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

BACKGROUND: Neurofibromatosis 1 (NF1) is an autosomal dominantly inherited disorder caused by a spectrum of mutations affecting the Nf1 gene. Affected patients develop benign and malignant tumors at an increased frequency. Clinical findings include multiple cutaneous café-au-lait pigmentations, neurofibromas, axillary freckling, optic gliomas, benign iris hamartomas (Lisch nodules), scoliosis, and poorly defined soft tissue lesions of the skeleton. Kerl first reported an association of NF1 with multiple central giant cell granulomas (CGCGs) of the jaws. There have since been 4 additional published cases of NF1 patients with CGCGs of the jaws. CLINICAL CASES: We report on 2 patients who presented with NF1 and aggressive CGCGs of the jaws. In both cases, the clinical course was characterized by numerous recurrences despite mechanical curettage and surgical resection. CONCLUSIONS: We review proposed mechanisms to explain the apparent association between NF1 and an increased incidence of CGCGs of the jaws. While the presence of CGCGs of the jaws in patients with NF1 could represent either a coincidental association or a true genetic linkage, we propose that this phenomenon is most likely related to NF1-mediated osseous dysplasia. Compared to normal bone, the Nf1-haploinsufficient bone in a patient with NF1 may be less able to remodel in response to as of yet unidentified stimuli (e.g. excessive mechanical stress and/or vascular fragility), and consequently may be more susceptible to developing CGCG-like lesions. Alternatively, the CGCG in NF1 patients could represent a true neoplasm, resulting from additional, as of yet unidentified, genetic alterations to Nf1-haploinsufficient bone.

Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases.

PURPOSE: Bisphosphonates are widely used in the management of metastatic disease to the bone and in the treatment of osteoporosis. We were struck in the past 3 years with a cluster of patients with necrotic lesions in the jaw who shared 1 common clinical feature, that they had all received chronic bisphosphonate therapy. The necrosis that was detected was otherwise typical of osteoradionecrosis, an entity that we rarely encountered at our center, with less than 2 patients presenting with a similar manifestation per year. PATIENTS AND METHODS: We performed a retrospective chart review of patients who presented to our Oral Surgery service between February 2001 and November 2003 with the diagnosis of refractory osteomyelitis and a history of chronic bisphosphonate therapy. RESULTS: Sixty-three patients have been identified with such a diagnosis. Fifty-six patients had received intravenous bisphosphonates for at least 1 year and 7 patients were on chronic oral bisphosphonate therapy. The typical presenting lesions were either a nonhealing extraction socket or an exposed jawbone; both were refractory to conservative debridement and antibiotic therapy. Biopsy of these lesions showed no evidence of metastatic disease. The majority of these patients required surgical procedures to remove the involved bone. CONCLUSIONS: In view of the current trend of increasing and widespread use of chronic bisphosphonate therapy, our observation of an associated risk of osteonecrosis of the jaw should alert practitioners to monitor for this previously unrecognized potential complication. An early diagnosis might prevent or reduce the morbidity resulting from advanced destructive lesions of the jaw bone.