RESUMO
BACKGROUND: Activation mutations of SH3BP2 gene have been demonstrated in cherubism and central giant cell lesion (CGCL). In the present study we first attempted to investigate the SH3BP2 gene in peripheral giant cell lesion (PGCL). The effect of SH3BP2 gene mutations on the transcription of the downstream genes nuclear factor of activated T cells (NFATc1) and the cytokine tumor necrosis factor-alpha (TNF-alpha) was also investigated together with the immunolocalization of NFATc1 protein in a set of cases of PGCL, CGCL and cherubism with and without SH3BP2 mutation. METHOD: Fresh samples of five PGCL, five CGCL and one cherubism cases were included in this study. One of the samples of CGCL presented a somatic heterozygous mutation c.1442A>T in exon 11. The cherubism case showed a heterozygotic substitution c.320C>T in both blood and lesion. These mutations were previously published. All coding and flanking regions of the SH3BP2 gene were sequenced in the cases of PGCL. The real-time polymerase chain reaction (RT-PCR) was performed to analyze the transcription of NFATc1 and TNF-alpha genes. The immunohistochemical analysis of the NFATc1 protein was also performed. RESULTS: No SH3BP2 gene mutation was found in PGCL. The RT-PCR showed increased expression of NFATc1 and decreased transcription of TNF-alpha in all the samples. The immunohistochemical analysis of the NFATc1 protein showed a predominant nuclear staining in the multinucleated giant cells. CONCLUSION: The development of giant cells lesions of the jaws and cherubism are possibly mediated by overexpression of NFAT in the nucleus of the multinucleated cells.
Assuntos
Querubismo/genética , Granuloma de Células Gigantes/genética , Doenças Maxilomandibulares/genética , Mutação/genética , Fatores de Transcrição NFATC/genética , Fator de Necrose Tumoral alfa/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenosina , Núcleo Celular/ultraestrutura , Querubismo/sangue , Querubismo/patologia , Citosina , Éxons/genética , Regulação da Expressão Gênica/genética , Células Gigantes/patologia , Glutamina/genética , Granuloma de Células Gigantes/patologia , Heterozigoto , Humanos , Doenças Maxilomandibulares/patologia , Leucina/genética , Metionina/genética , Fatores de Transcrição NFATC/análise , Polimorfismo Genético/genética , Treonina/genética , Timina , Transcrição Gênica/genética , Fator de Necrose Tumoral alfa/análise , Domínios de Homologia de src/genéticaRESUMO
The authors reviewed 24 cases of familial or nonfamilial cherubism. The age at onset was between 6 and 10 years. It was characterized by bilateral painless swelling of jaws and eyes-to-heaven appearance was visible when the maxillae were affected as well. Radiographs showed well-defined multilocular radiolucencies and with age, thick sclerotic borders were visible. A malocclusive and abnormal dentition, worse in the mandible can be seen. Histopathologically, numerous randomly distributed multinucleated giant cells and vascular spaces within a fibrous connective tissue stroma with or without eosinophilic collagen perivascular cuffing were apparent. Multinucleated giant cells were positive for osteoclastic specific markers, tartrate-resistant acid phosphatase and human alphaV beta3 integrin, 23C6. Results after follow-up were available for 14 cases. Of these, no treatment was carried out in five cases, cherubism resolved (three cases) or grew slowly (two cases); curettage or surgical contouring was performed in seven cases, during the rapid growth of the lesions. This not only gave good immediate results, but also arrested active growth of remnant cherubic lesions and even stimulated bone regeneration. Segmental mandibulectomy followed by reconstruction was performed in two cases with extensive lesion and the risk of pathologic fracture of the mandible, and excellent results were obtained.
Assuntos
Querubismo/patologia , Arcada Osseodentária/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Idade de Início , Substituição de Aminoácidos , Querubismo/sangue , Querubismo/genética , Querubismo/cirurgia , Criança , Pré-Escolar , Feminino , Genes Dominantes , Células Gigantes/patologia , Humanos , Imuno-Histoquímica , Arcada Osseodentária/diagnóstico por imagem , Masculino , Procedimentos Cirúrgicos Ortognáticos , Linhagem , Radiografia PanorâmicaRESUMO
Cherubism is a nonneoplastic disease of bone characterized by clinical, bilateral, painless enlargements of the jaws that are said to give the patient a cherubic appearance. Cherubism may appear in solitary cases or in many members of the family, often in multiple generations. On radiography the lesions have the appearance of bilateral multilocular radiolucent areas. On histopathologic evaluation the lesions show proliferating fibrous connective tissue containing numerous multinucleated giant cells. Since it was first described by Jones in 1933, many cases have been documented without restriction to any one country or ethnic group, but only a few cases have been reported in Japan, apparently because it is rare here. We report a case of cherubism in a 15-year-old boy and review the Japanese literature.
Assuntos
Querubismo/diagnóstico , Adolescente , Biópsia , Querubismo/sangue , Querubismo/diagnóstico por imagem , Gadolínio , Radioisótopos de Gálio , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Radiografia Panorâmica , Cintilografia , Medronato de Tecnécio Tc 99m , Tomografia Computadorizada por Raios XRESUMO
Cherubism is a non-neoplastic bone disease characterized by clinically evident bilateral, painless enlargements of the jaws that are said to give the patient a cherubic appearance. Cherubism may appear in solitary cases or in many members of the same family, often in multiple generations. On radiography, the lesions exhibit bilateral multilocular radiolucent areas. Histopathologic evaluation reveals proliferating fibrous connective tissue containing numerous multinucleated giant cells. Since the first description of this condition in 1933, almost 200 cases have been reported. We describe cherubism in 2 siblings and briefly review the literature on this subject.