Abstract
Background
Giant cell granulomas (GCGs) are benign tumours of the jaws of unknown aetiology. Aggressive lesions are difficult to manage and demonstrate a tendency to recur after surgical curettage. In the early 1980s, interferon alpha-2a was found to inhibit angiogenesis through a series of laboratory experiments and was subsequently used to treat a child with pulmonary haemangiomatosis. It has been hypothesised that GCGs are proliferative vascular lesions and would, therefor, be expected to respond to antiangiogenic therapy. The purpose of this study is to report a treatment protocol consisting of enucleation, followed by subcutaneous interferon alpha.
Methods
Patients with a biopsy-confirmed giant cell lesion satisfying criteria for “aggressive” giant cell tumours were included. All lesions were enucleated, and the patients commenced interferon alpha-2a (3,000,000 units/m2) 48–72 h post-operatively.
Results
Two patients satisfied the criteria for aggressive giant cell lesions. All tumours were enucleated. There were no post-operative complications, and all patients tolerated the interferon therapy well. To date, there has been no evidence of tumour recurrence. The follow-up periods were 144 and 81 months, respectively.
Conclusion
Antiangiogenic therapy, in combination with curettage, has proven to be a useful strategy for the management of these tumours. The use of interferon alpha-2a, following enucleation of these lesions, resulted in complete remission of all lesions, and decreased operative morbidity compared with conventional treatment.
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References
Austin LT, Dahlin CD, Royer QR (1959) Giant cell reparative granuloma and related conditions affecting the jawbones. Oral Surg Oral Med Oral Pathol 12:1285–1295
Cohen M, Hertzanu Y (1988) Radiologic features, including those seen with computed tomography, of central giant cell granuloma of the jaws. Oral Surg Oral Med Oral Pathol 65:255
Whitaker SB, Waldron CA (1993) Central giant cell lesions of the jaws. Oral Surg Oral Med Oral Pathol 75:199–208
de Lange J, van den Akker HP, Klip H (2004) Incidence and disease free survival after surgical therapy of central giant cell granulomas of the jaws in The Netherlands; 1990–1995. Head Neck 26:792–795
Jaffe HL (1953) Giant-cell reparative granuloma, traumatic bone cyst, and fibrous (fibro-osseous) dysplasia of the jaw bones. Oral Surg 6:159–175
Auclair Pl, Cuenin P, Kratochyil FJ, Slater LJ, Ellis GL (1988) A clinical and histomorphologic comparison of the central giant cell granuloma and the giant cell tumour. Oral Surg Oral Med Oral Pathol 66:197–208
Marx RE, Stern D (2002) Oral and maxillofacial pathology. Quintessence Publishing Co Ltd, Chicago
Cohen MM Jr, Gorlin RJ (1991) Noonan-like/multiple giant cell lesion syndrome. Am J Med Genet 40:159
de Lange J, van der Akker HP, van der Berg H (2007) 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 104:603–615
Ficarra G, Sapp P, Eversole LR (1993) Multiple peripheral odontogenic fibroma, World Health Organization type, and giant cell granuloma: a report of an unusual association. J Oral Maxillofac Surg 51:325–328
Ardekian L, Manor R, Peled M, Laufer D (1999) Bilateral central giant cell granulomas in a patient with neurofibromatosis: report of a case and review of the literature. J Oral Maxillofac Surg 57:869–872
Edwards PC, Fantasia JE, Saini T, Rosenberg TJ, Sachs SA, Ruggiero S (2006) Clinically aggressive central giant cell granulomas in two patients with neurofibromatosis 1. Ora Surg Oral Med Oral Pathol Oral Radiol Endod 102:765–772
Ueki Y, Tiziani V, Santanna C et al (2001) Mutations in the gene encoding c-Abl-binding protein SH3BP2 causes cherubism. Nat Genet 28:125–126
Ucar B, Okten A, Mocan H, Ercin C (1998) Noonan syndrome associated with central giant cell granuloma. Clin Genet 53:411–414
Hyckel P, Berndt A, Schleier P et al (2005) Cherubism-new hypothesis on pathogenesis and therapeutic consequences. J Craniomaxillofac Surg 33:61–68
Miah SM, Hatani T, Qu X, Yamamura H, Sada K (2004) Point mutations of 3BP2 identified in human inherited disease cherubism result in the loss of function. Genes Cells 9:993–1004
Idowu BD, Thomas G, Frow R et al (2008) Mutations in SH3BP2, the cherubism gene, were not detected in central or peripheral giant cell tumors of the jaw. Br J Oral Maxillofac Surg 46:229
Schütz P, El-Bassuoni KH, Munish J, Hamed HH, Padwa BL (2010) Aggressive central giant cell granuloma of the mandible. J Oral Maxillofac Surg 68(10):2537–2544
Liu B, Yu S-F, Li T-J (2003) Multinucleated giant cells in various forms of giant cell containing lesions of the jaws express features of osteoclasts. J Oral Pathol Med 32:367
Vered M, Buchner A, Dayan D (2006) Immunohistochemical expression of glucocorticoid and calcitonin receptors as a tool for selecting therapeutic approach in central giant cell granuloma of the jaw bones. Int J Oral Maxillofac Surg 35:756–760
Tiffee JC, Aufdemorte TB (1997) Markers for macrophage and osteoclast lineages in giant cell lesions of the oral cavity. J Oral Maxillofac Surg 55:1108–1112
Itonaga I, Hussein I, Kudo O et al (2003) Cellular mechanisms of osteoclast formation and lacunar resorption in giant cell granuloma of the jaw. J Oral Pathol Med 32:224–231
Vered M, Buchner A, Dayan D (2006) Giant cell granuloma of the jaw bones- a proliferative vascular lesion? Immunohistochemical study with vascular endothelial growth factor and basic fibroblast growth factor. J Oral Pathol Med 53:613–619
Chuong R, Kaban LB, Kozakewich H, Perez-Atayde A (1986) Central giant cell lesions of the jaw: a clinicopathologic study. J Oral Maxillofac Surg 44:708–713
Rawashdeh M, Bataineh A, Al-Khateeb T (2006) Long-term clinical and radiological outcomes of surgical management of central giant cell granuloma of the maxilla. Int J Oral Maxillofac Surg 35:60–66
Kaffe I, Ardekian L, Taicher S, Littner MM, Buchner A (1996) Radiologic features of central giant cell granuloma of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 81:720–726
Eckardt A, Pogrel MA, Kaban LB et al (1989) Central giant cell granulomas of the jaws: nuclear DNA analysis using image cytometry. Int J Oral Maxillofac Surg 18:3
Ficarra G, Kaban LB, Hansen LS (1987) Central giant cell lesions of the mandible and maxilla: a clinicopathologic and cytometric study. Oral Surg Oral Med Oral Pathol 64:44
O’Malley M, Pogrel MA, Stewart JC et al (1997) Central giant cell granulomas of the jaws: phenotype and proliferation-associated markers. J Oral Pathol Med 26:159
Dewsnup NC, Susarla SM, Abulikemu M et al (2008) Immunohistochemical evaluation of giant cell tumors of the jaws using CD34 density analysis. J Oral Maxillofac Surg 66:928
Webb DJ, Brockbank J (1986) Combined curettage and cryosurgical treatment for the aggressive “giant cell lesion” of the mandible. Int J Oral Maxillofac Surg 5:780
Eisenbud L, Stern M, Rothberg M et al (1988) Central giant cell granuloma of the jaws: experiences in the management of thirty-seven cases. J Oral Maxillofac Surg 46:376–384
Kruse-Losler B, Diallo R, Gaertner C, Mischke KL, Joos U, Kleinheinz J (2006) 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 101:346–354
Kaban LB, Troulis MJ, Wilkinson MJ et al (2007) Adjuvant antiangiogenic therapy for giant cell tumors of the jaws. J Oral Maxillofac Surg 65:2018
Minic A, Stajcic Z (1996) Prognostic significance of cortical perforation in the recurrence of central giant cell granulomas of the jaws. J Craniomaxillofac Surg 24:104
Bataineh A, Al-Khateeb T, Rawashdeh M (2002) The surgical treatment of central giant cell granuloma of the mandible. J Oral Maxillofac Surg 60:756–761
Flanagan AM, Nui B, Tinkler SMB et al (1988) The multinucleate cells in the giant cell granulomas of the jaw are osteoclasts. Cancer 62:1139
Pharoah MJ, Heersche JNM (1986) Dexamethasone inhibits formation of osteoclast-like cells in bone-marrow cultures. J Dent Res 65:1006
Jacoway JR, Howell FV, Terry BC (1988) Central giant cell granuloma—an alternative to surgical therapy (abstract). Oral Surg Oral Med Oral Pathol 66:572
Kermer C, Millesi W, Watzke IM (1994) Local injection of corticosteroids for central giant cell granuloma. A case report. Int J Oral Maxillofac Surg 23:366–368
Terry BC, Jacoway JR (1994) Management of giant cell lesions. Oral maxillofac Surg Clin N Am 6:579–600
Rajeevan NS, Soumithran CS (1998) Intralesional corticosteroid injection for central giant cell granuloma: a case report. Int J Oral Maxillofac Surg 27:303
Comert E, Turanli M, Ulu S (2006) Oral and intralesional steroid therapy in giant cell granuloma. Acta Otolaryngol 26:664
Kremer M, Judd J, Rifkin B, Auszmann J, Oursler MJ (1995) Estrogen modulation of osteoclast lysosomal enzyme secretion. J Cell Biochem 57:271–279
Dempster OW, Moonga BS, Stein LS, Horbert WR, Antakly T (1997) Glucocorticoids inhibit bone resorption in isolated rat osteoclasts by inducing apoptosis. J Endocrinol 154:397–406
Harris M (1993) Central giant cell granulomas of the jaws regress with calcitonin therapy. Br J Oral Maxillofac Surg 31:89
Pogrel MA (2003) Calcitonin therapy for central giant cell granuloma. J Oral Maxillofac Surg 61:649–653
de Lange J, Rosengerg AJWP, van der Akker HP, Koole R, Wirds JJ, van der Berg H (1999) Treatment of CGCG of the jaw with calcitonin. Int J Oral Maxillofac Surg 28:372–376
O’Regan EM, Gibb DH, Odell EW (2001) Rapid growth of giant cell granuloma in pregnancy treated with calcitonin. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 92:532–538
Pogrel MA, Regezi JA, Harris ST et al (1999) Calcitonin treatment for central giant cell granulomas of the mandible: report of two cases. J Oral Maxillofac Surg 57:848
de Lange J, van der Akker HP, van der Berg H, Richel DJ, Gortzak RA (2006) Limited regression of central giant cell granuloma by interferon alpha after failed calcitonin therapy: a report of 2 cases. Int J Oral Maxillofac Surg 35:865–869
Kaban KB, Mulliken JB, Ezekowitz RA, Ebb D, Smith PS, Folkman J (1999) Antiangiogenic therapy of a recurrent giant cell tumour of the mandible with interferon alpha-2a. Paediatrics 103:11145–11149
Dominguez CL, Martinez GC, Plasencia DJ, Suner M (2004) Intranasal calcitonin therapy for central giant cell granuloma. J Craniomaxillofac Surg 32(supp 1):244–245
Kaban LB, Troulis MJ, Ebb D, August M, Hornicek FJ, Dodson TB (2002) Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws. J Oral Maxillofac Surg 60:1103–1111
Brouty-Boye D, Zetter B (1980) Inhibition of cell motility by interferon. Science 208:516
Sidky YA, Borden EC (1987) Inhibition of angiogenesis by interferons: effects on tumour- and lymphocyte-induced vascular responses. Cancer Res 47:5155
White CW, Sondheimer HM, Crouch EC et al (1989) Treatment of pulmonary haemangiomatosis with recombinant interferon alpha-2a. N Engl J Med 320:1197
de Lange J, van Maarle MC, van den Akker HP et al (2007) DNA analysis of the SH3BP2 gene in patients with aggressive central giant cell granuloma. Br J Oral Maxillofac Surg 45:499
Tallan EM, Olsen KD, McCaffrey TV et al (1994) Advanced giant cell granuloma: a twenty-year study. Otolaryngol Head Neck Surg 110:413
Landesberg R, Eisig S, Fennoy I et al (2009) Alternative indications for bisphosphonate therapy. J Oral Maxillofac Surg 67(Suppl 1):27
de Lange J, van Rijn RR, van den Berg H et al (2009) Regression of central giant cell granuloma by a combination of imatinib and interferon: a case report. Br J Oral Maxillofac Surg 47:59
Orchard PJ, Smith CM, Woods WG et al (1989) Treatment of haemangioendotheliomas with alpha interferon. Lancet 2:565
Ezekowitz RAB, Mulliken JB, Folkman J (1992) Interferon alpha-2a therapy for life-threatening hemangiomas of infancy. N Eng J Med 326:1456 (erratum appears in N Engl J Med 1994, volume ID 330, p 300)
Hatley RM, Sabio H, Howell CG et al (1993) Successful management of an infant with a giant hemangioma of the retroperitoneum and Kasabach-Merritt syndrome with alpha-interferon. J Pediatr Surg 28:1356
Chang E, Boyd A, Nelson CC et al (1997) Successful treatment of infantile hemangiomas with interferon alpha-2b. J Pediatr Hematol Oncol 19:237
Yasko AW (2001) Interferon therapy for vascular tumors of bone. Curr Opin Orthop 12:514
Abukawa H, Kaban LB, Vacanti J et al (2002) Effect of interferon on porcine mesenchymal stem cells in vitro. J Dent Res 81:531–535
Abukawa H, Kaban LB, Williams WB et al (2006) Effect of interferon alpha-2b on porcine mesenchymal stem cells. J Oral Maxillofac Surg 64:1214
Goldman KE, Marshall MK, Alessandrini E, Bernstein ML (2005) Complications of alpha-interferon therapy for aggressive giant cell lesion of the maxilla. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100:285–291
Barlow CF, Priebe CJ, Mulliken JB et al (1988) Spastic diplegia as a complication of interferon alfa-2a treatment of hemangiomas of infancy. J Pediatr 132:527
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O’Connell, J.E., Kearns, G.J. Aggressive giant cell granuloma of the jaws treated with interferon alpha: a report of two cases. Ir J Med Sci 182, 163–170 (2013). https://doi.org/10.1007/s11845-012-0858-x
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DOI: https://doi.org/10.1007/s11845-012-0858-x