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.
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.
Department of Oral and Craniomaxillofacial Surgery, Eppendorf University Hospital, University of Hamburg, Hamburg, Germany. Electronic address: rfriedrich@uke.de.
Reinhard E
RE
Friedrich
Institute of Pathology, Eppendorf University Hospital, University of Hamburg, Hamburg, Germany.
Tobias J
TJ
Grob
Department of Human Genetics, Catholic University Leuven/University Hospital Leuven, Leuven, Belgium.
Silke
S
Hollants
Institute of Pathology, Royal National Orthopaedic Hospital NHS Trust, London, England, UK.
Jozef
J
Zustin
Department of Human Genetics, Catholic University Leuven/University Hospital Leuven, Leuven, Belgium.
Marijke
M
Spaepen
Department of Neurology, Eppendorf University Hospital, University of Hamburg, Hamburg, Germany.
Victor F
VF
Mautner
Institute of Pathology, Eppendorf University Hospital, University of Hamburg, Hamburg, Germany.
Andreas M
AM
Luebke
Institute of Neuropathology, Eppendorf University Hospital, University of Hamburg, Hamburg, Germany.
Christian
C
Hagel
Department of Human Genetics, Catholic University Leuven/University Hospital Leuven, Leuven, Belgium.
Eric
E
Legius
Department of Human Genetics, Catholic University Leuven/University Hospital Leuven, Leuven, Belgium.
Hilde
H
Brems
D000293:Adolescent; D018786:Bone Substitutes; D001932:Brain Neoplasms / Q000150:complications; D054893:Cone-Beam Computed Tomography; D005260:Female; D016514:Genes, Neurofibromatosis 1; D006101:Granuloma, Giant Cell / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008336:Mandibular Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000150:complications / Q000235:genetics; D011862:Radiography, Panoramic; D012008:Recurrence
D018786:Bone Substitutes
Dysembryoplastic neuroepithelial tumour; Giant cell granuloma mandible; Hashimoto's thyroiditis; Hypodontia; Neurofibromatosis type 1; Second hit mutation