PATHOLOGY
Treatment of a Rare Ganglioneuroma With Resection and Reconstruction of the Mandible: A Case Report and Literature Review Joseph Pierse, DMD, MA,* Edmund Ying-Peng Wun, DDS,y Robert Pellecchia, DDS,z and Jessica Wollenberg, DDSx Ganglioneuromas are rare neuroblastic tumors that develop from the neural crests of the sympathetic nervous system. Because ganglioneuromas of the mandible have been infrequent, they do not have a standardized management protocol. As of 2000, only 5 cases had been reported. Ganglioneuromas are unique tumors that can undergo histologic maturation from a malignancy to a benign variant. We present the case of a 15-year-old boy with a ganglioneuroma of the mandible and the results of surgical management, including immediate reconstruction with a free fibula microvascular flap. Ó 2014 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 72:748.e1-748.e9, 2014
Case Report A 15-year-old boy had been referred to the Geisinger Medical Center by his general dentist after an incidental finding on a panoramic radiograph of an osteolytic lesion of the right mandible. The patient had a previous history of stage IV neuroblastoma of the left abdomen and had undergone radiotherapy to the skull, left orbit, and femur and 2 cycles of neoadjuvant chemotherapy before adrenalectomy at 2 years of age. He had been receiving treatment from the pediatric hematology and oncology department. After obtaining a computed tomography (CT) scan of the mandible, the patient was referred to the oral and maxillofacial surgery department. The patient was asymptomatic and had no history of swelling or numbness. Secondary to his treatment of the neuroblastoma, he also presented with bilateral optic nerve atrophy, a bilateral hearing deficit, and hypothyroidism. The patient had no known allergies, and his social history was negative. His medications included levo-
thyroxine 50 mg/day. The patient’s vital signs were within normal limits, and the review of his systems was unremarkable. On physical examination, the patient was alert and fully oriented. He had moderate right facial asymmetry, without erythema, warmth, or tenderness to palpation. Moderate blunting of the inferior border of the right mandible was present. No lymphadenopathy was appreciated. The extraocular muscles were intact, and the pupils were equal, round, and reactive to light and accommodation. He had a slight visual acuity deficit bilaterally, and horizontal nystagmus was noted bilaterally. He had no nasal deformity. The floor of the mouth was soft, not tender, and not distended. The oropharynx was clear, with the uvula at the midline. No cant of the occlusal plane was noted. The occlusion was stable and reproducible. The maximum incisal opening was approximately 40 mm without deviation on opening or closing. No gross mobility of the dentition was present. Moderate buccal and lingual bony expansion of the right mandibular body and ramus was present. No evidence was seen of a
*Chief Resident, Department of Oral and Maxillofacial Surgery,
Geisinger Medical Center, 100 N Academy Ave, Danville, NY 17821;
INITIAL EXAMINATION
The Brooklyn Hospital Center, Brooklyn, NY.
e-mail: [email protected]
yAttending Physician, Geisinger Medical Center, Danville, PA.
Received September 16 2013
zChairman, Department of Oral and Maxillofacial Surgery and
Accepted December 17 2013
Dental Medicine, Geisinger Medical Center, Danville, PA. xChief Resident, Department of Oral Pathology, New York
Ó 2014 American Association of Oral and Maxillofacial Surgeons
Hospital, New York, NY.
http://dx.doi.org/10.1016/j.joms.2013.12.014
0278-2391/13/01545-0$36.00/0
Address correspondence and reprint requests to Dr Pellecchia: Department of Oral and Maxillofacial Surgery and Dental Medicine,
748.e1
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trigeminal or facial nerve deficit. The temporomandibular joint examination findings were also negative. A panoramic film showed a large, multilocular lesion extending inferiorly from the neck of the right condyle and anteriorly to the lower right first bicuspid. Marked root resorption was localized to the teeth of the lower right quadrant. The lesion did not cross the midline (Fig 1). A maxillofacial computed tomography scan showed the lesion measured 2.4 cm in the transverse dimension and 3.4 cm anteroposteriorly and 4.6 cm craniocaudally in its greatest dimensions. An axial cut bony window of the maxillofacial CT scan showed an expansile lesion of the right mandible in the buccal and lingual dimensions, with trabeculations noted posteriorly (Fig 2). These findings were consistent with those from the panoramic radiograph. A coronal cut tissue window also showed moderate buccal and lingual expansion of the right mandibular ramus and body. The buccal and lingual cortices remained intact. The density of the lesion was consistent with soft tissue, measuring 43.85 Hounsfield units at its center. A 3-dimensional reconstruction was completed, and stereolithic models were fabricated using the CT findings (Medical Modeling, Golden, CO; Fig 3). BIOPSY AND HISTOPATHOLOGIC FINDINGS
With the patient under general anesthesia, an 18gauge needle was inserted into the right body of the mandible with no evidence of fluid or blood
on aspiration. After the negative aspirate, an incisional biopsy was completed, using a 1.5 1.5cm bony window, in the lower right quadrant of the mandible. A deep soft tissue biopsy was obtained with sharp instrumentation for histologic evaluation. Two specimens were obtained from the biopsy site for frozen and permanent histopathologic study. The differential diagnosis included ameloblastoma, myxoma, odontogenic keratocyst, central giant cell granuloma, and mucoepidermoid carcinoma. The results of the frozen section examination were consistent with a benign entity of probable neural origin without evidence of cellular atypia. The second sample was evaluated at the Oral Pathology Laboratory (Flushing, NY). Histopathologic examination of the hematoxylin and eosin-stained slides showed a benign neural tumor composed of haphazardly crisscrossing bundles of Schwann cells. Clusters of variably sized ganglion cells were seen scattered throughout the neural stroma. The ganglion cells contained abundant eosinophilic cytoplasm and single to multiple nuclei without significant atypia (Figs 4, 5). Strong and diffuse staining was present in both the schwannian and ganglion cell components for S100, neurofilament protein, and synaptophysin. The histopathologic and immunohistochemical profile was consistent with the diagnosis of ganglioneuroma (Figs 6-8).
FIGURE 1. A panoramic radiograph showing a lesion of the right body and ramus extending inferior to the neck of the right condyle to the lower right quadrant, lower right first bicuspid. The lesion is mostly unilocular with multilocular components. Evidence of root resorption is present. The lesion did not cross the midline and was well-delineated anteriorly. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
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FIGURE 2. Maxillofacial computed tomography scan depicting a bony window, axial cut at the level of the mandible. Evidence of a gross expansile lesion bilaterally was present in the right mandible. Trabeculations were appreciated posteriorly. Note, no gross deviation of the airway was present. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
SURGICAL COURSE
After histopathologic examination and confirmation of the diagnosis of ganglioneuroma of the mandible, a surgical treatment plan was developed that included resection (Figs 9, 10) of the tumor with simultaneous reconstruction using a microvascular free fibula graft.1 The patient underwent successful resection with disease-free margins and immediate reconstruction using a free fibula graft. The 1-year follow-up examination revealed anatomic restoration of function with the absence of disease and recurrence (Fig 11).
Discussion Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma are the differential stages of peripheral neuroblastic tumors that develop from the sympathetic nervous system and are derived from neural crest tissue. Neuroblastoma is the most common extracranial
solid tumor in childhood, accounting for approximately 8 to 10% of tumors and 15% of all childhood cancer mortality. It often manifests in the adrenal gland, with the greatest incidence at 2 years of age. It is known to be a highly malignant and aggressive tumor. Neuroblastomas are often asymptomatic and can go undetected until a large abdominal mass or metastatic lesion develops. According to the published data, the prevalence of a neuroblastoma is approximately 1/700 live births. The male predilection has been slightly greater, at approximately 1.2:1. Most primary tumors occur within the abdomen, with the incidence of adrenal tumors greater in children (40%) than in infants (25%).2-11 Pathognomonic abnormalities are common and include deletion of the short arm of chromosome 1 distal to band p32, double minute chromatin bodies, and homogeneously staining regions. A translocation between chromosomes 1 and 17 and alterations in
PIERSE ET AL
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FIGURE 3. Fabrication of the stereolithic model from the computed tomography scans. Note, the extent of the tumor inferior to the right condyle to lower right first bicuspid. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
FIGURE 4. Low power photomicrograph depicting crisscrossing bundles of Schwann cells (hematoxylin and eosin stain, original magnification 4). Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
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FIGURE 5. Clusters of ganglion cells deposited in a neural background (hematoxylin and eosin stain, original magnification 10). Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
the N-myc oncogene could also play a significant role in determining the patient’s prognosis.3,6,8,9,12-16 As of 1999, the International Neuroblastoma Pathology Committee had modified the existing Shimada classification of neuroblastic tumors and defined 4
categories: 1) neuroblastoma (schwannian stroma– poor), undifferentiated, poorly differentiated, and differentiating; 2) ganglioneuroblastoma, intermixed (schwannian stroma–rich); 3) ganglioneuroma (schwannian stroma–dominant), maturing and mature;
FIGURE 6. Strong and diffuse staining for S100 protein (original magnification 10). Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
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FIGURE 7. Strongly diffuse staining of neurofilament protein (original magnification 10). Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
and 4) ganglioneuroblastoma, nodular (composite schwannian stroma–rich/stroma–dominant and stroma– poor). This is an age-linked classification according to the differentiation of neuroblasts, cellular turnover, and the presence or absence of schwannian stromal development.17-19 A rare feature of neuroblastoma is that it can undergo histologic maturation and differentiate and mature into a benign ganglioneuroma, which is counterintuitive when considering the natural progression from normal to malignant tissue. The published data have shown that this can occur after the treatment of a primary neuroblastoma. However, neuroblastoma metastasis to the mandible has been described in very few cases.20-24
Ganglioneuroma is the most differentiated form of the neuroblastic tumors composed of mature ganglion and bundles of Schwann cells. It has been most commonly identified in patients 10 to 40 years old, usually in the posterior mediastinum or retroperitoneum. For the present patient, collaboration with the hematology and oncology department suggested that the appropriate management would be surgical excision with disease-free margins. According to Bernardi et al,25 the definitive treatment for lesions in the retroperitoneum is surgical excision with radiotherapy and/or chemotherapy, depending on the tumor size. If not resected, a ganglioneuroma has the potential to differentiate back to a malignant
FIGURE 8. Strong staining of synaptophysin (original magnification 10). Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
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FIGURE 9. Resection of the tumor. Note, expansion of the mandible in the bilateral dimension. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
peripheral neuroblastic tumor.25 Similar to neuroblastoma, the presentation of a ganglioneuroma within the mandible is extremely rare. As of 2000, only 5 cases
had been reported.13,21,22,24 This theory was first proposed by Cushing and Wolbach26 in 1927, who reported a complex relationship between
FIGURE 10. Specimen of the right mandibular body and subcondylar segment. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
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FIGURE 11. Three-dimensional reconstruction of the graft approximately 1 year after resection and reconstruction. Note, novel bone growth present distal to tooth 27. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
ganglioneuroma and neuroblastoma, stating that the former was a more differentiated form of the latter. Subsequently, Young6 and Chou and Hansen12 described cases of jaw ganglioneuromas and also proposed that they were metastatic lesions from a primary neuroblastoma. Ganglioneuromas have been rare in the mandible and do not have a standardized protocol for their management. In our experience, the fibula free flap provided sufficient bone, given the size of this defect. The fibula is unique in that it is the only graft that provides enough bone length to address subtotal or total mandibular defects. Furthermore, the bone volume will be adequate to accept placement of endosteal dental implants, with the average cross-sectional area of the fibula 90 mm2. However, the use of the free fibula flap can create a height discrepancy with the native mandibular bone and could require a double barrel technique before prosthodontic rehabilitation.27-29 Owing to the size and linear dimension of the defect, we agreed that a fibula free flap was the procedure of choice for this reconstruction.
References 1. Ellis E, Zide MF: Surgical Approaches to the Facial Skeleton (ed 2). New York, Lippincott Williams & Wilkins, 2006. pp 151–189 2. Patterson AR, Barker CS, Loukota RA, Spencer J: Ganglioneuroma of the mandible resulting from metastasis of neuroblastoma. Int J Oral Maxillofac Surg 38:196, 2009 3. Bhattacharyya I, Williamson A, Cohen DM, Bever JL: Metastatic neuroblastoma with ganglioneuromatous differentiation and mandibular involvement. Oral Surg Oral Med Oral Pathol 88:586, 1999 4. Borle RM, Hazare VK, Bhowate RR, Borle SR: Neuroblastoma metastasis to the mandible. J Oral Maxillofac Surg 49:1124, 1991 5. Ghali VS, Gold JE, Raf VA, Cosgrove JM: Malignant peripheral nerve sheath tumour arising spontaneously from retroperitoneal ganglioneuroma: A case report, review of the literature, and immunohistochemical study. Hum Pathol 23:72, 1992 6. Young WG: Histopathologic study of ganglioneuroma of the mandible. J Oral Surg 25:327, 1967 7. Brodeur GM, Castleberry RP: Neuroblastoma, in Pizzo PA, Poplack DG (eds): Principles and Practice of Pediatric Oncology. Philadelphia, JB Lippincott, 1997, pp 761–797 8. Shimada H: Tumors of the neuroblastoma group. Pathology 2:43, 1993 9. Joshi VV, Silverman JF: Pathology of neuroblastic tumors. Semin Diagn Pathol 11:107, 1994 10. Kenney LB, Miller BA, Ries LA, et al: Increased incidence of cancer in infants in the US: 1980-1990. Cancer 82:1396, 1998 11. Groves A, Fregman A, Rauck A, et al: The National Cancer Data Base report on patterns of childhood cancer in the US. Cancer 80:2321, 1997
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12. Chou L, Hansen LS: Ganglioneuroma of the mandible. Oral Surg Oral Med Oral Pathol 68:201, 1989 13. Oeppen R, Brennan P, Stutley J: Ganglioneuroma of the mandible: Radiographic and pathologic findings of a rare tumor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 89:259, 2000 14. Joshi VV, Rao PV, Cantor AB, et al: Modified histologic grading of neuroblastomas by replacement of mitotic rate with mitosis karyorrhexis index: A clinicopathologic study of 223 cases from the Pediatric Oncology Group. Cancer 77:1582, 1996 15. Joshi VV, Cantor AB, Altshuler G, et al: Age-linked prognostic categorization based on a new histologic grading system of neuroblastomas: A clinicopathologic study of 211 cases from the Pediatric Oncology Group. Cancer 69:2197, 1992 16. Everson TC, Cole WH: Spontaneous regression of neuroblastoma, in Everson TC, Cole WH (eds): Spontaneous Regression of Cancer. Philadelphia, WB Saunders, 1966. pp 88–163 17. Shimada H, Chatten J, Newton WA Jr, et al: Histopathologic prognostic factors in neuroblastic tumors: Definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. J Natl Cancer Inst 73:504, 1984 18. Shimada H, Inge MA, Dehner LP, et al: Terminology and morphologic criteria of neuroblastic tumors, recommendations by the International Neuroblastoma Pathology Committee. Cancer 86:349, 1999 19. Shimada H, Ambros IM, Dehner LP, et al: The international neuroblastoma pathology classification (the Shimada System). Cancer 86:364, 1999
20. Antoine P, Raphael B, Bachelot H, et al: Primary neuroblastoma of the mandible—Apropos of the case. Rev Stomatol Chir Maxillofac 85:314, 1984 21. Wright BA, Jackson D: Neural tumors of the oral cavity: A review of the spectrum of benign and malignant oral tumors of the oral cavity and jaws. Oral Surg Oral Med Oral Pathol 49:509, 1980 22. Murphy J, Giunta JH: Atypical central neurilemmoma of the mandible. Oral Surg Oral Med Oral Pathol 59:275, 1985 23. Hustin J, Delire Y: Unusual intramandibular neural tumor. Oral Surg Oral Med Oral Pathol 71:593, 1991 24. Wilber MC, Woodcock JA: Ganglioneuromata in bone: Report of a case. J Bone Joint Surg 39A:1385, 1957 25. Bernardi B, Gambini C, Haupt R, et al: Retrospective study of childhood ganglioneuroma. J Clin Oncol 26:1710, 2008 26. Cushing H, Wolbach SB: Transformation of malignant paravertebral sympathicoblastoma into benign ganglioneuroma. Am J Pathol 2:203, 1927 27. Burley BB, Schmalbach CE, Coleman JR: Microvascular flaps, in Papel ID, Frodel JK, Holt GR (eds): Facial Plastic and Reconstructive Surgery. New York, Thieme Medical Publishers, 2009. pp 779–781 28. Roumonas ED, Markowitz BC, Lorant JA, et al: Reconstructed mandibular defects: Fibula free flaps and osseointegrated implants. Plast Reconstr Surg 99:356, 1997 29. He Y, Zhang ZY, Zhu HG, et al: Double-barrel fibula vascularized free flap with dental rehabilitation for mandibular reconstruction. J Oral Maxillofac Surg 69:2663, 2011
Treatment of a Rare Ganglioneuroma With Resection and Reconstruction of the Mandible: A Case Report and Literature Review Joseph Pierse, DMD, MA,* Edmund Ying-Peng Wun, DDS,y Robert Pellecchia, DDS,z and Jessica Wollenberg, DDSx Ganglioneuromas are rare neuroblastic tumors that develop from the neural crests of the sympathetic nervous system. Because ganglioneuromas of the mandible have been infrequent, they do not have a standardized management protocol. As of 2000, only 5 cases had been reported. Ganglioneuromas are unique tumors that can undergo histologic maturation from a malignancy to a benign variant. We present the case of a 15-year-old boy with a ganglioneuroma of the mandible and the results of surgical management, including immediate reconstruction with a free fibula microvascular flap. Ó 2014 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 72:748.e1-748.e9, 2014
Case Report A 15-year-old boy had been referred to the Geisinger Medical Center by his general dentist after an incidental finding on a panoramic radiograph of an osteolytic lesion of the right mandible. The patient had a previous history of stage IV neuroblastoma of the left abdomen and had undergone radiotherapy to the skull, left orbit, and femur and 2 cycles of neoadjuvant chemotherapy before adrenalectomy at 2 years of age. He had been receiving treatment from the pediatric hematology and oncology department. After obtaining a computed tomography (CT) scan of the mandible, the patient was referred to the oral and maxillofacial surgery department. The patient was asymptomatic and had no history of swelling or numbness. Secondary to his treatment of the neuroblastoma, he also presented with bilateral optic nerve atrophy, a bilateral hearing deficit, and hypothyroidism. The patient had no known allergies, and his social history was negative. His medications included levo-
thyroxine 50 mg/day. The patient’s vital signs were within normal limits, and the review of his systems was unremarkable. On physical examination, the patient was alert and fully oriented. He had moderate right facial asymmetry, without erythema, warmth, or tenderness to palpation. Moderate blunting of the inferior border of the right mandible was present. No lymphadenopathy was appreciated. The extraocular muscles were intact, and the pupils were equal, round, and reactive to light and accommodation. He had a slight visual acuity deficit bilaterally, and horizontal nystagmus was noted bilaterally. He had no nasal deformity. The floor of the mouth was soft, not tender, and not distended. The oropharynx was clear, with the uvula at the midline. No cant of the occlusal plane was noted. The occlusion was stable and reproducible. The maximum incisal opening was approximately 40 mm without deviation on opening or closing. No gross mobility of the dentition was present. Moderate buccal and lingual bony expansion of the right mandibular body and ramus was present. No evidence was seen of a
*Chief Resident, Department of Oral and Maxillofacial Surgery,
Geisinger Medical Center, 100 N Academy Ave, Danville, NY 17821;
INITIAL EXAMINATION
The Brooklyn Hospital Center, Brooklyn, NY.
e-mail: [email protected]
yAttending Physician, Geisinger Medical Center, Danville, PA.
Received September 16 2013
zChairman, Department of Oral and Maxillofacial Surgery and
Accepted December 17 2013
Dental Medicine, Geisinger Medical Center, Danville, PA. xChief Resident, Department of Oral Pathology, New York
Ó 2014 American Association of Oral and Maxillofacial Surgeons
Hospital, New York, NY.
http://dx.doi.org/10.1016/j.joms.2013.12.014
0278-2391/13/01545-0$36.00/0
Address correspondence and reprint requests to Dr Pellecchia: Department of Oral and Maxillofacial Surgery and Dental Medicine,
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trigeminal or facial nerve deficit. The temporomandibular joint examination findings were also negative. A panoramic film showed a large, multilocular lesion extending inferiorly from the neck of the right condyle and anteriorly to the lower right first bicuspid. Marked root resorption was localized to the teeth of the lower right quadrant. The lesion did not cross the midline (Fig 1). A maxillofacial computed tomography scan showed the lesion measured 2.4 cm in the transverse dimension and 3.4 cm anteroposteriorly and 4.6 cm craniocaudally in its greatest dimensions. An axial cut bony window of the maxillofacial CT scan showed an expansile lesion of the right mandible in the buccal and lingual dimensions, with trabeculations noted posteriorly (Fig 2). These findings were consistent with those from the panoramic radiograph. A coronal cut tissue window also showed moderate buccal and lingual expansion of the right mandibular ramus and body. The buccal and lingual cortices remained intact. The density of the lesion was consistent with soft tissue, measuring 43.85 Hounsfield units at its center. A 3-dimensional reconstruction was completed, and stereolithic models were fabricated using the CT findings (Medical Modeling, Golden, CO; Fig 3). BIOPSY AND HISTOPATHOLOGIC FINDINGS
With the patient under general anesthesia, an 18gauge needle was inserted into the right body of the mandible with no evidence of fluid or blood
on aspiration. After the negative aspirate, an incisional biopsy was completed, using a 1.5 1.5cm bony window, in the lower right quadrant of the mandible. A deep soft tissue biopsy was obtained with sharp instrumentation for histologic evaluation. Two specimens were obtained from the biopsy site for frozen and permanent histopathologic study. The differential diagnosis included ameloblastoma, myxoma, odontogenic keratocyst, central giant cell granuloma, and mucoepidermoid carcinoma. The results of the frozen section examination were consistent with a benign entity of probable neural origin without evidence of cellular atypia. The second sample was evaluated at the Oral Pathology Laboratory (Flushing, NY). Histopathologic examination of the hematoxylin and eosin-stained slides showed a benign neural tumor composed of haphazardly crisscrossing bundles of Schwann cells. Clusters of variably sized ganglion cells were seen scattered throughout the neural stroma. The ganglion cells contained abundant eosinophilic cytoplasm and single to multiple nuclei without significant atypia (Figs 4, 5). Strong and diffuse staining was present in both the schwannian and ganglion cell components for S100, neurofilament protein, and synaptophysin. The histopathologic and immunohistochemical profile was consistent with the diagnosis of ganglioneuroma (Figs 6-8).
FIGURE 1. A panoramic radiograph showing a lesion of the right body and ramus extending inferior to the neck of the right condyle to the lower right quadrant, lower right first bicuspid. The lesion is mostly unilocular with multilocular components. Evidence of root resorption is present. The lesion did not cross the midline and was well-delineated anteriorly. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
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FIGURE 2. Maxillofacial computed tomography scan depicting a bony window, axial cut at the level of the mandible. Evidence of a gross expansile lesion bilaterally was present in the right mandible. Trabeculations were appreciated posteriorly. Note, no gross deviation of the airway was present. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
SURGICAL COURSE
After histopathologic examination and confirmation of the diagnosis of ganglioneuroma of the mandible, a surgical treatment plan was developed that included resection (Figs 9, 10) of the tumor with simultaneous reconstruction using a microvascular free fibula graft.1 The patient underwent successful resection with disease-free margins and immediate reconstruction using a free fibula graft. The 1-year follow-up examination revealed anatomic restoration of function with the absence of disease and recurrence (Fig 11).
Discussion Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma are the differential stages of peripheral neuroblastic tumors that develop from the sympathetic nervous system and are derived from neural crest tissue. Neuroblastoma is the most common extracranial
solid tumor in childhood, accounting for approximately 8 to 10% of tumors and 15% of all childhood cancer mortality. It often manifests in the adrenal gland, with the greatest incidence at 2 years of age. It is known to be a highly malignant and aggressive tumor. Neuroblastomas are often asymptomatic and can go undetected until a large abdominal mass or metastatic lesion develops. According to the published data, the prevalence of a neuroblastoma is approximately 1/700 live births. The male predilection has been slightly greater, at approximately 1.2:1. Most primary tumors occur within the abdomen, with the incidence of adrenal tumors greater in children (40%) than in infants (25%).2-11 Pathognomonic abnormalities are common and include deletion of the short arm of chromosome 1 distal to band p32, double minute chromatin bodies, and homogeneously staining regions. A translocation between chromosomes 1 and 17 and alterations in
PIERSE ET AL
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FIGURE 3. Fabrication of the stereolithic model from the computed tomography scans. Note, the extent of the tumor inferior to the right condyle to lower right first bicuspid. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
FIGURE 4. Low power photomicrograph depicting crisscrossing bundles of Schwann cells (hematoxylin and eosin stain, original magnification 4). Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
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FIGURE 5. Clusters of ganglion cells deposited in a neural background (hematoxylin and eosin stain, original magnification 10). Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
the N-myc oncogene could also play a significant role in determining the patient’s prognosis.3,6,8,9,12-16 As of 1999, the International Neuroblastoma Pathology Committee had modified the existing Shimada classification of neuroblastic tumors and defined 4
categories: 1) neuroblastoma (schwannian stroma– poor), undifferentiated, poorly differentiated, and differentiating; 2) ganglioneuroblastoma, intermixed (schwannian stroma–rich); 3) ganglioneuroma (schwannian stroma–dominant), maturing and mature;
FIGURE 6. Strong and diffuse staining for S100 protein (original magnification 10). Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
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FIGURE 7. Strongly diffuse staining of neurofilament protein (original magnification 10). Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
and 4) ganglioneuroblastoma, nodular (composite schwannian stroma–rich/stroma–dominant and stroma– poor). This is an age-linked classification according to the differentiation of neuroblasts, cellular turnover, and the presence or absence of schwannian stromal development.17-19 A rare feature of neuroblastoma is that it can undergo histologic maturation and differentiate and mature into a benign ganglioneuroma, which is counterintuitive when considering the natural progression from normal to malignant tissue. The published data have shown that this can occur after the treatment of a primary neuroblastoma. However, neuroblastoma metastasis to the mandible has been described in very few cases.20-24
Ganglioneuroma is the most differentiated form of the neuroblastic tumors composed of mature ganglion and bundles of Schwann cells. It has been most commonly identified in patients 10 to 40 years old, usually in the posterior mediastinum or retroperitoneum. For the present patient, collaboration with the hematology and oncology department suggested that the appropriate management would be surgical excision with disease-free margins. According to Bernardi et al,25 the definitive treatment for lesions in the retroperitoneum is surgical excision with radiotherapy and/or chemotherapy, depending on the tumor size. If not resected, a ganglioneuroma has the potential to differentiate back to a malignant
FIGURE 8. Strong staining of synaptophysin (original magnification 10). Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
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FIGURE 9. Resection of the tumor. Note, expansion of the mandible in the bilateral dimension. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
peripheral neuroblastic tumor.25 Similar to neuroblastoma, the presentation of a ganglioneuroma within the mandible is extremely rare. As of 2000, only 5 cases
had been reported.13,21,22,24 This theory was first proposed by Cushing and Wolbach26 in 1927, who reported a complex relationship between
FIGURE 10. Specimen of the right mandibular body and subcondylar segment. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
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FIGURE 11. Three-dimensional reconstruction of the graft approximately 1 year after resection and reconstruction. Note, novel bone growth present distal to tooth 27. Pierse et al. Treatment of Rare Ganglioneuroma With Resection and Mandibular Reconstruction. J Oral Maxillofac Surg 2014.
ganglioneuroma and neuroblastoma, stating that the former was a more differentiated form of the latter. Subsequently, Young6 and Chou and Hansen12 described cases of jaw ganglioneuromas and also proposed that they were metastatic lesions from a primary neuroblastoma. Ganglioneuromas have been rare in the mandible and do not have a standardized protocol for their management. In our experience, the fibula free flap provided sufficient bone, given the size of this defect. The fibula is unique in that it is the only graft that provides enough bone length to address subtotal or total mandibular defects. Furthermore, the bone volume will be adequate to accept placement of endosteal dental implants, with the average cross-sectional area of the fibula 90 mm2. However, the use of the free fibula flap can create a height discrepancy with the native mandibular bone and could require a double barrel technique before prosthodontic rehabilitation.27-29 Owing to the size and linear dimension of the defect, we agreed that a fibula free flap was the procedure of choice for this reconstruction.
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