844 Perivascular Epithelioid Cell Tumors of the Urinary Bladder: A Clinicopathologic and Comprehensive Molecular Analysis including Microsatellite Instability Status and Tumor Mutational Burden in a Contemporary Cohort of 21 cases

Document Type

Conference Proceeding

Publication Date

3-24-2025

Publication Title

Lab Invest

Keywords

mammalian target of rapamycin, protein p53, adolescent, adult, bladder, bladder tumor, child, clinical article, cohort analysis, conference abstract, female, fluorescence in situ hybridization, follow up, genetic variability, genetic variation, high throughput sequencing, human, male, metastasis, microsatellite instability, middle aged, mitosis, muscle development, nonsense mutation, perivascular epithelioid cell tumor, school child, tumor mutational burden

Abstract

Disclosures: Anandi Lobo: None; Ankit Tiwari: None; Abbas Agaimy: None; Mahmut Akgul: None; Ankur Sangoi: None; Shivani Kandukuri: None; Andres Acosta: None; Khaleel Al-Obaidy: None; Shilpy Jha: None; Seema Kaushal: None; Swati Satturwar: None; Jasreman Dhillon: None; Adeboye Osunkoya: None; Sean Williamson: None; Dinesh Pradhan: None; Rajal Shah: None; Anil Parwani: None; Liang Cheng: None; Sambit Mohanty: None Background: Perivascular epithelioid cell tumor (PEComa) of the urinary bladder is a rare neoplasm showing distinct melanocytic and smooth muscle differentiation. PEComas have been described arising in most organ systems; however, only a small number of bladder PEComas have been reported. Although majority of them behave in an indolent fashion, a small subset may develop metastasis and cause death. Herein, we sought to describe the clinicopathologic and molecular characteristics in a cohort of 21 such tumors. Design: Twenty-one urinary bladder PEComa cases were collated. Clinicopathologic, IHC, molecular and outcome data were analysed. DNA and RNA NGS, FISH, microsatellite instability (MSI) and tumor mutational burden (TMB) was assessed in 17 tumors. Results: There were 21 patients (13 females, 8 males), with age ranging from 17-81 years (mean=47.6 years). Clinical follow-up data was available for 17 patients, follow-up period range 5-60 months (mean=19.4 months). Figures 1 and 2 summarize the microscopic, IHC and NGS results and Table 1 summarize the clinicopathologic features and matches it with the outcome data. TRIM63 ISH showed high sensitivity (89%) with poor specificity (11%) for TFE3 rearrangements by NGS. 17/17 PEComas showed mutations by NGS which are as follows: PSF::TFE3 fusion (7/17, 41%) and TSC1/2 missense and nonsense mutations (6/17, 35%), MTOR (3/17, 18%), and co-mutations of TSC/MTOR (2/17,12%). Additionally, co-mutations involving p53 were noted in 2 tumors (1 with PSF::TFE3/p53; 1 with MTOR/p53). The morphologic features significantly associated with metastatic disease included >2 mitoses/high-power field (n=7,88%; p=0.01), atypical mitoses (n=7,88%; p=0.01), necrosis (n=7,88%; p=0.01), ≥70% atypical epithelial cells (n=6, 75%; p=0.05) and vascular involvement (n=6, 75%; p=0.05). Four TFE3-rearranged tumors developed metastasis (OR=4.67), while 6 TSC/MTOR mutated tumors had metastatic disease (OR=0.19). [Formula presented] [Formula presented] [Formula presented] Conclusions: 1. The metastatic potential of bladder PEComas has a significant association with morphologic parameters such as ≥70% atypical epithelial cells, >2 mitoses/10 hpf, atypical mitoses, necrosis and vascular invasion. 2. TFE3-rearranged tumors have a slightly higher propensity towards an aggressive outcome in comparison to TSC/MTOR altered tumors. 3. Furthermore, as there is much genetic diversity within these tumors in the form of TSC/MTOR and TFE3-rearranged alterations, assessment of the molecular signature is essential for therapy selection and prognostication.

Volume

105

Issue

3

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