- Email: [email protected]
Cytogenetics of Central Giant Cell Granuloma of the Mandible
PATHOLOGY
Cytogenetics of Central Giant Cell Granuloma of the Mandible Esther Manor, PhD,* Leonid Kachko, MD, PhD,y Peter A. Brennan, MD,z and Lipa Bodner, DMDx Purpose: Central giant cell granuloma is a benign entity that commonly occurs in the mandible and maxilla. It is usually treated by surgical excision, varying from curettage to en bloc resection. Because the entity is more common in diseases such as neurofibromatosis, a genetic element may be involved in its pathogenesis. Cytogenetic studies of central giant cell granuloma affecting bone are rare, and to the authors’ knowledge, there are none reported in the literature for central giant cell granuloma of the mandible. Materials and Methods:
The authors investigated the cytogenetic profile of a case occurring in the mandible. Fresh biopsy tissue was minced and cultured in RPMI-1640 medium. Cells were fixed and stained, and cytogenetic analysis was performed according to standard procedures.
Results:
A clone with t(1;17;18) and other random numerical chromosomal changes was found.
Conclusions:
The significance of these findings in diagnosis and prognosis is currently unclear and further karyotyping studies are needed to more fully understand this tumor. Ó 2013 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 71:1541-1544, 2013
Central giant cell granuloma (CGCG) is a benign bone lesion that usually occurs in the mandible and maxilla and accounts for fewer than 7% of all benign tumors of the jaws.1 CGCG also can affect other facial and cranial bones and small long bones, such as those of the hands and feet.2 It is more common in adolescents and young adults.3 CGCGs consist of numerous multinucleated giant cells and mononuclear cells embedded in a fibrocellular stroma. Foci of hemosiderin pigment and newly formed osteoid or bone are occasionally observed.4 The clinical behavior of CGCG is variable, ranging from a slowly growing, asymptomatic osteolytic lesion to an aggressive process associated with pain, root resorption, cortical bone destruction, and a tendency to recur after surgical treatment.5,6 The pathogenesis of CGCG of the jawbones remains controversial, because speculations of whether it represents a reactive, inflammatory, infective, or neoplastic process are still debated.7
The relation of CGCG to giant cell tumor (GCT) in the jawbones also is controversial. Some investigators have suggested that, unlike CGCG, true GCT is very rare in the jaws, whereas others believe that GCT and CGCG represent a continuum of the same disease process and GCT can occur in jaw bones.8,9 CGCGs are classified as aggressive or nonaggressive lesions based on signs, symptoms, and histologic features.10 Cytogenetic studies of CGCG are very rare in the jaws and other bones. A report described chromosome abnormalities in a GCTof the long bones,11 and a clonal abnormality has been reported in 1 case of CGCG affecting the distal phalanx, namely t(X;4)(q22;q31.3).12 An unstable translocation (8;22) also was found in giant cell reparative granuloma of the first metacarpal thumb.13 In the jaws, a genetic profiling of CGCG using DNA microarray showed that the expressions of several genes were up- or downregulated,14 but comparative genomic hybridization of 6 clinically aggressive cases
*Head, Genetic Laboratories, Institute of Human Genetics,
Surgery, Soroka Medical Center, Faculty of Health Sciences, Ben-
Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion
Gurion University of the Negev, Beer-Sheva, Israel.
University of the Negev, Beer-Sheva, Israel.
Address correspondence and reprint requests to Dr Bodner:
ySenior Pathologist, Department of Pathology, Soroka Medical
Department of Oral and Maxillofacial Surgery, Soroka Medical Cen-
Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
ter, PO Box 151, Beer-Sheva 84101, Israel; e-mail: [email protected]
zConsultant, Department of Oral and Maxillofacial Surgery, Queen Alexandra Hospital, Portsmouth, United Kingdom. xProfessor and Chair, Department of Oral and Maxillofacial
Ó 2013 American Association of Oral and Maxillofacial Surgeons 0278-2391/13/00401-1$36.00/0 http://dx.doi.org/10.1016/j.joms.2013.03.026
1541
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CYTOGENETICS OF CENTRAL GIANT CELL GRANULOMA
FIGURE 1. A, Panoramic radiograph of a large central giant cell granuloma of the left mandible. B, Coronal computed tomogram of the left mandible shows a unilocular, expansile, osteolytic lesion surrounded by a thin bony shell. Manor et al. Cytogenetics of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2013.
of CGCG of the jaws did not show any unbalanced chromosomal alterations,6 and a reciprocal translocation 46,XY, t(2;10)(q23;q24) was found in the hard palate.15 The etiology of CGCG is still unknown, but the occurrence of CGCG in the jaws of patients with known genetic diseases, such as neurofibromatosis type 1, cherubism, and Noonan syndrome, indicates that a genetic-related etiology might be possible.16 To the authors’ knowledge, there are no reports of
the cytogenetic findings of mandibular CGCG published in the literature. The authors describe the first cytogenetic analysis of CGCG occurring in the mandible of a 63-year-old woman.
Report of Case A 63-year-old woman presented with a severalmonth history of tenderness in the left mandible. There was no previous trauma or contributory medical
1543
MANOR ET AL
history. Physical examination found a submucosal mass involving the left edentulous mandible. There was no cervical lymphadenopathy and the laboratory data were unremarkable. Panoramic radiograph and coronal computed tomogram of the mandible (Fig 1A, B) depicted a unilocular, expansile, radiolucent osteolytic lesion, surrounded by a thin bony shell. Incisional biopsy was taken and the lesion was later excised. At histology, cellular fibrous tissue was found, which contained multiple foci of hemorrhage, an aggregation of multinucleated giant cells, and some trabeculae of woven bone, consistent with CGCG (Fig 2).
CYTOGENETIC ANALYSIS
A fresh sample of tissue was minced, cultured in RPMI-1640 medium containing 10% autologous human plasma supplemented with antibiotics and glutamine (Bet-Haemek Biologic Industries, Kibbutz Bet-Haemek, Israel), and incubated at 37 C in a 5% CO2 atmosphere, as previously reported.17,18 Cells were fixed after 5 to 11 days of culture and analyzed according to standard procedures. Twenty-five metaphases were analyzed on G-banded slides and the karyotype was described for each culture according to guidelines of the International System for Human Cytogenetic Nomenclature.19 Cytogenetic analysis found an abnormal karyotype in 5 of 20 cells and these carried a complex translocation; the karyotype was 46,XY[15]/46,XY t(1;17;18)(p13;q11.2;q21)[5] (Fig 3).
FIGURE 2. Histopathology from the lesion shown in Figure 1 exhibits a cellular mass of vascular connective tissue with numerous interspersed multinucleated giant cells (hematoxylin and eosin stain; magnification, 100). Manor et al. Cytogenetics of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2013.
Discussion The pathogenesis of CGCG of the jaws is not completely understood, and it is still unclear whether it represents a reactive process or a neoplasm.1,7,20 It is possible that some lesions are merely reactive in origin, whereas in others a genetic abnormality might play a role.5,21 The occurrence of CGCG in the jaws of patients with a known genetic disease, such as neurofibromatosis type 1, cherubism, and Noonan syndrome,16 makes the tumorigenesis of CGCG even more intriguing (or complicated). The present results are different from previous cytogenetic reports. In GCT of a long bone, a loss in chromosomes 17 and 18 was found,11 whereas in CGCG of the distal phalanx, a t(X;4)(q22;q31.3) was identified.12 In CGCG of the palate, a reciprocal translocation t(2;10)(q23;q24) was found.15 From these results and the present findings, it would appear that jaw and other bone CGCGs do not have a characteristic cytogenetic anomaly. There are only a few cases of CGCG that have been examined cytogenetically or by comparative genomic hybridization, which is likely due to the rarity of this tumor and the limited availability of cytogenetic analysis. Although translocation t(1;17;18)(p13; q11.2; q21) has not been reported to date in CGCG of the mandible, the authors found the same translocation in an oral solitary fibrous tumor.22 It is interesting to find that CGCG is a bony tumor, whereas solitary fibrous tumor is a soft tissue tumor, yet the 2 tumors share an identical translocation. This translocation, t(1;17;18), has not been reported previously in any other benign or malignant tumors. Mechanisms underlying tumor progression in CGCG are still unknown. In solitary fibrous tumor, a malignant tumor may arise de novo or occur as a transformation within a pre-existing benign lesion.23 Therefore, based on this recent finding, it is possible that malignant transformation of CGCG may occur as a result of the same translocation. Expanding cytogenetic knowledge undoubtedly will strengthen the diagnostic and prognostic tools for CGCG (as they do for hematologic and other solid tumors) and expand the understanding of the tumorigenesis process of the different types of CGCG. Further cytogenetic studies, including karyotyping, are necessary to explore the tumorigenesis and progression of CGCG more fully. It also may be an additional indicator for the differentiation between aggressive and nonaggressive CGCG. The present report is a small step in that direction.
1544
CYTOGENETICS OF CENTRAL GIANT CELL GRANULOMA
FIGURE 3. Karyogram of 1 aberrant cell from a central giant cell granuloma of the mandible shows a karyotype of t(1;17;18)(p13;q11.2;q21). Manor et al. Cytogenetics of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2013.
References 1. Regezi JA, Pogrel MA: Comments on pathogenesis and medical treatment of central giant cell granulomas. J Oral Maxillofac Surg 62:116, 2004 2. Yamaguchi T, Dorfman HD: Giant cell reparative granuloma: A comparative clinicopathologic study of lesions in gnathic and extragnathic sites. Int J Surg Pathol 9: 189, 2001 3. Bodner L, Bar Ziv J: Radiographic features of central giant cell granuloma of the jaws in children. Pediatr Radiol 26:148, 1996 4. Kramer IRH, Pindborg JJ, Shear M: Histological Typing of Odontogenic Tumors. (ed 2). Berlin, Germany: Springer-Verlag, 1991, p 31 5. De Lange J, van den Akker HP: Clinical and radiological features of central giant-cell lesions of the jaw. Ora Surg Oral Med Ora Pathol Oral Radiol Endod 99:464, 2005 6. Kruse-Losler B, Diallano 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 7. Vered M, Buchner A, Dayan D: Giant cell granuloma of the jawbones—A proliferative vascular lesion? Immunohistochemical study with vascular growth factor and basic fibroblast growth factor. J Oral Pathol Med 35:613, 2006 8. Auclair PL, Cuenin P, Kratochvil FJ, et al: A clinical and histomorphometric comparison of the central giant cell granuloma and the giant cell tumor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 66:197, 1988 9. Kauzman A, Li SQ, Bradley G, et al: Central giant cell granuloma of the jaws: Assessment of cell cycle proteins. J Oral Pathol Med 33:170, 2004 10. Chuong R, Kaban LB, Kozakewich H, et al: Central giant cell lesions of the jaws: A clinicopathologic study. J Oral Maxillofac Surg 44:708, 1986
11. Zhu QS, Qiu JS: Cytogenetic analyses on giant cell tumor of bone. Zhonghua Bing Li Xue Za Zhi 23:162, 1994 12. Buresh CJ, Seemayer TA, Nelson M, et al: t(X;4)(q22;q31.3) in giant cell reparative granuloma. Cancer Genet Cytogenet 115:80, 1999 13. Johnson A, Collin A, Rydholm A, et al: Unstable translocation (8;22) in a case of giant cell reparative granuloma. Cancer Genet Cytogenet 177:59, 2007 14. Carinci F, Piattelli A, Martinelli M, et al: Genetic profiling of central giant cell granuloma of the jaws. J Craniofac Surg 16:399, 2005 15. Gleason BC, Kleinman PK, Debelenko LV, et al: Novel karyotypes in giant cell-rich lesions of bone. Am J Surg Pathol 31: 926, 2007 16. 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 Ora Pathol Oral Radiol Endod 104:603, 2007 17. Manor E, Joshua BZ, Brennan PA, et al: Chromosomal aberrations in minor salivary gland pleomorphic adenoma. J Oral Maxillofac Surg 70:2798, 2012 18. Manor E, Tetro S, Brennan PA, et al: Cytogenetic findings in benign and malignant oral tumors—The role of autologous human plasma. Br J Oral Maxillofac Surg 50:606, 2012 19. Shaffer LG, Slovak ML, Campbell LJ, (eds): ISCN 2009: An International System for Human Cytogenetic Nomenclature. Basel, Switzerland: S Karger, 2009 20. Pogrel MA: Calcitonin therapy for central giant cell granuloma. J Oral Maxillofac Surg 61:649, 2003 21. Regezi JA: Odontogenic cysts, odontogenic tumors, fibroosseous and giant cell lesions of the jaws. Mod Pathol 15:331, 2002 22. Manor E, Bodner L: Chromosomal aberrations in oral solitary fibrous tumor. Cancer Genet Cytogenet 174:170, 2007 23. Yokoi T, Tsuzuki T, Yatabe Y, et al: Solitary fibrous tumor: Significance of p53 and CD34 immunoreactivity in its malignant transformation. Histopathology 32:423, 1998
Cytogenetics of Central Giant Cell Granuloma of the Mandible Esther Manor, PhD,* Leonid Kachko, MD, PhD,y Peter A. Brennan, MD,z and Lipa Bodner, DMDx Purpose: Central giant cell granuloma is a benign entity that commonly occurs in the mandible and maxilla. It is usually treated by surgical excision, varying from curettage to en bloc resection. Because the entity is more common in diseases such as neurofibromatosis, a genetic element may be involved in its pathogenesis. Cytogenetic studies of central giant cell granuloma affecting bone are rare, and to the authors’ knowledge, there are none reported in the literature for central giant cell granuloma of the mandible. Materials and Methods:
The authors investigated the cytogenetic profile of a case occurring in the mandible. Fresh biopsy tissue was minced and cultured in RPMI-1640 medium. Cells were fixed and stained, and cytogenetic analysis was performed according to standard procedures.
Results:
A clone with t(1;17;18) and other random numerical chromosomal changes was found.
Conclusions:
The significance of these findings in diagnosis and prognosis is currently unclear and further karyotyping studies are needed to more fully understand this tumor. Ó 2013 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 71:1541-1544, 2013
Central giant cell granuloma (CGCG) is a benign bone lesion that usually occurs in the mandible and maxilla and accounts for fewer than 7% of all benign tumors of the jaws.1 CGCG also can affect other facial and cranial bones and small long bones, such as those of the hands and feet.2 It is more common in adolescents and young adults.3 CGCGs consist of numerous multinucleated giant cells and mononuclear cells embedded in a fibrocellular stroma. Foci of hemosiderin pigment and newly formed osteoid or bone are occasionally observed.4 The clinical behavior of CGCG is variable, ranging from a slowly growing, asymptomatic osteolytic lesion to an aggressive process associated with pain, root resorption, cortical bone destruction, and a tendency to recur after surgical treatment.5,6 The pathogenesis of CGCG of the jawbones remains controversial, because speculations of whether it represents a reactive, inflammatory, infective, or neoplastic process are still debated.7
The relation of CGCG to giant cell tumor (GCT) in the jawbones also is controversial. Some investigators have suggested that, unlike CGCG, true GCT is very rare in the jaws, whereas others believe that GCT and CGCG represent a continuum of the same disease process and GCT can occur in jaw bones.8,9 CGCGs are classified as aggressive or nonaggressive lesions based on signs, symptoms, and histologic features.10 Cytogenetic studies of CGCG are very rare in the jaws and other bones. A report described chromosome abnormalities in a GCTof the long bones,11 and a clonal abnormality has been reported in 1 case of CGCG affecting the distal phalanx, namely t(X;4)(q22;q31.3).12 An unstable translocation (8;22) also was found in giant cell reparative granuloma of the first metacarpal thumb.13 In the jaws, a genetic profiling of CGCG using DNA microarray showed that the expressions of several genes were up- or downregulated,14 but comparative genomic hybridization of 6 clinically aggressive cases
*Head, Genetic Laboratories, Institute of Human Genetics,
Surgery, Soroka Medical Center, Faculty of Health Sciences, Ben-
Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion
Gurion University of the Negev, Beer-Sheva, Israel.
University of the Negev, Beer-Sheva, Israel.
Address correspondence and reprint requests to Dr Bodner:
ySenior Pathologist, Department of Pathology, Soroka Medical
Department of Oral and Maxillofacial Surgery, Soroka Medical Cen-
Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
ter, PO Box 151, Beer-Sheva 84101, Israel; e-mail: [email protected]
zConsultant, Department of Oral and Maxillofacial Surgery, Queen Alexandra Hospital, Portsmouth, United Kingdom. xProfessor and Chair, Department of Oral and Maxillofacial
Ó 2013 American Association of Oral and Maxillofacial Surgeons 0278-2391/13/00401-1$36.00/0 http://dx.doi.org/10.1016/j.joms.2013.03.026
1541
1542
CYTOGENETICS OF CENTRAL GIANT CELL GRANULOMA
FIGURE 1. A, Panoramic radiograph of a large central giant cell granuloma of the left mandible. B, Coronal computed tomogram of the left mandible shows a unilocular, expansile, osteolytic lesion surrounded by a thin bony shell. Manor et al. Cytogenetics of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2013.
of CGCG of the jaws did not show any unbalanced chromosomal alterations,6 and a reciprocal translocation 46,XY, t(2;10)(q23;q24) was found in the hard palate.15 The etiology of CGCG is still unknown, but the occurrence of CGCG in the jaws of patients with known genetic diseases, such as neurofibromatosis type 1, cherubism, and Noonan syndrome, indicates that a genetic-related etiology might be possible.16 To the authors’ knowledge, there are no reports of
the cytogenetic findings of mandibular CGCG published in the literature. The authors describe the first cytogenetic analysis of CGCG occurring in the mandible of a 63-year-old woman.
Report of Case A 63-year-old woman presented with a severalmonth history of tenderness in the left mandible. There was no previous trauma or contributory medical
1543
MANOR ET AL
history. Physical examination found a submucosal mass involving the left edentulous mandible. There was no cervical lymphadenopathy and the laboratory data were unremarkable. Panoramic radiograph and coronal computed tomogram of the mandible (Fig 1A, B) depicted a unilocular, expansile, radiolucent osteolytic lesion, surrounded by a thin bony shell. Incisional biopsy was taken and the lesion was later excised. At histology, cellular fibrous tissue was found, which contained multiple foci of hemorrhage, an aggregation of multinucleated giant cells, and some trabeculae of woven bone, consistent with CGCG (Fig 2).
CYTOGENETIC ANALYSIS
A fresh sample of tissue was minced, cultured in RPMI-1640 medium containing 10% autologous human plasma supplemented with antibiotics and glutamine (Bet-Haemek Biologic Industries, Kibbutz Bet-Haemek, Israel), and incubated at 37 C in a 5% CO2 atmosphere, as previously reported.17,18 Cells were fixed after 5 to 11 days of culture and analyzed according to standard procedures. Twenty-five metaphases were analyzed on G-banded slides and the karyotype was described for each culture according to guidelines of the International System for Human Cytogenetic Nomenclature.19 Cytogenetic analysis found an abnormal karyotype in 5 of 20 cells and these carried a complex translocation; the karyotype was 46,XY[15]/46,XY t(1;17;18)(p13;q11.2;q21)[5] (Fig 3).
FIGURE 2. Histopathology from the lesion shown in Figure 1 exhibits a cellular mass of vascular connective tissue with numerous interspersed multinucleated giant cells (hematoxylin and eosin stain; magnification, 100). Manor et al. Cytogenetics of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2013.
Discussion The pathogenesis of CGCG of the jaws is not completely understood, and it is still unclear whether it represents a reactive process or a neoplasm.1,7,20 It is possible that some lesions are merely reactive in origin, whereas in others a genetic abnormality might play a role.5,21 The occurrence of CGCG in the jaws of patients with a known genetic disease, such as neurofibromatosis type 1, cherubism, and Noonan syndrome,16 makes the tumorigenesis of CGCG even more intriguing (or complicated). The present results are different from previous cytogenetic reports. In GCT of a long bone, a loss in chromosomes 17 and 18 was found,11 whereas in CGCG of the distal phalanx, a t(X;4)(q22;q31.3) was identified.12 In CGCG of the palate, a reciprocal translocation t(2;10)(q23;q24) was found.15 From these results and the present findings, it would appear that jaw and other bone CGCGs do not have a characteristic cytogenetic anomaly. There are only a few cases of CGCG that have been examined cytogenetically or by comparative genomic hybridization, which is likely due to the rarity of this tumor and the limited availability of cytogenetic analysis. Although translocation t(1;17;18)(p13; q11.2; q21) has not been reported to date in CGCG of the mandible, the authors found the same translocation in an oral solitary fibrous tumor.22 It is interesting to find that CGCG is a bony tumor, whereas solitary fibrous tumor is a soft tissue tumor, yet the 2 tumors share an identical translocation. This translocation, t(1;17;18), has not been reported previously in any other benign or malignant tumors. Mechanisms underlying tumor progression in CGCG are still unknown. In solitary fibrous tumor, a malignant tumor may arise de novo or occur as a transformation within a pre-existing benign lesion.23 Therefore, based on this recent finding, it is possible that malignant transformation of CGCG may occur as a result of the same translocation. Expanding cytogenetic knowledge undoubtedly will strengthen the diagnostic and prognostic tools for CGCG (as they do for hematologic and other solid tumors) and expand the understanding of the tumorigenesis process of the different types of CGCG. Further cytogenetic studies, including karyotyping, are necessary to explore the tumorigenesis and progression of CGCG more fully. It also may be an additional indicator for the differentiation between aggressive and nonaggressive CGCG. The present report is a small step in that direction.
1544
CYTOGENETICS OF CENTRAL GIANT CELL GRANULOMA
FIGURE 3. Karyogram of 1 aberrant cell from a central giant cell granuloma of the mandible shows a karyotype of t(1;17;18)(p13;q11.2;q21). Manor et al. Cytogenetics of Central Giant Cell Granuloma. J Oral Maxillofac Surg 2013.
References 1. Regezi JA, Pogrel MA: Comments on pathogenesis and medical treatment of central giant cell granulomas. J Oral Maxillofac Surg 62:116, 2004 2. Yamaguchi T, Dorfman HD: Giant cell reparative granuloma: A comparative clinicopathologic study of lesions in gnathic and extragnathic sites. Int J Surg Pathol 9: 189, 2001 3. Bodner L, Bar Ziv J: Radiographic features of central giant cell granuloma of the jaws in children. Pediatr Radiol 26:148, 1996 4. Kramer IRH, Pindborg JJ, Shear M: Histological Typing of Odontogenic Tumors. (ed 2). Berlin, Germany: Springer-Verlag, 1991, p 31 5. De Lange J, van den Akker HP: Clinical and radiological features of central giant-cell lesions of the jaw. Ora Surg Oral Med Ora Pathol Oral Radiol Endod 99:464, 2005 6. Kruse-Losler B, Diallano 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 7. Vered M, Buchner A, Dayan D: Giant cell granuloma of the jawbones—A proliferative vascular lesion? Immunohistochemical study with vascular growth factor and basic fibroblast growth factor. J Oral Pathol Med 35:613, 2006 8. Auclair PL, Cuenin P, Kratochvil FJ, et al: A clinical and histomorphometric comparison of the central giant cell granuloma and the giant cell tumor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 66:197, 1988 9. Kauzman A, Li SQ, Bradley G, et al: Central giant cell granuloma of the jaws: Assessment of cell cycle proteins. J Oral Pathol Med 33:170, 2004 10. Chuong R, Kaban LB, Kozakewich H, et al: Central giant cell lesions of the jaws: A clinicopathologic study. J Oral Maxillofac Surg 44:708, 1986
11. Zhu QS, Qiu JS: Cytogenetic analyses on giant cell tumor of bone. Zhonghua Bing Li Xue Za Zhi 23:162, 1994 12. Buresh CJ, Seemayer TA, Nelson M, et al: t(X;4)(q22;q31.3) in giant cell reparative granuloma. Cancer Genet Cytogenet 115:80, 1999 13. Johnson A, Collin A, Rydholm A, et al: Unstable translocation (8;22) in a case of giant cell reparative granuloma. Cancer Genet Cytogenet 177:59, 2007 14. Carinci F, Piattelli A, Martinelli M, et al: Genetic profiling of central giant cell granuloma of the jaws. J Craniofac Surg 16:399, 2005 15. Gleason BC, Kleinman PK, Debelenko LV, et al: Novel karyotypes in giant cell-rich lesions of bone. Am J Surg Pathol 31: 926, 2007 16. 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 Ora Pathol Oral Radiol Endod 104:603, 2007 17. Manor E, Joshua BZ, Brennan PA, et al: Chromosomal aberrations in minor salivary gland pleomorphic adenoma. J Oral Maxillofac Surg 70:2798, 2012 18. Manor E, Tetro S, Brennan PA, et al: Cytogenetic findings in benign and malignant oral tumors—The role of autologous human plasma. Br J Oral Maxillofac Surg 50:606, 2012 19. Shaffer LG, Slovak ML, Campbell LJ, (eds): ISCN 2009: An International System for Human Cytogenetic Nomenclature. Basel, Switzerland: S Karger, 2009 20. Pogrel MA: Calcitonin therapy for central giant cell granuloma. J Oral Maxillofac Surg 61:649, 2003 21. Regezi JA: Odontogenic cysts, odontogenic tumors, fibroosseous and giant cell lesions of the jaws. Mod Pathol 15:331, 2002 22. Manor E, Bodner L: Chromosomal aberrations in oral solitary fibrous tumor. Cancer Genet Cytogenet 174:170, 2007 23. Yokoi T, Tsuzuki T, Yatabe Y, et al: Solitary fibrous tumor: Significance of p53 and CD34 immunoreactivity in its malignant transformation. Histopathology 32:423, 1998