Definition/General
Introduction:
Endometrial epithelioid sarcoma is an extremely rare malignant soft tissue tumor occurring in the uterus
It is characterized by epithelioid morphology and loss of INI1 expression
It represents less than 0.1% of all uterine sarcomas
It has an aggressive clinical behavior.
Origin:
Arises from mesenchymal cells with epithelioid features
May develop from endometrial stroma
Uncertain cell of origin
Associated with SMARCB1 gene inactivation
Occurs as primary uterine tumor.
Classification:
Classified as soft tissue sarcoma with epithelioid features
High-grade malignancy
Classical and proximal-type variants
Defined by INI1/SMARCB1 loss
Aggressive clinical behavior.
Epidemiology:
Extremely rare in uterine location
Peak incidence in 2nd-4th decades (classical type)
Proximal type affects older patients
Young to middle-aged women affected
Associated with SMARCB1 mutations.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Pelvic mass
Pelvic pain
Rapidly growing tumor
Constitutional symptoms possible
Advanced disease at presentation.
Symptoms:
Heavy menstrual bleeding
Pelvic pressure
Abdominal pain
Weight loss
Fatigue
Systemic symptoms in advanced cases.
Risk Factors:
Young age (15-40 years for classical type)
Genetic predisposition (rhabdoid tumor predisposition syndrome)
SMARCB1 germline mutations
Family history of sarcomas.
Screening:
No specific screening recommendations
Genetic counseling for familial cases
High index of suspicion for soft tissue masses
Imaging studies for staging.
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Gross Description
Appearance:
Multinodular mass with infiltrative margins
Gray-white cut surface
Firm consistency
Areas of hemorrhage and necrosis
Pseudocapsule may be present.
Characteristics:
Size ranges from 2-10 cm
Irregular margins
Cut surface shows variegated appearance
Solid consistency
Necrotic areas common.
Size Location:
Variable size at presentation
Mean size 4-7 cm
Involves uterine corpus
May extend to parametrium
Infiltrative growth pattern.
Multifocality:
Usually unifocal presentation
Aggressive local growth
Lymph node metastases common
Distant metastases to lung
Skip lesions possible.
Microscopic Description
Histological Features:
Epithelioid cells arranged in sheets and nests
Abundant eosinophilic cytoplasm
Vesicular nuclei with prominent nucleoli
Central necrosis in nodules
High mitotic activity
Inflammatory infiltrate.
Cellular Characteristics:
Large epithelioid cells
Abundant pink cytoplasm
Vesicular nuclei
Prominent nucleoli
Rhabdoid features may be present
Multinucleated cells.
Architectural Patterns:
Nodular pattern with central necrosis
Granuloma-like appearance
Pseudocarcinomatous pattern
Solid sheets
Spindle cell areas (proximal type).
Grading Criteria:
Considered high-grade by definition
High mitotic rate (>10/10 HPF)
Marked nuclear atypia
Necrosis present
Aggressive behavior.
Immunohistochemistry
Positive Markers:
Cytokeratins (focal, variable)
EMA (focal)
Vimentin
CD34 (may be positive)
FLI-1 (may be positive)
ERG (variable).
Negative Markers:
INI1/SMARCB1 (loss of nuclear expression)
Desmin (negative)
S-100 (negative)
Melanoma markers (negative)
Muscle-specific actin (negative).
Diagnostic Utility:
INI1/SMARCB1 loss highly specific and diagnostic
Cytokeratin positivity (focal) may cause diagnostic confusion
CD34 positivity supportive
Negative smooth muscle and melanoma markers
Retained INI1 excludes diagnosis.
Molecular Subtypes:
SMARCB1 inactivation (gene deletion/mutation)
SMARCA4 alterations (rare)
Complex chromosomal alterations
INI1 protein loss.
Molecular/Genetic
Genetic Mutations:
SMARCB1 deletions (22q11.23)
SMARCB1 mutations
Biallelic inactivation
Germline mutations in familial cases
Complex karyotype.
Molecular Markers:
Loss of INI1/SMARCB1 expression
Chromosomal instability
High Ki-67 index
p16 overexpression
EZH2 upregulation.
Prognostic Significance:
Proximal type has worse prognosis than classical
Size >5 cm adverse prognostic factor
Age >30 years indicates poor outcome
Necrosis correlates with aggressive behavior
Germline mutations may indicate familial syndrome.
Therapeutic Targets:
EZH2 inhibitors (tazemetostat)
Immunotherapy (investigational)
Multi-kinase inhibitors
Conventional chemotherapy (limited response)
Radiation therapy (adjuvant).
Differential Diagnosis
Similar Entities:
Epithelioid malignant peripheral nerve sheath tumor
Synovial sarcoma
Carcinoma
Melanoma
Epithelioid angiosarcoma.
Distinguishing Features:
MPNST: S-100 positive, may retain INI1
Synovial sarcoma: TLE1 positive, INI1 retained
Carcinoma: Broad cytokeratin positivity
Epithelioid sarcoma: INI1 loss
Epithelioid sarcoma: CD34 positive.
Diagnostic Challenges:
Distinguishing from poorly differentiated carcinoma
Recognizing epithelioid morphology
Confirming INI1 loss
Identifying nodular growth pattern
INI1 immunostaining essential.
Rare Variants:
Classical epithelioid sarcoma
Proximal-type epithelioid sarcoma
Angiomatoid variant
Fibroma-like variant.
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.
Specimen Information
[specimen type], measuring [size] cm, firm consistency
Diagnosis
Epithelioid sarcoma of the endometrium
Classification
[Classical/Proximal-type] epithelioid sarcoma
Histological Features
Epithelioid cells in nodular pattern with central necrosis, mitoses: [count]/10 HPF
Morphologic Pattern
Pattern: [nodular/sheet-like/mixed], necrosis: [present/absent]
Immunohistochemistry
INI1/SMARCB1: [lost/retained] (nuclear expression)
Cytokeratins: [focal +/+/-], EMA: [+/-]
CD34: [+/-], Vimentin: [+/-]
Grade
High-grade sarcoma by definition
Final Diagnosis
[Classical/Proximal-type] epithelioid sarcoma with INI1/SMARCB1 loss