Recurrent Mandibular Giant Cell Lesion in Neurofibromatosis Type 1: Second Hit Mutation on the NF1 Gene in the Osseous Lesion

In the autosomal dominant hereditary disease neurofibromatosis type 1 (NF1), lesions of the jaw develop in isolated cases, which are diagnosed as central giant cell granuloma (CGCG). This study aimed to clarify the genetic basis of a bone lesion in a syndromic patient.The NF1 patient had developed a CGCG that recurred after local excision. Blood and tumor tissue were studied for NF1 mutations using advanced molecular genetic methods. Examinations of blood and tumor tissue provided evidence of the constitutive mutation in both samples. A further mutation was detected in the tumor, which was interpreted as a somatic mutation. The detection of somatic mutation in the tissue was successful both on native and routinely fixed material.The study supports current assessments of CGCG as a benign neoplasm. In NF1 patients, the phenotype seems to imply bi-allelic loss of the NF1 gene. The detection of both mutations in routinely fixed tissue allows studies of archived tissue samples with this diagnosis.