Clinically aggressive central giant cell granulomas in two patients with neurofibromatosis 1

Abstract

<h3>Background</h3> Neurofibromatosis 1 (NF1) is an autosomal-dominantly inherited genetic disorder caused by a spectrum of mutations affecting the NF1 gene, a gene located at 17q11.2 and spanning more than 350 kilobases. Affected patients develop a number of benign and malignant tumors at an increased frequency. Clinical findings include multiple café-au-lait spots, neurofibromas, axillary freckling, optic gliomas, benign iris hamartomas, scoliosis, and poorly defined hamartomatous lesions of the skeleton. Kerl (1971) first reported the association of NF1 with central giant cell granuloma (CGCG) of the jaws. There have since been 4 additional reports of NF1 patients with multiple CGCG of the jaws. (Molecular analysis of 1 of these cases uncovered a novel NF1 splice mutation in the proband.) An additional case involving the occipital bone and 1 of a patient with multiple peripheral giant cell granulomas have also been reported. <h3>Clinical cases</h3> We report on 2 patients who presented with NF1 and aggressive CGCG of the jaws. In both cases, the clinical course was characterized by numerous recurrences despite surgical treatment. <h3>Conclusion</h3> While the association between NF1 and CGCG could represent a genetic linkage, this association could also be coincidental since both NF1 and CGCG of the jaws are relatively common. For example, NF1 demonstrates phenotypic overlap with Noonan syndrome (short stature, ocular hypertelorism, pulmonic stenosis, webbed neck) in approximately 12% of patients. Watson syndrome, characterized by overlapping mild features of both NF1 and Noonan-like syndrome is linked to the NF1 gene. NF1-Noonan syndrome, an entity in its own right, is believed to be the result of the independent segregation of both a classical NF1 phenotype and a Noonan syndrome phenotype. Interestingly, multiple giant cell lesions have also been reported in a number of patients with Noonan syndrome.