Melanotic Neuroectodermal Tumor of Infancy

Clear cell sarcoma (CSS) is a rare melanin-producing soft tissue sarcoma most commonly arising from tendons and aponeuroses of lower extremities, especially feet. Other sites include ankle, knee, thigh, hand, gastrointestinal tract and penis. It is a tumor of young adults with male predominance. Although it shares morphologic features with cutaneous melanomas, it is biologically and genetically a distinct tumor. It presents as a deep-seated slowly growing mass attached to tendons and aponeuroses. It is composed of fusiform or spindle cells arranged in solid nests and fascicles separated by delicate fibrous septa. The tumor cells have clear or lightly eosinophilic cytoplasm, round vesicular nuclei and prominent nucleoli. Cytoplasmic melanin may not be readily evident grossly or microscopically. Multinucleated giant cells are present. It shows immunoreactivity for S-100, HMB-45, Melan-A, MiTF, Leu-7, NSE, CD56, and vimentin. In about 70% of cases, CSS is associated with a balanced chromosomal translocation t(12;22)(q13;q12) which fuses EWSR1 on chromosome 22 with ATF1 on chromosome 12. The EWSR1-ATF1 fusion protein activates the promoter for MiTF - the melanocyte transcription factor - which drives tumorigenesis. CSS is an aggressive tumor characterized by progressive disease, repeated local recurrences (15 to 40% of cases), and eventual distal metastases (lung, lymph nodes) in about 50% of cases.