Two cases of clear cell sarcoma with different clinical and genetic features: cutaneous type with BRAF mutation and...

Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, is a rare malignancy constituting approximately 1% of all soft-tissue sarcomas. It occurs predominantly in the lower extremities of young adults, manifesting as a deep, painless, slow-growing mass. CCS is sometimes confused with other types of melanoma because of its melanocytic differentiation. Although BRAF and KIT mutations are well-known melanocytic tumour-promoting mutations frequently found in cutaneous melanoma, they are rare or absent in CCS. We present two cases of CCS with different clinical and genetic features. Both female patients, aged 25 and 20 years, presented with a palpable nodule on a lower extremity. Biopsies of both tumours revealed features diagnostic of CCS. Each tumour cell was positive for S100 protein and HMB-45. However, one patient's tumour was localized to the dermis, with many multinucleated giant cells, whereas the other was located in the deep subcutaneous fat layer near bone. Fluorescence in situ hybridization demonstrated the presence of a characteristic Ewing sarcoma RNA-binding protein (EWSR)1 gene rearrangement in both cases. Reverse-transcription polymerase chain reaction (PCR) and sequencing of the PCR product revealed an EWSR1-activating transcription factor 1 type 1 fusion transcript in both cases. In addition, we detected BRAF mutation in the dermal type and KIT mutation in the subcutaneous type. It is of interest that the BRAF and KIT mutations are known to be very rare in CCS. On the basis of our observations, we suggest that mutation inhibitors may be useful in selected patients with mutated CCS lineages.