Answer: C - Urothelial carcinoma, lymphoepithelioma-like 

Sections show a papillary tumor with clusters of neoplastic urothelial cells in the stroma surrounded by a dense, but polymorphic. lymphoplasmacytic population, including scattered inflammatory cells within the urothelium. The epithelial cells are highlighted by urothelial markers (GATA3, P63 and CK20) and are negative for PAX8. P53 shows wildtype phenotype.

Lymphoepithelioma-like urothelial carcinoma (LELC) is a rare subtype of high-grade urothelial carcinoma composed of sheets and clusters of neoplastic cells with poorly defined cytoplasmic borders (reminiscent of syncytial structures). These tumors sometimes are associated with an in situ papillary component. Neoplastic cells have abundant cytoplasm and enlarged pleomorphic nuclei with prominent nucleoli, and there is a dense infiltration of lymphoplasmacytic and other inflammatory cells in the stroma. LELC has morphologic similarities to nasopharyngeal lymphoepithelioma; however, it shows no viral association (negative for EBV or HPV infection). Tumors with pure or predominant (>50%) LELC have been suggested to be associated with better overall survival and better response to therapy. Immunohistochemistry for urothelial markers highlights the neoplastic urothelial cells. The lymphoplasmacytic population are negative for epithelial markers (useful in differentiation from plasmacytoid subtype of urothelial carcinoma).

Secondary serous carcinoma of the bladder normally shows deeply invasive tumor clusters within the bladder wall, without a prominent in situ component (unlike this case). Also, absence of P53 mutation and negative PAX8 expression argue against a Mullerian origin.

Plasmacytoid subtype of urothelial carcinoma usually shows a diffuse growth pattern within the bladder wall, with neoplastic cells commonly expressing urothelial markers.

Warthin subtype of urothelial carcinoma is not defined in the current classification of urothelial carcinoma.

Bladder lymphoma is very rare and is seen more commonly in female patients. The tumor usually does not form papillary structures. In addition, the lymphocytes are clonal (unlike seen in this case).

Reference

WHO Classification of Tumours of the Urinary System and Male Genital Organs (5th edition). IARC: Lyon 2022. 

Mirsadraei L, Hodkoff A, Jones K, et al. Serous Carcinoma Mimicking Primary Urothelial Carcinoma on Clinical Evaluation and Pathology: A Potential Diagnostic Pitfall. Arch Pathol Lab Med. 2018 Feb;142(2):168-177.

Venyo AK. Lymphoma of the urinary bladder. Adv Urol. 2014;2014:327917.