Clear cell sarcoma of tendons and aponeuroses: A historical perspective and tribute to the man behind the entity

Clear cell sarcoma of tendons and aponeuroses is a unique sarcoma initially described by Dr Franz M. Enzinger. The tumor has a proclivity to involve the tendons and aponeuroses of distal extremities of relatively young individuals and is characterized by multiple local recurrences with late metastases and a high rate of tumor deaths. Since its seminal description in 1965, there have been many studies verifying the uniqueness of this entity and probing its differentiation. Ultrastructural and immunohistochemical studies have shown melanocytic differentiation, whereas molecular genetic studies have shown cytogenetic rearrangements resulting in a EWSR1-ATF1 fusion gene that is characteristic but not entirely unique for clear cell sarcoma (similar fusion genes are also seen in angiomatoid fibrous histiocytoma). Detection of this fusion gene and the absence of BRAF gene mutations clearly distinguish clear cell sarcoma from cutaneous melanoma. Adverse prognostic factors identified to date include larger tumor size and any microscopic tumor necrosis. Surgery is the mainstay of treatment for this high grade sarcoma, with chemotherapy having little effect. Although the melanocytic differentiation of clear cell sarcoma is indisputable, its precise lineage remains unclear. Thus, clear cell sarcoma maintains the status of a unique yet enigmatic clinicopathologic entity of ever increasing complexity 40 years after its original description by an extraordinarily gifted man.