Invasive micropapillary urothelial carcinoma of the bladder.
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.
Lopez-Beltran A
，Montironi R
，Blanca A
，Cheng L
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Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 30 pure and mixed cases.
Nested urothelial carcinoma (UC) is a rare histologic variant of UC, characterized by deceptively bland histologic features resembling von Brunn's nests but usually with a poor outcome. In our experience, this variant is frequently misclassified or underrecognized as its clinicopathologic spectrum is not well defined. In addition, its relationship to usual UC and response to traditional bladder cancer management are largely unknown. Herein we report the largest series to date of 30 UC cases with pure or predominant nested morphology to identify its associated histopathologic findings, clinical outcome, and immunophenotype. Patient age ranged from 41 to 83 years (average, 63 years) with a male-female ratio of 2.3:1. The architectural pattern of the nested component ranged from a predominantly disorderly proliferation of discrete, small, variably sized nests (90%) to focal areas demonstrating confluent nests (40%), cordlike growth (37%), and cystitis cystica-like areas (33%) to tubular growth pattern (13%). The deep tumor-stroma interface was invariably (100%) jagged and infiltrative. Despite overall banal cytology, tumor nests demonstrated focal random cytologic atypia (90%) and focal high-grade cytologic atypia centered within the base of the tumor (40%). The tumor stroma ranged from having minimal stromal response to focally desmoplastic and myxoid. A component of usual UC was present in 63% of cases. The nested component demonstrated an immunophenotype identical to usual UC, with CK7, CK20, p63, and CK903 expression in 93%, 68%, 92%, and 92% of cases, respectively. At resection, all but 1 case demonstrated invasive carcinoma-9% into lamina propria, 4% into muscularis propria, 65% into perivesical fat, and 17% into adjacent organ(s). When compared with pure high-grade UC, nested UC was associated with muscle invasion at transurethral resection (31% versus 70%; P < .0001), extravesical disease at cystectomy (33% versus 83%; P < 0.0001), and metastatic disease (19% versus 67%; P < .0001). Follow-up was available on 29 patients (97%) with a median of 12 months (range, 1-31 months) of follow-up; 3 (10%) died of disease, 16 (55%) are alive with persistent or recurrent disease, and 10 (34%) are alive without disease. Response to neoadjuvant chemotherapy was observed in 2 (13%) of 15 patients. Nested UC seen either in pure form or with a component of usual UC had similarly unfavorable outcomes (P = .78). Increased awareness and familiarity with the clinicopathologic spectrum is critical for confident recognition and adequate management of this very aggressive variant of UC.
Wasco MJ
，Daignault S
，Bradley D
，Shah RB
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