synovial sarcoma

Digital cases

 JRC:6541 : Synovial sarcoma of soft tissues.

Definition: Human synovial sarcomas are aggressive soft tissue tumors with relatively high rates of recurrences and metastases. They display a variable response to common treatment protocols such as radiation and chemotherapy.

Localization

 soft tissue
 nerve (intraneural synovial sarcoma) (14685256)
 kidney (renal synovial sarcoma)
 liver (hepatic synovial sarcoma) (16048399)

Variants

 monophasic synovial sarcoma
 with rhabdoid tumoral cells (14521444, 15105652)
 poorly differentiated synovial sarcoma

Immunochemistry

 Beta-catenin+ (16740029, 15375433, 11213832, 10189891)

• The synovial sarcoma translocation protein SYT-SSX2 recruits beta-catenin to the nucleus and associates with it in an active complex. (16462762)
• Aberrant beta-catenin expression has prognostic relevance. (16740029, 11274633, 11054718)
• +/- Association between aberrant (nuclear) beta-catenin expression and cyclin D1 accumulation (16740029, 16733209)

 Positive stains

• TLE1 : 80 - 90%, relatively specific and sensitive marker, but new studies are finding more tumors with TLE1 positivity (Am J Clin Pathol 2011;135:839, Mod Pathol 2009;22:872)

• Cytokeratins: 90%, variable positivity depending on the keratin polypeptide and the component (Virchows Arch 2000;437:275)
  • Epithelial component is consistently positive for CK7, CK8, CK14, CK18, CK19 and variable for CK17 (77%), CK13 (25%), CK6 (24%) and CK16 (23%)
  • Spindle cell component usually focal and variably positive for CK7 (79%), CK19 (60%), CK18 (46%), CK8 (45%), CK14 (28%), CK17 (10%), CK20 (6%)

• EMA: 29 - 90%, variable and focal, generally less than cytokeratins (Hum Pathol 1990;21:733, Am J Surg Pathol 2002;26:1434)

• BCL2: 79 - 100% (Cancer Genet Cytogenet 2009;193:1)
• Beta-catenin: 30 - 73%, (Oncogene 2014;33:5006)
• Calponin: at least focally positive in all tested cases (Histopathology 2003;42:588)
• CD99: 91%, CD56 100%, CD57 90%, calretinin 56 - 71%
• S100: 40% (Am J Clin Pathol 1999;112:641)
• NY-ESO-1: 76% strong and diffuse staining (Mod Pathol 2012;25:854)
• SYT: 87% , strong nuclear staining, may lack specificity (Mod Pathol 2007;20:522)
• ZO-1, claudin1 and occludin
• Glandular component of most biphasic cases were positive for ZO-1, claudin1 and occludin
• All monophasic synovial sarcomas were positive for ZO-1 yet only some were positive for claudin1 (29%) and occludin (21%) (Mod Pathol 2004;17:141)

 Negative stains

• CD34, desmin, h-Caldesmon, myogenin, MyoD1, FLI1, WT1 (nuclear staining)
• SOX10: 93% negative (Mod Pathol 2014;27:55)
• INI1: 69% show reduced expression (Mod Pathol 2010;23:981)
• H3K27me3: 60% show loss

Differential diagnosis

 fusiform cell tumors

• fibrosarcomas
  • adult-type fibrosarcoma

Molecular biology

Synovial sarcoma is characterized cytogenetically by the t(X;18)(p11;q11) translocation, resulting in fusion between the SS18 gene on chromosome 18 and one of the SSX genes on the X chromosome.

 SS18/SSX1
 SS18/SSX2
 SS18/SSX4

These three fusion genes account for more than 95% of the synovial sarcomas.

 SS18L1/SSX1 (12696068)

The SS18 and SSX genes encode nuclear proteins that exhibit opposite transcription regulatory activities, likely through epigenetic mechanisms. The SS18 protein functions as a transcriptional coactivator and interacts directly with members of the epigenetic chromatin remodeling and modification machineries.

In contrast, the SSX proteins function as transcriptional corepressors and are associated with several Polycomb group proteins. Since the domains involved in these apparently opposite transcription regulatory activities are retained in the SS18-SSX fusion proteins, these fusion proteins can function as "activator-repressors" of transcription.

Case records

 Case 11736: Axilary synovial sarcoma
 pathxchange.org #15007

See also

 Tumors

• Sarcomas
• fusiform cell tumors
• biphasic tumors
• synovial tumors

References

 Gene expression profiling of synovial sarcoma: distinct signature of poorly differentiated type. Nakayama R, Mitani S, Nakagawa T, Hasegawa T, Kawai A, Morioka H, Yabe H, Toyama Y, Ogose A, Toguchida J, Nakayama T, Yoshida T, Ichikawa H. Am J Surg Pathol. 2010 Nov;34(11):1599-607. PMID: 20975339

 Prospective Evaluation of TLE1 as a Diagnostic Immunohistochemical Marker in Synovial Sarcoma. Jagdis A, Rubin BP, Tubbs RR, Pacheco M, Nielsen TO. Am J Surg Pathol. 2009 Oct 3. PMID: 19809272

 de Bruijn DR, Nap JP, van Kessel AG. The (Epi)genetics of human synovial sarcoma. Genes Chromosomes Cancer. 2007 Feb;46(2):107-17. PMID: 17117414

 Kanemitsu S, Hisaoka M, Shimajiri S, Matsuyama A, Hashimoto H. Molecular detection of SS18-SSX fusion gene transcripts by cRNA in situ hybridization in synovial sarcoma using formalin-fixed, paraffin-embedded tumor tissue specimens. Diagn Mol Pathol. 2007 Mar;16(1):9-17. PMID: 17471153