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Radiolucent Lesion of the Posterior Mandible
CLINICOTHERAPEUTIC CONFERENCE J Oral Maxillofac Surg 67:862-866, 2009
Radiolucent Lesion of the Posterior Mandible Brian Cherry, DMD,* Pushkar Mehra, BDS, DMD,† Vikki Noonan, DMD, DMSc,‡ and Dale Baur, DDS, MD§ board-like expansion extending toward the midline of the floor of mouth and posteriorly into the lateral pharyngeal area. A plain film radiographic examination showed a large, osteolytic, radiolucent lesion of the right mandibular ramus and body, causing significant displacement of an unerupted third molar (Fig 1B).
Ameloblastic carcinoma is an uncommon, malignant odontogenic tumor with a predilection for occurrence in the posterior mandible. Only a limited number of cases have been reported. We report on a 16-year-old male with ameloblastic carcinoma. This appears to be the first description of ameloblastic carcinoma of the mandible treated with: 1) an initial bony reconstruction using a microvascular free fibular flap and subsequent augmentation with conventional autogenous bone grafts, 2) an initial soft-issue reconstruction using a microvascular free-flap transfer and subsequent replacement with keratinized tissue grafts, and 3) rehabilitation using an implant-supported prosthesis.
Treatment Recommendations Dale A. Baur, DDS, MD Malignant odontogenic tumors are fortunately a rare occurrence. In this very interesting case, an incisional biopsy of a rapidly enlarging mandibular lesion in a 16-year-old male demonstrated islands of odontogenic epithelium resembling an ameloblastoma. However, there are obvious malignant cytologic characteristics in the specimen including sheets of atypical spindled epithelial cells exhibiting nuclear pleomorphism, mitotic figures, multiple nucleoli, and hyperchromaticity. Historically, there are 2 malignant variants of the ameloblastoma, specifically the malignant ameloblastoma and the ameloblastic carcinoma. The malignant ameloblastoma is characterized cytologically by a benign appearance in the primary tumor location, but with documented evidence of distant metastasis. On the other hand, the ameloblastic carcinoma has a histological appearance of an ameloblastoma, but also contains cytological malignant features. Based on the photomicrographs provided in this case, the diagnosis is most consistent with an ameloblastic carcinoma. In 2005, the World Health Organization provided a classification of ameloblastic carcinomas.1 In this scheme, ameloblastic carcinomas are subdivided into primary and secondary types. The primary type has the overall histological pattern of ameloblastoma, in addition to malignant cytological patterns. Secondary types, also referred to as dedifferentiated types, arise within a pre-existing ameloblastoma. The secondary type of ameloblastic carcinomas is further subdivided into intraosseous and peripheral types. Unlike more common malignancies of the oral cavity and jaws, there is a paucity of literature on the origin, biologic behavior, and treatment of the ameloblastic carcinoma.2 Avon et al reported in 2003 that the lesion occurs primarily in the mandible, with no gender or race predilection.3 Clinical presentations range from asymptomatic expansion to those with obvious malignant features, as in this case, with rapid expansion, paresthesia, pain, and imaging studies demonstrating extensive bony destruction. The aggressive nature and tendency of this tumor to metastasize was noted in this review. Corio et al, in 1987, reported on 8 cases registered at the Armed Forces Institute of Pathology.4 This case series found a mean age of 30.1 years, with no gender predilection. Seven of these cases involved the mandible. All 8 cases had radiographic findings of a poorly defined destructive lesion. One case exhibited lymphatic spread to the neck. Rapid growth, expansion, and trismus were common findings. In this report, Corio et al also noted the tendency of this tumor to have
Case Presentation A healthy 16-year-old male was referred to the Department of Oral and Maxillofacial Surgery at Boston University Medical Center (Boston, MA) with a 2-month history of a progressively and rapidly enlarging, painful swelling of his right mandible. Physical examination revealed an expansile mass in the right mandibular angle region (Fig 1A). The mass extended from the right angle region superiorly toward the pinna and temporomandibular joint regions, and anteriorly towards the mid-mandibular body region. There was a deviation of the chin to the contralateral side, and localized areas of hypopigmentation were visible over the right lower face. There was no associated trismus, but there was paresthesia in the right inferior alveolar nerve distribution. An intraoral examination showed a hard,
*Former Resident, Department of Oral and Maxillofacial Surgery, Boston Medical Center and Boston University School of Dental Medicine, Boston, MA; Currently, Private Practice, Columbia, SC. †Director and Vice-Chairman, Department of Dentistry and Oral and Maxillofacial Surgery, Boston Medical Center, and Associate Professor and Director of Residency Training, Department of Oral and Maxillofacial Surgery, Boston University School of Dental Medicine, Boston, MA. ‡Assistant Professor, Department of Oral and Maxillofacial Pathology, Boston University School of Dental Medicine, Boston, MA. §Associate Professor and Chair, Department of Oral and Maxillofacial Surgery, Case Western Reserve University, Cleveland, OH. Address correspondence and reprint requests to Dr Mehra: Department of Oral and Maxillofacial Surgery, Boston University School of Dental Medicine, 100 East Newton Street, Suite G-407, Boston, MA 02118; e-mail: [email protected] © 2009 American Association of Oral and Maxillofacial Surgeons
0278-2391/09/6704-0023$36.00/0 doi:10.1016/j.joms.2008.01.061
862
CHERRY, MEHRA, AND NOONAN
863 tumor arose de novo, or dedifferentiated from an existing ameloblastoma is irrelevant, as my surgical management would be the same. I feel the work-up already completed in this case is clinically sufficient to proceed with surgery. As a first step in this case, strong consideration would be given to securing the airway with a temporary tracheostomy, which would be maintained in the early postoperative period. To improve surgical access to the tumor, I would perform a lip splitting incision of the lower lip, extending this incision inferiorly and posteriorly into the neck as the horizontal component of a “wine glass” type incision. A vertical component added to this incision extending inferiorly to the clavicle would complete surgical access for a neck dissection. The primary tumor should be removed in an en-bloc fashion, with 1 to 1.5 cm margins in all dimensions. The adequacy of the soft tissue margins need to be verified by frozen section control. Oncologically sound bony margins may be verified with scrapings of the marrow space in the proximal and distal segments submitted for frozen section analysis. If the overlying skin was freely movable and not fixed to the tumor, it would be maintained, which I would expect to be the case with this patient. In addition, if not encased in the tumor, I would
FIGURE 1. A, A facial photograph shows significant facial asymmetry because of an expansile lesion of the right posterior mandible and floor of the mouth. B, A panoramic radiograph shows a large, radiolucent lesion of the right mandibular ramus, with a displaced third molar. Cherry, Mehra, and Noonan. Radiolucent Lesion of the Posterior Mandible. J Oral Maxillofac Surg 2009.
frequent recurrences. Benlyazid et al reported on a case of a maxillary ameloblastic carcinoma and reviewed the literature in 2007.5 Of the 65 cases they reviewed in the international literature, they reported a median age of 44 years, with two thirds of the cases occurring in men. The mandible also showed a two thirds predominance for location. From their review, the estimated 5-year survival rate was 68%, with mortality generally due to metastatic spread to the lungs, brain, and other bones. In 2007, Akrish et al presented a comprehensive review of the literature and analyzed 37 cases of ameloblastic carcinoma reported from 1984 to 2004.6 In this review, they found a male to female incidence of almost 2:1. Age at diagnosis ranged from 15 to 84 years, with a mean age of 52 years. The mandible was the location of the tumor in 66% of the cases. In this case series, common presentations included expansion, pain, tooth mobility, ulceration, trismus, and paresthesia. Of the 37 cases reviewed, the survival status was available for 23 cases at the time of the original publication. Fourteen patients were alive, while 9 had expired. Of the 9 patients that expired, 7 had a reported recurrent or metastatic tumor. The exact cause of death was not determined for all 9 patients, but four patients were confirmed to have died from metastatic or uncontrolled local/regional recurrence. From the available literature over the last 20 years, one can conclude that the ameloblastic carcinoma, especially of the mandible, is a highly malignant neoplasm with a biological behavior necessitating an aggressive surgical approach to provide the best chance of survival.3,7-10 Whether this particular
FIGURE 2. A, Odontogenic epithelial islands show peripheral columnar differentiation, with reverse nuclear polarity and central stellate-reticulum-like areas (hematoxylin-eosin stain, original magnification, ⫻100). B, A proliferation of spindle cells shows numerous atypical mitotic figures, nuclear hyperchromaticity, and pleomorphism (hematoxylin-eosin stain, original magnification, ⫻200). Cherry, Mehra, and Noonan. Radiolucent Lesion of the Posterior Mandible. J Oral Maxillofac Surg 2009.
864
RADIOLUCENT LESION OF THE POSTERIOR MANDIBLE preserved, a reconstruction plate with a condylar prosthesis is an option. Consideration could be given for immediate reconstruction of the mandible with a microvascular free fibula graft, although delayed secondary reconstruction with a nonvascularized posterior iliac crest bone graft is a highly acceptable alternative. If a free flap was not done, and additional soft tissue was needed to close the oral defect, a pectoralis major flap would be another option. The role of postoperative radiation treatment is unknown for this malignant tumor, as there are too few cases to make a definitive recommendation.3 However, in this circumstance, radiation would be a consideration if there were multiple positive nodes in the pathologic examination of the neck. This patient would require close postoperative monitoring for local/regional recurrence or metastatic spread. For the first postoperative year, I would see this patient on a monthly basis. Periodic imaging of the head and neck, as well as distant sites (eg, chest x-ray) would be necessary to obtain postoperative baseline studies. A PET scan would also be a useful study to obtain to monitor for recurrence and or metastatic spread. After the first year, regular periodic assessment would be necessary to monitor for recurrence and/or the development of distant disease.
Subsequent Course An incisional biopsy was performed under local anesthesia in the office. A histopathologic examination of the biopsy
FIGURE 3. A, An axial computed tomography scan of the mandible showing a large, expansile mass in the left mandible region. B, Threedimensional coronal reconstruction image showing extensive bone destruction. Cherry, Mehra, and Noonan. Radiolucent Lesion of the Posterior Mandible. J Oral Maxillofac Surg 2009.
attempt to maintain the marginal mandibular branch of the facial nerve. Although the imaging obtained in this case did not demonstrate nodal involvement in the neck, I feel an elective neck dissection is indicated to address the risk of occult neck disease and improve overall survival. In this case, I would perform a selective neck dissection, sparing the spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle. It would be my intention to remove the tumor and neck contents en-bloc. The condylar neck appears to be free of involvement according to the imaging report. I would place a reconstruction plate from the condylar stump the symphysis area to restore continuity of the remaining mandible. If in order to maintain an oncologically sound surgery, the condyle was unable to be
FIGURE 4. A, An intraoperative view shows augmentation of the atrophic and fractured vascularized free flap, with autogenous, cancellous marrow grafts harvested from the iliac crest. B, A dental computed tomography scan shows a successfully augmented free fibular graft with radiopaque implant markers. Cherry, Mehra, and Noonan. Radiolucent Lesion of the Posterior Mandible. J Oral Maxillofac Surg 2009.
865
CHERRY, MEHRA, AND NOONAN
FIGURE 5. A panoramic radiograph shows the atrophic (and previously fractured) free fibular graft after the placement of 5 endosseous dental implants. Cherry, Mehra, and Noonan. Radiolucent Lesion of the Posterior Mandible. J Oral Maxillofac Surg 2009.
specimen showed islands of odontogenic epithelium that exhibited peripheral columnar epithelial cells, remarkable for palisading and reversed nuclear polarity (Fig 2A). In addition, sheets of atypical, spindled epithelial cells exhibited nuclear pleomorphism, occasional atypical mitotic figures, multiple nucleoli, and hyperchromaticity (Fig 2B). Keratin pearl formation was focally observed, with infiltrative tumor islands extending to the margins of the tissue sections examined. A final diagnosis of “malignant odontogenic tumor with features of ameloblastic differentiation” was established. Whether or not this neoplasm arose in a preexisting ameloblastoma cannot be unequivocally determined. Computed tomography (CT) scanning of the maxillofacial and neck regions showed a mass measuring 7 ⫻ 7 ⫻ 6 cm within the posterior body and angle of the mandible (Fig 3). There was associated cortical disruption, with a displaced third molar. The condylar neck showed no evidence of involvement. No significant lymphadenopathy was present, and the largest node was approximately 10 ⫻ 5 mm in measurement, and was located slightly anterior to the right submandibular gland. Magnetic resonance imaging was obtained for more complete evaluation, and confirmed the absence of nodal metastasis, and a lack of invasion into the soft tissues of the floor of the mouth and tongue. A CT examination of the chest and abdominal regions was unremarkable. In view of the rarity and complexity of the tumor, the patient was presented at a combined hospital tumor board for planning of comprehensive treatment. The proposed treatment included a disarticulation segmental resection with 2-cm bony margins, resection of the soft tissues to clear margins, a tracheostomy, modified radical neck dissection, and reconstruction of the mandible with a fibular, osteomyocutaneous, vascularized free flap, and postoperative radiation therapy. In preparation for surgery, a magnetic resonance angiogram of the lower extremities was obtained, and it showed good 3-vessel runoff. The patient underwent surgery without complications, and a histopathologic examination was consistent with a diagnosis of ameloblastic carcinoma. All bony surgical margins and lymph nodes were found to be free of tumor. However, the margins were close and less than 2 cm (but greater than 1 cm) in some areas. The case was discussed at the local hospital’s tumor board, and it was decided that additional surgery was not recommended at this stage. The patient had an unremarkable course in the immediate postoperative period. Radiation therapy was initiated, and the patient received a total dose of 6,000 cGy to the primary site and the neck in fractionated doses.
Approximately 1 year after free-flap reconstruction, the patient presented with intermittent swelling of the anterior fibular and mandibular area. Clinical and radiographic examinations showed a likely fracture in the anterior part of the microvascular graft. Some purulent discharge was present around the anterior fibular and mandibular region. Initially the infection was managed successfully with local debridement in the office, oral antibiotic therapy, and 30 dives of hyperbaric oxygen (HBO) therapy. The patient expressed a desire for prosthetic rehabilitation with endosseous dental implants. Because previous CT scanning revealed an atrophic fibula and mandible which had already fractured, a decision was made to augment the microvascular fibular graft with iliac crest bone grafts, followed by delayed implant placement. The mandibular reconstruction plate was removed, the area of the fracture was debrided, and augmentation of the graft was performed as an outpatient surgery procedure, with corticocancellous bone grafts harvested from the anterior iliac crest (Fig 4). Postoperatively, the patient received 10 additional HBO sessions, and healing was uneventful. Placement of 5 endosseous dental implants was performed approximately 5 months after grafting (Fig 5). Secondary softtissue reconstruction was performed 6 months after implant placement. This included debulking of the excessively thick intraoral skin-muscle tissue flap with a modified vestibuloplasty, using keratinized tissue grafts harvested from the palate. The patient was prosthetically rehabilitated with a mandibular hybrid prosthesis. As of the writing of this report, the patient has recently been diagnosed with metastases to the brain and lung regions. He has undergone frontal bone and dural resection, reconstruction of the frontal region with a pericranial flap, and lower left lobe lung removal. Chemotherapy treatment with paclitaxel and carboplatin is continuing.
Discussion Ameloblastoma is a locally infiltrative, benign, odontogenic neoplasm typically arising in the posterior regions of the jaws. Approximately 80% of ameloblastomas were reported to occur in the mandible, and 20% in the maxilla.10,11 A rare, malignant variant of ameloblastoma was first described in the medical literature in 1950.12 The World Health Organization separated this variant into its current subtypes, ie, malignant ameloblastoma and ameloblastic carcinoma, in 1972.13 This classification was further revised by Slootweg and Muller in 1984.14 The World Health Organization described malignant ameloblastoma as a tumor showing the histopathologic features of classic ameloblastoma with metastatic deposits, and defined ameloblastic carcinoma as an epithelial proliferation with histopathologic features of malignancy, either associated with an ameloblastoma (carcinoma ex-ameloblastoma) or representing a de novo carcinoma that resembles ameloblastoma histopathologically.15 The histopathologic features of both the primary and metastatic foci of malignant ameloblastoma are indistinguishable from conventional ameloblastoma. Thus, metastases must be present to establish a diagnosis of malignant ameloblastoma. Metastatic foci were reported in the lung (75%), cervical lymph nodes (15%), and spine (15%), and less frequently in the liver, skull, diaphragm, and brain.11 Conversely, ameloblastic carcinoma shows the histopathologic features of malignancy, with or without metastatic spread. This lesion may arise de novo, ex-ameloblastoma,
866 or ex-odontogenic cyst,14 and is remarkable for its aggressive clinical course. Ameloblastic carcinoma has a predilection for occurrence in the posterior mandible. Only a limited number of cases were reported in the maxilla.10,16 Although the tumor can present over a wide age range, the mean age of patients diagnosed with ameloblastic carcinoma is 30.1 years. Most patients present with cortical expansion and pain, and aggressive behavior and recurrence are frequently cited in the clinical course.4 A diagnosis of ameloblastic carcinoma was established in our patient, based on histopathologic features including evidence of ameloblastic differentiation together with the presence of nuclear pleomorphism and atypical mitotic figures. The lesion was rapidly growing and locally aggressive, with bone destruction, and showed no evidence of metastases. Wide, local excision with 2-to-3-cm bony margins is considered the treatment of choice.3,17 Neck dissections are usually recommended. Although postoperative radiotherapy should be strongly considered, especially for large lesions, there is a paucity of well-documented cases to ratify this protocol.16,18,19 Our patient had a composite resection of the hemimandible via combined extraoral and intraoral approaches. Although the condylar neck was spared from the tumor, a temporomandibular joint disarticulation resection was completed, sparing the meniscus, because the required surgical margins necessitated condylar sacrifice. Meniscal preservation was previously reported during disarticulation resections in the treatment of malignancies that spared the condylar neck region.20 A microvascular, osteocutaneous, fibular free flap was initially used to reconstruct the resultant hard-tissue and soft-tissue defects after tumor extirpation, because the patient preferred one-stage treatment (bone/soft-tissue resection, and concomitant reconstruction), compared with the conventional staged treatment with pedicled myocutaneous flaps and delayed bone grafting. In addition, reconstruction of the mandible with bone in the form of a free flap allowed for immediate postoperative radiation treatment, which was strongly recommended by the hospital’s tumor board, given the “close” soft-tissue margins. The development of a delayed fracture at the collapsed osteotomy site of the fibular graft was successfully treated with local debridement, antibiotics, HBO therapy, and simultaneous grafting with iliac-crest bone grafts in preparation for dental implants. All implants osseointegrated, and were restored without complications. Secondary soft-tissue reconstruction with keratinized grafts was unremarkable. Ameloblastic carcinoma has reported recurrence rates of between 15%19 and 60%,17 even when treated with aggressive surgical excision. Five-year survival rates were reported to be less than 40%.4,17 Because of recurrence and reported metastases to the lungs and lymph nodes,3,4,14,18,21 close, periodic clinical and radiographic re-evaluation of the patient is mandatory. Our patient has been recently diagnosed with metastatic lesions in the brain and lung.
RADIOLUCENT LESION OF THE POSTERIOR MANDIBLE
This appears to be the first report of ameloblastic carcinoma of the mandible treated with: 1) an initial bony reconstruction using a microvascular free fibular flap and subsequent augmentation with conventional autogenous bone grafts, 2) an initial soft-issue reconstruction using microvascular free-flap transfer and subsequent replacement with keratinized tissue grafts, and 3) complete, successful, dental prosthetic rehabilitation, using an implantsupported prosthesis in a radiated and reconstructed mandible after HBO therapy. However, despite these efforts and “presumably” adequate treatment, long-term prognosis for such patients remains poor.
References 1. Barnes L, Eveson JW, Reichart P, et al (eds): Pathology and Genetics: Head and Neck Tumors. Lyon, World Health Organization, 2005, pp 287-289. 2. Ward BB, Edlund S, Sciubba J, et al: Ameloblastic carcinoma (primary type) isolated in the anterior maxilla: Case report with review of the literature. J Oral Maxillofac Surg 65:1800, 2007 3. Avon SL, McComb J, Clokie C: Ameloblastic carcinoma: Case report and literature review. J Can Dent Assoc 69:573, 2003 4. Corio RL, Goldblatt LI, Edwards PA, et al: Ameloblastic carcinoma: A clinicopathologic study and assessment of eight cases. Oral Surg Oral Med Oral Pathol 64:570, 1987 5. Benlyazid A, Lacroix-Triki M, Aziza R, et al: Ameloblastic carcinoma of the maxilla: case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:e17, 2007 6. Akrish S, Buchner A, Shoshani Y, et al: Ameloblastic carcinoma: Report of a new case, literature review, and comparison to ameloblastoma. J Oral Maxillofac Surg 65:777, 2007 7. Hall JM, Weathers DR, Unni KK: Ameloblastic carcinoma: An analysis of 14 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103:799, 2007 8. Simko EJ, Brannon RB, Eibling DE: Ameloblastic carcinoma of the mandible. Head Neck 20:654, 1998 9. Goldenberg D, Sciubba J, Koch W, et al: Malignant odontogenic tumors: A 22-year experience. Laryngoscope 114:1770, 2004 10. Sastre J, Munoz M, Naval L, et al: Ameloblastic carcinoma of the maxilla: Report of a case. J Oral Maxillofac Surg 60:102, 2002 11. Verneuil A, Sapp P, Huang C, et al: Malignant ameloblastoma: Classification, diagnostic, and therapeutic challenges. Am J Otolaryngol 23:44, 2002 12. Thoma K: Oral Pathology. St Louis, MO, CV Mosby, 1950, pp 1270-1333 13. Pindborg J, Kramer I, Torloni H: Historical Typing of Odontogenic Tumors, Jaw Cysts, and Allied Lesions. Geneva, Switzerland, World Health Organization, 1972, pp 35-36 14. Slootweg PJ, Muller H: Malignant ameloblastoma or ameloblastic carcinoma. Oral Surg Oral Med Oral Pathol 57:168, 1984 15. World Health Organization: World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. Lyon, France, International Agency for Research on Cancer Press, 2005 16. Dhir K, Sciubba J, Tufano RP: Ameloblastic carcinoma of the maxilla. Oral Oncol 39:736, 2003 17. Marx RE, Stern D: Oral and Maxillofacial Pathlogy: A Rationale for Diagnosis and Treatment. Chicago, IL, Quintessence Publishing Co, Inc, 2003, p 657 18. Bruce RA, Jackson IT: Ameloblastic carcinoma. Report of an aggressive case and review of the literature. J Craniomaxillofac Surg 19:267, 1991 19. Datta R, Winston JS, Diaz-Reyes G, et al: Ameloblastic carcinoma: Report of an aggressive case with multiple bony metastases. Am J Otolaryngol 24:64, 2003 20. Carlson ER: Disarticulation resections of the mandible: A prospective review of 16 cases. J Oral Maxillofac Surg 60:176, 2002 21. Cizmecy O, Aslan A, Onel D, et al: Ameloblastic carcinoma ex ameloblastoma of the mandible: Case report. Otolaryngol Head Neck Surg 130:633, 2004
Radiolucent Lesion of the Posterior Mandible Brian Cherry, DMD,* Pushkar Mehra, BDS, DMD,† Vikki Noonan, DMD, DMSc,‡ and Dale Baur, DDS, MD§ board-like expansion extending toward the midline of the floor of mouth and posteriorly into the lateral pharyngeal area. A plain film radiographic examination showed a large, osteolytic, radiolucent lesion of the right mandibular ramus and body, causing significant displacement of an unerupted third molar (Fig 1B).
Ameloblastic carcinoma is an uncommon, malignant odontogenic tumor with a predilection for occurrence in the posterior mandible. Only a limited number of cases have been reported. We report on a 16-year-old male with ameloblastic carcinoma. This appears to be the first description of ameloblastic carcinoma of the mandible treated with: 1) an initial bony reconstruction using a microvascular free fibular flap and subsequent augmentation with conventional autogenous bone grafts, 2) an initial soft-issue reconstruction using a microvascular free-flap transfer and subsequent replacement with keratinized tissue grafts, and 3) rehabilitation using an implant-supported prosthesis.
Treatment Recommendations Dale A. Baur, DDS, MD Malignant odontogenic tumors are fortunately a rare occurrence. In this very interesting case, an incisional biopsy of a rapidly enlarging mandibular lesion in a 16-year-old male demonstrated islands of odontogenic epithelium resembling an ameloblastoma. However, there are obvious malignant cytologic characteristics in the specimen including sheets of atypical spindled epithelial cells exhibiting nuclear pleomorphism, mitotic figures, multiple nucleoli, and hyperchromaticity. Historically, there are 2 malignant variants of the ameloblastoma, specifically the malignant ameloblastoma and the ameloblastic carcinoma. The malignant ameloblastoma is characterized cytologically by a benign appearance in the primary tumor location, but with documented evidence of distant metastasis. On the other hand, the ameloblastic carcinoma has a histological appearance of an ameloblastoma, but also contains cytological malignant features. Based on the photomicrographs provided in this case, the diagnosis is most consistent with an ameloblastic carcinoma. In 2005, the World Health Organization provided a classification of ameloblastic carcinomas.1 In this scheme, ameloblastic carcinomas are subdivided into primary and secondary types. The primary type has the overall histological pattern of ameloblastoma, in addition to malignant cytological patterns. Secondary types, also referred to as dedifferentiated types, arise within a pre-existing ameloblastoma. The secondary type of ameloblastic carcinomas is further subdivided into intraosseous and peripheral types. Unlike more common malignancies of the oral cavity and jaws, there is a paucity of literature on the origin, biologic behavior, and treatment of the ameloblastic carcinoma.2 Avon et al reported in 2003 that the lesion occurs primarily in the mandible, with no gender or race predilection.3 Clinical presentations range from asymptomatic expansion to those with obvious malignant features, as in this case, with rapid expansion, paresthesia, pain, and imaging studies demonstrating extensive bony destruction. The aggressive nature and tendency of this tumor to metastasize was noted in this review. Corio et al, in 1987, reported on 8 cases registered at the Armed Forces Institute of Pathology.4 This case series found a mean age of 30.1 years, with no gender predilection. Seven of these cases involved the mandible. All 8 cases had radiographic findings of a poorly defined destructive lesion. One case exhibited lymphatic spread to the neck. Rapid growth, expansion, and trismus were common findings. In this report, Corio et al also noted the tendency of this tumor to have
Case Presentation A healthy 16-year-old male was referred to the Department of Oral and Maxillofacial Surgery at Boston University Medical Center (Boston, MA) with a 2-month history of a progressively and rapidly enlarging, painful swelling of his right mandible. Physical examination revealed an expansile mass in the right mandibular angle region (Fig 1A). The mass extended from the right angle region superiorly toward the pinna and temporomandibular joint regions, and anteriorly towards the mid-mandibular body region. There was a deviation of the chin to the contralateral side, and localized areas of hypopigmentation were visible over the right lower face. There was no associated trismus, but there was paresthesia in the right inferior alveolar nerve distribution. An intraoral examination showed a hard,
*Former Resident, Department of Oral and Maxillofacial Surgery, Boston Medical Center and Boston University School of Dental Medicine, Boston, MA; Currently, Private Practice, Columbia, SC. †Director and Vice-Chairman, Department of Dentistry and Oral and Maxillofacial Surgery, Boston Medical Center, and Associate Professor and Director of Residency Training, Department of Oral and Maxillofacial Surgery, Boston University School of Dental Medicine, Boston, MA. ‡Assistant Professor, Department of Oral and Maxillofacial Pathology, Boston University School of Dental Medicine, Boston, MA. §Associate Professor and Chair, Department of Oral and Maxillofacial Surgery, Case Western Reserve University, Cleveland, OH. Address correspondence and reprint requests to Dr Mehra: Department of Oral and Maxillofacial Surgery, Boston University School of Dental Medicine, 100 East Newton Street, Suite G-407, Boston, MA 02118; e-mail: [email protected] © 2009 American Association of Oral and Maxillofacial Surgeons
0278-2391/09/6704-0023$36.00/0 doi:10.1016/j.joms.2008.01.061
862
CHERRY, MEHRA, AND NOONAN
863 tumor arose de novo, or dedifferentiated from an existing ameloblastoma is irrelevant, as my surgical management would be the same. I feel the work-up already completed in this case is clinically sufficient to proceed with surgery. As a first step in this case, strong consideration would be given to securing the airway with a temporary tracheostomy, which would be maintained in the early postoperative period. To improve surgical access to the tumor, I would perform a lip splitting incision of the lower lip, extending this incision inferiorly and posteriorly into the neck as the horizontal component of a “wine glass” type incision. A vertical component added to this incision extending inferiorly to the clavicle would complete surgical access for a neck dissection. The primary tumor should be removed in an en-bloc fashion, with 1 to 1.5 cm margins in all dimensions. The adequacy of the soft tissue margins need to be verified by frozen section control. Oncologically sound bony margins may be verified with scrapings of the marrow space in the proximal and distal segments submitted for frozen section analysis. If the overlying skin was freely movable and not fixed to the tumor, it would be maintained, which I would expect to be the case with this patient. In addition, if not encased in the tumor, I would
FIGURE 1. A, A facial photograph shows significant facial asymmetry because of an expansile lesion of the right posterior mandible and floor of the mouth. B, A panoramic radiograph shows a large, radiolucent lesion of the right mandibular ramus, with a displaced third molar. Cherry, Mehra, and Noonan. Radiolucent Lesion of the Posterior Mandible. J Oral Maxillofac Surg 2009.
frequent recurrences. Benlyazid et al reported on a case of a maxillary ameloblastic carcinoma and reviewed the literature in 2007.5 Of the 65 cases they reviewed in the international literature, they reported a median age of 44 years, with two thirds of the cases occurring in men. The mandible also showed a two thirds predominance for location. From their review, the estimated 5-year survival rate was 68%, with mortality generally due to metastatic spread to the lungs, brain, and other bones. In 2007, Akrish et al presented a comprehensive review of the literature and analyzed 37 cases of ameloblastic carcinoma reported from 1984 to 2004.6 In this review, they found a male to female incidence of almost 2:1. Age at diagnosis ranged from 15 to 84 years, with a mean age of 52 years. The mandible was the location of the tumor in 66% of the cases. In this case series, common presentations included expansion, pain, tooth mobility, ulceration, trismus, and paresthesia. Of the 37 cases reviewed, the survival status was available for 23 cases at the time of the original publication. Fourteen patients were alive, while 9 had expired. Of the 9 patients that expired, 7 had a reported recurrent or metastatic tumor. The exact cause of death was not determined for all 9 patients, but four patients were confirmed to have died from metastatic or uncontrolled local/regional recurrence. From the available literature over the last 20 years, one can conclude that the ameloblastic carcinoma, especially of the mandible, is a highly malignant neoplasm with a biological behavior necessitating an aggressive surgical approach to provide the best chance of survival.3,7-10 Whether this particular
FIGURE 2. A, Odontogenic epithelial islands show peripheral columnar differentiation, with reverse nuclear polarity and central stellate-reticulum-like areas (hematoxylin-eosin stain, original magnification, ⫻100). B, A proliferation of spindle cells shows numerous atypical mitotic figures, nuclear hyperchromaticity, and pleomorphism (hematoxylin-eosin stain, original magnification, ⫻200). Cherry, Mehra, and Noonan. Radiolucent Lesion of the Posterior Mandible. J Oral Maxillofac Surg 2009.
864
RADIOLUCENT LESION OF THE POSTERIOR MANDIBLE preserved, a reconstruction plate with a condylar prosthesis is an option. Consideration could be given for immediate reconstruction of the mandible with a microvascular free fibula graft, although delayed secondary reconstruction with a nonvascularized posterior iliac crest bone graft is a highly acceptable alternative. If a free flap was not done, and additional soft tissue was needed to close the oral defect, a pectoralis major flap would be another option. The role of postoperative radiation treatment is unknown for this malignant tumor, as there are too few cases to make a definitive recommendation.3 However, in this circumstance, radiation would be a consideration if there were multiple positive nodes in the pathologic examination of the neck. This patient would require close postoperative monitoring for local/regional recurrence or metastatic spread. For the first postoperative year, I would see this patient on a monthly basis. Periodic imaging of the head and neck, as well as distant sites (eg, chest x-ray) would be necessary to obtain postoperative baseline studies. A PET scan would also be a useful study to obtain to monitor for recurrence and or metastatic spread. After the first year, regular periodic assessment would be necessary to monitor for recurrence and/or the development of distant disease.
Subsequent Course An incisional biopsy was performed under local anesthesia in the office. A histopathologic examination of the biopsy
FIGURE 3. A, An axial computed tomography scan of the mandible showing a large, expansile mass in the left mandible region. B, Threedimensional coronal reconstruction image showing extensive bone destruction. Cherry, Mehra, and Noonan. Radiolucent Lesion of the Posterior Mandible. J Oral Maxillofac Surg 2009.
attempt to maintain the marginal mandibular branch of the facial nerve. Although the imaging obtained in this case did not demonstrate nodal involvement in the neck, I feel an elective neck dissection is indicated to address the risk of occult neck disease and improve overall survival. In this case, I would perform a selective neck dissection, sparing the spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle. It would be my intention to remove the tumor and neck contents en-bloc. The condylar neck appears to be free of involvement according to the imaging report. I would place a reconstruction plate from the condylar stump the symphysis area to restore continuity of the remaining mandible. If in order to maintain an oncologically sound surgery, the condyle was unable to be
FIGURE 4. A, An intraoperative view shows augmentation of the atrophic and fractured vascularized free flap, with autogenous, cancellous marrow grafts harvested from the iliac crest. B, A dental computed tomography scan shows a successfully augmented free fibular graft with radiopaque implant markers. Cherry, Mehra, and Noonan. Radiolucent Lesion of the Posterior Mandible. J Oral Maxillofac Surg 2009.
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FIGURE 5. A panoramic radiograph shows the atrophic (and previously fractured) free fibular graft after the placement of 5 endosseous dental implants. Cherry, Mehra, and Noonan. Radiolucent Lesion of the Posterior Mandible. J Oral Maxillofac Surg 2009.
specimen showed islands of odontogenic epithelium that exhibited peripheral columnar epithelial cells, remarkable for palisading and reversed nuclear polarity (Fig 2A). In addition, sheets of atypical, spindled epithelial cells exhibited nuclear pleomorphism, occasional atypical mitotic figures, multiple nucleoli, and hyperchromaticity (Fig 2B). Keratin pearl formation was focally observed, with infiltrative tumor islands extending to the margins of the tissue sections examined. A final diagnosis of “malignant odontogenic tumor with features of ameloblastic differentiation” was established. Whether or not this neoplasm arose in a preexisting ameloblastoma cannot be unequivocally determined. Computed tomography (CT) scanning of the maxillofacial and neck regions showed a mass measuring 7 ⫻ 7 ⫻ 6 cm within the posterior body and angle of the mandible (Fig 3). There was associated cortical disruption, with a displaced third molar. The condylar neck showed no evidence of involvement. No significant lymphadenopathy was present, and the largest node was approximately 10 ⫻ 5 mm in measurement, and was located slightly anterior to the right submandibular gland. Magnetic resonance imaging was obtained for more complete evaluation, and confirmed the absence of nodal metastasis, and a lack of invasion into the soft tissues of the floor of the mouth and tongue. A CT examination of the chest and abdominal regions was unremarkable. In view of the rarity and complexity of the tumor, the patient was presented at a combined hospital tumor board for planning of comprehensive treatment. The proposed treatment included a disarticulation segmental resection with 2-cm bony margins, resection of the soft tissues to clear margins, a tracheostomy, modified radical neck dissection, and reconstruction of the mandible with a fibular, osteomyocutaneous, vascularized free flap, and postoperative radiation therapy. In preparation for surgery, a magnetic resonance angiogram of the lower extremities was obtained, and it showed good 3-vessel runoff. The patient underwent surgery without complications, and a histopathologic examination was consistent with a diagnosis of ameloblastic carcinoma. All bony surgical margins and lymph nodes were found to be free of tumor. However, the margins were close and less than 2 cm (but greater than 1 cm) in some areas. The case was discussed at the local hospital’s tumor board, and it was decided that additional surgery was not recommended at this stage. The patient had an unremarkable course in the immediate postoperative period. Radiation therapy was initiated, and the patient received a total dose of 6,000 cGy to the primary site and the neck in fractionated doses.
Approximately 1 year after free-flap reconstruction, the patient presented with intermittent swelling of the anterior fibular and mandibular area. Clinical and radiographic examinations showed a likely fracture in the anterior part of the microvascular graft. Some purulent discharge was present around the anterior fibular and mandibular region. Initially the infection was managed successfully with local debridement in the office, oral antibiotic therapy, and 30 dives of hyperbaric oxygen (HBO) therapy. The patient expressed a desire for prosthetic rehabilitation with endosseous dental implants. Because previous CT scanning revealed an atrophic fibula and mandible which had already fractured, a decision was made to augment the microvascular fibular graft with iliac crest bone grafts, followed by delayed implant placement. The mandibular reconstruction plate was removed, the area of the fracture was debrided, and augmentation of the graft was performed as an outpatient surgery procedure, with corticocancellous bone grafts harvested from the anterior iliac crest (Fig 4). Postoperatively, the patient received 10 additional HBO sessions, and healing was uneventful. Placement of 5 endosseous dental implants was performed approximately 5 months after grafting (Fig 5). Secondary softtissue reconstruction was performed 6 months after implant placement. This included debulking of the excessively thick intraoral skin-muscle tissue flap with a modified vestibuloplasty, using keratinized tissue grafts harvested from the palate. The patient was prosthetically rehabilitated with a mandibular hybrid prosthesis. As of the writing of this report, the patient has recently been diagnosed with metastases to the brain and lung regions. He has undergone frontal bone and dural resection, reconstruction of the frontal region with a pericranial flap, and lower left lobe lung removal. Chemotherapy treatment with paclitaxel and carboplatin is continuing.
Discussion Ameloblastoma is a locally infiltrative, benign, odontogenic neoplasm typically arising in the posterior regions of the jaws. Approximately 80% of ameloblastomas were reported to occur in the mandible, and 20% in the maxilla.10,11 A rare, malignant variant of ameloblastoma was first described in the medical literature in 1950.12 The World Health Organization separated this variant into its current subtypes, ie, malignant ameloblastoma and ameloblastic carcinoma, in 1972.13 This classification was further revised by Slootweg and Muller in 1984.14 The World Health Organization described malignant ameloblastoma as a tumor showing the histopathologic features of classic ameloblastoma with metastatic deposits, and defined ameloblastic carcinoma as an epithelial proliferation with histopathologic features of malignancy, either associated with an ameloblastoma (carcinoma ex-ameloblastoma) or representing a de novo carcinoma that resembles ameloblastoma histopathologically.15 The histopathologic features of both the primary and metastatic foci of malignant ameloblastoma are indistinguishable from conventional ameloblastoma. Thus, metastases must be present to establish a diagnosis of malignant ameloblastoma. Metastatic foci were reported in the lung (75%), cervical lymph nodes (15%), and spine (15%), and less frequently in the liver, skull, diaphragm, and brain.11 Conversely, ameloblastic carcinoma shows the histopathologic features of malignancy, with or without metastatic spread. This lesion may arise de novo, ex-ameloblastoma,
866 or ex-odontogenic cyst,14 and is remarkable for its aggressive clinical course. Ameloblastic carcinoma has a predilection for occurrence in the posterior mandible. Only a limited number of cases were reported in the maxilla.10,16 Although the tumor can present over a wide age range, the mean age of patients diagnosed with ameloblastic carcinoma is 30.1 years. Most patients present with cortical expansion and pain, and aggressive behavior and recurrence are frequently cited in the clinical course.4 A diagnosis of ameloblastic carcinoma was established in our patient, based on histopathologic features including evidence of ameloblastic differentiation together with the presence of nuclear pleomorphism and atypical mitotic figures. The lesion was rapidly growing and locally aggressive, with bone destruction, and showed no evidence of metastases. Wide, local excision with 2-to-3-cm bony margins is considered the treatment of choice.3,17 Neck dissections are usually recommended. Although postoperative radiotherapy should be strongly considered, especially for large lesions, there is a paucity of well-documented cases to ratify this protocol.16,18,19 Our patient had a composite resection of the hemimandible via combined extraoral and intraoral approaches. Although the condylar neck was spared from the tumor, a temporomandibular joint disarticulation resection was completed, sparing the meniscus, because the required surgical margins necessitated condylar sacrifice. Meniscal preservation was previously reported during disarticulation resections in the treatment of malignancies that spared the condylar neck region.20 A microvascular, osteocutaneous, fibular free flap was initially used to reconstruct the resultant hard-tissue and soft-tissue defects after tumor extirpation, because the patient preferred one-stage treatment (bone/soft-tissue resection, and concomitant reconstruction), compared with the conventional staged treatment with pedicled myocutaneous flaps and delayed bone grafting. In addition, reconstruction of the mandible with bone in the form of a free flap allowed for immediate postoperative radiation treatment, which was strongly recommended by the hospital’s tumor board, given the “close” soft-tissue margins. The development of a delayed fracture at the collapsed osteotomy site of the fibular graft was successfully treated with local debridement, antibiotics, HBO therapy, and simultaneous grafting with iliac-crest bone grafts in preparation for dental implants. All implants osseointegrated, and were restored without complications. Secondary soft-tissue reconstruction with keratinized grafts was unremarkable. Ameloblastic carcinoma has reported recurrence rates of between 15%19 and 60%,17 even when treated with aggressive surgical excision. Five-year survival rates were reported to be less than 40%.4,17 Because of recurrence and reported metastases to the lungs and lymph nodes,3,4,14,18,21 close, periodic clinical and radiographic re-evaluation of the patient is mandatory. Our patient has been recently diagnosed with metastatic lesions in the brain and lung.
RADIOLUCENT LESION OF THE POSTERIOR MANDIBLE
This appears to be the first report of ameloblastic carcinoma of the mandible treated with: 1) an initial bony reconstruction using a microvascular free fibular flap and subsequent augmentation with conventional autogenous bone grafts, 2) an initial soft-issue reconstruction using microvascular free-flap transfer and subsequent replacement with keratinized tissue grafts, and 3) complete, successful, dental prosthetic rehabilitation, using an implantsupported prosthesis in a radiated and reconstructed mandible after HBO therapy. However, despite these efforts and “presumably” adequate treatment, long-term prognosis for such patients remains poor.
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