CHERUBISM: CASE REPORT AND LITERATURE REVIEW Querubismo: relato de caso e revisão da literatura
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1 Cherubism: case report and literature review CHERUBISM: CASE REPORT AND LITERATURE REVIEW Querubismo: relato de caso e revisão da literatura Victor Perez Teixeira 1 Rogério Aparecido Dedivitis 2 André V. Guimarães 3 Alexandre Augusto Benetton 4 Cristiane Miranda França 5 Abstract Cherubism is a rare hereditary non-neoplastic bone disease characterized by clinically evident bilateral, painless enlargements of the jaws that are said to give the patient a cherubic appearance. A Caucasian eight-year-old male child was referred by his dentist with an history of bilateral mandibular slow growing enlargement from 18 months without inflammatory signals. The parents noticed mobility of the primary molars two months previously. On panoramic radiography and computed tomography, the lesions exhibit bilateral multilocular radiolucent areas with cortical expansion. Histopathologic examination revealed proliferating fibrous connective tissue containing numerous multinucleated giant cells identified as osteoclasts. The authors discuss their clinical decision in monitoring the case and review the literature on cherubism. Keywords: cherubism; jaw tumors; fibro-osseous lesions. Resumo Querubismo é uma doença óssea hereditária rara, não neoplásica, caracterizada por aumento de volume evidente dos maxilares, bilateral, indolor, que confere ao paciente afetado um aspecto de querubim. A paciente, uma menina de oito anos de idade, branca, foi encaminhada por seu cirurgião-dentista clínico com história de crescimento progressivo mandibular bilateral há 18 meses, sem sinais inflamatórios. Os pais observaram mobilidade dos molares decíduos dois meses antes da consulta. Exames imaginológicos (panorâmico e tomografia computadorizada) mostraram áreas radiolúcidas multiloculares bilaterais, com expansão de cortical. Exame histopatológico revelou proliferação de tecido conjuntivo fibroso contendo numerosas células gigantes multinucleadas, identificadas como osteoclastos. Os autores discutem a decisão clínica de acompanhamento do caso e revisam a literatura sobre querubismo. Palavras chave: Querubismo; Tumores dos maxilares; Lesões fibro-ósseas. 1 Graduation student, Faculty of Dentistry, Metropolitan University of Santos (UNIMES) 2 Chairman, MD, PhD, Department of Otorhinolaryngology - Head and Neck Surgery, Faculty of Medicine, UNIMES. 3 Assistant Professor, MD, MsD, Department of Otorhinolaryngology - Head and Neck Surgery, Faculty of Medicine, UNIMES. 4 DDS 5 Assistant Professor, DDS, PhD, Department of Pathology, Faculty of Dentistry, UNIMES. Rua Diana, 1001 apto 122, São Paulo, SP, Brasil. Phone/fax: (55 11) crispadron@uol.com.br Rev. de Clín. Pesq. Odontol., v.1, n.1, jul./ago
2 Introduction Cherubism is a non-neoplastic hereditary bone lesion characterized by a bilateral, painless swelling of the maxilla and mandible resulting in a fullness of the cheeks and retraction of the lower eyelids giving an upward turned appearance of the eyes comparable to a cherub angel (1). It is an autosomal dominant inheritance presenting an 80% of familial pattern. Typically the mandible is primarily affected and in 60% of the cases maxilla is also involved (2). Children are normal at birth. At the time of 14 months to five years of age, a symmetric enlargement of the jaws begins, progressing until puberty (3). The authors present a case of a caucasian eight-year-old male child with cherubism and compare the findings and clinical approach with current literature. Clinical case A caucasian eight-year-old male child with unremarkable past medical and familial histories was referred by his dentist with a complain of an slow growing asymptomatic mandibular swelling first detected 18 months previously. The patient presented a weight gain of 10 kilograms in the previous year. General physical exam was not relevant. Bilateral expansion of mandibular angles and ramus were extra-orally observed. The lesions were firm to palpation and there were no enlarged cervical lymph nodes. Intraoral examination showed bilateral expansion of the mandibular angle extending to the retromolar region and posterior region of the maxilla. Tooth 36 was tilted distally and 46 was partially erupted. The inferior deciduous molars presented a two month history of mobility. Panoramic radiography showed generalized multicystic bilateral lesions affecting mandible and maxilla. Several teeth buds were absent (teeth 17, 37, 31, 41, 25) and tooth bud of the 47 was rotated inside a multicystic area. Additionally, displacement of the inferior right alveolar canal was seen (figure 1). Axial computerized tomography (figure 2A and 2B) and coronal (figure 2C) scans confirmed the panoramic radiography findings and showed involvement of the posterior wall of maxillary sinus. A biopsy under general anesthesia was performed and a fragment from the lesion was removed. Histological examination revealed a fibrous tissue with a large number of multinucleated giant cells irregularly distributed and ovoid to spindleshaped fibroblasts in a collagenous well vascularized stroma. (figure 3) Discussion According to the World Health Organization, cherubism belongs to a group of non-neoplastic bony lesions affecting only the jaws (4). It is a rare benign condition, with autosomal dominant inheritance. The gene underlying cherubism was mapped to chromosome 4p16.3, between D4S127 and 4ptelomere (5,6). In about 20% of literature reports cherubism appears de novo in one member of a previously unaffected family, as in this case, and its occurrence is generally considered an example of spontaneous mutation. The classic clinical presentation is the result of an enlargement of orbital floor and fragile support of lower lids, with a superior globe displacement and sclera exposition. This classical clinical characteristic is not observed in every patient, once cherubism presents an 80 and 100% penetrance and variable expressivity (7). Our patient has both maxillae and mandible involved. The onset of the patient s symptoms begun at age of seven years, which differs from the literature mean age that ranges between 14 months to five years(3,7). The onset of the abnormalities of cherubism and their organrestricted characteristics may be related to dental developmental processes in children, when signals unique to the mandible and maxilla are transmitted through the extracellular matrix, triggered by the eruption of secondary teeth (8). A very common clinical aspect of cherubism, as seem in this case, is the absence of teeth, impacted or displaced teeth and root resorption. These anomalies are caused by the substitution of bone into a fibrous tissue, resulting in oclusopathologies (2,3,7,8). Intraoral examination of our patient showed inferior deciduous molars with mobility. This Rev. de Clín. Pesq. Odontol., v.1, n.1, jul./ago
3 may be because of cherubic changes of the bone or due to an acceleration of the primary teeth exfoliation process. Histological examination of the lesions reveals numerous multinucleated giant cells resembling osteoclasts in a dense fibrous stroma. Hemorragic foci may be observed (7). Although the nature and the mechanism involved in the formation of the multinucleated giant cells are not fully understood, enzime histochemical, immunohistochemical and molecular studies have proved that these cells present characteristics of the osteoclast phenotype (9). Many different pathological conditions as giant cell tumor, peripheral and central giant cell lesions and brown tumour of hyperparathyroidism may show the same histological picture as cherubism. Differential diagnosis is made on familial history, clinical, radiographical and histological basis10. Cherubism is generally a self-limiting lesion and spontaneously regresses with age. Jaw remodeling continues through the third decade of life, at the end of which the clinical abnormality may be subtle. The frequency of the remodeling is unknown, since most of the recorded cases have been surgically treated before reaching puberty 3,7,8,9. Curettage alone or in combination with surgical contouring has been considered the treatment of choice and some authors have reported a massive growth of the lesion after surgery, especially when this is performed during active growth fase 10,11. Liposuction has been used to change the contour of the jaws in patients with cherubism 3,7. Some authors point medical therapy in the form of calcitonin as a possibility to curtail the disease and obviate the need for surgery, but few data in the literature is available 7. The clinicians choice in monitoring the patient s condition was based in routine observation and literature data 3,7,9,10,11. Surgical treatment is unnecessary unless functional or emotional disturbances develop. Because the lesions were not causing any functional or social problem to the child, once cherubism diagnosis was performed, no treatment was given and the parents were advised to bring the child for periodic checkups to monitor the condition. References 1. Jones WA. Familial multilocular cystic disease of the jaws. Am J Cancer 1933;17: Stiller M, Urban M, Golder W, Tiziani V, Reichenberger E, Frege J et al Craniosynostosis in cherubism. Am J Med Gen 2000;95: Pulse CL, Moses MS, Greenman D, Rosenberg SN, Zegarelli DJ. Cherubism: case reports and literature review. Dent Today 2001;20: Pindborg JJ, Kramer IRH, Torloni H. Histological typing of odontogenic tumors, jaw cists and allied lesions. In: International histological classification of tumors. Geneve: World Health Organization 1971: Tiziani V, Reichenberger E, Buzzo CL, Niazi S, Fukai N, Stiller M, Peters H, Salzano FM, Raposo do Amaral CM, Olsen BR. The gene for cherubism maps to chromosome 4p16. Am J Hum Genet 1999;65: Ueki Y, Tiziani V, Santanna C, Fukai N, Maulik C, Garfinkle J. Mutations in the gene encoding c-abl-binding protein SH3BP2 cause cherubism. Nature Genetics 2001;28: Kozakiewicz M, Perczynska-Partyka W, Kobos J. Cherubism Clinical picture and treatment. Oral Dis 2001;7: Ongole R, Pillai RS, Pai KM. Cherubism in siblings: a case report. J Can Dent Ass 2003;69: Liu B, Yu SF, Li TJ. Multinucleated giant cells in various forms of giant cell containing lesions of the jaws express features of osteoclasts. J Oral Pathol Med 2003;32: Silva EC, Souza PEA, Barreto DC, Dias RP, Gomez RS. An extreme case of cherubism. Brit J Oral Maxillofac Surg 2002;40: Rev. de Clín. Pesq. Odontol., v.1, n.1, jul./ago
4 11. Colombo F, Cursiefen C, Neukam FW, Holbach LM. Orbital involvement in cherubism. Ophtalmol 2001;108: Rev. de Clín. Pesq. Odontol., v.1, n.1, jul./ago
5 FIGURE 1 Panoramic radiography shows generalized multicystic bilateral lesions affecting mandible and maxilla. Several teeth buds were absent (teeth 17, 37, 31, 41, 25). Tooth bud 47 was rotated inside a multicystic area. Displacement of the inferior right alveolar canal is seen (arrows). FIGURE 2 CT axial scan showing mandibular expansion (figure 2A), maxillary involvement (figure 2B). Coronal scans confirm the panoramic radiographic findings and show involvement of the posterior wall of maxillary sinus (figure 2C). a Rev. de Clín. Pesq. Odontol., v.1, n.1, jul./ago
6 FIGURE 3 Fibrous tissue with a large number of multinucleated giant cells irregularly distributed and ovoid to spindle-shaped fibroblasts in a collagenous well vascularized stroma (HE 100x ). Received in 05/05/2004; Accepted in 07/06/2004. Recebido em 05/05/2004; Aceito em 06/07/2004. Rev. de Clín. Pesq. Odontol., v.1, n.1, jul./ago
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