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Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. The main etiological agent is Merkel cell polyomavirus (MCPyV), detected in 80% of cases. About 5% of cases, called combined MCC, feature an admixture of neuroendocrine and non-neuroendocrine tumor cells. Reports of the presence or absence of MCPyV in combined MCC are conflicting, most favoring the absence, which suggests that combined MCC might have independent etiological factors and pathogenesis. These discrepancies might occur with the use of different virus identification assays, with different sensitivities. In this study, we aimed to determine the viral status of combined MCC by a multimodal approach. We histologically reviewed 128 cases of MCC and sub-classified them as “combined” or “conventional.” Both groups were compared by clinical data (age, sex, site, American Joint Committee on Cancer [AJCC] stage, immunosuppression, risk of recurrence, and death during follow-up) and immunochemical features (cytokeratin 20 and 7, thyroid transcription factor 1 [TTF1], p53, large T antigen [CM2B4], CD8 infiltrates). After a first calibration step with 12 conventional MCCs and 12 cutaneous squamous cell carcinomas as controls, all eight cases of combined MCC were investigated for MCPyV viral status by combining two independent molecular procedures. Furthermore, on multiplex genotyping assay, the samples were examined for the presence of other polyoma- and papillomaviruses. Combined MCC differed from conventional MCC in earlier AJCC stage, increased risk of recurrence and death, decreased CD8 infiltrates, more frequent TTF1 positivity (5/8), abnormal p53 expression (8/8), and frequent lack of large T antigen expression (7/8). With the molecular procedure, half of the combined MCC cases were positive for MCPyV in the neuroendocrine component. Beta papillomaviruses were detected in 5/8 combined MCC cases and 9/12 conventional MCC cases. In conclusion, the detection of MCPyV DNA in half of the combined MCC cases suggests similar routes of carcinogenesis for combined and conventional MCC.

Few histological data are known about patients with a first diagnosis of bladder cancer (BC) at the age ≥80 years. We describe the largest series in this patient group and their distinctive histological features. This unicentric retrospective study included patients at the age ≥80 years with a first diagnosis of bladder cancer between 2005 and 2015. All diagnosis was made by one senior uropathologist according to the WHO 2016 classification, pTNM 7th edition 2009. We examined samples of 185 patients, sex ratio M:W = 2.49:1, with ≥80 years at the time of first diagnosis of BC. The mean age was 85.1 years (84.8 for men and 85.8 for women). One hundred sixteen patients were diagnosed with NMIBC (non-muscle invasive bladder cancer) (62.7%). Sixty-nine patients were detected with MIBC (muscle invasive bladder cancer) (37.3%). In the MIBC, 20 (29.0%) cases, a divergent differentiation was reported. No patient had primary carcinoma in situ (Cis) at time of diagnosis, and concomitant Cis was observed in 18.9% (35 cases). According to our results, the histopathological findings are different from those of other patients’ groups. The study shows a higher number of MIBC and a high percentage of histological variants. We could show distinctive pathological features in this patient group.

The HOXB13 gene is a member of the homeobox gene family, and prostate development depends on HOXB13 function. HOXB13 is a very sensitive and specific marker of prostate tissue and prostate cancer. When the origin of a tumor in a resection specimen or in biopsy material is unclear, it allows determining the prostate as the primary. Our aim was to determine whether HOXB13 has similar sensitivity for determining prostate origin of lymph node and bone metastases. We retrieved cases of lymph node and bone metastases of histologically confirmed prostate cancer (PCa) and selected lymph node metastases of urothelial carcinoma (UCa). A panel of antibodies against HOXB13, PSA, ERG, Androgen receptors, p504S, p63, GATA-3, CK7, and Uroplakin 2 and 3 was tested on these tissue samples. Two pathologists analysed and scored staining as either 0 (negative) or + (positive). The selected cohort consisted of 74 cases of lymph node and 15 of bone metastases of PCa and 15 of lymph node metastases of UCa. HOXB13 was expressed in 93 % of lymph node and in 33 % of bone metastases of PCa. All lymph node metastases of UCa were negative. Sensitivity of HOXB13 as a marker for prostate origin in lymph node metastases was 93 % and for bone metastases 33 %. Inter-observer variability in assessment of staining was good, as only two (1.9 %) of lymph node metastasis of PCa were discordant. HOXB13 is a useful marker for prostate origin when doubt exists regarding the site of the primary of a metastatic lesion. On bone metastases, HOXB13 immunohistochemistry performed less well, probably due to the use of tissue decalcification.