Perivascular epithelioid cell tumors of the urinary bladder: a multi-institutional clinicopathologic and molecular analysis of 21 cases

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.

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Journal
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
Published
2025-10-04
DOI
https://doi.org/10.1007/s00428-025-04250-y
Citations
1
Primary Topic
Tuberous Sclerosis Complex Research
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article
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1.16
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article

Perivascular epithelioid cell tumors of the urinary bladder: a multi-institutional clinicopathologic and molecular analysis of 21 cases

Sean R. Williamson, Jasreman Dhillon, Mahmut Akgül, Abbas Agaimy et al.
1 citations
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
Tuberous Sclerosis Complex Research
1.16
article

Perivascular epithelioid cell tumors of the urinary bladder: a multi-institutional clinicopathologic and molecular analysis of 21 cases

Sean R. Williamson, Jasreman Dhillon, Mahmut Akgül, Abbas Agaimy, Sambit K. Mohanty, Khaleel I. Al‐Obaidy, Shivani Kandukuri, Adeboye O. Osunkoya, Dinesh Pradhan, Anandi Lobo, Seema Kaushal, Rajal B. Shah, Ankur R. Sangoi, Swati P. Satturwar, Anil Vasdev Parwani, Ankit Tiwari, Arndt Hartmann, Andres Acosta, Shilpy Jha, Liang Cheng
article en
1 citations

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.

Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
Indiana University Health (US), Brigham and Women's Hospital (US), All India Institute of Medical Sciences Raipur (IN), McLaren Regional Medical Center (US), Cleveland Clinic (US), Emory University (US), University of California, Irvine (US), Cold Spring Harbor Laboratory (US), Brown University (US), McLaren Health Care (US), The Ohio State University Wexner Medical Center (US), Moffitt Cancer Center (US), Universitätsklinikum Erlangen (DE), Southwestern Medical Center (US), Stanford Health Care (US), Stanford Medicine (US), Span Diagnostics (India) (IN), Manipal Hospital (IN), Southwestern Medical Center (US), Indiana University – Purdue University Indianapolis (US), University of Nebraska Medical Center (US), All India Institute of Medical Sciences (IN), The University of Texas Southwestern Medical Center (US)
Openalex Percentile: Top 17%
Tuberous Sclerosis Complex Research
1.16
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