Penarrocha.clinicalradiographicandhistologicalcomparisonof7Cases

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Arnott8 proposed a grading system for cherubism,according to lesion location and the degree of expan-sion. Accordingly, grade 1 cases are limited to bothascending rami of the mandible; grade 2 cases involvethe maxillary tuberosities and mandibular ascendingrami (resulting in congenital absence of the third andoccasionally the second molars); and grade 3 casescorrespond to massive involvement of both jaws ex-cept the coronoid processes and condyles, resultingin considerable facial disfigurement. Ramon and En-gelberg10 added grade 4 in application to cases whereall of the classical features of the disorder exceedinggrade 3 are present. The grade may change dependingon findings at follow-up examination.10,11

The lesions of cherubism are not distinctive histo-logically and are difficult to differentiate from othergiant cell-containing fibro-osseous disorders. As a re-sult, the diagnosis also depends on the clinical find-ings. Microscopy shows a highly vascular fibrous

stroma with unevenly distributed osteoclastic-likemultinucleated giant cells that tend to cluster nearhemorrhagic foci and deposits of hemosiderin.9 Vas-cular channels are well formed and lined by largeendothelial cells.12 The presence of eosinophilic, col-lagenous material around small capillaries is of valuein the diagnosis of cherubism.13 Mature lesions ex-hibit more dense fibrous tissue, while the number ofmultinucleated giant cells decreases.12

We studied 7 cases of cherubism in which weattempted to relate the clinical degree of the disorder,and the radiographic and histopathologic characteris-

tics of the lesions to the course of the disease.

Patients and Methods

This retrospective study involved 9 patients treatedover a 15-year period and diagnosed with cherubismat the Childrens Maxillofacial Surgery Department inconjunction with the Department of Oral Medicineand Surgery. We reviewed all patients diagnosed withcherubism and presenting a minimum follow-up of 1

year. Two patients were excluded from the studybecause of a lack of sufficient follow-up. Patients

were classified according to the grading system devel-oped by Arnott.8

A quantitative assessment of the histopathologicparameters was carried out (all histologic studies

were made by F.V., based on a 4-point scale: absent,few, moderate, or marked): giant multinucleated celldensity, interstitial hemorrhage, inflammatory activ-ity, and the density of fibrosis. Three subtypes wereconsidered: I, predominance of multinuclear cells; II,predominance of inflammatory activity; and III, pre-dominance of fibrosis (Table 1), characterized as fol-lows:

Subtype I: Great abundance of large giant cells totallyoccupying the lesion surface. High cell density: 160to 180 giant cells per 200 field, intermingling

with small areas of interstitial microhemorrhage.Subtype II: Lesser presence of giant cells, which rep-

resent only part of the lesion. Abundant active

inflammatory component, with extensive vascular-ization, associated to giant cells of variable size.Low cell density: 10 to 15 giant cells per 200field, intermingling with inflammatory and intersti-tial microhemorrhagic areas.

Subtype III: Abundant fibrosis with a reduced pres-ence of giant cells. The inflammatory component isscarce, although there may also be interstitial mi-crohemorrhagic areas. Low cell density: 5 to 8 giantcells per200 field, associated to an extensive andoften dense or highly cellular fibrotic component.

Patient evolution was also assessed by a 4-point scale:

1) improvement (lesion reduction during the pro-cess); 2) no change (no significant lesion changes);3) progression (slow and moderate lesion growth);and 4) marked progression (rapid and constantlesion growth, and/or alterations appearing inother systems).

Results

The 7 patients (4 girls, 3 boys) were between 2and 7 years of age at the onset of clinical evidenceof disease, and presented a mean age of 8.2 years atthe time of the diagnosis (Table 2). Five of the cases

described were nonfamilial, and cases 4 and 5 weresiblings; none of the remaining family members ofthese 2 patients were affected. In all cases, clinicalexamination revealed enlargement of the mandibu-lar angle. Maximum growth was recorded between4 and 5 and 7 and 8 years of age. Five patients(cases 2, 3, 4, 5, and 7) presented bilateral midfacialswelling caused by involvement of the upper jaw.In case 3, in which the involvement was greater,there was thickening of the maxillary alveolar pro-cesses, with partial obliteration of the palatal vault(Fig 1). In the permanent dentition, dental crowd-

Table 1. HISTOPATHOLOGIC SUBTYPES INCHERUBISM

Subtype I Subtype II Subtype III

Giantcells

/ /

Interstitial

hemorrhage

/ / /

Inflammatorycomponent

/

Fibrosis

Pearrocha et al. Cherubism. J Oral Maxillofac Surg 2006.

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FIGURE 1. Case 3. A, Facial appearance of the patient showing symmetrical swelling of the mandibular angles. B, Intraoral image showingthickening of the alveolar processes, with partial obliteration of the palatal vault. C, Panoramic radiograph showing bilateral, sharply defined,multilocular maxillary and mandibular radiotransparencies.


Table 2. CASES OF CHERUBISMSTUDY OF THE CLINICOPATHOLOGIC FEATURES AND PATIENT COURSE

Case No. Age (yr)Age On.

(yr) Gender TD (yr) TCGrade

Arnott Subtype Surgical Treatment Patient Course

1 20 2 F 11 9 1 II No Improvement2 14 3 M 13 1 3 III No No change3 12 3 F 4 8 2 II No Improvement

4* 8 4 M 5 3 2 III No Progression5* 10 7 F 7 3 2 III No No change6 12 6 M 10 2 1 III No No change7 14 4 F 4 10 4 I Curettage expanded

lesions (3 times)Marked

progression

Abbreviations: Age On., age at onset of symptoms; F, female; M, male; TD, age at diagnosis; TC, control time; FD, fibrous density; DH, focalhemosiderin deposits; PC, perivascular cuffing; GC, giant cells.

*Two siblings (case nos. 4 and 5).


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ing and/or malpositioning was observed in all pa-tients except 1 (case 6).

Radiographically, all patients exhibited symmet-rical multilocular transparencies in the mandibularrami and angles. Two patients (cases 2 and 7) alsoshowed involvement of the coronoid processes,and case 7 moreover presented involvement of themandibular symphysis. The condyles were unaf-fected in all cases. The upper jaw was affectedbilaterally in 5 patients (cases 2, 3, 4, 5, and 7), andin case 7 there was additional partial bilateral infil-tration of the maxillary sinuses. In all cases thex-rays revealed retained permanent teeth that weredisplaced from their usual position, and absentthird molars (with occasional absence of secondmolars as well). Maxillofacial computed tomogra-phy in 4 patients (cases 2, 4, 5, and 7) revealedthese bone alterations in greater detail (Fig 2). Case

2 showed mastoid bone involvement presumablyresulting from occupation of these structures bydysplastic soft tissues.

In all patients, the histopathology showed substitu-tion of bone by proliferating fibrous tissue exhibitingmature fibroblasts embedded within an intercellularmatrix, with a number of unevenly distributedmultinucleated giant cells. Eosinophilic vascular cuff-ing was seen in all cases, as well as focal hemosiderindeposits. Assessment of the histopathologic parame-ters is reported in Table 1 (Fig 3).

Of the 6 patients in whom surgical intervention

was limited to the obtainment of a biopsy, cases 1 and3 were found to improve clinically and radiologically,with a follow-up duration of 9 and 8 years, respec-tively. Cases 2, 5, and 6 remained practically withoutchange (up to ages 14, 10, and 12 years, respectively),

while case 4 showed progression between 5 to 7years of age, with a clear increase in bilateral midfacialswelling.

In case 7, at the age of 6 years, there was asignificant deformity of the mandibular rami, andbone remodeling was carried out. Posteriorly, thelesions suffered marked progression. This girl pro-

gressively lost all of her permanent teeth, withexfoliation of the resorbed roots. Serum calciumand phosphorous levels were normal. Starting atthe age of 12, several wine-red soft tissue massesdeveloped in the mandible (Fig 2G); these lesions

were ulcerated as a result of chewing trauma withthe upper jaw, and were excised on a number ofoccasions to facilitate chewing. Biopsies of theselesions always showed similar features, with abun-dant multinucleated giant cells. Nonetheless, thecontrol of disease progression proved elusive, andthe lesions continued to grow.

Discussion

Radiographically, cherubism is characterized by bi-lateral, multilocular, radiolucent areas within the jaw-bones. The lesions usually appear around the mandib-ular angle and spread to the ascending rami and bodyof the lower jaw. The maxillary processes may also be

involved, and lesions can spread to other facial bones.The extent of the lesions varies from minor to massiveinvolvement of both jaws.11 In our study, plain x-raysand computed tomography images demonstrated le-sions confined to the jaws in 6 cases, and with addi-tional facial bone involvement in case 2 (mastoidbone). According to the grading system developed by

Arnott,8 our cases would be classified as grade 1 (2cases), grade 2 (3 cases), grade 3 (1 case), and grade4 (1 case).

In general, cherubism does not have a poor prog-nosis. It has been noted that the condition does not

progress beyond puberty. As the patient grows toadulthood, the jawbone lesions tend to resolve, and aprogressively more normal jaw configuration is noted.11

Maxillary lesions are the first to regress, while man-dibular lesions are often still active at age 20.3 Ourpatients were followed up for an average of 8.7 yearsafter the onset of clinical manifestations. Two casesimproved spontaneously, 3 remained stable, andcases 4 and 7 worsened. In case 4, worsening wasnoted from 4 to 8 years (a critical age when thelesions complete their evolution), while in case 7progression was attributed to the particularly aggres-sive nature of the disease despite surgical treatment.

Because cherubism is considered to be a self-limit-ing condition that improves over time,14 treatmentdepends on the individual patients functional andesthetic needs. Most investigators prefer to wait untilthe end of puberty before performing surgery. Earlysurgical intervention is contraindicated because it ap-pears to predispose to recurrences.15 Surgery is onlyindicated in cases characterized by impaired speech,chewing or swallowing difficulties, or with the pres-ence of major deformities that may cause psycholog-ical problems for the patient.12 Clinical managementand surgical treatment decisions are dependent upon

individual evaluation in accordance with the degreeof disease involvement. Surgical treatment appears tobe unnecessary for grade 1 and 2 cases in the absenceof secondary disturbances. Excision of tissue throughenucleation or curettage appears to be necessary inmore aggressive cases (grade 3), to reduce maxillofa-cial deformity after puberty and to ensure a successfuloutcome without the risk of progression requiringadditional resection.11

The course of the disease was as expected in 6 ofour 7 patients, with worsening between 4 and 7 yearsof age, followed by clinical and radiographic evidence

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FIGURE 2. Case 7. A, Facial appearance. Note the marked bilateral facial swellings. B, Panoramic radiograph showing bilateral, sharplydefined, multilocular radiotransparencies in both jaws (age 7). C, Patient at 11 years of age. Note the extensive loss of teeth and root resorptionin the remaining teeth. D, The same patient, at 12 years of age, showing lesion progression. E, At age 14, the patient lost all remaining teeth;bilateral radiotransparencies persist. F, Coronal computed axial tomography view of the jaws, showing symmetrical bilateral involvement of themandibular rami. Note the maxillary expansion and lytic changes. G, Ulcerated soft tissue mass of the mandibular alveolar process (patient at age14).


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of improvement. The course was different in case 7,however, with worsening from 4 years of age untilcontrol was achieved at age 14. This was the only caserequiring surgical management because the patientalready had significant deformities including intraoralexophytic lesions.

Long-term studies have shown the convenienceand effectiveness of surgery in cherubism. Conserva-tive approaches to management are advisable.14

Among our patients, surgery was only performed incase 7, to correct bothersome lesions and facial de-formity. Curettage with remodeling of the corticallayer was carried out in the same procedure becausemost investigators regard this as the best ap-proach.15,16 Following surgery in a 5-year-old boy,Zachariades et al12 used homogeneous bone grafts toreplace the diseased tissue to avoid pathologic frac-ture of the mandible. Since then, these authors ob-served gradual involvement of other sites in the jaws,

with the displacement of teeth and tooth germs.Koury et al17 described a case in which the usual

course of the lesions changed dramatically duringtreatment, with unilateral growth associated with vas-cular proliferation after surgical recontouring. Themost active areas show a vascular, loose stroma andmore numerous giant cells, whereas slower-progress-ing lesions show increased collagen, fibrosis, and adecreased number of giant cells. These authors sug-gested that it is very possible that surgery caused such

vascular transformation.

In some cases of cherubism, giant cells may be soabundant that the histologic image alone can posegenuine differential diagnostic difficulties versus cen-tral giant cell granuloma or brown tumor of hyper-parathyroidism. Giant cell granuloma can be excludedon clinical grounds, because it is not a bilateral con-dition, is not inherited, does not regress in adulthood,and has a predilection for the anterior mandible. Inturn, bone changes in hyperparathyroidism rarelycause unilateral jaw lesions, but do produce abnormalserum calcium and phosphorus levels.18-20 Incherubism, eosinophilic collagen cuffing can be ob-

FIGURE 3. Microscopy reveals the following: A, Subtype I: great abundance of large giant cells totally occupying the lesion surface (hematoxylin-eosin stain; magnification 100); 160 to 180 giant cells per 200 field. B, Subtype II: lesser presence of giant cells, with abundant inflammatorycomponent (hematoxylin-eosin stain; magnification 100); 10 to 15 giant cells per 200 field. C, Subtype III: abundant connective tissue stromawith scattered multinucleated giant cells (hematoxylin-eosin stain; magnification 100); 5 to 8 giant cells per 200 field.


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Penarrocha.clinicalradiographicandhistologicalcomparisonof7Cases