High-Grade Urothelial Carcinoma with Divergent Prostatic Differentiation Mimicking a Collision Tumor in a Bladder Diverticulum

High-grade urothelial carcinoma (HGUC) shows marked morphologic plasticity with many recognized histologic subtypes that may coexist within the same tumor. These pose a diagnostic challenge and should be distinguished from collision tumors, defined by the coexistence of morphologically and genotypically distinct tumors at the same anatomic site. Herein, we present the first case report of HGUC with malignant prostatic differentiation mimicking a collision tumor in a bladder diverticulum. The patient was a 68-year-old male patient who presented with gross hematuria and was found to have a 2.2 cm tumor in a posterior bladder diverticulum. Initial transurethral resection (TUR) suggested HGUC, while re-TUR showed a component resembling prostatic ductal adenocarcinoma. Subsequent diverticulectomy specimen revealed two morphologically and immunohistochemically distinct tumor components: 1) a papillary component associated with urothelial carcinoma in situ, positive for keratin 34BE12 and GATA3, and compatible with HGUC of the bladder, and 2) a distinct abutting and focally admixed malignant glandular component, which was GATA3 negative, but positive for markers of prostatic differentiation such as NKX3.1, PSA and PSAP and displayed prostatic ductal adenocarcinoma features. These findings raised the possibility of a collision tumor between urothelial carcinoma and metastatic prostatic adenocarcinoma. However, the patient's PSA level was normal and magnetic resonance imaging of the prostate was unremarkable. To render an accurate diagnosis and guide patient management, these two tumor components were macrodissected and subjected to targeted massively parallel sequencing. Disease-associated variants in EGFR, DDR2, KMT2D, and RB1 were identified and were identical and shared among the two histologically distinct components. These findings suggest that the two components are part of the same neoplastic process and, given the presence of urothelial carcinoma in situ, possibly represent the first reported example of urothelial carcinoma with divergent prostatic differentiation. Awareness of divergent differentiation in urothelial carcinomas has important diagnostic, prognostic and therapeutic implications and can be resolved with the use of ancillary molecular studies.