Perivascular epithelioid cell tumors of the urinary bladder: a multi-institutional clinicopathologic and molecular analysis of 21 cases
Year: 2025
Type: article
Study design: Observational Study
Abstract: While perivascular epithelioid cell tumor (PEComas) have been described in most organ systems, only a few bladder PEComas have been reported. Although most behave in an indolent fashion, a subset may develop metastasis. Herein, we describe the clinicopathologic and molecular characteristics of 21 bladder PEComas, including biomarker analysis and comprehensive sequencing. Patients included 13 females and 8 males, with age ranging from 17-81 years (mean = 47.6 years). Clinical follow-up data was available for 17 patients (ranging 5-60 months; mean = 19.4 months). The morphologic features significantly associated with metastatic disease included ≥ 2 mitoses/10 high-power fields (p = 0.0023), atypical mitoses (p = 0.0152), and necrosis (p = 0.0023); the presence of ≥ 70% atypical epithelioid cells and vascular invasion did not meet statistical significance. The Biomarker profile (p16, p53, TRIM63 ISH, ATRX, RB1) found no statistical significance with metastasis. TRIM63 ISH showed high sensitivity (86%) with poor specificity (11%) for TFE3 rearrangements. NGS revealed TFE3 fusions in 8/17 cases (47%): 7 with SFPQ::TFE3 fusions and 1 with NONO::TFE3 fusion). Overall, mTOR pathway mutations were detected in 9 cases (53%): TSC1/2 mutations in 6 (35%), MTOR mutation in 1 (6%), and co-mutations of TSC/MTOR in 2 (12%) cases. Additionally, co-mutations involving p53 were noted in 2 tumors (1 SFPQ::TFE3/p53; 1 MTOR/p53). Metastasis was identified in 5 TFE3-rearranged PEComas (OR = 8.7509) and 2 TSC/MTOR- mutated tumors (OR = 0.1143). TFE3-rearranged bladder PEComas show a higher propensity towards aggressive behavior compared to TSC/MTOR- mutated tumors. Awareness of the molecular signature may be important for prognostic stratification and targeted therapeutic approaches.
Authors: Ankur R. Sangoi, Anandi Lobo, Ankit Tiwari, Mahmut Akgul, Shivani Kandukuri, Andres M. Acosta, Khaleel I. Al-Obaidy, Shilpy Jha, Seema Kaushal, Swati Satturwar, Jasreman Dhillon, Adeboye O. Osunkoya, Sean R. Williamson, Dinesh Pradhan, Rajal B. Shah, Anil V. Parwani, Liang Cheng, Arndt Hartmann, Sambit K. Mohanty, Abbas Agaimy
Institutions: Stanford Health Care, Stanford Medicine, Stanford University, Cold Spring Harbor Laboratory, Brigham and Women's Hospital, University of California, Irvine, Indiana University Health, McLaren Regional Medical Center, McLaren Health Care, All India Institute of Medical Sciences, The Ohio State University Wexner Medical Center, Moffitt Cancer Center, Emory University, Cleveland Clinic, University of Nebraska Medical Center, The University of Texas Southwestern Medical Center, Brown University, Universitätsklinikum Erlangen
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
Funder: Universitätsklinikum Erlangen
OpenAlex ID: W4414806346