Stanford School of Medicine

Surgical Pathology Criteria

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Synovial Sarcoma


  • Sarcoma, biphasic or monophasic with a t(X;18;p11;q11) translocation

Diagnostic Criteria

General features of both patterns

  • Keratin positivity
    • Epithelial component either keratin of EMA positive in essentially 100% of cases
    • Spindle cell component 50-80% positive
  • No more than mild pleomorphism
    • Moderate pleomorphism may be seen following radiation
  • May be circumscribed or infiltrative
  • t(X;18;p11;q11) is definitional
    • All soft tissue tumors with this translocation are considered synovial sarcomas
    • Because of this new definitional criterion, the histologic features described may in the future be expanded

Biphasic pattern most common

  • Contains both epithelial and spindle components
    • Components may merge or be distinct
    • Metastases may show different predominance of components
  • Epithelial component usually large pale or columnar cells
    • Occasionally cuboidal, flat or spindled
    • May form glands, tubules or papillae (rare)
      • May contain mucin, rarely mucin rich
    • Rare focal squamous differentiation
    • Round vesicular nuclei
  • Spindle component usually uniform small elongate plump cells
    • Dark, even stippled chromatin
    • Scant cytoplasm with indistinct cell margins
    • Usually sheets or fascicles
      • Occasionally with nodules or myxoid foci
  • Characteristic stromal features usually present
    • Thick ropy collagen bundles
      • Often surrounding cellular nodules
    • Hemangiopericytoma-like vessels
    • Calcification

Monophasic pattern

  • Pure epithelial pattern rare to nonexistent
  • Pure spindle pattern contains spindle cells with above features
  • Requires at least one of the following:
    • t(X;18;p11;q11)
    • Keratin reactivity
    • One of the three characteristic stromal features above
  • Frequently seen nonspecific features
    • Palisading
    • Pseudorosettes
    • Herringbone pattern
    • Retiform or microcystic pattern
    • Metaplastic bone or cartilage
    • Areas with slightly larger cells

Poorly differentiated patterns may be focal or pure

Richard L Kempson MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 7/31/07, 1/20/09, 8/22/09, 8/21/10, 3/8/12

Poorly differentiated pattern

  • t(X;18;p11;q11) is required for the identification of such tumors as synovial sarcoma
  • 2 of following in at least 2 low power fields proposed for designation by de Silva
    • Cellular areas with nuclear crowding
    • Nuclear irregularity
    • Prominent nucleoli
    • Irregular, clumped chromatin
  • Other frequently associated features
    • Increased mitotic figures (>10/10hpf)
    • Necrosis
    • Presence of hemangiopericytoma like vessels
  • Cell types may be epithelioid, spindled, small round
  • Occasional patterns
    • Herringbone
    • Desmoplastic stroma surrounding nodules of cells
    • Cord or strands of cells
    • Pseudorosettes
    • Rhabdoid cells
    • Clear cells
  • Uniform, small round to spindle cells
    • Solid, closely packed cells
    • Resembles small round blue cell tumors of childhood
  • May be focal or pure
    • May be seen focally in up to 46% of cases
    • Pure pattern requires cytogenetic confirmation for diagnosis
  • Keratin and EMA reported 33-100% positive, frequently focal
  • Presence of at least 2 low power fields or 20% by area indicates worse prognosis
    • Increased recurrence, metastasis, death
    • Increased percentage associated with increasingly worse behavior

Supplemental studies


  • Keratin
    • Epithelial component of biphasic tumors 95%
    • Monophasic spindled tumors 50-80%, focal
    • Keratins 7, 8, 18 and 19 are the most widely expressed
      • CK7 100% if epithelial component present
        • Less frequent in spindled component
      • CK20 27%
  • EMA similar to keratins, but generally less reactivity
  • TLE1 85-97% (see table below)
    • Strong nuclear is most specific
  • Vimentin >80% in spindled areas, <30% in epithelial areas
  • S100 30%, focal
  • CD99 60%
  • Calretinin 71%
  • BerEp4 90%
  • CD15 rare
  • WT1 negative
  • cKIT negative vs. positive conflicting reports
  • Poorly differentiated tumors
    • Broad spectrum anti-keratin 33-90%, variable
      • CK7 27%
      • CK20 neg
    • EMA >90%
    • S100 40-63%
    • CD99 positive
    • bcl2 positive
    • CD57 90%
    • CD56 100%
    • Calretinin 56%
TLE1 Reactivity
Tumor Type % pos
Synovial sarcoma 85-97
Endometrial stromal sarcoma 66
Schwannoma 31-82
Hemangiopericytoma 40
Epithelioid sarcoma 33
SFT 20-27
Cellular schwannoma 17
Carcinosarcoma 14
Clear cell sarcoma 14
MPNST 5-30
PNET / Ewing sarcoma 0-8
GIST 0-6
Strong nuclear staining may be more specific (Kussel)


Genetic study

  • t(X;18;p11;q11) consistently identified, results in SYT-SSX gene fusion
    • Now considered definitional
  • Required for diagnosis of pure poorly differentiated tumors and useful for some monophasic tumors

Differential Diagnosis

Biphasic synovial sarcoma

Monophasic synovial sarcoma, spindled

Synovial sarcoma with poorly differentiated areas

Malignant Peripheral Nerve Sheath Tumor, Glandular Biphasic Synovial Sarcoma
Spindle cells may be larger and pleomorphic Spindle cells small and bland
Frequently involves nerve or neurofibroma Rarely involves nerve
Frequently associated with von Recklinghausen No association
No ropy collagen Ropy collagen frequent
Calcification infrequent Calcification frequent
No hemangiopericytomatous vessels Hemangiopericytomatous vessels frequent
No SYT-SSX gene fusion SYT-SST gene fusion present
TLE1 5% TLE1 97%


Carcinoma Biphasic Synovial Sarcoma
Spindle cell component rare (carcinosarcoma, metaplastic carcinoma) Virtually always a spindle cell component
Usually older patient Usually teenagers or young adults
May be pleomorphic No more than mild pleomorphism
No SYT-SSX gene fusion SYT-SST gene fusion present
TLE1 14% (carcinosarcoma) TLE1 97%


Diffuse Type Tenosynovial Giant Cell Tumor Biphasic Synovial Sarcoma
No epithelial lining of spaces May have epithelial lined glands
Keratin negative Keratin positive
Usually involves joint Very rarely involves joint
Giant cells may be frequent Giant cells infrequent
No ropy collagen Ropy collagen frequent
Nuclei frequently round, some are grooved Nuclei elongated in spindle component
No SYT-SSX gene fusion SYT-SST gene fusion present


Adult Fibrosarcoma Monophasic Synovial Sarcoma
Usually extensive herringbone pattern Herringbone pattern usually only focal
Keratin, EMA negative Keratin, EMA often positive
No ropy collagen Ropy collagen frequent
Calcification rare Calcification may be present
No hemangiopericytomatous vessels Hemangiopericytomatous vessels frequent
Thin elongate nuclei Plump nuclei
Chromatin not stippled Stippled chromatin
No SYT-SSX gene fusion SYT-SST gene fusion present
TLE1 0% (0/3) TLE1 97%


Leiomyosarcoma Monophasic Synovial Sarcoma
Cells usually larger and pleomorphic Cells small and bland
Spindled cytoplasm Scant cytoplasm
Actin positive Actin negative
No ropy collagen Ropy collagen frequent
Calcification infrequent Calcification frequent
No hemangiopericytomatous vessels Hemangiopericytomatous vessels frequent
Chromatin not stippled Stippled chromatin
No SYT-SSX gene fusion SYT-SST gene fusion present
TLE1 2% TLE1 97%


Both may present as keratin positive spindle cell neoplasms
Epithelioid Sarcoma Monophasic Synovial Sarcoma
Usually superficial Usually deep
Necrosis frequently extensive Necrosis usually focal
CD34 50% positive CD34 negative
No ropy collagen Ropy collagen frequent
Calcification infrequent Calcification frequent
No hemangiopericytomatous vessels Hemangiopericytomatous vessels frequent
No SYT-SSX gene fusion SYT-SST gene fusion present
TLE1 0% (0/2) TLE1 97%
CA125 90% positive CA125 negative


Synovial Sarcoma Clear Cell Sarcoma
Dense nuclei with stippled chromatin Vesicular nuclei with prominent nucleoli
Keratin 50-80% positive Keratin negative (one report of 30% positive)
Melanin and HMB45 negative Melanin and HMB45 positive 80%
Calcification common Calcification uncommon
SYT-SSX gene fusion present t(11;12) frequent
TLE1 97% TLE1 14%


Palmar or Plantar Fibromatosis Synovial Sarcoma
Rare under age 20 Frequently under age 20
Multiple small nodules Single large mass
Not biphasic May be biphasic
Variable cellularity Uniformly hypercellular
Lacks ropy collagen, calcification and stag horn vessels May have ropy collagen, calcification and stag horn vessels
No SYT-SSX fusion SYT-SSX fusion present


Poorly differentiated areas of synovial sarcoma and some monophasic cases may be difficult to impossible to distinguish from tumors such as:

  • Malignant peripheral nerve sheath tumor
  • Fibrosarcoma
  • Hemangiopericytoma
  • Primitive peripheral neuroectodermal tumor
  • Focally poorly differentiated cases are distinguished by identification of typical areas
  • Pure poorly differentiated cases may require cytogenetic confirmation
  • FISH is indicated in such cases


  • Occurs primarily in teenagers and young adults
  • Most in extremities or adjacent trunk
    • May involve hands and feet
    • Actual joint involvement is rare
  • Other locations include
    • Head and neck
    • Retroperitoneum and mediastinum
    • Lung and pleura
    • Kidney
    • Heart
    • Stomach
  • May metastasize to lymph nodes
  • Survival
    • Size (over 5 cm) is primary predictor of metastasis and survival
    • No significant difference between biphasic and monophasic
    • Poorly differentiated areas indicates worse behavior
      • Two low-power fields or 20% by area cutoffs proposed
      • Increased recurrence, metastasis, death

Grading / Staging / Report

Increasing amount of poorly differentiated area indicates a worse prognosis

  • Percent poorly differentiated area should be reported

According to the guidelines of the ADASP, synovial sarcoma is not graded although it often metastasizes

French Federation of Cancer Centers System grading scheme for adult sarcomas

  • Tumor differentiation score = 3 for synovial sarcoma
  • Mitotic index
    • Score 1 0-9 mitoses per 10 hpf (0.1744 sq mm)
    • Score 2 10-19 mitoses per 10 hpf
    • Score 3 >19 mitoses per 10 hpf
  • Tumor cell necrosis
    • Score 0 No necrosis on any slide (one slide per 2 cm tumor diameter)
    • Score 1 <50% of tumor is necrotic on slides examined
    • Score 2 >50% of tumor is necrotic on slides examined
  • Final Grade (add the three scores above)
    • Grade 1 Sum of scores = 2 or 3
    • Grade 2 Sum of scores = 4 or 5
    • Grade 3 Sum of scores = 6 or more

Use TNM Staging

The surgical pathology report should contain or address the following:

  • Location
  • Type of resection or biopsy
  • Histologic diagnosis
  • Managerial category III (Local recurrence common, metastasis may occur)
  • Extent of tumor cell necrosis
  • Grade
    • Percent poorly differentiated area
  • Stage
  • Size
  • Depth (dermis, subcutis, below fascia, body cavity)
  • Margins
    • Involved
    • Not involved
      • If under 2 cm give all such distances and sites
      • If over 2 cm give minimum distance and site
  • Results of supplementary studies if performed
  • Relationship to other specimens from the same patient


Keratin positive soft tissue tumors (frequent and strong)

CD99 positive tumors (>50%)

Lesions that may demonstrate a prominent hemangiopericytoma-like vascular pattern


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