A 56-year-old man complained of a mass involving his right foot. MRI showed a 4 cm mass adjacent to and perhaps involving the anterior tibialis tendon. The mass was also closely approximated to the first metatarsal-phalangeal joint. A needle biopsy was performed and the resultant images are seen below.
The mass consists of a bland but hypercellular proliferation of spindled cells, some with more prominent vacuolated cytoplasm. Mitotic figures are scarce and there is no evidence of necrosis. The interface with the adjacent tissue is not easily visualized in this biopsy.
What is your diagnosis?
Additional studies were performed and the tumor cells were noted to be negative for cytokeratin, EMA, CD56, CD34, and desmin. They were positive for S100 protein, HMB-45, and Melan-A. The HMB-45 staining is seen below.
FISH studies showed that the SYT gene was intact, but the EWS gene was rearranged. Since breakapart probes were utilized, the fusion partner was not determined but is presumed to be the ATF1 or. less likely, the CREB1 gene.
Accordingly, this is an example of a clear cell sarcoma. Interestingtly, the heterogeneous group of neoplasms harboring EWS-ATF1/CREB1 mutations are somewhat unified by the strong, but not universal, tendancy for tumors in this group to have at least focally clear cytoplasm due to glycogen deposition.
Although once interpreted as "melanomas of soft parts" because of their often obvious melanogenesis, these tumors are fundamentally different from cutaneous or mucosal melanomas as the latter lack EWS-ATF1/CREB1 mutations and, instead, often contain BRAF mutations which are lacking in clear cell sarcomas. The tumors typically involve the deep tissues of the extremities and, as in this case, the foot is the most common location.
The microscopic appearance is somewhat variable with cells ranging from highly spindled to somewhat more epithelioid in appearance. A distinct nested or fascicular growth pattern is common. Cytoplasm varies from clear (due to cytoplasmic glycogen) to eosinophilic. Melanin may be visible microscopically and in some instances, grossly.
As noted in this case, melanoma-related markers such as S100 protein, HMB-45, Melan-A, MiTF and others are typically positive and of considerable diagnostic value.
Although rather bland in histologic appearance, and thus not amenable to conventional grading systems for soft tissue sarcomas, clear cell sarcoma is a high-grade malignancy with local recurrence rate of 15-40% and a metastatic rate, typically to lungs and lymph nodes, approaching 50%. Late metastases have been described several decades after original diagnosis, so long-term follow up is clearly required. Therapy is surgical and adjuvant methods have thus far had little effect.