Overlapping Morphologic and Immunophenotypic Features of Plasmacytoid Urothelial Carcinoma and Urothelial Carcinoma With Osteoclast-Like Giant Cells

Osteoclast-rich undifferentiated carcinoma of the urinary tract, herein referred to as urothelial carcinoma with osteoclast-like giant cells (UCOGC), is an uncommon tumor currently classified under "poorly differentiated" urothelial carcinoma subtype composed of osteoclast-like giant cells intermixed with abundant mononuclear cells. Not infrequently, the mononuclear component exhibits eccentric nuclear localization reminiscent of plasmacytoid urothelial carcinoma. Given an index tumor where the mononuclear component of UCOGC showed prominent plasmacytoid histology and concomitant plasmacytoid urothelial carcinoma immunophenotype (aberrant loss of membranous E-cadherin with cytoplasmic p120 expression), herein we explore E-cadherin/p120 immunoreactivity in 14 UCOGC with sequencing performed on 4 tumors. Plasmacytoid histology in the mononuclear was identified in all 14 (100%) UCOGC, extent ranging from 20% to 70% (mean = 40%). In 13 of 14 UCOGCs, the mononuclear component showed loss of membranous E-cadherin while strong cytoplasmic p120 staining was present in all 14 tumors. Four UCOGCs also contained separate elements of plasmacytoid subtype urothelial carcinoma, all exhibiting aberrant loss of membranous E-cadherin with cytoplasmic p120 expression. NGS testing showed no evidence of E-cadherin mutations in 4 tested UCOGCs. Although both plasmacytoid UC and UCOGC are associated with poor outcomes, given the established clinicopathologic and molecular features of plasmacytoid urothelial carcinoma, it is prudent to avoid misclassifying UCOGC as plasmacytoid urothelial carcinoma based on the shared aberrant immunoprofile of the mononuclear (loss of membranous E-cadherin with cytoplasmic p120 expression). Recognition of the intimately admixed osteoclast-like giant cells characteristic of UCOGC (often overlooked when sparse and/or in a small biopsy setting) is key for accurate diagnosis.