Alveolar Soft Part Sarcoma of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Cytogenetic Study of 10 Cases With Emphasis on its Distinction From Morphologic Mimics

Am J Surg Pathol. 2017 May;41(5):622-632. doi: 10.1097/PAS.0000000000000796.


Alveolar soft part sarcoma (ASPS) is a morphologically distinctive neoplasm of unknown differentiation that bears a characteristic gene fusion involving ASPSCR1 and TFE3. ASPS can occur in the female genital tract, but is rare. Eleven cases with an initial diagnosis of ASPS at female genital tract sites were evaluated for their morphologic features and immunoprofile using a panel of antibodies (TFE3, HMB45, melan-A, smooth muscle actin, desmin, and h-Caldesmon). In addition, the presence of TFE3 rearrangement and subsequent ASPSCR1-TFE3 fusion were determined by fluorescence in situ hybridization. Ten tumors retained their classification as ASPS based on their morphologic appearance, immunohistochemical profile, and demonstration of ASPSCR1-TFE3 fusion. The remaining case was reclassified as conventional-type PEComa due to its pattern of HMB45, melan-A, and desmin positivity as well as absence of TFE3 rearrangement. Sites of the 10 ASPS were uterine corpus (3), cervix (2), uterus not further specified (2), vagina (2), and vulva (1). The age of the patients ranged from 15 to 68 years (mean 34 y, median 32 y). The tumors demonstrated a spectrum of morphologic features, but all had a consistent immunophenotype of strong TFE3 nuclear expression and lack of muscle (smooth muscle actin, desmin, h-Caldesmon) and melanocytic (melan-A, HMB45) markers, except focal positivity for HMB45 in 1. Follow-up was available for 4 patients ranging from 1 to 35 months (mean 15 mo, median 25 mo) and they were alive and had no evidence of recurrence or metastasis at last follow-up. Distinguishing ASPS from its morphologic mimics, particularly PEComa, is important due to increasingly efficacious targeted agents such as MET-selective and VEGF signaling inhibitors in the former and mTOR inhibition therapy in the latter.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / analysis
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics*
  • Biopsy
  • Boston
  • Diagnosis, Differential
  • Female
  • Gene Fusion
  • Gene Rearrangement
  • Genital Neoplasms, Female / chemistry
  • Genital Neoplasms, Female / diagnosis*
  • Genital Neoplasms, Female / genetics
  • Genital Neoplasms, Female / pathology
  • Humans
  • Immunohistochemistry*
  • In Situ Hybridization, Fluorescence*
  • Intracellular Signaling Peptides and Proteins
  • Middle Aged
  • Molecular Diagnostic Techniques*
  • Oncogene Proteins, Fusion / genetics
  • Perivascular Epithelioid Cell Neoplasms / chemistry
  • Perivascular Epithelioid Cell Neoplasms / diagnosis*
  • Perivascular Epithelioid Cell Neoplasms / genetics
  • Perivascular Epithelioid Cell Neoplasms / pathology
  • Predictive Value of Tests
  • Prognosis
  • Sarcoma, Alveolar Soft Part / chemistry
  • Sarcoma, Alveolar Soft Part / diagnosis*
  • Sarcoma, Alveolar Soft Part / genetics
  • Sarcoma, Alveolar Soft Part / pathology
  • Sweden
  • Young Adult


  • ASPSCR1 protein, human
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins, Fusion
  • TFE3 protein, human