Orbit, 2015; 34(1): 33–37 ! Informa Healthcare USA, Inc. ISSN: 0167-6830 print / 1744-5108 online DOI: 10.3109/01676830.2014.950287
C ASE REPORT
Cherubism: Report of Three Cases and Literature Review Arash Mirmohammadsadeghi, Bahram Eshraghi, Azadeh Shahsanaei, and Raheleh Assari
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 04/24/15 For personal use only.
Ocular Plastic and Reconstructive Surgery Department, Tehran University of Medical Sciences, Farabi Eye Research Center, Tehran, Iran
ABSTRACT Purpose: To report 3 cases of cherubism, one of whom underwent surgery for orbital manifestations, and to provide a literature review. Case reports: Our patients were normal at birth and developed painless enlarging of the cheeks and jaws when they were 4–5 years old. Ophthalmologic examinations showed mild proptosis, superior globe displacement and inferior scleral show in all cases. Cases 2 and 3 had lower lid skin discoloration. Computed tomography (CT) scans demonstrated bilateral multicystic lesions in the maxilla and mandible with cortical thinning in all cases. In Case 3, left eye hyperglobus and anisometropic amblyopia was seen. In this case, the CT scan showed a round, well-defined and homogeneous mass, involving the anterior and superior walls of the maxillary sinus on the left side, extending into inferior orbit. Debulking of the mass was performed at the surgery. The pathologic findings were compatible with the diagnosis of giant cell reparative granuloma. He returned 1 year after surgery with recurrence of the mass. Discussion: A few cases were reported in the literature with histopathologically proven orbital cherubism. To our knowledge, lower lid skin discoloration in Cases 2 and 3 and anisometropic amblyopia in case 3 were not described elsewhere in cherubism cases. We recommend that all cases with cherubism must be examined by an ophthalmologist to diagnose and treat possible orbital manifestations. Keywords: Cherubism, giant cell granuloma, giant cell reparative granuloma
INTRODUCTION
CASE REPORTS
In 1933, a Canadian radiologist, W.A. Jones described a ‘‘familial multilocular cystic disease of the jaws’’ in 3 patients.1,2 The disease was named as ‘‘cherubism’’ because the appearance of these patients (‘‘full, round cheeks’’ and upward looking) was like angels that look toward the heaven in the Baroque art.1–10 A few cases were reported in the literature with histopathologically-proven orbital cherubism.2–6 In this article, we reported 3 cases of cherubism with some new findings. One of them (Case 3) underwent surgery for orbital manifestations.
Our patients were normal at birth and developed painless enlarging of the cheeks and jaws when they had been 4–5 years old. Ophthalmologic examinations showed mild proptosis, superior globe displacement, inferior scleral show, lower lid retraction, and medial canthus prominency in all cases. Case 2 and 3 had lower lid skin discoloration. Other slit-lamp exams, intraocular pressures, fundi and optic nerves were normal. Computed tomography (CT) scans demonstrated bilateral multicystic lesions in the maxilla and mandible with cortical thinning.
Received 10 December 2013; Revised 9 March 2014; Accepted 28 July 2014; Published online 29 September 2014 Correspondence: Bahram Eshraghi, Farabi Eye Hospital, Ghazvin Square, Tehran, Iran, Postal code: 1336616351, Tel: 00989122470416, Fax: 00982155409095, E-mail: [email protected]
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34 A. Mirmohammadsadeghi et al.
Cases 1 and 2 At the first visit, case 1 was 27 years old and case 2 was 26 years old. Both cases were female. They had no ocular complaints. In ophthalmologic examinations, only significant finding was mild restriction of both eye movements in inferior gaze (see Figures 1 and 2). First callout Figure 1 and Figure 2. Visual acuity was 20/20 in both cases. Exophthalmometry readings were 20 mm in the right eye and 19 mm in the left eye in case 1 and 19 mm in both eyes in case 2. No surgical procedure was done in these cases. There was no progression from 5 years ago in these cases.
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 04/24/15 For personal use only.
Case 3 Case 3 was a 21-year-old male. His parents noted enlarging cheeks and jaws when he was 5 years old. He noted that these manifestations had no progression from 6 years ago, but complained of upward deviation of the left eye from 3 years ago.
Best corrected visual acuity was 20/20 in the right eye and 20/50 in the left eye (see Figure 3). First callout Figure 3. Cycloplegic refraction was +1.00 in the right eye and +4.5–3.5 10 in the left eye. In strabismus examinations, left eye hyperglobus with no shift on alternate cover test was seen. Motility examinations showed moderate restriction of left eye movement in inferior gaze. Objective intorsion was found in fundus examination of the left eye. Optic nerves were normal in both eyes. No afferent papillary defect was present. Color vision tests, contrast sensitivity, and other ophthalmologic examinations were also normal in both eyes. Blood calcium, phosphorus, alkaline phosphatase, and parathyroid hormone were within normal limits. The CT scan showed a round, well-defined and homogeneous mass, involving the anterior and superior walls of the maxillary sinus on the left side, extending into inferior orbit. The globe and inferior rectus muscle were displaced into an upward position. Multilocular radiolucencies were seen in the mandible and some parts of the maxilla.
FIGURE 1. Case 1. Top left: Face appearance shows expansion of cheeks and jaws, upward globe displacement, lower lid retraction and mild proptosis in both eyes. Top right and bottom: The CT scan shows bilateral radiolucencies and multicystic lesions in the maxilla and mandible. Orbit
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 04/24/15 For personal use only.
Three Cases of Cherubism
35
FIGURE 2. Case 2. Top left: Face appearance shows expansion of cheeks and jaws, upward globe displacement, lower lid retraction and mild proptosis in both eyes. Lower lid discoloration is evident, especially in the right side. Top right and bottom: The CT scan shows bilateral multicystic lesions in the maxilla and mandible.
The surgery was performed with transconjunctival incision. After dissection, the inferior orbital wall was exposed. A large mass in the inferior orbital wall, involving infraorbital canal was seen. The mass had a thin bony capsule and soft brown material inside. There was massive bleeding from mass that controlled with cautery. Due to infraorbital canal involvement, only debulking and curettage of the mass were performed. In the pathology of the lesion, diffusely scattered osteoclastic type multinucleated giant cells in a background of uniform spindle cells and areas of hemorrhage with hemosiderin pigment deposition were seen. These findings were compatible with the pathologic diagnosis of giant cell reparative granuloma. After surgery, his Cosmesis was improved considerably. He returned 1 year after surgery with recurrence of the mass. Best corrected visual acuity was 20/20 in right eye and 20/40 in left eye. Cycloplegic refraction was the same as preoperative refraction. The CT scan was similar to preoperative CT scanning and demonstrated a mass in the !
2015 Informa Healthcare USA, Inc.
maxillary sinus and inferior orbit. He did not accept further surgery.
DISCUSSION Cherubism is a familial disorder of maxilla and mandible that inherited in an autosomal dominant manner with variable penetrance.2, 7 The mutations in the SH3-binding protein 2 (SH3BP2) gene on chromosome 4p16.3 found in some studies on cherubism cases.8 The mean age of the patients at presentation is 7 years old.2, 7 The symptoms began in our cases when they were 4–5 years old. The disease usually progresses until puberty and then stabilizes.3 Some of the patients experience resolution of the disease in adulthood.2 Painless expansion of the cheek and jaws is the main manifestation of this disorder.3 Several orbital manifestations of cherubism were reported in the literature: Proptosis, lower lid retraction, superior globe displacement,2–10 common canalicular
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 04/24/15 For personal use only.
36 A. Mirmohammadsadeghi et al.
FIGURE 3. Case 3. Top left: Face appearance shows enlargement of the cheeks and jaws on both sides and hyperglobus and lower lid discoloration on the left side. Top and bottom right: The CT scan shows bilateral radiolucencies in the maxilla and mandible, like two other cases. A round, well-defined and homogeneous mass is seen that involves anterior and superior walls of the maxillary sinus on the left side and extends into inferior orbit, displacing the globe and inferior rectus muscle upward. Bottom left: Histopathology of the lesion shows diffusely scattered osteoclastic type multinucleated giant cells in a background of uniform spindle cells and areas of hemorrhage (stain: hematoxylin-eosin, original magnification: 40).
obstruction,2 prominent medial canthus,9 A-pattern, superior oblique overaction, inferior oblique underaction, fundus intorsion,4 optic neuropathy, and macular striae.5 The orbital involvement may progress after puberty, when the other manifestations of cherubism are resolving (such as Case 3).3 In our cases, no signs of optic neuropathy were found. Visual loss in the left eye of Case 3 was probably due to anisometropic amblyopia induced by high with-therule astigmatism from childhood. To our knowledge, anisometropic amblyopia in Case 3 and lower lid skin discoloration in Cases 2 and 3 were not described elsewhere in cherubism cases. The CT scan shows bilateral radiolucencies that are cystic and multiloculated in the mandible and sometimes maxilla. CT scans of giant cell reparative granuloma demonstrate mass in the orbital floor and superior wall of maxillary sinus, displacing orbital contents superiorly.3,4,6 As we know, Case 3 is one of
the few reported cases of cherubism that recurrence of the mass after debulking of giant cell reparative granuloma was documented. Pathology of the lesions is similar to giant cell reparative granuloma4 and shows diffusely scattered multinucleated giant cells with foci of hemorrhage in a background of fibrous tissue.2,4 Multinucleated cells are of osteoclastic type.3,6 As we know, only few cases of cherubism with histopathologically-proven giant cell reparative granuloma were reported.4 The pathologic findings are not specific for the diagnosis of cherubism and must be interpreted in the context of clinical and radiologic findings.2,10 The differential diagnosis of cherubism includes: fibrous dysplasia, giant cell tumor, central giant cell granuloma of the bone, aneurismal bone cyst, and hyperparathyroidism.3 The clinician can differentiate cherubism from the above diseases, according to the Orbit
Three Cases of Cherubism
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 04/24/15 For personal use only.
age of onset, site of involvement, radiologic and pathologic findings, and normal serum calcium and parathyroid hormone.3 In mild cases only observation is recommended.2 In more severe cases (such as Case 3), surgical removal of the lesions with or without bone graft should be performed.10 Radiotherapy is not performed because of the risk of osteosarcoma transformation.5 The true incidence of orbital manifestations in cherubism may be more than those reported in the literature, because most reports of cherubism are found in otorhinolaryngology and maxillofacial journals that does not focus on orbital manifestations.5 So, we recommend that all cases with cherubism must be examined by an ophthalmologist to diagnose and treat possible orbital manifestations.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
!
2015 Informa Healthcare USA, Inc.
37
REFERENCES 1. Jones WA. Familial multilocular cystic disease of the jaws. Am J Cancer 1933;17:946–950. 2. Hawes MJ. Cherubism and its orbital manifestations. Ophthal Plast Reconstr Surg 1989;5:133–140. 3. Colombo F, Cursiefen C, Neukam FW, Holbach LM. Orbital involvement in cherubism. Ophthalmology 2001; 108:1884–1888. 4. Font RL, Blanco G, Soparkar CN, et al. Giant cell reparative granuloma of the orbit associated with cherubism. Ophthalmology 2003;110:1846–1849. 5. Ahmadi AJ, Pirinjian GE, Sires BS. Optic neuropathy and macular chorioretinal folds caused by orbital cherubism. Arch Ophthalmol 2003;121:570–573. 6. Carroll AL, Sullivan TJ. Orbital involvement in cherubism. Clin Experiment Ophthalmol 2001;29:38–40. 7. Peters WJ. Cherubism: a study of twenty cases from one family. Oral Surg 1979;47:307–311. 8. Tuna EB, Shimizu T, Seymen F, et al. Mutations of the SH3BP2 gene in 2 families of cherubism. Pediatr Dent 2012; 34:198–202. 9. Mehrotra D, Kesarwani A, Nandlal B. Cherubism: Case report with review of literature. J Maxillofac Oral Surg 2011; 10:64–70. 10. Zachariades N, Papanicolaou S, Xypolyta A, Constantinidis I. Cherubism. Int J Oral Surg 1985;14: 138–145.
C ASE REPORT
Cherubism: Report of Three Cases and Literature Review Arash Mirmohammadsadeghi, Bahram Eshraghi, Azadeh Shahsanaei, and Raheleh Assari
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 04/24/15 For personal use only.
Ocular Plastic and Reconstructive Surgery Department, Tehran University of Medical Sciences, Farabi Eye Research Center, Tehran, Iran
ABSTRACT Purpose: To report 3 cases of cherubism, one of whom underwent surgery for orbital manifestations, and to provide a literature review. Case reports: Our patients were normal at birth and developed painless enlarging of the cheeks and jaws when they were 4–5 years old. Ophthalmologic examinations showed mild proptosis, superior globe displacement and inferior scleral show in all cases. Cases 2 and 3 had lower lid skin discoloration. Computed tomography (CT) scans demonstrated bilateral multicystic lesions in the maxilla and mandible with cortical thinning in all cases. In Case 3, left eye hyperglobus and anisometropic amblyopia was seen. In this case, the CT scan showed a round, well-defined and homogeneous mass, involving the anterior and superior walls of the maxillary sinus on the left side, extending into inferior orbit. Debulking of the mass was performed at the surgery. The pathologic findings were compatible with the diagnosis of giant cell reparative granuloma. He returned 1 year after surgery with recurrence of the mass. Discussion: A few cases were reported in the literature with histopathologically proven orbital cherubism. To our knowledge, lower lid skin discoloration in Cases 2 and 3 and anisometropic amblyopia in case 3 were not described elsewhere in cherubism cases. We recommend that all cases with cherubism must be examined by an ophthalmologist to diagnose and treat possible orbital manifestations. Keywords: Cherubism, giant cell granuloma, giant cell reparative granuloma
INTRODUCTION
CASE REPORTS
In 1933, a Canadian radiologist, W.A. Jones described a ‘‘familial multilocular cystic disease of the jaws’’ in 3 patients.1,2 The disease was named as ‘‘cherubism’’ because the appearance of these patients (‘‘full, round cheeks’’ and upward looking) was like angels that look toward the heaven in the Baroque art.1–10 A few cases were reported in the literature with histopathologically-proven orbital cherubism.2–6 In this article, we reported 3 cases of cherubism with some new findings. One of them (Case 3) underwent surgery for orbital manifestations.
Our patients were normal at birth and developed painless enlarging of the cheeks and jaws when they had been 4–5 years old. Ophthalmologic examinations showed mild proptosis, superior globe displacement, inferior scleral show, lower lid retraction, and medial canthus prominency in all cases. Case 2 and 3 had lower lid skin discoloration. Other slit-lamp exams, intraocular pressures, fundi and optic nerves were normal. Computed tomography (CT) scans demonstrated bilateral multicystic lesions in the maxilla and mandible with cortical thinning.
Received 10 December 2013; Revised 9 March 2014; Accepted 28 July 2014; Published online 29 September 2014 Correspondence: Bahram Eshraghi, Farabi Eye Hospital, Ghazvin Square, Tehran, Iran, Postal code: 1336616351, Tel: 00989122470416, Fax: 00982155409095, E-mail: [email protected]
33
34 A. Mirmohammadsadeghi et al.
Cases 1 and 2 At the first visit, case 1 was 27 years old and case 2 was 26 years old. Both cases were female. They had no ocular complaints. In ophthalmologic examinations, only significant finding was mild restriction of both eye movements in inferior gaze (see Figures 1 and 2). First callout Figure 1 and Figure 2. Visual acuity was 20/20 in both cases. Exophthalmometry readings were 20 mm in the right eye and 19 mm in the left eye in case 1 and 19 mm in both eyes in case 2. No surgical procedure was done in these cases. There was no progression from 5 years ago in these cases.
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 04/24/15 For personal use only.
Case 3 Case 3 was a 21-year-old male. His parents noted enlarging cheeks and jaws when he was 5 years old. He noted that these manifestations had no progression from 6 years ago, but complained of upward deviation of the left eye from 3 years ago.
Best corrected visual acuity was 20/20 in the right eye and 20/50 in the left eye (see Figure 3). First callout Figure 3. Cycloplegic refraction was +1.00 in the right eye and +4.5–3.5 10 in the left eye. In strabismus examinations, left eye hyperglobus with no shift on alternate cover test was seen. Motility examinations showed moderate restriction of left eye movement in inferior gaze. Objective intorsion was found in fundus examination of the left eye. Optic nerves were normal in both eyes. No afferent papillary defect was present. Color vision tests, contrast sensitivity, and other ophthalmologic examinations were also normal in both eyes. Blood calcium, phosphorus, alkaline phosphatase, and parathyroid hormone were within normal limits. The CT scan showed a round, well-defined and homogeneous mass, involving the anterior and superior walls of the maxillary sinus on the left side, extending into inferior orbit. The globe and inferior rectus muscle were displaced into an upward position. Multilocular radiolucencies were seen in the mandible and some parts of the maxilla.
FIGURE 1. Case 1. Top left: Face appearance shows expansion of cheeks and jaws, upward globe displacement, lower lid retraction and mild proptosis in both eyes. Top right and bottom: The CT scan shows bilateral radiolucencies and multicystic lesions in the maxilla and mandible. Orbit
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 04/24/15 For personal use only.
Three Cases of Cherubism
35
FIGURE 2. Case 2. Top left: Face appearance shows expansion of cheeks and jaws, upward globe displacement, lower lid retraction and mild proptosis in both eyes. Lower lid discoloration is evident, especially in the right side. Top right and bottom: The CT scan shows bilateral multicystic lesions in the maxilla and mandible.
The surgery was performed with transconjunctival incision. After dissection, the inferior orbital wall was exposed. A large mass in the inferior orbital wall, involving infraorbital canal was seen. The mass had a thin bony capsule and soft brown material inside. There was massive bleeding from mass that controlled with cautery. Due to infraorbital canal involvement, only debulking and curettage of the mass were performed. In the pathology of the lesion, diffusely scattered osteoclastic type multinucleated giant cells in a background of uniform spindle cells and areas of hemorrhage with hemosiderin pigment deposition were seen. These findings were compatible with the pathologic diagnosis of giant cell reparative granuloma. After surgery, his Cosmesis was improved considerably. He returned 1 year after surgery with recurrence of the mass. Best corrected visual acuity was 20/20 in right eye and 20/40 in left eye. Cycloplegic refraction was the same as preoperative refraction. The CT scan was similar to preoperative CT scanning and demonstrated a mass in the !
2015 Informa Healthcare USA, Inc.
maxillary sinus and inferior orbit. He did not accept further surgery.
DISCUSSION Cherubism is a familial disorder of maxilla and mandible that inherited in an autosomal dominant manner with variable penetrance.2, 7 The mutations in the SH3-binding protein 2 (SH3BP2) gene on chromosome 4p16.3 found in some studies on cherubism cases.8 The mean age of the patients at presentation is 7 years old.2, 7 The symptoms began in our cases when they were 4–5 years old. The disease usually progresses until puberty and then stabilizes.3 Some of the patients experience resolution of the disease in adulthood.2 Painless expansion of the cheek and jaws is the main manifestation of this disorder.3 Several orbital manifestations of cherubism were reported in the literature: Proptosis, lower lid retraction, superior globe displacement,2–10 common canalicular
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 04/24/15 For personal use only.
36 A. Mirmohammadsadeghi et al.
FIGURE 3. Case 3. Top left: Face appearance shows enlargement of the cheeks and jaws on both sides and hyperglobus and lower lid discoloration on the left side. Top and bottom right: The CT scan shows bilateral radiolucencies in the maxilla and mandible, like two other cases. A round, well-defined and homogeneous mass is seen that involves anterior and superior walls of the maxillary sinus on the left side and extends into inferior orbit, displacing the globe and inferior rectus muscle upward. Bottom left: Histopathology of the lesion shows diffusely scattered osteoclastic type multinucleated giant cells in a background of uniform spindle cells and areas of hemorrhage (stain: hematoxylin-eosin, original magnification: 40).
obstruction,2 prominent medial canthus,9 A-pattern, superior oblique overaction, inferior oblique underaction, fundus intorsion,4 optic neuropathy, and macular striae.5 The orbital involvement may progress after puberty, when the other manifestations of cherubism are resolving (such as Case 3).3 In our cases, no signs of optic neuropathy were found. Visual loss in the left eye of Case 3 was probably due to anisometropic amblyopia induced by high with-therule astigmatism from childhood. To our knowledge, anisometropic amblyopia in Case 3 and lower lid skin discoloration in Cases 2 and 3 were not described elsewhere in cherubism cases. The CT scan shows bilateral radiolucencies that are cystic and multiloculated in the mandible and sometimes maxilla. CT scans of giant cell reparative granuloma demonstrate mass in the orbital floor and superior wall of maxillary sinus, displacing orbital contents superiorly.3,4,6 As we know, Case 3 is one of
the few reported cases of cherubism that recurrence of the mass after debulking of giant cell reparative granuloma was documented. Pathology of the lesions is similar to giant cell reparative granuloma4 and shows diffusely scattered multinucleated giant cells with foci of hemorrhage in a background of fibrous tissue.2,4 Multinucleated cells are of osteoclastic type.3,6 As we know, only few cases of cherubism with histopathologically-proven giant cell reparative granuloma were reported.4 The pathologic findings are not specific for the diagnosis of cherubism and must be interpreted in the context of clinical and radiologic findings.2,10 The differential diagnosis of cherubism includes: fibrous dysplasia, giant cell tumor, central giant cell granuloma of the bone, aneurismal bone cyst, and hyperparathyroidism.3 The clinician can differentiate cherubism from the above diseases, according to the Orbit
Three Cases of Cherubism
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 04/24/15 For personal use only.
age of onset, site of involvement, radiologic and pathologic findings, and normal serum calcium and parathyroid hormone.3 In mild cases only observation is recommended.2 In more severe cases (such as Case 3), surgical removal of the lesions with or without bone graft should be performed.10 Radiotherapy is not performed because of the risk of osteosarcoma transformation.5 The true incidence of orbital manifestations in cherubism may be more than those reported in the literature, because most reports of cherubism are found in otorhinolaryngology and maxillofacial journals that does not focus on orbital manifestations.5 So, we recommend that all cases with cherubism must be examined by an ophthalmologist to diagnose and treat possible orbital manifestations.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
!
2015 Informa Healthcare USA, Inc.
37
REFERENCES 1. Jones WA. Familial multilocular cystic disease of the jaws. Am J Cancer 1933;17:946–950. 2. Hawes MJ. Cherubism and its orbital manifestations. Ophthal Plast Reconstr Surg 1989;5:133–140. 3. Colombo F, Cursiefen C, Neukam FW, Holbach LM. Orbital involvement in cherubism. Ophthalmology 2001; 108:1884–1888. 4. Font RL, Blanco G, Soparkar CN, et al. Giant cell reparative granuloma of the orbit associated with cherubism. Ophthalmology 2003;110:1846–1849. 5. Ahmadi AJ, Pirinjian GE, Sires BS. Optic neuropathy and macular chorioretinal folds caused by orbital cherubism. Arch Ophthalmol 2003;121:570–573. 6. Carroll AL, Sullivan TJ. Orbital involvement in cherubism. Clin Experiment Ophthalmol 2001;29:38–40. 7. Peters WJ. Cherubism: a study of twenty cases from one family. Oral Surg 1979;47:307–311. 8. Tuna EB, Shimizu T, Seymen F, et al. Mutations of the SH3BP2 gene in 2 families of cherubism. Pediatr Dent 2012; 34:198–202. 9. Mehrotra D, Kesarwani A, Nandlal B. Cherubism: Case report with review of literature. J Maxillofac Oral Surg 2011; 10:64–70. 10. Zachariades N, Papanicolaou S, Xypolyta A, Constantinidis I. Cherubism. Int J Oral Surg 1985;14: 138–145.
