Answer: A. Small cell carcinoma arising in urothelial carcinoma

Histology: Tumor shows extensive areas composed of small cells with scant cytoplasm, hyperchromatic nuclei with nuclear molding, inconspicuous nucleoli, frequent mitoses and numerous apoptotic bodies. There are areas of overlying carcinoma in-situ and foci of spindling of tumor cells.

Discussion: Small cell carcinoma arising in any site is a highly proliferative, high-grade neuroendocrine tumor. Small cell carcinoma of the bladder originates from urothelial cells through specific activation of the neuronal pathways. In support of this divergent differentiation pathway, small cell carcinoma of the bladder is frequently associated with conventional urothelial carcinoma and other histologic variants of urothelial carcinoma with molecular evidence of clonality. Guidelines support use of platinum and etoposide chemotherapy in the neoadjuvant and frontline settings akin to small cell carcinoma of lung. Radical cystectomy is a standard consolidative management strategy for the majority of patients with small cell carcinoma of the bladder with localized disease with/without regional lymphadenopathy. The appropriate identification of a small cell carcinoma component is critical to guide appropriate management. The differential diagnoses include rhabdomyosarcoma, lymphoma, and PNET. While rhabdomyosarcoma could be positive for synaptophysin, in contrast to small cell carcinoma they are negative for cytokeratin and show expression of desmin and/or myogenin. Small cell carcinomas are negative for lymphoid markers but can be focally positive for CD99 and NKX2.2, which are markers of PNET, but similarly to rhabdomyosarcoma, PNETs do not have significant expression of cytokeratin and are diffusely positive for CD99 or NKX2.2.

References:
Hum Pathol. 2018 Sep; 79: 57–65.