Clear cell sarcoma of the tongue

Sir: Clear cell sarcoma (CCS) is a rare soft tissue sarcoma that shows melanocytic differentiation and typically presents in the distal extremities of young adults. A subset of CCS also occurs within the gastrointestinal tract, including a histological variant rich in osteoclast-type giant cells. Although these tumours are also S100-positive, they typically lack melanosomes and do not express other melanocytic markers, such as HMB45 and melan-A. Therefore, these gastrointestinal tumours probably represent a distinct entity from the CCS of soft tissue. However, lesions of CCS occurring outside of these two settings are very rare. We present here a case of CCS as a primary lesion in an oral location, which has not been previously reported. A 29-year-old woman presented with a nodular lesion at the tip of her tongue. It had been present for 2 months prior to presentation, and had grown slowly. The lesion was excised, and histology showed a tumour involving the subepithelial stroma and extending into skeletal muscle in an infiltrative pattern. The tumour was composed of nests and fascicles of predominantly spindle-shaped cells with a vesicular nucleus, a single prominent nucleolus, and finely granular eosinophilic cytoplasm (Figure 1A,B). Perineural invasion was identified, but lymphovascular invasion was not seen. The mitotic rate was 1/mm, and tumour margins were positive. Immunohistochemistry showed that the tumour cells were diffusely and strongly positive for S100 and HMB-45 (Figure 1C), and negative for melan-A, cytokeratins, and desmin. Fluorescence in-situ hybridization (FISH) with a break-apart probe for EWS gave a positive result (Figure 1D), and a t(12;22)(q13;q12) translocation involving the genes ATF1 and EWS was subsequently shown by reverse transcription PCR, thus supporting a diagnosis of CCS. A wider reexcision was performed, and showed no residual tumour; the patient remains well after limited followup of 12 months. Clear cell sarcoma is a rare soft tissue sarcoma that was originally described by Enzinger as a tumour affecting the tendons and aponeuroses of distal extremities, predominantly in young adults. The association between CCS and melanocytic differentiation was subsequently highlighted, and the tumour was given an alternative name of ‘melanoma of soft parts’. At the ultrastructural level, these tumours contain melanosomes, and are typically positive for melanocytic markers such as S100, HMB-45, microphthalmiaassociated transcription factor (MITF), melan-A, and tyrosinase. The tumour most commonly presents as a slowly growing elevated mass located in deep soft tissue. However, pure dermal and subcutaneous tumours have been described. The differential diagnosis primarily involves primary and metastatic melanoma. Other S100-positive tumours to consider include epithelioid malignant peripheral nerve sheath tumour and cellular blue naevus. Clear cell sarcoma is characterized by a t(12;22) (q13;q12) translocation, which results in fusion of EWS with the transcription factor gene ATF1. Functionally, the protein product of the ATF1–EWS fusion gene binds to and activates MITF, which is known to play an important role in melanocytic differentiation. This translocation is identified in >90% of CCS cases, whereas no cases of melanoma have been found to harbour this translocation. There is a CCS variant that occurs in the gastrointestinal tract, and, although primary lesions within the oral cavity have not been described, a case of CCS metastatic to this site has been reported. These gastrointestinal tumours may harbour the above translocation, but more commonly contain a novel t(2;22)(q32;q12) translocation resulting in an EWS–CREB1 fusion gene. The treatment of CCS remains predominantly surgical, and the overall 5-year survival rate is approximately 50–60%. Long-term follow-up is advocated, as recurrences and metastases may occur many years after initial treatment. A tumour size greater than 50 mm and the presence of tumour necrosis are associated with a poor prognosis. In summary, we report the first case of CCS presenting in the oral cavity, which also highlights the utility of using FISH analysis in excluding melanoma.