Synovial Sarcoma

 

Epidemiology and Etiology:

    • 20s to 40s
    • Cell of origin is still unclear – probably unrelated to synoviocytes
      • May be epithelial metaplasia of mesenchymal tissues

 

Common sites:

    • Deep soft tissue of the extremities near joints (but usually not involving joint)
      • Lower extremity (60-70%)
        • Knee and thigh especially
    • Neck (esp. retropharyngeal)
    • Anterior abdominal wall
    • Retroperitoneum
    • Mediastinum
    • Blood vessels
    • Nerves
    • Intra-articular (<10% or rare)
    • Any site
    • Mets:
      • Lung, skeleton
      • Lymph nodes occasionally (10-15%) (more than other sarcomas)

 

Gross features:

    • Well-circumscribed or infiltrative
    • Multinodular frequently
    • 3-10cm usually
    • Firm
    • Tan-gray
    • May be multicystic
    • Necrosis in poorly differentiated SS
    • Focal calcifications on X-ray frequently
      • Calcified synovial sarcomas have a better prognosis

 

Histologic features:

    • biphasic variant:
      • dual differentiation (epithelial-like and spindle cell)
    • epithelial component:
      • glands, cords, papillary structures, nests, rounded clusters
        • may be mistaken for adenocarcinoma if this component is prominent
      • cuboidal to columnar
      • uniform
      • ovoid nuclei
      • abundant cytoplasm
      • mucin-secreting
      • rarely squamous
    • spindle cell component:
      • densely cellular sheets or vague fascicles surrounding the epithelial cells
        • occasional nuclear palisading
        • focally whorled
        • hemangiopericytoma-like vascular pattern often
      • monotonous appearance
      • fibroblast appearance
        • plump, ovoid, pale nuclei
        • inconspicuous nucleoli
        • sparse cytoplasm
      • wiry stromal collagen
      • may have myxoid change
      • large number of mast cells often
    • monophasic variant:
      • only spindle cells (rarely only epithelial cells)
      • may be mistaken for fibrosarcoma or MPNST
      • calcified concretions are characteristic (check X-ray)
    • scarce mitoses
      • focal areas of numerous mitoses may be seen
    • you may see:
      • hyalinization
      • calcification
        • within gland lumena
        • lace-like osteoid mimicking osteosarcoma
      • osseous metaplasia (sometimes prominent)
      • myxoid
      • focal necrosis
    • poorly-differentiated SS:
      • predominating areas of:
        • high cellularity
        • numerous mitoses
        • necrosis
      • small round blue cell tumour appearance
      • same immunophenotype and translocation as regular SS

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Mucin (acid mucopolysaccharides) (in gland lumina) 

 

 

PAS (epithelial areas)

 

 

Reticulin (outline epithelial areas)

 

 

CK7, 14, 19 (epithelial and focal spindle areas)

90%

Absent in PNET and Ewing Sarcoma

desmoplakin

 

 

Vimentin (spindle cells)

 

 

EMA

>90%

often more widespread than CK

 

CEA

 

 

Calponin

Most

 

Desmin (neg)

 

 

MSA/SMA (focal)

occasionally

 

HBME-1

 

 

CD99

62%

ES/PNET positive

Bcl-2 (particularly spindle cell areas)

all

 

Her2/neu

 

 

MAGE-CT

 

 

S100

30%

 

Calretinin

Some (focal)

 

WT1 (neg)

 

 

CD34 (neg)

usually

 

 

Molecular features:

    • t(x;18) (p11.2;q11.2) (>90%) (sole in 1/3) (specific for SS)
      • der(X) is the oncogenic product
      • SYT-SSX1 fusion gene (mostly biphasic)
      • SYT-SSX2 fusion gene (mostly monophasic)
        • Better prognosis
      • SS18 (aka SYT or SSXT) from chromosome 18
      • SSX1, SSX2, and SSX4 from X chromosome
      • t(X;20)(q13;p11) variant
        • SS18L1/SSX1
    • Secondary abnormalities
      • Numerical changes:
        • Pseudodiploid (50%)
        • Hypodiploidy  > hyperdiploidy
        • Triploidy or tetraploid (10%)
        • (in order of frequency) (same frequency in primary, recurrent, and metastases)
          • +7
          • +8 (?more common in primaries)
            • 8q22-24
          • +12
          • -3
          • +9
          • +21
          • +2 (?more common in metastases)
            • 2q13-21
          • -14
          • -17
          • +4
          • -11
          • -17
          • +4
          • -11
          • +15
          • -22
      • Structural changes:
        • Unbalanced:
          • 3p12-26 loss
          • 17p13 loss
          • 12q gain / amp (poor prognosis in one study by array-CGH)

 

Other features:

    • EM:
      • Epithelial component similar to adenocarcinoma
        • Surface microvilli protruding into glandular lumen
      • Spindle cell component:
        • Featureless
        • May see abortive lumina with projecting microvilli
    • Good prognostic factors:
      • Calcified
      • Young
      • Distal site
      • <5cm
      • margins negative
      • <10 mitoses per 10HPF
      • <50% or no necrosis
      • no rhabdoid cells
      • simple cytogenetics and SS18-SSX2 fusion in one study (Panagopoulos et al, 2001)
    • bad prognostic factors:
      • rhabdoid cells
      • >50% necrosis
      • Complex karyotype and SS18-SSX1 fusion in one study (Panagopoulos et al, 2001)
    • 40% metastasize
    • may recur even after 30y

 

References:

    • Robbins 2005
    • Rosai 2004
    • WHO Soft Tissue and Bone Tumours (2002)
    • Sandberg AA & Bridge JA.  Updates on the cytogenetics and molecular genetics of bone and soft tissue tumours.  Synovial Sarcoma.  Cancer Genetics and Cytogenetics 133 (2002):1-23.
    • Heim & Mitelman.  Cancer Cytogenetics (2009)