Recurrent Multilocular Mandibular Giant Cell Granuloma in Neurofibromatosis Type 1: Evidence for Second Hit Mutation of NF1 Gene in the Jaw Lesion and Treatment with Curettage and Bone Substitute Materials

• Published in: Journal of cranio-maxillo-facial surgery 2016-08, Vol.44 (8), p.1054-1060
• Main Authors: Friedrich, Reinhard E., MD, DMD, PhD, FEBOMFS, Grob, Tobias J, Hollants, Silke, Zustin, Jozef, Spaepen, Marijke, Mautner, Victor F, Lübke, Andreas, Hagel, Christian, Legius, Eric, Brems, Hilde
• Format: Article
• Language: English
• Subjects: Adolescent; Bone Substitutes; Brain Neoplasms - complications; Cone-Beam Computed Tomography; Dentistry; Dysembryoplastic neuroepithelial tumour; Female; Genes, Neurofibromatosis 1; Giant cell granuloma mandible; Granuloma, Giant Cell - diagnostic imaging; Granuloma, Giant Cell - genetics; Granuloma, Giant Cell - surgery; Hashimoto's thyroiditis; Humans; Hypodontia; Image Processing, Computer-Assisted; Mandibular Diseases - diagnostic imaging; Mandibular Diseases - genetics; Mandibular Diseases - surgery; Mutation; Neurofibromatosis 1 - complications; Neurofibromatosis 1 - genetics; Neurofibromatosis type 1; Radiography, Panoramic; Recurrence; Second hit mutation; Surgery
• ISSN: 1010-5182; 1878-4119
• DOI: 10.1016/j.jcms.2016.05.010

Abstract Giant cell granuloma (GCG) of the jaw is a rare, well-known feature of neurofibromatosis type 1 (NF1), an inborn multisystem disorder. Recently, the development of GCG in NF1 was attributed to second hit mutations in the NF1 gene. The treatment of GCG is pragmatic with a preference for local curettage of lytic osseous areas. This report describes the surgical therapy of an NF1-affected female with multilocular mandibular GCG and hypodontia who additionally suffered from a brain tumour and Hashimoto’s thyroiditis. Although local recurrence of GCG was noted, augmentation of the curetted cavities with a bone substitute in successive interventions successfully restored the extensive periradicular local defects and stabilised the teeth. A meticulous in vitro study of the GCG specimen revealed a second hit mutation in the NF1 gene in the GCG spindle-cells. This study contributes to the increasing knowledge of the molecular basis for GCG in the jaw of NF1 patients, indicating that it is a neoplasm.