Multiple osteochondromas, formerly called multiple hereditary exostoses, is an autosomal dominant heterogeneous disorder that occurs in 1 in 50,000 births and is associated with mutations of the exostosin-1 (EXT1) and exostosin-2 (EXT2) genes. Both genes are putative tumor suppressors that encode glycosyltransferases, also known as exostosins, involved in the biosynthesis of heparin sulfate. Penetrance is very high: 96% in female patients and 100% in male patients. In 10% of affected individuals, hereditary multiple osteochondromas is the result of a new mutation. Clinical manifestations of this disease result in exostoses that generally involve the long bones and result in varying degrees of skeletal deformity and growth disturbances.

Malignant transformation, chondrosarcoma that arises in the cartilage cap, occurs in 5% of patients with multiple osteochondromas. Although certain risk and protective factors such as sex, number of lesions, the presence of EXT2 mutations, and the absence of EXT1 or EXT2 correlate with clinical disease severity, none predict malignant transformation.

In the article by Goud and colleagues, the observation that central chondroid tumors are associated with multiple osteochondromas is surprising, as, to my knowledge, it has not been previously reported. Central chondroid tumors, enchondromas, occur in association with exostoses in patients with metachondromatosis, a rare disease that generally affects the hands and feet and is not associated with growth disturbances. Unlike multiple osteochondromas, metachondromatosis is not associated with EXT1 or EXT2 mutations. Although peripheral chondrosarcomas are not uncommon in patients with multiple osteochondromas, there is only one case report of a patient with presumed metachondromatosis who developed a central chondrosarcoma.