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Clinicopathologic conference: Multiquadrant expansile fibro-osseous lesion in a juvenile
Vol. 113 No. 3 March 2012
CLINICOPATHOLOGIC CONFERENCE
Clinicopathologic conference: Multiquadrant expansile fibro-osseous lesion in a juvenile Vinay V. Kumar, BDS, MDS,a,b Supriya Ebenezer, BDS, MDS,b T.V. Narayan, BDS, MDS,c and Wilfried Wagner, DMD, PhD,d Haryana and Bangalore, India, and Mainz, Germany SWAMI DEVI DYAL HOSPITAL AND DENTAL COLLEGE, MEDICAL CENTER OF JOHANNES GUTENBERG UNIVERSITY, AND OXFORD DENTAL COLLEGE AND HOSPITAL
This paper intends to present clinical, radiologic, and histopathologic features of a case of gigantiform cementoma manifesting in a 14-year-old boy, without any familial involvement. He has been followed for 3 years. Further cases from the literature have been reviewed that confirm a similar clinicopathologic picture. This is the first case report that describes “nonfamilial gigantiform cementoma” after the World Health Organisation’s classification of 2005. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:286-292)
A 14-year-old boy was referred to the department of oral and maxillofacial surgery of a tertiary care teaching hospital, with a complaint of painless, slowly increasing swelling of different parts of the upper and lower jaws (Fig. 1). These enlargements had been noticed at least 2 years earlier but the parents had deferred reporting it, as they did not think it was significant, until the time that it seemed to definitively increase. The swellings were painless, slow growing, and not associated with paresthesia, visual disturbances, or nasal obstruction. There was no lymphadenopathy. The patient’s past medical history and family history were not significant. On examination, there was diffuse bony swelling of the maxilla and the mandible in the dentoalveolar region. The lesions were not tender and the skin and mucosa over the lesions appeared normal. Orthopantamogram (Fig. 2) and computed tomography (CT) scan (Fig. 3) revealed mixed density and expansile lesions with areas of sclerosis and groundglass attenuation involving bilateral maxilla, and body and rami of mandible. There was an increased severity of the lesions in the posterior regions of both the jaws.
Fig. 1. Frontal profile picture of the patient at initial presentation.
a
Senior Lecturer, Department of Oral and Maxillofacial Surgery, Swami Devi Dyal Hospital and Dental College, Haryana, India. b Research Scholar, Department of Oral and Maxillofacial Surgery, Medical Center of Johannes Gutenberg University, Mainz, Germany. c Professor and Head, Oral and Maxillofacial Pathology, Oxford Dental College and Hospital, Bangalore, India. d Director, Department of Oral and Maxillofacial Surgery, Medical Center of Johannes Gutenberg University, Mainz, Germany. Received for publication May 14, 2011; returned for revision Jul 7, 2011; accepted for publication Aug 7, 2011. © 2012 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter doi:10.1016/j.tripleo.2011.08.021
286
Fig. 2. Initial presentation of the patient. Orthopantamogram showing multiple radiolucent-radiopaque lesions involving all 4 quadrants of the jaw. Image is available in color at www.ooooe.net.
The lesions in the maxilla were seen to be extending into the respective sinuses, and causing significant buccal expansion. The maxillary canines had not erupted and were displaced. The mandibular lesions were posteriorly ex-
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Fig. 3. CT scan of the lesion at initial presentation. Top left is a coronal section revealing mixed radiopaque-radiolucent lesions involving posterior dentoalveolar regions of maxilla and mandible. Top right is an axial section through the mandible. The posterior regions of the mandible seen to be more affected than the anterior part of mandible. Bottom left is an axial section through the maxilla and ramus of the mandible. Bottom right is a 3-dimensional reconstructed image of the jaws showing the expansile nature of the lesion. Images are available in color at www.ooooe.net.
tending up to the ascending border of the ramus with a predominance of radiolucency in the ascending rami. There was a slight curvature of the roots of the mandibular molars when involved in the lesion, and the mandibular canal was displaced inferiorly. Root resorption was not evident. At this time, the parents were also radiographically screened but no abnormality was detected. A technitium pertechnetate bone scan (Fig. 4) revealed increased radiotracer uptake in both the bodies/ rami of the mandible and in the bilateral maxillae, with increased vascularity on blood pool images, which was suggestive of an infective/inflammatory/infiltrative pathology. The rest of the skeleton showed unremarkable tracer uptake.
DIFFERENTIAL DIAGNOSIS Assessing the clinical picture and the radiograph, it was evident that the lesion was a benign fibro-osseous lesion. Benign fibro-osseous lesions of the jaws are a diverse group of intraosseous disease processes that share clinical, radiographic, and microscopic features. Although some are diagnosable histologically, most
require a combined assessment of clinical, microscopic, and radiological features. Hence, our differential diagnosis involved most of the fibro-osseous entities that occur in this particular age group, and with extensive involvement of both the jaws. Fibrous dysplasia Fibrous dysplasia (FD) is a benign dysplastic process of altered osteogenesis that may occur within a single bone (monostotic) or multiple bones (polyostotic). Fibrous dysplasia was considered among our differential diagnosis list because it could manifest itself in multiple jawbones as the polyostotic fibrous dysplasia variant. Afflicted individuals usually present as young adults with a slowly growing painless swelling causing facial asymmetry.1 In the polyostotic form, patients may present with irregular café-au-lait spots. Maxillary and mandibular involvement may lead to displacement of teeth, malocclusion, and, rarely, root resorption. Radiographically, 3 different radiographic patterns of FD involving the maxillofacial skeleton have been
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Fig. 4. Technitium pertechnetate bone scan showing bilateral increased radiotracer uptake of both the maxilla and mandible. Images are available in color at www.ooooe.net.
described: cystic (radiolucent or lytic; early lesions), sclerotic (midphase lesions), and mixed radiolucent/ radiopaque (pagetoid: late lesions) comprising 21%, 23%, and 56% of cases, respectively.2 Asymmetric homogeneous radiopacities with “ground-glass” appearance that blend into normal bone, with thin cortices and bone expansion are highly characteristic for FD and best seen on CT scans on bone windows. In the jaws, superior displacement of the mandibular canal, narrowing of the periodontal ligament space, and effacing of the lamina dura are findings suggestive of FD.1 On clinical examination of our patient, however, there were no café-au-lait spots. More important, radiographically, the mandibular canal was displaced inferiorly, no narrowing of the periodontal ligament space was evident, nor was there any obliteration of the lamina dura. Cherubism Cherubism is a childhood disease that exhibits an autosomal dominant hereditary pattern with variable expression.3 The penetrance can be up to 100% in males and up to 70% in females; however, some sporadic cases with no familial involvement have also been noted.4 This uncommon condition generally affects children in the age group of 2 to 4 years and causes a progressive, painless, symmetric expansion of both the jaws, with a predilection toward the posterior mandible. Generally, the maximal enlargement occurs within 2 years of onset and by age 7, the lesions become static or progress relatively slowly until puberty, following which, in the late teens, the disease generally undergoes spontaneous regression. There have been cases reported in the literature where patients present themselves in the teens.5
Although unlikely, we included this entity in the list of differential diagnoses because milder cases of cherubism can present in cases without familial involvement who report in their teens with a similar clinicoradiological picture. Florid cemento-osseous dysplasia The term florid cemento-osseous dysplasia (FlCOD) had been used as a synonym for gigantiform cementoma (GC) in the past.6,7 A thorough literature search for cases of multiquadrant fibro-osseous lesions without a family history manifesting in the adolescent age group revealed a few isolated case reports that had been described as FlCOD. Ong and Siar8 reported a 20-yearold Chinese man who presented with a 2-year history of progressive painless swelling of the mandible and pressure on the left eye, whose radiograph showed that both jaws (except the symphysis menti and the ascending ramus), including bilateral antra, were completely filled with cemento-osseous lesions. The patient had no family history. They reported this condition as a case of FlCOD, the same term used by Miyake and Nagahata9 for their case report, although in the latter’s case there were similar lesions in the family. The case reported in this article seemed to have similar clinicopathologic features as the one reported by Ong and Siar8; however, the World Health Organization (WHO) classification in 200510 defined FlCOD as an extensive form of osseous dysplasia that occurs bilaterally in the mandible or also involving all 4 jaw quadrants, which mainly occurs in middle-aged black women. Within the framework of this classification system, the present case could not be considered as FlCOD.
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Gigantiform cementoma GC is an extremely rare form of fibro-osseous lesion that manifests itself as massive multifocal lesions that usually affect all 4 quadrants of the jaws.11 Almost all cases of GC have an autosomal dominant inheritance and are familial,’’ hence naming this disease entity as “familial gigantiform cementoma.” Among the few cases that have been reported, the gene appears to have a high level of penetrance with variable expressivity.12 Lesions arise during childhood and progressively expand to cause facial deformity during early adult years. One sporadic case without any familial involvement had been described in a report of 3 cases.11 GCs are restricted to the jaws and may arise in 2, 3, or all 4 quadrants. Expansile masses of the maxilla and mandible are readily apparent in most instances, and, radiographically, marked expansion is seen with a radiolucent mass containing floccular calcifications. Although the features of our patient seemed to match the nonfamilial variant of this disease entity, it was also kept in mind that nonfamilial GC (nFGC) is an extremely rare occurrence. Juvenile ossifying fibroma Juvenile ossifying fibroma (JOF) is an uncommon fibro-osseous neoplasm that arises within the craniofacial bones in individuals younger than 15 years. It is usually asymptomatic, achieving a large size and exhibiting aggressive behavior. The lesion is expansile and well demarcated from surrounding bone. These lesions generally tend to be solitary, with maxilla and paranasal sinuses being the most commonly involved regions.13 Although cases of multiple juvenile ossifying fibroma have been reported previously,14,15 there have been no reports of simultaneous involvement of all the 4 quadrants, as in this case. Juvenile trabecular ossifying fibroma and juvenile psammomatoid ossifying fibroma are 2 histologic variants of JOF.13 In the former type, cellular osteoid without osteoblastic rimming together with slender trabeculae of immature bone is seen, whereas the latter is characterized by a fibroblastic stroma containing small ossicles resembling psammoma bodies. Owing to the aggressive nature of JOF and its tendency for recurrence, surgical enucleation with adequate margins or an en bloc resection are the preferred treatment modalities.16
DIAGNOSIS During incisional biopsy, the lesion was found to be hard and gritty with bonelike consistency and was hemorrhagic. It could not be easily separated from the overlying bone and finding a cleavage plane was difficult.
Fig. 5. Histopathologic features of the lesion. Top is a lowmagnification pictogram showing hypercellular fibrous stroma and fibroblasts arranged in whorls, with basophilic droplets interspersed. (Hematoxylin-eosin stain; magnification ⫻10.) The bottom image is under high power magnification; the large basophilic cementicles show a spherical lammelated structure. (Hematoxylin-eosin stain; magnification ⫻40.)
Hematoxylin and eosin–stained sections from the incisional biopsy were examined histopathologically (Fig. 5). The lesion was predominated by an increased cellularity of whorls of spindle cells punctuated by large basophilic acellular lamellated masses of calcified tissue resembling cementum. In addition, there were large islands of irregularly shaped calcific masses with occasional cellular entrapment, which did not appear like either woven or trabecular bone. Mitotic figures were absent. After considering the clinical, radiographic, and gross features, along with the biopsy and histopathologic picture, the lesion was diagnosed as nFGC. The histopathologic examination ruled out fibrous dysplasia because of the presence of large basophilic masses; and it ruled out cherubism because of the lack
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Fig. 6. The patient after 3 years of follow-up. Left is a frontal profile photograph; right shows maculo-papular lesions on the patient’s arm.
of giant cells. The histopathologic picture had a similarity to psammamatoid variant of JOF because of the presence of cementicles; however, the gross description of ossifying fibromas is that of a shiny lesion, yellowish-white in color, well demarcated from surrounding bone, of moderately firm consistency, and with the cut surfaces white in color. These typical features of JOF differentiated it from the hard and not easily cleavable lesion of nFGC. The large spherical calcifications of GC seen in this lesion, well described by Eversole et al.12 as “After all, everything is big with gigantiform cementoma” was another differentiating factor in comparison with the smaller spherules seen in ossifying fibroma.
MANAGEMENT Because of the extensive involvement of both the jaws by this lesion, 2 options were provided to the patient (and his family). The first option was resection of the lesions in totality followed by immediate vascularized bone containing free-flap reconstruction. The second option was to maintain the patient under close follow-up and operate when symptomatic or when the lesion causes significant enlargement to be a hindrance to the patient’s daily life. In concurrence with his parent’s wishes, we decided to keep the patient under periodic observation. During the follow-up phase, he presented at times with complaints of the lesion having grown irregularly in certain areas like the antero-lateral part of the mandible. The patient did occasionally complain of intermittent mild pain in his jaw, which was well controlled after taking regular nonsteroidal anti-inflammatory drugs (ibuprofen 400 mg). After about 1 year from his
Fig. 7. Orthopantamogram after 3 years of follow-up.
initial presentation (when he was 16 years old), the patient developed multiple maculo-papular rashes all around his body, especially on his arms (Fig. 6). He was referred to the dermatologist, who started him on mild systemic steroids, but the lesions had not subsided. A correlation could not be ascertained between his jaw lesions and skin rashes. After 3 years of continuing follow-up (Fig. 6), an orthopantamogram (Fig. 7) and a CT scan (Fig. 8) were taken. They revealed a nearly similar picture to what he presented initially. There were generalized areas of increased radiopacity in the lesions, especially around the molar and premolar regions of all 4 quadrants. The maxillary left canine had progressed in eruption by approximately 2 to 3 mm, but the right maxillary and the right mandibular canines were seen at the same place. The radiolucency at the ascending ramus of the mandible had enlarged to involve the coronoid notch. Root resorption was still not evident and the molar
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Fig. 8. CT scan of the lesion after 3 years of follow-up. Top left, coronal section; top right, axial section through the mandible; bottom left, axial section through the maxilla; and bottom right, 3-dimensional reconstructed image of the jaws.
roots growing into the areas of radiopacity demonstrated an increase in the curvature of their root tips. The patient is still under regular follow-up and there has been no need for resection of the lesions.
DISCUSSION Fibro-cemento-osseous lesions with acellular spherical cemental bodies that manifest as multiple lesions affecting more than one quadrant of the jaw have been previously described by many names, such as GC,11 FlCOD,8,9 sclerotic cemental masses,17 multiple enostosis,18 diffuse sclerosing osteomyelitis, multiple ossifying fibroma,19 and bilateral ossifying fibroma.20 As some of these lesions are rare, owing to the paucity of adequate clinical material and confusing and interchangeable nomenclature of the entities, subclassification and accurate compartmentalization of these lesions have been difficult. Historically, the term “gigantiform cementoma” was coined by Norberg in 193021 to describe a condition characterized by diffuse radiopaque masses scattered throughout the jaws. In 1976, Melrose et al.22 used the name FlCOD to describe similar lesions. In time, these terms were used interchangeably and the 2 disease entities were considered as the same lesion.6,7 In 2001, Abdelsayeed et al.11 had differentiated a certain subtype of these lesions that manifests itself in young patients, with radiographically multiquadrant,
expansile, mixed radiopaque-radiolucent lesions and with histopathologic characteristics of cementicles and considered these lesions as GCs. They suggested that the term “gigantiform cementoma” be reserved for such lesions. In 2005, WHO classification categorized familial GC as a separate entity from FlCOD but considered both of these lesions as different types of osseous dysplasias.10 Although both lesions are extensive and occur bilaterally, the differentiating factor was that the latter was seen in middle-aged black women and was less deforming, whereas the former occurs at a young age, causing jaw expansion and most commonly occurs as an autosomal dominant trait. It was also mentioned that a few sporadic cases had been described in the literature that had no history of familial involvement. Eversole et al.,12 in their classification of fibro-osseous lesions, differentiated FlCOD from GC, and considered the former as a type of bone dysplasia and the latter as a neoplastic lesion. The case reported here showed typical characteristic clinical features of initial presentation in the early second decade of life. The lesions had affected more than one quadrant and were bilaterally involved. Although the teeth in both the jaws were displaced by a significant distance, there was no loss of vitality of the teeth, nor was there any obvious root resorption. While performing an incisional biopsy, the lesions were bony hard and gritty in consistency, were not easily separable
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from the uninvolved bone, and were hemorrhagic when incised. The histopathologic features of highly cellular fibrous stroma with spindle-shaped fibroblasts and plenty of large deposits of basophilic, round, laminated calcifications without cells resembling cementicles are characteristic of these lesions.10-12 Developmentally, these lesions seem to be arising from the tooth-bearing region of the jaws, which could be the reason for the downward displacement of the mandibular canal and the premolar teeth, as well as the reason for the maxillary sinus floor being pushed superiorly. It is to be noted that although nFGC has been differentiated from FlCOD and given a particular characteristic, the concept of nFGC has not yet been well categorized with uniform agreement, probably owing to the paucity of information on the clinical course of these lesions. The lesions have been considered as a form of osseous dysplasia10 and also as a neoplasm, akin to a multifocal variant of ossifying fibroma.12 Likewise, the protocol for treatment of these lesions has also not received uniform agreement. Certain cases of GC have been managed by surgical shaving, although there is a high possibility for recurrence.11,12 Resection of these lesions is definitively curative, but because of the extensiveness of the pathology, it may not be a practical solution. In our case, owing to the extensive and slow-growing nature of the lesion, radical surgical removal was not preferred, and the patient is under active follow-up. There has been no requirement for resection, although recontouring will be performed after the patient attains maturity. A practical solution would be to monitor the patient, and after he reaches maturity and on decreased activity of the lesion (confirmed by a bone scan), surgical contouring could be carried out. Further follow-up of such patients would determine the precise treatment modality that should be used in these interesting cases. With the limited evidence from the case presented, nFGC seems to be a type of osseous dysplasia rather than a neoplasm. Whether GC is a juvenile presentation (and hence more deforming) of the same clinical entity as FlCOD, has to be discerned after further follow-up studies of these interesting and rare lesions. REFERENCES 1. Jundt G. Fibrous dysplasia. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health Organization Classification of tumors. Pathology and genetics of head and neck tumors. Lyon: IARC Press; 2005. p. 322-3. 2. Mohammadi-Araghi H, Haery C. Fibro-osseous lesions of craniofacial bones. The role of imaging. Radiol Clin North Am 1993;31:121-34. 3. Penarrocha M, Bonet J, Minguez JM, Bagan JV, Vera F, Minguez I. Cherubism: a clinical; radiographic and histopathologic comparison of 7 cases. J Oral Maxillofac Surg 2006;64:924-30. 4. Kaugars GE, Niamtu J, Svirsky JA. Cherubism: diagnosis, treat-
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18. 19. 20.
21. 22.
ment, and comparison with central giant cell granulomas and giant cell tumors. Oral Surg Oral Med Oral Pathol 1992; 73:369-74. Carvalho Silva E, Carvalho Silva GC, Viera TC. Cherubism: clinicoradiographic features; treatment and long term follow-up of 8 cases. J Oral Maxillofac Surg 2007;65:517-22. Waldron CA. Fibro-osseous lesions of the jaws. J Oral Maxillofac Surg 1985;43:249-62. Kramer IRH, Pindborg JJ, Shear M. Histologic typing of odontogenic tumors. World Health Organization international classification of tumors. 2nd ed. London: Springer-Verlag; 1992. Ong ST, Siar CH. Florid cemento-osseous dysplasia in a young Chinese man. Case report. Aus Dent J 1997;42:404-8. Miyake M, Nagahata S. Florid cemento-osseous dysplasia. Report of a case. Int J Oral Maxillofac Surg 1999;28:56-7. Slootweg PJ. Osseous dysplasias. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health Organization classification of tumours. Pathology and genetics of head and neck tumors, Lyon; IARC Press; 2005. p. 323. Abdelsayed RA, Eversole LR, Singh BS, Scarbrough FE. Gigantiform cementoma: clinicopathologic presentation of 3 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001; 91:438-44. Eversole R, Su L, El Mofty S. Benign fibro-osseous lesions of the craniofacial complex. A review. Head Neck Pathol 2008;2: 177-202. Slootweg PJ, El Mofty SK. Ossifying fibroma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health Organization classification of tumors. Pathology and genetics of head and neck tumors. Lyon; IARC Press; 2005. p. 319-20. Khanna JN, Andrade NN. Giant ossifying fibroma. Case report on a bimaxillary presentation. Int J Oral Maxillofac Surg 1992;21:233-5. Bradley ES Jr, Leake D. Ossifying fibroma involving the maxilla and mandible; report of a case. Oral Surg Oral Med Oral Pathol 1968;26:606-14. Sun G, Chen X, Tang E, Li Z, Li J. Juvenile ossifying fibroma of the maxilla. Int J Oral Maxillofac Surg 2007;36:82-5. Waldron, CA, Giansanti JS, Browand BC. Sclerotic cemental masses of the jaws (so-called chronic sclerosing osteomyelitis, sclerosing osteitis, multiple enostosis and gigantiform cementoma). Oral Surg Oral Med Oral Pathol 1975;39:590-4. Bhaskar SN, Cutright DE. Multiple enostosis: report of 16 cases. J Oral Surg 1968;26:321. Takeda Y, Fujioka Y. Multiple cemento-ossifying fibroma. Int J Oral Maxillofac Surg 1987;16:368-71. Hauser, MS, Freije S, Payne RW, Timen S. Bilateral ossifying fibroma of the maxillary sinus. Oral Surg Oral Med Oral Pathol 1989;68:759-63. Norberg O. Zur kenntnis der dysontogenetischen geschwulste der keiferknocken. Vrtljsschr Zahn 1930;46:321-55. Melrose RJ, Abrams AM, Mills BG. Florid osseous dysplasia: a clinic-pathologic study of 34 cases. Oral Surg Oral Med Oral Pathol 1976;41:62-82.
Reprint requests: Vinay V. Kumar, BDS, MDS Department of Oral and Maxillofacial Surgery 5C, Cheloor Towers Poothole, Thrissur Kerala, India 680004 [email protected], [email protected]
CLINICOPATHOLOGIC CONFERENCE
Clinicopathologic conference: Multiquadrant expansile fibro-osseous lesion in a juvenile Vinay V. Kumar, BDS, MDS,a,b Supriya Ebenezer, BDS, MDS,b T.V. Narayan, BDS, MDS,c and Wilfried Wagner, DMD, PhD,d Haryana and Bangalore, India, and Mainz, Germany SWAMI DEVI DYAL HOSPITAL AND DENTAL COLLEGE, MEDICAL CENTER OF JOHANNES GUTENBERG UNIVERSITY, AND OXFORD DENTAL COLLEGE AND HOSPITAL
This paper intends to present clinical, radiologic, and histopathologic features of a case of gigantiform cementoma manifesting in a 14-year-old boy, without any familial involvement. He has been followed for 3 years. Further cases from the literature have been reviewed that confirm a similar clinicopathologic picture. This is the first case report that describes “nonfamilial gigantiform cementoma” after the World Health Organisation’s classification of 2005. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:286-292)
A 14-year-old boy was referred to the department of oral and maxillofacial surgery of a tertiary care teaching hospital, with a complaint of painless, slowly increasing swelling of different parts of the upper and lower jaws (Fig. 1). These enlargements had been noticed at least 2 years earlier but the parents had deferred reporting it, as they did not think it was significant, until the time that it seemed to definitively increase. The swellings were painless, slow growing, and not associated with paresthesia, visual disturbances, or nasal obstruction. There was no lymphadenopathy. The patient’s past medical history and family history were not significant. On examination, there was diffuse bony swelling of the maxilla and the mandible in the dentoalveolar region. The lesions were not tender and the skin and mucosa over the lesions appeared normal. Orthopantamogram (Fig. 2) and computed tomography (CT) scan (Fig. 3) revealed mixed density and expansile lesions with areas of sclerosis and groundglass attenuation involving bilateral maxilla, and body and rami of mandible. There was an increased severity of the lesions in the posterior regions of both the jaws.
Fig. 1. Frontal profile picture of the patient at initial presentation.
a
Senior Lecturer, Department of Oral and Maxillofacial Surgery, Swami Devi Dyal Hospital and Dental College, Haryana, India. b Research Scholar, Department of Oral and Maxillofacial Surgery, Medical Center of Johannes Gutenberg University, Mainz, Germany. c Professor and Head, Oral and Maxillofacial Pathology, Oxford Dental College and Hospital, Bangalore, India. d Director, Department of Oral and Maxillofacial Surgery, Medical Center of Johannes Gutenberg University, Mainz, Germany. Received for publication May 14, 2011; returned for revision Jul 7, 2011; accepted for publication Aug 7, 2011. © 2012 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter doi:10.1016/j.tripleo.2011.08.021
286
Fig. 2. Initial presentation of the patient. Orthopantamogram showing multiple radiolucent-radiopaque lesions involving all 4 quadrants of the jaw. Image is available in color at www.ooooe.net.
The lesions in the maxilla were seen to be extending into the respective sinuses, and causing significant buccal expansion. The maxillary canines had not erupted and were displaced. The mandibular lesions were posteriorly ex-
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Fig. 3. CT scan of the lesion at initial presentation. Top left is a coronal section revealing mixed radiopaque-radiolucent lesions involving posterior dentoalveolar regions of maxilla and mandible. Top right is an axial section through the mandible. The posterior regions of the mandible seen to be more affected than the anterior part of mandible. Bottom left is an axial section through the maxilla and ramus of the mandible. Bottom right is a 3-dimensional reconstructed image of the jaws showing the expansile nature of the lesion. Images are available in color at www.ooooe.net.
tending up to the ascending border of the ramus with a predominance of radiolucency in the ascending rami. There was a slight curvature of the roots of the mandibular molars when involved in the lesion, and the mandibular canal was displaced inferiorly. Root resorption was not evident. At this time, the parents were also radiographically screened but no abnormality was detected. A technitium pertechnetate bone scan (Fig. 4) revealed increased radiotracer uptake in both the bodies/ rami of the mandible and in the bilateral maxillae, with increased vascularity on blood pool images, which was suggestive of an infective/inflammatory/infiltrative pathology. The rest of the skeleton showed unremarkable tracer uptake.
DIFFERENTIAL DIAGNOSIS Assessing the clinical picture and the radiograph, it was evident that the lesion was a benign fibro-osseous lesion. Benign fibro-osseous lesions of the jaws are a diverse group of intraosseous disease processes that share clinical, radiographic, and microscopic features. Although some are diagnosable histologically, most
require a combined assessment of clinical, microscopic, and radiological features. Hence, our differential diagnosis involved most of the fibro-osseous entities that occur in this particular age group, and with extensive involvement of both the jaws. Fibrous dysplasia Fibrous dysplasia (FD) is a benign dysplastic process of altered osteogenesis that may occur within a single bone (monostotic) or multiple bones (polyostotic). Fibrous dysplasia was considered among our differential diagnosis list because it could manifest itself in multiple jawbones as the polyostotic fibrous dysplasia variant. Afflicted individuals usually present as young adults with a slowly growing painless swelling causing facial asymmetry.1 In the polyostotic form, patients may present with irregular café-au-lait spots. Maxillary and mandibular involvement may lead to displacement of teeth, malocclusion, and, rarely, root resorption. Radiographically, 3 different radiographic patterns of FD involving the maxillofacial skeleton have been
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Fig. 4. Technitium pertechnetate bone scan showing bilateral increased radiotracer uptake of both the maxilla and mandible. Images are available in color at www.ooooe.net.
described: cystic (radiolucent or lytic; early lesions), sclerotic (midphase lesions), and mixed radiolucent/ radiopaque (pagetoid: late lesions) comprising 21%, 23%, and 56% of cases, respectively.2 Asymmetric homogeneous radiopacities with “ground-glass” appearance that blend into normal bone, with thin cortices and bone expansion are highly characteristic for FD and best seen on CT scans on bone windows. In the jaws, superior displacement of the mandibular canal, narrowing of the periodontal ligament space, and effacing of the lamina dura are findings suggestive of FD.1 On clinical examination of our patient, however, there were no café-au-lait spots. More important, radiographically, the mandibular canal was displaced inferiorly, no narrowing of the periodontal ligament space was evident, nor was there any obliteration of the lamina dura. Cherubism Cherubism is a childhood disease that exhibits an autosomal dominant hereditary pattern with variable expression.3 The penetrance can be up to 100% in males and up to 70% in females; however, some sporadic cases with no familial involvement have also been noted.4 This uncommon condition generally affects children in the age group of 2 to 4 years and causes a progressive, painless, symmetric expansion of both the jaws, with a predilection toward the posterior mandible. Generally, the maximal enlargement occurs within 2 years of onset and by age 7, the lesions become static or progress relatively slowly until puberty, following which, in the late teens, the disease generally undergoes spontaneous regression. There have been cases reported in the literature where patients present themselves in the teens.5
Although unlikely, we included this entity in the list of differential diagnoses because milder cases of cherubism can present in cases without familial involvement who report in their teens with a similar clinicoradiological picture. Florid cemento-osseous dysplasia The term florid cemento-osseous dysplasia (FlCOD) had been used as a synonym for gigantiform cementoma (GC) in the past.6,7 A thorough literature search for cases of multiquadrant fibro-osseous lesions without a family history manifesting in the adolescent age group revealed a few isolated case reports that had been described as FlCOD. Ong and Siar8 reported a 20-yearold Chinese man who presented with a 2-year history of progressive painless swelling of the mandible and pressure on the left eye, whose radiograph showed that both jaws (except the symphysis menti and the ascending ramus), including bilateral antra, were completely filled with cemento-osseous lesions. The patient had no family history. They reported this condition as a case of FlCOD, the same term used by Miyake and Nagahata9 for their case report, although in the latter’s case there were similar lesions in the family. The case reported in this article seemed to have similar clinicopathologic features as the one reported by Ong and Siar8; however, the World Health Organization (WHO) classification in 200510 defined FlCOD as an extensive form of osseous dysplasia that occurs bilaterally in the mandible or also involving all 4 jaw quadrants, which mainly occurs in middle-aged black women. Within the framework of this classification system, the present case could not be considered as FlCOD.
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Gigantiform cementoma GC is an extremely rare form of fibro-osseous lesion that manifests itself as massive multifocal lesions that usually affect all 4 quadrants of the jaws.11 Almost all cases of GC have an autosomal dominant inheritance and are familial,’’ hence naming this disease entity as “familial gigantiform cementoma.” Among the few cases that have been reported, the gene appears to have a high level of penetrance with variable expressivity.12 Lesions arise during childhood and progressively expand to cause facial deformity during early adult years. One sporadic case without any familial involvement had been described in a report of 3 cases.11 GCs are restricted to the jaws and may arise in 2, 3, or all 4 quadrants. Expansile masses of the maxilla and mandible are readily apparent in most instances, and, radiographically, marked expansion is seen with a radiolucent mass containing floccular calcifications. Although the features of our patient seemed to match the nonfamilial variant of this disease entity, it was also kept in mind that nonfamilial GC (nFGC) is an extremely rare occurrence. Juvenile ossifying fibroma Juvenile ossifying fibroma (JOF) is an uncommon fibro-osseous neoplasm that arises within the craniofacial bones in individuals younger than 15 years. It is usually asymptomatic, achieving a large size and exhibiting aggressive behavior. The lesion is expansile and well demarcated from surrounding bone. These lesions generally tend to be solitary, with maxilla and paranasal sinuses being the most commonly involved regions.13 Although cases of multiple juvenile ossifying fibroma have been reported previously,14,15 there have been no reports of simultaneous involvement of all the 4 quadrants, as in this case. Juvenile trabecular ossifying fibroma and juvenile psammomatoid ossifying fibroma are 2 histologic variants of JOF.13 In the former type, cellular osteoid without osteoblastic rimming together with slender trabeculae of immature bone is seen, whereas the latter is characterized by a fibroblastic stroma containing small ossicles resembling psammoma bodies. Owing to the aggressive nature of JOF and its tendency for recurrence, surgical enucleation with adequate margins or an en bloc resection are the preferred treatment modalities.16
DIAGNOSIS During incisional biopsy, the lesion was found to be hard and gritty with bonelike consistency and was hemorrhagic. It could not be easily separated from the overlying bone and finding a cleavage plane was difficult.
Fig. 5. Histopathologic features of the lesion. Top is a lowmagnification pictogram showing hypercellular fibrous stroma and fibroblasts arranged in whorls, with basophilic droplets interspersed. (Hematoxylin-eosin stain; magnification ⫻10.) The bottom image is under high power magnification; the large basophilic cementicles show a spherical lammelated structure. (Hematoxylin-eosin stain; magnification ⫻40.)
Hematoxylin and eosin–stained sections from the incisional biopsy were examined histopathologically (Fig. 5). The lesion was predominated by an increased cellularity of whorls of spindle cells punctuated by large basophilic acellular lamellated masses of calcified tissue resembling cementum. In addition, there were large islands of irregularly shaped calcific masses with occasional cellular entrapment, which did not appear like either woven or trabecular bone. Mitotic figures were absent. After considering the clinical, radiographic, and gross features, along with the biopsy and histopathologic picture, the lesion was diagnosed as nFGC. The histopathologic examination ruled out fibrous dysplasia because of the presence of large basophilic masses; and it ruled out cherubism because of the lack
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Fig. 6. The patient after 3 years of follow-up. Left is a frontal profile photograph; right shows maculo-papular lesions on the patient’s arm.
of giant cells. The histopathologic picture had a similarity to psammamatoid variant of JOF because of the presence of cementicles; however, the gross description of ossifying fibromas is that of a shiny lesion, yellowish-white in color, well demarcated from surrounding bone, of moderately firm consistency, and with the cut surfaces white in color. These typical features of JOF differentiated it from the hard and not easily cleavable lesion of nFGC. The large spherical calcifications of GC seen in this lesion, well described by Eversole et al.12 as “After all, everything is big with gigantiform cementoma” was another differentiating factor in comparison with the smaller spherules seen in ossifying fibroma.
MANAGEMENT Because of the extensive involvement of both the jaws by this lesion, 2 options were provided to the patient (and his family). The first option was resection of the lesions in totality followed by immediate vascularized bone containing free-flap reconstruction. The second option was to maintain the patient under close follow-up and operate when symptomatic or when the lesion causes significant enlargement to be a hindrance to the patient’s daily life. In concurrence with his parent’s wishes, we decided to keep the patient under periodic observation. During the follow-up phase, he presented at times with complaints of the lesion having grown irregularly in certain areas like the antero-lateral part of the mandible. The patient did occasionally complain of intermittent mild pain in his jaw, which was well controlled after taking regular nonsteroidal anti-inflammatory drugs (ibuprofen 400 mg). After about 1 year from his
Fig. 7. Orthopantamogram after 3 years of follow-up.
initial presentation (when he was 16 years old), the patient developed multiple maculo-papular rashes all around his body, especially on his arms (Fig. 6). He was referred to the dermatologist, who started him on mild systemic steroids, but the lesions had not subsided. A correlation could not be ascertained between his jaw lesions and skin rashes. After 3 years of continuing follow-up (Fig. 6), an orthopantamogram (Fig. 7) and a CT scan (Fig. 8) were taken. They revealed a nearly similar picture to what he presented initially. There were generalized areas of increased radiopacity in the lesions, especially around the molar and premolar regions of all 4 quadrants. The maxillary left canine had progressed in eruption by approximately 2 to 3 mm, but the right maxillary and the right mandibular canines were seen at the same place. The radiolucency at the ascending ramus of the mandible had enlarged to involve the coronoid notch. Root resorption was still not evident and the molar
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Fig. 8. CT scan of the lesion after 3 years of follow-up. Top left, coronal section; top right, axial section through the mandible; bottom left, axial section through the maxilla; and bottom right, 3-dimensional reconstructed image of the jaws.
roots growing into the areas of radiopacity demonstrated an increase in the curvature of their root tips. The patient is still under regular follow-up and there has been no need for resection of the lesions.
DISCUSSION Fibro-cemento-osseous lesions with acellular spherical cemental bodies that manifest as multiple lesions affecting more than one quadrant of the jaw have been previously described by many names, such as GC,11 FlCOD,8,9 sclerotic cemental masses,17 multiple enostosis,18 diffuse sclerosing osteomyelitis, multiple ossifying fibroma,19 and bilateral ossifying fibroma.20 As some of these lesions are rare, owing to the paucity of adequate clinical material and confusing and interchangeable nomenclature of the entities, subclassification and accurate compartmentalization of these lesions have been difficult. Historically, the term “gigantiform cementoma” was coined by Norberg in 193021 to describe a condition characterized by diffuse radiopaque masses scattered throughout the jaws. In 1976, Melrose et al.22 used the name FlCOD to describe similar lesions. In time, these terms were used interchangeably and the 2 disease entities were considered as the same lesion.6,7 In 2001, Abdelsayeed et al.11 had differentiated a certain subtype of these lesions that manifests itself in young patients, with radiographically multiquadrant,
expansile, mixed radiopaque-radiolucent lesions and with histopathologic characteristics of cementicles and considered these lesions as GCs. They suggested that the term “gigantiform cementoma” be reserved for such lesions. In 2005, WHO classification categorized familial GC as a separate entity from FlCOD but considered both of these lesions as different types of osseous dysplasias.10 Although both lesions are extensive and occur bilaterally, the differentiating factor was that the latter was seen in middle-aged black women and was less deforming, whereas the former occurs at a young age, causing jaw expansion and most commonly occurs as an autosomal dominant trait. It was also mentioned that a few sporadic cases had been described in the literature that had no history of familial involvement. Eversole et al.,12 in their classification of fibro-osseous lesions, differentiated FlCOD from GC, and considered the former as a type of bone dysplasia and the latter as a neoplastic lesion. The case reported here showed typical characteristic clinical features of initial presentation in the early second decade of life. The lesions had affected more than one quadrant and were bilaterally involved. Although the teeth in both the jaws were displaced by a significant distance, there was no loss of vitality of the teeth, nor was there any obvious root resorption. While performing an incisional biopsy, the lesions were bony hard and gritty in consistency, were not easily separable
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from the uninvolved bone, and were hemorrhagic when incised. The histopathologic features of highly cellular fibrous stroma with spindle-shaped fibroblasts and plenty of large deposits of basophilic, round, laminated calcifications without cells resembling cementicles are characteristic of these lesions.10-12 Developmentally, these lesions seem to be arising from the tooth-bearing region of the jaws, which could be the reason for the downward displacement of the mandibular canal and the premolar teeth, as well as the reason for the maxillary sinus floor being pushed superiorly. It is to be noted that although nFGC has been differentiated from FlCOD and given a particular characteristic, the concept of nFGC has not yet been well categorized with uniform agreement, probably owing to the paucity of information on the clinical course of these lesions. The lesions have been considered as a form of osseous dysplasia10 and also as a neoplasm, akin to a multifocal variant of ossifying fibroma.12 Likewise, the protocol for treatment of these lesions has also not received uniform agreement. Certain cases of GC have been managed by surgical shaving, although there is a high possibility for recurrence.11,12 Resection of these lesions is definitively curative, but because of the extensiveness of the pathology, it may not be a practical solution. In our case, owing to the extensive and slow-growing nature of the lesion, radical surgical removal was not preferred, and the patient is under active follow-up. There has been no requirement for resection, although recontouring will be performed after the patient attains maturity. A practical solution would be to monitor the patient, and after he reaches maturity and on decreased activity of the lesion (confirmed by a bone scan), surgical contouring could be carried out. Further follow-up of such patients would determine the precise treatment modality that should be used in these interesting cases. With the limited evidence from the case presented, nFGC seems to be a type of osseous dysplasia rather than a neoplasm. Whether GC is a juvenile presentation (and hence more deforming) of the same clinical entity as FlCOD, has to be discerned after further follow-up studies of these interesting and rare lesions. REFERENCES 1. Jundt G. Fibrous dysplasia. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health Organization Classification of tumors. Pathology and genetics of head and neck tumors. Lyon: IARC Press; 2005. p. 322-3. 2. Mohammadi-Araghi H, Haery C. Fibro-osseous lesions of craniofacial bones. The role of imaging. Radiol Clin North Am 1993;31:121-34. 3. Penarrocha M, Bonet J, Minguez JM, Bagan JV, Vera F, Minguez I. Cherubism: a clinical; radiographic and histopathologic comparison of 7 cases. J Oral Maxillofac Surg 2006;64:924-30. 4. Kaugars GE, Niamtu J, Svirsky JA. Cherubism: diagnosis, treat-
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Reprint requests: Vinay V. Kumar, BDS, MDS Department of Oral and Maxillofacial Surgery 5C, Cheloor Towers Poothole, Thrissur Kerala, India 680004 [email protected], [email protected]