Abstract

Introduction: Here we present a case wherein an SS18 gene rearrangement consistent with synovial sarcoma was incorrectly identified in a tumor that was later found to be metastatic melanoma. Case Presentation: A 75-year-old man with a history of melanoma of the right shoulder presented three years later with a right axillary mass. Biopsy showed malignant melanoma with epithelioid morphology. However, the resection had spindled rather than epithelioid morphology. Immunohistochemical workup showed the tumor cells were positive for SOX10 (80%), S100 (focal), and C-MYC (faint) and negative for HMB-45, Melan-A, tyrosinase, desmin, p63, AE1/AE3, CD117, and CD34. Fluorescent in situ hybridization (FISH) showed 6 of 50 cells (12%) had a loss of 5’ SS18 signal with retention of 3’ signal, which was interpreted as an SS18 gene rearrangement consistent with synovial sarcoma. However, in synovial sarcoma, it is typical for most cells to show a rearrangement pattern with retention of 5’ signals or loss of 3’ signals. SS18/SSX RT-PCR was negative. DNA and RNA next-generation sequencing (NGS) and SNP microarray were performed. No SS18/SSX or rare SS18 fusions were detected. A pathogenic activating mutation of NRAS (NRAS p.Q61L) was identified, which is reported in 15-20% of cutaneous melanomas. Copy loss of CDKN2A was also identified, which is seen in 40-60% of melanomas. Finally, a complex copy number profile was identified, which is compatible with melanoma but would be unusual for synovial sarcoma. The original FISH study was reevaluated and reinterpreted as negative. Conclusions: Accurate interpretation of molecular studies is vital, and results must be interpreted within the context of clinical information. The patient’s history of melanoma prompted the pathologist to further investigate, leading to the diagnosis of metastatic melanoma.

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