December 2020 — Gynecological and Molecular

A 67-year-old woman had endometrial polypectomy followed by total hysterectomy and bilateral salpingo-oophorectomy (THBSO) due to a large uterine tumor. The surgical pathology specimen showed a 10 cm lesion involving only the uterus. Histologically, the lesion showed spindle cells with mild to moderate cytological atypia in a myxoid background as shown in the photomicrographs below (areas of necrosis were also noted). Polymerase Chain Reaction (PCR)-Based Next-Generation Sequencing demonstrated a fusion between the BCOR and ZC3H7B genes as schematically illustrated.

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Gene Fusion Schematic - Click on image to view larger.

What is the correct diagnosis?

  • High-grade endometrial stromal sarcoma
  • Myxoid leiomyosarcoma
  • Low-grade endometrial stromal sarcoma
  • Inflammatory myofibroblastic tumor

The correct answer is...

The correct answer is High-grade endometrial stromal sarcoma.

This a very nice example of a high-grade endometrial stromal sarcoma (HGESS) with ZC3H7B-BCOR fusion. HGESS is a category of ESS typically harboring YWHAE-NUTM2 (FAM22) genetic fusion as a result of t(10;17). However, in 2017 a new subtype of HGESS morphologically mimicking myxoid leiomyosarcoma was described. Histologically, these HGESS demonstrate mainly spindled cells with mild to moderate cytological atypia in an abundant myxoid stroma and brisk mitotic activity (yellow arrows point to mitotic figures). Immunohistochemically, they are positive for CD10 and Cyclin D1 (our particular case was shown to be positive for CD10 and PR, while negative for desmin, ALK-1, SMA and keratin). Molecularly, they harbor ZC3H7B-BCOR gene fusions which are usually revealed by sequencing or fluorescence in-situ hybridization. In terms of behavior, these malignancies have a prognosis in-between low-grade endometrial stromal sarcoma and undifferentiated uterine sarcomas.

1. Kurman RJ, At all. WHO Classification of Tumours of Female Reproductive Organs. IARC: Lyon 2014
2. Hoang LN, At all. Novel High-Grade Endometrial Stromal Sarcoma: A Morphologic Mimicker of Myxoid Leiomyosarcoma. Am J Surg Pathol. 2017 January ; 41(1): 12–24.
3. Ferreira J, At all. Recent advances in the histological and molecular classification of endometrial stromal neoplasms. Virchows Archiv (2018) 473:665–678.
4. Lewis N, At all. ZC3H7B-BCOR high-grade endometrial stromal sarcomas: a report of 17 cases of a newly defined entity. Modern Pathology (2018) 31, 674–684.
5. Cotzia P, At all. Undifferentiated Uterine Sarcomas Represent Underrecognized High-Grade Endometrial Stromal Sarcomas. Am J Surg Pathol. 2019 May ; 43(5): 662–669.

Photo of Simone Barreto Siqueira Parrilha Terra, M.D. Simone Barreto Siqueira Parrilha Terra, M.D.
Resident, Molecular Genetic Pathology
Mayo Clinic
Photo of Kevin Halling, M.D., Ph.D. Kevin Halling, M.D., Ph.D.
Consultant, Laboratory Genetics and Genomics
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

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