Definition/General

Introduction:
-Endometrial Stromal Sarcoma (ESS) is a malignant mesenchymal tumor composed of cells resembling endometrial stromal cells
-It accounts for 10-15% of uterine sarcomas
-It includes low-grade ESS and high-grade ESS
-It shows characteristic spiral artery-like vasculature.
Origin:
-Arises from endometrial stromal cells
-May originate from endometriosis
-Results from malignant transformation of stromal elements
-Genetic rearrangements drive pathogenesis
-Hormone-sensitive in low-grade cases.
Classification:
-WHO 2020 classification: Low-grade ESS
-High-grade ESS
-Undifferentiated uterine sarcoma (separate entity)
-FIGO staging system applies
-Molecular subtypes based on genetic alterations.
Epidemiology:
-Rare tumor: 2-5% of uterine malignancies
-Peak incidence in 4th-5th decades
-Lower grade more common than high-grade
-No racial predilection
-Hormone exposure may play role
-Associated with endometriosis.

Clinical Features

Presentation:
-Abnormal uterine bleeding (most common)
-Pelvic pain
-Enlarged uterus
-Pelvic mass
-Pressure symptoms
-Postmenopausal bleeding
-Weight loss (high-grade)
-Recurrent disease years later.
Symptoms:
-Menorrhagia and metrorrhagia
-Pelvic pain and pressure
-Abdominal distension
-Urinary symptoms
-Bowel symptoms
-Constitutional symptoms (high-grade)
-Dyspnea (pulmonary metastases).
Risk Factors:
-Age (perimenopausal)
-Nulliparity
-Endometriosis
-Tamoxifen therapy
-Previous pelvic radiation
-Lynch syndrome
-Hereditary cancer syndromes
-Unopposed estrogen.
Screening:
-Pelvic examination
-Transvaginal ultrasound
-MRI (preferred imaging)
-CT scan (staging)
-Endometrial biopsy (limited sensitivity)
-Hysteroscopy
-Tissue diagnosis often requires hysterectomy.

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Gross Description

Appearance:
-Polypoid masses protruding into cavity
-Tan-yellow cut surface
-Soft, fleshy consistency
-Worm-like extensions into vessels
-Infiltrative growth
-May show hemorrhage and necrosis
-Extrauterine extension possible.
Characteristics:
-Lobulated, polypoid appearance
-Tan to yellow coloration
-Soft consistency
-Infiltrative margins
-Vascular invasion characteristic
-Myometrial infiltration
-May have cystic areas.
Size Location:
-Variable size from small polyps to large masses
-Commonly involves endometrial cavity
-May extend into myometrium
-Parametrial extension
-Lymphovascular invasion
-Extrauterine spread common.
Multifocality:
-May be multifocal
-Vascular invasion prominent feature
-Serpentine growth in vessels
-Lymph node metastases
-Peritoneal implants
-Late recurrences characteristic (low-grade).

Microscopic Description

Histological Features:
-Uniform small cells resembling endometrial stroma
-Oval to spindle-shaped nuclei
-Minimal cytoplasm
-Spiral artery-like vasculature
-Infiltrative growth
-Vascular invasion
-Variable mitotic activity.
Cellular Characteristics:
-Small, uniform cells
-Round to oval nuclei
-Fine chromatin
-Inconspicuous nucleoli
-Scant cytoplasm
-Low-grade: <5 mitoses/10 HPF
-High-grade: >10 mitoses/10 HPF
-Nuclear pleomorphism variable.
Architectural Patterns:
-Diffuse growth pattern
-Tongue-like extensions
-Spiral arteries characteristic
-Endometrioid glandular differentiation possible
-Sex cord-like areas
-Smooth muscle differentiation
-Foam cell clusters.
Grading Criteria:
-Low-grade ESS: <5 mitoses/10 HPF, minimal atypia
-High-grade ESS: >10 mitoses/10 HPF, significant atypia
-Uniform cells in low-grade
-Pleomorphism in high-grade
-Necrosis more common in high-grade.

Immunohistochemistry

Positive Markers:
-CD10 positive (characteristic)
-ER positive (especially low-grade)
-PR positive
-WT1 positive
-Cyclin D1 positive
-Inhibin positive (focal)
-Calretinin positive
-Smooth muscle actin (focal).
Negative Markers:
-Desmin negative
-h-Caldesmon negative
-Cytokeratin negative
-EMA negative
-CD117 negative
-DOG1 negative
-S-100 negative.
Diagnostic Utility:
-CD10 most important marker
-ER/PR support diagnosis (especially low-grade)
-WT1 helpful marker
-Desmin negative excludes smooth muscle
-Cytokeratin negative excludes carcinoma
-Ki-67 higher in high-grade.
Molecular Subtypes:
-JAZF1-rearranged (most common low-grade)
-PHF1-rearranged
-MEAF6-rearranged
-ZC3H7B-rearranged
-High-grade: various alterations
-Undifferentiated: separate category.

Molecular/Genetic

Genetic Mutations:
-JAZF1-SUZ12 fusion (low-grade ESS)
-JAZF1-PHF1 fusion
-EPC1-PHF1 fusion
-MEAF6-PHF1 fusion
-ZC3H7B-BCOR fusion
-High-grade ESS: complex alterations
-TP53 mutations (high-grade).
Molecular Markers:
-JAZF1 rearrangement
-PHF1 rearrangement
-Cyclin D1 overexpression
-Beta-catenin expression
-p53 overexpression (high-grade)
-High Ki-67 (high-grade)
-Hormone receptor expression.
Prognostic Significance:
-Low-grade: indolent course, late recurrences
-High-grade: aggressive behavior
-5-year survival: 80-90% (low-grade), 50% (high-grade)
-Stage most important factor
-Molecular subtype affects behavior
-Hormone receptor status prognostic.
Therapeutic Targets:
-Complete surgical resection
-Hormonal therapy (low-grade, ER/PR+)
-Aromatase inhibitors
-Progestins
-GnRH agonists
-Chemotherapy (high-grade)
-Targeted therapy based on molecular profile.

Differential Diagnosis

Similar Entities:
-Endometrial stromal nodule
-Leiomyosarcoma
-Undifferentiated uterine sarcoma
-Adenosarcoma
-Carcinosarcoma
-Cellular leiomyoma
-Highly cellular endometrial polyp.
Distinguishing Features:
-ESS: CD10 positive, spiral arteries
-ESS: Uniform small cells
-Leiomyosarcoma: Smooth muscle markers positive
-Stromal nodule: Well-circumscribed, no invasion
-Undifferentiated sarcoma: CD10 negative, high-grade
-Adenosarcoma: Benign glands with malignant stroma.
Diagnostic Challenges:
-Distinguishing low-grade from high-grade
-Stromal nodule versus low-grade ESS
-Undifferentiated sarcoma versus high-grade ESS
-Cellular leiomyoma with stromal features
-Sampling adequacy
-Crush artifact.
Rare Variants:
-ESS with smooth muscle differentiation
-ESS with glandular differentiation
-ESS with sex cord-like areas
-ESS with rhabdoid features
-ESS with osseous/cartilaginous differentiation
-Extrauterine ESS.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Patient Information

Name: [Patient Name]\nAge: [X] years\nMRN: [Medical Record Number]\nDate of Procedure: [Date]

Clinical History

Clinical indication: [Abnormal uterine bleeding/Pelvic mass/Enlarged uterus/Recurrent disease]\nSymptoms: [Menorrhagia/Pelvic pain/Pressure symptoms/Weight loss]\nImaging: [Ultrasound/CT/MRI findings showing polypoid masses/vascular invasion]\nPrevious pathology: [Prior endometrial biopsy results if available]\nProcedure: [Total hysterectomy +/- staging procedures]

Specimen Received

Specimen type: [Total hysterectomy/Radical hysterectomy] +/- [bilateral salpingo-oophorectomy/pelvic lymph nodes]\nUterine weight: [X] grams\nTumor size: [X] cm\nAdditional specimens: [Omentum/Lymph nodes/Peritoneal biopsies] if submitted\nFixative: 10% neutral buffered formalin

Gross Examination

The uterus weighs [X] grams and measures [X] x [X] x [X] cm. [Polypoid masses/Infiltrative tumor] measuring up to [X] cm [protrude into the endometrial cavity/infiltrate the myometrium]. The tumor has a [tan-yellow/soft] appearance with [ill-defined/infiltrative] borders. Characteristic [worm-like extensions into vascular channels/serpentine growth pattern] are [identified/suspected]. Cut surface shows [soft, fleshy tissue with areas of hemorrhage/yellow-tan tissue]. The tumor [extends to the serosal surface/is confined to the myometrium/involves the cervix]. [Extrauterine extension/vascular invasion] is [grossly evident/not apparent]. Representative sections: [X] sections of tumor, [X] sections showing vascular invasion, [X] sections of uninvolved tissue.

Microscopic Examination

Sections show a malignant mesenchymal tumor composed of uniform small cells resembling endometrial stromal cells. The cells have [oval to spindle-shaped nuclei with fine chromatin/enlarged pleomorphic nuclei] and [scant/moderate] cytoplasm. The tumor demonstrates [characteristic spiral artery-like vasculature/prominent vascular pattern]. Growth pattern shows [diffuse infiltration with tongue-like extensions/sheet-like arrangement]. Mitotic activity is [low with X mitoses per 10 HPF/<5/10 HPF for low-grade][high with X mitoses per 10 HPF/>10/10 HPF for high-grade]. [Nuclear atypia is minimal/significant nuclear pleomorphism is present]. [Prominent lymphovascular invasion with serpentine growth pattern/vascular invasion] is present. [Sex cord-like areas/smooth muscle differentiation/glandular differentiation] are [present/absent].

Immunohistochemistry

CD10: [Diffusely positive] (characteristic of endometrial stroma)\nEstrogen Receptor: [Positive/Negative]\nProgesterone Receptor: [Positive/Negative]\nWT1: [Positive/Negative]\nCyclin D1: [Positive/Negative]\nInhibin: [Focal positive/Negative]\nSmooth Muscle Actin: [Focal positive/Negative]\nDesmin: [Negative]\nh-Caldesmon: [Negative]\nKi-67 proliferation index: [X]% ([low <10%/high >10%])

Molecular Studies (if performed)

JAZF1 rearrangement: [Positive/Negative/Not performed]\nPHF1 rearrangement: [Positive/Negative/Not performed]\nOther fusion studies: [Specify if performed]\nFISH analysis: [Results if available]\nNext-generation sequencing: [Results if available]

Staging Assessment

Tumor confined to uterus: [Yes/No]\nMyometrial invasion: [<50%/>50%]\nCervical involvement: [Present/Absent]\nExtrauterine extension: [Present/Absent - specify sites]\nLymphovascular invasion: [Present/Absent/Prominent]\nLymph node involvement: [Present/Absent/Not assessed]\nDistant metastases: [Present/Absent/Clinical correlation needed]\nFIGO Stage: [I/II/III/IV]

Final Diagnosis

[LOW-GRADE/HIGH-GRADE] ENDOMETRIAL STROMAL SARCOMA\n\nGrade: [Low-grade/High-grade] (WHO 2020)\nSize: [X] cm\nFIGO Stage: [I/II/III/IV]\nMitotic count: [X] per 10 HPF\nVascular invasion: [Present/Absent/Prominent]\nHormone receptors: ER [Pos/Neg], PR [Pos/Neg]\nCD10: [Positive]\nMolecular findings: [JAZF1/PHF1/Other rearrangement if detected]

Comments and Prognosis

• [Low-grade ESS: Indolent course with tendency for late recurrences. Generally hormone-sensitive. 5-year survival 80-90%.]\n• [High-grade ESS: More aggressive behavior with higher metastatic potential. 5-year survival approximately 50%.]\n• CD10 positivity confirms endometrial stromal differentiation.\n• Characteristic spiral artery-like vasculature and lymphovascular invasion pattern.\n• [Hormone receptor positivity suggests potential benefit from hormonal therapy (low-grade).]\n• Complete surgical staging and multidisciplinary team discussion recommended.\n• Long-term surveillance required due to potential for late recurrences.\n• [Consider molecular testing for treatment stratification and prognostication.]

Reported By

Dr. [Pathologist Name], MD\nConsultant Pathologist\nDate: [Report Date]\n\nReviewed by: Dr. [Senior Pathologist], MD (if applicable)