Maffucci syndrome complicated by three different central nervous system tumors sharing an IDH1 R132C mutation: case report

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Maffucci syndrome (MS) and Ollier disease (OD) are nonhereditary congenital diseases characterized by multiple enchondromas and/or chondrosarcomas. Recent studies have implicated somatic mosaic mutations of isocitrate dehydrogenase 1 or 2 (IDH1/2) as contributing to the pathogenesis of MS and OD. Occasionally, patients with these disorders may also present with central nervous system (CNS) tumors; however, detailed genetic analyses are limited. In this article, the authors report on a male patient with MS, harboring three CNS tumors that share a common genetic alteration. Over a 9-year period, three separate tumor resections were conducted for sellar, intraparenchymal brainstem, and osseous clival tumors. The histopathological diagnoses were pituitary adenoma, diffuse astrocytoma, and chondrosarcoma, respectively. Sanger sequencing revealed a common IDH1 R132C mutation among all three CNS tumors but not in blood DNA. Administering chemotherapy (nimustine) and subsequent radiation therapy to the brainstem glioma and the residual lesion in the clivus have kept the patient progression free for 18 months. This is the first report demonstrating an IDH1 mutation shared among three different CNS tumors in a single patient with MS. The findings support the hypothesis that in MS and OD, a single common IDH1 mutation triggers tumorigenesis in cells of different origins and locations in a somatic mosaic fashion.

ABBREVIATIONS ATRX = α-thalassemia/mental retardation syndrome x-linked; CNS = central nervous system; D2HG = D-2-hydroxyglutarate; EMA = epithelial membrane antigen; MS = Maffucci syndrome; OD = Ollier disease.
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Contributor Notes

Correspondence Shota Tanaka: Graduate School of Medicine, The University of Tokyo, Japan. tanakas-tky@umin.ac.jp.INCLUDE WHEN CITING Published online December 21, 2018; DOI: 10.3171/2018.6.JNS18729.Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
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