Lynch Syndrome: Its Impact on Urothelial Carcinoma.

Lynch syndrome, known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal-dominant familial cancer syndrome with an increased risk for urothelial cancer (UC). Mismatch repair (MMR) deficiency, due to pathogenic variants in MLH1, MSH2, MSH6, and PMS2, and microsatellite instability, are known for development of Lynch syndrome (LS) associated carcinogenesis. UC is the third most common cancer type in LS-associated tumors. The diversity of germline variants in the affected MMR genes and their following subsequent function loss might be responsible for the variation in cancer risk, suggesting an increased risk of developing UC in MSH2 mutation carriers. In this review, we will focus on LS-associated UC of the upper urinary tract (UUT) and bladder, their germline profiles, and outcomes compared to sporadic UC, the impact of genetic testing, as well as urological follow-up strategies in LS. In addition, we present a case of metastatic LS-associated UC of the UUT and bladder, achieving complete response during checkpoint inhibition since more than 2 years.

Small cell neuroendocrine prostate cancer with adenocarcinoma components-case report and literature review.

Background: Small cell neuroendocrine prostate cancer (SCNC) is a rare aggressive type of neuroendocrine prostate cancer (NEPC) characterized by aggressive clinical course and lack of response to hormone therapy. Case Description: We present a case report of a 60-year-old man diagnosed with a histologically confirmed primary metastatic (bone, lymph nodes and visceral) SCNC with small components of an adenocarcinoma with clinical symptoms mimicking an acute prostatitis. Of note, serum based neuroendocrine markers (carcinoembryonic antigen, chromogranin A) were negative and the patient had a prostate-specific antigen (PSA) elevation. Genetic testing of tumor tissue revealed breast cancer gene 2 (BRCA2) copy number loss and a retinoblastoma gene (RB1) mutation reflecting again the aggressiveness of the disease. Germline testing for the BRCA2 copy number loss was unremarkable. After 6 cycles of carboplatin and etoposide in combination with androgen deprivation therapy (ADT) the Eastern Cooperative Oncology Group (ECOG) performance status has improved from 3 to 0, in addition the patient was free of pain. In line with clinical improvement, both prostate-specific membrane antigen (PSMA) and fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) revealed a significant reduction of metastatic load. Currently, the patient is treated with ADT plus apalutamide. Conclusions: We demonstrate for the first time a case of a primary metastatic SCNC with adenocarcinoma components successfully treated by the combination of platinum-based chemotherapy plus hormonal therapy. In addition, we provide a literature overview on management of SCNC as there is no standard treatment established for this disease.

Secretagogin expression in tumours of the human brain and its coverings.

Secretagogin is a recently described calcium-binding protein, which is expressed in some neurons of the human brain. In this study we systematically investigated secretagogin expression in 245 tumours of the human brain and its coverings using immunohistochemistry. We found focal or widespread secretagogin expression in tumour cells in 1/18 oligoastrocytomas, 1/19 oligodendrogliomas, 2/20 anaplastic oligodendrogliomas, 2/9 ependymomas, 2/11 anaplastic ependymomas, 2/10 glioblastomas, 3/11 gangliogliomas and 1/2 anaplastic gangliogliomas, 10/10 central neurocytomas, 5/10 classic medulloblastomas, 4/5 desmoplastic medulloblastomas, 3/5 large cell/anaplastic medulloblastomas, 3/5 neuroblastomas, 3/10 meningiomas, 2/10 haemangioblastomas, and 13/19 pituitary adenomas. Further, we observed secretagogin expression in endothelial cells in 5/10 meningiomas, 2/5 haemangiopericytomas, and 2/10 haemangioblastomas. We detected no secretagogin expression in fibrillary astrocytoma, pilocytic astrocytoma, DNT, pineocytoma, pineoblastoma, subependymal giant cell astrocytoma (SEGA), atypical teratoid/rhabdoid tumour (AT/RT), or primary central nervous system lymphoma (PCNSL). We conclude that secretagogin is differentially expressed in human neuronal, glial, and embryonal brain tumours, meningial neoplasms and pituitary adenomas. Our findings indicate that secretagogin is involved in the calcium metabolism of tumour cells and endothelial cells in a subset of neoplasms of the brain and its coverings. Anti-secretagogin immunohistochemistry does not seem to be helpful in most differential diagnostic situations in surgical neuropathology.