Rare form of cherubism: Case report with review of literature.

Cherubism was first described by Jones in 1933 as "familial multilocular cystic disease of jaws." Renamed as cherubism in 1938 because of classical characteristics of full round cheeks and upward cast of the eyes to the angelic look of the cherubs immortalized by renaissance art. It is characterized by progressive painless bilateral swelling of jaws involving either maxilla or mandible producing chubby face. It is uncommon fibro-osseous disorder of bone. Mutation in the gene encoding SH3-binding protein 2 (SH3BP2) plays a role in the disease. There are indications that the gene SH3BP2 plays a role in regulating the increased osteoblast and osteoclast activities that are seen in normal tooth eruption and point mutations in the gene could cause pathologic activation of osteoclasts. The purpose of this paper is to present the uncommon form of cherubism and to review the clinicoradiographic, histopathologic features and treatment so as to facilitate diagnosis of disease.

Cherubism is an uncommon fibro-osseous disorder of the jaws that presents with varying degree of involvement and tendency toward spontaneous remission. It is classified as quiescent, non-aggressive and aggressive on the basis of clinical behavior and radiographic findings. Quiescent cherubic lesions are usually seen in older patients and do not demonstrate progressive growth. Non-aggressive lesions are most frequently present in teenagers. Lesions in the aggressive form of cherubism occur in young children and are large, rapidly growing and may cause tooth displacement, root resorption, thinning and perforation of cortical bone.

It is characterized by bilateral and symmetric fibro-osseous lesions limited to the mandible and maxilla. In most patients, cherubism is due to dominant mutations in the SH3-binding protein 2 (SH3BP2) gene on chromosome 4p16.3. Affected children appear normal at birth. Swelling of the jaws usually appears between 2 years and 7 years of age, after which, lesions proliferate and increase in size until puberty. The lesions subsequently begin to regress, fill with bone and remodel until age 30, when they are frequently not detectable. This article highlights the initial unilateral presentation of cherubism case and reviews the different aspect of clinical feature, radiographic feature and histopathological feature.

Case Report

A 9-year-old male child reported to the Oral Medicine Department with the chief complaint of swelling over the right side of face for the past 3 years. Swelling started initially as smaller in size at 6 years of age, which gradually increases in size to attain the present size. There was no associated pain. Family history revealed second degree consanguineous marriage of his parents. On extra-oral examination, facial asymmetry was detected. Diffuse swelling was noticed over right side of the face measuring about 5 cm × 4 cm [Figure 1]. Skin over the swelling was smooth. Inspectory findings such as site, size, shape, surface, extent secondary changes were confirmed. There was no local rise in temperature, no tenderness, hard in consistency. Skin over the swelling was freely movable. Two right submandibular lymph each measuring about 1.5 cm × 1 cm in dimension, smooth, freely movable, non-tender and oval in shape was noticed. A single left submandibular lymph each measuring about 1.5 cm × 1 cm in dimension, smooth, freely movable, non-tender and oval in shape was noticed. No submental, upper deep cervical, lower deep cervical and supraclavicular nodes were detected. On intraoral examination, there were displacement of 21, 31 and lingually erupted 41, Retained 81, Erupting 12 and 22 [Figure 2]. Clinically, missing 16, 46. On palpation of right posterior mandibular region it was nontender and hard. Expansion of cortical plates and right ramus region was felt.

Figure 1

Unilateral swelling right side of mandible

Figure 2

Intraoral view-displacement of teeth

Provisional diagnosis

Considering all these features with missing 46, associated painless expansion of buccal and lingual cortical plate in molar and ramus region we provisionally diagnosed as dentigerous cyst.

The other provisional diagnosis considered is ameloblastoma, fibrous dysplasia and cherubism.

Bio-chemical markers

Serum alkaline phosphatase – 236 IU/L (151-471 IU/L)

Serum calcium – 8.0 mg /dl (8.5-10.5 mg /dl)

Serum phosphorus – 6.8 mg /dl (2.1-5.6 mg /dl)

Radiographic findings

Orthopantamogram (OPG) revealed multilocular radiolucency on the right side mandible with well-defined sclerotic borders extending from molar area to coronoid process involving the entire ramus with sigmoid notch sparing the condyle. A well-defined unilocular radiolucency with sclerotic border was noted in relation to tooth bud of 47. On the left side also similar multilocular radiolucency with well-defined sclerotic border extending from mandibular molar area to coronoid process. There was an unerupted 16, 12, 22.46 impacted [Figure 3].

Figure 3

Orthopantamogram shows bilateral multilocular radiolucency of mandible

Posteroanterior (PA) view of skull showed greater cortical expansion of right ramus when compared to left side of mandible. These radiographic features are suggestive of Cherubism

Computed tomography (CT) showed replacement of mandibular bone by soft-tissue density involving right ramus region and also showed buccolingual bone expansion [Figure 4].

Figure 4

Computed tomography shows replacement of bone by soft tissue density over right ramus and buccolingual expansion

Radiographic differential diagnosis

Multilocular cyst

Central giant cell granuloma

Hyperparathyroidism

Odontogenic myxoma

Aneurysmal bone cyst

Metastatic tumors of jaws

Central hemangioma of bone

Biopsy

Incisional biopsy was done in relation to 85 under local anesthesia.

Histopathological report

A tissue section stained with H and E, showed a cellular lesion composed of loose fibrous stroma with interspersed with many multinucleated giant cells, small thin walled blood vessels and scattered sparse mononuclear inflammatory infiltrate [Figure 5]. Fragments of bone are seen in between the lesion. No atypia or evidence of malignancy.

Figure 5

Photomicrograph shows loose fibrous stroma with interspersed with multinucleated giant cells, small thin walled blood vessels and scattered sparse mononuclear inflammatory infiltrate

Final diagnosis

Final impression was intraosseous fibrous lesion of jaw consistent with cherubism of mandible.

By correlating clinical feature, radiographic feature, histopathological examination a final diagnosis of cherubism of mandible was made.

Pathogenesis

A molecular pathogenesis of cherubism has been proposed, with the detection of a mutation in the gene encoding SH3BP2[123] and possible degradation of the Msx-1 gene, which is involved in the regulation of mesenchymal interaction during craniofacial morphogenesis.[4] The most accepted theory regarding the pathogenesis of cherubism is its association with an autosomal dominant gene, i.e., family inheritance.[5] However, there are reports of the cases in which no criteria of heredity could be established, or in which an autosomal recessive pattern of inheritance was suggested.[6] In addition to genetic factors, Caballero and Vinals indicated other possible causes of cherubism such as mesenchymal alterations during jaw development, an odontogenic origin or even hormonal and traumatic factors.[7] There are indications that the gene SH3BP2 plays a role in regulating the increased osteoblast and osteoclast activities that are seen in normal tooth eruption and point mutations in the gene could cause pathologic activation of osteoclasts.[8] Mutation of the gene encoding for fibroblast growth factor receptor III has also been found in some cases of cherubism.

Treatment and follow-up

As the lesion tends to become static and show regression as the patient approaches puberty. No specific treatment was given. Patient was advised to report every 6 months for review. Patient was followed-up after 6 months. Showed a progressive increase in facial swelling both on the right and left side. Intraoral examination revealed an increase in buccal and palatal cortical expansion in relation to 55 region. OPG and PA view of skull did not show any significant change when compared to first visit [Figure 6]. However, CT scan showed large extensive lytic lesion with soft-tissue density present on both right and left ramus of mandible [Figure 7]. Patient was assured that the disease will regress after puberty and was asked to report after 6 months.

Figure 6

Follow-up orthopantamogram doesn't show significant change from first visit

Figure 7

Computed tomography shows large extensive lytic lesion with soft-tissue density present on both right and left ramus of mandible

Review

First described by Jones in 1933 as “familial miltilocular cystic disease of jaws.” Renamed as cherubism in 1938 because of classical characteristics of full round cheeks and upward cast of the eyes to the angelic look of the cherubs immortalized by renaissance art. It usually occurs between 2 years and 5 years of age followed by a phase of rapid growth until 7-8 years of age, a phase of slow growth until 12 or puberty, a phase of stabilization of lesions at or after puberty and finally a phase of remission at about 25-30 years. According to recent literature 150 cases reported. Cherubism is typically limited to the craniofacial region. However, there are three reports in the literature that refer to involvement of the ribs. Symptomless non-expansile lesions at the anterior ends of ribs.[9] The characteristic upward gaze of patients with cherubism provides the basis for the naming of the disease.[10]

Although rare, cherubism has a significant impact on affected children and their families. This is especially true in those cases where aggressive growth leads to facial deformity and functional problems. In majority of cases, cherubism is self-limiting and no surgical treatment is necessary apart from longitudinal clinical and radiographic observation, which should continue into adulthood. In cases of rapidly proliferating cherubism with significant functional consequences, resection may be indicated. Operative intervention does not change the disease progression, but may improve function and appearance.

Conclusion

This case report emphasize clinically unilateral bony expansion of mandible, but radiographically shows bilateral multilocular cystic lesion of mandible. Six months follow-up shows clinically bilateral swelling. CT shows expansile lytic lesion over both ramus and angle of mandible. Initial unilateral presentation may progress bilaterally. Cherubism should be included in the differential diagnosis when clinically unilateral bony expansion of mandible in the child of age 6-12 years. In this case, there was no positive inheritance and therefore, it is a non-familial/sporadic case.