Clinicopathologic and Molecular Characteristics of Familial Cherubism with Associated Odontogenic Tumorous Proliferations

Abstract

Cherubism is a rare autosomal dominant condition affecting the jaws and caused by mutations in the gene encoding for the adapter protein SH3BP2 that maps to chromosome 4p16.3. Cherubism is characterized by symmetrically developing bone lesions in the maxilla and mandible. The lesions have been radiographically and histopathologically well-described. Here, we present a family with cherubism with two of its members featuring odontogenic tumorous proliferations in association with persistent central giant cell lesions (CGCL). Specifically, the proband, a 25-year-old male, developed a radiolucent lesion characterized histologically by central odontogenic fibroma-like proliferation in association with a CGCL component, while his mother, at age 57, was diagnosed with primary intraosseous odontogenic carcinoma with areas of benign fibro-osseous lesions. In both patients the lesions occurred in the anterior mandible and presented with clinical enlargement. The son underwent incisional biopsy and did not have additional treatment. His mother underwent extensive mandibulectomy due to widespread tumor. The son has two affected children with classic cherubism while a third child at age 5, had not shown any features of the disease. Mutation analysis of three affected members resulted in the identification of a heterozygous mutation in SH3BP2 (c.1244G>C; p.Arg415Pro). To the best of our knowledge, association of cherubism with odontogenic neoplastic lesions has hitherto not been reported in the literature, thus suggesting a relationship between cherubism with disturbed odontogenesis.

Cherubism: Report of a Case

“…4 Initial cases may present with lymph node enlargement thus contributing to the cherubic appearance. 2,6 Infiltration of the orbital bone may lead to exophthalmos causing limitation of ocular movements and the typical "eyes raised to heaven" appearance. In the present case, bone involvement was restricted to the posterior mandible.…”

“…Cherubism has been associated with a central odontogenic fibroma-like proliferation. Argyris et al 6 reported the development of intraosseous squamous cell carcinoma in a long-standing case of cherubism. Osteosarcoma has been reported in cherubism cases treated with radiotherapy.…”

Regional Lymph Node Enlargement in Clinically Severe Cherubism

“…In our patient, odontogenic epithelial components were not identified by morphology or by pancytokeratin immunostain (data not shown). 13,14…”

“…In our patient, odontogenic epithelial components were not identified by morphology or by pancytokeratin immunostain (data not shown). 13,14 Submandibular and cervical lymph nodes are frequently enlarged during early stages of cherubism. 3 Meng et al 5 reported that the lymphadenopathy was observed in 10 out of 24 patients with cherubism.…”

Evolución clínica del querubismo en un paciente pediátrico

“…En este último escenario, la simetría facial del niño se observa distorsionada y la expansión ósea produce una cara redonda similar a un querubín, con mejillas prominentes, y una maloclusión con desplazamiento de las piezas dentales y dificultades de la masticación (1,2,4,8,9,(17)(18)(19). Otros signos y síntomas incluyen adenopatías cervicales y submandibulares, así como dificultades visuales, auditivas o respiratorias; además de dificultad para el habla y disfagia (1,4,17,(19)(20)(21).…”