Urothelial Carcinoma In Situ With Plasmacytoid Features A Clinicopathologic Study of 23 Cases

Although there are 5 well-described morphologic patterns of (nonglandular) urothelial carcinoma in situ (CIS), we have encountered a novel pattern of flat urothelial carcinoma with plasmacytoid features characterized by a triad of morphologic findings including abnormal architecture with cellular rounding, enlarged nuclei with eccentric nuclear localization, and dense globular eosinophilic cytoplasm. A total of 23 cases of plasmacytoid CIS (mean age: 74.1 y, range: 58 to 91 y) were collected and reviewed. We excluded cases in which the diagnostic biopsy had any of the following findings admixed in the same tissue biopsy sample as the plasmacytoid CIS: traditional patterns of CIS, noninvasive glandular CIS, papillary urothelial carcinoma, or invasive carcinoma. Immunostains for CK20, CD44, p53, and e-cadherin were performed on available blocks. History of prior urothelial neoplasia, prior treatment, and clinical follow-up were obtained from medical records and pathology re-review. Immunohistochemical analysis of plasmacytoid CIS showed diffuse/strong CK20 reactivity in 96% of cases (23/24), an abnormal p53 reactivity pattern (either overexpression or "null phenotype") in 37% of cases (7/19), absence of CD44 reactivity in the neoplastic cells in 63% of cases (15/24), and retained membranous e-cadherin expression in 100% of cases (18/18). Clinical follow-up (average follow-up time: 37.7 mo, range: 7 to 115 mo) showed recurrence/new occurrence in 52% of cases (12/23), including all 4 of the 23 patients who initially presented with de novo plasmacytoid CIS (ie, no prior or concomitant urothelial neoplasia). The histologic features, the immunophenotype, the association with other forms of urothelial neoplasia, and the risk of recurrence and progression in de novo lesions support that plasmacytoid CIS represents a novel pattern of flat urothelial carcinoma. These histologic features may be more subtle than in other more typical patterns of CIS and should be carefully distinguished from therapy-related/reactive changes.