A multicenter review of histopathology of variants in the context of upper urinary tract urothelial carcinoma and their impact on clinical outcomes

IntroductionSimilar to bladder cancer, about one third of upper tract urothelial carcinoma (UTUC) present variant histology (VH). We aim to evaluate the incidence, clinical characteristics and the impact on outcomes of VH in UTUC. MethodsWe consecutively enrolled 77 patients from 2009-2022 treated with radical surgery for UTUC from a secondary and a tertiary referral center. A central pathology review of all specimens was performed by one independent uropathologist for each center. We compared pure UTUC and UTUC with VH and the accuracy of endoscopic biopsy. Descriptive and comparative analysis were used to assess association with clinical characteristics and the Kaplan-Meier estimator to compare outcomes. ResultsMedian follow-up after surgery was 51 months. VH was present in 21/77 (28%) patients and 4/21 (19%) patients had multiple variants. The most frequent VH was squamous 12/21 (57%), followed by glandular 6/21 (29%) and micropapillary 3/21 (14%). Small cell neuroendocrine bladder carcinoma was present in two patients. Nested variant was found in one patient. Muscle invasive tumor ([&ge;]pT2) was present in 29/56 (52%) patients with pure UTUC and in 18/21 (86%) patients with VH (p <0.05). Presence of carcinoma in situ was seen in 14/56 (25%) patients with pure UTUC and in 15/21 (71%) with VH (p <0.05). Cumulative 8/56 (14%) with pure UTUC had a non-intravesical recurrence (6 patients with local and 2 distant recurrence) compared to 8/21 (38%) (3 local, 3 nodal, 2 distant) in the subgroup with VH (p <0.05). Opposite effect was noted for bladder recurrence: 60% for pure UTUC vs. 29% for tumors with VH (p <0.05). Review of preoperative endoscopic biopsy did not show the presence of VH in any patients. Differences in outcomes did not reach significance: 3yr-OS 63% vs 42% (p 0.28) and 3yr-CSS 77% vs. 50% (p 0.7). ConclusionAlmost a third of UTUC present VH. Presence of VH is related to more aggressive tumor characteristics and associated with unfavorable outcomes. Due to a higher rate of extravesical recurrences in UTUC with VH, Follow-up controls should include cross sectional imaging and cystoscopy.