Variant (divergent) histologic differentiation in urothelial carcinoma is under-recognized in community practice: Impact of mandatory central pathology review at a large referral hospital

Background and objective: Urothelial carcinoma (UC) demonstrating variant histologic differentiation is associated with poor outcomes, and certain variants exhibit differing therapeutic responses compared with pure conventional UC. Little is known about the awareness and reporting practices of UC with variant histology in community practice. Materials and Methods: Patients diagnosed with UC based on an outside pathologic review had their pathology centrally reviewed before instituting therapy. A discordant diagnosis was defined as the presence of variant histologic differentiation not reported by the referring institution. Variant histologic differentiation was quantitated as focal (10%-50%) or extensive (>50%). Results: Of 589 transurethral biopsies (TURBTs), 115 (19.5%) UCs demonstrated variant histologic differentiation. Muscle invasion at TURBT and extravesical disease at cystectomy was present in 69% and 52%, respectively. Of 56 patients with at least 1 year follow-up, recurrence-free survival was 56%. The majority (90%) showed a single variant histology, which was extensive in 58% of cases. Squamous differentiation (32%) was the most common variant histology identified, followed by small cell (16%), glandular (13%), micropapillary (12%), nested (8%), sarcomatoid (6%), lymphoepithelial (3%), and plasmacytoid (1%) type. Variant histologic differentiation was not documented by the referring institution in 44% of cases, of which 47% were extensive. Commonly under-recognized patterns included lymphoepithelial (2) and plasmacytoid (1) types (100%), nested (7, 87%), micropapillary (10, 83%), and small cell (7, 44%). Conclusions: This study emphasizes the importance of central pathology review in the management of bladder cancer patients and the need for increased awareness of this relatively common phenomenon in UC.