AJR 2004; 182:1051-1054
© American Roentgen Ray Society
Imaging Characteristics of Cherubism
Francesca D. Beaman1,
Laura W. Bancroft1,
Jeffrey J. Peterson1,
Mark J. Kransdorf1,2,
Mark D. Murphey2,3,4 and
David M. Menke5
1 Department of Radiology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL
32224-3899.
2 Department of Radiologic Pathology, Armed Forces Institute of Pathology,
Walter Reed Army Medical Center, 6825 16th St. NW, Bldg. 54, Washington, DC
20306-6000.
3 Department of Radiology and Nuclear Medicine, Uniformed Services University of
the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814-4799.
4 Department of Radiology, University of Maryland School of Medicine, 22 S
Greene St., Baltimore, MD 21201-1595.
5 Department of Pathology, Mayo Clinic, Jacksonville, FL 32224-3899.
Received July 21, 2003;
accepted after revision September 22, 2003.
Presented at the 2003 annual meeting of the American Roentgen Ray Society,
San Diego, CA.
The opinions or assertions contained herein are the private views of the
authors and are not to be construed as official or as reflecting the views of
the Department of the Army or the Department of Defense.
Address correspondence to M. J. Kransdorf.
Abstract
OBJECTIVE. We sought to describe the radiographic and imaging
features of cherubism.
CONCLUSION. Cherubism is a rare osseous disorder of children and
adolescents. Although the radiologic characteristics of cherubism are not
pathognomonic, the diagnosis is strongly suggested by bilateral relatively
symmetric jaw involvement that is limited to the maxilla and mandible. Imaging
typically shows expansile remodeling of the involved bones, thinning of the
cortexes, and multilocular radiolucencies with a coarse trabecular
pattern.
Introduction
Cherubism is a benign disease of childhood characterized by osseous
involvement limited specifically to the mandible and maxilla. It was first
described in 1933 by Jones [1]
as "familial multilocular cystic disease of the jaws," but the
term "cherubism" was later coined to describe the rounded facial
appearance resulting from jaw hypertrophy that was reminiscent of cherubs
depicted throughout Renaissance art (Fig.
1A). The condition was initially characterized as familial, but
both hereditary and sporadic cases have since been described.
Bilateral mandibular involvement is a distinguishing feature; only one case
report in the literature describes unilateral involvement, in an adolescent
[2]. Children typically present
as early as 2–3 years old with nontender enlargement of the jaw. The
lesions characteristically continue a pattern of variable enlargement until
puberty, and then they partially or fully regress and show sclerotic
involution in adulthood.
Cherubism is similar to fibrous dysplasia radiographically, especially when
the latter is confined to the jaw. The similarity in appearance has prompted
the suggestion that cherubism may be a familial form of fibrous dysplasia
localized to the jaw
[3–5].
We present our experience with 10 cases of cherubism and describe its
radiographic and imaging features.
Materials and Methods
This study was conducted with the approval of the Mayo Clinic institutional
review board, in accordance with the requirements for a retrospective review;
informed consent was not required.
Six patients were selected through an archival search of institutional
records via a review of computer-generated patient diagnoses. Four additional
patients were identified from the archives of the Armed Forces Institute of
Pathology. The diagnosis of cherubism was based in all cases on a combination
of histopathologic features, skeletal distribution of lesions, and patient
age.
The study group consisted of 10 patients, six males and four females,
5–19 years old (mean, 13.5 years). One patient's age was unknown.
Imaging types reviewed included radiography (n = 5), unenhanced CT
(n = 5), and unenhanced MRI (n = 1). MR images included
spin-echo T1-weighted images and fast spin-echo T2-weighted images with fat
suppression. Two patients underwent serial radiography, and one patient
underwent both CT and MRI. Three-dimensional CT reconstruction was available
in one case. None of the patients who underwent CT or MRI examinations
underwent radiography.
The clinical history and imaging characteristics were reviewed for each
patient. Clinical review incorporated the documentation of sex and age at the
time of imaging; physical findings, specifically dental derangement; and
family history. Radiographic and CT features included assessment for
bilaterality; location, in the mandible and maxilla; extent of involvement;
margin, between involved and uninvolved bone; matrix, defined as absent or
present; and the presence and extent of expansile remodeling, periosteal
reaction, cortical thinning, and trabeculation. When mineralized fibroosseous
matrix was identified, it was subjectively characterized as sclerotic or
densely sclerotic. In patients for whom serial radiographs had been obtained
or multiple imaging techniques were available, each case was initially
evaluated independently on the basis of the criteria just mentioned and then
in concert for assessment of progression or comparison between techniques. The
MR images were analyzed for signal intensity as compared with that of skeletal
muscle, fat, and simple fluid; signal homogeneity; lesion size; and lesion
location.
Results
All patients presented with progressive enlargement of the jaw or with the
complaint of facial swelling. One patient complained of associated facial
pain. Eight patients (80%) had associated dental derangement. The remaining
two (20%) had documented earlier dental interventions. Definitive family
history was available in only three cases, all of which were positive for
cherubism. One patient was in foster care, so family history was brief and
incomplete. No family history was available for the remaining six
patients.
All cases displayed bilateral mandibular involvement; six patients (60%)
showed concurrent maxillary disease (Fig.
2A,
2B,
2C). One patient had an osseous
extension from the mandibular body into the condyles. In seven cases (70%),
the entire mandible was abnormal. The remaining focal maxillary and mandibular
lesions ranged from 2 to 5 cm (mean, 3.3 cm)
(Fig. 3). All lesions revealed
expansile remodeling of the involved bones and thinning of the adjacent
cortical rims. One lesion was entirely radiolucent, and the remaining nine
(90%) showed increased opacity on radiography. CT results were compatible with
a fibroosseous matrix (Fig. 4A,
4B). The matrix showed varying
degrees of increased attenuation and was deemed densely sclerotic in two cases
(20%). Seven cases (70%) showed expansile osseous remodeling with a
multilocular appearance and a coarse trabecular pattern. None of the osseous
lesions showed adjacent periosteal reaction or associated soft-tissue
mass.
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Fig. 2B. —Cherubism in 9-year-old boy. Coronal CT scan displayed in
bone window shows extent of osseous involvement. Note osseous expansile
remodeling, cortical thinning, and multilocular contour with coarse trabecular
pattern. Maxillary disease resulting in dental derangement is also seen.
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Fig. 4A. —Cherubism in 16-year-old girl with massive mandibular
enlargement and difficulty swallowing. Three-dimensional surface-rendering
coronal oblique CT scan shows extensive osseous remodeling.
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Fig. 4B. —Cherubism in 16-year-old girl with massive mandibular
enlargement and difficulty swallowing. Coronal CT scan reveals variable
appearance of matrix, ranging from radiolucent to densely sclerotic. Note
expansile remodeling of bone and trabeculation.
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CT clearly depicted the bilateral osseous involvement and expansile
remodeling. CT also accurately delineated the extent of involvement and was
especially useful in characterizing the osseous matrix. MRI established the
lesions to be homogeneously isointense to skeletal muscle on T1-weighted
imaging and heterogeneously isointense to skeletal muscle on fat-suppressed
spin-echo T2-weighted imaging (Fig.
5A,
5B,
5C).
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Fig. 5B. —Cherubism in 12-year-old boy. Axial T1-weighted image (TR/TE,
600/20) (B) and fast spin-echo fat-suppressed T2-weighted image
(3,500/105) (C) of individual lesions show inconspicuous mandibular
lesions (arrows) that are isointense to skeletal muscle.
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Fig. 5C. —Cherubism in 12-year-old boy. Axial T1-weighted image (TR/TE,
600/20) (B) and fast spin-echo fat-suppressed T2-weighted image
(3,500/105) (C) of individual lesions show inconspicuous mandibular
lesions (arrows) that are isointense to skeletal muscle.
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Discussion
Cherubism has been described as a subtype of fibrous dysplasia,
specifically a hereditary craniofacial fibrous dysplasia
[3,
4], because of the radiographic
similarities between the conditions. Recent genetic analysis, however, has
shown them to be separate entities. The genetic basis for cherubism was
identified in 1999, when the gene responsible for it was mapped to chromosome
4p16.3 [5,
6]. Ueki et al.
[7] found a series of point
mutations resulting in amino acid substitutions in the SH-3 binding protein
SH3BP2 on chromosome 4p16.3. Of the four subtypes of fibrous dysplasia, three
(monostotic, polyostotic, and Mc-Cune-Albright syndrome) are known to be
related to mutations in the guanine nucleotide–binding protein gene
located on chromosome 20q. The fourth (craniofacial) subtype has not been
localized to this chromosome
[8]. After analyzing results
from a family with craniofacial fibrous dysplasia, Mangion et al.
[8] determined that cherubism
resulted from different mutations and was therefore a distinct entity at the
molecular level.
Radiographic images of cherubism in our study revealed a characteristic
pattern of expansile remodeling of the bone in all patients, mildly sclerotic
matrix in 60%, and internal trabeculation in 70%. No lesions displayed
associated periosteal reaction. CT clearly depicted the local extent of
lesions limited to the maxilla and mandible, a finding that is often difficult
to document on radiography because of the anatomic complexity of the facial
bones. Interestingly, all the lesions depicted on CT contained mildly
sclerotic matrix with expansile remodeling of the bone and cortical
thinning.
Our results are in agreement with those described in the literature
[4]. CT results for one case
also provided clear evidence of lesion extension and involvement in the
mandibular condyle. Sparing of the mandibular condyles has been described as a
pathognomonic feature of cherubism
[9], but Bianchi et al.
[4] found this not to be
invariably the case and described a patient with condylar involvement that was
seen on CT.
On MR images, cherubic lesions were homogeneously isointense to skeletal
muscle on T1-weighted imaging and heterogeneously hypointense to skeletal
muscle on fast spin-echo T2-weighted images with fat suppression. These
appearances are nonspecific, but they have not been previously described. MRI
provides an anatomic outline that allows accurate determination of lesion
location and extent.
Radiographic differential diagnosis for cherubism includes craniofacial
fibrous dysplasia, brown tumor of hyperparathyroidism, Jaffe-Campanacci
syndrome, and familial gigantiform cementoma. Although cherubism and
craniofacial fibrous dysplasia of individual lesions show radiologic
similarities, they may be distinguished clinically and histologically.
Features more specific for the diagnosis of cherubism include bilateral
mandibular involvement, limitation to the maxilla and mandible, and involution
at the time of puberty [8,
10]. In contrast, patients
with fibrous dysplasia typically do not present with swollen cheeks, upward
turning of the eyes, or dental derangement. All the probands in our series had
bilateral mandibular involvement, and more than half (60%) had concurrent
maxillary disease. Histologically, patients with cherubism typically have a
prominent number of multinucleated giant cells, which are rarely seen in
fibrous dysplasia. Brown tumor and Jaffe-Campanacci syndrome are readily
distinguished on clinical grounds and are easily eliminated from the
differential diagnosis.
Familial gigantiform cementoma is a rare osseous disorder characterized by
the production of cementum in the lesions. Mandibular and maxillary
involvement are often present. Finical et al.
[11] reviewed a series of
cases in a single family and described lesions extending into the orbits and
nasal septum, locations that exclude the diagnosis of cherubism. Also,
gigantiform cementoma lesions are located primarily in the maxilla and are
enlarged in a focal rather than diffuse manner. Histologically, cementomas
contain cementum and lack multinucleated giant cells.
Study limitations include the fact that this review was retrospective. Our
sample was small, and CT and MR images were not available in all cases. Also,
we did not perform genetic evaluation on the surgical specimens in our
sample.
Although the radiologic and histologic characteristics of cherubism are not
pathognomonic, the overall morphologic features are characteristic and
consistent among cases; these features therefore allow an accurate prospective
diagnosis in the appropriate clinical setting.
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Abstract
Introduction
