Clinicopathological and genomic characterization of BCORL1-driven high-grade endometrial stromal sarcomas

Mod Pathol. 2021 Dec;34(12):2200-2210. doi: 10.1038/s41379-021-00873-z. Epub 2021 Jul 23.


BCORL1 is a transcriptional corepressor homologous to BCOR. We describe 12 BCORL1-altered uterine sarcomas with striking resemblance to BCOR-altered endometrial stromal sarcoma (BCOR-ESS), including 5 with BCORL1 rearrangements (JAZF1-BCORL1, EP300-BCORL1, or internal BCORL1 rearrangement), 5 with inactivating BCORL1 mutations (T513fs*22, P600fs*1, R945*, R1196*, or R1265fs*4) and 2 with homozygous BCORL1 deletion. The median patient age was 57.5 years (range 33-79). An association with aggressive clinical behavior was identified. Diagnoses assigned prior to genomic testing varied: 7 tumors were previously diagnosed as ESS, 2 as high-grade uterine sarcomas, 2 as myxoid uterine leiomyosarcomas, and 1 as a uterine spindle cell neoplasm consistent with leiomyosarcoma. Tumors harbored frequent gelatinous, mucomyxoid-like appearance by gross examination and unique histology with morphological overlap with BCOR-ESS. Key microscopic features included (1) a spindle cell appearance, most often with at least focal myxoid stroma, (2) variable amounts of hypocellular fibromyxoid spindle areas with lower grade atypia and/or (3) variable amounts of epithelioid areas with higher grade atypia. Specifically, spindle and epithelioid components were present in 100 and 75% of sarcomas, respectively; myxoid stroma was identified in 83%, collagen plaques or fibrosis in 50%, and high-grade nuclear atypia was present in 42%. Like BCOR-ESS, 50% of BCORL1-altered sarcomas exhibited CDK4 amplification or CDKN2A loss. In contrast, 33% harbored NF1 alterations, while 25% had other alterations in the NF2-mTOR pathway, expanding potential therapeutic targets. In conclusion, inactivating BCORL1 genomic alterations may define a distinct subset of high-grade endometrial stromal sarcomas with biological overlap with BCOR-ESS, both of which may mimic myxoid leiomyosarcomas.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Databases, Factual
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Amplification
  • Gene Rearrangement
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Molecular Diagnostic Techniques
  • Mutation
  • Neoplasm Grading
  • Phenotype
  • Predictive Value of Tests
  • Repressor Proteins / genetics*
  • Retrospective Studies
  • Sarcoma, Endometrial Stromal / genetics*
  • Sarcoma, Endometrial Stromal / pathology


  • BCORL1 protein, human
  • Biomarkers, Tumor
  • Repressor Proteins