Can We Foresee Grade and Stage Progression in Mixed Low- and High-Grade Noninvasive Papillary Urothelial Carcinomas?

Noninvasive papillary urothelial carcinoma (NIPUC), currently classified in a two-tier system, frequently exhibits mixed low- and high-grade morphology. We aimed to determine the impact of histopathologic features on grade and stage progression in mixed NIPUCs. Primary and follow-up bladder specimens (n = 106) of 28 patients diagnosed with mixed NIPUC were retrieved. Pathological parameters included biopsy volume, percentages of 2-tier (low-high) and 4-tier (Grade 1-4) grades, discohesion, and whirling. Outcome measures were grade trend (decline or incline) and stage progression. The mean age was 65 (range, 35-81); all but two were male. Ten patients had a previous biopsy showing pure low-grade NIPUC. Patients with > 5% high-grade areas (n = 14) were classified as high-grade. The mean distributions of G1-G4 in mixed NIPUCs at zero-point were 42%, 42%, 15%, and 1%, respectively. Tumors with > 85% Grade 1 histology didn't exhibit an upward grade trend. Stage progression was significantly associated with tumors containing ≥ 5% Grades 3-4 (high-grade) areas (p = 0.031). Grade trend was directly correlated with stage progression (p = 0.012). Mixed NIPUC has heterogeneous clinical outcomes: a high proportion of Grade 1 areas (> 85%) predicts a non-inclining grade trend, whereas the presence of ≥ 5% high-grade (Grades 3 and 4) morphology suggests future stage progression.