Orbital Involvement in Cherubism

Fernando Colombo, MD,1,* Claus Cursiefen, MD,1,* Friedrich W. Neukam, MD,2 Leonard M. Holbach, MD1

Purpose: To demonstrate the clinical, radiologic, and histopathologic features of a patient with orbitalinvolvement in cherubism that prompted surgical treatment.

Design: Single interventional case report.Intervention: Findings of the ophthalmic evaluation, computed tomography (CT) scans, intraoperative

examination, and light microscopy of the specimens were analyzed.Main Outcome Measures: Globe displacement, orbital bony lesions detected on CT scans, histopathology,

and postoperative results were assessed.Results: A 27-year-old female was seen with a slowly progressive superonasal globe displacement and a

temporal orbital mass bilaterally of 6 years’ duration. She had a history of cherubism, but her cheeks and jawshad a normal appearance instead of the bilateral fullness of the lower half of the face typical of the disease. CTscans demonstrated multicystic bony lesions arising from the orbital floors bilaterally. The masses were excisedusing an anterior transcutaneous transseptal orbitotomy. Histopathology demonstrated numerous giant cells ina fibrovascular stroma, confirming the clinical diagnosis of cherubism. Postoperative recovery was complete.

Conclusions: Orbital involvement in cherubism may develop beyond puberty, after stabilization or regres-sion of the lesions in the jaws. Patients with cherubism should be routinely evaluated by an ophthalmologist.Ophthalmology 2001;108:1884–1888 © 2001 by the American Academy of Ophthalmology.

In 1933, Jones1 described three siblings affected by a con-dition of the jaws characterized clinically by a painlessexpansion of the region of the cheeks and jaws. He reportedthat “the full round cheeks and the upward cast of the eyesgive the children a peculiarly grotesque, cherubic appear-ance.” This originated the term “cherubism.” The diseaseusually worsens progressively until puberty, at which time itstabilizes and then gradually resolves.2–6 It displays a typ-ical radiographic appearance of bilateral, multilocular, radi-olucent areas within the jaw bones.2–5,7Histopathologically,the lesions show numerous giant cells in a stroma of spin-dle-shaped cells.2–6,8 Lesions involving the orbit arerare.9–11 To our knowledge, only two patients have beenreported in the ophthalmic literature.11 We describe a pa-tient who had orbital manifestations of cherubism developafter stabilization of the lesions in the jaws, promptingsurgical treatment.

Case Report

A 27-year-old female was seen with a slowly progressive supero-nasal displacement of both eyes—more accentuated in the right

eye—and a mass visible through the conjunctiva in the temporalarea bilaterally (Fig 1). At age 9, an irregular mandible wasnoticed. Radiology demonstrated bilateral multicystic lesions inthe mandible and in the maxilla compatible with cherubism, whichprompted referral to a maxillofacial service. An incisional biopsywas performed. Microscopically, the lesion showed giant cells in avascularized fibrous stroma, confirming the diagnosis ofcherubism. One year later the patient underwent extraction of fourteeth that were malformed or partially resorbed. The mandibularirregularity became less perceptible over the years. At age 21, a“bone-hard prominence” in the right lateral canthus was noticed.Six years later, the ophthalmic evaluation revealed bilaterally afixed bony tumor located in the anterior orbit temporally. Theglobes were displaced superonasally. Exophthalmometry readingswere 21 mm in the right eye and 19 mm in the left eye. The restof the examination was unremarkable except for an A-phenome-non and a slight reduction in oblique inferior muscle function.Computed tomography (CT) scans showed bilaterally a multicysticbony tumor of the orbital floor temporally, extending from theorbital rim deep into the orbit (Fig 2). Because the patient wasanxious about the nature of the tumor and the tumor was cosmet-ically unacceptable, surgery was performed. The right orbit wasoperated on first. The mass was exposed using an anterior trans-cutaneous transseptal orbitotomy. It showed a grayish, thin bonysurface and, when incised, a cavity partially filled with a jellyliketissue (Fig 3). The lesion was curettaged and reduced to the levelof the orbital floor. The left orbit was operated on in the samemanner 5 months later. Histopathologically, the lesions showednumerous multinucleated giant cells scattered in a fibrovascularstroma (Fig 4). Postoperatively, recovery was uneventful (Fig 5).The jaw lesions of childhood had regressed, and our patientshowed a normal configuration of the jaws and cheeks in adult-hood (Fig 6).

Discussion

Cherubism is a rare inherited disease of childhood charac-terized by expansion of the mandible and/or the maxilla

Originally received: May 24, 2000.Accepted: May 17, 2001. Manuscript no. 200306.1 Department of Ophthalmology and Eye Hospital, University of Erlangen-Nurnberg, Erlangen, Germany.2 Department of Oral and Maxillofacial Surgery, University of Erlangen-Nurnberg, Erlangen, Germany.

* Both authors contributed equally.

Partially supported by the DAAD (German Academic Exchange Service),Grant No. 331 4 04 001 (Dr. Colombo).

Reprint requests to Claus Cursiefen, MD, Department of Ophthalmologyand Eye Hospital, University of Erlangen-Nu¨rnberg, Schwabachanlage 6,D-91054 Erlangen, Germany.

1884 © 2001 by the American Academy of Ophthalmology ISSN 0161-6420/01/$–see front matterPublished by Elsevier Science Inc. PII S0161-6420(01)00757-6

resulting in different degrees of bilateral fullness of thelower half of the face.1–5,7,8 Involvement of the orbitalbones has seldom been reported.9–11To our knowledge, thisis the third case published in the ophthalmic literature. Twopatients were previously reported by Hawes in 1989.11 Onewas an 18-year-old female who had orbital manifestationsof cherubism develop at age 6 in one orbit and at age 11 in

the contralateral orbit. CT scans showed involvement of thefloor and lateral walls of the orbits. The lesion was subto-tally resected. Three years postoperatively there was noclinical evidence of regrowth. The other patient was a45-year-old female (the mother of the previous case) whohad a mass develop in her mandible at age 5. Fifteen yearslater there was proptosis of the right eye. CT scans demon-strated bony lesions of the orbital floor bilaterally. At age45, the right orbital lesion was subtotally resected. One yearpostoperatively there was no evidence of recurrence. Thepatient described here is unusual in that the orbital involve-ment arose in early adulthood, after the jaw lesions hadsubsided.

The disease is generally inherited as an autosomal dom-inant trait, with incomplete penetrance and variable expres-sivity.4 In a recent study of two families affected by thedisease, the gene locus was localized to chromosome4p16.3.12 Few patients without apparent familial involve-ment have been reported.2,9 Clinically, the size of the le-sions varies from minimal to massive involvement of bothjaws.7 Intraorally, aV-shaped palate; delay in the eruptionof teeth; and missing, displaced, malformed, and resorbedteeth may be present.3,8 Enlargement of the submandibular

Figure 1. A 27-year-old patient with bilateral superonasal displacement ofboth eyes and an orbital mass visible through the conjunctiva temporally(arrows).

Figure 2. A, Coronal computed tomography (CT) scan showing bilaterally a multicystic bony tumor on the orbital floor (arrowheads). B, Axial CT scanshowing that the lesions extend deep into the orbit (arrowheads).Figure 3. Right orbital lesion exposed during surgery (arrows). It displayed a bony surface and a cavity (arrowhead) filled with a jellylike tissue (asterisks,eyelids; N, nose).Figure 4. Histologic section showing numerous multinucleated giant cells (arrows) scattered in a fibrovascular stroma. Note bony wall (arrowheads) (stain,hematoxylin–eosin; original magnification, 3100).

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and, less frequently, the superior cervical lymph nodes hasalso been reported.3 The disorder becomes noticeable withinthe first years of life, usually when the patient is 2 to 4 yearsold, and worsens progressively until puberty, at which timeit stabilizes and then gradually resolves.2,3,5,6, Our patientshowed in adulthood a normal configuration of the jaws andcheeks (Fig 6). In contrast to the typical natural history ofthe disease, she was 21 years old when the orbital abnor-malities were noticed. Progression of the orbital involve-ment beyond puberty has been previously observed.10,11

However, it is difficult to determine the frequency andcharacteristics of orbital involvement in this disease, be-cause most reports have been published in the maxillofacialliterature and do not include ophthalmic evaluations.2–5,7–9

Radiologically, patients with cherubism display bilateral,multilocular, radiolucent areas within the jawbones.2–5,7

These radiologic features in conjunction with the clinicalpicture are distinctive, and a biopsy is done only to confirmthe diagnosis.2,3,5

Histopathologically, cherubic lesions exhibit numerousmultinucleated giant cells scattered in a stroma of vascular-ized fibrous connective tissue.2–6 Cyst formation and newlyformed bone may be present. Multinucleated cells in che-rubic lesions show a strong positivity for monoclonal anti-body 23c6 and tartrate-resistant acid phosphatase, which ischaracteristic of osteoclasts.6

The differential diagnosis of cherubism includes giantcell tumor of the jaw, central giant cell granuloma of bone,brown tumor of hyperparathyroidism, fibrous dysplasia, andaneurysmal bone cyst.2,3,6,11,13Giant cell tumor resemblescherubism histopathologically, but it is unusual in the jaw,affects patients between the ages of 20 and 40 years, and isseen unilaterally.2,3,13Central giant cell granuloma of boneusually affects patients between the ages of 10 and 30 yearsand involves predominantly the anterior mandible.2 In ad-dition, similar to brown tumor of hyperparathyroidism, his-topathologically it shows giant cells that are not scatteredthroughout the lesion—as in cherubism—but rather aregrouped in areas where there may be hemorrhage (“zonalpattern”).13 Brown tumor of hyperparathyroidism, in con-trast to cherubism, rarely affects the jaw in an isolatedmanner, and patients have abnormal serum concentrationsof parathyroid hormone and calcium.3,6 Fibrous dysplasiaexhibits prominent fibrous stroma containing Chinese-fig-urelike orC-shaped spicules of bone histologically.6,13 An-eurysmal bone cyst may also show giant cells, but its mainfeature is a nonendothelium-lined cavity.13

Because the disease is generally self-limiting and sub-sides with age, treatment is indicated only in cases withesthetic or functional problems. Curettage alone or in com-bination with surgical contouring has been considered thetreatment of choice.8 Some authors have reported a massive

growth of the lesion after surgery, especially when this isperformed during the active growth phase.8,14Radiotherapyhas been used, but it is not recommended because of thehigh incidence of complications.4,10

The word “cherub” originally designated a creature thatbelonged to the celestial chorus and that showed specificfeatures (Fig 7A): severe, staring eyes; eyes on the wingsand body; wheel below the feet. Angels with childishchubby faces became especially widespread in baroque art(Fig 7B): typical “angel” face with upward gaze and fullcheeks. Nowadays, a cherub fits this latter description. Thepreviously mentioned simile introduced by Jones1 betweenthe clinical appearance of affected patients and the baroquecherubs popularized the term “cherubism” to designate thedisorder. The term “cherubism” for the disease actually isnot fully correct, because the typical clinical picture doesnot resemble a classical cherub but a baroque angel.

In conclusion, we described a patient with cherubismwho had orbital involvement develop unusually late. Le-sions involving the orbits may appear and progress evenafter stabilization of the lesions in the jaws. Patients withcherubism should be routinely evaluated by an ophthalmol-ogist.

Acknowledgment. The authors thank Dr. Gisela Cursiefen,Dusseldorf for advice on historic art.

References

1. Jones WA. Familial multilocular cystic disease of the jaws.Am J Cancer 1933;17:946–50.

2. Kaugars GE, Niamtu J 3rd, Svirsky JA. Cherubism: diagnosis,treatment, and comparison with central giant cell granulomasand giant cell tumors. Oral Surg Oral Med Oral Pathol 1992;73:369–74.

3. Zachariades N, Papanicolaou S, Xypolyta A, Constantinidis I.Cherubism. Int J Oral Surg 1985;14:138–45.

4. Peters WJN. Cherubism: a study of twenty cases from onefamily. Oral Surg Oral Med Oral Pathol 1979;47:307–11.

5. Hitomi G, Nishide N, Mitsui K. Cherubism. Diagnostic im-aging and review of the literature in Japan. Oral Surg OralMed Oral Pathol Oral Radiol Endod 1996;81:623–8.

6. Southgate J, Sarma U, Townend JV, et al. Study of the cellbiology and biochemistry of cherubism. J Clin Pathol 1998;51:831–7.

7. Ayoub AF, el-Mofty SS. Cherubism: report of an aggressivecase and review of the literature. J Oral Maxillofac Surg1993;51:702–5.

8. Koury ME, Stella JP, Epker BN. Vascular transformation incherubism. Oral Surg Oral Med Oral Pathol 1993;76:20–7.

9. Ramon Y, Engelberg IS. An unusually extensive case ofcherubism. J Oral Maxillofac Surg 1986;44:325–8.

10. Marck PA, Kudryk WH. Cherubism. J Otolaryngol 1992;21:84–7.

Figure 5. Clinical picture taken 5 months after surgery of the right orbit and 6 days after surgery of the left orbit.Figure 6. Clinical picture taken 4.5 months after surgery of the right orbit and before surgery of the left orbit. Note that the jaws and cheeks show a rathernormal configuration.Figure 7. The term “cherubism” for the disease actually is not fully correct, because the typical clinical picture does not resemble a classical cherub buta baroque angel. A, Characteristic features of a cherub: severe, staring eyes; eyes on the wings and body; wheel below the feet; and four to six wings. B,Typical “angel” face with upward gaze and full cheeks.4™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™

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11. Hawes MJ. Cherubism and its orbital manifestations. OphthalPlast Reconstr Surg 1989;5:133–40.

12. Mangion J, Rahman N, Edkins S, et al. The gene forcherubism maps to chromosome 4p16.3. Am J Hum Genet1999;65:151–7.

13. Jakobiec FA, Bilyk JR, Font RL. Orbit. In: Spencer WH, ed.Ophthalmic Pathology: An Atlas and Textbook, 4th ed. Phil-adelphia: Saunders, 1996; vol 2459–860.

14. Thompson N. Cherubism: familial fibrous dysplasia of thejaw. Br J Plast Surg 1959;12:89–103.

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