Kyle C. Kurek, M.D., research
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2009 conference abstract
Metachondromatosis: Expanding the Clinicopathologic Spectrum

Kyle Kurek1,3, Margot Bowen1, Ingrid Holm2, James Kasser1, Matthew Warman1,2
Departments of Orthopaedic Surgery1, Genetics2, and Pathology3, Children’s Hospital Boston and Harvard Medical School,
Boston, MA.


Metachondromatosis is a rare autosomal-dominant disorder in which patients develop multiple benign cartilaginous tumors in
childhood. The primary tumor is an osteochondroma-like exostosis that, unlike an osteochondroma, usually occurs in the digits,
points towards the affected joints, and may regress spontaneously. The enchondromas, in distinction from those in
enchondromatoses, most often occur in the iliac crests and metaphyses of long bones. Patients may also develop periarticular
calcifications as well as avascular necrosis of the femoral head. Fewer than 50 cases of metachondromatosis have been reported
and the disorder has not been mapped in the human genome. Reported cases have not provided sufficient detail to define the
pathology of these unique tumors. Metachondromatosis shares features with the autosomal dominant disorder, Multiple
Hereditary Exostoses (MHE), in which patients develop multiple osteochondromas in the long bones. Loss of function mutations
in two genes, EXT1 and EXT2, involved in heparin sulfate polymerization, have been associated with HME, but not in the only
published metachondromatosis patient examined. We studied additional cases of metachondromatosis in order to expand our
understanding of the clinical syndrome and, in particular, to define the histopathology of this rare syndrome. The lesions were
compared with normal growth plates as well as with 50 osteochondromas, both sporadic and syndromic, from age-matched

We identified and reviewed 16 osteochondroma-like exostoses, which we have called metachondromas, excised from three
metachondromatosis patients followed at Children’s Hospital Boston in the last 20 years. Two patients were related as second
cousins and the third patient was from an unrelated family. All three lacked mutations in EXT1 and EXT2. The majority of tumors
were removed from the digits (11/16), six from the hands and five from the feet, and most often affected the proximal phalanx.
Five were removed from the long bones, two from the distal femur and three from the distal tibia. All excised lesions were
symptomatic, most obstructing joint function. Unlike the metaphyseal-based osteochondromas, excised metachondromas
extended from the metaphysis to the epiphysis, spanning the physis (11/16), or were exclusively epiphyseal (5/16). At least two
lesions were found to resolve with age, while others, including adjacent lesions, grew as the patients aged. All patients had
enchondromatous lesions on the digits and distal long bones, as well as multiple new exostoses that continued to develop into
adolescence that were not resected. One patient developed avascular necrosis of the femoral head in childhood.

The histologic features of metachondromas are unique. All were covered by an outer fibrous capsule and most (14/16) contained
only a partial hyaline cartilage cap with underlying bone. Unlike in osteochondromas, the predominant cartilage mass was within a
central core. The cap of both lesions was reminiscent of the growth plate, but more disorganized with prominent proliferative
and hypertrophic chondrocytes and incomplete zonation forming bone by endochondral ossification. The cartilaginous core of
metachondromas was even more hypertrophic and less organized with irregular or absent columns. Entrapped growth plate was
observed in some cases. Mild hypercellularity and binucleate chondrocytes were common, but clustering was not. The cells were
mildly pleomorphic with a large nucleus and a single prominent nucleolus. Excessive myxoid degeneration of the matrix was
common and islands of necrotic cartilage were present in several tumors. Unlike osteochondromas, metachondromas primarily
form bone on the outer surface of the central cartilage rather than beneath a cartilage cap, although the latter process also
occurs. In summary, we found that the exostoses of metachondromatosis shared some features with osteochondromas, but
have distinct clinical, radiographic, gross and histologic findings to warrant separate a classification, which we have called the
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