papillary renal cell carcinoma.

    PubMed

    Williamson, Sean R; Zhang, Shaobo; Eble, John N; Grignon, David J; Martignoni, Guido; Brunelli, Matteo; Wang, Mingsheng; Gobbo, Stefano; Baldridge, Lee Ann; Cheng, Liang

    2013-08-01

    Clear cell papillary renal cell carcinoma (CCPRCC) shares morphologic overlap with clear cell renal cell carcinoma, although it lacks chromosome 3p and VHL gene abnormalities. Rare cases have been reported in von Hippel-Lindau (VHL) patients (germline mutation of the VHL gene), the significance of which is uncertain. We analyzed morphologic, immunohistochemical, and molecular features in 14 CCPRCC-like tumors and 13 clear cell renal cell carcinomas from 12 patients with VHL disease. Gross appearance of CCPRCC-like tumors ranged from yellow-orange to tan, red-brown, or extensively cystic. Histologic features included: small papillary tufts (79%), branched tubules (71%), branched papillae (64%), flattened peripheral cysts (64%), and apically aligned nuclei (43%). Almost all CCPRCC-like tumors (82%) lacked the characteristic immunoprofile of sporadic CCPRCC (CK7, CAIX, CD10, AMACR), often showing diffuse CD10 labeling (64%), negative or focal CK7 reactivity (55%), or both (18%). Three tumors (27%) showed strong AMACR staining. Chromosome 3p deletion was often present (82%), similar to that observed in clear cell renal cell carcinomas (80%); no CCPRCC-like tumor had chromosome 7 or 17 abnormalities. In summary, tumors that histologically resemble CCPRCC sometimes occur in patients with VHL disease but usually lack the characteristic immunohistochemical and molecular profile, suggesting that they do not share the same pathogenesis. PMID:23648463

  19. Skull base metastasis from papillary thyroid carcinoma: a report of three cases

    PubMed Central

    Tunio, Mutahir A; Al Asiri, Mushabbab; Al-Qahtani, Khalid Hussain; Aldandan, Sadiq; Riaz, Khalid; Bayoumi, Yasser

    2015-01-01

    Skull base metastasis from differentiated thyroid carcinoma, including papillary and follicular thyroid carcinoma, is a rare manifestation. Herein, we present three cases of skull base metastasis of papillary thyroid carcinoma. The mean age of the patients was 68.6 (65–74) years, and the mean interval between initial diagnosis and skull base metastasis was 56.3 (28–89) months. Cranial nerve palsies were seen in all patients. Intensity modulated radiation therapy to deliver 6,000–6,600 cGy to the skull base metastasis was given to all patients, in addition to partial resection in one patient. At the time of last follow-up, all skull base metastases were well controlled. PMID:26203287

  20. Unusual Granular Cell Tumor of the Trachea Coexisting With Papillary Thyroid Carcinoma and Masquerading as Tracheal Invasion of Recurred Thyroid Carcinoma

    PubMed Central

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul

    2016-01-01

    Abstract This was an extremely rare case of unusual granular cell tumor of the trachea coexisting with recurrent papillary thyroid carcinoma. We initially misdiagnosed this patient as having tracheal invasion from recurrent thyroid carcinoma even after a computed tomography scan and fine-needle aspiration cytology. Clinicians should be aware of the possibility of granular cell tumor of the trachea occurring simultaneously with papillary thyroid carcinoma. PMID:27149467

  1. Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results from in vitro and in vivo studies with bromelain and N-acetylcysteine

    PubMed Central

    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

  2. Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results from in vitro and in vivo studies with bromelain and N-acetylcysteine.

    PubMed

    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. PMID:26436698

  3. Invasive Stratified Mucin-producing Carcinoma and Stratified Mucin-producing Intraepithelial Lesion (SMILE): 15 Cases Presenting a Spectrum of Cervical Neoplasia With Description of a Distinctive Variant of Invasive Adenocarcinoma.

    PubMed

    Lastra, Ricardo R; Park, Kay J; Schoolmeester, J Kenneth

    2016-02-01

    Stratified mucin-producing intraepithelial lesion (SMILE) is a cervical intraepithelial lesion, distinct from conventional squamous or glandular counterparts, believed to arise from embryonic cells at the transformation zone by transdifferentiation during high-risk HPV-associated carcinogenesis. It is characterized by stratified, immature epithelial cells displaying varying quantities of intracytoplasmic mucin throughout the majority of the lesional epithelium. We identified a distinct form of invasive cervical carcinoma with morphologic features identical to those in SMILE, which we have termed "invasive stratified mucin-producing carcinoma." Fifteen cases from 15 patients (mean 36 y; range, 22 to 64 y) were retrieved from the pathology archives of multiple institutions with a diagnosis of either SMILE or invasive cervical carcinoma with a description or comment about the invasive tumor's resemblance to SMILE. Seven cases had solely intraepithelial disease with a component of SMILE (mean 29 y; range, 22 to 40 y). The 8 other cases had invasive stratified mucin-producing carcinoma (mean 44; range, 34 to 64 y) in which SMILE was identified in 7. All cases of invasive stratified mucin-producing carcinoma demonstrated stratified, immature nuclei with intracytoplasmic mucin, which morphologically varied between cases from "mucin-rich" to "mucin-poor" in a similar manner to SMILE. All cases had mitotic figures and apoptotic debris, and an intralesional neutrophilic infiltrate was seen in the majority of cases. In cases of invasive carcinoma, the depth of invasion ranged from <1 to 19 mm. Follow-up information was available in 8 cases and ranged from 1 to 36 months (mean 11 mo). Three cases of invasive stratified mucin-producing carcinoma had biopsy or resection-proven metastatic carcinoma on follow-up. These 15 cases of cervical stratified mucin-producing lesions show a combination of intraepithelial and invasive growth patterns. Given that SMILE is well rooted as a

  4. Mucus retention in heterotopic pancreas of the gastric antrum. A lesion mimicking mucinous carcinoma.

    PubMed

    Nopajaroonsri, C

    1994-09-01

    This report describes mucus retention developing in heterotopic pancreas of the gastric antrum. This unusual complication of heterotopic pancreas was seen in a 54-year-old black man who presented with postprandial nausea, vomiting, and weight loss. Gastroscopy revealed a 2-cm pyloric polyp, which was seen to intermittently obstruct the pylorus. Exploratory laparotomy confirmed an intramural mass in the antrum with serosal thickening and nodules. Frozen-section examination of the serosal nodule revealed a pool of mucus containing epithelial clusters and chronic inflammatory cells with no verifiable pancreatic tissue. These findings suggested the possibility of a mucinous carcinoma involving the serosa. Following gastrectomy, however, heterotopic pancreatic tissue was identified in the outer muscular propria extending to the mucosa of the antrum with no evidence of carcinoma. This heterotopic pancreatic tissue showed ductal obstruction and mucus retention. As a result, some ducts were ruptured and transformed into small nodules of mucus lakes with clusters of residual ductal epithelium. We therefore concluded that the mucous extravasation nodules on the antral serosa represented a benign lesion resulting from mucus retention in the heterotopic pancreas. In contrast to mucinous carcinoma, these benign mucous extravasation nodules were closely associated with the heterotopic pancreas, and showed significant inflammation and fibrosis but no overt epithelial anaplasia. The significance of the mucous extravasation nodule in the heterotopic pancreas is its potential confusion with mucinous carcinoma. PMID:8067516

  5. Detection of Hot-Spot Mutations in Circulating Cell-Free DNA From Patients With Intraductal Papillary Mucinous Neoplasms of the Pancreas.

    PubMed

    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. PMID:27343369

  6. Comparison of Clinical and Ultrasonographic Features of Poorly Differentiated Thyroid Carcinoma and Papillary Thyroid Carcinoma

    PubMed Central

    Zhang, Bo; Niu, Hui-Min; Wu, Qiong; Zhou, Jiong; Jiang, Yu-Xin; Yang, Xiao; Li, Jian-Chu; Zhao, Rui-Na; Wang, Ming; Li, Kang-Ning; Zhu, Shen-Ling; Xia, Yu; Zhong, Ding-Rong

    2016-01-01

    Background: The clinical behavior and management of poorly differentiated thyroid carcinoma (PDTC) are very different from papillary thyroid carcinoma (PTC). By comparing the clinical and ultrasonographic features between the two tumors, we proposed to provide more possibilities for recognizing PDTC before treatment. Methods: The data of 13 PDTCs and 39 age- and gender-matched PTCs in Peking Union Medical College Hospital between December 2003 and September 2013 were retrospectively reviewed. The clinical and ultrasonic features between the two groups were compared. Results: The frequencies of family history of carcinoma, complication with other thyroid lesions, lymph node metastases, recurrent laryngeal nerve injuries, and distant metastases were higher in PDTCs (30.8%, 61.6%, 69.2%, 23.1%, and 46.2%, respectively) than those in PTCs (2.6%, 23.1%, 25.6%, 2.6%, and 2.6%, respectively) (P < 0.05). The mortality rate of PDTCs was greatly higher than PTCs (P < 0.01). Conventional ultrasound showed that the size of PDTCs was larger than that of PTCs (3.1 ± 1.9 cm vs. 1.7 ± 1.0 cm). Clear margins and rich and/or irregular blood flow were found in 92.3% of PDTCs, which differed substantially from PTCs (51.7% and 53.8%, respectively) (P < 0.05). Conclusions: PDTC is more aggressive and its mortality rate is higher than PTCs. Accordingly, more attention should be given to suspicious thyroid cancer nodules that show large size, regular shape, and rich blood flow signals on ultrasound to exclude the possibility of PDTCs. PMID:26830987

  7. Incidental papillary thyroid carcinoma: diagnostic findings in a series of 287 carcinomas.

    PubMed

    Pagni, Fabio; Jaconi, Marta; Delitala, Alberto; Garancini, Mattia; Maternini, Matteo; Bono, Francesca; Giani, Alessandro; Smith, Andrew

    2014-09-01

    The recent increase in the detection of papillary thyroid carcinoma (PTC) has been influenced by the finding of incidental tumours. To this group, carcinomas measuring less than 1 cm (the so-called microcarcinomas) as well as those above 1 cm belong. Analyzing a case series from our own experience, this paper focuses on the current pre-operative diagnostic challenges that can lead to PTC incidental discovery. For this retrospective study, 287 patients with a PTC diagnosis were selected. For each, the following variables were analysed: sex, age, ultrasound (US) appearance, number of thyroid nodules, PTC size, PTC variants and presence of other associated pathology. Pre-operative fine needle aspiration (FNA) results were classified according to the five-tiered SIAPEC system. For 281 patients, the US-guided FNA results were available. Cytohistological correlation was evaluated in terms of FNA sensitivity and false negative rate. An incidental PTC was found in 45.2 % of patients. The majority of these were due to unsuccessful US detection of malignant nodules (103 cases); incorrect cytological diagnosis was responsible for the other 24 cases. The most powerful clinical confounding factors were: multinodular background versus single nodule presentations (p < 0.001) and histotype (follicular vs conventional variant, p < 0.05). Of course, tumour size remains a strongly influential feature on pre-operative diagnosis, with greater difficulties arising for carcinomas <5 mm. Moreover, FNA sensitivity was lower also in large PTCs (>2 cm) due to tumour heterogeneity. Although with limitations related to the tumour's intrinsic features and the thyroid background, US-guided FNA, especially if performed by a dedicated multidisciplinary team, is a powerful diagnostic tool for detecting malignant thyroid nodules. To the state of the art, we propose a practical clinical-pathological cut-off for this procedure, setting it at 5 mm. PMID:24997780

  8. Coexistence of Malakoplakia and Papillary Urothelial Carcinoma of the Urinary Bladder.

    PubMed

    Lee, Song Liang Joshua; Teo, Jin Kiat; Lim, Sey Kiat Terence; Salkade, Hema Parag; Mancer, Kent

    2015-10-01

    Malakoplakia is a rare granulomatous disease that commonly involves the genitourinary tract, with the urinary bladder being the most frequently affected site. Grossly, malakoplakia can present as soft yellow plaques, nodules, bladder mass, or even without any visible lesion. In this article, we present a 74-year-old female with a background of hypertension, hyperlipidemia, and poorly controlled diabetes who presented with sepsis of unknown origin. During the course of the investigation of the source of her sepsis, an incidental bladder tumor was discovered. She subsequently underwent transurethral resection of the bladder tumor. Histology revealed ordinary low-grade papillary urothelial carcinoma that had small colonies of malakoplakia that appeared to have developed secondary to the tumor and presented concurrently. We seek to demonstrate the rare association of papillary urothelial carcinoma and malakoplakia. PMID:26194600

  9. Prognostic Significance and Molecular Features of Signet-Ring Cell and Mucinous Components in Colorectal Carcinoma

    PubMed Central

    Mima, Kosuke; Sukawa, Yasutaka; Li, Tingting; Yasunari, Mika; Zhang, Xuehong; Wu, Kana; Meyerhardt, Jeffrey A.; Fuchs, Charles S.

    2014-01-01

    Background Colorectal carcinoma (CRC) represents a group of histopathologically and molecularly heterogeneous diseases, which may contain signet-ring cell component and/or mucinous component to a varying extent under pathology assessment. However, little is known about the prognostic significance of those components, independent of various tumor molecular features. Methods Utilizing a molecular pathological epidemiology database of 1,336 rectal and colon cancers in the Nurses’ Health Study and the Health Professionals Follow-up Study, we examined patient survival according to the proportion of signet-ring cell and mucinous components in CRCs. Cox proportional hazards models were used to compute hazard ratio (HR) for mortality, adjusting for potential confounders including stage, microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Results Compared to CRC without signet-ring cell component, 1–50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 1.40 [95 % confidence interval (CI) 1.02–1.93], and >50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 4.53 (95 % CI 2.53–8.12) (Ptrend > 0.0001). Compared to CRC without mucinous component, neither 1–50 % mucinous component (multivariate HR 1.04; 95 % CI 0.81–1.33) nor >50 % mucinous component (multivariate HR 0.82; 95 % CI 0.54–1.23) was significantly associated with CRC-specific mortality (Ptrend < 0.57). Conclusions Even a minor (50 % or less) signet-ring cell component in CRC was associated with higher patient mortality, independent of various tumor molecular and other clinicopathological features. In contrast, mucinous component was not associated with mortality in CRC patients. PMID:25326395

  10. Papillary Thyroid Carcinoma Treated with Radiofrequency Ablation in a Patient with Hypertrophic Cardiomyopathy: A Case Report.

    PubMed

    Sun, Jianyi; Liu, Xiaosun; Zhang, Qing; Hong, Yanyun; Song, Bin; Teng, Xiaodong; Yu, Jiren

    2016-01-01

    Standard therapy has not been established for thyroid cancer when a thyroidectomy is contraindicated due to systemic disease. Herein, we reported a patient who had hypertrophic cardiomyopathy and papillary thyroid carcinoma treated by radiofrequency ablation because of inability to tolerate a thyroidectomy. Radiofrequency ablation can be used to treat thyroid cancer when surgery is not feasible, although the long-term outcome needs further observation. PMID:27390548

  11. Evaluation of the VE1 Antibody in Thyroid Cytology Using Ex Vivo Papillary Thyroid Carcinoma Specimens

    PubMed Central

    Kim, Yon Hee; Yim, Hyunee; Lee, Yong-Hee; Han, Jae Ho; Lee, Kyi Beom; Lee, Jeonghun; Soh, Euy Young; Jeong, Seon-Yong; Kim, Jang-Hee

    2016-01-01

    Background: Recently, VE1, a monoclonal antibody against the BRAFV600E mutant protein, has been investigated in terms of its detection of the BRAFV600E mutation. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in thyroid cytology samples is rarely performed, and its diagnostic value in cytology has not been well established. In present study, we explored VE1 immunoexpression in cytology samples from ex vivo papillary thyroid carcinoma specimens in order to minimize limitations of low cellularity and sampling/targeting errors originated from thyroid fineneedle aspiration and compared our results with those obtained using the corresponding papillary thyroid carcinoma tissues. Methods: The VE1 antibody was evaluated in 21 cases of thyroid cytology obtained directly from ex vivo thyroid specimens. VE1 immunostaining was performed using liquid-based cytology, and the results were compared with those obtained using the corresponding tissues. Results: Of 21 cases, 19 classic papillary thyroid carcinomas had BRAFV600E mutations, whereas two follicular variants expressed wild-type BRAF. VE1 immunoexpression varied according to specimen type. In detection of the BRAFV600E mutation, VE1 immunostaining of the surgical specimen exhibited 100% sensitivity and 100% specificity, whereas VE1 immunostaining of the cytology specimen exhibited only 94.7% sensitivity and 0% specificity. Conclusions: Our data suggest that VE1 immunostaining of a cytology specimen is less specific than that of a surgical specimen for detection of the BRAFV600E mutation, and that VE1 immunostaining of a cytology specimen should be further evaluated and optimized for clinical use. PMID:26657312

  12. Papillary Thyroid Carcinoma Treated with Radiofrequency Ablation in a Patient with Hypertrophic Cardiomyopathy: A Case Report

    PubMed Central

    Sun, Jianyi; Liu, Xiaosun; Zhang, Qing; Hong, Yanyun; Song, Bin; Teng, Xiaodong

    2016-01-01

    Standard therapy has not been established for thyroid cancer when a thyroidectomy is contraindicated due to systemic disease. Herein, we reported a patient who had hypertrophic cardiomyopathy and papillary thyroid carcinoma treated by radiofrequency ablation because of inability to tolerate a thyroidectomy. Radiofrequency ablation can be used to treat thyroid cancer when surgery is not feasible, although the long-term outcome needs further observation. PMID:27390548

  13. RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture.

    PubMed

    Santoro, Massimo; Melillo, Rosa Marina; Fusco, Alfredo

    2006-11-01

    Papillary thyroid carcinoma (PTC) is frequently associated with RET gene rearrangements that generate the so-called RET/PTC oncogenes. In this review, we examine the data about the mechanisms of thyroid cell transformation, activation of downstream signal transduction pathways and modulation of gene expression induced by RET/PTC. These findings have advanced our understanding of the processes underlying PTC formation and provide the basis for novel therapeutic approaches to this disease. PMID:17062879

  14. Clear cell papillary renal cell carcinoma: a clinicopathologic analysis of 6 cases.

    PubMed

    Yan, Wen-Xiu; Cao, Wen-Rong; Zhao, Jun; Zhang, Wei; Wang, Xue-Li; Yuan, Qian; Dang, Shou-Qin

    2015-01-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a newly described variant of renal cell carcinoma (RCC) which is composed mainly of cells with clear cytoplasm arranged in cystic and papillary patterns. We report the clinicopathologic features, prognosis and differential diagnosis of 6 Clear Cell Papillary Renal Cell Carcinomas. The clinical information and follow-up data were analyzed. The patients were six males with median age of 52.5 years. Case 1 revealed dense calcification and ossification. Cases 2 and 3 contain a variably prominent smooth muscle stromal component. CA-IX, CK7, PAX-8 and VIM were positive in all cases. TFE3 and AMACR were not expressed in any tumor. CD10 was negative in 5 of 6 cases .The patients were followed for 13~55 months with no local tumor recurrences and tumor metastasis. The CCPRCC was associated with a more favorable outcome. These were low-grade and low-stage renal tumors. No lymph node or distant metastasis of the six tumors. PMID:26191150

  15. Difficulty in management of intraductal papillary mucinous neoplasm-associated pancreatobiliary fistulas and the role of “pig-nose” appearance and intraductal ultrasonography in diagnosis

    PubMed Central

    Koizumi, Mitsuhito; Kumagi, Teru; Kuroda, Taira; Azemoto, Nobuaki; Yamanishi, Hirofumi; Ohno, Yoshinori; Yokota, Tomoyuki; Ochi, Hironori; Tange, Kazuhiro; Ikeda, Yoshiou; Hiasa, Yoichi

    2016-01-01

    Pancreatobiliary fistulas associated with intraductal papillary mucinous neoplasms (IPMN) often develop obstructive jaundice and cholangitis; thus, early diagnosis is important. However, computed tomography and cholangiography, the current methods for detecting pancreatobiliary fistulas, are not always effective. We previously reported a case of IPMN-associated pancreatobiliary fistula and proposed a potential new diagnostic marker: the “pig-nose” appearance of the duodenal papilla, which results from dilated pancreatic and bile ducts and can be visualized via endoscopy. In this study, we report another three cases of IPMN-associated pancreatobiliary fistulas detected by a different technology, intraductal ultrasonography (IDUS). As with our previously reported case, we confirmed the utility of the “pig-nose” appearance and IDUS in the diagnosis of IPMN-associated pancreatobiliary fistulas. In addition, we found it difficult to manage biliary obstruction that resulted from the flow of mucinous material through pancreatobiliary fistulas. The obstruction was treated with endoscopic nasal biliary drainage (ENBD), but this was not always successful. In two of our cases, additional treatment with a large diameter fully covered metal stent failed to improve jaundice. Therefore, we conclude that standard endoscopic stenting may not be effective, and that alternative endoscopic methods or surgery may be necessary. PMID:27092326

  16. Difficulty in management of intraductal papillary mucinous neoplasm-associated pancreatobiliary fistulas and the role of "pig-nose" appearance and intraductal ultrasonography in diagnosis.

    PubMed

    Koizumi, Mitsuhito; Kumagi, Teru; Kuroda, Taira; Azemoto, Nobuaki; Yamanishi, Hirofumi; Ohno, Yoshinori; Yokota, Tomoyuki; Ochi, Hironori; Tange, Kazuhiro; Ikeda, Yoshiou; Hiasa, Yoichi

    2016-04-01

    Pancreatobiliary fistulas associated with intraductal papillary mucinous neoplasms (IPMN) often develop obstructive jaundice and cholangitis; thus, early diagnosis is important. However, computed tomography and cholangiography, the current methods for detecting pancreatobiliary fistulas, are not always effective. We previously reported a case of IPMN-associated pancreatobiliary fistula and proposed a potential new diagnostic marker: the "pig-nose" appearance of the duodenal papilla, which results from dilated pancreatic and bile ducts and can be visualized via endoscopy. In this study, we report another three cases of IPMN-associated pancreatobiliary fistulas detected by a different technology, intraductal ultrasonography (IDUS). As with our previously reported case, we confirmed the utility of the "pig-nose" appearance and IDUS in the diagnosis of IPMN-associated pancreatobiliary fistulas. In addition, we found it difficult to manage biliary obstruction that resulted from the flow of mucinous material through pancreatobiliary fistulas. The obstruction was treated with endoscopic nasal biliary drainage (ENBD), but this was not always successful. In two of our cases, additional treatment with a large diameter fully covered metal stent failed to improve jaundice. Therefore, we conclude that standard endoscopic stenting may not be effective, and that alternative endoscopic methods or surgery may be necessary. PMID:27092326

  17. Primary salivary duct carcinoma of the lung, mucin-rich variant.

    PubMed

    Fishbein, Gregory A; Grimes, Brandon S; Xian, Rena R; Lee, Jay M; Barjaktarevic, Igor; Xu, Haodong

    2016-01-01

    Primary salivary gland-type lung cancer is a heterogeneous group of neoplasms arising from the seromucinous glands of the respiratory tract. Histopathologically, they are identical to salivary gland neoplasms of the head and neck. While mucoepidermoid carcinoma and adenoid cystic carcinoma are overwhelmingly the most common subtypes found in the lung, reports of uncommon subtypes can be found in the literature. We report a case of a 73-year-old woman with primary lung salivary duct carcinoma, mucin-rich variant--an exceedingly rare subtype of an already rare malignant salivary-type neoplasm. One case of primary lung salivary duct carcinoma has been reported in the literature; however, the mucin-rich variant has never been described in the lung. Furthermore, the tumor in our case bears a rare BRAF G464V mutation. To our knowledge, this is the first reported case of a BRAF G464V mutation detected in a salivary duct carcinoma or any other salivary-type neoplasm. PMID:26527521

  18. Primary peritoneal serous papillary carcinoma: a study of 25 cases and comparison with stage III-IV ovarian papillary serous carcinoma.

    PubMed

    Ben-Baruch, G; Sivan, E; Moran, O; Rizel, S; Menczer, J; Seidman, D S

    1996-03-01

    The clinical characteristics and treatment outcome of patients with primary peritoneal serous papillary carcinoma (PPSC) (n = 22) was compared with stage III-IV papillary serous ovarian carcinoma (PSOC) patients (n = 63). There were no statistically significant differences between the PPSC and PSOC patients with regard to the mean age, menopausal status, parity, ascites fluid volume, proportion of stage IV disease, and the rate of optimal debulking achieved. The median disease-free interval was 15 and 18 months; the median survival was 21 and 26 months; and the 5-year survival was 18 and 24% for the PPSC and PSOC groups, respectively. The median survival time for patients with a residual tumor > or = 2 cm was 20.5 and 24 months, and for residual tumor > or = 2 cm was 46 and 41 months, in PPSC and PSOC patients, respectively. Survival was thus better, in both groups, when residual disease at the end of the operation was < 2 cm, though this was statistically significant only for PSOC (P < 0.02). We conclude that patients with PPSC should be treated as other stage II-IV PSOC patients. Combining optimal debulking with a platinum-based chemotherapy may offer the patient the most effective treatment. PMID:8774644

  19. Unbalanced 5;16 translocation in a boy with papillary thyroid carcinoma

    SciTech Connect

    McDonald, M.; Maynard, S.; Sheldon, S.; Innis, J.

    1994-02-01

    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.

  20. Metastatic pure papillary thyroid carcinoma presenting as a toxic hot nodule.

    PubMed

    Cirillo, R L; Pozderac, R V; Caniano, D A; Falko, J M

    1998-06-01

    In the majority of cases, carcinoma of the thyroid presents as a cold nodule by radioiodine and Tc-99m sodium pertechnetate scintigraphy. Whereas the presence of a hot nodule usually implies a benign entity, it does not provide complete assurance against thyroid malignancy. Presented is a rare case of metastatic pure papillary thyroid carcinoma appearing as a hot nodule on Tc-99m sodium pertechnetate and I-123 sodium iodide scintigraphy. The implications of such a case, its management, and review of the pertinent literature are discussed. PMID:9619317

  1. Intraductal papillary neoplasm of the bile duct accompanying biliary mixed adenoneuroendocrine carcinoma.

    PubMed

    Onishi, Ichiro; Kitagawa, Hirohisa; Harada, Kenichi; Maruzen, Syogo; Sakai, Seisyo; Makino, Isamu; Hayashi, Hironori; Nakagawara, Hisatoshi; Tajima, Hidehiro; Takamura, Hiroyuki; Tani, Takashi; Kayahara, Masato; Ikeda, Hiroko; Ohta, Tetsuo; Nakanuma, Yasuni

    2013-05-28

    We present the first case of an intraductal papillary neoplasm of the bile duct (IPNB) accompanying a mixed adenoneuroendocrine carcinoma (MANEC). A 74-year-old woman presented with fever of unknown cause. Laboratory data revealed jaundice and liver injury. Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct, which exhibited early enhancement and papillary growth. Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater, characterized by its protruding and dilated orifice. Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct, but no invasive region was suggested by diagnostic imaging. Therefore, the initial diagnosis was IPNB. After endoscopic nasobiliary drainage, a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia, indicating pancreaticobiliary-type IPNB. In addition, solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident. Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component, diagnosing it as a neuroendocrine tumor (NET). Furthermore, the MIB-1 proliferation index of NET was higher than that of IPNB, and microinvasion of the NET component was found, indicating neuroendocrine carcinoma (NET G3). This unique case of MANEC, comprising IPNB and NET, provides insight into the pathogenesis of biliary NET. PMID:23716999

  2. Intraductal papillary neoplasm of the bile duct accompanying biliary mixed adenoneuroendocrine carcinoma

    PubMed Central

    Onishi, Ichiro; Kitagawa, Hirohisa; Harada, Kenichi; Maruzen, Syogo; Sakai, Seisyo; Makino, Isamu; Hayashi, Hironori; Nakagawara, Hisatoshi; Tajima, Hidehiro; Takamura, Hiroyuki; Tani, Takashi; Kayahara, Masato; Ikeda, Hiroko; Ohta, Tetsuo; Nakanuma, Yasuni

    2013-01-01

    We present the first case of an intraductal papillary neoplasm of the bile duct (IPNB) accompanying a mixed adenoneuroendocrine carcinoma (MANEC). A 74-year-old woman presented with fever of unknown cause. Laboratory data revealed jaundice and liver injury. Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct, which exhibited early enhancement and papillary growth. Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater, characterized by its protruding and dilated orifice. Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct, but no invasive region was suggested by diagnostic imaging. Therefore, the initial diagnosis was IPNB. After endoscopic nasobiliary drainage, a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia, indicating pancreaticobiliary-type IPNB. In addition, solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident. Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component, diagnosing it as a neuroendocrine tumor (NET). Furthermore, the MIB-1 proliferation index of NET was higher than that of IPNB, and microinvasion of the NET component was found, indicating neuroendocrine carcinoma (NET G3). This unique case of MANEC, comprising IPNB and NET, provides insight into the pathogenesis of biliary NET. PMID:23716999

  3. Expression of PAX8 Target Genes in Papillary Thyroid Carcinoma.

    PubMed

    Rosignolo, Francesca; Sponziello, Marialuisa; Durante, Cosimo; Puppin, Cinzia; Mio, Catia; Baldan, Federica; Di Loreto, Carla; Russo, Diego; Filetti, Sebastiano; Damante, Giuseppe

    2016-01-01

    PAX8 is a thyroid-specific transcription factor whose expression is dysregulated in thyroid cancer. A recent study using a conditional knock-out mouse model identified 58 putative PAX8 target genes. In the present study, we evaluated the expression of 11 of these genes in normal and tumoral thyroid tissues from patients with papillary thyroid cancer (PTC). ATP1B1, GPC3, KCNIP3, and PRLR transcript levels in tumor tissues were significantly lower in PTCs than in NT, whereas LCN2, LGALS1 and SCD1 expression was upregulated in PTC compared with NT. Principal component analysis of the expression of the most markedly dysregulated PAX8 target genes was able to discriminate between PTC and NT. Immunohistochemistry was used to assess levels of proteins encoded by the two most dyregulated PAX8 target genes, LCN2 and GPC3. Interestingly, GPC3 was detectable in all of the NT samples but none of the PTC samples. Collectively, these findings point to significant PTC-associated dysregulation of several PAX8 target genes, supporting the notion that PAX8-regulated molecular cascades play important roles during thyroid tumorigenesis. PMID:27249794

  4. Expression of PAX8 Target Genes in Papillary Thyroid Carcinoma

    PubMed Central

    Rosignolo, Francesca; Sponziello, Marialuisa; Durante, Cosimo; Puppin, Cinzia; Mio, Catia; Baldan, Federica; Di Loreto, Carla; Russo, Diego; Filetti, Sebastiano; Damante, Giuseppe

    2016-01-01

    PAX8 is a thyroid-specific transcription factor whose expression is dysregulated in thyroid cancer. A recent study using a conditional knock-out mouse model identified 58 putative PAX8 target genes. In the present study, we evaluated the expression of 11 of these genes in normal and tumoral thyroid tissues from patients with papillary thyroid cancer (PTC). ATP1B1, GPC3, KCNIP3, and PRLR transcript levels in tumor tissues were significantly lower in PTCs than in NT, whereas LCN2, LGALS1 and SCD1 expression was upregulated in PTC compared with NT. Principal component analysis of the expression of the most markedly dysregulated PAX8 target genes was able to discriminate between PTC and NT. Immunohistochemistry was used to assess levels of proteins encoded by the two most dyregulated PAX8 target genes, LCN2 and GPC3. Interestingly, GPC3 was detectable in all of the NT samples but none of the PTC samples. Collectively, these findings point to significant PTC-associated dysregulation of several PAX8 target genes, supporting the notion that PAX8-regulated molecular cascades play important roles during thyroid tumorigenesis. PMID:27249794

  5. A Case of Primary Mammary Analog Secretory Carcinoma (MASC) of the Thyroid Masquerading as Papillary Thyroid Carcinoma: Potentially More than a One Off.

    PubMed

    Reynolds, S; Shaheen, M; Olson, G; Barry, M; Wu, J; Bocklage, T

    2016-09-01

    We present the second reported mammary analog secretory carcinoma (MASC) apparently arising in the thyroid and propose a potential close relationship to ETV6-NTRK3 fusion papillary thyroid carcinoma. The patient, a 36 year old woman, presented with a neck mass of 1 year's duration. Imaging studies showed a tumor involving most of the thyroid with enlarged regional lymph nodes. FNA biopsy yielded a diagnosis of "papillary thyroid carcinoma". Resection revealed a 4.5 cm infiltrative tumor. Final diagnosis was "papillary thyroid carcinoma (PTC) consistent with diffuse sclerosing variant" with positive lymph nodes (2+/4) and margins. Histologic features included mixed microcystic, solid, follicular and papillary architecture, prominent nucleoli, abundant nuclear grooves and rare nuclear pseudo-inclusions. Despite radioactive iodine, radiotherapy and multiagent chemotherapy, the patient progressed over 6 years with local recurrence and additional lymph node involvement finally developing widespread distant metastases. Prompted by the breast carcinoma-like histopathology of a metastasis, immunohistochemical staining was performed and revealed strong expression of GATA3 and mammaglobin with no reactivity for thyroglobulin or TTF-1. The original tumor was then tested and showed the same immunoprofile. RT-PCR confirmed the presence of an ETV6-NTRK3 fusion consistent with a diagnosis of MASC. Our patient's clinical, imaging and morphologic features remarkably mimicked papillary thyroid carcinoma. At the molecular level, the ETV6-NTRK3 fusion in this patient involved exons reported in the rare "papillary thyroid carcinoma" with this translocation. Given the immunophenotype of this case, it is possible that at least some ETV6-NTRK3 fusion positive PTC are actually MASC masquerading as papillary thyroid carcinoma. PMID:27075025

  6. Clear Cell Renal Cell Carcinoma With Borderline Features of Clear Cell Papillary Renal Cell Carcinoma: Combined Morphologic, Immunohistochemical, and Cytogenetic Analysis.

    PubMed

    Williamson, Sean R; Gupta, Nilesh S; Eble, John N; Rogers, Craig G; Michalowski, Susan; Zhang, Shaobo; Wang, Mingsheng; Grignon, David J; Cheng, Liang

    2015-11-01

    Clear cell papillary renal cell carcinoma is increasingly recognized as a distinct tumor with unique morphology, immunohistochemistry, and cytogenetics. Histopathology often mimics clear cell renal cell carcinoma; however, metastasis has not been reported, emphasizing the clinical value of recognizing these likely nonaggressive tumors. We studied tumors with borderline morphology of clear cell papillary renal cell carcinoma, utilizing immunohistochemistry and fluorescence in situ hybridization or karyotyping. Tumors from 22 patients (ages 33 to 82 y) were analyzed. Clear cell papillary renal cell carcinoma-like morphology varied from 10% to 90% of the tumor (median 25%). Sources of resemblance included: branched glands (95%), nuclear alignment (68%), small papillary tufts (32%), focal branching papillae (27%), and prominent papillary structures (9%). Carbonic anhydrase IX uniformly revealed diffuse positivity. Staining for cytokeratin 7 (CK7) was focal (64%) or negative (18%) in most tumors (82%); however, >50% labeling was present in 4 (18%). Reactivity for both CD10 and α-methyl-acyl-CoA-racemase (AMACR) was usually present (median 80% and 60% of cells). Seven tumors showed reactivity for high-molecular weight keratin (32%). Chromosome 3p loss was confirmed in 15 tumors (68%), including 4/7 with labeling for high-molecular weight keratin or >50% reactivity for CK7. A discordant immunohistochemical pattern typically correlates with loss of material from chromosome 3p in tumors with incomplete morphology of clear cell papillary renal cell carcinoma, supporting classification as clear cell renal cell carcinoma. Diffuse labeling for CK7 can uncommonly be observed in clear cell renal cell carcinomas confirmed to have chromosome 3p loss, although these do not exhibit the expected staining pattern of clear cell papillary renal cell carcinoma, including positivity for CD10 and AMACR. PMID:26457355

  7. Stratified mucin-producing intraepithelial lesion with invasive carcinoma: 12 cases with immunohistochemical and ultrastructural findings.

    PubMed

    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. PMID:27237368

  8. Immunohistochemical analysis of steroidogenic enzymes in ovarian-type stroma of pancreatic mucinous cystic neoplasms: Comparative study of subepithelial stromal cells in intraductal papillary mucinous neoplasms of the pancreas.

    PubMed

    Ishida, Kazuyuki; Sasano, Hironobu; Moriya, Takuya; Takahashi, Yayoi; Sugimoto, Ryo; Mue, Yoshiharu; Murakami, Keigo; Fujishima, Fumiyoshi; Nakamura, Yasuhiro; Morikawa, Takanori; Motoi, Fuyuhiko; Suzuki, Takashi; Unno, Michiaki; Sugai, Tamotsu

    2016-05-01

    Mucinous cystic neoplasms (MCNs) are generally defined as cyst-forming epithelial neoplasms that arise in the pancreas and harbor characteristic ovarian-type stroma beneath the epithelium. In this study, we compared the immunoreactivity of steroid-related factors in these subepithelial stromal cells in MCNs to those in intraductal papillary mucinous neoplasms (IPMNs) to further characterize this unique MCN ovarian-type stroma through evaluation of sex steroid biosynthesis. Twenty MCNs and twenty IPMNs were examined. Immunoreactivity of steroid hormone receptors, including estrogen receptor (ERα and ERβ), progesterone receptor (PR, PR-A, and PR-B), and androgen receptor (AR), was more frequently detected in MCN ovarian-type stromal cells than in IPMN stromal cells (P < 0.01). The H-scores (mean ± SD) of steroidogenic factor (SF)-1 were also significantly higher in MCNs (112.3 ± 33.1) than in IPMNs (0.9 ± 1.2) (P < 0.01). The steroidogenic enzymes cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), cytochrome P450 17 alpha-hydroxylase (P450c17) and 3β-hydroxysteroid dehydrogenase (3β-HSD) showed immunoreactivity in 9/20 (45.0 %), 15/20 (75.0 %) and 13/20 (65.0 %), respectively, of ovarian-type stroma from MCN cases. These results demonstrate that the ovarian-type stroma of MCNs can express steroidogenic enzymes. Thus, the ovarian-type stroma of MCNs can produce sex steroids that may also act on these cells. PMID:27060902

  9. Current strategies for surgical management and adjuvant treatment of childhood papillary thyroid carcinoma.

    PubMed

    Thompson, Geoffrey B; Hay, Ian D

    2004-12-01

    Childhood papillary thyroid carcinoma is associated with more locally aggressive and more frequent distant disease than its adult counterpart. Recurrence rates tend to be higher in children, but cause-specific mortality remains low. Optimal initial treatment of childhood papillary thyroid carcinoma should include total or near-total thyroidectomy and central compartment node clearance. Modified neck dissections should be performed for biopsy-proven lateral neck disease. Every effort should be made to maintain parathyroid and laryngeal nerve function. Radical neck dissections are to be avoided. Radioiodine remnant ablation (RRA), appropriate thyroid hormone suppressive therapy (THST), and judicious use of therapeutic doses of (131)I are applied to achieve a disease-free status, which is most often confirmed by negative neck ultrasonography, negative whole-body scan (either withdrawal or recombinant human thyroid-stimulating hormone-stimulated), and extremely low levels of serum thyroglobulin. Appropriate utilization of (131)I, THST, repeat surgery, external beam radiotherapy, and rarely chemotherapy may provide long-term palliation and some cures in patients with recurrent/persistent disease. Follow-up should be lifelong, and the care of children after age 17 should subsequently be transferred to adult-care endocrinologists with expertise in managing thyroid neoplasia. Optimal surgical management can be achieved if adequate operations are routinely carried out by "high-volume" thyroid surgeons with expertise in the care of children. Nowhere is a multidisciplinary approach (endocrinologists, surgeons, nuclear medicine physicians, pediatricians, pathologists, oncologists) more critical than in the long-term management of papillary thyroid carcinoma that presents during childhood. PMID:15517490

  10. Application of a cervical low incision in the functional neck dissection of thyroid papillary carcinoma

    PubMed Central

    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

  11. Cytological and molecular diagnosis of solid variant of papillary thyroid carcinoma: A case report

    PubMed Central

    Troncone, Giancarlo; Russo, Maria; Malapelle, Umberto; Accardo, Marina; Ferraro, Angelo; Cozzolino, Immacolata; Palombini, Lucio

    2008-01-01

    Papillary thyroid carcinoma (PTC) composed by predominant solid areas is diagnosed as a distinct variant on histological samples. Here we present a case of PTC recognized preoperatively by fine needle cytology as a solid variant. This diagnosis was made by combining cytology with the detection of the BRAFVK600-1E mutation, the molecular hallmark of the solid variant of PTC. Histological and molecular evaluation of the surgical specimen confirmed this pre-operative diagnosis. Thus combining cytology to BRAF molecular analysis is useful to refine the cytological diagnosis of this variant also on FNC specimens. PMID:18353179

  12. Incidental Detection of Oxyphilic Papillary Thyroid Carcinoma by 18F-Fluorocholine PET/CT.

    PubMed

    Lalire, Paul; Zalzali, Mohamed; Garbar, Christian; Bruna-Muraille, Claire; Morland, David

    2016-06-01

    A 70-year-old man with prostate cancer and increased prostate-specific antigen level of 55 ng/mL underwent staging F-fluorocholine PET/CT, which demonstrated the primary prostate tumor and a focal area corresponding to a 2-cm hypodense nodule in the left thyroid lobe. Fine-needle aspiration and subsequent total thyroidectomy with central lymph node dissection showed an oxyphilic papillary thyroid carcinoma and a medullary microcarcinoma. Oxyphilic tumors represent a significant proportion of the few case reports of incidental focal thyroid fluorocholine thyroid uptake. PMID:26914574

  13. Identification of Protein Markers Specific for Papillary Renal Cell Carcinoma Using Imaging Mass Spectrometry

    PubMed Central

    Na, Chan Hyun; Hong, Ji Hye; Kim, Wan Sup; Shanta, Selina Rahman; Bang, Joo Yong; Park, Dongmin; Kim, Hark Kyun; Kim, Kwang Pyo

    2015-01-01

    Since the emergence of proteomics methods, many proteins specific for renal cell carcinoma (RCC) have been identified. Despite their usefulness for the specific diagnosis of RCC, such proteins do not provide spatial information on the diseased tissue. Therefore, the identification of cancer-specific proteins that include information on their specific location is needed. Recently, matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) based imaging mass spectrometry (IMS) has emerged as a new tool for the analysis of spatial distribution as well as identification of either proteins or small molecules in tissues. In this report, surgical tissue sections of papillary RCC were analyzed using MALDI-IMS. Statistical analysis revealed several discriminative cancer-specific m/z-species between normal and diseased tissues. Among these m/z-species, two particular proteins, S100A11 and ferritin light chain, which are specific for papillary RCC cancer regions, were successfully identified using LC-MS/MS following protein extraction from independent RCC samples. The expressions of S100A11 and ferritin light chain were further validated by immunohistochemistry of human tissues and tissue microarrays (TMAs) of RCC. In conclusion, MALDI-IMS followed by LC-MS/MS analysis in human tissue identified that S100A11 and ferritin light chain are differentially expressed proteins in papillary RCC cancer regions. PMID:26062552

  14. Mucinous Pleural Effusion in a Dog with a Pulmonary Adenocarcinoma and Carcinomatosis.

    PubMed

    Tropf, Melissa; Sellon, Rance; Paulson, Kathleen; Nelson, Danielle

    2015-01-01

    An 11 yr old castrated male greyhound presented to the Washington State University's Veterinary Teaching Hospital (WSU VTH) for evaluation of a 4 day history of pleural effusion. The pleural effusion had a gelatinous appearance, suggestive of mucus, and was characterized cytologically as a pyogranulomatous exudate with some features suggestive of a carcinoma. Postmortem examination identified a pulmonary mass with evidence of carcinomatosis. Pulmonary papillary adenocarcinoma with carcinomatosis was the histologic diagnosis. Abundant mucin production was present, consistent with a mucinous pulmonary adenocarcinoma. To the authors' knowledge, this is the first report of a mucinous pulmonary adenocarcinoma with mucus pleural effusion in a dog. PMID:26355581

  15. Needle tract implantation of papillary thyroid carcinoma after fine-needle aspiration biopsy.

    PubMed

    Ito, Yasuhiro; Tomoda, Chisato; Uruno, Takashi; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Matsuzuka, Fumio; Kuma, Kanji; Miyauchi, Akira

    2005-12-01

    Although fine-needle aspiration biopsy (FNAB) is a useful tool for diagnosing thyroid carcinoma, there are some risks of complications. In this study, we investigated tumor implantation by FNAB of papillary carcinoma. We compared the characteristics of the main tumors and implanted tumors of patients showing FNAB implantations. Between 1990 and 2002, 4912 patients underwent FNAB and were diagnosed as having papillary carcinoma. We encountered 7 cases of needle tract implantation, which account only for 0.14%. We reviewed these 7 cases as well as 3 other patients who underwent FNAB in other hospitals. The intervals between FNAB and detection of the implanted tumor ranged from 2 to 131 months. For these 10 patients, the main tumors in 6 were diagnosed as poorly differentiated carcinoma, and 7 showed extrathyroid extension. Five showed the development of implanted tumor after comparatively shorter intervals (2-68 months), and we classified these as the short interval group. The remaining 5 were classified as the long interval group, because tumor development occurred after 87-131 months. All 5 cases in the short interval group involved preoperatively detectable lymph node metastasis; those in the long interval group did not. The MIB-1 labeling index of the implanted tumor was high in 4 cases in the short interval group, but it was low in all cases in the long interval group. The implanted tumors could be surgically removed without recurrence at the focal sites. These findings indicate that, although high growth activity in the metastatic lesions may be a risk factor of FNAB, inducing the growth of implanted tumors along the needle tract within a short interval after the procedure, FNAB remains the most useful technique for diagnosing thyroid carcinoma. The incidence of implantation was low, and when it did occur, the tumors could be surgically removed without recurrence. PMID:16311845

  16. Clear cell papillary renal cell carcinoma and clear cell renal cell carcinoma arising in acquired cystic disease of the kidney: an immunohistochemical and genetic study.

    PubMed

    Kuroda, Naoto; Shiotsu, Tomoyuki; Kawada, Chiaki; Shuin, Taro; Hes, Ondrej; Michal, Michal; Ohe, Chisato; Mikami, Shuji; Pan, Chin-Chen

    2011-08-01

    Clear cell papillary renal cell carcinoma (RCC) is a recently established disease entity. However, there are few reports on genetic study of this entity. We report such a case with focus on genetic study. A 57-year-old Japanese man was found to have 3 renal tumors. Histologically, two tumors showed findings of clear cell RCC; and the other tumor showed findings of clear cell papillary RCC that was characterized by papillary growth pattern of neoplastic cells in cystic space with purely clear cell cytology. Immunohistochemically, tumor cells of clear cell papillary RCC were diffusely positive for PAX2 and cytokeratin 7, but negative for CD10, RCC Ma, and AMACR. In fluorescence in situ hybridization study for one clear cell papillary RCC, we detected polysomy for chromosome 7 and monosomy for chromosomes 17, 16, and 20. In addition, we detected mutation of VHL gene in clear cell RCC, but found no VHL gene mutation in clear cell papillary RCC. Finally, our results provide further evidence that clear cell papillary RCC may be both morphologically and genetically distinct entity from clear cell RCC and papillary RCC. PMID:20952286

  17. Krukenberg carcinoma metastasized from stomach resembling mucinous cystadenocarcinoma of the ovary.

    PubMed

    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. PMID:26259386

  18. Recurrent intestinal mucinous borderline tumors of the ovary: a report of 5 cases causing problems in diagnosis, including distinction from mucinous carcinoma.

    PubMed

    Irving, Julie A; Clement, Philip B

    2014-03-01

    Intestinal mucinous borderline tumors (IMBTs) of the ovary are generally associated with a highly favorable outcome and rarely recur. We describe 5 cases of IMBT initially treated by cystectomy or by salpingo-oophorectomy that was likely incomplete, with subsequent recurrences. Three cases were received in consultation, and in each of these, the clinical and intraoperative findings were worrisome for mucinous carcinoma, and diagnostic difficulty was encountered by the referring pathologist. The patient age ranged from 28 to 69 (median 53) yrs. All tumors were clinically Stage I at presentation; in at least 3 cases, extensive adhesiolysis was required during their removal. A pathologic diagnosis of IMBT was made in 4 cases; the remaining tumor was inadequately sampled (3 blocks from a 7.5-cm tumor showed predominantly benign to focally borderline mucinous epithelium). A total of 8 recurrences, all as IMBT, developed at mean follow-up of 26 (range, 6-102) mo; 6 of these occurred within ≤2 yr. In 4 cases, removal of recurrent tumor required an extensive operation because of bowel and/or vaginal involvement. Residual ovarian stroma was identified in all recurrences. There was no evidence of invasive mucinous carcinoma, pseudomyxoma peritonei, or a primary tumor elsewhere (including appendix) in any of the cases. Our findings indicate that patients with IMBTs who undergo cystectomy or oophorectomy requiring adhesiolysis are at increased risk of recurrence, which may occur early, be multiple, and potentially require extensive resection if sites such as bowel or vagina are involved. Recurrences of IMBT that develop in this setting likely represent regrowth of incompletely resected IMBT, or arise within residual ovarian tissue. This is the first detailed clinicopathologic study of such cases. PMID:24487471

  19. Impact of prophylactic central neck dissection on oncologic outcomes of papillary thyroid carcinoma: a review

    PubMed Central

    Mamelle, Elisabeth; Borget, Isabelle; Leboulleux, Sophie; Mirghani, Haïtham; Suárez, Carlos; Pellitteri, Phillip K.; Shaha, Ashok R.; Hamoir, Marc; Robbins, K. Thomas; Khafif, Avi; Rodrigo, Juan P.; Silver, Carl E.; Rinaldo, Alessandra; Ferlito, Alfio; Hartl, Dana M.

    2016-01-01

    Prophylactic neck dissection (PND) for papillary thyroid carcinoma (PTC) is controversial. Our aim was to assess current levels of evidence (LE) according to the Oxford Centre for Evidence-based Medicine (http://www.cebm.net/?O=1025) regarding the oncologic benefits of PND. Data were analyzed via MEDLINE key-words: PTC, differentiated thyroid carcinoma, PND, central lymph node metastases, central compartment, recurrence-free survival. There was conflicting evidence regarding the rate of reoperation for recurrence, with some studies showing a lower rate after PND with increased recurrence-free survival and a higher rate of undetectable pre- and post-ablation thyroglobulin levels (LE 4), whereas other studies did not show a difference (LE 4). Only one study (LE 4) showed improved disease-specific survival with PND. PND may improve recurrence-free survival, although this is supported by only a low LE. Current recommendations can only be based on low-level evidence. PMID:25022716

  20. Follicular variant of papillary thyroid carcinoma: an unusual cause of thyrotoxicosis.

    PubMed

    Rees, David Owen; Anthony, Victoria Angharad; Jones, Keston; Stephens, Jeffrey W

    2015-01-01

    Thyroid carcinoma presenting as a hyperfunctioning thyroid nodule is rare. A further complexity is added when interpretation of the histopathology itself is not straightforward. We describe a case of a 16-year-old girl presenting with clinical and biochemical evidence of thyrotoxicosis, and a 4 cm thyroid mass. An ultrasound and thyroid uptake scan demonstrated a toxic adenoma. Owing to the nodule size, fine needle aspiration of the thyroid adenoma was performed, which showed findings consistent with toxic adenoma. However, in view of the size of the nodule, a hemithyroidectomy was performed. Histological examination of the thyroid revealed a follicular variant of papillary carcinoma of the thyroid, and the patient underwent completion thyroidectomy. We report on the case and briefly review the available literature relating to the diagnostic challenge of this presentation. PMID:25948842

  1. Squamous Cell Carcinoma of the Larynx Arising in Multifocal Pharyngolaryngeal Oncocytic Papillary Cystadenoma

    PubMed Central

    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

  2. Two papillary renal cell carcinomas of different origin following renal transplantation (Case report).

    PubMed

    Gerth, Hans-Ulrich; Pohlen, Michele; Thoennissen, Nils-Heinrich; Suwelack, Barbara; Pavenstädt, Hermann-Josef; Störkel, Stefan; Abbas, Mahmoud; Spieker, Tilmann; Thölking, Gerold

    2012-07-01

    Papillary renal cell carcinoma (PRCC) is a rare malignant tumor entity compared to common clear cell renal carcinoma. In the present study, we report a patient who was diagnosed with PRCC twice and successfully treated each time following renal transplantation. The first PRCC was located in the left native kidney two years following transplantation, and the second PRCC was diagnosed in the allograft 13 years following transplantation. The two tumors were completely removed by surgery in stage I of the disease with sufficient conservation of the allograft function. Notably, the tumors had a different origin as indicated by the microsatellite analysis, which reflects the exceptional course of the case. Risk factors for PRCC were identified in our patient. We concluded that high-risk candidates for malignancies in renal transplant recipients should receive shorter ultrasonic screening intervals, which may facilitate early tumor detection and improve outcome rates. PMID:22807965

  3. Genetic imbalance on chromosome 17 in papillary serous carcinoma of the peritoneum.

    PubMed

    Bandera, C A; Muto, M G; Welch, W R; Berkowitz, R S; Mok, S C

    1998-07-01

    We extend the evaluation of allelic loss patterns on chromosome 17 to papillary serous carcinoma of the peritoneum (PSCP) which is histologically identical to papillary serous ovarian carcinoma (PSOC). DNA was obtained from 11 archival cases of PSCP, with 1-11 tumor sites per case. Using ten loci spanning chromosome 17, loss of heterozygosity (LOH) was identified in all 11 cases (100%). Furthermore, 75-100% of informative cases exhibited LOH at the loci p53, D17S1322 (intragenic to the tumor suppressor gene BRCA1), D17S1327 and MPO. PSCP cases exhibit a higher rate of LOH at most loci when compared with PSOC. Alternating allelic loss at different tumor sites was identified in three cases supporting a multifocal origin of PSCP. Microsatellite instability (MI) is an uncommon event which was identified in four cases. These data implicate chromosome 17 as a potential location of genetic events important in the pathogenesis of PSCP as well as ovarian cancer. PMID:9692553

  4. Langerhans Cell Histiocytosis of the Thyroid with Multiple Cervical Lymph Node Involvement Accompanying Metastatic Thyroid Papillary Carcinoma

    PubMed Central

    Ceyran, A. Bahar; Şenol, Serkan; Bayraktar, Barış; Özkanlı, Şeyma; Cinel, Z. Leyla; Aydın, Abdullah

    2014-01-01

    A 37-year-old male case was admitted with goiter. Ultrasonography of thyroid showed a 5 cm cystic nodule in the left lobe with a 1.5 cm solid component. Fine needle aspiration biopsy revealed atypia of undetermined significance or follicular lesion. The patient was operated on. The pathological diagnosis was reported as papillary thyroid carcinoma. The immunohistochemical examination showed multiple foci of Langerhans cell histiocytosis involving both lobes. The patient died due to cardiac arrest with respiratory causes in the early postoperative period. Langerhans cell histiocytosis is a rare primary condition which involves abnormal clonal proliferation of Langerhans cells in various tissues and organs. Thyroid involvement is infrequently seen. Although the etiology is unknown, genetic components may be linked to the disease. It is also associated with a family history of thyroid disease. Papillary thyroid carcinoma is the most common malignant epithelial tumor of the thyroid gland. Langerhans cell histiocytosis presenting with papillary thyroid carcinoma is rare. The privilege of our case is langerhans cell histiocytosis of the thyroid with multiple cervical lymph node involvement accompanying cervical lymph node metastatic thyroid papillary carcinoma. PMID:25349760

  5. Langerhans cell histiocytosis of the thyroid with multiple cervical lymph node involvement accompanying metastatic thyroid papillary carcinoma.

    PubMed

    Ceyran, A Bahar; Senol, Serkan; Bayraktar, Barış; Ozkanlı, Seyma; Cinel, Z Leyla; Aydın, Abdullah

    2014-01-01

    A 37-year-old male case was admitted with goiter. Ultrasonography of thyroid showed a 5 cm cystic nodule in the left lobe with a 1.5 cm solid component. Fine needle aspiration biopsy revealed atypia of undetermined significance or follicular lesion. The patient was operated on. The pathological diagnosis was reported as papillary thyroid carcinoma. The immunohistochemical examination showed multiple foci of Langerhans cell histiocytosis involving both lobes. The patient died due to cardiac arrest with respiratory causes in the early postoperative period. Langerhans cell histiocytosis is a rare primary condition which involves abnormal clonal proliferation of Langerhans cells in various tissues and organs. Thyroid involvement is infrequently seen. Although the etiology is unknown, genetic components may be linked to the disease. It is also associated with a family history of thyroid disease. Papillary thyroid carcinoma is the most common malignant epithelial tumor of the thyroid gland. Langerhans cell histiocytosis presenting with papillary thyroid carcinoma is rare. The privilege of our case is langerhans cell histiocytosis of the thyroid with multiple cervical lymph node involvement accompanying cervical lymph node metastatic thyroid papillary carcinoma. PMID:25349760

  6. Frequent KRAS mutation in complex mucinous epithelial lesions of the endometrium.

    PubMed

    Alomari, Ahmed; Abi-Raad, Rita; Buza, Natalia; Hui, Pei

    2014-05-01

    KRAS mutation correlates with mucinous differentiation in various human cancers, and recently, was found in a high proportion of a small cohort of papillary mucinous lesions of the endometrium. In this study, a large number of endometrial mucinous lesions were analyzed for the presence of KRAS mutation along with clinical progression. A total of 45 endometrial biopsy/curettage cases were included in the study and classified into the following categories: simple mucinous change (5 cases), complex mucinous change (33 cases) and mucinous adenocarcinoma (7 cases). Follow-up hysterectomy specimens were available in 14 of 33 patients (42%) with complex mucinous lesions, of which 9 cases (64%) showed atypical complex hyperplasia with an average interval of 21 weeks. None of the 5 cases of simple mucinous change showed KRAS mutation. KRAS mutation was observed in 18 of 33 patients with complex mucinous lesions (55%) and in 6 of 7 cases of mucinous adenocarcinoma (86%). Overall, KRAS mutation has a positive predictive value (PPV) of 88% (7/8 cases) for complex atypical hyperplasia or adenocarcinoma in the follow-up hysterectomy. In conclusion, the current data further emphasizes the architectural complexity as an important prognostic indicator for patients with mucinous endometrial lesions. The presence of KRAS mutation in both mucinous adenocarcinoma and complex mucinous changes indicates that KRAS mutational activation is implicated in the pathogenesis of a significant subset of endometrial mucinous carcinoma. With a high PPV, KRAS mutation analysis may offer an additional discriminatory power to refine risk stratification algorithm for patients with endometrial mucinous lesions. PMID:24186144

  7. BRAF and Epithelial-Mesenchymal Transition: Lessons From Papillary Thyroid Carcinoma and Primary Cutaneous Melanoma.

    PubMed

    Mitchell, Brendon; Dhingra, Jagdish K; Mahalingam, Meera

    2016-07-01

    The increased prevalence of BRAF mutations in thyroid carcinoma and primary cutaneous melanoma (PCM) hint that dysregulation of BRAF might contribute to the noted association between PCM and thyroid carcinoma. A recent study evaluating the rate of BRAFV600E mutations among patients who had been diagnosed with primary papillary thyroid carcinoma (PTC) and PCM showed that patients with either PCM or PTC were at an increased risk of developing the other as a second primary malignant neoplasm. Furthermore, the authors noted that samples from patients suffering from both malignancies exhibited a higher rate of incidence of the BRAFV600E mutation, compared with patients not suffering from both malignancies. These studies support the hypothesis that the pathogenesis of these 2 malignancies might share a conserved molecular pattern associated with dysregulation of the BRAF protein. One mechanism through which BRAF might contribute to PCM and thyroid carcinoma progression is through induction of epithelial-mesenchymal transition (EMT). Specifically, the Snail/E-cadherin axis has been demonstrated as a pathway dysregulated by BRAF, leading to EMT in both malignancies. Our analysis focuses on the results of these recent investigations, and through a review of select molecules relevant to EMT, looks to provide a context by which to better understand the relevance and role of stromal-parenchymal signaling and the BRAF mutation in the pathogenesis of PTC and PCM. PMID:27145091

  8. TROP-2 immunohistochemistry: a highly accurate method in the differential diagnosis of papillary thyroid carcinoma.

    PubMed

    Bychkov, Andrey; Sampatanukul, Pichet; Shuangshoti, Shanop; Keelawat, Somboon

    2016-08-01

    We aimed to evaluate the diagnostic utility of the novel immunohistochemical marker TROP-2 on thyroid specimens (226 tumours and 207 controls). Whole slide immunohistochemistry was performed and scored by automated digital image analysis. Non-neoplastic thyroid, follicular adenomas, follicular carcinomas, and medullary carcinomas were negative for TROP-2 immunostaining. The majority of papillary thyroid carcinoma (PTC) specimens (94/114, 82.5%) were positive for TROP-2; however, the pattern of staining differed significantly between the histopathological variants. All papillary microcarcinomas (mPTC), PTC classic variant (PTC cv), and tall cell variant (PTC tcv) were TROP-2 positive, with mainly diffuse staining. In contrast, less than half of the PTC follicular variant specimens were positive for TROP-2, with only focal immunoreactivity. TROP-2 could identify PTC cv with 98.1% sensitivity and 97.5% specificity. ROC curve analysis found that the presence of >10% of TROP-2 positive cells in a tumour supported a diagnosis of PTC. The study of intratumoural heterogeneity showed that low-volume cytological samples of PTC cv could be adequately assessed by TROP-2 immunostaining. The TROP-2 H-score (intensity multiplied by proportion) was significantly associated with PTC variant and capsular invasion in encapsulated PTC follicular variant (p<0.001). None of the baseline (age, gender) and clinical (tumour size, nodal disease, stage) parameters were correlated with TROP-2 expression. In conclusion, TROP-2 membranous staining is a very sensitive and specific marker for PTC cv, PTC tcv, and mPTC, with high overall specificity for PTC. PMID:27311870

  9. GNAS(R201H) and Kras(G12D) cooperate to promote murine pancreatic tumorigenesis recapitulating human intraductal papillary mucinous neoplasm.

    PubMed

    Taki, K; Ohmuraya, M; Tanji, E; Komatsu, H; Hashimoto, D; Semba, K; Araki, K; Kawaguchi, Y; Baba, H; Furukawa, T

    2016-05-01

    Intraductal papillary mucinous neoplasm (IPMN), the most common pancreatic cystic neoplasm, is known to progress to invasive ductal adenocarcinoma. IPMNs commonly harbor activating somatic mutations in GNAS and KRAS, primarily GNAS(R201H) and KRAS(G12D). GNAS encodes the stimulatory G-protein α subunit (Gsα) that mediates a stimulatory signal to adenylyl cyclase to produce cyclic adenosine monophosphate (cAMP), subsequently activating cAMP-dependent protein kinase A. The GNAS(R201H) mutation results in constitutive activation of Gsα. To study the potential role of GNAS in pancreatic tumorigenesis in vivo, we generated lines of transgenic mice in which the transgene consisted of Lox-STOP-Lox (LSL)-GNAS(R201H) under the control of the CAG promoter (Tg(CAG-LSL-GNAS)). These mice were crossed with pancreatic transcription factor 1a (Ptf1a)-Cre mice (Ptf1a(Cre/+)), generating Tg(CAG-LSL-GNAS);Ptf1a(Cre/+) mice. This mouse line showed elevated cAMP levels, small dilated tubular complex formation, loss of acinar cells and fibrosis in the pancreas; however, no macroscopic tumorigenesis was apparent by 2 months of age. We then crossed Tg(CAG-LSL-GNAS);Ptf1a(Cre/+) mice with LSL-Kras(G12D) mice, generating Tg(CAG-LSL-GNAS);LSL-Kras(G12D);Ptf1a(Cre/+) mice. We used these mice to investigate a possible cooperative effect of GNAS(R201H) and Kras(G12D) in pancreatic tumorigenesis. Within 5 weeks, Tg(CAG-LSL-GNAS);LSL-Kras(G12D);Ptf1a(Cre/+) mice developed a cystic tumor consisting of marked dilated ducts lined with papillary dysplastic epithelia in the pancreas, which closely mimicked the human IPMN. Our data strongly suggest that activating mutations in GNAS and Kras cooperatively promote murine pancreatic tumorigenesis, which recapitulates IPMN. Our mouse model may serve as a unique in vivo platform to find biomarkers and effective drugs for diseases associated with GNAS mutations. PMID:26257060

  10. Squamous esophageal carcinoma and mucinous adenocarcinoma of the colon - an unusual association.

    PubMed

    Mirea, Cecil Sorin; Vasile, Manuela Ioana; Vîlcea, Ionică Daniel; Vasile, Ion; Moraru, Emil; Ciorbagiu, Mihai Călin; Sfeclan, Maria Cristina; Marin, Cătălina; Obleagă, Vasile Cosmin; Gheonea, Ioana Andreea; Vîlcea, Alina Maria

    2016-01-01

    The existence of a simultaneous cancer of the esophagus and colon is a rare situation that recognizes an increased incidence in recent years in the world, probably as a result of the improved measures of diagnosis and treatment, as well as the development of screening programs. The aim of this work is to present a case of synchronous esophageal squamous carcinoma with mucinous adenocarcinoma of the hepatic angle of the colon. The patient was hospitalized to our Surgical Clinic with the thoracic squamous esophageal carcinoma diagnosis. On admission, symptoms were dominated by overall dysphagia, patient showing a weight loss of 10 kg for the last 30 days. Preoperative imaging tests did not revealed regional or distant metastatic disease. Preoperative colonoscopy was incomplete (only until the splenic angle of the left colon) due to the insufficient mechanical preparation. On laparotomy, a carcinoma of the hepatic angle of the colon, partially stenosing was discovered. An upper pole esogastrectomy with intrathoracic esogastrostomy and a right colectomy with ileotransversostomy were practiced, at the same operative session. Postoperative evolution was poor and the patient died on the ninth day from the surgery during an alcohol withdrawal crisis. PMID:27151719

  11. Polymorphic epithelial mucin (MUC-1)-containing circulating immune complexes in carcinoma patients.

    PubMed Central

    Gourevitch, M. M.; von Mensdorff-Pouilly, S.; Litvinov, S. V.; Kenemans, P.; van Kamp, G. J.; Verstraeten, A. A.; Hilgers, J.

    1995-01-01

    Circulating immune complexes (CICs) containing polymorphic epithelial mucin (PEM/MUC-1) were found in sera of 24.5% of 151 primary breast carcinoma patients and 18-21.4% of patients with advanced ovarian (n = 56) and breast carcinomas (n = 61), 37% of patients with benign breast tumours, but in only 2.1% of 96 healthy individuals. The incorporation of PEM into CICs affects the detection of circulating PEM in commercial immunoassays such as the CA 15-3 assay, as suggested by a negative correlation between levels of PEM-containing immune complexes (PEM-CICs) and CA 15-3 values, and confirmed by isolation of PEM from CA 15-3-negative sera containing high levels of PEM-CICs. The amounts of PEM masked by human antibodies correspond to significant values of the CA 15-3 assay when monitoring patients for carcinoma. Most antibodies in PEM-CICs were of IgG class, suggesting their specific nature to the PEM epitopes. Images Figure 3 PMID:7547243

  12. Intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia is a risk factor for the subsequent development of pancreatic ductal adenocarcinoma☆

    PubMed Central

    Rezaee, Neda; Barbon, Carlotta; Zaki, Ahmed; He, Jin; Salman, Bulent; Hruban, Ralph H.; Cameron, John L.; Herman, Joseph M.; Ahuja, Nita; Lennon, Anne Marie; Weiss, Matthew J.; Wood, Laura D.; Wolfgang, Christopher L.

    2015-01-01

    Background Non-invasive intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia and IPMN-associated invasive pancreatic ductal adenocarcinoma (PDAC) are frequently included under the term “malignancy”. The goal of this study is to clarify the difference between these two entities. Methods From 1996 to 2013, data of 616 patients who underwent pancreatic resection for an IPMN were reviewed. Results The median overall survival for patients with IPMN with high-grade dysplasia (92 months) was similar to survival for patients with IPMN with low/intermediate-grade dysplasia (118 months, p = 0.081), and superior to that of patients with IPMN-associated PDAC (29 months, p < 0.001). IPMN-associated PDAC had lymph node metastasis in 53%, perineural invasion in 58%, and vascular invasion in 33%. In contrast, no lymph node metastasis, perineural or vascular invasion was observed with high-grade dysplasia. None of the patients with IPMN with high-grade dysplasia developed recurrence outside the remnant pancreas. In stark contrast 58% of patients with IPMN-associated PDAC recurred outside the remnant pancreas. The rate of progression within the remnant pancreas was significant in patients with IPMN with high-grade (24%) and with low/intermediate dysplasia (22%, p = 0.816). Conclusion Non-invasive IPMN with high-grade dysplasia should not be considered a malignant entity. Compared to patients with IPMN with low/intermediate-grade dysplasia, those with high-grade dysplasia have an increased risk of subsequent development of PDAC in the remnant pancreas. PMID:27017163

  13. Deep Sequencing of Cancer-Related Genes Revealed GNAS Mutations to Be Associated with Intraductal Papillary Mucinous Neoplasms and Its Main Pancreatic Duct Dilation

    PubMed Central

    Takano, Shinichi; Fukasawa, Mitsuharu; Maekawa, Shinya; Kadokura, Makoto; Miura, Mika; Shindo, Hiroko; Takahashi, Ei; Sato, Tadashi; Enomoto, Nobuyuki

    2014-01-01

    Background To clarify the genetic mutations associated with intraductal papillary mucinous neoplasms (IPMN) and IPMN-related pancreatic tumours, we conducted cancer-related gene profiling analyses using pure pancreatic juice and resected pancreatic tissues. Methods Pure pancreatic juice was collected from 152 patients [nine with a normal pancreas, 22 with chronic pancreatitis (CP), 39 with pancreatic ductal adenocarcinoma (PDAC), and 82 with IPMN], and resected tissues from the pancreas were collected from 48 patients (six IPMNs and 42 PDACs). The extracted DNA was amplified by multiplexed polymerase chain reaction (PCR) targeting 46 cancer-related genes containing 739 mutational hotspots. The mutations were analysed using a semiconductor-based DNA sequencer. Results Among the 46 cancer-related genes, KRAS and GNAS mutations were most frequently detected in both PDAC and IPMN cases. In pure pancreatic juice, GNAS mutations were detected in 7.7% of PDAC cases and 41.5% of IPMN cases (p<0.001 vs. others). All PDAC cases with GNAS mutations (n = 3) were accompanied by IPMN. Multivariate analysis revealed that GNAS mutations in IPMN cases were associated with dilated main pancreatic ducts (MPD, p = 0.016), while no statistically independent associations with clinical variables were observed for KRAS mutations. In the resected pancreatic tissues, GNAS mutations were detected in 50% of PDAC cases concomitant with IPMN, 33.3% of PDAC cases derived from IPMN, and 66.7% of IPMN cases, while no GNAS mutations were detected in cases of PDAC without IPMN. Conclusions The GNAS mutation was specifically found in the cases with IPMN and it was speculated that some PDACs might be influenced by the concomitant but separately-located IPMN in their pathogenic mechanism. Furthermore, the GNAS mutation was significantly associated with MPD dilatation in IPMN cases, suggesting its role in mucus hypersecretion. PMID:24897499

  14. [Mucin-like carcinoma-associated antigen: sensitivity and specificity in metastatic breast cancer].

    PubMed

    Ammon, A; Eiffert, H; Alhusen, R; Weber, M; Rümelin, B; Groh, E; Bartsch, H; Marschner, N; Nagel, G A; Krieger, G

    1990-06-01

    The clinical usefulness of a tumor marker essentially depends on its sensitivity and specificity for a certain tumor. To prove, wheather the new tumor marker 'mucin-like carcinoma-associated antigen' could be used for the management of breast cancer patients, we determined its serum concentration in 50 healthy blood donors, 130 patients with various non-malignant diseases, 138 patients with different metastazised tumors and 137 breast cancer patients. 78 of the breast cancer patients had known metastases while 59 had no evidence of disease after initial surgical and adjuvant therapy. Only 2% of the blood donors and 3% of the patients with non-malignant diseases exceeded the cut-off level of 15 U/ml. In contrast to these findings, 28% of patients with various metastazised tumors and 77% of patients with metastazised breast cancer had serum levels above 15 U/ml. Breast cancer patients without evidence of disease had elevated marker values in only 3%. In breast cancer the serum levels of this antigen depends on the type of metastases. Maximal concentrations were found in mixed metastases while cutaneous or lymph-node metastases showed the lowest rate of positivity. Furthermore a good correlation of serial determined marker levels with the course of the disease was observed, so that we conclude, that mucin-like carcinoma-associated antigen can be used in follow-up of patients with metastazised breast cancer. Because of its high sensitivity and specificity it provides some advantage over other markers used in this disease. PMID:2204009

  15. MicroRNA Expression Profiles in Papillary Thyroid Carcinoma, Benign Thyroid Nodules and Healthy Controls

    PubMed Central

    Yoruker, Ebru Esin; Terzioglu, Duygu; Teksoz, Serkan; Uslu, Fatma Ezel; Gezer, Ugur; Dalay, Nejat

    2016-01-01

    MicroRNAs (miRNAs) represent a class of short endogenous non-coding RNAs that negatively regulate gene expression at the post-transcriptional level in many biological processes, including proliferation, differentiation, stress response and apoptosis. In this study we analyzed a set of seven miRNA molecules in sera of patients with papillary thyroid cancer, multinodular goiter and healthy controls to identify miRNA molecules that may have utility as markers for PTC. MiR-21 serum levels in the preoperative PTC and MG groups were significantly higher than the control group. Likewise, postoperative levels of miR-151-5p, miR-221 and miR-222 were significantly lower in patients with PTC. When serum miRNA levels were evaluated according to stage, postoperative levels of miR-151-5p and miR-222 were significantly lower in patients with advanced stages of the disease. The miRNA levels were also found associated with the size of the primary tumor. Our data imply that specific miRNA molecules which are differentially expressed in thyroid tumors may play role in the development of papillary thyroid carcinoma. PMID:27162538

  16. PSMA Expression in Papillary Thyroid Carcinoma: Opening a New Horizon in Management of Thyroid Cancer?

    PubMed

    Taywade, Sameer Kamalakar; Damle, Nishikant Avinash; Bal, Chandrasekhar

    2016-05-01

    Prostate-specific membrane antigen (PSMA) is a type 2 transmembrane protein highly expressed in prostate cancer cells. We present the case of a 50-year-old man with metastatic papillary carcinoma of the thyroid, with rising thyroglobulin level and negative whole-body radioiodine scan after total thyroidectomy. Considering the limited treatment options available, it was decided to perform Ga-PSMA-HBED-CC PET/CT scan. It revealed intense radiotracer uptake in mediastinal and left supraclavicular lymph nodes, brain metastases, bilateral lung nodules, and skeletal sites. Patient also underwent F-FDG PET/CT. It demonstrated similar findings; however, the number of lesions detected in brain was less compared with Ga-PSMA PET/CT. PMID:26914556

  17. Hashimoto's thyroiditis and papillary carcinoma in an adolescent girl: A case report

    PubMed Central

    DONG, LI-QUN; SUN, XIAO-MEI; XIANG, CHENG-FA; WU, JIN; YU, PING

    2016-01-01

    Hashimoto's thyroiditis with thyroid cancer in childhood is not as common in the adult population. Hashimoto's thyroiditis is an autoimmune disease associated with autoantibodies, and the association between Hashimoto's thyroiditis and papillary carcinoma of the thyroid remains controversial. The present study reported a 15-year-old adolescent girl with the diagnosis of Hashimoto's thyroiditis with thyroid cancer. With the complexity of the clinical manifestations of Hashimoto's thyroiditis, it can be expressed as not only hyperthyroidism or hypothyroidism, but also normal thyroid function. The long-term treatment, and for children with thyroid cancer, early diagnosis is particularly difficult. In the present case, the diagnosis of Hashimoto's thyroiditis is primarily based on clinical manifestations, anti-thyroglobulin antibody and anti-thyroid microsomal antibody. The only diagnostic imaging ultrasound was negative. The present study discussed the possible reason and the identification of this unique case of Hashimoto's thyroiditis with thyroid cancer. PMID:27330783

  18. Computer assisted detection and analysis of tall cell variant papillary thyroid carcinoma in histological images

    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.

  19. miR-101 inhibits cell proliferation by targeting Rac1 in papillary thyroid carcinoma

    PubMed Central

    LIN, XIAOJIE; GUAN, HONGYU; LI, HAI; LIU, LIEHUA; LIU, JUAN; WEI, GUOHONG; HUANG, ZHIMIN; LIAO, ZHIHONG; LI, YANBING

    2014-01-01

    Accumulating evidence suggests that some microRNAs (miRNAs) are involved in papillary thyroid carcinoma (PTC) progression. However, it remains necessary to elucidate the underlying molecular mechanisms involved. In the present study, we investigated the role of microRNA-101 (miR-101) in PTC via targeting of Ras-related C3 botulinum toxin substrate 1 (Rac1). The results showed that miR-101 was significantly downregulated in PTC tissues compared with adjacent normal tissues. Restoration of miR-101 expression significantly inhibited cell proliferation in the K1 PTC cell line. Moreover, algorithm-based and experimental strategies verified Rac1 as a direct target of miR-101 in the K1 cell line. Taken together, these findings suggest that miR-101 inhibited PTC growth via the downregulation of Rac1 expression, providing a better understanding of miRNA-modulated signaling networks for future cancer therapeutics. PMID:24649082

  20. Improving our understanding of papillary renal cell carcinoma with integrative genomic analysis

    PubMed Central

    Modi, Parth K.

    2016-01-01

    Papillary renal cell carcinoma (pRCC) is a heterogeneous and incompletely understood histologic subtype of kidney cancer. Recently, authors from The Cancer Genome Atlas Research Network performed a comprehensive molecular characterization of pRCC. Using multiple analytic methods, they identified 4 subgroups of pRCC with varied genotypic anomalies and probabilities of overall survival. This analysis elucidated the differences between type 1 and type 2 pRCC. Furthermore, type 2 pRCC was found to be heterogeneous itself, with at least 3 subtypes with distinct molecular features. This improved characterization and insight about potential driver mutations and altered pathways may lead to the development of more targeted agents and better patient stratification in clinical trials for pRCC. PMID:27162793

  1. Improving our understanding of papillary renal cell carcinoma with integrative genomic analysis.

    PubMed

    Modi, Parth K; Singer, Eric A

    2016-04-01

    Papillary renal cell carcinoma (pRCC) is a heterogeneous and incompletely understood histologic subtype of kidney cancer. Recently, authors from The Cancer Genome Atlas Research Network performed a comprehensive molecular characterization of pRCC. Using multiple analytic methods, they identified 4 subgroups of pRCC with varied genotypic anomalies and probabilities of overall survival. This analysis elucidated the differences between type 1 and type 2 pRCC. Furthermore, type 2 pRCC was found to be heterogeneous itself, with at least 3 subtypes with distinct molecular features. This improved characterization and insight about potential driver mutations and altered pathways may lead to the development of more targeted agents and better patient stratification in clinical trials for pRCC. PMID:27162793

  2. Clonality analysis of multifocal papillary thyroid carcinoma by using genetic profiles.

    PubMed

    Lu, Zheming; Sheng, Jindong; Zhang, Yujie; Deng, Jianhua; Li, Yong; Lu, Aiping; Zhang, Juan; Yu, Huan; Zhang, Min; Xiong, Zikai; Yan, Hai; Diplas, Bill H; Lu, Youyong; Liu, Baoguo

    2016-05-01

    Papillary thyroid carcinoma (PTC) is the most common adult thyroid malignancy and often presents with multiple anatomically distinct foci within the thyroid, known as multifocal papillary thyroid carcinoma (MPTC). The widespread application of the next-generation sequencing technologies in cancer genomics research provides novel insights into determining the clonal relationship between multiple tumours within the same thyroid gland. For eight MPTC patients, we performed whole-exome sequencing and targeted region sequencing to identify the non-synonymous point mutations and gene rearrangements of distinct and spatially separated tumour foci. Among these eight MPTCs, completely discordant mutational spectra were observed in the distinct cancerous nodules of patients MPTC1 and 5, suggesting that these nodules originated from independent precursors. In another three cases (MPTC2, 6, and 8), the distinct MPTC foci of these patients had no other shared mutations except BRAF V600E, also indicating likely independent origins. Two patients (MPTC3 and 4) shared almost identical mutational spectra amongst their separate tumour nodules, suggesting a common clonal origin. MPTC patient 7 had seven cancer foci, of which two foci shared 66.7% of mutations, while the remaining cancer foci displayed no common non-synonymous mutations, indicating that MPTC7 has multiple independent origins accompanied by intraglandular disease dissemination. In this study, we found that 75% of MPTC cases arose as independent tumours, which supports the field cancerization hypothesis describing multiple malignant lesions. MPTC may also arise from intrathyroidal metastases from a single malignant clone, as well as multiple independent origins accompanied by intrathyroidal metastasis. PMID:27071483

  3. Clear cell papillary renal cell carcinoma: a clinicopathological study emphasizing ultrastructural features and cytogenetic heterogeneity.

    PubMed

    Shi, Shan-Shan; Shen, Qin; Xia, Qiu-Yuan; Tu, Pin; Shi, Qun-Li; Zhou, Xiao-Jun; Rao, Qiu

    2013-01-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized renal neoplasm, which was initially described in end-stage renal disease (ESRD), but some cases have been reported in otherwise normal kidneys. We report a series of 11 CCPRCC (age range, 33-72 years; male-to-female ratio, 8:3). Follow-up was available for 8 patients. No patients developed local recurrence, distant or lymph-node metastasis, or cancer death. Histologically, all tumors exhibit morphologic features typical of CCPRCC including a mixture of cystic and papillary components, covered by small to medium-sized cuboidal cells with abundant clear cytoplasm. All 11 cases exhibited moderate to strong positivity for CK7, CA9, Vim, and HIF-1α, coupled with negative reactions for CD10, P504S, and RCC. We did not find any VHL gene mutations in all 11 cases. Losses of chromosomes 3 (monoploid chromosome 3) was detected in 3 cases. Ultrastructurally, the tumor cells composed of numerous glycogens with scanty cell organelles, reminiscent of clear cell renal cell carcinoma (CCRCC). In conclusion, the coexpression of CA9 and HIF-1α in the absence of VHL gene abnormalities in CCPRCC suggests activation of the HIF pathway by mechanisms independent of VHL gene mutation. Losses of chromosomes 3 (monosomies chromosome 3) was detected in 3 cases suggesting that at least some of these lesions have demonstrated abnormalities of chromosomes 3. Ultrastructurally, CCPRCC composed of numerous glycogens with scanty cell organelles, reminiscent of CCRCC suggesting the close pathogenesis relationship of CCPRCC with CCRCC. PMID:24294381

  4. Expression of MUC1 mucin in potentially malignant disorders, oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study

    PubMed Central

    Kumar, M Harish; Sanjai, Karpagaselvi; Kumarswamy, Jayalakshmi; Keshavaiah, Roopavathi; Papaiah, Lokesh; Divya, S

    2016-01-01

    Background: Mucins alteration in glycosylation is associated with the development and progression of malignant diseases. Therefore, mucins are used as valuable markers to distinguish normal and disease conditions. Many studies on MUC1 expression have been conducted on variety of neoplastic lesions other than head and neck region. None of the study has made an attempt to show its significance in potentially malignant disorders (PMDs) and oral squamous cell carcinoma (OSCC). Hence, ours is one of the pioneer studies done to assess and evaluate the same. Aims: This study aims to compare and correlate the expression of MUC1 mucin protein in normal oral mucosa (NOM), PMD's and OSCC by immunohistochemical method. Materials and Methods: Institutional study, archived tissue sections of OSCC (n = 20), PMD's (n = 20) and NOM (n = 20) were immunostained for MUC1 mucin and percentage of positive cells evaluated. Results obtained were statistically analyzed using Kruskal–Wallis test, Mann–Whitney test and Student's t-test. Results: The mean MUC1 mucin positive cells in the study groups were as follows, 40% in OSCC, 28% in PMD's and 0.75% in NOM. Higher mean immunohistochemical score was observed in OSCC group followed by PMD's group and NOM group. The difference in immunohistochemical score among the groups was found to be statistically significant (P < 0.001). Conclusion: The result of the current study suggests that determination of MUC1 mucin expression may be a parameter in the diagnosis of malignant behavior of PMD's to OSCC. MUC1 mucin expression may be a useful diagnostic marker for prediction of the invasive/metastatic potential of OSCC. PMID:27601811

  5. The role of IgG4 (+) plasma cells in the association of Hashimoto's thyroiditis with papillary carcinoma.

    PubMed

    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

  6. Cribriform-morular variant of papillary thyroid carcinoma at pediatric age - case report and review of the literature.

    PubMed

    Brehar, Andreea Cristiana; Terzea, Dana Cristina; Ioachim, Dumitru Lucian; Procopiuc, Camelia; Brehar, Felix Mircea; Bulgăr, Alexandra Cătălina; Ghemigian, Mircea Vasile; Dumitrache, Constantin

    2016-01-01

    Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare tumor, which exceptionally occurs at pediatric age. CMV-PTC may develop in patients with familial adenomatous polyposis (FAP) or may be a sporadic tumor. The authors present a case of CMV-PTC in a 10-year-old girl patient without FAP history, who presented with a left neck mass. The patient underwent total thyroidectomy with central compartment neck dissection. Histopathological diagnosis was compatible with cribriform-morular variant of papillary thyroid carcinoma and Hashimoto's thyroiditis. Immunostaining was positive for thyroglobulin, β-catenin, CD10 and p53. Molecular test showed the absence of BRAF, K-RAS mutations, deletions or duplications of APC (adenomatosis polyposis coli) gene and showed the presence of RET÷PTC (rearranged during transfection÷papillary thyroid carcinoma) rearrangements. At 32 months follow-up, the patient was without signs of recurrence. This particular form of thyroid carcinoma should raise suspicion of a possible familial cancer syndrome, therefore early diagnosis and thoroughly evaluation, which includes colonoscopy and genetic screening are mandatory. PMID:27516030

  7. Colloid (mucinous non-cystic) carcinoma of the pancreas: A case report

    PubMed Central

    GAO, YANG; ZHU, YA-YUN; YUAN, ZHOU

    2015-01-01

    Colloid carcinoma (CC) of the pancreas, also known as mucinous non-cystic carcinoma, is a rare histological variant of pancreatic cancer. The present study reports the case of a 65-year-old male with a pancreatic head tumor 4.6×3.1 cm in size. The tumor had not invaded the superior mesenteric or celiac arteries. Laboratory data showed elevated alkaline phosphatase, γ-gluytamyl transpeptidase and cancer antigen 19-9 (CA19-9) levels. The patient underwent a pancreaticoduodenectomy (PD), and the pathology revealed CC extending to the submucosa of the duodenum, with mild atypical hyperplasia of the pancreatic duct. The patient was negative for circulating tumor cells, indicating a good prognosis. The CA19-9 concentration decreased to within the normal range following surgery. The present study reports a rare case of CC of the pancreas presenting with obstructive jaundice, in which a PD procedure was performed. Primary surgical treatment with curative intent is the optimal management and this subtype of pancreatic cancer is associated with a better prognosis compared with pancreatic ductal adenocarcinoma. PMID:26722311

  8. Anaplastic Carcinoma Arising in a Mucinous Cystic Neoplasm Masquerading as Pancreatic Pseudocyst.

    PubMed

    Aldaoud, Najla; Joudeh, Amani; Al-Momen, Sami; Alnahawi, Mamdouh; Al-Abbadi, Mousa A

    2016-06-01

    Mucinous cystic neoplasms (MCN) of the pancreas can vary from benign to premalignant and malignant. Preoperative diagnosis is essential to offer the patient appropriate treatment. Occasionally these cases may harbor anaplastic carcinoma while clinically masquerade as a pseudocyst. Here in, we report an unusual case of a 37-year old female presented with recurrent abdominal pain that was suspected clinically and by imaging studies to have a pseudocyst. EUS-FNA with internal drainage of the cyst was performed. Cytological evaluation of the cyst fluid showed numerous inflammatory cells composed mainly of many neutrophils admixed with macrophages reminiscent of the usual pseudocyst content but there were scattered rare dyscohesive malignant cells which were highly pleomorphic with multinucleation. Immunostains on the cell block showed immunoreactivity of these cells including the multinucleated cells for Cam 5.2 and AE1/AE3 and focally for Ber-Ep4, Moc -31, and CA19-9. The subsequent resection confirmed the presence of anaplastic (undifferentiated) carcinoma (AC) arising in a MCN of the pancreas. Diagn. Cytopathol. 2016;44:538-542. © 2016 Wiley Periodicals, Inc. PMID:27028547

  9. Follicular variant of papillary thyroid carcinoma: accuracy of FNA diagnosis and implications for patient management.

    PubMed

    Ustun, Berrin; Chhieng, David; Prasad, Manju L; Holt, Elizabeth; Hammers, Lynwood; Carling, Tobias; Udelsman, Robert; Adeniran, Adebowale J

    2014-09-01

    Follicular variant of papillary thyroid carcinoma (FVPTC) creates a continuous diagnostic dilemma among pathologists because of the paucity of nuclear changes of papillary carcinoma and overlapping features with benign and other neoplastic follicular lesions. Current guidelines for the management of thyroid nodules recommend surgery for confirmed PTC, suspicious for PTC, and follicular neoplasm cases, while further immediate diagnostic studies or treatment are not routinely required if the nodule is benign on cytology. This study is designed to determine the accuracy of cytology in the diagnosis of FVPTC, based on the Bethesda classification system, and determine the implications for patient management based on the current recommendation. Based on a retrospective review of cytologic diagnoses between January 2008 and December 2011, thyroid fine needle aspiration (FNA) cytology specimens with subsequent surgical intervention and a final diagnosis of FVPTC were selected. The cytologic diagnoses were compared with the final diagnoses, and the percentage of cases contributing to the final diagnosis of FVPTC was calculated for each diagnostic category. Triage efficiency and diagnostic accuracy were calculated. One hundred and fifty-two cases with histologic confirmation of FVPTC were identified (representing 128 patients-101 female, 27 male). All patients had undergone either lobectomy with completion thyroidectomy or total thyroidectomy. The cytologic diagnosis of "positive for malignancy" accounted for only 27 % of the final histologic diagnosis of FVPTC, while suspicious for carcinoma, follicular neoplasm, follicular lesion of undetermined significance, and benign accounted for 11, 23, 23, and 16 % of the final diagnosis of FVPTC, respectively. Only 18 % of the 55 cases tested were positive for BRAF mutation. The subtle nuclear features of FVPTC pose challenges for an accurate diagnosis. Therefore, a better approach is to triage these cases for surgical intervention

  10. Identification of Genes Associated with Papillary Thyroid Carcinoma (PTC) for Diagnosis by Integrated Analysis.

    PubMed

    Li, W-B; Zhou, J; Xu, L; Su, X-L; Liu, Q; Pang, H

    2016-04-01

    Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, and our understanding of its pathogenesis is incomplete. To elucidate the mechanisms underlying such progression and identify novel diagnostic markers, we aimed to discover the underlying gene associated with PTC. Integrated analysis of microarray datasets was performed to identify differentially expressed genes (DEGs) between PTCs and normal tissues. GO enrichment analysis and KEGG pathway enrichment analysis were then performed to uncover the functions of DEGs. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed. Five GEO datasets were obtained. Totally, 154 DEGs across the studies were identified, including 26 upregulated and 128 downregulated DEGs. In the PPI network, MLLT1, DLG2, and EFEMP1 were the hub proteins, in which DLG2 and EFEMP1 were involved in tumor progression. Among the top 10 up- and downregulated genes, the dysregulation genes of TPO, CDH16, and MPPED2 may be closely related to the tumorigenesis of PTC. By integrated analysis of multiple gene expression profiles, we propose that the dysregulation genes of TPO and MPPED2 will be the promising diagnostic markers for PTCs. PMID:26756467

  11. Anterior gradient protein 2 promotes survival, migration and invasion of papillary thyroid carcinoma cells

    PubMed Central

    2014-01-01

    Background Through a transcriptome microarray analysis, we have isolated Anterior gradient protein 2 (AGR2) as a gene up-regulated in papillary thyroid carcinoma (PTC). AGR2 is a disulfide isomerase over-expressed in several human carcinomas and recently linked to endoplasmic reticulum (ER) stress. Here, we analyzed the expression of AGR2 in PTC and its functional role. Methods Expression of AGR2 was studied by immunohistochemistry and real time PCR in normal thyroids and in PTC samples. The function of AGR2 was studied by knockdown in PTC cells and by ectopic expression in non-transformed thyroid cells. The role of AGR2 in the ER stress was analyzed upon treatment of cells, expressing or not AGR2, with Bortezomib and analyzing by Western blot the expression levels of GADD153. Results PTC over-expressed AGR2 at mRNA and protein levels. Knockdown of AGR2 in PTC cells induced apoptosis and decreased migration and invasion. Ectopic expression of AGR2 in non-transformed human thyroid cells increased migration and invasion and protected cells from ER stress induced by Bortezomib. Conclusions AGR2 is a novel marker of PTC and plays a role in thyroid cancer cell survival, migration, invasion and protection from ER stress. PMID:24976026

  12. mRNA Expression in Papillary and Anaplastic Thyroid Carcinoma: Molecular Anatomy of a Killing Switch

    PubMed Central

    Hébrant, Aline; Dom, Geneviève; Dewaele, Michael; Andry, Guy; Trésallet, Christophe; Leteurtre, Emmanuelle; Dumont, Jacques E.; Maenhaut, Carine

    2012-01-01

    Anaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid neoplasia and represents the end stage of thyroid tumor progression. No effective treatment exists so far. ATC frequently derive from papillary thyroid carcinomas (PTC), which have a good prognosis. In this study, we analyzed the mRNA expression profiles of 59 thyroid tumors (11 ATC and 48 PTC) by microarrays. ATC and PTC showed largely overlapping mRNA expression profiles with most genes regulated in all ATC being also regulated in several PTC. 43% of the probes regulated in all the PTC are similarly regulated in all ATC. Many genes modulations observed in PTC are amplified in ATC. This illustrates the fact that ATC mostly derived from PTC. A molecular signature of aggressiveness composed of 9 genes clearly separates the two tumors. Moreover, this study demonstrates gene regulations corresponding to the ATC or PTC phenotypes like inflammatory reaction, epithelial to mesenchymal transition (EMT) and invasion, high proliferation rate, dedifferentiation, calcification and fibrosis processes, high glucose metabolism and glycolysis, lactate generation and chemoresistance. The main qualitative differences between the two tumor types bear on the much stronger EMT, dedifferentiation and glycolytic phenotypes showed by the ATC. PMID:23115614

  13. [A case of serous surface papillary carcinoma of the peritoneum metastatic to the brain].

    PubMed

    Sakakibara, Yohtaro; Endo, Shu; Yoshida, Yasuyuki; Tanaka, Yuichiro; Hashimoto, Takuo; Ohara, Tatsuru

    2011-06-01

    A case of brain metastasis from peritoneal serous surface papillary carcinoma (SSPC) was reported. This 68-year-old woman was admitted to our department because of decreased consciousness level for the last few days. Her medical past history revealed breast cancer and SSPC of the peritoneum at the age of 64. On admission she was comatose and irritable. Serum and urine examination revealed the syndrome of inappropriate secretion of antidiuretic hormone that was treated with strict restriction of water intake. MRI of the brain demonstrated a nonspecific mass in the subcortical area of the right superior parietal lobule. The mass was successfully removed in en bloc fashion. Pathological diagnosis was SSPC that was compatible with the previous diagnosis obtained from the peritoneum four years previously. Although the patient received whole brain radiation therapy postoperatively, her condition deteriorated rapidly. She died four months after brain surgery. SSPC of the peritoneum is a rare malignant tumor that is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. Because of the prolongation of survival resulting from advanced chemotherapy for SSPC of the peritoneum, more patients live long enough to develop brain metastasis. Therefore, SSPC of the peritoneum should be kept in mind in the differential diagnosis of a primary site for brain metastasis. PMID:21628741

  14. Molecular genetics of childhood papillary thyroid carcinomas after irradiation: high prevalence of RET rearrangement.

    PubMed

    Rabes, H M; Klugbauer, S

    1998-01-01

    Epidemiological studies have revealed a connection between thyroid carcinogenesis and a history of radiation. The molecular mechanisms involved are not well understood. It has been claimed that RAS, p53 or GSP mutations and RET or TRK rearrangements might play a role in adult thyroid tumors. In childhood, the thyroid gland is particularly sensitive to ionizing radiation. The reactor accident in Chernobyl provided a unique chance to study molecular genetic aberrations in a cohort of children who developed papillary thyroid carcinomas after a short latency time after exposure to high doses of radioactive iodine isotopes. According to the concepts of molecular genetic epidemiology, exposure to a specific type of irradiation might result in a typical molecular lesion. Childhood papillary thyroid tumors after Chernobyl exhibit a high prevalence of RET rearrangement as almost the only molecular alteration. The majority showed RET/PTC3 (i.e., ELE/RET rearrangements), including several subtypes. Less frequently, RET/PTC1 (i.e., H4/RET rearrangements), and a novel type (RET/PTC5, i.e., RFG5/RET) were observed. Proof of reciprocal transcripts suggests that a balanced intrachromosomal inversion leads to this rearrangement. Breakpoint analyses revealed short homologous nucleotide stretches at the fusion points. In all types of rearrangement, the RET tyrosine kinase domain becomes controlled by 5' fused regulatory sequences of ubiquitously expressed genes that display coiled-coil regions with dimerization potential. Oncogenic activation of RET is apparently due to ligand-independent constitutive ectopic RET tyrosine kinase activity. The analysis of this cohort of children with radiation-induced thyroid tumors after Chernobyl provides insights into typical molecular aberrations in relation to a specific mode of environmental exposure and may serve as a paradigm for molecular genetic epidemiology. PMID:10027005

  15. Papillary urothelial carcinoma with squamous differentiation in association with human papilloma virus: case report and literature review

    PubMed Central

    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

    Background: 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. Case presentation: 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. Conclusions: 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. PMID:27069958

  16. Vitamin D receptor expression is linked to potential markers of human thyroid papillary carcinoma.

    PubMed

    Izkhakov, Elena; Somjen, Dalia; Sharon, Orli; Knoll, Esther; Aizic, Asaf; Fliss, Dan M; Limor, Rona; Stern, Naftali

    2016-05-01

    Genes regulated cell-cell and cell-matrix adhesion and degradation of the extracellular matrix (ECM) have been screened as potential markers of malignant thyroid nodules. The mRNA expression levels of two of them, the ECM protein-1 (ECM1) and the type II transmembrane serine protease-4 (TMPRSS4), were shown to be an independent predictor of an existing thyroid carcinoma. The vitamin D receptor (VDR) is expressed in epithelial cells of the normal thyroid gland, as well as in malignant dividing cells, which respond to the active metabolite of vitamin D by decreased proliferative activity in vitro. We evaluated the relationship between mRNA gene expressions of TMPRSS4, ECM1 and VDR in 21 papillary thyroid carcinoma samples and compared it to 21 normal thyroid tissues from the same patients. Gene expression was considered as up- or down-regulated if it varied by more or less than 2-fold in the cancer tissue relative to the normal thyroid tissue (Ca/N) from the same patient. We found an overall significant adjusted correlation between the mRNA expression ratio (ExR) of VDR and that of ECM1 in Ca/N thyroid tissue (R=0.648, P<0.001). There was a high ExR of VDR between Ca/N thyroid tissue from the same patient (3.06±2.9), which also exhibited a high Ca/N ExR of ECM1 and/or of TMPRSS4 (>2, P=0.05).The finding that increased VDR expression in human thyroid cancer cells is often linked to increased ECM1 and/or TPMRSS4 expression warrants further investigation into the potential role of vitamin D analogs in thyroid carcinoma. PMID:26907966

  17. Clinical Significance of Positive Pelvic Washings in Uterine Papillary Serous Carcinoma Confined to an Endometrial Polyp.

    PubMed

    Hanley, Krisztina Z; Fadare, Oluwole; Fisher, Kevin E; Atkins, Kristen A; Mosunjac, Marina B

    2016-05-01

    Uterine papillary serous carcinoma (UPSC) represents 10% of endometrial carcinomas. Significant number of patients initially present with extrauterine disease. The role of adjuvant treatment in low stage, especially polyp-confined UPSC is controversial. This multi-institutional study evaluated the significance of positive pelvic washing (PW) and adjuvant treatment on disease recurrence in a setting of endometrial polyp-confined UPSC. Surgical pathology files from 3 institutions were searched for cases of endometrial polyp-confined UPSC. Following histologic review, cases were clinically staged as Stage I, without myoinvasion or lymphovascular invasion. Clinicopathologic characteristics, results of PW, and type of adjuvant therapy were recorded. Statistical analysis using the Kaplan-Meier method for survival and Fisher exact test were performed. Thirty-three patients were included in the study. All patients were diagnosed with polyp-confined UPSC. The size of the polyp ranged from 0.3 to 4.3 cm. PW was positive for tumor cells in 8/33 (24%) patients. Twenty-two patients (66.6%) received some type of adjuvant treatment. Six patients (18%) developed recurrent disease. There was no significant difference in disease-free survival in the patients receiving adjuvant treatment versus not (P=0.375). However, there was significant association (P=0.0013) between positive PW and disease recurrence. Data are conflicting whether positive PW affects prognosis in low-stage endometrial carcinomas. Our study showed that in UPSC, malignant cells can be present in PW without lymphovascular invasion or myoinvasion and may have negative prognostic implication. Our data also reflect the controversies in the role of adjuvant treatment in endometrium-confined UPSC. PMID:26535985

  18. Urachal adenocarcinoma that metastasized to breast was misinterpreted as primary breast mucinous carcinoma: A rare case report and literature review

    PubMed Central

    Zhao, Xiang-Rong; Gao, Chao; Zhang, Yong; Kong, Lei; Qu, Wei; Li, Jia; Gao, Yong-Sheng; Yu, Yong-Hua

    2016-01-01

    Abstract Background: The urachus is a vestigial tubular structure that connects the urinary bladder to the allantois during early embryonic development. Urachal carcinoma develops in the urachus, which is an embryological remnant of the urogenital sinus and allantois. The estimated annual incidence of urachal carcinoma in the general population is 0.01% of all cancers in adults. Moreover, urachal carcinoma accounts for 0.34% to 0.7% of all bladder carcinoma cases. And breast metastasis is extremely rarer. Methods and Results: A 42-year-old woman was admitted to our hospital with a palpable mass in the outer upper quadrant of the right breast, which was misinterpreted as a carcinoma that originated from the breast. Subsequently, she underwent surgery without any further meticulous examination. Immunohistochemistry analysis revealed positivity for CK20, Villin, and CDX-2 and negativity for CK7. After further inspection, a mass was found in the bladder dome using 18F-fluorodeoxyglucose positron emission tomography and computed tomography. The mass was surgically removed. Conclusion: Pathologic and immunohistochemical examination confirmed that the mass was urachal mucinous adenocarcinoma and mucinous adenocarcinoma to the right breast. The patient has been followed up without recurrence for 8 months. PMID:27583877

  19. MDCT findings of renal cell carcinoma associated with Xp11.2 translocation and TFE3 gene fusion and papillary renal cell carcinoma.

    PubMed

    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. PMID:25714283

  20. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma: A name change to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features would help prevent overtreatment.

    PubMed

    Thompson, Lester Dr

    2016-07-01

    Encapsulated follicular variant of papillary thyroid carcinoma is a common thyroid gland cancer, with a highly indolent behavior. Recently, reclassification as a non-malignant neoplasm has been proposed. There is no comprehensive, community hospital based longitudinal evaluation of encapsulated follicular variant of papillary thyroid carcinoma. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma were identified in a review of all thyroid gland surgeries performed in 2002 within the Southern California Permanente Medical Group. All histology slides were reviewed and follow-up obtained. Seventy-five women and nineteen men, aged 20-80 years (mean 45.6 years), had a single (n=61), multiple (same lobe; n=20), or bilateral (n=13) tumor(s), ranging in size from 0.7 to 9.5 cm in diameter (mean 3.3 cm). Histologically, all cases demonstrated a well-formed tumor capsule, with capsular and/or lymphovascular invasion in 17 and no invasion in 77 cases. Lymph node metastases were not identified. The tumors had a follicular architecture, without necrosis or >3 mitoses/10 high-power fields (HPFs). Classical papillary thyroid carcinoma nuclear features were seen in at least three HPFs per 3 mm of tumor diameter, including enlarged, elongated, crowded, and overlapping nuclei, irregular nuclear contours, nuclear grooves, and nuclear chromatin clearing. Lobectomy alone (n=41), thyroidectomy alone (n=34), or completion thyroidectomy (n=19) was the initial treatment combined with post-op radioablative iodine in 25 patients. All patients were without evidence of disease after a median follow-up of 11.8 years. Encapsulated follicular variant of papillary thyroid carcinoma showed benign behavior, supporting conservative surgery alone and reclassification of these tumors to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP). PMID:27102347

  1. Clear cell papillary renal cell carcinoma is the fourth most common histologic type of renal cell carcinoma in 290 consecutive nephrectomies for renal cell carcinoma.

    PubMed

    Zhou, Haijun; Zheng, Shaojiang; Truong, Luan D; Ro, Jae Y; Ayala, Alberto G; Shen, Steven S

    2014-01-01

    Clear cell papillary renal cell carcinoma (CCP-RCC) has recently been recognized as a distinct subtype of renal cell carcinoma (RCC) due to its unique morphologic, immunohistochemical, and genetic features and indolent clinical behavior. However, the incidence of this tumor in a nephrectomy series for renal mass has not been fully investigated. Twelve cases of CCP-RCC were identified from a total of 290 consecutive partial (n = 137) or radical nephrectomies (n = 153) for RCC from 2010 to 2012 in our hospital. In this series, CCP-RCC was the fourth most common (4.1%) kidney tumor following clear cell (conventional) (70%), papillary (16.6%), and chromophobe (5.9%) RCCs. The average age of the CCP-RCC patients was 58.2 years (range, 18-81 years), with an equal sex distribution. Four cases (33.3%) were associated with end-stage renal disease. Of the 12 CCP-RCCs, 9 presented as solitary tumors; 2 coexisted with clear cell RCC; and 1 with papillary RCC. The average size of tumors was 2.5 cm (range, 0.8-6.0 cm). All tumors were pT1 (10 pT1a and 2 pT1b). Two cases were initially misclassified as clear cell RCC. Strong positive cytokeratin 7 stain and negative stains with α-methylacyl-CoA racemase and RCC marker differentiate CCP-RCC from low-grade clear cell RCC with similar histologic features. We conclude that CCP-RCC is a common renal neoplastic entity, representing the fourth most common (4.1%) RCC. It can be easily misclassified due to its overlapping features with low-grade clear cell RCC. In equivocal cases, immunohistochemical stains with a small panel of markers (cytokeratin 7, α-methylacyl-CoA racemase, RCC marker, or CD10) are warranted in making the correct histologic classification. PMID:24182559

  2. Renal-cell carcinomas in end-stage kidneys: a clinicopathological study with emphasis on clear-cell papillary renal-cell carcinoma and acquired cystic kidney disease-associated carcinoma.

    PubMed

    Bhatnagar, Ramneesh; Alexiev, Borislav A

    2012-02-01

    Clear-cell papillary renal-cell carcinoma (CCPC) and acquired cystic kidney disease-associated carcinoma (ACDAC) are neoplasms with distinct morphological characteristics that behave less aggressively than conventional renal-cell carcinomas. End-stage kidney specimens from 61 patients (47 males and 14 females) with 109 renal-cell carcinomas were selected. Papillary renal-cell carcinoma was the most common malignancy (61/109, 56%), followed by CCPC (20/109, 18%). The CCPC showed a papillary or tubular/solid architecture, clear cytoplasm, low nuclear grade, and a distinct immunohistochemical profile (RCC-, vimentin+, CK7+, p504S-). ACDAC displayed a variety of architectural patterns, eosinophilic cytoplasm, high nuclear grade, intratumoral calcium oxalate deposits, and an immunohistochemical profile similar to type 2 papillary renal-cell carcinoma (RCC+, vimentin+, CK7-/+, p504S+). Less than 5% (3/69) of pathologically staged renal-cell carcinomas in end-stage kidneys presented with lymphogenous and/or hematogenous metastases. PMID:21791489

  3. Papillary Renal Cell Carcinoma Arising in a Lymph Node Metastasis of a Testicular Teratoma: A Very Rare Occurrence.

    PubMed

    Ozturk Sari, Sule; Ozluk, Yasemin; Taskin, Orhun Cig; Polat, Beldan; Ozturk, Ilker; Ekenel, Meltem; Kilicaslan, Isin; Bilgic, Bilge

    2016-08-01

    We present a case of a teratoma with somatic type malignancy (TSM) in the form of papillary renal cell carcinoma (pRCC) within supraclavicular and retroperitoneal lymph node metastases of a testicular pure teratoma. Resection of both masses revealed a teratoma without any other germ cell tumor component. A papillary carcinoma component was also detected intermingled with the teratomatous elements. The carcinoma cells displayed eosinophilic cytoplasm and prominent nucleoli. Groups of foamy histiocytes in the fibrovascular cores was a striking finding that brought pRCC to mind. Immunoreactivity for CK7, PAX8, AMACR, CD10, napsin, and vimentin along with morphologic findings confirmed renal cell differentiation. No radiological evidence of a primary renal cell carcinoma was found in the kidney. Consequently, pRCC arising in a teratoma was diagnosed. TSM is described as teratoma with a malignant component that is typically encountered in other organs and tissues. TSM in the form of pRCC is an extremely rare entity. Our case is the second example of a testicular germ cell tumor metastasis with a somatic malignancy in the form of pRCC. In conclusion, carcinomas of renal cell differentiation should be kept in mind as a rare form of TSM, especially in metastatic germ cell tumors. PMID:26936856

  4. Renal mucinous tubular and spindle cell carcinoma: report of four cases and literature review.

    PubMed

    Wang, Hui; Xie, Jun; Lu, Changqing; Zhang, Dachuan; Jiang, Jingting

    2015-01-01

    Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an unusual renal tumor. It is important to increase the recognition of the clinicopathological features of MTSCC-K and improve its clinical and differential diagnosis. This report described four cases of MTSCC-K with clinical, imaging, and pathological examination and showed that the tumor boundaries of MTSCC-K were clear, and tumor cells arranged into tubules and cord-like beams, between which was lightly stained myxoid stroma. The tumor cells were smaller and cube- or oval-shaped, with single small eosinophilic nucleoli, low-grade nuclei, and little nuclear fission. The myxoid stroma was scattered around lymphocytes and plasma cells. Immunohistochemical markers including CK7, CD117, EMA (epithelial membrane antigen), vimentin, and CK8/18, showed positive expression in tumor cells, but the tumor cells were negative for CD10 and villin. The proliferation index of Ki-67 was 5-10%. Since MTSCC-K is a rare low-grade malignancy, with unique histological and immunohistochemical characteristics, it is important for clinicians and pathologists to have a defined awareness of this tumor type in order to decrease the rate of misdiagnosis. PMID:26045827

  5. The Roles of the Epithelial-Mesenchymal Transition Marker PRRX1 and miR-146b-5p in Papillary Thyroid Carcinoma Progression

    PubMed Central

    Hardin, Heather; Guo, Zhenying; Shan, Weihua; Montemayor-Garcia, Celina; Asioli, Sofia; Yu, Xiao-Min; Harrison, April D.; Chen, Herbert; Lloyd, Ricardo V.

    2015-01-01

    Thyroid carcinoma is the most common endocrine malignancy, and papillary thyroid carcinoma represents the most common thyroid cancer. Papillary thyroid carcinomas that invade locally or metastasize are associated with a poor prognosis. We found that, during epithelial–mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1), papillary thyroid carcinoma cells acquired increased cancer stem cell-like features and the transcription factor paired-related homeobox protein 1 (PRRX1; alias PRX-1), a newly identified EMT inducer, was markedly up-regulated. miR-146b-5p was also transiently up-regulated during EMT, and in siRNA experiments miR-146b-5p had an inhibitory role on cell proliferation and invasion during TGF-β1–induced EMT. We conclude that papillary thyroid carcinoma tumor cells exhibit increased cancer stem cell-like features during TGF-β1–induced EMT, that miR-146b-5p has a role in cell proliferation and invasion, and that PRRX1 plays an important role in papillary thyroid carcinoma EMT and disease progression. PMID:24946010

  6. Papillary thyroid carcinoma risk factors in the Yunnan plateau of southwestern China

    PubMed Central

    Zeng, Rong; Shou, Tao; Yang, Kun-xian; Shen, Tao; Zhang, Jin-ping; Zuo, Rong-xia; Zheng, Yong-qing; Yan, Xin-ming

    2016-01-01

    Objective This study investigated clinical and pathological characteristics and risk factors in papillary thyroid carcinoma (PTC) patients’ native to Yunnan plateau in southwestern China. Methods Clinical data from 1,198 patients diagnosed with PTC (n=578) and control subjects (n=620) with benign thyroid disease (ie, thyroid nodule disease, benign thyroid diseases [BTD]) in Yunnan province were analyzed retrospectively. Results The mean patient age was lower for PTC than for BTD. Positive ratios of thyroid peroxidase antibody, thyroglobulin antibody (TGAb), and thyrotrophin receptor antibody (TRAb) were higher in PTC than in BTD patients. The ratio of PTC coexisting with Hashimoto’s thyroiditis (HT) or with lymphocytic thyroiditis was higher than that of BTD. The number of patients whose age at menarche was ≤13 years, who had given birth to less than or equal to two children, or who were in premenopause were higher in the PTC than in the BTD group. Multivariate conditional logistic regression analyses revealed that age >45 years, nodal size >1 cm, and elevated TG levels were protective factors against PTC. Abnormally elevated TGAb and TRAb levels were independent risk factors for PTC in females. Conclusion HT was not an independent risk factor for but was associated with PTC. TRAb is a risk factor for PTC in individuals living in the Yunnan plateau, but not for those in the plains region. PMID:27418831

  7. SRGAP1 Is a Candidate Gene for Papillary Thyroid Carcinoma Susceptibility

    PubMed Central

    He, Huiling; Bronisz, Agnieszka; Liyanarachchi, Sandya; Nagy, Rebecca; Li, Wei; Huang, Yungui; Akagi, Keiko; Saji, Motoyasu; Kula, Dorota; Wojcicka, Anna; Sebastian, Nikhil; Wen, Bernard; Puch, Zbigniew; Kalemba, Michal; Stachlewska, Elzbieta; Czetwertynska, Malgorzata; Dlugosinska, Joanna; Dymecka, Kinga; Ploski, Rafal; Krawczyk, Marek; Morrison, Patrick J.; Ringel, Matthew D.; Kloos, Richard T.; Jazdzewski, Krystian; Symer, David E.; Vieland, Veronica J.; Ostrowski, Michael; Jarząb, Barbara

    2013-01-01

    Background: Papillary thyroid carcinoma (PTC) shows high heritability, yet efforts to find predisposing genes have been largely negative. Objectives: The objective of this study was to identify susceptibility genes for PTC. Methods: A genome-wide linkage analysis was performed in 38 families. Targeted association study and screening were performed in 2 large cohorts of PTC patients and controls. Candidate DNA variants were tested in functional studies. Results: Linkage analysis and association studies identified the Slit-Robo Rho GTPase activating protein 1 gene (SRGAP1) in the linkage peak as a candidate gene. Two missense variants, Q149H and A275T, localized in the Fes/CIP4 homology domain segregated with the disease in 1 family each. One missense variant, R617C, located in the RhoGAP domain occurred in 1 family. Biochemical assays demonstrated that the ability to inactivate CDC42, a key function of SRGAP1, was severely impaired by the Q149H and R617C variants. Conclusions: Our findings suggest that SRGAP1 is a candidate gene in PTC susceptibility. SRGAP1 is likely a low-penetrant gene, possibly of a modifier type. PMID:23539728

  8. Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma.

    PubMed

    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. PMID:26598713

  9. Shear wave elastography diagnosis of the diffuse sclerosing variant of papillary thyroid carcinoma: A case report

    PubMed Central

    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.

  10. Onco-lncRNA HOTAIR and its functional genetic variants in papillary thyroid carcinoma.

    PubMed

    Zhu, Hui; Lv, Zheng; An, Changming; Shi, Meng; Pan, Wenting; Zhou, Liqing; Yang, Wenjun; Yang, Ming

    2016-01-01

    The role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) and its functional single nucleotide polymorphisms (SNPs) in papillary thyroid carcinoma (PTC) is still largely unclear. Therefore, we investigated the involvement of lncRNA HOTAIR and its three haplotype-tagging SNPs (htSNPs) in PTC. There was higher expression of HOTAIR in PTC tissues compared to normal tissues. A series of gain-loss assays demonstrated that HOTAIR acts as a PTC oncogene via promoting tumorigenic properties of PTC cells. Additionally, the functional HOTAIR rs920778 genetic variant was a PTC susceptibility SNP. Subjects with the HOTAIR rs920778 TT genotype had an odds ratio (OR) of 1.88, 1.25 and 1.61 (P = 6.0 × 10(-6), P = 0.028 and P = 3.2 × 10(-5)) for developing PTC in Shandong, Jiangsu and Jilin case-control sets compared with subjects with the CC genotype. This statistically significant associations were only found between the rs920778 genetic polymorphism and PTC risk in females but not in males. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was confirmed both in vitro and in vivo. Our results demonstrate that functional SNPs influencing lncRNA regulation may explain a part of PTC genetic basis. PMID:27549736

  11. 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.

  12. Association between Tumor Size and Bilateral Involvement in Papillary Thyroid Carcinoma

    PubMed Central

    Erkilic, Suna; Celenk, Fatih; Bozdag, Zehra

    2016-01-01

    Background. Tumor multifocality and bilaterality of papillary thyroid carcinoma (PTC) are important factors when selecting the most appropriate surgical procedure. The aim of this study was to assess the bilaterality rate in PTC and the relationship between the tumor size and bilaterality. Materials and Methods. Thyroidectomy specimens with a diagnosis of PTC were retrospectively reviewed in the Pathology Department of a tertiary care medical center. Specimens were divided into three groups according to the size of the primary and contralateral tumor foci. Tumors less than or equal to 1 cm in each lobe were included in group 1. Group 2 consisted of tumors greater than 1 cm in one lobe and less than 1 cm in the other lobe. Tumors greater than 1 cm in each lobe were included in group 3. Results. We identified 868 total thyroidectomy specimens with a diagnosis of PTC between 2001 and 2011. Of these cases, both thyroid lobes were involved in 262 cases (32%). There were 109 (42%), 121 (46%), and 32 cases (12%) in group 1, group 2, and group 3, respectively. Conclusion. Bilaterality is frequent in PTC and is not related to tumor size. Accordingly, the high frequency of bilateral disease in PTC should be kept in mind when determining the extent of the surgical procedure.

  13. Long-term survival in a patient with brain metastases of papillary thyroid carcinoma.

    PubMed

    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

  14. Diagnostic usefulness of PCR profiling of the differentially expressed marker genes in thyroid papillary carcinomas.

    PubMed

    Hamada, Aiko; Mankovskaya, Svetlana; Saenko, Vladimir; Rogounovitch, Tatiana; Mine, Mariko; Namba, Hiroyuki; Nakashima, Masahiro; Demidchik, Yuri; Demidchik, Eugeny; Yamashita, Shunichi

    2005-06-28

    The study was set out to determine whether characteristic changes in the gene expression profile in papillary thyroid carcinoma (PTC) discovered by microarray assays can be used for conventional molecular diagnosis. Expression levels of five reported to be overexpressed and three underexpressed genes were examined in PTC and normal human tissues by real-time PCR and semi-quantitative duplex PCR. Stepwise logistic regression analysis, duplex PCR data evaluation with recursive partition machine algorithm and hierarchical cluster analysis identified SFTPB (upregulated) and TFF3 (downregulated) gene combination as most favorable for differential molecular diagnosis of PTC. Sensitivity, specificity and accuracy obtained in a series of histologically characterized thyroid tumor and normal tissue samples were 88.9, 96.7 and 94.9%, respectively. Applicability of the method to fine needle aspiration biopsy (FNAB) samples was demonstrated using a collection of needle washouts. In spite individual thyroid tumor and normal tissues as well as FNAB samples displayed a substantial degree of variability in the expression levels of analyzed genes, simultaneous molecular analysis of a panel of optimal markers allows making a high probability predictive estimate and may be considered as an informative method of preoperative PTC diagnosis. PMID:15914279

  15. BRAF V600E and TERT Promoter Mutations in Papillary Thyroid Carcinoma in Chinese Patients

    PubMed Central

    Gao, Jie; Ren, Xinyu; Teng, Lianghong; Duan, Huanli; Lin, Yansong; Li, Xiaoyi; Zhang, Bo; Liang, Zhiyong

    2016-01-01

    Background The BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations have been reported in papillary thyroid carcinoma (PTC). The aim of this retrospective cross-sectional study was to add further information regarding the prevalence of the BRAF V600E and TERT promoter mutations in Chinese PTC and their clinicopathological associations. Methods We detected the BRAF V600E mutation and TERT promoter mutations in 455 Chinese PTC patients and analyzed the association of these mutations with several clinicopathological features. Results The BRAF V600E mutation was detected in 343 (75.4%) of 455 cases and was significantly associated with older age (p<0.001) and conventional subtype (p = 0.003). TERT promoter mutations were detected in 19 (4.4%) of 434 PTCs and were associated with older age (p<0.001), larger tumor size (p = 0.024), and advanced TNM stage(p<0.001). Of the 19 patients that were positive for TERT promoter mutations, 18 (94.7%) also harbored the BRAF V600E mutation. Conclusion We determined the prevalence and clinicopathological associations of BRAF V600E and TERT promoter mutations in Chinese PTC patients. TERT promoter mutations but not the BRAF V600E mutation were associated with more advanced TNM stage upon diagnosis. PMID:27064992

  16. Hypoglossal nerve palsy following the robotic thyroidectomy for the papillary thyroid carcinoma: A case report

    PubMed Central

    Ahn, Suk-Won; Kang, Kyung Ho

    2015-01-01

    Background Endoscopic surgical techniques with robotic system in the thyroid cancer have been reported to show good results and advantages; however the risk of these techniques has not been fully documented. Presentation of the case We experienced an uncommon complicated case of a 20-year-old woman with a papillary thyroid carcinoma. After the robotic thyroidectomy, she complained of the tongue deviation, speech and swallowing difficulties of hypoglossal nerve palsy. Discussion In this case, a few etiologies could be suggested for the development of hypoglossal nerve palsy. It might be associated with direct stretching or entrapment of hypoglossal nerve during tumor resection; lateral placement of the laryngoscope on the tongue base; the hyperinflation of the laryngeal mask airway; and histological disruption of the intraneural connective tissue and blood circulation. Conclusion Although the robotic surgery is a creative technique and has been known to be safe and effective, the risk of this surgery including traumatic nerve injury should be taken into account before surgery. PMID:26275736

  17. Report of a case of papillary thyroid carcinoma in association with Hashimoto's thyroiditis.

    PubMed

    Okani, Chukwudi Onyeaghana; Otene, Benjamin; Nyaga, Terhemba; Ngbea, Joseph; Eke, Agaba; Edegbe, Felix; Anyiam, Daniel

    2015-01-01

    Hashimoto thyroiditis (HT) is an autoimmune disease, known to be the most common cause of hypothyroidism in nonendemic goitrous areas. It is usually characterized by symmetric, painless, and diffused but sometimes localized swelling of the thyroid gland with features of hypothyroidism. Papillary thyroid carcinoma (PTC), on the other hand, is the most common yet less aggressive form of thyroid cancer, especially in iodine-deficient areas. The coexistence of the two diseases is possible but not common. This case study reports a 50-year-old female with a 10-year history of a huge goiter, which was essentially symptom-free until about 3 months prior to presentation when the patient started complaining of neck pain, dysphagia, productive cough, and cold intolerance. Physical examination revealed focal cystic and tender area in the multinodular swelling and associated cervical lymphadenopathy on the left side of the neck. The serum thyroid stimulating hormone was high, sub-normal T3, and the T4 was low. The fine needle aspiration cytology yielded 10 ml of aspirate of pus admixed with altered blood which on microscopy showed a few suspicious follicular epithelial cells with open nuclei admixed with mainly neutrophil polymorphs, siderophages, and foam cells in a hemorrhagic background. The patient had an incision biopsy that showed areas displaying PTC and HT. PMID:26903704

  18. miR-199a-3p displays tumor suppressor functions in papillary thyroid carcinoma

    PubMed Central

    De Cecco, Loris; Dugo, Matteo; Cassinelli, Giuliana; Pilotti, Silvana; Degl'Innocenti, Debora; Lanzi, Cinzia; Casalini, Patrizia; Pierotti, Marco A.; Greco, Angela; Borrello, Maria Grazia

    2014-01-01

    Thyroid cancer incidence is rapidly increasing. Papillary Thyroid Carcinoma (PTC), the most frequent hystotype, usually displays good prognosis, but no effective therapeutic options are available for the fraction of progressive PTC patients. BRAF and RET/PTC are the most frequent driving genetic lesions identified in PTC. We developed two complementary in vitro models based on RET/PTC1 oncogene, starting from the hypothesis that miRNAs modulated by a driving PTC-oncogene are likely to have a role in thyroid neoplastic processes. Through this strategy, we identified a panel of deregulated miRNAs. Among these we focused on miR-199a-3p and showed its under-expression in PTC specimens and cell lines. We demonstrated that miR-199a-3p restoration in PTC cells reduces MET and mTOR protein levels, impairs migration and proliferation and, more interesting, induces lethality through an unusual form of cell death similar to methuosis, caused by macropinocytosis dysregulation. Silencing MET or mTOR, both involved in survival pathways, does not recapitulate miR-199a-3p-induced cell lethality, thus suggesting that the cooperative regulation of multiple gene targets is necessary. Integrated analysis of miR-199a-3p targets unveils interesting networks including HGF and macropinocytosis pathways. Overall our results indicate miR-199a-3p as a tumor suppressor miRNA in PTC. PMID:24810336

  19. Papillary Thyroid Carcinoma: A Malignant Tumor with Increased Antioxidant Defense Capacity.

    PubMed

    Rovcanin, Branislav R; Gopcevic, Kristina R; Kekic, Dusan Lj; Zivaljevic, Vladan R; Diklic, Aleksandar Dj; Paunovic, Ivan R

    2016-01-01

    Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy worldwide for which the radiation exposure is the most influential risk factor. The levels of oxidative stress in PTC are not well characterized on the tissue level. The objective of this study was to evaluate total oxidant status (TOS) and total antioxidant status (TAS) in PTC and benign goiter (BG) tissues and to examine their association with clinicopathological characteristics. Tumor and normal thyroid tissue samples were collected from 59 PTC patients, and goiter tissues were collected from 50 BG patients. TOS and TAS were quantified in the tissue homogenates by spectrophotometric assays. TOS values in tumor tissues did not differ significantly from normal and goiter tissues; however, PTC tissues have significantly higher TAS values than normal and goiter tissues. TOS values correlated with retrosternal growth in BG patients. The significant correlations were found between TOS and TAS values and thyroid function parameters. In 17 PTC patients with multiple tumor foci (multicentric phenotype), TAS values were significantly lower, compared to 42 patients with unicentric PTC. TAS and TOS are the most useful predictors of thyroid capsular invasion by PTC. The age, sex, body mass index, smoking, familial history of thyroid disease and nodule size did not influence TOS and TAS in PTC or BG patients. In conclusion, we show the profiles of TOS and TAS in PTC and BG tissues. Importantly, PTC tissues possess increased antioxidant capacity. The redox status influences the parameters of the thyroid function and tumor's biological behavior. PMID:27615359

  20. Arachidonate 5 Lipoxygenase Expression in Papillary Thyroid Carcinoma Promotes Invasion via MMP-9 Induction

    PubMed Central

    Kummer, Nicolas T.; Nowicki, Theodore S; Azzi, Jean Paul; Reyes, Ismael; Iacob, Codrin; Xie, Suqing; Swati, Ismatun; Suslina, Nina; Schantz, Stimson; Tiwari, Raj K.; Geliebter, Jan

    2012-01-01

    Arachidonate 5-lipoxygenase (ALOX5) expression and activity has been implicated in tumor pathogenesis, yet its role in papillary thyroid carcinoma (PTC) has not been characterized. ALOX5 protein and mRNA were upregulated in PTC compared to matched, normal thyroid tissue, and ALOX5 expression correlated with invasive tumor histopathology. Evidence suggests that PTC invasion is mediated through the induction of matrix metalloproteinases (MMPs) that can degrade and remodel the extracellular matrix (ECM). A correlation between MMP-9 and ALOX5 protein expression was established by immunohistochemical analysis of PTC and normal thyroid tissues using a tissue array. Transfection of ALOX5 into a PTC cell line (BCPAP) increased MMP-9 secretion and cell invasion across an ECM barrier. The ALOX5 product, 5(S)-hydroxyeicosatetraenoic acid also increased MMP-9 protein expression by BCPAP in a dose-dependent manner. Inhibitors of MMP-9 and ALOX5 reversed ALOX5-enhanced invasion. Here we describe a new role for ALOX5 as a mediator of invasion via MMP-9 induction; this ALOX5/MMP9 pathway represents a new avenue in the search for functional biomarkers and/or potential therapeutic targets for aggressive PTC. PMID:22253131

  1. The pros and cons of prophylactic central neck dissection in papillary thyroid carcinoma

    PubMed Central

    Glover, Anthony R.; Gundara, Justin S.; Norlén, Olov; Lee, James C.

    2013-01-01

    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. PMID:25083483

  2. [BRAF mutation in progression and therapy of melanoma, papillary thyroid carcinoma and colorectal adenocarcinoma].

    PubMed

    Zaleśna, Izabela; Hartman, Mariusz L; Czyż, Małgorzata

    2016-01-01

    BRAF is mutated at a high frequency in various malignancies, including melanoma, papillary thyroid carcinoma and colorectal adenocarcinoma. BRAF is an element of the RAS/RAF/MEK/ERK (MAPK) pathway, which when constitutively active can lead to increased proliferation rate, enhanced survival, invasion and metastasis. The development of small molecule inhibitors of mutant BRAF kinase has changed the care of patients, especially with melanoma. Despite the success in treating melanoma with inhibitors of mutant BRAF and other elements of RAS/RAF/MEK/ERK (MAPK) pathway, resistance limits the long-term responsiveness to these drugs. The resistance mechanisms to MAPK pathway inhibition are complex, occur at genomic and phenotypic levels, and frequently the same patient can simultaneously develop diverse mechanisms of resistance in different progressive metastases or even in the same lesion. In the current review, we summarize recent research on mutations in BRAF and their importance for the development of tumor. This review will also give an overview on the current knowledge concerning therapies for patients harboring mutation in BRAF and discusses the diverse mechanisms of resistance developed in response to these targeted therapies. PMID:27180965

  3. Onco-lncRNA HOTAIR and its functional genetic variants in papillary thyroid carcinoma

    PubMed Central

    Zhu, Hui; Lv, Zheng; An, Changming; Shi, Meng; Pan, Wenting; Zhou, Liqing; Yang, Wenjun; Yang, Ming

    2016-01-01

    The role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) and its functional single nucleotide polymorphisms (SNPs) in papillary thyroid carcinoma (PTC) is still largely unclear. Therefore, we investigated the involvement of lncRNA HOTAIR and its three haplotype-tagging SNPs (htSNPs) in PTC. There was higher expression of HOTAIR in PTC tissues compared to normal tissues. A series of gain-loss assays demonstrated that HOTAIR acts as a PTC oncogene via promoting tumorigenic properties of PTC cells. Additionally, the functional HOTAIR rs920778 genetic variant was a PTC susceptibility SNP. Subjects with the HOTAIR rs920778 TT genotype had an odds ratio (OR) of 1.88, 1.25 and 1.61 (P = 6.0 × 10−6, P = 0.028 and P = 3.2 × 10−5) for developing PTC in Shandong, Jiangsu and Jilin case-control sets compared with subjects with the CC genotype. This statistically significant associations were only found between the rs920778 genetic polymorphism and PTC risk in females but not in males. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was confirmed both in vitro and in vivo. Our results demonstrate that functional SNPs influencing lncRNA regulation may explain a part of PTC genetic basis. PMID:27549736

  4. Diagnosis and Treatment of Pancreatic Metastases of a Papillary Thyroid Carcinoma

    PubMed Central

    Eichhorn, Waltraud; Fottner, Christian; Hansen, Torsten; Schad, Arno; Schadmand-Fischer, Simin; Weber, Matthias M.; Schreckenberger, Mathias; Lang, Hauke; Musholt, Thomas J.

    2010-01-01

    Background Apart from regional lymph node metastases, systemic metastases occur sporadically in papillary thyroid carcinomas (PTC). The lung and bones are the most frequent localizations. Additionally known but extremely rare locations are metastases of the skeletal muscles, ovaries, submandibular gland, sphenoidal sinus, brain, adrenals, and, as shown in only two previously published cases to date, the pancreas. Summary In this article we report about two additional patients with pancreatic metastases from PTC. There is almost no prior experience about therapeutic approaches to this type of metastases. In both patients distant metastases within the pancreas were successfully removed. Postoperative histology confirmed the diagnoses. Supplemental genetic analysis did not demonstrate a BRAF V600E mutation or expression of a RET/PTC1 rearrangement in one case, but revealed a BRAF V600E mutation in the second case. Surgery avoided impending complications maintaining quality of life. One patient had a tumor-specific survival of 42 months. The other patient has occult disease. Conclusions Our two patients benefited of a calculated aggressive surgical action. Thus, if low perioperative mortality and morbidity can be warranted, surgical measures are justifiable in selected cases. PMID:20025539

  5. Genomic copy number analysis of Chernobyl papillary thyroid carcinoma in the Ukrainian-American Cohort.

    PubMed

    Selmansberger, Martin; Braselmann, Herbert; Hess, Julia; Bogdanova, Tetiana; Abend, Michael; Tronko, Mykola; Brenner, Alina; Zitzelsberger, Horst; Unger, Kristian

    2015-11-01

    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

  6. Comparative transcriptional and functional profiling of clear cell and papillary renal cell carcinoma.

    PubMed

    Diegmann, Julia; Tomiuk, Stefan; Sanjmyatav, Jimsgene; Junker, Kerstin; Hindermann, Winfried; von Eggeling, Ferdinand

    2006-09-01

    Renal cell carcinoma (RCC) is known to effectively prevent immune recognition. However, little is known about the mechanisms that underlie this phenomenon. Thus, the identification of immunogenic molecules associated with RCC and the elucidation of the corresponding signaling pathways are crucial to the development of effective treatments. We performed transcriptional and functional profiling with cDNA microarrays (1070 cDNA probes) on a total of 17 RCCs, 11 clear cell and 6 papillary, and on corresponding normal tissue. Samples were clustered based on their expression profiles. We found a total of 45 genes to be regulated equally by both tumor types compared to the normal tissue. A set of 13 differentially expressed genes was identified between the examined tumor subtypes. Functional analysis was performed for both gene sets and showed a significant enrichment of cell surface genes regulated in both tumor subtypes. Within these we found five surface marker genes to be upregulated (TNFRSF10B, CD70, TNFR1, PDGFRB, and BAFF) which are involved in immune responses via the regulation of lymphocytes and can also induce apoptosis. Their overexpression in both tumor subtypes suggests a possible involvement in the immune escape strategies of RCC. The combination of transcriptional and functional profiling revealed potential target molecules for novel therapy strategies that must be studied in more detail. PMID:16865223

  7. HER2 immunohistochemistry significantly overestimates HER2 amplification in uterine papillary serous carcinomas.

    PubMed

    Mentrikoski, Mark J; Stoler, Mark H

    2014-06-01

    Recently, there have been numerous reports showing that HER2 overexpression or amplification occurs in a variable number of uterine papillary serous carcinoma (UPSC) cases, leading to a current clinical trial targeting this pathway. Although approved algorithms exist for scoring HER2 overexpression/amplification in breast and gastroesophageal carcinomas, scoring criteria and the optimal methodology for assessing HER2 in UPSC are currently unknown. Most frequently, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) breast carcinoma algorithms have been utilized for UPSC, wherein cases are screened with immunohistochemistry (IHC), followed by fluorescence in situ hybridization for equivocal cases. However, interpreting HER2 IHC can be prone to significant subjectivity, often leading to false-positive results. To better correlate HER2 IHC results with underlying amplification in UPSC, we compared HER2 overexpression by IHC with HER2 amplification with chromogenic in situ hybridization (CISH). A total of 69 cases of UPSC-57 pure and 12 mixed-were identified over a 10-year period. All were included in a tissue microarray, and HER2 IHC and CISH were performed. Each case was scored according to the most recent 2013, as well as the 2007, ASCO/CAP scoring guidelines for breast carcinoma. Whole-tissue sections were also examined in cases with amplification by CISH on initial screening, as well as an equal number of negative cases, to account for intratumoral heterogeneity. Nine (13%) cases showed HER2 amplification by CISH, whereas 14 (20%) and 28 (40%) cases showed overexpression with IHC when the 2007 or 2013 ASCO/CAP criteria were utilized, respectively. The overall concordance rate between CISH and IHC was 64% (9/14) with the 2007 ASCO/CAP criteria and 32% (9/28) with the 2013 ASCO/CAP criteria. Intratumoral heterogeneity was seen in 3 (33%) amplified cases. No additional amplified cases were identified on subsequent whole

  8. Identification of potential therapeutic targets for papillary thyroid carcinoma by bioinformatics analysis

    PubMed Central

    ZHAO, MING; WANG, KE-JING; TAN, ZHUO; ZHENG, CHUAN-MING; LIANG, ZHONG; ZHAO, JIAN-QIANG

    2016-01-01

    The aim of the present study was to identify potential therapeutic targets for papillary thyroid carcinoma (PTC) and to investigate the possible mechanism underlying this disease. The gene expression profile, GSE53157, was downloaded from the Gene Expression Omnibus database. Only 10 chips, including 3 specimens of normal thyroid tissues and 7 specimens of well-differentiated thyroid carcinomas, were analyzed in the present study. Differentially-expressed genes (DEGs) between PTC patients and normal individuals were identified. Next, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of DEGs were performed. Modules in the protein-protein interaction (PPI) network were identified. Significant target genes were selected from the microRNA (miRNA) regulatory network. Furthermore, the integrated network was constructed with the miRNA regulatory and PPI network modules, and key target genes were screened. A total of 668 DEGs were identified. Modules M1, M2 and M3 were identified from the PPI network. From the modules, DEGs of cyclin-dependent kinase inhibitor 1A, S100 calcium binding protein A6 (S100A6), dual specificity phosphatase 5, keratin 19, met proto-oncogene (MET) and lectin galactoside-binding soluble 3 were included in the Malacards database. In the miRNA regulatory and integrated networks, genes of cyclin-dependent kinase inhibitor 1C (CDKN1C), peroxisome proliferator-activated receptor γ, aryl hydrocarbon receptor, basic helix-loop-helix family, member e40 and reticulon 1 were the key target genes. S100A6, MET and CDKN1C may exhibit key roles in the progression and development of PTC, and may be used as specific therapeutic targets in the treatment of PTC. However, further experiments are required to confirm these results. PMID:26870166

  9. Genetic mutations in accordance with a low malignant potential tumour are not demonstrated in clear cell papillary renal cell carcinoma.

    PubMed

    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-06-01

    Clear cell papillary renal cell carcinoma (CCPRCC) cases were evaluated for mutations on the following genes: KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR. Four male and three female patients of age 42-74 years were evaluated. All cases were incidentally detected by ultrasound and ranged 1.8-3.5 cm. Microscopic examination showed variably tubulopapillary, tubular acinar, cystic architecture and the characteristic linear arrangement of nuclei. The cells were reactive with CK7 (strong), CA IX (cup-shape) and 34 β E12. CD10, AMACR/RACEMASE and GATA3 were negative. There were no mutations on any of the investigated genes. This preliminary observation supports the concept that CCPRCC might be indeed an indolent tumour worth it to be named as clear cell papillary neoplasm of low potential. PMID:26941183

  10. Microfocus of Anaplastic Carcinoma Arising in Mural Nodule of Ovarian Mucinous Borderline Tumor With Very Rapid and Fatal Outcome.

    PubMed

    Mhawech-Fauceglia, Paulette; Ramzan, Amin; Walia, Saloni; Pham, Huyen Q; Yessaian, Annie

    2016-07-01

    A 36-yr-old woman presented with abdominal discomfort. A computed tomography scan revealed a large left cystic and solid pelvic mass without evidence of metastatic disease. Total hysterectomy with bilateral salpingo-oophorectomy and tumor staging was performed. Grossly, the ovarian mass measured 20×18 cm and the cut surface was multiloculated with 1 single mural nodule measuring 2×1.5 cm. The histologic diagnosis of ovarian mucinous borderline tumor with a microfocus of anaplastic carcinoma arising in sarcoma-like mural nodule, FIGO Stage IA was rendered. After 3 mo, the patient returned with symptomatic anemia. A computed tomography scan showed enlarged retroperitoneal and pelvic lymph nodes. Image-guided biopsy of the pelvic lymph node showed a metastatic anaplastic carcinoma from her primary ovarian carcinoma. Chemotherapy was initiated, but the patient developed fulminant disseminated intravascular coagulation within <1 wk of her presentation which was fatal. PMID:26598983

  11. [The utility of aspiration cytology for the distinction of aggressive and non-aggressive papillary carcinoma of the thyroid].

    PubMed

    Caprara, G; Collina, G

    2007-06-01

    Preoperative identification of the aggressive variants of papillary thyroid carcinoma (PTC) by fine needle aspiration (FNAC) has been suggested and different systems for distinguishing them from classical variant of PTC have been employed, including a point-based cytology grading system as suggested by Damiani et al., that we currently use in our Institution. The aim of this paper is to verify if distinction of PTC in aggressive or nonaggressive variants impacts on surgical treatment. In 7 years, from 1998 to 2005, 13586 cases of FNAC of thyroid have been performed; among them 156 PTC. The cytological material of thirty complete thyroidectomies with histology proven papillary thyroid carcinoma were reviewed. 11/30 cases were correctly stratified into the appropriate low or high-grade category. The cytological grading system was discordant with the final histopathological diagnosis in 9/30 cases while in 10 cases the grade was not assessed. Eight cases were downgraded and therefore the low grade papillary carcinoma diagnosed at cytological level turned to be high grade at histology. When those cases were reviewed, the histology of seven cases diagnosed as tall cell variant of PTC failed to show a percentage of tumour cells higher than 50% and therefore it would be better to diagnose them as classical variant of PTC. One case was under-graded at FNAC. The case that was cytologically upgraded was a follicular variant of PTC in Hashimoto thyroiditis with a focus of tall cells. All patients underwent thyroidectomy or thyroidectomy plus lymphadenectomy and from our results the pre-operative diagnosis did not effect the surgical treatment. No patient died of the disease. PMID:17987724

  12. Dose-dependent expression of CLIP2 in post-Chernobyl papillary thyroid carcinomas

    PubMed Central

    Selmansberger, Martin; Kaiser, Jan Christian; Hess, Julia; Güthlin, Denise; Likhtarev, I.; Shpak, Victor; Tronko, Mykola; Brenner, Alina; Abend, Michael; Blettner, Maria; Unger, Kristian; Jacob, Peter; Zitzelsberger, Horst

    2015-01-01

    A previous study on papillary thyroid carcinomas (PTC) in young patients who were exposed to 131iodine from the Chernobyl fallout revealed an exclusive gain of chromosomal band 7q11.23 in exposed cases compared to an age-matched control cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially expressed between exposed and non-exposed cases at messenger RNA and protein level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been developed in a follow-up study. Here we used CLIP2 typing data on 117 post-Chernobyl PTCs from two cohorts of exposed patients with individual dose estimates and 24 non-exposed controls to investigate a possible quantitative dose-response relationship of the CLIP2 marker. The ‘Genrisk-T’ cohort consisted of 45 PTCs and the ‘UkrAm’ cohort of 72 PTCs. Both cohorts differed in mean dose (0.59 Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (AaE) (2 years Genrisk-T, 8 years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was comparable. We analyzed the association between the binary CLIP2 typing and continuous thyroid dose with logistic regression. A clear positive dose-response relationship was found for young PTC cases [age at operation (AaO) < 20 years, AaE < 5 years]. In the elder age group a higher proportion of sporadic tumors is assumed due to a negligible dose response, suggesting different molecular mechanisms in sporadic and radiation-induced cases. This is further supported by the association of elder patients (AaO > 20 years) with positivity for BRAF V600E mutation. PMID:25957251

  13. Intramedullary spinal cord metastasis arising from papillary thyroid carcinoma: A case report and review of literature

    PubMed Central

    Tripathy, Soubhagya R.; Deo, Rama C.; Mishra, Sanjib; Dhir, Manmath K.; Nath, Pratap C.; Satapathy, Mani C.

    2016-01-01

    Background: Intramedullary spinal cord metastases (IMSCM) are typically drop lesions from intracranial metastases and are a rare manifestation of systemic malignancy (8.5% of central nervous system metastases). They arise from primaries such as the lungs, breast, kidney, melanoma, or lymphoma. On the other hand, they arise very rarely from papillary thyroid carcinoma (PTC), even though it is the most common type of primary thyroid malignancy. Case Description: A 54-year-old male presented with pain in the lower back along with tingling, numbness, and weakness in the bilateral lower limbs. This was associated with urine incontinence for 1½ months. In the previous month, he developed a left-sided solitary thyroid nodule. Fine needle aspiration cytology and ultrasonography were suggestive of metastasis. Furthermore, the thoracolumbar magnetic resonance imaging showed T1-hypo and T2-hyper-intense D11-D12 level intramedullary lesion, with intense enhancement, which was consistent with an intramedullary lesion involving the conus. At surgery, a firm, brownish yellow, friable, vascular tumour was removed en toto. Upon discharge, the patient was neurologically intact except for residual bladder incontinence. Conclusion: In an extensive literature review (pubmed), IMSCM metastasis from PTC primary is confirmed as a rarity and this may be the fourth documented case. Moreover, this may be the first report of a case of PTC metastatic neurological deterioration “even before the treatment of the primary was undertaken.” Early diagnosis and microsurgical resection can result in improvement of neurological deficits and in the quality of life of patients with IMSCM. PMID:27274413

  14. Bioinformatics analyses of significant prognostic risk markers for thyroid papillary carcinoma.

    PubMed

    Min, Xiao-Shan; Huang, Peng; Liu, Xu; Dong, Chao; Jiang, Xiao-Lin; Yuan, Zheng-Tai; Mao, Lin-Feng; Chang, Shi

    2015-09-01

    This study was aimed to identify the prognostic risk markers for thyroid papillary carcinoma (TPC) by bioinformatics. The clinical data of TPC and their microRNAs (miRNAs) and genes expression profile data were downloaded from The Cancer Genome Atlas. Elastic net-Cox's proportional regression hazards model (EN-COX) was used to identify the prognostic associated factors. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve were used to screen the significant prognostic risk miRNA and genes. Then, the target genes of the obtained miRNAs were predicted followed by function prediction. Finally, the significant risk genes were performed literature mining and function analysis. Total 1046 miRNAs and 20531 genes in 484 cases samples were identified after data preprocessing. From the EN-COX model, 30 prognostic risk factors were obtained. Based on the 30 risk factors, 3 miRNAs and 11 genes were identified from the ROC and KM curves. The target genes of miRNA-342 such as B-cell CLL/lymphoma 2 (BCL2) were mainly enriched in the biological process related to cellular metabolic process and Disease Ontology terms of lymphoma. The target genes of miRNA-93 were mainly enriched in the pathway of G1 phase. Among the 11 prognostic risk genes, v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue F (MAFF), SRY (sex-determining region Y)-box 4 (SOX4), and retinoic acid receptor, alpha (RARA) encoded transcription factors. Besides, RARA was enriched in four pathways. These prognostic markers such as miRNA-93, miRNA-342, RARA, MAFF, SOX4, and BCL2 may be used as targets for TPC chemoprevention. PMID:25908172

  15. Sub-Classification of Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma by Pathologic Criteria

    PubMed Central

    Jeon, Min Ji; Kim, Won Gu; Jang, Eun Kyung; Choi, Yun Mi; Song, Dong Eun; Sung, Tae-Yon; Yoon, Jong Ho; Chung, Ki-Wook; Hong, Suck Joon; Ryu, Jin-Sook; Han, Ji Min; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

    2015-01-01

    Background Lateral cervical lymph node (LCLN) metastasis, or pathologic N1b disease, is an important risk factor in papillary thyroid carcinoma (PTC). However, many patients have favorable prognosis even with pathologic N1b patients in clinical practice. The study aims to identify high- and intermediate-risk groups based on initial pathologic characteristics in these patients. Patients This study included 518 classical PTC patients confirmed as pathologic N1b at initial surgery between 2001 and 2010. All patients underwent a single fixed activity (5.6 GBq) of radioactive I-131 remnant ablation. Results Patients with a primary tumor larger than 4 cm, gross extrathyroidal extension, metastatic LN larger than 3 cm, or greater than 10 metastatic LCLN were classified as high-risk group. These comprehensive pathologic criteria were retrieved from cox proportional hazard models. Twenty two percent of patients (n = 113) were classified as high-risk and 78% (n = 405) as intermediate-risk group. Successful ablation was identified in only 32% of the patients in the high-risk group and 61% in the intermediate-risk group (p < 0.001). The difference between the two risk groups was independent to gender. There was a significant difference in disease-free survival between the high- and intermediate- risk N1b groups during 5.1 years of median follow-up (84% vs. 59%, p < 0.001). Distant metastasis was more prevalent in the high-risk group (20%) than in the intermediate-risk group (4%, p < 0.001). Conclusions The prognosis of PTC patients with LCLN metastasis varies depending on initial pathologic characteristics. We proposed the comprehensive pathologic criteria for sub-classification of N1b into high- and intermediate-risk groups and this sub-classification may permit personalized management of N1b PTC patients. PMID:26186205

  16. Family of microRNA-146 Regulates RARβ in Papillary Thyroid Carcinoma

    PubMed Central

    Czajka, Agnieszka Anna; Wójcicka, Anna; Kubiak, Anna; Kotlarek, Marta; Bakuła-Zalewska, Elwira; Koperski, Łukasz; Wiechno, Wiesław; Jażdżewski, Krystian

    2016-01-01

    Retinoic acid is a promising tool in adjuvant cancer therapies, including refractory thyroid cancer, and its biological role is mediated by the retinoic acid receptor beta (RARβ). However, expression of RARβ is lowered in papillary thyroid carcinoma (PTC), contributing to promotion of tumor growth and inefficiency of retinoic acid and radioactive iodine treatment. The causes of aberrant RARB expression are largely unknown. We hypothesized that the culpable mechanisms include the action of microRNAs from the miR-146 family, previously identified as significantly upregulated in PTC tumors. To test this hypothesis, we assessed the expression of RARB as well as miR-146a-5p and miR-146b-5p in 48 PTC tumor/normal tissue pairs by Taqman assay to reveal that the expression of RARB was 3.28-fold decreased, and miR-146b-5p was 28.9-fold increased in PTC tumors. Direct interaction between miRs and RARB was determined in the luciferase assay and further confirmed in cell lines, where overexpression of miR-146a-5p and miR-146b-5p caused a 31% and 33% decrease in endogenous RARB mRNA levels. Inhibition of miR-146a and miR-146b resulted in 62.5% and 45.4% increase of RARB, respectively, and a concomitant decrease in proliferation rates of thyroid cancer cell lines, analyzed in xCELLigence system.We showed that two microRNAs of the miR-146 family directly regulate RARB. Inhibition of miRs resulted in restoration of RARB expression and decreased rates of proliferation of thyroid cancer cells. By restoring RARB levels, microRNA inhibitors may become part of an adjuvant therapy in thyroid cancer patients. PMID:27011326

  17. Development and Characterization of Six New Human Papillary Thyroid Carcinoma Cell Lines

    PubMed Central

    Henderson, Ying C.; Ahn, Soon-Hyun; Ryu, Junsun; Chen, Yunyun; Williams, Michelle D.; El-Naggar, Adel K.; Gagea, Mihai; Schweppe, Rebecca E.; Haugen, Bryan R.; Lai, Stephen Y.

    2015-01-01

    Context: Cell lines are a widely used tool in cancer research. However, despite the relatively high incidence of papillary thyroid carcinoma (PTC), there are only four PTC cell lines available for international research audience. Objective: The objective of this study was to establish and characterize new PTC cell lines that represent primary tumor biology. Surgical specimens were obtained to generate PTC cell lines. Short tandem repeat profiling was used to confirm the uniqueness of the cell lines against databases of known cell lines and mutations were assessed using Sequenom. The expression of thyroid-specific genes was examined using real-time PCR. Tumorigenicity was determined using an orthotopic thyroid xenograft tumor mouse model. Results: Six PTC cell lines (five conventional PTCs and one follicular variant of PTC) were generated and found to be unique when compared by short tandem repeat profiling against databases of all existing cell lines. The five conventional PTC cell lines carry the BRAF V600E mutation and the follicular variant of PTC cell line had an NRAS mutation. Five of the six cell lines had a mutation in the promoter of the human telomerase reverse transcriptase gene. None of the cell lines have RET/PTC rearrangements. Three cell lines were tumorigenic in the orthotopic thyroid xenograft tumor mouse model. Conclusions: These five characterized conventional PTC cell lines and the unique follicular variant of PTC cell line should be valuable reagents for thyroid cancer research. The three tumorigenic cell lines can be used for in vivo testing of targeted therapeutic and novel agents. PMID:25427145

  18. Ultrasonographic features and clinical characteristics of Warthin-like variant of papillary thyroid carcinoma.

    PubMed

    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. PMID:26806192

  19. Papillary renal cell carcinoma: a clinicopathological and whole-genome exon sequencing study

    PubMed Central

    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

  20. Effects of endocrine therapy on the prognosis of elderly patients after surgery for papillary thyroid carcinoma.

    PubMed

    Xia, Qing; Dong, Shuai; Bian, Ping-Da; Wang, Jue; Li, Cheng-Jiang

    2016-04-01

    Papillary thyroid carcinoma (PTC) is a common thyroid malignancy. Elderly patients have more severe disease and more complications following postoperative endocrine therapy to control thyroid-stimulating hormone (TSH) levels. We aimed to identify optimal postoperative serum TSH levels in elderly patients to prevent recurrence and metastasis and minimize complications. This retrospective cohort study collected data of 87 consecutive elderly patients (age >75) who underwent surgery for PTC with postoperative levothyroxine therapy (50-150 μg/d) between January 2006 and June 2008 and were followed until 2013. After 24 patients with TSH fluctuations and incomplete data were excluded, 73 patients were grouped based on postoperative TSH levels: Group A, 0.3-0.5 mIU/mL; Group B, 0.1-0.3 mIU/mL; and Group C <0.1 mIU/mL (n = 24, 25, 24, respectively). Subjects' baseline, preoperative data, postoperative complications and 1-, 3- and 5-year follow-up data were compared between groups. No significant differences in gender, age (median age of 80 years old), surgery type or clinical characteristics were found between groups (all p value >0.05). Postoperatively, all subjects had normal ECG and neck ultrasound, no osteoporosis, and no differences in survival rate or metastasis. Five-year follow-up revealed significant differences in development of arrhythmias, osteoporosis, insomnia and anxiety between Groups B (0.1-0.3 mIU/mL) and C (<0.1 mIU/mL) compared to Group A (0.3-0.5 mIU/mL). Postoperative incidence of PTC recurrence and metastasis remained stable in elderly patients undergoing thyroid surgery and endocrine therapy but complications increased significantly with increasing TSH levels. Controlling TSH to lower limits of normal may help prevent PTC recurrence and metastasis and reduce complications in this high-risk population. PMID:25744048

  1. Intravascular extension of papillary thyroid carcinoma to the internal jugular vein: A case report

    PubMed Central

    Al-Jarrah, Q.; Abou-Foul, Ak.; Heis, H.

    2014-01-01

    INTRODUCTION Papillary thyroid cancer (PTC) is the most common thyroid malignancy and usually spreads via lymphatic system. PTC can sometimes show microscopic vascular invasion, but rarely causes tumour thrombus in the internal jugular vein (IJV) or other great veins of the neck. PRESENTATION OF CASE We report a case of a 62-year-old female presented with symptomatic central neck mass. Clinical examination revealed a hard solitary right-sided thyroid nodule with ipsilateral cervical lymphadenopathy. Ultrasonography (US) confirmed the clinical diagnosis and visualised a dilated ipsilateral IJV. Fine-needle aspiration cytology revealed PTC cells so total thyroidectomy with right neck dissection was done. A tumour thrombus was discovered in the distended right IJV and was cleared successfully. The patient recovered well after the operation with no local or distant metastasis detected. DISCUSSION Tumour vascular spread is observed in tumours with angio-invasive features including follicular carcinoma of the thyroid gland where great cervical veins can be affected. PTC commonly spreads to the lymph nodes and vascular spread via direct intravascular extension is extremely rare. Neck US has an important role in the diagnosis, and operators should attempt to detect signs of tumour thrombi in all patients with thyroid masses. Aggressive surgical treatment with vascular repair is recommended whenever possible to minimise the risk of potentially fatal complications of the intraluminal masses. CONCLUSION Intravascular tumour extension of PTC is rare but with serious consequences. Diagnosis with neck US is possible but some cases are only discovered intraoperatively. Thrombectomy with vascular repair or reconstruction is usually possible. PMID:25044067

  2. Family of microRNA-146 Regulates RARβ in Papillary Thyroid Carcinoma.

    PubMed

    Czajka, Agnieszka Anna; Wójcicka, Anna; Kubiak, Anna; Kotlarek, Marta; Bakuła-Zalewska, Elwira; Koperski, Łukasz; Wiechno, Wiesław; Jażdżewski, Krystian

    2016-01-01

    Retinoic acid is a promising tool in adjuvant cancer therapies, including refractory thyroid cancer, and its biological role is mediated by the retinoic acid receptor beta (RARβ). However, expression of RARβ is lowered in papillary thyroid carcinoma (PTC), contributing to promotion of tumor growth and inefficiency of retinoic acid and radioactive iodine treatment. The causes of aberrant RARB expression are largely unknown. We hypothesized that the culpable mechanisms include the action of microRNAs from the miR-146 family, previously identified as significantly upregulated in PTC tumors. To test this hypothesis, we assessed the expression of RARB as well as miR-146a-5p and miR-146b-5p in 48 PTC tumor/normal tissue pairs by Taqman assay to reveal that the expression of RARB was 3.28-fold decreased, and miR-146b-5p was 28.9-fold increased in PTC tumors. Direct interaction between miRs and RARB was determined in the luciferase assay and further confirmed in cell lines, where overexpression of miR-146a-5p and miR-146b-5p caused a 31% and 33% decrease in endogenous RARB mRNA levels. Inhibition of miR-146a and miR-146b resulted in 62.5% and 45.4% increase of RARB, respectively, and a concomitant decrease in proliferation rates of thyroid cancer cell lines, analyzed in xCELLigence system.We showed that two microRNAs of the miR-146 family directly regulate RARB. Inhibition of miRs resulted in restoration of RARB expression and decreased rates of proliferation of thyroid cancer cells. By restoring RARB levels, microRNA inhibitors may become part of an adjuvant therapy in thyroid cancer patients. PMID:27011326

  3. Long noncoding RNA are aberrantly expressed in human papillary thyroid carcinoma

    PubMed Central

    YANG, MEILIU; TIAN, JINLI; GUO, XIN; YANG, YING; GUAN, RUHUA; QIU, MINGYUE; LI, YUKAI; SUN, XUELING; ZHEN, YANFENG; ZHANG, YAZHONG; CHEN, CHUNYOU; LI, YANBING; FANG, HUI

    2016-01-01

    Long noncoding RNAs (lncRNAs) have emerged as key regulatory molecules at almost every level of gene expression regulation. The altered expression of lncRNAs is a characteristic of numerous types of cancer, and lncRNAs have been demonstrated to promote the development, invasion and metastasis of tumors through various mechanisms. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) remain unclear. In the present study, differentially expressed lncRNAs and mRNAs were detected by human lncRNA microarray in three pairs of PTC and adjacent noncancerous samples. The microarray results revealed that 675 lncRNAs and 751 mRNAs were abnormally expressed in the three PTC samples compared with adjacent noncancerous samples (fold change ≥2.0; P<0.05). To validate the microarray results, 8 differentially expressed lncRNAs were randomly selected for quantitative polymerase chain reaction (qPCR). The results of qPCR were consistent with the microarray data; the 8 lncRNAs had an aberrant expression in the PTC samples compared with the adjacent noncancerous samples. Gene ontology and pathway analysis indicated that there were 7 downregulated pathways and 29 upregulated pathways in PTC. LncRNA classification and subgroup analysis revealed 7 pairs of enhancer-like lncRNA-mRNA, 9 pairs of antisense lncRNA-mRNA and 45 pairs of lncRNA-mRNA were differentially expressed between PTC and their paired noncancerous samples. In conclusion, the present study identified a series of novel PTC-associated lncRNAs. Further study with these lncRNAs is instrumental for the identification of novel target molecules that could lead to improved diagnosis and treatment for PTC. PMID:27347178

  4. Role of charcoal tattooing in localization of recurred papillary thyroid carcinoma: initial experiences

    PubMed Central

    Kwon, Hyungju; Tae, Soon Young; Kim, Su-Jin; Jung, Kyeong Cheon; Kim, Ji-Hoon; Youn, Yeo-Kyu

    2015-01-01

    Purpose Surgical excision is the definitive treatment for localized recurrence of papillary thyroid carcinoma. Reoperation for recurrence, however, is challenging and associated with increased operative times and complication rates. For safe and effective reoperation, ultrasound-guided charcoal tattooing localization can be used. The aim of this study was to investigate the feasibility and safety of the ultrasound-guided charcoal tattooing localization. Methods Between November 2012 and August 2013, ten patients underwent preoperative charcoal tattooing localization for twelve recurrent lesions. Patient demographics, pathologic features, and operation results were reviewed. Results The technical success rate of charcoal tattooing was 100%. Eight patients had one recurrent lesion, and two patients had double lesions. Among these 12 recurrent lesions, three (25%) were found in level II, four (33%) in level IV, four (33%) in level VI, and one (8%) was found in the thyroidectomy bed site. The mean size of lesions was 0.87 ± 0.35 cm. Of these 10 patients, eight patients underwent selective lymph node dissection, one patient underwent modified radical neck dissection, and one patient underwent recurrent mass excision. Transient hypocalcemia developed in one patient, and no recurrent laryngeal nerve palsy occurred. There were no major complications related to the injection of the charcoal. The mean follow-up period after reoperation was 8.6 ± 2.7 months; in the follow-up ultrasound, there were no remnant lesions in all patients. Conclusion Preoperative ultrasound-guided charcoal tattooing localization for recurrent thyroid cancer appears to be a feasible and safe procedure for reoperation. Further evaluation is warranted in larger patients' cohorts. PMID:25741493

  5. Discrepancies between the ultrasonographic and gross pathological size of papillary thyroid carcinomas

    PubMed Central

    2016-01-01

    Purpose: The goal of this study was to investigate the level of agreement between tumor sizes measured on ultrasonography (US) and in pathological specimens of papillary thyroid carcinomas (PTCs) and to identify the US characteristics contributing to discrepancies in these measurements. Methods: We retrospectively reviewed the US findings and pathological reports of 490 tumors in 431 patients who underwent surgery for PTC. Agreement was defined as a difference of <20% between the US and pathological tumor size measurements. Tumors were divided by size into groups of 0.5-1 cm, 1-2 cm, 2-3 cm, and ≥3 cm. We compared tumors in which the US and pathological tumor size measurements agreed and those in which they disagreed with regard to the following parameters: taller-than-wide shape, infiltrative margin, echogenicity, microcalcifications, cystic changes in tumors, and the US diagnosis. Results: The rate of agreement between US and the pathological tumor size measurements was 64.1% (314/490). Statistical analysis indicated that the US and pathological measurements significantly differed in tumors <1.0 cm in size (P=0.033), with US significantly overestimating the tumor size by 0.2 cm in such tumors (P<0.001). Cystic changes were significantly more frequent in the tumors where US and pathological tumor size measurements disagreed (P<0.001). Conclusion: Thyroid US may overestimate the size of PTCs, particularly for tumors <1.0 cm in size. This information may be helpful in guiding decision making regarding surgical extent. PMID:26983767

  6. Mucocele-like tumor associated with ductal carcinoma in situ diagnosed as mucinous carcinoma by fine-needle aspiration cytology: report of a case.

    PubMed

    Kikuchi, Shoichi; Nishimura, Reiki; Osako, Tomofumi; Okumura, Yasuhiro; Hayashi, Mitsuhiro; Toyozumi, Yasuo; Arima, Nobuyuki

    2012-02-01

    Mucocele-like tumors (MLTs) of the breast are rare, with only 11 cases reported from Japan and 35 cases from other countries. MLTs of the breast were first described by Rosen in 1986. They are believed to be related to atypical ductal hyperplasia, ductal carcinoma, or mucinous carcinoma. It is difficult to diagnose this tumor preoperatively, and especially difficult to differentiate between benign and malignant forms. We report a case of MLT associated with ductal carcinoma in situ, which was initially diagnosed as fibroadenoma by mammography and ultrasonography, and as mucinous carcinoma by fine-needle aspiration cytology. We discuss the characteristic findings of imaging and the appropriate clinical treatment of this tumor. The characteristic image first signals the possibility of this tumor, following which the diagnosis can be confirmed by pathological examination of a fully excised tumor specimen. Breast-conserving surgery is recommended because of the low risk of high-grade malignancy, even when malignancy is confirmed, and lymph node dissection may be avoided. PMID:22237901

  7. RET/PTC Translocations and Clinico-Pathological Features in Human Papillary Thyroid Carcinoma

    PubMed Central

    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

  8. Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

    SciTech Connect

    Kim, Anne; Schreiber, David; Rineer, Justin; Choi, Kwang; Rotman, Marvin

    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: We 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.

  9. Expression profile of mucin-associated sialyl-Tn antigen in Chinese patients with different colorectal lesions (adenomas, carcinomas)

    PubMed Central

    Xu, Feng; Fan, Cuizhen; Fan, Shanshan; Liu, Fuquan; Wen, Tao; An, Guangyu; Feng, Guosheng

    2015-01-01

    Background: The sialyl-Tn (sTn) antigen is a mucin-associated carbohydrate antigen expressed by numerous human carcinomas, and is also claimed to be a prognostic factor in colorectal cancer. But the associations between sTn and colorectal cancer remain elusive and controversial. Here, we investigated the expression profile of sTn antigen in a series of human colorectal tissue samples including normal colon, colorectal adenomas, and colorectal carcinomas (CRCs), with an aim to analyzing whether sTn plays a role in the progression and development of Chinese patients with CRCs. Methods: Immunohistochemical staining of sTn antigen was performed in formalin-fixed, paraffin-embedded colonic sections from 4 healthy controls, 44 patients with colorectal adenomas, and 186 patients with primary CRCs. Results: No sTn antigen was detected in normal colonic tissues. There were 41 of 44 patients with colorectal adenomas (93.2%), and 141 of 186 patients with CRCs (75.8%) found to express sTn antigen. The patterns of sTn localization were different in adenomas and carcinomas of colonic tissues. Colorectal adenomas showed predominant supranuclear distribution of sTn antigen, while carcinomas revealed apical membrane, mucin droplet and diffuse cytoplasmic localization. Notably, sTn was significantly associated with the degree of differentiation (P = 0.006) and perineural invasion (P = 0.041) of the tumors, but was independent of age, gender, tumor location, depth of penetration, status of lymph nodes, lymphovascular invasion and TNM stage. Conclusions: These results indicate that sTn may play a role in initiating colorectal carcinogenesis and promoting tumor progression. Determination of sTn expression and localization may assist in evaluating malignant status of colorectal lesions. PMID:26617889

  10. Activating BRAF Mutations Detected in Mixed Hürthle Cell Carcinoma and Multifocal Papillary Carcinoma of the Thyroid Gland: Report of an Unusual Case and Review of the Literature.

    PubMed

    Sinno, Sara; Choucair, Mahmoud; Nasrallah, Mona; Wadi, Lara; Jabbour, Mark N; Nassif, Samer

    2016-09-01

    Despite the increase in the incidence of thyroid carcinomas, the occurrence of collision tumors in the thyroid remains a rare event. We present the case of a 69-year-old female who presented to the emergency department with a chief complaint of painful neck swelling. Imaging revealed a large right hemithyroid mass and a left hemithyroid nodule. Fine needle aspiration of the lesions and subsequent total thyroidectomy revealed a Hürthle cell carcinoma in the right lobe and bilateral multicentric papillary carcinoma foci, including 2 foci with a classical pattern and 1 encapsulated follicular variant in the isthmus. BRAF gene mutation analysis revealed V600E gene mutation in the classical variants of papillary carcinoma and in the Hürthle cell carcinoma. The focus of follicular variant of papillary carcinoma in the isthmus and a sample from normal thyroid tissue did not harbor BRAF mutations. This case is remarkable in being an unusual report of a follicular Hürthle cell carcinoma harboring the BRAF V600E mutation and occurring in collision with multifocal papillary carcinoma. Documentation of such cases is important as it helps better understand the pathogenesis, clinical behavior, and radiologic findings of such rare lesions and to determine the optimal treatment modalities. PMID:27006301

  11. A Rare Case of Concomitant Maxilla and Mandible Brown Tumours, Papillary Thyroid Carcinoma, Parathyroid Adenoma, and Osteitis Fibrosa Cystica

    PubMed Central

    Nunes, Thaís Borguezan; Bologna, Sheyla Batista; Witzel, Andréa Lusvarghi; Nico, Marcello Menta Simonsen; Lourenço, Silvia Vanessa

    2016-01-01

    Objective. The brown tumour of hyperparathyroidism is a result of a metabolic disorder caused by primary hyperparathyroidism. Report. We described a case of a 37-year-old female patient presenting bimaxillary intraoral lesions and swelling in the neck. Incisional biopsy of the oral lesion was performed and histopathological examination revealed a central giant cell lesion composed by intense haemorrhagic exudate, abundant presence of giant cells, and areas with hemosiderin pigment. The patient also presented high levels of serum calcium and parathyroid hormone, hyperfunctioning parathyroid tissue, bilateral parenchymal nephropathy, and densitometry lower than expected, showing an advanced stage of osteitis fibrosa cystica. Synchronous parathyroid adenoma and papillary thyroid carcinoma were confirmed by imaging exams and histopathologically. Conclusion. The composition of all the clinical, pathological, and imaging findings led to the final diagnosis of brown tumour of hyperparathyroidism. The occurrence of parathyroid adenoma, papillary thyroid carcinoma, and brown tumours of hyperparathyroidism in their late stage (osteitis fibrosa cystica) associated with oral brown tumours involving the mandible and maxilla is extremely rare. PMID:26881146

  12. Coexistence of Papillary Thyroid Carcinoma With Thyroid MALT Lymphoma in a Patient With Hashimoto's Thyroiditis: A Clinical Case Report.

    PubMed

    Shen, Guohua; Ji, Ting; Hu, Shuang; Liu, Bin; Kuang, Anren

    2015-12-01

    Papillary thyroid carcinoma (PTC) is the most common type of thyroid neoplasias; however, primary thyroid gland lymphoma (PTL) is uncommon and their simultaneous occurrence is very rare.Herein, we reported a 25-year-old female patient with Hashimoto's thyroiditis (HT), who developed a small goiter with a palpable 1.2-cm nodule in the right lobe. A fine-needle aspiration (FNA) biopsy revealed atypical follicular epithelial cells and lymphoid cells in a background of lymphocytic thyroiditis. A total thyroidectomy was performed. The pathology showed multicentric papillary thyroid carcinoma, concomitant thyroid mucosa-associated lymphoid tissue (MALT) lymphoma, and Hashimoto's thyroiditis. Postoperatively, he received chemotherapy and radioactive iodine ablation treatment. Nowadays the thyroglobulin of the patient is undetectable, without recurrences at 2 years of follow-up.It is concluded that the PTC and MALT lymphoma can exist concomitantly, especially in patients with HT. For the diagnostic workup and optional management of this rare coexistence, a multidisciplinary approach and close surveillance are needed. PMID:26717396

  13. The Clinical Relevance of Psammoma Body and Hashimoto Thyroiditis in Papillary Thyroid Carcinoma

    PubMed Central

    Cai, Ye-Feng; Wang, Qing-Xuan; Ni, Chun-Jue; Guo, Gui-Long; Li, Quan; Wang, Ou-Chen; Wu, Liang; Du, Hai-Yan; You, Jie; Zhang, Xiao-Hua

    2015-01-01

    Abstract This study aims to investigate the impact of psammoma body (PB) on papillary thyroid carcinoma (PTC), and evaluate the association among PB, Hashimoto thyroiditis (HT), and other clinicopathologic characteristics in PTC patients. We conducted a retrospective case-control study involving 1052 PTC patients who underwent total thyroidectomy or lobectomy with lymph node dissection. Psammoma body was observed in 324 out of 1052 PTC (30.8%) patients. Ultrasonographic (US) calcification (P < 0.001), multifocality of the tumor (P = 0.047), lymph node metastasis (LNM) (P < 0.001), HT (P < 0.001), and Primary tumor (T), Regional lymph nodes (N), Distant metastasis (M) staging (P = 0.001) were significantly related to the presence of PB. The presence of PB was significantly associated with US microcalcification (P < 0.001). In the subgroup with HT, compared with the patients without PB, the patients with PB exhibited a higher frequency of central LNM (54.7% vs 32.1%; P < 0.001) and US microcalcification (94.7% vs 38.8%; P < 0.001), as well as smaller tumors (0.9 ± 0.6 vs 1.3 ± 0.9 cm; P < 0.001). In the subgroup without HT, the patients with PB displayed a higher incidence of lateral LNM (25.8% vs 14.6%; P < 0.001), US microcalcification (87.3% vs 52.5%; P < 0.001), and extrathyroidal extension (47.2% vs 34.8%; P = 0.001), as well as larger tumors (1.3 ± 0.9 vs 1.0 ± 0.8 cm; P < 0.001) than without PB. Moreover, in the subgroup with PB, the PTC patients with HT showed a higher LNM (77.9% vs 57.2%; P < 0.001) and a lower frequency of extrathyroidal extension (20.0% vs 47.2%; P < 0.001) than without HT. Psammoma body is a useful predictor of aggressive tumor behavior in PTC patients. HT with PB shows more aggressive behaviors than non-HT with PB in PTC patients. PMID:26554782

  14. MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma.

    PubMed

    Romitti, Mírian; Wajner, Simone Magagnin; Ceolin, Lucieli; Ferreira, Carla Vaz; Ribeiro, Rafaela Vanin Pinto; Rohenkohl, Helena Cecin; Weber, Shana de Souto; Lopez, Patrícia Luciana da Costa; Fuziwara, Cesar Seigi; Kimura, Edna Teruko; Maia, Ana Luiza

    2016-03-01

    Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in human PTC cell lines (K1 and TPC-1 cells) or tumor samples. DIO3 mRNA and activity were evaluated by real-time PCR and ion-exchange column chromatography respectively. Western blot analysis was used to determine the levels of D3 protein. DIO3 gene silencing was performed via siRNA transfection. DIO3 mRNA levels and activity were readily detected in K1 (BRAF(V6) (0) (0E)) and, at lower levels, in TPC-1 (RET/PTC1) cells (P<0.007 and P=0.02 respectively). Similarly, DIO3 mRNA levels were higher in PTC samples harboring the BRAF(V600E) mutation as compared with those with RET/PTC1 rearrangement or negative for these mutations (P<0.001). Specific inhibition of BRAF oncogene (PLX4032, 3 μM), MEK (U0126, 10-20 μM) or p38 (SB203580, 10-20 μM) signaling was associated with decreases in DIO3 expression in K1 and TPC-1 cells. Additionally, the blockage of the sonic hedgehog (SHH) pathway by cyclopamine (10 μM) resulted in markedly decreases in DIO3 mRNA levels. Interestingly, siRNA-mediated DIO3 silencing induced decreases on cyclin D1 expression and partial G1 phase cell cycle arrest, thereby downregulating cell proliferation. In conclusion, sustained activation of the MAPK and SHH pathways modulate the levels of DIO3 expression in PTC. Importantly, DIO3 silencing was associated with decreases in cell proliferation, thus suggesting a D3 role in tumor growth and aggressiveness. PMID:26825960

  15. Papillary thyroid carcinoma: different clinical behavior among pT3 tumors.

    PubMed

    Santos, Maria Joana; Bugalho, Maria João

    2016-09-01

    pT3 papillary thyroid carcinoma (PTC) can be divided into three subgroups according to the largest diameter >4 cm or evidence of minimal extrathyroidal extension (ETE): A >4 cm, no ETE; B ≤4 cm, with ETE; and C >4 cm, with ETE. The aim of this study was to analyze whether these subgroups are clinically different. A retrospective analysis of clinicopathological data of patients with pT3 PTC, with a minimum follow-up of 2 years, at a referral center was conducted. Outcome was evaluated after primary treatment and after 2 and 5 years of follow-up. Patients were classified as no evidence of disease (NED), biochemical evidence of disease (BED), and structural evidence of disease (SED) either locoregional (SED-L) or at distance (SED-D). The study patients were classified into three groups as follows: Group A (n = 91), Group B (n = 101), and Group C (n = 23). Most patients were female (80.0 %); mean age at diagnosis was 49.9 ± 16.5 years. 214 patients underwent total thyroidectomy; 208 patients were treated with (131)I. Median follow-up was 6.0 years. After primary treatment, the condition of NED was significantly different between the groups (A-87.9 %, B-68.3 %, C-43.5 %; p < 0.001). Recurrence rate, either biochemical or structural, was 8.8, 7.2, and 30.0 % in groups A, B, and C, respectively. Clinical status after 2 years anticipated clinical status after 5 years, except for Group B. ETE and tumor size were found to be predictors of disease status after primary treatment and after 2 years. ETE appeared as the strongest predictor of persistence of disease after primary treatment as well as of evidence of disease, either biochemical or structural, after 2 years of follow-up. PMID:27000081

  16. Downregulation of long noncoding RNA NONHSAT037832 in papillary thyroid carcinoma and its clinical significance.

    PubMed

    Lan, Xiabin; Sun, Wei; Zhang, Ping; He, Liang; Dong, Wenwu; Wang, Zhihong; Liu, Siming; Zhang, Hao

    2016-05-01

    Long noncoding RNA (lncRNA) is a kind of RNA that is longer than 200 nucleotides with limited or no protein-coding potential. Studies have proved that lncRNAs play important regulatory roles in gene expression and contribute to oncogenesis and cancer metastasis. However, the expression level of lncRNAs and their clinicopathologic significance in papillary thyroid carcinoma (PTC) have not been well studied. In this study, we investigated the expression level of a novel lncRNA NONHSAT037832 in PTC and paired noncancerous thyroid tissues as well as some cell lines by quantitative real-time polymerase chain reaction. The association between the expression level of NONHSAT037832 and clinicopathologic characteristics of patients with PTC was further analyzed. Three receiver operating characteristic curves (ROCs) were established to evaluate the diagnostic value of NONHSAT037832. The results suggested that the expression level of NONHSAT037832 was significantly decreased in PTC compared with paired noncancerous tissues (P < 0.01). And, NONHSAT037832 was also significantly downregulated in two PTC cell lines (K1 and IHH-4) compared to normal thyroid follicular epithelial cell line Nthy-ori 3-1 (P < 0.01). Downregulated NONHSAT037832 was significantly associated with lymph node metastasis (P = 0.015) and tumor size (P = 0.032). The ROCs revealed that NONHSAT037832 had a high diagnostic value for differentiating between PTC and noncancerous diseases as well as identifying PTC with lymph node metastasis and larger tumors (≥3 cm). The area under curve was up to 0.897 (95%CI = 0.852-0.942, P = 0.000), 0.641 (95%CI = 0.519-0.762, P = 0.033), and 0.702 (95%CI = 0.567-0.827, P = 0.008), respectively. This study indicated that NONHSAT037832 might serve as a potential biomarker of PTC. PMID:26611646

  17. The Utility of Sentinel Lymph Node Biopsy in Papillary Thyroid Carcinoma with Occult Lymph Nodes

    PubMed Central

    Yan, Xingqiang; Zeng, Ruichao; Ma, Zhaosheng; Chen, Chengze; Chen, Endong; Zhang, Xiaohua; Cao, Feilin

    2015-01-01

    Background The sentinel lymph node (SLN) is defined as the first draining node from the primary lesion, and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. The aim of this study was to evaluate the clinical application of SLN biopsy (SLNB) in papillary thyroid carcinoma (PTC) with occult lymph nodes. Methods From April 2006 to October 2012, 212 consecutive PTC patients were treated with SLNB using carbon nanoparticle suspension (CNS). Then, the stained nodes defined as SLN were collected, and prophylactic central compartment neck dissection (CCND) followed by total thyroidectomy or subtotal thyroidectomy were performed. All the samples were sent for pathological examination. Results There were 78 (36.8%) SLN metastasis (SLNM)-positive cases and 134 (63.2%) SLNM-negative cases. The sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates of SLNB were 78.8%, 100%, 100%, 84.3%, 0%, and 21.2%, respectively. The PTC patients with SLNM were more likely to be male (48.2% vs. 32.7%, p = 0.039) and exhibited multifocality (52.6% vs. 33.3%, p = 0.025) and extrathyroidal extension (56.7% vs. 33.5%, p = 0.015). A greater incidence of non-SLN metastases in the central compartment was found in patients with SLNM (41/78, 52.6%) than in those without SLNM (21/134, 15.7%; p < 0.05). However, the SLNM-negative PTC patients with non-SLN metastases were more likely to be male (37.9% vs. 9.5%, p < 0.05). Conclusions The application of SLNB using CNS is technically feasible, safe, and useful, especially for male patients with co-existing multifocality and extrathyroidal extension. However, the sensitivity of SLNB must be improved and its false-negative rate reduced before it can be a routine procedure and replace prophylactic CCND. More attention should be paid to PTC patients (especially males) without SLNM for signs of non-SLN metastases. PMID:26046782

  18. Expression of Notch 1 receptor associated with tumor aggressiveness in papillary thyroid carcinoma

    PubMed Central

    Fu, Hongliang; Ma, Chao; Guan, Wenbin; Cheng, Weiwei; Feng, Fang; Wang, Hui

    2016-01-01

    Aim The aim of this study was to assess if the expression of Notch 1 receptor is associated with tumor aggressiveness in papillary thyroid carcinomas (PTCs). Patients and methods By searching the electronic medical record system of Xin Hua Hospital, all cases of PTC patients who underwent thyroidectomy in the hospital between 2013 and 2014 were retrieved. Then, the cases of patients who had a history of any other malignancy or whose thyroid tumor specimen was not available for assay were rejected. Finally, 68 cases of PTC patients were obtained. Formalin-fixed paraffin-embedded tissue blocks of these patients were studied by immunohistochemistry to learn the expression of Notch 1 receptor. Meanwhile, the clinical data of these patients including sex, age, size of the tumor, presence of node metastasis or distant metastasis, and presence of capsule invasion and tumor multicentricity were collected. Pearson’s chi-square test or Fisher’s exact test was used for measuring statistical differences in categorical variables. All the statistical tests were two-sided. A P-value <0.05 was considered to be statistically significant. Results A total of 19 male and 49 female PTC patients with a mean age of 44.8±13.6 years (range 18–78 years) were studied. Notch 1 receptor expression was found in 15/68 (22%) samples of PTC. The expression of Notch 1 receptor was significantly associated with tumor size (P=0.021), distant metastasis (P=0.008), capsule invasion (P=0.001), tumor multicentricity (P=0.018), and age (P=0.033). However, the expression of Notch 1 receptor was not significantly correlated with node metastasis (P=0.096) and sex (P=0.901). Conclusion The expression of Notch 1 receptor is associated with tumor aggressiveness in PTC, and may be used as a molecular marker of tumor invasiveness in PTC. PTC patients who show positive expression of Notch 1 receptor may benefit from radioiodine remnant ablation. PMID:27042120

  19. Effect of BRAF mutational status on expression profiles in conventional papillary thyroid carcinomas

    PubMed Central

    2015-01-01

    Background Whereas 40 % to 70 % of papillary thyroid carcinomas (PTCs) are characterized by a BRAF mutation (BRAFmut), unified biomarkers for the genetically heterogeneous group of BRAF wild type (BRAFwt) PTCs are not established yet. Using state-of-the-art technology we compared RNA expression profiles between conventional BRAFwt and BRAFmut PTCs. Methods Microarrays covering 36,079 reference sequences were used to generate whole transcript expression profiles in 11 BRAFwt PTCs including five micro PTCs, 14 BRAFmut PTCs, and 7 normal thyroid specimens. A p-value with a false discovery rate (FDR) < 0.05 and a fold change > 2 were used as a threshold of significance for differential expression. Network and pathway utilities were employed to interpret significance of expression data. BRAF mutational status was established by direct sequencing the hotspot region of exon 15. Results We identified 237 annotated genes that were significantly differentially expressed between BRAFwt and BRAFmut PTCs. Of these, 110 genes were down- and 127 were upregulated in BRAFwt compared to BRAFmut PTCs. A number of molecules involved in thyroid hormone metabolism including thyroid peroxidase (TPO) were differentially expressed between both groups. Among cancer-associated molecules were ERBB3 that was downregulated and ERBB4 that was upregulated in BRAFwt PTCs. Two microRNAs were significantly differentially expressed of which miR492 bears predicted functions relevant to thyroid-specific molecules. The protein kinase A (PKA) and the G protein-coupled receptor pathways were identified as significantly related signaling cascades to the gene set of 237 genes. Furthermore, a network of interacting molecules was predicted on basis of the differentially expressed gene set. Conclusions The expression study focusing on affected genes that are differentially expressed between BRAFwt and BRAFmut conventional PTCs identified a number of molecules which are connected in a network and affect

  20. A Primary Retroperitoneal Mucinous Tumor

    PubMed Central

    Heelan Gladden, Alicia A.; Wohlauer, Max; McManus, Martine C.; Gajdos, Csaba

    2015-01-01

    A twenty-five-year-old female presented with a large retroperitoneal mass. Workup included history and physical exam, imaging, biopsy, colonoscopy, and gynecologic exam. After surgical resection, the mass was determined to be a primary retroperitoneal mucinous tumor (PRMT). Clinically and histologically, these tumors are similar pancreatic and ovarian mucinous neoplasms. PRMTs are rare and few case reports have been published. PRMTs are divided into mucinous cystadenomas, mucinous borderline tumors of low malignant potential, and mucinous carcinoma. These tumors have malignant potential so resection is indicated and in some cases adjuvant chemotherapy and/or surveillance imaging. PMID:25874152

  1. Oncocytic papillary renal cell carcinoma: a clinicopathological study emphasizing distinct morphology, extended immunohistochemical profile and cytogenetic features.

    PubMed

    Xia, Qiu-Yuan; Rao, Qiu; Shen, Qin; Shi, Shan-Shan; Li, Li; Liu, Biao; Zhang, Jin; Wang, Yan-Fen; Shi, Qun-Li; Wang, Jian-Dong; Ma, Heng-Hui; Lu, Zhen-Feng; Yu, Bo; Zhang, Ru-Song; Zhou, Xiao-Jun

    2013-01-01

    Papillary renal cell carcinoma (PRCC) is traditionally classified into type 1 and type 2. Recently, an oncocytic variant of PRCC has been described. We report a series of 6 oncocytic renal papillary tumors (OPRCC) which tended to occur in older patients (mean, 56.8 years) with a male preference (male-to-female ratio is 5:1). All 6 patients are alive with no evidence of disease after initial resection, showing an indolent clinical behavior. Histologically, tumors exhibited predominant papillary structure with delicate fibrovascular cores. Papillae were lined by single layers of cells with large, deeply eosinophilic and finely granular cytoplasms and round regular nucleus. The phagocytosis of tumor cells was frequently and evidently seen in our cases that hemosiderin-laden tumor cells and foamy tumor cells were noticed in five and four cases respectively. All tumors were immunoreactive for racemase, vimentin, CD10, and MET and negative for CD117. While E-cadherin, EMA, and cytokeratin 7 exhibited variable immunopositivity. FISH analysis was performed in five of six cases and found heterogeneous results. Trisomy of chromosomes 7 was found in three cases and trisomy of chromosomes 17 in two cases. Loss of chromosome Y was noted in one of four tumors in male patients. MET gene status was also investigated by direct sequencing in all 6 cases and found no distinct mutation in any case. These results suggest that OPRCC shows distinct morphology, indolent clinical behavior, and similar immunohistochemical and cytogenetic features with PRCC, seems to be a variant in the PRCC group. Whether the strong expression of MET indicates a potential therapeutic target is still unknown and requires further investigation in clinical trials. PMID:23826421

  2. Downregulation of LSD1 suppresses the proliferation, tumorigenicity and invasion of papillary thyroid carcinoma K1 cells

    PubMed Central

    KONG, LING-LING; MAN, DONG-MEI; WANG, TIAN; ZHANG, GUO-AN; CUI, WEN

    2016-01-01

    The present study aimed to evaluate the effects of lysine-specific demethylase 1 (LSD1) downregulation, induced by small interfering RNA (siRNA) transfection, on the proliferation, colony formation, migration and invasion of the papillary thyroid carcinoma K1 cell line. The siRNA targeting LSD1 and scrambled non-targeting siRNA were each transfected into papillary thyroid carcinoma K1 cells. Downregulation of LSD1 mRNA and protein level was evaluated by reverse transcription-quantitative polymerase chain reaction, and immunocytochemical (ICC) analysis and western blotting, respectively. A Cell Counting kit-8 assay was applied to estimate the effect of LSD1-siRNA on cell growth. Migration and invasion abilities were estimated by Transwell chamber assay. A soft agar colony formation assay was performed to estimate the effect of LSD1-siRNA on tumorigenicity in vitro. ICC data showed that LSD1 protein was strongly expressed in the blank and control K1 cells compared with the LSD1-siRNA cells (F=15.192, P<0.01). Compared with the control cells, cells transfected with siRNA targeting LSD1 exhibited significant downregulation of LSD1 mRNA (t=6.845, P<0.01) and protein (F=53.764, P<0.01) levels. siRNA targeting LSD1 also downregulated cell proliferation following transfection for 24, 48 and 72 h (t=4.777, P<0.001; t=3.302, P=0.003; and t=3.017, P=0.006, respectively). Compared with the control group, the amount of cell invasion was gradually reduced in the LSD1-siRNA group (t=12.301, P<0.01). The number of migrating cells was significantly higher in the negative control group compared with the LSD1-siRNA group (t=7.911, P<0.01), and the ability of colony formation in the LSD1-siRNA cells was notably reduced in the soft agar formation assay (t=3.612, P=0.005). siRNA targeting LSD1 efficiently inhibits the proliferation, colony formation, migration and invasion of papillary thyroid carcinoma K1 cells. PMID:27073501

  3. Thyroid-like Follicular Carcinoma of the Kidney and Papillary Renal Cell Carcinoma with Thyroid-like Feature: Comparison of Two Cases and Literature Review.

    PubMed

    Li, Congcong; Dong, Hongyan; Fu, Weiwei; Qi, Mei; Han, Bo

    2015-01-01

    Thyroid-like follicular carcinoma of the kidney (TLFCK) is a provisional new entity of renal cell carcinoma (RCC). We herein reported and compared one TLFCK case and one PRCC case with thyroid-like feature. The former entirely consisted of thyroid-like follicular architecture and the tumor cells were diffusely positive for PAX-8, but negative for CK7, AMACR, and CD10. By contrast, both papillary architecture (~60%) and thyroid-like follicular architecture (~40%) were identified in the latter. Tumor cells in both histological components exhibited diffusely positive staining for PAX-8, CK7, AMACR, but negative for CD10. FISH analysis showed no aberration in TLFCK case but trisomy of chromosome 17 in PRCC case. Along with a brief literature review, we presented that recognition of TLFCK is important to distinguish it from other conditions that show thyroid-like features. Additionally, a diagnosis of TLFCK should be cautiously made when papillary component is present in the tumor. PMID:26663803

  4. Papillary Renal Carcinoma Presenting as a Cancer of Unknown Primary (CUP) and Diagnosed through Gene Expression Profiling

    PubMed Central

    Sorscher, Steven M.; Greco, Frank Anthony

    2012-01-01

    Cancer of unknown primary (CUP) is a clinical syndrome representing many types of cancers and diagnoses are typically made after review of clinical presentation, pathology (including immunohistochemical staining) and imaging studies. Treatment with systemic chemotherapy has been shown to result in fairly reproducible objective response rates. Herein, a case of a patient who was initially diagnosed with a poorly differentiated adenocarcinoma of unknown origin is reported. After mRNA gene expression profiling (commercially available CancerTYPE ID), a specific diagnosis of papillary renal cell carcinoma (RCC) was made and then confirmed with additional immunohistochemical staining. The patient was treated with targeted therapy and an objective radiographic response was seen. A literature review suggests this to be the first patient with papillary RCC, identified by molecular profiling, and benefitting from a targeted agent that otherwise would not have been considered in the setting of CUP. This case underscores the importance of considering the use of newer testing technologies in the interest of offering patients more specific, targeted therapy in order to improve efficacy and spare patients toxicities of less specific, empiric chemotherapeutic regimens. PMID:22679428

  5. Mucinous cystadenoma of the appendix associated with adenocarcinoma of the sigmoid colon and hepatocellular carcinoma of the liver: Report of a case

    PubMed Central

    Djuranovic, Srdjan P; Spuran, Milan M; Kovacevic, Nada V; Ugljesic, Milenko B; Kecmanovic, Dragutin M; Micev, Marjan T

    2006-01-01

    Mucinous cystadenoma of the appendix is a rare condition and represents one of the three entities with the common name mucocele of the appendix. It is characterized by a cystic dilatation of the lumen with stasis of mucus inside it. Histopathologically mucocele is divided into three groups: focal or diffuse mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma. This condition is often associated with other neoplasia, especially adenocarcinoma of the colon and ovaries. We here describe a 57 year old male patient who presented with abdominal discomfort, constipation, fresh blood in stool and frequent urination. He had a big cystadenoma of the appendix associated with adenocarcinoma of the colon and hepatocellular carcinoma of the liver. The patient underwent right haemicolectomy, sigmoid colon resection and segmental resection of the liver. Now 3 years later he has no evidence of disease relapse. According to this, we stress the need of accurate preoperative diagnosis and intraoperative exploration of the whole abdomen in these patients. PMID:16610012

  6. Intracellular Signal Transduction and Modification of the Tumor Microenvironment Induced by RET/PTCs in Papillary Thyroid Carcinoma

    PubMed Central

    Menicali, Elisa; Moretti, Sonia; Voce, Pasquale; Romagnoli, Serena; Avenia, Nicola; Puxeddu, Efisio

    2012-01-01

    RET gene rearrangements (RET/PTCs) represent together with BRAF point mutations the two major groups of mutations involved in papillary thyroid carcinoma (PTC) initiation and progression. In this review, we will examine the mechanisms involved in RET/PTC-induced thyroid cell transformation. In detail, we will summarize the data on the molecular mechanisms involved in RET/PTC formation and in its function as a dominant oncogene, on the activated signal transduction pathways and on the induced gene expression modifications. Moreover, we will report on the effects of RET/PTCs on the tumor microenvironment. Finally, a short review of the literature on RET/PTC prognostic significance will be presented. PMID:22661970

  7. Ectopic papillary thyroid carcinoma in the mediastinum without any tumoral involvement in the thyroid gland. A Case report

    PubMed Central

    Shafiee, Susan; Sadrizade, Ali; Jafarian, Amirhosein; Zakavi, Seyed Rasoul; Ayati, Narjess

    2013-01-01

    Ectopic thyroid tissue results from abnormal embryologic development and migration of the thyroid gland. True malignant transformation in ectopic thyroid tissue is extremely rare and is always diagnosed after surgical excision of the lesion by pathology examinations. There are well-documented cases of ectopic thyroid cancer while primary tumoral lesion occurs in the orthotopic thyroid, but only rare cases of ectopic PTC without any evidence of occult thyroid cancer in the orthotopic thyroid or cervical lymph nodes have been reported. We report on a 39 year old woman who was operated for a mediastinal mass. The initial diagnosis was a malignant thymic lesion, which was later confirmed to be a papillary thyroid carcinoma. Consequently, total thyroidectomy was performed and pathology report showed normal thyroid tissue with no evidence of any neoplastic involvement. Until now, only one similar case has been reported.

  8. Human papillomavirus-58 and -73-associated digital squamous cell carcinoma in a patient with aggressive digital papillary adenocarcinoma.

    PubMed

    DePond, William; Kure, Kiyoe; Lankachandra, Kamani; Gidwani, Raja; Nelson, Brook V; Zimmerman, Hannah; Talboy, Glenn E; Miranda, Roberto N

    2009-06-01

    Aggressive digital papillary adenocarcinoma (ADPA) is a rare tumor that is considered to arise from eccrine sweat glands of the skin. It occurs predominantly in men with a mean age in the sixth decade. It shows a strong tendency for local recurrence and has the potential to metastasize to distant sites. Prompt diagnosis and regular follow-up are important to ensure the best possible outcome. We discuss a case of recurrent ADPA associated with subsequent squamous cell carcinoma (SCC) in different contralateral digits in a 55-year-old man. One SCC lesion tested positive for human papillomavirus (HPV)-58. HPV-associated digital SCCs have been reported; most cases are HPV-16 positive. This report describes a rare case of an HPV-58-positive invasive digital SCC and an HPV-73-positive SCC in situ associated with ADPA. PMID:19461243

  9. Recurrent Papillary Thyroid Carcinoma with Pleural Metastasis Diagnosed by Effusion Cytology: A Report of Cases with Clinicopathologic Correlation

    PubMed Central

    Sakamoto, Reid I; Sumida, Lauren C; Lum, Christopher AK

    2015-01-01

    Papillary thyroid carcinoma (PTC) is typically an indolent disease characterized by slow growth and a favorable prognosis. In rare instances, this disease may metastasize to the pleura and manifest as a malignant pleural effusion. We report 3 female patients of Japanese/Okinawan ancestry with a history of PTC who presented with hydrothorax. Cytologic examination in conjunction with immunohistochemical staining enabled a definitive diagnosis of metastatic PTC. Molecular analysis of the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways demonstrated the presence of the v-raf murine sarcoma viral oncogene homolog B (BRAF)V600E mutation in 2 of our 3 patients, with the absence of any other clinically significant mutations in all cases. Further investigation is necessary to elucidate the molecular and environmental mechanisms involved in this aggressive manifestation of PTC. PMID:25755913

  10. [Advances in the research of BRAF(V600E) gene mutation correlated with papillary thyroid carcinoma].

    PubMed

    Xu, X Q; Wang, X H; Jing, J X

    2016-08-01

    The increase in the incidence of papillary thyroid carcinoma (PTC) is a serious threat to public health. V-raf murine sarcoma viral oncogene homolog B(BRAF)(V600E) gene mutation is not only the common genetics factors, but also is the early event in process of thyroid carcinogenesis. We mainly illustrate the mechanism of BRAF(V600E) gene in genesis and development of PTC and the correlation of BRAF(V600E) gene mutation and the clinicopathological characteristics of PTC. Finally, we briefly summarize some scientific achievements about tyrosine kinase inhibitors targeted for BRAF(V600E) gene and their clinical prospect in terms of translation medicine concept. In summary, BRAF(V600E) gene is expected to be a new molecular marker of PTC, which will take a new hope for individualized precise treatment for patients with PTC. PMID:27625138

  11. Abdominal Wall Metastasis of Uterine Papillary Serous Carcinoma in a Post-Menopausal Woman: A Case Report

    PubMed Central

    Park, Jung-Woo

    2014-01-01

    Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer characterized by a high recurrence rate and poor prognosis. We report a case of a 58-year-old post-menopausal woman with an abdominal wall metastasis in stage IA UPSC. After surgical staging, she did not receive additional adjuvant therapy. An egg sized palpable mass developed in the right lower abdomen after 8 months. Both Abdominopelvic computed tomography (CT) and positron emission tomography (PET)-CT revealed a metastatic lesion in the abdominal wall. Hence, surgical excision was performed. The pathological findings showed metastatic UPSC with clear resection margin. After the diagnosis of UPSC metastasis in the abdominal wall, she received chemotherapy utilizing paclitaxel and carboplatin. After 3 years, no evidence of recurrence was found. Therefore, we suggest that even when UPSC is confined to the endometrium without lymph node metastasis and without lymphovascular invasion, chemotherapy should be considered as a postoperative adjuvant therapy. PMID:25371890

  12. Abdominal wall metastasis of uterine papillary serous carcinoma in a post-menopausal woman: a case report.

    PubMed

    Park, Jung-Woo; Hwang, Sung-Ook

    2014-04-01

    Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer characterized by a high recurrence rate and poor prognosis. We report a case of a 58-year-old post-menopausal woman with an abdominal wall metastasis in stage IA UPSC. After surgical staging, she did not receive additional adjuvant therapy. An egg sized palpable mass developed in the right lower abdomen after 8 months. Both Abdominopelvic computed tomography (CT) and positron emission tomography (PET)-CT revealed a metastatic lesion in the abdominal wall. Hence, surgical excision was performed. The pathological findings showed metastatic UPSC with clear resection margin. After the diagnosis of UPSC metastasis in the abdominal wall, she received chemotherapy utilizing paclitaxel and carboplatin. After 3 years, no evidence of recurrence was found. Therefore, we suggest that even when UPSC is confined to the endometrium without lymph node metastasis and without lymphovascular invasion, chemotherapy should be considered as a postoperative adjuvant therapy. PMID:25371890

  13. Pediatric Papillary Renal Cell Carcinoma in a Horseshoe Kidney: A Case Report with Review of the Literature.

    PubMed

    Loya-Solis, Abelardo; Alemán-Meza, Lucía; Canales-Martínez, Luis Carlos; Franco-Márquez, Rodolfo; Rincón-Bahena, Alim Adriana; Nuñez-Barragán, Karla María; Garza-Guajardo, Raquel; Ponce-Camacho, Marco Antonio

    2015-01-01

    Renal cell carcinoma is the most common malignancy of the kidney in adults. In children, however, it only accounts for an estimated 1.8 to 6.3% of all pediatric malignant renal tumors. Papillary renal cell carcinoma is the second most common type of renal cell carcinoma in children. We present the case of a 12-year-old boy with a 2-month history of abdominal pain, unexplained weight loss, and gross hematuria. Computed tomography revealed a horseshoe kidney and a well-defined mass of 4 cm arising from the lower pole of the right kidney. Microscopically the tumor was composed of papillae covered with cells with abundant eosinophilic cytoplasm and high-grade nuclei with prominent nucleoli. Immunohistochemistry was performed; EMA, Vimentin, and AMACR were strongly positive while CK7, CD10, RCC antigen, TFE3, HMB-45, and WT-1 were negative. Currently, 10 months after the surgical procedure, the patient remains clinically and radiologically disease-free. PMID:26301110

  14. Peroperative diagnosis and treatment of metastases to the regional lymph nodes in papillary carcinoma of the thyroid gland

    SciTech Connect

    Hamming, J.F.; van de Velde, C.J.; Goslings, B.M.; Fleuren, G.J.; Hermans, J.; Delemarre, J.F.; van Slooten, E.A. )

    1989-08-01

    The management of two groups of patients with papillary carcinoma of the thyroid gland (n = 165) was evaluated retrospectively. Total thyroidectomy was the standard procedure in both groups, but the peroperative diagnosis and treatment of metastases to the regional lymph nodes differed. In group 1 (n = 84), only clinically positive lymph nodes were resected, and if residual postoperative 131I uptake was found, an ablation dose of {sup 131}I was given. In group 2 (n = 81), all of the tissue in the tracheoesophageal groove was removed routinely at total thyroidectomy and frozen section was done of the lymph nodes lying along the internal jugular vein. If metastases were found, a modified radical dissection of the neck was performed on the affected side. The two patient groups were comparable with regard to risk factors--local tumor stage, age and sex. Almost twice as many patients were found to have metastases to the lymph nodes in group 2. There was no significant difference in the ten year over-all or recurrence free survival time between the two groups. In group 1, there were more recurrences on the explored side of the neck but fewer distant metastases; however, both findings were not significant. In group 2, significantly more instances of hypoparathyroidism and palsy of the accessory nerve were found (p less than 0.05). Thus, when a more extensive search was carried out, more metastases to the lymph node were discovered and treated, but this did not prevent recurrences in the neck nor did it improve survival time. This approach resulted in more postoperative morbidity. There seems to be no justification for prophylactic removal of regional lymph nodes in instances of papillary carcinoma of the thyroid gland, but modified radical neck dissection may be beneficial if clinically suspect regional lymph nodes are present in the lateral part of the neck. 52 references.

  15. Incidental Finding of Papillary Thyroid Carcinoma in the Patients with Primary Hyperparathyroidism

    PubMed Central

    Yazici, Pinar; Mihmanli, Mehmet; Bozdag, Emre; Aygun, Nurcihan; Uludag, Mehmet

    2015-01-01

    Objective: The relationship between primary hyperparathyroidism (pHPT) and papillary thyroid cancer (PTC) still remains unclear. We aimed to investigate the incidence of the co-existence of pHPT and PTC. Materials and Methods: Between 2010 and 2013, all patients with pHPT were retrospectively reviewed and those undergoing concomitant thyroid surgery were recorded. Of these, patients with a pathological result showing papillary or micro-papillary thyroid cancer were included into the study. A chart review of 228 patients who underwent surgery for pHPT revealed 86 (37.7%) patients with concurrent thyroid disease requiring surgical treatment. Results: Thyroid cancer was noted in six female patients (6.9%) undergoing thyroid resection, and 2.6% of all patients with pHPT. Four patients underwent total thyroidectomy while lobectomy was applied in the remaining two. None of the cases with lobectomy required a completion thyroidectomy. Conclusion: We demonstrated the concurrence of PTC and pHPT at a rate of 2.6% which appeared as a coincidental pathology; however, thyroid disorders, seen in one of three patients with pHPT, were not uncommon. Further research is still needed to develop a reliable explanation for relationship between pHPT and non-medullary thyroid cancer. PMID:26644769

  16. Effects of tamoxifen and somatostatin analogue on growth of human medullary, follicular, and papillary thyroid carcinoma cell lines: tissue culture and nude mouse xenograft studies.

    PubMed

    Weber, C J; Marvin, M; Krekun, S; Koschitzky, T; Karp, F; Benson, M; Feind, C R

    1990-12-01

    The knowledge that (1) the normal thyroid contains somatostatin, (2) polypeptide growth factors influence thyroid cell function, and (3) thyroid cells contain steroid hormone receptors prompted us to add somatostatin analogue No. 201-995 (SMS) (5 ng/ml) and/or tamoxifen citrate (TAM) (5 mumol/L) to 7-day monolayer cultures (50,000 cells/well) of three separate human thyroid carcinoma cell lines: DR081 (medullary), WR082 (follicular), and NPA'87 (papillary). Results, tabulated as cell numbers/well (X10(5) on day 7, revealed that TAM inhibited growth of medullary and follicular cells and that TAM plus SMS inhibited growth of papillary cells. In vivo studies of subcutaneous tumor cell xenografts in nude mice have documented that TAM (5 mg subcutaneous pellet) significantly inhibits the growth of medullary implants. Flow cytometric DNA studies of medullary cell cultures demonstrated a reduced G2 + M phase with TAM treatment. For papillary cell implants, TAM plus SMS (5 micrograms subcutaneously, twice daily) did not suppress tumor growth. All three cell lines were negative for estrogen receptor; addition of estradiol (5 ng/ml) to medullary cell cultures neither stimulated replication nor reversed the inhibitory effects of TAM in vitro. We conclude that (1) TAM slowed the growth of a cell line of human medullary carcinoma, both in vitro and in vivo; (2) this effect was not reversed by estradiol; (3) TAM plus SMS inhibited replication of a papillary carcinoma cell line in vitro, but not in vivo; and (4) TAM alone and TAM plus SMS inhibited replication of cultures of a human follicular thyroid carcinoma cell line. TAM and SMS may be useful in treatment of some human thyroid carcinomas. PMID:1978945

  17. Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma

    PubMed Central

    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

  18. Clinicopathological Characteristics and Survival Outcomes in Invasive Papillary Carcinoma of the Breast: A SEER Population-Based Study

    PubMed Central

    Zheng, Yi-Zi; Hu, Xin; Shao, Zhi-Ming

    2016-01-01

    To investigate the clinicopathological characteristics and survival outcomes of invasive papillary carcinoma (IPC), we identified 233,171 female patients in the Surveillance, Epidemiology, and End Results (SEER) database who had IPC (n = 524) or infiltrating ductal carcinoma (IDC) (n = 232,647). Generally, IPCs occurred in older women (≥50 years old) and presented with smaller sizes, lower grades, higher rates of oestrogen receptor (ER) and progesterone receptor (PR) positivity, and reduced lymph node (LN) involvement and were less likely to be treated with mastectomy than patients with IDC. The five-year disease-specific survival (DSS) rates were significantly better in IPC than in IDC (97.5% vs. 93%, respectively; P < 0.001). In the multivariate analysis, patients with IPC showed a DSS that was similar to that of IDC (hazard ratio = 0.556, 95% confidence interval 0.289–1.070, P = 0.079). No significant difference was observed in DSS between matched IPC and IDC groups (P = 0.085). Differences in outcomes may be partially explained by differences in tumour grade, LN status, and ER and PR status between the 2 groups. Gaining an improved clinical and biological understanding of IPC might result in more tailored and effective therapies in breast cancer patients. PMID:27053333

  19. Clinicopathological Characteristics and Survival Outcomes in Invasive Papillary Carcinoma of the Breast: A SEER Population-Based Study.

    PubMed

    Zheng, Yi-Zi; Hu, Xin; Shao, Zhi-Ming

    2016-01-01

    To investigate the clinicopathological characteristics and survival outcomes of invasive papillary carcinoma (IPC), we identified 233,171 female patients in the Surveillance, Epidemiology, and End Results (SEER) database who had IPC (n = 524) or infiltrating ductal carcinoma (IDC) (n = 232,647). Generally, IPCs occurred in older women (≥ 50 years old) and presented with smaller sizes, lower grades, higher rates of oestrogen receptor (ER) and progesterone receptor (PR) positivity, and reduced lymph node (LN) involvement and were less likely to be treated with mastectomy than patients with IDC. The five-year disease-specific survival (DSS) rates were significantly better in IPC than in IDC (97.5% vs. 93%, respectively; P < 0.001). In the multivariate analysis, patients with IPC showed a DSS that was similar to that of IDC (hazard ratio = 0.556, 95% confidence interval 0.289-1.070, P = 0.079). No significant difference was observed in DSS between matched IPC and IDC groups (P = 0.085). Differences in outcomes may be partially explained by differences in tumour grade, LN status, and ER and PR status between the 2 groups. Gaining an improved clinical and biological understanding of IPC might result in more tailored and effective therapies in breast cancer patients. PMID:27053333

  20. Lymph node status of lateral neck compartment in patients with N1b papillary thyroid carcinoma.

    PubMed

    Park, Young Min; Wang, Soo-Geun; Shin, Dong Hoon; Kim, In-Ju; Son, Seok-Man; Lee, Byung-Joo

    2016-01-01

    Conclusion Loco-regional recurrence-free survival was significantly decreased in the papillary thyroid cancer patients with > 6 metastatic lymph nodes and a lymph node ratio > 0.22. Also, the risk of lung metastasis was significantly increased in cases with bilateral neck node metastases. Objective This study focused on the metastatic lymph node status of the lateral neck compartment to understand its prognostic significance for loco-regional recurrence and distant metastasis. Methods Between January 2004 and December 2009, 1040 patients were diagnosed with papillary thyroid cancer and underwent treatment. Results In a multivariate analysis, sex, the number of metastatic lymph nodes, and the lymph node ratio was significantly associated with loco-regional recurrence. The sensitivity/specificity of > 6 metastatic lymph nodes for predicting recurrence was 64.0%/69.7%. The 5-year loco-regional recurrence-free survival of patients with 0-6 metastatic lymph nodes and > 6 metastatic lymph nodes were 93.4% and 79.2%, respectively. The 5-year loco-regional recurrence-free survival of patients with a lymph node ratio ≤ 0.22 and a lymph node ratio > 0.22 were 97.1% and 78.8%, respectively. In the multivariate analysis, only bilateral neck node metastases were significantly associated with lung metastasis. PMID:26635131

  1. A comparison of uterine papillary serous, clear cell carcinomas, and grade 3 endometrioid corpus cancers using 2009 FIGO staging system

    PubMed Central

    Kim, Ha-Jeong; Kim, Tae-Joong; Lee, Yoo-Young; Choi, Chel Hun; Lee, Jeong-Won; Bae, Duk-Soo

    2013-01-01

    Objective This study was designed to compare survival outcomes of patients with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CC) to those of patients with grade 3 endometrioid carcinoma (G3EC) according to 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) staging systems. Methods We retrospectively reviewed all patients with endometrial cancer treated at a single institution between 1995 and 2009. Among the 647 patients with endometrial cancer, 51 with G3EC and 46 with UPSC and CC histology were confirmed. Results 1988 FIGO stage, 2009 FIGO stage, and extrauterine metastasis were significantly different between the UPSC and CC group and G3EC group (p=0.002, p=0.041, and p=0.020, respectively). Restaging from the 1988 FIGO to the 2009 FIGO criteria increased the number of stage I cases by 10 (11.0%). Overall, 8 in the UPSC and CC and 2 in the G3EC group were down-staged to stage I. In the UPSC and CC group, the 3-year overall survival for 1988 FIGO stage I was 92.9%. When UPSC and CC patients were restaged using the 2009 staging system, the 3-year overall survival of 2009 FIGO stage I dropped to 81.6%. UPSC and CC was associated with poor OS outcome compared with G3EC, after adjustment for 2009 FIGO stage and other clinicopathologic factors. Conclusion We observed that UPSC and CC patients had different prognosis according to the old and new FIGO staging system. Our results suggest that UPSC and CC compared with the G3EC may retain the 1988 FIGO to be a slightly better discriminator than 2009 FIGO. PMID:23653828

  2. Incidence of Clear Cell Papillary Renal Cell Carcinoma in Low-Grade Renal Cell Carcinoma Cases: A 12-Year Retrospective Clinicopathologic Study From a Single Cancer Center.

    PubMed

    Gill, Simpal; Kauffman, Eric C; Kandel, Sirisa; George, Saby; Schwaab, Thomas; Xu, Bo

    2016-05-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized subtype of renal cell carcinoma entity after 2004 World Health Organization classification of renal tumors. CCPRCC has unique histomorphological and immunohistochemical characteristics. The distinction of CCPRCC from renal cell carcinoma (RCC) with clear cell morphology is crucial because the former is considered to have a favorable clinical outcome. CCPRCC may be interpreted in the past as other renal cell carcinomas, particularly low-grade clear cell RCC. In this study, the frequency of CCPRCC in previously diagnosed low-grade RCC and its clinicopathologic features were examined. A total of 126 cases of stage T1a with low nuclear grade RCC were identified from 625 consecutive RCCs removed by radical/partial nephrectomy over 12-year period (2000-2011). Archival tissue sections were retrospectively reviewed along with patient medical charts. Eight cases (1.3% of all RCC, 6.3% of pT1a low grade RCC) with characteristic histologic features of CCPRCC were confirmed by immunohistochemical studies. Seven cases were previously diagnosed as clear cell RCC and one as multilocular cystic RCC. Radiographically, CCPRCC favored a mid-pole location in the kidneys. At a median follow-up period of 52 months (range 20-114.5 months), there were no cases of local or distant recurrence. In conclusion, CCPRCC is not uncommon among small low-grade RCC tumors. CCPRCC can be correctly recognized by its unique histomorphological features and confirmed by immunohistochemistry studies, which is important due to the excellent clinical outcome following resection. PMID:26510859

  3. Mucinous tubular and spindle cell carcinoma of the kidney: A case report and review of the literature.

    PubMed

    Sun, Nao; Fu, Yaowen; Wang, Yuantao; Tian, Tengzheng; An, Wei; Yuan, Tong

    2014-03-01

    Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an unusual renal tumor. It is important to increase the recognition of MTSCC-K and improve the level of clinical diagnosis. The current study presents a case of MTSCC-K with clinical, imaging and pathological examination. A 60-year-old female presented to the First Hospital of Jilin University suffering from lumbodorsalgia on the right side for approximately one month, without gross hematuria and fever. Imaging examination by abdominal computed tomography scan revealed a ~6.5×5.0-cm solid mass in the inferior pole of the right kidney. The patient underwent laparoscopic radical resection of the right kidney. Pathological examination showed that the tumor was composed of small, elongated cords or tubules, in a tightly packed arrangement. Myxoid stroma was shown to be interspersed among the tubular cells, and appeared to exhibit slender tubular spindle cell-like structures. Tumor cells were smaller and cube-shaped or oval, with single small eosinophilic nucleoli and low-grade nuclei. Occasionally, necrosis and foam cell infiltration were observed. Myxoid stroma was stained by acidic mucus. Immunohistochemical markers, including CK7, CK19, EMA, Vimentin and P504S (AMACR) showed positive expression in tumoral cells, but the tumoral cells were CD10-negative. The MTSCC-K is a low-grade polymorphic renal epithelial neoplasm, which may be diagnosed by immunohistochemistry. The patients are likely to have an improved prognosis following surgery compared with patients with other renal cell carcinomas. PMID:24520298

  4. Mucinous tubular and spindle cell carcinoma of the kidney: Diagnosis by fine needle aspiration and review of the literature

    PubMed Central

    Huimiao, Jiang; Chepovetsky, Julie; Zhou, Ming; Sun, Wei; Simsir, Aylin; Cohen, Deirdre; Leung, Allen

    2015-01-01

    Renal mucinous tubular and spindle cell carcinoma (MTSCC) was recently described as a distinct subtype of renal cell carcinoma (RCC) in the 2004 World Health Organization classification of kidney tumors. MTSCC is a rare low grade malignancy with < 100 cases reported in the literature. To the best of our knowledge, there are 5 case reports with a total of 6 patients describing its diagnosis by fine needle aspiration (FNA). All of these cases were diagnosed as conventional RCC on FNA. Subsequent excisions proved them to be MTSCC. We herein report a case in a 67-year-old male. He presented with abdominal pain and was found to have a new colon adenocarcinoma with metastasis to the liver and lungs. The extent of disease made the patient ineligible for surgical excision, and he received chemotherapy. Work-up also revealed a kidney mass which was later biopsied by FNA and core biopsy. The tumor was composed of epithelial and spindled cell components embedded in a myxoid background. It was positive for CK7, AMCAR, vimentin, and epithelial membrane antigen. The tumor was diagnosed as MTSCC. One year later the kidney mass remained stable. However, the patient developed new metastasis to the liver from colonic primary. The kidney mass was not resected. Although rarely encountered in FNA cytology of the kidney, we believe the cytologic features of this tumor are distinctive and are different from conventional and other subtypes of RCC. Therefore, its accurate diagnosis on FNA is possible once pathologists are aware that MTSCC should be considered in the differential diagnosis of kidney tumors. PMID:26884801

  5. Renal Neoplasms With Overlapping Features of Clear Cell Renal Cell Carcinoma and Clear Cell Papillary Renal Cell Carcinoma: A Clinicopathologic Study of 37 Cases From a Single Institution.

    PubMed

    Dhakal, Hari P; McKenney, Jesse K; Khor, Li Yan; Reynolds, Jordan P; Magi-Galluzzi, Cristina; Przybycin, Christopher G

    2016-02-01

    Clear cell papillary renal cell carcinoma (CCPRCC) was recently included in the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia as a subtype of RCC that is morphologically, immunohistochemically, and genetically distinct from both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma. In our clinical practice we have observed tumors with overlapping histologic features of CCPRCC and CCRCC; therefore, our aim was to describe the morphologic, immunohistochemical, and clinical characteristics of these tumors. We examined a large series of consecutive nephrectomies diagnosed as CCRCC and found 37 tumors with morphologic overlap between CCRCC and CCPRCC, identifying 2 patterns. Pattern 1 tumors (N=19) had areas diagnosable as CCRCC admixed with foci having a prominent linear arrangement of nuclei away from the basement membrane imparting a resemblance to CCPRCC; however, other morphologic features commonly seen in CCPRCC (such as branching acini and cystic spaces with papillary tufts) were not typical and, when present, were focal or poorly developed. Pattern 2 (N=18) tumors had 2 discrete areas, one area with an appearance strongly resembling CCPRCC and the other with higher grade nuclei and features diagnosable as CCRCC, sometimes including rhabdoid differentiation, sarcomatoid differentiation, necrosis, and high-stage disease. Four (21%) of the pattern 1 tumors had grade 3 nuclei in the CCRCC-like areas, and 4 were high stage (pT3a). Of the 16 immunostained pattern 1 tumors, all expressed cytokeratin 7 (CK7) at least focally in the CCPRCC-like areas, strongly and diffusely in 9 (56%) cases; 12 (75%) showed negative to focal and/or weak CK7 expression in the CCRCC-like areas. CD10, α-methylacyl-CoA-racemase, high-molecular-weight cytokeratin, and carbonic anhydrase IX (CA IX) had no significant differential expression between these foci. No cup-like staining pattern was seen with CA IX. Two (11%) patients

  6. Functional evaluation of TERT-CLPTM1L genetic variants associated with susceptibility of papillary thyroid carcinoma

    PubMed Central

    Ge, Minghua; Shi, Meng; An, Changming; Yang, Wenjun; Nie, Xilin; Zhang, Jian; Lv, Zheng; Li, Jinliang; Zhou, Liqing; Du, Zhongli; Yang, Ming

    2016-01-01

    TERT is the catalytic subunit of telomerase which plays an essential part in cellular immortality by maintaining telomere integrity. TERT is commonly over-expressed in human malignancies, indicating its key role in cell transformation. The chromosome 5p15.33 TERT-CLPTM1L region has been associated with susceptibility of multiple cancers via a genome-wide association approach. However, the involvement of this locus in papillary thyroid carcinoma (PTC) etiology is still largely unknown. We analyzed 15 haplotype-tagging single nucleotide polymorphisms (htSNPs) of the TERT-CLPTM1L region in a two stage case-control design. After genotyping 2300 PTC patients and frequency-matched 2300 unaffected controls, we found that TERT rs2736100 genetic variant is significantly associated with elevated PTC risk. Ex vivo reporter gene assays indicated that the PTC susceptibility rs2736100 polymorphism locating in a potential TERT intronic enhancer has a genotype-specific effect on TERT expression. Correlations between rs2736100 genotypes and tissue-specific TERT expression supported the regulatory function of this genetic variant in vivo. Our data demonstrated that the functional TERT rs2736100 SNP as a novel genetic component of PTC etiology. This study, together with recent studies in other cancers, unequivocally establishes an essential role of TERT in cancers. PMID:27185198

  7. 2-Deoxy-d-Glucose Can Complement Doxorubicin and Sorafenib to Suppress the Growth of Papillary Thyroid Carcinoma Cells

    PubMed Central

    Wang, Shuo-Yu; Wei, Yau-Huei; Shieh, Dar-Bin; Lin, Li-Ling; Cheng, Shih-Ping; Wang, Pei-Wen; Chuang, Jiin-Haur

    2015-01-01

    Tumor cells display a shift in energy metabolism from oxidative phosphorylation to aerobic glycolysis. A subset of papillary thyroid carcinoma (PTC) is refractory to surgery and radioactive iodine ablation. Doxorubicin and sorafenib are the drugs of choice for treating advanced thyroid cancer but both induce adverse effects. In this study, we assessed the anti-cancer activity of 2-deoxy-d-glucose (2-DG) alone and in combination with doxorubicin or sorafenib in PTC cell lines with (BCPAP) and without (CG3) the BRAFV600E mutation. BCPAP cells were more glycolytic than CG3 cells, as evidenced by their higher extracellular l-lactate production, lower intracellular ATP level, lower oxygen consumption rate (OCR), and lower ratio of OCR/extracellular acidification rate. However, dose-dependent reduction in cell viability, intracellular ATP depletion, and extracellular l-lactate production were observed after 2-DG treatment. Regression analysis showed that cell growth in both cell lines was dependent on ATP generation. 2-DG increased the chemosensitivity of BCPAP and CG3 cell lines to doxorubicin and sorafenib. These results demonstrate that the therapeutic effects of low combined doses of 2-DG and doxorubicin or sorafenib are similar to those of high doses of doxorubicin or sorafenib alone in PTC cell lines regardless of the BRAFV600E mutation. PMID:26134286

  8. miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma

    SciTech Connect

    Zhu, Hongling; Fang, Jin; Zhang, Jichen; Zhao, Zefei; Liu, Lianyong; Wang, Jingnan; Xi, Qian; Gu, Mingjun

    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 of 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.

  9. Analysis of Risk Factors Contributing to Recurrence of Papillary Thyroid Carcinoma in Chinese Patients Who Underwent Total Thyroidectomy

    PubMed Central

    Zhang, Wei; Jiao, De; Liu, Baoguo; Sun, Shanping

    2016-01-01

    Background Thyroid cancer is a very common endocrine malignancy, with a rate of total thyroidectomy reported to be up to 27.8%. However, studies analyzing the risk factors that contribute to recurrence of papillary thyroid carcinoma (PTC) after total thyroidectomy in China are still scarce. Material/Methods A total of 536 patients with PTC who underwent total thyroidectomy were retrospectively analyzed. Patients were divided into 2 groups: patients with no recurrent tumor were included in group 1 and patients with tumor recurrence were included in group 2. Results Of 536 patients, 65 patients (12.1%) developed a recurrence of PTC, and 471 patients (87.9%) did not have a recurrence. Univariate analysis indicated that male sex, age ≥50 years, tumor ≥1 cm, poor differentiation, lymph node metastasis, bilaterality, and multifocality may be related to PTC recurrence. Additionally, the results of the logistic regression analysis indicated that male sex, age ≥50 years, primary tumor ≥1 cm, poor dedifferentiation of the tumor, lymph node metastasis, and multifocality may be independent factors contributing to PTC recurrence. Conclusions Male sex, age more than 50 years, primary tumor larger than 1 cm, poor dedifferentiation of the primary tumor, lymph node metastasis, and multifocality were found to increase the risk of PTC recurrence in patients who underwent total thyroidectomy. Additionally, it is necessary to use strictly aggressive and extensive surgery, as well as close monitoring, after the operation. PMID:27084873

  10. Functional evaluation of TERT-CLPTM1L genetic variants associated with susceptibility of papillary thyroid carcinoma.

    PubMed

    Ge, Minghua; Shi, Meng; An, Changming; Yang, Wenjun; Nie, Xilin; Zhang, Jian; Lv, Zheng; Li, Jinliang; Zhou, Liqing; Du, Zhongli; Yang, Ming

    2016-01-01

    TERT is the catalytic subunit of telomerase which plays an essential part in cellular immortality by maintaining telomere integrity. TERT is commonly over-expressed in human malignancies, indicating its key role in cell transformation. The chromosome 5p15.33 TERT-CLPTM1L region has been associated with susceptibility of multiple cancers via a genome-wide association approach. However, the involvement of this locus in papillary thyroid carcinoma (PTC) etiology is still largely unknown. We analyzed 15 haplotype-tagging single nucleotide polymorphisms (htSNPs) of the TERT-CLPTM1L region in a two stage case-control design. After genotyping 2300 PTC patients and frequency-matched 2300 unaffected controls, we found that TERT rs2736100 genetic variant is significantly associated with elevated PTC risk. Ex vivo reporter gene assays indicated that the PTC susceptibility rs2736100 polymorphism locating in a potential TERT intronic enhancer has a genotype-specific effect on TERT expression. Correlations between rs2736100 genotypes and tissue-specific TERT expression supported the regulatory function of this genetic variant in vivo. Our data demonstrated that the functional TERT rs2736100 SNP as a novel genetic component of PTC etiology. This study, together with recent studies in other cancers, unequivocally establishes an essential role of TERT in cancers. PMID:27185198

  11. miR-204-5p suppresses cell proliferation by inhibiting IGFBP5 in papillary thyroid carcinoma

    SciTech Connect

    Liu, Lianyong; Wang, Jingnan; Li, Xiangqi; Ma, Junhua; Shi, Chao; Zhu, Hongling; Xi, Qian; Zhang, Jichen; Zhao, Xuemei; Gu, Mingjun

    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 suppressor 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.

  12. A germline mutation in SRRM2, a splicing factor gene, is implicated in papillary thyroid carcinoma predisposition

    PubMed Central

    Tomsic, Jerneja; He, Huiling; Akagi, Keiko; Liyanarachchi, Sandya; Pan, Qun; Bertani, Blake; Nagy, Rebecca; Symer, David E.; Blencowe, Benjamin J.; Chapelle, Albert de la

    2015-01-01

    Papillary thyroid carcinoma (PTC) displays strong but so far largely uncharacterized heritability. Here we studied genetic predisposition in a family with six affected individuals. We genotyped all available family members and conducted whole exome sequencing of blood DNA from two affected individuals. Haplotype analysis and other genetic criteria narrowed our list of candidates to a germline variant in the serine/arginine repetitive matrix 2 gene (SRRM2). This heterozygous variant, c.1037C > T (Ser346Phe or S346F; rs149019598) cosegregated with PTC in the family. It was not found in 138 other PTC families. It was found in 7/1,170 sporadic PTC cases and in 0/1,404 controls (p = 0.004). The encoded protein SRRM2 (also called SRm300) is part of the RNA splicing machinery. To evaluate the possibility that the S346F missense mutation affects alternative splicing, we compared RNA-Seq data in leukocytes from three mutation carriers and three controls. Significant differences in alternative splicing were identified for 1,642 exons, of which a subset of 7 exons was verified experimentally. The results confirmed a higher ratio of inclusion of exons in mutation carriers. These data suggest that the S346F mutation in SRRM2 predisposes to PTC by affecting alternative splicing of unidentified downstream target genes. PMID:26135620

  13. BRAF-activated long non-coding RNA contributes to cell proliferation and activates autophagy in papillary thyroid carcinoma

    PubMed Central

    WANG, YONG; GUO, QINHAO; ZHAO, YAN; CHEN, JIEJING; WANG, SHUWEI; HU, JUN; SUN, YUEMING

    2014-01-01

    Long non-coding RNAs (lncRNAs) are novel regulators in cancer biology. BRAF-activated lncRNA (BANCR) is overexpressed in melanoma and has a potential functional role in melanoma cell migration. However, little is known about the role of BANCR in the development of papillary thyroid carcinoma (PTC). In the present study, BANCR expression was examined in six pairs of PTC and matched adjacent normal tissues. The results revealed that BANCR levels were significantly higher in the PTC tissues and PTC IHH-4 cells compared with the normal controls. Knockdown of BANCR in the IHH-4 cells inhibited proliferation and increased apoptosis of the cells in vitro. Further investigation of the underlying mechanisms revealed that BANCR markedly activated autophagy. Overexpression of BANCR inhibited apoptosis in the IHH-4 cells, whereas inhibition of autophagy stimulated apoptosis in the BANCR-overexpressed cells. BANCR overexpression also increased cell proliferation and the inhibition of autophagy abrogated BANCR overexpression-induced cell proliferation. In addition, the overexpression of BANCR resulted in an increase in the ratio of LC3-II/LC3-I, a marker for autophagy, while the knockdown of BANCR decreased the ratio of LC3-II/LC3-I. These results revealed that BANCR expression levels are upregulated in PTC. Additionally, BANCR increases PTC cell proliferation, which could activate autophagy. PMID:25289082

  14. The advantages of subtotal thyroidectomy and suppression of TSH in the primary treatment of papillary carcinoma of the thyroid

    SciTech Connect

    Crile, G. Jr.; Antunez, A.R.; Esselstyn, C.B. Jr.; Hawk, W.A.; Skillern, P.G.

    1985-06-01

    Patients between the ages of 6 and 45 years with distant metastases from papillary carcinoma of the thyroid can be treated as effectively by subtotal thyroidectomy and suppressive doses of thyroid hormone as by total thyroidectomy followed by treatment with iodine 131 (/sup 131/I). Moreover, distant metastases can be treated by either /sup 131/I or suppression as effectively after they are apparent on x-ray as they can be when treated in a subclinical stage. Therefore, in patients younger than 45 years old it is rarely necessary to perform a total thyroidectomy or to do frequent postoperative scans. In patients older than 44 or younger than 7 who have distant metastases or extensive involvement of both lobes, total or almost total thyroidectomy is justified if it can be done with minimal morbidity. In patients of this age group whose tumors fail to respond to suppressive doses of thyroid, /sup 131/I should be used. In view of the importance of diagnostic related groups (DRG) to the economy of hospitals, we note that the cost of total thyroidectomy, ablation by /sup 131/I, and intermittent body scans is at least three times that of less radical procedures which, in conjunction with suppression by thyroid feeding, give the same survival with less morbidity.

  15. Effect of ret/PTC 1 rearrangement on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model

    PubMed Central

    Cahill, Susanne; Smyth, Paul; Finn, Stephen P; Denning, Karen; Flavin, Richard; O'Regan, Esther M; Li, Jinghuan; Potratz, Astrid; Guenther, Simone M; Henfrey, Richard; O'Leary, John J; Sheils, Orla

    2006-01-01

    Background microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nt in length that have been found to control cell growth, differentiation and apoptosis. miRNAs negatively regulate their target genes and recently have been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. ret/PTC 1 is an oncogene with constitutive kinase activity implicated in the development of papillary thyroid carcinoma (PTC). This rearrangement leads to aberrant MAPK activation that is implicated in PTC tumourigenesis. Aim The aim of this study was to identify the effect that ret/PTC 1 has on transcription and post-transcriptional regulation in PTC by using DNA microarray and microRNA analysis. Results DNA microarray analysis revealed a group of genes differentially expressed between normal thyroid cell lines and those harbouring a ret/PTC 1 rearrangement. Furthermore, a unique miRNA expression signature differentiated between PTC cell lines with ret/PTC 1 and a normal thyroid cell line. 21 miRNAs showed significant overexpression and 14 miRNAs showed underexpression in these cell lines when compared to normal thyroid. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis. PMID:17156473

  16. Association between a functional insertion/deletion polymorphism in IL1A gene and risk of papillary thyroid carcinoma.

    PubMed

    Gao, Linbo; Zhu, Xinxin; Li, Zhihui; Li, Lijuan; Wang, Tao; Hu, Huaizhong; Guo, Wanli; Chen, Peng; Zhu, Jingqiang; Zhang, Lin

    2014-04-01

    The aim of this study was to evaluate whether an insertion/deletion polymorphism (rs3783553) locating in the miR-122 target gene IL1A 3' untranslated region was related to the risk of papillary thyroid carcinoma (PTC). Genomic DNA was extracted from peripheral venous blood of 273 patients with PTC and 509 controls. The IL1A rs3783553 polymorphism was genotyped by using a polymerase chain reaction assay. No significant difference of the distribution of the IL1A rs3783553 polymorphism was observed between PTC patients and controls. However, patients carrying the IL1A rs3783553 ins/ins genotype and ins allele had significantly decreased risks for developing T3 and T4 when compared with patients carrying the IL1A rs3783553 del/del genotype and del allele (ins/ins vs. del/del: OR = 0.22, 95% confidence interval (CI), 0.09-0.54; ins vs. del: OR = 0.58, 95% CI, 0.41-0.83, respectively). These results suggest that the rs3783553 polymorphism may be used as a genetic marker to predict the size/extension of PTC. PMID:24453029

  17. An Appraisal of Proliferation and Apoptotic Markers in Papillary Thyroid Carcinoma: An Automated Analysis

    PubMed Central

    Lamba Saini, Monika; Bouzin, Caroline; Weynand, Birgit; Marbaix, Etienne

    2016-01-01

    Introduction Proliferation and apoptosis are opposing processes by which the cell numbers are kept in a delicate balance, essential for tissue homeostasis, whereas uncontrolled growth of cells is a hallmark of cancer. Papillary thyroid cancer (PTC) is the commonest type of thyroid cancer, with some PTC following an indolent course, whereas the other ones are more aggressive. Aim To evaluate respective contribution of proliferation and apoptosis in the tumorigenesis of PTC by automated analysis. Materials and Methods We investigated the immunolabeling of phosphorylated histone H3 (pHH3), cyclin D1, active caspase-3, and bcl-2 in thirteen cases each of metastatic PTC, follicular variant of PTC (FVPTC), papillary microcarcinoma (PMC) and well differentiated tumor of uncertain malignant potential (WDT-UMP). FVPTC cases comprised seven encapsulated and six unencapsulated cases. Results Proliferation, as assessed by pHH3 and cyclin D1 immunolabeling, was increased in all PTC variants, including the putative precursor lesion WDT-UMP, compared to normal thyroid tissue. pHH3 was immunolabeled in more cells of metastatic PTC than of PMC and of encapsulated FVPTC. Surprisingly, metastatic PTC and unencapsulated FVPTC also demonstrated more cleaved caspase-3 immunolabeled cells than the other types. In contrast, increased expression of bcl-2 protein was seen in normal thyroid areas, encapsulated FVPTC and PMC as compared to metastatic PTC. Metastatic PTC shows higher proliferation than other types of PTC but unexpectedly also higher apoptotic levels. Similar results were also seen with unencapsulated FVPTC, thus suggesting that unencapsulated FVPTC has a potential for adverse outcome. Bcl-2 was immunolabeled in a low percentage of cells in WDT-UMP. Conclusions The expression of the proliferative protein pHH3 together with the apoptotic marker cleaved caspase-3 may indicate an aggressive behaviour of PTC and loss of apoptosis inhibition by bcl-2 protein can further amplify the

  18. An analysis of current treatment practice in uterine papillary serous and clear cell carcinoma at two high volume cancer centers

    PubMed Central

    Knickerbocker, Abhay; Shah, Chirag A.; Schiff, Melissa A.; Isacson, Christina; Garcia, Rochelle L.; Goff, Barbara A.

    2015-01-01

    Objective Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC), they contribute disproportionately to endometrial cancer deaths. Sufficient clinical information regarding treatment and prognosis is lacking. The aim of this study is to evaluate treatment outcomes in a rare cancer cohort based on the experience at two tertiary care cancer centers. Methods Clinicopathologic data were retrospectively collected on 279 patients with UPSC and UCCC treated between 1995 to 2011. Mode of surgery, use of adjuvant treatment, and dissection of paraaoritc lymph nodes were evaluated for their association with overall survival (OS) and progression-free survival (PFS). Results 40.9% of patients presented with stage I disease, 6.8% of patients presented with stage II disease and 52.3% of patients presented with stages III and IV. Median follow-up was 31 months (range, 1 to 194 months). OS and PFS at 5 years were 63.0% and 51.9%, respectively. OS and PFS were not affected by mode of surgery (open vs. robotic approach; OS: hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.28 to 1.62; PFS: HR, 0.78; 95% CI, 0.40 to 1.56). Adjuvant treatment was associated with improved OS in stages IB-II (HR, 0.14; 95% CI, 0.02 to 0.78; p=0.026) but not in stage IA disease. There was no difference in OS or PFS based on the performance of a paraaoritc lymph node dissection. Conclusion Minimally invasive surgical staging appears a reasonable strategy for patients with non-bulky UPSC and UCCC and was not associated with diminished survival. Adjuvant treatment improved 5-year survival in stages IB-II disease. PMID:25376917

  19. Calvarium and dura mater as delayed sites of distant metastasis from papillary thyroid carcinoma

    PubMed Central

    AL-Qahtani, Khalid Hussain; Tunio, Mutahir A; Al Asiri, Mushabbab; Fatani, Hanadi; Bayoumi, Yasser

    2015-01-01

    Background Skull calvarium and dura mater are rare sites of distant metastasis, and mostly have been reported in lung, breast, and prostate malignancies. However, the calvarial and dural metastases from papillary thyroid cancer (PTC) are rare entities and pose diagnostic and therapeutic challenges. To date, only seven cases of calvarial metastasis with intracranial extension from PTC have been reported in literature. However, true dural metastasis from PTC has not yet been reported. Case presentation A 65-year-old Saudi woman presented with 6 months history of painful posterior scalp lump, 7 years after initial diagnosis of PTC. Computed tomography and magnetic resonance imaging showed occipitoparietal calvarial lesion with massive intracranial extension. Another para-sagittal lesion was found at the top of corpus callosum mimicking a meningioma. Histopathology of para-sagittal lesion and the biopsy of calvarial mass confirmed the diagnosis of metastatic PTC. After surgical resection, residual tumors were treated with postoperative intensity-modulated radiation therapy. At 13 months of follow-up, patient was alive and without any signs of recurrence. Conclusion Calvarial and dural metastases from PTC are extremely rare clinical entities. Surgical resection followed by postoperative radiotherapy is the treatment of choice. However, for such cases, multidisciplinary approach can prolong the treatment outcome and survival. PMID:26527901

  20. Low Prevalence of Somatic TERT Promoter Mutations in Classic Papillary Thyroid Carcinoma

    PubMed Central

    Sim, Soyoung; Lim, Seonhee; Kwon, Hyemi; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

    2016-01-01

    Background Transcriptional activating mutations of telomerase reverse transcriptase (TERT) are associated with more aggressive thyroid cancer. We evaluated the significance of TERT promoter mutations in Korean patients with classic papillary thyroid cancer (PTC). Methods Genomic DNA was isolated from four thyroid cancer cell lines and 35 fresh-frozen PTC tissues. TERT promoter mutations (C228T and C250T) and the BRAF V600E mutation were evaluated by polymerase chain reaction amplification and direct sequencing. Results The CC228229TT mutation in the TERT promoter was detected in BCPAP cells and the C250T mutation was found in 8505C cells. No TERT promoter mutation was observed in Cal-62 or ML-1 cells. The C228T mutation was found in only 1 of 35 (2.8%) PTCs and no C250T mutations were detected in any of the study subjects. The BRAF V600E mutation was found in 20 of 35 (57.1%) PTCs. One patient with the C228T TERT mutation also harbored the BRAF V600E mutation and developed a recurrence. Conclusion The prevalence of somatic TERT promoter mutations was low in Korean patients with classic PTC. Therefore, the prognostic role of TERT promoter mutations might be limited in this patient cohort. PMID:26676331

  1. CEACAM6 as detected by the AP11 antibody is a marker notable for mucin-producing adenocarcinomas.

    PubMed

    Lee, Ok-Jun; Son, Seung-Myoung; Hong, Kwon Pyo; Lee, Yong-Moon; Kim, Min-Young; Choi, Jae-Woon; Lee, Sang-Jeon; Song, Young-Jin; Kim, Hak Soon; Kim, Wun-Jae; Shin, See-Ok; Song, Hyung Geun

    2015-02-01

    A new monoclonal antibody recognizing CEACAM6, which we named AP11, was generated by immunizing BALB/c mice with phytohemagglutinin-activated human peripheral blood mononuclear cells. This study aims to evaluate whether CEACAM6 can serve as a tumor marker using AP11. We examined the expression of CEACAM6 with AP11 in 11 human carcinoma cell lines by flow cytometry and 439 human tissues including 282 tumor tissues and 157 normal tissues by immunohistochemistry. CEACAM6 epitope recognized by AP11 was well preserved in formalin-fixed and paraffin-embedded tissues. Adenocarcinomas of the stomach (86%), colorectum (95%), pancreas (100%), and lung (83%), urinary bladder (100%), and mucinous ovarian tumors (88%) had a high rate of CEACAM6 immunoreactivity. We observed a variable expression of CEACAM6 in hepatocellular carcinomas (35%), squamous cell carcinomas of the lung (60%), renal cell carcinomas (14%), urothelial carcinomas (13%), serous carcinomas of the ovary (17%), and breast carcinomas (11%). Small-cell carcinomas of the lung, prostatic adenocarcinomas, papillary thyroid carcinomas, malignant melanomas, giant cell tumors, and osteosarcomas were negative for CEACAM6. All normal tissues of various organs were negative for CEACAM6. In conclusion, CEACAM6 as detected by AP11, may serve as a marker for mucin-producing adenocarcinomas of the gastrointestinal tract and ovary as well as non-small cell lung cancer. Thus, AP11 represents a valuable diagnostic tool for detecting CEACMA6-positive cancers. PMID:25427744

  2. Characterization of the novel tumor-suppressor gene CCDC67 in papillary thyroid carcinoma

    PubMed Central

    Lei, Mengyuan; Li, Hongqiang; Wang, Yongfei; Liu, Zhen; Zhou, Yubing; Xing, Mingzhao

    2016-01-01

    Background Some studies showed an association of coiled-coil domain-containing (CCDC) genes with cancers. Our previous limited data specifically suggested a possible pathogenic role of CCDC67 in papillary thyroid cancer (PTC), but this has not been firmly established. The present study was to further investigate and establish this role of CCDC67 in PTC. Results The expression of CCDC67, both at mRNA and protein levels, was sharply down-regulated in PTC compared with normal thyroid tissues. Lower CCDC67 expression was significantly associated with aggressive tumor behaviors, such as advanced tumor stages and lymph node metastasis, as well as BRAF mutation. Introduced expression of CCDC67 in TPC-1 cells robustly inhibited cell proliferation, colony formation and migration, induced G1 phase cell cycle arrest, and increased cell apoptosis. Methods Primary PTC tumors and matched normal thyroid tissues were obtained from 200 unselected patients at the initial surgery for detection of CCDC67 mRNA and protein by RT-PCR and Western blotting analyses, respectively. Genomic DNA sequencing was performed to detect BRAF mutation in PTC tumors. Clinicopathological data were retrospectively reviewed for correlation analyses. PTC cell line TPC-1 with stable transfection of CCDC67 was used to investigate the functions of CCDC67. Conclusions This large study demonstrates down-regulation of CCDC67 in PTC, an inverse relationship between CCDC67 expression and PTC aggressiveness and BRAF mutation, and a robust inhibitory effect of CCDC67 on PTC cellular activities. These results are consistent with CCDC67 being a novel and impaired tumor suppressor gene in PTC, providing important prognostic and therapeutic implications for this cancer. PMID:26716505

  3. Mucin-Based Vaccines

    NASA Astrophysics Data System (ADS)

    Richardson, Jonathan P.; MacMillan, Derek

    Mucins are heavily O-glycosylated cell surface and secreted glycoproteins . In addition to orchestrating cell-extracellular matrix and cell-cell interactions in healthy organisms mucins are also the major carriers of altered glycosylation in carcinomas. Tumor-associated antigens displayed by cancer cells comprise oligosaccharide and glycopeptide motifs not encountered in the same locale or at the same frequency in healthy cells, and potentially confer a selective advantage to the tumor. Frequently tumor-associated antigens are under-glycosylated and prematurely sialylated, and it is these relatively simple saccharide and glycopeptide structures that have been targeted to serve as drug candidates in most cases. A major goal is to assemble glycopeptide vaccine candidates based on partial mucin sequences and displaying tumor-associated antigens that can mount a potent immunological tumor-specific response when, in reality, the tumor has already coerced the immune system into a state of co-existence.

  4. Clinical Outcome of Radioiodine Therapy in Low-intermediate Risk Papillary Thyroid Carcinoma with BRAF(V600E) Mutation.

    PubMed

    Jiao, L I; Tao, Yang; Teng, Zhao; Jun, Liang; Yan-Song, Lin

    2016-06-10

    Objective To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). Methods Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. Results There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). Conclusion For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population. PMID:27544995

  5. miR-137 acts as a tumor suppressor in papillary thyroid carcinoma by targeting CXCL12.

    PubMed

    Dong, Su; Jin, Meishan; Li, Ye; Ren, Peiyou; Liu, Jia

    2016-04-01

    Accumulating evidence has shown that aberrantly expressed microRNAs (miRs) are extensively involved in tumorigenesis. microRNA-137 (miR-137) has been reported as a tumor suppressor in various types of cancer. However, the biological function and underlying molecular mechanism of miR-137 in papillary thyroid carcinoma (PTC) remain largely unknown. Therefore, the present study aimed to investigate the expression pattern of miR-137 and its functional significance in PTC. Quantitative RT-PCR (qRT-PCR) assay showed that miR-137 expression was significantly downregulated in human PTC tissues, and its expression was significantly negatively correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Functional assays showed that forced expression of miR-137 in PTC cells significantly inhibited proliferation, colony formation, migration and invasion in vitro. Importantly, on the basis of bioinformatic analysis and luciferase reporter assay, we found that miR-137 directly targeted the 3'-untranslated region (3'-UTR) of C-X-C motif chemokine 12 (also known as SDF-1) (CXCL12). qRT-PCR and western blot analysis further verified the results and demonstrated that miR-137 could downregulate CXCL12 expression in PTC cells. We also confirmed that CXCL12 expression was increased in PTC tissues and was inversely correlated with miR-137. In addition, our results also showed that downregulation of CXCL12 mimicked the effects of miR-137 overexpression, and upregulation of CXCL12 partially reversed the inhibitory effects of miR-137 in PTC cells. These results showed that miR-137 may function as a tumor suppressor in PTC by targeting CXCL12, suggesting that miR-137 may act as a potential target for PTC treatment. PMID:26847706

  6. An evaluation and recommendation of the optimal methodologies to detect RET gene rearrangements in papillary thyroid carcinoma.

    PubMed

    Zhang, Tianwei; Lu, Yachao; Ye, Qingqing; Zhang, Meizhuo; Zheng, Li; Yin, Xiaolu; Gavine, Paul; Sun, Zhongsheng; Ji, Qunsheng; Zhu, Guanshan; Su, Xinying

    2015-03-01

    To recommend a reliable and clinically realistic RET/PTC rearrangement detection assay for papillary thyroid carcinoma (PTC), we compared multiplex quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). RET/PTC rearrangement was detected using either RET break-apart FISH followed by multicolor FISH to confirm CCDC6/RET or NCOA4/RET fusions, or by multiplex qPCR to detect 14 RET/PTC subtypes with simultaneous RET mRNA expression. RET protein expression was detected by IHC. The specificity and sensitivity of multiplex qPCR and IHC were calculated using break-apart FISH as a reference. Among 73 PTC patients with sufficient tissue available for FISH and multiplex qPCR, 10 cases were defined as RET/PTC positive by both assays, including eight CCDC6/RET and two NCOA4/RET fusions with relatively high RET mRNA. In addition, multiplex qPCR identified another two CCDC6/RET fusion positive cases, but with low RET mRNA expression. IHC staining identified 11 RET positive cases among 39 patients with available samples. In comparison to FISH, multiplex qPCR displayed 100% sensitivity and 97% specificity to detect RET/PTC fusions, while IHC was neither sensitive nor specific. Our data reveal that both multiplex qPCR and FISH assays are equally applicable for detection of RET/PTC rearrangements. Break-apart FISH methodology is highly recommended for the wider screening of RET rearrangements (regardless of partner genes), while multiplex qPCR is preferred to identify all known fusion types using one assay, provided mRNA expression is also measured. IHC analysis could potentially provide an additional method of fusion detection dependent on further optimization of assay conditions and scoring cutoffs. PMID:25407564

  7. Surgical procedures for papillary thyroid carcinoma located in the thyroid isthmus: an intention-to-treat analysis

    PubMed Central

    Lei, Jianyong; Zhu, Jinqiang; Li, Zhihui; Gong, Rixiang; Wei, Tao

    2016-01-01

    Objective We sought to evaluate and compare the outcomes of different surgical protocols for papillary thyroid cancer (PTC) located in the isthmus in a retrospective intention-to-treat analysis. Patients and methods The data of 3,068 patients who received thyroidectomy due to thyroid cancer in our center were reviewed. Of these, 103 patients had a dominant carcinoma located in the isthmus. Various baseline and tumor characteristics and surgical outcomes were evaluated and compared with respect to the different surgical protocols (85 cases with total thyroidectomy and 18 cases with less-than-total thyroidectomy). Univariate and multivariate analyses were performed to identify resected patients who developed recurrence with isthmic PTC. Results The postoperative complication rates were comparable between the two groups (17.6% versus 11.1%, P=0.500). Although the total thyroidectomy group showed a much higher rate (P=0.004) and number (P<0.001) of parathyroidectomies, long-term follow-up indicated that parathyroid autotransplantation did not significantly damage the function of the parathyroid (P>0.05). Tumor recurrence was observed in five patients, including two patients in the total thyroidectomy group and three patients in the less-than-total thyroidectomy group; the tumor recurrence rate in the total thyroidectomy group was significantly lower than that in the less-than-total thyroidectomy group (P=0.040). Univariate and multivariate analyses indicated less-than-total thyroidectomy as a risk factor for tumor recurrence in PTC cases with tumors located at the isthmus (hazard ratio: 1.870, 95% confidence interval: 1.320–2.218, P<0.001). Conclusion Our findings indicate that total thyroidectomy is an appropriate initial surgical protocol for isthmic PTC due to the lower recurrence rate, comparable postoperative complication rate, and parathyroid function recovery. PMID:27578987

  8. Methylation of sodium iodide symporter promoter correlated with aggressiveness and metastasis in papillary thyroid carcinoma: a meta-analysis

    PubMed Central

    Zhao, Jun-Yu; Wang, Huan-Jun; Wang, Hai-Peng; Yao, Jin-Ming; Wu, Xiao-Yun; Shang, Hong-Xia; Zhang, Rui; Zhu, Huan-Gao; Dong, Jian-Jun; Liao, Lin

    2015-01-01

    Background: Methylation of sodium iodide symporter promoter has been reported to increase the incidence of papillary thyroid carcinoma (PTC). In this meta-analysis stratified via methylation of sodium iodide symporter promoter, we evaluate the relationship between methylation of sodium iodide symporter promoter and PTC. The association between methylation with aggressiveness and metastasis potential of PTC is also discussed. Methods: We searched electronic databases for original articles and references of included studies both in English and Chinese from 1966 to 2014. Two reviewers selected the case-control study and extracted data from relevant literature independently. Results: Seven articles, including 360 cases and 268 controls, were involved in this meta-analysis. The prevalence of PTC in patients with methylated sodium iodide symporter promoter was significantly higher than those with non-methylated promoter (OR=7.36, 95% CI: 4.25-12.74, P<0.001). Stratified analysis showed that PTC patients with multiple lesions, capsule invasion and lymphatic metastasis had significantly higher rates of methylation (OR=2.22, 95% CI: 1.12-4.41, P=0.02; OR=2.14, 95% CI: 1.12-4.08, P=0.02; OR=3.56, 95% CI: 1.97-6.46, P<0.0001). But no relationship was found among the methylation of sodium iodide symporter and age, gender and size of tumor. Conclusions: The methylation of sodium iodide symporter promoter is related with PTC and its aggressive and metastatic potential. Due to the limited sample size, more clinical researches should be taken in the future. PMID:26379865

  9. Combined analysis of circulating epithelial cells and serum thyroglobulin for distinguishing disease status of the patients with papillary thyroid carcinoma

    PubMed Central

    Lin, Hung-Chih; Liou, Miaw-Jene; Hsu, Hsung-Ling; Hsieh, Jason Chia-Hsun; Chen, Yi-An; Tseng, Ching-Ping; Lin, Jen-Der

    2016-01-01

    Papillary thyroid carcinoma (PTC) accounts for about 80% of the cases in thyroid cancer. Routine surveillance by serum thyroglobulin (Tg) and medical imaging is the current practice to monitor disease progression of the patients. Whether enumeration of circulating epithelial cells (CECs) helps to define disease status of PTC patients was investigated. CECs were enriched from the peripheral blood of the healthy control subjects (G1, n = 17) and the patients at disease-free status (G2, n = 26) or with distant metastasis (G3, n = 22). The number of CECs expressing epithelial cell adhesion molecule (EpCAM) or thyroid-stimulating hormone receptor (TSHR) was determined by immunofluorescence microscopy analyses. The medium number of EpCAM+-CECs was 6 (interquartile range 1-11), 12 (interquartile range 7-16) and 91 (interquartile range 31-206) cells/ml of blood for G1, G2 and G3, respectively. EpCAM+-CEC counts were significantly higher in G3 than in G1 (p < 0.05) and G2 (p < 0.05). The medium number of TSHR+-CECs was 9 (interquartile range 3-13), 16 (interquartile range 10-24) and 100 (interquartile range 31-226) cells/ml of blood for G1, G2 and G3, respectively. The TSHR+-CEC counts also distinguished G3 from G1 (p < 0.05) and G2 (p < 0.05). With an appropriate cut off value of CEC count, the disease status for 97.9% (47/48) of the cases was clearly defined. Notably, the metastatic disease for all patients in G3 (22/22) was revealed by combined analysis of serum Tg and CEC. This study implicates that CEC testing can supplement the current standard methods for monitoring disease status of PTC. PMID:26684026

  10. miR-451a is underexpressed and targets AKT/mTOR pathway in papillary thyroid carcinoma

    PubMed Central

    Minna, Emanuela; Romeo, Paola; Dugo, Matteo; De Cecco, Loris; Todoerti, Katia; Pilotti, Silvana; Perrone, Federica; Seregni, Ettore; Agnelli, Luca; Neri, Antonino; Greco, Angela; Borrello, Maria Grazia

    2016-01-01

    Papillary Thyroid Carcinoma (PTC) is the most frequent thyroid cancer. Although several PTC-specific miRNA profiles have been reported, only few upregulated miRNAs are broadly recognized, while less consistent data are available about downregulated miRNAs. In this study we investigated miRNA deregulation in PTC by miRNA microarray, analysis of a public dataset from The Cancer Genome Atlas (TCGA), literature review and meta-analysis based on a univocal miRNA identifier derived from miRBase v21. A list of 18 miRNAs differentially expressed between PTC and normal thyroid was identified and validated in the TCGA dataset. Furthermore, we compared our signature with miRNA profiles derived from 15 studies selected from literature. Then, to select possibly functionally relevant miRNA, we integrated our miRNA signature with those from two in vitro cell models based on the PTC-driving oncogene RET/PTC1. Through this strategy, we identified commonly deregulated miRNAs, including miR-451a, which emerged also by our meta-analysis as the most frequently reported downregulated miRNA. We showed that lower expression of miR-451a correlates with aggressive clinical-pathological features of PTC as tall cell variant, advanced stage and extrathyroid extension. In addition, we demonstrated that ectopic expression of miR-451a impairs proliferation and migration of two PTC-derived cell lines, reduces the protein levels of its recognized targets MIF, c-MYC and AKT1 and attenuates AKT/mTOR pathway activation. Overall, our study provide both an updated overview of miRNA deregulation in PTC and the first functional evidence that miR-451a exerts tumor suppressor functions in this neoplasia. PMID:26871295

  11. miR-451a is underexpressed and targets AKT/mTOR pathway in papillary thyroid carcinoma.

    PubMed

    Minna, Emanuela; Romeo, Paola; Dugo, Matteo; De Cecco, Loris; Todoerti, Katia; Pilotti, Silvana; Perrone, Federica; Seregni, Ettore; Agnelli, Luca; Neri, Antonino; Greco, Angela; Borrello, Maria Grazia

    2016-03-15

    Papillary Thyroid Carcinoma (PTC) is the most frequent thyroid cancer. Although several PTC-specific miRNA profiles have been reported, only few upregulated miRNAs are broadly recognized, while less consistent data are available about downregulated miRNAs. In this study we investigated miRNA deregulation in PTC by miRNA microarray, analysis of a public dataset from The Cancer Genome Atlas (TCGA), literature review and meta-analysis based on a univocal miRNA identifier derived from miRBase v21. A list of 18 miRNAs differentially expressed between PTC and normal thyroid was identified and validated in the TCGA dataset. Furthermore, we compared our signature with miRNA profiles derived from 15 studies selected from literature. Then, to select possibly functionally relevant miRNA, we integrated our miRNA signature with those from two in vitro cell models based on the PTC-driving oncogene RET/PTC1. Through this strategy, we identified commonly deregulated miRNAs, including miR-451a, which emerged also by our meta-analysis as the most frequently reported downregulated miRNA. We showed that lower expression of miR-451a correlates with aggressive clinical-pathological features of PTC as tall cell variant, advanced stage and extrathyroid extension. In addition, we demonstrated that ectopic expression of miR-451a impairs proliferation and migration of two PTC-derived cell lines, reduces the protein levels of its recognized targets MIF, c-MYC and AKT1 and attenuates AKT/mTOR pathway activation.Overall, our study provide both an updated overview of miRNA deregulation in PTC and the first functional evidence that miR-451a exerts tumor suppressor functions in this neoplasia. PMID:26871295

  12. Radioactive iodine ablation may not decrease the risk of recurrence in intermediate-risk papillary thyroid carcinoma.

    PubMed

    Kim, Seo Ki; Woo, Jung-Woo; Lee, Jun Ho; Park, Inhye; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo

    2016-05-01

    The use of radioactive iodine (RAI) ablation in patients with intermediate-risk papillary thyroid carcinoma (PTC) who show microscopic extrathyroidal extension (ETE), regional lymph node (LN) metastasis, tumors with aggressive histology, or vascular invasion has been debated due to the lack of data regarding long-term prognosis in this risk group. Therefore, the purpose of this study was to resolve the controversy surrounding the prognostic benefit of RAI ablation, especially in intermediate-risk PTC patients. We retrospectively reviewed the medical records of 8297 intermediate-risk PTC patients who underwent primary total thyroidectomy with or without neck dissection at the Thyroid Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, between January 1997 and June 2015. Of these 8297 patients, 7483 (90.2%) received RAI ablation. After adjusting for clinicopathological characteristics, RAI ablation did not significantly decrease the risk of loco-regional recurrence (LRR) (adjusted hazard ratio (HR) 0.852, P 0.413). Moreover, RAI ablation did not decrease the risk of LRR even in intermediate-risk PTC patients with aggressive features such as BRAF positivity (adjusted HR 0.729, P 0.137), tumor size >1 cm (adjusted HR 0.762, P 0.228), multifocality (adjusted HR 1.032, P 0.926), ETE (adjusted HR 0.870, P 0.541), and regional LN metastasis (adjusted HR 0.804, P 0.349). Furthermore, high-dose RAI ablation (>100 mCi) did not significantly decrease the risk of LRR (adjusted HR 0.942, P 0.843). Therefore, RAI ablation in intermediate-risk PTC patients should be considered on the basis of tailored risk restratification. PMID:26917553

  13. The Oncogenic Activity of RET Point Mutants for Follicular Thyroid Cells May Account for the Occurrence of Papillary Thyroid Carcinoma in Patients Affected by Familial Medullary Thyroid Carcinoma

    PubMed Central

    Melillo, Rosa Marina; Cirafici, Anna Maria; De Falco, Valentina; Bellantoni, Marie; Chiappetta, Gennaro; Fusco, Alfredo; Carlomagno, Francesca; Picascia, Antonella; Tramontano, Donatella; Tallini, Giovanni; Santoro, Massimo

    2004-01-01

    Activating germ-line point mutations in the RET receptor are responsible for multiple endocrine neoplasia type 2-associated medullary thyroid carcinoma (MTC), whereas somatic RET rearrangements are prevalent in papillary thyroid carcinomas (PTCs). Some rare kindreds, carrying point mutations in RET, are affected by both cancer types, suggesting that, under specific circumstances, point mutations in RET can drive the generation of PTC. Here we describe a family whose siblings, affected by both PTC and MTC, carried a germ-line point mutation in the RET extracellular domain, converting cysteine 634 into serine. We tested on thyroid follicular cells the transforming activity of RET(C634S), RET(K603Q), another mutant identified in a kindred with both PTC and MTC, RET(C634R) a commonly isolated allele in MEN2A, RET(M918T) responsible for MEN2B and also identified in kindreds with both PTC and MTC, and RET/PTC1 the rearranged oncogene that characterizes bona fide PTC in patients without MTC. We show that the various RET point mutants, but not wild-type RET, scored constitutive kinase activity and exerted mitogenic effects for thyroid PC Cl 3 cells, albeit at significantly lower levels compared to RET/PTC1. The low mitogenic activity of RET point mutants paralleled their reduced kinase activity compared to RET/PTC. Furthermore, RET point mutants maintained a protein domain, the intracellular juxtamembrane domain, that exerted negative effects on the mitogenic activity. In conclusion, RET point mutants can behave as dominant oncogenes for thyroid follicular cells. Their transforming activity, however, is rather modest, providing a possible explanation for the rare association of MTC with PTC. PMID:15277225

  14. Mixed low- and high-grade papillary urothelial carcinoma: histopathogenetic and clinical significance.

    PubMed

    Mai, Kien T; Flood, Trevor A; Williams, Phillip; Kos, Zuzana; Belanger, Eric C

    2013-10-01

    There are two pathways of urothelial carcinogenesis: low-grade urothelial carcinoma (LGUC) with low rates of gene alterations and high-grade urothelial carcinoma (HGUC) with numerous gene alterations. HGUC often displays strong reactivity for cytokeratin 20 (CK20) and p16. Despite distinct molecular changes, urothelial carcinoma (UC) with both low- and high-grade features is not uncommon. We examined cases with patterns of mixed low- and high-grade UC (MLHGUC). Consecutive cases of UC at our institution were reviewed. There were 45 cases that showed a mixture of both LGUC and HGUC. IHC for CK5, CK20, CD44, p16, and Ki67 was performed. Areas of HGUC displayed strong and diffuse reactivity for p16, CK20, and Ki67 in 20-50 % of the tumor, while LGUC areas had negative or focal reactivity for CK20 and Ki67 in 10-30 %. There were two distinct cohorts of MLHGUC: patients with a history of LGUC (group A) and those without (group B). Group A patients (n = 8) had a history of LGUC for 1-10 years. The tumor specimens weighed 1.5 ± 1.7 g and had HGUC components of 25 ± 20 % of the tissue. Superficial invasion was present in one case. All tumors had BCG treatment with one recurrence. In group B (n = 37), tumor specimens weighed 3 ± 3.9 g and had HGUC components in 43 ± 21 % of the tissue. Superficial invasion was present in five cases, and muscle invasion with lung metastasis occurred in one case. Four cases were refractory to BCG with an increased proportion of HGUC, and one case requiring cystectomy. Differences in size and proportion of HGUC between groups A and B MLHGUC were significant (P < 0.05), with group B presenting with a higher tumor burden and proportion of HGUC. MLHGUC is diagnostically challenging and is commonly assigned high grade since this determines prognosis. Group A MLHGUC likely develops as a result of progression from LGUC, whereas group B MLHGUC likely develops de novo, is associated with larger tumors, shows a

  15. FAP Associated Papillary Thyroid Carcinoma: A Peculiar Subtype of Familial Nonmedullary Thyroid Cancer

    PubMed Central

    Cetta, Francesco

    2015-01-01

    Familial Nonmedullary Thyroid Carcinoma (FNMTC) makes up to 5–10% of all thyroid cancers, also including those FNMTC occurring as a minor component of familial cancer syndromes, such as Familial Adenomatous Polyposis (FAP). We give evidence that this extracolonic manifestation of FAP is determined by the same germline mutation of the APC gene responsible for colonic polyps and cancer but also shows some unusual features (F : M ratio = 80 : 1, absence of LOH for APC in the thyroid tumoral tissue, and indolent biological behaviour, despite frequent multicentricity and lymph nodal involvement), suggesting that the APC gene confers only a generic susceptibility to thyroid cancer, but perhaps other factors, namely, modifier genes, sex-related factors, or environmental factors, are also required for its phenotypic expression. This great variability is against the possibility of classifying all FNMTC as a single entity, not only with a unique or prevalent causative genetic factor, but also with a unique or common biological behavior and a commonly dismal prognosis. A new paradigm is also suggested that could be useful (1) for a proper classification of FAP associated PTC within the larger group of FNMTC and (2) for making inferences to sporadic carcinogenesis, based on the lesson from FAP. PMID:26697262

  16. Risk Factors for Central Lymph Node Metastasis in CN0 Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis

    PubMed Central

    Sun, Wei; Lan, Xiabin; Zhang, Hao; Dong, Wenwu; Wang, Zhihong; He, Liang; Zhang, Ting; Liu, Siming

    2015-01-01

    Background Central lymph node metastasis (CLNM) is common in papillary thyroid carcinoma (PTC). Prophylactic central lymph node dissection (PCLND) for patients with clinically negative central compartment lymph nodes (CN0) remains controversial. The phrase “clinically negative” is used to indicate that patients exhibited no clinical evidence of CLNM by ultrasonography (US) or computerized tomography (CT) preoperatively. In this study, we analyze the risk factors for CLNM in CN0 patients. Methods The PUBMED and SCIE databases were systematically searched for works published through January 31, 2015. All of the patients included in this study underwent thyroidectomy+PCLND. Revman 5.3 software was used to analyze the data. Results Twenty studies and 9084 patients were included in this meta-analysis. The following variables were associated with an increased risk of CLNM in CN0 patients: age < 45 years (OR = 1.59, 95% CI = 1.42–1.78, p<0.00001), male sex (OR = 1.95, 95% CI = 1.63–2.32, p<0.00001), multifocality (OR = 1.43, 95% CI = 1.22–1.67, p<0.00001), tumor size > 2 cm for PTC patients (OR = 2.98, 95% CI 2.08–4.28, p<0.00001) or tumor size > 0.5 cm for papillary thyroid microcarcinoma (PTMC) patients (OR = 2.30, 95% CI = 1.71–3.09, p<0.00001), location of the primary tumor in the central area and low pole (OR = 1.86, 95% CI = 1.48–2.33, p<0.00001), lymphovascular invasion (OR = 4.35, 95% CI = 2.24–8.46, p<0.0001), extrathyroidal extension (OR = 2.27, 95% CI = 1.76–2.94, p<0.00001), and capsular invasion (OR = 1.72, 95% CI = 1.39–2.41, p<0.00001). PTC (tumor size>1cm) exhibited a higher risk factor associated with CLNM than PTMC (tumor size<1cm) (OR = 2.83, 95% CI = 2.15–3.72, p<0.00001). Bilateral tumors (OR = 1.21, 95% CI = 0.92–1.58, p = 0.17) and lymphocytic thyroiditis (OR = 0.88, 95% CI = 0.71–1.09, p = 0.25) had no association with CLNM in CN0 patients. Conclusions Our systematic review identified several clinical features associated

  17. Renal cell carcinoma: Evolving and emerging subtypes.

    PubMed

    Crumley, Suzanne M; Divatia, Mukul; Truong, Luan; Shen, Steven; Ayala, Alberto G; Ro, Jae Y

    2013-12-16

    Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. PMID:24364021

  18. Renal cell carcinoma: Evolving and emerging subtypes

    PubMed Central

    Crumley, Suzanne M; Divatia, Mukul; Truong, Luan; Shen, Steven; Ayala, Alberto G; Ro, Jae Y

    2013-01-01

    Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. PMID:24364021

  19. Comparison of microarray expression profiles between follicular variant of papillary thyroid carcinomas and follicular adenomas of the thyroid

    PubMed Central

    2015-01-01

    Background Follicular variant of papillary thyroid carcinoma (FVPTC) and follicular adenoma (FA) are histologically closely related tumors and differential diagnosis remains challenging. RNA expression profiling is an established method to unravel molecular mechanisms underlying the histopathology of diseases. Methods BRAF mutational status was established by direct sequencing the hotspot region of exon 15 in six FVPTCs and seven FAs. Whole-transcript arrays were employed to generate expression profiles in six FVPTCs, seven FAs and seven normal thyroid tissue samples. The threshold of significance for differential expression on the gene and exon level was a p-value with a false discovery rate (FDR) < 0.05 and a fold change cutoff > 2. Two dimensional average linkage hierarchical clustering was generated using differentially expressed genes. Network, pathway, and alternative splicing utilities were employed to interpret significance of expression data on the gene and exon level. Results Expression profiling in FVPTCs and FAs, all of which were negative for a BRAF mutation, revealed 55 transcripts that were significantly differentially expressed, 40 of which were upregulated and 15 downregulated in FVPTCs vs. FAs. Amongst the most significantly upregulated genes in FVPTCs were GABA B receptor, 2 (GABBR2), neuronal cell adhesion molecule (NRCAM), extracellular matrix protein 1 (ECM1), heparan sulfate 6-O-sulfotransferase 2 (HS6ST2), and retinoid X receptor, gamma (RXRG). The most significantly downregulated genes in FVPTCs included interaction protein for cytohesin exchange factors 1 (IPCEF1), G protein-coupled receptor 155 (GPR155), Purkinje cell protein 4 (PCP4), chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1), and glutamate receptor interacting protein 1 (GRIP1). Alternative splicing analysis detected 87 genes, 52 of which were also included in the list of 55 differentially expressed genes. Network analysis demonstrated multiple interactions

  20. Expression profiles of pivotal microRNAs and targets in thyroid papillary carcinoma: an analysis of The Cancer Genome Atlas

    PubMed Central

    Cong, Dan; He, Mengzi; Chen, Silin; Liu, Xiaoli; Liu, Xiaodong; Sun, Hui

    2015-01-01

    In the present study, we analyzed microRNA (miRNA) and gene expression profiles using 499 papillary thyroid carcinoma (PTC) samples and 58 normal thyroid tissues obtained from The Cancer Genome Atlas database. A pivotal regulatory network of 18 miRNA and 16 targets was identified. Upregulated miRNAs (miR-222, miR-221, miR-146b, miR-181a/b/d, miR-34a, and miR-424) and downregulated miRNAs (miR-9-1, miR-138, miR-363, miR-20b, miR-195, and miR-152) were identified. Among them, the upregulation of miR-424 and downregulation of miR-363, miR-195, and miR-152 were not previously identified. The genes CCNE2 (also known as cyclin E2), E2F1, RARA, CCND1 (cyclin D1), RUNX1, ITGA2, MET, CDKN1A (p21), and COL4A1 were overexpressed, and AXIN2, TRAF6, BCL2, RARB, HSP90B1, FGF7, and PDGFRA were downregulated. Among them, CCNE2, COL4A1, TRAF6, and HSP90B1 were newly identified. Based on receiver operating characteristic curves, several miRNAs (miR-222, miR-221, and miR-34a) and genes (CCND1 and MET) were ideal diagnostic indicators, with sensitivities and specificities greater than 90%. The combination of inversely expressed miRNAs and targets improved diagnostic accuracy. In a clinical feature analysis, several miRNAs (miR-34a, miR-424, miR-20b, and miR-152) and genes (CCNE2, COL4A1, TRAF6, and HSP90B1) were associated with aggressive clinical features, which have not previously been reported. Our study not only identified a pivotal miRNA regulatory network associated with PTC but also provided evidence that miRNAs and target genes can be used as biomarkers in PTC diagnosis and clinical risk evaluation. PMID:26345235

  1. Comparing Clinicopathologic and Radiographic Findings Between TT-UMP, Classical, and Non-Encapsulated Follicular Variants of Papillary Thyroid Carcinomas.

    PubMed

    Baser, Husniye; Topaloglu, Oya; Tam, Abbas Ali; Alkan, Afra; Kilicarslan, Aydan; Ersoy, Reyhan; Cakir, Bekir

    2016-09-01

    Thyroid tumors of uncertain malignant potential (TT-UMP) comprise an accepted subgroup of follicular-patterned thyroid tumors for which benignancy or malignancy cannot be precisely assessed. We aimed to evaluate the demographic characteristics, ultrasound (US) findings, and cytological results of patients with TT-UMP and compare these findings to a classical variant of papillary thyroid carcinoma (CV-PTC) and non-encapsulated follicular variant of PTC (NEFV-PTC) patients; we also evaluated the immunohistochemical characteristics of patients with TT-UMP. Twenty-four patients with TT-UMP, 672 with CV-PTC, and 132 with NEFV-PTC were included in the study. Mean longitudinal nodule size and median nodule volume were higher in the TT-UMP group than in the CV-PTC and NEFV-PTC groups (p < 0.001 and p < 0.001 for CV-PTC; p < 0.001 and p = 0.008 for NEFV-PTC). The presence of halo and peripheral vascularization was observed more frequently in the TT-UMP group than in the CV-PTC group (p = 0.002 and p = 0.024). Benign and follicular neoplasm/suspicious for follicular neoplasm cytological results were higher in the TT-UMP group than in the CV-PTC group (p = 0.030 and p = 0.001). US findings were similar between TT-UMP and NEFV-PTC groups (all, p > 0.05). However, none of the patients with TT-UMP were called malignant; 105 patients (31.2 %) of CV-PTC and 11 patients (9.5 %) of NEFV-PTC (infiltrative FV) were classified as malignant cytologically. Tumor size was higher in the TT-UMP group than in the CV-PTC and NEFV-PTC groups (p < 0.001 and p = 0.006). In the TT-UMP group, positive expression of HBME-1, CK-19, and Gal-3 was found in 50, 33.3, and 25 % of patients, respectively. This study demonstrated that none of the TT-UMP patients were evaluated as malignant in preoperative cytology. However, patients with TT-UMP had higher nodule and tumor sizes than CV-PTC and NEFV-PTC patients; US features were similar between NEFV-PTC and TT

  2. Aberrant expressions of c-KIT and DOG-1 in mucinous and nonmucinous colorectal carcinomas and relation to clinicopathologic features and prognosis.

    PubMed

    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. PMID:26272691

  3. FGFR3b Extracellular Loop Mutation Lacks Tumorigenicity In Vivo but Collaborates with p53/pRB Deficiency to Induce High-grade Papillary Urothelial Carcinoma

    PubMed Central

    Zhou, Haiping; He, Feng; Mendelsohn, Cathy L.; Tang, Moon-shong; Huang, Chuanshu; Wu, Xue-Ru

    2016-01-01

    Missense mutations of fibroblast growth factor receptor 3 (FGFR3) occur in up to 80% of low-grade papillary urothelial carcinoma of the bladder (LGP-UCB) suggesting that these mutations are tumor drivers, although direct experimental evidence is lacking. Here we show that forced expression of FGFR3b-S249C, the most prevalent FGFR3 mutation in human LGP-UCB, in cultured urothelial cells resulted in slightly reduced surface translocation than wild-type FGFR3b, but nearly twice as much proliferation. When we expressed a mouse equivalent of this mutant (FGFR3b-S243C) in urothelia of adult transgenic mice in a tissue-specific and inducible manner, we observed significant activation of AKT and MAPK pathways. This was, however, not accompanied by urothelial proliferation or tumorigenesis over 12 months, due to compensatory tumor barriers in p16-pRB and p19-p53-p21 axes. Indeed, expressing FGFR3b-S249C in cultured human urothelial cells expressing SV40T, which functionally inactivates pRB/p53, markedly accelerated proliferation and cell-cycle progression. Furthermore, expressing FGFR3b-S243C in transgenic mouse urothelium expressing SV40T converted carcinoma-in-situ to high-grade papillary urothelial carcinoma. Together, our study provides new experimental evidence indicating that the FGFR3 mutations have very limited urothelial tumorigenicity and that these mutations must collaborate with other genetic events to drive urothelial tumorigenesis. PMID:27157475

  4. FGFR3b Extracellular Loop Mutation Lacks Tumorigenicity In Vivo but Collaborates with p53/pRB Deficiency to Induce High-grade Papillary Urothelial Carcinoma.

    PubMed

    Zhou, Haiping; He, Feng; Mendelsohn, Cathy L; Tang, Moon-Shong; Huang, Chuanshu; Wu, Xue-Ru

    2016-01-01

    Missense mutations of fibroblast growth factor receptor 3 (FGFR3) occur in up to 80% of low-grade papillary urothelial carcinoma of the bladder (LGP-UCB) suggesting that these mutations are tumor drivers, although direct experimental evidence is lacking. Here we show that forced expression of FGFR3b-S249C, the most prevalent FGFR3 mutation in human LGP-UCB, in cultured urothelial cells resulted in slightly reduced surface translocation than wild-type FGFR3b, but nearly twice as much proliferation. When we expressed a mouse equivalent of this mutant (FGFR3b-S243C) in urothelia of adult transgenic mice in a tissue-specific and inducible manner, we observed significant activation of AKT and MAPK pathways. This was, however, not accompanied by urothelial proliferation or tumorigenesis over 12 months, due to compensatory tumor barriers in p16-pRB and p19-p53-p21 axes. Indeed, expressing FGFR3b-S249C in cultured human urothelial cells expressing SV40T, which functionally inactivates pRB/p53, markedly accelerated proliferation and cell-cycle progression. Furthermore, expressing FGFR3b-S243C in transgenic mouse urothelium expressing SV40T converted carcinoma-in-situ to high-grade papillary urothelial carcinoma. Together, our study provides new experimental evidence indicating that the FGFR3 mutations have very limited urothelial tumorigenicity and that these mutations must collaborate with other genetic events to drive urothelial tumorigenesis. PMID:27157475

  5. Thyroid cancer - papillary carcinoma

    MedlinePlus

    ... some noncancerous childhood conditions Radiation exposure from nuclear plant disasters Radiation given through a vein (through an IV) during medical tests and treatments does not increase the risk of developing thyroid cancer.

  6. Thyroid cancer - papillary carcinoma

    MedlinePlus

    ... non-cancerous childhood conditions Radiation exposure from nuclear plant disasters Radiation given through a vein (through an IV) during medical tests and treatments does not increase the risk of developing thyroid cancer.

  7. Curcumin inhibits metastasis in human papillary thyroid carcinoma BCPAP cells via down-regulation of the TGF-β/Smad2/3 signaling pathway.

    PubMed

    Zhang, Li; Cheng, Xian; Gao, Yanyan; Zhang, Chiyu; Bao, Jiandong; Guan, Haixia; Yu, Huixin; Lu, Rongrong; Xu, Qiang; Sun, Yang

    2016-02-15

    Thyroid cancers usually possess a good prognosis while the risks of recurrence and metastasis turn out to be a disturbing issue. Curcumin [bis(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione] is a natural polyphenolic compound mainly found in turmeric (Curcuma longa). Our previous studies have demonstrated that curcumin showed proliferation-inhibitory and apoptosis-inducing effects on K1 papillary thyroid cancer cells. However, the mechanism underlying the inhibition effects of curcumin on thyroid cancer cells remains unclear. Herein, we demonstrated that curcumin remarkably increased the expression of the epithelial marker E-cadherin and repressed the expression of the mesenchymal marker vimentin in human papillary thyroid carcinoma BCPAP cells. Curcumin also suppressed multiple metastatic steps of BCPAP cells, including cell attachment, spreading as well as migration. In addition, the transcription, secretion and activation of matrix metalloproteinases (MMPs) induced by transforming growth factor-β1 (TGF-β1) in BCPAP cells were mitigated upon curcumin treatment. Further evidence showed that curcumin decreased TGF-β1-mediated phosphorylation of Smad2 and Smad3. These results revealed that curcumin inhibited the TGF-β1-induced epithelial-mesenchymal transition (EMT) via down-regulation of Smad2/3 signaling pathways. Our findings provide new evidence that the anti-metastatic and anti-EMT activities of curcumin may contribute to the development of chemo-preventive agents for thyroid cancer treatment. PMID:26826337

  8. Regulation of Mucin 1 and multidrug resistance protein 1 by honokiol enhances the efficacy of doxorubicin-mediated growth suppression in mammary carcinoma cells

    PubMed Central

    Thulasiraman, Padmamalini; Johnson, Andrea Butts

    2016-01-01

    Understanding the link between chemoresistance and cancer progression may identify future targeted therapy for breast cancer. One of the mechanisms by which chemoresistance is attained in cancer cells is mediated through the expression of multidrug resistance proteins (MRPs). Acquiring drug resistance has been correlated to the emergence of metastasis, accounting for the progression of the disease. One of the diagnostic markers of metastatic progression is the overexpression of a transmembrane protein called Mucin 1 (MUC1) which has been implicated in reduced survival rate. The objective of this study was to understand the relationship between MUC1 and MRP1 using natural phenolic compound isolated from Magnolia grandiflora, honokiol, in mammary carcinoma cells. We provide evidence that honokiol suppresses the expression level of MUC1 and MRP1 in mammary carcinoma cells. In a time-dependent manner, honokiol-mediated reduction of MUC1 is followed by a reduction of MRP1 expression in the breast cancer cells. Additionally, silencing MUC1 suppresses the expression level of MRP1 and enhances the efficacy of doxorubicin, an MRP1 substrate. Taken together, these findings suggest MUC1 regulates the expression of MRP1 and provides a direct link between cancer progression and chemoresistance in mammary carcinoma cells. PMID:27221150

  9. Regulation of Mucin 1 and multidrug resistance protein 1 by honokiol enhances the efficacy of doxorubicin-mediated growth suppression in mammary carcinoma cells.

    PubMed

    Thulasiraman, Padmamalini; Johnson, Andrea Butts

    2016-08-01

    Understanding the link between chemoresistance and cancer progression may identify future targeted therapy for breast cancer. One of the mechanisms by which chemoresistance is attained in cancer cells is mediated through the expression of multidrug resistance proteins (MRPs). Acquiring drug resistance has been correlated to the emergence of metastasis, accounting for the progression of the disease. One of the diagnostic markers of metastatic progression is the overexpression of a transmembrane protein called Mucin 1 (MUC1) which has been implicated in reduced survival rate. The objective of this study was to understand the relationship between MUC1 and MRP1 using natural phenolic compound isolated from Magnolia grandiflora, honokiol, in mammary carcinoma cells. We provide evidence that honokiol suppresses the expression level of MUC1 and MRP1 in mammary carcinoma cells. In a time-dependent manner, honokiol-mediated reduction of MUC1 is followed by a reduction of MRP1 expression in the breast cancer cells. Additionally, silencing MUC1 suppresses the expression level of MRP1 and enhances the efficacy of doxorubicin, an MRP1 substrate. Taken together, these findings suggest MUC1 regulates the expression of MRP1 and provides a direct link between cancer progression and chemoresistance in mammary carcinoma cells. PMID:27221150

  10. Incidental finding of papillary thyroid carcinoma with BRAFV600E mutation in a patient with coexistent primary hyperparathyroidism and Graves’ hyperthyroidism

    PubMed Central

    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

  11. Effect of Iodine Intake on p14ARF and p16INK4a Expression in Thyroid Papillary Carcinoma in Rats

    PubMed Central

    Sun, Ruimei; Wang, Jinde; Li, Xiaojiang; Li, Lei; Yang, Jie; Ren, Yanxin; Xi, Yan; Sun, Chuanzheng

    2015-01-01

    Background Iodine intake is related to thyroid disease. This study investigated the effect of the amount of iodine intake on p14ARF and p16INK4a expression of thyroid papillary carcinoma in rats. Material/Methods A cohort of 240 SD rats were randomly divided into control group, low iodine, normal iodine, and high iodine groups (n=60 per group). We inoculated 2×105 papillary thyroid carcinoma (PTC) cells on the left side of the thyroid gland. After 6 and 12 weeks, serum thyroid hormone level and urine iodine level were measured in addition to morphological observations of tumor tissues. Expression of p14ARF, p16INK4a was detected by immunohistochemical staining. Results The expression of p14ARF, p16INK4a, FT3, and FT4 levels in all iodine-treated animals were significantly lower than in the control group, while TSH level was significantly higher (P<0.05). Compared to the normal iodine group, the low and high groups had lower p14ARF and p16INK4a expression, lower FT3 and FT4 levels, higher TSH levels, and heavier tumors (P<0.05). In a further between-group comparison, p14ARF and p16INK4a expression and FT3 and FT4 levels at 12 weeks were lower than at 6 weeks. Expression of p14ARF and p16INK4a were positively correlated with FT3 and FT4, and negatively correlated with TSH and tumor weight. Conclusions Low and high iodine diet intake could reduce p14ARF and p16INK4a expressions and promote tumor development. PMID:26248224

  12. Using Diffusion-Weighted MRI to Predict Aggressive Histological Features in Papillary Thyroid Carcinoma: A Novel Tool for Pre-Operative Risk Stratification in Thyroid Cancer

    PubMed Central

    Lu, Yonggang; Moreira, Andre L.; Hatzoglou, Vaios; Stambuk, Hilda E.; Gonen, Mithat; Mazaheri, Yousef; Deasy, Joseph O.; Shaha, Ashok R.

    2015-01-01

    Background: Initial management recommendations of papillary thyroid carcinoma (PTC) are very dependent on preoperative studies designed to evaluate the presence of PTC with aggressive features. The purpose of this study was to evaluate whether diffusion-weighted magnetic resonance imaging (DW-MRI) before surgery can be used as a tool to stratify tumor aggressiveness in patients with PTC. Methods: In this prospective study, 28 patients with PTC underwent DW-MRI studies on a three Tesla MR scanner prior to thyroidectomy. Due to image quality, 21 patients were finally suitable for further analysis. Apparent diffusion coefficients (ADCs) of normal thyroid tissues and PTCs for 21 patients were calculated. Tumor aggressiveness was defined by surgical histopathology. The Mann-Whitney U test was used to compare the difference in ADCs among groups of normal thyroid tissues and PTCs with and without features of tumor aggressiveness. Receiver operating characteristic (ROC) analysis was performed to assess the discriminative specificity, sensitivity, and accuracy of and determine the cutoff value for the ADC in stratifying PTCs with tumor aggressiveness. Results: There was no significant difference in ADC values between normal thyroid tissues and PTCs. However, ADC values of PTCs with extrathyroidal extension (ETE; 1.53±0.25×10–3 mm2/s) were significantly lower than corresponding values from PTCs without ETE (2.37±0.67×10–3 mm2/s; p<0.005). ADC values identified 3 papillary carcinoma patients with extrathyroidal extension that would have otherwise been candidates for observation based on ultrasound evaluations. The cutoff value of ADC to discriminate PTCs with and without ETE was determined at 1.85×10–3 mm2/s with a sensitivity of 85%, specificity of 85%, and ROC curve area of 0.85. Conclusion: ADC value derived from DW-MRI before surgery has the potential to stratify ETE in patients with PTCs. PMID:25809949

  13. Comparison of two- and three-dimensional sonography for the prediction of the extrathyroidal extension of papillary thyroid carcinomas

    PubMed Central

    Yi, Yang Seon; Kim, Sang Soo; Kim, Won Jin; Bae, Min Jung; Kang, Ji Hyun; Choi, Bo Gwang; Jeon, Yun Kyung; Kim, Bo Hyun; Lee, Byung Joo; Wang, Soo Geun; Kim, In Joo; Kim, Yong Ki

    2016-01-01

    Background/Aims: The purpose of this study was to compare the diagnostic validity of two-dimensional (2D) and three-dimensional (3D) ultrasonography (US) when predicting the extrathyroidal extension of papillary thyroid cancer. Methods: All 2D data were interpreted in real time and 3D data were stored, rendered using tomographic ultrasound imaging (TUI), and then reviewed retrospectively. Results: Extrathyroidal extension was present in 17 papillary thyroid cancers(24.3%) on pathology reports. The presence of contact was significantly associated with extrathyroidal extension on both 2D and 3D US (p = 0.007 and p = 0.003), and the sensitivity and specificity were not significantly different between 2D and 3D US (p = 1.000 and p = 0.754). The coexistence of protrusion and contact was not significantly associated with extrathyroidal extension on either 2D or 3D sonogram. Conclusions: Three-dimensional images rendered with TUI algorithms alone do not seem to be markedly superior to real-time 2D US in predicting the extrathyroidal extension of papillary thyroid cancer. PMID:26701230

  14. Brain-Only Metastases Seen on FDG PET as First Relapse of Papillary Thyroid Carcinoma Two Years Post-Thyroidectomy.

    PubMed

    Naddaf, Sleiman Y; Syed, Ghulam Mustafa Shah; Hadb, Abdulrahman; Al-Thaqfi, Saif

    2016-09-01

    We report a case of a 60-year-old man diagnosed with papillary thyroid cancer who had a relapse seen only in the brain at FDG PET on standard images. Total thyroidectomy was performed in July 2013 after initial diagnosis. Patient received I ablation in December 2013, followed by external beam radiotherapy to the neck. In September 2015, the patient presented with neurological symptoms. Brain MRI showed multiple brain metastases later confirmed on histopathology. An FDG PET/CT scan was performed to evaluate the whole body in November 2015. Multiple hypermetabolic lesions were identified in the brain with no other lesion up to mid thighs. PMID:27405041

  15. The incidence of pelvic and para-aortic lymph node metastasis in uterine papillary serous and clear cell carcinoma according to the SEER registry

    PubMed Central

    Lee, Jennifer C.; Metzger, Daniel J.; Ashamalla, Hani; Katsoulakis, Evangelia

    2015-01-01

    Objective In this study we utilized the Surveillance, Epidemiology and End-Results (SEER) registry to identify risk factors for lymphatic spread and determine the incidence of pelvic and para-aortic lymph node metastases in patients with uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) who underwent complete surgical staging and lymph node dissection. Methods Nine hundred seventy-two eligible patients diagnosed between 1998 to 2009 with International Federation of Gynecology and Obstetrics (FIGO) 1988 stage IA-IVA UPSC (n=685) or UCCC (n=287) were identified for analysis. Binomial logistic regression was used to determine risk factors for lymph node metastasis, with the incidence of pelvic and para-aortic lymph node metastases reported for each FIGO primary tumor stage. The Cox proportional hazards regression model was used to determine factors associated with overall survival. Results FIGO primary tumor stage was the only independent risk factor for lymph node metastasis (p<0.01). The incidence of pelvis-only and para-aortic lymph node involvement according to the FIGO primary tumor stage were as follows: IA (2.3%/3.8%), IB (7.5%/5.2%), IC (22.5%/16.9%), IIA (20.8%/13.2%), IIB (25.7%/14.9%), and III/IV (25.7%/24.3%). Prognostic factors for overall survival included lymph node involvement (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.09 to 1.85; p<0.01), patient age >60 years (HR, 1.70; 95% CI, 1.21 to 2.41; p<0.01), and advanced FIGO primary tumor stage (p<0.01). Tumor grade, histologic subtype, and patient race did not predict for either lymph node metastasis or overall survival. Conclusion There is a high incidence of both pelvic and para-aortic lymph node metastases for FIGO stages IC and above uterine papillary serous and clear cell carcinomas, suggesting a potential role for lymph node-directed therapy for these patients. PMID:25310855

  16. Testicular Metastasis of a Upper Urinary Tract High-grade Papillary Urothelial Carcinoma, 2 Years After Nephroureterectomy

    PubMed Central

    Kubiak, M.; Klein, J.; de Perrot, T.; Tille, J.C.; Iselin, C.E.

    2015-01-01

    Urothelial carcinomas are the fourth most common tumors in men. Upper tract urinary carcinomas (UTUCs) are uncommon and represent only 5–10% of urothelial carcinomas.1 Metastatic testicular cancers are rare and primary tumor sources are the prostate, lung, and gastrointestinal tract. We report the first case of testicular metastasis 2 years after initial curative surgery for a high-grade UTUC, all other reported cases weren't proceed by curative surgery.3 PMID:26793571

  17. Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation.

    PubMed

    Bartolome, Aleksandar; Boskovic, Srdjan; Paunovic, Ivan; Bozic, Vesna; Cvejic, Dubravka

    2016-04-01

    Stomatin-like protein 2 (SLP-2), a member of the stomatin protein family, has emerged as a potential molecular hallmark of tumor progression in several human malignancies. The aim of this study was to analyze SLP-2 expression pattern in benign and malignant thyroid tumors (n = 210) and to examine its relationship with clinicopathological parameters and BRAFV600E mutation in thyroid cancer. SLP-2 immunohistochemical expression was not detected in benign adenomas and was absent/weak in follicular and anaplastic carcinomas. High expression levels of SLP-2, found only in papillary thyroid carcinoma (PTC), particularly in the classical variant, were significantly associated with adverse clinicopathological parameters: lymph node metastasis (p = 0.002), extrathyroid invasion (p < 0.001), pT status (p < 0.001), and advanced tumor stage (p = 0.001). Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases. The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated PTC and that SLP-2 evaluation could be clinically useful in identification of high-risk PTC patients. PMID:26750533

  18. Papillary thyroid carcinoma with extensive squamous dedifferentiation metastatic to the lung: BRAF mutational analysis as a useful tool to rule out tumor to tumor metastasis.

    PubMed

    Acosta, Andres M; Pins, Michael R

    2016-02-01

    Tumors containing elements of both papillary thyroid carcinoma (PTC) and squamous cell carcinoma (SCC) are rare but well documented. When they present initially as metastatic disease in an organ that can harbor a primary SCC, the possibility of a tumor to tumor metastasis (TTM) must be considered. The aim of this case study is to illustrate how BRAF mutational analysis can be used to help differentiate between these two diagnoses. We report a 63-year-old male with a longstanding history of PTC metastatic to the brain and lymph nodes who presented to our institution with a right lower lobe lung mass after a 2-year recurrence-free interval. Histopathologic and immunohistochemical analysis revealed a composite neoplasm with distinct elements of both PTC and SCC. We performed BRAF (V600E) (c.1799 T > A) mutational analysis to help elucidate the origin of each component. This is the first time that BRAF sequencing has been used to discriminate between dedifferentiated PTC and TTM, to the best of our knowledge. In the context of metastatic PTC with SCC dedifferentiation, the presence of the identical BRAF (V600E) (c.1799 T > A) mutation in both components might help rule out tumor to tumor metastasis. PMID:26521063

  19. Wnt/β-Catenin Signaling Pathway Is a Direct Enhancer of Thyroid Transcription Factor-1 in Human Papillary Thyroid Carcinoma Cells

    PubMed Central

    Gilbert-Sirieix, Marie; Makoukji, Joelle; Kimura, Shioko; Talbot, Monique; Caillou, Bernard; Massaad, Charbel; Massaad-Massade, Liliane

    2011-01-01

    The Wnt/β-catenin signaling pathway is involved in the normal development of thyroid gland, but its disregulation provokes the appearance of several types of cancers, including papillary thyroid carcinomas (PTC) which are the most common thyroid tumours. The follow-up of PTC patients is based on the monitoring of serum thyroglobulin levels which is regulated by the thyroid transcription factor 1 (TTF-1): a tissue-specific transcription factor essential for the differentiation of the thyroid. We investigated whether the Wnt/β-catenin pathway might regulate TTF-1 expression in a human PTC model and examined the molecular mechanisms underlying this regulation. Immunofluorescence analysis, real time RT-PCR and Western blot studies revealed that TTF-1 as well as the major Wnt pathway components are co-expressed in TPC-1 cells and human PTC tumours. Knocking-down the Wnt/β-catenin components by siRNAs inhibited both TTF-1 transcript and protein expression, while mimicking the activation of Wnt signaling by lithium chloride induced TTF-1 gene and protein expression. Functional promoter studies and ChIP analysis showed that the Wnt/β-catenin pathway exerts its effect by means of the binding of β-catenin to TCF/LEF transcription factors on the level of an active TCF/LEF response element at [−798, −792 bp] in TTF-1 promoter. In conclusion, we demonstrated that the Wnt/β-catenin pathway is a direct and forward driver of the TTF-1 expression. The localization of TCF-4 and TTF-1 in the same area of PTC tissues might be of clinical relevance, and justifies further examination of these factors in the papillary thyroid cancers follow-up. PMID:21814573

  20. Clear cell papillary renal cell carcinoma in patients with von Hippel-Lindau syndrome--clinicopathological features and comparative genomic analysis of 3 cases.

    PubMed

    Rao, Priya; Monzon, Federico; Jonasch, Eric; Matin, Surena F; Tamboli, Pheroze

    2014-09-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a renal neoplasm that has recently received widespread recognition in the literature. There have been several reports of this tumor arising in a sporadic setting and in patients with end-stage renal disease; however, there is limited information available about the clinical, pathologic, and genetic characteristics of this tumor in the setting of von Hippel-Lindau (VHL) disease. We herein report a series of 3 patients who developed CCPRCC in this unique clinical setting. The histology and immunohistochemical profile for all 3 cases was similar to that which has been previously reported for CCPRCC. All tumors were diffusely and strongly positive for cytokeratin 7, negative for α-methyl-CoA-racemase, and showed at least focal staining for CD10. Comparative genomic analysis was performed on tumors from all 3 patients. One tumor demonstrated monosomy 3, and the other 2 tumors showed normal chromosomal content. All 3 patients were alive without evidence of disease progression 5, 3, and 3 years after surgery. CCPRCC represents a distinct tumor type that may occur in the setting of VHL disease and should be considered in the differential diagnosis of extensively cystic renal tumors arising in this clinical setting. Molecular analysis in our series of cases suggests that CCPRCC does indeed represent a unique histologic subtype and must be distinguished from clear cell renal cell carcinoma due to different biological potentials. Ancillary studies for accurate classification are recommended due to significant morphologic overlap with clear cell renal cell carcinoma. PMID:25081542

  1. Decreased expression of mucin 18 is associated with unfavorable postoperative prognosis in patients with clear cell renal cell carcinoma

    PubMed Central

    Bai, Qi; Liu, Li; Long, Qilai; Xia, Yu; Wang, Jiajun; Xu, Jiejie; Guo, Jianming

    2015-01-01

    Background: MUC18 is correlated with tumor progression and metastasis in types of malignancy. But the role of MUC18 in clear cell renal cell carcinoma remains unclear. In this study, we aimed to investigate the expression of MUC18 and its correlation with clinical outcomes in clear cell renal cell carcinoma. Patients and Methods: Immunohistochemical staining was performed in samples from 288 patients with clear cell renal cell carcinoma. We used Kaplan-Meier method and Cox proportional hazard models to value the association between MUC18 expression and clinical outcome. Nomogram was constructed to predict overall survival at 5 and 8 years after nephrectomy. Results: MUC18 expression was significantly decreased in tumor compared to non-tumor tissue (P<0.001). Lower MUC18 expression in tumor predicted a shorter survival time (P=0.007). By multivariate cox analysis, MUC18 was defined as an independent prognostic factor (P=0.006). The nomogram performed better in predicting 5- and 8-year overall survival than the TNM stage alone in clear cell renal cell carcinoma. Conclusion: MUC18 is an independent prognostic factor for clear cell renal cell carcinoma and could be incorporated with the other parameters to predict 5- and 8-year overall survival for clear cell renal cell carcinoma patients. PMID:26617818

  2. Transforming Growth Factor β1 Could Influence Thyroid Nodule Elasticity and Also Improve Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma.

    PubMed

    Li, Yi; Wang, Yan; Wu, Qiong; Hu, Bing

    2015-11-01

    Ultrasound elastography has been a very useful tool in predicting the risk of malignant thyroid tumor for several years. The objective of this study was to determine if there is a correlation between strain ratio (SR), collagen deposition and transforming growth factor β1 (TGF-β1) expression in different types of thyroid nodules and if TGF-β1 is related to cervical lymph node metastasis. 102 nodules from 81 patients who underwent thyroid resection surgery in our hospital were retrospectively studied. All of these patients had undergone ultrasound elastography scanning before surgery. Masson staining and immunohistochemical staining were used to evaluate the ratio of expression of collagen deposition and TGF-β1. There was a significant difference between benign and malignant thyroid nodules in SR (8.913 ± 11.021 vs. 1.732 ± 0.727, p = 0.000), collagen content (0.371 ± 0.125 vs. 0.208 ± 0.057, p = 0.000) and TGF-β1 expression (0.336 ± 0.093 vs. 0.178 ± 0.071, p = 0.000). A cutoff of 2.99 for SR measurement was selected for the highest Youden index for predicting malignant thyroid nodules, which yielded 87.88% sensitivity, 100% specificity, 100% positive predictive value, 83.72% negative predictive value and 92.15% accuracy. Expression of collagen and TGF-β1 was positively correlated with SR measurements (coefficient = 0.839 for collagen and 0.855 for TGF-β1, p = 0.000). Among 61 nodules with papillary thyroid carcinoma, the average SR for the metastasis group was higher than that for the non-metastasis group (10.955 ± 13.805 and 7.852 ± 7.931, respectively), but without statistical significance (p = 0.287). Collagen deposition was significantly higher in the metastasis group than in the non-metastasis group (0.421 ± 0.091 vs. 0.353 ± 0.118, p = 0.011). TGF-β1 expression was also significantly higher in the metastasis group than in the non-metastasis group (0.378 ± 0.0.69 vs. 0.328 ± 0.091, p = 0.016). To conclude, TGF-β1 may contribute to thyroid

  3. MiR-34a targets GAS1 to promote cell proliferation and inhibit apoptosis in papillary thyroid carcinoma via PI3K/Akt/Bad pathway

    SciTech Connect

    Ma, Yanfei; Qin, Huadong; Cui, Yunfu

    2013-11-29

    Highlights: •MiR-34a is up- and GAS1 is down-regulated in papillary thyroid carcinoma. •GAS1 is a direct target for miR-34a. •MiR-34a promotes PTC cells proliferation and inhibits apoptosis through PI3K/Akt/Bad pathway. -- Abstract: MicroRNAs (miRNAs) are fundamental regulators of cell proliferation, differentiation, and apoptosis, and are implicated in tumorigenesis of many cancers. MiR-34a is best known as a tumor suppressor through repression of growth factors and oncogenes. Growth arrest specific1 (GAS1) protein is a tumor suppressor that inhibits cancer cell proliferation and induces apoptosis through inhibition of RET receptor tyrosine kinase. Both miR-34a and GAS1 are frequently down-regulated in various tumors. However, it has been reported that while GAS1 is down-regulated in papillary thyroid carcinoma (PTC), miR-34a is up-regulated in this specific type of cancer, although their potential roles in PTC tumorigenesis have not been examined to date. A computational search revealed that miR-34a putatively binds to the 3′-UTR of GAS1 gene. In the present study, we confirmed previous findings that miR-34a is up-regulated and GAS1 down-regulated in PTC tissues. Further studies indicated that GAS1 is directly targeted by miR-34a. Overexpression of miR-34a promoted PTC cell proliferation and colony formation and inhibited apoptosis, whereas knockdown of miR-34a showed the opposite effects. Silencing of GAS1 had similar growth-promoting effects as overexpression of miR-34a. Furthermore, miR-34a overexpression led to activation of PI3K/Akt/Bad signaling pathway in PTC cells, and depletion of Akt reversed the pro-growth, anti-apoptotic effects of miR-34a. Taken together, our results demonstrate that miR-34a regulates GAS1 expression to promote proliferation and suppress apoptosis in PTC cells via PI3K/Akt/Bad pathway. MiR-34a functions as an oncogene in PTC.

  4. The correlation of sodium iodide symporter and BRAF(V600E) mutation in classical variant papillary thyroid carcinoma.

    PubMed

    Yazgan, Aylin; Yıldırım, Nilüfer; Gözalan, Ayşegül; Gümüştaş, Sinem; Kılıçarslan, Aydan; Balci, Serdar; Aydın, Cevdet; Ersoy, Reyhan; Cakir, Bekir; Güler, Gülnur

    2016-06-01

    BRAF(V600E) mutation was analyzed by real-time polymerase chain reaction in 96 consecutive cases with classical variant papillary thyroid cancer, and immunohistochemical staining of Na+/I- symporter (NIS) protein was evaluated. Localization (intracellular or membranous), density, and the intensity of cytoplasmic staining were characterized semiquantitatively. Extrathyroidal invasion, surgical margin positivity, and lymph node metastasis were compared with BRAF(V600E) mutation and NIS expression. Eighty-eight patients who had at least 24-month follow-up were also included in survival analysis. BRAF(V600E) mutation was determined in 78.1% (75/96) and functional NIS activity in 74% (71/96) of the cases. There were statistically significant differences in mean ages between BRAF(V600E) mutation-positive (48.6) and BRAF(V600E) mutation-negative cases (37.3; Levene test, P=.419; Student t test, P=.001). The surgical margin positivity (46.7%) and extrathyroidal extension percentage (54.7%) in the BRAF(V600E) mutation-positive group were higher than the negative (28.6% and 33.3%, respectively) group, without statistical significance (P=.138 and P=.084, respectively). Functional NIS activity was higher in BRAF(V600E) mutation-positive cases (78.1%) than mutation-negative ones (57.1%; P=.047). The possibility of moderate and intense cytoplasmic staining in BRAF(V600E) mutation-positive cases (72%) was 6.3 times higher than the possibility of weak staining (28%) in the mutation-positive cases (95% confidence interval, 2.2-18.8; P=.001). Functional NIS expression is higher in patients with classical variant papillary thyroid cancer with BRAF(V600E) mutation. However, the clinical features were not found to be associated with NIS expression. There may be different mechanisms determining the outcome of therapy. PMID:27180062

  5. Increasing expression of gastrointestinal phenotypes and p53 along with histologic progression of intraductal papillary neoplasia of the liver.

    PubMed

    Shimonishi, Tomonori; Zen, Yoh; Chen, Tse-Ching; Chen, Miin-Fu; Jan, Yi-Yin; Yeh, Ta-Sen; Nimura, Yuji; Nakanuma, Yasuni

    2002-05-01

    Intraductal papillary neoplasia of the liver (IPN-L) was recently proposed as the name for intraductal papillary proliferation of neoplastic biliary epithelium with a fine fibrovascular stalk resembling intraductal papillary mucinous neoplasm of the pancreas. We histochemically and immunohistochemically examined IPN-L alone or associated with hepatolithiasis, with an emphasis on the gastrointestinal metaplasia, nuclear p53 expression, and histologic progression. A total of 66 cases of IPN-L were divided into 4 groups: group 1, IPN-L with low-grade dysplasia (13 cases); group 2, IPN-L with high-grade dysplasia (20 cases); group 3, IPN-L lined with carcinoma in situ and no or microinvasion (19 cases); and group 4, group 3 with distinct invasive carcinoma (14 cases). It is suggested that IPN-L progresses from group 1 to group 4. As controls, 20 cases of nonneoplastic intrahepatic large bile ducts and 17 cases of nonpapillary invasive intrahepatic cholangiocarcinoma (ICC) were used. Biliary epithelial hypersecretion of sialomucin rather than sulfomucin was prevalent in IPN-L, and this was associated with the progression of INP-L. Immunohistochemically, cytokeratin (CK) 20 and MUC2, a gastrointestinal marker, were expressed more frequently in IPN-L than in nonneoplastic bile ducts and nonpapillary ICC (P <0.01), and their incidence were significantly increased in parallel with the progression of IPN-L (P < 0.01). In contrast, expression of CK 7, a biliary marker, was decreased in IPN-L compared with nonpapillary ICC. Nuclear p53 immunostaining was detected in 30% of IPN-L as a whole and increased in tandem with the progression of IPN-L (P < 0.01). It is suggested that IPN-L forms a spectrum of biliary epithelial neoplasia with frequent gastrointestinal metaplasia, different from the usual nonpapillary ICC, and shows stepwise progression from the perspective of mucin profile, gastrointestinal metaplasia, and p53 nuclear expression. PMID:12094375

  6. Mucin1 promotes the migration and invasion of hepatocellular carcinoma cells via JNK-mediated phosphorylation of Smad2 at the C-terminal and linker regions

    PubMed Central

    Wang, Juan; Liu, Guomu; Li, Qiongshu; Wang, Fang; Xie, Fei; Zhai, Ruiping; Guo, Yingying; Chen, Tanxiu; Zhang, Nannan; Ni, Weihua; Yuan, Hongyan; Tai, Guixiang

    2015-01-01

    Mucin1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas. In this study, wound-healing, transwell migration and matrigel invasion assays showed that MUC1 promotes human hepatocellular carcinoma (HCC) cell migration and invasion by MUC1 gene silencing and overexpressing. Treatment with exogenous transforming growth factor beta (TGF-β)1, TGF-β type I receptor (TβRI) inhibitor, TGF-β1 siRNAs, or activator protein 1 (AP-1) inhibitor to MUC1-overexpressing HCC cells revealed that MUC1-induced autocrine TGF-β via JNK/AP-1 pathway promotes the cell migration and invasion. In addition, the migration and invasion of HCC cells were more significantly inhibited by JNK inhibitor compared with that by TβRI inhibitor or TGF-β1 siRNAs. Further studies demonstrated that MUC1-mediated JNK activation not only enhances the phosphorylation of Smad2 C-terminal at Ser-465/467 site (Smad2C) through TGF-β/TβRI, but also directly enhances the phosphorylation of Smad2 linker region at Ser-245/250/255 site (Smad2L), and then both of them collaborate to upregulate matrix metalloproteinase (MMP)-9-mediated cell migration and invasion of HCC. These results indicate that MUC1 is an attractive target in liver cancer therapy. PMID:26057631

  7. The human epithelial carcinoma antigen recognized by monoclonal antibody AE3 is expressed on a sulfoglycolipid in addition to neoplastic mucins

    PubMed Central

    Palma, Angelina S.; Liu, Yan; Childs, Robert A.; Herbert, Colin; Wang, Denong; Chai, Wengang; Feizi, Ten

    2011-01-01

    The term human epithelial carcinoma antigen (HCA) has been applied collectively to mucin-type high molecular weight (>1000 kDa) glycoproteins that are over-expressed in epithelial cancers. Since the 1990s, over 40 monoclonal antibodies have been raised that recognize HCA. There has been evidence that the antigenic determinants are mostly carbohydrates, but details have been elusive. Here we have carried out carbohydrate microarray in analyses of one of the monoclonal antibodies, AE3, that has been regarded the ‘most carcinoma specific’ in respect to its ability to detect HCA in sera of patients with epithelial cancers. The microarrays encompassed a series of 492 sequence-defined glycan probes in the form of glycolipids and neoglycolipids. We have thus established that the antigen recognized by antibody AE3 is a carbohydrate sequence distinct from the A, B, H, Lewisa/b, Lewisx/y and T antigens, but that it is strongly expressed on the monosulfated tetra-glycosyl ceramide, SM1a, Galβ1-3GalNAcβ1-4(3-O-sulfate)Galβ1-4GlcCer. This is the first report of an anti-HCA to be characterized with respect to its recognition sequence and of the occurrence of the antigen on a glycolipid as well as on glycoproteins. Knowledge of a discrete glycan sequence as target antigen now opens the way to its exploration as a serologic cancer biomarker, namely to determine if the antigen elicits an autoantibody response in early non-metastatic cancer, or if it is shed and immunochemically detectable in more advanced disease. PMID:21527252

  8. Intracholecystic papillary-tubular neoplasms (ICPN) of the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are ≥1.0 cm): clinicopathologic and immunohistochemical analysis of 123 cases.

    PubMed

    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. PMID:22895264

  9. The diagnostic utility of the triple markers Napsin A, TTF-1, and PAX8 in differentiating between primary and metastatic lung carcinomas.

    PubMed

    El-Maqsoud, Nehad M R Abd; Tawfiek, Ehab Rifat; Abdelmeged, Ayman; Rahman, Mohamed Fathy Abdel; Moustafa, Alaa A E

    2016-03-01

    Napsin A and thyroid transcription factor-1 (TTF-1) are useful biomarkers for differentiating lung adenocarcinoma from squamous cell carcinoma and also for differentiating primary lung adenocarcinoma from metastatic lung carcinoma. Pair-boxed 8 (PAX8) can help in distinguishing primary lung carcinoma from metastatic carcinomas and help to determine the primary sites of metastatic carcinomas. Immunohistochemistry for Napsin A, TTF-1, and PAX8 were performed on 193 cases of carcinoma: 50 primary lung carcinoma and 143 carcinomas from other sites. Napsin A and TTF-1 were positive in 54, 52 % of lung carcinomas cases, respectively. While in adenocarcinoma cases, their expressions were 86.7 and 83.3 %, respectively. PAX8 was negative in all lung carcinomas. TTF-1 and PAX8 were positive in 93.3 and 96.7 % of thyroid carcinoma cases and in 87.5 and 93.8 % of papillary carcinoma respectively, and both were positive in 100 % of follicular carcinoma. Napsin A was negative in all thyroid carcinomas. Napsin A and PAX8 were positive in 50 and 93.3 % of renal carcinoma cases and in 81.8 and 100 % of papillary carcinoma, 38.5 and 92.3 % of clear cell carcinoma, and 16.7 and 83.3 % of chromophobe carcinoma respectively. TTF-1 was negative in all renal carcinomas. PAX8 was positive in 80 % of ovarian carcinoma cases; 100 and 60 % of serous mucinous carcinomas, respectively. It was also positive in 100 % of endometrial carcinoma. Napsin A and TTF-1 were negative in both ovarian and endometrial carcinomas. Our data demonstrated that combined use of Napsin A, TTF-1, and PAX8 may help in differentiating between primary lung adenocarcinoma and metastatic lung carcinomas. PMID:26427663

  10. Type 1 papillary renal cell carcinoma in a patient with schwannomatosis: Mosaic versus loss of SMARCB1 expression in respectively schwannoma and renal tumor cells.

    PubMed

    Hulsebos, Theo J M; Kenter, Susan; Baas, Frank; Nannenberg, Eline A; Bleeker, Fonnet E; van Minkelen, Rick; van den Ouweland, Ans M W; Wesseling, Pieter; Flucke, Uta

    2016-04-01

    In schwannomatosis, germline SMARCB1 or LZTR1 mutations predispose to the development of multiple benign schwannomas. Besides these, other tumors may occur in schwannomatosis patients. We present a 45-year-old male patient who developed multiple schwannomas and in addition a malignant type 1 papillary renal cell carcinoma (pRCC1). We identified a duplication of exon 7 of SMARCB1 on chromosome 22 in the constitutional DNA of the patient (c.796-2246_986 + 5250dup7686), resulting in the generation of a premature stop codon in the second exon 7 copy (p.Glu330*). The mutant SMARCB1 allele proved to be retained in three schwannomas and in the pRCC1 of the patient. Loss of heterozygosity analysis demonstrated partial loss of the wild-type SMARCB1 allele containing chromosome 22, suggesting loss of that chromosome in only a subset of tumor cells, in all four tumors. Immunohistochemical staining with a SMARCB1 antibody revealed a mosaic SMARCB1 expression pattern in the three benign schwannomas, but absence of expression in the malignant tumor cells of the pRCC1. To our knowledge, this difference in SMARCB1 protein expression has not been reported before. We conclude that a germline SMARCB1 mutation may predispose to the development of pRCC1, thereby further widening the spectrum of tumors that can develop in the context of schwannomatosis. PMID:26799435

  11. First-Line Use of Vemurafenib to Enable Thyroidectomy and Radioactive Iodine Ablation for BRAF-Positive Metastatic Papillary Thyroid Carcinoma

    PubMed Central

    Lingvay, Ildiko; Sailors, Joseph; Landay, Michael; Shapiro, Gabriel

    2015-01-01

    Background. Patients with metastatic or radioactive iodine refractory papillary thyroid carcinoma (PTC) have poor prognosis due to ineffective therapy for this condition beyond surgery and radioactive iodine (RAI or 131I). BRAF mutation occurs in more than 44% of PCT. Tyrosine kinase inhibitors, the most commonly used agents for these patients, have weak BRAF inhibition activity. BRAF inhibitors have demonstrated promising efficacy in relapsed metastatic PCT after standard treatment, though they are not currently approved for this indication. Case Presentation. We present the case of a 48-year-old Hispanic male who initially presented with columnar-cell variant subtype of PTC and positive BRAFV600E mutation. The patient had widespread bulky metastases to lungs, chest wall, brain, and bone. Discussion. Initial use of vemurafenib demonstrated a 42% cytoreduction of targeted pulmonary metastases and facilitated thyroidectomy and RAI treatment. The patient achieved a durable response over 21 months in the setting of widely metastatic disease. Conclusion. Vemurafenib may be effectively used for cytoreduction in patients with bulky metastatic PTC to bridge them to thyroidectomy and RAI treatment. PMID:26904701

  12. [Treatment with (131)I of thyroid remnants in a patient with papillary thyroid carcinoma and end-stage chronic renal failure].

    PubMed

    Andres, A; Tardín, L; Santapau, A; Razola, P; Prats, E; Parra, A; Rivas, M A; Ruiz, P; Alvarez, R; Camara, A; Banzo, J

    2010-01-01

    The follow-up and treatment of thyroid cancer presents several aspects subject to discussion, such as its management in patients with End-Stage Renal Failure (ESRF). We present a patient with ESRF and papillary thyroid carcinoma, which had to be coordinated among different departments (Endocrinology, Nuclear Medicine, Nephrology and Physics and Radiation Protection). Both the diagnostic scintigraphy with (123)I and the ablative treatment with (131)I performed later were performed with the administration of rh TSH. The room in which the metabolic therapy was to be performed was prepared for the patient's periodic hemodialysis. The (131)I dose used was 80% of the usual dose. This made it possible to assure the therapeutic effect and that the patient's stay in hospital would only be for 5 days. Throughout the whole diagnostic and therapeutic process, no adverse effects attributable to rh TSH or radioiodine were observed. The coordination among the departments involved enabled an effective and safe process for the patient. PMID:20018412

  13. BRAFV600E status and clinical characteristics in solitary and multiple papillary thyroid carcinoma: experience of 512 cases at a clinical center in China

    PubMed Central

    2012-01-01

    Background Papillary thyroid carcinoma (PTC) is one of the most frequent endocrine malignancies. In most cases, it often presents as multifocal tumor. It has been reported that multifocal tumors are associated with elevated risk of lymph node and distant metastases. Multifocality is also one of the factors predicting prognosis. Recent studies show that BRAFV600E mutation occurs more frequently in aggressive PTC. The purpose of this study was to evaluate BRAFV600E status and clinicopathological features in multiple and solitary PTC. Methods We performed a retrospective study to analyze 512 PTC cases who received surgery, including 376 solitary PTCs and 136 multiple PTCs. Results Multiple PTC is more related to lymph node metastasis and vascular invasion than solitary PTC. However, the distant metastasis rate and 10-year survival rate showed no difference between these two groups. BRAFV600E mutation status was more frequent in multiple PTC patients with lymph node metastasis and late stage at diagnosis. Conclusion BRAFV600E mutation is most commonly associated with extra-thyroidal extension and lymph node metastasis in PTC. Multiple PTC patients with young age, large tumors and BRAFV600E mutation should be followed carefully. Our study provides useful information for PTC patients’ followup and treatment. PMID:22681706

  14. Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201).

    PubMed

    El-Sahwi, Karim; Bellone, Stefania; Cocco, Emiliano; Casagrande, Francesca; Bellone, Marta; Abu-Khalaf, Maysa; Buza, Natalia; Tavassoli, Fattaneh A; Hui, Pei; Rüttinger, Dominik; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Pecorelli, Sergio; Santin, Alessandro D

    2010-01-01

    We evaluated the expression of epithelial cell adhesion molecule (EpCAM) and the potential of MT201 (adecatumumab), a human monoclonal antibody against EpCAM, in uterine serous papillary carcinoma (USPC). EpCAM expression was evaluated by real-time PCR and immunohistochemistry in a total of 56 USPC fresh-frozen biopsies and paraffin-embedded tissues. EpCAM surface expression was also evaluated by flow cytometry and immunohistochemistry in six USPC cell lines. Sensitivity to MT201 antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity was tested against a panel of primary USPC cell lines expressing different levels of EpCAM in standard 5-h (51)Cr release assays. EpCAM transcript was significantly overexpressed in fresh-frozen USPC when compared with normal endometrial cells (NEC). Median (minimum-maximum) copy number was 943.8 (31.5-1568.3) in tumor samples versus 12.9 (1.0-37.0) in NEC (P < 0.001). By immunohistochemistry, EpCAM expression was found in 96% (26 out of 27) of USPC samples with significantly higher expression compared with NECs (P < 0.001). High surface expression of EpCAM was found in 83% (five out of six) of the USPC cell lines tested by flow cytometry. EpCAM-positive cell lines were found highly sensitive to MT201-mediated antibody-dependent cellular cytotoxicity in vitro, whereas primary USPC cell lines were resistant to natural killer cell-dependent cytotoxicity. Human plasma IgG did not significantly inhibit MT201-mediated cytotoxicity against USPC. EpCAM is highly expressed in uterine serous carcinoma at mRNA and protein levels, and primary USPC are highly sensitivity to MT201-mediated cytotoxicity. MT201 might represent a novel therapeutic strategy in patients harboring advanced/recurrent or metastatic USPC refractory to standard treatment modalities. PMID:20053761

  15. Invasion rather than nuclear features correlates with outcome in encapsulated follicular tumors: further evidence for the reclassification of the encapsulated papillary thyroid carcinoma follicular variant.

    PubMed

    Ganly, Ian; Wang, Laura; Tuttle, R Michael; Katabi, Nora; Ceballos, Gustavo A; Harach, H Ruben; Ghossein, Ronald

    2015-05-01

    The prognosis of the encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) and its relationship to encapsulated follicular carcinoma (EFC) and follicular adenoma (FA) is subject to controversy. All EFVPTCs, EFCs, and FAs identified at a single institution between 1981 and 2003 were analyzed microscopically. A cohort of FAs from a different hospital was also examined. EFVPTCs were subdivided into noninvasive EFVPTC (NIEFVPTC) and invasive EFVPTC (IEFVPTC) displaying capsular/vascular invasion. There were 83 EFVPTCs (57 noninvasive, 26 invasive), 14 EFCs, and 52 FAs. Similar to FA, over a median follow-up of 9.5 years, none of the NIEFVPTCs manifested lymph node metastasis (LNM) or recurred. Furthermore, with a median follow-up of 10.5 years, none of 39 NIEFVPTCs without radioactive iodine therapy recurred. Four (15%) of 26 IEFVPTCs and none of 14 EFCs harbored distant metastasis (P = .29). There was no difference in LNM rate and degree of vascular or capsular invasion between IEFVPTC and EFC (P > .1). All 4 IEFVPTCs with adverse behavior presented with distant metastasis and no LNM. Sixteen percent of IEFVPTCs had poor outcome, whereas there was none in the NIEFVPTCs (P = .007). In conclusion, NIEFVPTC seems to behave similarly to FA, whereas IEFVPTC can metastasize and spread like EFC. Thus, invasion rather than nuclear features drives outcome in encapsulated follicular tumors. Non-IEFVPTC could be treated in a conservative manner sparing patients unnecessary total thyroidectomy and radioactive iodine therapy. The position of the EFVPTC in the classification of thyroid neoplasia should be reconsidered. PMID:25721865

  16. Invasion rather than nuclear features correlates with outcome in encapsulated follicular tumors: further evidence for the reclassification of the encapsulated papillary thyroid carcinoma follicular variant☆

    PubMed Central

    Ganly, Ian; Wang, Laura; Tuttle, R. Michael; Katabi, Nora; Ceballos, Gustavo A.; Harach, H. Ruben; Ghossein, Ronald

    2016-01-01

    Summary The prognosis of the encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) and its relationship to encapsulated follicular carcinoma (EFC) and follicular adenoma (FA) is subject to controversy. All EFVPTCs, EFCs, and FAs identified at a single institution between 1981 and 2003 were analyzed microscopically. A cohort of FAs from a different hospital was also examined. EFVPTCs were subdivided into noninvasive EFVPTC (NIEFVPTC) and invasive EFVPTC (IEFVPTC) displaying capsular/vascular invasion. There were 83 EFVPTCs (57 noninvasive, 26 invasive), 14 EFCs, and 52 FAs. Similar to FA, over a median follow-up of 9.5 years, none of the NIEFVPTCs manifested lymph node metastasis (LNM) or recurred. Furthermore, with a median follow-up of 10.5 years, none of 39 NIEFVPTCs without radioactive iodine therapy recurred. Four (15%) of 26 IEFVPTCs and none of 14 EFCs harbored distant metastasis (P = .29). There was no difference in LNM rate and degree of vascular or capsular invasion between IEFVPTC and EFC (P > .1). All 4 IEFVPTCs with adverse behavior presented with distant metastasis and no LNM. Sixteen percent of IEFVPTCs had poor outcome, whereas there was none in the NIEFVPTCs (P = .007). In conclusion, NIEFVPTC seems to behave similarly to FA, whereas IEFVPTC can metastasize and spread like EFC. Thus, invasion rather than nuclear features drives outcome in encapsulated follicular tumors. Non-IEFVPTC could be treated in a conservative manner sparing patients unnecessary total thyroidectomy and radioactive iodine therapy. The position of the EFVPTC in the classification of thyroid neoplasia should be reconsidered. PMID:25721865

  17. BRAFV600E-Associated Gene Expression Profile: Early Changes in the Transcriptome, Based on a Transgenic Mouse Model of Papillary Thyroid Carcinoma

    PubMed Central

    Rusinek, Dagmara; Swierniak, Michal; Chmielik, Ewa; Kowal, Monika; Kowalska, Malgorzata; Cyplinska, Renata; Czarniecka, Agnieszka; Piglowski, Wojciech; Korfanty, Joanna; Chekan, Mykola; Krajewska, Jolanta; Szpak-Ulczok, Sylwia; Jarzab, Michal; Widlak, Wieslawa; Jarzab, Barbara

    2015-01-01

    Background The molecular mechanisms driving the papillary thyroid carcinoma (PTC) are still poorly understood. The most frequent genetic alteration in PTC is the BRAFV600E mutation–its impact may extend even beyond PTC genomic profile and influence the tumor characteristics and even clinical behavior. Methods In order to identify BRAF-dependent signature of early carcinogenesis in PTC, a transgenic mouse model with BRAFV600E-induced PTC was developed. Mice thyroid samples were used in microarray analysis and the data were referred to a human thyroid dataset. Results Most of BRAF(+) mice developed malignant lesions. Nevertheless, 16% of BRAF(+) mice displayed only benign hyperplastic lesions or apparently asymptomatic thyroids. After comparison of non-malignant BRAF(+) thyroids to BRAF(−) ones, we selected 862 significantly deregulated genes. When the mouse BRAF-dependent signature was transposed to the human HG-U133A microarray, we identified 532 genes, potentially indicating the BRAF signature (representing early changes, not related to developed malignant tumor). Comparing BRAF(+) PTCs to healthy human thyroids, PTCs without BRAF and RET alterations and RET(+), RAS(+) PTCs, 18 of these 532 genes displayed significantly deregulated expression in all subgroups. All 18 genes, among them 7 novel and previously not reported, were validated as BRAFV600E-specific in the dataset of independent PTC samples, made available by The Cancer Genome Atlas Project. Conclusion The study identified 7 BRAF-induced genes that are specific for BRAF V600E-driven PTC and not previously reported as related to BRAF mutation or thyroid carcinoma: MMD, ITPR3, AACS, LAD1, PVRL3, ALDH3B1, and RASA1. The full signature of BRAF-related 532 genes may encompass other BRAF-related important transcripts and require further study. PMID:26625260

  18. Overexpression of EpCAM in Uterine Serous Papillary Carcinoma: Implications for EpCAM-specific Immunotherapy with Human Monoclonal Antibody Adecatumumab (MT201)

    PubMed Central

    El-Sahwi, Karim; Bellone, Stefania; Cocco, Emiliano; Casagrande, Francesca; Bellone, Marta; Abu-Khalaf, Maysa; Buza, Natalia; Tavassoli, Fattaneh A.; Hui, Pei; Rüttinger, Dominik; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.; Rutherford, Thomas J.; Pecorelli, Sergio; Santin, Alessandro D.

    2009-01-01

    We evaluated the expression of epithelial-cell-adhesion-molecule (EpCAM) and the potential of MT201 (adecatumumab), a human monoclonal antibody against EpCAM, in uterine serous papillary carcinoma (USPC). EpCAM expression was evaluated by real-time-PCR and immunohistochemistry (IHC) in a total of 56 USPC fresh-frozen biopsies and paraffin-embedded-tissues. EpCAM surface expression was also evaluated by flow cytometry and IHC in 6 USPC cell lines. Sensitivity to MT201 antibody-dependent-cellular-cytotoxicity (ADCC) and complement-dependent-cytotoxicity (CDC) was tested against a panel of primary USPC cell lines expressing different levels of EpCAM in standard 5-h 51Cr release-assays. EpCAM transcript was significantly overexpressed in fresh-frozen USPC when compared to normal-endometrial-cells (NEC). Median (minimum–maximum) copy number was 943.8 (31.5–1568.3) in tumor samples versus 12.9 (1.0–37.0) in NEC (P < 0.001). By immunohistochemistry, EpCAM expression was found in 96% (26 out of 27) of USPC samples with significantly higher expression compared to normal endometrial cells (P < 0.001). High surface expression of EpCAM was found in 83% (5 out of 6) of the USPC cell lines tested by flow cytometry. EpCAM-positive cell lines were found highly sensitive to MT201-mediated ADCC in vitro, while primary USPC cell lines were resistant to natural killer (NK) cell-dependent cytotoxicity. Human plasma IgG did not significantly inhibit MT201-mediated-cytotoxicity against USPC. EpCAM is highly expressed in uterine serous carcinoma at mRNA and protein levels and primary USPC are highly sensitivity to MT201-mediated cytotoxicity. MT201 might represent a novel therapeutic strategy in patients harboring advanced/recurrent or metastatic USPC refractory to standard treatment modalities. PMID:20053761

  19. Decreased expression of 14-3-3σ is predictive of poor prognosis for patients with human uterine papillary serous carcinoma.

    PubMed

    Suzuki, Fumihiko; Nagase, Satoru; Suzuki, Kichiya; Oba, Etsuko; Hiroki, Eri; Matsuda, Yukika; Akahira, Jun-Ichi; Nishigori, Hidekazu; Sugiyama, Takashi; Otsuki, Takeo; Yoshinaga, Kousuke; Takano, Tadao; Niikura, Hitoshi; Ito, Kiyoshi; Sasano, Hironobu; Yaegashi, Nobuo

    2013-01-01

    Uterine papillary serous carcinoma (UPSC) morphologically resembles ovarian serous carcinoma and is categorized as a type II endometrial cancer. UPSC comprises about 10% of all types of endometrial cancer and has an aggressive clinical course and a poor prognosis. The 14-3-3σ gene was originally discovered as a p53-inducible gene; its expression is induced by DNA damage in a p53-dependent manner, which leads to G2 arrest and repair of damaged DNA. Moreover, it has been reported that expression of 14-3-3σ is frequently lost in various types of human cancer, including ovarian cancer. We therefore examined the association between 14-3-3σ expression determined by immunohistochemistry and clinical outcomes of 51 patients with UPSC. UPSC was considered positive for 14-3-3σ when > 30% of tumor cells were stained with a specific antibody. Of these patients, 29 (58.7%) showed positive immunoreactivity for 14-3-3σ and 22 (41.3%) had decreased 14-3-3σ staining. Decreased immunoreactivity for 14-3-3σ was associated with stage (P = 0.001) and lymphovascular space involvement (P = 0.005). Moreover, decreased 14-3-3σ expression was an independent risk factor for reduced overall survival (P = 0.0416) in multivariate analysis. Direct bisulfite sequencing was performed to evaluate the methylation status of the 27 CpG islands in the promoter region and first exon of the 14-3-3σ gene. These CpG islands were hypermethylated in 30% of 14-3-3σ-positive UPSC and 80% of 14-3-3σ-negative UPSC, although the difference was not statistically significant. These findings suggest that decreased expression of immunoreactive 14-3-3σ may be a predictor of poor prognosis in patients with UPSC. PMID:24201220

  20. Clinicopathological and prognostic impact of human epidermal growth factor receptor type 2 (HER2) and hormone receptor expression in uterine papillary serous carcinoma.

    PubMed

    Togami, Shinichi; Sasajima, Yuko; Oi, Takateru; Ishikawa, Mitsuya; Onda, Takashi; Ikeda, Shun-Ichi; Kato, Tomoyasu; Tsuda, Hitoshi; Kasamatsu, Takahiro

    2012-05-01

    Uterine papillary serous carcinoma (UPSC) is a rare and aggressive variant of endometrial carcinoma. Little is known about the pathological and biological features of this tumor. Human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) expression have an important role in tumor behavior and clinical outcome, but their relevance in UPSC is not clear. In the present study, the immunohistochemical expression of HER2 and HR was assessed in 27 patients with Stage I disease, 13 with Stage II disease, 25 with Stage III disease, and 6 with Stage IV disease. Correlations between HER2 and HR expression and the clinicopathological parameters of UPSC were evaluated using Cox's univariate and multivariate analyses. For all patients, the 5-year recurrence-free survival (RFS) and overall survival (OS) rates were 51% and 66%, respectively; in patients with Stage I, II, III and IV disease, the RFS and OS were 67%/81%, 59%/77%, 43%/54% and 0%/0%, respectively. Of all 71 patients, 14% (10/71) were positive for HER2 and 52% (37/71) were positive for HR. Overexpression of HER2 was correlated with lower OS (P = 0.01), whereas HR overexpression was correlated with higher OS (P = 0.008). In multivariate models, HER2, HR, and histologic subtype were identified as independent prognostic indicators for RFS (P = 0.022, P = 0.018, and P = 0.01, respectively), but HR was the only independent factor associated with OS (P = 0.044). Thus, HER2 and HR are prognostic variables in UPSC, with HR an independent prognostic factor for OS. PMID:22329832

  1. Dynamic Contrast-Enhanced CT Characterization of Xp11.2 Translocation/TFE3 Gene Fusions versus Papillary Renal Cell Carcinomas

    PubMed Central

    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

  2. BRAF and TERT promoter mutations in the aggressiveness of papillary thyroid carcinoma: a study of 653 patients

    PubMed Central

    Dong, Siyang; Cai, Yefeng; Zhang, Xiangjian; Zhou, Yili; Zeng, Ruichao; Yang, Fan; Pan, Chuanmeng; Liu, Yehuan; Wu, Weili; Xing, Mingzhao; Zhang, Xiaohua; Wang, Ouchen

    2016-01-01

    The role of telomerase reverse transcriptase (TERT) gene promoter mutations in the aggressiveness of papillary thyroid cancer (PTC) remains to be further investigated. Here we examined the relationship of TERT promoter mutations and BRAF V600E with the clinicopathological features of PTC in 653 patients. Sanger sequencing of genomic DNA from primary PTC tumors was performed for mutation detection and genotype-clinicopathological correlation of the tumor was analyzed. BRAF V600E and TERT promoter mutations were found in 63.7% (416 of 653) and 4.1% (27 of 653) of patients, respectively; the latter became 9.8% when only tumors ≥ 1.5 cm were analyzed. TERT promoter mutations occurred more frequently in BRAF mutation-positive cases compared to wild-type cases, being 5.3% in the former versus 2.1% in the latter (P = 0.050). BRAF and TERT promoter mutations were each significantly associated with high-risk clinicopathological features of PTC, such as old patient age, large tumor size, extrathyroidal invasion, capsular invasion, and advanced disease stages. Coexistence of BRAF V600E and TERT promoter mutations was particularly associated with high-risk clinicopathological features, as exemplified by extrathyroidal invasion seen in 54.5% (12/22) of patients harboring both mutations versus 9.9% (23/232) of patients harboring neither mutation (P < 0.001). Thus, this study, the largest on TERT mutation so far, demonstrates a significant role of BRAF V600E and TERT promoter mutations in the aggressiveness of PTC, which is particularly robust and cooperative when the two mutations coexist. These results, together with previous studies, establish a significant role of these mutations in the aggressiveness of PTC. PMID:26943032

  3. [Dose-Response Dependences for Frequency of RET/PTC Gene Rearrangements in Papillary Thyroid Carcinoma after Irradiation. Simple Pooling Analysis of Molecular Epidemiological Data].

    PubMed

    Koterov, A N; Ushenkova, L N; Biryukov, A P

    2016-01-01

    On the basis of all possible publications on the theme included in the previously formed base of sources on molecular epidemiology of RET/PTC rearrangements in thyroid papillary carcinoma a pooled analysis ("simple pooling data") on determination of the dose-effect dependences for RET/PTC frequency in radiogenic carcinomas of various irradiated groups was performed. (They are groups subjected to radiotherapeutic exposure, residents near the Chernobyl nuclear power plant (CNPP) and victims of nuclear bombing). The tendency to Pearson linear correlation (r = 0.746; p = 0.148) between the frequency of RET/PTC and the estimated dose on thyroid in the regions affected by the CNPP accident was revealed. But this tendency was recognized to be random owing to abnormally low values of the indicator for the most contaminated Gomel region. The method tentatively called "case-control" showed reliable differences in thyroid dose values for carcinomas with RET/PTC and without those. The versatility of changes was found: the lack of RET/PTC for radiotherapeutic impacts was associated with higher doses, whereas in case of the CNPP accident and for nuclear bombing victims it was the opposite. Probably, in the first case the "cellular cleaning" phenomenon after exposure to very high doses took place. Search of direct Pearson correlations between average/median thyroid doses on groups and RET/PTC frequency in carcinomas of these groups showed a high reliability for the dose-effect dependences- at the continuous dose scale (for RET/PTC in total and RET/PTC1 respectively: r = 0.830; p = 0.002 and r = 0.906; p = 0.0003); while there was no significant correlation received for RET/PTC3. When using the weighting least square regression analysis (proceeding from the number of carcinomas in samples), the specified regularities remained. Attempts to influence the strength of correlation by exception ofthe data of all the samples connected with the accident on the CNPP did not significantly

  4. Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms

    PubMed Central

    Nishikawa, G; Sekine, S; Ogawa, R; Matsubara, A; Mori, T; Taniguchi, H; Kushima, R; Hiraoka, N; Tsuta, K; Tsuda, H; Kanai, Y

    2013-01-01

    Background: The molecular basis for the development of appendiceal mucinous tumours, which can be a cause of pseudomyxoma peritonei, remains largely unknown. Methods: Thirty-five appendiceal mucinous neoplasms were analysed for GNAS and KRAS mutations. A functional analysis of mutant GNAS was performed using a colorectal cancer cell line. Results: A mutational analysis identified activating GNAS mutations in 16 of 32 low-grade appendiceal mucinous neoplasms (LAMNs) but in none of three mucinous adenocarcinomas (MACs). KRAS mutations were found in 30 LAMNs and in all MACs. We additionally analysed a total of 186 extra-appendiceal mucinous tumours and found that GNAS mutations were highly prevalent in intraductal papillary mucinous tumours of the pancreas (88%) but were rare or absent in mucinous tumours of the colorectum, ovary, lung and breast (0–9%). The prevalence of KRAS mutations was quite variable among the tumours. The introduction of the mutant GNAS into a colorectal cancer cell line markedly induced MUC2 and MUC5AC expression, but did not promote cell growth either in vitro or in vivo. Conclusion: Activating GNAS mutations are a frequent and characteristic genetic abnormality of LAMN. Mutant GNAS might play a direct role in the prominent mucin production that is a hallmark of LAMN. PMID:23403822

  5. 026. Papillary adenoma of the lung: a case report

    PubMed Central

    Baliaka, Aggeliki; Tryfon, Stavros; Papaemmanouil, Styliani; Cheva, Angeliki; Papastergiou, Christos; Sakkas, Leonidas

    2015-01-01

    Background Papillary adenoma of the lung is a rare neoplasm with only 24 cases reported in the current literature. It occurs in individuals range in age, from 7-60 years with a male predominance and is usually detected incidentally on chest radiographs. Objective The report of a rare case of pulmonary papillary adenoma. Methods A 70-year-old male presented to our Hospital with cough and expectoration. The chest radiological examination demonstrated a nodular shadow two cm in size at the upper lobe of the left lung. Bronchoscopic lung biopsy was performed and the tissue sample was sent for histological examination. Results Pathology examination revealed a lesion consisting of a papillary growth pattern of cuboidal to columnar, ciliated epithelial cells lining the surface of fibrovascular cores. Occasional eosinophilic intranuclear inclusions were noted, but nuclear atypia or mitosis were almost absent. The histological features were consistent with pulmonary papillary adenoma. Conclusions Papillary adenoma of the lung is a benign, circumscribed papillary neoplasm (WHO 2004). Its rarity and shared histologic features of other benign and malignant tumors, such as alveolar adenoma, papillary adenocarcinomas including metastatic thyroid carcinoma, bronchoalveolar carcinoma and papillary carcinoid tumor, demand special attention for diagnosis. In our case, the pathologic criteria, such as papillary growth pattern and cytologic features, were sufficient to confirm the diagnosis of papillary adenoma of the lung.

  6. A Metabolic Phenotype Based on Mitochondrial Ribosomal Protein Expression as a Predictor of Lymph Node Metastasis in Papillary Thyroid Carcinoma

    PubMed Central

    Lee, Jandee; Seol, Mi-Youn; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Shin, Dong Yeob; Nam, Kee-Hyun; Lee, Eun Jig; Chung, Woong Youn; Jo, Young Suk

    2015-01-01

    Abstract Metabolic reprogramming has been regarded as an essential component of malignant transformation. However, the clinical significance of metabolic heterogeneity remains poorly characterized. The aim of this study was to characterize metabolic heterogeneity in thyroid cancers via the analysis of the expression of mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative phosphorylation (OxPhos), and investigate potential prognostic correlations. Gene set enrichment analysis (GSEA) verified by reverse transcription polymerase chain reaction and gene network analysis was performed using public repository data. Cross-sectional observational study was conducted to classify papillary thyroid cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to investigate the clinicopathological features. GSEA clearly showed that the expression of OxPhos and MRP gene sets was significantly lower in primary thyroid cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid tumors (16.3%) in the public repository did not show a reduction in OxPhos mRNA expression. Remarkably, strong positive correlations between MRPL44 expression and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 α subcomplex, 5; succinate dehydrogenase complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5 (MRPS5) (P < 0.0001) were clearly denoted, suggesting that MRPL44 is a representative marker of OxPhos and MRP expressions. In laboratory experiments, metabolic heterogeneity in oxygen consumption, extracellular acidification rates (ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP, TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to OxPhos amount defined by expression of MRPL44 mRNA was significantly related to lymph node metastasis (LNM) (P

  7. A metabolic phenotype based on mitochondrial ribosomal protein expression as a predictor of lymph node metastasis in papillary thyroid carcinoma.

    PubMed

    Lee, Jandee; Seol, Mi-Youn; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Shin, Dong Yeob; Nam, Kee-Hyun; Lee, Eun Jig; Chung, Woong Youn; Jo, Young Suk

    2015-01-01

    Metabolic reprogramming has been regarded as an essential component of malignant transformation. However, the clinical significance of metabolic heterogeneity remains poorly characterized. The aim of this study was to characterize metabolic heterogeneity in thyroid cancers via the analysis of the expression of mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative phosphorylation (OxPhos), and investigate potential prognostic correlations. Gene set enrichment analysis (GSEA) verified by reverse transcription polymerase chain reaction and gene network analysis was performed using public repository data. Cross-sectional observational study was conducted to classify papillary thyroid cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to investigate the clinicopathological features. GSEA clearly showed that the expression of OxPhos and MRP gene sets was significantly lower in primary thyroid cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid tumors (16.3%) in the public repository did not show a reduction in OxPhos mRNA expression. Remarkably, strong positive correlations between MRPL44 expression and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 α subcomplex, 5; succinate dehydrogenase complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5 (MRPS5) (P < 0.0001) were clearly denoted, suggesting that MRPL44 is a representative marker of OxPhos and MRP expressions. In laboratory experiments, metabolic heterogeneity in oxygen consumption, extracellular acidification rates (ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP, TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to OxPhos amount defined by expression of MRPL44 mRNA was significantly related to lymph node metastasis (LNM) (P < 0

  8. Downregulation of uPAR inhibits migration, invasion, proliferation, FAK/PI3K/Akt signaling and induces senescence in papillary thyroid carcinoma cells.

    PubMed

    Nowicki, Theodore S; Zhao, Hong; Darzynkiewicz, Zbigniew; Moscatello, Augustine; Shin, Edward; Schantz, Stimson; Tiwari, Raj K; Geliebter, Jan

    2011-01-01

    Papillary thyroid carcinoma (PTC) is the most common endocrine and thyroid malignancy.  The urokinase plasminogen activator receptor (uPAR) plays an important role in cancer pathogenesis, including breakdown of the extracellular matrix, invasion, and metastasis.  Additionally, there is increasing evidence that uPAR also promotes tumorigenesis via the modulation of multiple signaling pathways.  BRAFV600E, the most common initial genetic mutation in PTC, leads to ERK1/2 hyperphosphorylation, which has been shown in numerous cancers to induce uPAR.  Treatment of the BRAFV600E-positive PTC cell line, BCPAP, with the MEK/ERK inhibitor U0126 reduced uPAR RNA levels by 90%.  siRNA-mediated down-regulation of uPAR in BCPAP cells resulted in greatly decreased activity in the focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway.  This phenomenon was concurrent with drastically reduced proliferation rates and decreased clonigenic survival, as well as demonstrated senescence-associated nuclear morphology and induction of b-galactosidase activity. uPAR-knockdown BCPAP cells also displayed greatly reduced migration and invasion rates, as well as a complete loss of the cells' ability to augment their invasiveness following plasminogen supplementation. Taken together, these data provide new evidence of a novel role for uPAR induction (as a consequence of constitutive ERK1/2 activation) as a central component in PTC pathogenesis, and highlight the potential of uPAR as a therapeutic target. PMID:21191179

  9. Oncologic Safety of Robot Thyroid Surgery for Papillary Thyroid Carcinoma: A Comparative Study of Robot versus Open Thyroid Surgery Using Inverse Probability of Treatment Weighting

    PubMed Central

    Sung, Tae-Yon; Yoon, Jong Ho; Han, Minkyu; Lee, Yi Ho; Lee, Yu-mi; Song, Dong Eun; Chung, Ki-Wook; Kim, Won Bae; Shong, Young Kee; Hong, Suck Joon

    2016-01-01

    The aim of this study was to evaluate the oncologic safety of robot thyroid surgery compared to open thyroid surgery for papillary thyroid carcinoma (PTC). We enrolled 722 patients with PTC who underwent a total thyroidectomy with central compartment node dissection (CCND) from January 2009 to December 2010. These patients were classified into open thyroid surgery (n = 610) or robot thyroid surgery (n = 112) groups. We verified the impact of robot thyroid surgery on clinical recurrence and ablation/control-stimulated thyroglobulin (sTg) levels predictive of non-recurrence using weighted logistic regression models with inverse probability of treatment weighting (IPTW). Age, sex, thyroid weight, extent of CCND, and TNM were significantly different between the two groups (p < 0.05); however, there was no significant difference in recurrence between the open and robot groups (1.5% vs. 2.7%; p = 0.608). The proportion of patients with ablation sTg < 10.0 ng/mL and control sTg < 1.0 ng/mL was comparable between the two groups (p > 0.05). Logistic regression with IPTW using the propensity scores estimated by adjusting all of the parameters demonstrated that robot thyroid surgery did not influence the clinical recurrence (OR; 0.784, 95% CI; 0.150–3.403, p = 0.750), ablation sTg (OR; 0.950, 95% CI; 0.361–2.399, p = 0.914), and control sTg levels (OR; 0.498, 95% CI; 0.190–1.189, p = 0.130). Robot thyroid surgery is comparable to open thyroid surgery with regard to oncologic safety in PTC patients. PMID:27285846

  10. Significance of the BRAF mRNA Expression Level in Papillary Thyroid Carcinoma: An Analysis of The Cancer Genome Atlas Data

    PubMed Central

    Jee, Hyeon-Gun; Kim, Young A; Kim, Ju Han; Xing, Mingzhao; Lee, Kyu Eun

    2016-01-01

    Background BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC), and it is associated with high-risk prognostic factors. However, the significance of the BRAF mRNA level in PTC remains unknown. We evaluated the significance of BRAF mRNA expression level by analyzing PTC data from The Cancer Genome Atlas (TCGA) database. Methods Data from 499 patients were downloaded from the TCGA database. After excluding other PTC variants, we selected 353 cases of classic PTC, including 193 cases with BRAFV600E and 160 cases with the wild-type BRAF. mRNA abundances were measured using RNA-Seq with the Expectation Maximization algorithm. Results The mean BRAF mRNA level was significantly higher in BRAFV600E patients than in patients with wild-type BRAF (197.6 vs. 179.3, p = 0.031). In wild-type BRAF patients, the mean BRAF mRNA level was higher in cases with a tumor > 2 cm than those with a tumor ≤ 2.0 cm (189.4 vs. 163.8, p = 0.046), and was also higher in cases with lymph node metastasis than in those without lymph node metastasis (188.5 vs. 157.9, p = 0.040). Within BRAFV600E patients, higher BRAF mRNA expression was associated with extrathyroidal extension (186.4 vs. 216.4, p = 0.001) and higher T stage (188.1 vs. 210.2, p = 0.016). Conclusions A higher BRAF mRNA expression level was associated with tumor aggressiveness in classic PTC regardless of BRAF mutational status. Evaluation of BRAF mRNA level may be helpful in prognostic risk stratification of PTC. PMID:27410688

  11. Quality of life and cosmetic result of single-port access endoscopic thyroidectomy via axillary approach in patients with papillary thyroid carcinoma

    PubMed Central

    Huang, Jian-kang; Ma, Ling; Song, Wen-hua; Lu, Bang-yu; Huang, Yu-bin; Dong, Hui-ming

    2016-01-01

    Background Endoscopic thyroidectomy for minimally invasive thyroid surgery has been widely applied in the past decade. The present study aimed to evaluate the effects of single-port access transaxillary totally endoscopic thyroidectomy on the postoperative outcomes and functional parameters, including quality of life and cosmetic result in patients with papillary thyroid carcinoma (PTC). Patients and methods Seventy-five patients with PTC who underwent endoscopic thyroidectomy via a single-port access transaxillary approach were included (experimental group). A total of 123 patients with PTC who were subjected to conventional open total thyroidectomy served as the control group. The health-related quality of life and cosmetic and satisfaction outcomes were assessed postoperatively. Results The mean operation time was significantly increased in the experimental group. The physiological functions and social functions in the two groups were remarkably augmented after 6 months of surgery. However, there was no significant difference in the scores of speech and taste between the two groups at the indicated time of 1 month and 6 months. In addition, the scores for appearance, satisfaction with appearance, role-physical, bodily pain, and general health in the experimental group were better than those in the control group at 1 month and 6 months after surgery. Conclusion The single-port access transaxillary totally endoscopic thyroidectomy is safe and feasible for the treatment of patients with PTC. The subjects who underwent this technique have a good perception of their general state of health and are likely to participate in social activities. It is worthy of being clinically used for patients with PTC. PMID:27445496

  12. Induction of ROS-independent DNA damage by curcumin leads to G2/M cell cycle arrest and apoptosis in human papillary thyroid carcinoma BCPAP cells.

    PubMed

    Zhang, Li; Cheng, Xian; Gao, Yanyan; Bao, Jiandong; Guan, Haixia; Lu, Rongrong; Yu, Huixin; Xu, Qiang; Sun, Yang

    2016-01-01

    Previously we found that curcumin, the active constituent of dietary spice turmeric, showed potent inhibitory effects on the cell growth of thyroid cancer cells. However, the detailed anti-cancer mechanism of curcumin is still unknown. In this study, we have reported that curcumin induces significant DNA damage in human papillary thyroid carcinoma BCPAP cells in a dose-dependent manner as evidenced by the upregulated phosphorylation of H2A.X at Ser139, which was further confirmed by the long tails in the comet assay and the increase in the number of TUNEL-positive cells. Subsequently, curcumin treatment caused a significant accumulation of cells at the G2/M phase that eventually resulted in a caspase-dependent apoptosis in BCPAP cells. DNA agarose gel electrophoresis revealed that curcumin-induced DNA damage in BCPAP cells was independent of DNA conformational change. Pretreatment with reactive oxygen species (ROS) scavengers failed to block the phosphorylation of H2A.X, suggesting the non-involvement of ROS in curcumin-mediated DNA damage. Interestingly, ATM/ATR activation by curcumin induced phosphorylation of Chk2 (Thr68) followed by that of Cdc25C (Ser216) and Cdc2 (Tyr15), and Cyclin B1 accumulation. In addition, the ATM-specific inhibitor KU-55933 reversed curcumin-induced phosphorylation of H2A.X. These results collectively show that curcumin treatment induced the DNA damage response via triggering an ATM-activated Chk2-Cdc25C-Cdc2 signaling pathway. These observations provide novel mechanisms and potential targets for the better understanding of the anti-cancer mechanisms of curcumin. PMID:26442630

  13. Oncologic Safety of Robot Thyroid Surgery for Papillary Thyroid Carcinoma: A Comparative Study of Robot versus Open Thyroid Surgery Using Inverse Probability of Treatment Weighting.

    PubMed

    Sung, Tae-Yon; Yoon, Jong Ho; Han, Minkyu; Lee, Yi Ho; Lee, Yu-Mi; Song, Dong Eun; Chung, Ki-Wook; Kim, Won Bae; Shong, Young Kee; Hong, Suck Joon

    2016-01-01

    The aim of this study was to evaluate the oncologic safety of robot thyroid surgery compared to open thyroid surgery for papillary thyroid carcinoma (PTC). We enrolled 722 patients with PTC who underwent a total thyroidectomy with central compartment node dissection (CCND) from January 2009 to December 2010. These patients were classified into open thyroid surgery (n = 610) or robot thyroid surgery (n = 112) groups. We verified the impact of robot thyroid surgery on clinical recurrence and ablation/control-stimulated thyroglobulin (sTg) levels predictive of non-recurrence using weighted logistic regression models with inverse probability of treatment weighting (IPTW). Age, sex, thyroid weight, extent of CCND, and TNM were significantly different between the two groups (p < 0.05); however, there was no significant difference in recurrence between the open and robot groups (1.5% vs. 2.7%; p = 0.608). The proportion of patients with ablation sTg < 10.0 ng/mL and control sTg < 1.0 ng/mL was comparable between the two groups (p > 0.05). Logistic regression with IPTW using the propensity scores estimated by adjusting all of the parameters demonstrated that robot thyroid surgery did not influence the clinical recurrence (OR; 0.784, 95% CI; 0.150-3.403, p = 0.750), ablation sTg (OR; 0.950, 95% CI; 0.361-2.399, p = 0.914), and control sTg levels (OR; 0.498, 95% CI; 0.190-1.189, p = 0.130). Robot thyroid surgery is comparable to open thyroid surgery with regard to oncologic safety in PTC patients. PMID:27285846

  14. Whole exome sequencing identifies lncRNA GAS8-AS1 and LPAR4 as novel papillary thyroid carcinoma driver alternations.

    PubMed

    Pan, Wenting; Zhou, Liqing; Ge, Minghua; Zhang, Bin; Yang, Xinyu; Xiong, Xiangyu; Fu, Guobin; Zhang, Jian; Nie, Xilin; Li, Hongmin; Tang, Xiaohu; Wei, Jinyu; Shao, Mingming; Zheng, Jian; Yuan, Qipeng; Tan, Wen; Wu, Chen; Yang, Ming; Lin, Dongxin

    2016-05-01

    Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. However, we know little of mutational spectrum in the Chinese population. Thus, here we report the identification of somatic mutations for Chinese PTC using 402 tumor-normal pairs (Discovery: 91 pairs via exome sequencing; validation: 311 pairs via Sanger sequencing). We observed three distinct mutational signatures, evidently different from the two mutational signatures among Caucasian PTCs. Ten significantly mutated genes were identified, most previously uncharacterized. Notably, we found that long non-coding RNA (lncRNA) GAS8-AS1 is the secondary most frequently altered gene and acts as a novel tumor suppressor in PTC. As a mutation hotspot, the c.713A>G/714T>C dinucleotide substitution was found among 89.1% patients with GAS8-AS1 mutations and associated with advanced PTC disease (P = 0.009). Interestingly, the wild-type lncRNA GAS8-AS1 (A713T714) showed consistently higher capability to inhibit cancer cell growth compared to the mutated lncRNA (G713C714). Further studies also elucidated the oncogene nature of the G protein-coupled receptor LPAR4 and its c.872T>G (p.Ile291Ser) mutation in PTC malignant transformation. The BRAF c.1799T>A (p.Val600Glu) substitution was present in 59.0% Chinese PTCs, more frequently observed in patients with lymph node metastasis (P = 1.6 × 10(-4)). Together our study defines a exome mutational spectrum of PTC in the Chinese population and highlights lncRNA GAS8-AS1 and LPAR4 as potential diagnostics and therapeutic targets. PMID:26941397

  15. Notch and TGF-β/Smad3 pathways are involved in the interaction between cancer cells and cancer-associated fibroblasts in papillary thyroid carcinoma.

    PubMed

    Zhang, Jie; Wang, Yuan; Li, Dan; Jing, Shanghua

    2014-01-01

    Accumulating evidence suggests that cancer-associated stromal fibroblasts (CAFs) contribute to tumor growth by actively communicating with cancer cells. Our aim was to identify the signaling pathways that are involved in tumor-stromal cell interactions in human papillary thyroid carcinoma (PTC). Immunohistochemical analyses were performed with 127 archived formalin-fixed and paraffin-embedded thyroid tissue samples that included 70 cases of PTC, 35 cases of nodular goiter (NG), and 22 cases of normal thyroid tissues. The results showed that the expression levels of Notch1, transforming growth factor β (TGF-β1), and p-Smad3 in PTC cells and α-smooth muscle actin (α-SMA) in the stroma of PTC were all significantly higher than in NG and normal thyroid tissues. Further analysis showed that in PTC, higher expression levels of Notch1 and TGF-β1 were closely related with lymph node metastasis (P < 0.05), whereas for α-SMA and p-Smad3, the percent expression increased significantly with advanced tumor stages (P < 0.05). Correlation analysis revealed that TGF-β1 expression increased with increased Notch1 and p-Smad3 levels in PTC cells (P < 0.05). Moreover, a significant correlation was found between higher TGF-β1 expression in PTC cells and increased α-SMA levels in the fibroblasts surrounding the cancer cells (P < 0.05). We identified TGF-β1 as an important factor from PTC cells that act in a paracrine manner to influence the activation of stromal fibroblasts. These data suggest that the activation of Notch and TGF-β/Smad3 pathways in cancer cells influence tumor growth. Moreover, cancer cell-derived-TGF-β ligands also affect stromal cells in a paracrine fashion and enhance tumor growth. PMID:23918305

  16. Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF (V600E) Harboring Pediatric Papillary Thyroid Carcinomas.

    PubMed

    Onder, Semen; Ozturk Sari, Sule; Yegen, Gulcin; Sormaz, Ismail Cem; Yilmaz, Ismail; Poyrazoglu, Sukran; Sanlı, Yasemin; Giles Senyurek, Yasemin; Kapran, Yersu; Mete, Ozgur

    2016-06-01

    This study is aimed to investigate the BRAF (V600E) and TERT promoter mutation profile of 50 pediatric papillary thyroid carcinomas (PTCs) to refine their clinicopathological correlates. The median age at the time of surgery was 16 years (range, 6-18). No TERT promoter mutations were identified in this series. The BRAF (V600E) mutation was present in 15 (30 %) tumors. From genotype-histologic variant correlation perspective, 13 of 24 classic variant PTCs and 2 of 7 diffuse sclerosing variant PTCs were found to harbor BRAF (V600E) mutation. One cribriform-morular variant, 3 solid variant, and 15 follicular variant PTCs were BRAF wild type. While tumors with distant metastasis were BRAF wild type, two of five tumors with extrathyroidal extension (ETE) harbored BRAF (V600E) mutation. Nine of 15 BRAF (V600E) harboring tumors had central lymph node metastases. There was no significant correlation with BRAF (V600E) mutation and age, gender, tumor size, ETE, central lymph node metastasis, the status of pT, pN1a-b, and distant metastasis. An adverse correlation between BRAF (V600E) mutation and disease-free survival (DFS) was noted in the entire cohort; however, the predictive value of BRAF (V600E) mutation disappeared within the group of tumors displaying classic architecture as well as classic variant PTCs. The present cohort identifies that the classic architecture with multicentricity and local recurrence are correlates of BRAF (V600E) harboring pediatric PTCs. While the small size of this cohort is one of the limitations, neither the BRAF mutation status nor the classic tumor architecture does seem to be an independent prognosticator of DFS in this series. Evidence also suggests that TERT promoter mutations do not seem to play a major role in the pathogenesis of pediatric PTCs. PMID:26951110

  17. Influence of body habitus on the surgical outcomes of bilateral axillo-breast approach robotic thyroidectomy in papillary thyroid carcinoma patients

    PubMed Central

    Lee, Hee Seung; Chai, Young Jun; Kim, Su-Jin; Choi, June Young

    2016-01-01

    Purpose Obesity is associated with a number of medical comorbidities and is considered a risk factor for surgical complications. The purpose of this study was to analyze the influence of body habitus including obesity on the surgical outcomes of the Bilateral axillo-breast approach (BABA) robotic thyroidectomy (RoT) in papillary thyroid carcinoma (PTC) patients. Methods The medical records of 456 PTC patients who underwent BABA RoT between January 2011 and December 2012 were reviewed, and 310 women PTC patients who had undergone BABA robotic total thyroidectomy with central lymph node dissection were examined. Body habitus were evaluated by measuring body mass index (BMI), body surface area, and neck circumference. We divided the patients into BMI < 25 kg/m2 and BMI ≥ 25 kg/m2 groups. Clinicopathological data, surgical outcomes, and postoperative complications were evaluated. Results Clinicopathological characteristics did not differ between the 2 BMI groups. The creation of working space time (P = 0.210) and other surgical outcomes showed no significant differences between the groups. There were no statistically significant differences between body habitus indexes and postoperative length of hospital stay, number of retrieved central lymph nodes, postoperative thyroglobulin levels, occurrence of hypoparathyoidism, recurrent laryngeal nerve injury and wound complication. Conclusion Patient with large body habitus undergoing BABA RoT were not at an increased risk of surgical complications and showed good surgical outcomes. BABA RoT may be a good alternative operative method for PTC patients for whom cosmetic outcome is an important consideration. PMID:27433458

  18. A prospective phase II study of chemoradiation followed by adjuvant chemotherapy for FIGO stage I-IIIa (1988) uterine papillary serous carcinoma of the endometrium

    PubMed Central

    Jhingran, Anuja; Ramondetta, Lois M.; Bodurka, Diane C.; Slomovitz, Brian M.; Brown, Jubilee; Levy, Lawrence B.; Garcia, Michael E.; Eifel, Patricia J.; Lu, Karen H.; Burke, Thomas W.

    2015-01-01

    Objective To prospectively evaluate tumor control, survival, and toxic effects in patients with International Federation of Gynecology and Obstetrics (1988) stage I-IIIA papillary serous carcinoma of the endometrium treated with concurrent chemoradiation and adjuvant chemotherapy. Methods Thirty-two patients were enrolled from October 2001 through July 2009. Patients underwent full surgical disease staging and postoperative concurrent weekly paclitaxel (50 mg/m2) and pelvic RT to 45 Gy plus a vaginal cuff boost followed by 4 cycles of adjuvant paclitaxel (135 mg/m2). Results Thirty patients (94%) were evaluable (3 with stage IA disease, 11 IB, 3 IC, 1 IIB, and 12 IIIA). Eighteen patients (60%) received all 5 planned courses of concurrent chemotherapy, 10 (33%) received 4 courses, and 2 (7%) received 3 courses. All 30 patients received RT; 27 (90%) received the full dose, 2 received 43.2 Gy, and 1 received 39.6 Gy owing to toxic effects. Twenty-three patients (77%) completed all 4 cycles of adjuvant paclitaxel, 3 (10%) completed 3 cycles, 2 (7%) completed 2 cycles, and 2 received no adjuvant therapy. Overall survival (OS), progression-free survival (PFS), and local control rates for all patients were 93%, 87%, and 87%, respectively, at 2 years and 85%, 83%, and 87%, respectively, at 5 years. Six patients developed (20%) grade 3/4 toxcities from the treatment. Four patients (13%) had grade 3 or more severe bowel complications and two patients developed symptomatic pelvic fractures. Conclusions Treatment with concurrent paclitaxel and pelvic RT followed by 4 courses of systemic paclitaxel produced favorable results in patients with surgically staged I-III UPSC. PMID:23385150

  19. Papillary adenoma —

    Cancer.gov

    Consists primarily of papillary structures lined by cuboidal to columnar cells. Cells forming papillary structures are frequently more hyperchromatic and atypical, which is regarded as indication of potential progression towards malignancy.

  20. Familial Adenomatous Polyposis-Associated Papillary Thyroid Cancer

    PubMed Central

    Abdullah Suhaimi, Shahrun Niza; Nazri, Nadzrin; Nani Harlina, Mat Latar; Md. Isa, Nurismah; Muhammad, Rohaizak

    2015-01-01

    Papillary thyroid carcinoma (PTC) associated with familial adenomatous polyposis (FAP) is rare. It is usually associated with the cribriform-morular variant of PTC, with unusual patterns on detailed histology examination. This variant is known to have a good prognosis. Papillary thyroid carcinoma associated with FAP commonly occurs in females in their 30s and rarely in the elderly. We report a case of a 69-year-old female presenting with thyroid swelling and a history of FAP. PMID:26715910

  1. Expression of REG4 in ovarian mucinous tumors.

    PubMed

    Huang, Qiong; Chen, Xiaoduan; Lu, Weiguo; Lai, Maode; Lu, Bingjian

    2014-04-01

    Regenerating islet-deprived gene family, number 4 (REG4), is a novel marker for intestinal differentiation. We performed immunohistochemical studies on REG4, cytokeratin (CK)7, CK20, and caudal type homeobox 2 (CDX2) in 291 ovarian mucinous tumors. There were 226 primary tumors and 65 metastatic tumors. The primary tumors comprised 69/226 mucinous cystadenomas, 79/226 mucinous borderline tumors (64/79 intestinal-type and 15/79 endocervical-like tumors), and 78/226 mucinous carcinomas. We found that REG4 expression was significantly higher in mucinous borderline tumors (30/79, 38.0%) and primary mucinous carcinomas (26/78, 33.3%) than in mucinous cystadenomas (4/69, 5.8%; P<0.05). However, REG4 expression was more commonly associated with intestinal-type, borderline, mucinous tumors rather than the endocervical-like type (30/64 vs. 0/15, P<0.001). There was a significant correlation between the REG4 and CDX2 expression profiles in primary ovarian mucinous tumors (r=0.772, P<0.001). REG4, CDX2, and diffuse CK20 had higher expression frequencies in metastatic lower gastrointestinal adenocarcinoma than in primary mucinous tumors (P<0.01). The CK7/REG4 coordinate expression profile was comparable in diagnostic value to CK7/CK20 or CK7/CDX2 profile. We conclude that REG4 expression is common in mucinous borderline tumors of the intestinal type as it is absent in the endocervical-like form in this series. Expression of CK7/REG4 may contribute to the differential diagnosis between primary and metastatic ovarian mucinous tumors. PMID:23958547

  2. The impact of combined radiation and chemotherapy on outcome in uterine papillary serous carcinoma compared to chemotherapy alone

    PubMed Central

    Nutter, Benjamin; Abdul-Karim, Fadi; Amarnath, Sudha; Rose, Peter G

    2016-01-01

    Objective To investigate the impact of pelvic radiation on survival in patients with uterine serous carcinoma (USC) who received adjuvant chemotherapy. Methods Patients with stage I-IV USC were identified from the Surveillance, Epidemiology, and End Results program 2000 to 2009. Patients were included if treated with surgery and chemotherapy. Patients were divided into two groups: those who received chemotherapy and pelvic radiation therapy (CT_RT) and those who received chemotherapy only (CT). Kaplan-Meier curves and Cox regression proportional hazard models were used. Results Of the 1,838 included patients, 1,272 (69%) were CT and 566 (31%) were CT_RT. Adjuvant radiation was associated with significant improvement in overall survival (OS; p<0.001) and disease-specific survival (DSS; p<0.001) for entire cohort. These findings were consistent for the impact of radiation on OS (p<0.001) and DSS (p<0.001) in advanced stage (III-IV) disease but not for early stage (I–II) disease (p=0.21 for OS and p=0.82 for DSS). In multivariable analysis adjusting for age, stage, race and extent of lymphadenectomy, adjuvant radiation was a significant predictor of OS and DSS for entire cohort (p=0.003 and p=0.05) and in subset of patients with stage III (p=0.02 and p=0.07) but not for patients with stage I (p=0.59 and p=0.49), II (p=0.83 and p=0.82), and IV USC (p=0.50 and p=0.96). Other predictors were stage, positive cytology, African American race and extent of lymphadenectomy. Conclusion In USC patients who received adjuvant chemotherapy, adjuvant radiation was associated with significantly improved outcome in stage III disease but not for other stages. Positive cytology, extent of lymphadenectomy and African race were significant predictors of outcome. PMID:26463437

  3. Intraductal Oncocytic Papillary Neoplasms of the Pancreas.

    PubMed

    Kallen, Michael E; Naini, Bita V

    2016-09-01

    Intraductal oncocytic papillary neoplasms (IOPNs) are cystic neoplasms with intraductal growth and complex papillae composed of oncocytic cells. IOPNs have been reported both in the pancreas and biliary tree, and are most likely closely related in these 2 locations. In the pancreas, these rare tumors are now considered 1 of the 4 histologic subtypes of intraductal papillary mucinous neoplasm (IPMN). Significant differences in histology, immunophenotype, and molecular genetics have been reported between IOPNs and other IPMN subtypes. However, there are limited data regarding the clinical behavior and prognosis of IOPNs in comparison to other subtypes of IPMN. We review features of pancreatic IOPNs and discuss the differential diagnosis of other intraductal lesions in the pancreas. PMID:27575268

  4. Heart Failure as First Sign of Development of Cardiac Metastases in a Patient with Diagnosis of Papillary Thyroid Carcinoma on Treatment with Tyrosine-Kinase Inhibitors: Differential Diagnoses and Clinical Management

    PubMed Central

    Bruixola, Gema; Segura, Ángel; Caballero, Javier; Andrés, Ana; Reche, Encarnación; Escoín, Corina; Díaz-Beveridge, Roberto

    2014-01-01

    Background Cardiac metastases from papillary thyroid carcinoma are very uncommon. Their incidence is rising due to improvements in survival and diagnosis; nevertheless, our patient is the fourth case reported up to date. There are no clinical trials available in this scenario. Therefore, treatment choice is made based on clinical experience and case reports; notably, the largest case report series was prior to the approval for using tyrosine-kinase inhibitors in thyroid cancer. Patient A 73-year-old lady had dedifferentiated papillary thyroid cancer with ongoing sorafenib. After 9 months on this treatment, she presented with dyspnea and heart failure. Differential diagnosis included infection, progression of disease and cardiotoxicity. After a comprehensive assessment (echocardiography, computed tomography, PET, magnetic resonance), we found progression of lung disease, and the appearance of heart metastases. Results After recovering from the basal status, she started on second-line treatment with sunitinib, which was well-tolerated. She achieved stable disease with a decrease in tumor marker levels. Conclusions We should include cardiac metastases in the differential diagnosis of heart failure in cancer patients. Magnetic resonance imaging is the gold standard for assessment. Sorafenib is the mainstay of the first-line therapy in metastatic thyroid cancer, achieving long-term disease control with good tolerance. Sunitinib could be a safe second-line treatment option (not cardiotoxicity related) with promising results. Therefore, our report presents a sequence of treatment with tyrosine-kinase inhibitors in metastatic thyroid carcinoma with an encouraging outcome, which deserves further investigation. PMID:25298765

  5. Preoperative Prediction of Cervical Lymph Node Metastasis Using Primary Tumor SUVmax on 18F-FDG PET/CT in Patients with Papillary Thyroid Carcinoma

    PubMed Central

    Jung, Ji-hoon; Kim, Choon-Young; Son, Seung Hyun; Kim, Do-Hoon; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol

    2015-01-01

    Objectives The aim of the current study was to evaluate the value of preoperative 18F-FDG (FDG) PET/CT in predicting cervical lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC). Methods One hundred and ninety-three newly diagnosed PTC patients (M: F = 25:168, age = 46.8 ± 12.2) who had undergone pretreatment FDG PET/CT and had neck node dissection were included in this study. The FDG avidity of the primary tumor and the SUVmax of the primary tumor (pSUVmax) were analyzed for prediction of LN metastasis. Detectability by ultrasonography (US) and FDG PET/CT for cervical LN metastasis were also assessed and compared with the pSUVmax. Results The FDG avidity of the primary tumor was identified in 118 patients (FDG avid group: 61.0%, M: F = 16:102, age 47.0 ± 12.7 years) and pSUVmax ranged from 1.3 to 35.6 (median 4.6) in the FDG avid group. The tumor size in the FDG avid group was bigger and there was a higher incidence of LN metastasis compared to the FDG non-avid group (0.93 vs. 0.59 cm, p <0.001 and 49.2 vs. 33.3%, p <0.05). In the FDG avid group, patients with LN metastasis had higher pSUVmax than patients without LN metastasis (8.7 ± 8.3 vs. 5.7 ± 5.1, p <0.001). The incidence of central LN metastasis in patients with a pSUVmax >4.6 was 54%; however, the detectability of central LN metastasis by US and FDG PET/CT were 10.3% and 3.6%, respectively. Conclusion A high FDG avidity of the primary tumor was related to LN metastasis in PTC patients. Therefore, patients with a high pSUVmax should be cautiously assessed for LN metastasis and might need a more comprehensive surgical approach. PMID:26636824

  6. The Value of HBME-1 and Claudin-1 Expression Profile in the Distinction of BRAF-Like and RAS-Like Phenotypes in Papillary Thyroid Carcinoma.

    PubMed

    Gucer, Hasan; Bagci, Pelin; Bedir, Recep; Sehitoglu, Ibrahim; Mete, Ozgur

    2016-09-01

    This study compared the expression profile of HBME-1 and claudin-1 in 90 papillary thyroid carcinomas (PTCs) with respect to the tumor architecture and invasive growth as reflected in 46 BRAF-like, 31 non-invasive RAS, and 13 invasive RAS-like phenotypes. Individual tumors were given an expression score (max 300) by multiplying the percent positive tumor cells by the intensity score (range 0-3). The higher expression of HBME-1 and claudin-1 distinguished BRAF-like phenotype from RAS-like phenotype. The same correlation was also retained for both markers when comparing BRAF-like phenotype with non-invasive and invasive RAS-like phenotypes. The expression scores and positivity rates for both markers did not yield any statistical difference among BRAF-like PTCs. Except the higher positivity rate of HBME-1, invasive RAS-like tumors were not statistically different than their non-invasive counterparts with respect to the positivity rate of claudin-1 and the expression scores of both markers. A central lymph node dissection or selective lymph node sampling was available in 20 specimens. The absence of claudin-1 expression has not been a feature of lymph node metastasis in this series. Despite the limited number of nodal sampling, BRAF-like phenotype and claudin-1 positivity status have been considered the best determinants of positive predictive value and negative predictive value in the prediction of lymph node metastasis among variables, respectively. Adoption of the simplified architectural classification approach to PTCs showed distinct biomarker expression profile in this series; however, immunohistochemistry for HBME-1 and claudin-1 does not seem to be useful in the distinction of invasive RAS-like PTCs from their non-invasive counterparts. Given the overlapping molecular signatures within the RAS-like phenotype, further studies with additional biomarkers are still needed to identify distinct protein expression signatures of non-invasive RAS-like phenotype as this

  7. Effects of siRNA on RET/PTC3 Junction Oncogene in Papillary Thyroid Carcinoma: From Molecular and Cellular Studies to Preclinical Investigations

    PubMed Central

    Ali, Hafiz Muhammad; Urbinati, Giorgia; Chapuis, Hubert; DesmaEle, Didier; Bertrand, Jean-Rémi; Couvreur, Patrick; Massaad-Massade, Liliane

    2014-01-01

    RET/PTC3 junction oncogene is typical of radiation-induced childhood papillary thyroid carcinoma (PTC) with a short latency period. Since, RET/PTC3 is only present in the tumour cells, thus represents an interesting target for specific therapy by small interfering RNA (siRNA). Our aim is to demonstrate in vitro and in vivo molecular and cellular effects of siRNA on RET/PTC3 knockdown for therapeutic application.First, we established a novel cell line stably expressing RET/PTC3 junction oncogene, named RP3 which was found tumorigenic in nude mice compared to NIH/3T3 mouse fibroblasts. Among four siRNAs and five concentrations tested against RET/PTC3, an efficient siRNA RET/PTC3 and an appropriate dose (50 nM) were selected which showed significant inhibition (p<0.001) of gene (RT-qPCR) and protein (Western blot) expressions. This siRNA was found efficient in RP3 cells (harbouring RET/PTC3) but non-efficient in BHP10-3 SCmice cell line (harbouring RET/PTC1) showing that a specific siRNA against fusion sequence is required to target the junction oncogene. In vitro siRNA RET/PTC3 showed significant (p<0.001) inhibitory effects on RP3 cell viability (MTT assay) and on invasion/migration (IncuCyte scratch test) with blockage of cell cycle at G0/G1 phase (flow cytometry) and induced apoptosis by caspase-3 and PARP1 cleavage (WB). After intravenous injection in nude mice, respective squalene (SQ) nanoparticles (NPs) of siRNA RET/PTC3 significantly (p<0.001) reduced RP3 tumour growth, oncogene and oncoprotein expressions, induced apoptosis and partially restored differentiation (decrease in Ki67). Hence, our findings highly support the use of siRNA RET/PTC3-SQ NPs as a new promising treatment for patients affected by PTC expressing RET/PTC3. PMID:24759995

  8. Metastasis-associated MCL1 and P16 copy number alterations dictate resistance to vemurafenib in a BRAFV600E patient-derived papillary thyroid carcinoma preclinical model

    PubMed Central

    Duquette, Mark; Sadow, Peter M.; Fischer, Andrew H.; Song, Chen; Castellanos-Rizaldos, Elena; Makrigiorgos, G. Mike; Kurebayashi, Junichi; Nose, Vania; Van Hummelen, Paul; Bronson, Roderick T.; Vinco, Michelle; Giordano, Thomas J.; Dias-Santagata, Dora; Pandolfi, Pier Paolo; Nucera, Carmelo

    2015-01-01

    BRAFV600E mutation exerts an essential oncogenic function in many tumors, including papillary thyroid carcinoma (PTC). Although BRAFV600E inhibitors are available, lack of response has been frequently observed. To study the mechanism underlying intrinsic resistance to the mutant BRAFV600E selective inhibitor vemurafenib, we established short-term primary cell cultures of human metastatic/recurrent BRAFV600E-PTC, intrathyroidal BRAFV600E-PTC, and normal thyroid (NT). We also generated an early intervention model of human BRAFV600E-PTC orthotopic mouse. We find that metastatic BRAFV600E-PTC cells elicit paracrine-signaling which trigger migration of pericytes, blood endothelial cells and lymphatic endothelial cells as compared to BRAFWT-PTC cells, and show a higher rate of invasion. We further show that vemurafenib therapy significantly suppresses these aberrant functions in non-metastatic BRAFV600E-PTC cells but lesser in metastatic BRAFV600E-PTC cells as compared to vehicle treatment. These results concur with similar folds of down-regulation of tumor microenvironment–associated pro-metastatic molecules, with no effects in BRAFWT-PTC and NT cells. Our early intervention preclinical trial shows that vemurafenib delays tumor growth in the orthotopic BRAFWT/V600E-PTC mice. Importantly, we identify high copy number gain of MCL1 (chromosome 1q) and loss of CDKN2A (P16, chromosome 9p) in metastatic BRAFV600E-PTC cells which are associated with resistance to vemurafenib treatment. Critically, we demonstrate that combined vemurafenib therapy with BCL2/MCL1 inhibitor increases metastatic BRAFV600E-PTC cell death and ameliorates response to vemurafenib treatment as compared to single agent treatment. In conclusion, short-term PTC and NT cultures offer a predictive model for evaluating therapeutic response in patients with PTC. Our PTC pre-clinical model suggests that combined targeted therapy might be an important therapeutic strategy for metastatic and refractory BRAFV600

  9. Ovarian mucinous tumor with malignant mural nodules: dedifferentiation or collision?

    PubMed

    Desouki, Mohamed M; Khabele, Dineo; Crispens, Marta A; Fadare, Oluwole

    2015-01-01

    Ovarian mucinous tumors with mural nodules are rare surface epithelial-stromal tumors. The mural nodules are divergent neoplasms that may be benign or malignant. The latter may be in the form of a sarcoma, carcinosarcoma, anaplastic carcinoma, or a variety of other recognized histotypes of carcinoma, which raises the question of whether malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors or whether they represent collision tumors. We recently reported the K-RAS gene mutation status in a case of ovarian mucinous adenocarcinoma with mural nodule of high-grade sarcoma. The mucinous and sarcomatous components revealed a mutation in codon 12 of the K-RAS gene of a different nucleotide substitution, indicating that these 2 tumor components were different clones of the same tumor. Herein, we are reporting another case of a 20-yr-old woman who presented with 22 cm pelvic mass, omental caking, and ascites. A diagnosis of invasive mucinous carcinoma with mural nodules of anaplastic carcinoma was rendered. K-RAS gene mutation studies revealed p.G12V, c.35G>T mutation in the 2 components of the tumor, which is the most common mutation reported in mucinous tumors of the ovary. The fact that sarcomatous or anaplastic carcinomatous mural nodules in ovarian mucinous tumors display the same K-RAS mutations as their underlying mucinous neoplasms provides supportive evidence that at least some malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors, rather than a collision of 2 divergent tumor types. PMID:25473748

  10. The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors

    PubMed Central

    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

  11. Hereditary Papillary Renal Cell Carcinoma

    MedlinePlus

    ... is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to have children who do not carry the mutation. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain ...

  12. Primary Retroperitoneal Mucinous Cystadenoma

    PubMed Central

    Han, Weon Cheol

    2016-01-01

    Mucinous cystadenomas and cystadenocarcinomas of the ovary are clinically and histopathologically well-established common tumors. However, primary retroperitoneal mucinous cystic tumors are extremely rare, and although their histopathogenesis is still uncertain, several theories have been proposed. Most authors suggest that they develop through mucinous metaplasia in a preexisting mesothelium-lined cyst. An accurate preoperative diagnosis of these tumors is difficult because no effective diagnostic measures have been established. Delay in diagnosis and treatment of this tumor may be fatal for the patient because of complications such as rupture, infection, and malignant transformation. We describe the case of a 31-year-old woman with abdominal pain and a palpable mass. Computed tomography of the abdomen revealed a retroperitoneal cystic mass, which was resected successfully through laparoscopy. Histopathological examination of the resected mass confirmed the diagnosis of a primary retroperitoneal mucinous cystadenoma. The patient was discharged on postoperative day 5 without any complications. PMID:26962534

  13. Anaplastic Transformation of Papillary Thyroid Cancer in the Retroperitoneum

    PubMed Central

    Solomon, James P.; Wen, Fang; Jih, Lily J.

    2015-01-01

    Anaplastic thyroid carcinoma is an aggressive variant of thyroid cancer that in most cases arises from anaplastic transformation of terminally differentiated thyroid carcinomas. This process usually occurs in the thyroid or cervical lymph nodes. Anaplastic transformation in distant metastatic sites is exceedingly rare, only previously documented in a few case reports. We report a rare case of anaplastic transformation of papillary thyroid carcinoma within a large retroperitoneal metastasis in a 64-year-old male 30 years after the initial diagnosis. PMID:26351607

  14. The management of papillary breast lesions on core biopsy: the contentious issues.

    PubMed

    Rozen, Warren M; Joseph, Samuel; Murphy, Craig

    2007-06-01

    The management of papillary lesions of the breast diagnosed on core needle biopsy is highly contentious. Papillary lesions are epithelial proliferations of breast tissue and are on a continuum of mutations with atypical hyperplastic lesions and in situ carcinoma. With the current literature suggesting that excisional biopsy of papillary lesions might not be required, we discuss a unique case that suggests otherwise. We present a 21-year-old woman with multiple papillary lesions on core biopsy of a breast lesion, and a subsequent excisional biopsy revealing extensive in situ carcinoma of the breast. This finding necessitated total mastectomy. This unique case highlights that core biopsy specimens are unable to effectively exclude adjacent in situ carcinoma and suggests that papillary lesions diagnosed on core needle biopsy require excisional biopsy. PMID:17592679

  15. Renal papillary necrosis

    MedlinePlus

    ... renal papillary necrosis, especially after taking over-the-counter pain medicines ... diabetes or sickle cell anemia may reduce your risk. To prevent renal ... over-the-counter pain relievers. Do not take more than the ...

  16. Advanced Stage Mucinous Adenocarcinoma of the Ovary is both Rare and Highly Lethal: A Gynecologic Oncology Group Study

    PubMed Central

    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

  17. A case of papillary microcarcinoma of the thyroid with abundant colloid (masquerading as colloid goiter with papillary hyperplasia): Cytological evaluation with histopathological correlation.

    PubMed

    Muthalagan, Elancheran; Subashchandrabose, Priya; Sivasubramanian, Priya Banthavi; Venkateswaran, Sarada

    2015-01-01

    Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid. On fine-needle aspiration (FNA) cytology smears of conventional PTC, the background usually shows scanty, bubble gum-like colloid. But the macrofollicular variant and papillary microcarcinoma reveals abundant thin colloid in the background. We report a case of papillary carcinoma of thyroid in a 37-year-old female with abundant thin colloid, obscuring the nuclear morphology in many clusters, along with the presence of typical nuclear features within occasional clusters in FNA cytology and hence, masquerading as colloid goiter with papillary hyperplasia. Histopathological examination of the total thyroidectomy specimen revealed papillary microcarcinomatous focus in a background of nodular hyperplasia. The differential diagnosis of PTC should be entertained even in colloid-rich FNA smears if the typical nuclear features are present. Hence, a meticulous search for any fragment with nuclear features of PTC is mandatory before labeling the smears as benign nodular hyperplasia. PMID:26811580

  18. A case of papillary microcarcinoma of the thyroid with abundant colloid (masquerading as colloid goiter with papillary hyperplasia): Cytological evaluation with histopathological correlation

    PubMed Central

    Muthalagan, Elancheran; Subashchandrabose, Priya; Sivasubramanian, Priya Banthavi; Venkateswaran, Sarada

    2015-01-01

    Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid. On fine-needle aspiration (FNA) cytology smears of conventional PTC, the background usually shows scanty, bubble gum-like colloid. But the macrofollicular variant and papillary microcarcinoma reveals abundant thin colloid in the background. We report a case of papillary carcinoma of thyroid in a 37-year-old female with abundant thin colloid, obscuring the nuclear morphology in many clusters, along with the presence of typical nuclear features within occasional clusters in FNA cytology and hence, masquerading as colloid goiter with papillary hyperplasia. Histopathological examination of the total thyroidectomy specimen revealed papillary microcarcinomatous focus in a background of nodular hyperplasia. The differential diagnosis of PTC should be entertained even in colloid-rich FNA smears if the typical nuclear features are present. Hence, a meticulous search for any fragment with nuclear features of PTC is mandatory before labeling the smears as benign nodular hyperplasia. PMID:26811580

  19. Mucin-Type O-Glycosylation in Gastric Carcinogenesis.

    PubMed

    Duarte, Henrique O; Freitas, Daniela; Gomes, Catarina; Gomes, Joana; Magalhães, Ana; Reis, Celso A

    2016-01-01

    Mucin-type O-glycosylation plays a crucial role in several physiological and pathological processes of the gastric tissue. Modifications in enzymes responsible for key glycosylation steps and the consequent abnormal biosynthesis and expression of their glycan products constitute well-established molecular hallmarks of disease state. This review addresses the major role played by mucins and associated O-glycan structures in Helicobacter pylori adhesion to the gastric mucosa and the subsequent establishment of a chronic infection, with concomitant drastic alterations of the gastric epithelium glycophenotype. Furthermore, alterations of mucin expression pattern and glycan signatures occurring in preneoplastic lesions and in gastric carcinoma are also described, as well as their impact throughout the gastric carcinogenesis cascade and in cancer progression. Altogether, mucin-type O-glycosylation alterations may represent promising biomarkers with potential screening and prognostic applications, as well as predictors of cancer patients' response to therapy. PMID:27409642

  20. Cystic mucinous adenocarcinoma of the lung: a case report

    PubMed Central

    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

  1. Expression of osteopontin and CD44 molecule in papillary renal cell tumors.

    PubMed

    Matusan, Koviljka; Dordevic, Gordana; Mozetic, Vladimir; Lucin, Ksenija

    2005-01-01

    The aim of the study was to analyze the expression of CD44 adhesion molecule and its ligand osteopontin in papillary renal cell tumors, and to assess the possible prognostic significance of CD44 and osteopontin expression in papillary renal cell carcinomas. The expression of the standard and v6 exon containing isoforms of CD44 molecule, as well as of its ligand osteopontin, was immunohistochemically evaluated in 43 papillary renal cell tumors, which included 5 adenomas and 38 carcinomas. In order to assess their prognostic significance, the results obtained in papillary renal cell carcinomas were compared to usual clinicopathological parameters such as tumor size, histological grade, pathological stage, and Ki-67 proliferation index. Normal renal tissue was negative for CD44s and v6 isoforms, while the expression of osteopontin was found in distal tubular epithelial cells in the form of cytoplasmic granular positivity. CD44s and v6 isoforms were upregulated in 22 (58%) and 12 (32%) out of 38 carcinomas, respectively. Among all clinicopathological parameters examined, we only found significant association of CD44s-positive carcinomas with lower pathological stage (p=0.026). Papillary renal cell adenomas were generally negative for CD44s, except for focal positivity found in one sample. The osteopontin protein was detected in all adenomas and all papillary renal cell carcinomas, except one. Our results show constitutive expression of osteopontin in papillary renal tumors, including papillary renal cell adenomas. The upregulation of CD44s and v6 isoforms, although found in a considerable number of papillary renal cell carcinomas, does not appear to have any prognostic value in this type of renal cancer. PMID:15999156

  2. Efficacy of a novel mucolytic agent on pseudomyxoma peritonei mucin, with potential for treatment through peritoneal catheters.

    PubMed

    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

  3. Efficacy of a novel mucolytic agent on pseudomyxoma peritonei mucin, with potential for treatment through peritoneal catheters

    PubMed Central

    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

  4. Ciliated muconodular papillary tumor: a solitary peripheral lung nodule in a teenage girl.

    PubMed

    Lau, Kah Weng; Aubry, Marie-Christine; Tan, Gek San; Lim, Chong Hee; Takano, Angela Maria

    2016-03-01

    Papillary tumors of the peripheral lung containing ciliated cells and extracellular mucin include solitary peripheral ciliated glandular papilloma, ciliated muconodular papillary tumor, and well-differentiated papillary adenocarcinoma with cilia formation. We report the case of a 19-year-old woman who was a nonsmoker and presented with an incidental small peripheral lung nodule. The resection specimen showed a soft grayish nodule. Histologic examination further revealed a relatively circumscribed mucinous nodule featuring a tubulopapillary tumor composed of ciliated columnar cells and goblet cells, accompanied with abundant extracellular mucin. No lepidic growth pattern was evident. The tumor cells were immunoreactive for cytokeratin 7, thyroid transcription factor-1, and carcinoembryonic antigen, whereas p63 and cytokeratin 5/6 highlighted the presence of basal cells. Next-generation sequencing did not identify any genetic alterations in targeted regions and mutational hotspots of a panel of 22 genes commonly implicated in lung and colon cancers. Taken together, our case was most likely a ciliated muconodular papillary tumor. PMID:26826405

  5. Undifferentiated Carcinoma With Osteoclastic Giant Cells of the Pancreas: Clinicopathologic Analysis of 38 Cases Highlights a More Protracted Clinical Course Than Currently Appreciated.

    PubMed

    Muraki, Takashi; Reid, Michelle D; Basturk, Olca; Jang, Kee-Taek; Bedolla, Gabriela; Bagci, Pelin; Mittal, Pardeep; Memis, Bahar; Katabi, Nora; Bandyopadhyay, Sudeshna; Sarmiento, Juan M; Krasinskas, Alyssa; Klimstra, David S; Adsay, Volkan

    2016-09-01

    Undifferentiated carcinomas with osteoclastic giant cells of the pancreas (OGC) are rare tumors. The current impression in the literature is that they are highly aggressive tumors similar in prognosis to ductal adenocarcinomas. In this study, the clinicopathologic characteristics of 38 resected OGCs were investigated and contrasted with 725 resected pancreatic ductal adenocarcinomas without osteoclastic cells (PDCs). The frequency among systematically reviewed pancreatic cancers was 1.4%. OGCs showed a slight female predominance (62.9%, vs. 51.4% in PDCs). The mean age was 57.9 years (vs. 65.0). The mean size of invasive cancer was 5.3 cm (vs. 3.2). They were characterized by nodular, pushing-border growth, and 8 arose in tumoral intraepithelial neoplasms (4 in mucinous cystic neoplasms, 4 in intraductal papillary mucinous neoplasms type lesions), and 23 (61%) also showed prominent intraductal/intracystic growth. Twenty-nine (76%) had an invasive ductal/tubular adenocarcinoma component. Osteoid was seen in 12. Despite their larger size, perineural invasion and nodal metastasis were uncommon (31.6% and 22.6%, vs. 85.5% and 64.0%, respectively). Immunohistochemistry performed on 24 cases revealed that osteoclastic cells expressed the histiocytic marker CD68, and background spindle cells and pleomorphic/giant carcinoma cells often showed p53 and often lacked cytokeratin. Survival of OGCs was significantly better than that of PDCs (5 yr, 59.1% vs. 15.7%, respectively, P=0.0009). In conclusion, pancreatic OGCs present with larger tumor size and in slightly younger patients than PDC, 21% arise in mucinous cystic neoplasms/intraductal papillary mucinous neoplasms, and 61% show intraductal/intracystic polypoid growth. OGCs have a significantly better prognosis than is currently believed in the literature. PMID:27508975

  6. Residual mucin and response after neoadjuvant chemotherapy (NAC) in breast cancer.

    PubMed

    Jove, Maria; Verghese, Eldo; Sharma, Nisha; Lane, Sally

    2016-01-01

    Neoadjuvant chemotherapy (NAC) is the standard of care for patients with breast cancer with inoperable disease or smaller tumours who might benefit from a conservative surgery after downstaging of their disease. Nevertheless, evidence shows that preoperative and postoperative chemotherapy are equivalent in terms of long-term survival. Response and histological changes after NAC have been widely studied in invasive ductal carcinoma not otherwise specified, but there is a paucity of characterisation of patterns of response to chemotherapy in less frequent histological types. We report extensive residual mucin deposits after chemotherapy in a woman with locally advanced breast cancer and a prominent mucinous component at diagnosis. Interestingly, residual mucin was co-located with the initial tumour, in the breast as well as in the axillary lymph nodes. The distribution of mucin may be a valuable marker of the extent of mucinous carcinomas prior to NAC. PMID:27154986

  7. Co-occurrence of subacute granulomatous thyroiditis and papillary microcarcinoma.

    PubMed

    Şenel, Fatma; Karaman, Hatice; Ertan, Tamer

    2016-01-01

    Subacute thyroiditis, which is most commonly observed after a viral infection and may heal spontaneously, is an inflammatory thyroid disease. The co-occurrence of subacute thyroiditis and papillary carcinoma is quite rare. A 58-year-old male patient who applied to our hospital with the complaints of sore throat and neck swelling was performed total thyroidectomy following physical examination, ultrasound, and laboratory analysis. In histopathological examination, many granuloma structures were observed in both lobes, and a papillary microcarcinoma focus of 2 mm in diameter was seen in the left lobe. The co-occurrence of subacute thyroiditis and papillary carcinoma was deemed worthy of presentation as it is rarely observed. PMID:27405083

  8. Identification of Intermediate- to High-Risk Papillary Thyroid Carcinoma Patients Who May Be Safely Managed without the Performance of Delayed Stimulated Thyroglobulin Measurements following Total Thyroidectomy and Radioactive Iodine Therapy.

    PubMed

    Kim, Kyung-Hee; Kim, Min-Hee; Lim, Ye-Jee; Lee, Ihn Suk; Bae, Ja-Seong; Lim, Dong-Jun; Baek, Ki Hyun; Lee, Jong Min; Kang, Moo-Il; Cha, Bong-Yun

    2015-01-01

    Background. The measurement of stimulated thyroglobulin (sTg) after total thyroidectomy and remnant radioactive iodine (RAI) ablation is the gold standard for monitoring disease status in patients with papillary thyroid carcinomas (PTCs). The aim of this study was to determine whether sTg measurement during follow-up can be avoided in intermediate- and high-risk PTC patients. Methods. A total of 346 patients with PTCs with an intermediate or high risk of recurrence were analysed. All of the patients underwent total thyroidectomy as well as remnant RAI ablation and sTg measurements. Preoperative and postoperative parameters were included in the analysis. Results. Among the preoperative parameters, age below 45 years and preoperative Tg above 19.4 ng/mL were significant risk factors for predicting detectable sTg during follow-up. Among the postoperative parameters, thyroid capsular invasion, lymph node metastasis, and ablative Tg above 2.9 ng/mL were independently correlated with a detectable sTg range. The combination of ablative Tg less than 2.9 ng/mL with pre- and postoperative independent risk factors for detectable sTg increased the negative predictive value for detectable sTg up to 98.5%. Conclusions. Based on pre- and postoperative parameters, a substantial proportion of patients with PTCs in the intermediate- and high-risk classes could avoid aggressive follow-up measures. PMID:25649811

  9. hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor for immunotherapy of uterine serous papillary carcinoma

    PubMed Central

    Cocco, E; Hu, Z; Richter, C E; Bellone, S; Casagrande, F; Bellone, M; Todeschini, P; Krikun, G; Silasi, D-A; Azodi, M; Schwartz, P E; Rutherford, T J; Buza, N; Pecorelli, S; Lockwood, C J; Santin, A D

    2010-01-01

    Background: Uterine serous papillary adenocarcinoma (USPC) is a highly aggressive variant of endometrial cancer. Human immuno-conjugate molecule (hI-con1) is an antibody-like molecule targeted against tissue factor (TF), composed of two human Factor VII (fVII) as the targeting domain, fused to human immunoglobulin (Ig) G1 Fc as an effector domain. We evaluated hI-con1 potential activity against primary chemotherapy-resistant USPC cell lines expressing different levels of TF. Methods: A total of 16 formalin-fixed, paraffin-embedded USPC samples were evaluated by immunohistochemistry (IHC) for TF expression. Six primary USPC cell lines, half of which overexpress the epidermal growth factor type II (HER2/neu) receptor at 3+ levels, were assessed by flow cytometry and real-time PCR for TF expression. Sensitivity to hI-con1-dependent cell-mediated cytotoxicity (IDCC) was evaluated in 5-hour-chromium release assays. Finally, to investigate the effect of interleukin-2 (IL-2) on IDCC, 5-h 51Cr assays were also conducted in the presence of low doses of IL-2 (i.e., 50–100 IU ml−1). Results: Cytoplasmic and/or membrane TF expression was observed in all 16 (100%) USPC samples tested by IHC, but not in normal endometrium. High expression of TF was found in 50% (three out of six) of the USPC cell lines tested by real-time PCR and flow cytometry when compared with normal endometrial cells (NECs; P<0.001). Uterine serous papillary adenocarcinoma cell lines overexpressing TF, regardless of their high or low HER2/neu expression, were highly sensitive to IDCC (mean killing±s.d., 65.6±3.7%, range 57.5–77.0%, P<0.001), although negligible cytotoxicity against USPC was seen in the absence of hI-con1 or in the presence of Rituximab control antibody. The addition of low doses of IL-2 further increased the cytotoxic effect induced by hI-con1 against chemotherapy-resistant USPC. Conclusion: hI-con1 induces strong cytotoxicity against primary chemotherapy-resistant USPC cell

  10. Expression profile of mucins in ovarian mucinous tumors: distinguishing primary ovarian from metastatic tumors.

    PubMed

    Wang, Jayson; El-Bahrawy, Mona A

    2014-03-01

    Ovarian mucinous tumors (OMTs) of the intestinal type share morphologic features with primary tumors of other sites, and it can often be difficult to distinguish primary ovarian from metastatic mucinous tumors. MUC1, MUC2, MUC5AC, and MUC6 expressions were studied by immunohistochemistry in 36 OMTs of intestinal type (17 malignant, 19 borderline), 18 pancreatic, 12 biliary, 15 esophageal, 9 gastric, and 7 colorectal/appendiceal adenocarcinomas. All samples were from primary sites, except for colorectal tumors which were from ovarian metastases. Borderline and malignant OMTs show similar mucin immunoprofile, being strongly and uniformly positive for MUC5AC (97.2% of cases), whereas only focally positive for MUC1 (19.4%), MUC2 (38.9%), and MUC6 (22.2%). The positive frequencies of pancreatic adenocarcinomas for MUC1, MUC2, MUC5AC, and MUC6, respectively, were 100%, 16.7%, 94.4%, and 61.1%; for biliary (cholangiocarcinomas) were 91.7%, 0%, 16.7%, and 8.3%; for esophageal carcinomas were 73.3%, 33.3%, 53.3%, and 26.7%; for gastric carcinomas were 44.4%, 44.4%, 44.4%, and 0% and for lower gastrointestinal tract cancers were 28.6%, 85.7%, 42.9%, and 0%. Our study shows that OMTs are usually MUC5AC+/MUC1-, which is different from pancreatic, biliary, esophageal, gastric, and colorectal/appendiceal carcinomas. We recommend that these mucin stains be added to the panel of immunostains to differentiate metastatic tumors to the ovary from primary OMTs. PMID:24487472

  11. A multi-gene approach to differentiate papillary thyroid carcinoma from benign lesions: gene selection using support vector machines with bootstrapping

    PubMed Central

    Fujarewicz, Krzysztof; Jarząb, Michał; Eszlinger, Markus; Krohn, Knut; Paschke, Ralf; Oczko-Wojciechowska, Małgorzata; Wiench, Małgorzata; Kukulska, Aleksandra; Jarząb, Barbara; Świerniak, Andrzej

    2007-01-01

    Selection of novel molecular markers is an important goal of cancer genomics studies. The aim of our analysis was to apply the multivariate bioinformatical tools to rank the genes – potential markers of papillary thyroid cancer (PTC) according to their diagnostic usefulness. We also assessed the accuracy of benign/malignant classification, based on gene expression profiling, for PTC. We analyzed a 180-array dataset (90 HG-U95A and 90 HG-U133A oligonucleotide arrays), which included a collection of 57 PTCs, 61 benign thyroid tumors, and 62 apparently normal tissues. Gene selection was carried out by the support vector machines method with bootstrapping, which allowed us 1) ranking the genes that were most important for classification quality and appeared most frequently in the classifiers (bootstrap-based feature ranking, BBFR); 2) ranking the samples, and thus detecting cases that were most difficult to classify (bootstrap-based outlier detection). The accuracy of PTC diagnosis was 98.5% for a 20-gene classifier, its 95% confidence interval (CI) was 95.9–100%, with the lower limit of CI exceeding 95% already for five genes. Only 5 of 180 samples (2.8%) were misclassified in more than 10% of bootstrap iterations. We specified 43 genes which are most suitable as molecular markers of PTC, among them some well-known PTC markers (MET, fibronectin 1, dipeptidylpeptidase 4, or adenosine A1 receptor) and potential new ones (UDP-galactose-4-epimerase, cadherin 16, gap junction protein 3, sushi, nidogen, and EGF-like domains 1, inhibitor of DNA binding 3, RUNX1, leiomodin 1, F-box protein 9, and tripartite motif-containing 58). The highest ranking gene, metallophosphoesterase domain-containing protein 2, achieved 96.7% of the maximum BBFR score. PMID:17914110

  12. Clear cell-papillary renal cell carcinoma of the kidney not associated with end-stage renal disease: clinicopathologic correlation with expanded immunophenotypic and molecular characterization of a large cohort with emphasis on relationship with renal angiomyoadenomatous tumor.

    PubMed

    Aron, Manju; Chang, Elena; Herrera, Loren; Hes, Ondrej; Hirsch, Michelle S; Comperat, Eva; Camparo, Philippe; Rao, Priya; Picken, Maria; Michal, Michal; Montironi, Rodolfo; Tamboli, Pheroze; Monzon, Federico; Amin, Mahul B

    2015-07-01

    Clear cell-papillary renal cell carcinoma (CC-Pap RCC) is a recently described renal tumor initially reported in the setting of end-stage renal disease (ESRD). It has unique morphologic and immunohistochemical features that differentiate it from the more common clear cell RCC and papillary RCC. Recently, these tumors have also been described in a sporadic setting. We studied 64 cases of CC-Pap RCC not associated with ESRD (57 CC-Pap RCCs and 7 cases with features of renal angiomyoadenomatous tumors [RAT] including 5 initially diagnosed as such). The morphologic features of all cases and the immunohistochemical profile of 59 cases were studied along with the clinical and molecular features of 30 and 12 cases, respectively. All the tumors were well circumscribed with a mean tumor size of 2.6 cm and showed a wide array of architectural patterns, usually mixed, including tubular (77%), papillary (62%), tubulocystic (52%), and compact nested (21%). Seventy-three percent of the cases showed areas in which the tumor nuclei had a distinct orientation away from the basement membrane. Ninety-two percent of the cases had a low Fuhrman nuclear grade (nuclear grade 2%-86%, and nuclear grade 1%-6%); however, 8% cases showed foci of Fuhrman nuclear grade 3. In 4 cases, epithelial tumor comprised <5% of the tumor; >95% of the tumor was cystic or hyalinized. The stroma varied from being minimal to occasionally prominent myxoid to hyalinized and rarely with organized amianthoid fibers or well-defined smooth muscle bundles. Pathologic stage was reliably assigned in 60 cases, of which 93.3% (56 cases) were pT1, 3.3% (2 cases) were pT2, and 3.3% (2 cases) were pT3a with extension into the perinephric fat. One case had coagulative necrosis; sarcomatoid change and vascular invasion was not identified. The tumors showed a fairly typical immunoprofile characterized by positivity for CK7 (100%), HMCK (96%), CAIX (94%), and vimentin (100%) with negativity for AMACR, RCC, and TFE3; CD10 was

  13. Detecting, visualising, and quantifying mucins.

    PubMed

    Harrop, Ceri A; Thornton, David J; McGuckin, Michael A

    2012-01-01

    The extreme size, extensive glycosylation, and gel-forming nature of mucins make them a challenge to work with, and methodologies for the detection of mucins must take into consideration these features to ensure that one obtains both accurate and meaningful results. In understanding and appreciating the nature of mucins, this affords the researcher a valuable toolkit which can be used to full advantage in detecting, quantifying, and visualising mucins. The employment of a combinatorial approach to mucin detection, using antibody, chemical, and lectin detection methods, allows important information to be gleaned regarding the size, extent of glycosylation, specific mucin species, and distribution of mucins within a given sample. In this chapter, the researcher is guided through considerations into the structure of mucins and how this both affects the detection of mucins and can be used to full advantage. Techniques including ELISA, dot/slot blotting, and Western blotting, use of lectins and antibodies in mucin detection on membranes as well as immunohistochemistry and immunofluorescence on both tissues and cells grown on Transwell™ inserts are described. Notes along with each section advice the researcher on best practice and describe any associated limitations of a particular technique from which the researcher can further develop a particular protocol. PMID:22259129

  14. Mucin1 mediates autocrine transforming growth factor beta signaling through activating the c-Jun N-terminal kinase/activator protein 1 pathway in human hepatocellular carcinoma cells.

    PubMed

    Li, Qiongshu; Liu, Guomu; Shao, Dan; Wang, Juan; Yuan, Hongyan; Chen, Tanxiu; Zhai, Ruiping; Ni, Weihua; Tai, Guixiang

    2015-02-01

    In a previous study, we observed by global gene expression analysis that oncogene mucin1 (MUC1) silencing decreased transforming growth factor beta (TGF-β) signaling in the human hepatocellular carcinoma (HCC) cell line SMMC-7721. In this study, we report that MUC1 overexpression enhanced the levels of phosphorylated Smad3 linker region (p-Smad3L) (Ser-213) and its target gene MMP-9 in HCC cells, suggesting that MUC1 mediates TGF-β signaling. To investigate the effect of MUC1 on TGF-β signaling, we determined TGF-β secretion in MUC1 gene silencing and overexpressing cell lines. MUC1 expression enhanced not only TGF-β1 expression at the mRNA and protein levels but also luciferase activity driven by a TGF-β promoter, as well as elevated the activation of c-Jun N-terminal kinase (JNK) and c-Jun, a member of the activation protein 1 (AP-1) transcription factor family. Furthermore, pharmacological reduction of TGF-β receptor (TβR), JNK and c-Jun activity inhibited MUC1-induced autocrine TGF-β signaling. Moreover, a co-immunoprecipitation assay showed that MUC1 directly bound and activated JNK. In addition, both MUC1-induced TGF-β secretion and exogenous TGF-β1 significantly increased Smad signaling and cell migration, which were markedly inhibited by either TβR inhibitor or small interfering RNA silencing of TGF-β1 gene in HCC cells. The high correlation between MUC1 and TGF-β1 or p-Smad3L (Ser-213) expression was shown in tumor tissues from HCC patients by immunohistochemical staining analysis. Collectively, these results indicate that MUC1 mediates autocrine TGF-β signaling by activating the JNK/AP-1 pathway in HCC cells. Therefore, MUC1 plays a key role in HCC progression and could serve as an attractive target for HCC therapy. PMID:25526895

  15. Stromal modulation and its role in the diagnosis of papillary patterned thyroid lesions.

    PubMed

    Daoud, Sahar Aly; Esmail, Reham Shehab El Nemr; Hareedy, Amal Ahmed; Khalil, Abdullah

    2015-01-01

    The papillary patterned lesion of thyroid may be challenging with many diagnostic pitfalls. Tumor stroma plays an important part in the determination of the tumor phenotype. CD34 is thought to be involved in the modulation of cell adhesion and signal transduction as CD34(+) fibrocytes are potent antigen-presenting cells. Smooth muscle actin (SMA) positivity could be diagnostic for fibroblast activation during tumorigenesis. We aimed to examine the expression of CD34 and alphaSMA in the stroma of papillary thyroid hyperplasia, papillary thyroid carcinoma and papillary tumors of uncertain malignant potential in order to elucidate their possible differential distribution and roles. A total number of 54 cases with papillary thyroid lesions were studied by routine HandE staining, CD34 and ASMA immunostaining. ASMA was not expressed in benign papillary hyperplastic lesions while it was expressed in papillary carcinoma, indicating that tumors have modulated stroma. Although the stroma was not well developed in papillary lesions with equivocal features of uncertain potentiality, CD34 was notable in such cases with higher incidence in malignant cases. So ASMA as well as CD34 could predict neoplastic behavior, pointing to the importance of the stromal role. Differences between groups suggest that the presence of CD34 + stromal cells is an early event in carcinogensis and is associated with neoplasia, however ASMA+ cells are more likely to be associated with malignant behavior and metastatic potential adding additional tools to the light microscopic picture helping in diagnosis of problematic cases with HandE. PMID:25921136

  16. Salivary Mucin 19 Glycoproteins

    PubMed Central

    Culp, David J.; Robinson, Bently; Cash, Melanie N.; Bhattacharyya, Indraneel; Stewart, Carol; Cuadra-Saenz, Giancarlo

    2015-01-01

    Saliva functions in innate immunity of the oral cavity, protecting against demineralization of teeth (i.e. dental caries), a highly prevalent infectious disease associated with Streptococcus mutans, a pathogen also linked to endocarditis and atheromatous plaques. Gel-forming mucins are a major constituent of saliva. Because Muc19 is the dominant salivary gel-forming mucin in mice, we studied Muc19−/− mice for changes in innate immune functions of saliva in interactions with S. mutans. When challenged with S. mutans and a cariogenic diet, total smooth and sulcal surface lesions are more than 2- and 1.6-fold higher in Muc19−/− mice compared with wild type, whereas the severity of lesions are up to 6- and 10-fold higher, respectively. Furthermore, the oral microbiota of Muc19−/− mice display higher levels of indigenous streptococci. Results emphasize the importance of a single salivary constituent in the innate immune functions of saliva. In vitro studies of S. mutans and Muc19 interactions (i.e. adherence, aggregation, and biofilm formation) demonstrate Muc19 poorly aggregates S. mutans. Nonetheless, aggregation is enhanced upon adding Muc19 to saliva from Muc19−/− mice, indicating Muc19 assists in bacterial clearance through formation of heterotypic complexes with salivary constituents that bind S. mutans, thus representing a novel innate immune function for salivary gel-forming mucins. In humans, expression of salivary MUC19 is unclear. We find MUC19 transcripts in salivary glands of seven subjects and demonstrate MUC19 glycoproteins in glandular mucous cells and saliva. Similarities and differences between mice and humans in the expression and functions of salivary gel-forming mucins are discussed. PMID:25512380

  17. Benign mucinous metaplasia of the penis. A lesion resembling extramammary Paget's disease.

    PubMed

    Val-Bernal, J F; Hernández-Nieto, E

    2000-02-01

    Benign mucinous metaplasia in the surface epithelium of the genital area is rare and has only been reported once in the vulva. A unique case of benign mucinous metaplasia of the prepuce in a 65-year-old man is reported here. The lesion measured 0.6 cm, was located in the mucous surface of the foreskin, and showed acid mucin containing cells. We regard benign mucinous metaplasia as a reactive rather than a neoplastic process. The main lesions to be considered in the differential diagnosis are mucinous syringometaplasia, extramammary Paget's disease, cutaneous squamous cell carcinoma in situ with mucinous metaplasia, superficial spreading malignant melanoma, and epidermotropic metastasis. The confinement of mucin-containing cells to the epidermis, the absence of nuclear atypia, the basal orientation of the nuclei, the predominant location of the cells in the upper layers of the epithelium, and the fact that the mucinous cells are replacing the squamous epithelium rather that infiltrating it, all assist in recognizing mucinous metaplasia of the penis as a specific and benign entity. PMID:10678702

  18. Characterization of pig colonic mucins.

    PubMed Central

    Fogg, F J; Hutton, D A; Jumel, K; Pearson, J P; Harding, S E; Allen, A

    1996-01-01

    Pig colonic mucins isolated from the adherent mucus gel in the presence of proteinase inhibitors were solubilized by homogenization and the component mucins fractionated by CsC1 density-gradient centrifugation. Polymeric and reduced pig colonic mucin were both largely excluded on Sepharose CL-2B, papain-digested colonic mucin was included. The M(r) values of polymeric, reduced and digested mucins were 5.5 x 10(6), 2.1 x 10(6) and 0.6 x 10(6) respectively. This suggests that pig colonic mucin is comprised of 2-3 subunits, each subunit containing 3-4 glycosylated regions. The intrinsic viscosities of polymeric, reduced and digested mucin were 240 ml.g-1, 100 ml.g-1 and 20 ml.g-1 respectively. Polymeric pig colonic mucin comprised 16% protein per mg of glycoprotein and was rich in serine, threonine and proline (43% of total amino acids). There were approx. 150 disulphide bridges and 53 free thiol groups per mucin polymer. A seventh of the protein content was lost on reduction. This protein was particularly rich in proline and the hydrophobic amino acids. Papain-digested pig colonic mucin contained 11% protein per mg of glycoprotein and was rich in serine, threonine, glutamate and aspartate. All types of amino acids with the exception of aspartate were lost on digestion. The amino acid analysis of the proteolytically digested regions of pig colonic mucin are markedly different to the tandem repeat regions of the human mucin genes shown to be expressed in the colon. PMID:8670173

  19. Villous Tumor of the Urinary Bladder Resembling Low-grade Mucinous Neoplasm of the Appendix

    PubMed Central

    Ito, Ayako; Sakura, Yuma; Sugimoto, Mikio; Kakehi, Yoshiyuki; Kuroda, Naoto

    2016-01-01

    Mucinous neoplasms of the urinary tract are very rare. We present a 63-year-old-women who had a sessile papillary villous tumor in urinary bladder. Although transurethral resection of the bladder tumor (TURBT) was performed, the villous tumor repetitively recurred and gradually spread to the entire surface of bladder lumen. Histopathologic and immunohistochemical examination showed that the lesion was very similar to low-grade mucinous neoplasm arising in appendix vermiformis. There are no reports on appendiceal metaplasia of urinary bladder mucosa. In this case, we describe this unprecedented neoplasm as “villous tumor of the urinary bladder resembling low-grade mucinous neoplasm of the appendix.” PMID:27169015

  20. Mucinous tumors of the ovary: current thoughts on diagnosis and management.

    PubMed

    Brown, Jubilee; Frumovitz, Michael

    2014-06-01

    Mucinous tumors of the ovary represent a spectrum of neoplastic disorders, including benign mucinous cystadenoma, pseudomyxoma peritonei, mucinous tumors of low malignant potential (borderline), and invasive mucinous ovarian carcinoma. These tumors are related closely to each other and are distinct from other histologic subtypes of epithelial ovarian neoplasms from a clinical, histologic, and molecular standpoint. A continuum appears to be present from benign to borderline to malignant, which is different from other types of epithelial ovarian cancer. Mutational profiles are also distinct, as KRAS mutations are common, but p53 and BRCA mutations are infrequent. These characteristics lead to specific biologic behavior and guide both clinical management and research efforts in patients with mucinous ovarian tumors. PMID:24777667

  1. Papillary adenocarcinoma of the renal pelvis with renal calculus: A rare case report

    PubMed Central

    LI, JIANLONG; LI, QING; YU, YI

    2016-01-01

    Papillary adenocarcinoma of the renal pelvis is a rare clinicopathology of a kidney tumor with renal calculus. In the present case report, percutaneous renal biopsy, nephroscope lithotripsy and radical nephroureterectomy within a papillary adenocarcinoma of the renal pelvis accompanied with renal calculus was performed on a 65-year-old patient, also including a report on the patient's data and a literature review. The histopathological features confirmed the diagnosis of papillary adenocarcinoma of the renal pelvis. Tumors of the renal pelvis are uncommon features of urothelial carcinoma, and papillary adenocarcinoma of the renal pelvis is a very unusual entity. The present case report describes papillary adenocarcinoma of the renal pelvis with renal calculus, which has rarely been previously reported. PMID:27123287

  2. Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic study of 11 cases.

    PubMed

    Din, Nasir Ud; Fatima, Saira; Kayani, Naila

    2016-06-01

    Mammary analogue secretory carcinoma (MASC) is a recently described tumor sharing the histologic, immunohistochemical, and molecular profile of secretory carcinoma of breast. We aimed to evaluate the morphologic and histochemical features needed/required for the diagnosis of MASC without adjunct of molecular analysis. Six retrospective cases suspicious for MASC and 5 prospective cases reported as MASC were included in the study. Molecular analysis of ETV6 by fluorescence in situ hybridization was performed at the University of Pittsburg, USA. The ages of the patients ranged from 9 to 60 years (mean, 27.5 years). Histologically, all tumors showed mixed growth patterns including microcystic, macrocystic, papillary, tubular, and solid, papillary the being most common pattern. The tumor cells showed round to oval vesicular nuclei with small nucleoli, and eosinophilic to vacuolated cytoplasm. All cases demonstrated luminal and cytoplasmic mucin on periodic acid-Schiff with and without diastase digestion and alcian blue stain. ETV6 fusion gene rearrangement by fluorescence in situ hybridization was detected in 10 of 11 tumors. Recurrences occurred in 3 patients, and 1 patient died of disease 5 years after surgery. In conclusion, MASC is a relatively rare salivary gland malignancy exhibiting distinct histologic and histochemical features which can help to differentiate it from other mimics. Histologically, papillary-cystic and microcystic patterns are the main clues to diagnosis. The follicular pattern of acinic cell carcinoma might represent MASC, as 4 cases in our series had this pattern. Two patients in our series were 9 and 9½ years old respectively, which are the youngest ages ever recorded for MASC. PMID:27180060

  3. Two Cases of Renal Cell Carcinoma Harboring a Novel STRN-ALK Fusion Gene.

    PubMed

    Kusano, Hironori; Togashi, Yuki; Akiba, Jun; Moriya, Fukuko; Baba, Katsuyoshi; Matsuzaki, Naomi; Yuba, Yoshiaki; Shiraishi, Yusuke; Kanamaru, Hiroshi; Kuroda, Naoto; Sakata, Seiji; Takeuchi, Kengo; Yano, Hirohisa

    2016-06-01

    Anaplastic lymphoma kinase (ALK) translocation renal cell carcinomas (RCCs) have been reported by several independent groups in recent times. The clinical behavior and histopathologic characteristics of these carcinomas are not fully understood because of the paucity of cases reported. Here, we describe 2 cases of RCC harboring a novel striatin (STRN)-ALK fusion. The first case was a 33-year-old woman with no sickle cell trait who underwent nephrectomy for right renal mass and had late recurrence in para-aortic lymph nodes twice 10 and 12 years after initial surgery. After the second recurrence, she was carefully observed without any treatment. Twenty-six years after the initial nephrectomy, the second para-aortic lymphadenectomy was performed, and gastrectomy was performed for newly developed primary gastric cancer. The resected para-aortic lymph nodes were largely replaced by metastatic carcinoma. The second case was a 38-year-old man with no sickle cell trait who underwent cytoreductive nephrectomy followed by sunitinib therapy for metastatic RCC. In both cases, the tumor showed solid, papillary, tubular, and mucinous cribriform structures. Psammoma bodies were occasionally seen in the stroma. Tumor cells had a large nucleus and prominent nucleoli with predominantly eosinophilic cytoplasm. Rhabdoid cells and signet-ring cells were also observed. Intracytoplasmic mucin deposition and background mucinous stroma were confirmed. In the second case, tumor necrosis was seen in some areas. Tumor cells exhibited diffuse positive staining for ALK in both cases. ALK translocation was confirmed by fluorescent in situ hybridization, and further gene analysis revealed a STRN-ALK fusion. These cases provide great insights into ALK translocation RCCs. PMID:26848800

  4. Non-pancreatic retroperitoneal mucinous neoplasms and a discussion of the differential diagnosis

    PubMed Central

    Cobb, Camilla; Raza, Anwar Sultana

    2016-01-01

    Retroperitoneal mucinous neoplasms are common and have a wide range of differential diagnoses to consider. It is of utmost importance to maintain a multidisciplinary approach when evaluating these lesions. Clinical history, surgical impression and radiographic studies should be obtained and used in conjunction with morphology and immunohistochemistry to help guide the pathologist to the correct diagnosis. We recently encountered a case of a 51-year-old man who presented with an 11.5 cm left-sided retroperitoneal mucinous neoplasm. This lesion was initially diagnosed as a low-grade mucinous carcinoma of probable pancreatic origin at an outside facility, and he was subsequently treated with chemotherapy. One year later he presented to our institution and underwent retroperitoneal en bloc resection of the 7-cm residual multiloculated mucinous neoplasm. When discussed at tumor board additional medical history was obtained, and review of the patient’s chart revealed a remote history of left orchiectomy for a mixed malignant germ cell tumor and metastatic embryonal carcinoma in 2 of 34 retroperitoneal/para-aortic lymph nodes. With no clinical evidence of tumor in the pancreas or extension from it, the predominately para-aortic location of the tumor favors a mucinous carcinoma arising from a rest of mature metastatic/proliferating teratoma that persisted after chemotherapy. This case illustrates the importance of a thorough history, however remote, and correlation with imaging in the development of differential diagnoses, as well as, the need to consider non-pancreaticobiliary sources of retroperitoneal mucinous tumors. PMID:27034817

  5. [Allelic disbalance in 1q32 area and microsatellite instability renal papillary adenocarcinoma].

    PubMed

    Moskvinina, L V; Mikhaĭlenko, D S; Andreeva, Iu Iu; Strel'nikov, V V; Zaletaev, D V

    2012-01-01

    Papillary adenocarcinoma is an abundant form of renal cell carcinoma. At present any diagnostic and prognostic molecular markers of papillary adenocarcinoma are absent, however some cytogenetic and molecular-genetic features of disease are known. According to literary data, the 1q32 duplication is associated with progressive deterioration of primary tumor. We have done a genetic typing (D1S2142 and D1S3465 locus) of 39 papillary adenocarcinoma cases, used PCR and fragment analyses of the 1q32 area. Frequency of the allelic disbalance was 36.8%; the microsatellite instability was found out in 48.7% of cases. The association of genetic disturbances with clinic-morphological features of papillary adenocarcinoma wasn't revealed. In some cases genetic heterogeneity of tumor-adjacent renal parenchyma and primary tumors was found out at multifocal renal carcinoma. For the first time we ve demonstrated that the allelic disbalance in 1q32 area and the microsatellite instability are frequent molecular-genetic disturbances in sporadic papillary carcinomas at all stages of the disease. Probably, the microsatellite instability is connected with progressive deterioration of primary tumor at renal papillary adenocarcinoma. PMID:22880406

  6. Giant papillary conjunctivitis.

    PubMed Central

    Donshik, P C

    1994-01-01

    Giant papillary conjunctivitis is a syndrome found frequently as a complication of contact lenses. Many variables can affect the onset and severity of the presenting signs and symptoms. Rigid gas permeable contact lenses appear to result in less severe signs and symptoms, with a longer time before the development of giant papillary conjunctivitis. Nonionic, low-water-content soft contact lenses tend to produce less severe signs and symptoms than ionic, low-water-content soft contact lenses. Enzymatic treatment appears to lessen the severity of signs and symptoms. The association of an allergy appears to play a role in the onset of the severity of the signs and symptoms but does not appear to affect the final ability of the individual to wear contact lenses. Using multiple treatment options, such as changing the polymer to a glyceryl methyl methacrylate or a rigid lens, or utilizing a soft lens on a frequent-replacement basis, can result in a success rate of over 90%. In individuals who still have a return of symptoms, the use of topical mast cell stabilizers or a nonsteroidal anti-inflammatory drug as an adjunctive therapy offers the added possibility of keeping these patients in contact lenses. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 11 A FIGURE 11 B FIGURE 11 C FIGURE 11 D PMID:7886881

  7. Molecular-genetic analysis is essential for accurate classification of renal carcinoma resembling Xp11.2 translocation carcinoma.

    PubMed

    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

  8. RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis

    PubMed Central

    Tsuta, K; Kohno, T; Yoshida, A; Shimada, Y; Asamura, H; Furuta, K; Kushima, R

    2014-01-01

    Background: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. Methods: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcription–PCR (RT–PCR) were performed to detect RET gene rearrangement. Results: In all, 22 cases (1.2%) showed RET rearrangements; all cases were of ADC histology. Of the 22 patients, 19 possessed KIF5B–RET fusion genes, whereas 3 possessed CCDC6–RET fusion genes. The RET-rearranged tumours were significantly more common in younger patients (P=0.038) and tended to occur in patients with no history of smoking (P=0.051). In addition, RET rearrangements were not associated with gender, occupational history (particularly radioactive exposure), tumour size, lymph node status, tumour stage, or patient survival. The predominant growth pattern in RET-rearranged ADCs was lepidic in 6 cases, papillary in 9 cases, acinar in 2 cases, micropapillary in 1 case, and solid in 4 cases. Cells with cytoplasmic mucin production were at least focally present in 12 of the 22 (54.5%) RET-rearranged ADC cases. Among the 21 analysed RET-rearranged tumours, RET immunopositivity was observed in 15 cases (71.4%), and was significantly associated with RET rearrangement (P<0.001). Conclusions: The RET rearrangements were observed in 1.2% of NSCLCs. All cases of RET rearrangement were ADCs. The RET rearrangements were more likely to be observed in younger patients. Although cytoplasmic mucin production was at least focally present in 54.5% of RET-rearranged ADCs, specific histological features were not detected. PMID:24504365

  9. [Mucinous ovarian neoplasms. Prognostically mostly excellent, infrequently a wolf in sheep's clothing].

    PubMed

    Lax, S; Staebler, A

    2014-07-01

    Mucinous ovarian neoplasms represent the second largest group of epithelial ovarian tumors after serous neoplasms, of which benign cystadenomas constitute more than 80 %. Mucinous cystadenomas and carcinomas cannot be distinguished by the clinical features or the mean age of onset of the disease. They typically occur unilaterally, are confined to the adnexae (FIGO stage I) and clinically present with non-specific abdominal symptoms or are diagnosed by chance. The mean age of disease onset is around 50 years old. The prognosis is excellent. Implants, peritoneal metastases and bilateral occurrence of ovarian mucinous neoplasms should lead to the suspicion of metastasis particularly from a gastrointestinal tumor. Neither microinvasion defined as a maximum extent of invasion of 5 mm, nor intraepithelial carcinoma characterized by high grade atypia without invasion, affect the prognosis of mucinous borderline tumors. Mucinous carcinomas typically show confluent glandular, expansile growth that leads to a labyrinth-like pattern. A destructive infiltrative or nodular growth pattern, however, should lead to the consideration of metastasis. Mural nodules that may reveal a spindle cell sarcomatous or anaplastic carcinomatous pattern occur infrequently in mucinous and do not affect the prognosis. Pax8 positivity is indicative of a primary ovarian neoplasm. In this case, however, mucinous tumors associated with teratomas may show the colonic immunoreaction pattern (CK7-/CK20+/CDX2+). The rare mucinous tumors with endocervical differentiation are now designated as seromucinous tumors and consist of two or more distinct cell types, are frequently associated with endometriosis and seem to show a molecular genetic relationship to endometrioid neoplasms. PMID:24962632

  10. Cytopathological Analysis of Cyst Fluid Enhances Diagnostic Accuracy of Mucinous Pancreatic Cystic Neoplasms

    PubMed Central

    Utomo, Wesley K.; Braat, Henri; Bruno, Marco J.; van Eijck, Casper H.J.; Koerkamp, Bas Groot; Krak, Nanda C.; van de Vreede, Adriaan; Fuhler, Gwenny M.; Peppelenbosch, Maikel P.; Biermann, Katharina

    2015-01-01

    Abstract Widespread use of cross-sectional imaging and increasing age of the general population has increased the number of detected pancreatic cystic lesions. However, several pathological entities with a variety in malignant potential have to be discriminated to allow clinical decision making. Discrimination between mucinous pancreatic cystic neoplasms (PCNs) and nonmucinous pancreatic lesions is the primary step in the clinical work-up, as malignant transformation is mostly associated with mucinous PCN. We performed a retrospective analysis of all resected PCN in our tertiary center from 2000 to 2014, to evaluate preoperative diagnostic performance and the results of implementation of the consensus guidelines over time. This was followed by a prospective cohort study of patients with an undefined pancreatic cyst, where the added value of cytopathological mucin evaluation to carcinoembryonic antigen (CEA) in cyst fluid for the discrimination of mucinous PCN and nonmucinous cysts was investigated. Retrospective analysis showed 115 patients operated for a PCN, with a correct preoperative classification in 96.2% of the patients. High-grade dysplasia or invasive carcinoma was observed in only 32.3% of mucinous PCN. In our prospective cohort (n = 71), 57.7% of patients were classified as having a mucinous PCN. CEA ≥192 ng/mL had an accuracy of 63.4%, and cytopathological mucin evaluation an accuracy of 73.0%. Combining these 2 tests further improved diagnostic accuracy of a mucinous PCN to 76.8%. CEA level and mucin evaluation were not predictive of the degree of dysplasia. These findings show that adding cytopathology to cyst fluid biochemistry improves discrimination between mucinous PCN and nonmucinous cysts.

  11. Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-07-12

    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

  12. Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2016-03-16

    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

  13. Magnifying Endoscopy with Narrow Band Imaging of Early Gastric Cancer: Correlation with Histopathology and Mucin Phenotype

    PubMed Central

    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

  14. Complex papillary hyperplasia of the endometrium: an uncommon case report with cytopathological features and diagnostic implications.

    PubMed

    Rekhi, Bharat; Menon, Santosh; Maheshwari, Amita

    2015-02-01

    Papillary proliferations of the endometrium, without atypia have been uncommonly documented, including on cytology specimens. Herein, we present an uncommon case of a 55-year-old obese lady, on antihypertensive medications, who presented with history of irregular perimenopausal bleeding. A year ago, she was diagnosed with simple cystic hyperplasia on dilation and curettage specimen. Presently, she underwent endometrial aspiration. Cytology smears were prepared from the collected tissue specimen that was further submitted for histopathological analysis. Although the smears were initially diagnosed as negative for malignancy, the tissue sections were reported as a uterine papillary serous carcinoma (UPSC). Review of the smears revealed prominent overlapping clusters and papillary arrangements of relatively banal endometrial cells exhibiting focal metaplasia. Histopathology sections confirmed diagnosis of complex papillary hyperplasia (CPH). Immunohistochemical (IHC) stains reinforced this impression with diffuse estrogen receptor positivity, low Ki-67/MIB1, and lack of diffuse p53 immunostaining. Subsequent hysterectomy, at the time of intraoperative consultation showed a small residual focus of CPH, restricted to endometrium with intramural leiomyomas and adenomyosis. This case is presented to highlight the fact that despite lack of significant atypia, cytological features like overlapping, clustering, and papillary formations are indicators of papillary lesions of the endometrium, including CPH, especially in postmenopausal women. On histopathology, in spite of conspicuous papillary formations, lack of significant nuclear pleomorphism, and tumor invasion are helpful features in avoiding an overdiagnosis of UPSC in such cases. IHC stains are supportive. Correct identification has significant therapeutic implications. PMID:24825243

  15. [Establishment and pathological study of a new poorly differentiated mucinous gastric cancer cell line].

    PubMed

    Uesugi, H; Atari, E

    1995-01-01

    We succeeded in establishing a human gastric carcinoma cell line (KE-97) from oncocytes obtained from the mesentery disseminated metastatic focus of a 52-year-old male stomach cancer patient. From a histopathological point of view the gastric carcinoma was clearly a mucin-producing mucinous carcinoma, portion of which were mixed with poorly differentiated adenocarcinoma and signet-ring cell carcinoma. The oncocytes were fused into a mass and exhibited a suspended proliferating system, with a doubling time of about 28.8 hours. Transplantation of the cancer cells into skid mice resulted in a tumor system in all cases, and histologically, mucinous vacuoles were found in the cell membranes. With immunological staining they were found to be positive for anti-CEA antibodies, anti-CA19-9 antibodies and anti-ICAM-1 antibodies. Autopsy found extensive hematogenous metastasis (lung, liver) and cancerous peritonitis. KE-97 is mucinous carcinoma, and it was reported with the belief that it is a useful cell line upon the investigation of its cancer metastasis mechanism and cytological characteristics. PMID:7861622

  16. A distinct molecular profile associated with mucinous epithelial ovarian cancer

    PubMed Central

    Heinzelmann-Schwarz, V A; Gardiner-Garden, M; Henshall, S M; Scurry, J P; Scolyer, R A; Smith, A N; Bali, A; Bergh, P Vanden; Baron-Hay, S; Scott, C; Fink, D; Hacker, N F; Sutherland, R L; O'Brien, P M

    2006-01-01

    Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of ovarian cancer. To determine the genetic basis of MOC and to identify potential tumour markers, gene expression profiling of 49 primary ovarian cancers of different histological subtypes was performed using a customised oligonucleotide microarray containing >59 000 probesets. The results show that MOC express a genetic profile that both differs and overlaps with other subtypes of epithelial ovarian cancer. Concordant with its histological phenotype, MOC express genes characteristic of mucinous carcinomas of varying epithelial origin, including intestinal carcinomas. Differences in gene expression between MOC and other histological subtypes of ovarian cancer were confirmed by RT–PCR and/or immunohistochemistry. In particular, galectin 4 (LGALS4) was highly and specifically expressed in MOC, but expressed at lower levels in benign mucinous cysts and borderline (atypical proliferative) tumours, supporting a malignant progression model of MOC. Hence LGALS4 may have application as an early and differential diagnostic marker of MOC. PMID:16508639

  17. Transmembrane mucins as novel therapeutic targets

    PubMed Central

    Constantinou, Pamela E; Danysh, Brian P; Dharmaraj, Neeraja; Carson, Daniel D

    2011-01-01

    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. PMID:22201009

  18. Differential expression of mucins in Middle Eastern patients with colorectal cancer

    PubMed Central

    AL-KHAYAL, KHAYAL; ABDULLA, MAHA; AL-OBAID, OMAR; ZUBAIDI, AHMAD; VAALI-MOHAMMED, MANSOOR-ALI; ALSHEIKH, ABDULMALIK; AHMAD, REHAN

    2016-01-01

    Mucin overexpression has been implicated in the tumorigenesis and progression of colorectal carcinoma (CRC). However, data obtained on the prognostic importance of mucin expression in CRC is inconsistent. Due to lack of data on mucin expression and the increase in CRC incidence in Saudi Arabia, the aim of the present study was to analyze the mucin expression profile in patients with CRC in this ethnic group. The present study consisted of 22 patients that underwent surgery for CRC. Histopathological and immunohistochemical staining was performed on CRC tumor and adjacent normal tissues. A tissue microarray was prepared from the tumor and normal adjacent samples to investigate the mucin expression profile using immunohistochemistry. Formalin-fixed paraffin-embedded human colorectal cancer tissues were immunostained with mucin 1 (MUC1), mucin 2 (MUC2) and mucin 5AC (MUC5AC) antibodies. Associations between mucin expression and histopathological variables were evaluated. The present study indicated that MUC1 was highly expressed in early (stage I and II; P=0.0016) and late (stage III and IV; P<0.0001) stage CRC tissues compared to normal adjacent tissues. However, MUC2 expression was observed to be downregulated in early and late stage CRC tissues compared to normal and adjacent tissues. Furthermore, serum MUC1 levels were observed to be increased in early and late stage CRC. The present findings indicate that MUC1 expression was significantly higher in early and late stage CRC tissues and MUC2 was downregulated in CRC tissues compared with normal adjacent tissues, and serum MUC1 protein was significantly higher in CRC patients compared to control serum. In conclusion, during colorectal tumorigenesis the pattern of MUC1 and MUC2 expression is altered in Saudi Arabian patients with CRC compared with normal. A higher expression of MUC1 may be used as an independent biomarker in various stages of CRC tumors, which would aid in the early detection of CRC. PMID:27347157

  19. Mucin overproduction in chronic inflammatory lung disease

    PubMed Central

    Hauber, Hans-Peter; Foley, Susan C; Hamid, Qutayba

    2006-01-01

    Mucus overproduction and hypersecretion are commonly observed in chronic inflammatory lung disease. Mucins are gel-forming glycoproteins that can be stimulated by a variety of mediators. The present review addresses the mechanisms involved in the upregulation of secreted mucins. Mucin induction by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction are also discussed. PMID:16983448

  20. The Diffuse Sclerosing Variant of Papillary Thyroid Cancer Presenting as Innumerable Diffuse Microcalcifications in Underlying Adolescent Hashimoto's Thyroiditis: A Case Report.

    PubMed

    Jeong, Sun Hye; Hong, Hyun Sook; Lee, Eun Hye; Kwak, Jeong Ja

    2016-03-01

    Hashimoto's thyroiditis is the most common diffuse thyroid disease and is characterized by diffuse lymphocytic infiltration. However, the ultrasonographic findings of papillary thyroid carcinomas that arise from Hashimoto's thyroiditis in the pediatric and adolescent population are not well known.We report a rare ultrasonographic finding in a 22-year-old woman diagnosed with the diffuse sclerosing variant of papillary thyroid carcinoma that arose from underlying Hashimoto's thyroiditis: innumerable diffuse microcalcifications instead of a typical malignant-appearing nodule. PMID:27015194

  1. Barrett's esophagus. Correlation between mucin histochemistry, flow cytometry, and histologic diagnosis for predicting increased cancer risk.

    PubMed Central

    Haggitt, R. C.; Reid, B. J.; Rabinovitch, P. S.; Rubin, C. E.

    1988-01-01

    A predominance of sulfated mucin in the nongoblet columnar cells of Barrett's specialized metaplastic epithelium has been postulated to be a form of mild dysplasia and to indicate an increased risk of adenocarcinoma. Flow cytometry for the analysis of nuclear DNA content and cell cycle parameters has also been postulated to be an objective aid in the diagnosis of dysplasia and carcinoma in Barrett's esophagus. The authors investigated the relationship among sulfated mucin, flow cytometric data, and histologic diagnosis in each of 152 biopsies from 42 patients who had Barrett's specialized metaplastic epithelium. Sulfated mucin, as detected by the high iron diamine-Alcian blue stain, was present in biopsies from 8 of 11 (73%) patients with the histologic diagnosis of dysplasia or carcinoma, in 7 of 9 (78%) patients whose biopsies were indefinite for dysplasia, and in 12 of 22 (55%) patients whose biopsies were negative for dysplasia (P = 0.37). Sulfated mucins predominated in 9%, 22%, and 9% of the patients, respectively (P = 0.56). Abnormal flow cytometry (aneuploidy or increased G2/tetraploid fraction) was found in all patients with the histologic diagnosis of dysplasia or carcinoma, in 3 of 9 (33%) indefinite for dysplasia, and in 1 of 22 (5%) negative for dysplasia (P = less than 0.0001). Neither the presence nor the predominance of sulfated mucin in the specialized metaplastic epithelium of Barrett's esophagus has sufficiently high sensitivity or specificity for dysplasia or carcinoma to be of value in managing patients. Abnormal flow cytometry shows excellent correlation with the histologic diagnosis of dysplasia and carcinoma; it detects a subset of patients whose biopsies are histologically indefinite or negative for dysplasia, but who have flow cytometric abnormalities similar to those otherwise seen only in dysplasia and carcinoma. Images Figure 1 Figure 2 Figure 3 PMID:3354644

  2. 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.

  3. High Volume Washing of the Abdomen in Increasing Survival After Surgery in Patients With Pancreatic Cancer That Can Be Removed by Surgery

    ClinicalTrials.gov

    2016-05-03

    Acinar Cell Carcinoma; Ampulla of Vater Adenocarcinoma; Cholangiocarcinoma; Duodenal Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary Mucinous Neoplasm, Pancreatobiliary-Type; Periampullary Adenocarcinoma

  4. [Hereditary renal cell carcinomas].

    PubMed

    Hartmann, A; Stöhr, C G; Junker, K

    2010-10-01

    Renal cell carcinomas occur in several hereditary tumor syndromes. These renal tumors frequently have a specific histopathological appearance which can be a sign for a hereditary cause of the disease. The genetic alterations responsible for most of these tumor syndromes were identified in recent years. Interestingly, renal cell carcinomas show specific histopathological features in each of the hereditary renal cancer syndromes. Clear cell and often cystic renal cell carcinomas occur in von Hippel-Lindau syndrome (VHL), while oncocytomas and chromophobe renal cell carcinomas are found in the Birt-Hugg-Dube syndrome, often also as hybrid tumors. Well differentiated papillary carcinomas (Type 1 according to the WHO) are found in the hereditary papillary renal cell carcinoma (HPRC). In contrast, poorly diffentiated papillary renal cell carcinomas (Type 2 according to the WHO) occur in combination with leiomyomas and leiomyosarcomas of the skin and uterus in hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC). The various genetic causes for these hereditary tumor syndromes open up new therapeutic possibilities, some of which are already being investigated in clinical studies. PMID:20960197

  5. Papillary Thyroid Cancer in a Child with Progressive Transformation of Germinal Centers.

    PubMed

    Mohan, Suresh; DeNardo, Bradley; Stachurski, Dariusz; Greene Welch, Jennifer; Groblewski, Jan C

    2016-01-01

    Objectives. To describe the presentation and management of a child with Progressive Transformation of Germinal Centers (PTGC), an uncommon condition characterized by significant persistent lymphadenopathy, who developed papillary thyroid carcinoma and to explore and review potential links between PTGC and neoplastic processes in the head and neck. Methods. Case presentation and literature review are used. Results. A 10-year-old female presented with a right parotid mass and cervical lymphadenopathy. Multiple biopsies revealed PTGC without malignancy. Two years later, she developed fatigue and weight gain, and a thyroid nodule was found. Fine needle aspiration was strongly suggestive of papillary thyroid carcinoma. The patient underwent total thyroidectomy and central neck dissection without surgical management of the longstanding right lateral neck lymphadenopathy. Final pathology confirmed papillary thyroid carcinoma. She was treated with radioactive iodine therapy postoperatively and remains free of disease at three years of follow-up. Conclusions. PTGC is considered a benign condition but has previously been associated with Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL). This is the first reported case of papillary thyroid cancer in a child with preexisting cervical PTGC and no defined risk factors for thyroid malignancy. No link has been established with thyroid carcinoma, but patients with PTGC may have a defect in immune surveillance that predisposes them to malignancy. PMID:27069706

  6. Papillary Thyroid Cancer in a Child with Progressive Transformation of Germinal Centers

    PubMed Central

    Mohan, Suresh; DeNardo, Bradley; Stachurski, Dariusz; Greene Welch, Jennifer; Groblewski, Jan C.

    2016-01-01

    Objectives. To describe the presentation and management of a child with Progressive Transformation of Germinal Centers (PTGC), an uncommon condition characterized by significant persistent lymphadenopathy, who developed papillary thyroid carcinoma and to explore and review potential links between PTGC and neoplastic processes in the head and neck. Methods. Case presentation and literature review are used. Results. A 10-year-old female presented with a right parotid mass and cervical lymphadenopathy. Multiple biopsies revealed PTGC without malignancy. Two years later, she developed fatigue and weight gain, and a thyroid nodule was found. Fine needle aspiration was strongly suggestive of papillary thyroid carcinoma. The patient underwent total thyroidectomy and central neck dissection without surgical management of the longstanding right lateral neck lymphadenopathy. Final pathology confirmed papillary thyroid carcinoma. She was treated with radioactive iodine therapy postoperatively and remains free of disease at three years of follow-up. Conclusions. PTGC is considered a benign condition but has previously been associated with Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL). This is the first reported case of papillary thyroid cancer in a child with preexisting cervical PTGC and no defined risk factors for thyroid malignancy. No link has been established with thyroid carcinoma, but patients with PTGC may have a defect in immune surveillance that predisposes them to malignancy. PMID:27069706

  7. Analysis of the Distribution of Mucins in Adult Human Gastric Mucosa and Its Functional Significance

    PubMed Central

    2016-01-01

    Introduction Mucins are complex composition of carbohydrates seen in the epithelial cells lining the gastrointestinal tract (GIT). Normal distribution of such mucins in different part of the GIT and its alteration in various inflammatory, benign and malignant lesions of GIT has aroused interest in the field of histochemistry. Aim By applying variety of histochemical techniques an attempt has been made to draw a map of mucin secretion by the different epithelial cell types in different parts of the stomach. Materials and Methods Fifty samples were taken each from different parts of the stomach like fundus, body and pylorus, from dissected fresh specimens (total of 150 specimens). Tissue samples were subjected for routine process and studied for histological and different histochemical staining. Results Mucin pattern in adult predominantly secretes neutral mucosubstances. Surface epithelium shows predominant neutral mucin while cardiac and gastric glands with foveolar cells show moderate amount. Sialomucin is present in a few cells of the surface epithelium, foveolar cells and in most of the mucous neck cells. Small amount of sialomucin and sulphomucin are found in surface epithelial foveolar cells while traces of sulphomucin are found in deep foveolar cells. Mucous neck cells secrete both sulphomucin and sialomucin. Conclusion Normal gastric mucosa adjacent to gastric ulcers and malignant tumours of stomach secretes mucins which differ histochemically and biochemically from that of normal. Early recognition of such changes could be useful in recognizing the different type of carcinomas and their prognosis. PMID:27042436

  8. Mucinous Adenocarcinoma Involving the Ovary: Comparative Evaluation of the Classification Algorithms using Tumor Size and Laterality

    PubMed Central

    Jung, Eun Sun; Bae, Jeong Hoon; Choi, Yeong Jin; Park, Jong-Sup; Lee, Kyo-Young

    2010-01-01

    For intraoperative consultation of mucinous adenocarcinoma involving the ovary, it would be useful to have approaching methods in addition to the traditional limited microscopic findings in order to determine the nature of the tumors. Mucinous adenocarcinomas involving the ovaries were evaluated in 91 cases of metastatic mucinous adenocarcinomas and 19 cases of primary mucinous adenocarcinomas using both an original algorithm (unilateral ≥10 cm tumors were considered primary and unilateral <10 cm tumors or bilateral tumors were considered metastatic) and a modified cut-off size algorithm. With 10 cm, 13 cm, and 15 cm size cut-offs, the algorithm correctly classified primary and metastatic tumors in 82.7%, 87.3%, and 89.1% of cases and in 80.6%, 84.9%, and 87.1% of signet ring cell carcinoma (SRC) excluded cases. In total cases and SRC excluded cases, 98.0% and 97.2% of bilateral tumors were metastatic and 100% and 100% of unilateral tumors <10 cm were metastatic, respectively. In total cases and SRC excluded cases, 68.4% and 68.4% of unilateral tumors ≥15 cm were primary, respectively. The diagnostic algorithm using size and laterality, in addition to clinical history, preoperative image findings, and operative findings, is a useful adjunct tool for differentiation of metastatic mucinous adenocarcinomas from primary mucinous adenocarcinomas of the ovary. PMID:20119573

  9. Genomic Loss of DUSP4 Contributes to the Progression of Intraepithelial Neoplasm of Pancreas to Invasive Carcinoma.

    PubMed

    Hijiya, Naoki; Tsukamoto, Yoshiyuki; Nakada, Chisato; Tung Nguyen, Lam; Kai, Tomoki; Matsuura, Keiko; Shibata, Kohei; Inomata, Masafumi; Uchida, Tomohisa; Tokunaga, Akinori; Amada, Kohei; Shirao, Kuniaki; Yamada, Yasunari; Mori, Hiromu; Takeuchi, Ichiro; Seto, Masao; Aoki, Masahiro; Takekawa, Mutsuhiro; Moriyama, Masatsugu

    2016-05-01

    The progression from precursor lesions of pancreatic cancer, including pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm (IPMN), to invasive disease is characterized by stepwise accumulation of genetic alterations. However, it remains unclear whether additional alterations are required for the progression of high-grade neoplasms to invasive pancreatic carcinoma. We compared the genomic profiles of paired noninvasive and invasive carcinoma tissues collected from patients with IPMN. We demonstrate that the frequency of genomic copy-number aberrations significantly increased during the course of invasion, and the loss of 8p11.22-ter was more often associated with invasive tissues. Expression profiling in pancreatic cancer cell lines with and without 8p11.22-ter revealed that DUSP4, an MAPK phosphatase, was significantly downregulated in cells lacking 8p11.22-ter as well as in invasive carcinomas due to genomic loss. Restoration of DUSP4 expression in pancreatic cancer cells significantly suppressed invasiveness and anoikis resistance via ERK inactivation. Accordingly, we found that blockade of ERK signaling by MEK inhibition was effective in an orthotopic xenograft model and significantly extended survival. Collectively, our findings demonstrate a genetic mechanism by which pancreatic precursor lesions progress to invasive carcinomas and highlight DUSP4 as a novel invasion suppressor that can be therapeutically exploited through manipulation of ERK signaling. Cancer Res; 76(9); 2612-25. ©2016 AACR. PMID:26941286

  10. KRAS mutation positive mucinous adenocarcinoma originating in mature ovarian teratoma: case report and review of literature.

    PubMed

    Hershkovitz, Dov; Vlodavsky, Euvgeni; Simon, Einav; Ben-Izhak, Ofer

    2013-12-01

    Mature ovarian teratomas rarely undergo transformation into malignancy. Carcinomas, mostly squamous cell carcinoma, are the most common malignancy arising in mature cystic teratoma. In the present report we describe a 13-year-old girl who developed a large mass in her ovary. Fine needle biopsy identified intestinal type mucinous adenocarcinoma, which was also identified in the full surgical specimen. Extensive sampling of the surgical specimen also identified areas of mature cystic teratoma. Interestingly, molecular analysis of DNA extracted from various components of the lesion identified KRAS mutation in the carcinoma, borderline mucinous tumor and benign intestinal-type epithelium but not in the epidermal component of the teratoma. To the best of our knowledge this is the first report of KRAS mutation in mucinous carcinoma originating in mature cystic teratoma. We discuss the importance of extensive tissue sampling to differentiate between carcinoma originating in teratoma and metastatic colorectal carcinoma to the ovary. Additionally, the identification of KRAS mutation in the morphologically benign intestinal-type epithelium indicated that it is an early event in the carcinogenic sequence and that the molecular pathway of carcinogenesis in teratoma is similar to that in the carcinogenic process of somatic tissue. PMID:24422958

  11. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker.

    PubMed

    Lehtinen, Laura; Vesterkvist, Pia; Roering, Pia; Korpela, Taina; Hattara, Liisa; Kaipio, Katja; Mpindi, John-Patrick; Hynninen, Johanna; Auranen, Annika; Davidson, Ben; Haglund, Caj; Iljin, Kristiina; Grenman, Seija; Siitari, Harri; Carpen, Olli

    2016-01-01

    Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer. PMID:26981633

  12. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker

    PubMed Central

    Lehtinen, Laura; Vesterkvist, Pia; Roering, Pia; Korpela, Taina; Hattara, Liisa; Kaipio, Katja; Mpindi, John-Patrick; Hynninen, Johanna; Auranen, Annika; Davidson, Ben; Haglund, Caj; Iljin, Kristiina; Grenman, Seija; Siitari, Harri; Carpen, Olli

    2016-01-01

    Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer. PMID:26981633