883 Osteoclast-Rich Undifferentiated Urothelial Carcinoma: An Expanded Immunohistochemical and Molecular Profiling with Classification Re-assessment

Document Type

Conference Proceeding

Publication Date

3-24-2025

Publication Title

Lab Invest

Keywords

cathepsin K, chlordane, chorionic gonadotropin, cilmostim, colony stimulating factor 1, transcription factor GATA 3, valproic acid, anaplastic carcinoma, cell differentiation, clinical article, conference abstract, diagnosis, female, giant cell, giant cell tumor, giant cell tumor of tendon sheath, high throughput sequencing, histology, human, human cell, human tissue, immunofluorescence, immunohistochemistry, in situ hybridization, molecular fingerprinting, mononuclear cell, osteoclast, osteoclastoma, synovium, transitional cell carcinoma, urinary tract carcinoma, urothelium

Abstract

Disclosures: Carol Rizkalla: None; Maria Tretiakova: None; Carlos Suarez: None; Sean Williamson: None; Khaleel Al-Obaidy: None; Andres Acosta: None; Muhammad Idrees: None; Emily Chan: None; Susan Potterveld: None; Ankur Sangoi: None Background: Osteoclast-rich undifferentiated carcinoma of the urinary tract (ORUC) is a rare tumor currently classified under the "poorly differentiated urothelial carcinoma" subtype. Neoplasms with similar morphology have been reported in bone, soft tissue, synovium, and visceral organs. To date, only limited study into the immunoprofile of ORUC has been performed without assessment of novel histiocytic/osteoclastic markers. Moreover, there is limited data on the molecular profiling of ORUC. Design: Clinicopathologic features of 14 ORUCs were recorded with immunohistochemistry (IHC) performed using CD68, CD163, PU.1, SATB2, cathepsin K, pankeratin, p63, GATA3, H3.G34W, and HCG. In situ hybridization (ISH) for CS1 was also performed. Semi-quantitative staining results for both the mononuclear (MN) and giant cell (GC) components of ORUC were scored (0-3). Comparative staining was performed on 6 urothelial carcinomas (UC) with trophoblastic differentiation and 5 UC with pleomorphic giant cells. Next-generation sequencing (NGS) was performed on 4 ORUC tumors. Results: All ORUCs showed classic biphasic morphology of osteoclast-like giant cells intermixed with mononuclear cells. The extent of ORUC elements in the urothelial carcinomas ranged from 5% to 95% (mean=44%), and often included other UC morphologies (Figure 1). IHC revealed distinct profiles with some overlap for MN and GC (Figure 2). The MN cells averaged high scores for histiocytic markers (CD68, CD163, PU.1) and osteoclastic markers (SATB2, cathepsin K, CSF1 ISH), was moderate for urothelial markers (GATA3, p63), and low for pankeratin. In contrast, the GCs showed variable scores for both histiocytic and osteoclastic markers and no staining for urothelial markers or pankeratin. Both MN/GC were negative for H3.G34W and HCG. The multinucleated cells from all UC with trophoblastic differentiation and UC with pleomorphic GCs were negative for histiocytic and osteoclastic markers. NGS from all 4 tested ORUC showed mutations consistent with urothelial carcinoma without any fusions identified. [Formula presented] [Formula presented] Conclusions: The expression ofUC markers in the MN component along with a molecular profile and concomitant backgroundUC histology overall support urothelial origin to ORUC. Moreover, as ORUC exhibits both morphologic and immunophenotypic overlap with other tumor types (e.g., tenosynovial giant cell tumor, giant cell tumor of bone, giant cell tumor of soft parts), it may warrant re-categorization as UC with osteoclast-rich differentiation.

Volume

105

Issue

3

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