IDH1 mutation in chondrosarcoma and glioma of a patient with Ollier disease

Objectives: To report IDH1 mutation in a patient with Ollier disease Methods: Ollier disease (enchondromatosis) is a rare typically non-familial syndrome associated with multiple, intramedullary or central cartilaginous neoplasms. These neoplasms can undergo malignant transformation and develop other neoplasms like diffuse gliomas. We searched our institutional, pathology database for cases of enchondroma, chondrosarcoma, and Ollier disease. We found 103 patients and 104 tumour specimens. We searched for any of these patients with both cartilaginous and diffuse glial neoplasms with tissue available for testing for IDH1/IDH2 mutations. We found one patient meeting these criteria. The patient is a 22-year-old man with Ollier disease based upon the presence of multiple central enchondromas and an atypical chondroma of the left skull base. He developed progressive non-enhancing, T2 hyperintense abnormalities involving the bifrontal and left temporal, insular, and parietal regions. Approximately 5 years after initial onset of these cerebral abnormalities, a right frontal biopsy was performed. Result(s): Pathology revealed a low-grade diffuse glioma, with uniform round-to-oval nuclei, perinuclear halos, and scant mitoses, diagnosed as oligodendroglioma, WHO Grade II. Fluorescence in situ hybridization showed loss of chromosomal arms 1p and 19q. Immunohistochemistry for the mutant IDH1 R132H protein (Dianova, Germany) was diffusely and strongly positive in the glioma cells. We treated him with six cycles of adjuvant temozolomide. Tissue from the chondrosarcoma was tested retrospectively, and immunohistochemistry for the mutant IDH1 R132H protein was also diffusely and strongly positive in the tumour cells. Conclusion(s): To our knowledge, this is the first reported case demonstrating identical IDH mutations involving the cartilaginous and non-cartilaginous neoplasia in a patient with Ollier disease. Likewise, this case suggests somatic mosaicism of IDH mutations may lead to development of both cartilaginous and glial neoplasms in these patients, and may provide molecular insights into the pathogenesis of both tumour types. Awareness of this genetic predisposition is essential when evaluating neurological complaints and interpreting neuroimaging results in patients with Ollier disease.