Uterus

Stromal tumors

High grade endometrial stromal sarcoma



Topic Completed: 17 November 2021

Minor changes: 17 November 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed search: High grade endometrial stromal sarcoma [title]

Lisa Han, M.D.
Jennifer A. Bennett, M.D.
Page views in 2020: 5,698
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Cite this page: Han L, Bennett JA. High grade endometrial stromal sarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusESShighgrade.html. Accessed December 3rd, 2021.
Definition / general
  • Malignant uterine mesenchymal tumor originating from the endometrial stroma
Essential features
  • Cellular tumor with high grade round or spindle cells, sometimes with an associated low grade component
  • Variable positivity for BCOR, cyclin D1 and CD10, depending on molecular alteration present; often negative or only focally positive for smooth muscle markers and hormone receptors
  • Major subtypes include sarcomas with YWHAE-NUTM2A/B fusions, BCOR rearranged and BCOR internal tandem duplication (ITD)
Terminology
  • Undifferentiated endometrial sarcoma, uniform type
  • High grade endometrial stromal sarcoma with YWHAE-FAM22 fusions
ICD coding
  • ICD-O: 8930/3 - endometrial stromal sarcoma, high grade
  • ICD-10: C54.1 - malignant neoplasm of endometrium
Epidemiology
Sites
Pathophysiology
Etiology
  • Unknown
Clinical features
  • Pelvic pain, pelvic mass, abnormal uterine bleeding
Diagnosis
  • Hysterectomy needed for definitive diagnosis
  • Rarely diagnosed on endometrial biopsy / curettage
Radiology description
Radiology images

Images hosted on other servers:
MRI findings

MRI findings

Prognostic factors
  • Intermediate prognosis between low grade endometrial stromal sarcoma and undifferentiated uterine sarcoma
  • Limited number of cases reported with limited followup information to identify favorable / unfavorable prognostic factors
Case reports
Treatment
Gross description
Gross images

Contributed by Ondrej Ondič, M.D., Ph.D.
Pale yellow-white, soft and friable masses

Pale yellow-white, soft and friable masses

Frozen section description
  • High grade sarcoma with spindled and epithelioid cells, defer to permanent sections and ancillary (immunohistochemical and molecular) studies
Microscopic (histologic) description
  • YWHAE-NUTM2A/B fusions (Am J Surg Pathol 2012;36:641, Mod Pathol 2013;26:1390, Histopathology 2015;67:1, Pathology 2018;50:162):
    • Permeative (tongue-like) invasion
    • Vaguely nested growth of round cells with scant (small round blue cell appearance) to moderate eosinophilic cytoplasm and uniform nuclear atypia
    • Brisk mitoses (> 10/10 high power fields)
    • Tumor cell necrosis and lymphovascular invasion common
    • Delicate network of arborizing or curvilinear vessels
    • 50% associated with a low grade spindle cell component resembling low grade endometrial stromal sarcoma
      • Admixed or occasionally well demarcated
      • Monomorphic bland spindle cells
      • Fibrous to fibromyxoid matrix
      • Low mitoses (≤ 3/10 high power fields)
      • Typically lacks necrosis
    • Variant features include pseudoglandular or pseudopapillary appearance, sex cord-like differentiation, rosette-like formations
    • Overt nuclear pleomorphism rare
  • BCOR rearranged (Mod Pathol 2018;31:674, Pathology 2018;50:162):
    • Often involves endometrium and myometrium
    • Tongue-like invasion or broad front with infiltrative borders
    • Haphazard fascicles of uniformly atypical spindle cells with scant to moderate and eosinophilic or abundant and blue-gray cytoplasm
    • Extensive myxoid stroma
    • Collagen plaques in ~50%
    • Brisk mitoses (≥ 10/10 high power fields)
    • Small arterioles without perivascular whorling of tumor cells
    • Lymphovascular invasion in ~50%
    • Infarct type necrosis more common than tumor cell necrosis
    • Overt nuclear pleomorphism rare
    • No low grade component present
  • BCOR ITD (Mod Pathol 2017;30:1251, Am J Surg Pathol 2018;42:335, Oncology 2019;96:101, Am J Surg Pathol 2019;43:662):
    • Tongue-like invasion
    • High grade round cell component with uniform atypia, high grade spindle cell component with uniform atypia, low grade fibromyxoid spindle cell component
    • Myxoid matrix
    • Brisk mitoses (≥ 10/10 high power fields)
    • Lymphovascular invasion and tumor cell necrosis
    • Overt nuclear pleomorphism rare
  • High grade transformation of low grade endometrial stromal sarcoma (Mod Pathol 2020;33:1861):
    • High grade transformation may occur in the primary, metastatic or recurrent tumor
    • High grade component usually easily recognized from low grade component on low power magnification but occasionally is a gradual transition
    • High grade component:
      • Comprises 10 - 90% of tumor
      • Sharply demarcated nodules often associated with sclerotic or less commonly myxoid stroma
      • Rounded epithelioid cells with increased atypia (often uniform) and brisk mitoses (median, 16/10 high power fields)
      • Delicate vasculature without perivascular tumor cell whorls
      • Tumor cell necrosis uncommon
    • Low grade component:
      • Conventional low grade endometrial stromal sarcoma
      • May show variant morphology (fibroblastic, smooth muscle differentiation, myxoid matrix, sex cord-like differentiation)
Microscopic (histologic) images

Contributed by Elizabeth Kertowidjojo, M.D., Ph.D., M.P.H. and Jennifer A. Bennett, M.D.
Mitotically active spindle cells

Mitotically active spindle cells

Myxoid stroma

Myxoid stroma

Collagen plaques

Collagen plaques

Round cell component

Round cell component

Low grade spindle cell component

Low grade spindle cell component

High grade transformation

High grade transformation


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

Virtual slides

Images hosted on other servers:
<i>YWHAE-NUTM2A/B</i> high grade endometrial stromal sarcoma <i>YWHAE-NUTM2A/B</i> high grade endometrial stromal sarcoma

YWHAE-NUTM2A/B high grade endometrial stromal sarcoma

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Uterus, fallopian tubes and ovaries, hysterectomy and bilateral salpingo-oophorectomy:
    • ZC3H7B-BCOR rearranged high grade endometrial stromal sarcoma (14 cm) (see comment and synoptic report)
    • Comment: The tumor shows tongue-like myometrial invasion and is composed of enlarged, hyperchromatic spindle cells percolating within a myxoid stroma. Mitoses number up to 15 per 10 high power fields. It is positive for BCOR, cyclin D1 and CD10 but negative for desmin, caldesmon and SMA. Molecular testing confirmed a ZC3H7B-BCOR fusion.
Differential diagnosis
Board review style question #1

A 51 year old woman presents with vaginal bleeding. Histologic sections of the hysterectomy reveal an infiltrative spindle cell neoplasm. Immunohistochemically, the tumor is positive for CD10, cyclin D1 and BCOR but negative for smooth muscle actin, desmin and caldesmon. Next generation sequencing study reveals ZC3H7B-BCOR gene fusion. What is the correct diagnosis?

  1. High grade endometrial stromal sarcoma
  2. Inflammatory myofibroblastic tumor
  3. Leiomyosarcoma
  4. Low grade endometrial stromal sarcoma
  5. Undifferentiated uterine sarcoma
Board review style answer #1
A. 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 involving YWHAE or BCOR or internal tandem duplication of BCOR gene
  2. Immunohistochemical coexpression 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 involving YWHAE or BCOR or internal tandem duplication of BCOR gene

Comment Here

Reference: High grade endometrial stromal sarcoma
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