Novel High-grade Endometrial Stromal Sarcoma: A Morphologic Mimicker of Myxoid Leiomyosarcoma

Am J Surg Pathol. 2017 Jan;41(1):12-24. doi: 10.1097/PAS.0000000000000721.

Abstract

Endometrial stromal sarcomas (ESS) are often underpinned by recurrent chromosomal translocations resulting in the fusion of genes involved in epigenetic regulation. To date, only YWHAE-NUTM2 rearrangements are associated with distinctive high-grade morphology and aggressive clinical behavior. We identified 3 ESS morphologically mimicking myxoid leiomyosarcoma of the uterus and sought to describe their unique histopathologic features and identify genetic alterations using next-generation sequencing. All cases displayed predominantly spindled cells associated with abundant myxoid stroma and brisk mitotic activity. Tumors involved the endometrium and demonstrated tongue-like myometrial infiltration. All 3 were associated with an aggressive clinical course, including multisite bony metastases in 1 patient, progressive peritoneal disease after chemotherapy in another, and metastases to the lung and skin in the last patient. All 3 ESS were found to harbor ZC3H7B-BCOR gene fusions by targeted sequencing and fluorescence in situ hybridization. On the basis of the review of these cases, we find that ESS with ZC3H7B-BCOR fusion constitutes a novel type of high-grade ESS and shares significant morphologic overlap with myxoid leiomyosarcoma.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics*
  • Diagnosis, Differential*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology*
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Leiomyosarcoma / genetics
  • Leiomyosarcoma / pathology
  • Middle Aged
  • Neoplasm Grading
  • Oncogene Fusion / genetics
  • Oncogene Proteins, Fusion / genetics
  • Proto-Oncogene Proteins / genetics*
  • RNA-Binding Proteins / genetics*
  • Repressor Proteins / genetics*
  • Sarcoma, Endometrial Stromal / genetics
  • Sarcoma, Endometrial Stromal / pathology*

Substances

  • BCOR protein, human
  • Biomarkers, Tumor
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • ZC3H7B protein, human