Uterine PEComas: correlation between melanocytic marker expression and TSC alterations/TFE3 fusions

Mod Pathol. 2022 Apr;35(4):515-523. doi: 10.1038/s41379-021-00855-1. Epub 2021 Jun 15.


Uterine PEComas often present a diagnostic challenge as they share morphological and immunohistochemical features with smooth muscle tumors. Herein we evaluated a series of 19 uterine PEComas to compare the degree of melanocytic marker expression with their molecular profile. Patients ranged from 32-77 (median 48) years, with six tumors classified as malignant based on the modified gynecologic-specific prognostic algorithm. All patients with malignant PEComas were alive with disease or dead of disease at last follow-up, while all those of uncertain malignant potential were alive and well (median follow-up, 47 months).Seventeen of 19 (89%) PEComas harbored either a TSC1 or TSC2 alteration. One of the two remaining tumors showed a TFE3 rearrangement, but the other lacked alterations in all genes evaluated. All showed at least focal (usually strong) positivity for HMB-45, with 15/19 (79%) having >50% expression, while the tumor lacking TSC or TFE3 alterations was strongly positive in 10% of cells. Melan-A and MiTF were each positive in 15/19 (79%) tumors, but staining extent and intensity were much more variable than HMB-45. Five of six (83%) malignant PEComas also harbored alterations in TP53, ATRX, or RB1, findings not identified in any tumors of uncertain malignant potential. One malignant PEComa was microsatellite-unstable/mismatch repair protein-deficient.In summary, TSC alterations/TFE3 fusions and diffuse (>50%) HMB-45 expression are characteristic of uterine PEComas. In morphologically ambiguous mesenchymal neoplasms with myomelanocytic differentiation, especially those with metastatic or recurrent disease, next-generation sequencing is recommended to evaluate for TSC alterations; as such, patients can be eligible for targeted therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / genetics
  • Biomarkers, Tumor / genetics
  • Female
  • Humans
  • Perivascular Epithelioid Cell Neoplasms* / genetics
  • Perivascular Epithelioid Cell Neoplasms* / pathology
  • Smooth Muscle Tumor*
  • Tuberous Sclerosis Complex 1 Protein* / genetics
  • Tuberous Sclerosis Complex 2 Protein* / genetics


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Biomarkers, Tumor
  • TFE3 protein, human
  • TSC1 protein, human
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein