Urothelial carcinoma with trophoblastic differentiation: case report and review of literature.

UNLABELLED: Urothelial carcinoma with trophoblastic differentiation (UCTD) is a rare histological variant of urothelial carcinoma characterized by the presence of trophoblastic elements and expression of β-human chorionic gonadotropin (β-hCG). Published evidence is limited, and the clinical behavior of this variant remains incompletely understood. The objective of this study is to review the available literature regarding the incidence, clinicopathological characteristics, treatment modalities, recurrence patterns, survival outcomes, and prognostic implications and to present the case of a patient with UCTD. A 66-year-old male patient presented in February 2025 with a 2-month history of progressive left inguinal swelling and recurrent left hydrocele. Past medical history revealed: radical cystectomy with ileal neobladder, pelvic lymphadenectomy (for bladder pT2G3 recurrent BCG resistant bladder tumor) performed on the 28th of June 2018. Full body contrast CT scan had been performed on the 24th of December 2024 and revealed a left inguinal adenopathy conglomerate 9.93 cm in length, with the largest lymph node measuring 2.5 cm, bilateral peritesticular fluid collections (hydrocele) with no evidence of local tumor recurrence in the neobladder or prostate bed and a supradiaphragmatic, calcified pleural mass (3.4 × 1.8 cm). Scrotal ultrasound revealed: large bilateral hydrocele, left epididymal and upper testicular pole tumor (~2 cm in size) with increased Doppler vascularity and a large left inguinal adenopathy conglomerate (~10 cm in size) with increased Doppler vascularity. Testicular cancer serum markers were performed and a serum β-hCG of 5893 mIU/ml, was found. Ultrasonographical assessment and positive testicular cancer biomarkers prompted us to suspect a testicular tumor with inguinal lymph node metastases. Patient was referred for surgery. Left inguinal radical orchidectomy was performed along with left inguinal lymphadenectomy. Histopathological examination of the testicle revealed testicular and epididymal inflammation. Lymph node examination revealed urothelial carcinoma with squamous and trophoblastic differentiation, PDL1(22C3) positive, CK7 positive, GATA3 positive, CK20 positive, p16 negative and beta HCG positive on 10% of cells. Patient was started on platinum-based chemotherapy with rapid disease progression and died of metastatic complications approximately 11 months after the initial recurrence signs were visible on the CT scan. CONCLUSIONS: UCTD is a rare and aggressive variant of urothelial carcinoma associated with unfavorable oncological outcomes. Available evidence supports aggressive treatment and prolonged follow-up. To our knowledge, this may represent one of the few reported, very late recurrences after radical cystectomy.