Definition/General
Introduction:
Endometrial synovial sarcoma is an extremely rare malignant mesenchymal tumor occurring in the uterus
It represents less than 1% of all uterine sarcomas
It shows characteristic biphasic or monophasic patterns
It is defined by SS18-SSX fusion gene.
Origin:
Arises from primitive mesenchymal cells rather than synovial tissue
May develop from endometrial stroma
Not related to synovial joints
Molecular alteration drives oncogenesis
Occurs as primary uterine tumor.
Classification:
Classified as spindle cell sarcoma by WHO classification
Biphasic (epithelial and spindle components)
Monophasic (predominantly spindle cells)
Poorly differentiated variant
Defined by SS18-SSX translocation.
Epidemiology:
Extremely rare in uterine location
Peak incidence in 3rd-4th decades (younger than other uterine sarcomas)
Reproductive age women predominantly affected
No clear racial predilection
Associated with t(X;18) translocation.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Enlarging pelvic mass
Menorrhagia in young women
Pelvic pain and pressure
Rapid growth pattern.
Symptoms:
Heavy menstrual bleeding
Intermenstrual bleeding
Pelvic pain
Abdominal distension
Weight loss
Dysmenorrhea
Urinary frequency.
Risk Factors:
Young age (20-40 years)
No established risk factors
Genetic predisposition unclear
Previous radiation exposure (rare)
Familial cancer syndromes (rare association).
Screening:
No specific screening recommendations
High suspicion in young women with rapidly growing masses
Imaging studies for evaluation
Molecular testing essential for diagnosis.
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Gross Description
Appearance:
Well-circumscribed to infiltrative mass
Gray-white cut surface with focal hemorrhage
Firm consistency
May show cystic areas
Pseudocapsule may be present.
Characteristics:
Size ranges from 3-10 cm
Lobulated external surface
Cut surface shows whorled pattern
Areas of necrosis and hemorrhage
Calcifications may be present.
Size Location:
Variable size at presentation
Mean size 5-8 cm
Involves uterine corpus
May extend to cervix
Extrauterine extension uncommon at presentation.
Multifocality:
Usually unifocal presentation
Infiltrative margins
May show satellite nodules
Lymph node metastases possible
Distant metastases to lung.
Microscopic Description
Histological Features:
Biphasic pattern with epithelial and spindle components
Glandular structures lined by epithelial cells
Spindle cell fascicles
Hemangiopericytoma-like vasculature
Moderate to high mitotic activity.
Cellular Characteristics:
Epithelial component: Cuboidal to columnar cells
Spindle component: Uniform spindle cells
Oval vesicular nuclei
Minimal nuclear pleomorphism
Scant cytoplasm.
Architectural Patterns:
Biphasic: Epithelial glands and spindle areas
Monophasic: Predominantly spindle cells
Fascicular pattern
Herringbone pattern
Staghorn vasculature.
Grading Criteria:
Low-grade: Minimal atypia, low mitotic rate
High-grade: Increased atypia, >10 mitoses/10 HPF
Poorly differentiated: Round cell morphology, high-grade features.
Immunohistochemistry
Positive Markers:
TLE1 (nuclear, highly sensitive and specific)
Bcl-2 (diffuse positivity)
CD99 (variable)
Vimentin
Epithelial component: Cytokeratins
EMA (epithelial areas).
Negative Markers:
S-100 (negative)
Desmin (negative)
Smooth muscle actin (negative)
CD34 (negative)
CD117 (negative)
Calretinin (negative).
Diagnostic Utility:
TLE1 positivity highly suggestive of synovial sarcoma
Bcl-2 diffuse staining supportive
Cytokeratin positivity in epithelial areas
SS18-SSX fusion confirmatory
Negative smooth muscle markers exclude leiomyosarcoma.
Molecular Subtypes:
SS18-SSX1 fusion (biphasic type)
SS18-SSX2 fusion (monophasic type)
SS18-SSX4 fusion (rare)
SYT-SSX fusion protein expression.
Molecular/Genetic
Genetic Mutations:
t(X;18)(p11;q11) translocation (>95% cases)
SS18-SSX1 fusion gene
SS18-SSX2 fusion gene
TP53 mutations (poor prognosis)
CDKN2A deletions.
Molecular Markers:
SS18-SSX fusion protein
TLE1 overexpression
EGR1 overexpression
IGF2 overexpression
High Ki-67 in high-grade areas.
Prognostic Significance:
SS18-SSX1 associated with biphasic morphology
SS18-SSX2 associated with monophasic morphology
Fusion type may influence prognosis
Size >5 cm indicates poor prognosis
High grade correlates with poor outcome.
Therapeutic Targets:
IGF-1R inhibitors
mTOR pathway inhibitors
HDAC inhibitors
Immunotherapy (NY-ESO-1 vaccines)
Pazopanib (multi-kinase inhibitor)
Trabectedin.
Differential Diagnosis
Similar Entities:
Leiomyosarcoma (smooth muscle differentiation)
Endometrial stromal sarcoma (stromal features)
Fibrosarcoma (purely fibrous)
Malignant peripheral nerve sheath tumor
Carcinosarcoma (epithelial malignancy).
Distinguishing Features:
Leiomyosarcoma: Smooth muscle actin positive
ESS: CD10 positive, ER/PR positive
Synovial sarcoma: TLE1 positive
Synovial sarcoma: SS18-SSX fusion
MPNST: S-100 positive.
Diagnostic Challenges:
Distinguishing monophasic from other spindle cell sarcomas
Recognizing biphasic pattern
Confirming SS18-SSX fusion
Excluding metastatic synovial sarcoma
Molecular testing essential.
Rare Variants:
Biphasic synovial sarcoma
Monophasic synovial sarcoma
Poorly differentiated synovial sarcoma
Calcifying synovial sarcoma
Cystic synovial sarcoma.
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
Synovial sarcoma of the endometrium
Classification
WHO Classification: [Biphasic/Monophasic/Poorly differentiated] synovial sarcoma
Morphologic Pattern
Pattern: [biphasic/monophasic], epithelial component [present/absent]
Grade
Grade: [low/high], mitoses: [count]/10 HPF
Immunohistochemistry
TLE1: [+/-], Bcl-2: [+/-]
Cytokeratins: [+/-] (epithelial areas)
Negative: S-100, Desmin, SMA
Molecular Studies
SS18-SSX fusion: [SS18-SSX1/SS18-SSX2/not detected/pending]
Final Diagnosis
[Subtype] synovial sarcoma of endometrium, [grade]