Extraskeletal myxoid chondrosarcoma: a light microscopic, immunohistochemical, ultrastructural and immuno-ultrastructural study indicating neuroendocrine differentiation

Aims: Extraskeletal myxoid chondrosarcoma is a rare low-grade soft-tissue s arcoma with locally aggressive and metastasizing potential. Extraskeletal m yxoid chondrosarcoma has distinctive clinical. light microscopic, immunophe notypic, cytogenetic and ultrastructural features. Evidence that extraskele tal myxoid chondrosarcoma often shows neuroendocrine features was first pro vided by Chhieng et al.(9) on the basis of an immunohistochemical and ultra structural study of seven cases. Our study aims to further confirm by immun ohistochemistry and ultrastructural studies, including immunoelectron micro scopy. that extraskeletal myxoid chondrosarcoma indeed may show neuroendocr ine differentiation. Methods and results: Fifteen cases of extraskeletal myxoid chondrosarcoma a nd seven control cases of skeletal chondrosarcomas were studied. Extensive immunohistochemical analysis was performed in all cases and ultrastructural studies were done in I I extraskeletal myxoid chondrosarcomas and three sk eletal chondrosarcomas. Immunoelectron microscopy was performed on one case each of extraskeletal myxoid chondrosarcoma and skeletal chondrosarcoma. E xtraskeletal myxoid chondrosarcomas expressed neuron-specific enolase (100% ,), synaptophysin (87%), S100 (50%). PGP 9.5 (40%), and epithelial membrane antigen (25%). Co-expression of synaptophysin and PGP 9.5 was observed in six tumours. Skeletal chondrosarcomas showed expression of S100 protein, vi mentin and neuron-specific enolase in all cases. Synaptophysin. chromograni n and PGP 9.5 were not expressed in any skeletal chondrosarcoma case. Ultra structurally. extraskeletal myxoid chondrosarcoma was characterized by dist inct cords of cells immersed in a glycosaminoglycan-rich matrix. The cells were rich in mitochondria, had well-developed Golgi apparatus and there wer e numerous smooth vesicles. In three cases there were easily found 140-180 nm diameter membrane-bound dense-core granules in cell bodies and in proces ses, unrelated to the Golgi, compatible with neurosecretory granules. Fewer such granules were present in the remaining extraskeletal myxoid chondrosa rcoma cases, three of which also contained intracisternal tubules typical o f extraskeletal myxoid chondrosarcoma. The skeletal chondrosarcomas had sca lloped cell surfaces. prominent rough endoplasmic reticulum focally distend ed with secretory product, and lacked neurosecretory granules. Intermediate filaments were prominent in both extraskeletal myxoid chondrosarcoma and s keletal chondrosarcomas. Immunoelectron microscopy showed synaptophysin exp ression in the extraskeletal myxoid chondrosarcoma but not in the skeletal chondrosarcoma case. Conclusions: This study confirms that a substantial proportion of extraskel etal myxoid chondrosarcomas show immunophenotypic and/or ultrastructural ev idence of neuroendocrine differentiation, and are unlikely to be related to conventional skeletal chondrosarcomas.