Various Histomorphologic Patterns of Urothelial Carcinoma in TURBT Specimen

Objective: To evaluate the various morphologic patterns of urothelial carcinoma in transurethral resection specimen of urinary bladder. Method: One hundred ninty three biopsies of transurethral resection of bladder from different age groups without exception of sex and race were included in this study from year 2013-2019 in Services Hospital Lahore. Result: Eighty-eight cases from 193 biopsies from services hospital Lahore in 2013 to 2019 were reported as high-grade urothelial carcinoma. While 52out of 193 cases were diagnosed as nested variant of urothelial carcinoma.03 cases neuroendocrine differentiation of urothelial carcinoma is identified and 21 cases having squamous and 12 cases with sarcomatoid differentiation of urothelial carcinoma is reported. Conclusion: Urothelial carcinoma has many histological variants each having different prognosis and clinical implications. So accurate subtyping of the tumor is important for patient's better management. Key Words: Urothelial carcinoma, sarcomatoid, divergent differentiation How to Cite: Kareem H, Jahan A, Nadeem I, Sameen S, Liaqat R, Liaquat T. Various histomorphologic patterns of urothelial carcinoma in TURBT specimen. Esculapio.2020;16(04):66-69.

Nested Variant of Urothelial Carcinoma Is a Luminal Bladder Tumor With Distinct Coexpression of the Basal Marker Cytokeratin 5/6

Objectives The nested variant of urothelial carcinoma (NVUC) is a rare bladder tumor that may possess a luminal molecular phenotype. We sought to determine whether a small immunohistochemical (IHC) panel using common surrogates for molecular phenotypes would reliably classify a cohort of pure NVUC cases. Methods IHC staining with a panel composed of markers for basal subtypes (CK5/6, CK14) and luminal subtypes (FOXA1, GATA3) was performed on pure small NVUC cases (n = 23) and 5 large NVUC cases (n = 5). Scoring of IHC stains was performed semiquantitatively. Individual cases were analyzed using previously reported IHC-based surrogates for molecular subtype. Results The phenotype of NVUC was classified as luminal from 60.1% (FOXA1+/CK5/6−) to 100% (GATA3+/CK14−) of cases using composite phenotypes. No cases possessed a basal or squamous cell carcinoma–like phenotype. The majority of small NVUC cases (69.5%) showed subset CK5/6 expression distinctly localized to the basal layers of tumor cell nests. Intratumoral heterogeneity was also noted in CK5/6 (21.7% of small NVUC cases) but no other markers. Conclusions NVUC appears to express markers of both basal and luminal bladder tumors. Definitive gene expression profiling may be valuable to further characterize this unique histologic variant.

Pure Large Nested Variant of Urothelial Carcinoma (LNUC) Is the Prototype of an FGFR3 Mutated Aggressive Urothelial Carcinoma with Luminal-Papillary Phenotype

Since 2016, large nested urothelial carcinoma (LNUC) has been included within the WHO classification of urothelial tumors. Limited reports with mainly small case series have confirmed the malignant behavior of LNUC despite its bland morphological appearance. We evaluated, for the first time, markers for new immunooncological or targeted therapies including FGFR3 mutational status and PD-L1 status, the frequency of TERT-promoter mutations and the molecular subtype in a cohort of 25 LNUC using SNaPshot analysis and immunohistochemistry. Of the 25 cases, 17 were pure LNUC, with 13 showing an additional exophytic papillary/papillary-like component. Seven mixed LNUCs presented areas of classical nested variant urothelial carcinoma (NVUC) and one showed a component of conventional urothelial carcinoma. Of the 17 evaluable pure LNUCs, 16 were FGFR3-mutated with identical mutations in their concomitant papillary/papillary-like components. An FGFR3 mutation was found in 1/7 evaluable mixed LNUCs combined with NVUC. TERT-promoter mutations were detected in 86.7% pure and 83.3% mixed tumors. Immunohistochemistry revealed a luminal phenotype; PD-L1 was negative in the majority of tumor cells and tumor-associated immune cells. Pure LNUC is a prime example of a luminal, FGFR3-mutated, mostly PD-L1-negative tumor. In contrast, FGFR3 mutations seem to be rare in mixed LNUC, which may indicate a different pathway of tumor development.