Synovial sarcoma is a rare, aggressive soft tissue sarcoma which, despite its name, arises from mesenchymal cells and not intra-articular synovium. Though it is more commonly found in the deep soft tissue of the extremities, particularly the lower extremity near the knee or in the foot, it can arise anywhere in the body. It is unique from other sarcomas in that it equally affects both sexes and presents at a younger mean age than other soft tissue sarcomas (mean age at diagnosis is 39 years old). It generally presents as a slow growing, often painful mass, contrasted with the large, rapidly growing, painless masses seen in other soft tissue sarcomas.

Synovial sarcoma typically presents on cytology with bland, monotonous spindle cells arranged in fascicles or clusters, with ovoid nuclei, scant, amphiphilic cytoplasm, inconspicuous nucleoli, and low mitotic activity. In biphasic synovial sarcoma, epithelial-like cells are also seen, and may form gland-like epithelial structures, whereas monophasic synovial sarcoma consists primarily of spindle cells. Synovial sarcoma is typically positive for CD99, BCL-2, and TLE1 immunohistochemical (IHC) stains. EMA and cytokeratin positivity can highlight epithelial components, but may be focal or patchy. EMA is more sensitive than cytokeratin, but is not specific, so may need to be correlated with other epithelial markers in atypical cases.

Synovial sarcoma is defined by the pathognomonic translocation of t(X;18) which results in the fusion of the SS18 gene with SSX1, SSX2, or SSX4. This translocation is found in greater than 95% of cases and can be detected by fluorescence in-situ hybridization (FISH) using an SS18 break apart probe, reverse transcription polymerase chain reaction (RT-PCR) targeting the fusion gene, or immunohistochemistry (IHC) using a novel antibody that targets the SS18-SSX fusion protein.

The fusion-specific antibody is reported to be both highly sensitive (95%) and specific (100%), equivalent to RT-PCR, and exceeding FISH in sensitivity. In cases with strong, diffuse staining and histology consistent with synovial sarcoma, IHC can support a definitive diagnosis, avoiding the higher cost and turn around time of ancillary testing. In atypical or challenging cases, molecular testing, if available, should be performed to ensure diagnostic accuracy.

This case presented with characteristic cytologic morphology in the most common age group, but in a unique location. The cytologic differential diagnosis of spindle cell neoplasms can be narrowed based on the anatomic site, although only 5-7% of synovial sarcomas are found in the head and neck region. As in our case, a targeted panel of immunohistochemical stains can help to significantly narrow the differential, and with the recently available SS18::SSX fusion-specific IHC stain, synovial sarcoma can be diagnosed in adequate FNA specimens with a high degree of sensitivity and specificity.