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Aetiologically linked to HPV infection, malignancies of the anal canal have substantially increased in incidence over the last 20 years. Although most anal squamous cell carcinomas (SCCs) respond well to chemoradiotherapy, about 30% of patients experience a poor outcome, for undetermined reasons. Despite cumulative efforts for discovering independent predictors of overall survival, both nodal status and tumour size are still the only reliable factors predicting patient outcome. Recent efforts have revealed that the biology of HPV-related lesions in the cervix is strongly linked to the originally infected cell population. To address the hypothesis that topography also influences both gene expression profile and behaviour of anal (pre)neoplastic lesions, we correlated both proteomic signatures and clinicopathological features of tumours arising from two distinct portions of the anal canal: the lower part (squamous zone) and the more proximal anal transitional zone. Although microdissected cancer cells appeared indistinguishable by morphology (squamous phenotype), unsupervised clustering analysis of the whole proteome significantly highlighted the heterogeneity that exists within anal canal tumours. More importantly, two region-specific subtypes of SCC were revealed. The expression profile (sensitivity/specificity) of several selected biomarkers (keratin filaments) further confirmed the subclassification of anal (pre)cancers based on their cellular origin. Less commonly detected compared to their counterparts located in the squamous mucosa, SCCs originating in the transitional zone more frequently displayed a poor or basaloid differentiation, and were significantly correlated with reduced disease-free and overall survivals. Taken together, we present direct evidence that anal canal SCC comprises two distinct entities with different cells of origin, proteomic signatures, and survival rates. This study forms the basis for a dualistic classification of anal carcinoma, with implications for management, outcome expectations, and possibly therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Cervical cancer is the second leading cause of cancer deaths among women worldwide. The objective of this study was to describe the most common oncogenic mutations in cervical cancers and to explore genomic differences between the 2 most common histologic subtypes: adenocarcinoma and squamous cell carcinoma.A high-throughput genotyping platform, termed Oncomap, was used to interrogate 80 cervical tumors for 1250 known mutations in 139 cancer genes. Samples were analyzed using a mass spectrometry-based genotyping platform and were validated using orthogonal chemistry. Epidermal growth factor receptor (EGFR) mutations were further validated by massive parallel sequencing. Human papilloma virus (HPV) genotyping also was performed.Validated mutations were detected in 48 of 80 tumors (60%) examined. The highest mutation rates were in the genes phosphatidylinositol 3-kinase, catalytic subunit α (PIK3CA) (31.3%); Kirsten rat sarcoma viral oncogene homolog (KRAS) (8.8%); and EGFR (3.8%). PIK3CA mutation rates did not differ significantly between adenocarcinomas and squamous cell carcinomas (25% vs 37.5%, respectively; P = .33). In contrast, KRAS mutations were identified only in adenocarcinomas (17.5% vs 0%; P = .01), and a novel EGFR mutation was detected only in squamous cell carcinomas (0% vs 7.5%; P = .24). There were no associations between HPV-16 or HPV-18 and somatic mutations or overall survival. In adjusted analyses, PIK3CA mutations were associated with shorter survival (67.1 months vs 90.3 months; hazard ratio, 9.1; 95% confidence interval, 2.8-29.5 months; P.001).Cervical cancers harbor high rates of potentially targetable oncogenic mutations. In addition, cervical squamous cell carcinoma and adenocarcinoma have distinct molecular profiles, suggesting that clinical outcomes may be improved with the use of more tailored treatment strategies, including PI3K and MEK inhibitors.

Trpkov K, Yilmaz A, Uzer D, Dishongh K M, Quick C M, Bismar T A & Gokden N (2010) Histopathology57, 893–906 Renal oncocytoma revisited: a clinicopathological study of 109 cases with emphasis on problematic diagnostic features Aim: To evaluate problematic diagnostic features in renal oncocytoma. Methods and results: One hundred and nine cases of oncocytoma were reviewed and the problematic gross and microscopic features recorded. Multifocal and bilateral neoplasms were found in 12 (11%) and five (4.6%) cases, respectively. Haemorrhage was seen grossly in 30 (27.5%) neoplasms and a central scar was identified in 35 (32.1%). On microscopy, perinephric fat extension was present in 17 (15.6%) neoplasms and vascular extension was identified in four (3.7%) oncocytomas. Rare mitoses and focal coagulative necrosis were identified in two (1.8%) cases each. Focal clear cell changes were found in 16 (14.7%) oncocytomas, typically within hyalinized areas. Limited foci with chromophobe-like histology (not exceeding 5% of the neoplasm) were found in 13 (11.9%) oncocytomas. In 12 (11%) oncocytomas, rare papillary formations were noted in the lumina of microcysts. Significant nuclear atypia, oncoblasts and entrapped tubules were identified in 27 (24.8%), 41 (37.6%) and 40 (36.7%) neoplasms, respectively. After a median follow-up of 52 months (range 1–113 months), there was no disease recurrence, progression or death attributed to oncocytoma. Conclusions: The recognition of the spectrum of morphological changes observed in renal oncocytoma should help pathologists establish a diagnosis of oncocytoma in problematic cases.

Nuclear localization of β-catenin in epithelial cells characterizes the epithelial-mesenchymal transition (EMT) and is associated with tumor progression in numerous malignancies. Factors that contr...

Objective: In a 9-week anatomy course, collaboration between Anatomy and Pathology faculty members facilitated the pairing of an investigative approach with traditional dissection to: encourage sel...

Vulvar squamous cell carcinoma (vSCC) is a disfiguring malignancy that represents 4% of all gynecological cancers. A pathological feature that is commonly used in determining clinical prognosis and...