Accepted Manuscript Aggressive central giant cell granuloma of the mandible treated with conservative surgical enucleation and interferon alpha 2-a. Complete remission with long-term follow up A. Tarsitano, MD, G. Del Corso, DDS, A. Pizzigallo, MD, C. Marchetti, MD PII:
S0278-2391(15)00488-7
DOI:
10.1016/j.joms.2015.04.029
Reference:
YJOMS 56793
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 1 April 2015 Revised Date:
21 April 2015
Accepted Date: 21 April 2015
Please cite this article as: Tarsitano A, Del Corso G, Pizzigallo A, Marchetti C, Aggressive central giant cell granuloma of the mandible treated with conservative surgical enucleation and interferon alpha 2a. Complete remission with long-term follow up, Journal of Oral and Maxillofacial Surgery (2015), doi: 10.1016/j.joms.2015.04.029. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Aggressive central giant cell granuloma of the mandible treated with conservative surgical
Authors: Tarsitano A1, Del Corso G2, Pizzigallo A3, Marchetti C4.
1
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Affiliations:
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enucleation and interferon alpha 2-a. Complete remission with long-term follow up.
MD, Researcher. Department of Biomedical and Neuromotor Sciences, University of Bologna,
2
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Section of Maxillo-facial Surgery at Policlinico S. Orsola-Malpighi, Bologna (Italy). DDS, Department of Biomedical and Neuromotor Sciences, Section of Oral Science, University of
Bologna (Italy). 3
MD, Department of Biomedical and Neuromotor Sciences, University of Bologna, Section of
4
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Maxillo-facial Surgery at Policlinico S. Orsola-Malpighi, Bologna (Italy). MD, Professor of Oral and Maxillofacial Surgery, Department of Biomedical and Neuromotor
Sciences, University of Bologna, Section of Maxillo-facial Surgery at Policlinico S. Orsola-
AC C
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Malpighi, Bologna (Italy).
Correspondence to: Dr. Giacomo Del Corso, DDS, Department of Biomedical and Neuromotor Sciences (Italy). E-mail: [email protected]
ACCEPTED MANUSCRIPT Abstract Central giant cell granuloma (CGCG) is a benign tumor of the jaws. Aggressive lesions present a high-tendency of recurrence after surgical enucleation; thus, en bloc resection and microvascular bone free flap transfer are usually performed. However, in young patients aggressive surgical
RI PT
treatment is a not always suitable solution. In this case report a young female patient, after the diagnosis and the enucleation of a CGCG of the mandible, developed an aggressive recurrence of the lesion. A surgical enucleation associated with interferon alpha 2-a subcutaneous injection was
SC
achieved. The patient was evaluated every six weeks, and after 6 months a radiographic evidence of complete bone regeneration was obtained. No sign of recurrence was seen after eight years of
M AN U
follow-up. The review of the literature proves the interferon treatment as an effective strategy in
AC C
EP
TE D
order to avoid extensive surgery in patient with aggressive CGCG.
1
ACCEPTED MANUSCRIPT Introduction Central giant cell granuloma (CGCG) is a rare benign lesion of the bones that occurs in the jaws in less than 7% of all benign lesions of the jaws [1]. It affects more women than men, with more than 60% of the cases occurring before the age of 30 years [2]. Approximately 65% of CGCG are seen in
RI PT
the mandible, equally distributed between the anterior and the posterior branch [3]. The lesion usually is asymptomatic and slow-growing. It causes a swelling of the jaw, while the displacement of teeth could be a secondary effect.
SC
Giant cell tumors are classified due to their biological behavior in aggressive, intermediate and nonaggressive lesions [4]. The classification used for of this study was reported by Chuong et al. in
M AN U
1986 [5]. Aggressive giant cell tumors present at least 3 of these features: size of greater than 5 cm, rapid growth, root resorption, tooth displacement, cortical bone thinning, cortical bone perforation, recurrence after curettage. Moreover, giant cell tumors with a size equal or greater than 5 cm and/or tumors that recurred after curettage are classified as aggressive [4].
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There are different therapeutic approaches depending on this classification. In nonaggressive CGCG the curettage is usually a good choice. However, the aggressive forms of CGCG presents a 70% recurrence rate after the curettage or the enucleation [6]. Different therapeutic strategies to
EP
treat aggressive CGCG have been proposed:
en bloc resection with 0.5 cm margins of healthy tissue [7];
-
corticosteroids injection to inhibit bone resorption [8];
-
calcitonin therapy, because giant cells express calcitonin receptor [9];
-
interferon due to its anti-angiogenic effect or by enhancing bone formation [10].
AC C
-
Some articles described the different therapeutic techniques showing partial or complete regression of the lesion. The majority of cases are treated with radical surgery; however, frequent recurrence is described. We report a case of aggressive mandibular CGCG treated with conservative surgery and interferon according to the protocol of Kaban et al. [4].
2
ACCEPTED MANUSCRIPT Case Report A 26 yeas-old female patient was referred in September 2005 to the Maxillo-Facial Unit of the Sant’Orsola Hospital in Bologna, Italy. An osteolitic lesion of the left mandible without signs of root resorption was diagnosed (Fig.1). The lesion was initially treated with enucleation and
RI PT
curettage. Histological diagnosis was CGCG (Fig.2). Six months later, during post-operative follow-up, panoramic radiographic and CT scan revealed an aggressive recurrence (Fig. 3-4). The aggressive CGCG was treated with a surgical enucleation associated with interferon alpha 2-a
SC
after the blood and liver function examination. In particular, the lesion was enucleated along with the preservation of teeth and the inferior alveolar nerve (Fig.5-6), and interferon alpha 2-a was
M AN U
started 48 hours later at a dose of 3,000,000 units/m2. The interferon was administered daily via subcutaneous injection. Clinical and radiographic evaluation was monitored monthly, with particular attention to the side-effects of the interferon.
After 6 months, radiographic (panoramic radiograph and CT scan) evidence of complete bone
TE D
regeneration in the defect was obtained (Fig.7-8). Five years after treatment no evidence of
signs of recurrence.
Discussion
EP
recurrence was seen on panoramic radiography (Fig.9). To date, after 8 years the patient has no
AC C
The aggressive type of CGCG represents a rare benign tumor with unknown etiology. The features of aggressive CGCGC are: size more than 5 cm, rapid growth, tooth displacement, cortical bone resorption and frequent recurrence after the surgical curettage [5]. The radiological findings include resorption of the roots of teeth involved in the lesion and cortical expansion. The lesion is radiolucent, ranging from unilocular to multilocular appearance. The aggressive behavior of CGCG is described in 19% of patients with this lesion [11]. No immunohistochemical markers to predict the behavior of the lesions has been found. The aggressive lesions are characterized by a higher
3
ACCEPTED MANUSCRIPT number of giant cells and a great number of nucleolar organization areas compared with nonaggressive tumors [12]. Different therapeutic strategies were proposed for CGCG during the years. Surgery is considered the best treatment in small and non-aggressive lesions. In particular, the excision with curettage
RI PT
represents the traditional treatment with few cases of recurrence. However, in aggressive CGCG surgery performed is usually the en bloc resection. This type of surgery represents the best surgical option to avoid recurrence; however, but the young age of the patients and the benign nature of the
SC
lesion usually suggests avoidance of such a radical treatment choice.
Interferon alpha 2-a has been proposed because of its anti-angiogenic action and because it can
M AN U
differentiate mesenchymal cells into osteoblasts enhancing bone formation [13]. Interferon administered as mono-therapy is not capable of inhibiting proliferating tumor cells. Thus, interferon should be added to surgery [10]. Table 1 reports the literature review about the complete remission of CGCG treated by interferon alpha 2-a. In particular, Kaban et al. reported the major number of
TE D
patients successfully treated with the surgical enucleation of the lesion followed by the injection of interferon alpha 2-a. In 1999 he reported the first case of complete remission of CGCG after the failure of the surgical treatment [14]. Then, in 2002 and 2007 he reported 7 and 16 cases
EP
successfully treated with the combination of surgical enucleation of the lesion followed by the injection of interferon alpha 2-a, as a novel treatment protocol for the management of CGCG [4,
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15]. In 2005, Goldman et al. reported a case treated with interferon alpha 2-a after the failure of surgical debulking, steroid injection and calcitonin therapy. After a long series of complications, the lesion was described as cured by the pathologist who describes a calcification of the lesion [16]. However, the patient was not followed-up. In 2010, Schutz et al. reported a case of CGCG treated with curettage and interferon alpha 2-a injection after the failure of calcitonin and triamcinolone therapy [17]. They obtained a complete remission of the lesion in one-year follow-up. However, two-year follow-up is required to be sure of the effectiveness of the therapy. In 2013, O’Connell et al. described a complete remission of 2 cases of CGCG treated using the same protocol of Kaban et 4
ACCEPTED MANUSCRIPT al. [4] in 141 and 81 months of follow-up [18]. Thus, if we considered at least two years of followup, 26 cases of CGCG successfully treated with interferon alpha 2-a can be found. Our case represent the 27th case described in the literature. In young patients aggressive surgical treatment is not a suitable solution due to functional and
RI PT
aesthetically poor outcomes. However, due to the lack of RCT studies evaluating which is the best treatment between surgical and non-surgical therapy [19], there is still not a clear treatment option in the management of aggressive CGCG. Our case report describes the successful efficacy of
SC
conservative surgical enucleation associated with interferon alpha 2-a to avoid the en bloc surgery resection and microvascular reconstruction in a young female patient. Further studies, assessing the
M AN U
biological characteristics of this tumor, are needed to better understand the behavior of the lesion in
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EP
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order to avoid the recurrence.
5
ACCEPTED MANUSCRIPT Bibliography 1.
Kashyap B, Reddy SP, Desai R, et al: Computer assisted histomorphologic comparison and the expression of AgNORs in the central and peripheral giant cell lesions of the oral cavity and giant cell tumor of the long bone. J Oral Maxillofac Pathol 18(Suppl 1): p. S54-9, 2014.
2.
Cohen MA and Hertzanu Y: Radiologic features, including those seen with computed
RI PT
tomography, of central giant cell granuloma of the jaws. Oral Surg Oral Med Oral Pathol 65(2): p. 255-61, 1998. 3.
De Lange J and Van den Akker HP: Clinical and radiological features of central giant-cell lesions of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99(4): p. 464-70,
4.
SC
2005.
Kaban LB, Troulis MJ, Ebb D, et al: Antiangiogenic therapy with interferon alpha for giant
5.
M AN U
cell lesions of the jaws. J Oral Maxillofac Surg 60(10): p. 1103-11; discussion 1111-3, 2002. Chuong R, Kaban LB, Kozakewich H, et al: Central giant cell lesions of the jaws: a clinicopathologic study. J Oral Maxillofac Surg 44(9): p. 708-13, 1986. 6.
Tosco P, Tanteri G, Iaquinta C, et al: Surgical treatment and reconstruction for central giant cell granuloma of the jaws: a review of 18 cases. J Craniomaxillofac Surg 37(7): p. 380-7, 2009.
Bataineh AB, Al-Khateeb T, Rawashdeh MA. The surgical treatment of central giant cell
TE D
7.
granuloma of the mandible. J Oral Maxillofac Surg 60(7): p. 756-61, 2002. 8.
Abdo EN, Alves LC, Rodrigues AS, et al: Treatment of a central giant cell granuloma with intralesional corticosteroid. Br J Oral Maxillofac Surg 43(1): p. 74-6, 2005. Nicholson GC, Horton MA, Sexton PM, et al: Calcitonin receptors of human osteoclastoma.
EP
9.
Horm Metab Res 19(11): p. 585-9, 1987. de Lange J, van den Akker HP, van den Berg H: Central giant cell granuloma of the jaw: a
AC C
10.
review of the literature with emphasis on therapy options. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104(5): p. 603-15, 2007. 11.
de Lange J, van den Akker HP, Veldhuijzen van Zanten GO, et al: Calcitonin therapy in central giant cell granuloma of the jaw: a randomized double-blind placebo-controlled study. Int J Oral Maxillofac Surg 35(9): p. 791-5, 2006.
12.
Ficarra G, Kaban LB, Hansen LS: Central giant cell lesions of the mandible and maxilla: a clinicopathologic and cytometric study. Oral Surg Oral Med Oral Pathol 64(1): p. 44-9, 1987.
13.
Abukawa H, Kaban LB, Williams WB, et al: Effect of interferon-alpha-2b on porcine mesenchymal stem cells. J Oral Maxillofac Surg 64(8): p. 1214-20, 2006. 6
ACCEPTED MANUSCRIPT 14.
Kaban LB, Mulliken JB, Ezekowitz RA, et al: Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a. Pediatrics 103(6 Pt 1): p. 1145-9, 1999.
15.
Kaban LB, Troulis MJ, Wilkinson MS, et al: Adjuvant antiangiogenic therapy for giant cell tumors of the jaws. J Oral Maxillofac Surg 65(10): p. 2018-24, 2007.
16.
Goldman KE, Marshall MK, Alessandrini E, et al: Complications of alpha-interferon
Pathol Oral Radiol Endod 100(3): p. 285-91, 2005. 17.
Schutz P, El-Bassouni KH, Munish J, et al: Aggressive central giant cell granuloma of the mandible. J Oral Maxillofac Surg 68(10): p. 2537-44, 2010.
O'Connell JE, Kearns GJ: Aggressive giant cell granuloma of the jaws treated with
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18.
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therapy for aggressive central giant cell lesion of the maxilla. Oral Surg Oral Med Oral
interferon alpha: a report of two cases. Ir J Med Sci 182(2): p. 163-70, 2013. Suarez-Roa Mde L, Reveiz L, Ruiz-Godoy Rivera LM, et al: Interventions for central giant
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cell granuloma (CGCG) of the jaws. Cochrane Database Syst Rev (4): p. CD007404, 2009.
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19.
7
ACCEPTED MANUSCRIPT Figure Legend
Figure 1: Radiographic panoramic shows an osteolytic lesion of the left mandible not involving the
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teeth.
Figure 2: Histologic section of aggressive CGCG (hematoxylin and eosin stain).
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Figure 3: Panoramic radiograph reveals the aggressive recurrence of the lesion after 6 months of
Figure 4: CT scan of the recurrence.
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post-operative follow-up. CT scan shows the cortical bone erosion.
Figure 5-6: Intraoperative images show the enucleation of the lesion with preservation of teeth and
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the inferior alveolar nerve.
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Figure 7-8: Panoramic radiograph and CT scan show bone regeneration after 6 months of treatment.
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Figure 9: Panoramic radiograph reveals no evidence of recurrence after 5 years of follow-up.
8
ACCEPTED MANUSCRIPT Table 1: shows the literature review about the complete remission of CGCG treated with interferon 2-alpha. Patients
Treatment
Administration and dose
Effect
Kaban et al. 1999
1
Injection 1.1 to 6.16x106 IU/day
Complete remission
Kaban et al. 2002
7
After two surgical treatment the lesion was treated by interferon alpha 2-a Enucleation followed by interferon alpha 2-a
Median follow-up 3 years
Injection 3x106 IU/day
Complete remission
1.9 years
Goldman et al. 2005
1
Injection 1.51x106 – 9.106 IU/day
Kaban et al. 2007
16
Interferon alpha 2-a after failure of surgical debulking, steroid injection and calcitonin therapy Enucleation followed by interferon alpha 2-a
Schutz et al. 2010
1
Injection 3 MIU/day
O’Connell et al. 2013
2
Curettage and interferon alpha-2-a after failure of calcitonin and triamcinolone Enucleation followed by interferon alpha 2-a
Present case 2015
1
Curettage followed by interferon alpha 2-a
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Author
Complete remission, calcification of the lesion, severe complications
4 months
Complete remission
2.9 years
Complete remission
1 year
Injection 3x106 IU/day
Complete remission
144 and 81 months
Injection 3x106 IU/day
Complete remission
8 years
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Injection 1x106 IU/day
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S0278-2391(15)00488-7
DOI:
10.1016/j.joms.2015.04.029
Reference:
YJOMS 56793
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 1 April 2015 Revised Date:
21 April 2015
Accepted Date: 21 April 2015
Please cite this article as: Tarsitano A, Del Corso G, Pizzigallo A, Marchetti C, Aggressive central giant cell granuloma of the mandible treated with conservative surgical enucleation and interferon alpha 2a. Complete remission with long-term follow up, Journal of Oral and Maxillofacial Surgery (2015), doi: 10.1016/j.joms.2015.04.029. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Aggressive central giant cell granuloma of the mandible treated with conservative surgical
Authors: Tarsitano A1, Del Corso G2, Pizzigallo A3, Marchetti C4.
1
SC
Affiliations:
RI PT
enucleation and interferon alpha 2-a. Complete remission with long-term follow up.
MD, Researcher. Department of Biomedical and Neuromotor Sciences, University of Bologna,
2
M AN U
Section of Maxillo-facial Surgery at Policlinico S. Orsola-Malpighi, Bologna (Italy). DDS, Department of Biomedical and Neuromotor Sciences, Section of Oral Science, University of
Bologna (Italy). 3
MD, Department of Biomedical and Neuromotor Sciences, University of Bologna, Section of
4
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Maxillo-facial Surgery at Policlinico S. Orsola-Malpighi, Bologna (Italy). MD, Professor of Oral and Maxillofacial Surgery, Department of Biomedical and Neuromotor
Sciences, University of Bologna, Section of Maxillo-facial Surgery at Policlinico S. Orsola-
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EP
Malpighi, Bologna (Italy).
Correspondence to: Dr. Giacomo Del Corso, DDS, Department of Biomedical and Neuromotor Sciences (Italy). E-mail: [email protected]
ACCEPTED MANUSCRIPT Abstract Central giant cell granuloma (CGCG) is a benign tumor of the jaws. Aggressive lesions present a high-tendency of recurrence after surgical enucleation; thus, en bloc resection and microvascular bone free flap transfer are usually performed. However, in young patients aggressive surgical
RI PT
treatment is a not always suitable solution. In this case report a young female patient, after the diagnosis and the enucleation of a CGCG of the mandible, developed an aggressive recurrence of the lesion. A surgical enucleation associated with interferon alpha 2-a subcutaneous injection was
SC
achieved. The patient was evaluated every six weeks, and after 6 months a radiographic evidence of complete bone regeneration was obtained. No sign of recurrence was seen after eight years of
M AN U
follow-up. The review of the literature proves the interferon treatment as an effective strategy in
AC C
EP
TE D
order to avoid extensive surgery in patient with aggressive CGCG.
1
ACCEPTED MANUSCRIPT Introduction Central giant cell granuloma (CGCG) is a rare benign lesion of the bones that occurs in the jaws in less than 7% of all benign lesions of the jaws [1]. It affects more women than men, with more than 60% of the cases occurring before the age of 30 years [2]. Approximately 65% of CGCG are seen in
RI PT
the mandible, equally distributed between the anterior and the posterior branch [3]. The lesion usually is asymptomatic and slow-growing. It causes a swelling of the jaw, while the displacement of teeth could be a secondary effect.
SC
Giant cell tumors are classified due to their biological behavior in aggressive, intermediate and nonaggressive lesions [4]. The classification used for of this study was reported by Chuong et al. in
M AN U
1986 [5]. Aggressive giant cell tumors present at least 3 of these features: size of greater than 5 cm, rapid growth, root resorption, tooth displacement, cortical bone thinning, cortical bone perforation, recurrence after curettage. Moreover, giant cell tumors with a size equal or greater than 5 cm and/or tumors that recurred after curettage are classified as aggressive [4].
TE D
There are different therapeutic approaches depending on this classification. In nonaggressive CGCG the curettage is usually a good choice. However, the aggressive forms of CGCG presents a 70% recurrence rate after the curettage or the enucleation [6]. Different therapeutic strategies to
EP
treat aggressive CGCG have been proposed:
en bloc resection with 0.5 cm margins of healthy tissue [7];
-
corticosteroids injection to inhibit bone resorption [8];
-
calcitonin therapy, because giant cells express calcitonin receptor [9];
-
interferon due to its anti-angiogenic effect or by enhancing bone formation [10].
AC C
-
Some articles described the different therapeutic techniques showing partial or complete regression of the lesion. The majority of cases are treated with radical surgery; however, frequent recurrence is described. We report a case of aggressive mandibular CGCG treated with conservative surgery and interferon according to the protocol of Kaban et al. [4].
2
ACCEPTED MANUSCRIPT Case Report A 26 yeas-old female patient was referred in September 2005 to the Maxillo-Facial Unit of the Sant’Orsola Hospital in Bologna, Italy. An osteolitic lesion of the left mandible without signs of root resorption was diagnosed (Fig.1). The lesion was initially treated with enucleation and
RI PT
curettage. Histological diagnosis was CGCG (Fig.2). Six months later, during post-operative follow-up, panoramic radiographic and CT scan revealed an aggressive recurrence (Fig. 3-4). The aggressive CGCG was treated with a surgical enucleation associated with interferon alpha 2-a
SC
after the blood and liver function examination. In particular, the lesion was enucleated along with the preservation of teeth and the inferior alveolar nerve (Fig.5-6), and interferon alpha 2-a was
M AN U
started 48 hours later at a dose of 3,000,000 units/m2. The interferon was administered daily via subcutaneous injection. Clinical and radiographic evaluation was monitored monthly, with particular attention to the side-effects of the interferon.
After 6 months, radiographic (panoramic radiograph and CT scan) evidence of complete bone
TE D
regeneration in the defect was obtained (Fig.7-8). Five years after treatment no evidence of
signs of recurrence.
Discussion
EP
recurrence was seen on panoramic radiography (Fig.9). To date, after 8 years the patient has no
AC C
The aggressive type of CGCG represents a rare benign tumor with unknown etiology. The features of aggressive CGCGC are: size more than 5 cm, rapid growth, tooth displacement, cortical bone resorption and frequent recurrence after the surgical curettage [5]. The radiological findings include resorption of the roots of teeth involved in the lesion and cortical expansion. The lesion is radiolucent, ranging from unilocular to multilocular appearance. The aggressive behavior of CGCG is described in 19% of patients with this lesion [11]. No immunohistochemical markers to predict the behavior of the lesions has been found. The aggressive lesions are characterized by a higher
3
ACCEPTED MANUSCRIPT number of giant cells and a great number of nucleolar organization areas compared with nonaggressive tumors [12]. Different therapeutic strategies were proposed for CGCG during the years. Surgery is considered the best treatment in small and non-aggressive lesions. In particular, the excision with curettage
RI PT
represents the traditional treatment with few cases of recurrence. However, in aggressive CGCG surgery performed is usually the en bloc resection. This type of surgery represents the best surgical option to avoid recurrence; however, but the young age of the patients and the benign nature of the
SC
lesion usually suggests avoidance of such a radical treatment choice.
Interferon alpha 2-a has been proposed because of its anti-angiogenic action and because it can
M AN U
differentiate mesenchymal cells into osteoblasts enhancing bone formation [13]. Interferon administered as mono-therapy is not capable of inhibiting proliferating tumor cells. Thus, interferon should be added to surgery [10]. Table 1 reports the literature review about the complete remission of CGCG treated by interferon alpha 2-a. In particular, Kaban et al. reported the major number of
TE D
patients successfully treated with the surgical enucleation of the lesion followed by the injection of interferon alpha 2-a. In 1999 he reported the first case of complete remission of CGCG after the failure of the surgical treatment [14]. Then, in 2002 and 2007 he reported 7 and 16 cases
EP
successfully treated with the combination of surgical enucleation of the lesion followed by the injection of interferon alpha 2-a, as a novel treatment protocol for the management of CGCG [4,
AC C
15]. In 2005, Goldman et al. reported a case treated with interferon alpha 2-a after the failure of surgical debulking, steroid injection and calcitonin therapy. After a long series of complications, the lesion was described as cured by the pathologist who describes a calcification of the lesion [16]. However, the patient was not followed-up. In 2010, Schutz et al. reported a case of CGCG treated with curettage and interferon alpha 2-a injection after the failure of calcitonin and triamcinolone therapy [17]. They obtained a complete remission of the lesion in one-year follow-up. However, two-year follow-up is required to be sure of the effectiveness of the therapy. In 2013, O’Connell et al. described a complete remission of 2 cases of CGCG treated using the same protocol of Kaban et 4
ACCEPTED MANUSCRIPT al. [4] in 141 and 81 months of follow-up [18]. Thus, if we considered at least two years of followup, 26 cases of CGCG successfully treated with interferon alpha 2-a can be found. Our case represent the 27th case described in the literature. In young patients aggressive surgical treatment is not a suitable solution due to functional and
RI PT
aesthetically poor outcomes. However, due to the lack of RCT studies evaluating which is the best treatment between surgical and non-surgical therapy [19], there is still not a clear treatment option in the management of aggressive CGCG. Our case report describes the successful efficacy of
SC
conservative surgical enucleation associated with interferon alpha 2-a to avoid the en bloc surgery resection and microvascular reconstruction in a young female patient. Further studies, assessing the
M AN U
biological characteristics of this tumor, are needed to better understand the behavior of the lesion in
AC C
EP
TE D
order to avoid the recurrence.
5
ACCEPTED MANUSCRIPT Bibliography 1.
Kashyap B, Reddy SP, Desai R, et al: Computer assisted histomorphologic comparison and the expression of AgNORs in the central and peripheral giant cell lesions of the oral cavity and giant cell tumor of the long bone. J Oral Maxillofac Pathol 18(Suppl 1): p. S54-9, 2014.
2.
Cohen MA and Hertzanu Y: Radiologic features, including those seen with computed
RI PT
tomography, of central giant cell granuloma of the jaws. Oral Surg Oral Med Oral Pathol 65(2): p. 255-61, 1998. 3.
De Lange J and Van den Akker HP: Clinical and radiological features of central giant-cell lesions of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99(4): p. 464-70,
4.
SC
2005.
Kaban LB, Troulis MJ, Ebb D, et al: Antiangiogenic therapy with interferon alpha for giant
5.
M AN U
cell lesions of the jaws. J Oral Maxillofac Surg 60(10): p. 1103-11; discussion 1111-3, 2002. Chuong R, Kaban LB, Kozakewich H, et al: Central giant cell lesions of the jaws: a clinicopathologic study. J Oral Maxillofac Surg 44(9): p. 708-13, 1986. 6.
Tosco P, Tanteri G, Iaquinta C, et al: Surgical treatment and reconstruction for central giant cell granuloma of the jaws: a review of 18 cases. J Craniomaxillofac Surg 37(7): p. 380-7, 2009.
Bataineh AB, Al-Khateeb T, Rawashdeh MA. The surgical treatment of central giant cell
TE D
7.
granuloma of the mandible. J Oral Maxillofac Surg 60(7): p. 756-61, 2002. 8.
Abdo EN, Alves LC, Rodrigues AS, et al: Treatment of a central giant cell granuloma with intralesional corticosteroid. Br J Oral Maxillofac Surg 43(1): p. 74-6, 2005. Nicholson GC, Horton MA, Sexton PM, et al: Calcitonin receptors of human osteoclastoma.
EP
9.
Horm Metab Res 19(11): p. 585-9, 1987. de Lange J, van den Akker HP, van den Berg H: Central giant cell granuloma of the jaw: a
AC C
10.
review of the literature with emphasis on therapy options. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104(5): p. 603-15, 2007. 11.
de Lange J, van den Akker HP, Veldhuijzen van Zanten GO, et al: Calcitonin therapy in central giant cell granuloma of the jaw: a randomized double-blind placebo-controlled study. Int J Oral Maxillofac Surg 35(9): p. 791-5, 2006.
12.
Ficarra G, Kaban LB, Hansen LS: Central giant cell lesions of the mandible and maxilla: a clinicopathologic and cytometric study. Oral Surg Oral Med Oral Pathol 64(1): p. 44-9, 1987.
13.
Abukawa H, Kaban LB, Williams WB, et al: Effect of interferon-alpha-2b on porcine mesenchymal stem cells. J Oral Maxillofac Surg 64(8): p. 1214-20, 2006. 6
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Kaban LB, Mulliken JB, Ezekowitz RA, et al: Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a. Pediatrics 103(6 Pt 1): p. 1145-9, 1999.
15.
Kaban LB, Troulis MJ, Wilkinson MS, et al: Adjuvant antiangiogenic therapy for giant cell tumors of the jaws. J Oral Maxillofac Surg 65(10): p. 2018-24, 2007.
16.
Goldman KE, Marshall MK, Alessandrini E, et al: Complications of alpha-interferon
Pathol Oral Radiol Endod 100(3): p. 285-91, 2005. 17.
Schutz P, El-Bassouni KH, Munish J, et al: Aggressive central giant cell granuloma of the mandible. J Oral Maxillofac Surg 68(10): p. 2537-44, 2010.
O'Connell JE, Kearns GJ: Aggressive giant cell granuloma of the jaws treated with
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therapy for aggressive central giant cell lesion of the maxilla. Oral Surg Oral Med Oral
interferon alpha: a report of two cases. Ir J Med Sci 182(2): p. 163-70, 2013. Suarez-Roa Mde L, Reveiz L, Ruiz-Godoy Rivera LM, et al: Interventions for central giant
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cell granuloma (CGCG) of the jaws. Cochrane Database Syst Rev (4): p. CD007404, 2009.
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Figure 1: Radiographic panoramic shows an osteolytic lesion of the left mandible not involving the
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teeth.
Figure 2: Histologic section of aggressive CGCG (hematoxylin and eosin stain).
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Figure 3: Panoramic radiograph reveals the aggressive recurrence of the lesion after 6 months of
Figure 4: CT scan of the recurrence.
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post-operative follow-up. CT scan shows the cortical bone erosion.
Figure 5-6: Intraoperative images show the enucleation of the lesion with preservation of teeth and
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the inferior alveolar nerve.
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Figure 7-8: Panoramic radiograph and CT scan show bone regeneration after 6 months of treatment.
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Figure 9: Panoramic radiograph reveals no evidence of recurrence after 5 years of follow-up.
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Treatment
Administration and dose
Effect
Kaban et al. 1999
1
Injection 1.1 to 6.16x106 IU/day
Complete remission
Kaban et al. 2002
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After two surgical treatment the lesion was treated by interferon alpha 2-a Enucleation followed by interferon alpha 2-a
Median follow-up 3 years
Injection 3x106 IU/day
Complete remission
1.9 years
Goldman et al. 2005
1
Injection 1.51x106 – 9.106 IU/day
Kaban et al. 2007
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Interferon alpha 2-a after failure of surgical debulking, steroid injection and calcitonin therapy Enucleation followed by interferon alpha 2-a
Schutz et al. 2010
1
Injection 3 MIU/day
O’Connell et al. 2013
2
Curettage and interferon alpha-2-a after failure of calcitonin and triamcinolone Enucleation followed by interferon alpha 2-a
Present case 2015
1
Curettage followed by interferon alpha 2-a
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Complete remission, calcification of the lesion, severe complications
4 months
Complete remission
2.9 years
Complete remission
1 year
Injection 3x106 IU/day
Complete remission
144 and 81 months
Injection 3x106 IU/day
Complete remission
8 years
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