Rizkalla Carol N, Tretiakova Maria, Williamson Sean R, Akgul Mahmut, Al-Obaidy Khaleel I, Acosta Andres M, Idrees Muhammad T, Chan Emily, Sangoi Ankur R
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Department of Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
Int J Surg Pathol. 2025 Aug 19:10668969251363267. doi: 10.1177/10668969251363267.
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.
富含破骨细胞的泌尿道未分化癌，在此称为伴有破骨细胞样巨细胞的尿路上皮癌（UCOGC），是一种罕见肿瘤，目前归类于“低分化”尿路上皮癌亚型，由破骨细胞样巨细胞与大量单核细胞混合组成。单核细胞成分常常表现出核偏心定位，让人联想到浆细胞样尿路上皮癌。鉴于有一例索引肿瘤，其中UCOGC的单核细胞成分显示出显著的浆细胞样组织学特征以及伴发的浆细胞样尿路上皮癌免疫表型（膜性E-钙黏蛋白异常缺失伴细胞质p120表达），在此我们探讨了14例UCOGC中E-钙黏蛋白/p120的免疫反应性，并对4例肿瘤进行了测序。在所有14例UCOGC中均发现单核细胞中有浆细胞样组织学特征，范围为20%至70%（平均=40%）。在14例UCOGC中的13例中，单核细胞成分显示膜性E-钙黏蛋白缺失，而在所有14例肿瘤中均存在强细胞质p120染色。4例UCOGC还包含浆细胞样亚型尿路上皮癌的单独成分，均表现出膜性E-钙黏蛋白异常缺失伴细胞质p120表达。二代测序检测显示，4例检测的UCOGC中没有E-钙黏蛋白突变的证据。尽管浆细胞样尿路上皮癌和UCOGC均与不良预后相关，但鉴于浆细胞样尿路上皮癌已明确的临床病理和分子特征，基于单核细胞共享的异常免疫表型（膜性E-钙黏蛋白缺失伴细胞质p120表达）而将UCOGC误分类为浆细胞样尿路上皮癌是谨慎的做法。识别UCOGC特有的紧密混合的破骨细胞样巨细胞（在稀疏和/或小活检情况下常被忽视）是准确诊断的关键。
