A spectrum of tumorigenesis in an IDH1-mosaic patient with Ollier disease, acute myeloid leukaemia, and parathyroid adenoma

We report the case of an 18-year-old woman with a childhood diagnosis of Ollier disease—a rare skeletal dysplasia marked by multiple enchondromas and a high risk of malignant transformation into chondrosarcoma. She later developed acute myeloid leukaemia (AML) and a parathyroid adenoma, where the same pathogenic IDH1 variant [c.394C>T (p.Arg132Cys)] was identified in an enchondroma, AML cells, and the parathyroid adenoma. This gain-of-function variant leads to aberrant production of D-2-hydroxyglutarate, which promotes tumorigenesis through mechanisms such as DNA hypermethylation and impaired cellular differentiation. The presence of this variant in neoplasms arising from both mesodermal tissues (bone marrow, enchondromas) and a predominantly endodermal tissue (parathyroid), with the variant allele frequencies ranging from 37% to 44%, suggests an early postzygotic mosaic event. This case illustrates the broad oncogenic potential of IDH1 mosaicism and underscores the importance of long-term multidisciplinary surveillance. In particular, the risks of chondrosarcoma and glioma that were previously reported in association with IDH1- related Ollier disease support the need for regular surveillance of enchondromas and brain imaging in affected individuals. This case represents the third reported incidence of Ollier disease associated with AML and the first reported incident demonstrating the same IDH1 (p.Arg132Cys) variant across enchondroma, AML, and parathyroid adenoma, further supporting a broader tumour spectrum associated with IDH1 mosaicism.