Uterus
Stromal tumors
High grade endometrial stromal sarcoma

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Editor-in-Chief: Debra L. Zynger, M.D.

Minor changes: 14 December 2020

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PubMed search: High grade endometrial stromal sarcoma [title]

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Cite this page: Ondič O. High grade endometrial stromal sarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusESShighgrade.html. Accessed January 15th, 2021.
Definition / general
  • Very rare biologically aggressive mesenchymal tumor of the uterus originating in the endometrial stroma
Essential features
ICD coding
  • ICD-O: 8930/3 - endometrial stromal sarcoma, high grade
  • ICD-10: C54.1 - malignant neoplasm of endometrium
Epidemiology
Sites
  • Mostly uterine corpus
  • Rarely uterine isthmus
Pathophysiology
  • Gene rearrangement: YWHAE-NUTM2 (NUTM2 synonym FAM22)
  • Gene rearrangement: ZC3H7B-BCOR (reciprocal)
  • Gene internal tandem duplication (ITD): BCOR (Am J Surg Pathol 2018;42:335)
  • Possibly other so far unknown or unconfirmed pathogenic gene fusions
  • High grade transformation of low grade endometrial stromal sarcomas with JAZF1-SUZ12, JAZF1-PHF1, EPC1-PHF1 or BRD8-PHF1 (Mod Pathol 2020;33:1861)
Etiology
  • Unknown
Clinical features
  • Nonspecific presentation including pelvic pain, menorrhagia, postcoital bleeding
Diagnosis
  • Hysterectomy
Radiology description
  • Doppler ultrasound finding may imitate:
    • Uterine leiomyosarcoma
    • Endometrioid endometrial carcinoma with myometrial invasion
  • As per PET / MR, it may be diagnosed as unspecified uterine malignancy with high metabolic activity
Radiology images

Contributed by Jan Kosťun, M.D., Pavel Vlasák, M.D. and Eva Ferdová, M.D.
Doppler US with sarcoma features

Doppler ultrasound with sarcoma features

Dopler US with endometrioid cancer features Doppler US with endometrioid cancer features

Doppler ultrasound with endometrioid cancer features

High metabolic activity tumor

High metabolic activity tumor

Prognostic factors
  • Stage (the single most important prognostic factor)
  • Type of surgical procedure (morcellation is an unfavorable prognostic factor)
  • Recurrence and overall prognosis cannot be assessed due to insufficient data
Case reports
Treatment
  • Abdominal hysterectomy and bilateral adnexectomy
  • Above followed by (mostly) doxorubicin or ifosfamide monotherapy or gemcitabine / docetaxel combination therapy (Obstet Gynecol 2013;122:676)
  • Alternatively, oral antiangiogenic tyrosine kinase inhibitor (TKI) pazopanib (BMC Cancer 2018;18:92)
Gross description
Gross images

Contributed by Ondrej Ondič, M.D., Ph.D.

High grade endometrial stromal sarcoma

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Ondrej Ondič, M.D., Ph.D.
Spindle cell morphology

Spindle cell morphology

High grade component

High grade component

Signet ring-like change

Myxoid stroma and signet ring-like change

Tongue-like infiltration

Tongue-like infiltration

Small round cells

Small round cells

Positive stains
Negative stains
Molecular / cytogenetics description
  • Gene rearrangement involving BCOR, ZC3H7B, YWHAE, NUTM2A, NUTM2B genes, with breaks at different exons, can be detected by FISH showing split signal
  • Internal tandem duplication (ITD) of BCOR gene - tandem duplications of different sizes affecting exon 15 (Am J Surg Pathol 2018;42:335, Mod Pathol 2020;33:1669)
  • Rare BCOR gene rearrangement partners: BCOR- L3MBTL2, EP300- BCOR, BCOR- NUTM2G, BCOR- RALGPS1, BCOR- MAP7D2, RGAG1-BCOR, ING3- BCOR, BCOR- NUGGC, KMT2D- BCOR, CREBBP- BCOR (Gynecol Oncol 2020;157:357)
  • Some BCOR rearranged cases present with co-occurence of associated alteration of CDK4 pathway members (CDK4 amplification or CDKN2A loss) (Gynecol Oncol 2020;157:357)
  • In some cases there can be no gene rearrangement detected by the means of currently used NGS gene panels
Sample pathology report
  • Uterus, hysterectomy and bilateral adnexectomy:
    • ZC3H7B-BCOR rearranged high grade endometrial stromal sarcoma (see comment, see synoptic report)
    • Comment: Polypoid high grade mesenchymal tumor consisting of a spindle cell population with focal myxoid stroma and up to 15 mitoses per 10 high power fields. Tumor border is tongue-like, infiltrating less than half of the myometrial wall thickness. Immunohistochemically, BCOR and CD10 are positive and desmin, h-caldesmon, alpha smooth muscle actin are negative. Molecular genetic testing confirmed reciprocal ZC3H7B-BCOR gene rearrangement.
Differential diagnosis
Additional references
Board review style question #1

A 51 year old woman presents with brown vaginal discharge. The surgical resection shows a cellular infiltrative spindle cell uterine neoplasm. Immunohistochemically, there is negative expression of smooth muscle actin, desmin, h-caldesmon paired with positive expression of CD10, cyclin D1, BCOR. NGS study reveals ZC3H7B-BCOR gene fusion. What is the correct diagnosis?

  1. Leiomyosarcoma
  2. Low grade endometrial stromal sarcoma
  3. Synovial sarcoma
  4. ZC3H7B-BCOR rearranged high grade endometrial stromal sarcoma
Board review style answer #1
D. ZC3H7B-BCOR rearranged high grade endometrial stromal sarcoma

Comment Here

Reference: High grade endometrial stromal sarcoma
Board review style question #2
A subclassification of high grade endometrial stromal sarcoma as per WHO 2020 is based on

  1. Identification of specific gene rearrangement containing YWHAE or BCOR gene or internal tandem duplication (ITD) of BCOR gene
  2. Immunohistochemical co-expression of cyclin D1 and BCOR
  3. Immunohistochemical expression of BCOR
  4. Presence of myxoid stromal change
Board review style answer #2
A. Identification of specific gene rearrangement containing YWHAE or BCOR gene or internal tandem duplication (ITD) of BCOR gene

Comment Here

Reference: High grade endometrial stromal sarcoma
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