PATHOLOGY
Total Spontaneous Regression of a Central Giant Cell Granuloma After Incisional Biopsy: A Four-Year Follow-Up Case Report der Ricardo Biasoli, DDS, PhD,y R ubia da Rocha Vieira, DDS,* E Marcelo Macedo Crivelini, DDS, PhD,z and Glauco Issamu Miyahara, DDS, PhDx Central giant cell granuloma (CGCG) of the jaws represents a localized and benign neoplastic lesion sometimes characterized by aggressive osteolytic proliferation. The World Health Organization defines it as an intraosseous lesion composed of cellular and dense connective tissues that contain multiple hemorrhagic foci, an aggregation of multinucleated giant cells, and occasional bone tissue trabeculae. The origin of this lesion is uncertain; however, factors such as local trauma, inflammation, intraosseous hemorrhage, and genetic abnormalities have been identified as possible causes. CGCG generally affects those younger than 30 years and occurs more frequently in women (2:1). This lesion corresponds to approximately 7% of all benign tumors of the jaws, with prevalence in the anterior region of the jaw. Aggressive lesions are characterized by symptoms, such as pain, numbness, rapid growth, cortical perforation, root resorption, and a high recurrence rate after curettage. In contrast, nonaggressive CGCGs have a slow rate of growth, may contain sparse trabeculation, and are less likely to move teeth or cause root resorption or cortical perforation. Nonaggressive CGCGs are generally asymptomatic lesions and thus are frequently found on routine dental radiographs. Radiographically, the 2 forms of CGCG present as radiolucent, expansive, unilocular or multilocular masses with well-defined margins. The histopathology of CGCG is characterized by multinucleated giant cells, surrounded by round, oval, and spindle-shaped mononuclear cells, scattered in dense connective tissue with hemorrhagic and abundant vascularization foci. The final diagnosis is determined by histopathologic analysis of the biopsy specimen. The preferred treatment for CGCG consists of excisional biopsy, curettage with a safety margin, and partial or total resection of the affected bone. Conservative treatments include local injections of steroids, calcitonin, and antiangiogenic therapy. Drug treatment using antibiotics, painkillers, and corticosteroids and clinical and radiographic monitoring are necessary for approximately 10 days after surgery. There are only a few cases of spontaneous CGCG regression described in the literature; therefore, a detailed case report of CGCG regression in a 12-yearold boy with a 4-year follow-up is presented and compared with previous studies. Ó 2014 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 72:730-736, 2014 Central giant cell granuloma (CGCG) of the jaws represents a localized and benign neoplastic lesion sometimes characterized by aggressive osteolytic proliferation.1 The World Health Organization defines it as an intraosseous lesion composed of cellular and dense
connective tissues that contain multiple hemorrhagic foci, an aggregation of multinucleated giant cells, and occasional bone tissue trabeculae.2,3 The origin of this lesion is uncertain4; however, factors such as local trauma, inflammation, intraosseous hemorrhage, and
Received from the Arac¸atuba School of Dentistry, Universidade
tologia de Arac¸atuba, Universidade Estadual Paulista, Rua Jose
Estadual Paulista, Arac¸atuba, S~ao Paulo, Brazil.
Bonifacio, 1.193, CEP 16015-050 Arac¸atuba, S~ao Paulo, Brazil;
*Postgraduate Student, Oral Oncology Center and Department of
e-mail: [email protected]
Pathology and Clinical Propaedeutics.
Received August 13 2013
yProfessor, Oral Oncology Center and Department of Pathology
Accepted October 8 2013 Ó 2014 American Association of Oral and Maxillofacial Surgeons
and Clinical Propaedeutics. zProfessor, Department of Pathology and Clinical Propaedeutics. xProfessor, Oral Oncology Center and Department of Pathology
0278-2391/13/01321-9$36.00/0 http://dx.doi.org/10.1016/j.joms.2013.10.009
and Clinical Propaedeutics. Address correspondence and reprint requests to Dr Miyahara: Departamento de patologia e proped^eutica clınica, Faculdade de Odon-
730
731
VIEIRA ET AL
FIGURE 1. Initial panoramic radiograph shows a radiolucent lesion with radiopaque and well-defined areas in the periapical region of the mandibular anterior teeth and the presence of supernumerary teeth. Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
genetic abnormalities have been identified as possible causes.5 CGCG generally affects those younger than 30 years and occurs more frequently in women (2:1).6 This lesion corresponds to approximately 7% of all benign tumors of the jaws,7,8 with prevalence in the anterior region of the jaw.9 Chuong et al10 classified CGCGs as aggressive or nonaggressive, depending on the symptomatic and histopathologic characteristics. Aggressive lesions are characterized by symptoms such as pain, numbness, rapid growth, cortical perforation, root resorption, and a high recurrence rate after curettage.11,12 In contrast, nonaggressive CGCGs have a slow rate of growth, may contain sparse trabeculation,6,11 and are less likely to move teeth or cause root resorption or cortical perforation.13,14 Because nonaggressive CGCGs are generally asymptomatic lesions, they are frequently found on routine dental radiographs.15 Radiographically, the 2 forms of CGCG present as radiolucent, expansive, unilocular, or multilocular masses with well-defined margins. The histopathology of CGCG is characterized by multinucleated giant cells, surrounded by round, oval, and spindle-shaped mononuclear cells, scattered in dense connective tissue with hemorrhagic and abundant vascularization foci.16 Because CGCG is generally radiographically and clinically similar to other lesions, the final diagnosis is determined by histopathologic analysis of the biopsy specimen.17 Some differential diagnoses that must be considered along-
side CGCG are the aneurysmal bone cyst and the brown tumor of hyperparathyroidism.18 The preferred treatment for CGCG is surgical and consists of excisional biopsy, curettage with a safety margin, and partial or total resection of the affected bone.11,19 Conservative treatments include local injections of steroids, calcitonin, and antiangiogenic therapy.20,21 Drug treatment using antibiotics, painkillers, and corticosteroids and clinical and radiographic monitoring are necessary for approximately 10 days after surgery.19 The CGCG recurrence rate ranges from 13 to 49%, typical of aggressive lesions.22,23 Currently, there are only a few cases of spontaneous CGCG regression described in the literature; therefore, a detailed case report of CGCG regression in a 12-year-old boy with a 4-year follow-up is presented and compared with previous studies.
Report of Case A 12-year old boy was referred by a dentist for the treatment of a radiolucent jaw lesion to the Arac¸atuba School of Dentistry, Universidade Estadual Paulista (Arac¸atuba, S~ao Paulo, Brazil). Abnormalities were not observed during the extrabuccal examination. During the intrabuccal examination, a scar tissue line was located in the vestibular fornix in the anterior mandibular region. This finding was a result of a previous biopsy, which was diagnosed as fibrous dysplasia of the bone. A panoramic radiograph indicated a radiolucent
732
REGRESSION OF CENTRAL GIANT CELL GRANULOMA
FIGURE 2. Central giant cell granuloma, typical proliferation of mononuclear cells, and multinucleated giant cells in a fibrovascular stroma (hematoxylin and eosin stain; magnification, 200). Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
FIGURE 3. Central giant cell granuloma with cellular elements, especially multinucleated giant cells, ovoid mesenchymal cells, and red blood cells dispersed in a stroma of fibrillar collagen (hematoxylin and eosin stain; magnification, 400). Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
lesion with well-defined radiopaque areas in the periapical region of the mandibular anterior teeth and the presence of supernumerary teeth (Fig 1). Because these characteristics did not support the diagnosis of fibrous dysplasia of the bone, a pathologic slide was requested for re-evaluation, but without success. Thus, a new incisional biopsy was performed and an important clinical characteristic observed during the surgical procedure was the presence of a tissue mass inside the bone cavity. A sample of the tissue mass was collected for histopathologic analysis. The histopathologic evaluation showed proliferation of mononuclear cells and multinucleated giant cells in addition to ovoid mesenchymal cells and red blood cells scattered in a stroma of fibrillar collagen (Figs 2 to 5), which are characteristics supporting the CGCG diagnosis. Biochemical blood tests were performed to exclude the diagnosis of brown tumor of hyperparathyroidism and showed normal calcium and phosphorus levels and an increase in the alkaline phosphatase level
733
VIEIRA ET AL
FIGURE 4. Photomicrograph from a histologic slice displaying a variable number of giant cells (arrows) (hematoxylin and eosin stain; magnification, 20). Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
(799 m/l). Based on these data, the initially proposed treatment to the patient was lesion excision with cryotherapy. However, the caregiver of the patient did not authorize the treatment because she wanted to hear a second opinion from another treatment
center. Eight months later, the patient and his caregiver returned to the Oral Oncology Center because the other treatment center had proposed excision of the lesion in addition to extraction of the mandibular incisors, which was a more drastic
FIGURE 5. Photomicrograph from a histologic slice showing a variable number of giant cells (arrows) (hematoxylin and eosin stain; magnification, 400). Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
734
REGRESSION OF CENTRAL GIANT CELL GRANULOMA
FIGURE 6. Panoramic radiograph 8 months after initial diagnosis. The presence of a radiopaque area at the same place as the lesion suggests bone repair. Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
intervention than the one initially proposed. While carrying out a new radiographic examination and comparing it with previous radiographs, surprisingly,
a spontaneous regression of the lesion was noticed, because the radiographic examination displayed a radiopaque area in the same location as the previous
FIGURE 7. Panoramic radiograph at 4-year follow-up confirms total spontaneous regression of the lesion. Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
735
VIEIRA ET AL
lesion (Fig 6). At this time, no additional surgical intervention was performed, and the patient was scheduled for annual follow-up visits (Fig 7). This study was completed with the written approval of the patient, which followed the guidelines of investigation according to the Declaration of Helsinki.
Discussion With respect to the characteristics of the studied lesion, it is important to note that this is a rare case of spontaneous CGCG regression in a male patient at an atypical age. Whitaker and Bouquot24 stated that the group most affected by CGCG lesions are female individuals younger than 30 years18; however, de Lange et al20 reported a peak incidence in girls 15 to 19 years old and in boys 10 to 14 years old.25,26 In this case study, the CGCG lesion affected the anterior mandibular region, an area that is less likely to be affected by this type of lesion. Bataineh et al4 stated that the molar and ramus region (37%) is the most affected area, followed by the incisor and canine region (28%), the premolar and molar region (22%), and the premolars (11%). In addition, Imad et al27 reported that 50% of lesions affect the premolar and molar region. Through thorough analysis of the clinical characteristics of the present case, the diagnosis of a CGCG was strongly supported because the lesion appeared asymptomatically, clinically causing only a slight deviation in the lower anterior teeth. The CGCG diagnosis was supported by histopathologic characteristics found in the sample biopsy and by radiographic analysis, characteristics that were in agreement with data in the literature.13,16,28 The treatment of CGCG generally consists of surgical removal or the use of alternative therapies.4 However, in the present case, if the caregiver of the patient had not decided to seek a second opinion at another treatment center, the proposed initial treatment certainly would have been performed and any lesion regression would have been believed to occur from the surgical intervention. In the literature, there are few reports on spontaneous regressions of CGCG. Worth29 reported some cases of CGCG that spontaneously regressed in 1963. These cases were not treated surgically, but were radiographically monitored. Years later, biopsies were performed in some of these cases and only fibrous scars were found. Berti et al30 reported another clinical case of partial spontaneous CGCG regression after an incisional biopsy in a 53-year-old woman, which is similar to the present case. Although the age, gender, and affected area were different, the case development was very similar. In the case described by Berti et al,30 an incisional biopsy was performed and the patient
was referred for an endocrinologic evaluation. Nineteen months later, owing to difficulty obtaining the evaluation, the patient returned to proceed with the initially proposed treatment, and a new panoramic radiograph displayed a radiopaque area in place of the lesion, suggesting bone repair. In the literature, there are some pieces of evidence that may explain how spontaneous CGCG regression occurs. Liu et al31 and Itonaga et al12 stated that in CGCG lesions, multinucleated giant cells concentrate in hemorrhagic areas adjacent to blood vessels. Jaffe32 reported that these same cells exhibit a phagocytic response to hemorrhage. Furthermore, Berti et al30 suggested that surgical intervention of the lesion results in an intraosseous blood clot, decreasing osteoclastic activity and promoting osteoblastic activity, resulting in new bone formation. Therefore, the incisional biopsy procedure performed in the present case study may have promoted or induced CGCG regression. The present case report describes a rare clinical situation that deviated from routine procedures by chance, because no treatment was carried out after the biopsy; nevertheless, spontaneous regression occurred, which was confirmed by 4-year clinical and radiographic follow-up of the patient. The spontaneous regression observed in this study indicates that more research is needed to evaluate treatment options for CGCG lesions.
References 1. Potter BJ, Tiner BD: Central giant cell granuloma. Report of a case. Oral Surg Oral Med Oral Pathol 75:286, 1993 2. Kramer IR, Pindborg JJ, Shear M: The World Health Organization histological typing of odontogenic tumours. Introducing the second edition. Eur J Cancer B Oral Oncol 29B:169, 1993 3. Motamedi MH, Eshghyar N, Jafari SM, et al: Peripheral and central giant cell granulomas of the jaws: A demographic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103:e39, 2007 4. Bataineh AB, Al-Khateeb T, Rawashdeh MA: The surgical treatment of central giant cell granuloma of the mandible. J Oral Maxillofac Surg 60:756, 2002 5. Lin YJ, Chen HS, Chen HR: Central giant cell granuloma of the mandible in a 7-year-old boy: A case report. Quintessence Int 38:253, 2007 6. Carlos R, Sedano HO: Intra-lesional corticosteroids as an alternative treatment for central giant cell granuloma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93:161, 2002 7. Austin LT, Dahlin DC, Royer RQ: Giant cell reparative granuloma and related conditions affecting the jaw bones. Oral Surg Oral Med Oral Pathol 12:1285, 1959 8. Suarez-Roa MDL, Reveiz L, Ruız-Godoy-Rivera LM, et al: Primary surgical versus primary non-surgical interventions for central giant cell granuloma (CGCG) of the jaws (protocol). Cochrane Database Syst Rev 7: CD007404, 2009 9. Sidhu MS, Parkash H, Sidhu SS: Central giant cell granulomas of jaws: Review of 19 cases. Br J Oral Maxillofac Surg 33:43, 1995 10. Chuong R, Kaban LB, Kozakewich H: Central giant cell lesions of the jaws: A clinicopathologic study. J Oral Maxillofac Surg 44: 708, 1986 11. Farrier SL, Farrier JN, Smart MK, et al: A 10-year review of the occurrence and treatment of central giant cell granuloma, in a district general hospital. J Oral Pathol Med 35: 332, 2006
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12. Itonaga I, Hussein I, Kudo O: Cellular mechanisms of osteoclast formation and lacunar resorption in giant cell granuloma of the jaw. J Oral Pathol Med 32:224, 2003 13. G€ ung€ orm€ us M, Akg€ ul HM: Central giant cell granuloma of the jaws: A clinical and radiologic study. J Contemp Dent Pract 4:87, 2003 14. Kaffe I, Ardekian L, Taicher S, et al: Radiologic features of central giant cell granuloma of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 81:720, 1996 15. Pilch BZ: Head and Neck Surgical Pathology. Philadelphia, PA, Lippincott and Wilkins, 2001, pp 456–458 16. Ahmed S, Babu I, Priya SP: Central giant cell granuloma—A case report. J Oral Maxillofac Pathol 7:111, 2003 17. Daryani D, Gopakumar R: Central giant cell granuloma mimicking an adenomatoid odontogenic tumor. Contemp Clin Dent 2:249, 2011 18. Ustundag E, Iseri M, Keskin G, et al: Central giant cell granuloma. Int J Pediatr Otorhinolaryngol 65:143, 2002 19. Uzbek UH, Mushtaq I: Giant cell granuloma of the maxilla. J Ayub Med Coll Abbottabad 19:93, 2007 20. de Lange J, van den Akker HP, van den Berg H: Central giant cell granuloma of the jaw: A review of the literature with emphasis on therapy options. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:603, 2007 21. Regezi JA: Odontogenic cysts, odontogenic tumors, fibroosseous and giant cell lesions of the jaws. Mod Pathol 15:331, 2002 22. Adornato MC, Paticoff KA: Intralesional corticosteroid injection for treatment of central giant-cell granuloma. J Am Dent Assoc 132:186, 2001 23. Losler BK, Diallo R, Gaertner C, et al: Central giant cell granuloma of the jaws: A clinical, radiologic, and histopathologic
study of 26 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:346, 2006 Whitaker SB, Bouquot JE: Estrogen and progesterone receptor status of central giant cell lesions of the jaws. Oral Surg Oral Med Oral Pathol 77:641, 1994 Barnes L, Eveson JW, Reichart P, et al, (eds): World Health Organization Classification of Tumours: Head and Neck Tumours. Lyon, France, IARC Press, 2005 Waldron CA, Shafer WG: The central giant cell reparative granuloma of the jaws. An analysis of 38 cases. Am J Clin Pathol 45: 437, 1966 Imad Abu-El-Naaj I, Ardekian L, Liberman R: Central giant cell granuloma of the mandibular condyle: A rare presentation. J Oral Maxillofac Surg 60:939, 2002 Whitaker SB, Waldron CA: Central giant cell lesions of the jaws. A clinical, radiologic, and histopathologic study. Oral Surg Oral Med Oral Pathol Oral 75:199, 1993 Worth HM: Principles and Practice or Oral Radiology Interpretation. Chicago, IL, Chicago Yearbook Medical Publishers, 1963, pp 498–505 Berti SA, Souza PHC, Jacobs R, et al: Spontaneous resolution of a central giant-cell granuloma after incisional biopsy: A case report. J Oral Maxillofac Surg 67:1543, 2009 Liu B, Yu S-F, Li T-J: Multinucleated giant cells in various forms of giant cell containing lesions of the jaws express features of osteoclasts. J Oral Pathol Med 32:367, 2003 Jaffe HL: Giant cell reparative granuloma, traumatic bone cysts, and fibrous-osseous dysplasia of the jawbones. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 6:150, 1953
24.
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31.
32.
Total Spontaneous Regression of a Central Giant Cell Granuloma After Incisional Biopsy: A Four-Year Follow-Up Case Report der Ricardo Biasoli, DDS, PhD,y R ubia da Rocha Vieira, DDS,* E Marcelo Macedo Crivelini, DDS, PhD,z and Glauco Issamu Miyahara, DDS, PhDx Central giant cell granuloma (CGCG) of the jaws represents a localized and benign neoplastic lesion sometimes characterized by aggressive osteolytic proliferation. The World Health Organization defines it as an intraosseous lesion composed of cellular and dense connective tissues that contain multiple hemorrhagic foci, an aggregation of multinucleated giant cells, and occasional bone tissue trabeculae. The origin of this lesion is uncertain; however, factors such as local trauma, inflammation, intraosseous hemorrhage, and genetic abnormalities have been identified as possible causes. CGCG generally affects those younger than 30 years and occurs more frequently in women (2:1). This lesion corresponds to approximately 7% of all benign tumors of the jaws, with prevalence in the anterior region of the jaw. Aggressive lesions are characterized by symptoms, such as pain, numbness, rapid growth, cortical perforation, root resorption, and a high recurrence rate after curettage. In contrast, nonaggressive CGCGs have a slow rate of growth, may contain sparse trabeculation, and are less likely to move teeth or cause root resorption or cortical perforation. Nonaggressive CGCGs are generally asymptomatic lesions and thus are frequently found on routine dental radiographs. Radiographically, the 2 forms of CGCG present as radiolucent, expansive, unilocular or multilocular masses with well-defined margins. The histopathology of CGCG is characterized by multinucleated giant cells, surrounded by round, oval, and spindle-shaped mononuclear cells, scattered in dense connective tissue with hemorrhagic and abundant vascularization foci. The final diagnosis is determined by histopathologic analysis of the biopsy specimen. The preferred treatment for CGCG consists of excisional biopsy, curettage with a safety margin, and partial or total resection of the affected bone. Conservative treatments include local injections of steroids, calcitonin, and antiangiogenic therapy. Drug treatment using antibiotics, painkillers, and corticosteroids and clinical and radiographic monitoring are necessary for approximately 10 days after surgery. There are only a few cases of spontaneous CGCG regression described in the literature; therefore, a detailed case report of CGCG regression in a 12-yearold boy with a 4-year follow-up is presented and compared with previous studies. Ó 2014 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 72:730-736, 2014 Central giant cell granuloma (CGCG) of the jaws represents a localized and benign neoplastic lesion sometimes characterized by aggressive osteolytic proliferation.1 The World Health Organization defines it as an intraosseous lesion composed of cellular and dense
connective tissues that contain multiple hemorrhagic foci, an aggregation of multinucleated giant cells, and occasional bone tissue trabeculae.2,3 The origin of this lesion is uncertain4; however, factors such as local trauma, inflammation, intraosseous hemorrhage, and
Received from the Arac¸atuba School of Dentistry, Universidade
tologia de Arac¸atuba, Universidade Estadual Paulista, Rua Jose
Estadual Paulista, Arac¸atuba, S~ao Paulo, Brazil.
Bonifacio, 1.193, CEP 16015-050 Arac¸atuba, S~ao Paulo, Brazil;
*Postgraduate Student, Oral Oncology Center and Department of
e-mail: [email protected]
Pathology and Clinical Propaedeutics.
Received August 13 2013
yProfessor, Oral Oncology Center and Department of Pathology
Accepted October 8 2013 Ó 2014 American Association of Oral and Maxillofacial Surgeons
and Clinical Propaedeutics. zProfessor, Department of Pathology and Clinical Propaedeutics. xProfessor, Oral Oncology Center and Department of Pathology
0278-2391/13/01321-9$36.00/0 http://dx.doi.org/10.1016/j.joms.2013.10.009
and Clinical Propaedeutics. Address correspondence and reprint requests to Dr Miyahara: Departamento de patologia e proped^eutica clınica, Faculdade de Odon-
730
731
VIEIRA ET AL
FIGURE 1. Initial panoramic radiograph shows a radiolucent lesion with radiopaque and well-defined areas in the periapical region of the mandibular anterior teeth and the presence of supernumerary teeth. Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
genetic abnormalities have been identified as possible causes.5 CGCG generally affects those younger than 30 years and occurs more frequently in women (2:1).6 This lesion corresponds to approximately 7% of all benign tumors of the jaws,7,8 with prevalence in the anterior region of the jaw.9 Chuong et al10 classified CGCGs as aggressive or nonaggressive, depending on the symptomatic and histopathologic characteristics. Aggressive lesions are characterized by symptoms such as pain, numbness, rapid growth, cortical perforation, root resorption, and a high recurrence rate after curettage.11,12 In contrast, nonaggressive CGCGs have a slow rate of growth, may contain sparse trabeculation,6,11 and are less likely to move teeth or cause root resorption or cortical perforation.13,14 Because nonaggressive CGCGs are generally asymptomatic lesions, they are frequently found on routine dental radiographs.15 Radiographically, the 2 forms of CGCG present as radiolucent, expansive, unilocular, or multilocular masses with well-defined margins. The histopathology of CGCG is characterized by multinucleated giant cells, surrounded by round, oval, and spindle-shaped mononuclear cells, scattered in dense connective tissue with hemorrhagic and abundant vascularization foci.16 Because CGCG is generally radiographically and clinically similar to other lesions, the final diagnosis is determined by histopathologic analysis of the biopsy specimen.17 Some differential diagnoses that must be considered along-
side CGCG are the aneurysmal bone cyst and the brown tumor of hyperparathyroidism.18 The preferred treatment for CGCG is surgical and consists of excisional biopsy, curettage with a safety margin, and partial or total resection of the affected bone.11,19 Conservative treatments include local injections of steroids, calcitonin, and antiangiogenic therapy.20,21 Drug treatment using antibiotics, painkillers, and corticosteroids and clinical and radiographic monitoring are necessary for approximately 10 days after surgery.19 The CGCG recurrence rate ranges from 13 to 49%, typical of aggressive lesions.22,23 Currently, there are only a few cases of spontaneous CGCG regression described in the literature; therefore, a detailed case report of CGCG regression in a 12-year-old boy with a 4-year follow-up is presented and compared with previous studies.
Report of Case A 12-year old boy was referred by a dentist for the treatment of a radiolucent jaw lesion to the Arac¸atuba School of Dentistry, Universidade Estadual Paulista (Arac¸atuba, S~ao Paulo, Brazil). Abnormalities were not observed during the extrabuccal examination. During the intrabuccal examination, a scar tissue line was located in the vestibular fornix in the anterior mandibular region. This finding was a result of a previous biopsy, which was diagnosed as fibrous dysplasia of the bone. A panoramic radiograph indicated a radiolucent
732
REGRESSION OF CENTRAL GIANT CELL GRANULOMA
FIGURE 2. Central giant cell granuloma, typical proliferation of mononuclear cells, and multinucleated giant cells in a fibrovascular stroma (hematoxylin and eosin stain; magnification, 200). Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
FIGURE 3. Central giant cell granuloma with cellular elements, especially multinucleated giant cells, ovoid mesenchymal cells, and red blood cells dispersed in a stroma of fibrillar collagen (hematoxylin and eosin stain; magnification, 400). Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
lesion with well-defined radiopaque areas in the periapical region of the mandibular anterior teeth and the presence of supernumerary teeth (Fig 1). Because these characteristics did not support the diagnosis of fibrous dysplasia of the bone, a pathologic slide was requested for re-evaluation, but without success. Thus, a new incisional biopsy was performed and an important clinical characteristic observed during the surgical procedure was the presence of a tissue mass inside the bone cavity. A sample of the tissue mass was collected for histopathologic analysis. The histopathologic evaluation showed proliferation of mononuclear cells and multinucleated giant cells in addition to ovoid mesenchymal cells and red blood cells scattered in a stroma of fibrillar collagen (Figs 2 to 5), which are characteristics supporting the CGCG diagnosis. Biochemical blood tests were performed to exclude the diagnosis of brown tumor of hyperparathyroidism and showed normal calcium and phosphorus levels and an increase in the alkaline phosphatase level
733
VIEIRA ET AL
FIGURE 4. Photomicrograph from a histologic slice displaying a variable number of giant cells (arrows) (hematoxylin and eosin stain; magnification, 20). Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
(799 m/l). Based on these data, the initially proposed treatment to the patient was lesion excision with cryotherapy. However, the caregiver of the patient did not authorize the treatment because she wanted to hear a second opinion from another treatment
center. Eight months later, the patient and his caregiver returned to the Oral Oncology Center because the other treatment center had proposed excision of the lesion in addition to extraction of the mandibular incisors, which was a more drastic
FIGURE 5. Photomicrograph from a histologic slice showing a variable number of giant cells (arrows) (hematoxylin and eosin stain; magnification, 400). Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
734
REGRESSION OF CENTRAL GIANT CELL GRANULOMA
FIGURE 6. Panoramic radiograph 8 months after initial diagnosis. The presence of a radiopaque area at the same place as the lesion suggests bone repair. Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
intervention than the one initially proposed. While carrying out a new radiographic examination and comparing it with previous radiographs, surprisingly,
a spontaneous regression of the lesion was noticed, because the radiographic examination displayed a radiopaque area in the same location as the previous
FIGURE 7. Panoramic radiograph at 4-year follow-up confirms total spontaneous regression of the lesion. Vieira et al. Regression of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2014.
735
VIEIRA ET AL
lesion (Fig 6). At this time, no additional surgical intervention was performed, and the patient was scheduled for annual follow-up visits (Fig 7). This study was completed with the written approval of the patient, which followed the guidelines of investigation according to the Declaration of Helsinki.
Discussion With respect to the characteristics of the studied lesion, it is important to note that this is a rare case of spontaneous CGCG regression in a male patient at an atypical age. Whitaker and Bouquot24 stated that the group most affected by CGCG lesions are female individuals younger than 30 years18; however, de Lange et al20 reported a peak incidence in girls 15 to 19 years old and in boys 10 to 14 years old.25,26 In this case study, the CGCG lesion affected the anterior mandibular region, an area that is less likely to be affected by this type of lesion. Bataineh et al4 stated that the molar and ramus region (37%) is the most affected area, followed by the incisor and canine region (28%), the premolar and molar region (22%), and the premolars (11%). In addition, Imad et al27 reported that 50% of lesions affect the premolar and molar region. Through thorough analysis of the clinical characteristics of the present case, the diagnosis of a CGCG was strongly supported because the lesion appeared asymptomatically, clinically causing only a slight deviation in the lower anterior teeth. The CGCG diagnosis was supported by histopathologic characteristics found in the sample biopsy and by radiographic analysis, characteristics that were in agreement with data in the literature.13,16,28 The treatment of CGCG generally consists of surgical removal or the use of alternative therapies.4 However, in the present case, if the caregiver of the patient had not decided to seek a second opinion at another treatment center, the proposed initial treatment certainly would have been performed and any lesion regression would have been believed to occur from the surgical intervention. In the literature, there are few reports on spontaneous regressions of CGCG. Worth29 reported some cases of CGCG that spontaneously regressed in 1963. These cases were not treated surgically, but were radiographically monitored. Years later, biopsies were performed in some of these cases and only fibrous scars were found. Berti et al30 reported another clinical case of partial spontaneous CGCG regression after an incisional biopsy in a 53-year-old woman, which is similar to the present case. Although the age, gender, and affected area were different, the case development was very similar. In the case described by Berti et al,30 an incisional biopsy was performed and the patient
was referred for an endocrinologic evaluation. Nineteen months later, owing to difficulty obtaining the evaluation, the patient returned to proceed with the initially proposed treatment, and a new panoramic radiograph displayed a radiopaque area in place of the lesion, suggesting bone repair. In the literature, there are some pieces of evidence that may explain how spontaneous CGCG regression occurs. Liu et al31 and Itonaga et al12 stated that in CGCG lesions, multinucleated giant cells concentrate in hemorrhagic areas adjacent to blood vessels. Jaffe32 reported that these same cells exhibit a phagocytic response to hemorrhage. Furthermore, Berti et al30 suggested that surgical intervention of the lesion results in an intraosseous blood clot, decreasing osteoclastic activity and promoting osteoblastic activity, resulting in new bone formation. Therefore, the incisional biopsy procedure performed in the present case study may have promoted or induced CGCG regression. The present case report describes a rare clinical situation that deviated from routine procedures by chance, because no treatment was carried out after the biopsy; nevertheless, spontaneous regression occurred, which was confirmed by 4-year clinical and radiographic follow-up of the patient. The spontaneous regression observed in this study indicates that more research is needed to evaluate treatment options for CGCG lesions.
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