Molecular confirmation that fibrocartilaginous dysplasia is a variant of fibrous dysplasia.

Aims: Fibrocartilaginous dysplasia (FCD) is a subvariant of fibrous dysplasia (FD). This study aims to retrospectively elucidate the clinicopathological and separate genetic features of the cartilaginous and fibro-osseous components of FCD.

Methods: In total, 24 patients (14 men and 10 women) with FCD were included in our cohort. The diagnosis was confirmed morphologically and immunohistochemically, and genetic features were determined via Sanger sequencing.

Results: Five patients were polyostotic, and 19 were monostotic, predominantly concerning the femur. Radiography revealed a well-demarcated ground glass appearance with ring-like or scattered calcification. Histologically, the lesions were characterised by proliferative fibroblasts, immature woven bone and highly differentiated hyaline cartilage. The fibro-osseous components exhibited positive immunoreaction with SATB2 and a low Ki-67 proliferation index. The fibro-osseous and cartilaginous components shared mutations at codon 201 in exon 8 of the guanine nucleotide-binding protein/a-subunit (GNAS) gene, specifically CGT>CAT (p.R201H) in four patients and the wild-type isocitrate dehydrogenase (IDH)1/IDH2 gene. Telomerase reverse transcriptase (TERT) promoter mutations (C288T and C229G) occurred in both fibro-osseous and cartilaginous components in two patients.

Conclusions: FCD encompasses areas of conventional FD with additional cartilage. Importantly, the presence or absence of mutations in the GNAS gene and/or the TERT promoter is common between the fibro-osseous and cartilaginous components of the disease. These results further confirmed FCD as a variant of FD.