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Sample records for cell carcinoma implications

  1. Genomics of chromophobe renal cell carcinoma: implications from a rare tumor for pan-cancer studies

    PubMed Central

    Rathmell, Kimryn W.; Chen, Fengju; Creighton, Chad J.

    2015-01-01

    Chromophobe Renal Cell Carcinoma (ChRCC) is a rare subtype of the renal cell carcinomas, a heterogenous group of cancers arising from the nephron. Recently, The Cancer Genome Atlas (TCGA) profiled this understudied disease using multiple data platforms, including whole exome sequencing, whole genome sequencing (WGS), and mitochondrial DNA (mtDNA) sequencing. The insights gained from this study would have implications for other types of kidney cancer as well as for cancer biology in general. Global molecular patterns in ChRCC provided clues as to this cancer's cell of origin, which is distinct from that of the other renal cell carcinomas, illustrating an approach that might be applied towards elucidating the cell of origin of other cancer types. MtDNA sequencing revealed loss-of-function mutations in NADH dehydrogenase subunits, highlighting the role of deregulated metabolism in this and other cancers. Analysis of WGS data led to the discovery of recurrent genomic rearrangements involving TERT promoter region, which were associated with very high expression levels of TERT, pointing to a potential mechanism for TERT deregulation that might be found in other cancers. WGS data, generated by large scale efforts such as TCGA and the International Cancer Genomics Consortium (ICGC), could be more extensively mined across various cancer types, to uncover structural variants, mtDNA mutations, themes of tumor metabolic properties, as well as noncoding point mutations. TCGA's data on ChRCC should continue to serve as a resource for future pan-cancer as well as kidney cancer studies, and highlight the value of investigations into rare tumor types to globally inform principals of cancer biology. PMID:25859550

  2. Molecular biology of anal squamous cell carcinoma: implications for future research and clinical intervention.

    PubMed

    Bernardi, Maria-Pia; Ngan, Samuel Y; Michael, Michael; Lynch, A Craig; Heriot, Alexander G; Ramsay, Robert G; Phillips, Wayne A

    2015-12-01

    Anal squamous cell carcinoma is a human papillomavirus-related disease, in which no substantial advances in treatment have been made in over 40 years, especially for those patients who develop disease relapse and for whom no surgical options exist. HPV can evade the immune system and its role in disease progression can be exploited in novel immunotherapy platforms. Although several studies have investigated the expression and inactivation (through loss of heterozygosity) of tumour suppressor genes in the pathways to cancer, no clinically valuable biomarkers have emerged. Regulators of apoptosis, including survivin, and agents targeting the PI3K/AKT pathway, offer opportunities for targeted therapy, although robust data are scarce. Additionally, antibody therapy targeting EGFR may prove effective, although its safety profile in combination with standard chemoradiotherapy has proven to be suboptimal. Finally, progress in the treatment of anal cancer has remained stagnant due to a lack of preclinical models, including cell lines and mouse models. In this Review, we discuss the molecular biology of anal squamous cell carcinoma, clinical trials in progress, and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a resource for investigation of new molecular pathways and for testing novel targets.

  3. Vismodegib in basal cell carcinoma.

    PubMed

    Amaria, R N; Bowles, D W; Lewis, K D; Jimeno, A

    2012-07-01

    Vismodegib is a novel, small-molecule inhibitor of smoothened, a key component of the hedgehog signaling pathway. Increased hedgehog pathway signaling is critical in the development of hereditary and spontaneous basal cell carcinomas of the skin, and has been implicated in the development of a number of other tumors. In preclinical models, vismodegib demonstrated potent antitumor activity in hedgehog-dependent tumors, particularly basal cell carcinomas. Clinically, phase I and II studies showed dramatic anticancer activity in patients with advanced basal cell carcinomas. In January 2012, vismodegib was approved by the FDA for the treatment of unresectable or metastatic basal cell carcinomas of the skin.

  4. Clinical Implications of FADD Gene Amplification and Protein Overexpression in Taiwanese Oral Cavity Squamous Cell Carcinomas

    PubMed Central

    Chien, Huei-Tzu; Cheng, Sou-De; Chuang, Wen-Yu; Liao, Chun-Ta; Wang, Hung-Ming; Huang, Shiang-Fu

    2016-01-01

    Amplification of 11q13.3 is a frequent event in human cancers, including head and neck squamous cell carcinoma. This chromosome region contains several genes that are potentially cancer drivers, including FADD (Fas associated via death domain), an apoptotic effector that was previously identified as a novel oncogene in laryngeal/pharyngeal cancer. This study was designed to explore the role of FADD in oral squamous cell carcinomas (OSCCs) samples from Taiwanese patients, by assessing copy number variations (CNVs) and protein expression and the clinical implications of these factors in 339 male OSCCs. The intensity of FADD protein expression, as determined by immunohistochemistry, was strongly correlated with gene copy number amplification, as analyzed using a TaqMan CNV assay. Both FADD gene copy number amplification and high protein expression were significantly associated with lymph node metastasis (P < 0.001). Patients with both FADD copy number amplification and high protein expression had the shortest disease-free survival (DFS; P = 0.074 and P = 0.002) and overall survival (OS; P = 0.011 and P = 0.027). After adjusting for primary tumor status, tumor differentiation, lymph node metastasis and age at diagnosis, DFS was still significantly lower in patients with either copy number amplification or high protein expression (hazard ratio [H.R.] = 1.483; 95% confidence interval [C.I.], 1.044–2.106). In conclusion, our data reveal that FADD gene copy number and protein expression can be considered potential prognostic markers and are closely associated with lymph node metastasis in patients with OSCC in Taiwan. PMID:27764170

  5. Robust Differences in p16-Dependent Oropharyngeal Squamous Cell Carcinoma Distant Metastasis: Implications for Targeted Therapy.

    PubMed

    Jaber, James J; Murrill, Lauren; Clark, Joseph I; Johnson, Jonas T; Feustel, Paul J; Mehta, Vikas

    2015-08-01

    Historically, head and neck squamous cell carcinoma (HNSCC) has been earmarked a lymphatic malignancy. Recently, this has been called into question. Our study aims to (1) illustrate the robust differences in distant metastases between p16+ and p16- oropharyngeal squamous cell carcinoma (OPSCC) and (2) provide support that p16+ OPSCC has a predilection toward vasculature invasion and hematogenous spread. Multi-institutional, case series with chart review. Four academic institutions. Within a group of 1113 patients with primary OPSCC who received treatment between 1979 and 2013, those who developed distant metastasis (DM) were divided into 2 cohorts based on p16 status. Intergroup and intragroup univariate analysis was performed as well as descriptive analysis of end-organ sites. Of the 1058 patients included, 89 developed DM. Thirty were p16- and 59 were p16+. Of the p16- patients with DM, only 10% had disseminated disease (distant metastases at ≥2 sites) compared with 74% of p16+ patients. Distant disease in p16+ patients included brain, abdomen, and a distinct pattern of pulmonary metastases. Our large, multi-institutional study supports published reports that p16+ OPSCC metastasizes with a unique phenotype that is hematogenous and widely disseminated with atypical end-organ sites. Our data suggest that p16+ OPSCC has a predilection toward active vasculature invasion as evidenced by the results and illustrative radiologic and pathohistologic examples. These findings may have implications for future targeted therapy when treating p16+ OPSCC. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  6. Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology.

    PubMed

    Chiba, Tetsuhiro; Iwama, Atsushi; Yokosuka, Osamu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSC) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSC play a central role in tumor development, metastasis and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSC have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSC has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSC. Although inhibitors of CSC show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSC are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology. © 2015 The Japan Society of Hepatology.

  7. Aristolochic acid exposure in Romania and implications for renal cell carcinoma

    PubMed Central

    Turesky, Robert J; Yun, Byeong Hwa; Brennan, Paul; Mates, Dana; Jinga, Viorel; Harnden, Patricia; Banks, Rosamonde E; Blanche, Helene; Bihoreau, Marie-Therese; Chopard, Priscilia; Letourneau, Louis; Lathrop, G Mark; Scelo, Ghislaine

    2016-01-01

    Background: Aristolochic acid (AA) is a nephrotoxicant associated with AA nephropathy (AAN) and upper urothelial tract cancer (UUTC). Whole-genome sequences of 14 Romanian cases of renal cell carcinoma (RCC) recently exhibited mutational signatures consistent with AA exposure, although RCC had not been previously linked with AAN and AA exposure was previously reported only in localised rural areas. Methods: We performed mass spectrometric measurements of the aristolactam (AL) DNA adduct 7-(deoxyadenosin-N6-yl) aristolactam I (dA-AL-I) in nontumour renal tissues of the 14 Romanian RCC cases and 15 cases from 3 other countries. Results: We detected dA-AL-I in the 14 Romanian cases at levels ranging from 0.7 to 27 adducts per 108 DNA bases, in line with levels reported in Asian and Balkan populations exposed through herbal remedies or food contamination. The 15 cases from other countries were negative. Interpretation: Although the source of exposure is uncertain and likely different in AAN regions than elsewhere, our results demonstrate that AA exposure in Romania exists outside localised AAN regions and provide further evidence implicating AA in RCC. PMID:26657656

  8. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  9. Genomic portfolio of Merkel cell carcinoma as determined by comprehensive genomic profiling: implications for targeted therapeutics.

    PubMed

    Cohen, Philip R; Tomson, Brett N; Elkin, Sheryl K; Marchlik, Erica; Carter, Jennifer L; Kurzrock, Razelle

    2016-04-26

    Merkel cell carcinoma is an ultra-rare cutaneous neuroendocrine cancer for which approved treatment options are lacking. To better understand potential actionability, the genomic landscape of Merkel cell cancers was assessed. The molecular aberrations in 17 patients with Merkel cell carcinoma were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine, Cambridge, MA) using next-generation sequencing (182 or 236 genes) and analyzed by N-of-One, Inc. (Lexington, MA). There were 30 genes harboring aberrations and 60 distinct molecular alterations identified in this patient population. The most common abnormalities involved the TP53 gene (12/17 [71% of patients]) and the cell cycle pathway (CDKN2A/B, CDKN2C or RB1) (12/17 [71%]). Abnormalities also were observed in the PI3K/AKT/mTOR pathway (AKT2, FBXW7, NF1, PIK3CA, PIK3R1, PTEN or RICTOR) (9/17 [53%]) and DNA repair genes (ATM, BAP1, BRCA1/2, CHEK2, FANCA or MLH1) (5/17 [29%]). Possible cognate targeted therapies, including FDA-approved drugs, could be identified in most of the patients (16/17 [94%]). In summary, Merkel cell carcinomas were characterized by multiple distinct aberrations that were unique in the majority of analyzed cases. Most patients had theoretically actionable alterations. These results provide a framework for investigating tailored combinations of matched therapies in Merkel cell carcinoma patients.

  10. Vismodegib for the treatment of basal cell carcinoma: results and implications of the ERIVANCE BCC trial.

    PubMed

    Dessinioti, Clio; Plaka, Michaela; Stratigos, Alexander J

    2014-05-01

    The need for effective treatment of patients with locally advanced or metastatic basal cell carcinoma (BCC), in conjunction with major advances in the elucidation of the molecular basis of this tumor has led to the advent of new targeted therapies - namely, hedgehog inhibitors. The rationale for their use in patients with advanced BCC is based on their inhibitory effect on the hedgehog pathway, which is aberrantly activated in BCCs due to mutations of its primary components, PTCH1 and SMO genes. Vismodegib (GDC-0449) is an orally bioavailable hedgehog pathway inhibitor that selectively inhibits SMO. The ERIVANCE BCC study is a Phase II, international, multicenter clinical trial evaluating the efficacy and safety of vismodegib 150 mg once daily in patients with locally advanced or metastatic BCC. Vismodegib has been approved for the treatment of adult patients with metastatic BCC, or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy. This article will outline the rationale, design and available results from the ERIVANCE BCC study and discuss the clinical implications of vismodegib in the management of patients with BCC. Challenges regarding vismodegib use include the recurrence of BCC after drug discontinuation, the development of acquired resistance, the dramatic efficacy in patients with Gorlin syndrome, and class-related drug toxicity. Ongoing clinical trials aim to explore the role of vismodegib in the neoadjuvant setting prior to surgery, the potential use of alternate dosing regimens in order to limit chronic adverse events, as well as the identification of patients with BCC that are more likely to respond to this targeted therapy based on genotypic and/or phenotypic characteristics.

  11. Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

    PubMed Central

    Ashouri, Kenan; Mohseni, Sophia; Tourtelot, John; Sharma, Pranav

    2015-01-01

    Von Hippel-Lindau syndrome (VHLS) is a rare hereditary neoplastic disorder caused by mutations in the vhl gene leading to the development of tumors in several organs including the central nervous system, pancreas, kidneys, and reproductive organs. Manifestations of VHLS can present at different ages based on the affected organ and subclass of disease. In the subclasses of VHLS that cause renal disease, renal involvement typically begins closer to the end of the second decade of life and can present in different ways ranging from simple cystic lesions to solid tumors. Mutations in vhl are most often associated with clear cell renal carcinoma, the most common type of renal cancer, and also play a major role in sporadic cases of clear cell renal carcinoma. The recurrent, multifocal nature of this disease presents difficult challenges in the long-term management of patients with VHLS. Optimization of renal function warrants the use of several different approaches common to the management of renal carcinoma such as nephron sparing surgery, enucleation, ablation, and targeted therapies. In VHLS, renal lesions of 3 cm or bigger are considered to have metastatic potential and even small lesions often harbor malignancy. Many of the aspects of management revolve around optimizing both oncologic outcome and long-term renal function. As new surgical strategies and targeted therapies develop, the management of this complex disease evolves. This review will discuss the key aspects of the current management of VHLS.

  12. ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma12

    PubMed Central

    Arias-González, Laura; Moreno-Gimeno, Inmaculada; del Campo, Antonio Rubio; Serrano-Oviedo, Leticia; Valero, María Llanos; Esparís-Ogando, Azucena; de la Cruz-Morcillo, Miguel Ángel; Melgar-Rojas, Pedro; García-Cano, Jesús; Cimas, Francisco José; Hidalgo, María José Ruiz; Prado, Alfonso; Callejas-Valera, Juan Luis; Nam-Cha, Syong Hyun; Giménez-Bachs, José Miguel; Salinas-Sánchez, Antonio S; Pandiella, Atanasio; del Peso, Luis; Sánchez-Prieto, Ricardo

    2013-01-01

    Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas. PMID:23730213

  13. FGFR1 amplifications in squamous cell carcinomas of the lung: diagnostic and therapeutic implications

    PubMed Central

    Schildhaus, Hans-Ulrich; Nogova, Lucia; Wolf, Jürgen

    2013-01-01

    Fibroblast growth factor receptor 1 (FGFR1) is a type 4 receptor tyrosine kinase. The receptor and its ligands play an important role in development and physiology. However, constitutive activation of FGFR1 by gene amplification, translocation or mutation is associated with various malignancies as, for example, breast cancer or myeloproliferative diseases. We have recently reported that FGFR1 amplification occurs in 20% of pulmonary squamous cell carcinomas, and preclinical tests have shown that these alterations are therapeutically tractable. These findings make FGFR1 amplification a potential biomarker for lung cancer treatment. Squamous cell carcinomas of the lung are characterized by an uneven FGFR1 gene copy number distribution. Therefore, fluorescence in situ hybridization assays need to address focality and heterogeneity of FGFR1 in these tumors. Here, we review our proposal for a reading and evaluation strategy. Furthermore, we highlight the emerging landscape of clinical trials with selective and unselective FGFR inhibitors and provide first response data from early clinical trials. PMID:25806220

  14. Chromophobe cell renal carcinoma.

    PubMed

    Megumi, Y; Nishimura, K

    1998-01-01

    Chromophobe cell renal carcinoma is a recently established subtype of renal cell carcinoma. Herein we report a case of chromophobe cell renal carcinoma in a 67-year-old male patient who occasionally underwent computed tomography. In a microscopic study with hematoxylin and eosin stain, clear eosinophilic cytoplasm, and a moderately atypical nucleus were observed. And it was stained positively by Hale's colloidal iron. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. From these results, this tumor was pathologically diagnosed as chromophobe cell renal carcinoma.

  15. VHL Inactivation in Renal Cell Carcinoma: Implications for Diagnosis, Prognosis, and Treatment

    PubMed Central

    Rathmell, W. Kimryn; Chen, Shufen

    2010-01-01

    Clear cell renal cell carcinoma (ccRCC) provides a tumor paradigm for the integration of genetics, molecular biology, therapeutic target validation, and the introduction of high impact treatment strategies. Most cases of sporadic as well as familial ccRCC acquire somatic inactivating mutations of the von Hippel-Lindau tumor suppressor gene, VHL. pVHL, VHL gene product and a protein member of the E3 ubiquitin ligase family, acts in normal cells to direct the degradation and clearance of the hypoxia inducible factor (HIFα) transcription factor family, such that in its absence, as in ccRCC, the HIF proteins stabilize, accumulate to supraphysiologic levels, and activate the transcription of genes such as vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF), which contributes substantially to the physiology of the tumor, and has been assessed indirectly as a prognostic factor. Molecularly targeted therapy blocking components of this pathway has been successfully introduced to the clinic with a substantive impact on clinical parameters of RCC. This review will examine the regulation of these molecular pathways in RCC and discuss the impact on the clinical management of patients with RCC. PMID:18095884

  16. Murine model of neuromuscular electrical stimulation on squamous cell carcinoma: Potential implications for dysphagia therapy

    PubMed Central

    Linkov, Gary; Branski, Ryan C.; Amin, Milan; Chernichenko, Natalya; Chen, Chun-Hao; Alon, Gad; Langmore, Susan; Wong, Richard J.; Kraus, Dennis H.

    2013-01-01

    Background Dysphagia is a potential consequence of treatment for head and neck cancer. Neuromuscular electrical stimulation (NMES) has evolved as a treatment option, with the goal of improved swallow function in patients with chronic dysphagia. However, the effects of NMES on tumorigenicity are unknown and often confound the initiation of this therapy, potentially limiting its efficacy in treating patients with head and neck cancer. Methods Squamous cell carcinoma was grown in the flank of athymic, nude mice. Mice were randomized into treatment and control groups; the experimental group received daily NMES directly to the flank for 8 days. Results Tumor volumes, recorded on days 0, 3, 7, and 10, demonstrated no significant differences between groups on each day of measurement. Immunohistochemical analysis of apoptosis, proliferation, and vascularization also failed to demonstrate statistically significant differences between treated and untreated groups. Conclusions NMES does not promote the growth of underlying tumor in our model. These data may provide preliminary evidence that applying electrical stimulation over the muscles of the anterior neck does not increase the risk of tumorigenicity. Early initiation of NMES in this challenging population may be feasible from an oncologic standpoint. PMID:22083666

  17. Primary squamous cell carcinoma of the rectum: An update and implications for treatment

    PubMed Central

    Guerra, Glen R; Kong, Cherng H; Warrier, Satish K; Lynch, Andrew C; Heriot, Alexander G; Ngan, Samuel Y

    2016-01-01

    AIM: To provide an update on the aetiology, pathogenesis, diagnosis, staging and management of rectal squamous cell carcinoma (SCC). METHODS: A systematic review was conducted according to the preferred reporting items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was performed with the reference list of selected articles reviewed to ensure all relevant publications were captured. The search strategy was limited to the English language, spanning from 1946 to 2015. A qualitative analysis was undertaken examining patient demographics, clinical presentation, diagnosis, staging, treatment and outcome. The quantitaive analysis was limited to data extracted on treatment and outcomes including radiological, clinical and pathological complete response where available. The narrative and quantitative review were synthesised in concert. RESULTS: The search identified 487 articles in total with 79 included in the qualitative review. The quantitative analysis involved 63 articles, consisting of 43 case reports and 20 case series with a total of 142 individual cases. The underlying pathogenesis of rectal SCC while unclear, continues to be defined, with increasing evidence of a metaplasia-dysplasia-carcinoma sequence and a possible role for human papilloma virus in this progression. The presentation is similar to rectal adenocarcinoma, with a diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCC’s are in fact an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this distinction. Staging is most accurately reflected by the tumour-node-metastasis classification for rectal adenocarcinoma. It involves examining locoregional disease by way of magnetic resonance imaging and/or endorectal ultrasound, with systemic spread excluded by way of computed tomography. Positron emission tomography is integral in the workup to exclude an external site of primary SCC with metastasis to the rectum. While the

  18. Primary squamous cell carcinoma of the rectum: An update and implications for treatment.

    PubMed

    Guerra, Glen R; Kong, Cherng H; Warrier, Satish K; Lynch, Andrew C; Heriot, Alexander G; Ngan, Samuel Y

    2016-03-27

    To provide an update on the aetiology, pathogenesis, diagnosis, staging and management of rectal squamous cell carcinoma (SCC). A systematic review was conducted according to the preferred reporting items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was performed with the reference list of selected articles reviewed to ensure all relevant publications were captured. The search strategy was limited to the English language, spanning from 1946 to 2015. A qualitative analysis was undertaken examining patient demographics, clinical presentation, diagnosis, staging, treatment and outcome. The quantitaive analysis was limited to data extracted on treatment and outcomes including radiological, clinical and pathological complete response where available. The narrative and quantitative review were synthesised in concert. The search identified 487 articles in total with 79 included in the qualitative review. The quantitative analysis involved 63 articles, consisting of 43 case reports and 20 case series with a total of 142 individual cases. The underlying pathogenesis of rectal SCC while unclear, continues to be defined, with increasing evidence of a metaplasia-dysplasia-carcinoma sequence and a possible role for human papilloma virus in this progression. The presentation is similar to rectal adenocarcinoma, with a diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCC's are in fact an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this distinction. Staging is most accurately reflected by the tumour-node-metastasis classification for rectal adenocarcinoma. It involves examining locoregional disease by way of magnetic resonance imaging and/or endorectal ultrasound, with systemic spread excluded by way of computed tomography. Positron emission tomography is integral in the workup to exclude an external site of primary SCC with metastasis to the rectum. While the optimal treatment remains as

  19. Basal cell carcinoma: pathophysiology.

    PubMed

    Sehgal, Virendra N; Chatterjee, Kingshuk; Pandhi, Deepika; Khurana, Ananta

    2014-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer in humans, which typically appears over the sun-exposed skin as a slow-growing, locally invasive lesion that rarely metastasizes. Although the exact etiology of BCC is unknown, there exists a well-established relationship between BCC and the pilo-sebaceous unit, and it is currently thought to originate from pluri-potential cells in the basal layer of the epidermis or the follicle. The patched/hedgehog intracellular signaling pathway plays a central role in both sporadic BCCs and nevoid BCC syndrome (Gorlin syndrome). This pathway is vital for the regulation of cell growth, and differentiation and loss of inhibition of this pathway is associated with development of BCC. The sonic hedgehog protein is the most relevant to BCC; nevertheless, the Patched (PTCH) protein is the ligand-binding component of the hedgehog receptor complex in the cell membrane. The other protein member of the receptor complex, smoothened (SMO), is responsible for transducing hedgehog signaling to downstream genes, leading to abnormal cell proliferation. The importance of this pathway is highlighted by the successful use in advanced forms of BCC of vismodegib, a Food and Drug Administration-approved drug, that selectively inhibits SMO. The UV-specific nucleotide changes in the tumor suppressor genes, TP53 and PTCH, have also been implicated in the development of BCC.

  20. Contemporary management of renal cell carcinoma (RCC) in Victoria: implications for longer term outcomes and costs.

    PubMed

    Ta, Anthony D; Bolton, Damien M; Dimech, Margaret K; White, Victoria; Davis, Ian D; Coory, Michael; Millar, Jeremy; Giles, Graham

    2013-11-01

    To describe the contemporary patterns of care for renal cell carcinoma (RCC) using a whole of population series from Victoria. Retrospective review of medical records of all patients diagnosed and treated for RCC in Victoria in 2009. Patients were identified via the State-wide Victorian Cancer Registry. Patient demographic characteristics, symptoms, stage, and first-line treatment were assessed. Associations between case residential location (metropolitan or rural) and treatment were examined using multivariate logistic regression after adjusting for age, sex, socioeconomic status, treatment in private or public hospital and comorbidity. Data were obtained for 499 of 577 eligible patients. In all, 413 patients (83%) underwent surgery. Laparoscopic radical nephrectomy (RN) was the most common procedure for Stage I pT1a/pT1b tumours (51.2%); partial nephrectomy (PN) was performed for 27% of Stage I RCC In multivariate analysis, regional patients were less likely to receive PN (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.18-0.85) for Stage I RCC, and less likely to receive systemic therapy for Stage IV RCC (OR 0.06, 95% CI 0.01-0.41). Multidisciplinary team meetings were recorded for only 25% of patients and 3% were enrolled in a clinical trial. Most contemporary patients diagnosed with RCC are still treated with RN, including those with smaller tumours amenable to PN. This may impact future outcomes, including increased risk of chronic kidney disease and its potential financial healthcare burden. Patterns of treatment also appear to differ between metropolitan and regional populations. © 2013 The Authors. BJU International published by John Wiley & Sons Ltd.

  1. Association of HIV Status With Local Immune Response to Anal Squamous Cell Carcinoma: Implications for Immunotherapy.

    PubMed

    Yanik, Elizabeth L; Kaunitz, Genevieve J; Cottrell, Tricia R; Succaria, Farah; McMiller, Tracee L; Ascierto, Maria L; Esandrio, Jessica; Xu, Haiying; Ogurtsova, Aleksandra; Cornish, Toby; Lipson, Evan J; Topalian, Suzanne L; Engels, Eric A; Taube, Janis M

    2017-07-01

    The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients. To compare the local tumor immune microenvironment (TME) in anal SCCs from HIV-positive and HIV-negative patients. Anal SCC tumor specimens derived from the AIDS and Cancer Specimen Resource (National Cancer Institute) and Johns Hopkins Hospital included specimens. Tumors were subjected to immunohistochemical analysis for immune checkpoints (PD-L1, PD-1, LAG-3) and immune cell (IC) subsets (CD3, CD4, CD8, CD68). Expression profiling for immune-related genes was performed on select HIV-positive and HIV-negative cases in PD-L1+ tumor areas associated with ICs. Programmed death-ligand 1 expression on tumor cells and ICs, PD-L1 patterns (adaptive vs constitutive), degree of IC infiltration, quantified densities of IC subsets, and gene expression profiles in anal SCCs from HIV-positive vs HIV-negative patients. Approximately half of 40 tumor specimens from 23 HIV-positive and 17 HIV-negative patients (29 men and 11 women; mean [SD] age, 51 [9.9] years) demonstrated tumor cell PD-L1 expression, regardless of HIV status. Median IC densities were not significantly decreased in HIV-associated tumors for any cellular subset studied. Both adaptive (IC-associated) and constitutive PD-L1 expression patterns were observed. Immune cell PD-L1 expression correlated with increasing intensity of IC infiltration (r = 0.52; 95% CI, 0.26-0.78; P < .001) and with CD8+ T-cell density (r = 0.35; 95% CI, 0.11-0.59; P

  2. Basal Cell Carcinoma

    PubMed Central

    Lanoue, Julien

    2016-01-01

    Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID:27386043

  3. Nevoid basal cell carcinoma syndrome

    MedlinePlus

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic condition. The gene linked to the syndrome is known as PTCH (" ...

  4. Clinical implications of nonspecific pulmonary nodules identified during the initial evaluation of patients with head and neck squamous cell carcinoma.

    PubMed

    Kwon, Minsu; Lee, Sang Hoon; Lee, Yoon Se; Lee, Choong Wook; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

    2017-09-01

    We aimed to identify the clinical implications of nonspecific pulmonary nodules (NPNs) detected in the initial staging workup for patients with head and neck squamous cell carcinoma (HNSCC). Medical records of patients who had been diagnosed and treated in our hospital were retrospectively analysed. After definite treatment, changes of NPNs detected on initial evaluation were monitored via serial chest computed tomography. The associations between NPNs and the clinicopathological characteristics of primary HNSCC were evaluated. Survival analyses were performed according to the presence of NPNs. The study consisted of 158 (49.4%) patients without NPNs and 162 (50.6%) patients with NPNs. The cumulative incidence of probabilities of pulmonary malignancy (PM) development at 2 years after treatment were 9.0% and 6.2% in NPN-negative and NPN-positive patients, respectively. Overall and PM-free survival rates were not significantly different according to NPN status. Cervical lymph node (LN) involvement and a platelet-lymphocyte ratio (PLR) ≥126 increased the risk of PMs (both P <0.05). NPNs detected in the initial evaluation of patients with HNSCC did not predict the risk of pulmonary malignancies. Cervical LN involvement and PLR ≥126 may be independent prognostic factors affecting PM-free survival regardless of NPN status. • We aimed to identify the clinical implications of nonspecific pulmonary nodules (NPNs). • NPNs in head and neck cancer patients do not lead to pulmonary malignancies (PMs). • NPNs are not associated with overall or PM-free survival (PMFS). • Cervical lymph node involvement is an independent prognostic factor affecting PMFS. • Platelet-lymphocyte ratio ≥126 is another predictor of PMFS regardless of NPN presence.

  5. Subungual squamous cell carcinoma*

    PubMed Central

    Padilha, Carolina Barbosa de Sousa; Balassiano, Laila Klotz de Almeida; Pinto, Julyana Calegari; de Souza, Flávia Crespo Schueler; Kac, Bernard Kawa; Treu, Curt Mafra

    2016-01-01

    Although subungual squamous cell carcinoma is rare, it is the most common primary malignant neoplasms in this location. The higher incidence occurs in the fingernails, but involvement of the toenails is also possible. Subungual squamous cell carcinoma often looks like other more common benign lesions, such as fungal infection, onychomycosis, or viral wart. These factors, together with a general lack of awareness of this disease among physicians, often result in delayed diagnosis. Therefore, it is underdiagnosed, with few reports in the literature. The authors present a case of a man with a diagnosis of subungual squamous cell carcinoma in the hallux, without bone involvement, which was submitted to the appropriate surgical treatment. PMID:28099608

  6. [Imaging renal cell carcinoma].

    PubMed

    Bazan, F; Busto, M

    2014-01-01

    Renal cell carcinoma is the eighth most common malignancy in adults and the most common malignancy in the kidney. It is thus a very common disease for radiologists. This review aims to provide a general overview of the imaging techniques used to diagnose, characterize, and help plan the treatment of renal cell carcinoma as well as to review basic aspects related to staging, imaging-guided percutaneous treatment, and follow-up in the most common clinical scenarios. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  7. Variants of SCARB1 and VDR Involved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma

    PubMed Central

    Pośpiech, Ewelina; Ligęza, Janusz; Wilk, Wacław; Gołas, Aniela; Jaszczyński, Janusz; Stelmach, Andrzej; Ryś, Janusz; Blecharczyk, Aleksandra; Wojas-Pelc, Anna; Jura, Jolanta; Branicki, Wojciech

    2015-01-01

    The current data are still inconclusive in terms of a genetic component involved in the susceptibility to renal cell carcinoma. Our aim was to evaluate 40 selected candidate polymorphisms for potential association with clear cell renal cell carcinoma (ccRCC) based on independent group of 167 patients and 200 healthy controls. The obtained data were searched for independent effects of particular polymorphisms as well as haplotypes and genetic interactions. Association testing implied position rs4765623 in the SCARB1 gene (OR = 1.688, 95% CI: 1.104–2.582, P = 0.016) and a haplotype in VDR comprising positions rs739837, rs731236, rs7975232, and rs1544410 (P = 0.012) to be the risk factors in the studied population. The study detected several epistatic effects contributing to the genetic susceptibility to ccRCC. Variation in GNAS1 was implicated in a strong synergistic interaction with BIRC5. This effect was part of a model suggested by multifactor dimensionality reduction method including also a synergy between GNAS1 and SCARB1 (P = 0.036). Significance of GNAS1-SCARB1 interaction was further confirmed by logistic regression (P = 0.041), which also indicated involvement of SCARB1 in additional interaction with EPAS1 (P = 0.008) as well as revealing interactions between GNAS1 and EPAS1 (P = 0.016), GNAS1 and MC1R (P = 0.031), GNAS1 and VDR (P = 0.032), and MC1R and VDR (P = 0.035). PMID:25945350

  8. Variants of SCARB1 and VDR Involved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma.

    PubMed

    Pośpiech, Ewelina; Ligęza, Janusz; Wilk, Wacław; Gołas, Aniela; Jaszczyński, Janusz; Stelmach, Andrzej; Ryś, Janusz; Blecharczyk, Aleksandra; Wojas-Pelc, Anna; Jura, Jolanta; Branicki, Wojciech

    2015-01-01

    The current data are still inconclusive in terms of a genetic component involved in the susceptibility to renal cell carcinoma. Our aim was to evaluate 40 selected candidate polymorphisms for potential association with clear cell renal cell carcinoma (ccRCC) based on independent group of 167 patients and 200 healthy controls. The obtained data were searched for independent effects of particular polymorphisms as well as haplotypes and genetic interactions. Association testing implied position rs4765623 in the SCARB1 gene (OR = 1.688, 95% CI: 1.104-2.582, P = 0.016) and a haplotype in VDR comprising positions rs739837, rs731236, rs7975232, and rs1544410 (P = 0.012) to be the risk factors in the studied population. The study detected several epistatic effects contributing to the genetic susceptibility to ccRCC. Variation in GNAS1 was implicated in a strong synergistic interaction with BIRC5. This effect was part of a model suggested by multifactor dimensionality reduction method including also a synergy between GNAS1 and SCARB1 (P = 0.036). Significance of GNAS1-SCARB1 interaction was further confirmed by logistic regression (P = 0.041), which also indicated involvement of SCARB1 in additional interaction with EPAS1 (P = 0.008) as well as revealing interactions between GNAS1 and EPAS1 (P = 0.016), GNAS1 and MC1R (P = 0.031), GNAS1 and VDR (P = 0.032), and MC1R and VDR (P = 0.035).

  9. Clinicopathological analysis of basal cell carcinoma of the anal region and its distinction from basaloid squamous cell carcinoma.

    PubMed

    Patil, Deepa T; Goldblum, John R; Billings, Steven D

    2013-10-01

    Basal cell carcinoma of the anal region is rare and morphologically difficult to distinguish from basaloid squamous cell carcinoma, particularly on biopsies. This distinction has therapeutic and prognostic implications. We reviewed morphological features of 9 basal cell carcinomas and 15 basaloid squamous cell carcinomas from the anal region diagnosed during 1993-2011 and determined the utility of Ber-EP4, BCL2, TP63, CK5/6, CDKN2A, and SOX2 as diagnostic tools. Immunostains were scored in a semi-quantitative manner (1+-1-10%, 2+-11-50%, 3+->50%). All basal cell carcinomas were located in the perianal region, while all basaloid squamous cell carcinomas originated in the anal canal/anorectum. Nodular subtype of basal cell carcinoma was the most common subtype. Retraction artifact was the only significant distinguishing histological feature of basal cell carcinoma compared with basaloid squamous cell carcinoma (88% vs 26%; P=0.04). Atypical mitoses were more common in basaloid squamous cell carcinomas (71% vs 11%; P=0.05). An in situ component was only present in basaloid squamous cell carcinomas, and was noted in 6/15 cases. Basal cell carcinomas had 2-3+ Ber-EP4 (basal cell carcinoma 100% vs basaloid squamous cell carcinoma 40%; P<0.001) and BCL2 immunoreactivity (basal cell carcinomas 100% vs basaloid squamous cell carcinoma 33%; P<0.001). Diffuse CDKN2A and SOX2 expression was seen only in basaloid squamous cell carcinomas (basal cell carcinoma 0% vs basaloid squamous cell carcinoma 93%; P<0.001). There was no difference in TP63 and CK5/6 expression. Perianal location, retraction artifact, and lack of atypical mitoses are histological features that help distinguish basal cell carcinoma from basaloid squamous cell carcinoma. An in situ component, when present, supports the diagnosis of basaloid squamous cell carcinoma. Immunostains are extremely helpful as diffuse Ber-EP4 and BCL2 expression is a feature of basal cell carcinoma and basaloid squamous cell carcinoma

  10. Does a venous tumor thrombus exclude renal transitional cell carcinoma? Implications for neo-adjuvant treatment strategies.

    PubMed

    Huber, Johannes; Teber, Dogu; Hatiboglu, Gencay; Popeneciu, Valentin; Jakobi, Hildegard; Hallscheidt, Peter; Pahernik, Sascha; Hohenfellner, Markus

    2014-02-01

    A venous tumor thrombus (VTT) is well-known in renal cell carcinoma, but we experienced a series of five patients with VTT due to renal transitional cell carcinoma (TCC). Our study aimed to determine the incidence and clinical relevance of this entity. From our prospectively-maintained tumor database, we identified 102 patients with renal TCC according to postoperative histology and analyzed the incidence of VTT in renal TCC from 1990 to 2010. Five out of 102 patients with TCC (5%) had a VTT. None of these five patients experienced gross haematuria and we presumed correct diagnosis preoperatively in one out of five patients. Univariate analysis revealed that TNM stage and resection status were inferior in the VTT group. All five patients from the VTT group died from their disease, with a median survival of 8.9 months. With regard to all diagnosed VTT, the effective incidence of vena cava involvement in RCC was 48-fold higher than in renal TCC. A VTT is very suggestive of renal cell carcinoma. However, before neo-adjuvant treatment, the diagnosis should be assured whenever there is doubt.

  11. [High-risk human papilloma virus associated oropharynx squamous cell carcinomas: clinical, biological implications and therapeutical perspectives].

    PubMed

    Guihard, S; Jung, A-C; Noël, G

    2012-02-01

    The infection of the head and neck epithelium by high-risk human papillomaviruses (HPV) is a risk factor for cancer onset and development. The incidence of HPV-related head and neck squamous cell carcinoma is currently increasing. These lesions display distinct clinical features. HPV positive patients are often younger and have a smaller history of tobacco smoking and alcohol drinking, but have a history of virus-transmitting sex practices. HPV-related tumours are mainly found in the oropharynx, are more associated to a local lymph node invasion and display a poorly differentiated morphology. Despite these more aggressive features, HPV-positive head and neck squamous cell carcinomas correlate with an improved local control, disease-free and global survival. It is thought that HPV-driven specific biologic abnormalities underlie higher tumour sensitivity to chemotherapeutic drugs and ionizing radiations. The expression of the HPV E6 and E7 oncoproteins induce cell transformation by interfering with cell signalling pathways involved in apoptosis, cell cycle, angiogenesis and induce the overexpression of the CDKN2A gene. Therefore, alternative treatments based on therapies targeting these pathways in combination with radiation dose de-escalation could be proposed to HPV-positive patients, if they are properly and reliably identified.

  12. Endomandibular acinic cell carcinoma.

    PubMed

    Bondi, R; Nardi, P; Urso, C

    1989-01-01

    A rare case of endomandibular acinic cell carcinoma (ACC) in a white woman aged 79 is reported. Radiologic examination revealed an osteolytic area within the jaw, extending from the left molar region to the ascending branch. The tumor was located within a cavity of the mandible and did not seem to infiltrate the bone. Histologically, it was composed of large epithelial cells with granular cytoplasm, arranged in solid nests, sometimes displaying microcystic spaces. ACC generally occurs in salivary glands. In the reported case, the tumor was considered to arise from ectopic salivary tissue enclosed in the jaw, as no lesion was found in minor salivary glands.

  13. Fallacious Carcinoma- Spindle Cell Variant of Squamous Cell Carcinoma

    PubMed Central

    Bavle, Radhika M; Govinda, Girish; Muniswamappa, Sudhakara; Venugopal, Reshma

    2016-01-01

    Spindle cell carcinoma is a unique, rare and peculiar biphasic tumour of head and neck which is not frequently observed in the oral cavity. This variant of squamous cell carcinoma although of monophasic epithelial origin, simulates a sarcoma and is an aggressive carcinoma with high frequency of recurrence and metastasis. A correct and timely diagnosis is of paramount importance. Most of the tumours require an Immunohistochemistry (IHC) panel for confirmation or diagnosis. We report a case of spindle cell carcinoma with varied histopathological morphology and clinical presentation in a middle aged female with a brief review of literature. PMID:27630965

  14. Merkel cell carcinoma

    PubMed Central

    Koljonen, Virve

    2006-01-01

    Background Merkel cell carcinoma (MCC) is an unusual primary neuroendocrine carcinoma of the skin. MCC is a fatal disease, and patients have a poor chance of survival. Moreover, MCC lacks distinguishing clinical features, and thus by the time the diagnosis is made, the tumour usually have metastasized. MCC mainly affects sun-exposed areas of elderly persons. Half of the tumours are located in the head and neck region. Methods MCC was first described in 1972. Since then, most of the cases reported, have been in small series of patients. Most of the reports concern single cases or epidemiological studies. The present study reviews the world literature on MCC. The purpose of this article is to shed light on this unknown neuroendocrine carcinoma and provide the latest information on prognostic markers and treatment options. Results The epidemiological studies have revealed that large tumour size, male sex, truncal site, nodal/distant disease at presentation, and duration of disease before presentation, are poor prognostic factors. The recommended initial treatment is extensive local excision. Adjuvant radiation therapy has recently been shown to improve survival. Thus far, no chemotherapy protocol have achieved the same objective. Conclusion Although rare, the fatality of this malignancy makes is important to understand the etiology and pathophysiology. During the last few years, the research on MCC has produced prognostic markers, which can be translated into clinical patient care. PMID:16466578

  15. Factors involved in depletion of glutathione from A549 human lung carcinoma cells: implications for radiotherapy. [Buthionine sulfoximine

    SciTech Connect

    Biaglow, J.E.; Varnes, M.E.; Epp, E.R.; Clark, E.P.

    1984-08-01

    The rate of GSH resynthesis has been measured in plateau phase cultures of A549 human lung carcinoma cells subjected to a fresh medium change. Buthionine sulfoximine (BSO) blocks this resynthesis. Diethyl maleate (DEM) causes a decrease in accumulation of GSH. If DEM is added concurrently with BSO there is a rapid decline in GSH that is maximal in the presence of 0.5 mM DEM. GSH depletion rapidly occurs when BSO is added to log phase cultures which initially are higher in GSH content. Twenty-four hr treatment of A549 cells with BSO results in cells that are more radiosensitive in air and show a slight hypoxic radiation response. A 2 hr treatment with DEM results in some hypoxic sensitization and little increase in the aerobic radiation response. Cells treated simultaneously with BSO + DEM show little increase in the hypoxic radiation response, compared to DEM alone, but are more sensitive under aerobic conditions. Decreased cell survival for aerobically irradiated log phase A549 cells occurs within minutes after addition of a mixture of BSO + DEM. The authors suggest that the enhanced aerobic radiation response is related to an inability of GSH depleted cells to inactivate either peroxy radicals or hydroperoxides that may be produced during irradiation of BSO treated cells. Furthermore, enhancement of the aerobic radiation response may be useful in vivo if normal tissue responses are not also increased.

  16. Squamous cell carcinoma.

    PubMed

    Webb, Julie L; Burns, Rachel E; Brown, Holly M; LeRoy, Bruce E; Kosarek, Carrie E

    2009-03-01

    Squamous cell carcinoma (SCC) is a relatively common, malignant neoplasm of dogs and cats that can arise in a variety of locations. The gross appearance of SCC can be variable and nonspecific, so definitive diagnosis requires microscopic examination of the tissue (cytology or histology). Several treatment modalities exist, but surgical excision, if possible, is regarded as the best treatment option. Early diagnosis and treatment of SCC are key because small, early-stage tumors are the most amenable to treatment and carry the best prognosis.

  17. Lobomycosis and squamous cell carcinoma*

    PubMed Central

    Nogueira, Lisiane; Rodrigues, Luciana; Rodrigues, Carlos Alberto Chirano; Santos, Mônica; Talhari, Sinésio; Talhari, Carolina

    2013-01-01

    The occurence of squamous cell carcinoma on long-lasting ulcers is classic. Malignant transformation may occur on burn scars and chronic ulcers of varying etiology, including infectious agents. Transformation of old lobomycosis lesion scars into squamous cell carcinoma has been rarely reported. Careful and long-term follow-up of such patients is important to avoid carcinomatous transformation. PMID:23739701

  18. Targeting Ovarian Carcinoma Stem Cells

    DTIC Science & Technology

    2012-05-01

    expertise with expertise in gynecologic oncology /ovarian carcinoma and in animal models of cancer this proposal will: 1) Identify, isolate, and...more numerous differentiated progeny characterizing the malignancy . Although the clinical significance of these cancer stem cells (CSC) has been...the dramatic initial response rates in ovarian carcinoma represent therapeutic effectiveness against the differentiated cancer cells making up the

  19. Coexisting tubular adenoma with a neuroendocrine carcinoma of colon allowing early surgical intervention and implicating a shared stem cell origin

    PubMed Central

    Soliman, Mahmoud L; Tiwari, Ashish; Zhao, Qing

    2017-01-01

    High-grade colonic neuroendocrine carcinomas (NECs) are uncommon but extremely aggressive. Their co-existence with tubular adenoma (TA) has rarely been reported. We present a 68-year-old man who was found on routine colonoscopy to have multiple colorectal TAs and an ulcerated lesion in the ascending colon. Microscopically, a poorly-differentiated invasive carcinoma juxtaposed with a TA was identified. Differential diagnosis included a poorly-differentiated adenocarcinoma, medullary carcinoma, high-grade NEC and lymphoma. The immunohistochemical profile showed positive staining for keratins, synaptophysin and chromogranin but negative for LCA, CDX2, CK7, CK20, TTF-1 and PSA, supporting the NEC diagnosis. Upon subsequent laparoscopic right hemicolectomy, the tumor was identified as a 3.0 cm umbilicated and ulcerated mass with an adjacent TA. Both TA and NEC showed positive staining for β-catenin indicating a shared colonic origin. The mitotic counts (77/10 high power fields) and a high proliferation rate (75% by Ki-67) corroborated a high-grade stratification. Mutational analysis indicated a wild-type BRAF and KRAS with mismatch repair proficiency. The AJCC (7th edition) pathologic stage is pT3, pN0, pMx. The patient received adjuvant chemotherapy with cisplatin/etoposides for three cycles and will be followed up for a year to detect recurrence. In conclusion, the co-existence of TA with high grade-NEC in our case allowed early identification and intervention of the otherwise asymptomatic but aggressive tumor. In addition, the finding of a high-grade NEC within a large TA in this case suggests a link between the two lesions and could represent a shared stem cell origin. PMID:28246485

  20. Spindle cell carcinoma in maxilla

    PubMed Central

    Samuel, Soumi; Sreelatha, S V; Hegde, Nidarsh; Nair, Preeti P

    2013-01-01

    Spindle cell carcinomas (sarcomatoid carcinomas) are rare tumours. It is a variant of squamous cell carcinoma which has spindled tumour cells, which simulate a true sarcoma, but are epithelial in origin. They are extremely uncommon in the head and neck region. Only five cases with maxillary origin have been discussed in the literature. As compared to squamous cell carcinoma of maxilla, this variant is associated with poor diagnosis and advanced disease at presentation, as is demonstrated in the case presented. There are no standard recommendations for management owing to the rarity of this histology. Surgery and radiotherapy form the mainstays of treatment. We report a rare case of spindle cell carcinoma involving the maxilla. PMID:23632620

  1. Expression of CD163, interleukin-10, and interferon-gamma in oral squamous cell carcinoma: mutual relationships and prognostic implications.

    PubMed

    Wang, Shan; Sun, Miao; Gu, Chuanwen; Wang, Xiaolong; Chen, Dong; Zhao, Eryang; Jiao, Xiaohui; Zheng, Jinhua

    2014-06-01

    Tumor-associated macrophages (TAMs) and their associated inflammatory cytokines represent the major inflammatory component of the stroma of many tumors and can affect prognosis in the case of neoplasms. The objective of this study was to determine the prognostic significance of CD163(+) cells, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) in oral lesions associated with oral squamous cell carcinoma (OSCC). The levels of CD163, IFN-γ, and IL-10 in the tissue samples of 240 patients with OSCC and 58 patients with other oral lesions were assessed by immunohistochemistry. Individuals with low IFN-γ levels, high IL-10 levels, and low CD163 levels were of special concern with respect to OSCC progression. We found that high levels of CD163, or a combination of low IFN-γ levels, high IL-10 levels, and low CD163 levels, were associated with poorer overall survival (OS). CD163(+) cells provide better predictive power for OS in comparison with traditional markers, such as clinical stage and lymph node metastasis. Therefore, CD163(+) cells may be effective prognostic predictors of OSCC. IL-10 may also indicate poor outcomes when IFN-γ secretion is low and the cells are CD163(-) . © 2014 Eur J Oral Sci.

  2. Treatment of margin positive basal cell carcinoma with vismodegib: case report and consideration of treatment options and their implications.

    PubMed

    Bayers, Stephanie; Kapp, Daniel L; Beer, Kenneth R; Slavin, Benjamin

    2013-10-01

    Historically, basal cell carcinomas (BCCs) that are neither surgically resectable nor candidates for radiation therapy have had few treatment options. The hedgehog pathway inhibitor, vismodegib, represents a new opportunity for the treatment of such patients. Vismodegib has approval from the United States Food and Drug Administration for treatment of metastatic BCC, locally advanced BCC recurring after surgery, and BCC that is not treatable via surgery or radiation. We present the case of a patient with a BCC infiltrating the spinal column that was neither possible to fully remove surgically nor a candidate for primary treatment with radiation. Treatment with vismodegib followed by adjuvant radiation therapy resulted in complete disease clearance. Vismodegib represents a promising treatment option for patients with surgically non-resectable BCCs that are not candidates for radiation therapy. Mechanism of action, benefits, and adverse events of vismodegib are reviewed, along with a brief discussion on newer options in the hedgehog inhibitor class.

  3. Basal Cell Carcinoma is as Common as the Sum of all Other Cancers: Implications for Treatment Capacity.

    PubMed

    Holm, Ann-Sofie; Nissen, Christoffer V; Wulf, Hans Christian

    2016-05-01

    Reliable estimates of disease incidence are fundamental to planning future healthcare services. However, in many countries registration of basal cell carcinoma (BCC) is often non-existent. This study examines how many BCC treatments were carried out in Denmark in 2013. The Danish Cancer Registry and the Danish Pathology Registry were used to examine how many BCC treatments were registered, and a test sample was taken from Bispebjerg Hospital to examine the number treated but not registered. The study showed that 21.7% of BCC treatments were performed solely on a clinical diagnosis. Furthermore, some records are inadequate in relation to BCC registration, as BCCs treated are 3 times the number of individuals in the Danish Cancer Registry, and there are nearly as many BCCs as the sum of all other cancers. The increasing BCC incidence will result in difficulties in ensuring treatment capacity.

  4. Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers: implications for personalized cancer therapy.

    PubMed

    Li, Mengjiao; Li, Haoran; Liu, Fei; Bi, Rui; Tu, Xiaoyu; Chen, Lihua; Ye, Shuang; Cheng, Xi

    2017-02-10

    It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC). Seven candidate drug-based molecular biomarkers, human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), breast cancer susceptibility gene 2 (BRCA2) and programmed death-ligand 1 (PD-L1) were measured in 96 ovarian CCC and 113 HGSC by immunohistochemistry in paraffin embedded tissues. The relationship between these biomarkers and clinicopathological factors were explored. The expression level of four of the seven drug-based molecular biomarkers was markedly different between HGSC and CCC. High expression levels of HER2 and PD-L1 were more commonly observed in CCC patients (12.6% vs 2.7%, 21.1% vs 11.6%, P = 0.006, 0.064, respectively), while loss of BRCA1 and BRCA2 expression were more frequently occurred in HGSC patients (72.6% vs 54.3%, 89.4% vs 79.8%, P = 0.007, 0.054, respectively). Survival analysis showed that five of seven biomarkers had prognostic values but varied between subtypes. Furthermore, EGFR expressed frequently in CCC patients with endometriosis than in HGSC patients (44.4% vs 8.3%, P = 0.049). AURKA and PD-L1 correlated with the resistance to platinum-based chemotherapy in CCC patients (P = 0.043, 0.028, respectively) while no similar

  5. Implications of FGF19 on sorafenib-mediated nitric oxide production in hepatocellular carcinoma cells - a short report.

    PubMed

    Gao, Lixia; Shay, Chloe; Lv, Fenglin; Wang, Xuli; Teng, Yong

    2017-10-05

    Hepatocellular carcinoma (HCC), a primary neoplasm derived from hepatocytes, is the second leading cause of cancer mortality worldwide. Previous work has shown that fibroblast growth factor 19 (FGF19), an oncogenic driver, acts as a negative regulator of the therapeutic efficacy of the tyrosine kinase inhibitor sorafenib in HCC cells. The FGF19-mediated mechanism affecting sorafenib treatment, however, still remains to be resolved. Here, we hypothesize that the FGF19-FGFR4 axis may affect the effectiveness of sorafenib in the treatment of HCC. FGF19 and FGFR4 cDNAs were cloned into a pcDNA3.1 vector and subsequently used for exogenous over-expression analyses. FGF19 knockdown cells were generated using a lentiviral-mediated short hairpin RNA (shRNA) methodology and FGFR4 knockout cells were generated using a CRISPR-Cas9 methodology. FGFR4 activation in HCC cells was inhibited by BLU9931. The effects of exogenous gene over-expression, expression knockdown and knockout, as well as drug efficacies in HCC cells, were validated using Western blotting. HCC cell proliferation was assessed using a CellTiter 96(®) AQueous One Solution Cell Proliferation Assay, whereas NO levels were assessed using DAF-FM DA staining in conjunction with electrochemical biosensors. We found that FGF19, when exogenously overexpressed, results in a reduced sorafenib-induced NO generation and a decreased proliferation of HCC cells. In contrast, we found that either FGF19 silencing or knockout of its receptor FGFR4 sensitized HCC cells to sorafenib through the induction of NO generation. Concordantly, we found that inactivation of FGFR4 by BLU9931 enhanced the sensitivity of HCC cells to sorafenib. From our data we conclude that the FGF19-FGFR4 axis may play a critical role in the effects elicited by sorafenib in HCC cells. Blocking the FGF19-FGFR4 axis may provide novel opportunities to improve the efficacy of sorafenib in the treatment of patients with HCC.

  6. [Basal cell carcinoma and rare form variants].

    PubMed

    Liersch, J; Schaller, J

    2014-09-01

    Basal cell carcinomas are the most common primary cutaneous malignant neoplasms. The diagnosis of basal cell carcinoma represents a common and routine task for pathologists and dermatopathologists. The aim of this review is the clinical and histopathological presentation of the most common subtypes of basal cell carcinoma. Furthermore, the rare variants of basal cell carcinoma and their differential diagnoses are also discussed.

  7. Photosensitization of phycocyanin extracted from Microcystis in human hepatocellular carcinoma cells: implication of mitochondria-dependent apoptosis.

    PubMed

    Wang, Chun-yan; Wang, Xinyan; Wang, Yu; Zhou, Tao; Bai, Yu; Li, Yu-cheng; Huang, Bei

    2012-12-05

    The aim of this study was to explore the possibility that Microcystis phycocyanin (MC-PC) functions as a photosensitizer and to investigate the mechanism for the apoptosis induced by Microcystis phycocyanin-mediated photodynamic therapy (MC-PC-PDT) in human hepatocellular carcinoma cells (HepG2). After incubation with MC-PC, HepG2 cells were exposed to a He-Ne Laser beam and the cell survival rate was detected by MTT and Colony forming assay. The mechanism of apoptosis was determined by ultrastructural observation, reactive oxygen species (ROS) and mitochondrial membrane potential (Δψm) assay, activity detection of caspase-3 and cytosol cytochrome c and flow cytometry (FCM) for cell cycle analysis. Our results demonstrated that MC-PC-PDT effectively inhibits HepG2 proliferation with a half-lethal dose of 100 μg/mL and induces apoptosis at 24h with a dose of 200 μg/mL MC-PC. MC-PC was found to localized in mitochondria, it could induce a high level of ROS accumulation at 16 h after PDT treatment, cause mitochondrial damage and the release of mitochondrial cytochrome c into the cytosol. These cellular changes are accompanied by a reduction of the Δψm, activation of caspase-3 and G2/M phase arrest, finally leading to apoptosis through a mitochondria-dependent pathway after 24h. Meanwhile, necrosis was also contributed to cell death in MC-PC PDT process. The present study also identified a new source of phycocyanin from Microcystis as a safe and effective photosensitizer.

  8. Human papillomavirus and head and neck squamous cell carcinomas in the South-East of France: prevalence, viral expression, and prognostic implications.

    PubMed

    Gavid, Marie; Pillet, Sylvie; Pozzetto, Bruno; Oriol, Mathieu; Dumollard, Jean-Marc; Timoshenko, Andrei P; Martin, Christian; Prades, Jean-Michel

    2013-05-01

    Human papillomavirus (HPV) infection, especially by HPV 16, is frequently detected in oropharyngeal squamous cell carcinoma (OSCC). The expression of viral oncoproteins in tumoral tissues of OSCCs suggests the implication of HPV in tumorogenesis. It should now be systematically detected and considered in each patient's treatment and outcome. To investigate the prevalence of HPV infection, the oncogenic role of HPV in patients from the South-East of France with head and neck squamous cell carcinoma (HNSCC), and the resulting clinical implications. Biopsy samples from 200 patients with HNSCC were analyzed. For each patient, one or two biopsies of tumoral tissue were analyzed simultaneously with a biopsy of healthy tissue. Fresh frozen tissues were tested by molecular techniques for HPV DNA detection and genotyping as well as mRNA expression of oncoproteins E6 and E7. Expression of p16 was also analyzed by immunohistochemical staining. HPV DNA tested positive in 11.5% of biopsy samples. The HPV prevalence was higher in OSCCs (91.3 vs 27.3, p < 0.0001) and in patients not consuming tobacco (65.2% vs 95.4%, p < 0.0001). The estimated 3-year overall survival rates were 67.0% for HPV-infected patients versus 39.9% for non-infected patients. The high-risk HPV 16 was the most common type detected (65.2%). In 12 of 18 patients exhibiting DNA of high-risk HPV in their tumor tissue, the same viral genome was also present in normal tissue. E6 and E7 expression was found in 9 of 14 tumoral biopsies tested for these markers.

  9. Uncoupling of PUMA Expression and Apoptosis Contributes to Functional Heterogeneity in Renal Cell Carcinoma - Prognostic and Translational Implications.

    PubMed

    Zhou, Xiaoguang; Li, Jielin; Marx, Christina; Tolstov, Yanis; Rauch, Geraldine; Herpel, Esther; Macher-Goeppinger, Stephan; Roth, Wilfried; Grüllich, Carsten; Pahernik, Sascha; Hohenfellner, Markus; Duensing, Stefan

    2015-12-01

    Renal cell carcinoma (RCC) is characterized by a profound disruption of proapoptotic signaling networks leading to chemo- and radioresistance. A key mediator of DNA damage-induced apoptosis is the BH3-only protein PUMA. Given its central role in proapoptotic signaling, we analyzed a series of more than 600 precision-annotated primary RCC specimens for PUMA protein expression. We found a reduced expression of PUMA in 22.6% of RCCs analyzed. Unexpectedly, however, PUMA deficiency was not associated with more aggressive tumor characteristic as expected. Instead, a reduced PUMA expression was associated with a lower TNM stage, lower histopathologic grade, and more favorable cancer-specific patient survival. A direct correlation in a separate patient cohort revealed a profound disconnection between PUMA expression and apoptosis as exemplified by the fact that the tumor with the highest level of apoptotic cells was PUMA deficient. In a series of in vitro studies, we corroborated these results and discovered the highest propensity to undergo apoptosis in an RCC cell line with virtually undetectable PUMA expression. At the same time, PUMA expression was not necessarily associated with stronger apoptosis induction, which underscores the striking functional heterogeneity of PUMA expression and apoptosis in RCC. Collectively, our findings suggest that PUMA-independent mechanisms of cell death exist and may play an important role in suppressing malignant progression. They underscore the functional heterogeneity of RCCs and suggest that PUMA expression alone may not be a suitable predictive biomarker. A better understanding of alternative proapoptotic pathways, however, may help to design novel therapeutic strategies for patients with advanced RCC.

  10. Urothelial carcinoma: Stem cells on the edge

    PubMed Central

    Brandt, William D.; Matsui, William; Rosenberg, Jonathan E.; He, Xiaobing; Ling, Shizhang; Schaeffer, Edward M.

    2010-01-01

    Tumors are heterogeneous collections of cells with highly variable abilities to survive, grow, and metastasize. This variability likely stems from epigenetic and genetic influences, either stochastic or hardwired by cell type-specific lineage programs. That differentiation underlies tumor cell heterogeneity was elegantly demonstrated in hematopoietic tumors, in which rare primitive cells (cancer stem cells (CSCs)) resembling normal hematopoietic stem cells are ultimately responsible for tumor growth and viability. Because of the compelling clinical implications CSCs pose—across the entire spectrum of cancers—investigators applied the CSC model to cancers arising in tissues with crudely understood differentiation programs. Instead of relying on differentiation, these studies used empirically selected markers and statistical arguments to identify CSCs. The empirical approach has stimulated important questions about “stemness” in cancer cells as well as the validity and stoichiometry of CSC assays. The recent identification of urothelial differentiation programs in urothelial carcinomas (UroCas) supports the idea that solid epithelial cancers (carcinomas) develop and differentiate analogously to normal epithelia and provides new insights about the spatial localization and molecular makeup of carcinoma CSCs. Importantly, CSCs from invasive UroCas (UroCSCs) appear well situated to exchange important signals with adjacent stroma, to escape immune surveillance, and to survive cytotoxic therapy. These signals have potential roles in treatment resistance and many participate in druggable cellular pathways. In this review, we discuss the implications of these findings in understanding CSCs and in better understanding how UroCas form, progress, and should be treated. PMID:20012172

  11. Stages of Merkel Cell Carcinoma

    MedlinePlus

    ... other organs . Sun exposure and having a weak immune system can affect the risk of Merkel cell carcinoma. ... ultraviolet A (PUVA) therapy for psoriasis . Having an immune system weakened by disease, such as chronic lymphocytic leukemia ...

  12. Renal cell carcinoma.

    PubMed

    Hsieh, James J; Purdue, Mark P; Signoretti, Sabina; Swanton, Charles; Albiges, Laurence; Schmidinger, Manuela; Heng, Daniel Y; Larkin, James; Ficarra, Vincenzo

    2017-03-09

    Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance. Localized RCC can be successfully managed with surgery, whereas metastatic RCC is refractory to conventional chemotherapy. However, over the past decade, marked advances in the treatment of metastatic RCC have been made, with targeted agents including sorafenib, sunitinib, bevacizumab, pazopanib and axitinib, which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGFR), and everolimus and temsirolimus, which inhibit mechanistic target of rapamycin complex 1 (mTORC1), being approved. Since 2015, agents with additional targets aside from VEGFR have been approved, such as cabozantinib and lenvatinib; immunotherapies, such as nivolumab, have also been added to the armamentarium for metastatic RCC. Here, we provide an overview of the biology of RCC, with a focus on ccRCC, as well as updates to complement the current clinical guidelines and an outline of potential future directions for RCC research and therapy.

  13. Laser-induced fluorescence made simple: implications for the diagnosis and follow-up monitoring of basal cell carcinoma.

    PubMed

    Drakaki, Eleni; Dessinioti, Clio; Stratigos, Alexander J; Salavastru, Carmen; Antoniou, Christina

    2014-03-01

    Noninvasive treatments are increasingly being used for the management of basal cell carcinoma (BCC), the predominant type of nonmelanoma skin cancer, making the development of noninvasive diagnostic technologies highly relevant for clinical practice. Laser-induced fluorescence (LIF) spectroscopy emerges as an attractive diagnostic technique for the diagnosis and demarcation of BCC due to its noninvasiveness, high sensitivity, real-time measurements, and user-friendly methodology. LIF relies on the principle of differential fluorescence emission between abnormal and normal skin tissues (ex vivo and in vivo) in response to excitation by a specific wavelength of light. Fluorescence originates either from endogenous fluorophores (autofluorescence) or from exogenously administered fluorophores (photosensitizers). The measured optical properties and fluorophore contributions of normal skin and BCC are significantly different from each other and correlate well with tissue histology. Photodynamic diagnosis (PDD) is based on the visualization of a fluorophore, with the ability to accumulate in tumor tissue, by the use of fluorescence imaging. PDD may be used for detecting subclinical disease, determining surgical margins, and following-up patients for residual tumor or BCC relapse. In this review, we will present the basic principles of LIF and discuss its uses for the diagnosis, management, and follow-up of BCC.

  14. Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process

    PubMed Central

    Warren, Timothy A.; Broit, Natasa; Simmons, Jacinta L.; Pierce, Carly J.; Chawla, Sharad; Lambie, Duncan L. J.; Quagliotto, Gary; Brown, Ian S.; Parsons, Peter G.; Panizza, Benedict J.; Boyle, Glen M.

    2016-01-01

    Squamous cell carcinoma (SCC) is the second most common cancer worldwide and accounts for approximately 30% of all keratinocyte cancers. The vast majority of cutaneous SCCs of the head and neck (cSCCHN) are readily curable with surgery and/or radiotherapy unless high-risk features are present. Perineural invasion (PNI) is recognized as one of these high-risk features. The molecular changes during clinical PNI in cSCCHN have not been previously investigated. In this study, we assessed the global gene expression differences between cSCCHN with or without incidental or clinical PNI. The results of the analysis showed signatures of gene expression representative of activation of p53 in tumors with PNI compared to tumors without, amongst other alterations. Immunohistochemical staining of p53 showed cSCCHN with clinical PNI to be more likely to exhibit a diffuse over-expression pattern, with no tumors showing normal p53 staining. DNA sequencing of cSCCHN samples with clinical PNI showed no difference in mutation number or position with samples without PNI, however a significant difference was observed in regulators of p53 degradation, stability and activity. Our results therefore suggest that cSCCHN with clinical PNI may be more likely to contain alterations in the p53 pathway, compared to cSCCHN without PNI. PMID:27665737

  15. Clinical implication of computed tomography findings in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx.

    PubMed

    Ryu, In Sun; Lee, Jeong Hyun; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon; Cho, Kyung-Ja

    2015-10-01

    Accurate tumor staging including involvement of laryngeal cartilage is important to treatment planning. Clinicians rely on imaging findings and determine initial laryngectomy for T4-stage cancer with functionless larynx or extralaryngeal spread (ELS). We examined the accuracy and prognostic value of preoperative CT findings for tumor staging in patients with locally advanced laryngeal and hypopharyngeal cancer. Ninety-four consecutive patients with clinically T3-T4-stage squamous cell carcinoma of the larynx or hypopharynx who underwent curative resection of primary tumor were reviewed. Preoperative CT findings were interpreted by a radiologist without pathologic information. Pathologic findings were used as the gold standard for correlating radiographic findings. CT imaging identified 23 (72%) of 32 cases of pathologically documented thyroid cartilage penetration and 24 (73%) of 33 cases of pathologically documented ELS. The positive predictive values for thyroid cartilage penetration and ELS were 70 and 80%, respectively. Pretreatment CT imaging up-staged 6 of 46 pT3 cases and all of 8 pT2 cases, while it down-staged 7 of 40 pT4 cases. The accuracy for clinical staging by CT imaging was 78%. Subglottic extension of the CT image was an independent variable for predicting thyroid cartilage penetration and ELS (P = 0.014). Thyroid cartilage penetration with or without ELS on CT scans is significantly associated with unfavorable DFS outcome of patients (P = 0.020). CT imaging is suboptimal in diagnosing TCP or ELS of advanced laryngeal cancer, but may be useful to predict patient survival by identifying clinically TCP.

  16. Recurrence pattern of squamous cell carcinoma in the midthoracic esophagus: implications for the clinical target volume design of postoperative radiotherapy

    PubMed Central

    Wang, Xiaoli; Luo, Yijun; Li, Minghuan; Yan, Hongjiang; Sun, Mingping; Fan, Tingyong

    2016-01-01

    Background Postoperative radiotherapy has shown positive efficacy in lowering the recurrence rate and improving the survival rate for patients with esophageal squamous cell carcinoma (ESCC). However, controversies still exist about the postoperative prophylactic radiation target volume. This study was designed to analyze the patterns of recurrence and to provide a reference for determination of the postoperative radiotherapy target volume for patients with midthoracic ESCC. Patients and methods A total of 338 patients with recurrent or metastatic midthoracic ESCC after radical surgery were retrospectively examined. The patterns of recurrence including locoregional and distant metastasis were analyzed for these patients. Results The rates of lymph node (LN) metastasis were 28.4% supraclavicular, 77.2% upper mediastinal, 32.0% middle mediastinal, 50.0% lower mediastinal, and 19.5% abdominal LNs. In subgroup analyses, the rate of abdominal LN metastasis was significantly higher in patients with histological node-positive than that in patients with histological node-negative (P=0.033). Further analysis in patients with histological node-positive demonstrated that patients with three or more positive nodes are more prone to abdominal LN metastasis, compared with patients with one or two positive nodes (χ2=4.367, P=0.037). The length of tumor and histological differentiation were also the high-risk factors for abdominal LN metastasis. Conclusion For midthoracic ESCC with histological node-negative, or one or two positive nodes, the supraclavicular and stations 2, 4, 5, and 7 LNs should be delineated as clinical target volume of postoperative prophylactic irradiation, and upper abdominal LNs should be excluded. While for midthoracic ESCC with three or more positive nodes, upper abdominal LNs should also be included. The length of tumor and histological differentiation should be considered comprehensively to design the clinical target volume for radiotherapy. PMID

  17. Close relation of large cell carcinoma to adenocarcinoma by hierarchical cluster analysis: implications for histologic typing of lung cancer on biopsies.

    PubMed

    Hammer, Stephan H; Prall, Friedrich

    2015-09-01

    Determining histologic types of lung cancer on biopsies can be difficult. This study addresses the role of immunohistochemistry in histologic typing, using a tissue microarray (TMA) as "model biopsies," and presents a classification generated by an unsupervised hierarchical cluster analysis. A TMA was made from resection specimens of a consecutive series of 165 lung tumors. In a "tissue-spot review" with hematoxylin and eosin sections all the large cell carcinomas (N=22) were assigned to the noncommittal class of non-small cell lung cancer (NSCLC), as were an additional 37 tumors of defined histologic types. Adenocarcinomas and squamous cell carcinomas included with these NSCLC could be diagnosed by immunohistochemistry with antibodies against TTF-1, Napsin A, cytokeratin (CK)7, p40, p63, and CK5/6 with moderate to good sensitivities and specificities. Unsupervised hierarchical clustering was done with these data and additional high-molecular-weight cytokeratins, CD56, synaptophysin, and chromogranin immunohistochemistry. This delineated separate clusters for adenocarcinomas, large cell carcinomas, neuroendocrine tumors, and squamous cell carcinomas. Notably, adenocarcinoma and large cell carcinoma clusters were closely related and clearly set off from the squamous cell carcinoma cluster. As would be expected for a clinically well-staged series CDX2, GATA3, estrogen, and progesterone receptor immunohistochemistry remained negative in the vast majority of the tumors and, if positive, were restricted to very few cells. These results, the clustering data in particular, underpin the pragmatic recommendation canvassed with the IASLC/ATS/ERS classification of lung cancers that adenocarcinoma-type molecular studies should include NSCLC with a nonsquamous cell carcinoma immunophenotype.

  18. Sorafenib in renal cell carcinoma.

    PubMed

    Davoudi, Ehsan Taghizadeh; bin-Noordin, Mohamed Ibrahim; Javar, Hamid Akbari; Kadivar, Ali; Sabeti, Bahare

    2014-01-01

    Cancer is among most important causes of death in recent decades. Whoever the renal cell carcinoma incidence is low but it seems it is more complicated than the other cancers in terms of pathophysiology and treatments. The purpose of this work is to provide an overview and also deeper insight to renal cell carcinoma and the steps which have been taken to reach more specific treatment and target therapy, in this type of cancer by developing most effective agents such as Sorafenib. To achieve this goal hundreds of research paper and published work has been overviewed and due to limitation of space in a paper just focus in most important points on renal cell carcinoma, treatment of RCC and clinical development of Sorafenib. The information presented this paper shows the advanced of human knowledge to provide more efficient drug in treatment of some complicated cancer such as RCC in promising much better future to fight killing disease.

  19. Potential targets for lung squamous cell carcinoma

    Cancer.gov

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  20. [Primary orbital squamous cell carcinoma].

    PubMed

    Campos Arbulú, Ana L; Sadava, Emmanuel E; Sánchez Ruiz, Alejandro; Fernández Vila, Juan M; Dillon, Horacio S; Mezzadri, Norberto A

    2017-01-01

    Primary orbital squamous cell carcinoma is a rare entity. There is little published literature. We report a case of primary squamous cell carcinoma of the orbital soft tissues. Surgical resection offered the best treatment for the patient. Complete resection of the lesion was achieved. The patient received adjuvant radiotherapy due to the proximity of the lesion to the surgical margins. Surgical treatment is feasible and should be considered as part of the surgeon's arsenal. However, therapeutic decisions must be made on a case-by-case basis.

  1. Genomics and epigenomics of renal cell carcinoma.

    PubMed

    Maher, Eamonn R

    2013-02-01

    Kidney cancer accounts for about 2% of all cancers and worldwide >250,000 new cases of kidney cancer are diagnosed each year. Renal cell carcinoma (RCC) is the most common form of adult kidney cancer and this review describes our current knowledge of the genetic and epigenetic basis of sporadic RCC. Though to date major advances in understanding the underlying the molecular basis of renal cell carcinoma (RCC) have often been derived from studies of rare familial forms of renal cell carcinoma, large-scale genomic and epigenomic studies of sporadic tumours are beginning to provide clearer pictures of the genomic and epigenomic landscape of RCC and the key pathways implicated in the initiation and progression of the disease. Although current knowledge of the molecular pathogenesis of RCC is incomplete, and mostly relates to clear cell (conventional) RCC, the next five years will see an unprecedented flood of genomic and epigenomic data and the key future challenges will relate to the utilisation of this data to develop novel genetic and epigenetic markers for diagnosis and prognosis and to develop novel targeted therapies in order to enable an age of personalised medicine.

  2. MicroRNA-125a reduces proliferation and invasion of oral squamous cell carcinoma cells by targeting estrogen-related receptor α: implications for cancer therapeutics.

    PubMed

    Tiwari, Ankana; Shivananda, Swamy; Gopinath, Kodaganur S; Kumar, Arun

    2014-11-14

    Estrogen-related receptor α (ESRRA) functions as a transcription factor and regulates the expression of several genes, such as WNT11 and OPN. Up-regulation of ESRRA has been reported in several cancers. However, the mechanism underlying its up-regulation is unclear. Furthermore, the reports regarding the role and regulation of ESRRA in oral squamous cell carcinoma (OSCC) are completely lacking. Here, we show that tumor suppressor miR-125a directly binds to the 3'UTR of ESRRA and represses its expression. Overexpression of miR-125a in OSCC cells drastically reduced the level of ESRRA, decreased cell proliferation, and increased apoptosis. Conversely, the delivery of an miR-125a inhibitor to these cells drastically increased the level of ESRRA, increased cell proliferation, and decreased apoptosis. miR-125a-mediated down-regulation of ESRRA impaired anchorage-independent colony formation and invasion of OSCC cells. Reduced cell proliferation and increased apoptosis of OSCC cells were dependent on the presence of the 3'UTR in ESRRA. The delivery of an miR-125a mimic to OSCC cells resulted in marked regression of xenografts in nude mice, whereas the delivery of an miR-125a inhibitor to OSCC cells resulted in a significant increase of xenografts and abrogated the tumor suppressor function of miR-125a. We observed an inverse correlation between the expression levels of miR-125a and ESRRA in OSCC samples. In summary, up-regulation of ESRRA due to down-regulation of miR-125a is not only a novel mechanism for its up-regulation in OSCC, but decreasing the level of ESRRA by using a synthetic miR-125a mimic may have an important role in therapeutic intervention of OSCC and other cancers.

  3. Epidemiology of basal cell carcinoma.

    PubMed

    Chinem, Valquiria Pessoa; Miot, Hélio Amante

    2011-01-01

    Basal cell carcinoma is the most common malignant neoplasm in humans and its incidence has increased over the last decades. Its high frequency significantly burdens the health system, making the disease a public health issue. Despite the low mortality rates and the rare occurrence of metastases, the tumor may be locally invasive and relapse after treatment, causing significant morbidity. Exposure to ultraviolet radiation is the main environmental risk factor associated with its cause. However, other elements of risk are described, such as light skin phototypes, advanced age, family history of skin carcinoma, light eyes and blond hair, freckles in childhood and immunosuppression. Behavioral aspects such as occupational sun exposure, rural labor and sunburns at a young age also play a role. Between 30% and 75% of the sporadic cases are associated with patched hedgehog gene mutation, but other genetic changes are also described. The tumor is commonly found in concomitance with skin lesions related to chronic sun exposure, such as actinic keratoses, solar lentigines and facial telangiectasia. The prevention of basal cell carcinoma is based on the knowledge of risk factors, early diagnosis and treatment, as well as on the adoption of specific measures, particularly in susceptible populations. The authors present a review of the epidemiology of basal cell carcinoma.

  4. Regulator role of HPV E7 protein on miR-21 expression in cervical carcinoma cells and its functional implication

    PubMed Central

    Kong, Qingqin; Wang, Wenfeng; Li, Ping

    2015-01-01

    Cervical cancer is the second leading malignant tumor in women. Human papillomavirus 16 (HPV16) is one risk factor for cervical cancer, with its expressed E7 protein can facilitate the transformation of cervical epithelial cells. MicroRNA-21 (miR-21) is one important tumor growth regulatory factor involving in angiogenesis, tumor invasion and metastasis. This study thus aimed to investigate the role of high-risk HPV16 E7 protein in regulating miR-21 expression in cervical carcinoma and its related functions. Hela cells were transfected with pcDNA-HPV16 E7 expressing vectors. The expression level of E7 was determined by Western blotting, while miR-21 level was quantified by real-time PCR. The alternation of tumor cell proliferation is determined by transfecting miR-21 inhibitor into E7-overexpressing Hela cells. Cell apoptosis was studied by caspase-3 assay, while cell invasion was illustrated in Transwell chamber. The overexpression of HPV E7 protein facilitated the expression of miR-21, which potentiated Hela cell proliferation and invasion. The inhibition of miR-21 in E7-overexpressin Hela cells can inhibit both proliferation and invasion, but without significant effects on caspase-3 activity. HPV16 E7 protein can up-regulate host miR-21 expression, thus elevating cervical carcinoma cell growth, proliferation and invasion. Therefore, E7 protein is one critical factor in occurrence and progression of cervical carcinoma. PMID:26884851

  5. Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications.

    PubMed

    Amin, Mahul B

    2009-06-01

    It is well established that invasive urothelial carcinoma, involving the urinary bladder and renal pelvis, has marked propensity for divergent differentiation. In recent years, several 'variant' morphologies have been described and most have been recognized in the 2004 World Health Organization Classification. These histological variants of urothelial carcinoma have clinical significance at various levels, including diagnostic, that is, awareness of the morphological variant is essential in order to avoid diagnostic misinterpretations; prognostic for patient risk stratification; and therapeutic, where a diagnostic assignment of a particular variant may be associated with the administration of a therapy distinctive from that used in conventional invasive urothelial carcinoma. The diagnoses of micropapillary urothelial carcinoma, small-cell carcinoma, lymphoepithelioma-like carcinoma and sarcomatoid carcinoma are prime examples where treatment protocols may be different than the usual muscle-invasive bladder cancer. This review discusses the variants of urothelial carcinoma, outlining for each the diagnostic features, differential diagnostic considerations and the clinical significance.

  6. Merkel cell carcinoma in an immunosuppressed patient*

    PubMed Central

    Góes, Heliana Freitas de Oliveira; Lima, Caren dos Santos; Issa, Maria Cláudia de Almeida; Luz, Flávio Barbosa; Pantaleão, Luciana; da Paixão, José Gabriel Miranda

    2017-01-01

    Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.

  7. Carbonic anhydrase IX as a specific biomarker for clear cell renal cell carcinoma: comparative study of Western blot and immunohistochemistry and implications for diagnosis.

    PubMed

    Giménez-Bachs, José M; Salinas-Sánchez, Antonio S; Serrano-Oviedo, Leticia; Nam-Cha, Syong H; Rubio-Del Campo, Antonio; Sánchez-Prieto, Ricardo

    2012-10-01

    This study aimed to evaluate the usefulness of carbonic anhydrase IX (CA-IX) expression in clear cell renal cell carcinoma (CCRCC) using two different techniques to detect protein expression. An experimental, cross-sectional, analytical study was conducted to analyse proteins in renal tumour and healthy tissue specimens from 38 consecutive patients who underwent nephrectomy for renal cancer. CA-IX protein expression was measured by immunohistochemistry and Western blot analysis and quantified. Statistical analysis was performed with the positive and negative specific agreements and kappa coefficient. The sensitivity and specificity of both techniques were assessed. Statistical tests were conducted to analyse the association between CA-IX expression quantitation and normal prognosis factors (TNM stage and Fuhrman nuclear grade), only in CCRCC. The mean patient age was 65 years, 78.9% of patients were men and 57.9% of tumours were CCRCC. CA-IX protein expression was positive in 63.2% of tumours by immunohistochemistry and in 60.5% by Western blot. Both techniques detected CA-IX expression only in CCRCC and unclassifiable tumours. High concordance indices were observed for CCRCC diagnosis. Western blot and immunohistochemistry had a sensitivity of 95.5% and 100%, respectively; the specificity was 100% in both techniques. CA-IX expression quantitation did not correlate with tumour stage or Fuhrman nuclear grade. Immunochemistry and Western blot techniques can be used to detect abnormal CA-IX protein expression in CCRCC and to support morphology-based diagnostic techniques.

  8. Biomarkers of renal cell carcinoma.

    PubMed

    Ngo, Tin C; Wood, Christopher G; Karam, Jose A

    2014-04-01

    The incidence of renal cell carcinoma (RCC) has increased steadily in past few decades and is partially attributable to the increased utilization of cross-sectional imaging. Many of these carcinomas are small incidental discoveries, although a subset leads to locally advanced or distant disease. Although its molecular pathophysiology is not completely understood, knowledge of hereditary RCCs has shed light on some of the pathways involved. More recently, the rapid advances in genomics, proteomics, and metabolomics have allowed for a deeper and more nuanced understanding of the genetic aberrations that lead up to and result from the transformation of a renal tubular epithelial cell into a carcinoma. These discoveries have allowed for the development of novel therapeutics that target these pathways. They have also led to the development of diagnostic, prognostic, and predictive biomarkers that could radically change the way RCC is diagnosed and treated. Although some of the current investigations are nascent and it remains to be seen which biomarkers will become clinically available, many candidate biomarkers show promise and require external validation. Ultimately, biomarkers may allow for cost-effective screening of high-risk patients, the identification of aggressive cancers among small renal masses, the identification of high-risk patients, the detection of recurrences postoperatively with minimal imaging, and the ability to choose appropriate targeted therapies for patients with metastatic disease.

  9. Photodynamic therapy for basal cell carcinoma.

    PubMed

    Fargnoli, Maria Concetta; Peris, Ketty

    2015-11-01

    Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

  10. Simultaneous development of renal cell carcinoma and multifocal urothelial carcinoma.

    PubMed

    Chuang, Heng-Chang; Chuang, Cheng-Keng; Ng, Kwai-Fong

    2008-01-01

    Simultaneous occurrence of multifocal urothelial carcinoma (UC) and ipsilateral renal cell carcinoma (RCC) is rare. We report a 67-year-old woman with multifocal, infiltrating urothelial carcinoma and unilateral renal cell carcinoma. She was referred to our department because of painless gross hematuria. Cystoscopy, computed tomography and retrograde pyelography studies revealed bladder, bilateral renal and ureter UC. She was treated with transurethral resection of the bladder tumor followed by bilateral nephroureterectomy. The pathological diagnosis was high-grade UC over the bladder and both renal pelves and ureters. A second tumor in the upper pole of the right kidney was reported as clear cell RCC. The patient was alive and still under careful surveillance at this writing.

  11. Plasmablastic multiple myeloma following clear cell renal cell carcinoma

    PubMed Central

    Padhi, Somanath; Mokkappan, Sudhagar; Varghese, Renu G’ Boy; Veerappan, Ilangovan

    2014-01-01

    We aim to describe the clinicohaematological profile of an elderly male with plasmablastic multiple myeloma (MM) (IgG λ, International System Stage II) with an unfavourable outcome following chemotherapy. The serum interleukin-6 level was found to be markedly elevated (2464 pg/mL, reference; <50 pg/mL). Thirty-six months prior to MM diagnosis, he underwent left radical nephrectomy for a stage III (pT3N0M0) clear cell renal cell carcinoma (RCC, Fuhrman grade 2). The unique MM-RCC association, shared risk factors, myeloma pathobiology and clinical implications are discussed with a brief literature review. PMID:25103318

  12. Anaplastic giant cell thyroid carcinoma.

    PubMed

    Wallin, G; Lundell, G; Tennvall, J

    2004-01-01

    Anaplastic (giant cell) thyroid carcinoma (ATC), is one of the most aggressive malignancies in humans with a median survival time after diagnosis of 3-6 months. Death from ATC was earlier seen because of local growth and suffocation. ATC is uncommon, accounting for less than 5 % of all thyroid carcinomas. The diagnosis can be established by means of multiple fine needle aspiration biopsies, which are neither harmful nor troublesome for the patient. The cytological diagnosis of this high-grade malignant tumour is usually not difficult for a well trained cytologist. The intention to treat patients with ATC is cure, although only few of them survive. The majority of the patients are older than 60 years and treatment must be influenced by their high age. We have by using a combined modality regimen succeeded in achieving local control in most patients. Every effort should be made to control the primary tumour and thereby improve the quality of remaining life and it is important for patients, relatives and the personnel to know that cure is not impossible. Different treatment combinations have been used since 30 years including radiotherapy, cytostatic drugs and surgery, when feasible. In our latest combined regimen, 22 patients were treated with hyper fractionated radiotherapy 1.6Gy x 2 to a total target dose of 46 Gy given preoperatively, 20 mg doxorubicin was administered intravenously once weekly and surgery was carried out 2-3 weeks after the radiotherapy. 17 of these 22 patients were operated upon and none of these 17 patients got a local recurrence. In the future we are awaiting the development of new therapeutic approaches to this aggressive type of carcinoma. Inhibitors of angiogenesis might be useful. Combretastatin has displayed cytotoxicity against ATC cell lines and has had a positive effect on ATC in a patient. Sodium iodide symporter (NIS) genetherapy is also being currently considered for dedifferentiated thyroid carcinomas with the ultimate aim of

  13. Small cell carcinoma of the bladder

    PubMed Central

    Calado, Bruno Nagel; Maron, Paulo Eduardo Goulart; Vedovato, Bruno César; Barrese, Tomas Zecchini; Fernandes, Roni de Carvalho; Perez, Marjo Deninson Cardenuto

    2015-01-01

    Small cell carcinoma of the urinary bladder is an extremely aggressive and rare tumor. Even though small cell carcinoma most commonly arises from the lungs there are several reports of small cell carcinoma in extrapulmonary sites. Due to its low frequency there is no well-established management for this disease. We report the case of a 61 year-old man with small cell carcinoma of the bladder who underwent radical cystectomy following neoadjuvant chemotherapy. We also reviewed the literature for the optimal treatment strategy. PMID:25517085

  14. Small cell-like change in prostatic intraepithelial neoplasia, intraductal carcinoma, and invasive prostatic carcinoma: a study of 7 cases.

    PubMed

    Lee, Stephen; Han, Jeong S; Chang, Alex; Ross, Hillary M; Montironi, Rodolfo; Yorukoglu, Kutsal; Lane, Zhaoli; Epstein, Jonathan I

    2013-03-01

    Small cell carcinoma of the prostate is associated with poor prognosis and different treatment from conventional acinar adenocarcinoma. Given the important clinicopathologic implications of a diagnosis of small cell carcinoma, we report 7 cases showing unusual, extensive small cell-like change in intraductal carcinoma and invasive carcinoma. Prostatic biopsies from 3 patients and radical prostatectomy specimens from 4 patients showed variably extensive small cell-like high-grade prostatic intraepithelial neoplasia and intraductal carcinoma. Five cases were associated with conventional acinar adenocarcinoma (2 cases with Gleason score 4 + 3 = 7; 3 cases with Gleason 3 + 4 = 7). No small cell carcinoma was seen. Small and large ducts with small cell-like change showed solid and cribriform proliferations of atypical cells with abrupt transition between centrally located populations of small cells and more typical large dysplastic cells at the duct periphery. Rosette-like formations were noted within some involved ducts. Small cell-like change was characterized by crowded cells with uniformly bland vesicular nuclei and minimal cytoplasm and no significant mitotic or apoptotic activity. In 3 cases, similar small cell-like morphology was noted focally in invasive carcinoma. The small cell-like areas were negative for synaptophysin and chromogranin, focally positive for TTF-1, and weakly positive for racemase. Ki-67 labeled less than 5% with predominant labeling of the larger atypical cells and minimal reactivity in the small cell-like population. In summary, small cell-like change in prostatic intraepithelial neoplasia, intraductal carcinoma, and invasive carcinoma is not associated with small cell carcinoma; shows no immunohistochemical evidence of neuroendocrine differentiation; and likely is not an adverse prognostic feature.

  15. Genetics Home Reference: head and neck squamous cell carcinoma

    MedlinePlus

    ... Health Conditions head and neck squamous cell carcinoma head and neck squamous cell carcinoma Printable PDF Open All Close ... body cavities such as the airways and intestines. Head and neck squamous cell carcinoma (HNSCC) develops in the mucous ...

  16. 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

  17. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma*

    PubMed Central

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado Filho, Carlos D'Apparecida Santos

    2016-01-01

    Background Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Methods Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). Results The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. Conclusion The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment. PMID:27828631

  18. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

    PubMed

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

    2016-01-01

    Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

  19. Renal Clear Cell Carcinoma and Tonsil Metastasis

    PubMed Central

    Marcotullio, Dario; Iannella, Giannicola; Zelli, Melissa; Magliulo, Giuseppe

    2013-01-01

    Renal cell carcinoma is the most common renal tumor in adults. Clear cell carcinoma represents 85% of all histological subtypes. In February 2012 a 72-year-old woman came to our department due to the appearance of massive hemoptysis and pharyngodinia. Previously, this patient was diagnosed with a renal cell carcinoma treated with left nephrectomy. We observed an exophytic, grayish, and ulcerated mass in the left tonsillar lodge and decided to subject the patient to an immediate tonsillectomy. Postoperative histology showed nests of cells with highly hyperchromatic nuclei and clear cytoplasm. These features enabled us to make the diagnosis of renal clear cell carcinoma metastasis. Only few authors described metastasis of renal cell carcinoma in this specific site. PMID:24455373

  20. Renal clear cell carcinoma and tonsil metastasis.

    PubMed

    Marcotullio, Dario; Iannella, Giannicola; Macri, Gian Franco; Marinelli, Caterina; Zelli, Melissa; Magliulo, Giuseppe

    2013-01-01

    Renal cell carcinoma is the most common renal tumor in adults. Clear cell carcinoma represents 85% of all histological subtypes. In February 2012 a 72-year-old woman came to our department due to the appearance of massive hemoptysis and pharyngodinia. Previously, this patient was diagnosed with a renal cell carcinoma treated with left nephrectomy. We observed an exophytic, grayish, and ulcerated mass in the left tonsillar lodge and decided to subject the patient to an immediate tonsillectomy. Postoperative histology showed nests of cells with highly hyperchromatic nuclei and clear cytoplasm. These features enabled us to make the diagnosis of renal clear cell carcinoma metastasis. Only few authors described metastasis of renal cell carcinoma in this specific site.

  1. Giant metastatic Merkel cell carcinoma.

    PubMed

    Bognet, Rachel; Thompson, Christina; Campanelli, Carmen

    2013-01-01

    A 68-year-old man presented with a rapidly growing, asymptomatic mass on his left mid-back for the past 3 months. The patient's medical history revealed an intentional 60-pound weight loss over the previous 2 years along with smoking approximately 1 pack of cigarettes per day. On physical examination, a fungating, 11-cm red tumor with palpable broader underlying extension (23 cm total) was present on the left mid-back with distinct red dermal nodules in a dermatomal distribution. In close proximity were two ulcerated nodules, proven histologically to be basal cell carcinomas. In the left groin was massive, fixed lymphadenopathy. A punch biopsy of the tumor was performed, which showed a dense infiltrate of small, round hyperchromatic blue cells that stained positive for CD 56 and pancytokeratin in a perinuclear dot pattern. Tumor cells were negative for CK20, TTF, CK7, and LCA.

  2. Transitional cell bladder carcinoma with presentation mimicking ovarian carcinoma.

    PubMed

    Erickson, D R; Dabbs, D J; Olt, G J

    1996-05-01

    In the case described here, the patient's initial presentation suggested ovarian carcinoma. She had recurrent ascites, a pelvic mass, elevated CA-125, and extensive peritoneal carcinomatosis with transitional cell histology. The presence of hematuria prompted a cystoscopy, which revealed the true site of origin to be the urinary bladder rather than ovaries. This presentation is extremely rare for bladder cancer. Since transitional cell tumors from the bladder have a much worse prognosis than those of ovarian origin, it is important to identify the primary site correctly. Therefore, cystoscopy is essential for patients with hematuria, and should be considered in cases of apparent primary peritoneal carcinoma with transitional cell histology.

  3. Surgical treatment of basal cell carcinoma and squamous cell carcinoma.

    PubMed

    Gualdi, G; Monari, P; Apalla, Z; Lallas, A

    2015-08-01

    Non melanoma skin cancers (NMSC) are the most common human neoplasms, encompassing basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but also cutaneous lymphomas, adnexal tumors, merckel cell carcinoma and other rare tumors. The incidence of BCC and SCC varies significantly among different populations, and the overall incidence of both tumors has increased over the last decades. Although generally associated with a favorable prognosis, recent evidence suggests that the mortality rates of SCC might have been underestimated up-to-date.1 According to Medicare data, NMSC is the fifth most expensive cancer for health care systems. This increased economic burden is not associated with the cost of treating an individual patient, but with the large number of affected patients and the recurrence rates.2 Therefore, the adequate management of the primary tumor with a complete excision becomes a priority not only for the patient but also for the public health systems. Multiple treatment modalities are currently usedin clinicalpractice for the treatment of NMSC. While surgical excision (SE) remains the gold standard of care, non-surgical techniques have gained appreciation due to lower morbidity and better cosmetic results. The optimal management of treatment includes a complete tumor clearance, preservation of the normal tissue function, and the best possible cosmetic outcome.3 Surgery with a predefined excision margin is the treatment of choice for most NMSCs, with Mohs micrographic surgery being recommended for tumors considered to be at a higher recurrence risk or those developing on cosmetically sensitive areas.4, 5 Therefore, the surgical approach of a NMSC consists with three different and equally important steps. First the preoperative clinical assessment of the tumor margins, which can be facilitated by the use of dermoscopy. Second, the definition of the surgical margins depending on the tumor subtype and its biological behavior. Finally, the surgical

  4. Clear cell carcinoma of ovary and uterus.

    PubMed

    Glasspool, Rosalind M; McNeish, Iain A

    2013-12-01

    Clear cell carcinomas of the female genital tract are rare tumours with a fearsome reputation for having poor responses to conventional platinum-based chemotherapy and poor prognosis. However, it is now clear that early-stage ovarian clear cell carcinoma has an excellent prognosis and may not require any adjuvant therapy. In addition, radiotherapy may also have a key role to play in adjuvant management of clear cell tumours. Identification of patients who truly do not need adjuvant chemotherapy is important. The past 3 years has seen a significant improvement in our understanding of clear cell carcinoma biology-in particular, the role of mutations in the chromatin remodelling gene ARID1A as key drivers that are common to clear cell carcinomas of ovarian and endometrial origin. Moreover, gynaecological clear cell carcinomas appear to share many features with renal clear cell tumours, suggesting a common pathogenesis. This raises the possibility of clinical trials that include patients with clear cell tumours from different organs of origin. Dissecting the role of disordered chromatin organisation in clear cell carcinoma pathogenesis is a key priority. Finally, the role of endometriosis and the attendant chronic inflammation are recognised. The inflammatory cytokine interleukin-6 appears to play a key role in clear cell carcinoma biology and is an excellent potential therapeutic target.

  5. [Basal cell carcinoma with matrical differentiation].

    PubMed

    Goldman-Lévy, Gabrielle; Frouin, Eric; Soubeyran, Isabelle; Maury, Géraldine; Guillot, Bernard; Costes, Valérie

    2015-04-01

    Basal cell carcinoma with matrical differentiation is a very rare variant of basal cell carcinoma. To our knowledge, less than 30 cases have been reported. This tumor is composed of basaloid lobules showing a differentiation toward the pilar matrix cells. Recently, it has been demonstrated that beta-catenin would interfer with physiopathogenesis of matrical tumors, in particular pilomatricomas, but also basal cell carcinomas with matrical differentiation. This is a new case, with immunohistochemical and molecular analysis of beta-catenin, in order to explain its histogenesis.

  6. [Therapy of basal cell carcinoma].

    PubMed

    Schmitz, L; Dirschka, T

    2016-06-01

    Basal cell carcinoma (BCC) represents the most common malignant skin tumour in fair-skinned people. Despite low metastatic potential, BCC can cause decisive tissue destruction and disfigurement by invasive growth. In addition to clinical and histologic diagnosis modern imaging techniques as optical coherence tomography and confocal laser microscopy have been introduced. BCCs with aggressive growth pattern and/or increased risk of relapse are preferentially treated surgically. For superficial BCCs various topical treatments and photodynamic therapy are available. Inhibitors of the sonic hedgehog pathway have been approved for symptomatic treatment of metastatic BCC and locally advanced BCC inappropriate for surgery or radiotherapy. Detailed knowledge of the clinical spectrum of BCC and an appropriate choice of therapy are mandatory for the successful treatment of BCC.

  7. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    PubMed

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  8. [Acinar cell carcinoma of submaxillary gland].

    PubMed

    Comeche, C; Calabuig, C; Barona, R

    1997-01-01

    Although acine cell neoplasms have for a long time been regarded as benign tumors, they are presently considered to represent the carcinomas. These rare tumors mainly affect the parotid glands, and only exceptionally involve other salivary glands. Clinically, acic cell carcinoma present as isolated tumors simulating a pleomorphic adenoma. The diagnosis is histopathological, and complete surgical removal of the tumor is the treatment of choice, with cervical lymphatic voiding and/or postoperative radiotherapy in selected cases. A prolonged patient follow-up is required, for the tumor may recur many years after surgery. We report a case of acinic cell carcinoma in submaxillary gland.

  9. Chromophobe renal cell carcinoma with sarcomatoid transformation.

    PubMed

    Abrahams, Neil A; Ayala, Alberto G; Czerniak, Bogdan

    2003-10-01

    We present a rare case of a chromophobe renal cell carcinoma that progressed to a high-grade spindle cell sarcoma. The tumor affected a 50-year-old man who had presented with right upper quadrant discomfort and hematuria and subsequently underwent a right radical nephrectomy. Microscopically, the tumor was composed of two distinct components, a chromophobe renal cell carcinoma and a sarcomatoid component. The sarcomatoid component had exhibited aggressive behavior by spreading to a regional lymph node. This case report shows that chromophobe carcinoma can develop a sarcomatoid transformation with a high propensity for invasive growth and metastasis.

  10. Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

    PubMed

    Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

    2016-02-05

    Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

  11. Expression of TNF-α and CD44 is implicated in poor prognosis, cancer cell invasion, metastasis and resistance to the sunitinib treatment in clear cell renal cell carcinomas.

    PubMed

    Mikami, Shuji; Mizuno, Ryuichi; Kosaka, Takeo; Saya, Hideyuki; Oya, Mototsugu; Okada, Yasunori

    2015-04-01

    Tumor necrosis factor-α (TNF-α) is involved in epithelial-mesenchymal transition (EMT) and expression of CD44, a cancer stem cell marker, in several cancers. This study was performed to clarify the significance of TNF-α and CD44 in clear cell renal cell carcinomas (ccRCCs). Expression of TNF-α and CD44 was examined by immunohistochemistry in 120 ccRCCs. Involvement of TNF-α in EMT and induction of CD44 was analyzed by monitoring expression of EMT-related genes and CD44, and invasion in cultured ccRCC cell lines. TNF-α and CD44 were immunolocalized mainly to carcinoma cells of high-grade ccRCCs with positive correlations with primary tumor stage. A positive correlation was also obtained between TNF-α and CD44 expression, and co-upregulation of TNF-α and CD44 was associated with primary tumor stage, distant metastasis, and poor prognosis. TNF-α enhanced migration and invasion of ccRCC cells together with down-regulation of E-cadherin expression and up-regulation of matrix metalloproteinase 9 and CD44 expression. TNF-α also up-regulated the expression of TNF-α itself in ccRCC cells. Among the 25 ccRCC patients treated with sunitinib for metastatic disease, high CD44 expression was associated with poor treatment outcome. Importantly, residual carcinoma cells in the sunitinib-treated metastatic ccRCCs were strongly positive for CD44, and the CD44 expression was significantly higher in the tumors from the sunitinib-treated patients than in those from untreated ones. Our data show that TNF-α plays an important role in progression of ccRCCs by inducing EMT and CD44 expression, and suggest that CD44 induced by TNF-α may be involved in the resistance to the sunitinib treatment. © 2014 UICC.

  12. Targeted therapy for orbital and periocular basal cell carcinoma and squamous cell carcinoma.

    PubMed

    Yin, Vivian T; Pfeiffer, Margaret L; Esmaeli, Bita

    2013-01-01

    To review the literature on targeted therapy for orbital and periocular basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) and provide examples of patients recently treated with such therapy. The authors reviewed the literature on clinical results of targeted therapy and the molecular basis for targeted therapy in orbital and periocular BCC and cutaneous SCC. The authors also present representative cases from their practice. Mutation in the patched 1 gene (PTCH1) has been implicated in BCC, and overexpression of epidermal growth factor receptor (EGFR) has been shown in SCC. Vismodegib, an inhibitor of smoothened, which is activated upon binding of hedgehog to Ptc, has been shown to significantly decrease BCC tumor size or even produce complete resolution, especially in cases of basal cell nevus syndrome. Similarly, EGFR inhibitors have been shown to significantly decrease SCC tumor size in cases of locally advanced and metastatic disease. The authors describe successful outcomes after vismodegib treatment in a patient with basal cell nevus syndrome with numerous bulky lesions of the eyelid and periocular region and erlotinib (EGFR inhibitor) treatment in a patient with SCC who was deemed not to be a good surgical candidate because of advanced SCC of the orbit with metastasis to the regional lymph nodes, advanced age, and multiple medical comorbidities. Targeted therapy using hedgehog pathway and EGFR inhibitors shows significant promise in treatment of orbital and periocular BCC and cutaneous SCC, respectively. Such targeted therapy may be appropriate for patients who are not good candidates for surgery.

  13. Basosquamous cell carcinoma: a survey of 76 patients and a comparative analysis of basal cell carcinomas and squamous cell carcinomas.

    PubMed

    Betti, Roberto; Crosti, Carlo; Ghiozzi, Simona; Cerri, Amilcare; Moneghini, Laura; Menni, Silvano

    2013-01-01

    Basosquamous carcinoma (BSC) is a rare epithelial tumor with a still confusing terminology. Since 2005 a more comprehensive and broader classification has existed. To retrospectively review our cases of BSC according to the new WHO definition and to re-evaluate their clinical and demographic characteristics and the margin involvement after traditional surgical excision. The data were compared with the same results obtained by basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). Histologically confirmed carcinomas observed in our Department during a sixteen-year period (1994-2011) were studied. Surgical excision was evaluated following the international guidelines. Histopathologic subtypes of BSC were classified in accordance with accepted criteria. Seventy-six patients had a BSC, 305 a SCC, 3,643 a BCC. There were significant differences among the median age of BSCs, the total BCCs and Non-Aggressive BCCs (74.7, 68.8 and 68.3 years respectively; p<0.05). BSC was more significantly located on head-neck region than Non-Aggressive BCC (p<0.04), and less on trunk than Mixed Histology BCC (p<0.01) and Non-Aggressive BCC (p<0.005). BSC has higher prevalence of positive margins after excision than total (p<0.03) and Non-Aggressive BCC (p<0.001). Basosquamous carcinoma fits to a tumor type with a different behavior pattern from non-aggressive basal cell carcinoma and more similar to squamous cell carcinoma or aggressive variants of basal cell carcinoma. Its infiltrative growth and the stromal reaction patterns give enough evidence to support the notion of considering basosquamous carcinoma as a relatively aggressive tumor.

  14. Molecular Characterization and Clinical Implications of Spindle Cells in Nasopharyngeal Carcinoma: A Novel Molecule-Morphology Model of Tumor Progression Proposed

    PubMed Central

    Luo, Weiren; Yao, Kaitai

    2013-01-01

    Up to now, the precise molecular and morphological changes underlying the invasive and metastatic properties of nasopharyngeal carcinoma (NPC) remain largely unresolved. We speculate that neoplastic spindle cells, which are prominently found in the invasive tumor front and the surrounding stroma, might be responsible for the aggressive patterns. Expression profiling of various biomarkers relevant to cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) was performed by tissue microarray-based immunohistochemistry in NPC samples. The expression of EBER and LMP1 was detected by in situ hybridization and immunohistochemistry, respectively. We found that overexpression of CSCs-related markers (ALDH1, Nanog and ABCG2) and up-regulation of EMT markers (Fibronectin, MMP-2, Periostin, SPARC, Snail and Slug), together with E- to N-cadherin switching, occurred preferentially in tumors containing a large proportion of spindle-shaped malignant cells. Furthermore, CSCs-like properties were highly present in spindle cells compared with non-spindle cells of tumors, and correlated strongly with EMT features. In addition, EBV-related factors EBER and LMP1 were highly expressed and correlated strongly with CSCs and EMT characteristics in neoplastic spindle cells. Importantly, high proportion of spindle cells (≥20%) correlated significantly with various aggressive aspects including lymph node metastasis (P = 0.031) and local recurrence (P = 0.014). Patients with high proportion of spindle cells had poor survival (P = 0.004), though it was not an independent value. In conclusion, we demonstrate that spindle cells could be valuable morphological indicators of tumor progression and unfavorable prognosis of NPC. An integrated molecule-morphology model of NPC firstly constructed may shed significant light on the metastatic cascade and clinical relevance of patients. PMID:24349446

  15. Sunitinib benefits patients with renal cell carcinoma

    Cancer.gov

    Findings from clinical trial patients with metastatic renal cell carcinoma, a common kidney cancer, show they did not have accelerated tumor growth after treatment with sunitinib, in contrast to some study results in animals.

  16. Paraneoplastic Cough and Renal Cell Carcinoma

    PubMed Central

    Sullivan, Stephen

    2016-01-01

    A case of patient with intractable cough due to renal cell carcinoma is reported. The discussion reviews the literature regarding this unusual paraneoplastic manifestation of renal malignancy. PMID:27445553

  17. Perioperative Considerations in Metastatic Renal Cell Carcinoma

    PubMed Central

    Flavin, Kate; Vasdev, Nikhil; Ashead, Jim; Lane, Tim; Hanbury, Damian; Nathan, Paul; Gowrie-Mohan, Shanmugasundaram

    2016-01-01

    Patients with metastatic renal cell carcinoma are complex, with the potential for significant complications, and require extensive pre-, peri-, and postoperative management. This article discusses, in depth, the necessary considerations in the treatment of these patients. PMID:27833463

  18. Treatment Option Overview (Merkel Cell Carcinoma)

    MedlinePlus

    ... other organs . Sun exposure and having a weak immune system can affect the risk of Merkel cell carcinoma. ... ultraviolet A (PUVA) therapy for psoriasis . Having an immune system weakened by disease, such as chronic lymphocytic leukemia ...

  19. Treatment Options by Stage (Merkel Cell Carcinoma)

    MedlinePlus

    ... other organs . Sun exposure and having a weak immune system can affect the risk of Merkel cell carcinoma. ... ultraviolet A (PUVA) therapy for psoriasis . Having an immune system weakened by disease, such as chronic lymphocytic leukemia ...

  20. General Information about Merkel Cell Carcinoma

    MedlinePlus

    ... other organs . Sun exposure and having a weak immune system can affect the risk of Merkel cell carcinoma. ... ultraviolet A (PUVA) therapy for psoriasis . Having an immune system weakened by disease, such as chronic lymphocytic leukemia ...

  1. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    PubMed

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  2. Apigenin inhibits renal cell carcinoma cell proliferation.

    PubMed

    Meng, Shuai; Zhu, Yi; Li, Jiang-Feng; Wang, Xiao; Liang, Zhen; Li, Shi-Qi; Xu, Xin; Chen, Hong; Liu, Ben; Zheng, Xiang-Yi; Xie, Li-Ping

    2017-03-21

    Apigenin, a natural flavonoid found in vegetables and fruits, has antitumor activity in several cancer types. The present study evaluated the effects and mechanism of action of apigenin in renal cell carcinoma (RCC) cells. We found that apigenin suppressed ACHN, 786-0, and Caki-1 RCC cell proliferation in a dose- and time-dependent manner. A comet assay suggested that apigenin caused DNA damage in ACHN cells, especially at higher doses, and induced G2/M phase cell cycle arrest through ATM signal modulation. Small interfering RNA (siRNA)-mediated p53 knockdown showed that apigenin-induced apoptosis was likely p53 dependent. Apigenin anti-proliferative effects were confirmed in an ACHN cell xenograft mouse model. Apigenin treatment reduced tumor growth and volume in vivo, and immunohistochemical staining revealed lower Ki-67 indices in tumors derived from apigenin-treated mice. These findings suggest that apigenin exposure induces DNA damage, G2/M phase cell cycle arrest, p53 accumulation and apoptosis, which collectively suppress ACHN RCC cell proliferation in vitro and in vivo. Given its antitumor effects and low in vivo toxicity, apigenin is a highly promising agent for treatment of RCC.

  3. Cardiac metastasis of oral squamous cell carcinoma.

    PubMed

    Pattni, Neeraj; Rennie, Andrew; Hall, Timothy; Norman, Aidan

    2015-09-09

    We present a case of isolated cardiac metastasis of oral squamous cell carcinoma. An 89-year-old woman was due to undergo curative resection of a histologically proven squamous cell carcinoma of the retromolar region. On admission, it was noted that there were ECG changes, and following further investigations, the patient was diagnosed with a cardiac metastasis of her oral malignancy. The presentation, including the diagnostic difficulties, as well as the clinical features of this rare case, are discussed.

  4. Resection of intraocular squamous cell carcinoma.

    PubMed Central

    Char, D H; Crawford, J B; Howes, E L; Weinstein, A J

    1992-01-01

    A patient with recurrent squamous cell carcinoma of the conjunctiva was referred with 20/20 vision in an eye with obvious intraocular extension. A modified iridocyclochoroidectomy was performed and the tumour was removed. Three and a half years later the patient's vision is 20/30 and there is no recurrence. This is the first case in which an eye has been successfully salvaged with documented intraocular squamous cell carcinoma of the conjunctiva. Images PMID:1739709

  5. Clear cell myoepithelial carcinoma ex pleomorphic adenoma.

    PubMed

    Rabade, Nikhil R; Goel, Naina A

    2014-01-01

    Pleomorphic adenoma is the most common epithelial neoplasm of lacrimal gland. A clear cell myoepithelial carcinoma arising in the background of pleomorphic adenoma is common in the salivary glands but very rare in the lacrimal glands. We report the case of a 27 year old man whose lacrimal gland pleomorphic adenoma recurred several times over a period of four years and ultimately evolved into a clear cell myoepithelial carcinoma ex pleomorphic adenoma.

  6. Renal Cell Carcinoma Metastasized to Pagetic Bone

    PubMed Central

    Ramirez, Ashley; Liu, Bo; Rop, Baiywo; Edison, Michelle; Valente, Michael

    2016-01-01

    Paget’s disease of the bone, historically known as osteitis deformans, is an uncommon disease typically affecting individuals of European descent. Patients with Paget’s disease of the bone are at increased risk for primary bone neoplasms, particularly osteosarcoma. Many cases of metastatic disease to pagetic bone have been reported. However, renal cell carcinoma metastasized to pagetic bone is extremely rare. A 94-year-old male presented to the emergency department complaining of abdominal pain. A computed tomography scan of the abdomen demonstrated a large mass in the right kidney compatible with renal cell carcinoma. The patient was also noted to have Paget’s disease of the pelvic bones and sacrum. Within the pagetic bone of the sacrum, there was an enhancing mass compatible with renal cell carcinoma. A subsequent biopsy of the renal lesion confirmed renal cell carcinoma. Paget’s disease of the bone places the patient at an increased risk for bone neoplasms. The most commonly reported sites for malignant transformation are the femur, pelvis, and humerus. In cases of malignant transformation, osteosarcoma is the most common diagnosis. Breast, lung, and prostate carcinomas are the most common to metastasize to pagetic bone. Renal cell carcinoma associated with Paget’s disease of the bone is very rare, with only one prior reported case. Malignancy in Paget's disease of the bone is uncommon with metastatic disease to pagetic bone being extremely rare. We report a patient diagnosed with concomitant renal cell carcinoma and metastatic disease within Paget’s disease of the sacrum. Further research is needed to assess the true incidence of renal cell carcinoma associated with pagetic bone. PMID:27660736

  7. Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma

    SciTech Connect

    Vainshtein, Jeffrey M.; Kabarriti, Rafi; Mehta, Keyur J.; Roy-Chowdhury, Jayanta; Guha, Chandan

    2014-07-15

    Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local disease control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment

  8. Gingival squamous cell carcinoma: A diagnostic impediment

    PubMed Central

    Koduganti, Rekha Rani; Sehrawat, Sangeeta; Reddy, P. Veerendra Nath

    2012-01-01

    Oral squamous cell carcinomas represent 3% of cancers in men and 2% of cancers in women. More than 90% of oral cancer occurs in people older than 45 years Lesions of gingiva account for approximately 10% of the oral squamous cell carcinomas and may present clinically as an area of ulceration, exophytic mass, or red/white speckled patches. The proximity to the underlying periosteum may invite early bone invasion. Carcinoma of gingiva constitutes an extremely important group of neoplasms as the lesion frequently mimics the reactive and inflammatory conditions affecting the periodontium, delaying the diagnosis and making the prognosis of the patient poorer. A rare case of gingival squamous cell carcinoma has been reported here, in a 40 Year old male patient. Careful recording of the case history and results of clinical examination, radiographic, and laboratory investigations, along with a critical review of similar conditions led to the diagnosis, and treatment was initiated. PMID:22628973

  9. [Lichen sclerosus and squamous cell carcinoma].

    PubMed

    Gutiérrez-Pascual, M; Vicente-Martín, F J; López-Estebaranz, J L

    2012-01-01

    Lichen sclerosus is a chronic inflammatory disease that can progress to malignancy. The literature indicates an association with anogenital squamous cell carcinoma and verrucous carcinoma. Two pathogenic pathways, differentiated vulvar and penile intraepithelial neoplasias, which have recently been described in relation to squamous cell carcinoma, are both highly associated with genital lichen sclerosus independently of human papilloma virus (HPV) infection. Furthermore, tumor-promoting molecular changes unrelated to HPV infection have been demonstrated and may explain the malignant potential of lichen sclerosus. The possible relationship between HPV and genital lichen sclerosus currently remains open to discussion, and the prognostic importance of the overlapping of these 2 diseases is still unclear. This review considers the relationship between lichen sclerosus and squamous cell and verrucous carcinomas, the possible oncogenic mechanisms involved, and their possible association with HPV infection.

  10. Lichen sclerosus and squamous cell carcinoma.

    PubMed

    Gutiérrez-Pascual, M; Vicente-Martín, F J; López-Estebaranz, J L

    2012-01-01

    Lichen sclerosus is a chronic inflammatory disease that can progress to malignancy. The literature indicates an association with anogenital squamous cell carcinoma and verrucous carcinoma. Two pathogenic pathways, differentiated vulvar and penile intraepithelial neoplasias, which have recently been described in relation to squamous cell carcinoma, are both highly associated with genital lichen sclerosus independently of human papilloma virus (HPV) infection. Furthermore, tumor-promoting molecular changes unrelated to HPV infection have been demonstrated and may explain the malignant potential of lichen sclerosus. The possible relationship between HPV and genital lichen sclerosus currently remains open to discussion, and the prognostic importance of the overlapping of these 2 diseases is still unclear. This review considers the relationship between lichen sclerosus and squamous cell and verrucous carcinomas, the possible oncogenic mechanisms involved, and their possible association with HPV infection.

  11. Pulmonary CYP2A13 levels are associated with early occurrence of lung cancer-Its implication in mutagenesis of non-small cell lung carcinoma.

    PubMed

    Chiang, Huai-Chih; Lee, Huei; Chao, How-Ran; Chiou, Yu-Hu; Tsou, Tsui-Chun

    2013-10-01

    CYP2A13, a human pulmonary specific cytochrome P450 enzyme, plays an important role in susceptibility to tobacco-specific nitrosamines (TSNAs)-induced lung cancer in humans. The pattern of CYP2A13 distribution in respiratory tract affects the susceptibility of the lung to carcinogens. CYP2A13 is expressed in the epithelium of trachea and bronchi; however its pattern of expression in human lung cancer remains largely unknown. This study aimed to determine the CYP2A13 expression in specimens from human non-small cell lung carcinomas (NSCLCs), i.e., adenocarcinoma and squamous carcinoma, by immunohistochemical (IHC) analysis and to identify the potential linkage between tumor CYP2A13 levels and some clinicopathological characteristics of NSCLC patients in Taiwan. The tumor CYP2A13 IHC staining signal was strong in 76% of the 112 study subjects. Study subjects (especially non-smoking or lung adenocarcinoma patients) with higher tumor CYP2A13 levels were younger. Multiple logistic regression analysis revealed that in younger subjects (age ≤ 66) and heavy smokers (pack-years ≥ 40), the odds ratio (OR) for positive tumor CYP2A13 staining was significantly higher than that for negative tumor CYP2A13 staining. Moreover, the association of EGFR gene mutations and positive tumor CYP2A13 staining was also revealed. In conclusion, these findings suggest the potential involvement of pulmonary CYP2A13 in the early occurrence of NSCLC as well as in the development of EGFR gene mutations.

  12. Basal cell carcinoma and rhinophyma.

    PubMed

    Leyngold, Mark; Leyngold, Ilya; Letourneau, Peter R; Zamboni, William A; Shah, Himansu

    2008-10-01

    Rhinophyma, the end stage in the development of acne rosacea, is characterized by sebaceous hyperplasia, fibrosis, follicular plugging, and telangiectasia. Although it is commonly considered a cosmetic problem, it can result in gross distortion of soft tissue and airway obstruction. Basal cell carcinoma (BCC) is a rare finding in patients with rhinophyma. The objective of this study is to review the literature of BCC in rhinophyma and report on a case. A 70-year-old male presented with long-standing rosacea that resulted in a gross nasal deformity. The patient suffered from chronic drainage and recurrent infections that failed conservative treatment with oral and topical antibiotics. The patient decided to proceed with surgical intervention and underwent tangential excision and dermabrasion in the operating room. Since 1955 there have been 11 cases reported in the literature. In our case, the pathology report noted that the specimen had an incidental finding of a completely resected BCC. The patient did well postoperatively and at follow-up remains tumor-free. Despite the uncommon occurrence of BCC in resection specimens for rhinophyma, we recommend that all specimens be reviewed by a pathologist. If BCC is detected, re-excision may be necessary and careful follow-up is mandatory. Larger studies would be needed to determine the correlation between the 2 conditions.

  13. Metastatic giant basal cell carcinoma: a case report

    PubMed Central

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M’rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy. PMID:27795755

  14. Metastatic giant basal cell carcinoma: a case report.

    PubMed

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

  15. Synchronous Renal Neoplasm: Clear Cell Renal Cell Carcinoma and Papillary Urothelial Carcinoma in the Same Kidney.

    PubMed

    Benavides-Huerto, Miguel Armando; Chávez-Valencia, Venice; Lagunas-Rangel, Francisco Alejandro

    2017-02-01

    Abdominal computed tomography in a 64 year-old male presenting hematuria showed two malignant tumors in the left kidney, thus radical nephrectomy was realized. In histological preparations a clear cell renal cell carcinoma and a papillary urothelial carcinoma were identified occurring synchronously, which is a rare occurrence having only about 50 cases reported in the literature.

  16. Molecular profiling of tumour budding implicates TGFβ-mediated epithelial-mesenchymal transition as a therapeutic target in oral squamous cell carcinoma.

    PubMed

    Jensen, D H; Dabelsteen, E; Specht, L; Fiehn, A M K; Therkildsen, M H; Jønson, L; Vikesaa, J; Nielsen, F C; von Buchwald, C

    2015-08-01

    Although tumour budding is an adverse prognostic factor for many cancer types, the molecular mechanisms governing this phenomenon are incompletely understood. Therefore, understanding the molecular basis of tumour budding may provide new therapeutic and diagnostic options. We employ digital image analysis to demonstrate that the number of tumour buds in cytokeratin-stained sections correlates with patients having lymph node metastases at diagnosis. The tumour bud count was also a predictor of overall survival, independent of TNM stage. Tumour buds and paired central tumour areas were subsequently collected from oral squamous cell carcinoma (OSCC) specimens, using laser capture microdissection, and examined with RNA sequencing and miRNA-qPCR arrays. Compared with cells from the central parts of the tumours, budding cells exhibited a particular gene expression signature, comprising factors involved in epithelial-mesenchymal transition (EMT) and activated TGFβ signalling. Transcription factors ZEB1 and PRRX1 were up-regulated concomitantly with the decreased expression of mesenchymal-epithelial (MET) transcription factors (eg OVOL1) in addition to Krüppel-like factors and Grainyhead-like factors. Moreover, miR-200 family members were down-regulated in budding tumour cells. We used immunohistochemistry to validate five markers of the EMT/MET process in 199 OSCC tumours, as well as in situ hybridization in 20 OSCC samples. Given the strong relationship between tumour budding and the development of lymph node metastases and an adverse prognosis, therapeutics based on inhibiting the activation of TGFβ signalling may prove useful in the treatment of OSCC.

  17. Leukemoid reaction in epidermal squamous cell carcinoma.

    PubMed

    Kiyosawa, T; Hirano, S; Nakamura, J; Murata, S; Demitsu, T; Kato, H; Yaoita, H

    1996-08-01

    There have been no previous concrete reports of leukemoid reactions associated with squamous cell carcinoma originating in cutaneous tissue. Here we report a case of epidermal squamous cell carcinoma of the sacral region and an associated leukemoid reaction. The tumor invaded deeply and destroyed both the sacrum and coccyx. The white blood cell count was greater than 20,000/mm3. After resection of the tumor, white blood cells transiently decreased, but did not fall under 10,000/mm3. Post-operative infection by methicillin-resistant Staphylococcus aureus and Bacteroides caccae caused sepsis and further elevation of the leukocytes to greater than 50,000/mm3. The leukemoid reaction in the case appeared to have been caused initially by direct invasion of bone by epidermal squamous cell carcinoma and later by severe infection.

  18. Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: An update with special reference to HPV-related carcinomas

    PubMed Central

    2014-01-01

    Accurate identification of the microscopic risk factors of oral and oropharyngeal (OP) squamous cell carcinomas (SCC) and their morphologic variants is of at most importance, as these generally determine treatment modalities, prognosis and overall patient outcome. The great majority of oral and oropharyngeal squamous cell carcinomas are microscopically described as kerartinizing squamous cell carcinoma (KSCC). They bear certain resemblance to keratinizing stratified squamous epithelium. Tobacco habits and excessive consumption of alcoholic beverages have been considered to be the main etiologic agents in these carcinomas. The tumors occurred in older patients more commonly affected the oral tongue and floor of the mouth with well established morphologic risk factors including tumor grade, pattern of invasion and perineural involvement. Within the last 30 years however, the advent and expanding prevalence of high risk human papillomavirus (HPV) as an important etiologic agent for head and neck squamous cell carcinoma, particularly in the OP, has resulted in a significant change in the established morphologic criteria for risk assessment. The majority of HPV relate carcinomas of the OP are nonkeratinizing squamous cell carcinoma (NKSCC). These tumors are found to be more responsive to treatment with a favorable patient outcome and good prognosis. Consequently, alterations in treatment protocols aimed at de-escalation are currently being evaluated. More recently, other morphologic variants that are HPV positive are reported with increasing frequency in the OP and other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, whether the virus is biologically active in these tumors and involved in their pathogenesis, and second, what are the clinical implications with regard to patient management and outcome in the HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here are

  19. Resectable pancreatic small cell carcinoma

    PubMed Central

    Winter, Jordan M.; Narang, Amol K.; Mansfield, Aaron S.; Herman, Joseph M.; Cameron, John L.; Laheru, Dan; Eckhauser, Fred E.; Olson, Mathew T.; Hruban, Ralph H.; Miller, Robert C.; Andersen, Dana K.

    2011-01-01

    Primary pancreatic small cell carcinoma (SCC) is rare, with just over 30 cases reported in the literature. Only 7 of these patients underwent surgical resection with a median survival of 6 months. Prognosis of SCC is therefore considered to be poor, and the role of adjuvant therapy is uncertain. Here we report two institutions' experience with resectable pancreatic SCC. Six patients with pancreatic SCC treated at the Johns Hopkins Hospital (4 patients) and the Mayo Clinic (2 patients) were identified from prospectively collected pancreatic cancer databases and re-reviewed by pathology. All six patients underwent a pancreaticoduodenectomy. Clinicopathologic data were analyzed, and the literature on pancreatic SCC was reviewed. Median age at diagnosis was 50 years (range 27–60). All six tumors arose in the head of the pancreas. Median tumor size was 3 cm, and all cases had positive lymph nodes except for one patient who only had five nodes sampled. There were no perioperative deaths and three patients had at least one postoperative complication. All six patients received adjuvant therapy, five of whom were given combined modality treatment with radiation, cisplatin, and etoposide. Median survival was 20 months with a range of 9–173 months. The patient who lived for 9 months received chemotherapy only, while the patient who lived for 173 months was given chemoradiation with cisplatin and etoposide and represents the longest reported survival time from pancreatic SCC to date. Pancreatic SCC is an extremely rare form of cancer with a poor prognosis. Patients in this surgical series showed favorable survival rates when compared to prior reports of both resected and unresectable SCC. Cisplatin and etoposide appears to be the preferred chemotherapy regimen, although its efficacy remains uncertain, as does the role of combined modality treatment with radiation. PMID:21464878

  20. Differentiation between pancreatic metastases from renal cell carcinoma and hypervascular neuroendocrine tumour: Use of relative percentage washout value and its clinical implication.

    PubMed

    Kang, Tae Wook; Kim, Seong Hyun; Lee, Jisun; Kim, Ah Yeong; Jang, Kyung Mi; Choi, Dongil; Kim, Min Ji

    2015-11-01

    To compare computed tomography (CT) findings in patients with pancreatic metastasis from renal cell carcinoma (pRCC) and patients with hypervascular pancreatic neuroendocrine tumour (pNET) with a focus on the relative percentage washout (RPW). We evaluated 16 patients with 37 pRCCs and 28 patients with 31 hypervascular pNETs using a protocol consisting of arterial and portal phase CT. Imaging findings were analyzed for comparison between the two groups. The RPW of each tumour using biphasic CT was obtained by two observers for evaluation of diagnostic performance. Interobserver agreement of each value and optimal cut-off level of RPW for discrimination between groups were evaluated. Tumour multiplicity showed significant difference in both groups. The mean RPW of the pRCC group (observer 1, 27.0%; observer 2, 29.4%) was significantly higher than that of the pNET group (observer 1, 0.5%; observer 2, 3.2%) (p<0.001 for each observer). Interobserver agreement for both attenuation values and RPWs was excellent. A RPW value of 19% was selected as the optimal cut-off for pRCC determination, and showed good performance (accuracy 83.8%, sensitivity 83.8%, and specificity 83.9%). With multiplicity, RPW of the tumour on CT could be helpful for differentiating pRCCs from hypervascular pNETs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. The prognostic implications of microvascular density and lymphatic vessel density in esophageal squamous cell carcinoma: Comparative analysis between the traditional whole sections and the tissue microarray.

    PubMed

    Chen, Bo; Fang, Wang-Kai; Wu, Zhi-Yong; Xu, Xiu-E; Wu, Jian-Yi; Fu, Jun-Hui; Yao, Xiao-Dong; Huang, Jian-Hao; Chen, Jie-Xin; Shen, Jin-Hui; Zheng, Chun-Peng; Wang, Shao-Hong; Li, En-Min; Xu, Li-Yan

    2014-05-01

    Focal distribution of microvascular and lymphatic vessels is a critical issue in cancer, and is measured by tissue microarray (TMA) construction from paraffin-embedded surgically obtained tissues, a process that may not accurately reflect true focal distribution. The aim of this study was to assess the concordance of microvascular density (MVD) and lymphatic vessel density (LVD) in TMAs with corresponding whole sections, and to correlate the MVD or LVD with clinicopathological parameters in 124 cases of esophageal squamous cell carcinoma (ESCC). MVD, determined by CD105 immunohistochemistry of whole sections, was strongly associated with lymph node metastasis (p=0.000) and pTNM stage (p=0.001). Kaplan-Meier survival analysis showed that increasing CD105 microvessel count correlated with decreasing survival (p<0.001). The same result was acquired when MVD was calculated from tissue microarrays. Analysis of continuous data showed a highly significant correlation between whole sections and TMA data (Pearson r=0.522, p<0.001). Increasing LVD, as determined by D2-40 immunohistochemistry of whole sections, correlated with decreasing survival, but this relationship was undetectable using TMAs. In conclusion, we demonstrate that for the selected endothelial markers, TMAs can provide a realistic and reliable estimate of the extent of MVD, but not LVD in ESCC samples. Copyright © 2013 Elsevier GmbH. All rights reserved.

  2. Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2015-04-29

    Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx

  3. TERT promoter mutations are frequent in cutaneous basal cell carcinoma and squamous cell carcinoma.

    PubMed

    Griewank, Klaus G; Murali, Rajmohan; Schilling, Bastian; Schimming, Tobias; Möller, Inga; Moll, Iris; Schwamborn, Marion; Sucker, Antje; Zimmer, Lisa; Schadendorf, Dirk; Hillen, Uwe

    2013-01-01

    Activating mutations in the TERT promoter were recently identified in up to 71% of cutaneous melanoma. Subsequent studies found TERT promoter mutations in a wide array of other major human cancers. TERT promoter mutations lead to increased expression of telomerase, which maintains telomere length and genomic stability, thereby allowing cancer cells to continuously divide, avoiding senescence or apoptosis. TERT promoter mutations in cutaneous melanoma often show UV-signatures. Non-melanoma skin cancer, including basal cell carcinoma and squamous cell carcinoma, are very frequent malignancies in individuals of European descent. We investigated the presence of TERT promoter mutations in 32 basal cell carcinomas and 34 cutaneous squamous cell carcinomas using conventional Sanger sequencing. TERT promoter mutations were identified in 18 (56%) basal cell carcinomas and in 17 (50%) cutaneous squamous cell carcinomas. The recurrent mutations identified in our cohort were identical to those previously described in cutaneous melanoma, and showed a UV-signature (C>T or CC>TT) in line with a causative role for UV exposure in these common cutaneous malignancies. Our study shows that TERT promoter mutations with UV-signatures are frequent in non-melanoma skin cancer, being present in around 50% of basal and squamous cell carcinomas and suggests that increased expression of telomerase plays an important role in the pathogenesis of these tumors.

  4. Identification of Prognostic Biomarkers for Progression of Invasive Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-12-19

    Carcinoma, Squamous Cell; Carcinoma, Squamous; Squamous Cell Carcinoma; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms

  5. Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma

    PubMed Central

    Sekulic, Aleksandar; Migden, Michael R.; Oro, Anthony E.; Dirix, Luc; Lewis, Karl D.; Hainsworth, John D.; Solomon, James A.; Yoo, Simon; Arron, Sarah T.; Friedlander, Philip A.; Marmur, Ellen; Rudin, Charles M.; Chang, Anne Lynn S.; Low, Jennifer A.; Mackey, Howard M.; Yauch, Robert L.; Graham, Richard A.; Reddy, Josina C.; Hauschild, Axel

    2017-01-01

    BACKGROUND Alterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal-cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma. METHODS In this multicenter, international, two-cohort, nonrandomized study, we enrolled patients with metastatic basal-cell carcinoma and those with locally advanced basal-cell carcinoma who had inoperable disease or for whom surgery was inappropriate (because of multiple recurrences and a low likelihood of surgical cure, or substantial anticipated disfigurement). All patients received 150 mg of oral vismodegib daily. The primary end point was the independently assessed objective response rate; the primary hypotheses were that the response rate would be greater than 20% for patients with locally advanced basal-cell carcinoma and greater than 10% for those with metastatic basal-cell carcinoma. RESULTS In 33 patients with metastatic basal-cell carcinoma, the independently assessed response rate was 30% (95% confidence interval [CI], 16 to 48; P = 0.001). In 63 patients with locally advanced basal-cell carcinoma, the independently assessed response rate was 43% (95% CI, 31 to 56; P<0.001), with complete responses in 13 patients (21%). The median duration of response was 7.6 months in both cohorts. Adverse events occurring in more than 30% of patients were muscle spasms, alopecia, dysgeusia (taste disturbance), weight loss, and fatigue. Serious adverse events were reported in 25% of patients; seven deaths due to adverse events were noted. CONCLUSIONS Vismodegib is associated with tumor responses in patients with locally advanced or metastatic basal-cell carcinoma. (Funded by Genentech; Erivance BCC ClinicalTrials.gov number, NCT00833417

  6. Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

    PubMed Central

    Woods, Robbie SR; O’Regan, Esther M; Kennedy, Susan; Martin, Cara; O’Leary, John J; Timon, Conrad

    2014-01-01

    Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities. PMID:24945004

  7. Merkel cell carcinoma (primary neuroendocrine carcinoma of skin) mimicking basal cell carcinoma with review of different histopathologic features.

    PubMed

    Succaria, Farah; Radfar, Arash; Bhawan, Jag

    2014-02-01

    Merkel cell carcinoma (MCC) is a rare but highly aggressive malignancy, which often has typical histopathologic and immunohistochemical (IHC) features. Sometimes the diagnosis is missed because of atypical histological or aberrant IHC findings. A case of MCC that showed irregular lobules of basaloid cells with keratotic areas on the initial shave biopsy is being reported. IHC showed positive staining for high-molecular weight cytokeratin but negative staining for cytokeratin 20, findings consistent with basal cell carcinoma. Subsequent excision specimen showed histopathologic features more typical of MCC. IHC still was negative for cytokeratin 20 but positive for synaptophysin. Review of the literature shows other examples of MCC with basal cell carcinoma-like features. Various other histopathologic differentiations of MCC include those that demonstrate squamous cell and eccrine carcinoma features and those that show melanocytic, lymphomatous, sarcomatous, muscular, and atypical fibroxanthoma-like features. Different histopathologic patterns and mimics of MCC are reviewed to help prevent dermatopathologists from misdiagnosing this aggressive tumor.

  8. Undifferentiated sinonasal carcinoma in a patient with nevoid basal cell carcinoma syndrome.

    PubMed

    Sobota, Amy; Pena, Maria; Santi, Mariarita; Ali Ahmed, Atif

    2007-07-01

    Nevoid basal cell carcinoma syndrome is an autosomal dominant multisystem disorder characterized by developmental anomalies and occurrence of multiple basal cell carcinomas and other tumors in early childhood. In this article, the authors report a case of a 19-year-old African American male with nevoid basal cell carcinoma syndrome and a history of medulloblastoma at age 2, meningioma at age 14, thyroid follicular adenomas with papillary carcinoma at age 15, and 2 basal cell carcinomas at ages 16 and 18. Recently, he developed sinonasal undifferentiated carcinoma (SNUC). The radiology and pathology of the sinonasal carcinoma are presented in this report. Review of the literature reveals that this is the first case of SNUC occurring in a patient with nevoid basal cell carcinoma syndrome.

  9. The molecular genetics underlying basal cell carcinoma pathogenesis and links to targeted therapeutics.

    PubMed

    Iwasaki, Julie K; Srivastava, Divya; Moy, Ronald L; Lin, Henry J; Kouba, David J

    2012-05-01

    Mutations in the sonic hedgehog signaling pathway play a key role in the development of basal cell carcinomas. Specifically, mutations in the PTCH1 (also known as PTCH or PTC1) and SMO genes cause tumor formation through constitutive activation of the pathway. Misregulation of the pathway has also been implicated in the nevoid basal cell carcinoma syndrome and other tumors. Understanding the function of the sonic hedgehog pathway has led to novel strategies for treatment. In this review we highlight the role of the pathway in the pathogenesis of basal cell carcinoma and review potential targeted therapies. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  10. Human Papilloma Virus (HPV) Induced Head & Neck Squamous Cell Carcinoma: A Comprehensive Retrospect

    PubMed Central

    Nishat, Roquaiya; Ramachandra, Sujatha; Kumar, Harish; Bandyopadhyay, Alokenath

    2015-01-01

    Head and Neck Squamous Cell Carcinoma accounts for the sixth most common malignancy occurring worldwide with tobacco and alcohol being the two well established risk factors. In the recent years, substantial evidence has been obtained that Human Papilloma Virus (HPV) associated head and neck cancers are on the rise. This article provides an insight into the structure of HPV genome, molecular pathogenesis, detection methods and clinical implications of HPV positive Head and Neck Squamous Cell Carcinoma. PMID:26266234

  11. [Vasculogenic mimicry in tongue squamous cell carcinoma].

    PubMed

    Zhang, Xiaogen; Liu, Chundong; Luo, Luqiao; Cai, Xiaohui

    2013-04-01

    To investigate the presence of vasculogenic mimicry (VM) in tongue squamous cell carcinoma and explore its clinical significance. Forty-two surgical specimens of tongue squamous cell carcinoma were examined for the presence of VM using HE staining and double staining of CD34 and PAS. Of the 42 specimens, 18 (42.86%) showed the presence of VM. VM was not correlated with the patients' age or gender, but with lymph node metastasis and the grade of tumor differentiation. Compared with tumors without VM, the tumors with VM had a significantly higher rate of lymph node metastasis (P<0.05) and a lower grade of differentiation (P<0.05). VM can be present in tongue squamous cell carcinoma, and the poorly differentiated tumors contain more VM, which is associated with a greater likeliness of lymph node metastasis and a poorer prognosis.

  12. Squamous cell carcinoma in Kauai, Hawaii.

    PubMed

    Chuang, T Y; Reizner, G T; Elpern, D J; Stone, J L; Farmer, E R

    1995-06-01

    It is estimated that over 100,000 new cases of squamous cell carcinoma are diagnosed in the United States annually. This number is compounded by an increasing concern over the ozone layer depletion and the continued sunbathing behavior of many individuals. This could be particularly acute in Hawaii, which may have the highest rates of skin cancer in the country. We believe the updated information on skin cancer is essential to address the magnitude of the problem. A prospective 5-year population-based incidence study was conducted on Kauai, Hawaii, between 1983 and 1987 to investigate the frequency of squamous cell carcinomas in resident Caucasians. A total of 58 residents, 37 men and 21 women, were identified with an initial episode of squamous cell carcinoma during the 5-year period. The average annual incidence rate per 100,000 Kauai Caucasian residents, standardized to the 1980 U.S. white population, was 153 for men and 92 for women with a combined rate of 118. The average patient age was 66.4 years. The head and neck was the most common anatomic site, with the extremities second. Subsequent new squamous cell carcinoma occurred in 13.8% of patients. Only one patient (2%) developed a recurrence after treatment. Twenty-five patients (43%) had basal cell carcinoma simultaneously or at other earlier times. In Kauai the incidence rate of squamous cell carcinoma is the highest yet documented in the United States. No consistent trend in incidence rates was appreciated during this 5-year period.

  13. Construction of differential mRNA-lncRNA crosstalk networks based on ceRNA hypothesis uncover key roles of lncRNAs implicated in esophageal squamous cell carcinoma

    PubMed Central

    Li, Yixue

    2016-01-01

    Increasing evidence has indicated that lncRNAs acting as competing endogenous RNAs (ceRNAs) play crucial roles in tumorigenesis, metastasis and diagnosis of cancer. However, the function of lncRNAs as ceRNAs involved in esophageal squamous cell carcinoma (ESCC) is still largely unknown. In this study, clinical implications of two intrinsic subtypes of ESCC were identified based on expression profiles of lncRNA and mRNA. ESCC subtype-specific differential co-expression networks between mRNAs and lncRNAs were constructed to reveal dynamic changes of their crosstalks mediated by miRNAs during tumorigenesis. Several well-known cancer-associated lncRNAs as the hubs of the two networks were firstly proposed in ESCC. Based on the ceRNA mechanism, we illustrated that the“loss” of miR-186-mediated PVT1-mRNA and miR-26b-mediated LINC00240-mRNA crosstalks were related to the two ESCC subtypes respectively. In addition, crosstalks between LINC00152 and EGFR, LINC00240 and LOX gene family were identified, which were associated with the function of “response to wounding” and “extracellular matrix-receptor interaction”. Furthermore, functional cooperation of multiple lncRNAs was discovered in the two differential mRNA-lncRNA crosstalk networks. These together systematically uncovered the roles of lncRNAs as ceRNAs implicated in ESCC. PMID:27966444

  14. A Foreigner in Squamous Cell Carcinoma!

    PubMed Central

    Patil, Shankargouda; Rao, Roopa S; Ganavi, B S

    2013-01-01

    Giant cells are the soldiers of defensive system of our body. They differ based on the stimuli that provoked their formation. On the other hand, squamous cell carcinoma (SCC) being the most common oral cancer, presents with varied histopathological features based on the degree of differentiation. Keratinizing islands of dysplastic squamous epithelial cells & a dense inflammatory response form the major component of well differentiated SCC. This keratin component may sometimes trigger foreign body giant cell (FBGC) reaction in the stroma, which may mislead the pathologist to aggressive forms of SCC containing pleomorphic giant cells. We encountered such an interesting case of foreign body giant cell reaction in oral SCC. Thus, the present article aims to provide a thorough knowledge on FBGC including their appearance, pathogenesis & significance in oral SCC. How to cite this article: Patil S, Rao RS, Ganavi BS. A Foreigner in Squamous Cell Carcinoma!. J Int Oral Health 2013;5(5):147-50. PMID:24324320

  15. [Basal cell carcinoma, squamous cell carcinoma and premalignant skin lesions--how to treat?].

    PubMed

    Pitkänen, Sari; Jeskanen, Leila; Ylitalo, Leea

    2014-01-01

    Increasing exposure to UV radiation is considered the most important etiologic factor of nonmelanoma skin cancers. Consequently, exposed areas such as the scalp and face, are the primary areas for developing non-melanoma skin cancers. Once a patient has presented with one tumor, additional lesions are common. The diagnosis is based on typical clinical picture and biopsy or excision for histopathological analysis. Various non-surgical treatment options have been established. Superficial basal cell carcinoma, superficial carcinoma in situ and all actinic keratoses are preferentially treated non-surgically. Most other basal cell and squamous cell carcinomas should be surgically removed.

  16. Basal cell carcinoma of the nail unit.

    PubMed

    Forman, Seth B; Ferringer, Tammie C; Garrett, Algin B

    2007-05-01

    We report a case of a 70-year-old white male with a basal cell carcinoma of the left thumb nail unit. Excision of the tumor via Mohs micrographic surgery was completed in 2 stages. The defect was repaired with a full thickness skin graft. Five months later the nail unit healed without complications. Prior to this report, 21 cases of basal cell carcinoma have been reported in the world literature. This case, as well as the prior reports, are reviewed with a focus on time to diagnosis, location, excisional technique, and method of repair.

  17. Patterns of Failure after Radical Surgery among Patients with Thoracic Esophageal Squamous Cell Carcinoma: Implications for the Clinical Target Volume Design of Postoperative Radiotherapy

    PubMed Central

    Wu, Bin; Zhu, Zheng-Fei; Chen, Hai-Quan; Fu, Xiao-Long

    2014-01-01

    Background This study evaluated patterns of treatment failure (especially locoregional failure; LRF) after radical esophagectomy and proposes a clinical target volume (CTV) for postoperative radiotherapy (PORT) among patients with thoracic esophageal squamous cell carcinoma (SCC). Methods All patients who were followed up in our center after radical esophagectomy between 2007 and 2011 were retrospectively enrolled. The patterns of first discovered failure were assessed, and LRFs (including anastomotic and regional lymph node recurrences) were evaluated to determine whether our proposed PORT CTV encompassed these areas. The clinicopathologic factors predictive of lymphatic recurrence type were analyzed. Results Of the 414 patients who underwent surgery and were followed up over the study, 207 experienced recurrent or metastatic diseases. The median time to progression was 11.0 months. Of the 173 patients with locoregional recurrence, nodal failure recurred in 160; supraclavicular and superior mediastinal lymph nodes had the highest metastasis rates. All 233 recurrent sites across the 160 patients were located in a standard CTV area, including the bilateral supraclavicular areas, the entire mediastinum, and the left gastric lymphatic drainage region. A total of 203 sites (87.2%) were located in either the bilateral supraclavicular areas or the entire mediastinum, and 185 sites (79.4%) were located in either the bilateral supraclavicular areas or the upper mediastinum. A multivariate analysis revealed the lymph node metastatic ratio (LNMR) and tumor differentiation were risk factors for nodal failure. Conclusions Locoregional recurrence (especially lymph node recurrence) was the most common and potentially preventable type of initial treatment failure after curative surgery among patients with thoracic esophageal SCC. The proposed PORT CTV covered most LRF sites. The lymphatic drainage regions for PORT are selective, and the supraclavicular and superior mediastinal

  18. Incidence of Small Lymph Node Metastases With Evidence of Extracapsular Extension: Clinical Implications in Patients With Head and Neck Squamous Cell Carcinoma

    SciTech Connect

    Ghadjar, Pirus; Simcock, Mathew; Schreiber-Facklam, Heide; Zimmer, Yitzhak; Graeter, Ruth; Evers, Christina; Arnold, Andreas; Wilkens, Ludwig; Aebersold, Daniel M.

    2010-12-01

    Purpose: Small lymph nodes (LN) show evidence of extracapsular extension (ECE) in a significant number of patients. This study was performed to determine the impact of ECE in LN {<=}7 mm as compared with ECE in larger LN. Methods and Materials: All tumor-positive LN of 74 head and neck squamous cell carcinoma (HNSCC) patients with at least one ECE positive LN were analyzed retrospectively for the LN diameter and the extent of ECE. Clinical endpoints were regional relapse-free survival, distant metastasis-free survival, and overall survival. The median follow-up for the surviving patients was 2.1 years (range, 0.3-9.2 years). Results: Forty-four of 74 patients (60%) had at least one ECE positive LN {<=}10 mm. These small ECE positive LN had a median diameter of 7 mm, which was used as a cutoff. Thirty patients (41%) had at least one ECE positive LN {<=}7 mm. In both univariate and multivariate Cox regression analyses, the incidence of at least one ECE positive LN {<=}7 mm was a statistically significant prognostic factor for decreased regional relapse-free survival (adjusted hazard ratio [HR]: 2.7, p = 0.03, 95% confidence interval [CI]: 1.1-6.4), distant metastasis-free survival (HR: 2.6, p = 0.04, 95% CI: 1.0-6.6), and overall survival (HR: 2.5, p = 0.03, 95% CI: 1.1-5.8). Conclusions: The incidence of small ECE positive LN metastases is a significant prognostic factor in HNSCC patients. Small ECE positive LN may represent more invasive tumor biology and could be used as prognostic markers.

  19. Lack of selectivity of protoporphyrin IX fluorescence for basal cell carcinoma after topical application of 5-aminolevulinic acid: implications for photodynamic treatment.

    PubMed

    Martin, A; Tope, W D; Grevelink, J M; Starr, J C; Fewkes, J L; Flotte, T J; Deutsch, T F; Anderson, R R

    1995-01-01

    Clinical trials of topical ALA in photodynamic therapy (PDT) of basal cell carcinoma (BCC) show significant recurrence rates. Exogenous 5-aminolevulinic acid (ALA) is converted by intracellular enzymes to photoactive protoporphyrin IX (PpIX) in human tissues. PpIX generates cytotoxic singlet oxygen when irradiated with visible light in the 400-640 nm range. To evaluate variability and heterogeneity in PpIX production by tumors in such trials, and to assess the usefulness of PpIX for marking skin tumors, we measured PpIX fluorescence distribution in BCC after topical application of 20% ALA cream. ALA cream was applied under occlusion for periods ranging from 3 to 18 h (average 6.9 h, SD 4 h) to 16 BCCs. ALA conversion to PpIX in the BCCs was assessed by in vivo photography, ex vivo video fluorescence imaging, and fluorescence microscopy. External macroscopic PpIX fluorescence, as assessed by in vivo and ex vivo imaging, correlated with the clinical presence of BCC. Examination by a digital imaging fluorescence microscope revealed inter- and intratumor fluorescence variability and heterogeneity. PpIX fluorescence corresponding to full tomor thickness was found in six superficial and four nodular tumors, and partial-thickness fluorescence was observed in five nodular tumors, but no PpIX fluorescence was observed in some areas of superficial, nodular and infiltrating tumors. In a significant number of nodular and infiltrating BCCs, topical ALA appeared to provide little or no PpIX in deep tumor lobules. In addition, no selectivity for tumor tissue versus normal epidermis was seen. The grossly brighter external PpIX fluorescence over tumors may be due, therefore, to enhanced penetration through tumor-reactive stratum corneum and to the tumor thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Squamous Cell Carcinoma of the Anal Canal: Patterns and Predictors of Failure and Implications for Intensity-Modulated Radiation Treatment Planning

    SciTech Connect

    Wright, Jean L.; Patil, Sujata M.; Temple, Larissa K.F.; Minsky, Bruce D.; Saltz, Leonard B.; Goodman, Karyn A.

    2010-11-15

    Purpose: Intensity-modulated radiation treatment (IMRT) is increasingly used in the treatment of squamous cell carcinoma of the anal canal (SCCAC). Prevention of locoregional failure (LRF) using IMRT requires appropriate clinical target volume (CTV) definition. To better define the CTV for IMRT, we evaluated patterns and predictors of LRF in SCCAC patients given conventional radiation treatment. Methods and Materials: We reviewed records of 180 SCCAC patients treated with conventional radiation with or without chemotherapy at our institution between January 1990 and March 2007. All patients received radiation; the median primary tumor dose was 45 Gy. A total of 173 patients also received mitomycin-based chemotherapy. Results: Median follow-up was 40 months. Actuarial 3-year colostomy-free survival was 89% and overall survival (OS) 88%. Actuarial 3-year LRF was 23%. A total of 45 patients had LRF, with 35 (78%) occurring locally in the primary site (25 local only, 10 local and regional); however, 20 (44%) had regional components of failure within the pelvis or inguinal nodes (10 regional only, 10 local and regional). Cumulative sites of LRF (patients may have one or more site of failure) were as follows: primary, 35; inguinal, 8; external perianal, 5; common iliac, 4; presacral, 3; distal rectum, 2; external iliac, 2; and internal iliac, 2. All patients with common iliac failure had cT3 or N+ disease. Conclusions: The observed patterns of failure support inclusion of the inguinal and all pelvic nodal groups in the CTV for IMRT. In patients with advanced tumor or nodal stage, common iliac nodes should also be included in the CTV.

  1. Basal Cell Carcinoma Arising in a Tattooed Eyebrow

    PubMed Central

    Lee, Jong-Sun; Park, Jin; Kim, Seong-Min; Kim, Han-Uk

    2009-01-01

    Malignant skin tumors, including squamous cell carcinoma and malignant melanoma, have occurred in tattoos. Seven documented cases of basal cell carcinoma associated with tattoos have also been reported in the medical literature. We encountered a patient with basal cell carcinoma in a tattooed eyebrow. We report on this case as the eighth reported case of a patient with basal cell carcinoma arising in a tattooed area. PMID:20523804

  2. Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

    PubMed

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

    The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

  3. A Case of Squamous Cell Carcinoma in the External Auditory Canal Previously Treated for Verrucous Carcinoma

    PubMed Central

    Nam, Soo Jung; Yang, Chan Joo

    2016-01-01

    Carcinoma in the external auditory canal (EAC) is a rare malignancy with an annual incidence of one per one million people, accounting for less than 0.2% of all head and neck cancers. The most common histopathological type of EAC cancer is squamous cell carcinoma. Verrucous carcinoma is a well-differentiated, low-grade variant of squamous cell carcinoma. It is a locally destructive, invasive, and slow growing tumor that rarely metastasizes. Verrucous carcinoma occurs predominantly in the oral cavity and larynx, and its occurrence in the EAC is extremely rare. In this report, we present a histologically confirmed case of verrucous carcinoma in the EAC and temporal bone, which for several years had been classified as epithelial hyperplasia. Two-and-a-half years after diagnosis of verrucous carcinoma, a recurrent mass was found and the lesion was then confirmed to be squamous cell carcinoma. PMID:27942606

  4. A Case of Squamous Cell Carcinoma in the External Auditory Canal Previously Treated for Verrucous Carcinoma.

    PubMed

    Nam, Soo Jung; Yang, Chan Joo; Chung, Jong Woo

    2016-12-01

    Carcinoma in the external auditory canal (EAC) is a rare malignancy with an annual incidence of one per one million people, accounting for less than 0.2% of all head and neck cancers. The most common histopathological type of EAC cancer is squamous cell carcinoma. Verrucous carcinoma is a well-differentiated, low-grade variant of squamous cell carcinoma. It is a locally destructive, invasive, and slow growing tumor that rarely metastasizes. Verrucous carcinoma occurs predominantly in the oral cavity and larynx, and its occurrence in the EAC is extremely rare. In this report, we present a histologically confirmed case of verrucous carcinoma in the EAC and temporal bone, which for several years had been classified as epithelial hyperplasia. Two-and-a-half years after diagnosis of verrucous carcinoma, a recurrent mass was found and the lesion was then confirmed to be squamous cell carcinoma.

  5. HPV-associated oropharyngeal squamous cell carcinoma.

    PubMed

    Smith, Timothy J; Mendez, Anthony; Donald, Carrlene; Nagel, Thomas Harold

    2017-01-01

    Human papillomavirus (HPV) can infect the tonsillar tissues of the oropharynx and is associated with oropharyngeal squamous cell carcinoma. This article provides an overview to guide primary care providers in screening patients for oropharyngeal cancer and making appropriate referrals. The article also reviews available HPV vaccines and immunization adherence rates.

  6. Squamous cell carcinoma associated with lupus vulgaris.

    PubMed

    Gooptu, C; Marks, N; Thomas, J; James, M P

    1998-05-01

    Squamous cell carcinomas are known to arise in certain chronic, scarring dermatoses and also to be associated with exposure to ultraviolet radiation. We now report a case arising in a plaque of lupus vulgaris, the patient having received radiation from a Finsen lamp as a child for a tuberculous abscess in that region.

  7. Presumed choroidal metastasis of Merkel cell carcinoma

    SciTech Connect

    Small, K.W.; Rosenwasser, G.O.; Alexander, E. III; Rossitch, G.; Dutton, J.J. )

    1990-05-01

    Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both the skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma.

  8. Squamous cell carcinoma arising in a meningomyelocele.

    PubMed Central

    Saksun, J. M.; Fisher, B. K.

    1978-01-01

    Squamous cell carcinoma developed in the meningomyelocele of a 25-year-old man. This is the third such case reported. The possibility of malignant disease arising in this congenital defect must be taken into account when treatment is being considered. Images FIG. 1 FIG. 2 FIG. 3 PMID:709475

  9. MET Inhibition in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Xie, Zuoquan; Lee, Young H.; Boeke, Marta; Jilaveanu, Lucia B.; Liu, Zongzhi; Bottaro, Donald P.; Kluger, Harriet M.; Shuch, Brian

    2016-01-01

    Background: Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer. Small molecule VEGFR inhibitors are widely used but are not curative and various resistance mechanisms such as activation of the MET pathway have been described. Dual MET/VEGFR2 inhibitors have recently shown clinical benefit but limited preclinical data evaluates their effects in ccRCC. Methods: An interrogation of the Cancer Genome Atlas (TCGA) dataset was performed to evaluate oncogenic alterations in the MET/VEGFR2 pathway. We evaluated the in vitro effects of Cabozantinib, a dual MET/VEGFR2 inhibitor, using a panel of ccRCC cell lines. Drug effects of cell viability and proliferation, migration, cell scatter, anchorage independent growth, and downstream MET/VEGFR2 signaling pathways were assessed. Results: Twelve percent of TCGA cases had possible MET/HGF oncogenic alterations with co-occurrence noted (p<0.001). MET/HGF altered cases had worse overall survival (p=0.044). Cabozantinib was a potent inhibitor of MET and VEGFR2 in vitro in our cell line panel. PI3K, MAPK and mTOR pathways were also suppressed by cabozantinib, however the effects on cell viability in vitro were modest. At nanomolar concentrations of cabozantinib, HGF-stimulated migration, invasion, cellular scattering and soft agar colony formation were inhibited. Conclusions: We provide further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. While the MET pathway is implicated in VEGFR resistance, dual inhibitors may have direct anti-tumor effects in a patient subset with evidence of MET pathway involvement. Cabozantinib is a potent dual MET/VEGFR2 inhibitor, significantly inhibits cell migration and invasion in vitro and likely has anti-angiogenic effects similar to other VEGFR tyrosine kinase inhibitors. Future work involving in vivo models will be useful to better define mechanisms of potential anti-tumor activity. PMID:27390595

  10. Psammomatous Squamous Cell Carcinoma of the Skin.

    PubMed

    Schuler, Andrew; Smith, Emily; Chen, Stephanie; Chan, May P; Harms, Paul W

    2017-09-20

    Psammoma bodies (PBs) are concentric, lamellated calcifications commonly observed in malignancies such as papillary thyroid carcinoma and serous carcinoma of the ovary in which they may serve prognostic value. PBs are rare in cutaneous squamous cell carcinoma (cSCC), with only 1 previously reported case. Here, we present 3 cases of cSCC displaying PBs. One case occurred in the setting of end-stage renal disease, whereas the other 2 cases were in patients who did not have comorbid conditions that might predispose to hypercalcemia and dystrophic calcification. All 3 tumors demonstrated classic immunophenotypic findings of cSCC. Our findings indicate that PBs are a rare but recurrent phenomenon in cSCC, with unknown prognostic significance. The potential for PB formation in cSCC should be kept in mind, as this may represent a diagnostic pitfall in tumors with limited sampling or unusual morphologies.

  11. A Case of Acantholytic Squamous Cell Carcinoma

    PubMed Central

    Lim, Ji Yeon; Do, Mi Ok; Kim, Seong Hyun; Hahm, Jeong Hee

    2008-01-01

    Acantholytic squamous cell carcinoma is a well-defined variant of squamous cell cancer in which significant portions of the neoplastic proliferation show a pseudoglandular or tubular microscopic pattern. It usually presents as a nodule with various colors, and it is accompanied by scaling, crusting, and ulceration on the sun-exposed areas of older aged individuals. Histologically, the tumor consists of a nodular, epidermal-derived proliferation that forms island-like structures. At least focally or sometimes extensively, the tumor cells shows a loss of cohesion within the central gland-like or tubular spaces. This tumor resembles the structure of eccrine neoplasms, but it is negative for dPAS, CEA and mucicarmine and it is only positive for EMA and cytokeratins. Herein we report a case of acantholytic squamous cell carcinoma that occurred on the face of an 82-year-old woman. PMID:27303210

  12. [Single prostatic metastasis of a small cell lung carcinoma].

    PubMed

    Gonzalez Yañez, Isabel; Perez Lopez, Maria Eva; Rodriguez Lopez, Jose Angel; Arias Santos, Maria Dolores; Garcia Gomez, Jesus; Garcia Mata, Jesus

    2009-03-01

    To make the difference between two uncommon entities, small cell prostate carcinoma and prostatic metastasis of small cell lung cancer. We describe a case of single extrapulmonar metastasis in the prostate from small lung carcinoma. We describe a case of single extrapulmonar metastasis in the prostate from small lung carcinoma. Clinical and radiographic findings and inmunohistochemistry allow differential diagnosis.

  13. Laryngeal Dysplasia, Squamous Cell Carcinoma, and Variants.

    PubMed

    Thompson, Lester D R

    2017-03-01

    Squamous cell carcinoma (SCC) is a malignant epithelial tumor showing evidence of squamous differentiation. It is the most common malignancy of the larynx, with several variants (verrucous, exophytic or papillary, spindle-cell, basaloid, acantholytic, adenosquamous) recognized, with well-established precursor lesions. Dysplasia is now separated into only low-grade and high-grade categories. Each SCC variant has unique cytomorphologic features and histologic differential diagnoses that are important to consider, as management and outcomes are different.

  14. Advanced Basal Cell Carcinoma: Epidemiology and Therapeutic Innovations.

    PubMed

    Mohan, Shalini V; Chang, Anne Lynn S

    2014-01-01

    Advanced basal cell carcinomas are a subset of basal cell carcinomas that can be difficult to treat either due to their local invasiveness, proximity to vital structures, or metastasis. The incidence of all basal cell carcinoma is increasing in the United States, although it is not known whether advanced basal cell carcinomas (aBCCs) are also increasing. Recently, highly targeted therapy based on knowledge of the basal cell carcinoma pathogenesis has become available either commercially or through human clinical trials. These orally available drugs inhibit the Hedgehog signaling pathway, and lead to advanced basal cell carcinoma shrinkage that can enable preservation of adjacent vital organs. In this review, we outline the role of Hedgehog pathway inhibitors as well as other treatment modalities such as excision, radiotherapy and more traditional chemotherapy in treating advanced basal cell carcinomas. We also highlight current gaps in knowledge regarding the use and side effects of this targeted therapy.

  15. [Primary squamous cell carcinoma of the breast: rare form carcinoma].

    PubMed

    Maksimović, Sinisa

    2009-01-01

    Primary squamous cell carcinoma (SCC) is a rare form of breast carcinoma. Incidence is reported to be 0.1-3.6%. We report a case of a young woman, 37-year-old, with history of a lump in the upper outer quadrant of the left breast with ulceration of the skin surface. Menarche occurred at age of 12. The patient was married, had two deliveries and had her first child at age of 26. She did not use contraceptive pills. Diagnosis of the tumour of the breast was made at the Department of surgery in General Hospital in Bijeljina in September 2007. Clinical examination, mammography and ultrasonography were performed. Physical examination revealed a circumscribed and firm mass measuring 60 x 60 x 80 mm. Mammogram showed a round, high-density mass with almost regular but partially irregular margin. Ultrasonogram of the left breast tumor identified an irregularly shaped hypoechoic lesion. After clinical staging of the disease, we performed incision biopsy of the skin and tumour of the left breast with histopathology examination (standard hematoxylin and eosin). Patient had estrogen and progesteron receptors negative and was HER2/neu negative. After histopathology, patient's case was presented to the working group for breast tumors which decided to start with the neoadjuvant chemotherapy using platinum. After six cycles of neoadjuvant chemotherapy, regression of breast tumor was confirmed. Working group decided that radical mastectomy of left breast should be performed.

  16. Constitutive Activation of NF-kappaB in Prostate Carcinoma Cells Through a Positive Feedback Loop: Implication of Inducible IKK-Related Kinase (IKKi)

    DTIC Science & Technology

    2006-08-01

    strongly suggests that GR is constitutively active in both normal and hyperplastic prostate glands. In contrast, GR levels were low or below detection... BPH ; (b) PC (Gleason score 7); (c) HGPIN and (d) prostate stroma. Note: Low GR expression in PC (B1) and high GR expression in apparently normal...was increased in human prostate carcinomas in comparison to BPH samples (see progress report for FY02), these recent results suggest an important

  17. Mechanisms behind signet ring cell carcinoma formation.

    PubMed

    Fukui, Yasuhisa

    2014-08-08

    Signet ring cell carcinomas are highly malignant dedifferentiated adenocarcinomas. There are no cell-cell interactions between these round-shaped cells. They contain huge numbers of vacuoles, filled with mucins, which are secreted from the cells. The mechanism behind this phenotype has recently begun to be elucidated. In highly differentiated adenocarcinomas the ErbB2/ErbB3 complex is activated, which is followed by phosphatidylinositol 3-kinase (PI3K) activation. p38 MAP kinase is activated downstream of PI3K and adherens junctions are disrupted via Rac1 activation. Loss of adherens junctions leads to the disappearance of tight junctions, which results in a loss of cell-cell interactions. Secretion of mucin is enhanced by activation of PI3K. One of the mucins - Muc4 - can activate ErbB2. Under normal conditions Muc4 and ErbB2 are separated by adherens and tight junctions, however in signet ring cells they are able to interact, since these junctions have been lost. Therefore, an activation loop is formed, consisting of ERbB2/ErbB3-Muc4-ErbB2/ErbB3. As a result, the ErbB2/ErbB3 signaling pathway becomes constitutively activated, cell-cell interactions are lost, and signet ring carcinomas are formed. As a result of constitutive activation of the ErbB2/ErbB3 complex, cell growth is continuously enhanced. Some signet ring cell carcinomas have been found to have mutations in the E-cadherin gene, which fits the above hypothesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Clinical implications of basic research in hepatocellular carcinoma.

    PubMed

    Dhanasekaran, Renumathy; Venkatesh, Sudhakar K; Torbenson, Michael S; Roberts, Lewis R

    2016-03-01

    A 58-year old Caucasian female has compensated hepatitis C related cirrhosis. Her surveillance ultrasound showed hypodense liver nodules and subsequent triple phase CT scan showed five tumor nodules with diameters ranging from 3-5cms involving both hepatic lobes. The nodules showed characteristic radiologic findings on the CT scan and she was diagnosed with hepatocellular carcinoma (HCC) based on non-invasive criteria. There was also associated right portal vein tumor thrombosis. Her functional capacity at diagnosis was slightly limited, but she was capable of performing all activities of daily living and self-care. Her laboratory tests at diagnosis were as follows: sodium 129mmol/L, potassium 3.6mmol/L, blood urea nitrogen 22mg/dL, creatinine 1.0mg/dL, albumin 2.9g/dl, bilirubin 1.8mg/dl, alanine aminotransferase 87U/L, aspartate aminotransferase 68U/L, alkaline phosphatase 139U/L, white blood cell 3.5x10(9)/L, hemoglobin 10.4, platelet count 73x10(9)/L, international normalized ratio 1.9 and alpha-fetoprotein 5200ng/ml. An upper endoscopy was negative for esophageal or gastric varices. Based on the tumor burden, presence of macrovascular invasion, ECOG performance status of 1 and Child-Pugh class A she was classified to have BCLC stage C HCC. She was started on sorafenib therapy at 400mg oral twice daily but unfortunately this had to be discontinued since she experienced severe diarrhea and skin rash. She now returns for follow-up and requests information on the available therapeutic options. This particular case scenario is not uncommon and does raise several clinically relevant questions: This review provides a comprehensive overview of the current state of HCC management and also examines the clinical implications of recent basic research in HCC. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. Laminin receptor on human breast carcinoma cells.

    PubMed Central

    Terranova, V P; Rao, C N; Kalebic, T; Margulies, I M; Liotta, L A

    1983-01-01

    Human MCF-7 breast carcinoma cells possess a receptor-like moiety on their surface that has a high binding affinity (Kd = 2 nM) for laminin, a glycoprotein localized in basement membranes. Laminin preferentially stimulates (8-fold) MCF-7 cells to attach to type IV (basement membrane) collagen, whereas fibronectin stimulates attachment only 2-fold for these cells on type I collagen. The attachment properties of two other human breast carcinoma cell lines to type IV collagen were also studied. The attachment of ZR-75-1 cells was stimulated 4-fold by laminin and 5-fold by fibronectin, whereas T47-D cell attachment was stimulated 2-fold by laminin and 7-fold by fibronectin. By employing protease-derived fragments of laminin, the major domains of the laminin molecule that participate in MCF-7 cell attachment to type IV collagen were identified. The whole laminin molecule has the configuration of a four-armed cross with three short arms and one long arm. A major cell-binding domain was found to reside near the intersection point of the short arms, and the type IV collagen-binding domain was associated with the globular end regions of the short arms. The receptor for laminin on the surface of these tumor cells may be involved in the initial interaction of tumor cells via laminin with the vascular basement membrane to facilitate invasion and subsequent promotion of metastasis. Images PMID:6300843

  20. Frequent Mismatch Repair Protein Deficiency in Mixed Endometrioid and Clear Cell Carcinoma of the Endometrium.

    PubMed

    Köbel, Martin; Tessier-Cloutier, Basile; Leo, Joyce; Hoang, Lien N; Gilks, C Blake; Soslow, Robert A; Delair, Deborah; Stewart, Colin J R; Lee, Cheng-Han

    2017-01-20

    Mixed endometrioid and clear cell carcinoma of the endometrium refers to a scenario in which the tumor exhibits histologic features of both endometrioid and clear cell carcinoma. We observed a tendency for these tumors to occur in a mismatch repair (MMR) protein-deficient molecular background in a prior study that examined a small cohort of mixed-type endometrial carcinomas. The aim of this study was to determine the rate of MMR protein deficiency in a larger series of endometrial mixed endometrioid and clear cell carcinomas, through a retrospective survey of MLH1, PMS2, MSH2, and MSH6 expression in such tumors at 5 tertiary centers. A total of 41 cases were identified and 27 (66%) tumors demonstrated MMR protein deficiency with a comparable frequency across the contributing centers (ranging from 56% to 83%). Among the MMR protein-deficient cases, 59% showed concurrent MLH1 and PMS2 loss, 33% showed concurrent MSH2 and MSH6 loss, and 4% showed isolated PMS2 or MSH6 loss. Compared with a previously published series of 15 pure endometrial clear cell carcinomas, mixed endometrioid and clear cell carcinomas are associated with significantly better disease-specific survival (P=0.02). In summary, endometrial carcinomas with mixed endometrioid and clear cell histology are frequently MMR protein deficient. This finding has implications both for our understanding of its tumor biology and for the identification of patients with potential Lynch syndrome.

  1. Cell survival curve for primary hepatic carcinoma cells and relationship between SF2 of hepatic carcinoma cells and radiosensitivity

    PubMed Central

    Liu, Zhi-Zhong; Huang, Wen-Ying; Lin, Ju-Sheng; Li, Xiao-Sheng; Lan, Xiao; Cai, Xiao-Kun; Liang, Kuo-Huan; Zhou, Hai-Jun

    2005-01-01

    AIM: To establish the cell survival curve for primary hepatic carcinoma cells and to study the relationship between SF2 of primary hepatic carcinoma cells and radiosensitivity. METHODS: Hepatic carcinoma cells were cultured in vitro using 39 samples of hepatic carcinoma at stages II-IV. Twenty-nine samples were cultured successfully in the fifth generation cells. After these cells were radiated with different dosages, the cell survival ratio and SF2 were calculated by clonogenic assay and SF2 model respectively. The relationship between SF2 and the clinical pathological feature was analyzed. RESULTS: Twenty-nine of thirty-nine samples were successfully cultured. After X-ray radiation of the fifth generation cells with 0, 2, 4, 6, 8 Gy, the cell survival rate was 41%, 36.5%, 31.0%, 26.8%, and 19%, respectively. There was a negative correlation between cell survival and irradiation dosage (r = -0.973, P<0.05). SF2 ranged 0.28-0.78 and correlated with the clinical stage and pathological grade of hepatic carcinoma (P<0.05). There was a positive correlation between SF2 and D0.5 (r = 0.773, P<0.05). CONCLUSION: SF2 correlates with the clinical stage and pathological grade of hepatic carcinoma and is a marker for predicting the radiosensitivity of hepatic carcinomas. PMID:16437614

  2. Basaloid squamous cell carcinoma with 'monster' cells: a mimic of pleomorphic basal cell carcinoma.

    PubMed

    Defty, Clare L; Segen, Joseph; Carter, Jonathan J; Ahmed, Imtiaz; Carr, Richard A

    2011-04-01

    Pleomorphic giant or 'monster' cells represent a well-recognized yet uncommon finding associated with basal cell carcinoma (BCC), usually of nodular type. We present a case of basaloid squamous cell carcinoma (basaloid SCC) with 'monster' cells that closely mimicked those described in pleomorphic nodular BCC. Clinically, the lesion presented as a fleshy, hyperkeratotic nodule in an 82-year-old woman. Histopathology revealed a basaloid lesion with lobulated borders and focal retraction artifact but a lack of prominent palisading or stromal mucin. There were areas of necrosis and small foci of keratinization. Striking bizarre monstrous pleomorphic nuclei were widely scattered throughout the lesion. Ber-EP4 immunohistochemistry proved to be negative and epithelial membrane antigen (EMA) expression was moderate to strong in 70% of the basaloid epithelium. Monster cells have not previously been highlighted in cutaneous SCC or in its uncommon cutaneous basaloid variant. The prognostic significance of monster cells is unknown but, given the relative paucity of keratinization in basaloid SCC, these lesions should probably be regarded as poorly differentiated. We have not previously encountered an SCC that so closely resembles nodular BCC with pleomorphic monster cells and believe that this is the first such report in the literature.

  3. Dermoscopic criteria and basal cell carcinoma.

    PubMed

    Del Busto-Wilhelm, Isabel; Malvehy, Josep; Puig, Susana

    2016-12-01

    Basal cell carcinoma (BCC) is nowadays the most frequent skin cancer in the fair-skinned population. Clinical suspicion for BCC diagnosis can be easy in advance cases, but it sometimes sets a real challenge wherein dermoscopy has proven to be a useful tool. Dermoscopy is a non-invasive diagnostic technique that improves the clinical diagnosis of pigmented and non-pigmented BCC representing a link between macroscopic clinical dermatology and microscopic dermatopathology. The dermoscopy of basal cell carcinoma is currently very well-known, as well as the clinical and histopathological features of BCC subtypes. Recently some flowcharts and algorithms for the most common subtypes of BCC have been proposed. We review the latest literature on the topic to describe the most frequent dermoscopy patterns for each subtype.

  4. Laryngeal acinic cell carcinoma following thyroid irradiation

    SciTech Connect

    Reibel, J.F.; McLean, W.C.; Cantrell, R.W.

    1981-01-01

    Only three examples of acinic cell carcinoma of the larynx or trachea are found in the recent literature. A case of acinic cell carcinoma of the subglottic larynx and trachea was diagnosed and treated at the University of Virginia Medical Center. To our knowledge this is the first such case with a prior history of radiation to the neck. The patient is a 56-year-old woman who was irradiated for hyperthyroidism 46 years ago. When seen she also had parathyroid hyperplasia and multiple thyroid adenomas, conditions that frequently follow irradiation of the thyroid in children. These findings in this case support the concept that radiation may be responsible for inducing this tumor, which otherwise rarely occurs in this location. The use of electron microscopy was extremely useful in the diagnosis of this tumor. She was treated with total laryngectomy and right neck dissection and is now free of disease one year after surgery.

  5. Metastatic squamous cell carcinoma in a cat.

    PubMed

    Dhaliwal, Ravinder S; Kufuor-Mensah, Eric

    2007-02-01

    A 7-year-old, spayed female Persian cat was referred for evaluation of progressive paraplegia. The cat was thin, cachectic and paraplegic on presentation. The survey radiographs showed a left caudal pulmonary lesion and lytic skeletal lesions at the right iliac crest and left distal scapula. Due to a poor prognosis for complete recovery, the owner opted for euthanasia. Post-mortem examination revealed bilaterally small and irregular kidneys, lysis of the left iliac crest and left distal scapula and a dilated left ventricular lumen with a thin interventricular septum. Histologically, all the lesions were determined to be squamous cell carcinoma. It appears that the origin or the primary site of the malignancy in this case is pulmonary as cardiac and skeletal tissues are primarily mesenchymal in origin and are less likely to develop a primary epithelial malignancy. To the best of our knowledge, there is no description of cardiac or skeletal metastatic squamous cell carcinoma in a cat.

  6. Immunotherapy for Esophageal Squamous Cell Carcinoma.

    PubMed

    Kojima, Takashi; Doi, Toshihiko

    2017-05-01

    Esophageal squamous cell carcinoma have been frustrating to treat, with slow progress made on extending survival. Immunotherapy targeting immune checkpoints, T cells, and infiltrating lymphocytes has shown promise in early studies. The efficacy of pembrolizumab and nivolumab is encouraging. Anti-chemokine receptors and oncolytic viruses are also making headway against these stubborn tumors; improved results when immune checkpoint inhibitors are combined with radiation therapy are eagerly anticipated. Adoptive T cell therapy and vaccines are also under development. The importance of a multidisciplinary approach cannot be emphasized enough.

  7. [Squamous cell carcinoma in lupus vulgaris].

    PubMed

    Kimmritz, Jens; Hermes, Barbara; Schewe, Christiane; Haas, Norbert

    2004-02-01

    Lupus vulgaris and carcinoma in lupo have become rare events that take place in the developed countries only under special circumstances. A 53-year-old woman developed such a carcinoma. She suffered from alcoholism, a well known risk factor for tuberculosis. The diagnosis of lupus vulgaris was confirmed by biopsy when an erythematous lesion on her arm that had been present for 25 years enlarged and subsequently ulcerated. Chemotherapy was discontinued because of lack of compliance and the ulcer grew markedly over the following 16 months. Therefore the entire lesion was excised. Histology showed a squamous cell carcinoma within the ulcer. Neither further systemic manifestations of tuberculosis nor metastases of the carcinoma were found. Under continuous combined antituberculous therapy, the patient remained free of symptoms. This case underlines the problems associated with a disease that has been nearly forgotten in the western countries. It also shows that alcoholism is a risk factor for tuberculosis, along with debilitating diseases such as lymphoma and AIDS as well as immunosuppressive therapy.

  8. Genetic associations of transitional cell carcinoma.

    PubMed

    Herring, D W; Cartwright, R A; Williams, D D

    1979-04-01

    A series of 101 cases of transitional cell carcinoma (TCC) was contrasted with a control series for several genetic parameters. Three genetic associations were demonstrated with the TCC patients having A gene frequencies, HLA B5 and HLA CW4 genes all higher than might be expected by chance. A classification of the natural history of the disease is used to show that the HLA frequencies vary with the more or the less severe forms of the disease.

  9. Nursing Management of Advanced Merkel Cell Carcinoma.

    PubMed

    Lowry, Pamela A; Freeman, Morganna L; Russell, Jeffery S

    2016-11-01

    Merkel cell carcinoma (MCC) is a rare and lethal skin cancer with few known treatment options. Management of this disease is challenging, and oncology nurses must understand the medical, physical, and psychosocial burden that MCC places on the patient and family caregivers. Patients must navigate a complex medical and insurance network that often fails to support patients with rare cancers. Nurses must advocate for these patients to ensure quality comprehensive cancer care.

  10. Gastric metastasis by lung small cell carcinoma

    PubMed Central

    Casella, Giovanni; Bella, Camillo Di; Cambareri, Antonino Roberto; Buda, Carmelo Antonio; Corti, Gianluigi; Magri, Filippo; Crippa, Stefano; Baldini, Vittorio

    2006-01-01

    Metastatic tumors of the gastrointestinal tract are rare. We describe a case of gastric metastasis due to primary lung cancer, revealed by an upper gastrointestinal endoscopy (UGIE). Haematogenous metastases to the stomach are a rare event. To our knowledge, only 55 cases have been described in the international literature. In these patients, the prognosis is very poor. We report herein a case of gastric metastasis by lung small cell carcinoma, with a review of the literature about this rare entity. PMID:16810769

  11. [Radiotherapy for small cell lung carcinoma].

    PubMed

    Pourel, N

    2016-10-01

    Radiotherapy for small cell lung carcinoma has known significant improvements over the past 10 years especially through routine use of PET-CT in the initial work-up and contouring before treatment. Prophylactic cranial irradiation remains a standard of care for locally advanced disease and is a subject of controversy for metastatic disease. A new indication for thoracic radiotherapy may soon arise for metastatic disease, still confirmation studies are ongoing.

  12. CT features of nonfunctioning islet cell carcinoma

    SciTech Connect

    Eelkema, E.A.; Stephens, D.H.; Ward, E.M.; Sheedy, P.F. II

    1984-11-01

    To determine the computed tomographic (CT) characteristics of nonfunctioning islet cell carcinoma of the pancreas, the CT scans of 27 patients with that disease were reviewed. The pancreatic tumor was identified as a mass in 26 patients (96%) Of the 25 tumors evaluated with contrast enhancement, 20 became partially diffusely hyperdense relative to nearby normal pancreatic tissue. Hepatic metastases were identified in 15 patients (56%), regional lymphadenopathy in 10 (37%), atrophy of the gland proximal to the tumor in six (22%), dilatation of the biliary ducts in five (19%), and dilatation of the pancreatic duct in four (15%). The CT appearances of the nonfunctioning islet cell tumors were compared with those of 100 ordinary (ductal) pancreatic adenocarcinomas. Although the two types of tumors were sometimes indistinguishable, features found to be more characteristic of islet cell carcinoma included a pancreatic mass of unusually large size, calcification within the tumor, and contrast enhancement of either the primary tumor or hepatic metastases. Involvement of the celiac axis or proximal superior mesenteric artery was limited to ductal carcinoma.

  13. Nevoid Basal Cell Carcinoma Syndrome

    MedlinePlus

    ... other skin problems a person has experienced. Early treatment of basal cell skin cancer reduces the amount of surgery and scarring. Regular ... sun . People with NBCCS should not receive radiation therapy, as this will ... cell skin cancers. Screening recommendations may change over time as new ...

  14. Diagnosis and treatment of Basal cell and squamous cell carcinoma.

    PubMed

    Firnhaber, Jonathon M

    2012-07-15

    Family physicians are regularly faced with identifying, treating, and counseling patients with skin cancers. Nonmelanoma skin cancer, which encompasses basal cell and squamous cell carcinoma, is the most common cancer in the United States. Ultraviolet B exposure is a significant factor in the development of basal cell and squamous cell carcinoma. The use of tanning beds is associated with a 1.5-fold increase in the risk of basal cell carcinoma and a 2.5-fold increase in the risk of squamous cell carcinoma. Routine screening for skin cancer is controversial. The U.S. Preventive Services Task Force cites insufficient evidence to recommend for or against routine whole-body skin examination to screen for skin cancer. Basal cell carcinoma most commonly appears as a pearly white, dome-shaped papule with prominent telangiectatic surface vessels. Squamous cell carcinoma most commonly appears as a firm, smooth, or hyperkeratotic papule or plaque, often with central ulceration. Initial tissue sampling for diagnosis involves a shave technique if the lesion is raised, or a 2- to 4-mm punch biopsy of the most abnormal-appearing area of skin. Mohs micrographic surgery has the lowest recurrence rate among treatments, but is best considered for large, high-risk tumors. Smaller, lower-risk tumors may be treated with surgical excision, electrodesiccation and curettage, or cryotherapy. Topical imiquimod and fluorouracil are also potential, but less supported, treatments. Although there are no clear guidelines for follow-up after an index nonmelanoma skin cancer, monitoring for recurrence is prudent because the risk of subsequent skin cancer is 35 percent at three years and 50 percent at five years.

  15. Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma

    PubMed Central

    Lopez, Jose Ignacio

    2016-01-01

    A multifocal biphasic squamoid alveolar renal cell carcinoma in a 68-year-old man is reported. Four different peripheral tumor nodules were identified on gross examination. A fifth central tumor corresponded to a conventional clear cell renal cell carcinoma. Biphasic squamoid alveolar renal cell carcinoma is a rare tumor that has been very recently characterized as a distinct histotype within the spectrum of papillary renal cell carcinoma. Immunostaining with cyclin D1 seems to be specific of this tumor subtype. This is the first reported case with multifocal presentation. PMID:27158455

  16. Anogenital squamous cell carcinoma in neglected patient.

    PubMed

    Svecova, D; Havrankova, M; Weismanova, E; Babal, P

    2012-01-01

    Skin squamous cell carcinomas (SCCs) are arguably the second most common carcinoma of the skin and are responsible for the majority of non-melanoma skin cancer deaths. Gynecologist treated a Caucasian 56-years old female patient for genital wart with podophyllotoxin cream. She did not achieve complete response and therefore she has interrupted the therapy and the collaboration with the gynecologist. At the time of evaluation the lesion had a size of man's palm in anogenital region and showed characteristic features of neoplasm. The regional lymph nodes have produced infiltrated painful bubo. PCR analysis for HPV proved negative. Histopathology revealed well-differentiated squamous cell keratinizing carcinoma from the tumor as well as from the regional lymph node packet. Staging computed tomography scans proved negative and pelvis scans disclosed regional lymphadenopathy underlying the tumor. Palliative radiation therapy (by linear accelerator) was administered for the oversized tumor to the total TD 50.0Gy. The patient died 6 months after diagnostic assessment from cardio-respiratory failure. Staging computed tomography before her death did not disclose distinct metastases in her inner organs. Well-differentiated squamous cell keratinizing carcinoma could be growing endophytically affecting the underlying adipose tissue and musculature, with spreading into the regional lymph nodes. The rate of metastases into inner organs seems to vary according to the aggressiveness and metastatic behavior of each SCC. The case report calls for attention to the importance of collaboration among various specialists assisting in the diagnosis and management of skin neoplasm (Fig. 5, Ref. 12). Full Text in PDF www.elis.sk.

  17. Hereditary Papillary Renal Cell Carcinoma

    MedlinePlus

    ... removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed ... question. The parents can then choose to transfer embryos that do not have the mutation. PGD has ...

  18. Desmosomal defects in acantholytic squamous cell carcinomas

    PubMed Central

    O’Shea, Charlene; Fitzpatrick, James E.; Koch, Peter J.

    2014-01-01

    Background Acantholytic squamous cell carcinoma (Acantholytic SCC) are epithelial tumors characterized by a loss of cell adhesion between neoplastic keratinocytes. The mechanism underlying loss of cell-cell adhesion in these tumors is not understood. Methods A retrospective analysis of acantholytic SCC (n=17) and conventional SCC (n=16, controls not showing acantholysis) was conducted using a set of desmosomal and adherens junction protein antibodies. Immunofluorescence microscopy was used to identify tumors with loss of adhesion protein expression. Results The vast majority of acantholytic SCC (89%) showed focal loss of at least one desmosomal cell adhesion protein. Most interestingly, 65% of these tumors lost expression of two or more desmosomal proteins. Conclusions Loss of cell adhesion in acantholytic SCC is most likely linked to the focal loss of desmosomal protein expression, thus providing potential mechanistic insight into the patho-mechanism underlying this malignancy. PMID:25264142

  19. Histologic pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients

    PubMed Central

    Ko, Jennifer S; Prieto, Victor G; Elson, Paul; Vilain, Ricardo E; Pulitzer, Melissa; Scolyer, Richard A; Reynolds, Jordan P; Piliang, Melissa; Ernstoff, Marc S; Gastman, Brian; Billings, Steven D

    2016-01-01

    facilitates risk stratification of Merkel cell carcinoma patients that may have management implications. PMID:26541273

  20. Primary oat cell carcinoma of the larynx

    SciTech Connect

    Aguilar, E.A. III; Robbins, K.T.; Stephens, J.; Dimery, I.W.; Batsakis, J.G.

    1987-02-01

    The aggressiveness of small (oat) cell carcinoma of the larynx presents a therapeutic challenge to the oncologist. Since the first description of this type of carcinoma in 1972, 52 patients have been reported in the literature and a variety of treatment regimens have been used. The purpose of this study was to report two new cases and review all previous reports to determine the disease's biological behavior, clinical manifestations, and optimum treatment. Thirty-five percent of the tumors were transglottic, and 27% were supraglottic. Fifty-four percent of patients had regional metastases at initial presentation and 17.6% had distant metastases. The median survival was 10 months for all patients. Patients who were treated with chemotherapy with or without other modalities had the best 2-year survival rates (52.2%). Forty-one percent of patients had regional recurrence only, 12.5% had regional recurrence and distant metastases, and 2% developed distant metastases only. We conclude that patients with oat cell carcinoma of the larynx should be treated with combination chemotherapy and radiation therapy. Surgery is best reserved for persistent and recurrent disease at the primary site and neck.

  1. The prognostic implication of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in primary locally advanced oral squamous cell carcinoma cases: a tissue microarray study.

    PubMed

    Solomon, Monica Charlotte; Vidyasagar, M S; Fernandes, Donald; Guddattu, Vasudev; Mathew, Mary; Shergill, Ankur Kaur; Carnelio, Sunitha; Chandrashekar, Chetana

    2016-12-01

    Oral squamous cell carcinomas comprise a heterogeneous tumor cell population with varied molecular characteristics, which makes prognostication of these tumors a complex and challenging issue. Thus, molecular profiling of these tumors is advantageous for an accurate prognostication and treatment planning. This is a retrospective study on a cohort of primary locally advanced oral squamous cell carcinomas (n = 178) of an Indian rural population. The expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in a cohort of primary locally advanced oral squamous cell carcinomas was evaluated. A potential biomarker that can predict the tumor response to treatment was identified. Formalin-fixed paraffin-embedded tumor blocks of (n = 178) of histopathologically diagnosed cases of locally advanced oral squamous cell carcinomas were selected. Tissue microarray blocks were constructed with 2 cores of 2 mm diameter from each tumor block. Four-micron-thick sections were cut from these tissue microarray blocks. These tissue microarray sections were immunohistochemically stained for EGFR, p53, Bcl-2, cyclin D1 and p16. In this cohort, EGFR was the most frequently expressed 150/178 (84%) biomarker of the cases. Kaplan-Meier analysis showed a significant association (p = 0.038) between expression of p53 and a poor prognosis. A Poisson regression analysis showed that tumors that expressed p53 had a two times greater chance of recurrence (unadjusted IRR-95% CI 2.08 (1.03, 4.5), adjusted IRR-2.29 (1.08, 4.8) compared with the tumors that did not express this biomarker. Molecular profiling of oral squamous cell carcinomas will enable us to categorize our patients into more realistic risk groups. With biologically guided tumor characterization, personalized treatment protocols can be designed for individual patients, which will improve the quality of life of these patients.

  2. Squamous cell carcinoma of the anal sacs in three dogs.

    PubMed

    Mellett, S; Verganti, S; Murphy, S; Bowlt, K

    2015-03-01

    Anal sac squamous cell carcinoma is rare in dogs. Five cases have been previously reported, treatment of which involved surgery alone. This report describes three further cases of canine anal sac squamous cell carcinoma which underwent medical (meloxicam) management alone, resulting in survival of up to seven months. No metastases were identified. Squamous cell carcinoma, although extremely uncommon, should be considered as a possible differential diagnosis when a dog is presented for investigation of an anal sac mass.

  3. Small Cell Neuroendocrine Carcinoma of the Cervix: A Rare Entity

    PubMed Central

    V, Pavithra; Shalini, C.N. Sai; Priya, Shanmuga; Rani, Usha; Rajendiran, S; Joseph, Leena Dennis

    2014-01-01

    Small cell carcinoma of the cervix is a rare and a very aggressive tumour. Once being considered to be a rare type of squamous cell carcinoma, evidence has proven that most of the tumours express one or more markers of neuroendocrine differentiation. The behaviour of this rare malignancy is different from that of squamous cell carcinomas, with a high propensity for nodal and distant metastases. Hence, there is a need to highlight this histopathological entity. PMID:24701511

  4. c-Met in chromophobe renal cell carcinoma.

    PubMed

    Erlmeier, Franziska; Ivanyi, Philipp; Hartmann, Arndt; Autenrieth, Michael; Wiedemann, Max; Weichert, Wilko; Steffens, Sandra

    2017-02-01

    c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for c-Met expression by immunohistochemistry. Expression data were associated with clinicopathological parameters including patient survival. Eighty-one chRCC patients were eligible for analysis. Twenty-four (29.6%) patients showed a high c-Met expression (c-Met(high), staining intensity higher than median). Our results showed an association between c-Met(high) expression and the existence of lymph node metastasis (p = 0.007). No further significant clinicopathological associations with c-Met were identified, also regarding c-Met expression and overall survival. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of c-Met in a considerably large cohort of chRCC. High c-Met expression is associated with the occurrence of lymph node metastasis. This indicates that c-Met might be implicated into metastatic progression in chRCC.

  5. Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

    PubMed

    Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

    2016-08-01

    Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid.

  6. Pigmented basal cell carcinoma mimicking a superficial spreading melanoma.

    PubMed

    Hasbún Acuña, Paula; Cullen Aravena, Roberto; Maturana Donaire, César; Ares Mora, Raúl; Porras Kusmanic, Ninoska

    2016-12-20

    Basal cell carcinoma is the most common form of skin cancer, especially in elderly people. Pigmented basal cell carcinoma is a rare subtype and has been described in the literature as a nodular and hyperpigmented lesion; rarely, it can appear as an extensive pigmented plate, which may be clinically indistinguishable from superficial spreading melanoma and Bowen disease. Dermatoscopy has a high sensitivity in the diagnosis of basal cell carcinoma. When Menzies criteria are used; however, the final diagnosis is made by histopathology. The objective of the present report is to analyze the case of a patient with pigmented basal cell carcinoma simulating a superficial spreading melanoma.

  7. Photodynamic Therapy With HPPH in Treating Patients With Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2016-04-19

    Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity

  8. USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma.

    PubMed

    Zhao, Guang-Yin; Lin, Zong-Wu; Lu, Chun-Lai; Gu, Jie; Yuan, Yun-Feng; Xu, Feng-Kai; Liu, Rong-Hua; Ge, Di; Ding, Jian-Yong

    2015-03-01

    In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles and mechanisms in lung squamous cell carcinoma and large cell carcinoma need to be clarified. The USP7 expression was examined in NSCLC tumors (excluding adenocarcinoma), their corresponding non-tumorous tissues, and NSCLC cells. Then, the prognostic role of USP7 was analyzed in 110 NSCLC samples (excluding the adenocarcinoma). Finally, the roles and mechanisms of USP7 in the proliferation, metastasis, and invasion of a NSCLC cell were assessed using a specific vshRNA. The USP7 expression was higher in NSCLC tissues compared to non-tumorous samples, accordingly, the high level of USP7 was detected in NSCLC cell lines compared with HBE cell. After the USP7 downregulation, the H460 cells exhibited decreased metastasis/invasion in vitro and in vivo. The preliminary mechanism study indicated overexpression of USP7 might regulate the p53-MDM2 pathway by inducing the MDM2 de-ubiquitination and subsequent stabilization, which resulted in the upregulation of the Bad phosphorylation. Additionally, we also found that USP7 might induce cell epithelial-mesenchymal transition to enhance the cell invasive ability. Clinically, USP7 overexpression significantly correlated with malignant phenotype. Furthermore, the 5-year overall survival in patients with USP7(low) was higher than that of USP7(high). Multivariate analysis showed USP7 overexpression was an independent prognostic marker for these cancers. USP7 overexpression may regulate the survival and invasive properties of squamous cell carcinoma and large cell carcinoma cells, and may serve as a molecular target.

  9. Implications of hyperechoic lesions in small hepatocellular carcinoma.

    PubMed

    Kanno, T; Kurioka, N; Kim, S; Tamori, A; Kim, K; Oka, H; Kuroki, T; Mizoguchi, Y; Kobayashi, K

    1989-10-01

    Of 34 solitary small hepatocellular carcinomas (HCC) 2 cm in diameter or less, 13 with hyperechoic lesions were observed serially by sonography, and 11 of these were examined histologically. Serial examination showed that hypoechoic areas appeared at the periphery of or within, the hyperechoic tumor, and that these areas expanded more with tumor growth than the hyperechoic areas as if compressing or displacing the existing hyperechoic areas. Histologically, the hyperechoic lesions were composed mostly of well-differentiated cancer cells containing fat droplets, whereas the hypoechoic lesions were composed of cancer cells without fat droplets. In the two tumors that were formed almost completely of cancer cells showing fatty metamorphosis, cancer cells without fat droplets proliferated mainly in the periphery of the tumor. These findings suggest that, in hyperechoic HCC, cancer cells with fat droplets appear in the early stage of HCC, and probably change into concer cells without fat droplets by the time that a certain tumor size is reached, with gradual displacement by the latter type of cell during tumor growth.

  10. Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors

    PubMed Central

    Ruiz-Morales, José Manuel; Cano-García, Fernando

    2016-01-01

    Lung cancer is the principal cause of cancer-related death worldwide. The use of targeted therapies, especially tyrosine kinase inhibitors (TKIs), in specific groups of patients has dramatically improved the prognosis of this disease, although inevitably some patients will develop resistance to these drugs during active treatment. The most common cancer-associated acquired mutation is the epidermal growth factor receptor (EGFR) Thr790Met (T790M) mutation. During active treatment with targeted therapies, histopathological transformation to small-cell lung carcinoma (SCLC) can occur in 3–15% of patients with non-small-cell lung carcinoma (NSCLC) tumors. By definition, SCLC is a high-grade tumor with specific histological and genetic characteristics. In the majority of cases, a good-quality hematoxylin and eosin (H&E) stain is enough to establish a diagnosis. Immunohistochemistry (IHC) is used to confirm the diagnosis and exclude other neoplasia such as sarcomatoid carcinomas, large-cell carcinoma, basaloid squamous-cell carcinoma, chronic inflammation, malignant melanoma, metastatic carcinoma, sarcoma, and lymphoma. A loss of the tumor-suppressor protein retinoblastoma 1 (RB1) is found in 100% of human SCLC tumors; therefore, it has an essential role in tumorigenesis and tumor development. Other genetic pathways probably involved in the histopathological transformation include neurogenic locus notch homolog (NOTCH) and achaete-scute homolog 1 (ASCL1). Histological transformation to SCLC can be suspected in NSCLC patients who clinically deteriorate during active treatment. Biopsy of any new lesion in this clinical setting is highly recommended to rule out a SCLC transformation. New studies are trying to assess this histological transformation by noninvasive measures such as measuring the concentration of serum neuron-specific enolase. PMID:27652204

  11. Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-02-08

    Cancer of Head and Neck; Head and Neck Cancer; Neoplasms, Head and Neck; Carcinoma, Squamous Cell of Head and Neck; Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma, Head and Neck

  12. Laser printing of pluripotent embryonal carcinoma cells.

    PubMed

    Ringeisen, Bradley R; Kim, Heungsoo; Barron, Jason A; Krizman, David B; Chrisey, Douglas B; Jackman, Shawna; Auyeung, R Y C; Spargo, Barry J

    2004-01-01

    A technique by which to print patterns and multilayers of scaffolding and living cells could be used in tissue engineering to fabricate tissue constructs with cells, materials, and chemical diversity at the micron scale. We describe here studies using a laser forward transfer technology to print single-layer patterns of pluripotent murine embryonal carcinoma cells. This report focuses on verifying cell viability and functionality as well as the ability to differentiate cells after laser transfer. We find that when cells are printed onto model tissue scaffolding such as a layer of hydrogel, greater than 95% of the cells survive the transfer process and remain viable. In addition, alkaline comet assays were performed on transferred cells, showing minimal single-strand DNA damage from potential ultraviolet-cell interaction. We also find that laser-transferred cells express microtubular associated protein 2 after retinoic acid stimulus and myosin heavy chain protein after dimethyl sulfoxide stimulus, indicating successful neural and muscular pathway differentiation. These studies provide a foundation so that laser printing may next be used to build heterogeneous multilayer cellular structures, enabling cell growth and differentiation in heterogeneous three-dimensional environments to be uniquely studied.

  13. Small cell sweat gland carcinoma of childhood

    PubMed Central

    Drut, R; Giménez, O P; Oliva, J

    2005-01-01

    Small cell sweat gland carcinoma appears to represent a very unusual histological type of sweat gland anlage tumour presenting in children. The differential diagnosis from other small blue cell tumours involving the skin is often difficult. The present report confirms the original observation describing two patients of 2 and 5 years of age harbouring cutaneous tumours. The histology of these lesions showed a monomorphic proliferation of small cells with a high mitotic rate and areas of necrosis. Immunohistochemically, the cells were negative for desmin, cytokeratin 7, cytokeratin 20, Cam 5.2, CD99, chromogranin, CD56, synaptophysin, and S-100, and focally positive for the pancytokeratin marker AE1/AE3, carcinoembryonic antigen (one case), and neurone specific enolase (one case). The prognosis of this type of tumour seems to be good. As more cases are added, the clinical pathological spectrum of the lesion will become better defined. PMID:16311358

  14. Combination therapy for metastatic renal cell carcinoma

    PubMed Central

    Buonerba, Carlo; Di Lorenzo, Giuseppe

    2016-01-01

    Current therapy for metastatic clear cell renal cell carcinoma (RCC) consists of the serial administration of single agents. Combinations of VEGF and mTOR inhibitors have been disappointing in previous randomized trials. However, the combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as FGF receptors, and everolimus demonstrated promising results in a randomized phase II trial. Moreover, the emergence of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors has spawned the investigation of combinations of these agents with VEGF inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors. These ongoing phase III trials in conjunction with the development of predictive biomarkers and agents inhibiting novel therapeutic targets may provide much needed advances in this still largely incurable disease. PMID:27047959

  15. [Expression of promyelocytic leukaemia protein in Bowen's disease, skin squamous cell carcinoma and basal cell carcinoma].

    PubMed

    Wang, Qiongyu; Ma, Huiqun; Wang, Shijie; Ma, Yunyun; Zou, Xingwei; Li, Ruilian

    2013-07-01

    To investigate the expression of promyelocytic leukaemia (PML) protein of PML protein in Bowen's disease (BD), skin squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) and explore the role of PML in the pathogenesis of these diseases. PML protein in normal skin tissues and lesions of Bowen's disease, SCC and BCC were detected with immunohistochemistry. Normal skin tissues did not express PML protein. In BCC, PML showed rather low expressions in the skin lesions (8.69% in cell nuclei and 4.35% in cytoplasm). The lesions in BD and SCC (grade I and II) showed obvious overexpression of PML protein in the cell nuclei and cytoplasm, and its expression in the cell nuclei of these lesions was significantly higher than that in grade III-IV SCC. PML protein may play an important role in the early stage of SCC, and its overexpression may contribute to the carcinogenesis and metastasis of SCC.

  16. Immunological Microenvironment of Hepatocellular Carcinoma and Its Clinical Implication.

    PubMed

    Nishida, Naoshi; Kudo, Masatoshi

    2017-01-01

    Despite recent advances in the treatment of hepatocellular carcinoma (HCC), the prognosis of patients with advanced stage of disease remains unfavorable. Several immune therapies have been applied to HCC, and their responses have not been satisfactory. The immune response to cancer is determined by the balance between the antigenicity of the tumor and the microenvironment of cancer tissues. Generally, accumulated genetic mutations are observed in HCC, which may lead to increased neoantigens on cancer cells with high antigenicity. However, cancer cells may evade the immune system because of alterations in molecules and cellular pathways involved in antigen processing and presentation. In addition, hypoxia in tissue induces several cytokines, chemokines, and immunosuppressive molecules from HCC cells and stromal cells. These cells also produce cytokines that attract regulatory T cells infiltrating tumor tissues and contribute to establishing an immunosuppressive microenvironment. Some cancers show a good response to immune checkpoint therapy. However, prolonged stabilization of disease for this treatment is reportedly 12-41% in patients with advanced cancer. Therefore, immunosuppressive forces in the microenvironment of HCC may cause resistance to immune therapy, and modification of the tumor microenvironment may restore normal anticancer immunity. In this review, we focus on the immunological microenvironment of HCC tissues and discuss how the immunosuppressive environment of HCC should be modulated to achieve a favorable response to immune therapy, such as immune checkpoint therapy, in HCC. © 2016 S. Karger AG, Basel.

  17. [Descriptive study on basal cell eyelid carcinoma].

    PubMed

    Pfeiffer, M J; Pfeiffer, N; Valor, C

    2015-09-01

    To describe a series of cases of basal cell carcinomas of the eyelid. A descriptive and retrospective study was conducted by reviewing the medical outcome, histopathological history, and photographic images of 200 patients with basal cell eyelid carcinomas. All were treated in the Herzog Carl Theodor Eye Hospital in Munich, Germany, between 2000 and 2013. In the present study, it was found that females are more affected than males. The mean age of presentation of the tumor occurred at the age of 70 years. In 50% of the cases the tumor was found on the lower lid, especially medially from the center of the lid. The lid margin was involved in 47% of all tumors. The mean diameter was 9.2mm. The recurrence rate after surgery with histologically clear resection margins was 5%. There was a significant relationship between tumor diameter and age. As tumors where located farther away from medial and closer to the lid margin, they became larger. There is a predominance of women affected by this tumor. This may be related to the fact that the sample was taken from those attending an oculoplastic surgery clinic, where there are generally more women than men attending. The formation of basal cell carcinomas increases with age. The infrequent involvement of the upper lid could be explained by the protection of the the eyebrow. The frequent involvement of the lower lid may be due to the light reflection (total reflection) by the cornea on the lower lid margin. Also chemical and physical effects of the tears may be more harmful on the lower lid. Patients tend to ask for medical help when they are females, younger, when the tumor is closer to the medial canthus or when the tumor is away from the lid margin. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  18. Tubulocystic Renal Cell Carcinoma: A Great Imitator

    PubMed Central

    Banerjee, Indraneel; Yadav, Sher Singh; Tomar, Vinay; Yadav, Suresh; Talreja, Shyam

    2016-01-01

    Tubulocystic renal cell carcinoma (TCRC) is a rare renal tumor. Patients are usually asymptomatic; it is usually detected incidentally, during imaging studies for Bosniak type III and type IV renal cysts. These tumors rarely metastasize. The role of targeted therapy in such rare tumors is still controversial. We report a case of TCRC initially presented as a Bosniak type II renal cyst and was discovered ultimately to be a metastatic disease. This type of presentation might broaden our understanding of this rare disease. PMID:27601972

  19. [Renal cell carcinoma secondary to tuberculous nephritis].

    PubMed

    El Mejjad, Amine; Fekak, Hamid; Debbagh, Adili; Joual, Abdenbi; Bennani, Saad; El Mrini, Mohamed

    2005-04-01

    The combination of renal tuberculosis and renal cancer is rare. The authors report the case of a patient who was followed for multifocal pulmonary, hepatic and renal tuberculosis. The diagnosis of associated renal tumour was raised in the presence of suggestive radiological images. Tumourectomy was performed after tuberculostatic therapy, and histological examination revealed renal cell carcinoma associated with caseo-follicular tuberculous granulomas. The outcome was favourable after a follow-up of 2 years. The objective of this study is to analyse the pathogenesis, diagnostic features and treatment modalities of this exceptional combination.

  20. Advanced treatment for basal cell carcinomas.

    PubMed

    Atwood, Scott X; Whitson, Ramon J; Oro, Anthony E

    2014-07-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists.

  1. Advanced Treatment for Basal Cell Carcinomas

    PubMed Central

    Atwood, Scott X.; Whitson, Ramon J.; Oro, Anthony E.

    2014-01-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists. PMID:24985127

  2. Contemporary Treatment of Metastatic Renal Cell Carcinoma

    PubMed Central

    Stukalin, Igor; Alimohamed, Nimira; Heng, Daniel Y.C.

    2016-01-01

    The introduction of targeted therapy has revolutionized the treatment of patients with metastatic renal cell carcinoma (mRCC). The current standard of care focuses on the inhibition of angiogenesis through the targeting of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR). Over the past few years, research exploring novel targeted agents has blossomed, leading to the approval of various targeted therapies. Furthermore, results from the CheckMate025 and the METEOR trials have brought about two additional novel options: the programmed cell death 1 (PD-1) checkpoint inhibitor nivolumab and the MET/VEGFR/AXL inhibitor cabozantinib, respectively. With the variety of therapeutic agents available for treatment of mRCC, research examining appropriate sequencing and combinations of the drugs is ongoing. This review discusses the role of prognostic criteria, such as those from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. It also covers the current standard of treatment for mRCC with targeted therapy in first-, second-, and third-line setting. Additionally, the novel mechanism of action of nivolumab and cabozantinib, therapeutic sequencing and ongoing clinical trials are discussed. PMID:27471582

  3. Treatment of lung large cell neuroendocrine carcinoma.

    PubMed

    Lo Russo, Giuseppe; Pusceddu, Sara; Proto, Claudia; Macerelli, Marianna; Signorelli, Diego; Vitali, Milena; Ganzinelli, Monica; Gallucci, Rosaria; Zilembo, Nicoletta; Platania, Marco; Buzzoni, Roberto; de Braud, Filippo; Garassino, Marina Chiara

    2016-06-01

    Lung large cell neuroendocrine carcinoma (L-LCNEC) is a rare, aggressive, and difficult-to-treat tumor. It is classified as a neuroendocrine subtype of large cell lung carcinoma (LCLC) belonging to the non-small cell lung cancer (NSCLC) group, but it is also included in the neuroendocrine tumor (NET) group. Most of the available data related to its treatment derive from retrospective analyses or small case series. For patients with L-LCNEC, prognosis is generally very poor. In early stages (I-II-III), surgery is recommended but does not seem to be sufficient. Platinum-based adjuvant chemotherapy may be useful while the role of neoadjuvant chemotherapy is still not well defined. In patients with advanced L-LCNEC, the chemotherapy regimens used in SCLC still remain the standard of treatment, but results are not satisfactory. Due to their peculiar clinical and biological features and the lack of literature data, there is an emerging need for a consensus on the best treatment strategy for L-LCNEC and for the identification of new therapeutic options. In this review, we will discuss the key aspects of L-LCNEC management with the aim to clarify the most controversial issues.

  4. Percutaneous Cryoablation for Renal Cell Carcinoma

    PubMed Central

    Georgiades, Christos

    2015-01-01

    Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults. Nephron sparing resection (partial nephrectomy) has been the “gold standard” for the treatment of resectable disease. With the widespread use of cross sectional imaging techniques, more cases of renal cell cancers are detected at an early stage, i.e. stage 1A or 1B. This has provided an impetus for expanding the nephron sparing options and especially, percutaneous ablative techniques. Percutaneous ablation for RCC is now performed as a standard therapeutic nephron-sparing option in patients who are poor candidates for resection or when there is a need to preserve renal function due to comorbid conditions, multiple renal cell carcinomas, and/or heritable renal cancer syndromes. During the last few years, percutaneous cryoablation has been gaining acceptance as a curative treatment option for small renal cancers. Clinical studies to date indicate that cryoablation is a safe and effective therapeutic method with acceptable short and long term outcomes and with a low risk, in the appropriate setting. In addition it seems to offer some advantages over radio frequency ablation (RFA) and other thermal ablation techniques for renal masses.

  5. Ameloblastic carcinoma with features of ghost cell odontogenic carcinoma in a patient with suspected Gardner syndrome.

    PubMed

    Fitzpatrick, S G; Hirsch, S A; Listinsky, C M; Lyu, D J-H; Baur, D A

    2015-04-01

    Ameloblastic carcinoma and ghost cell odontogenic carcinoma are rare malignancies arising in odontogenic epithelium within the jaws. Gardner syndrome is a multifaceted autosomal dominant condition, which results in multiple dentofacial anomalies along with premalignant colon polyp formation and tumor formation in the skin and other organs. We report a case of ameloblastic carcinoma with features of ghost cell odontogenic carcinoma and extensive clear cell change and melanin pigmentation in a patient with clinical features of Gardner syndrome. To the best of our knowledge, odontogenic carcinoma arising in a patient with features of Gardner syndrome has not been reported previously. The clinical, radiographic, and histologic features of the case are discussed along with a review of the relevant literature.

  6. Autocrine Human Growth Hormone Stimulates Oncogenicity of Endometrial Carcinoma Cells

    PubMed Central

    Pandey, Vijay; Perry, Jo K.; Mohankumar, Kumarasamypet M.; Kong, Xiang-Jun; Liu, Shu-Min; Wu, Zheng-Sheng; Mitchell, Murray D.; Zhu, Tao; Lobie, Peter E.

    2008-01-01

    Recent published data have demonstrated elevated levels of human GH (hGH) in endometriosis and endometrial adenocarcinoma. Herein, we demonstrate that autocrine production of hGH can enhance the in vitro and in vivo oncogenic potential of endometrial carcinoma cells. Forced expression of hGH in endometrial carcinoma cell lines RL95-2 and AN3 resulted in an increased total cell number through enhanced cell cycle progression and decreased apoptotic cell death. In addition, autocrine hGH expression in endometrial carcinoma cells promoted anchorage-independent growth and increased cell migration/invasion in vitro. In a xenograft model of human endometrial carcinoma, autocrine hGH enhanced tumor size and progression. Changes in endometrial carcinoma cell gene expression stimulated by autocrine hGH was consistent with the altered in vitro and in vivo behavior. Functional antagonism of hGH in wild-type RL95-2 cells significantly reduced cell proliferation, cell survival, and anchorage-independent cell growth. These studies demonstrate a functional role for autocrine hGH in the development and progression of endometrial carcinoma and indicate potential therapeutic relevance of hGH antagonism in the treatment of endometrial carcinoma. PMID:18450952

  7. Expression and function of FERMT genes in colon carcinoma cells.

    PubMed

    Kiriyama, Kenji; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Kubo, Terufumi; Tamura, Yasuaki; Kanaseki, Takayuki; Takahashi, Akari; Nakazawa, Emiri; Saka, Eri; Ragnarsson, Charlotte; Nakatsugawa, Munehide; Inoda, Satoko; Asanuma, Hiroko; Takasu, Hideo; Hasegawa, Tadashi; Yasoshima, Takahiro; Hirata, Koichi; Sato, Noriyuki

    2013-01-01

    Invasion into the matrix is one of hallmarks of malignant diseases and is the first step for tumor metastasis. Thus, analysis of the molecular mechanisms of invasion is essential to overcome tumor cell invasion. In the present study, we screened for colon carcinoma-specific genes using a cDNA microarray database of colon carcinoma tissues and normal colon tissues, and we found that fermitin family member-1 (FERMT1) is overexpressed in colon carcinoma cells. FRRMT1, FERMT2 and FERMT3 expression was investigated in colon carcinoma cells. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that only FERMT1 had cancer cell-specific expression. Protein expression of FERMT1 was confirmed by western blotting and immunohistochemical staining. To address the molecular functions of FERMT genes in colon carcinoma cells, we established FERMT1-, FERMT2- and FERMT3-overexpressing colon carcinoma cells. FERMT1-overexpressing cells exhibited greater invasive ability than did FERMT2- and FERMT3-overexpressing cells. On the other hand, FERMT1-, FERMT2- and FERMT3-overexpressing cells exhibited enhancement of cell growth. Taken together, the results of this study indicate that FERMT1 is expressed specifically in colon carcinoma cells, and has roles in matrix invasion and cell growth. These findings indicate that FERMT1 is a potential molecular target for cancer therapy.

  8. Constitutive Activation of NF-kappaB in Prostate Carcinoma Cells Through a Positive Feedback Loop: Implication of Inducible IKK-Related Kinase (IKKi)

    DTIC Science & Technology

    2004-08-01

    staining was similar in BPH and in PCs, however, the nuclear expression was higher in PCs. Treatment of PC cells with different NF-icB inducers such as...microarrays and individual sections) of BPH, and PCs using four different antibodies against IKKi. The analysis of IKKi staining in prostate tissue samples...intensity of IKKi staining was similar in BPH and in PCs with Gleason scores 6-9, however, the nuclear expression was higher in PCs. Treatment of PC

  9. Renal adenocarcinoma, hepatocellular carcinoma, and pancreatic islet cell carcinoma in a binturong (Arctictis binturong).

    PubMed

    Klaphake, Eric; Shoieb, Ahmed; Ramsay, Ed; Schumacher, Juergen; Craig, Linden

    2005-03-01

    A 19-yr-old binturong (Arctictis binturong) with acute upper respiratory disease was euthanized. Postmortem findings included hepatocellular carcinoma, pancreatic islet cell carcinoma, and renal adenocarcinoma with metastasis to the spleen, pleura, and pericardium. A link between primary hepatic and renal neoplasms has been noted in older humans.

  10. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion

    PubMed Central

    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis. PMID:27757356

  11. Sonic hedgehog in oral squamous cell carcinoma: An immunohistochemical study

    PubMed Central

    Srinath, Sahana; Iyengar, Asha R; Mysorekar, Vijaya

    2016-01-01

    Background: Recent studies have revealed the involvement of hedgehog (Hh) signaling component in proliferation and invasive behavior of many carcinomas. Aim: This study aims to identify the expression of sonic Hh (SHH) protein of SHH pathway in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) using SHH (H-160) (Santa Cruz, sc-9042) which could have therapeutic implication in future. Materials and Methods: A total of 250 cases comprising 50 normal oral mucosa, 50 cases of oral epithelial dysplasia, 50 well, 50 moderate and 50 poorly differentiated OSCCs were included in the study. Immunohistochemical evaluation of SHH protein expression was conducted using monoclonal antibody. Interpretation of the expression was done by immunoreactive score of Remmele and Stegner (IRS) scoring method. Statistical Analysis: Chi-Square test was used to analyze the results. Results: The study showed that SHH signaling molecules are highly expressed in OSCC, and their expression was mainly in the cytoplasm of epithelial cells. Conclusion: The SHH signaling component is associated with the pathological parameter in OSCC and oral epithelial dysplasia. PMID:27721600

  12. Small-cell Carcinomas of the Urinary Bladder and Prostate: TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma.

    PubMed

    Priemer, David S; Wang, Mingsheng; Zhang, Shaobo; Lopez-Beltran, Antonio; Kouba, Erik; Montironi, Rodolfo; Davidson, Darrell D; MacLennan, Gregory T; Wang, Lisha; Osunkoya, Adeboye O; Deng, Youping; Emerson, Robert E; Cheng, Liang

    2017-03-31

    Small-cell carcinoma (SCC) of the urinary bladder frequently appears alongside urothelial carcinoma, suggesting common clonality. TERT promoter mutations have been recently implicated in urothelial carcinogenesis. To investigate the degree to which TERT promoter mutations are involved in SCC of the urinary bladder, the linked tumorigenesis between urothelial carcinoma and SCC of the urinary bladder, and the molecular distinctions between SCC of the urinary bladder and of the prostate. We investigated TERT promoter mutations in 53 cases of SCC of the urinary bladder and in 26 cases of SCC of the prostate using laboratory-based studies of tissue samples and clinical data. We measured the frequency of TERT promoter mutations in SCCs of the urinary bladder and prostate, and concordance of the mutation status between concurrent urinary bladder SCC and urothelial carcinoma. TERT promoter mutations were detected in 29/53 (55%) cases of urinary bladder and 0/26 (0%) cases of prostate SCC. Of 25 cases with concurrent urinary bladder SCC and non-small-cell components, all cases harbored identical TERT promoter mutation status in both phenotypes. TERT promoter mutations are found in more than half of urinary bladder SCCs. Mutation status is also identical in urothelial carcinoma and SCC components of concomitant malignancies, providing evidence of a common clonality. TERT promoter mutation status can differentiate SCC of the urinary bladder from prostate SCC, suggesting potential diagnostic use. Small-cell carcinoma of the urinary bladder shares a common clonal origin with conventional urothelial carcinoma and may arise from a heterogeneous subclone. TERT promoter mutations may have utility as a differential biomarker for determining the primary site of a genitourinary small-cell carcinoma. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  13. Squamous cell carcinoma of the extremities

    SciTech Connect

    Lifeso, R.M.; Bull, C.A.

    1985-06-15

    Between January 1976 and January 1983, 37 cases of squamous cell carcinoma of the extremities have been treated at the King Faisal Specialist Hospital and Research Centre by the authors. Each case has arisen in an area of preexisting scar or sinus. Twenty-nine cases were treated by definitive amputation, with 2 local recurrences and 12 nodal metastases. Seven cases had local excision, with three local recurrences and two nodal metastases. Recurrence rate was highest in Grade II and Grade III lesions, and 11 of 15 cases with Grade II disease had metastases to the regional lymph nodes an average of 5 months after surgery. With Grade I disease patients, 4 of 15 had nodal metastases an average of 5 months after surgery. Prophylactic regional nodal irradiation or node dissection was performed in seven cases. None of these cases have shown nodal metastases at an average of 24 months following definitive surgery and radiation. Routine prophylactic regional node irradiation is recommended in all cases of peripheral squamous cell carcinoma.

  14. Multiphoton imaging of basal cell carcinoma (BCC)

    NASA Astrophysics Data System (ADS)

    Cicchi, R.; Carli, P.; Massi, D.; Sestini, S.; Stambouli, D.; Pavone, F. S.

    2006-02-01

    We used two-photon microscopy towards the imaging of cutaneous basal cell carcinoma (BCC). Our aim was to evaluate the morphology of BCC using two-photon fluorescence excitation and to establish a correlation with histopathology. We built a custom two-photon microscope and we measured the system capabilities. The system allowed to perform a preliminary measurement on a fresh human skin tissue sample. A human skin tissue sample of BCC excised during dermatological surgery procedures were used. The clinical diagnosis of BCC was confirmed by subsequent histopathological examination. The sample was imaged using endogenous tissue fluorescence within 2-3 hours from the excision with a two photon laser scanning fluorescence microscope. The acquired images allowed an obvious discrimination of the neoplastic areas toward normal tissue, based on morphological differences and aberrations of the intensity of the fluorescence signal. Our results showed that BCC tissue has a more homogeneous structure in comparison to normal tissue as well as a higher fluorescent response. The images obtained by two photon microscopy were further compared to the images acquired by an optical microscope after the conventional histopathological examination on one part of the respective sample. Our suggested method may represent a new diagnostic tool that improves the diagnostic accuracy of clinical examination alone, enabling the accurate discrimination of basal cell carcinoma from normal tissue.

  15. Intraventricular metastatic clear cell renal carcinoma.

    PubMed

    Sava, I; Sava, Anca; Şapte, Elena; Mihailov, Claudia; Dumitrescu, Gabriela; Poeată, I; Sava, Florina; Haba, Danisia

    2013-01-01

    Intraventricular tumors represent a diagnostic problem, due to a wide range of differential diagnosis, with an important variability of tumoral histological types in adult and pediatric population. Patient, Our case is represented by a patient, aged 48 years, without any history of significant personal pathology, accusing nausea, vomiting, and intensive headache. In the morning, he became confused, having hallucinations for a short period of time, and has accused drowsiness for several weeks. Imaging (CT and MRI) shows a neoformation in the third ventricle, accompanied by bilateral lateral ventricles dilatation, with predominantly annular enhancement. During surgery, through the middle third transcallosal interhemispheric approach, it was revealed a reddish, well-demarcated intraventricular mass, well vascularized and with a firm consistency. Final pathologic diagnosis was metastatic clear cell renal carcinoma. Initial postoperative evolution was good, and then neurological and respiratory condition worsened as a bronchopneumonia lead to patient's death in 12 days after surgery. Clear cell carcinoma metastasis located in the third ventricle should be taken into consideration for patients presenting a single intraventricular lesion even they have no documented primary malignancy.

  16. [Squamous cell carcinoma in localized scleroderma].

    PubMed

    Durčanská, V; Jedličková, H; Sláma, O; Velecký, L; Březinová, E; Vašků, V

    2014-01-01

    We present a case of a young 26-year-old woman, who has been suffering from localised scleroderma (morphea) for 15 years. Recently, a lesion on the dorsum of her right foot ulcerated. Based on a CT scan and X-ray a diagnosis of ulcerative osteomyellitis was established. The patient was treated with a combination of antibiotics. Subsequent histological examinations showed granulomatous tissue and chronic inflammatory changes on top of pseudoepiteliomatous hyperplasia. The patients status was deteriorating, which resulted in a limb amputation under the knee. Three months later, there was a metastasis of squamous cell carcinoma found in the patients inguinal lymph node. In spite of combined therapy (surgery, radioterapy and systemic chemotherapy), new metastases occurred and the patient succumbed to the disease several months afterwards. The case was concluded as a squamous cell carcinoma camouflaged by osteomyelitis. Malignant turn of localised sclerodema is very rare. It usually occurs on the lower extremities of patients with a long course of the disease and is associated with pansclerotic or generalised variants of morphea.

  17. A Case of Hereditary Leiomyomatosis and Renal Cell Carcinoma

    PubMed Central

    Mehrtens, Sarah; Veitch, David; Kulakov, Elizabeth; Perrett, Conal M.

    2016-01-01

    A 49-year-old lady presented with multiple recurring painful lesions over her thighs, arms, and back. Past medical history included a left sided nephrectomy for renal cell carcinoma and a hysterectomy for multiple uterine fibroids (leiomyomas). Histopathological examination revealed changes consistent with pilar leiomyomas. Gene mutation analysis confirmed a diagnosis of hereditary leiomyomatosis and renal cell carcinoma. Hereditary leiomyomatosis and renal cell carcinoma is an uncommon autosomal dominant condition characterised by the concurrent presentation of cutaneous and uterine leiomyomas. Renal cell carcinoma associated with this condition is more aggressive and a significant cause of mortality. Due to this association with potentially fatal renal cell carcinoma we felt that it was important to highlight this case with an update on pathophysiology and management. PMID:27144040

  18. Advances in the management of cutaneous squamous cell carcinoma

    PubMed Central

    Parikh, Sonal A.

    2014-01-01

    Cutaneous squamous cell carcinoma is one of the most common non-melanoma skin cancers worldwide. While most cutaneous squamous cell carcinomas are easily managed, there is a high-risk subset of tumors that can cause severe morbidity and mortality. Tumor characteristics as well as patient characteristics contribute to the classification of cutaneous squamous cell carcinomas as low-risk vs. high-risk. Advances in the treatment of cutaneous squamous cell carcinomas largely relate to the management of this high-risk subset. Surgical and non-surgical management options, including newer targeted molecular therapies, will be discussed here. Larger, multicenter studies are needed to determine the exact significance of individual risk factors with respect to aggressive clinical behavior and the risks of metastasis and death, as well as the role of surgical and adjuvant therapies in patients with high-risk cutaneous squamous cell carcinomas. PMID:25165569

  19. Secondary Signet Ring Cell Carcinoma of Prostate

    PubMed Central

    Khan, Kalyan; Bandyopadhyay, Arghya; Gangopadhyay, Mimi; Chakraborty, Subrata; Bera, Pranati

    2012-01-01

    True metastases to prostate from solid tumors are reported only in 0.2% of all surgical prostatic specimens and 2.9% of all male postmortems. Clinical context, morphological features, and immunohistochemical localization of prostate specific antigen (PSA) are supposed to clarify the differential diagnosis between a secondary and a primary tumor. We report an unusual and rare case of secondary signet ring cell carcinoma (SRCC) of prostate in which the clinical data and signet ring cell morphology pointed toward the diagnosis of a primary SRCC. Immunohistochemistry (IHC) for PSA not only proved the case to be a secondary SRCC but also initiated the process for diagnosis of the occult primary malignancy in the patient′s stomach. PMID:24027389

  20. Pembrolizumab Combined With Cetuximab for Treatment of Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-03-28

    HNSCC; Lip SCC; Oral Cavity Cancer; Oropharynx Cancer; Larynx Cancer; Hypopharynx Cancer; Nasopharynx Cancer; Sinonasal Carcinoma; Cutaneous Squamous Cell Carcinoma; Head and Neck Neoplasms; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

  1. Basal cell carcinoma of the prostate: unusual subtype of prostatic carcinoma.

    PubMed

    Komura, Kazumasa; Inamoto, Teruo; Tsuji, Motomu; Ibuki, Naokazu; Koyama, Kohei; Ubai, Takanobu; Azuma, Haruhito; Katsuoka, Yoji

    2010-12-01

    Basal cell carcinoma of the prostate, which has been generally considered to be indolent, is an unusual histological type of prostatic carcinoma and is extremely rare. This tumor has been classified according to the prevalent pattern of growth as adenoid cystic carcinoma or basaloid cell carcinoma (BCC), with the former growth pattern being considered to be the main feature of this entity. A 67-year-old Japanese man was admitted to a general hospital with obstructive urinary symptoms. His prostate was slightly enlarged, stony hard, and with a rough surface on digital rectal examination, while serum prostate-specific antigen and prostatic acid phosphatase concentrations were within the normal ranges (0.007 and 0.9 ng/mL, respectively). 2-Fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) exhibited multiple accumulations suspicious for cancer metastases. Specimens obtained by prostatic needle biopsy showed immunohistochemical reactivity for cytokeratin 34βE12 and P63, findings that were identical to those seen in basal cell carcinoma. Basal cell carcinoma of the prostate is a rare tumor, reported in 56 cases so far, and among all these, the pure form of BCC is extremely rare. Immunohistochemistry is indispensable to distinguish this neoplasm from other unusual histological types of prostatic carcinomas. Our findings reveal that tumors with a basaloid cell-predominant pattern have significant potential for a poor prognosis, in contrast with the conventional understanding regarding this neoplasm.

  2. Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

    SciTech Connect

    Lacko, Martin; Braakhuis, Boudewijn J.M.; Sturgis, Erich M.; Boedeker, Carsten C.; Suárez, Carlos; Rinaldo, Alessandra; Ferlito, Alfio; Takes, Robert P.

    2014-05-01

    Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives of research on genetic susceptibility in HNSCC are discussed.

  3. The somatic genomic landscape of chromophobe renal cell carcinoma

    PubMed Central

    Davis, Caleb F.; Ricketts, Christopher; Wang, Min; Yang, Lixing; Cherniack, Andrew D.; Shen, Hui; Buhay, Christian; Kang, Hyojin; Kim, Sang Cheol; Fahey, Catherine C.; Hacker, Kathryn E.; Bhanot, Gyan; Gordenin, Dmitry A.; Chu, Andy; Gunaratne, Preethi H.; Biehl, Michael; Seth, Sahil; Kaipparettu, Benny A.; Bristow, Christopher A.; Donehower, Lawrence A.; Wallen, Eric M.; Smith, Angela B.; Tickoo, Satish K.; Tamboli, Pheroze; Reuter, Victor; Schmidt, Laura S.; Hsieh, James J.; Choueiri, Toni K.; Hakimi, A. Ari; Chin, Lynda; Meyerson, Matthew; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A. Gordon; Laird, Peter W.; Henske, Elizabeth P.; Kwiatkowski, David J.; Park, Peter J.; Morgan, Margaret; Shuch, Brian; Muzny, Donna; Wheeler, David A.; Linehan, W. Marston; Gibbs, Richard A.; Rathmell, W. Kimryn; Creighton, Chad J.

    2014-01-01

    Summary We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations. PMID:25155756

  4. The somatic genomic landscape of chromophobe renal cell carcinoma.

    PubMed

    Davis, Caleb F; Ricketts, Christopher J; Wang, Min; Yang, Lixing; Cherniack, Andrew D; Shen, Hui; Buhay, Christian; Kang, Hyojin; Kim, Sang Cheol; Fahey, Catherine C; Hacker, Kathryn E; Bhanot, Gyan; Gordenin, Dmitry A; Chu, Andy; Gunaratne, Preethi H; Biehl, Michael; Seth, Sahil; Kaipparettu, Benny A; Bristow, Christopher A; Donehower, Lawrence A; Wallen, Eric M; Smith, Angela B; Tickoo, Satish K; Tamboli, Pheroze; Reuter, Victor; Schmidt, Laura S; Hsieh, James J; Choueiri, Toni K; Hakimi, A Ari; Chin, Lynda; Meyerson, Matthew; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A Gordon; Laird, Peter W; Henske, Elizabeth P; Kwiatkowski, David J; Park, Peter J; Morgan, Margaret; Shuch, Brian; Muzny, Donna; Wheeler, David A; Linehan, W Marston; Gibbs, Richard A; Rathmell, W Kimryn; Creighton, Chad J

    2014-09-08

    We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.

  5. Prognostic factors in early glottic carcinoma implications for treatment.

    PubMed

    Nur, Demiral Ayse; Oguz, Cetinayak; Kemal, Erdag Taner; Ferhat, Eyiler; Sülen, Sarioglu; Emel, Ada; Münir, Kinay; Ann, Cooper Sen Rachel; Mehmet, Sen

    2005-01-01

    In this study we aimed to determine the prognostic factors affecting local control (LC) in limited glottic carcinoma treated with definitive radiotherapy (RT). Between June 1991 and December 2001, 114 patients with early squamous-cell carcinoma of the glottis were treated with definitive RT at our institution. Only four (3.5%) patients were women. The median age was 60 (27-79). Fifteen percent, 72% and 13% of the patients had Tis, T1 and T2 tumors, respectively. Forty-three (37.7%) patients had anterior commissure invasion. Prior to RT 35 (31%) patients had undergone vocal cord stripping and two (2%) cordectomy. A median dose of 66 Gy (50-70.2) was given over a median period of 46 days (20-60). Univariate and multivariate analyses were performed for LC. The prognostic parameters analyzed for LC were T classification, anterior commissure involvement, total RT dose, and overall treatment time. Five-year local and regional control rates were 84.2% and 97.7%. RTOG grade 3-4 late side effects were observed only in one (0.9%) patient. In 15 patients with local failure, salvage treatment consisted of partial laryngectomy in eight patients and total laryngectomy in five. One of the remaining two patients was medically inoperable, and the other refused salvage surgery. In one of the three patients with regional failure, salvage surgery was applied and the other two were given palliative chemotherapy because of unresectable disease. Following salvage treatments, the ultimate five-year LC rate was 96.9% and the five-year larynx preservation rate was 91.1%. Second primary cancer was diagnosed in 17 (14.9%) patients. Only one patient developed distant metastases and two patients died of laryngeal cancer. While T2 disease and anterior commissure involvement were found to be unfavorable prognostic factors significantly influencing LC in univariate analyses, only T2 disease remained independent in multivariate analysis. In patients with early glottic carcinoma, T classification

  6. Targeting HIF2 in Clear Cell Renal Cell Carcinoma.

    PubMed

    Cho, Hyejin; Kaelin, William G

    2016-12-08

    Inactivation of the von Hippel-Lindau tumor-suppressor protein (pVHL) is the signature "truncal" event in clear cell renal cell carcinoma, which is the most common form of kidney cancer. pVHL is part of a ubiquitin ligase the targets the α subunit of the hypoxia-inducible factor (HIF) transcription factor for destruction when oxygen is available. Preclinical studies strongly suggest that deregulation of HIF, and particularly HIF2, drives pVHL-defective renal carcinogenesis. Although HIF2α was classically considered undruggable, structural and chemical work by Rick Bruick and Kevin Gardner at University of Texas Southwestern laid the foundation for the development of small molecule direct HIF2α antagonists (PT2385 and the related tool compound PT2399) by Peloton Therapeutics that block the dimerization of HIF2α with its partner protein ARNT1. These compounds inhibit clear cell renal cell carcinoma growth in preclinical models, and PT2385 has now entered the clinic. Nonetheless, the availability of such compounds, together with clustered regularly interspaced short palindromic repeat (CRISPR)-based gene editing approaches, has revealed a previously unappreciated heterogeneity among clear cell renal carcinomas and patient-derived xenografts with respect to HIF2 dependence, suggesting that predictive biomarkers will be needed to optimize the use of such agents in the clinic.

  7. Establishment and characterization of a human uterine endometrial undifferentiated carcinoma cell line, TMG-L.

    PubMed

    Hasegawa, Kiyoshi; Suzuki, Machiko; Ishikawa, Kunimi; Yasue, Akira; Kato, Rina; Nakamura, Azumi; Kuroki, Jun; Udagawa, Yasuhiro

    2003-03-01

    A new cell line of human uterine endometrial undifferentiated carcinoma, designated as TMG-L, was established from the metastatic lymph node of 56-year-old patient TMG-L cells have been cultured with Ham's F-12 medium supplemented with 10% FCS and grew as a loosely adherent monolayer with polygonal or spindle-shaped cells exhibiting poor cell-cell contact and piled up against each other, showing a tendency to grow as floating cells. The doubling time of this cell line was about 48 hours, and chromosomal analysis revealed aneuploidy at passage 25. The cells formed tumors in SCID mouse, the histology of which was similar to that of undifferentiated carcinoma component of primary tumor. TMG-L cells showed the loss of expression and membranous localization of either E-cadherin or alpha-catenin, implied corresponding loss of their adhesive function. And this dysfunction implicated the biological aggressive behavior of uterine endometrial undifferentiated carcinoma. This cell line appears to provide a useful system for studying uterine undifferentiated carcinoma in vivo and in vitro.

  8. Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth

    PubMed Central

    Wang, Jin Dao; Chen, Xiao Ying; Ji, Ke Wei; Tao, Feng

    2016-01-01

    Bruton’s tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer. PMID:27508020

  9. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches.

    PubMed

    Peterson, Shelby C; Eberl, Markus; Vagnozzi, Alicia N; Belkadi, Abdelmadjid; Veniaminova, Natalia A; Verhaegen, Monique E; Bichakjian, Christopher K; Ward, Nicole L; Dlugosz, Andrzej A; Wong, Sunny Y

    2015-04-02

    Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as "hot spots" for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis.

  10. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma

    PubMed Central

    2017-01-01

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  11. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma.

    PubMed

    Cohen, Philip R

    2017-03-22

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  12. Galectin-3 inhibition sensitizes human renal cell carcinoma cells to arsenic trioxide treatment

    PubMed Central

    Xu, Yangyang; Gu, Xin; Gong, Mancheng; Guo, Guiying; Han, Kaiyu; An, Ruihua

    2013-01-01

    The anti-tumor effects of arsenic trioxide (ATO) were well established in acute promyelocytic leukemia, but not in renal cell carcinoma (RCC). Recent evidences indicate that galectin-3 (Gal-3) plays an anti-apoptotic role in chemotherapy induced tumor cell death. This study was intended to clarify the exact roles of Gal-3 performed in ATO-induced apoptosis in RCC cells. Weak apoptosis was observed in Gal-3-positive RCC cells (Caki-1, Caki-2, 786-0, and ACHN) following ATO treatment. However, ATO treatment upregulated Gal-3 expression concurrently caused a Synexin-cooperated translocation of Gal-3 from the nucleus to the cytoplasm. Gal-3-knockdown cells were more sensitive to ATO treatment as indicated by a strong mitochondria-dependent apoptosis following ATO treatment. Meanwhile, Gal-3 was found to inhibit ATO-induced apoptosis through enhancing Bcl-2 expression and stabilizing mitochondria. To confirm the results obtained from genetic method, we employed a Gal-3 inhibitor, modified citrus prectin (MCP), and co-treated the RCC cells with ATO. The cells showed an increased apoptosis in the syngeneic application of Gal-3 inhibition and ATO compared with ATO application alone. Based on these results, we conclude that Gal-3 inhibition sensitizes human renal cell carcinoma cells to ATO treatment through increasing mitochondria-dependent apoptosis. Our studies implicate synergetic application of ATO and Gal-3 inhibition as a potential strategy for RCC treatment. PMID:23917726

  13. Basal cell carcinoma: clinical and pathological features.

    PubMed

    Di Stefani, A; Chimenti, S

    2015-08-01

    Basal cell carcinoma (BCC) is a slow-growing, locally invasive malignant epidermal skin neoplasm that represents the most common malignancy in Caucasians. The clinical presentation of BCC can be extremely variable: nodular, ulcerative, superficial, morpheiform, pigmented, and fibroepithelioma of Pinkus are the main clinical variants described. Clinical factors influencing negatively prognosis of BCC are: anatomic location, recurrence and/or persistance at site after treatment, and tumor size. A precise correlations between clinical and histopathological variants is not always possible, especially in biopsy samples. From a histopathological point of view various subtypes has been described: nodular, superficial, infiltrating, morpheiform, micronodular, fibroepithelial BCC and basosquamous carcinoma. A classification system based by growth pattern allows the identification of high-risk subtypes with potential tumor recurrence and aggressive biologic behavior such as infiltrating, morpheiform, micronodular and basosquamous subtypes. Further histopathological aspects determining high risk clinical morbidity are the level of invasion, perineural and lymphovascular invasion, involved surgical margins. The awareness of these clinicopathological features is helpful to better select the appropriate treatment management.

  14. Metaplastic carcinoma of the breast with transformation from adenosquamous carcinoma to osteosarcomatoid and spindle cell morphology.

    PubMed

    Chuthapisith, Suebwong; Warnnissorn, Malee; Amornpinyokiat, Nattawut; Pradniwat, Kanapon; Angsusinha, Tamnit

    2013-09-01

    Metaplastic carcinoma of the breast refers to a heterogenous group of mammary carcinomas that contain a mixture of various cell types, including squamous cells, spindle cells and/or a mesenchymal component, such as bone or cartilage. To the best of our knowledge, the clinical course of a tumour that has undergone a transformation from one type of metaplastic carcinoma to another subtype has not previously been reported. The present study reports the five-year clinical and pathological course of a metaplastic breast carcinoma in a 55-year-old female, who was diagnosed with a sclerosing fibroadenomatous nodule with osseous metaplasia and focal atypia. A recurrent tumour was documented four years later, showing a predominant component of osteosarcoma with adenosquamous carcinoma. Upon pathological review of the initial mass, the diagnosis was changed to low-grade adenosquamous carcinoma. The patient was treated with breast conserving therapy. However, one year later, a recurrent metaplastic carcinoma with spindle cell morphology was documented and surgically removed by mastectomy. Subsequently, pulmonary invasion of the chest wall occurred and the patient eventually succumbed due to the invasive nature of the disease.

  15. Squamous cell carcinoma in a capybara (Hydrochoerus hydrochaeris).

    PubMed

    Hamano, Takahisa; Terasawa, Fumio; Tachikawa, Yoshiharu; Murai, Atsuko; Mori, Takashi; El-Dakhly, Khaled; Sakai, Hiroki; Yanai, Tokuma

    2014-09-01

    A 4-year and 2-month-old male capybara (Hydrochoerus hydrochaeris) was diagnosed with squamous cell carcinoma on the buttocks after chronic recurrent dermatosis. The capybara was euthanized, examined by computed tomography and necropsied; the tumor was examined histologically. Computed tomography showed a dense soft tissue mass with indistinct borders at the buttocks. Histological examination of the tumor revealed islands of invasive squamous epithelial tumor cells with a severe desmoplastic reaction. Based on the pathological findings, the mass was diagnosed as a squamous cell carcinoma. This is the first study to report squamous cell carcinoma in a capybara.

  16. Squamous Cell Carcinoma in a Capybara (Hydrochoerus hydrochaeris)

    PubMed Central

    HAMANO, Takahisa; TERASAWA, Fumio; TACHIKAWA, Yoshiharu; MURAI, Atsuko; MORI, Takashi; EL-DAKHLY, Khaled; SAKAI, Hiroki; YANAI, Tokuma

    2014-01-01

    ABSTRACT A 4-year and 2-month-old male capybara (Hydrochoerus hydrochaeris) was diagnosed with squamous cell carcinoma on the buttocks after chronic recurrent dermatosis. The capybara was euthanized, examined by computed tomography and necropsied; the tumor was examined histologically. Computed tomography showed a dense soft tissue mass with indistinct borders at the buttocks. Histological examination of the tumor revealed islands of invasive squamous epithelial tumor cells with a severe desmoplastic reaction. Based on the pathological findings, the mass was diagnosed as a squamous cell carcinoma. This is the first study to report squamous cell carcinoma in a capybara. PMID:24909968

  17. Snail heterogeneity in clear cell renal cell carcinoma.

    PubMed

    Zaldumbide, Laura; Erramuzpe, Asier; Guarch, Rosa; Pulido, Rafael; Cortés, Jesús M; López, José I

    2016-03-08

    Intratumor heterogeneity may be responsible of the unpredictable aggressive clinical behavior that some clear cell renal cell carcinomas display. This clinical uncertainty may be caused by insufficient sampling, leaving out of histological analysis foci of high grade tumor areas. Although molecular approaches are providing important information on renal intratumor heterogeneity, a focus on this topic from the practicing pathologist' perspective is still pending. Four distant tumor areas of 40 organ-confined clear cell renal cell carcinomas were selected for histopathological and immunohistochemical evaluation. Tumor size, cell type (clear/granular), Fuhrman's grade, Staging, as well as immunostaining with Snail, ZEB1, Twist, Vimentin, E-cadherin, β-catenin, PTEN, p-Akt, p110α, and SETD2, were analyzed for intratumor heterogeneity using a classification and regression tree algorithm. Cell type and Fuhrman's grade were heterogeneous in 12.5 and 60 % of the tumors, respectively. If cell type was homogeneous (clear cell) then the tumors were low-grade in 88.57 % of cases. Immunostaining heterogeneity was significant in the series and oscillated between 15 % for p110α and 80 % for Snail. When Snail immunostaining was homogeneous the tumor was histologically homogeneous in 100 % of cases. If Snail was heterogeneous, the tumor was heterogeneous in 75 % of the cases. Average tumor diameter was 4.3 cm. Tumors larger than 3.7 cm were heterogeneous for Vimentin immunostaining in 72.5 % of cases. Tumors displaying negative immunostaining for both ZEB1 and Twist were low grade in 100 % of the cases. Intratumor heterogeneity is a common event in clear cell renal cell carcinoma, which can be monitored by immunohistochemistry in routine practice. Snail seems to be particularly useful in the identification of intratumor heterogeneity. The suitability of current sampling protocols in renal cancer is discussed.

  18. Chromophobe renal cell carcinoma-like thyroid carcinoma: A novel clinicopathologic entity possibly associated with tuberous sclerosis complex.

    PubMed

    Hirokawa, Mitsuyoshi; Miyauchi, Akira; Kihara, Minoru; Kudo, Takumi; Hashimoto, Yuko; Suzuki, Shinichi; Daa, Tsutomu; Vuong, Huy Gia; Mitsutake, Norisato

    2017-07-06

    We report three cases of chromophobe renal cell carcinoma-like thyroid carcinoma as a novel clinicopathologic entity possibly associated with tuberous sclerosis complex. A 15-year-old female, a 19-year-old male, and a 21-year-old male presented with primary thyroid carcinoma. Two of the patients had associated tuberous sclerosis complex. Macroscopically, the carcinomas showed invasive growth. Histologically, the carcinoma cells showed a trabecular pattern with thin vascular stroma, and were characterized by abundant eosinophilic cytoplasm with perinuclear clearing, a prominent cell border, a wrinkled nuclear membrane, and binucleation, which are all features of chromophobe renal cell carcinoma. Immunohistochemically, the carcinoma cells were positive for thyroglobulin, TTF1, and PAX8, and negative for CD10, calcitonin, and carcinoembryonic antigen. Vascular invasion was visible in all cases, but distant metastasis was not detected during follow-up. The original pathological diagnoses of the three cases were widely invasive follicular thyroid carcinoma, poorly differentiated thyroid carcinoma, and oxyphilic variant of papillary thyroid carcinoma. Thus, the cases were similar to chromophobe renal cell carcinoma associated with tuberous sclerosis complex as they were characterized by histologic findings consistent with chromophobe renal cell carcinoma, occurrence in an adolescent or young adult, and favorable prognosis regardless of the presence of vascular invasion and an infiltrating growth pattern resembling poorly differentiated carcinoma. The etiopathogenesis also seemed to suggest the presence of the tuberous sclerosis complex genetic abnormality.

  19. Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery

    ClinicalTrials.gov

    2017-07-07

    Head and Neck Squamous Cell Carcinoma; Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Laryngeal Verrucous Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oral Cavity Verrucous Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma

  20. [Current recommendations in the treatment of basal cell carcinoma and squamous cell carcinoma of the skin].

    PubMed

    Kunte, C; Konz, B

    2007-05-01

    The incidence of the most common tumors of the skin, basal cell carcinoma and squamous cell carcinoma, has risen rapidly in recent years. Dermatologists see in their daily practice many different clinical and histological variants of these tumors. They must be able to develop therapeutic strategies adapted to the tumor and the patient. Surgical excision remains the standard treatment. Micrographic histological evaluation should be employed in difficult locations, for large tumors and when there is increased risk of recurrence or metastasis. For initial or superficial lesions, other approaches such as radiation therapy, as well as curettage, cryosurgery, laser therapy and photodynamic therapy can be employed. An additional option is topical treatment with imiquimod or 5-flourouracil.

  1. Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: an update with special reference to HPV-related carcinomas.

    PubMed

    El-Mofty, Samir K

    2014-07-01

    Accurate identification of the microscopic risk factors of oral and oropharyngeal (OP) squamous cell carcinomas (SCC) and their morphologic variants is of at most importance, as these generally determine treatment modalities, prognosis and overall patient outcome. The great majority of oral and oropharyngeal squamous cell carcinomas are microscopically described as kerartinizing squamous cell carcinoma (KSCC). They bear certain resemblance to keratinizing stratified squamous epithelium. Tobacco habits and excessive consumption of alcoholic beverages have been considered to be the main etiologic agents in these carcinomas. The tumors occurred in older patients more commonly affected the oral tongue and floor of the mouth with well established morphologic risk factors including tumor grade, pattern of invasion and perineural involvement. Within the last 30 years however, the advent and expanding prevalence of high risk human papillomavirus (HPV) as an important etiologic agent for head and neck squamous cell carcinoma, particularly in the OP, has resulted in a significant change in the established morphologic criteria for risk assessment. The majority of HPV relate carcinomas of the OP are nonkeratinizing squamous cell carcinoma (NKSCC). These tumors are found to be more responsive to treatment with a favorable patient outcome and good prognosis. Consequently, alterations in treatment protocols aimed at de-escalation are currently being evaluated. More recently, other morphologic variants that are HPV positive are reported with increasing frequency in the OP and other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, whether the virus is biologically active in these tumors and involved in their pathogenesis, and second, what are the clinical implications with regard to patient management and outcome in the HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here are

  2. Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-04-14

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Major Salivary Gland Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  3. Renal cell carcinoma in kidney allografts: histologic types, including biphasic papillary carcinoma.

    PubMed

    Troxell, Megan L; Higgins, John P

    2016-11-01

    Kidney transplant recipients are at increased risk for malignancy, with about 5% incidence of cancer in native end-stage kidneys. Carcinoma in the renal allograft is far less common. Prior studies have demonstrated a propensity for renal cell carcinomas (RCCs) of papillary subtypes in end-stage kidneys, and perhaps in allograft kidneys, but most allograft studies lack detailed pathologic review and predate the current classification system. We reviewed our experience with renal carcinoma in kidney allografts at 2 academic centers applying the International Society of Urological Pathology classification, informed by immunohistochemistry. The incidence of renal allograft carcinoma was about 0.26% in our population. Of 12 allograft carcinomas, 6 were papillary (50%), 4 were clear cell (33%), 1 was clear cell (tubulo)papillary, and 1 chromophobe. Two of the papillary carcinomas had distinctive biphasic glomeruloid architecture matching the newly named "biphasic squamoid alveolar" pattern and were difficult to classify on core biopsies. The 2 cell types had different immunophenotypes in our hands (eosinophilic cells: RCC-/CK34betaE12+ weight keratin +/cyclin D1+; clear cells: RCC+/cytokeratin high molecular weight negative to weak/cyclin D1-). None of the patients experienced cancer recurrences or metastasis. Our study confirms the predilection for papillary RCCs in kidney allografts and highlights the occurrence of rare morphologic variants. Larger studies are needed with careful pathologic review, which has been lacking in the literature.

  4. Inflammatory Cell Distribution in Primary Merkel Cell Carcinoma

    PubMed Central

    Wheat, Rachel; Roberts, Claudia; Waterboer, Tim; Steele, Jane; Marsden, Jerry; Steven, Neil M.; Blackbourn, David J.

    2014-01-01

    Merkel cell carcinoma (MCC) is an aggressive poorly differentiated neuroendocrine cutaneous carcinoma associated with older age, immunodeficiency and Merkel cell polyomavirus (MCPyV) integrated within malignant cells. The presence of intra-tumoural CD8+ lymphocytes reportedly predicts better MCC-specific survival. In this study, the distribution of inflammatory cells and properties of CD8+ T lymphocytes within 20 primary MCC specimens were characterised using immunohistochemistry and multicolour immunofluorescent staining coupled to confocal microscopy. CD8+ cells and CD68+ macrophages were identified in 19/20 primary MCC. CD20+ B cells were present in 5/10, CD4+ cells in 10/10 and FoxP3+ cells in 7/10 specimens. Only two specimens had almost no inflammatory cells. Within specimens, inflammatory cells followed the same patchy distribution, focused at the edge of sheets and nodules and, in some cases, more intense in trabecular areas. CD8+ cells were outside vessels on the edge of tumour. Those few within malignant sheets typically lined up in fine septa not contacting MCC cells expressing MCPyV large T antigen. The homeostatic chemokine CXCL12 was expressed outside malignant nodules whereas its receptor CXCR4 was identified within tumour but not on CD8+ cells. CD8+ cells lacked CXCR3 and granzyme B expression irrespective of location within stroma versus malignant nodules or of the intensity of the intra-tumoural infiltrate. In summary, diverse inflammatory cells were organised around the margin of malignant deposits suggesting response to aberrant signaling, but were unable to penetrate the tumour microenvironment itself to enable an immune response against malignant cells or their polyomavirus. PMID:24961933

  5. A pan inhibitor of DASH family enzymes induces immunogenic modulation and sensitizes murine and human carcinoma cells to antigen-specific cytotoxic T lymphocyte killing: implications for combination therapy with cancer vaccines.

    PubMed

    Donahue, Renee N; Duncan, Brynn B; Fry, Terry J; Jones, Barry; Bachovchin, William W; Kiritsy, Christopher P; Lai, Jack H; Wu, Wengen; Zhao, Peng; Liu, Yuxin; Tsang, Kwong-Yok; Hodge, James W

    2014-05-30

    Recent studies have suggested that pan inhibitors of dipeptidyl peptidase-4 activity and/or structure homologs (DASH), including ARI-4175, can mediate tumor regression by immune-mediated mechanisms. This study assessed the potential of combining ARI-4175 with cancer vaccines. We evaluated ARI-4175's effect on immunogenic modulation, ability to sensitize tumor cells to antigen-specific CTL killing, effect on immune-cell subsets and function, and antitumor activity in 2 tumor models, both as a monotherapy and in combination with a recombinant viral or dendritic cell (DC)-based tumor-cell vaccine. ARI-4175's effects on the growth, surface phenotype, and antigen-specific CTL-mediated lysis of murine and human carcinoma cell lines were assessed in vitro. In vivo, C57BL-6 mice were treated orally with ARI-4175, after which splenocytes were assessed by flow cytometry and functional assays. Antitumor studies were performed in murine models of colon carcinoma (MC38-CEA(+) in CEA-transgenic C57BL-6 mice) and rhabdomyosarcoma (M3-9-M in C57BL-6 mice). Mice received oral ARI-4175 alone or in combination with a vaccine consisting of recombinant vaccinia/fowlpox CEA-TRICOM (colon model) or a DC-based tumor-cell vaccine (rhabdomyosarcoma model). Exposure to ARI-4175 had no effect on the proliferation or viability of carcinoma cells in vitro; however, it did alter tumor phenotype, making murine and human tumor cells more sensitive to antigen-specific CTL killing. Assessment of immune-cell subsets and function indicated that ARI-4175 increased levels of natural killer cells and DCs. Detrimental immune effects, including reduced T effector cells and increased immunosuppressive cells (Tregs, MDSCs), were normalized when treatment stopped, suggesting that scheduling is critical when combining this agent with vaccine. As a monotherapy, ARI-4175 had potent antitumor activity in both tumor models, and had even greater effects when combined with a vaccine (either DC-based or poxviral

  6. Downregulated Chibby in laryngeal squamous cell carcinoma with increased expression in laryngeal carcinoma Hep-2 cells.

    PubMed

    Xu, Jue; Ren, Gang; Zhao, De-An; Li, Bo-An; Cai, Cheng-Fu; Zhou, Yi; Luo, Xian-Yang

    2014-11-01

    Chibby (Cby) inhibits Wnt/β-catenin-mediated transcriptional activation by competing with Lef-1 (the transcription factor and target of β-catenin) to bind to β-catenin. This suggests that Cby could be a tumor suppressor protein. In the present study, we examined Cby expression in laryngeal squamous cell carcinoma (LSCC) and its function and mechanism in laryngeal carcinoma cell lines. Cby expression levels were investigated by immunohistochemistry in a panel of 36 LSCC patient cases. The expression of β-catenin, c-myc and cyclin D1 in Hep-2 were determined through RT-PCR and western blot analysis. Activity of Wnt/β-catenin signaling pathway after overexpression of Cby was measured by TCF/LEF luciferase reporter gene assay. Proliferation, clone forming ability, cell cycle distribution and cell apoptosis of Hep-2 cells were detected by MTT assay, plate colony forming assay, flow cytometry and TUNEL assay, respectively. This study showed that expression of Cby protein was strongly downregulated in LSCC tumor tissues in comparison to normal laryngeal mucosa samples. No significant correlation was found between the expression of Cby in tumor tissue and gender, age, clinical stage and tumor differentiation of laryngeal cancer patients. When Cby was overexpressed in Hep-2 cells, the expression of cyclin D1 was reduced and β-catenin activity was inhibited. Proliferation and plate colony forming assays revealed a significant inhibitory effect of Cby on growth and colony formation ability of Hep-2 cells after Cby overexpression in comparison to control and mock-infected cells. In addition, we also found that upregulated expression of Cby resulted in accumulation of numbers of cells in G0/G1 phase with concomitant decrease in S phase by cell cycle assay. TUNEL staining demonstrated that, compared with the control group, the rate of apoptosis in the plv-cs2.0-Cby group was significantly increased. Taken together, downregulation of Cby was observed in LSCC, but with no

  7. Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma

    PubMed Central

    Han, Xiangkun; Li, Fuming; Fang, Zhaoyuan; Gao, Yijun; Li, Fei; Fang, Rong; Yao, Shun; Sun, Yihua; Li, Li; Zhang, Wenjing; Ma, Huimin; Xiao, Qian; Ge, Gaoxiang; Fang, Jing; Wang, Hongda; Zhang, Lei; Wong, Kwok-kin; Chen, Haiquan; Hou, Yingyong; Ji, Hongbin

    2014-01-01

    Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that reduction of lysyl oxidase (Lox) in Lkb1-deficient lung ADC decreases collagen disposition and triggers extracellular matrix remodelling and upregulates p63 expression, a SCC lineage survival oncogene. Pharmacological Lox inhibition promotes the transdifferentiation, whereas ectopic Lox expression significantly inhibits this process. Notably, ADC and SCC show differential responses to Lox inhibition. Collectively, our findings demonstrate the de novo transdifferentiation of lung ADC to SCC in mice and provide mechanistic insight that may have important implications for lung cancer treatment. PMID:24531128

  8. Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

    SciTech Connect

    Lin, Charles; Tripcony, Lee; Keller, Jacqui; Poulsen, Michael; Martin, Jarad; Jackson, James; Dickie, Graeme

    2012-01-01

    Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

  9. The dermatoscopic universe of basal cell carcinoma.

    PubMed

    Lallas, Aimilios; Apalla, Zoe; Argenziano, Giuseppe; Longo, Caterina; Moscarella, Elvira; Specchio, Francesca; Raucci, Margaritha; Zalaudek, Iris

    2014-07-01

    Following the first descriptions of the dermatoscopic pattern of basal cell carcinoma (BCC) that go back to the very early years of dermatoscopy, the list of dermatoscopic criteria associated with BCC has been several times updated and renewed. Up to date, dermatoscopy has been shown to enhance BCC detection, by facilitating its discrimination from other skin tumors and inflammatory skin diseases. Furthermore, upcoming evidence suggests that the method is also useful for the management of the tumor, since it provides valuable information about the histopathologic subtype, the presence of clinically undetectable pigmentation, the expansion of the tumor beyond clinically visible margins and the response to non-ablative treatments. In the current article, we provide a summary of the traditional and latest knowledge on the value of dermatoscopy for the diagnosis and management of BCC.

  10. Hürthle cell carcinoma: current perspectives

    PubMed Central

    Ahmadi, Sara; Stang, Michael; Jiang, Xiaoyin “Sara”; Sosa, Julie Ann

    2016-01-01

    Hürthle cell carcinoma (HCC) can present either as a minimally invasive or as a widely invasive tumor. HCC generally has a more aggressive clinical behavior compared with the other differentiated thyroid cancers, and it is associated with a higher rate of distant metastases. Minimally invasive HCC demonstrates much less aggressive behavior; lesions <4 cm can be treated with thyroid lobectomy alone, and without radioactive iodine (RAI). HCC has been observed to be less iodine-avid compared with other differentiated thyroid cancers; however, recent data have demonstrated improved survival with RAI use in patients with HCC >2 cm and those with nodal and distant metastases. Patients with localized iodine-resistant disease who are not candidates for a wait-and-watch approach can be treated with localized therapies. Systemic therapy is reserved for patients with progressive, widely metastatic HCC. PMID:27853381

  11. Lupus vulgaris with squamous cell carcinoma.

    PubMed

    Motswaledi, Mojakgomo Hendrick; Doman, Chantal

    2007-12-01

    Tuberculosis is still a significant problem in developing countries. Cutaneous forms of tuberculosis account for approximately 10% of all cases of extrapulmonary tuberculosis. Cutaneous tuberculosis may be because of true infection with Mycobacterium tuberculosis or because of tuberculids. Tuberculids are immunological reactions to haematogenously spread antigenic components of M. tuberculosis. True cutaneous tuberculosis may be because of inoculation or haematogenous spread of M. tuberculosis to the skin. Lupus vulgaris is the commonest form of true cutaneous tuberculosis. Other forms of true cutaneous tuberculosis are tuberculous chancre, tuberculosis verrucosa cutis, scrofuloderma, periorificial tuberculosis and miliary tuberculosis of the skin. Lupus vulgaris is usually chronic and progressive. It occurs in patients with moderate to high immunity against M. tuberculosis as evidenced by strongly positive tuberculin test. Long-standing cases of lupus vulgaris may be complicated by squamous cell carcinoma (SCC). We describe a patient who had undiagnosed lupus vulgaris for 35 years until she developed SCC on the lesion of lupus vulgaris.

  12. Metabolic alterations in renal cell carcinoma.

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Brunelli, Matteo; Piva, Francesco; Modena, Alessandra; Bimbatti, Davide; Fantinel, Emanuela; Santini, Daniele; Cheng, Liang; Cascinu, Stefano; Montironi, Rodolfo; Tortora, Giampaolo

    2015-11-01

    Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). We analyzed the key metabolic abnormalities underlying RCC carcinogenesis, highlighting those altered pathways that may represent potential targets for the development of more effective therapeutic strategies.

  13. Sequential Therapy in Metastatic Renal Cell Carcinoma

    PubMed Central

    Burke, John M.; Agrawal, Manish; Hauke, Ralph J.; Hutson, Thomas E.; Doshi, Gury; Fleming, Mark T.; Vogelzang, Nicholas J.

    2016-01-01

    The treatment of metastatic renal cell carcinoma (mRCC) has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network’s Genitourinary Research Committee. We outline our thought process in approaching sequential therapy of mRCC and the use of real-world data to inform our approach. We also highlight the evolving literature that will impact practicing oncologists in the near future. PMID:28326277

  14. CMV chemotherapy for advanced transitional cell carcinoma.

    PubMed Central

    Jeffery, G. M.; Mead, G. M.

    1992-01-01

    Between May 1986 and September 1990 a total of 43 patients with metastatic transitional cell carcinoma (TCC) of the urinary tract have been treated at our institution with combination chemotherapy (CMV) consisting of cisplatin 100 mg m-2 i.v. day 2; methotrexate 30 mg m-2 i.v. days 1.8; and vinblastine 4 mg m-2 i.v. days 1.8. Chemotherapy was recycled on day 22 and continued for a maximum of six cycles in responding patients. Of 33 patients with measurable disease 8 (24%) achieved a complete remission (CR). The median survival for patients achieving a CR was 13 months (range 5-29+) whilst the median survival for all 43 patients was 7 months (range 1-29+). Only three patients are still alive--two are disease free. More effective and/or less toxic chemotherapy regimens are needed for the treatment of patients with metastatic TCC. PMID:1520591

  15. Squamous cell carcinoma arising from neglected meningocele

    PubMed Central

    Wani, Abrar A.; Raswan, Uday K.; Malik, Nayil K.; Ramzan, Altaf U.; Lone, Iqbal

    2016-01-01

    Background: A neural tube defect (NTD) is a common congenital anomaly with an incidence of 6.57–8.21 per 1000 live births. Patients usually present early because of obvious swelling or due to neurological deficit. However, neglecting the obvious cystic swelling on the back till its transformation into malignant tumor is rare. Case Description: We describe a case of malignant transformation of meningocele in a 60-year-old man. Magnetic resonance imaging showed sacral meningocele. Neurological examination revealed intact motor and sensory examination with normal bladder and bowel function. There were no signs of meningitis and hydrocephalus. Excision was done and biopsy revealed it as squamous cell carcinoma. Conclusion: Meningocele should be treated early and possibility of malignant change should be kept in mind in neglected cases presenting in adulthood. PMID:28194302

  16. Sunitinib resistance in renal cell carcinoma

    PubMed Central

    2014-01-01

    Of the many targeted therapies introduced since 2006, sunitinib has carved its way to become the most commonly used first-line therapy for the treatment of metastatic renal cell carcinoma (RCC). Despite significant improvements in progression-free survival, 30% of the patients are intrinsically resistant to sunitinib and the remaining 70% who respond initially will eventually become resistant in 6–15 months. While the molecular mechanisms of acquired resistance to sunitinib have been unravelling at a rapid rate, the mechanisms of intrinsic resistance remain elusive. Combination therapy, sunitinib rechallenge and sequential therapy have been investigated as means to overcome resistance to sunitinib. Of these, sequential therapy appears to be the most promising strategy. This mini review summarises our emerging understanding of the molecular mechanisms, and the strategies employed to overcome sunitinib resistance.

  17. Computed tomography in metastatic renal cell carcinoma.

    PubMed

    Griffin, Nyree; Grant, Lee Alexander; Bharwani, Nishat; Sohaib, S Aslam

    2009-08-01

    Recent developments in chemotherapy have resulted in several new drug treatments for metastatic renal cell carcinoma (RCC). These therapies have shown improved progression-free survival and are applicable to many more patients than the conventional cytokine-based treatments for metastatic RCC. Consequently imaging is playing a greater part in the management of such patients. Computed tomography (CT) remains the primary imaging modality with other imaging modalities playing a supplementary role. CT is used in the diagnosis and staging of metastatic RCC. It is used in the follow-up of patients after nephrectomy, in assessing the extent of metastatic disease, and in evaluating response to treatment. This review looks at the role of CT in patients with metastatic RCC and describes the appearances of metastatic RCC before and following systemic therapy.

  18. The dermatoscopic universe of basal cell carcinoma

    PubMed Central

    Lallas, Aimilios; Apalla, Zoe; Argenziano, Giuseppe; Longo, Caterina; Moscarella, Elvira; Specchio, Francesca; Raucci, Margaritha; Zalaudek, Iris

    2014-01-01

    Following the first descriptions of the dermatoscopic pattern of basal cell carcinoma (BCC) that go back to the very early years of dermatoscopy, the list of dermatoscopic criteria associated with BCC has been several times updated and renewed. Up to date, dermatoscopy has been shown to enhance BCC detection, by facilitating its discrimination from other skin tumors and inflammatory skin diseases. Furthermore, upcoming evidence suggests that the method is also useful for the management of the tumor, since it provides valuable information about the histopathologic subtype, the presence of clinically undetectable pigmentation, the expansion of the tumor beyond clinically visible margins and the response to non-ablative treatments. In the current article, we provide a summary of the traditional and latest knowledge on the value of dermatoscopy for the diagnosis and management of BCC. PMID:25126452

  19. Topical tretinoin treatment in basal cell carcinoma.

    PubMed

    Brenner, S; Wolf, R; Dascalu, D I

    1993-03-01

    The efficiency of topical tretinoin was examined in a patient with basal cell carcinomas (BCC) for which conventional means of removal was inappropriate. Topical tretinoin was used to treat multiple arsenic-induced superficial BCCs in a 64-year-old woman. Topical tretinoin (0.05% twice daily) was administered to four lesions for 3 weeks followed by a 3-week interruption. After three cycles of treatment clinical healing of all the lesions was observed. Histopathological examination of the lesional biopsies showed no evidence of a tumor. However, 9 months later all four lesions relapsed and surgical excision disclosed BCC. The data indicate that topical tretinoin treatment of multiple superficial BCCs induces clinical and pathological regression of the lesions with a high rate of relapse. This report suggests that topical tretinoin is not an effective therapy for the cure of arsenic-induced superficial BCCs.

  20. Unilateral Blepharoptosis from Renal Cell Carcinoma

    PubMed Central

    Sabatino, Lorenzo; Sabatino, Francesco; Casale, Manuele; Quattrocchi, Carlo Cosimo; Zobel, Bruno Beomonte

    2016-01-01

    Blepharoptosis is the drooping or inferior displacement of the upper eyelid. Blepharoptosis can be either congenital or acquired. Tumour metastasis is one of the acquired causes of blepharoptosis. The lungs, locoregional lymph nodes, bone and liver are the usual sites of metastases of renal cell carcinoma (RCC); however, unusual locations of RCC have also been reported. Herein, we describe a case of a 47-year-old man with unilateral ptosis and blurred vision due to metastatic RCC. We describe the different causes of blepharopstosis, the path that led to the diagnosis, and how RCC can metastasize to unusual anatomical regions such as the orbit. Symptoms such as exophthalmos, lid edema, diplopia, ptosis, cranial nerve paralysis or blurred vision may mime a benign disease; however, they could also be the symptoms of a systemic malignancy. PMID:28326282

  1. Burden of basal cell carcinoma in USA.

    PubMed

    Wu, Xinyuan; Elkin, Elena E; Marghoob, Ashfaq A

    2015-11-01

    Basal cell carcinoma (BCC) is the most common malignancy diagnosed in the USA and its incidence continues to increase. While BCC is still most prevalent in the older segments of the population, it is becoming ever more frequent in younger individuals. The costs of treatment and morbidity associated with BCCs place a heavy public health and economic burden on patients, their families and the American healthcare system and underscore the importance of efficient management and prevention efforts directed toward this malignancy. In this article, we address economic aspects of BCC using evidence from large-scale epidemiological studies. This information may help clinicians in developing better and more cost-effective methods for dealing with the most common cancer in America and in the world.

  2. Renal Cell Carcinoma Metastatic to the Scalp

    PubMed Central

    Errami, Mounir; Margulis, Vitali; Huerta, Sergio

    2016-01-01

    Because of the asymptomatic natural history of renal cell carcinoma (RCC), by the time a diagnosis is made, metastatic disease is present in about one third of the cases. Thus, the overall survival of patients with RCC remains poor. Ultimately up to 50% of patients with RCC will develop metastases. Metastatic lesions from RCC are usually observed in the lungs, liver or bone. Metastases to the brain or the skin from RCC are rare. Here we present a patient diagnosed with RCC, found to have no evidence of metastases at the time of nephrectomy, who presented two years later with metastases to the scalp. We review the literature of patients with this rare site of metastasis and outline the overall prognosis of this lesion compared to other site of metastases from RCC. PMID:28191289

  3. Oral Carcinoma Cuniculatum: A New Entity in the Clinicopathological Spectrum of Oral Squamous Cell Carcinoma

    PubMed Central

    Kale, Alka; Mane, Deepa

    2017-01-01

    Carcinoma cuniculatum is principally recognized as a variant of carcinoma involving foot. The World Health Organization (WHO) recognizes Oral Carcinoma Cuniculatum (OCC) as a distinct and rare clinicopathological variant of Oral Squamous Cell Carcinoma (OSCC). OCC is confused clinically and histologically with Verrucous Carcinoma (VC) and is often misdiagnosed as either VC or OSCC. To best of our knowledge, till date, only 50 cases of this tumour have been reported in oral cavity (including the present case) and only limited number of cases have been reported from Indian subcontinent. Pathognomonic feature of OCC is proliferation of stratified squamous epithelium and its infiltration into underlying stroma forming a complex pattern of keratin cores and keratin filled crypts. These complex crypts give it a likeness of rabbit burrow hence, the name cuniculatum (cuniculatus=‘rabbit warren’). The report aims to present a case of OCC of mandibular gingiva, discuss its diagnostic features and highlight its differences from VC and OSCC. PMID:28274074

  4. Developments in the pathology of penile squamous cell carcinomas.

    PubMed

    Chaux, Alcides; Velazquez, Elsa F; Algaba, Ferran; Ayala, Gustavo; Cubilla, Antonio L

    2010-08-01

    Most penile cancers are squamous cell carcinoma (SCC) originating in the epithelium covering glans, coronal sulcus, and foreskin. Several histologic subtypes have been described, each with distinctive clinicopathologic and outcome features. The most common subtype is the usual SCC, representing one half to two thirds of penile carcinomas. Penile verruciform tumors encompass verrucous, warty (condylomatous), and papillary, not otherwise specified, carcinomas. As a group, verruciform tumors are low grade, with low metastatic and mortality rates. In contrast, basaloid and sarcomatoid carcinomas are among the most aggressive penile tumors. Other SCC variants, such as carcinoma cuniculatum and pseudohyperplastic, adenosquamous and acantholytic carcinomas, are rare. The most relevant clinicopathologic and outcome features are outlined for each of these SCC subtypes, and an algorithm that might aid the pathologist in the histologic classification is presented. In addition, recommendations for handling penile cancer specimens, frozen section specimens, and pathology reports are provided.

  5. [Treatment of metastatic renal cell carcinoma].

    PubMed

    Thuret, R; Maurin, C; Sun, M; Perrotte, P; Karakiewicz, P I

    2011-04-01

    The median survival of patients with metastatic renal cell carcinoma (mRCC) increased from 10 to more than 40 months since the advent of targeted therapy. The transformation of mRCC from an initially lethal disease to a more favorable entity, albeit incurable, occurred with the transition from best supportive care, to cytokines, to finally sequential targeted therapies. Sunitinib and bevacizumab (level 1b) represent the first-line standard of care for patients with clear-cell mRCC vs temsirolimus (level 2) for those with high-risk features. Additionally, exploratory analyses of the temsirolimus data indicate important benefits for those with nonclear-cell mRCC histological subtypes. In second-line, everolimus proved its efficacy (level 1b). Nonetheless, sunitinib and sorafenib are also effective for nonclear-cell histological subtypes and after failure of other first-line treatment. The PFS benefits of first- and subsequent treatment-lines were confirmed in virtually all subgroup analyses. Potential survival benefits can be derived from cytoreductive nephrectomy (CNT), as was shown for cytokines in the general population, in sunitinib and bevacizumab-exposed patients. Phase III studies are ongoing to address the importance of CNT. This information is crucial to ensure timely delivery of a combination of medical and surgical therapies in this patient population.

  6. Neuroendocrine differentiation in basal cell carcinoma.

    PubMed

    Houcine, Yoldez; Chelly, Ines; Zehani, Alia; Belhaj Kacem, Linda; Azzouz, Haifa; Rekik, Wafa; C, Hend; Haouet, Slim; Kchir, Nidhameddine

    2017-05-26

    Basal cell carcinoma (BCC) is the prototypical basaloid tumor of the skin. It may show various patterns simulating other cutaneous tumors due to its pleomorphism. It may have an unusal pattern of differentiation such as squamous, sebaceous, apocrine, eccrine, pilar, and endocrine differentiation. In order to establish the relative frequency of neuroendocrine differentiation in BCC, we performed a retrospective study of 33 consecutive BCCs using conventional immunohistochemistry with two neuroendocrine antibodies: Chromogranine A and synaptophysine. The age of the patients ranged from 17-83 years with mean of 65 years. The male to female ratio was 16:17. In immunohistochimestry, Chromogranine A was seen in 72.2% (24/33) while Synaptophysine was positive in 9.09% (3/33). Their expression was cytoplasmic and membranous and was seen in the periphery of these tumors in the overlying cells. Positive staining of chromogranine A was high (75-100% of tumors cells) in 9%, intermediate (25-75% of tumors cells) in 33% of cases and relatively low (<25%) in 30.3% of cases.

  7. Is cutaneous leishmaniasis a risk factor for basal cell carcinoma?

    PubMed

    Chisti, M; Almasri, R; Hamadah, I

    2016-05-01

    Basal cell carcinoma (BCC) is the most common epithelial neoplasm of skin. Risk factors for the development of BCC include intermittent intense sun exposure, radiation therapy, family history of BCC, immune suppression and fair complexion, especially red hair. It can originate in scars like small pox, vaccination, chicken pox or surgical scars. We present a case of basal cell carcinoma arising in a leishmania scar on the nose, sixty years after the primary lesion. Although rare, BCC's have arisen in leishmania scars. Thus the possibility of basal cell carcinoma should be considered while dealing with such patients. Even though a causal relationship, if any, cannot be ascertained at present.

  8. MANDIBULAR SQUAMOUS CELL CARCINOMA IN A BOBCAT (LYNX RUFUS).

    PubMed

    Sladakovic, Izidora; Burnum, Anne; Blas-Machado, Uriel; Kelly, Lisa S; Garner, Bridget C; Holmes, Shannon P; Divers, Stephen J

    2016-03-01

    A 23-yr-old female spayed bobcat (Lynx rufus) presented with a 1-wk history of hypersalivation. On examination, the right mandible was markedly thickened, the right mandibular dental arcade was missing, and the oral mucosa over the right mandible was ulcerated and thickened. Skull radiographs and fine needle aspirate cytology were supportive of squamous cell carcinoma. The bobcat was euthanized as a result of its poor prognosis. Necropsy confirmed a diagnosis of oral squamous cell carcinoma of the mandible. To the authors' knowledge, this is the first report of oral squamous cell carcinoma in a bobcat.

  9. A patient with Multiple myeloma and Renal cell carcinoma.

    PubMed

    Shahi, Farhad; Ghalamkari, Marziye; Mirzania, Mehrzad; Khatuni, Mahdi

    2016-01-01

    The coexistence of two malignancies is rarely seen. A little association between hematologic malignancies especially multiple myeloma and renal cell carcinoma has been reported in the recent past. Several case series revealed a bidirectional association between these two malignancies which may be due to the common risk factors, similar cytokine growth requirements and clinical presentation. Here, we aim to describe a patient who had multiple myeloma and in his work up renal cell carcinoma was found out incidentally. We would like to create awareness among clinicians for the coincidence of Renal cell carcinoma and Multiple myeloma.

  10. A patient with Multiple myeloma and Renal cell carcinoma

    PubMed Central

    Shahi, Farhad; Ghalamkari, Marziye; Mirzania, Mehrzad; Khatuni, Mahdi

    2016-01-01

    The coexistence of two malignancies is rarely seen. A little association between hematologic malignancies especially multiple myeloma and renal cell carcinoma has been reported in the recent past. Several case series revealed a bidirectional association between these two malignancies which may be due to the common risk factors, similar cytokine growth requirements and clinical presentation. Here, we aim to describe a patient who had multiple myeloma and in his work up renal cell carcinoma was found out incidentally. We would like to create awareness among clinicians for the coincidence of Renal cell carcinoma and Multiple myeloma. PMID:27047652

  11. 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.

  12. Single-cell analyses of transcriptional heterogeneity in squamous cell carcinoma of urinary bladder

    PubMed Central

    Hou, Yong; Xu, Liqin; Li, Weidong; Zou, Zhihui; Liu, Chunxiao; Xu, Abai; Wu, Song

    2016-01-01

    Cell-to-cell expression heterogeneity within a single tumor is a common phenotype among various cancer types including squamous cell carcinoma. To further study the fundamentals and importance of heterogeneity of cell functions and its potential mechanisms, we performed single-cell RNA-seq (scRNA-seq) on human squamous cell carcinoma of the bladder (SCCB) and its corresponding physiologically normal epithelia. Extensive differentially expressed genes were uncovered by comparing cancer and normal single cells, which were preferentially enriched in cancer-correlated pathways, such as p53 signaling and bladder cancer pathway. Furthermore, the most diversely expressed genes were particularly enriched in MAPK signaling pathway, such as CACNG4, CACNA1E and CACNA1H, which involve in cancer evolution and heterogeneity formation. Co-expression network and hub-gene analyses revealed several remarkable “hub genes” of each regulatory module. Some of them are cancer related, such as POU2F3, NKD1 and CYP2C8, while LINC00189, GCC2 and OR9Q1 genes are rarely reported in human diseases. The genes within an interesting module are highly correlated with others, which could be treated as potential targets for SCCB patients. Our findings have fundamental implications for SCCB biology and therapeutic strategies. PMID:27602771

  13. Detection of squamous carcinoma cells using gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Dai, Wei-Yun; Lee, Sze-tsen; Hsu, Yih-Chih

    2015-03-01

    The goal of this study is to use gold nanoparticle as a diagnostic agent to detect human squamous carcinoma cells. Gold nanoparticles were synthesized and the gold nanoparticle size was 34.3 ± 6.2 nm. Based on the over-expression of epidermal growth factor receptor (EGFR) biomarkers in squamous carcinoma cells, we hypothesized that EGFR could be a feasible biomarker with a target moiety for detection. We further modified polyclonal antibodies of EGFR on the surface of gold nanoparticles. We found selected squamous carcinoma cells can be selectively detected using EGFR antibody-modified gold nanoparticles via receptor-mediated endocytosis. Cell death was also examined to determine the survival status of squamous carcinoma cells with respect to gold nanoparticle treatment and EGFR polyclonal antibody modification.

  14. Telomere length and risk of melanoma, squamous cell carcinoma, and basal cell carcinoma

    PubMed Central

    Anic, Gabriella M.; Sondak, Vernon K; Messina, Jane L; Fenske, Neil A.; Zager, Jonathan S.; Cherpelis, Basil S.; Lee, Ji-Hyun; Fulp, William J.; Burnette, Pearlie K.; Park, Jong Y.; Rollison, Dana E.

    2013-01-01

    Background Telomeres help maintain chromosomal structure and may influence tumorigenesis. We examined the association between telomere length and skin cancer in a clinic-based case-control study of 198 melanoma cases, 136 squamous cell carcinoma (SCC) cases, 185 basal cell carcinoma (BCC) cases, and 372 healthy controls. Methods Cases were histologically-confirmed patients treated at the Moffitt Cancer Center and University of South Florida Dermatology Clinic in Tampa, FL. Controls self-reported no history of cancer and underwent a skin cancer screening exam at study enrollment to rule out the presence of skin cancer. Quantitative real time PCR was used to measure telomere length in peripheral blood samples. Results Melanoma patients had longer telomeres than controls (odds ratio (OR) = 3.75; 95% confidence interval (CI): 2.02 – 6.94 for highest versus lowest tertile) (p trend = <0.0001). In contrast, longer telomere length was significantly inversely associated with SCC (OR = 0.01; 95% CI: 0.00 - 0.05 for highest versus lowest tertile) (p for trend = <0.0001) and BCC (OR = 0.10; 95% CI: 0.06 - 0.19 for highest versus lowest tertile) (p for trend = <0.0001). Conclusion Telomere length may be involved in the development of skin cancer, although the effect on cancer risk differs for melanoma and non-melanoma carcinomas. Our findings suggest that long telomere length is positively associated with melanoma while inversely associated with SCC and BCC. PMID:23523330

  15. Telomere length and risk of melanoma, squamous cell carcinoma, and basal cell carcinoma.

    PubMed

    Anic, Gabriella M; Sondak, Vernon K; Messina, Jane L; Fenske, Neil A; Zager, Jonathan S; Cherpelis, Basil S; Lee, Ji-Hyun; Fulp, William J; Epling-Burnette, Pearlie K; Park, Jong Y; Rollison, Dana E

    2013-08-01

    Telomeres help maintain chromosomal structure and may influence tumorigenesis. We examined the association between telomere length and skin cancer in a clinic-based case-control study of 198 melanoma cases, 136 squamous cell carcinoma (SCC) cases, 185 basal cell carcinoma (BCC) cases, and 372 healthy controls. Cases were histologically confirmed patients treated at the Moffitt Cancer Center and University of South Florida Dermatology Clinic in Tampa, FL. Controls self-reported no history of cancer and underwent a skin cancer screening exam at study enrollment to rule out the presence of skin cancer. Quantitative real time PCR was used to measure telomere length in peripheral blood samples. Melanoma patients had longer telomeres than controls (odds ratio (OR)=3.75; 95% confidence interval (CI): 2.02-6.94 for highest versus lowest tertile) (P for trend=<0.0001). In contrast, longer telomere length was significantly inversely associated with SCC (OR=0.01; 95% CI: 0.00-0.05 for highest versus lowest tertile) (P for trend=<0.0001) and BCC (OR=0.10; 95% CI: 0.06-0.19 for highest versus lowest tertile) (P for trend=<0.0001). Telomere length may be involved in the development of skin cancer, although the effect on cancer risk differs for melanoma and non-melanoma carcinomas. Our findings suggest that long telomere length is positively associated with melanoma while inversely associated with SCC and BCC. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. An Immune Atlas of Clear Cell Renal Cell Carcinoma.

    PubMed

    Chevrier, Stéphane; Levine, Jacob Harrison; Zanotelli, Vito Riccardo Tomaso; Silina, Karina; Schulz, Daniel; Bacac, Marina; Ries, Carola Hermine; Ailles, Laurie; Jewett, Michael Alexander Spencer; Moch, Holger; van den Broek, Maries; Beisel, Christian; Stadler, Michael Beda; Gedye, Craig; Reis, Bernhard; Pe'er, Dana; Bodenmiller, Bernd

    2017-05-04

    Immune cells in the tumor microenvironment modulate cancer progression and are attractive therapeutic targets. Macrophages and T cells are key components of the microenvironment, yet their phenotypes and relationships in this ecosystem and to clinical outcomes are ill defined. We used mass cytometry with extensive antibody panels to perform in-depth immune profiling of samples from 73 clear cell renal cell carcinoma (ccRCC) patients and five healthy controls. In 3.5 million measured cells, we identified 17 tumor-associated macrophage phenotypes, 22 T cell phenotypes, and a distinct immune composition correlated with progression-free survival, thereby presenting an in-depth human atlas of the immune tumor microenvironment in this disease. This study revealed potential biomarkers and targets for immunotherapy development and validated tools that can be used for immune profiling of other tumor types. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Diabetes and Risk of Renal Cell Carcinoma

    PubMed Central

    Habib, Samy L; Prihoda, Thomas J; Luna, Maria; Werner, Sherry A

    2012-01-01

    Background and objectives: There is evidence that the incidence of solid tumors is markedly increased in patients with diabetes mellitus. In the current study, we investigate the association between diabetes and renal cancer. Patients and Methods: A single-center retrospective analysis of 473 patients who underwent nephrectomy for renal cell carcinoma (RCC) was performed. Diabetic RCC patients were screened for age, gender, ethnicity, HgA1C, glucose levels and renal function. Results: Of the 473 cases with RCC, we identified 120 patients (25.4%) with a history of diabetes. The incidence of diabetes in RCC patients was higher in female than male subjects and in Hispanic compared to White and Other ethnic backgrounds. At diagnosis, the majority of diabetic RCC patients were 50-59 years of age. In diabetic RCC cases, clear cell type histology (92.0%), nuclear grade 2 (56.1%) and tumor size range from 1-5 cm (65.7%) were the most common in each category. Conclusion: Our findings indicate that diabetic RCC patients have a predominance of localized, small clear cell RCC. In addition, females with a history of RCC have a higher frequency of diabetes compared to males. This is the first report of clinical and histopathological features of RCC associated with diabetes. PMID:22232697

  18. Basal Cell Carcinoma. Part 1: Basal Cell Carcinoma Has Come of Age.

    PubMed

    Deng, Min; Marsch, Amanda F; Petronic-Rosic, Vesna

    2015-01-01

    Almost 2 centuries after its recognition, basal cell carcinoma (BCC) remains the most common cancer worldwide, with a 30% overall lifetime risk in the United States and an incidence that continues to increase annually. The increasing incidence of BCC is multifactorial and likely correlates to multiple risk factors, including exposure to both ionizing and UV radiation. Despite its relatively indolent growth, what was once referred to as a rodent ulcer or basal cell epithelioma is now identified as a full-fledged malignancy. The authors describe the societal burden of this disease and characterize its malignant potential, emphasizing associated clinical and histopathologic prognostic features.

  19. Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion.

    PubMed

    Yan, Xia; Zhou, Huiling; Zhang, Tingting; Xu, Pan; Zhang, Shusen; Huang, Wei; Yang, Linlin; Gu, Xingxing; Ni, Runzhou; Zhang, Tianyi

    2015-12-01

    Hepatocellular carcinoma (HCC) is a major health concern with a high morbidity and mortality rate worldwide. However, the mechanism underlying hepatocarcinogenesis remains unclear. Forkhead box P2 (FOXP2) has been implicated in various human cancer types. However, the role of FOXP2 in HCC remains unknown. Western blot and immunohistochemistry were used to measure the expression of FOXP2 protein in HCC and adjacent normal tissues in 50 patients. Wound healing and transwell assays were used to determine the cell invasion ability. We showed that the level of FOXP2 was significantly reduced in HCC compared with the adjacent non-tumorous tissue. There was statistical significance between the expression of FOXP2 and vein invasion (P = 0.017), number of tumor nodes (P = 0.028), and AFP (P = 0.033). Low expression of FOXP2 correlated with poor survival. Moreover, wound healing and transwell assays showed that FOXP2 could decrease cell invasion and affect the expression of vimentin and E-cadherin. Our results suggested that FOXP2 expression was downregulated in HCC tumor tissues, and reduced FOXP2 expression was associated with poor overall survival. In addition, downregulation of FOXP2 significantly enhanced cell invasiveness. These findings uncover that FOXP2 might be a new prognostic factor and be closely correlated with HCC cell invasion.

  20. Sorafenib Tosylate, Cisplatin, and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2017-03-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  1. Biphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to each other, but distinct from, non-sarcomatoid renal carcinomas.

    PubMed

    Sircar, Kanishka; Yoo, Suk-Young; Majewski, Tadeusz; Wani, Khalida; Patel, Lalit R; Voicu, Horatiu; Torres-Garcia, Wandaliz; Verhaak, Roel G W; Tannir, Nizar; Karam, Jose A; Jonasch, Eric; Wood, Christopher G; Tamboli, Pheroze; Baggerly, Keith A; Aldape, Kenneth D; Czerniak, Bogdan

    2015-10-01

    Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma. Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we sought to characterize molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma and compare them to non-sarcomatoid clear cell renal cell carcinoma. We examined the transcriptome of the epithelioid and sarcomatoid components of advanced stage sarcomatoid clear cell renal cell carcinoma (n=43) and non-sarcomatoid clear cell renal cell carcinoma (n=37) from independent discovery and validation cohorts using the cDNA microarray and RNA-seq platforms. We analyzed DNA copy number profiles, generated using SNP arrays, from patients with sarcomatoid clear cell renal cell carcinoma (n=10) and advanced non-sarcomatoid clear cell renal cell carcinoma (n=155). The epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma had similar gene expression and DNA copy number signatures that were, however, distinct from those of high-grade, high-stage non-sarcomatoid clear cell renal cell carcinoma. Prognostic clear cell renal cell carcinoma gene expression profiles were shared by the biphasic components of sarcomatoid clear cell renal cell carcinoma and the sarcomatoid component showed a partial epithelial-to-mesenchymal transition signature. Our genome-scale microarray-based transcript data were validated in an independent set of sarcomatoid and non-sarcomatoid clear cell renal cell carcinomas using RNA-seq. Sarcomatoid clear cell renal cell carcinoma is molecularly distinct from non-sarcomatoid clear cell renal cell carcinoma, with its genetic programming largely shared by its biphasic morphological components. These data explain why a low percentage of sarcomatoid histology augurs a poor prognosis; suggest the

  2. Biphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to each other, but distinct from, non‐sarcomatoid renal carcinomas

    PubMed Central

    Sircar, Kanishka; Yoo, Suk‐Young; Majewski, Tadeusz; Wani, Khalida; Patel, Lalit R.; Voicu, Horatiu; Torres‐Garcia, Wandaliz; Verhaak, Roel G. W.; Tannir, Nizar; Karam, Jose A.; Jonasch, Eric; Wood, Christopher G.; Tamboli, Pheroze; Baggerly, Keith A.

    2015-01-01

    Abstract Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma. Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we sought to characterize molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma and compare them to non‐sarcomatoid clear cell renal cell carcinoma. We examined the transcriptome of the epithelioid and sarcomatoid components of advanced stage sarcomatoid clear cell renal cell carcinoma (n=43) and non‐sarcomatoid clear cell renal cell carcinoma (n=37) from independent discovery and validation cohorts using the cDNA microarray and RNA‐seq platforms. We analyzed DNA copy number profiles, generated using SNP arrays, from patients with sarcomatoid clear cell renal cell carcinoma (n=10) and advanced non‐sarcomatoid clear cell renal cell carcinoma (n=155). The epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma had similar gene expression and DNA copy number signatures that were, however, distinct from those of high‐grade, high‐stage non‐sarcomatoid clear cell renal cell carcinoma. Prognostic clear cell renal cell carcinoma gene expression profiles were shared by the biphasic components of sarcomatoid clear cell renal cell carcinoma and the sarcomatoid component showed a partial epithelial‐to‐mesenchymal transition signature. Our genome‐scale microarray‐based transcript data were validated in an independent set of sarcomatoid and non‐sarcomatoid clear cell renal cell carcinomas using RNA‐seq. Sarcomatoid clear cell renal cell carcinoma is molecularly distinct from non‐sarcomatoid clear cell renal cell carcinoma, with its genetic programming largely shared by its biphasic morphological components. These data explain why a low percentage of sarcomatoid histology

  3. [Cytology of basaloid squamous cell carcinoma and small cell carcinoma of lung: a comparative study].

    PubMed

    He, S R; Bai, Y P; Gong, H; Di, J; Chen, L; Dai, W D; Hu, S T; Liu, D G

    2016-04-08

    To evaluate the roles of cytomorphology and immunohistochemistry in distinguishing between basaloid squamous cell carcinoma (BSC) and small cell carcinoma (SCC) of lung. The direct smears and/or liquid-based cytology preparation (ThinPrep) of bronchial brushing/washing and fine-needle aspiration (FNA) specimens from 17 cases of biopsy-proven BSC of lung were retrospectively reviewed and compared with those from 17 cases of SCC. The cytomorphologic parameters analyzed included proportion of cohesive cell clusters, cell palisades/rosettes, adenoid cystic features, crushing artifact, nuclear maximum diameter, nuclear molding, scantiness of cytoplasm,"salt-and-pepper"nuclei, distinct nucleoli, spindly configuration, individual cell keratinization, necrosis, hyaline material, apoptosis and mitotic activity. Immunocytochemical/immunohistochemical study of 25 cases was performed. Ten FNA samples of basaloid squamous cell carcinoma were also analyzed for epidermal growth factor receptor mutations in exons 18, 19, 20 and 21 using amplification refractory mutation system. Most of the 17 BSC cases (15/17) showed a predominance of tightly cohesive tumor cell clusters. The proportion of isolated tumor cells was high in SCC (more than 60% in 14 cases). The nuclear maximum diameter of BSC was slightly larger than that of SCC (9 to 11 μm in BSC versus 7 to 9 μm in SCC)."Salt-in-pepper"nuclei, nuclear molding and crushing artifact were detected in all SCC cases (15/17, 17/17 and 14/17, respectively). These features were only occasionally found in BSC group. Nucleoli were present in BSC and rarely (2/17) in SCC. Only 9 of 17 BSC cases showed individual cell keratinization. The differences in the above-mentioned cytomorphologic features were statistically significance (P<0.05). The results of immunohistochemistry performed on the cell block sections and immunocytochemistry performed on the ThinPrep slides were identical to that performed on the corresponding biopsy specimens. The

  4. Clear cell papillary renal cell carcinoma: micro-RNA expression profiling and comparison with clear cell renal cell carcinoma and papillary renal cell carcinoma.

    PubMed

    Munari, Enrico; Marchionni, Luigi; Chitre, Apurva; Hayashi, Masamichi; Martignoni, Guido; Brunelli, Matteo; Gobbo, Stefano; Argani, Pedram; Allaf, Mohamad; Hoque, Mohammad O; Netto, George J

    2014-06-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal neoplasm with morphological characteristics mimicking both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). However, despite some overlapping features, their morphological, immunohistochemical, and molecular profiles are distinct. Micro-RNAs (miRNAs) are small noncoding RNAs that play a crucial role in regulating gene expression and are involved in various biological processes, including cancer development. To better understand the biology of this tumor, we aimed to analyze the miRNA expression profile of a set of CCPRCC using microarray and quantitative reverse transcription-polymerase chain reaction. A total of 15 cases diagnosed as CCPRCC were used in this study. Among the most differentially expressed miRNA in CCPRCC, we found miR-210, miR-122, miR-34a, miR-21, miR-34b*, and miR-489 to be up-regulated, whereas miR-4284, miR-1202, miR-135a, miR-1973, and miR-204 were down-regulated compared with normal renal parenchyma. To identify consensus of differentially regulated miRNA between CCPRCC, CCRCC, and PRCC, we additionally determined differential miRNA expression using 2 publically available microarray data sets from the NCBI Gene Expression Omnibus database (GSE41282 and GSE3798). This comparison revealed that the miRNA expression profile of CCPRCC shows some overlapping characteristics between CCRCC and PRCC. Moreover, CCPRCC lacks dysregulation of important miRNAs typically associated with aggressive behavior. In summary, we describe the miRNA expression profile of a relatively infrequent type of renal cancer. Our results may help in understanding the molecular underpinning of this newly recognized entity.

  5. MCM10 overexpression implicates adverse prognosis in urothelial carcinoma

    PubMed Central

    Li, Wei-Ming; Huang, Chun-Nung; Ke, Hung-Lung; Li, Ching-Chia; Wei, Yu-Ching; Yeh, Hsin-Chih; Chang, Lin-Li; Huang, Chun-Hsiung; Liang, Peir-In; Yeh, Bi-Wen; Chan, Ti-Chun; Li, Chien-Feng; Wu, Wen-Jeng

    2016-01-01

    Urothelial carcinoma (UC) occurs in the upper urinary tract (UTUC) and the urinary bladder (UBUC). The molecular pathogenesis of UC has not been fully elucidated. Through data mining of a published transcriptome of UBUC (GSE31684), we identified Minichromosome Maintenance Complex Component 2 (MCM2) and MCM10 as the two most significantly upregulated genes in UC progression among the MCM gene family, the key factors for the initiation of DNA replication. To validate the clinical significance of MCM2 and MCM10, immunohistochemistry, evaluated by H-score, was used in a pilot study of 50 UTUC and 50 UBUC samples. Only a high expression level of MCM10 predicted worse disease-specific survival (DSS) and inferior metastasis-free survival (MeFS) for both UTUC and UBUC. Correspondingly, evaluation of MCM10 mRNA expression in 36 UTUCs and 30 UBUCs showed significantly upregulated levels in high stage UC, suggesting its role in tumor progression. Evaluation of 340 UTUC and 296 UBUC tissue samples, respectively, demonstrated that high MCM10 immunoexpression was significantly associated with advanced primary tumors, nodal status, and the presence of vascular invasion in both groups of UCs. In multivariate Cox regression analyses, adjusted for standard clinicopathological features, MCM10 overexpression was independently associated with DSS (UTUC hazard ratio [HR]=2.401, P = 0.013; UBUC HR=4.323, P=0.001) and with MeFS (UTUC HR=3.294, P<0.001; UBUC HR=1.972, P=0.015). In vitro, knockdown of MCM10 gene significantly suppressed cell proliferation in both J82 and TCCSUP cells. In conclusion, MCM10 overexpression was associated with unfavorable clinicopathological characteristics and independent negative prognostic effects, justifying its potential theranostic value in UC. PMID:27780919

  6. Increased Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma.

    PubMed

    Mohan, Shalini V; Chang, Julia; Li, Shufeng; Henry, A Solomon; Wood, Douglas J; Chang, Anne Lynn S

    2016-05-01

    Smoothened inhibitors (SIs) are a new type of targeted therapy for advanced basal cell carcinoma (BCC), and their long-term effects, such as increased risk of subsequent malignancy, are still being explored. To evaluate the risk of developing a non-BCC malignancy after SI exposure in patients with BCC. A case-control study at Stanford Medical Center, an academic hospital. Participants were higher-risk patients with BCC diagnosed from January 1, 1998, to December 31, 2014. The dates of the analysis were January 1 to November 1, 2015. The exposed participants (cases) comprised patients who had confirmed prior vismodegib treatment, and the nonexposed participants (controls) comprised patients who had never received any SI. Because vismodegib was the first approved SI, only patients exposed to this SI were included. Hazard ratio for non-BCC malignancies after vismodegib exposure, adjusting for covariates. The study cohort comprised 180 participants. Their mean (SD) age at BCC diagnosis was 56 (16) years, and 68.9% (n = 124) were male. Fifty-five cases were compared with 125 controls, accounting for age, sex, prior radiation therapy or cisplatin treatment, Charlson Comorbidity Index, clinical follow-up time, immunosuppression, and basal cell nevus syndrome status. Patients exposed to vismodegib had a hazard ratio of 6.37 (95% CI, 3.39-11.96; P < .001), indicating increased risk of developing a non-BCC malignancy. Most non-BCC malignancies were cutaneous squamous cell carcinomas, with a hazard ratio of 8.12 (95% CI, 3.89-16.97; P < .001), accounting for age and basal cell nevus syndrome status. There was no significant increase in other cancers. Increased risk for cutaneous squamous cell carcinomas after vismodegib therapy highlights the importance of continued skin surveillance after initiation of this therapy.

  7. Incidentally detected clear cell renal cell carcinoma with rhabdoid differentiation.

    PubMed

    Krishnamoorthy, Venkatesh; Gowda, Kiran Krishne; Rao, Raman Narayana

    2016-01-01

    Renal cell carcinoma with rhabdoid differentiation (RCC-R) has an aggressive biologic behavior and poor prognosis. A recent consensus statement of the International Society of Urological Pathology (ISUP) proposed a nucleolar grading system (ISUP grade) for RCC to replace Fuhrman system and recommended reporting the presence of rhabdoid differentiation and considering tumors with rhabdoid differentiation to be ISUP Grade 4. We report a case of incidentally detected clear cell RCC-R in a 52-year-old man. This is one of the earliest cases of RCC-R (pT1b) detected and first such case from Indian subcontinent.

  8. Caffeic Acid Expands Anti-Tumor Effect of Metformin in Human Metastatic Cervical Carcinoma HTB-34 Cells: Implications of AMPK Activation and Impairment of Fatty Acids De Novo Biosynthesis

    PubMed Central

    Tyszka-Czochara, Malgorzata; Konieczny, Pawel; Majka, Marcin

    2017-01-01

    The efficacy of cancer treatments is often limited and associated with substantial toxicity. Appropriate combination of drug targeting specific mechanisms may regulate metabolism of tumor cells to reduce cancer cell growth and to improve survival. Therefore, we investigated the effects of anti-diabetic drug Metformin (Met) and a natural compound caffeic acid (trans-3,4-dihydroxycinnamic acid, CA) alone and in combination to treat an aggressive metastatic human cervical HTB-34 (ATCC CRL­1550) cancer cell line. CA at concentration of 100 µM, unlike Met at 10 mM, activated 5'-adenosine monophosphate-activated protein kinase (AMPK). What is more, CA contributed to the fueling of mitochondrial tricarboxylic acids (TCA) cycle with pyruvate by increasing Pyruvate Dehydrogenase Complex (PDH) activity, while Met promoted glucose catabolism to lactate. Met downregulated expression of enzymes of fatty acid de novo synthesis, such as ATP Citrate Lyase (ACLY), Fatty Acid Synthase (FAS), Fatty Acyl-CoA Elongase 6 (ELOVL6), and Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells. In conclusion, CA mediated reprogramming of glucose processing through TCA cycle via oxidative decarboxylation. The increased oxidative stress, as a result of CA treatment, sensitized cancer cells and, acting on cell biosynthesis and bioenergetics, made HTB-34 cells more susceptible to Met and successfully inhibited neoplastic cells. The combination of Metformin and caffeic acid to suppress cervical carcinoma cells by two independent mechanisms may provide a promising approach to cancer treatment. PMID:28230778

  9. Radiation sensitivity of Merkel cell carcinoma cell lines

    SciTech Connect

    Leonard, J.H.; Ramsay, J.R.; Birrell, G.W.

    1995-07-30

    Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after {gamma} irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to {gamma} irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution. 25 refs., 3 figs., 1 tab.

  10. Helicobacter Pylory infection in patients with esophageal squamous cell carcinoma

    PubMed Central

    Poyrazoglu, Omer Bilgehan; Dulger, Ahmet Cumhur; Gultepe, Bilge Sumbul

    2017-01-01

    OBJECTIVE: Esophageal squamous cell carcinoma is one of the most common esophageal diseases in the developing world, but the relationship between esophageal squamous cell carcinoma and Helicobacter pylori infection remains a neglected topic. The primary objective of this study was to determine the association between Helicobacter pylori infection and esophageal squamous cell carcinoma. A second purpose was to determine the incidence and factors associated with Helicobacter pylori infection following esophagectomy. METHOD: The microorganism was identified by testing the gastric biopsy materials from 95 esophageal squamous cell carcinoma patients (66 females; 39 were esophagectomized) for urease activity in a medium containing urea and a power of hydrogen detection reagent and comparing the results with those from a healthy population. Differences in patient characteristics were assessed with chi-square tests and t-tests for categorical and continuous factors, respectively. RESULTS: The patients with esophageal squamous cell carcinoma had a significantly lower prevalence of Helicobacter pylori compared with the healthy population (p<0.001). The naive and esophagectomized patients, in contrast, showed no significant differences in Helicobacter pylori infection (p>0.005). Patients with esophageal squamous cell carcinoma showed a significant association between leukocytosis and hypoglobulinemia and the presence of Helicobacter pylori infection (p=0.023 and p=0.045, respectively). CONCLUSION: These results suggest that Helicobacter pylori is not an etiological factor in patients with esophageal squamous cell carcinoma. We found a statistically significant negative correlation between esophageal squamous cell cancer and Helicobacter pylori infection. These findings may guide new strategies for esophageal squamous cell carcinoma therapy. PMID:28355360

  11. Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

    PubMed Central

    Lo Muzio, Lorenzo

    2008-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

  12. Nevoid basal cell carcinoma syndrome (Gorlin syndrome).

    PubMed

    Lo Muzio, Lorenzo

    2008-11-25

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5-10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

  13. Understanding Papillary Renal Cell Carcinoma | Center for Cancer Research

    Cancer.gov

    Renal cell carcinoma (RCC), the most common form of kidney cancer in adults, is not a single disease but rather a collection of different tumor types driven by distinct genetic changes that arise within the same tissue.

  14. Recent advances in the management of renal cell carcinoma

    PubMed Central

    Molina, Ana M.; Nanus, David M.

    2016-01-01

    Therapeutic options for patients with metastatic renal cell carcinoma have significantly improved over the past few years with the recent approval of two new agents resulting in prolonged progression-free and overall survival. PMID:27019698

  15. Squamous cell carcinoma of cervix metastatic to ileal loop

    SciTech Connect

    Hulecki, S.J.; Klein, F.A.; Davis, J.E.

    1985-12-01

    A case is presented of squamous cell carcinoma of the cervix with an isolated metastasis to an ileal loop six years after diversion and seven years after definitive treatment of the primary lesion with irradiation.

  16. Senescent fibroblast-derived Chemerin promotes squamous cell carcinoma migration

    PubMed Central

    Gatzka, Martina; Treiber, Nicolai; Schneider, Lars A.; Mulaw, Medhanie A.; Lucas, Tanja; Kochanek, Stefan; Dummer, Reinhard; Levesque, Mitchell P.; Wlaschek, Meinhard; Scharffetter-Kochanek, Karin

    2016-01-01

    Aging is associated with a rising incidence of cutaneous squamous cell carcinoma (cSCC), an aggressive skin cancer with the potential for local invasion and metastasis. Acquisition of a senescence-associated secretory phenotype (SASP) in dermal fibroblasts has been postulated to promote skin cancer progression in elderly individuals. The underlying molecular mechanisms are largely unexplored. We show that Chemerin, a previously unreported SASP factor released from senescent human dermal fibroblasts, promotes cSCC cell migration, a key feature driving tumor progression. Whereas the Chemerin abundance is downregulated in malignant cSCC cells, increased Chemerin transcripts and protein concentrations are detected in replicative senescent fibroblasts in vitro and in the fibroblast of skin sections from old donors, indicating that a Chemerin gradient is built up in the dermis of elderly. Using Transwell® migration assays, we show that Chemerin enhances the chemotaxis of different cSCC cell lines. Notably, the Chemerin receptor CCRL2 is remarkably upregulated in cSCC cell lines and human patient biopsies. Silencing Chemerin in senescent fibroblasts or the CCRL2 and GPR1 receptors in the SCL-1 cSCC cell line abrogates the Chemerin-mediated chemotaxis. Chemerin triggers the MAPK cascade via JNK and ERK1 activation, whereby the inhibition impairs the SASP- or Chemerin-mediated cSCC cell migration. Taken together, we uncover a key role for Chemerin, as a major factor in the secretome of senescent fibroblasts, promoting cSCC cell migration and possibly progression, relaying its signals through CCRL2 and GPR1 receptors with subsequent MAPK activation. These findings might have implications for targeted therapeutic interventions in elderly patients. PMID:27907906

  17. Heparanase expression and glycosaminoglycans profile in renal cell carcinoma.

    PubMed

    Batista, Lucas Teixeira E Aguiar; Matos, Leandro Luongo; Machado, Leopoldo Ruiz; Suarez, Eloah Rabello; Theodoro, Thérèse Rachell; Martins, João Roberto Maciel; Nader, Helena Bonciani; Pompeo, Antonio Carlos Lima; Pinhal, Maria Aparecida da Silva

    2012-11-01

    A better understanding of the molecular mechanisms of renal cell carcinogenesis could contribute to a decrease in the mortality rate of this disease. The aim of this study was to evaluate the glycosaminoglycans profile and heparanase expression in renal cell carcinoma. The study included 24 patients submitted to nephrectomy with confirmed pathological diagnosis of renal cell carcinoma. The majority of the samples (87.5%) were classified in the initial stage of renal cell carcinoma (clinical stages I and II). Heparanase messenger ribonucleic acid expression was evaluated by quantitative real-time reverse transcription polymerase chain reaction, and sulfated glycosaminoglycans were identified and quantified by agarose gel electrophoresis of renal cell carcinoma samples or non-neoplastic tissues obtained from the same patients (control group). The sulfated glycosaminoglycans and hyaluronic acid were analyzed in urine samples of the patients before and after surgery. The data showed a significant statistical increase in chondroitin sulfate, and a decrease in heparan sulfate and dermatan sulfate present in neoplastic tissues compared with non-neoplastic tissues. Higher heparanase messenger ribonucleic acid expression in the neoplastic tissues was also shown, compared with the non-neoplastic tissues. The urine glycosaminoglycans profile showed no significant difference between renal cell carcinoma and control samples. Extracellular matrix changes observed in the present study clarify that heparanase is possibly involved with heparan sulfate turnover, and that heparanase and the glycosaminoglycans can modulate initial events of renal cell carcinoma development.

  18. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

    PubMed

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-03-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (P<0.05) than those in benign ovarian epithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

  19. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells

    PubMed Central

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-01-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1-ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (P<0.05) than those in benign ovarian epithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma. PMID

  20. Small cell neuroendocrine carcinoma of cervix--a case report.

    PubMed

    Chatterjee, Sanhita; Chakravorty, Shilaj; Kapoor, Poonam; Chattopadhyay, Debjit

    2005-07-01

    Small cell neuroendocrine carcinoma of uterine cervix is a rare variant of cervical carcinoma with features of high aggressiveness. It is difficult to manage these tumors. It is often diagnosed at an advanced stage and its prognosis is generally poor. The present report describes a 65 year old woman who presented with postmenopausal bleeding and had a friable polypoidal growth hanging from the cervix. Microscopic examination of the growth showed features of small cell carcinoma. Neuroendocrine cellular characteristics were assessed by using antibodies against neuron specific enolase. The case is being reported to create awareness of this rare entity

  1. Wnt Signaling in Renal Cell Carcinoma

    PubMed Central

    Xu, Qi; Krause, Mirja; Samoylenko, Anatoly; Vainio, Seppo

    2016-01-01

    Renal cell carcinoma (RCC) accounts for 90% of all kidney cancers. Due to poor diagnosis, high resistance to the systemic therapies and the fact that most RCC cases occur sporadically, current research switched its focus on studying the molecular mechanisms underlying RCC. The aim is the discovery of new effective and less toxic anti-cancer drugs and novel diagnostic markers. Besides the PI3K/Akt/mTOR, HGF/Met and VHL/hypoxia cellular signaling pathways, the involvement of the Wnt/β-catenin pathway in RCC is commonly studied. Wnt signaling and its targeted genes are known to actively participate in different biological processes during embryonic development and renal cancer. Recently, studies have shown that targeting this pathway by alternating/inhibiting its intracellular signal transduction can reduce cancer cells viability and inhibit their growth. The targets and drugs identified show promising potential to serve as novel RCC therapeutics and prognostic markers. This review aims to summarize the current status quo regarding recent research on RCC focusing on the involvement of the Wnt/β-catenin pathway and how its understanding could facilitate the identification of potential therapeutic targets, new drugs and diagnostic biomarkers. PMID:27322325

  2. Merkel cell polyomavirus infection in both components of a combined Merkel cell carcinoma and basal cell carcinoma with ductal differentiation; each component had a similar but different novel Merkel cell polyomavirus large T antigen truncating mutation.

    PubMed

    Iwasaki, Takeshi; Kodama, Hajime; Matsushita, Michiko; Kuroda, Naoto; Yamasaki, Yoshikazu; Murakami, Ichiro; Yamamoto, Osamu; Hayashi, Kazuhiko

    2013-03-01

    Merkel cell polyomavirus infects up to 80% of patients with Merkel cell carcinoma. Combined Merkel cell carcinoma and cutaneous tumors occur occasionally. Previous reports have suggested that Merkel cell polyomavirus is absent from combined Merkel cell carcinoma and squamous cell carcinomas. This is the first report that Merkel cell polyomavirus infected in both lesions of a combined Merkel cell carcinoma and basal cell carcinoma. A 92-year-old Japanese man presented with a right thigh small subcutaneous mass. Histologic examination revealed a combined tumor with Merkel cell carcinoma and basal cell carcinoma with ductal differentiation. Both tumors and intermingled Merkel cells in basal cell carcinoma expressed Merkel cell polyomavirus large T antigen, and 17 and 240 copies of Merkel cell polyomavirus/cell were detected in the microdissected Merkel cell carcinoma and basal cell carcinoma specimens, respectively. Mutation analysis of Merkel cell polyomavirus large T antigen revealed a novel truncating mutation in Merkel cell carcinoma and a similar but different mutation in the basal cell carcinoma. These results suggest that each was infected by a different Merkel cell polyomavirus subclone derived from a single Merkel cell polyomavirus.

  3. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2017-01-19

    Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  4. [Renal Cell Carcinoma metastases in the maxillofacial area: Case series.

    PubMed

    Ruiz-Oslé, Sara; Prol, Carlos; Lardies, Rosa; Gaafar, Ayman; Barbier, Luis; Arruza, Antón

    2017-10-01

    Renal cell carcinoma is an unpredictable malignancy. Sometimes, metastases are the disease debut. On the other hand, metastases could present years after treatment of the primary tumor. Four clinical cases of atypical metastases in the head and neck location are presented: parotid gland, mandibular bone, attached molar gingiva and masticator space. Physiopathology, clinics, histology and management of metastatic renal cell carcinoma at those anatomical regions are reviewed.

  5. Corneal squamous cell carcinoma in a Border Collie.

    PubMed

    Busse, Claudia; Sansom, Jane; Dubielzig, R R; Hayes, Alison

    2008-01-01

    A 6-year-old, female, spayed Border Collie was presented to the Unit of Comparative Ophthalmology at the Animal Health Trust with a 6-month history of a progressive nonpainful opacity of the left cornea. A keratectomy was performed and the tissue submitted for histopathology. The diagnosis was squamous cell carcinoma. There has been no recurrence of the neoplasm to date (5 months). Canine corneal squamous cell carcinoma (SCC) has not been reported previously in the UK.

  6. 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

  7. The relation between dermoscopy and histopathology of basal cell carcinoma*

    PubMed Central

    Emiroglu, Nazan; Cengiz, Fatma Pelin; Kemeriz, Funda

    2015-01-01

    BACKGROUND: Basal cell carcinoma is the most frequent cancer in fair-skinned populations and dermoscopy is an important, non-invasive technique that aids in the diagnosis of Basal cell carcinoma. OBJECTIVES: The aim of this study was to evaluate the relationship between histopathological subtypes and dermoscopic features of Basal cell carcinoma. METHODS: This study included 98 patients with clinically and histopathologically confirmed Basal cell carcinomas. The dermoscopic features of the lesions from each patient were analyzed before the histopathological findings were evaluated. RESULTS: Dermoscopic structures were observed in all 98 patients and irregular vascularity was identified in 78 patients (79.6%). The most common vascular pattern was the presence of arborizing vessels (42 patients, 42.9%) followed by arborizing microvessels (21 patients, 21.4%) and short fine telangiectasias (SFTs; 15 patients, 15.3%). White streaks (38 patients, 38.8%), translucency (31 patients, 31.6%), a milky-pink to red background (42 patients, 42.9%), and erosion/ulceration (29 patients, 29.6%) were also observed. Pigmented islands were seen as blue-gray globules (7 patients, 7.1%) and blue-gray ovoid nests (42 patients, 42.9%). The pigment distribution pattern was maple leaf-like areas in 9 patients (9.2 %) and spoke wheel-like areas in 6 patients (6.1%). CONCLUSIONS: Basal cell carcinomas show a wide spectrum of dermoscopic features. Arborizing vessels were the most common dermoscopic findings in Basal cell carcinomas, while superficial Basal cell carcinomas displayed mainly milky-pink to red areas, and arborizing microvessels. The most common dermoscopic features of pigmented types were islands of pigment (blue-gray globules, blue-gray ovoid nests). In conclusion, dermoscopy can be used as a valuable tool for the diagnosis of Basal cell carcinomas and prediction of their histopathological subtypes. PMID:26131865

  8. The relation between dermoscopy and histopathology of basal cell carcinoma.

    PubMed

    Emiroglu, Nazan; Cengiz, Fatma Pelin; Kemeriz, Funda

    2015-01-01

    Basal cell carcinoma is the most frequent cancer in fair-skinned populations and dermoscopy is an important, non-invasive technique that aids in the diagnosis of Basal cell carcinoma. The aim of this study was to evaluate the relationship between histopathological subtypes and dermoscopic features of Basal cell carcinoma. This study included 98 patients with clinically and histopathologically confirmed Basal cell carcinomas. The dermoscopic features of the lesions from each patient were analyzed before the histopathological findings were evaluated. Dermoscopic structures were observed in all 98 patients and irregular vascularity was identified in 78 patients (79.6%). The most common vascular pattern was the presence of arborizing vessels (42 patients, 42.9%) followed by arborizing microvessels (21 patients, 21.4%) and short fine telangiectasias (SFTs; 15 patients, 15.3%). White streaks (38 patients, 38.8%), translucency (31 patients, 31.6%), a milky-pink to red background (42 patients, 42.9%), and erosion/ulceration (29 patients, 29.6%) were also observed. Pigmented islands were seen as blue-gray globules (7 patients, 7.1%) and blue-gray ovoid nests (42 patients, 42.9%). The pigment distribution pattern was maple leaf-like areas in 9 patients (9.2 %) and spoke wheel-like areas in 6 patients (6.1%). Basal cell carcinomas show a wide spectrum of dermoscopic features. Arborizing vessels were the most common dermoscopic findings in Basal cell carcinomas, while superficial Basal cell carcinomas displayed mainly milky-pink to red areas, and arborizing microvessels. The most common dermoscopic features of pigmented types were islands of pigment (blue-gray globules, blue-gray ovoid nests). In conclusion, dermoscopy can be used as a valuable tool for the diagnosis of Basal cell carcinomas and prediction of their histopathological subtypes.

  9. Oral Squamous Cell Carcinoma in Three Related Kowari (Dasyuroides byrnei).

    PubMed

    Saunders, Richard; Killick, Rowena; Barrows, Michelle; Stidworthy, Mark

    2017-02-11

    We report three kowari (Dasyuroides byrnei) with squamous cell carcinoma affecting the gingiva. These cases occurred in rapid succession in a related group of individuals of similar age, suggesting a familial tendency to this condition and a typical age of presentation. Other conditions affecting the oral cavity can mimic the appearance of oral squamous cell carcinoma in this species, and so knowledge of this condition can assist the veterinarian in making rapid decisions regarding prognosis and improving the welfare of these animals.

  10. [Small cell prostatic carcinoma detected at the stage of metastases].

    PubMed

    Rabii, Redouane; Meziane, Anas; Taha, Abdelatif; Joual, Abdenabi; El Mrini, Mohamed

    2004-09-01

    Small cell prostatic carcinoma is rare, with a poor prognosis. The authors report a case of small cell prostatic carcinoma in a 30-year-old patient diagnosed at the stage of metastases. Immunohistochemistry showed positive anti-neuron-specific enolase (NSE.) and anti-synaptophysin antibodies, while serum PSA was normal (1.2 ng/ml). The patient was treated by cisplatin-etoposide combination chemotherapy, but died 20 days after the first course.

  11. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

    PubMed

    Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-14

    Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

  12. Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma

    PubMed Central

    Pulitzer, Melissa P; Brannon, A Rose; Berger, Michael F; Louis, Peter; Scott, Sasinya N; Jungbluth, Achim A; Coit, Daniel G; Brownell, Isaac; Busam, Klaus J

    2016-01-01

    Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven ‘pure’ Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52–89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression. PMID:26022453

  13. Transesophageal echocardiography-guided thrombectomy of intracardiac renal cell carcinoma without cardiopulmonary bypass

    PubMed Central

    Souki, Fouad Ghazi; Demos, Michael; Fermin, Lilibeth; Ciancio, Gaetano

    2016-01-01

    Advanced renal cell carcinoma (RCC) resection has important anesthetic management implications, particularly when tumor extends, suprahepatic, into the right atrium. Use of transesophageal echocardiogram (TEE) is essential in identifying tumor extension and guiding resection. Latest surgical approach avoids venovenous and cardiopulmonary bypass yet requires special precautions and interventions on the anesthesiologist's part. We present a case of Level IV RCC resected without cardiopulmonary bypass and salvaged by TEE guidance and detection of residual intracardiac tumor. PMID:27716710

  14. Merkel cell carcinoma – description of five cases

    PubMed Central

    Kwiatkowski, Robert; Nenko, Dorota Katarzyna

    2013-01-01

    Merkel cell carcinoma (MCC) is a rare but very aggressive skin cancer that derives from neuroendocrine cells of the skin. Merkel cell carcinoma morbidity has been continuously increasing for the last few years. Increasing reported incidence of MCC is probably connected with increasing occurrence of this kind of malignancy or with development of histological and immunohistochemical methods of sample examinations which have allowed for more precise diagnosis of skin tumor that might have previously not been accurately recognized. Merkel cell carcinoma develops as nodules early recognized as basocellular carcinoma, squamous cell carcinoma, amelanotic melanoma or skin lymphoma. Merkel cell carcinoma can be morphologically similar to skin metastasis as well as mild changes such as lipoma, cysts, fibroma or vessel changes. Accurate diagnosis is very important because it determines successful management and risk of progression of disease. We describe 5 patients with MCC who underwent surgical excision and then, after estimation of stage of disease, complementary treatment. Our observations prove that every tumor with MCC should be cut out with wide margins and regional lymphadenectomy or sentinel node biopsy is compulsory. After cutting out MCC involved-field radiotherapy is necessary and improves prognosis. Presence of metastases in lymphatic nodes is an indication for complementary chemotherapy. PMID:24596523

  15. Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-08

    Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

  16. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells

    PubMed Central

    1991-01-01

    The ability of carcinomas to invade and to metastasize largely depends on the degree of epithelial differentiation within the tumors, i.e., poorly differentiated being more invasive than well-differentiated carcinomas. Here we confirmed this correlation by examining various human cell lines derived from bladder, breast, lung, and pancreas carcinomas. We found that carcinoma cell lines with an epithelioid phenotype were noninvasive and expressed the epithelium-specific cell- cell adhesion molecule E-cadherin (also known as Arc-1, uvomorulin, and cell-CAM 120/80), as visualized by immunofluorescence microscopy and by Western and Northern blotting, whereas carcinoma cell lines with a fibroblastoid phenotype were invasive and had lost E-cadherin expression. Invasiveness of these latter cells could be prevented by transfection with E-cadherin cDNA and was again induced by treatment of the transfected cells with anti-E-cadherin mAbs. These findings indicate that the selective loss of E-cadherin expression can generate dedifferentiation and invasiveness of human carcinoma cells, and they suggest further that E-cadherin acts as an invasion suppressor. PMID:2007622

  17. Sarcomatoid renal cell carcinoma in a binturong (Arctictis binturong).

    PubMed

    Childs-Sanford, Sara E; Peters, Rachel M; Morrisey, James K; Alcaraz, Ana

    2005-06-01

    An adult, female binturong (Arctictis binturong) was examined due to lethargy, inappetence, and an abdominal mass. Diagnostic investigations, including radiographs, abdominal ultrasound, clinical laboratory findings, and a fine-needle aspirate of the mass, were suggestive of a sarcoma with metastasis. Necropsy and histopathologic findings confirmed a widely disseminated sarcomatoid variant of a renal cell carcinoma, likely originating in the left kidney, with metastasis to the right kidney, spleen, pancreas, liver, mesenteric lymph nodes, and lungs. This is the first report of this neoplasm in a binturong and only the second report in the veterinary literature. Sarcomatoid renal cell carcinoma is a rare histologic variant of renal cell carcinoma that is aggressive, commonly metastatic, and associated with a very poor prognosis in humans. Accurate antemortem diagnosis of this tumor may be complicated by its biphasic morphology, which may resemble carcinoma or sarcoma (or both), often necessitating the use of immunohistochemical techniques.

  18. Renal Cell Carcinoma in Tuberous Sclerosis Complex

    PubMed Central

    Yang, Ping; Cornejo, Kristine M.; Sadow, Peter M.; Cheng, Liang; Wang, Mingsheng; Xiao, Yu; Jiang, Zhong; Oliva, Esther; Jozwiak, Sergiusz; Nussbaum, Robert L.; Feldman, Adam S.; Paul, Elahna; Thiele, Elizabeth A.; Yu, Jane J.; Henske, Elizabeth P.; Kwiatkowski, David J.; Young, Robert H.; Wu, Chin-Lee

    2014-01-01

    Renal cell carcinoma (RCC) occurs in 2-4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathological and molecular features, enabling separation of these 46 tumors into three groups. The largest subset of tumors (n=24) had a distinct morphological, immunological and molecular profile, including prominent papillary architecture and uniformly deficient SDHB expression prompting the novel term “TSC-associated papillary RCC.” The second group (n=15) was morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT) while the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated papillary RCCs (PRCC) had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were the International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCC showed strong, diffuse labeling for CA-IX (100%), CK7 (94%), vimentin (88%), CD10 (83%), and were uniformly negative for succinate dehydrogenase subunit B (SDHB), TFE3 and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes which may help to expand the morphologic spectrum of TSC-associated RCC. PMID:24832166

  19. A Rare Constellation of Hürthle Cell Thyroid Carcinoma and Parathyroid Carcinoma.

    PubMed

    Zakerkish, Mehrnoosh; Rajaei, Elham; Dargahi, Mehrdad; Bahadoram, Mohammad

    2015-12-01

    Separate occurrence of thyroid and parathyroid carcinoma in patients is extremely rare, and to the best of our knowledge, only 7 patients with documented parathyroid and papillary thyroid carcinomas have been described formerly in published reports. We report a patient with an extremely unusual clinical presentation of Hürthle cell carcinoma in thyroid and parathyroid carcinoma. The patient displayed a rare presentation of life-threatening hypercalcaemia after total para-thyroidectomy and failed to respond to standard therapy. Our review of available literature yielded insufficient evidence in managing such. When a patient with thyroid cancer is diagnosed, checking for serum calcium is advised. This is considered a useful method for detecting possible incidental parathyroid lesion and screening the probable concealed parathyroid pathology.

  20. Neuropilin-1 antagonism in human carcinoma cells inhibits migration and enhances chemosensitivity.

    PubMed

    Jia, H; Cheng, L; Tickner, M; Bagherzadeh, A; Selwood, D; Zachary, I

    2010-02-02

    Neuropilin-1 (NRP1) is a non-tyrosine kinase receptor for vascular endothelial growth factor (VEGF) recently implicated in tumour functions. In this study we used a specific antagonist of VEGF binding to the NRP1 b1 domain, EG3287, to investigate the functional roles of NRP1 in human carcinoma cell lines, non-small-cell lung A549, kidney ACHN, and prostate DU145 cells expressing NRP1, and the underlying mechanisms involved. EG3287 potently displaced the specific binding of VEGF to NRP1 in carcinoma cell lines and significantly inhibited the migration of A549 and ACHN cells. Neuropilin-1 downregulation by siRNA also decreased cell migration. EG3287 reduced the adhesion of A549 and ACHN cells to extracellular matrix (ECM), and enhanced the anti-adhesive effects of a beta1-integrin function-blocking antibody. EG3287 increased the cytotoxic effects of the chemotherapeutic agents 5-FU, paclitaxel, or cisplatin on A549 and DU145 cells, through inhibition of integrin-dependent cell interaction with the ECM. These findings indicate that NRP1 is important for tumour cell migration and adhesion, and that NRP1 antagonism enhances chemosensitivity, at least in part, by interfering with integrin-dependent survival pathways. A major implication of this study is that therapeutic strategies targeting NRP1 in tumour cells may be particularly useful in combination with other drugs for combating tumour survival, growth, and metastatic spread independently of an antiangiogenic effect of blocking NRP1.

  1. The ROCK isoforms differentially regulate the morphological characteristics of carcinoma cells.

    PubMed

    Jerrell, Rachel J; Leih, Mitchell J; Parekh, Aron

    2017-06-26

    Rho-associated kinase (ROCK) activity drives cell migration via actomyosin contractility. During invasion, individual cancer cells can transition between 2 modes of migration, mesenchymal and amoeboid. Changes in ROCK activity can cause a switch between these migration phenotypes which are defined by distinct morphologies. However, recent studies have shown that the ROCK isoforms are not functionally redundant as previously thought. Therefore, it is unclear whether the ROCK isoforms play different roles in regulating migration phenotypes. Here, we found that ROCK1 and ROCK2 differentially regulate carcinoma cell morphology resulting in intermediate phenotypes that share some mesenchymal and amoeboid characteristics. These findings suggest that the ROCK isoforms play unique roles in the phenotypic plasticity of mesenchymal carcinoma cells which may have therapeutic implications.

  2. PLK1 promotes epithelial-mesenchymal transition and metastasis of gastric carcinoma cells

    PubMed Central

    Cai, Xiao Peng; Chen, Liang Dong; Song, Hai Bin; Zhang, Chun Xiao; Yuan, Ze Wei; Xiang, Zhen Xian

    2016-01-01

    Cancer cell epithelial-mesenchymal transition (EMT) is the crucial event for cancer progression and plays a vital role in the metastasis of cancer cells. Activation of Polo-like kinase 1 (PLK1) signaling has been implicated as the critical event in several tumor metastasis and EMT, however, whether PLK1 participates in gastric carcinoma metastasis and EMT still remains unclear. For this study, we elucidated the potential physiological function of PLK1 in the metastasis of gastric tumors, as well its distinct role in cells EMT and subsequently determined the mechanism involved in PLK1 regulated. Immunoblotting assay and Oncomine data mining analysis indicated that PLK1 expression was highly up-regulated in gastric carcinoma. Kaplan-Meier survival analysis for the relationship between survival outcomes and PLK1 expression in gastric carcinoma was performed with an online Kaplan-Meier plotter (http://kmplot.com/analysis/). Over-expression of PLK1 in gastric cancer cells SGC-7901 and MKN-28 significantly promoted cells profound morphological changes and enhanced metastatic ability of tumor cells. On the contrary, silencing of PLK1 induced mesenchymal epithelial transition (MET)-like morphological and inhibited the metastatic process. Furthermore, we found that the metastatic characters promoting effects of PLK1 in gastric carcinoma was related to the activation of protein kinase B (AKT). Our mechanistic investigations revealed that AKT inhibition reversed PLK1-induced EMT, blocked gastric carcinoma cells invasiveness and metastasis. Additionally, over-expression of AKT promoted the migratory and invasion ability of the two cell lines, which was disrupted by PLK1 down-regulation. To conclude, our findings demonstrate that PLK1 accelerates the metastasis and epithelial-mesenchyme transition of gastric cancer cells through regulating the AKT pathway. PMID:27830001

  3. Coexistence of Condylomata Acuminata with Warty Squamous Cell Carcinoma and Squamous Cell Carcinoma

    PubMed Central

    Erman-Vlahovic, Mirna; Vlahovic, Jelena; Mrcela, Milanka; Hrgovic, Zlatko

    2017-01-01

    Introduction: Condyloma acuminatum has previously been considered to be a benign growth with no malignant potential, but a review of the literature supports the concept that condylomata acuminata may precede or be associated with invasive squamous cell carcinoma (ISCC) or warty squamous cell carcinoma (WSCC). Case report: We present a clinical case of a 58-year old woman with large, slow-growing, exophytic tumor of external genitalia shaped like a cauliflower with the propagation to both legs and behind. We performed multiple biopsies to detect potential malignancy but malignancy was not confirmed histologically. The presence of HPV (human papilloma virus) low and high risk was discovered. Inguinal lymph nodes were enlarged both sides, but cytologic examination identified no malignant cells. The patient was initially treated by the loop electro surgical excision procedure (LEEP) and podophilin solution on the rest of the condylomas. Condyloma acuminatum was confirmed histologically. Later, we performed a wide surgical excision of the rest of the condylomas. The new changes on the previously treated region were removed using LEEP. WSCC and ISCC were confirmed histologically so were radical vulvectomy and inguinal lymphadenectomy performed. The patient was advised to remain under close follow-up. PMID:28428680

  4. Development of squamous cell carcinoma into basal cell carcinoma under treatment with Vismodegib.

    PubMed

    Saintes, C; Saint-Jean, M; Brocard, A; Peuvrel, L; Renaut, J J; Khammari, A; Quéreux, G; Dréno, B

    2015-05-01

    Basal cell carcinoma (BCC) is the most common cancer in humans. Vismodegib, a Hedgehog pathway inhibitor, has proved its effectiveness in treating non-resectable advanced BCC. However, its action on squamous cell carcinoma (SCC) is unknown. We present three SCC cases developed into BCC in vismodegib-treated patients. We have described three cases of patients developing SCC during treatment by vismodegib for BCC. Patient 1 was treated with vismodegib for five facial BCC. Due to the progression of one of the lesions at month 3 (M3), a biopsy was performed and showed SCC. Patient 2 was treated with vismodegib for a large facial BCC. A biopsy was performed at M2 on a BCC area not responding to treatment and showed SCC. Patient 3 was treated with vismodegib for a BCC on the nose. Due to vismodegib ineffectiveness, a biopsy was performed and showed SCC. Two similar cases have been described in the literature. This could be due to the appearance of the squamous contingent of a metatypical BCC or to the squamous differentiation of stem cells through inhibition of the hedgehog pathway. In practice, any dissociated response of a BCC to vismodegib should be biopsied. © 2014 European Academy of Dermatology and Venereology.

  5. Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell Carcinoma.

    PubMed

    Dusingize, Jean Claude; Olsen, Catherine M; Pandeya, Nirmala P; Subramaniam, Padmini; Thompson, Bridie S; Neale, Rachel E; Green, Adèle C; Whiteman, David C

    2017-08-01

    Sunlight is the principal environmental risk factor for keratinocyte cancers, but other carcinogens have also been implicated, including tobacco smoke. Findings have been conflicting, however. We investigated associations between cigarette smoking and incidence of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in QSkin, a prospective study of skin cancer (N = 43,794). Smoking history was self-reported at baseline; newly diagnosed BCCs and SCCs were ascertained through data linkage and verified by histopathology reports. We restricted analyses to white participants who at baseline reported no past history of skin cancer excisions and no more than five destructively treated actinic skin lesions. We fitted Cox proportional hazards models, adjusted for known confounders. Compared with never smokers, current smokers had significantly lower risks of BCC (hazard ratio = 0.6; 95% confidence interval = 0.4-0.9) but significantly higher risks of SCC (hazard ratio = 2.3; 95% confidence interval = 1.5-3.6). Former smokers had similar risks for BCC and SCC as never smokers. Among smokers, we observed no dose-response trends with duration of smoking, intensity, or time since quitting. On further analysis, current smokers had fewer skin examinations and procedures than never smokers, suggesting greater opportunities for detection among never smokers. Strengths include large sample size, prospective design, and virtually complete follow-up; however, histologic details were missing for a proportion of excised tumors. In conclusion, current smokers had a lower incidence of BCC (possibly because of detection bias) but higher rates of SCC. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Cannabinoid CB₁ receptor is downregulated in clear cell renal cell carcinoma.

    PubMed

    Larrinaga, Gorka; Sanz, Begoña; Pérez, Itxaro; Blanco, Lorena; Cándenas, María L; Pinto, Francisco M; Gil, Javier; López, José I

    2010-12-01

    Several studies in cell cultures and in animal models have demonstrated that cannabinoids have important antitumoral properties. Because many of these effects are mediated through cannabinoid (CB) receptors CB₁ and CB₂, the study of their expression in human neoplasms has become of great interest in recent years. Fresh and formalin-fixed tissue samples of 20 consecutive clear cell renal cell carcinomas (CCRCCs) were collected prospectively and analyzed for the expression of both CB receptors by using RT-PCR, Western blot (WB), and immunohistochemical techniques. RT-PCR assays demonstrated the expression of mRNA encoding the CB₁ in tumor tissue and in adjacent non-neoplastic kidney. Conversely, WB and IHC revealed a marked downregulation of CB₁ protein in tumor tissue; CB₂ was not expressed. The obtained data suggest a possible implication of the endocannabinoid system in renal carcinogenesis. A posttranscriptional downregulation of CB₁ and the absence of expression of CB₂ characterize CCRCC.

  7. Potential relationship between BK virus and renal cell carcinoma.

    PubMed

    Bulut, Yasemin; Ozdemir, Enver; Ozercan, Halil Ibrahim; Etem, Ebru Onalan; Aker, Fugen; Toraman, Zulal Asci; Seyrek, Adnan; Firdolas, Fatih

    2013-06-01

    The objective of the present study was to investigate the potential association between the presence of BK virus (BKV) DNA and mRNA and renal cell carcinoma and bladder transitional cell carcinoma. The formalin-fixed and paraffin-embedded tissue samples were obtained from 50 cancer patients with renal cell carcinoma, 40 cancer patients with bladder transitional cell carcinoma, 45 control patients with the benign renal pathology, and from another 25 control patients with benign bladder pathology. The samples were subjected to nested PCR for detection of BKV DNA and real-time reverse transcription PCR (real-time RT-PCR) for determining mRNA levels of BKV. The results of the nested PCR indicated that 23 (14.3%) of 160 samples were positive for BKV DNA. The relationship between the cancer and the presence of BKV DNA was significant (P < 0.05). The BKV DNA positivity was significantly associated with the histological diagnosis of renal cell carcinoma (P = 0.03), but not with that of bladder transitional cell carcinoma. The results of real-time RT-PCR showed that the mRNA of BKV VP1 was present in 69.5% of the BKV DNA positive samples. The levels of BKV mRNA were significantly higher in the renal cell cancer samples than in the control samples (P < 0.05). The results of the present study confirm the association between BKV and renal cell cancer. The findings also indicated that the presence of BKV DNA resulted in a fivefold increase in the risk of development of renal cell carcinoma.

  8. Carcinomas of ovary and lung with clear cell features: can immunohistochemistry help in differential diagnosis?

    PubMed

    Howell, Nicole R; Zheng, Wenxin; Cheng, Liang; Tornos, Carmen; Kane, Philip; Pearl, Michael; Chalas, Eva; Liang, Sharon X

    2007-04-01

    Metastatic lung carcinomas with clear cell morphology can be confused with primary ovarian clear cell carcinomas. We performed immunohistochemical stains in 14 cases of non-small cell lung carcinomas with clear cell features and 14 cases of ovarian clear cell carcinomas using a panel of markers, including thyroid transcription factor 1 (TTF-1), carcinoembryonic antigen (CEA), Wilms tumor gene 1, octamer-binding transcription factor 4 (OCT-4), cancer antigen 125 (CA-125), estrogen receptor, and progesterone receptor. Among non-small cell lung carcinomas with clear cell features, 87.5% of adenocarcinomas (or 50% overall frequency in lung carcinomas) were positive for TTF-1, whereas none of the ovarian clear cell carcinomas were positive (P = 0.002). All 14 ovarian clear cell carcinomas stained for CA-125 as compared with 1 non-small cell lung carcinoma (P < 0.001). On the other hand, 85% of non-small cell lung carcinomas stained for CEA, whereas none of the ovarian clear cell carcinomas did (P < 0.001). Interestingly, 4 ovarian clear cell carcinomas (28%) showed positive staining for the germ cell marker OCT-4. Either lung or ovarian carcinomas stained for Wilms tumor gene 1, estrogen receptor, or progesterone receptor very infrequently; and the difference between the 2 groups was not statistically significant. Our results suggest that an immunohistochemical panel consisting of TTF-1, CEA, CA-125, and OCT-4 is helpful in distinguishing most pulmonary and ovarian carcinomas with clear cell features.

  9. Anabolic androgens affect the competitive interactions in cell migration and adhesion between normal mouse urothelial cells and urothelial carcinoma cells.

    PubMed

    Huang, Chi-Ping; Hsieh, Teng-Fu; Chen, Chi-Cheng; Hung, Xiao-Fan; Yu, Ai-Lin; Chang, Chawnshang; Shyr, Chih-Rong

    2014-09-26

    The urothelium is constantly rebuilt by normal urothelial cells to regenerate damaged tissues caused by stimuli in urine. However, the urothelial carcinoma cells expand the territory by aberrant growth of tumor cells, which migrate and occupy the damaged tissues to spread outside and disrupt the normal cells and organized tissues and form a tumor. Therefore, the interaction between normal urothelial cells and urothelial carcinoma cells affect the initiation and progression of urothelial tumors if normal urothelial cells fail to migrate and adhere to the damages sites to regenerate the tissues. Here, comparing normal murine urothelial cells with murine urothelial carcinoma cells (MBT-2), we found that normal cells had less migration ability than carcinoma cells. And in our co-culture system we found that carcinoma cells had propensity migrating toward normal urothelial cells and carcinoma cells had more advantages to adhere than normal cells. To reverse this condition, we used anabolic androgen, dihyrotestosterone (DHT) to treat normal cells and found that DHT treatment increased the migration ability of normal urothelial cells toward carcinoma cells and the adhesion capacity in competition with carcinoma cells. This study provides the base of a novel therapeutic approach by using anabolic hormone-enforced normal urothelial cells to regenerate the damage urothelium and defend against the occupancy of carcinoma cells to thwart cancer development and recurrence.

  10. Hereditary leiomyomatosis and renal cell carcinoma

    PubMed Central

    Schmidt, Laura S; Linehan, W Marston

    2014-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal-dominant hereditary syndrome, which is caused by germline mutations in the FH gene that encodes the tricarboxylic acid cycle enzyme fumarate hydratase (FH). HLRCC patients are predisposed to develop cutaneous leiomyomas, multiple, symptomatic uterine fibroids in young women resulting in early hysterectomies, and early onset renal tumors with a type 2 papillary morphology that can progress and metastasize, even when small. Since HLRCC-associated renal tumors can be more aggressive than renal tumors in other hereditary renal cancer syndromes, caution is warranted, and surgical intervention is recommended rather than active surveillance. At-risk members of an HLRCC family who test positive for the familial germline FH mutation should undergo surveillance by annual magnetic resonance imaging from the age of 8 years. Biochemical studies have shown that FH-deficient kidney cancer is characterized by a metabolic shift to aerobic glycolysis. It is hoped that through ongoing clinical trials evaluating targeted molecular therapies, an effective form of treatment for HLRCC-associated kidney cancer will be developed that will offer an improved prognosis for individuals affected with HLRCC-associated kidney cancer. PMID:25018647

  11. Chemoradiotherapy for anal squamous cell carcinoma.

    PubMed

    Houlihan, Orla A; O'Neill, Brian D P

    2016-08-01

    Anal cancer is a relatively rare cancer, making up approximately 0.4% of all new diagnoses of cancer.(1) The incidence of anal cancer, however, has increased in recent years.(2) The aim of this paper is to review current treatment of anal squamous cell carcinoma (SCC), the most common type of anal cancer. This review article focuses on recent and ongoing trials studying the outcomes of various chemoradiotherapy (CRT) regimens in the treatment of anal SCC. PubMed was initially searched for relevant trials. This search was then supplemented by hand searches of reference lists and abstracts of relevant conferences. CRT with mitomycin C (MMC) and 5-fluorouracil (5-FU) has been proven to have effective results in the treatment of anal SCC. Salvage surgery has a role in some patients in the treatment of persistent or recurrent disease beyond 26 weeks. The addition of induction or maintenance chemotherapy to CRT has not been shown to have any benefit. Primary CRT with MMC and 5-FU is the current standard treatment for anal SCC. There is currently no role for induction or maintenance chemotherapy. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  12. Systemic adjuvant therapies in renal cell carcinoma

    PubMed Central

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-01-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  13. New basal cell carcinoma susceptibility loci.

    PubMed

    Stacey, Simon N; Helgason, Hannes; Gudjonsson, Sigurjon A; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T; Halldorsson, Bjarni V; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I; Gudbjartsson, Daniel F; Olafsson, Jon H; Stefansson, Kari

    2015-04-09

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10(-12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10(-16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained.

  14. Squamous cell carcinoma of the breast.

    PubMed

    Aparicio, I; Martínez, A; Hernández, G; Hardisson, D; De Santiago, J

    2008-04-01

    Pure squamous cell carcinoma (SCC) of the breast is a rare tumour and its clinical behaviour is not correctly known. The aim of the study is to evaluate the prevalence, epidemiological and clinical characteristics of the cases of SCC studied in our institution. The breast department's database was searched for patients diagnosed with breast SCC between September 1979 and June 2006. Pathological features, outcome aspects and prognosis were studied. All specimens were reviewed by our pathologist who performed inmunohistochemistry for hormone receptors. Eleven patients were identified (0.19%) between 5771 cases of breast cancer. Mean age was 64 (37-76) years and mean follow-up was 46 (6-216) months. Mean disease free survival (DFS) was 92 months (S.E.=33), with a 36% DFS rate at 5 years and the mean overall survival was 93 months (S.E.=34). Mean survival from the time recurrent disease was recognized was 9 (1-16) months. Tumours were hormone receptor negative. SCC of the breast is aggressive and often treatment-refractory. The role of different new chemotherapy regimens need to be explored.

  15. New basal cell carcinoma susceptibility loci

    PubMed Central

    Stacey, Simon N.; Helgason, Hannes; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A.; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G.; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M.; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T.; Halldorsson, Bjarni V.; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I.; Gudbjartsson, Daniel F.; Olafsson, Jon H.; Stefansson, Kari

    2015-01-01

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10−12), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10−9), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10−12) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10−16). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained. PMID:25855136

  16. Basal cell carcinoma in skin of color.

    PubMed

    Ahluwalia, Jesleen; Hadjicharalambous, Elena; Mehregan, Darius

    2012-04-01

    Non-melanoma skin cancer most commonly affects Caucasians, and only rarely affects darker-skinned individuals. However, skin cancer in these groups is associated with greater morbidity and mortality. Ultraviolet radiation is the major etiologic factor in basal cell carcinoma (BCC) and likely plays a pivotal role in the development of other forms of skin cancer. Yet it is commonly thought among patients as well as physicians that darker pigmentation inherently affords complete protection from skin cancer development. This low index of suspicion results in delayed diagnoses and poorer outcomes. This review follows a detailed computer search that cross-matched the diagnosis of BCC with skin color type in a large commercial dermatopathology facility. The reported skin types, all Fitzpatrick skin types IV, V, and VI, and histories were confirmed. A predominance of pigmented BCCs was found in sun-exposed areas of these older individuals. Although less common in darker-skinned ethnic groups, BCC does occur and can pose significant morbidity. Thus, it is essential that dermatologists are familiar with the epidemiology and clinical presentation of all cutaneous malignancies in darker skin so that these patients are fully aware of risks as well as prevention of the disease.

  17. Emerging therapeutics in refractory renal cell carcinoma.

    PubMed

    Koshkin, Vadim S; Rini, Brian I

    2016-06-01

    Metastatic renal cell carcinoma (mRCC) has seen the introduction of numerous new treatments over the past decade. However, the efficacy of these therapies has plateaued, and new treatment options are needed for the majority of patients with mRCC whose disease inevitably progresses through one or more standard therapies ('refractory' mRCC). Recently approved agents in this space have shown great promise. This article reviews the evidence behind current management strategies for mRCC. After reviewing clinical trials that established current first-line therapies and agents used in the refractory setting, we address new ideas for the treatment of refractory disease including combination therapies and novel targeted agents. In particular, we focus on targeted immunotherapy in refractory mRCC. We conclude by considering future directions in combination treatments utilizing these novel agents. Numerous approaches have produced tangible benefits for the treatment of patients with mRCC. These include development of next generation VEGFR/TKIs, targeted immunotherapy agents, and the development of combined regimens. In particular, immunotherapy agents targeting the PD1/PD-L1 pathway have shown great promise with a robust survival advantage seen in patients treated with nivolumab. A tolerable side effect profile of immunotherapy agents makes them amenable for use in combination therapies and ongoing trials are addressing this question.

  18. Histological subtypes of periocular basal cell carcinoma.

    PubMed

    Wu, Albert; Sun, Michelle T; Huilgol, Shyamala C; Madge, Simon; Selva, Dinesh

    2014-01-01

    To determine the proportion of different subtypes of periocular BCC in South Australia. Retrospective review. One thousand seven hundred thirteen consecutive periocular basal cell carcinoma (BCC) excision specimens. Histological analysis of consecutive periocular BCC specimens. Date of resection, patient age at resection, gender, tumour location, histological subtype and perineural invasion. From 2006 to 2012, a total of 1713 consecutive periocular BCC excision specimens were analysed. The mean age at resection was 68.8 years (median: 71, range: 21-101). Most specimens (56.4%) were removed from male patients. 52.7% involved the lower eyelid, 29.0% the medial canthus, 10.9% the lateral canthus and 7.5% the upper eyelid. The main histological subtypes identified were nodular (65.7%), infiltrative (17.5%), superficial (12.6%) and micronodular (4.2%). Of the specimens, 25.6% had more than one subtype. The most common subtype combinations were nodular with infiltrative (49.7%), and nodular with superficial (26.0%). The majority of periocular BCC were located on the lower lid and classified histologically as nodular. Infiltrative BCC occurred more frequently than the superficial subtype. As the proportion of mixed BCC containing aggressive subtypes is high, surgical excision with margin control should be considered for periocular BCC. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

  19. Pediatric and adolescent renal cell carcinoma.

    PubMed

    Young, Ezekiel E; Brown, Christopher T; Merguerian, Paul A; Akhavan, Ardavan

    2016-01-01

    Renal cell carcinoma (RCC) is an uncommon malignancy among children and adolescents. Because of this, there has been relatively sparse research and evidence on the topic. As the body of research regarding pediatric and adolescent RCC has developed in recent years, it has become increasingly clear that it demonstrates important differences from the much more common adult-type RCC. This review aims to examine and summarize the current literature, with a focus on the ways that pediatric and adolescent RCC differ from the adult disease, and to make recommendations for evaluation and management based on this evidence whenever possible. A thorough search of all articles relating to pediatric and adolescent RCC has been undertaken using PubMed. The reference lists from all relevant articles have been further reviewed, to ensure inclusion of all pertinent literature. The most significant development in recent years has been the realization that most of the pediatric and adolescent RCC cases, but only a very small fraction of adult RCC cases, demonstrate "translocation tumor" pathology. It is likely that such differences may eventually explain many of the previous observations regarding differences in behavior of RCC among children and teenagers. At this point, however, the relevance of translocation pathology to clinical management remains unclear, and so most continue to treat these patients in much the same way as those with the more conventional tumor subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. [Hyalinizing clear cell carcinoma of the maxilla].

    PubMed

    Chatelain, B; Curlier, A; Euvrard, E; Vitte, F; Ricbourg, B; Meyer, C

    2011-06-01

    Hyalinizing clear cell carcinoma (HCCC) of minor salivary glands (MSG) is a rare low-grade malignant neoplasm accounting for less than 1% of all salivary gland tumors. It usually affects the palate and the base of the tongue, and more rarely the parotid gland. We report a very rare maxillary localization. A 48-year-old male patient, without prior medical history, was referred to us for a painless gingival lesion of the right maxilla, extending from tooth 14 to 17, having appeared a few months before. The clinical examination was otherwise normal. Biopsy proved the diagnosis of HCCC. The CT scan revealed extension in maxillary sinus with bone osteolysis, and suspicion of cervical lymph nodes metastasis. The treatment was subtotal maxillectomy, cervical lymph node dissection, and postoperative radiotherapy because of incomplete bony resection. HCCC localization in the maxilla is extremely rare. This tumor may recur. The risk of metastasis is low; it concerns mainly lymph nodes. There is no treatment protocol consensus because the tumor is rare. Nevertheless, a wide local excision, with or without postoperative radiotherapy, seems to be the gold standard treatment. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  1. [Vismodegib Therapy for Periocular Basal Cell Carcinoma].

    PubMed

    Keserü, M; Green, S; Dulz, S

    2017-01-01

    Background Basal cell carcinoma (BCC) is the commonest periorbital tumour. Mohs' micrographic surgery and secondary reconstruction is the therapeutic gold standard for periorbital BCC. In cases of inoperability for any reason, therapeutic alternatives are needed. Since the approval of vismodegib, an orally administered, targeted BCC therapy is available. Nevertheless there is little information on the use of vismodegib for periorbital BCC. Patients and Methods In a retrospective study, we analysed the data of 4 patients treated with vismodegib since 2014. The patients' mean age before starting therapy was 87 years. The mean maximum tumour diameter was 22.0 mm. Results The median follow-up was 17 months. The median treatment duration was 7.5 months. In 75 % of patients, complete clinical remission of BCC was achieved. In 25 % of patients, interim stabilisation of tumour growth was possible. The most common side effect of therapy was muscle spasm. Conclusion Vismodegib is an effective treatment option for patients with periorbital BCC, in whom surgical treatment is not possible for any reason. Georg Thieme Verlag KG Stuttgart · New York.

  2. Prognostic significance of metallothionein expression in renal cell carcinoma

    PubMed Central

    Mitropoulos, Dionisios; Kyroudi-Voulgari, Aspasia; Theocharis, Stamatis; Serafetinides, Efraim; Moraitis, Epaminondas; Zervas, Anastasios; Kittas, Christos

    2005-01-01

    Background Metallothionein (MT) protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. The purpose of the study was to examine the expression of MT expression in human renal cell carcinoma (RCC) and to correlate MT positivity, the pattern and extent of MT expression with tumor histologic cell type and nuclear grade, pathologic stage and patients' survival. Patients and methods The immunohistochemical expression of MT was determined in 43 formalin-fixed and paraffin-embedded RCC specimens, using a mouse monoclonal antibody that reacts with both human MT-I and MT-II. Correlation was sought between immunohistochemical (MT positivity, intensity and extension of staining) and clinico-pathological data (histological cell type, tumor nuclear grade, pathologic stage and patients' survival). Results Positive MT staining was present in 21 cases (49%), being mild/moderate and intense in 8 and 13 cases, respectively. The pattern was cytoplasmic in 7 cases and was both cytoplasmic and nuclear in 14 cases. MT expression in a percentage of up to 25% of tumor cells (negative MT staining included) was observed in 31 cases, in a percentage 25–50% of tumor cells in 7 cases, and in a percentage of 50–75% of tumor cells in 5 cases. There was no significant correlation of MT intensity of staining to histological type, stage and patients' survival, while it was inversely correlated to higher tumor nuclear grade. MT extent of staining did not correlate with histological type, nuclear grade, and pathologic stage while a statistically significant association was found with patients' survival. Conclusions The inverse correlation between MT staining intensity and tumor nuclear grade in RCC suggests a role of MT in tumor differentiation process. Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic parameter. PMID

  3. Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.

    PubMed

    2015-01-01

    Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented

  4. Chemically induced bidirectional differentiation of embryonal carcinoma cells in vitro.

    PubMed Central

    Speers, W. C.; Birdwell, C. R.; Dixon, F. J.

    1979-01-01

    N,N-dimethylacetamide, hexamethylene bisacetamide, and Polybrene induced rapid and extensive differentiation in vitro in an otherwise slowly differentiating subline of embryonal carcinoma cells. The type of differentiated cell induced was dependent on the spatial organization of the stem cells during drug treatment. In monalayer culture "epithelial" cells were produced exclusively. However, treatment of aggregated suspension cultures yielded predominantly "fibroblast-like" cells. The undifferentiated embryonal carcinoma cells and the two differentiated cell types were morphologically distinct when examined by light microscopy, scanning electron microscopy, and transmission electron microscopy; and they had differences in cell surface antigens. Both differential cell types produced large amounts of fibronectin, whereas the embryonal carcinoma cells produced only minimal amounts. This system provides a convenient way to induce relatively synchronous differentiation of embryonal carcinoma cells into specific differentiated cell types. Images Figure 5 Figure 6 Figure 1 Figure 2 Figure 3 Figure 4 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:507191

  5. Squamous Cell Carcinoma of Pancreas: Mystery and Facts.

    PubMed

    Raghavapuram, Saikiran; Vaid, Arjun; Rego, Rayburn F

    2015-08-01

    Squamous cell carcinoma of the pancreas is very rare as pancreas does not have any squamous cells. Only a few cases have been reported in the literature so far. We describe such a case where in the patient presented with painless jaundice. CT and EUS confirmed the pancreatic mass biopsy of which showed squamous cell cancer.

  6. Signet ring cell colorectal carcinoma: a distinct subset of mucin-poor microsatellite-stable signet ring cell carcinoma associated with dismal prognosis.

    PubMed

    Hartman, Douglas J; Nikiforova, Marina N; Chang, Daniel T; Chu, Edward; Bahary, Nathan; Brand, Randall E; Zureikat, Amer H; Zeh, Herbert J; Choudry, Haroon; Pai, Reetesh K

    2013-07-01

    We evaluated a consecutive series of signet ring cell colorectal carcinomas in an attempt to correlate the histopathologic pattern of infiltration with molecular alterations and prognosis. Of the 4760 primary colorectal carcinomas surgically resected between the years 2002 and 2012, 53 (1%) were composed of >50% signet ring cells. Of the 53 signet ring cell carcinomas, 40 (75%) were composed of >50% extracellular mucin with signet ring cells floating within pools of mucin and were subclassified as mucin-rich signet ring cell carcinomas. Thirteen (25%) carcinomas were characterized by diffusely infiltrating carcinomas with minimal to no extracellular mucin and were subclassified as mucin-poor signet ring cell carcinomas. All 13 mucin-poor signet ring cell carcinomas were either stage III or IV, whereas many cases of mucin-rich signet ring cell carcinoma were stage I or II (17 cases) (P=0.005). Compared with mucin-rich tumors, mucin-poor signet ring cell carcinomas more frequently demonstrated adverse histologic features such as lymphatic invasion (13/13, 100% vs. 22/40, 55%; P=0.002), venous invasion (6/13, 46% vs. 3/40, 8%; P=0.004), and perineural invasion (11/13, 85% vs. 9/40, 23%; P=0.0001). Twenty-three of 53 (43%) signet ring cell carcinomas demonstrated high levels of microsatellite instability (MSI-H). Twenty-two of 23 (96%) MSI-H signet ring cell carcinomas were mucin rich; only 1 MSI-H signet ring carcinoma was mucin poor (P=0.0033). Mucin-poor signet ring cell carcinoma had significantly reduced overall and recurrence-free survival compared with mucin-rich signet ring cell carcinomas (P=0.0035 and 0.0001, respectively), even when adjusting for tumor stage. Mucin-poor signet ring cell carcinoma had a higher propensity for peritoneal dissemination (5/13, 38%) compared with mucin-rich signet ring cell carcinoma (5/40, 12.5%), although this was not statistically significant (P=0.052). Finally, MSI-H and microsatellite-stable signet ring cell carcinomas had

  7. Renal cell carcinoma: histological classification and correlation with imaging findings.

    PubMed

    Muglia, Valdair F; Prando, Adilson

    2015-01-01

    Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes.

  8. Renal cell carcinoma: histological classification and correlation with imaging findings*

    PubMed Central

    Muglia, Valdair F.; Prando, Adilson

    2015-01-01

    Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes. PMID:26185343

  9. Comparison of circulating and intratumoral regulatory T cells in patients with renal cell carcinoma.

    PubMed

    Asma, Gati; Amal, Gorrab; Raja, Marrakchi; Amine, Derouiche; Mohammed, Chebil; Amel, Ben Ammar Elgaaied

    2015-05-01

    The clear evidence that tumor-infiltrating lymphocytes (TIL) exists in the tumor microenvironment raises the question why renal cell carcinoma (RCC) progresses. Numerous studies support the implication of CD4(+)CD25(high) regulatory T (Treg) cells in RCC development. We aimed in this study to characterize the phenotype and function of circulating and intratumoral Treg cells of RCC patient in order to evaluate their implication in the inhibition of the local antitumor immune response. Our results demonstrate that the proportion of Treg in TIL was, in average, similar to that found in circulating CD4(+) T cells of patients or healthy donors. However, intratumoral Treg exhibit a marked different phenotype when compared with the autologous circulating Treg. A higher CD25 mean level, HLA-DR, Fas, and GITR, and a lower CD45RA expression were observed in intratumoral Treg, suggesting therefore that these cells are effector in the tumor microenvironment. Additionally, intratumoral Treg showed a higher inhibitory function on autologous CD4(+)CD25(-) T cells when compared with circulating Treg that may be explained by an overexpression of FoxP3 transcription factor. These findings suggest that intratumoral Treg could be major actors in the impairment of local antitumor immune response for RCC patients.

  10. Basal cell carcinoma vs basaloid squamous cell carcinoma of the skin: an immunohistochemical reappraisal.

    PubMed

    Webb, David V; Mentrikoski, Mark J; Verduin, Lindsey; Brill, Louis B; Wick, Mark R

    2015-04-01

    Typical cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are morphologically dissimilar. It is well known, however, that poorly differentiated SCC may assume a basaloid phenotype, complicating the histologic distinction between these 2 neoplasms. Selected immunohistochemical stains have been used in the past to aid in that differential diagnosis. In the current study, additional markers were evaluated to determine whether they would be helpful in that regard. Twenty-nine cases of metatypical (squamoid) BCC (MBCC) and 25 examples of basaloid SCC (BSCC) were studied using the antibodies Ber-EP4 and MOC-31 as well as a plant lectin preparation from Ulex europaeus I (UEA-1). The resulting immunostains were interpreted independently by 3 pathologists, and the results showed that MBCCs demonstrated strong and diffuse staining for Ber-EP4 (25/29) and MOC-31 (29/29). In contrast, BSCCs tended to be only sporadically reactive for both markers (4/25 and 1/25 cases, respectively). Labeling for UEA-1 was observed in almost all BSCCs (24/25), but only 6 of 29 cases of MBCC showed limited, focal staining with that lectin. These data suggest that MOC-31 is a useful marker in the specified differential diagnosis, especially when used together with UEA-1.

  11. Basal cell carcinoma and squamous cell carcinoma growth rates and determinants of size in community patients.

    PubMed

    Kricker, Anne; Armstrong, Bruce; Hansen, Vibeke; Watson, Alan; Singh-Khaira, Gurpreet; Lecathelinais, Christophe; Goumas, Chris; Girgis, Afaf

    2014-03-01

    Cutaneous basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) have poorer outcomes if treated when large. We sought to estimate the growth rate of BCCs and SCCs and examine the relationship of personal, pathway, and cancer factors with cancer size (diameter). We surveyed patients, pathology, and treatment for invasive BCCs and SCCs in 1 Australian region in 2000 through 2001. BCC size increased with increasing time since first noticed. Relative to mean size at 0 to 2 months, the mean size ratio was 1.10 at 2 to 8 months and increased steadily to 1.81 at 5 to 10 years (P < .001). Few BCCs were untreated beyond 10 years. There was no consistent evidence that SCC size increased with increasing time. Larger BCCs were independently associated with older age, male sex, no skin checks by a physician, aggressive tumor type, ulceration and lesion-associated scar tissue, and larger SCCs with male sex, skin checks by a physician every 1 to 3 months, and location on limbs. Patient recall of dates and lack of thickness for SCCs are limitations. Earlier diagnosis of BCCs, perhaps through skin checks by a physician, may reduce their size and improve outcome. SCC size did not evidently increase with time. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  12. Nevoid Basal Cell Carcinoma Syndrome: Report from the Zurich Nevoid Basal Cell Carcinoma Syndrome Cohort.

    PubMed

    Rehefeldt-Erne, Susanne; Nägeli, Mirjam C; Winterton, Nina; Felderer, Lea; Weibel, Lisa; Hafner, Jürg; Dummer, Reinhard

    2016-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin-Goltz syndrome) presents various symptoms and can disfigure patients. The estimated prevalence is around 1:100,000. To systematically investigate the clinical manifestations of NBCCS patients of the Zurich register and compare them with those described in 4 epidemiological studies performed in other countries. We analyzed patient characteristics and clinical manifestations in a register of 30 NBCCS patients in Zurich, Switzerland. We compared our findings to the results of 4 epidemiological studies performed in America, Australia, Japan and the UK. We obtained information concerning basal cell carcinomas (BCCs) and jaw cysts from 28 patients out of our population of 30 NBCCS patients. The mean age at onset of the first BCC was 24 years, and the mean age at diagnosis of the first jaw cyst was 15.6 years. The average number of jaw cysts was 8.4; the average number of BCCs was 207. 72.5% of the examined BCCs showed a nodular histology, but we also found scirrhous and superficial types. The disease burden associated with NBCCS diagnosed in Swiss patients is significant and comparable to that of other countries. Regular skin examination and oromaxillary examinations should be performed early in diagnosis, and patients should undergo early UV protection. Nodular BCC is the most common BCC subtype in this patient population. © 2016 S. Karger AG, Basel.

  13. Risk of cutaneous squamous cell carcinoma after treatment of basal cell carcinoma with vismodegib.

    PubMed

    Bhutani, Tina; Abrouk, Michael; Sima, Camelia S; Sadetsky, Natalia; Hou, Jeannie; Caro, Ivor; Chren, Mary-Margaret; Arron, Sarah T

    2017-10-01

    Vismodegib is a first-in-class agent targeting the hedgehog signaling pathway for treatment of patients with locally advanced basal cell carcinoma (BCC) and metastatic BCC. There have been concerns about the development of squamous cell carcinoma (SCC) in patients treated with this drug. We sought to determine whether treatment with vismodegib is associated with an increase in the risk of cutaneous SCC. In this retrospective cohort study, patients treated with vismodegib as part of phase I and II clinical studies were compared with participants from the University of California, San Francisco, Nonmelanoma Skin Cancer Cohort who received standard therapy for primary BCC. In total, 1675 patients were included in the analysis, and the development of SCC after vismodegib exposure was assessed. The use of vismodegib was not associated with an increased risk of subsequent development of SCC (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28-1.16). Covariates including age, sex, history of previous nonmelanoma skin cancer, and number of visits per year were significantly associated with the development of SCC. A limitation of the study was that a historic control cohort was used as a comparator. Vismodegib was not associated with an increased risk of subsequent SCC when compared with standard surgical treatment of BCC. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  14. Epithelial-to-mesenchymal transition in penile squamous cell carcinoma.

    PubMed

    Masferrer, Emili; Ferrándiz-Pulido, Carla; Masferrer-Niubò, Magalí; Rodríguez-Rodríguez, Alfredo; Gil, Inmaculada; Pont, Antoni; Servitje, Octavi; García de Herreros, Antonio; Lloveras, Belen; García-Patos, Vicenç; Pujol, Ramon M; Toll, Agustí; Hernández-Muñoz, Inmaculada

    2015-02-01

    Epithelial-to-mesenchymal transition is a phenomenon in epithelial tumors that involves loss of intercellular adhesion, mesenchymal phenotype acquisition and enhanced migratory potential. While the epithelial-to-mesenchymal transition process has been extensively linked to metastatic progression of squamous cell carcinoma, studies of the role of epithelial-to-mesenchymal transition in squamous cell carcinoma containing high risk human papillomaviruses are scarce. Moreover, to our knowledge epithelial-to-mesenchymal transition involvement in human penile squamous cell carcinoma, which can arise through transforming HPV infections or independently of HPV, has not been investigated. We evaluated the presence of epithelial-to-mesenchymal transition markers and their relationship to HPV in penile squamous cell carcinoma. We assessed the expression of E-cadherin, vimentin and the epithelial-to-mesenchymal transition related transcription factors Twist, Zeb1 and Snail by immunohistochemical staining in 64 penile squamous cell carcinoma cases. HPV was detected by polymerase chain reaction amplification. Simultaneous loss of membranous E-cadherin expression and vimentin over expression were noted in 43.5% of penile squamous cell carcinoma cases. HPV was significantly associated with loss of membranous E-cadherin but not with epithelial-to-mesenchymal transition. Recurrence and mortality rates were significantly higher in cases showing epithelial-to-mesenchymal transition. Our findings indicate that in penile squamous cell carcinoma epithelial-to-mesenchymal transition is associated with poor prognosis but not with the presence of HPV. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. [Exenteration of the Orbit for Basal Cell Carcinoma].

    PubMed

    Furdová, A; Horkovičová, K; Krčová, I; Krásnik, V

    2015-08-01

    Primary treatment of basal cell carcinoma of the lower eyelid and the inner corner is essentially surgical, but advanced lesions require extensive surgical interventions. In some cases it is necessary to continue with the mutilating surgery--exenteration of the orbit. In this work we evaluate the indications of radical solutions in patients with basal cell carcinoma invading the orbit and the subsequent possibility for individually made prosthesis to cover the defect of the cavity. Indications to exenteration of the orbit in patients with basal cell carcinoma findings in 2008-2013. Case report of 2 patients. In period 2008-20013 at the Dept. of Ophthalmology, Comenius University in Bratislava totally 221 patients with histologically confirmed basal cell carcinoma of the eyelids and the inner corner were treated. In 5 cases (2.7 %) with infiltration of the orbit the radical surgical procedure, exenteration was necessary. In 3 patients exenteration was indicated as the first surgical procedure in the treatment of basal cell carcinoma, since they had never visited ophthalmologist before only at in the stage of infiltration of the orbit (stage T4). In one case was indicated exenteration after previous surgical interventions and relapses. After healing the cavity patients got individually prepared epithesis. Surgical treatment of basal cell carcinoma involves the radical removal of the neoplasm entire eyelid and stage T1 or T2 can effectively cure virtually all tumors with satisfactory cosmetic and functional results. In advanced stages (T4 stage) by infiltrating the orbit by basal cell carcinoma exenteration of the orbit is necessary. This surgery is a serious situation for the patient and also for his relatives. Individually made prosthesis helps the patient to be enrolled to the social environment.

  16. Export of microRNAs: A Bridge between Breast Carcinoma and Their Neighboring Cells

    PubMed Central

    Jahagirdar, Devashree; Purohit, Shruti; Jain, Aayushi; Sharma, Nilesh Kumar

    2016-01-01

    Breast cancer is a leading type of cancer among women in India as well as worldwide. According to the WHO 2015 report, it has been anticipated that there would be a twofold rise in the death due to breast cancer among women. The heterogeneous property of breast carcinoma has been suggested to be linked with dedicated set of communication and signaling pathway with their surroundings, which culminate into progression and development of the cancer. Among the plethora of communication tools in the hand of breast carcinoma cells is the recently appreciated exocytosis of the tightly packed short non-coding RNA molecules, predominantly the microRNAs (miRNAs). Recent studies suggest that miRNAs may work as courier messengers to participate in endocrine and paracrine signaling to facilitate information transfer between breast carcinoma and their neighboring cells. Evidence suggests that breast tumor cells communicate via packaged miRNAs in the tumor-released microvesicles, which enrich the tumor microenvironment. There is a strong view that dissecting out the mechanistic and regulatory aspects of miRNA export and role may uncover many prospects for overcoming the signaling defects and thereby controlling aberrant cell division. The detection of circulating miRNAs associated with breast carcinoma can also be used as biomarkers for early diagnosis. This review article is an attempt to provide updated knowledge on implications of short RNAs and their transport in the breast cancer pathophysiology. PMID:27379209

  17. Spontaneous regression and recurrence of stage III Merkel cell carcinoma

    PubMed Central

    Jansen, Sandra Catharina Petronella; Groeneveld-Haenen, Christine P M; Klinkhamer, Paul J J M; Roumen, Rudi M H

    2015-01-01

    Merkel cell carcinoma (MCC) is a malignant neuroendocrine carcinoma originating in the skin. It is typically aggressive with a tendency to recur locally and metastasise. There have been several case reports about spontaneous regression of MCC over the past years, but to the best of our knowledge this is the first case of a regional lymph node metastasised MCC with complete spontaneous regression and recurrence. In addition, the primary tumour has an unusual localisation on the foot. PMID:25716042

  18. Primary small-cell carcinoma of the breast

    PubMed Central

    Dao, Tuoc; Howard, Evan; Bredeweg, Arthur

    2017-01-01

    Early diagnosis of rare breast cancers is expected to occur more frequently as screening compliance improves and diagnostic modalities become more sensitive. Well-defined treatment algorithms exist for the management of ductal and lobular carcinomas; however, less information is available to guide the treatment of atypical breast cancers. This case report describes a 38-year-old African American woman with primary small cell carcinoma of the breast and her treatment.

  19. Retinopathy secondary to radiation therapy for squamous cell carcinoma

    SciTech Connect

    Groomer, A.E.; Gutwein, D.E. )

    1989-09-01

    This report discusses a case of radiotherapy-induced retinopathy following treatment of squamous cell carcinoma. Treatment of the carcinoma with external beam radiotherapy to the supraorbital region and base of the skull was followed by the onset of retinopathy. The sensory retina, as well as other central nervous system tissues, is highly resistant to radiation damage; however, the retinal vasculature is extremely sensitive to radiation damage, producing a retinopathy that is characteristic of other vascular occlusive diseases. Management is discussed.

  20. Bilateral synchronous squamous cell tonsil carcinoma treated with chemoradiotherapy.

    PubMed

    Bakkal, Bekir Hakan; Ugur, Mehmet Birol; Bahadir, Burak

    2014-04-01

    The incidence of numerous head and neck tumours is a known issue though bilateral synchronous tonsillar carcinoma reports are so uncommon that only 20 cases were found in a literature review. Most of these patients were treated with bilateral tonsillectomy followed by adjuvant radiotherapy. We report, to our knowledge, the first case of bilateral synchronous tonsillar squamous cell carcinoma treated only with chemoradiotherapy without tonsillectomy.

  1. Utility of MRI features in differentiation of central renal cell carcinoma and renal pelvic urothelial carcinoma.

    PubMed

    Wehrli, Natasha E; Kim, Min Ju; Matza, Brent W; Melamed, Jonathan; Taneja, Samir S; Rosenkrantz, Andrew B

    2013-12-01

    The purpose of this article is to evaluate the utility of various morphologic and quantitative MRI features in differentiating central renal cell carcinoma (RCC) from renal pelvic urothelial carcinoma. Sixty patients (39 men and 21 women; mean [± SD] age, 65 ± 14 years; 48 with central RCC and 12 with renal pelvic urothelial carcinoma) who underwent MRI, including diffusion-weighted imaging (b values, 0, 400, and 800 s/mm(2)) and dynamic contrast-enhanced imaging, before histopathologic confirmation were included. Tumor T2 signal intensity and apparent diffusion coefficients (ADCs) were measured and normalized to muscle and CSF (hereafter referred to as normalized T2 signal and normalized ADC, respectively) and then were compared using receiver operating characteristic analysis. Also, two blinded radiologists independently assessed all tumors for various qualitative features, which were compared with the Fisher exact test and unpaired Student t test. Urothelial carcinoma exhibited significantly lower normalized ADC than did RCC (p = 0.008), but no significant difference was seen in ADC or normalized T2 signal intensity (p = 0.247-0.773). Normalized ADC had the highest area under the curve (0.757); normalized ADC below an optimal threshold of 0.451 was associated with sensitivity of 83% and specificity of 71% for diagnosing urothelial carcinoma. Features that were significantly more prevalent in urothelial carcinoma included global impression of urothelial carcinoma, location centered within the collecting system, collecting system defect, extension to the ureteropelvic junction, preserved renal shape, absence of cystic or necrotic areas, absence of hemorrhage, homogeneous enhancement, and hypovascularity (all p < 0.033). Increased T1 signal intensity suggestive of hemorrhage was significantly more prevalent in RCC (p = 0.02). Interreader agreement for the subjective features ranged from 61.7% to 98.3%. In addition to various qualitative MRI parameters, normalized

  2. Clear cell renal cell carcinoma with intratumoral and nodal extramedullary megakaryopoiesis: a potential diagnostic pitfall.

    PubMed

    Williamson, Sean R; Mast, Kelley J; Cheng, Liang; Idrees, Muhammad T

    2014-06-01

    Clear cell renal cell carcinoma is occasionally associated with erythrocytosis, hypothesized to result from tumoral production of erythropoietin. Rarely, intratumoral erythropoiesis has been identified, although intratumoral megakaryopoiesis has not, to our knowledge, been previously described. We report the case of an 81-year-old man with myelofibrosis who underwent resection of a 9.8-cm clear cell renal cell carcinoma. Numerous megakaryocytes were present within the renal cell carcinoma; regional lymph nodes; and, to a lesser extent, the nonneoplastic kidney, glomeruli, and renal hilar soft tissue, in some areas associated with trilineage hematopoiesis. Immunohistochemistry verified the megakaryocytic lineage of the atypical cells (CD61, CD42b, and von Willebrand factor +; cytokeratin -). Intratumoral extramedullary megakaryopoiesis is a novel finding in clear cell renal cell carcinoma with potential to mimic high-grade carcinoma and involvement of lymph nodes. Careful attention to morphology, presence of other hematopoietic elements, and immunoprofile can facilitate recognition of this rare phenomenon.

  3. Morphine enhances renal cell carcinoma aggressiveness through promotes survivin level.

    PubMed

    Ma, Yabing; Ren, Zhongzhong; Ma, Shuyong; Yan, Wenjun; He, Man; Wang, Dong; Ding, Peiyan

    2017-11-01

    Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. Unfortunately, the results obtained by these studies are still contradictory. In this study, we investigated the effect of morphine in human clear cell renal cell carcinoma 786-O, RLC-310 cells and whether morphine affects on tumor growth in human clear cell renal cell carcinoma 786-O, RLC-310 cells. The cell proliferation was determined by MTT assay, cell proliferation, migration and invasion assays. Immunofluorescence staining and Q-PCR was used to determine the Survivin expression. It was shown that morphine enhances proliferation of 786-O, RLC-310 cells, whereas morphine promoted the growth and aggressive phenotype of 786-O and RLC-310 cells in vitro though Survivin-dependent signaling. Our data showed that morphine promotes RCC growth and increases RCC progression via over-expression of Survivin.

  4. Fusion-derived epithelial cancer cells express hematopoietic markers and contribute to stem cell and migratory phenotype in ovarian carcinoma.

    PubMed

    Ramakrishnan, Mallika; Mathur, Sandeep R; Mukhopadhyay, Asok

    2013-09-01

    For a long time, the external milieu of cancer cells was considered to be of secondary importance when compared with its intrinsic properties. That has changed now as the microenvironment is considered to be a major contributing factor toward the progression of tumor. In this study, we show that in human and mouse epithelial ovarian carcinoma and mouse lung carcinoma, the interaction between tumor-infiltrating hematopoietic cells and epithelial cancer cells results in their fusion. Intriguingly, even after the fusion event, cancer cells retain the expression of the pan-hematopoietic marker (CD45) and various markers of hematopoietic lineage, including those of hematopoietic stem cells, indicating that the hematopoietic genome is not completely reprogrammed. This observation may have implications on the bone marrow contribution to the cancer stem cell population. Interestingly, it was seen that in both cancer models, the expression of chemokine receptor CXCR4 was largely contributed to by the fused compartment of cancer cells. We hypothesize that the superior migratory potential gained by the cancer cells due to the fusion helps in its dissemination to various secondary organs upon activation of the CXCR4/CXCL12 axis. We are the first to report the presence of a hemato-epithelial cancer compartment, which contributes to stem cell markers and CXCR4 in epithelial carcinoma. This finding has repercussions on CXCR4-based therapeutics and opens new avenues in discovering novel molecular targets against fusion and metastasis.

  5. Synchronous occurrence of neuroendocrine colon carcinoma and hairy cell leukemia.

    PubMed

    Salemis, Nikolaos S; Pinialidis, Dionisios; Tsiambas, Evangelos; Gakis, Christos; Nakos, Georgios; Sambaziotis, Dimitrios; Christofyllakis, Charalambos

    2011-09-01

    BACKGROUND-PURPOSE: The risk of secondary malignancy development in patients with hairy cell leukemia has been evaluated in several studies with varying results. The aim of this study is to describe a case of synchronous occurrence of neuroendocrine colon carcinoma and hairy cell leukemia. A 69-year-old man presented with rectal bleeding. Colonoscopy revealed a rectal tumor, whereas biopsy specimens revealed a poorly differentiated carcinoma. During the preoperative evaluation, pancytopenia was detected. At laparotomy, a mass was detected 16 cm from the anal verge and an anterior resection of the rectum was performed. Detailed histological and immunohistochemical analyses revealed a poorly differentiated neuroendocrine carcinoma of the rectum. Postoperative evaluation of pancytopenia revealed hairy cell leukemia. The patient was initially treated with chemotherapy for hairy cell leukemia followed by chemotherapy for neuroendocrine colon carcinoma. Survival was 44 months. To our knowledge, synchronous occurrence of neuroendocrine colon carcinoma and hairy cell leukemia has not been previously reported in the literature. Given the rare incidence of both entities in the general population, it is highly unlikely that they occurred together by chance. Further research is needed to determine what would be the optimal management options of patients with simultaneous hairy cell leukemia and a neuroendocrine colon cancer.

  6. Induction of p16INK4A mediated by beta-catenin in a TCF4-independent manner: implications for alterations in p16INK4A and pRb expression during trans-differentiation of endometrial carcinoma cells.

    PubMed

    Saegusa, Makoto; Hashimura, Miki; Kuwata, Takeshi; Hamano, Mieko; Okayasu, Isao

    2006-11-15

    Excessive beta-catenin is considered to contribute to tumor progression by inducing transcription of cell cycle-related genes such as cyclin D1 and c-myc. In contrast, our recent studies demonstrated that beta-catenin could inhibit cell proliferation through activation of p14(ARF)/p53/p21(WAF1) pathway during trans-differentiation toward morular phenotype of endometrial carcinoma (Em Ca) cells. Here, we focused on associations with alterations in p16(INK4A) and pRb expression during this process. In clinical cases, p16(INK4A) immunoreactivity was found to frequently overlap with nuclear beta-catenin accumulation in small-sized morules and surrounding glandular carcinomas (Sur-Ca), demonstrating a significant positive correlation (r = 0.447, p < 0.0001) overall, while the immunoreactions showed stepwise decrease in enlarged morules, despite persistent accumulation of beta-catenin and p21(WAF1) in nuclei. Immunoreactivity for both total pRb and its phosphorylated form was apparently decreased in all morules as compared to Sur-Ca lesions, with a significantly positive correlation. In cell lines, transcriptional activation of p16(INK) (4A) promoter by active form beta-catenin, as well as p21(WAF1), occurred through the region from -385 to -280 bp relative to the translation start site, in a TCF4-independent manner. Moreover, cell proliferation was accompanied with phosphorylation of pRb and increased p16(INK4A) expression, while its inhibition by serum starvation caused decreased expression of total pRb but not p16(INK4A), resulting in high relative amounts of the latter. These findings indicate that induction of p16(INK4A) mediated by nuclear beta-catenin and p21(WAF1), along with loss of pRb expression, may be important for initial steps during trans-differentiation of Em Ca cells. In addition, its down-regulation is associated with progression of lesions.

  7. Spindle cell carcinoma progressed from transitional cell carcinoma of the urinary bladder

    PubMed Central

    Terada, Tadashi

    2012-01-01

    The author reports a very rare case of spindle cell carcinoma (SpCC) of the urinary bladder progressed from ordinary papillary transitional cell carcinoma (TCC). A 63-year-old man complained of hematuria. A transurethral endoscopic examination revealed a papillary tumor, and transuthetral resection of bladder tumor (TUR-BT) was performed and was diagnosed as ordinary papillary urothelial TCC. Since then, he was treated with TUR-BT eight times. Chemotherapy, radiation, radical cystectomy and lymph nodes dissection were performed 16 years after the first TUR-BT. However, he developed rectal mucosal metastasis. He is now alive 17 years after the first presentation. All the TUR-BT specimens were ordinary papillary TCCs without invasion (pTa). Immunohistochemically, the TUR-BT specimens were positive for pancytokeratin, high molecular weight cytokeratin (CK), CK 5/6, CK 7, CK 18, CK 19, CK 20, p53, p63, Ki-67 (10%), and negative for other antigens examined including vimentin. The cystectomy bladder specimens show broad ulcers and polypoid lesions, and malignant spindle cells (SpCC) invading into muscular layer were present. No TCC elements were recognized. The tumor cells were positive strongly for vimentin, and less strongly for pancytokeratin, high molecular weight cytokeratin, CK 5/6, CK 14, CK 18, p53, p63 and Ki-67 (95%), and negative for other antigens examined. The rectal metastatic lesion showed SpCC without TCC elements, and were strongly positive for vimentin, and weakly positive for pancytokeratin, S100 protein, p53, p63, Ki-67 (90%), neuron-specific enolase, CD56, KIT and PDGFRA. It was negative for other antigen examined. It is strongly suggested that the present SpCC were progressed from ordinary TCC. PMID:22295151

  8. A subset of prostatic basal cell carcinomas harbor the MYB rearrangement of adenoid cystic carcinoma.

    PubMed

    Bishop, Justin A; Yonescu, Raluca; Epstein, Jonathan I; Westra, William H

    2015-08-01

    Adenoid cystic carcinoma (ACC) is a basaloid tumor consisting of myoepithelial and ductal cells typically arranged in a cribriform pattern. Adenoid cystic carcinoma is generally regarded as a form of salivary gland carcinoma, but it can arise from sites unassociated with salivary tissue. A rare form of prostate carcinoma exhibits ACC-like features; it is no longer regarded as a true ACC but rather as prostatic basal cell carcinoma (PBCC) and within the spectrum of basaloid prostatic proliferations. True ACCs often harbor MYB translocations resulting in the MYB-NFIB fusion protein. MYB analysis could clarify the true nature of prostatic carcinomas that exhibit ACC features and thus help refine the classification of prostatic basaloid proliferations. Twelve PBCCs were identified from the pathology consultation files of Johns Hopkins Hospital. The histopathologic features were reviewed, and break-apart fluorescence in situ hybridization for MYB was performed. All 12 cases exhibited prominent basaloid histology. Four were purely solid, 7 exhibited a cribriform pattern reminiscent of salivary ACC, and 1 had a mixed pattern. The MYB rearrangement was detected in 2 (29%) of 7 ACC-like carcinomas but in none (0%) of the 5 PBCCs with a prominent solid pattern. True ACCs can arise in the prostate as is evidenced by the presence of the characteristic MYB rearrangement. When dealing with malignant basaloid proliferations in the prostate, recommendations to consolidate ACCs with other tumor types may need to be reassessed, particularly in light of the rapidly advancing field of biologic therapy where the identification of tumor-specific genetic alterations presents novel therapeutic targets.

  9. Pancreatic-type Acinar Cell Carcinoma of the Stomach Included in Multiple Primary Carcinomas.

    PubMed

    Yonenaga, Yoshikuni; Kurosawa, Manabu; Mise, Masahiro; Yamagishi, Miki; Higashide, Shunichi

    2016-06-01

    Pancreatic-type acinar cell carcinoma (ACC) in the stomach is extraordinarily rare. We pathologically examined two cases with multiple primary carcinomas, including gastric tumors. Gastric cancer specimens were examined by immunostaining and electron microscopy. Both cases had cancer cells with acinar patterns, resembling pancreatic ACC. The cancer cells in the first case were positive for exocrine markers, including chymotrypsin, lipase and alpha-1 antichymotrypsin (ACT), as well as neuroendocrine markers, including chromogranin A and synaptophysin. The cancer cells in the second case were positive for chymotrypsin and alpha-1 ACT, while being slightly positive for chromogranin A and synaptophysin. Ultrastructurally, cancer cells contained zymogen granules in both cases. The final diagnosis was pancreatic mixed acinar-neuroendocrine carcinoma and pure pancreatic ACC, respectively. We confirmed two cases with gastric pancreatic-type ACC included in multiple primary carcinomas. This type of double cancer has not been reported previously. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Chemoprevention of esophageal squamous cell carcinoma

    SciTech Connect

    Stoner, Gary D. Wang Lishu; Chen Tong

    2007-11-01

    Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, and to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.

  11. Clear cell odontogenic carcinoma. A review.

    PubMed

    Hadj Saïd, M; Ordioni, U; Benat, G; Gomez-Brouchet, A; Chossegros, C; Catherine, J-H

    2017-08-30

    Clear cell odontogenic carcinoma (CCOC) is described as an exceptional and hard to diagnose malignant tumor which was first reported by Hansen in 1985. The purpose of this review article is to show that CCOC is a not that rare entity and to discuss its various aspects in order to enhance the diagnosis. A search in the English language literature was performed using the Scopus, ScienceDirect, PubMed and Medline databases between 1985 and 2016. Data were collected on epidemiologic, clinical, radiographic, histological, immunohistochemistrical, cytogenetic, management, follow-up and prognosis features of CCOC. Sixty-five studies from which a total of 95 case reports were included in the review. CCOC was generally seen in the fifth decade and the most common site was mandibular. The most frequently found symptoms were swelling, tooth mobility and pain. Radiologically, the image was radiolucent and could look like a cyst or a periodontal lesion. In situ hybridization techniques frequently expressed a gene fission of EWSR1. The treatment was mostly a radical surgical excision of the tumor with or without adjuvant radiotherapy or chemotherapy. CCOC showed high rates of recurrence and mortality related with the presence of distance metastasis. Fission of EWSR1 gene could be the main element it the diagnosis of CCOC. A multidisciplinary approach, including a radiologist, pathologist and an oral & maxillofacial surgeon may be helpful in the evaluation and management of these lesions. With 95 reports found in English literature, we cannot say that CCOC is extremely rare anymore. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Perianal basal cell carcinoma: a comparative histologic, immunohistochemical, and flow cytometric study with basaloid carcinoma of the anus.

    PubMed

    Alvarez-Cañas, M C; Fernández, F A; Rodilla, I G; Val-Bernal, J F

    1996-08-01

    Perianal basal cell carcinoma is a very rare tumor accounting for only 0.2% of the anorectal tumors. It must be distinguished from basaloid carcinoma of the anus, which resembles it histologically but shows a much more aggressive behavior, metastasizes early, and often proves fatal, thus requiring different therapy. Differential diagnosis of both entities by light microscopy may be difficult. Five cases of perianal basal cell carcinoma and five cases of basaloid carcinoma were studied by means of immunohistochemistry and flow cytometry. Some immunohistochemical markers, such as epithelial membrane antigen, carcinoembrionic antigen, and keratins, as well as the lectin Ulex europaeus agglutinin I stained basaloid carcinoma and were negative for basal cell carcinoma. In contrast, the monoclonal antibody Ber-EP4 seems to be a good marker for perianal basal cell carcinoma and useful in differentiating it from basaloid carcinoma of the anus. Basaloid carcinomas are associated with a significantly higher S-phase fraction than are perianal basal cell carcinomas (p < 0.01).

  13. An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.

    PubMed

    Hakimi, A Ari; Reznik, Ed; Lee, Chung-Han; Creighton, Chad J; Brannon, A Rose; Luna, Augustin; Aksoy, B Arman; Liu, Eric Minwei; Shen, Ronglai; Lee, William; Chen, Yang; Stirdivant, Steve M; Russo, Paul; Chen, Ying-Bei; Tickoo, Satish K; Reuter, Victor E; Cheng, Emily H; Sander, Chris; Hsieh, James J

    2016-01-11

    Dysregulated metabolism is a hallmark of cancer, manifested through alterations in metabolites. We performed metabolomic profiling on 138 matched clear cell renal cell carcinoma (ccRCC)/normal tissue pairs and found that ccRCC is characterized by broad shifts in central carbon metabolism, one-carbon metabolism, and antioxidant response. Tumor progression and metastasis were associated with metabolite increases in glutathione and cysteine/methionine metabolism pathways. We develop an analytic pipeline and visualization tool (metabolograms) to bridge the gap between TCGA transcriptomic profiling and our metabolomic data, which enables us to assemble an integrated pathway-level metabolic atlas and to demonstrate discordance between transcriptome and metabolome. Lastly, expression profiling was performed on a high-glutathione cluster, which corresponds to a poor-survival subgroup in the ccRCC TCGA cohort.

  14. Molecular characterisation of sinonasal carcinomas and their clinical implications.

    PubMed

    López, Fernando; Llorente, José Luis; Costales, María; García-Inclán, Cristina; Pérez-Escuredo, Jhudit; Alvarez-Marcos, César; Hermsen, Mario; Suárez, Carlos

    2013-01-01

    Sinonasal carcinomas are rare tumours with an unfavourable prognosis whose management is difficult and complex, leading to high morbidity and mortality despite improvements in the field of surgery and radiotherapy. An elevated number of these tumours can be attributed to occupational exposure. In comparison with other head and neck malignancies, studies of molecular changes in these tumours are infrequent. This review was focused on findings about the epidemiology and molecular and phenotypic characterisation of sinonasal carcinomas, which can potentially be useful for diagnosis and treatment. The increasing knowledge about the molecular biology that underlies their carcinogenesis may help to identify precursor lesions, prognostic markers and markers that predict chemoradiotherapy response and, finally, to identify potential molecular targets that will expand treatment options.

  15. CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma

    SciTech Connect

    Zhang, Heyu; Nan, Xu; Li, Xuefen; Chen, Yan; Zhang, Jianyun; Sun, Lisha; Han, Wenlin; Li, Tiejun

    2014-05-02

    Highlights: • Down-regulation of CMTM5 expression in OSCC tissues was found. • The promoter methylation status of CMTM5 was measured. • CMTM5-v1 inhibited cell proliferation and migration and induced apoptosis. • CMTM5 might act as a putative tumor suppressor gene in OSCC. - Abstract: Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) has been recently implicated as a tumor suppressor gene in several cancer types. Herein, we examined the expression and function of CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous cell lines and tumor samples from patients with promoter methylation. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored CMTM5 expression. In the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly inhibited cell proliferation and migration and induced apoptosis. In addition, CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a putative tumor suppressor gene through promoter methylation in oral squamous cell carcinoma.

  16. A rare bladder cancer - small cell carcinoma: review and update

    PubMed Central

    2011-01-01

    Small cell carcinoma of the bladder (SCCB) is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC). Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease (< or = cT1-4aN0M0) should be managed with multimodal therapy associating chemotherapy, surgery and/or radiotherapy. Neoadjuvant chemotherapy using four chemotherapy cycles followed by radical cystectomy is the most effective therapeutic sequence. Patients with unresectable disease (> or = cT4bN+M+) should be managed with palliative chemotherapy based on neuroendocrine type regimens comprising a platinum drug (cisplatin in fit patients). The prognosis of the disease is poor mainly in the case of pure small cell carcinoma. Other research programs are needed to improve the outcome of SCCB. PMID:22078012

  17. [Pancreatic acinar cell carcinoma: diagnostic and surgical treatment strategy].

    PubMed

    Guo, Jun-chao; Zhan, Han-xiang; Zhang, Tai-ping; Zhao, Yu-pei

    2013-03-01

    To investigate the clinical features, diagnostic and therapeutic strategy of pancreatic acinar cell carcinoma. The data of pancreatic acinar cell carcinoma patients who underwent surgical operations from January 2002 to January 2012 were retrospectively reviewed. Six cases of pancreatic acinar cell carcinoma, identified with pathology were collected, including 3 males and 3 females with the average of 47.8 yeas old. Upper abdominal pain was present in 5 cases, weight loss was present in 4 cases with the average of 12.5 kg. Other symptoms included nausea/vomiting, back pain and obstructive jaundice. The serum CA19-9 and CA24-2 level were significantly elevated in 2 cases. CT scan, MRI and DSA were the main imaging methods to diagnose this disease. However, no case was diagnosed as pancreatic acinar cell carcinoma before operation. All cases were confirmed by the pathological examination. Relatively high rates of surgical resection, long operative time, more blood loss and combined multi-organ resection were the characteristics of this disease's operative surgical procedures. The average period of postoperative follow-up process was 60 months, and the mean survival time was (32 ± 8) months. The clinical features and biological behavior of pancreatic acinar cell carcinoma are different from those of ductal adenocarcinoma, while the relatively specific clinical manifestations and imaging changes will be helpful for qualitative diagnosis before operation. As it has high rate of resection and better prognosis, more radical surgical strategies should be carried out for patients of this disease.

  18. Head and neck squamous cell carcinoma in Hajjah, Yemen.

    PubMed

    Nasr, A H; Khatri, M L

    2000-06-01

    Incidence of head and neck squamous cell carcinoma seems to be relatively high in Yemen but not well documented. The purpose of this study is to analyze the clinical profile of the Yemeni patients of squamous cell carcinoma of the head and neck and to evaluate the possible relationship to kath chewing. With the help of a special protocol, all the patients of head and neck squamous cell carcinoma seen between October 1997 and December 1998 at the Ear, Nose and Throat and Dermatology Clinics of Saudi Hospital, Hajjah, Yemen Republic were subjected to detailed analysis. The diagnosis was confirmed by histopathologic studies in all the cases. All the 36 patients (23 male and 13 female) were Yemani nationals, aged 18 to 80 years (median age 50 years). Thirty patients were Kath addicts. The tumor was localized to the oral cavity in 17 (47%) patients, oropharynx in 1 (3%) patient, nasopharynx in 15 (42%) patients and larynx in 3 (8%) patients. The incidence of head and neck squamous cell carcinoma seems to be relatively high, especially the oral squamous cell carcinoma, all of whom had a habit of kath chewing, which may be considered as an important contributing factor.

  19. [Merkel cell carcinoma experience in a reference medical center.

    PubMed

    Roesch-Dietlen, Federico; Devezé-Bocardi, Raúl; Ruiz-Juárez, Isabel; Grube-Pagola, Peter; Romero-Sierra, Graciela; Remes-Troche, José María; Silva-Cañetas, Carmen Sofía; Lozoya-López Escalera, Hilda

    2013-01-01

    Background: Merkel cell carcinoma is a rare tumor that occurs on areas exposed to ultraviolet light. It is usually asymptomatic and it is diagnosed late often. The treatment is surgical, associated with adjuvant radiotherapy. The objective was to present the experience in the management of Merkel cell carcinoma in a reference medical center. Methods: all patients with Merkel cell carcinoma treated at the Instituto de Investigaciones Médico-Biológicas of the Universidad Veracruzana during the period 2008 to 2011 were studied. Sex, age, evolution time, tumor localization, size, metastases and treatment were analyzed. Results: of 3217 patients treated, three cases were Merkel cell carcinoma (0.09 %), their age was 52.1 ± 14.17, male predominance of 66.67 %; the evolution time was of 29.66 ± 35.36 months; the tumour localization was on inguinal region, anterior chest and left arm; the noodle size was of 6.0 ± 5.19 cm; two patients had lymph node metastases. In two cases, resection and lymphadenectomy were performed. They all received radiation therapy and chemotherapy in one case. Histologically the medium variant predominated; immunohistochemistry was positive in the three cases. One patient died ten months after the study was done. Conclusions: our experience is similar with others authors, Merkel cell carcinoma is a rare tumor, usually diagnosed late, and it has poor survival.

  20. Current diagnosis and treatment of basal cell carcinoma.

    PubMed

    Alter, Mareike; Hillen, Uwe; Leiter, Ulrike; Sachse, Michael; Gutzmer, Ralf

    2015-09-01

    Basal cell carcinoma represents is most common tumor in fair-skinned individuals. In Germany, age-standardized incidence rates are 63 (women) and 80 (men) per 100,000 population per year. Early lesions may be difficult to diagnose merely on clinical grounds. Here, noninvasive diagnostic tools such as optical coherence tomography and confocal laser scanning microscopy may be helpful. The clinical diagnosis is usually confirmed by histology. Standard therapy consists of complete excision with thorough histological examination, either by means of micrographic surgery or, depending on tumor size and location as well as infiltration, using surgical margins of 3-5 mm or more. In particular, multiple basal cell carcinomas (such as in Gorlin-Goltz syndrome) and locally advanced as well as rarely also metastatic basal cell carcinoma may pose a therapeutic challenge. In superficial basal cell carcinoma, nonsurgical therapies such as photodynamic therapy or topical agents may be considered. In case of locally advanced or metastatic basal cell carcinoma, an interdisciplinary tumor board should issue therapeutic recommendations. These include radiation therapy as well as systemic therapy with a hedgehog inhibitor. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  1. A Phase I Study of LJM716 in Squamous Cell Carcinoma of Head and Neck, or HER2+ Breast Cancer or Gastric Cancer

    ClinicalTrials.gov

    2014-04-21

    HER2 + Breast Cancer, HER2 + Gastric Cancer, Squamous Cell Carcinoma of Head and Neck, Esophageal Squamous Cell Carcinoma; HER2 + Breast Cancer; HER2 + Gastric Cancer; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma

  2. Renal cell carcinoma: complete pathological response in a patient with gastric metastasis of renal cell carcinoma.

    PubMed

    García-Campelo, Rosario; Quindós, Maria; Vázquez, Diana Dopico; López, Margarita Reboredo; Carral, Alberto; Calvo, Ovidio Fernández; Soto, José Manuel Rois; Grande, Enrique; Durana, Jesús; Antón-Aparicio, Luis Miguel

    2010-01-01

    A 75-year-old-man, with a 2-month history of abdominal pain, underwent a standard diagnostic workup that included a CT scan that showed a large right renal mass and subcentimeter nodes in the right and left lung lobes. In December 2003, the patient underwent right nephrectomy with adrenalectomy and a diagnosis of renal cell carcinoma (pT3N0M0 stage) was made. No further treatment was proposed and patient was followed up regularly. In October 2006, the annual gastrointestinal endoscopy showed asymptomatic multilobulated and polypoid masses in the gastric fundus and gastric body that corresponded to metastasis of the renal carcinoma that had been resected three years ago. Surgical treatment was refused and oral treatment with sunitinib (50 mg/day consecutively for 4 weeks followed by 2 weeks off) was initiated. Patient completed one cycle and development of acute toxicity (grade 3 asthenia, anorexia and mucositis) led to treatment interruption. After recovering from acute toxicity, the patient was proposed to reinitiate treatment with dose reduction, but he refused any medical treatment. At the follow-up visit, three months later, the gastrointestinal endoscopy showed four unspecific 2 mm nodules without malignant evidence. The whole-body CT did not reveal any other abnormality except for the known lung nodes. PET scan six months after treatment confirmed complete gastric response.

  3. Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration.

    PubMed

    Takagi, Kiyoshi; Miki, Yasuhiro; Tanaka, Sota; Hashimoto, Chiaki; Watanabe, Mika; Sasano, Hironobu; Ito, Kiyoshi; Suzuki, Takashi

    2016-01-01

    Nucleobindin 2 (NUCB2) is a multifunctional protein containing several functional domains, and associated with wide variety of biological process such as food intake and energy homeostasis. Recently, NUCB2 has been implicated in not only normal human tissues but also some kinds of human malignancies. However, its clinical and/or biological significance has largely remained unknown in endometrial carcinomas. We therefore immunolocalized NUCB2 protein in 87 endometrial carcinoma tissues and examined its clinical significance. NUCB2 immunoreactivity was detected in 19 out of 87 (22%) of endometrial carcinoma cases examined, and positively correlated with Ki67 labeling index, while there was no significant correlation between NUCB2 and stage, histological grade, and progesterone receptor status. Furthermore, NUCB2 immunoreactivity was significantly correlated with increased risk of recurrence and worse clinical outcome regardless of stage or histological grade. Subsequent multivariate analyses did reveal that NUCB2 immunoreactivity was an independent prognostic factor for both disease-free survival and endometrial cancer specific survival. In vitro experiments demonstrated that knockdown of NUCB2 using specific siRNA for NUCB2 significantly impaired cell proliferation and migration of the endometrial carcinoma cell lines, Ishikawa and Sawano cells, and that nesfatin-1 treatment significantly promoted cell proliferation and migration in Ishikawa cells. These findings possibly suggested that NUCB2 and/or nesfatin-1 had pivotal roles in the progression of endometrial carcinomas. Immunohistochemical NUCB2 status may therefore serve as a potent biomarker for endometrial carcinomas.

  4. Case report. Acinar cell carcinoma with fatty change arising from the pancreas.

    PubMed

    Chung, W-S; Park, M-S; Kim, D W; Kim, K W

    2011-12-01

    Acinar cell carcinoma of the pancreas is a rare malignant tumour developing from acinar cells, accounting for approximately 1% of pancreatic exocrine tumours. We experienced a case of an acinar cell carcinoma with fatty change. To the best of our knowledge, this is the first case report of an acinar cell carcinoma with fatty change in the clinical literature.

  5. Basaloid Squamous Cell Carcinoma of the Anus Revisited.

    PubMed

    Graham, Rondell P; Arnold, Christina A; Naini, Bita V; Lam-Himlin, Dora M

    2016-03-01

    Basaloid squamous cell carcinoma (SCC) of the anus, previously called cloacogenic carcinoma, is a subtype of SCC. There are very few data on the morphologic variation within basaloid SCC of the anus, which may contribute to misdiagnosis. We retrospectively evaluated cases originally diagnosed as basaloid SCC for histologic characterization. We retrieved and reviewed cases of basaloid SCC from 1994 to 2013. Ten (27%) cases were reclassified after review, including basal cell carcinoma (n=6), melanoma (n=2), and neuroendocrine carcinoma (n=2). The final group of basaloid SCC (n=27) showed a female predominance (median age=60 y; range, 42 to 92 y). Morphologically, basaloid SCC could be categorized into 4 groups: transitional carcinoma like (n=10), basaloid with peripheral palisade (n=13), adenoid cystic carcinoma like (n=3), and mucinous microcystic (n=1). In 19 cases the histologic patterns were pure and were mixed in the remainder. CK5/6, p16, and high-risk HPV were positive in all cases (n=27). SOX2 was positive in 18/22 cases. Clinical follow-up was available on 60% of cases; 9 patients (53%) developed local recurrence or metastasis, and 5 (29%) died of disease. Basaloid SCC of the anus is characterized by 4 major histologic patterns and is consistently HPV driven.

  6. Verrucoid Variant of Invasive Squamous Cell Carcinoma in Oral Submucous Fibrosis: A Clinicopathological Challenge

    PubMed Central

    Ramani, Priya; Krithika, C.; Ananthalakshmi, R.; Jagdish, Praveena; Janardhanan, Sunitha; Jeevakarunyam, Sathiyajeeva

    2016-01-01

    Verrucous carcinoma (VC) is an exophytic, low-grade, well-differentiated variant of squamous cell carcinoma. It is described as a lesion appearing in the sixth or seventh decade of life that has minimal aggressive potential and, in long-standing cases, has been shown to transform into squamous cell carcinoma. Oral submucous fibrosis (OSMF) is a potentially malignant disorder, and about one-third of the affected population develop oral squamous cell carcinoma. The histopathological diagnosis of verrucous carcinoma is challenging, and the interpretation of early squamous cell carcinoma requires immense experience. Here we present a rare case of a 24-year-old male with OSMF transforming to verrucous carcinoma with invasive squamous cell carcinoma. Even though the case had a straightforward clinical diagnosis, the serial sectioning done for pathological diagnosis disclosed the squamous cell carcinoma.

  7. Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

    PubMed Central

    Chockalingam, Ramya; Downing, Christopher; Tyring, Stephen K.

    2015-01-01

    Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC) are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV) of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the E6 and E7 proteins of HPV. Specific immunosuppressive medications, such as the calcineurin inhibitors and azathioprine, are associated with a higher incidence of post-transplant SCCs compared to other immunosuppressive agents. Compared to other immunosuppressives, mTOR inhibitors and mycophenolate mofetil have been associated with a decreased risk of developing post-transplant non-melanoma skin cancers. As a result, they may represent ideal immunosuppressive medications in organ transplant recipients. Treatment options for post-transplant SCCs include surgical excision, Mohs micrographic surgery, systemic retinoid therapy, adjunct topical therapy, electrodessication and curettage, and radiation therapy. This review will discuss the epidemiology, risk factors, and management options of post-transplant SCCs. In addition, the underlying mechanisms of beta-HPV mediated carcinogenesis will be discussed. PMID:26239556

  8. Merkel cell carcinoma: emerging biology, current approaches, and future directions.

    PubMed

    Tothill, Richard; Estall, Vanessa; Rischin, Danny

    2015-01-01

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cutaneous cancer that predominantly occurs in patients who are older, and is associated with a high rate of distant failure and mortality. Current management strategies that incorporate surgery and radiotherapy achieve high rates of locoregional control, but distant failure rates remain problematic, highlighting the need for new effective systemic therapies. Chemotherapy can achieve high response rates of limited duration in the metastatic setting, but its role in definitive management remains unproven. Recent developments in our knowledge about the biology of MCC have led to the identification of new potential therapeutic targets and treatments. A key finding has been the discovery that a human polyomavirus may be a causative agent. However, emerging data suggests that MCC may actually be two distinct entities, viral-associated and viral-negative MCC, which is likely to have implications for the management of MCC in the future and for the development of new treatments. In this review, we discuss recent discoveries about the biology of MCC, current approaches to management, and new therapeutic strategies that are being investigated.

  9. Morphological Spectrum of Basal Cell Carcinoma in Southern Karnataka

    PubMed Central

    Lobo, Flora Dorothy; Naik, Ramdas; Khadilkar, Urmila Niranjan; Kini, Hema; Kini, Ullal Anand

    2016-01-01

    Introduction Basal Cell Carcinoma (BCC) is the most common skin cancer worldwide, which appears over sun-exposed skin as slow-growing, locally invasive lesion that rarely metastasizes. Many phenotypic presentations are possible. BCCs are more common in males and tend to occur in older people. Majority is found on the head and neck. Many histopathological subtypes have been defined including nodular, micronodular, cystic, superficial, pigmented, adenoid, infiltrating, sclerosing, keratotic, infundibulocystic, metatypical, basosquamous and fibroepitheliomatous. Mixed patterns are common. Aim The aim was to study morphological spectrum of BCC in a tertiary care hospital in southern Karnataka. Materials and Methods This was a retrospective analysis of 100 cases of BCCs reported in the Department of Pathology over a 9-year period from 2006 to 2014. Results The mean age of presentation was 62 years. There was slight female preponderance (56%). The most common location was face (65%) and the most common presentation was ulceration (45%). Of the 100 BCCs, 50% were nodular, 13% infiltrating, 6% basosquamous, 4% superficial, 3% keratotic, 3% multinodular and 1% mixed. Conclusion BCC, besides being the commonest cutaneous cancer, is also known for its numerous histological patterns which are shown to have prognostic implications. This study reveals the frequency of the various histological patterns of BCC in southern Karnataka, where it has been rarely studied before. PMID:27504291

  10. Systemic Therapies for Metastatic Renal Cell Carcinoma in Older Adults

    PubMed Central

    Pal, Sumanta K.; Vanderwalde, Ari; Hurria, Arti; Figlin, Robert A.

    2016-01-01

    The introduction of targeted therapies has radically changed the treatment paradigm for metastatic renal cell carcinoma (mRCC). However, multiple clinical dilemmas have emerged. For instance, limited data are available to juxtapose the safety and efficacy profile of targeted therapies between older and younger adults. Herein, pivotal trials of vascular endothelial growth factor (VEGF)- and mammalian target of rapamycin (mTOR)-directed therapies are assessed in the context of their implications in treating older adults with mRCC. In general, subset analyses from these pivotal studies suggest similar efficacy of targeted therapies amongst older adults. Aging is accompanied by a multitude of physiological changes, as well as an increased prevalence of co-morbidities. The age-related toxicity profiles of targeted agents for mRCC are detailed to provide a framework for the risks and benefits of these therapies in older adults. Ultimately, tools such as the Comprehensive Geriatric Assessment (CGA) that account for physiological (as opposed to chronological) age may prove useful in the evaluation and treatment of older adults with mRCC. PMID:21812499

  11. Basal cell epithelioma (carcinoma) in children and teenagers

    SciTech Connect

    Rahbari, H.; Mehregan, A.H.

    1982-01-15

    Among over 390,000 routine dermatopathologic specimens there were 85 cases diagnosed as basal cell epithelioma (carcinoma) (BCE) in persons 19 years old or younger. This number was refined to 40 cases de novo BCE in children and teenagers. Basal cell epithelioma unrelated to other conditions is rare in the young and it should be differentiated from similar fibroepithelial growths.

  12. Vismodegib resistance in basal cell carcinoma: not a smooth fit.

    PubMed

    Ridky, Todd W; Cotsarelis, George

    2015-03-09

    In this issue of Cancer Cell, two complementary papers by Atwood and colleagues and Sharpe and colleagues show that basal cell carcinomas resistant to the Smoothened (SMO) inhibitor vismodegib frequently harbor SMO mutations that limit drug binding, with mutations at some sites also increasing basal SMO activity.

  13. Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-07-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  14. Para-toluenesulfonamide induces tongue squamous cell carcinoma cell death through disturbing lysosomal stability.

    PubMed

    Liu, Zhe; Liang, Chenyuan; Zhang, Zhuoyuan; Pan, Jian; Xia, Hui; Zhong, Nanshan; Li, Longjiang

    2015-11-01

    Para-toluenesulfonamide (PTS) has been implicated with anticancer effects against a variety of tumors. In the present study, we investigated the inhibitory effects of PTS on tongue squamous cell carcinoma (Tca-8113) and explored the lysosomal and mitochondrial changes after PTS treatment in vitro. High-performance liquid chromatography showed that PTS selectively accumulated in Tca-8113 cells with a relatively low concentration in normal fibroblasts. Next, the effects of PTS on cell viability, invasion, and cell death were determined. PTS significantly inhibited Tca-8113 cells' viability and invasive ability with increased cancer cell death. Flow cytometric analysis and the lactate dehydrogenase release assay showed that PTS induced cancer cell death by activating apoptosis and necrosis simultaneously. Morphological changes, such as cellular shrinkage, nuclear condensation as well as formation of apoptotic body and secondary lysosomes, were observed, indicating that PTS might induce cell death through disturbing lysosomal stability. Lysosomal integrity assay and western blot showed that PTS increased lysosomal membrane permeabilization associated with activation of lysosomal cathepsin B. Finally, PTS was shown to inhibit ATP biosynthesis and induce the release of mitochondrial cytochrome c. Therefore, our findings provide a novel insight into the use of PTS in cancer therapy.

  15. Oral squamous cell carcinoma. Cytometric parameters of prognostic interest.

    PubMed

    Saiz-Bustillo, Ramón; Corchero-Martín, Guadalupe; García-Montesinos-Perea, Belén; Gonzalez-Terán, Tomás; Sánchez-Santolino, Sergio

    2005-01-01

    The present study was made in order to find possible prognostic factors in oral squamous cell carcinoma, given that it is a frequent disease (3-4% of all malignant tumors) and is the cause of a high morbidity and mortality which justifies any attempt to contribute something towards the understanding of this pathology. 81 oral squamous cell carcinomas, treated with the same procedure, and retrieved from the archive of the Hospital Universitario Marqués de Valdecilla (Santander) were studied. Flow cytometry was carried out on 67 of the samples. No statistically significant differences were found between the cellular proliferative index and the mitotic index, ploidy and the S-phase factor. Likewise, none of the cytometric variables studied presented any association with the appearance of local relapse, distant metastases or survival. These variables cannot be used as a prognostic factors in squamous cell carcinomas of the oral cavity.

  16. Nuclear morphometry and chromatin textural characteristics of basal cell carcinoma.

    PubMed

    Mendaçolli, Paola Jung; Brianezi, Gabrielli; Schmitt, Juliano Vilaverde; Marques, Mariângela Esther Alencar; Miot, Hélio Amante

    2015-01-01

    Histological subtypes of basal cell carcinoma have biological, evolutionary and distinct prognostic behavior. The analysis of characteristics of the nucleus can provide data on their cellular physiology and behavior. The authors of this study evaluated nuclear morphological parameters and textural patterns of chromatin from different subtypes of basal cell carcinoma: nodular (n=37), superficial (n=28) and sclerodermiform (n=28). The parameters were compared between neoplasms' subtypes and with unaffected adjacent basal epithelium. Nuclear area and diameter of sclerodermiform neoplasms were superior to the other subtypes. Chromatin's color intensity and fractal dimension were less intense in superficial subtypes. Nuclear roundness and chromatin's entropy presented lower values in tumors than in normal epithelium. There was significant correlation between morphological and textural variables of normal skin and tumors. Morphometric elements and textural chromatin's homogeneity of basal cell carcinomas may be related to evolutionary, biological and behavior particularities related to each histotype.

  17. Case report: microcystic transitional cell carcinoma of the urinary bladder.

    PubMed

    Radopoulos, Demetrios; Kalyvas, Konstantinos; Kotakidou, Rodi; Panagiotopoulou, Konstantina; Katsikas, Vasilios; Papathanasiou, Michalis

    2005-01-01

    We report a rare case of microcystic transitional cell carcinoma involving the urinary bladder, in a 38-year-old man, and we add our experience in the treatment of this neoplasm. The tumor was muscle invasive, and a radical cystectomy was performed. The patient received no postoperative chemotherapy or radiotherapy, and he has not signs of local recurrence or distal metastasis after 3 years of intense follow up. Even though the number of cases documented so far, is insufficient to draw safe conclusions regarding the optimal treatment of the microcystic variant of transitional cell carcinoma. Our case indicates that even in cases of microcystic transitional cell carcinoma with infiltrative nature, aggressive therapy is associated with good control of the disease locally and distally.

  18. Primary invasive ocular squamous cell carcinoma in a horse.

    PubMed

    Kaps, Simone; Richter, Marianne; Philipp, Martin; Bart, Madeleine; Eule, Corinna; Spiess, Bernhard M

    2005-01-01

    A 12-year-old Haflinger gelding was presented to the veterinary medical teaching hospital of the University of Zurich with a light-pink raised mass on the temporal limbus and conjunctiva of the left eye. Squamous cell carcinoma was confirmed histologically after keratectomy and cryotherapy. Seven months later, a smooth pink, progressively enlarging mass was observed within the cornea of the left eye. Ultrasonographically, the mass was not only infiltrating the corneal stroma but seemed to protrude into the anterior chamber. The globe was surgically removed and submitted for pathology. A histologic diagnosis of corneal ocular squamous cell carcinoma with deep stromal invasion, infiltration of the uveoscleral meshwork and iridocorneal angle and resulting intraocular extension was made. This is the first detailed description of a limbal squamous cell carcinoma with invasion into the cornea and uvea in the horse.

  19. Nuclear morphometry and chromatin textural characteristics of basal cell carcinoma*

    PubMed Central

    Mendaçolli, Paola Jung; Brianezi, Gabrielli; Schmitt, Juliano Vilaverde; Marques, Mariângela Esther Alencar; Miot, Hélio Amante

    2015-01-01

    Histological subtypes of basal cell carcinoma have biological, evolutionary and distinct prognostic behavior. The analysis of characteristics of the nucleus can provide data on their cellular physiology and behavior. The authors of this study evaluated nuclear morphological parameters and textural patterns of chromatin from different subtypes of basal cell carcinoma: nodular (n=37), superficial (n=28) and sclerodermiform (n=28). The parameters were compared between neoplasms' subtypes and with unaffected adjacent basal epithelium. Nuclear area and diameter of sclerodermiform neoplasms were superior to the other subtypes. Chromatin's color intensity and fractal dimension were less intense in superficial subtypes. Nuclear roundness and chromatin's entropy presented lower values in tumors than in normal epithelium. There was significant correlation between morphological and textural variables of normal skin and tumors. Morphometric elements and textural chromatin's homogeneity of basal cell carcinomas may be related to evolutionary, biological and behavior particularities related to each histotype. PMID:26734870

  20. Familial renal cell carcinoma: clinical and molecular genetic aspects

    PubMed Central

    Maher, E.R.; Yates, J.R.W.

    1991-01-01

    Renal cell carcinoma (RCC) accounts for 2% of all human cancer, but familial cases are infrequent. Riches (1963) and Griffin et al. (1984) in a population-based case-control study found a family history of renal cell carcinoma in 2.4% of affected patients compared to 1.4% of controls. Nevertheless the importance of inherited tumours in clinical practice and medical research is disproportionate to their frequency. In clinical practice recognition of familial RCC can provide opportunities to prevent morbidity and mortality by appropriate screening. In medical research recent advances in molecular genetics offer the prospect of isolating the genes involved in the pathogenesis of familial RCC and of the more common sporadic cases. In this article we review the clinical and molecular genetics of inherited renal cell carcinoma (adenocarcinoma or hypernephroma). PMID:1997093

  1. Expansion of CCR8+ inflammatory myeloid cells in cancer patients with urothelial and renal carcinomas

    PubMed Central

    Eruslanov, Evgeniy; Stoffs, Taryn; Kim, Wan-Ju; Daurkin, Irina; Gilbert, Scott M.; Su, Li-Ming; Vieweg, Johannes; Daaka, Yehia; Kusmartsev, Sergei

    2013-01-01

    Purpose Chemokines are involved in cancer-related inflammation and malignant progression. In this study we evaluated expression of CCR8 and its natural cognate ligand CCL1 in patients with urothelial carcinomas of bladder and renal cell carcinomas. Experimental Design We examined CCR8 expression in peripheral blood and tumor tissues from patients with bladder and renal carcinomas. CCR8-positive myeloid cells were isolated from cancer tissues with magnetic beads and tested in vitro for cytokine production and ability to modulate T cell function. Results We demonstrate that monocytic and granulocytic myeloid cell subsets in peripheral blood of cancer patients with urothelial and renal carcinomas display increased expression of chemokine receptor CCR8. Up-regulated expression of CCR8 is also detected within human cancer tissues and primarily limited to tumor-associated macrophages (TAMs). When isolated, CD11b+CCR8+ cell subset produces the highest levels of pro-inflammatory and pro-angiogenic factors among intratumoral CD11b myeloid cells. Tumor-infiltrating CD11b+CCR8+ cells selectively display activated Stat3 and are capable of inducing FoxP3 expression in autologous T lymphocytes. Primary human tumors produce substantial amounts of the natural CCR8 ligand CCL1. Conclusions This study provides the first evidence that CCR8+ myeloid cell subset is expanded in cancer patients. Elevated secretion of CCL1 by tumors, increased presence of CCR8+ myeloid cells in peripheral blood and cancer tissues indicate that CCL1/CCR8 axis is a component of cancer-related inflammation and may contribute to immune evasion. Obtained results also implicate that blockade of CCR8 signals may provide an attractive strategy for therapeutic intervention in human urothelial and renal cancers. PMID:23363815

  2. Computational Modelling of Metastasis Development in Renal Cell Carcinoma

    PubMed Central

    Baratchart, Etienne; Benzekry, Sébastien; Bikfalvi, Andreas; Colin, Thierry; Cooley, Lindsay S.; Pineau, Raphäel; Ribot, Emeline J; Saut, Olivier; Souleyreau, Wilfried

    2015-01-01

    The biology of the metastatic colonization process remains a poorly understood phenomenon. To improve our knowledge of its dynamics, we conducted a modelling study based on multi-modal data from an orthotopic murine experimental system of metastatic renal cell carcinoma. The standard theory of metastatic colonization usually assumes that secondary tumours, once established at a distant site, grow independently from each other and from the primary tumour. Using a mathematical model that translates this assumption into equations, we challenged this theory against our data that included: 1) dynamics of primary tumour cells in the kidney and metastatic cells in the lungs, retrieved by green fluorescent protein tracking, and 2) magnetic resonance images (MRI) informing on the number and size of macroscopic lesions. Critically, when calibrated on the growth of the primary tumour and total metastatic burden, the predicted theoretical size distributions were not in agreement with the MRI observations. Moreover, tumour expansion only based on proliferation was not able to explain the volume increase of the metastatic lesions. These findings strongly suggested rejection of the standard theory, demonstrating that the time development of the size distribution of metastases could not be explained by independent growth of metastatic foci. This led us to investigate the effect of spatial interactions between merging metastatic tumours on the dynamics of the global metastatic burden. We derived a mathematical model of spatial tumour growth, confronted it with experimental data of single metastatic tumour growth, and used it to provide insights on the dynamics of multiple tumours growing in close vicinity. Together, our results have implications for theories of the metastatic process and suggest that global dynamics of metastasis development is dependent on spatial interactions between metastatic lesions. PMID:26599078

  3. Osteopontin Facilitates Ultraviolet B-induced Squamous Cell Carcinoma Development

    PubMed Central

    Chang, Pi-Ling; Hsieh, Yu-Hua; Wang, Chao-Cheng; Juliana, M. Margaret; Tsuruta, Yuko; Timares, Laura; Elmets, Craig; Ho, Kang-Jey

    2014-01-01

    Background Osteopontin (OPN) is a matricellular glycoprotein that is markedly expressed in cutaneous squamous cell carcinomas (cSCCs) and in actinic keratoses implicating its role in photocarcinogenesis. Objective To determine whether OPN facilitates the development of cSCC and its function. Methods cSCCs development was compared between wild-type (WT) and OPN-null mice subjected to UVB irradiation for 43 weeks. UVB-induced OPN expression was determined by Western blot, immunoprecipitation, ELISA, and semi-quantitative RT-PCR. Epidermal layer and TUNEL analyses assessed if OPN mediates UVB-induced epidermal hyperplasia or suppresses UVB-induced apoptosis of basal keratinocytes, respectively. In vitro experiments determined whether OPN enhances cell survival of UVB-induced apoptosis and its potential mechanisms. Immunohistochemical analyses of epidermis assessed the expression of CD44 and focal adhesion kinase (FAK), molecules that mediate OPN survival function. Results Compared to female WT mice, OPN-null mice did not develop cSCCs. UVB irradiation stimulated OPN protein expression in the dorsal skin by 11 h and remains high at 24 to 48h.OPN did not mediate UVB-induced epidermal hyperplasia; instead, it protected basal keratinocytes from undergoing apoptosis upon UVB exposure. Likewise, the addition of OPN suppressed UVB-induced OPN-null cSCC cell apoptosis, the activation of caspase-9 activity, and increased phosphorylation of FAK at Y397. Furthermore, the expression of CD44 and FAK in WT mice epidermis was greater than that of OPN-null mice prior to and during early acute UVB exposure. Conclusion These data support the hypothesis that chronic UVB-induced OPN expression protects the survival of initiated basal keratinocytes and, consequently, facilitates cSCC develop. PMID:24888687

  4. Computational Modelling of Metastasis Development in Renal Cell Carcinoma.

    PubMed

    Baratchart, Etienne; Benzekry, Sébastien; Bikfalvi, Andreas; Colin, Thierry; Cooley, Lindsay S; Pineau, Raphäel; Ribot, Emeline J; Saut, Olivier; Souleyreau, Wilfried

    2015-11-01

    The biology of the metastatic colonization process remains a poorly understood phenomenon. To improve our knowledge of its dynamics, we conducted a modelling study based on multi-modal data from an orthotopic murine experimental system of metastatic renal cell carcinoma. The standard theory of metastatic colonization usually assumes that secondary tumours, once established at a distant site, grow independently from each other and from the primary tumour. Using a mathematical model that translates this assumption into equations, we challenged this theory against our data that included: 1) dynamics of primary tumour cells in the kidney and metastatic cells in the lungs, retrieved by green fluorescent protein tracking, and 2) magnetic resonance images (MRI) informing on the number and size of macroscopic lesions. Critically, when calibrated on the growth of the primary tumour and total metastatic burden, the predicted theoretical size distributions were not in agreement with the MRI observations. Moreover, tumour expansion only based on proliferation was not able to explain the volume increase of the metastatic lesions. These findings strongly suggested rejection of the standard theory, demonstrating that the time development of the size distribution of metastases could not be explained by independent growth of metastatic foci. This led us to investigate the effect of spatial interactions between merging metastatic tumours on the dynamics of the global metastatic burden. We derived a mathematical model of spatial tumour growth, confronted it with experimental data of single metastatic tumour growth, and used it to provide insights on the dynamics of multiple tumours growing in close vicinity. Together, our results have implications for theories of the metastatic process and suggest that global dynamics of metastasis development is dependent on spatial interactions between metastatic lesions.

  5. Renal cell carcinoma metastatic to a pituitary FSH/LH adenoma: case report and review of the literature.

    PubMed

    Magnoli, Francesca; Finzi, Giovanna; Riva, Cristina; Capella, Carlo

    2014-12-01

    Abstract Metastases to the pituitary occur more frequently in patients with widespread cancer and mainly involve the posterior lobe. A few cases of metastatic carcinoma to a pituitary adenoma have been described so far. Here, the authors present an additional case of a clear cell renal cell carcinoma (CCRCC) metastatic to a FSH/LH/α-subunit pituitary adenoma and systematically review the literature. Immunohistochemistry and electron microscopy were performed to characterize both neoplastic components at the morphological level. Moreover, it was hypothesized that expression of VEGF and of the corresponding receptor VEGFR1 could be implicated in the development of the carcinomatous metastasis within the adenoma.

  6. Are primary renal cell carcinoma and metastases of renal cell carcinoma the same cancer?

    PubMed

    Semeniuk-Wojtaś, Aleksandra; Stec, Rafał; Szczylik, Cezary

    2016-05-01

    Metastasis is a process consisting of cells spreading from the primary site of the cancer to distant parts of the body. Our understanding of this spread is limited and molecular mechanisms causing particular characteristics of metastasis are still unknown. There is some evidence that primary renal cell carcinoma (RCC) and metastases of RCC exhibit molecular differences that may effect on the biological characteristics of the tumor. Some authors have detected differences in clear cell and nonclear cell component between these 2 groups of tumors. Investigators have also determined that primary RCC and metastases of RCC diverge in their range of renal-specific markers and other protein expression, gene expression pattern, and microRNA expression. There are also certain proteins that are variously expressed in primary RCCs and their metastases and have effect on clinical outcome, e.g., endothelin receptor type B, phos-S6, and CD44. However, further studies are needed on large cohorts of patients to identify differences representing promising targets for prognostic purposes predicting disease-free survival and the metastatic burden of a patient as well as their suitability as potential therapeutic targets. To sum up, in this review we have attempted to summarize studies connected with differences between primary RCC and its metastases and their influence on the biological characteristics of renal cancer.

  7. An unusual combined thymic carcinoma composed of squamous cell carcinoma and type AB thymoma: a rare case report.

    PubMed

    Jiang, Yufeng; Liu, Yang; Shi, Xiuying; Mao, Xiaoyun; Zhao, Yang; Fan, Chuifeng

    2017-01-17

    Combined thymic carcinoma is a malignant neoplasm of the thymus recently added to the 4th edition of the World Health Organization (WHO) classification of tumors of the lung, pleura, thymus and heart. It involves at least one type of thymic carcinoma and another thymic epithelial tumor. The previously used term "combined thymic epithelial tumor" has been abandoned. Here, we present an unusual case of combined thymic carcinoma of the thymus in a 44-year-old male who had suffered from fever, chest pain, chest tightness and shortness of breath. Magnetic resonance imaging (MRI) detected a mass approximately 6.4 cm × 4.2 cm in the anterior mediastinum, and a nonencapsulated tumor approximately 5.0 cm × 3.5 cm × 2.5 cm with an irregular shape was resected. The morphological features and the immunostaining pattern of the tumor revealed it to be an unusual combined thymic carcinoma consisting of type AB thymoma and squamous cell carcinoma. There were cysts of various sizes, some of which had crack-like structures, in the type AB thymoma area. A gradual transition could be seen between these structures and the squamous cell carcinoma, indicating that the carcinoma portion may have originated from the composition of the thymoma. Combined thymic carcinoma composed of type AB thymoma and squamous cell carcinoma is rare, and the carcinoma portion may have originated from epithelial structures in the type AB thymoma.

  8. Percutaneous radiofrequency ablation of renal cell carcinoma.

    PubMed

    Chiou, Yi-You; Hwang, Jen-I; Chou, Yi-Hong; Wang, Jia-Hwia; Chiang, Jen-Huey; Chang, Cheng-Yen

    2005-05-01

    Preliminary data regarding the use of percutaneous radiofrequency ablation (RFA) for the treatment of renal cell carcinoma (RCC) are encouraging, and show the technique to be associated with minimal morbidity. Thus, the current study was designed to evaluate the clinical applications, treatment efficacy, and complications of percutaneous RFA in RCC. From February 2003 to February 2004, 12 consecutive patients with histopathologically proven RCC underwent imaging-guided percutaneous RFA. The mean age of the patients (8 men and 4 women) was 76 years (range, 56-87 years), and mean tumor diameter was 3.7 cm (range, 2.2-8.0 cm). The efficacy of RFA was evaluated with contrast-enhanced, dynamic computed tomography (CT) performed 1 month after treatment, and then every 3 months. A Radionics device with an internally cooled electrode was used in 7 patients, and a radiofrequency interstitial tissue ablation (RITA) device with an expandable needle electrode was used in 5. Complete necrosis was defined as a lack of contrast enhancement in the treated region on follow-up CT studies. Overall, 16 sessions of RFA were performed for 12 solitary renal tumors in 12 patients: 8 patients underwent a single RFA session, whereas 4 had 2 sessions. Dynamic CT after RFA showed complete necrosis in 9 of 12 tumors. In 3 patients with tumors of 4.5-8.0 cm in diameter, enhancement of residual tissue was observed after RFA treatment, thus indicating residual tumor. Complete tumor necrosis was seen in all 5 tumors (100%) of diameter < or = 3.0 cm; 3 of 4 tumors (75%) of diameter 3.1-5.0 cm; and 1 of 3 tumors (33%) of diameter > 5.0 cm. A big subcapsular hematoma, which was found in 1 patient after RFA, resolved completely within 10 months without treatment; no serious complications occurred in the other 11 patients. Percutaneous RFA is effective in the treatment of RCC. It is most successful for tumors not larger than 3 cm in diameter, and has a satisfactory success rate in tumors of 3-5 cm in

  9. CT findings of small cell lung carcinoma

    PubMed Central

    Lee, Dongjun; Rho, Ji Young; Kang, Seunghun; Yoo, Koun Joy; Choi, Hye Jeong

    2016-01-01

    Abstract The purpose of this study was to clarify the recognizable computed tomography (CT) features of small cell lung carcinoma (SCLC). Contrast enhanced CT scans were reviewed retrospectively for mass location, mediastinal extension, and other concomitant findings in 142 patients with pathologically proven SCLC. SCLC was classified into hilar mass only (type I), hilar mass with ipsilateral mediastinal extension (type II), hilar mass with bilateral mediastinal extension (type III), and peripheral mass (type IV). When mediastinal lymphadenopathy (m-LAP) was indistinguishable from a hilar mass, we defined it as a mediastinal conglomerate mass (m-CM). Type IIa or IIIa had ipsilateral or bilateral m-LAP and type IIb, IIIb or IIIc had ipsilateral or bilateral m-CM. Type I (n = 8, 5.6%), type II (n = 58, 40.8%), type III (n = 55, 38.8%), and type IV (n = 21, 14.8%) were manifested. The combination of a hilar mass and m-CM was found in 68 patients (47.9%). Type IV masses showed lobulation in 11, microlobulation in 4, both lobulated and irregular margins in 4, and spiculation in 2. A total of 120 patients (84.5%) had a bronchial stenosis/obstruction; single (n = 52) and 2 or more (n = 68). Ninety-five patients (67.0%) had vascular invasion including main/lobar pulmonary artery and superior vena cava, and 55 (38.7%) had pleural effusion and/or pleural nodules. Concomitant parenchymal findings (n = 92, 64.8%) were noted: contiguous consolidation/nodule (n = 45), hematogeneous spread (n = 32), lymphangitic spread (n = 21), obstructive pneumonia (n = 22), and obstructive atelectasis (n = 14). In conclusion, the recognizable CT features of SCLC were a hilar mass with m-CM. Most of the hilar masses showed 2 or more bronchial stenoses/obstructions. Most cases of peripheral SCLC manifested as a lobulated mass rather than a spiculated mass. Vascular invasion and concomitant parenchymal findings were observed commonly. PMID:27893684

  10. Clinicopathological characteristics of distant metastases of adenocarcinoma, squamous cell carcinoma and urothelial carcinoma: An autopsy study of older Japanese patients.

    PubMed

    Matsuda, Yoko; Seki, Atsuko; Nonaka, Keisuke; Kakizaki, Mototsune; Wang, Tan; Aida, Junko; Ishikawa, Naoshi; Nakano, Yuta; Kaneda, Daita; Takata, Tadayuki; Takahashi-Fujigasaki, Junko; Murayama, Shigeo; Takubo, Kaiyo; Ishiwata, Toshiyuki; Sawabe, Motoji; Arai, Tomio

    2017-09-15

    We aimed to clarify the characteristics of malignancies in older adults focusing on distant metastasis in the whole body. We retrospectively evaluated 7710 cases of autopsies (4011 men, 3699 women, median age of 80 years), and analyzed the characteristics of metastasis of adenocarcinoma, squamous cell carcinoma and urothelial carcinoma in each organ. The total number of cases with adenocarcinoma, squamous cell carcinoma or urothelial carcinoma was 2856, and most of them were adenocarcinomas. Among them, 1604 had metastatic lesions, and patients with metastasis were younger than those without metastasis. The major primary organs of adenocarcinoma were the stomach, colon, lung, prostate, gallbladder and pancreas, whereas those for squamous cell carcinoma were the lung, esophagus and uterus. Urothelial carcinoma cases were found in the urinary bladder, kidney and ureter. Metastatic adenocarcinomas mainly originated from the stomach, colon, lung, pancreas and gallbladder. Metastatic squamous cell carcinomas were from the lung, esophagus and uterus, whereas the kidney, bladder and ureter were the primary origins of metastatic urothelial carcinomas. Squamous cell carcinoma showed the highest incidence of metastasis, suggestive of it being of an aggressive phenotype. Furthermore, metastatic ability and the preferred metastatic sites varied among primary organs. We revealed an accurate incidence and the characteristics of metastatic cancer in a large-scale autopsy study of older Japanese patients from one institution. Identifying these features might prompt screening for malignancies, and consequently improve quality of life for older adults. Geriatr Gerontol Int 2017; ••: ••-••. © 2017 Japan Geriatrics Society.

  11. Oblimersen in Treating Patients With Merkel Cell Carcinoma

    ClinicalTrials.gov

    2013-06-03

    Recurrent Neuroendocrine Carcinoma of the Skin; Stage I Neuroendocrine Carcinoma of the Skin; Stage II Neuroendocrine Carcinoma of the Skin; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Neuroendocrine Carcinoma of the Skin

  12. Focus Issue: Neck Dissection for Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    Van Abel, Kathryn M.; Moore, Eric J.

    2012-01-01

    The staging and prognosis of oropharyngeal squamous cell carcinoma is intimately tied to the status of the cervical lymph nodes. Due to the high risk for occult nodal disease, most clinicians recommend treating the neck for these primary tumors. While there are many modalities available, surgical resection of nodal disease offers both a therapeutic and a diagnostic intervention. We review the relevant anatomy, nodal drainage patterns, clinical workup, surgical management and common complications associated with neck dissection for oropharyngeal squamous cell carcinoma. PMID:22586518

  13. Unexpected Anal Squamous Cells Carcinoma after Open Hemorrhoidectomy

    PubMed Central

    Luca, Navarra; Valentina, Abruzzese; Federico, Sista; Renato, Pietroletti

    2015-01-01

    We report a case of unexpected anal squamous cells carcinoma found in hemorrhoidectomy specimen. The patient had a 3-year history of prolapsing hemorrhoids. A prolapsing hemorrhoid was present at eleven o'clock in lithotomy. Milligan-Morgan was performed and gross examination of the specimen was unremarkable. Histopathologic evaluation showed noninvasive squamous cells carcinoma. The present case report evidences the opportunity of routine histopathologic analysis of hemorrhoidal specimens particularly in case of long-standing prolapse. Questions arise in the option of those techniques where no specimens are collected or tissue is excised far from deceased area. PMID:25922781

  14. Tubulocystic Renal Cell Carcinoma: A Rare Renal Tumor

    PubMed Central

    Bindroo, Sandiya; Varshney, Neha; Mittal, Vijay

    2014-01-01

    Tubulocystic renal cell carcinoma of the kidney is a rare entity with less than one hundred cases reported so far. It was previously considered to have some similarities to various other renal cancers although this tumor has distinct macroscopic, microscopic and immuno-histochemical features. It is now a well-established entity in renal neoplastic pathology and has been recognized as a distinct entity in the 2012 Vancouver classification of renal tumors. This review aims to give an overview of tubulocystic renal cell carcinoma after extensive literature search using PubMed and CrossRef.

  15. HPV-Related Head and Neck Squamous Cell Carcinomas.

    PubMed

    Marszałek, Andrzej; Szylberg, Łukasz

    Since more than 5 years, it becomes evident that there is a new group of patients with squamous cell carcinomas of the head and neck area, namely human papillomavirus (HPV)-related (caused) tumors. As clinical statistics indicate, those patients have better prognosis, even despite more advanced stage compared to those with HPV-negative tumors. In fact, as a surrogate of HPV infection for clinical studies, an immunohistochemical expression of p16 protein is used. In the following chapter, the spectrum of squamous cell carcinomas variants with indication of the percentage cases with proved HPV infection will be presented.

  16. Basal cell carcinoma in two Hermann's tortoises (Testudo hermanni).

    PubMed

    Hellebuyck, Tom; Ducatelle, Richard; Bosseler, Leslie; Van Caelenberg, Annemie; Versnaeyen, Han; Chiers, Koen; Martel, An

    2016-11-01

    Neoplastic disorders are frequently encountered in the practice of reptile medicine. Herein we report the clinical behavior, antemortem diagnosis, and histopathologic characteristics of a recurrent intraoral keratinizing basal cell carcinoma (BCC) and a metastatic BCC of the carapace in 2 Hermann's tortoises (Testudo hermanni). Although squamous cell carcinomas (SCCs) in tortoises show similar predilection sites and gross pathologic features, the BCCs described in our report were characterized by a remarkably fast and highly infiltrative growth in comparison to SCCs. Accordingly, early diagnosis including reliable discrimination from SCC is essential toward the management of this neoplastic entity in tortoises. © 2016 The Author(s).

  17. Squamous cell carcinoma arising in a multiple verrucous epidermal nevus*

    PubMed Central

    Yarak, Samira; Machado, Taila Yuri Siqueira; Ogawa, Marilia Marufuji; Almeida, Mirian Luzia da Silva; Enokihara, Milvia Maria Simões e Silva; Porro, Adriana Maria

    2016-01-01

    Verrucous epidermal nevi are hamartomatous lesions of the epidermis that, unlike other epidermal nevi (such as sebaceous nevus or nevus comedonicus), are rarely associated with malignant neoplasms. The majority of squamous cell carcinoma develop in linear or multiple epidermal nevus and rarely in solitary epidermal nevus. In general, the prognosis is favorable. We report a case of well-differentiated invasive squamous cell carcinoma arising from a multiple verrucous epidermal nevus. Although there is no consensus on prophylactic removal of epidermal nevus, its removal and biopsy should be considered if changes occur. PMID:28300931

  18. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    SciTech Connect

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang Zhang, Yi

    2013-11-01

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.

  19. Immunohistochemical characterization of mammary squamous cell carcinoma of the dog.

    PubMed

    Sassi, Francesco; Sarli, Giuseppe; Brunetti, Barbara; Morandi, Federico; Benazzi, Cinzia

    2008-11-01

    Squamous cell carcinoma of the mammary gland is rare in both veterinary and human medicine. Whereas human metaplastic and squamous variants are known, the objectives of the current study were to ascertain the presence of such entities in canine mammary tumors and to distinguish them from other (epidermal, sweat gland) squamous tumors that may develop in the same area. A panel of antibodies (anti-cytokeratin [CK] 19, CK 14, CK 5/6, pancytokeratin, and vimentin) was used on 18 mammary gland malignancies with squamous features and 16 malignant skin tumors (11 squamous cell carcinomas of the skin and 5 sweat glands). Fifteen of the 18 mammary carcinomas were classified as metaplastic carcinomas, and the remaining 3 were classified as squamous cell carcinomas. The 2 most useful markers to establish the histogenesis of mammary tumors were pancytokeratin and CK 19. All other antibodies were equally expressed (CK 14 and 5/6) in all histotypes. The antibody panel discriminated primary epidermal squamous tumors (pancytokeratin positive and CK 19 negative) from gland-derived squamous neoplasms (pancytokeratin positive and CK 19 positive) but failed to distinguish primary mammary tumors from other squamous tumors of glandular origin.

  20. Renal cell carcinoma in functional renal graft: Toward ablative treatments.

    PubMed

    Tillou, Xavier; Guleryuz, Kerem; Collon, Sylvie; Doerfler, Arnaud

    2016-01-01

    The occurrence of a kidney transplant tumor is a rare but serious issue with a double risk: the return to dialysis and the development of metastatic cancer. Publications on this topic are mainly case reports. The purpose of this review was to report an exhaustive literature review of functional graft renal cell carcinomas to highlight the impact of tumors on the renal graft outcomes. 201 de novo renal carcinomas in functional renal grafts from 69 publications were included. Incidence was estimated at 0.18%. Graft tumors were mostly asymptomatic (85.9%). Whatever the discovery circumstances of graft tumors, they were mostly documented by graft ultrasounds supplemented by CT-scanning or MR imaging. Nephron sparing surgery (95 patients) was the first treatment performed followed by radiofrequency ablation (38 patients) and cryotherapy (10 patients). The most common tumor graft histology was clear cell carcinoma (46.4%), followed by papillary carcinoma (43.7%). Specific mortality was 2.9% with 6 deaths. Renal graft cell carcinoma is a rare pathology with a low specific death. When possible, conservative treatment should be the first choice. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Vismodegib and the hedgehog pathway: a new treatment for basal cell carcinoma.

    PubMed

    Cirrone, Frank; Harris, Christy S

    2012-10-01

    Vismodegib is an oral inhibitor of the Hedgehog pathway approved by the US Food and Drug Administration. It is the first systemic treatment for patients with locally advanced or metastatic basal cell carcinoma that is not amenable to surgery and radiation. This is the first drug to use the Hedgehog pathway to inhibit the proliferation of tumors and is also implicated in the development of other cancers such as medulloblastoma. The goal of this review was to summarize the development, pharmacology, efficacy, and safety of vismodegib. Relevant English-language literature was identified and then evaluated based on results from database searches of MEDLINE and EMBASE from 1975 to June 19, 2012. The terms searched included, but were not limited to, vismodegib, Erivedge, GDC-0449, basal cell carcinoma, and 2-chloro-N-[4-chloro-3-(pyridin-2-yl)phenyl]-4-(methylsulfonyl)benzamide. Additional literature was identified by assessing the reference lists of previously identified articles and through abstracts presented by the American Society of Clinical Oncology. A total of 70 full text citations were identified although two national conference proceedings were then excluded. An additional 10 published abstracts were also identified. A Phase II, nonrandomized, multicenter, international study demonstrated a 30.3% objective response rate in metastatic basal cell carcinoma and a 42.9% objective response rate in locally advanced basal cell carcinoma. The adverse effect profile for vismodegib is similar to other identified Hedgehog pathway inhibitors; muscle cramps (71.7%), alopecia (63.8%), and dysgeusia (55.1%) were the most common adverse effects seen in trials. A Phase II, randomized, placebo-controlled trial in Gorlin syndrome patients with basal cell carcinoma concluded that vismodegib was significantly better than placebo at reducing new basal cell carcinoma lesions (P < 0.001) and at decreasing the sum of the longest diameter of existing lesions (P = 0.003). For patients

  2. Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma.

    PubMed

    Nagata, Masayoshi; Sakurai-Yageta, Mika; Yamada, Daisuke; Goto, Akiteru; Ito, Akihiko; Fukuhara, Hiroshi; Kume, Haruki; Morikawa, Teppei; Fukayama, Masashi; Homma, Yukio; Murakami, Yoshinori

    2012-03-15

    Renal clear cell carcinoma (RCCC) is the most frequent subpopulation of renal cell carcinoma and is derived from the proximal uriniferous tubules. We have previously reported that an actin-binding protein, 4.1B/DAL-1, is expressed in renal proximal tubules, whereas it is inactivated in 45% of RCCC by promoter methylation. In the lung and several epithelial tissues, 4.1B is shown to associate with a tumor suppressor protein, CADM1, belonging to the immunoglobulin-superfamily cell adhesion molecules. Here, we demonstrate by immunohistochemistry that another member of the CADM-family protein, CADM4, as well as 4.1B is expressed specifically in human proximal tubules, while CADM1 and 4.1N, another member of the 4.1 proteins, are expressed in the distal tubules. Immunoprecipitation analysis coupled with Western blotting revealed that CADM4 associated with 4.1B, while CADM1 associated with 4.1N in the lysate from normal human kidney, implicating that a cascade of CADM4 and 4.1B plays an important role in normal cell adhesion of the proximal tubules. On the other hand, CADM4 expression was lost or markedly reduced in 7 of 10 (70%) RCC cell lines and 28 of 40 (70%) surgically resected RCCC, including 10 of 16 (63%) tumors with T1a. CADM4 expression was more preferentially lost in RCCC with vascular infiltration (p = 0.04), suggesting that loss of CADM4 is involved in tumor invasion. Finally, introduction of CADM4 into an RCC cell line, 786-O, dramatically suppressed tumor formation in nude mice. These findings suggest that CADM4 is a novel tumor suppressor candidate in RCCC acting with its binding partner 4.1B. Copyright © 2011 UICC.

  3. Existence of a squamous cell carcinoma antigen-immunoglobulin complex causes a deviation between squamous cell carcinoma antigen concentrations determined using two different immunoassays: first report of squamous cell carcinoma antigen coupling with immunoglobulin A.

    PubMed

    Mori, Eriko; Kurano, Makoto; Tobita, Akiko; Shimosaka, Hironori; Yatomi, Yutaka

    2017-01-01

    Background Squamous cell carcinoma antigen is used as a tumour marker and is routinely measured in clinical laboratories. We validated two different immunoassays and found three cases in which the squamous cell carcinoma antigen concentrations deviated greatly between the two immunoassays. Here, we aimed to elucidate the mechanisms responsible for these deviations. Methods The squamous cell carcinoma antigen concentrations were determined using the ARCHITECT SCC (CLIA method) and the ST AIA-PACK SCC (FEIA method). We performed polyethylene glycol precipitation and size exclusion chromatography to assess the molecular weight and spike recovery and absorption tests to examine the presence of an autoantibody. Results Both methods exhibited good performances for the measurement of squamous cell carcinoma antigen, although a correlation test showed large differences in the squamous cell carcinoma antigen concentrations measured using the two methods in three cases. The results of polyethylene glycol treatment and size exclusion chromatography indicated the existence of a large molecular weight squamous cell carcinoma antigen in these three cases. The spike recovery tests suggested the possible presence of an autoantibody against squamous cell carcinoma antigen. Moreover, the absorption test revealed that large squamous cell carcinoma antigen complexes were formed by the association of squamous cell carcinoma antigen with IgG in two cases and with both IgG and IgA in one case. Conclusions This study describes the existence of large molecular weight squamous cell carcinoma antigen that has complexed with immunoglobulin in the serum samples. The reason for the deviations between the two immunoassays might be due to differences of their reactivities against the squamous cell carcinoma antigen immune complexes with their autoantibody. To our knowledge, this is the first report to describe the coupling of squamous cell carcinoma antigen with IgA.

  4. Multiple skin cancers in a single patient: Multiple pigmented Bowen's disease, giant basal cell carcinoma, squamous cell carcinoma.

    PubMed

    Saini, Ravi; Sharma, Nidhi; Pandey, Kritika; Puri, K J P S

    2015-01-01

    Basal cell carcinoma (BCC) and squamous cell carcinoma are the most common type of nonmelanoma skin cancers (NMSCs). Bowen's disease (BD), a premalignant condition, has a marginal potential (3-5%) to progress to invasive carcinoma. We report here a rarest of a rare case of multiple pigmented BD with overlying squamous cell cancer along with a giant neglected BCC on the scalp of a 76-year-old man. The occurrence of multiple BD and NMSC in a single patient compelled us to explore the following hypothesis: (1) The multiple precancerous and cancerous lesions can be due to common etiopathogenesis. Chronic ultraviolet exposure, immunosupresssion, human papillomavirus infection, dietary factors, and environmental factors including arsenic exposure were probed in to. (2) There is evolution of precancerous lesions into a different type of cancers in different time frame. (3) The new cancerous lesions are subsequent cancers that developed after neglected untreated primary cancer.

  5. Tumor necrosis factor-{alpha} enhanced fusions between oral squamous cell carcinoma cells and endothelial cells via VCAM-1/VLA-4 pathway

    SciTech Connect

    Song, Kai; Zhu, Fei; Zhang, Han-zhong; Shang, Zheng-jun

    2012-08-15

    Fusion between cancer cells and host cells, including endothelial cells, may strongly modulate the biological behavior of tumors. However, no one is sure about the driving factors and underlying mechanism involved in such fusion. We hypothesized in this study that inflammation, one of the main characteristics in tumor microenvironment, serves as a prominent catalyst for fusion events. Our results showed that oral cancer cells can fuse spontaneously with endothelial cells in co-culture and inflammatory cytokine tumor necrosis factor-{alpha} (TNF-{alpha}) increased fusion of human umbilical vein endothelium cells and oral cancer cells by up to 3-fold in vitro. Additionally, human oral squamous cell carcinoma cell lines and 35 out of 50 (70%) oral squamous carcinoma specimens express VLA-4, an integrin, previously implicated in fusions between human peripheral blood CD34-positive cells and murine cardiomyocytes. Expression of VCAM-1, a ligand for VLA-4, was evident on vascular endothelium of oral squamous cell carcinoma. Moreover, immunocytochemistry and flow cytometry analysis revealed that expression of VCAM-1 increased obviously in TNF-{alpha}-stimulated endothelial cells. Anti-VLA-4 or anti-VCAM-1 treatment can decrease significantly cancer-endothelial adhesion and block such fusion. Collectively, our results suggested that TNF-{alpha} could enhance cancer-endothelial cell adhesion and fusion through VCAM-1/VLA-4 pathway. This study provides insights into regulatory mechanism of cancer-endothelial cell fusion, and has important implications for the development of novel therapeutic strategies for prevention of metastasis. -- Highlights: Black-Right-Pointing-Pointer Spontaneous oral cancer-endothelial cell fusion. Black-Right-Pointing-Pointer TNF-{alpha} enhanced cell fusions. Black-Right-Pointing-Pointer VCAM-1/VLA-4 expressed in oral cancer. Black-Right-Pointing-Pointer TNF-{alpha} increased expression of VCAM-1 on endothelial cells. Black

  6. Rapid induction of senescence in human cervical carcinoma cells

    NASA Astrophysics Data System (ADS)

    Goodwin, Edward C.; Yang, Eva; Lee, Chan-Jae; Lee, Han-Woong; Dimaio, Daniel; Hwang, Eun-Seong

    2000-09-01

    Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.

  7. Expression of ZNF396 in basal cell carcinoma.

    PubMed

    Bai, Juncheng; Kito, Yusuke; Okubo, Hiroshi; Nagayama, Tomoko; Takeuchi, Tamotsu

    2014-05-01

    Zfp191 represses differentiation and keeps various cells in the stem/progenitor stage. Here, we report that a Zfp191 homolog protein, ZNF396, is expressed in basal cell carcinoma (BCC) and possibly represses the expression of a Notch system effector molecule, Hes1 (hairy and enhancer of split-1), and prevents BCC cells from undergoing Notch-mediated squamous cell differentiation. ZNF396 immunoreactivity was found in the nucleus of 35 of 38 cutaneous BCC and 4 of 74 squamous cell carcinoma tissue specimens. In non-tumorous epidermal tissues, ZNF396 immunoreactivity was restricted in basal cells. siRNA-mediated silencing of ZNF396 induced the expression of Notch2, Hes1, and involucrin in cultured BCC cells. Finally, we found that siRNA-mediated silencing of ZNF396 gene inhibited the proliferation of TE354.T basal cell carcinoma cells. ZNF396 might repress Notch-Hes1 signaling axis and prevent tumor cells from undergoing squamous differentiation in BCC.

  8. Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma

    SciTech Connect

    Kim, Ji-Hee; Lkhagvadorj, Sayamaa; Lee, Mi-Ra; Hwang, Kyu-Hee; Chung, Hyun Chul; Jung, Jae Hung; Cha, Seung-Kuy; Eom, Minseob

    2014-05-23

    Highlights: • Orai1 channel is highly expressed in clear cell renal cell carcinoma (ccRCC) tissues. • Orai1 and STIM1 constitute a native store-operated Ca{sup 2+} entry in ccRCC cells. • Orai1 and STIM1 promote cell migration and proliferation of ccRCC cells. - Abstract: The intracellular Ca{sup 2+} regulation has been implicated in tumorigenesis and tumor progression. Notably, store-operated Ca{sup 2+} entry (SOCE) is a major Ca{sup 2+} entry mechanism in non-excitable cells, being involved in cell proliferation and migration in several types of cancer. However, the expression and biological role of SOCE have not been investigated in clear cell renal cell carcinoma (ccRCC). Here, we demonstrate that Orai1 and STIM1, not Orai3, are crucial components of SOCE in the progression of ccRCC. The expression levels of Orai1 in tumor tissues were significantly higher than those in the adjacent normal parenchymal tissues. In addition, native SOCE was blunted by inhibiting SOCE or by silencing Orai1 and STIM1. Pharmacological blockade or knockdown of Orai1 or STIM1 also significantly inhibited RCC cell migration and proliferative capability. Taken together, Orai1 is highly expressed in ccRCC tissues illuminating that Orai1-mediated SOCE may play an important role in ccRCC development. Indeed, Orai1 and STIM1 constitute a native SOCE pathway in ccRCC by promoting cell proliferation and migration.

  9. Papillary carcinoma of the breast: diagnostic agreement and management implications.

    PubMed

    Rakha, Emad A; Ahmed, Mohamed A; Ellis, Ian O

    2016-11-01

    Papillary carcinoma (PC), which is a rare type of breast cancer, comprises a heterogeneous group of tumours. The diagnostic categorization of PC as in-situ and invasive disease remains a matter of debate with respect to interpretation of its overlapping histological features, and with respect to the uncertainty in clinical behaviour that this dilemma raises. The aim of this study was to assess the diagnostic agreement regarding PC among reporting breast pathologists. Six cases of PC included in the UK National Health Service Breast Screening Programme breast pathology interpretive external quality assurance scheme in the last 10 years were reviewed. In this scheme, one representative haematoxylin and eosin-stained slide from each case is circulated to an average of 600 participants. Data on diagnostic categories were collected and slides were reviewed according to the World Health Organization (WHO) diagnostic criteria. The number of final diagnoses of malignancy (in situ or invasive) was highest for invasive PC (99% of the participants diagnosed it as malignant), followed by solid PC (94% and 95%, respectively), encapsulated PC (92% and 92%, respectively), and papillary ductal carcinoma in situ (DCIS) (88%). Most cases of papillary DCIS were correctly classified as in-situ disease (77%), but 28% of the participants classified invasive PC cases as in-situ disease. Of the participants, 24% reported encapsulated PC as invasive disease. Of the two solid PC cases, one showed some features consistent with the WHO description of invasive solid PC, whereas the other showed features of classic (non-invasive) solid PC. Both cases were reported as invasive by 75% and 77% of participants, respectively. Breast specialists more frequently classified PC as an in-situ carcinoma than did non-specialist participants, and the difference was significant (P = 0.013). Recognition of PC as a malignant entity (in situ or invasive) is high, but concordance of its classification into in

  10. Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma

    SciTech Connect

    Nakamura, Tomoyuki; Sato, Yuko; Watanabe, Daisuke; Ito, Hideki; Shimonohara, Nozomi; Tsuji, Takahiro; Nakajima, Noriko; Suzuki, Yoshio; Matsuo, Koma; Nakagawa, Hidemi; Sata, Tetsutaro; Katano, Harutaka

    2010-03-15

    To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal in any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases.

  11. 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.

  12. UOK 268 Cell Line for Hereditary Leiomyomatosis and Renal Cell Carcinoma | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Urologic Oncology Branch seeks parties to co-develop the UOK 262 immortalized cell line as research tool to study aggressive hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated recurring kidney cancer.

  13. Keap1/Nrf2 pathway in kidney cancer: frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma

    PubMed Central

    Copetti, Massimiliano; la Torre, Annamaria; Sparaneo, Angelo; Fontana, Andrea; Poeta, Luana; Gallucci, Michele; Sentinelli, Steno; Graziano, Paolo; Parente, Paola; Pompeo, Vincenzo; Salvo, Laura De; Simone, Giuseppe; Papalia, Rocco; Picardo, Francesco; Balsamo, Teresa; Flammia, Gerardo Paolo; Trombetta, Domenico; Pantalone, Angela; Kok, Klaas; Paranita, Ferronika

    2017-01-01

    The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal cell carcinoma (RCC), but data concerning the molecular basis and the clinical effect of its deregulation remain incomplete. Here we present a molecular profiling of the KEAP1 and NFE2L2 genes in five different Renal Cell Carcinoma histotypes by analysing 89 tumor/normal paired tissues (clear cell Renal Carcinoma, ccRCCs; Oncocytomas; Papillary Renal Cell Carcinoma Type 1, PRCC1; Papillary Renal Cell Carcinoma Type 2, PRCC2; and Chromophobe Cell Carcinoma). A tumor-specific DNA methylation of the KEAP1 gene promoter region was found as a specific feature of the ccRCC subtype (18/37, 48.6%) and a direct correlation with mRNA levels was confirmed by in vitro 5-azacytidine treatment. Analysis of an independent data set of 481 ccRCC and 265 PRCC tumors corroborates our results and multivariate analysis reveals a significant correlation among ccRCCs epigenetic KEAP1 silencing and staging, grading and overall survival. Our molecular results show for the the first time the epigenetic silencing of KEAP1 promoter as the leading mechanism for modulation of KEAP1 expression in ccRCCs and corroborate the driver role of Keap1/Nrf2 axis deregulation with potential new function as independent epigenetic prognostic marker in renal cell carcinoma. PMID:28061437

  14. Keap1/Nrf2 pathway in kidney cancer: frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma.

    PubMed

    Fabrizio, Federico Pio; Costantini, Manuela; Copetti, Massimiliano; la Torre, Annamaria; Sparaneo, Angelo; Fontana, Andrea; Poeta, Luana; Gallucci, Michele; Sentinelli, Steno; Graziano, Paolo; Parente, Paola; Pompeo, Vincenzo; De Salvo, Laura; Simone, Giuseppe; Papalia, Rocco; Picardo, Francesco; Balsamo, Teresa; Flammia, Gerardo Paolo; Trombetta, Domenico; Pantalone, Angela; Kok, Klaas; Paranita, Ferronika; Muscarella, Lucia Anna; Fazio, Vito Michele

    2017-02-14

    The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal cell carcinoma (RCC), but data concerning the molecular basis and the clinical effect of its deregulation remain incomplete.Here we present a molecular profiling of the KEAP1 and NFE2L2 genes in five different Renal Cell Carcinoma histotypes by analysing 89 tumor/normal paired tissues (clear cell Renal Carcinoma, ccRCCs; Oncocytomas; Papillary Renal Cell Carcinoma Type 1, PRCC1; Papillary Renal Cell Carcinoma Type 2, PRCC2; and Chromophobe Cell Carcinoma).A tumor-specific DNA methylation of the KEAP1 gene promoter region was found as a specific feature of the ccRCC subtype (18/37, 48.6%) and a direct correlation with mRNA levels was confirmed by in vitro 5-azacytidine treatment. Analysis of an independent data set of 481 ccRCC and 265 PRCC tumors corroborates our results and multivariate analysis reveals a significant correlation among ccRCCs epigenetic KEAP1 silencing and staging, grading and overall survival.Our molecular results show for the the first time the epigenetic silencing of KEAP1 promoter as the leading mechanism for modulation of KEAP1 expression in ccRCCs and corroborate the driver role of Keap1/Nrf2 axis deregulation with potential new function as independent epigenetic prognostic marker in renal cell carcinoma.

  15. A review of drugs in development for the personalized treatment of head and neck squamous cell carcinoma

    PubMed Central

    Birkeland, Andrew C.; Swiecicki, Paul L.; Brenner, J. Chad; Shuman, Andrew G.

    2017-01-01

    Introduction Head and neck squamous cell carcinoma remains a highly morbid and fatal disease, with poor survival rates among patients with advanced and recurrent disease. Recent advances in next generation sequencing, targeted therapeutics, and precision medicine trials are expanding treatment options for head and neck cancers; thus greater awareness of this rapidly evolving field is important. Areas Covered Recent next-generation sequencing studies in head and neck squamous cell carcinoma, targeted therapy clinical trials involving head and neck squamous cell carcinoma. Expert Commentary This review discusses the current state of head and neck cancer treatment, and considerations and implications for the incorporation of personalized medicine and targeted therapy for head and neck cancers in a dynamic clinical landscape. PMID:28251187

  16. The molecular biology of colorectal carcinoma and its implications: a review.

    PubMed

    Harrison, Sanjay; Benziger, Harrison

    2011-08-01

    Colorectal carcinoma is one of the most common cancers encountered in the western world and increasingly in the developing world as well. This conditions results in considerable morbidity and mortality. As a result of the impact colorectal carcinoma has on society, a considerable amount of research has gone into elucidating the molecular mechanisms of this disease. This has led to a proliferation in the understanding of the molecular aetiology of the disease. Such research has revealed the underlying mechanisms to be complex and diverse, with no single molecular cause for the development of colorectal cancer. In this review, we look at the basic underlying molecular mechanisms of colorectal cancer and also briefly explore its implications with regards to clinical applications. We look at how this information relates to the prognosis and also its potential use in screening. A medline and pubmed search was conducted using the keywords colorectal carcinoma, molecular biology of colorectal carcinoma, mutations, and the relevant articles were used for this review. Bibliographies of these articles were also searched for relevant articles. There is considerable information available on the pathogenesis of colorectal carcinoma and such knowledge is beginning to impact on clinical practice. Copyright © 2011 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  17. Clear cell and endometrioid carcinomas: are their differences attributable to distinct cells of origin?

    PubMed

    Cochrane, Dawn R; Tessier-Cloutier, Basile; Lawrence, Katherine M; Nazeran, Tayyebeh; Karnezis, Anthony N; Salamanca, Clara; Cheng, Angela S; McAlpine, Jessica N; Hoang, Lien N; Gilks, C Blake; Huntsman, David G

    2017-09-01

    Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis-derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype-specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to identify a single class of mutations that was exclusively present in one histotype and not the other. This lack of genomic differences led us to an alternative hypothesis that these cancers could arise from distinct cells of origin within endometrial tissue, and that it is the cellular context that accounts for their differences. In a proteomic screen, we identified cystathionine γ-lyase (CTH) as a marker for clear cell carcinoma, as it is expressed at high levels in clear cell carcinomas of the ovary and endometrium. In the current study, we analysed normal Müllerian tissues, and found that CTH is expressed in ciliated cells of endometrium (both eutopic endometrium and endometriosis) and fallopian tubes. We then demonstrated that other ciliated cell markers are expressed in clear cell carcinomas, whereas endometrial secretory cell markers are expressed in endometrioid carcinomas. The same differential staining of secretory and ciliated cells was demonstrable in a three-dimensional organoid culture system, in which stem cells were stimulated to differentiate into an admixture of secretory and ciliated cells. These data suggest that endometrioid carcinomas are derived from cells of the secretory cell lineage, whereas clear cell carcinomas are derived from, or have similarities to, cells of the ciliated cell lineage. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  18. Effect of chaetocin on renal cell carcinoma cells and cytokine-induced killer cells.

    PubMed

    Rombo, Roman; Weiher, Hans; Schmidt-Wolf, Ingo G H

    2016-01-01

    We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC) cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK) assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer.

  19. Effect of chaetocin on renal cell carcinoma cells and cytokine-induced killer cells

    PubMed Central

    Rombo, Roman; Weiher, Hans; Schmidt-Wolf, Ingo G.H.

    2016-01-01

    We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC) cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK) assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer. PMID:27141211

  20. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches

    PubMed Central

    Peterson, Shelby C.; Eberl, Markus; Vagnozzi, Alicia N.; Belkadi, Abdelmadjid; Veniaminova, Natalia A.; Verhaegen, Monique E.; Bichakjian, Christopher K.; Ward, Nicole L.; Dlugosz, Andrzej A.; Wong, Sunny Y.

    2015-01-01

    SUMMARY Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well-established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as “hot spots” for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis. PMID:25842978

  1. Expression of lactate dehydrogenase C correlates with poor prognosis in renal cell carcinoma.

    PubMed

    Hua, Yibo; Liang, Chao; Zhu, Jundong; Miao, Chenkui; Yu, Yajie; Xu, Aimin; Zhang, Jianzhong; Li, Pu; Li, Shuang; Bao, Meiling; Yang, Jie; Qin, Chao; Wang, Zengjun

    2017-03-01

    Lactate dehydrogenase C is an isoenzyme of lactate dehydrogenase and a member of the cancer-testis antigens family. In this study, we aimed to investigate the expression and functional role of lactate dehydrogenase C and its basic mechanisms in renal cell carcinoma. First, a total of 133 cases of renal cell carcinoma samples were analysed in a tissue microarray, and Kaplan-Meier survival curve analyses were performed to investigate the correlation between lactate dehydrogenase C expression and renal cell carcinoma progression. Lactate dehydrogenase C protein levels and messenger RNA levels were significantly upregulated in renal cell carcinoma tissues, and the patients with positive lactate dehydrogenase C expression had a shorter progression-free survival, indicating the oncogenic role of lactate dehydrogenase C in renal cell carcinoma. In addition, further cytological experiments demonstrated that lactate dehydrogenase C could prompt renal cell carcinoma cells to produce lactate, and increase metastatic and invasive potential of renal cell carcinoma cells. Furthermore, lactate dehydrogenase C could induce the epithelial-mesenchymal transition process and matrix metalloproteinase-9 expression. In summary, these findings showed lactate dehydrogenase C was associated with poor prognosis in renal cell carcinoma and played a pivotal role in the migration and invasion of renal cell carcinoma cells. Lactate dehydrogenase C may act as a novel biomarker for renal cell carcinoma progression and a potential therapeutic target for the treatment of renal cell carcinoma.

  2. Two different scenarios of squamous cell carcinoma within advanced Basal cell carcinomas: cases illustrating the importance of serial biopsy during vismodegib usage.

    PubMed

    Zhu, Gefei A; Sundram, Uma; Chang, Anne Lynn S

    2014-09-01

    Vismodegib is a Hedgehog signaling pathway inhibitor recently approved by the US Food and Drug Administration for advanced basal cell carcinoma. We present 2 cases of clinically significant squamous cell carcinoma within the tumor bed of locally advanced basal cell carcinoma found during vismodegib treatment. The first case is that of a patient with locally advanced basal cell carcinoma responsive to vismodegib but with an enlarging papule within the tumor bed. On biopsy, this papule was an invasive acantholytic squamous cell carcinoma. The second case is that of a patient with Gorlin syndrome with a locally advanced basal cell carcinoma that was stable while the patient was receiving therapy with vismodegib for 2.5 years but subsequently increased in size. Biopsy specimens from this tumor showed invasive squamous cell carcinoma, spindle cell subtype. In both cases, the squamous cell carcinomas were surgically resected. These cases highlight the importance of repeated biopsy in locally advanced basal cell carcinomas in 2 clinical situations: (1) when an area within the tumor responds differentially to vismodegib, and (2) when a tumor stops being suppressed by vismodegib. Timely diagnosis of non-basal cell histologic characteristics is critical to institution of effective therapy.

  3. Small-cell carcinoma of the ovary in peritoneal fluid.

    PubMed

    Selvaggi, S M

    1994-01-01

    Two cases of small-cell carcinoma of the ovary in the ascitic fluid and peritoneal/pelvic washings of a 30- and 28-yr-old woman, respectively, are presented and discussed. Smear preparations from the ascitic fluid showed loose clusters and single malignant cells with scant cytoplasm and nuclei with smooth to irregular nuclear membranes, granular chromatin, and small nucleoli. In the second case peritoneal/pelvic washing specimens contained clusters and single malignant cells with a moderate amount of cytoplasm and nuclei with smooth nuclear membranes, granular, clumped chromatin, and prominent nucleoli. Hisology confirmed the diagnosis of small-cell carcinoma of the ovary. These are the first reported cases of this rare ovarian neoplasm present on fluid cytology. Its differentiation from other small-cell neoplasms on peritoneal fluid cytology from young women is discussed.

  4. Significance of chemokine and chemokine receptors in head and neck squamous cell carcinoma: A critical review.

    PubMed

    da Silva, Janine Mayra; Soave, Danilo Figueiredo; Moreira Dos Santos, Tálita Pollyanna; Batista, Aline Carvalho; Russo, Remo Castro; Teixeira, Mauro Martins; da Silva, Tarcília Aparecida

    2016-05-01

    Chemokines are small chemotactic proteins that coordinate circulation of immune/inflammatory cells throughout body compartments. Because of this property chemokines and their cell surface receptors are implicated in several physiological and pathological conditions, including cancer. These molecules are expressed by neoplastic or stromal cells and have effects at tumor primary site (e.g. stimulating angiogenesis and tumor cells motility) and lymph nodes (creating a gradient to direct migration of neoplastic cells). In this article we review the current knowledge about the function(s) of chemokines and receptors in squamous cell carcinoma from the oral cavity and head and neck region. Accumulating evidence suggests some chemokine(s) and receptor(s) as potential targets in adjuvant therapies for these malignancies.

  5. Immunotherapy for metastatic renal cell carcinoma.

    PubMed

    Unverzagt, Susanne; Moldenhauer, Ines; Nothacker, Monika; Roßmeißl, Dorothea; Hadjinicolaou, Andreas V; Peinemann, Frank; Greco, Francesco; Seliger, Barbara

    2017-05-15

    Since the mid-2000s, the field of metastatic renal cell carcinoma (mRCC) has experienced a paradigm shift from non-specific therapy with broad-acting cytokines to specific regimens, which directly target the cancer, the tumour microenvironment, or both.Current guidelines recommend targeted therapies with agents such as sunitinib, pazopanib or temsirolimus (for people with poor prognosis) as the standard of care for first-line treatment of people with mRCC and mention non-specific cytokines as an alternative option for selected patients.In November 2015, nivolumab, a checkpoint inhibitor directed against programmed death-1 (PD-1), was approved as the first specific immunotherapeutic agent as second-line therapy in previously treated mRCC patients. To assess the effects of immunotherapies either alone or in combination with standard targeted therapies for the treatment of metastatic renal cell carcinoma and their efficacy to maximize patient benefit. We searched the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), ISI Web of Science and registers of ongoing clinical trials in November 2016 without language restrictions. We scanned reference lists and contacted experts in the field to obtain further information. We included randomized controlled trials (RCTs) and quasi-RCTs with or without blinding involving people with mRCC. We collected and analyzed studies according to the published protocol. Summary statistics for the primary endpoints were risk ratios (RRs) and mean differences (MD) with their 95% confidence intervals (CIs). We rated the quality of evidence using GRADE methodology and summarized the quality and magnitude of relative and absolute effects for each primary outcome in our 'Summary of findings' tables. We identified eight studies with 4732 eligible participants and an additional 13 ongoing studies. We categorized studies into comparisons, all against standard therapy accordingly as first-line (five comparisons) or second-line therapy (one comparison

  6. Follicular atrophoderma with multiple basal cell carcinomas (Bazex).

    PubMed

    Gould, D J; Barker, D J

    1978-10-01

    Five patients from a single family are reported who have an inherited condition of which the main features are follicular atrophoderma, abnormalities of scalp hair and multiple basal cell carcinomas. Thes abnormalities are consistent with the syndrome described by Bazex et al. (1964). The pattern of inheritance of this condition is discussed.

  7. Metastatic transitional cell carcinoma in proximal humerus of a dog

    PubMed Central

    Malek, Sarah; Murphy, Kimberly A.; Nykamp, Stephanie G.; Allavena, Rachel

    2011-01-01

    Transitional cell carcinoma (TCC) was diagnosed in the proximal humerus of a dog that was presented with persistent right forelimb lameness with no clinical signs of urinary tract involvement. A diagnosis of TCC was made from surgical biopsy of the humeral lesion with subsequent necropsy revealing the prostatic urethra as the primary site of the tumor. PMID:22379204

  8. Terahertz pulse imaging of ex vivo basal cell carcinoma.

    PubMed

    Woodward, Ruth M; Wallace, Vincent P; Pye, Richard J; Cole, Bryan E; Arnone, Donald D; Linfield, Edmund H; Pepper, Michael

    2003-01-01

    Terahertz pulse imaging has been used for the first time to study basal cell carcinoma ex vivo, the most common form of skin cancer. This noninvasive technique uses part of the electromagnetic spectrum in the frequency range 0.1-2.7 THz. A total of 21 samples were imaged; the study was performed blind and results were compared to histology. Each image consisted of possible diseased tissue and normal tissue from the same patient. The diseased tissue showed an increase in absorption compared to normal tissue, which is attributed to either an increase in the interstitial water within the diseased tissue or a change in the vibrational modes of water molecules with other functional groups. Seventeen of the images showed a significant difference between the normal and the diseased tissue. These were confirmed by histology to be basal cell carcinomas. Of the remaining four cases, three showed no contrast and were confirmed as blind controls of normal tissue; the fourth case was a suspected basal cell carcinoma but showed no contrast, and histology showed no tumor. Cross-sections of the terahertz images, showing the terahertz absorption, were compared to histology. Regions of increased terahertz absorption agreed well with the location of the tumor sites. Resolutions at 1 THz of 350 microm laterally and 40 microm axially in skin were attainable with our system. These results demonstrate the ability of terahertz pulse imaging to distinguish basal cell carcinoma from normal tissue, and this macroscopic technique may, in the future, help plan surgery.

  9. A dog with squamous cell carcinoma in the middle ear.

    PubMed

    Yoshikawa, Hiroto; Mayer, Monique N; Linn, Kathleen A; Dickinson, Ryan M; Carr, Anthony P

    2008-09-01

    An 8-year-old, castrated male golden retriever was referred for lethargy and inappetance. Severe pain was elicited on palpation of the left temporomandibular joint region. Computed tomography revealed aggressive bone destruction of the left bulla. Squamous cell carcinoma was diagnosed. Malignant tumor in the canine middle ear is rare.

  10. Unusual Presentation of Ulcerative Postauricular Swelling as Sebaceous Cell Carcinoma

    PubMed Central

    Chand, Prem; Kumar, Ashok; Singh, Paramjit; Singla, Lakshay

    2016-01-01

    Sebaceous glands have high concentration over head and neck region. Despite high concentration, sebaceous cell adenoma and carcinomas are infrequent. Sebaceous cell carcinoma is an uncommon, cutaneous aggressive tumor arising from the sebaceous glands and seen almost exclusively on the eyelids (75%). It accounts for just 0.2–0.7% of all eyelid tumors in the USA and very few cases that have originated in areas other than the eyelids have been reported. A 67-year-old male presented with swelling (3 cm × 4 cm), on the right postauricular region, since about 1-month. The swelling became ulcerative and associated with progressive tinnitus and hoarseness of voice. The patient was investigated. Fine-needle aspiration cytology suggested sebaceous cell carcinoma. Then excision biopsy was done, and histopathological examination of excised tissue confirmed the diagnosis. Extraorbital sebaceous cell carcinoma is an aggressive and invasive malignancy. It clinically mimics other diseases and is difficult to diagnose. Hence, an accurate and prompt diagnosis is crucial because of its fulminant course, serious associations with Muir-Torre syndrome and high potential for regional and distant metastasis. PMID:27843279

  11. Human papillomavirus type 16 DNA in periungual squamous cell carcinomas

    SciTech Connect

    Moy, R.L.; Eliezri, Y.D.; Bennett, R.G. ); Nuovo, G.J.; Siverstein, S. Columbia Univ., New York, NY ); Zitelli, J.A. )

    1989-05-12

    Ten squamous cell carcinomas (in situ or invasive) of the fingernail region were analyzed for the presence of DNA sequences homologous to human papilloma-virus (HPV) by dot blot hybridization. In most patients, the lesions were verrucae of long-term duration that were refractory to conventional treatment methods. Eight of the lesions contained HPV DNA sequences, and in six of these the sequences were related to HPV 16 as deduced from low-stringency nucleic acid hybridization followed by low- and high-stringency washes. Furthermore, the restriction endonuclease digestion pattern of DNA isolated from four of these lesions was diagnostic of episomal HPV 16. The high-frequency association of HPV 16 with periungual squamous cell carcinoma is similar to that reported for HPV 16 with squamous cell carcinomas on mucous membranes at other sites, notably the genital tract. The findings suggest that HPV 16 may play an important role in the development of squamous cell carcinomas of the finger, most notably those lesions that are chronic and located in the periungual area.

  12. [Care of Merkel cell carcinoma and role of the radiotherapy].

    PubMed

    Rehailia-Blanchard, Amel; Pigné, Grégoire; Guy, Jean-Baptiste; Vallard, Alexis; El Meddeb Hamrouni, Anis; Rancoule, Chloé; Magné, Nicolas

    2017-01-01

    Merkel cell carcinoma is a rare neuro-endocrine tumor of skin with a poor prognosis. Data available in literature are scarce. Current treatment for locoregional disease is based on combined treatment by surgery and radiotherapy. However these treatments are controversial. The aim of the present review is to sum up the different available studies and to compare national and international guidelines.

  13. [Successful therapy of metastatic basal cell carcinoma with vismodegib].

    PubMed

    Zutt, M; Mazur, F; Bergmann, M; Lemke, A J; Kaune, K M

    2014-11-01

    A 71-year-old man presented with giant basal cell carcinoma on the abdomen which had metastasized. He was treated with oral vismodegib. Both the primary ulcerated tumor on the abdomen and the metastases responded. Vismodegib was well tolerated without significant side effects. The tumor recurred promptly after vismodegib was discontinued, and then was resistant to therapy when vismodegib was re-administered.

  14. Subungual Squamous Cell Carcinoma: The Diagnostic Challenge and Clinical Pearls

    PubMed Central

    Kok, Wai Leong; Lee, Joyce Siong See; Chio, Martin Tze-wei

    2016-01-01

    Subungual squamous cell carcinoma is a rare entity and difficult to diagnose as its clinical presentation may resemble benign conditions. This case report highlights the need to maintain a high clinical index of suspicion, and recommends a practical approach for subungual conditions. Dermoscopy and a biopsy for histology are important adjuncts to clinch the diagnosis. PMID:27920677

  15. Metastatic renal cell carcinoma in a meningioma: a case report.

    PubMed

    Han, H S; Kim, E Y; Han, J Y; Kim, Y B; Hwang, T S; Chu, Y C

    2000-10-01

    Tumor-to-tumor metastasis is rare. We report a case of metastatic renal cell carcinoma in meningioma. A 67-year-old woman presented a two-week history of motor dysphagia and decreased short-term memory. She had undergone a left radical nephrectomy for a renal cell carcinoma 7 years ago, and had not received any adjuvant therapy. MRI disclosed a 3.0 x 3.0 x 3.0-cm sized round tentorial-based extraaxial mass with peritumoral edema in the left posterior temporal lobe. During operation, the tumor was found to be an encapsulated mass firmly attached to the tentorium. Histologically, the tumor was a meningotheliomatous meningioma extensively infiltrated by metastatic renal cell carcinoma, accompanying widespread coagulative necrosis. Immunohistochemical staining for cytokeratin revealed strong positivity only in the renal cell carcinoma component. The patient's postoperative course was uneventful. Post-operative radiation therapy was applied to the whole brain. Three months after operation, the patient developed right hemiparesis and dysphagia. Brain MRI at that time did not reveal recurrence or any other causative lesions, although the whole body scan disclosed uptake at the second lumbar vertebra and rib. The patient refused further treatment.

  16. Discovering Biomarkers within the Genomic Landscape of Renal Cell Carcinoma

    PubMed Central

    A, Sankin

    2016-01-01

    Recent advances in molecular sequencing technology have led to the discovery of numerous biomarkers in renal cell carcinoma (RCC). These biomarkers have the potential to predict clinical outcomes and aid in clinical management decisions. The following commentary is a review of the preliminary data on some of the most promising genetic biomarker candidates. PMID:27104219

  17. Discovering Biomarkers within the Genomic Landscape of Renal Cell Carcinoma.

    PubMed

    A, Sankin

    2016-02-01

    Recent advances in molecular sequencing technology have led to the discovery of numerous biomarkers in renal cell carcinoma (RCC). These biomarkers have the potential to predict clinical outcomes and aid in clinical management decisions. The following commentary is a review of the preliminary data on some of the most promising genetic biomarker candidates.

  18. Differential expression of aquaporin 5 and aquaporin 3 in squamous cell carcinoma and adenoid cystic carcinoma.

    PubMed

    Ishimoto, Shunsuke; Wada, Koichiro; Usami, Yu; Tanaka, Noriaki; Aikawa, Tomonao; Okura, Masaya; Nakajima, Atsushi; Kogo, Mikihiko; Kamisaki, Yoshinori

    2012-07-01

    Aquaporins (AQPs) are a membrane protein family involved in the selective transport of water across cell membranes. Recent studies have reported the expression of AQP5 in several tumor types such as gastric, pulmonary, ovarian, pancreatic and colorectal cancer. We have previously reported the expression on tumor cells and the important role of AQP3 on cell growth in tongue cancer. However, little is known about the expression and precise role of AQP5 on squamous cell carcinoma (SCC) of the tongue. We investigated the expression of AQP5 and AQP3 in human oral SCC and adenoid cystic carcinoma (ACC). Overexpression of both AQP5 and AQP3 were immunohistochemically observed on tumor cells in SCC, whereas ACC cells were faintly stained with those antibodies against AQPs. Treatment with pan-AQP inhibitor or specific AQP5-siRNA showed inhibition of cell growth in SCC cell lines via the inhibition of integrins and the mitogen-activated protein kinase pathway. AQPs play important roles in cell growth in SCC rather than ACC.

  19. Comparison of seven cell lines derived from human gastric carcinomas.

    PubMed

    Motoyama, T; Hojo, H; Watanabe, H

    1986-01-01

    In an attempt to elucidate various histological features of gastric cancers, seven human gastric adenocarcinomas were studied in vitro and in nude mice. Growth pattern of each cultured cell line in vitro corresponded well to the histological type of parent tumor. The cell lines, MKN7, MKN74, and MKN28 derived from differentiated carcinomas showed morphological characteristics of intestinal differentiation in cell polarity and microvilli with core-filaments in vitro as well as in nude mice. However, they gradually diminished the characteristics in course of time. The cell lines, MKN 45 and OKAJIMA, derived from undifferentiated carcinomas, had natures of not only ordinary gastric mucosa but also intestinal metaplastic mucosa. They seem to have multipotentiality for differentiation, and preserved well the natures for long periods of culture. The KWS-I cell line composed of undifferentiated cells in vitro displayed the potential for differentiation in nude mice. However, the differentiation of KATO-III cells derived from a signet-ring cell carcinoma was suppressed in nude mice. The common abnormality of chromosome was not found, and the growth rate in vitro was not dependent on the histological type of parent tumor.

  20. Comprehensive molecular characterization of clear cell renal cell carcinoma.

    PubMed

    2013-07-04

    Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.

  1. COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

    PubMed Central

    2013-01-01

    Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (e.g. VHL) and the maintenance of chromatin states (e.g. PBRM1). We surveyed more than 400 tumors using different genomic platforms and identified 19 significantly mutated genes. The PI3K/Akt pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodeling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving down-regulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, up-regulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 and GRB10. Remodeling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumor stage and severity and offers new views on the opportunities for disease treatment. PMID:23792563

  2. The epigenetic landscape of clear-cell renal cell carcinoma

    PubMed Central

    Kluzek, Katarzyna; Bluyssen, Hans A

    2015-01-01

    Clear cell renal cell carcinoma (ccRCC) is the most common subtype of all kidney tumors. During the last few years, epigenetics has emerged as an important mechanism in ccRCC pathogenesis. Recent reports, involving large-scale methylation and sequencing analyses, have identified genes frequently inactivated by promoter methylation and recurrent mutations in genes encoding chromatin regulatory proteins. Interestingly, three of detected genes (PBRM1, SETD2 and BAP1) are located on chromosome 3p, near the VHL gene, inactivated in over 80% ccRCC cases. This suggests that 3p alterations are an essential part of ccRCC pathogenesis. Moreover, most of the proteins encoded by these genes cooperate in histone H3 modifications. The aim of this review is to summarize the latest discoveries shedding light on deregulation of chromatin machinery in ccRCC. Newly described ccRCC-specific epigenetic alterations could potentially serve as novel diagnostic and prognostic biomarkers and become an object of novel therapeutic strategies. PMID:28326264

  3. Inhibitory effects of xanthohumol from hops (Humulus lupulus L.) on human hepatocellular carcinoma cell lines.

    PubMed

    Ho, Yi-Chien; Liu, Chi-Hsien; Chen, Chien-Nan; Duan, Kow-Jen; Lin, Ming-Tse

    2008-11-01

    Xanthohumol is one of the main flavonoids in hop extracts and in beer. Very few investigations of xanthohumol have studied hepatocellular carcinoma. In this study, the inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines were investigated. The IC(50) values of xanthohumol for two hepatocellular carcinoma cell lines and one normal hepatocyte cell line were 108, 166 and 211 microm, respectively. Normal murine hepatocyte cell line had more resistance to xanthohumol than hepatocellular carcinoma cell lines. Besides, the inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines were attributed to apoptosis as indicated in the results of flow cytometry, fluorescent nuclear staining and electrophoresis of oligonucleosomal DNA fragments. Hop xanthohumol was more efficient in the growth inhibition of hepatocellular carcinoma cell lines than the flavonoids silibinin and naringin from thistle and citrus. It was shown for the first time that xanthohumol from hops effectively inhibits proliferation of human hepatocellular carcinoma cells in vitro.

  4. GLUT-1 immunoexpression in oral epithelial dysplasia, oral squamous cell carcinoma, and verrucous carcinoma.

    PubMed

    Angadi, Vidya C; Angadi, Punnya V

    2015-06-01

    Glucose transporters, such as GLUT-1, mediate the important mechanisms involved in cellular glucose influx, allowing cells to proliferate and survive. The significance of GLUT-1 expression in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) has been less explored, and no study has investigated it in relation to verrucous carcinoma (VC). We evaluated 30 cases each of OED, OSCC, and VC, graded further on the basis of their differentiation, immunohistochemically for GLUT-1 expression, along with 10 specimens of normal oral mucosa (NOM) as controls. In OSCC, GLUT-1 expression increased with the degree of dysplasia and increasing grade (P < 0.001). The expression in VC was predominantly membranous and intense, resembling well differentiated OSCC. This increase of GLUT-1 expression in OSCC along with the degree of dysplasia and the histologic grade reflects the expanding glycolytic response to hypoxia. This is the first study to have revealed prominent GLUT-1 expression in VC, highlighting its inherent metabolic capacity.

  5. A case of mixed medullary and follicular cell carcinoma of the thyroid.

    PubMed

    Ueki, Ikuko; Ando, Takao; Haraguchi, Ai; Horie, Ichiro; Imaizumi, Misa; Hayashi, Tomayoshi; Uga, Tatsuya; Usa, Toshiro; Kawakami, Atsushi

    2011-01-01

    A medullary thyroid carcinoma is a malignant tumor derived from the C-cells of the thyroid. Despite their distinct embryological origin, medullary thyroid carcinomas are exceptionally accompanied by a tumor derived from the follicular cells; this is defined as mixed medullary and follicular cell carcinoma. There have been controversies regarding the origin of this rare mixed thyroid carcinoma questioning whether or not a mixed carcinoma originates from a common cancer stem cell. We present a case of mixed medullary and follicular cell carcinoma in which two thyroid carcinomas were found intermingled in the thyroid as well as in the metastatic cervical lymph nodes. We examined the tumor by immunostaining with thyroglobulin, calcitonin, and thyroid transcription factor-1, and also reviewed the literature and discuss the origin of this rare mixed thyroid carcinoma.

  6. Unusual localization of a common cutaneous neoplasm: basal cell carcinoma.

    PubMed

    Tecimer, Rukiye Selin; Yildiz, Kürsat Demir; Aktürk, Aysun Sikar; Bilen, Nilgün

    2013-06-01

    Basal cell carcinoma (BCC) is the most common form of the skin carcinomas and ultraviolet radiation is the major risk factor in the etiopathogenesis. However, reports of unusual sites for BCC are increased in the literature. Authors draw attention to possibility of other etiological agents for BCC like local trauma, ageing, ionizing radiation, arsenic, chronic inflammation, and immune deficiency. Here, we reported a 74-year-old male patient with nodular BCC on groin. We thought that ageing or local trauma may have a role in its formation.

  7. Isolated adrenal masses in nonsmall-cell bronchogenic carcinoma

    SciTech Connect

    Oliver, T.W. Jr.; Bernardino, M.E.; Miller, J.I.; Mansour, K.; Greene, D.; Davis, W.A.

    1984-10-01

    Computed tomography has become an important diagnostic modality in the preoperative staging of patients with bronchogenic carcinoma. The adrenal glands represent one of the most frequent sites of metastasis. Therefore, an isolated adrenal mass discovered on preoperative thoracoabdominal CT poses a diagnostic problem. Three hundred thirty patients with histologically proved nonsmall-cell bronchogenic carcinoma were evaluated. Thirty-two had adrenal masses without further evidence of disease in the abdomen, Eight of these 32 masses were metastases, 17 were proved adenomas, and 7 did not undergo biopsy. Thus an isolated adrenal mass is more likely benign than metastatic, and biopsy is advocated prior to withholding potentially curative surgery.

  8. [Synchronous bilateral chromophobe cell renal carcinoma: a case report].

    PubMed

    Mukai, Masatoshi; Imamura, Ryoichi; Takayama, Hitoshi; Nishimura, Kazuo; Nonomura, Norio; Okuyama, Akihiko

    2009-09-01

    An 81-year-old female presented with abdominal discomfort. Computed tomography scan showed a 26 x 22 mm tumor in the left kidney and 43 x 37 mm tumor in the right kidney. Clinical diagnosis was bilateral renal cell carcinoma, left; cT1a, right; cT1bN0M0. We planned primary unilateral partial nephrectomy, followed by secondary contralateral radical nephrectomy. Left partial nephrectomy was performed and 4 months later, laparoscopic right renal nephrectomy was performed without serious postoperative renal dysfunction. Pathological diagnosis of both tumors was chromophobe renal carcinoma. The patient has been doing well without any evidence of recurrence or metastasis.

  9. Primary signet ring cell carcinoma of the colon and rectum.

    PubMed

    Arifi, Samia; Elmesbahi, Omar; Amarti Riffi, Afaf

    2015-10-01

    Colorectal primary signet ring cell carcinoma (SRCC) is a rare entity accounting for nearly 1% of all colorectal carcinomas. It is an independent prognostic factor associated with less favorable outcome. This aggressiveness is mainly due to the intrinsic biology of these tumors. Here is an overview of the literature related to clinicopathological features, molecular biology, and management of SRCC of the colon and the rectum. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  10. Perineural Spread of Cutaneous Squamous Cell Carcinoma Manifesting as Ophthalmoplegia

    PubMed Central

    Koukkoulli, Antigoni; Koutroumanos, Nikolas; Kidd, Desmond

    2015-01-01

    ABSTRACT An 89-year-old female presented with horizontal diplopia and was diagnosed with VI nerve palsy attributed to a microvascular event. She subsequently progressed to develop an orbital apex syndrome, with neuroimaging demonstrating tumour invasion. Eighteen months earlier, she had squamous cell carcinoma of the forehead excised with clear margins. Intraneural and perineural spread of squamous carcinoma from the face to the cranial cavity is an important cause of delayed cranial nerve palsies after local excision of the skin tumour. PMID:27928347

  11. Bortezomib With or Without Irinotecan in Treating Patients With Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2014-05-07

    Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous