Mediastinum
Other malignancies
Synovial sarcoma

Senior Author: Jennifer M. Boland, M.D.
Editorial Board Member: Andrey Bychkov, M.D., Ph.D.
Editor-in-Chief: Debra Zynger, M.D.

Topic Completed: 3 January 2019

Revised: 8 January 2019

Copyright: (c) 2003-2019, PathologyOutlines.com, Inc.

PubMed Search: Synovial sarcoma mediastinum
Page views in 2018: 171
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Cite this page: Terra SBSP, Boland JM. Synovial sarcoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/mediastinumsynovial.html. Accessed February 18th, 2019.
Definition / general
  • Malignant mesenchymal tumor of uncertain lineage that most often presents in the extremities of young adults
  • While synovial sarcoma occurs in the pleuropulmonary parenchyma with some frequency, it is very rare in the mediastinum (Mod Pathol 2007;20:760)
Essential features
  • Translocation associated sarcoma characterized by SS18-SSX1/2 fusion
  • Monomorphic spindle cell sarcoma with or without areas of epithelial differentiation (monophasic or biphasic, respectively)
  • Accounts for ≤ 10% of thoracic synovial sarcoma cases, with most arising in the lungs or pleura (Mod Pathol 2007;20:760)
Terminology
  • Monophasic synovial sarcoma composed only of spindled cells
  • Biphasic synovial sarcoma composed of spindled and epithelial cells
ICD coding
  • ICD-10: C38.3 - Malignant neoplasm of mediastinum, unspecified
  • ICD-10: C49.9 - Malignant neoplasm of connective and soft tissue, unspecified
Epidemiology
Sites
  • May involve any mediastinal compartment including anterior (prevascular), posterior (paravertebral), middle (visceral) and superior mediastinum (Am J Surg Pathol 2018;42:761)
Clinical features
  • Typically presents with symptoms related to a large mediastinal mass, which may include pain (chest, back, epigastric, shoulder), chest tightness, dyspnea, cough, dysphagia, hemoptysis, Horner syndrome, hemothorax, obstructive pneumonia or syncope (Am J Surg Pathol 2018;42:761)
  • Constitutional symptoms may also include poor appetite, fatigue, etc. (Am J Surg Pathol 2018;42:761)
Radiology description
  • Usually observed as a lobulated round to oval mass
  • Often reach very large size (> 10 cm) (Am J Surg Pathol 2018;42:761)
  • May compress or encase surrounding critical structures including pericardium, heart or great vessels
Radiology images

Contributed by Jennifer M. Boland, M.D.

CT scan

Prognostic factors
  • Seem to be particularly aggressive with a worse prognosis than soft tissue counterparts
    • ~70% of patients die from disease < 3 years from diagnosis (Am J Surg Pathol 2018;42:761)
    • Aggressive clinical course is probably due to site specific factors, such as proximity to critical anatomic structures as well as late detection with large tumor size at diagnosis
    • Adverse outcome may also be related to the high rate of poorly differentiated morphology
  • No known differences are noted in the clinical behavior of monophasic and biphasic synovial sarcoma; therefore, this distinction is not important for clinical management purposes
  • Poorly differentiated morphology is associated with older age at presentation and poor prognosis
Case reports
Treatment
  • Surgery with or without adjuvant chemotherapy / radiotherapy is the treatment of choice, if feasible
  • For patients with inoperable tumors, chemotherapy and radiation are typically employed (Am J Surg Pathol 2018;42:761)
Gross description
  • Average tumor size is large, ~13 cm (range 5 - 23 cm) (Am J Surg Pathol 2018;42:761)
  • Tumors are grossly tan-white, soft to rubbery cut surface with hemorrhage and necrosis
  • May show cystic degeneration and gelatinous change
  • Often appear grossly well circumscribed / lobulated but usually show subtle invasive growth into adjacent structures, including chest wall, great vessels, heart, pericardium, pleura, ribs or vertebra (Mod Pathol 2007;20:760, Am J Surg Pathol 2005;29:569)
Microscopic (histologic) description
  • Can show monophasic or biphasic morphology but monophasic is more common in the mediastinum (Am J Surg Pathol 2018;42:761, ISRN Oncol 2014;2014:412527, Mod Pathol 2007;20:760, Am J Surg Pathol 2005;29:569)
    • Monophasic
      • Consist solely of monomorphic spindled cells with nuclear monotony; marked pleomorphism is usually absent
      • Mitotic activity and necrosis are common
      • Orderly fascicular / herringbone growth pattern
      • Hemangiopericytoma-like vascular pattern
      • Hyalinized collagen and calcifications may be present
    • Biphasic
      • Comprised of variable proportions of monomorphic spindled cells as described above and epithelial cells
      • Epithelial cells can form glands or solid nests and cords; seldom show squamous metaplasia or granular cell change
    • Poorly differentiated
      • Form of tumor progression with some deviation from classical morphology; areas of conventional morphology are usually also present
      • Poorly differentiated areas are very cellular and may be composed of primitive round cells, epithelioid cells or high grade spindled cells
      • Usually demonstrate elevated mitotic activity, frequent rhabdoid change and necrosis
Microscopic (histologic) images

Contributed by Jennifer M. Boland, M.D.

Monophasic synovial sarcoma

EMA

TLE1


Biphasic synovial sarcoma

Poorly differentiated synovial sarcoma

Virtual slides

Images hosted on other servers:

Monophasic synovial sarcoma

Positive stains
  • Pankeratins and EMA (Virchows Arch 2000;437:275):
    • Usually very limited expression in the spindle cell component
    • Often restricted to single cells or sometimes highlights glandular structures that are unapparent on H&E
    • Glandular areas of biphasic examples are usually robustly positive, if present
    • May be completely negative if only the spindle cell component is present, especially on small biopsies
    • Spindle cell areas generally do not show diffuse immunoreactivity (in contrast to sarcomatoid carcinomas, mesotheliomas and thymomas)
  • TLE1 (Am J Clin Pathol 2011;135:839):
    • Highly sensitive nuclear marker of synovial sarcoma
    • Not specific, since other tumors can show staining
    • Most valuable to identify cases in which molecular genetic testing is likely to be positive (i.e. a negative stain is a good "rule out" marker but positive stain should be confirmed by molecular studies if the diagnosis is in doubt)
  • CD99 (Mod Pathol 2006;19:659):
    • Often positive but poor specificity as other entities in differential diagnosis (i.e. Ewing sarcoma) also express this marker
  • S100 (Mod Pathol 2006;19:659):
Molecular / cytogenetics description
  • Definitive diagnosis often requires ancillary molecular genetic testing due to the rare primary site; these tests are possible even on small biopsies
  • t(X;18)(p11;q11)
Molecular / cytogenetics images

Contributed by Jennifer M. Boland, M.D.

SS18(SYT)-SSX1 fusion

Differential diagnosis
Board review question #1
A 37 year old man presented with shortness of breath and dull chest pain. He was found to have a 15 cm mass in the anterior mediastinum. Representative photomicrographs from the needle biopsy are shown below. What is the most likely molecular alteration in this tumor?



  1. EWSR1-FLI1
  2. FUS-DDIT3
  3. NAB2-STAT6
  4. SS18-SSX1
  5. WWTR-CAMTA
Board review answer #1
D. SS18-SSX1. t(X;18)(p11;q11) is characteristically seen in synovial sarcoma and leads to the fusion of SS18 (also known as SYT or SST) with one of the SSX genes. It can be detected by next generation sequencing, RT-PCR or FISH. SYT-SSX1 is the most common fusion in synovial sarcoma, present in 67% of cases. The tumors characterized by the other fusion genes listed would not be expected to show the cellular monomorphic spindle cell sarcoma observed in the photomicrograph. EWSR1-FLI occurs in Ewing sarcoma; FUS-DDIT3 is observed in myxoid liposarcoma; NAB2-STAT6 fusion characterizes solitary fibrous tumor; and WWTR-CAMTA fusion is present in epithelioid hemangioendothelioma.

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Board review question #2
Which of the following features essentially excludes a monophasic synovial sarcoma from the differential diagnosis in a mediastinal needle biopsy of a spindle cell tumor?

  1. Focal CD99 expression
  2. Focal S100 expression
  3. Lack of keratin expression
  4. Marked nuclear pleomorphism
  5. Small round blue cell morphology
Board review answer #2
D. Marked nuclear pleomorphism. Monophasic synovial sarcomas are spindle cell sarcomas with striking nuclear monotony and generally should not show marked nuclear pleomorphism, even in poorly differentiated examples. The lack of keratin expression, especially on small biopsies, does not exclude the diagnosis if the correct morphology is observed and molecular confirmation could be considered in this context. Focal S100 expression can be observed in synovial sarcoma and in this setting, molecular analysis may be needed to differentiate it from malignant peripheral nerve sheath tumor. Poorly differentiated examples of synovial sarcoma can show small round blue cell morphology, often resembling Ewing sarcoma, which also may require molecular analysis since both entities can express CD99.

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