Uterus
Stromal tumors
Endometrial stromal neoplasms


Topic Completed: 29 July 2019

Revised: 27 September 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed search: endometrial stromal tumors uterine [title](free full text[sb])

Özlem Isiksacan Özen, M.D.
Ayse Ayhan, M.D., Ph.D.
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Cite this page: Özen Ö, Ayhan A. Endometrial stromal neoplasms. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusessgeneral.html. Accessed December 7th, 2019.
Definition / general
Essential features
  • Represents the second most common category of uterine mesenchymal tumors
  • Due to a greater understanding of tumor genetics, mutations have unifying features for several subgroups:
    • Most common genetic alteration for low grade endometrial stromal tumors is (7;17) resulting in JAZF1-SUZ12 changes and those areas with sex cord morphology contain PHF1 gene rearrangements
    • BCOR alterations and ZC3H7B-BCOR categorize high grade as a distinct entity (Int J Gynecol Pathol 2018 Jun 12 [Epub ahead of print])
    • YWHAE-FAM22 is seen in undifferentiated endometrial / uterine sarcoma (Oncotarget 2017;8:4062)
  • When invasion cannot be assessed in a biopsy / curettage specimen, it is recommended to report as endometrial stromal tumor, defer definitive classification to the hysterectomy specimen (Adv Anat Pathol 2014;21:383)
Terminology
  • First described by Norris and Taylor as endolymphatic stromal myosis for low grade and stromal sarcoma for high grade (Cancer 1966;19:755) (terms no longer recommended)
  • Benign and low grade endometrial stromal tumors may be classified as endometrial stromal tumor and endometrial stromal nodule
    • Endometrial stromal nodule: no or minimal myoinvasion (< 3 mm) and < 3 protrusions in number, no lymphovascular invasion
    • Endometrial stromal tumor with limited infiltration: more infiltration than endometrial stromal nodule but does not qualify as stromal sarcoma, no lymphovascular invasion
  • Endometrial stromal sarcoma: endometrial stromal nodule with myometrial or lymphovascular invasion
  • High grade endometrial stromal sarcoma with variable morphology, high grade sarcoma not otherwise specified subgrouping by morphology and ancillary tests; combination of low grade and high grade components
  • Recently may be classified based on the genetic alteration, for which also several morphologic implications
    • YWHAE-FAM22 endometrial stromal sarcoma (undifferentiated endometrial stromal sarcoma, uniform type)
    • ZC3H7B-FAM22 endometrial stromal sarcoma
    • BCOR-ITD endometrial stromal sarcoma
ICD coding
    ICD-0:
  • 8931/3 - low grade endometrial stromal sarcoma
  • 8930/3 - high grade endometrial stromal sarcoma
  • 8805/3 - undifferentiated uterine sarcoma
Epidemiology
  • All three subtypes of endometrial stromal sarcoma comprise 6 - 20% of uterine sarcomas and < 1% of all the uterus primary malignancies (Adv Anat Pathol 2014;21:383, Nucci: Diagnostic Pathology - Gynecological, 2nd Edition, 2018)
  • Low grade endometrial stromal sarcoma is the most common subtype
  • Wide age range for all, only BCOR internal tandem duplication (BCOR-ITD)
  • May have relation to hyperestrogenism, tamoxifen therapy and radiation of endometriosis
Sites
Pathophysiology
Etiology
Clinical features
Diagnosis
  • Curettage specimens are not adequate to diagnose low grade endometrial stromal sarcoma
  • Since endometrial stromal nodule and low grade endometrial stromal sarcoma have similar morphologic, immunohistochemical and molecular features and are distinguished on the basis of a myoinvasive growth pattern and lymphovascular invasion, thorough sampling of the tumor-myometrial interface on hysterectomy specimens is important (Adv Anat Pathol 2014;21:383, Int J Gynecol Pathol 2019 Feb 21 [Epub ahead of print])
Radiology description
  • Ultrasonography: mixed echogenicity / not reliable, may lead to incorrect diagnosis of adenomyosis or uterine leiomyoma
  • Transvaginal color Doppler: low impedance flow compared with other benign tumors
  • MRI: irregular margin, nodular extensions at margin, into myometrium or into ligaments, fallopian tubes, ovaries and along the vessels; low signal intensity bands at T2 at the site of myometrial involvement representing preserved myometrial bundles (AJR Am J Roentgenol 2004;182:1531, Adv Anat Pathol 2000;7:257)
Prognostic factors
Case reports
Treatment
  • Low grade and high grade, stage I: hysterectomy and bilateral salpingo-oophorectomy (Adv Anat Pathol 2014;21:383); may also receive adjuvant radiation or hormonal treatment with progestational agents or aromatase inhibitors
  • Undifferentiated: should be treated by hysterectomy and bilateral salpingo-oophorectomy and adjuvant radiation or chemotherapy
Gross description
Gross images

Contributed by Ayse Ayhan, M.D., Ph.D.
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Low grade endometrial stromal sarcoma

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High grade endometrial stromal sarcoma

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Undifferentiated uterine sarcoma

Microscopic (histologic) description
  • Low grade endometrial stromal sarcoma:
  • High grade endometrial stromal sarcoma:
    • Consists predominantly of high grade round cells and sometimes associated with a low grade most commonly fibromyxoid spindle cell component (Int J Gynaecol Obstet 2018;143:51)
    • Mitotic activity is striking (typically > 10/10 HPFs)
    • Necrosis is usually present
    • Rarely, areas of conventional low grade endometrial stromal sarcoma are seen
  • Undifferentiated endometrial sarcoma:
    • Exhibits myometrial invasion, severe nuclear pleomorphism, high mitotic activity or tumor cell necrosis and lack smooth muscle or endometrial stromal differentiation (Int J Gynaecol Obstet 2018;143:51)
Microscopic (histologic) images

Contributed by Ayse Ayhan, M.D., Ph.D.
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Low grade endometrial stromal sarcoma

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CD10

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Cyclin D1


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High grade endometrial stromal sarcoma


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Estrogen receptor (alpha isoform)

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Progesterone receptor

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Unusual features in endometrial stromal sarcoma

Positive stains
Negative stains
Molecular / cytogenetics description
  • Low grade: most common cytogenetic abnormality is a recurrent translocation involving chromosomes 7 and 17 t(7;17) (p15;q21)], which results in a fusion between JAZF1-SUZ12
  • High grade: typically harbors the YWHAE-FAM22 genetic fusion as a result of t(10;17) (q22;p13)
  • Undifferentiated: exhibits a complex karyotype with no specific translocation pattern (Int J Cancer 2015;136:1608)
Sample pathology report
  • Uterus, hysterectomy:
    • Endometrial stromal sarcoma (with smooth muscle differentiation or with sex cord elements or with glandular element), low grade (see synoptic report)
      • Comment: Tumor cells are positive for CD10, ER and PR and negative for h-caldesmon and desmin.
Differential diagnosis
Board review question #1

    A 51 year old woman presented with vaginal bleeding and workup revealed a large uterine mass. Hysterectomy and bilateral salpingo-oophorectomy is performed. Pathology is consistent with a low grade endometrial sarcoma. Which of the following statements is correct?

  1. Harbors the YWHAE-FAM22 genetic fusion
  2. Tumor cells strongly immunoreactive for CD10, negative for ER and PR
  3. Tumor consists of high grade round-cells with brisk mitotic activity
  4. Uterine mass showing irregular infiltrating borders to the myometrium
Board review answer #1
D. Uterine mass showing irregular infiltrating borders to the myometrium

Comment Here

Reference: Endometrial stromal neoplasms
Board review question #2
    Which of the following statements about endometrial stroma sarcoma is correct?

  1. High grade endometrial stromal sarcoma is the most common subtype
  2. Hormonal treatment is the only standard therapy for stage I tumors
  3. Mitotic rate is the most important prognostic factor for the prognosis
  4. Thorough sampling of the tumor-myometrial interface is essential to diagnose low grade endometrial stromal sarcoma
Board review answer #2
D. Thorough sampling of the tumor-myometrial interface is essential to diagnose low grade endometrial stromal sarcoma

Comment Here

Reference: Endometrial stromal neoplasms
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