Cherubism is a rare genetic disorder characterized by extensive growth of a bilateral granuloma of the jaws, resulting in facial disfigurement.
Histologically, the lesions consist of a fibrotic stroma with osteoclastic-like multinuclear giant cells (MGC). Cherubism is caused by gain-of-function mutations in the SH3BP2 protein. SH3BP2 is an intracellular adaptor protein positively regulating the activity of the nuclear factor of activated T-cells c1 (NFATc1), a regulator of osteoclastogenesis. Lysosomal enzyme tartrate resistant acid phosphatase (TRAP) activity is also known to increase with the osteoclastogenesis.
The expressiveness of the disease is highly variable, ranging from almost asymptomatic forms to some life threatening. Presently, there are no prognostic factors clearly identified concerning the severity of cherubism in the literature. The aim of this study is to evaluate the NFATc1 staining and TRAP activity in cherubism tumor, and correlate the results to clinical, radiological, and pathological features to define prognostic factors of the disease.
We performed a retrospective study in nine cherubism patients. Severity of cherubism was graded according to their radiological jaw involvement and to their evolution after surgery. Genetic mutations, pathological features, NFTAc1 staining and TRAP activity were evaluated for each patients.
Three cherubism were graded as low aggressiveness (grade A), four moderate aggressiveness (grade B), and two very severe diseases (grade D). SH3BP2 mutations were found in seven patients, six mutations 1244 and one mutation 1353.Pathological examinations were non significantly different between the three grade groups. In grade A and grade B tumors, all GMC were TRAP negative and negative for NFTAc1 nuclear staining. In all grade D tumors, MGC were all TRAP positive, and displayed nuclear NFTAc1 staining. TRAP activity and NFTAc1 staining were significantly different from grade D tumors to B and A.
TRAP Activity and nuclear NFTAc1 staining is associated with severe cherubism. These two tests can be added to routine pathological examination, to evaluate the prognosis of cherubism, and to adapt treatment. These results suggest that MGC displayed osteoclast characteristic in aggressive tumor, and macrophages characteristic in non-aggressive tumors. Nuclear NFTAc1 activity in aggressive tumor suggest that medical therapy, such as anti-calcineurin could be appropriate to cure aggressive cherubism
Source of funding: grant from the Association pour le développement de la stomatologie, Grant from Agence Nationale de la recherché (ANR).
Disclosure: The authors declared no competing interests.
27 - 30 Jun 2015