Invasive micropapillary urothelial carcinoma of the bladder

Abstract

In this report, we present the clinicopathologic features of 13 cases of the invasive micropapillary variant of urothelial carcinoma. This is a rare and aggressive variant of bladder cancer recognized by the current World Health Organization classification of urologic tumors. The micropapillary component varied from 50% to 100% of the tumor specimen; in 10 cases, the micropapillary component composed greater than 70% of the tumor, with 5 cases showing pure micropapillary carcinoma. The architectural pattern of the tumor varied from solid expansile nests with slender papillae within tissue retraction spaces to pseudoglandular growth with prominent ring-like structures (2 cases, 15%) and invasive micropapillary carcinoma with squamous differentiation (2 cases, 15%); a streaking solid architectural pattern of micropapillary carcinoma was additionally present in 2 cases (15%). At histology, the individual tumor cells had abundant eosinophilic cytoplasm and nuclei with prominent nucleoli and irregular distribution of chromatin, and frequent mitotic figures. Most neoplastic cells had nuclei of low to intermediate nuclear grade with occasional nuclear pleomorphism. Eight mixed cases had concurrent conventional high-grade urothelial carcinoma with squamous or glandular differentiation in 3 and 1 case(s), respectively. All patients had advanced-stage cancer (>pT2), and 8 (62%) had lymph node metastasis. Immunohistochemical staining demonstrated that both micropapillary and associated conventional urothelial carcinomas were positive for MUC1 and 2, cytokeratin 7, PTEN, p53, and Ki-67. Her2Neu, uroplakin, cytokeratin 20, 34betaE12, CA125, and p16 were positive in 4, 10, 8, 7, 3, and 3 cases, respectively. MUC5A, MUC6, and CDX2 were negative in all micropapillary cases. Follow-up information was available in all cases (range, 2-21 months; mean, 10 months). Eleven of patients died of disease from 2 to 14 months, and 2 patients were alive with disease at 14 and 21 months. Univariate statistical analysis showed survival differences between invasive micropapillary and conventional urothelial carcinomas (P < .0001). In summary, invasive micropapillary variant of urothelial carcinoma is an aggressive variant associated with poor prognosis that presents at an advanced clinical stage. The immunophenotype of invasive micropapillary carcinoma supports urothelial origin; the immunoreactivity to Her2Neu and PTEN might be relevant in terms of future targeting therapy. The morphologic diversity of micropapillary carcinoma may represent a diagnostic pitfall in limited samples, where its distinction from conventional urothelial carcinoma is critical for its clinical management.