Definition/General
Introduction:
Synovial sarcoma is a malignant soft tissue tumor
Shows epithelial and spindle cell components
Represents 8-10% of soft tissue sarcomas
FNAC shows biphasic morphology with specific translocation.
Origin:
Arises from primitive mesenchymal cells
Not from synovium (misnomer)
Can occur anywhere
Bipotential differentiation
Shows epithelial and mesenchymal features.
Classification:
WHO classification: Malignant soft tissue tumor
Types: Biphasic synovial sarcoma
Monophasic fibrous
Monophasic epithelial (rare)
Poorly differentiated.
Epidemiology:
Peak incidence 3rd-4th decades
Slight male predominance
Adolescents and young adults
Accounts for 15-20% of sarcomas in young adults.
Clinical Features
Presentation:
Slow-growing mass
Para-articular location
Extremities (90%)
Deep-seated typically
Painful (30%)
Large size at presentation.
Symptoms:
Mass (most common)
Pain (variable)
Functional limitation
Swelling
Calcification on imaging
Slow growth over years.
Risk Factors:
Young age (15-40 years)
No known risk factors
Not associated with prior radiation
No genetic syndromes
Equal racial distribution.
Screening:
Clinical examination
MRI for characterization
FNAC/Biopsy
Molecular studies essential
Staging workup.
Master Synovial Sarcoma FNAC Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Well-circumscribed mass
Multinodular
Gray-white cut surface
Solid and cystic areas
Calcification (30%)
Hemorrhage and necrosis.
Characteristics:
Pseudocapsule
Firm consistency
Whorled pattern
Cystic spaces
Gritty areas (calcification)
Variable vascularity.
Size Location:
Lower extremities (70%)
Upper extremities (20%)
Head/neck, trunk (10%)
Para-articular but not intra-articular
Size: 5-15 cm average.
Multifocality:
Usually solitary
Local recurrence (10-50%)
Metastases to lung (80%)
Lymph node metastases (10-20%)
Bone metastases (10%).
Microscopic Description
Histological Features:
FNAC shows biphasic pattern
Spindle cells and epithelial cells
Uniform spindle cells
Glandular structures
Moderate atypia
Variable mitotic activity.
Cellular Characteristics:
Uniform spindle cells
Oval nuclei
Fine chromatin
Moderate cytoplasm
Epithelial clusters
Glandular formations.
Architectural Patterns:
Fascicular spindle cells
Epithelial clusters
Glandular spaces
Hemangiopericytoma-like areas
Clean background
Calcification (when present).
Grading Criteria:
Intermediate to high grade
Nuclear grade
Mitotic activity
Necrosis
Size >5 cm: Higher grade
Poorly differentiated: High grade.
Immunohistochemistry
Positive Markers:
TLE1 - positive (nuclear, sensitive)
Cytokeratin - positive (epithelial component)
EMA - positive
Bcl-2 - positive
CD99 - positive
Calretinin - positive.
Negative Markers:
S-100 - negative
Desmin - negative
CD34 - negative
SMA - negative
MyoD1 - negative
CD117 - negative.
Diagnostic Utility:
TLE1 most useful marker (nuclear)
Cytokeratin in epithelial areas
Bcl-2 helps differentiate
Ki-67 variable (5-40%)
Molecular confirmation essential.
Molecular Subtypes:
All types: TLE1+, t(X;18)
Biphasic: Cytokeratin+ in epithelial component
Monophasic: Focal cytokeratin+
SYT-SSX fusion in all types.
Molecular/Genetic
Genetic Mutations:
t(X;18)(p11;q11) - pathognomonic (>95%)
SYT-SSX1 fusion (biphasic, worse prognosis)
SYT-SSX2 fusion (monophasic, better prognosis)
SYT-SSX4 (rare)
Simple karyotype.
Molecular Markers:
SYT-SSX fusion transcript
SSX protein expression
TLE1 overexpression
EGR1 overexpression
Low mutational burden
Specific gene signature.
Prognostic Significance:
SYT-SSX1: Worse prognosis
SYT-SSX2: Better prognosis
Size <5 cm: Better outcome
Age <20 years: Better prognosis
Biphasic: Variable outcome.
Therapeutic Targets:
Anthracycline-based chemotherapy
Ifosfamide effective
Pazopanib (advanced)
Targeted therapy (investigational)
Immunotherapy trials.
Differential Diagnosis
Similar Entities:
Fibrosarcoma
MPNST
Hemangiopericytoma
Ewing sarcoma
Spindle cell carcinoma
Solitary fibrous tumor.
Distinguishing Features:
Synovial sarcoma: TLE1+, t(X;18), biphasic
Fibrosarcoma: TLE1-, no specific translocation
MPNST: S-100+/-, nerve association
Ewing: CD99+, t(11;22)
Carcinoma: Organ-specific markers.
Diagnostic Challenges:
Monophasic type lacks epithelial component
TLE1 can be positive in other tumors
Molecular confirmation essential
Poorly differentiated areas challenging.
Rare Variants:
Calcifying synovial sarcoma
Cystic synovial sarcoma
With neural differentiation
With cartilaginous differentiation.
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
Fine needle aspiration from [site], [size] cm para-articular mass
Clinical History
[age]/[sex] with [duration] history of slowly enlarging mass near [joint]
Microscopic Examination
Smears show biphasic pattern with uniform spindle cells and epithelial cell clusters. Glandular formations noted. Moderate nuclear atypia and variable mitotic activity.
Immunocytochemistry
TLE1: Positive (nuclear), Cytokeratin: Positive (epithelial component), Bcl-2: Positive, S-100: Negative
Molecular Studies
SYT-SSX fusion: [Positive/Pending], Fusion type: [SYT-SSX1/SYT-SSX2]
Cytological Diagnosis
Cytological and molecular features consistent with SYNOVIAL SARCOMA
Comments
Molecular confirmation with SYT-SSX fusion essential for diagnosis. Multidisciplinary sarcoma team evaluation required. Intermediate to high-grade malignancy.