Low grade endometrial stromal sarcoma

Uterus

Stromal tumors

Authors: Elizabeth Kertowidjojo, M.D., Ph.D., M.P.H., Lora Hedrick Ellenson, M.D.

Editorial Board Member: Gulisa Turashvili, M.D., Ph.D.

Deputy Editor-in-Chief: Jennifer A. Bennett, M.D.

Minor changes: 3 May 2021

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

PubMed search: low grade endometrial stromal sarcoma [title] uterus

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Table of Contents

Cite this page: Kertowidjojo E, Ellenson LH. Low grade endometrial stromal sarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusESSlowgrade.html. Accessed May 7th, 2021.

Definition / general

Malignant mesenchymal tumor comprised of cells resembling proliferative phase endometrial stroma with infiltrative growth or lymphovascular invasion

Essential features

Histologic features include permeative tongue-like islands of tumor cells composed of monotonous oval to spindle cells with minimal cytologic atypia, often demonstrating whorling around blood vessels; smooth muscle and sex cord-like differentiation are common
Diagnosis may require extensive sampling of the tumor myometrial interface to evaluate for invasion and exclude endometrial stromal nodule
Recurrent rearrangements involving JAZF1 and PHF1 are common, though absence does not preclude the diagnosis

Terminology

Endolymphatic stromal myosis

ICD coding

ICD-O: 8931/3 - endometrial stromal sarcoma, low grade
ICD-11: 2B5C & XH1S94 - endometrial stromal sarcoma, primary site and endometrial stromal sarcoma, low grade

Epidemiology

Second most common uterine sarcoma (Histopathology 2009;54:355)
Wide age range but with predilection for premenopausal and perimenopausal women (mean: 52 years, range: 16 - 83 years) (Br J Cancer 2008;99:1210)
Risk factors: prolonged estrogen or tamoxifen use, pelvic radiation (Gynecol Oncol 1985;21:135, J Clin Pathol 1995;48:596, Cancer 1986;58:2003)

Sites

Uterus: more commonly the corpus than the cervix
Rarely extrauterine, usually associated with endometriosis

Clinical features

Abnormal uterine bleeding (most common), pelvic pain, uterine mass
Occasionally, patients present with metastases (most commonly lung, adnexal or nodal) (Adv Anat Pathol 2000;7:257)

Diagnosis

Radiologic findings on magnetic resonance imaging (MRI) (see radiology description)
Endometrial sampling may obtain diagnostic material in ~30%
- However, the lesion is indistinguishable from endometrial stromal nodule in a curettage specimen (Mod Pathol 2016;29 Suppl 1:S92)

Radiology description

MRI: highest sensitivity
- Endometrial or myometrial mass, mostly solid but may display cystic degeneration (Int J Gynecol Cancer 2017;27:1877)
- Nodular worm-like intramyometrial lesions with irregular margin (Eur Radiol 2001;11:28)
- Lower apparent diffusion coefficient (ADC) value compared to T2 hyperintense leiomyoma (Cancer Imaging 2019;19:63)
- Less frequent necrosis, hemorrhage and feather-like enhancement compared to high grade endometrial stromal sarcoma (Cancer Imaging 2019;19:63)

Radiology images

Images hosted on other servers:

T2 and T1 weighted images

MRI of low grade endometrial stromal sarcoma

Prognostic factors

Typically indolent, with an overall 5 year survival of > 90% and a 10 year survival of 75%
Factor affecting prognosis: stage
Controversial factors: older age (> 50 years), mitotic index, necrosis (Oncology 2006;71:333)
Factors of uncertain significance: tumor size, lymphovascular invasion, hormonal status, ploidy (Adv Anat Pathol 2010;17:113)

Case reports

42 year old woman with pelvic pain and endometriosis (Gynecol Oncol Rep 2017;21:119)
48 year old woman status post uterine morcellation (Case Rep Obstet Gynecol 2020;2020:7201930)
50 year old woman with a pancreatic mass (Diagn Pathol 2019;14:30)

Treatment

Hysterectomy and bilateral salpingo-oophorectomy
- Higher risk of recurrence if hysterectomy alone (Int J Gynecol Cancer 2013;23:488)
Radiation therapy may control local recurrences but does not improve overall survival (Int J Gynecol Cancer 2009;19:1232)
Hormonal therapy (GnRH analogs, progestins and aromatase inhibitors) (Crit Rev Oncol Hematol 2008;65:129)

Gross description

Poorly circumscribed soft yellow-tan to white nodules extending from the endometrium and invading into the myometrium
Worm-like plugs of tumor may be seen in the myometrium or lymphovascular channels (Am J Surg Pathol 1990;14:415)
Often with a polypoid endometrial component
May appear deceptively well circumscribed: extensive sampling of the tumor myometrial interface is necessary to rule out endometrial stromal nodule (Int J Gynecol Pathol 2014;33:374)
Hemorrhage and necrosis may be seen

Gross images

Contributed by Elizabeth Kertowidjojo, M.D., Ph.D., M.P.H.

Tan-yellow uterine mass

Fleshy lobulated mass

Images hosted on other servers:

Yellow-brown
tumor mass and
additional infiltrating
tumor nodules

Macroscopically,
sarcoma resembles
uterine leiomyomas

Yellow tumor nodule with necrosis

Frozen section description

Spindle to oval cells with permeative growth into the myometrium
May be associated with a polypoid growth
Minimal cytologic atypia and low mitotic count
May display smooth muscle or sex cord-like differentiation

Frozen section images

Contributed by Elizabeth Kertowidjojo, M.D., Ph.D., M.P.H.

Polypoid mass

Low grade spindle cells

Infiltrative mass

Microscopic (histologic) description

Irregular cellular islands, forming permeative tongue-like pattern of myometrial invasion with frequent vascular invasion
Monotonous oval to spindle cells with minimal cytologic atypia, vesicular chromatin and scant cytoplasm
Mitotic count is usually low (< 5/10 high power fields), necrosis is usually absent
Tumor cells may whorl around delicate arteriolar type vessels, reminiscent of proliferative phase endometrial stroma
May have admixed collagen bands / plaques and foamy histiocytes
May have smooth muscle differentiation, particularly in a starburst morphology, with collagen bands radiating towards the periphery of the nodule
Other reported types of differentiation: fibromyxoid / fibrous, sex cord-like, epithelioid, rhabdoid, endometrioid glands, pseudopapillae, clear cells, bizarre cells, adipose tissue (Mod Pathol 2016;29:S92)

Microscopic (histologic) images

Contributed by Elizabeth Kertowidjojo, M.D., Ph.D., M.P.H.

Tongue-like invasion

Monotonous tumor cells

Whorling around vasculature

Smooth muscle differentiation

Desmin

Sex cord-like growth

Endometrial curetting

AFIP images

Dilated and thin walled vessels

Dilated vessels and sex cord-like structures

Extensive myometrial infiltration

Myometrial infiltration by uniform small tumor cells

Nests and sex cord-like arrangements

Myometrial lymphatics

Cytology description

Resembles benign endometrial stromal cells
Moderate to marked cellularity composed of single cells and clusters of bland cells with scant cytoplasm, small round to spindle nuclei with fine chromatin (Acta Cytol 2007;51:461)
Interspersed delicate blood vessels may be present
Distinction between low grade endometrial stromal sarcoma and endometrial stromal nodule cannot be made based on cytology, as it requires evaluation of the tumor myometrium interface
Distinction between low grade endometrial stromal sarcoma and other monomorphic spindle cell neoplasm is difficult on cytology, especially without immunohistochemistry

Cytology images

Contributed by Elizabeth Kertowidjojo, M.D., Ph.D., M.P.H.

Lung fine needle aspiration

Lung fine needle aspiration cell block

Positive stains

CD10 (75 - 100% sensitivity)
IFITM1 (Int J Gynecol Pathol 2018;37:372)
WT1, ER (40 - 100%), PR (69 - 100%)
Keratins: AE1 / AE3, CAM5.2, MNF 116, CK8 / 18
Smooth muscle markers (SMA, desmin, caldesmon) often positive in areas of smooth muscle differentiation
Sex cord markers (inhibin, calretinin, CD99, MelanA, WT1) may be positive in areas of sex cord differentiation
Beta catenin: nuclear staining without associated mutation (Mod Pathol 2008;21:756)

Negative stains

DOG1, BCOR, FOXL2
Cyclin D1, c-kit: may be focally positive without associated mutations (Gynecol Oncol 2003;91:9)
Wild type p53

Molecular / cytogenetics description

Most common: JAZF1-SUZ12 t(7;17)(p15;q21) fusion (50%)
Other translocations: JAZF1-PHF1 t(6;7)(p21;p15) in 6% of cases, EPC1-PHF1 t(10;17)(q22;p13) in 4%, MEAF6-PHF1 t(1;6)(p34;p21) in 3% and MBTD1-Cxorf67 t(X;17)(p11.2;q21.33) in 2% (Am J Surg Pathol 2011;35:1364, Genes Chromosomes Cancer 2016;55:834)

Molecular / cytogenetics images

Images hosted on other servers:

JAZF1-SUZ12 dual fusion probe

MBTD1-CXorf67 dual fusion probe

Videos

Endometrial stromal sarcoma

Uterine mesenchymal neoplasms

Sample pathology report

Uterus, hysterectomy:
- Endometrial stromal sarcoma, low grade (see synoptic report)
- Tumor size: 9 cm
- Lymphovascular invasion identified
- Surgical margins uninvolved

Differential diagnosis

Endometrial stromal nodule:
- Absent to minimal myometrial invasion (≤ 3 protrusions, each measuring < 3 mm) and no lymphovascular invasion
High grade endometrial stromal sarcoma:
- Presence of a high grade component with cytologic atypia and elevated mitotic count
- Frequently positive for cyclin D1 and BCOR while negative for ER
- YWHAE-NUTM2A/B fusion, BCOR fusions or internal tandem duplication
Cellular leiomyoma:
- Fascicular growth, large thick walled blood vessels, cleft-like spaces
- Lack JAZF1 or PHF1 fusions
Leiomyosarcoma:
- Marked cytologic atypia, mitotic activity and necrosis
- Large thick walled blood vessels
- Lack JAZF1 or PHF1 fusions
Uterine tumor resembling ovarian sex cord tumor:
- Absence of any conventional endometrial stromal component
- ESR1 or GREB1 fusions in a subset
Endometrial polyp:
- No expansile growth or displacement of adjacent endometrium
Gland poor adenomyosis:
- No confluent growth or displacement of myometrium

Board review style question #1

The uterine tumor illustrated in the figures above is best diagnosed as

Cellular leiomyoma
Endometrial stromal nodule
Endometrioid carcinoma
Low grade endometrial stromal sarcoma
Uterine tumor resembling ovarian sex cord tumor

Board review style answer #1

D. Low grade endometrial stromal sarcoma. The tumor shows a polypoid component, as well as a characteristic permeative tongue-like invasion pattern seen on low power. The presence of invasion rules out an endometrial stromal nodule (answer B) and cellular leiomyoma (answer A). The lack of any glandular component rules out endometrioid carcinoma (answer C). While low grade endometrial stromal sarcoma can have sex cord-like differentiation, the presence of conventional low grade endometrial stromal sarcoma rules out uterine tumor resembling ovarian sex cord tumor (answer E).

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Reference: Low grade endometrial stromal sarcoma

Board review style question #2

Which of the following can reliably diagnose low grade endometrial stromal sarcoma?

Endometrial biopsy
Hysterectomy
Myomectomy
Presenting symptoms and clinical history
Ultrasound

Board review style answer #2

B. Hysterectomy. The presenting symptoms and clinical findings in low grade endometrial stromal sarcoma are nonspecific, including abnormal uterine bleeding, pelvic pain and uterine mass. While ultrasound can detect a uterine mass, distinguishing low grade endometrial stromal sarcoma from other entities such as endometrial stromal nodule and leiomyoma can be difficult. While biopsy and myomectomy may obtain diagnostic material, low grade endometrial stromal sarcoma is distinguished from endometrial stromal nodule by its invasive growth pattern, which cannot be appreciated on limited sampling.

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Reference: Low grade endometrial stromal sarcoma