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Synovial Sarcoma

DEFINITION AND PATHOGENESIS

  • Aka Synovial Cell Sarcoma, synoviosarcoma, malignant synovioma
  • Often a biphasic tumor composed of epithelial and fibrous components forming "clefts" histogically (name derived from this synovium-like appearance)

IMPORTANCE

  • 4th most common soft tissue sarcoma after HGPUS, liposarcoma, and rhabdomyosarcoma
  • Represents 36% of nonrhabdomyosarcoma soft tissue sarcomas in children (most common)
  • Most common soft tissue sarcoma of the hand in some reports (epithelioid sarcoma in others)
  • Most common soft tissue sarcoma associated with calcification
  • Has been reported associated with a previously placed THA
  • Has been reported after intraarterial perfusion of doxorubicin for osteosarcoma
  • Has been reported (paraspinal) after radiation in pediatric abdominal neuroblastoma

CLINICAL FEATURES

  • Usually occurs within 7cm of a joint, but uncommon to be intra-articular (<5%)
  • Most prevalent between 15-40 years (average age 35)
  • M:F = 1.2:1
  • Pain associated with the deep seated mass in 50%, not uncommonly present for 2-4 years
    • Carpal tunnel syndrome has been a presenting finding in volar wrist location
  • Most commonly located around the knee
  • Unusual locations
    • Frontal sinus
    • Tongue
    • Tonsil
    • Parapharyngeal
    • Larynx
    • Trachea
    • TMJ
    • Parotid
    • Pleura
    • Atrium
      • ~ 1% of all primary cardiac tumors
    • Vulva
    • Fallopian tube
    • Intradural mass at the C6-7 foramen
  • Spontaneous pneumothorax has been reported from occult parapharyngeal metastases
  • Tumor-induced hypercalcemia
    • (18.3 mg/dl) has been reported
    • [Ca++] normalized with bisphosphonates and after resection
  • Has been reported in the same limb as a 14-year-old boy with osteofibrous dysplasia
  • Has been reported associated 12 yrs after a Charnley-Müller THA with polyethylene cup and PMMA

RADIOLOGIC FEATURES

  • Rounded or oval soft tissue density, with up to 20-30% having focal calcification(often in periphery of tumor) or ossification on x-rays, with periosteal reaction or cortical erosion (11-20%) if in a juxtacortical location
  • Angiogram shows prominent vascular blush
    • Vasculogenic mimicry
      • Formation of fluid-conducting channels by highly invasive and genetically dysregulated tumor cells
        • Patterned matrix type in synovial sarcoma
  • MRI best study for determining anatomic extent and adjacent structures
    • + gadolinium enhancement
    • T1-weighted images: isointense to muscle
    • T2-weighted images: marked heterogeneity, multilocular configuration with internal septation
    • ? changes compatible with previous hemorrhage (>40%)
    • Fluid-fluid levels (10-25%) corresponding to spread of hemorrhage
    • Soft tissue calcifications appear as areas of ? signal intensity on all pulse sequences
    • "Bowl-of-fruit" appearance
    • Areas of ? signal intensity on T1- and T2-weighted images correspond to areas of hemorrhage and
    • hematoma
    • Areas of ? signal intensity on T1- and T2-weighted images correspond to areas of viable fibrous tumor tissue
    • Areas of ? signal intensity on T1- and ? on T2-weighted images also correspond to areas of viable tumor

GROSS PATHOLOGY

  • Slow growing lesions are well circumscribed with a pseudocapsule, ??prominent cyst formation, firmly attached to fascia or tendons
  • Rapidly growing lesions may be friable and hemorrhagic with cysts on the cut surface

HISTOLOGIC FEATURES

  • Histologic types:
    • Biphasic
    • Monophasic fibrous
    • Monophasic epithelial
    • Poorly differentiated
  • Epithelial cells resemble carcinoma
  • Spindle cells are not stromal cells, but tumor cells as well
  • Rarely have > 2 mitoses/HPF except poorly differentiated lesions
  • Calcifications or osseous metaplasia may be sparse or very prominant
  • Mast cells typically seen
  • Vascularity may be prominant and hemangiopericytoma-like
  • ±?lack of cellular cohesion forming pseudoalveolar pattern
  • ±?nuclear palisading
  • ±?pseudorosettes
  • ±?myxoid changes
  • Rarely with round cells as in Ewing sarcoma
  • Special stains:
    • Epithelial cell secretions:
      • + PAS
      • + for colloidal Fe++
      • + alcian blue
      • + mucicarmine
    • Spindle cell mucin:
      • + for colloidal Fe++ and alcian blue
  • Cytogenetics:
    • Translocation: t(X;18)(p11.2;q11.2) can be diagnostic in poorly differentiated lesions (t(X;18) not specific for synovial sarcoma)
    • Fusion of SYT gene on 18q11.2 with either SSX1 or SSX2 gene on Xp11.2
      • SSX2 identified as the cancer testis antigen HOM-Mel-40
        • Some melanoma pts have IgG antibody immune responses specific for SSX2
          • SSX2 expressionin tumor samples
            • 50% of melanoma samples
            • 30% of hepatocellular carcinoma samples
            • 25% of colon and prostate samples
            • 20% of breast cancers
            • Indicates SSX2 is upregulated independently from fusion events with SS18
      • SSX homologues
        • SSX1
        • SSX2
        • SSX3
        • SSX4
        • SSX5
        • SSX6
        • SSX7
        • SSX8
        • SSX9
        • ?SSX10
          • Only one not on the X chromosome
          • Located on chromosome 6
    • bcl-2 overexpression
    • 69% with SMARCB1/INI1 mRNA expression reduced
      • A suggested post-transcriptional SMARCB1/INI1 regulatory mechanism proposed
    • Chromogenic in situ hybridization (CISH)
  • Immunochemistries:
    • + cytokeratin typically seen in the spindle cell component
    • + epithelial membrane antigen
  • EM:
    • Epithelial cells:
    • Dense chromatin within nuclei, prominent Golgi, with junctional complexes interconnecting cells
  • Spindle cells:
  • Early epithelial differentiation

DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS

  • Ossification in liposarcoma, extraskeletal myxoid chondrosarcoma or osteosarcoma, or rhabdomyosarcoma
  • Angiosarcoma or hemangiopericytoma
  • Hemangioma
  • Epithelioid sarcoma
  • Clear cell sarcoma
  • Malignant peripheral nerve sheath tumor (up to 75% have been reported to have t(X;18))
  • Fibrosarcoma (uncommonly reported to have t(X;18))
  • Metastatic carcinoma
  • Ewing sarcoma
  • Peripheral neuroepithelioma
  • Mesothelioma
  • MFH (uncommonly reported to have t(X;18))
  • Neurofibroma (uncommonly reported to have t(X;18))

DISEASE COURSE AND TREATMENT

  • ?50-80% 5 yr survival
  • Prognosis worse if:
    • >20 years of age, proximal location, >5cm in size, poor differentiation and high mitotic rate, high nuclear grade and aneuploidy, monophasic histology, large % of necrosis, vascular invasion, < wide resection
  • <5cm in size: 88% 10-yr survival reported
  • 5-10cm in size: 38% 10-yr survival reported; 3.1-fold ? risk of death
  • >10cm in size: 8% 10-yr survival reported; 18-fold ? risk of death
  • SYT-SSX1 gene product (SYT-SSX2 has a better prognosis)
  • ? metastasis-free survival rage
  • ? overall survival rate
  • Wide to radical resection is indicated ? XRT
  • Chemotherapy, esp in poorly differentiated lesions, lesions > 5cm in size, and SYT-SSX1 gene product
    • German and Italian Pediatric Soft Tissue Sarcoma Cooperative Groups between 1975-2002 gave rhabdomyosarcoma chemotherapeutic protocols to pediatric pts with synovial sarcoma without noted assessable benefit
  • Novel txs
    • Luteolin significantly inhibited IL-1beta-induced MMPs (MMP-1 and -3) and cytokines (TNF-alpha and IL-6) in human synovial line SW982
  • Metastases to lungs, lymph nodes, and bone marrow (may be many yrs after the primary, even > 15 yrs))
    • Unusual metastatic sites: peripheral nerve
  • XRT to LN if involved preferable to LN dissection
  • Stereotactic XRT reported for pulmonary metastases

SPECIAL CONSIDERATIONS

  • Cystic Synovial Sarcoma

    • Must be differentiated from other less aggressive lesions and treated appropriately
  • Intravascular Synovial Sarcoma

    • Extremely rare occuring within large veins of the LEs or trunk in women
      • Superior vena cava syndrome has been reported
  • Poorly Differentiated Type Synovial Sarcoma

    • Characterized by predominantly round or short-spindled cell morphology
    • Characterized by down-regulation of genes associated with neuronal and skeletal development and cell adhesion
    • Upregulation of genes on the chromosome locus, 8q21.11 has been reported

 

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