This patient presented with an unusually large tumor on the lower leg, which she had allowed to grow for approximately 1 year. Due to the physical appearance and large presenting size, the diagnosis of sarcoma was made. The tumor location near the knee with a biopsy showing an uninvolved epidermis, positive staining with S-100 and HMB-45, and lack of melanin suggested a possibility of CCSTA. However, with more in-depth testing, the proper diagnosis of amelanotic malignant melanoma was confirmed.
Melanoma is the most aggressive of the cutaneous malignancies, causing more than 9,000 deaths in the past year in the United States. It is responsible for 80% of deaths from skin cancer despite accounting for only 4% of all dermatological cancers . Abnormal growth of melanocytes in MM is due to activation of the mitogen-activated protein kinase (MAPK) via various mechanisms such as N-RAS or BRAF mutations . Diagnosis is typically made histologically, but recent studies have shown promise for application of FISH for differentiating between nevi and several melanoma types [8, 9]. The prognosis and tumor behavior varies according to the stage of the melanoma. In stage I and II (localized) melanomas, the best survival predictors are tumor thickness, mitotic rate and ulceration . The prognosis of stage III melanomas is extremely variable depending on tumor burden, number of involved nodes, and ulceration. 5 year survival rates of such patients can vary from 13 to 69% . Stage IV melanoma carries a grim prognosis, but those with metastasis to non-visceral sites and/or the lungs have better 1 year survival rates than those with metastasis to other visceral organs . Furthermore, recent biomarker research has shown that high MCM3 expression is a sign of poor prognosis that correlates with reduced RBM3 expression .
Clear cell sarcoma is a rare but distinct clinic-pathologic entity, which predominantly affects tendons and aponeuroses of adolescents and young adults. It was first described in 21 cases in 1965 and given the name clear cell sarcoma of tendons and aponeuroses . It later also became known as malignant melanoma of the soft parts, although this name has fallen out of favor as it has become more clear that the cells of origin are not melanocytes . The tumor tends to remain localized, with tumor size being the primary determinant of prognosis.
For CSSTA, surgical resection with wide local margins is the primary treatment, resulting in 5 and 10 year survival rates of 59% and 41% respectively . If margins are close, then local radiotherapy is indicated. There is currently not established benefit to chemotherapy for CSSTA, but in aggressive cases adjuvant therapy is often used . Primary treatment of MM is wide-margin surgical resection. Sentinel lymph node biopsy is recommended for patients with lesions larger than 1 mm, as well as those with lesions that are ulcerated or have high mitotic rate [15, 16]. Definitive diagnosis from the nodes is made with fixation and staining with hemotoxylin and eosin, along with immunohistochemical stains such as S-100, MART-1, and HMB-45 . In contrast to CSSTA, systemic therapy has proven benefit for those with advanced or metastatic MM. Options include dacarbazine, temozolomide, IL-2, paclitaxel, cisplatin, carboplatin, IFN-α2b, and ipilimumab .
MM and CCSTA are very similar histologically, which led Chung and Enzinger to propose “malignant melanoma of soft parts” as a preferred name for clear cell sarcoma in 1983 . The two are often difficult to differentiate because 70-90% of clear cell sarcomas express melanin due to fusion of the EWS and ATF1 genes from chromosomes 22q12 and 12q13 respectively. Further complicating differentiation between the two cancers is the fact that histological samples of both CCSTA and MM will stain positively for S-100 and HMB-45 . Proper identification can be attained through use of MART-1 and MITF melanoma stains, and via FISH to detect EWS gene rearrangement . Also, diagnosis of malignant melanoma can be made if a BRAF mutation is found . This case was particularly difficult to diagnose due to the lack of V600E BRAF mutation and negative EWS rearrangement, either of which could have greatly clarified the diagnosis.