J Oral Maxillofac Surg 70:1109-1113, 2012
Pulmonary Metastasis in a 65-Year-Old Man With Mandibular Ameloblastoma: A Case Report and Review of the Literature Ioannis Georgakas, MD,* Maria Lazaridou, MD, DDS,† Ioannis Dimitrakopoulos, MD, DDS,‡ Ioannis Tilaveridis, MD, DDS,§ Argiro Sekouli, MD,㛳 Despina Papakosta, MD,¶ and Theodore Kontakiotis, MD, PhD# Ameloblastoma is the second most common odontogenic neoplasm after odontoma, accounting for 1% of all jaw tumors.1,2 Although the 1992 World Health Organization classification characterizes ameloblastoma as a benign but locally invasive epithelial odontogenic neoplasm, its aggressive biologic behavior evokes wide differences of opinion among investigators concerning its position in the neoplastic spectrum. This has led some investigators to refer to ameloblastoma as a low-grade malignant tumor because it is prone to recur, capable of aggressive local invasion, and capable of metastasizing to distant sites.3,4 Ameloblastoma occurs in all areas of the jaws, but 80% of cases arise in the mandible.5,6 Despite being locally aggressive, metastases are not generally expected because they are extremely rare. Nevertheless, regional and distant metastases have been reported in the literature and are well documented.1,6-9 Metastatic ameloblastoma is known as malignant ameloblastoma. Malignant ameloblastoma is described in the World Health Organization classification as a neoplasm in which the features of ameloblastoma exist in
Received from Aristotle University of Thessaloniki, Thessaloniki, Greece. *Internist, Respiratory Failure Unit. †Surgeon, Department of Oral and Maxillofacial Surgery. ‡Surgeon, Department of Oral and Maxillofacial Surgery. §Surgeon, Department of Oral and Maxillofacial Surgery. 㛳Pathologist, Department of Pathology. ¶Assistant Professor, Department of Pulmonology. #Assistant Professor, Department of Pulmonology. Address correspondence and reprint requests to Dr Kontakiotis: Department of Pulmonology, Aristotle University of Thessaloniki, P Kavda 13, N 751 Panorama, Thessaloniki, Greece; e-mail: kon[email protected]
auth.gr © 2012 American Association of Oral and Maxillofacial Surgeons
the primary tumor and in the metastatic site. It presents as a multilocular radiolucent jaw expansion typical of a benign ameloblastoma, but with the presence of a concomitant metastatic focus, usually (75% to 80%) in the lung.10 Metastatic ameloblastoma must be distinguished from ameloblastic carcinoma because the former retains benign histopathologic features in the primary and metastatic sites, whereas the latter shows histologic features of malignancy in the primary site regardless of whether it has metastasized.11 To our knowledge there have been numerous case reports4,6,7,12 of ameloblastoma and coexisting pulmonary metastases arising several years after the surgical procedure. There have been reports of pulmonary metastases occurring as many as 45 years after the initial diagnosis. Another case of mandibular ameloblastoma and pulmonary metastases is presented this report. In the present case, the metastases were intraluminal as visualized by fiberoptic bronchoscopy.
Report of a Case A 55-year-old white man presented in the Department of Oral and Maxillofacial Surgery, Papanikolaou General Hospital for evaluation of an exophytic mass at the left retromandibular tuberosity. The patient had undergone extraction of the left third molar and curettage of the tooth socket 10 days previously. His medical history was significant for hypertension adequately controlled with medication. He was a lifelong cigarette smoker. A biopsy was performed and histopathology confirmed ameloblastoma. Computed tomographic (CT) scan displayed an endosseous lesion that extended from the body of the left mandible in the region of molars to the left coronoid process. Enucleation and curettage of the lesion was performed. The pathologic features of the tumor confirmed the initial diagnosis of ameloblastoma. After this initial treatment, the patient presented at 58 years of age with intraoral swelling in the region of the left mandibular body and ramus. The patient underwent hemimandibulectomy and excision of part of the zygomatic arch. Histopathologic examination was conclusive for ameloblastoma. Despite radical excision, the patient presented with persistent facial
MANDIBULAR AMELOBLASTOMA/PULMONARY METASTASIS
FIGURE 1. Computed tomogram shows the tumor occupying the infratemporal fossa and extending to the pterygoid plates. Georgakas et al. Mandibular Ameloblastoma/Pulmonary Metastasis. J Oral Maxillofac Surg 2012.
swelling 2 months later. CT scan showed a lesion at the infratemporal fossa extending to the temporalis muscle, the masseter muscle, and the parotid gland (Fig 1). The patient underwent a new operative procedure. A Weber-Fergusson incision with a Barbosa extension was used to obtain access to the tumor. The tumor was found to infiltrate the pterygoid plates and the posterior wall of the left sinus cavity. Enucleation of the tumor was performed and part of the maxilla was simultaneously excised. Once again, biopsy disclosed an ameloblastoma (Fig 2). Two years later, the patient presented with a lesion on the skin of his left cheek, which proved to be a sinus tract that led to a new recurrent lesion. The sinus tract and the new lesion were excised, and the defect was reconstructed with temporalis muscle flap and cervical rotational flap. Histopathologic examination again disclosed ameloblastoma. The patient received radiotherapy (4,000 rad) in an
effort to prevent a new recurrence, which would probably extend to the base of the skull. The patient was reviewed on a regular basis for 4 years. He showed no signs of local recurrence. At 65 years of age, chest radiography was performed because the patient complained of cough, sputum, and fatigue. Chest radiograph showed widening of the mediastinum, a shadow on the right upper lobe, and prominent hila (Fig 3). Physical examination showed decrement of breath sounds in the 2 upper lung zones. Complete blood cell count and routine blood chemistry data were obtained. All values recorded were within normal ranges except for a mild increase in serum calcium levels. Spirometric pulmonary function tests indicated restrictive impairment (forced expiratory volume in the first second of expiration, 77%; force vital capacity, 68%; ratio of forced expiratory volume in the first second of expiration to force vital capacity,
FIGURE 2. Primary ameloblastoma presents a predominantly plexiform pattern within a stroma with moderate collagenation (hematoxylin and eosin stain; original magnification, ⫻100).
FIGURE 3. Chest radiograph shows widening of the mediastinum, a shadow on the right upper lobe (arrow), and prominent hilar shadows.
Georgakas et al. Mandibular Ameloblastoma/Pulmonary Metastasis. J Oral Maxillofac Surg 2012.
Georgakas et al. Mandibular Ameloblastoma/Pulmonary Metastasis. J Oral Maxillofac Surg 2012.
GEORGAKAS ET AL
FIGURE 4. Left, Computed tomogram of the thorax shows enlarged preaortic (blue arrow) and right paratracheal (red arrow) lymph nodes with a mass on the right upper lobe (yellow arrow) adjacent to the hilum. Right, Computed tomogram shows a mass on the right upper lobe and a second mass on the left upper lobe (arrows). Georgakas et al. Mandibular Ameloblastoma/Pulmonary Metastasis. J Oral Maxillofac Surg 2012.
116%; maximum mid-expiratory flow, 88%). CT scan of the thorax showed metastatic lesions on the left upper lobe and adjacent to the right hilum with marked enlargement of right paratracheal, right hilar, and preaortic lymph nodes (Fig 4). Fiberoptic bronchoscopy (Fig 5) showed endobronchial lesions that completely obstructed the lumen of the right and left upper bronchi (including the upper division and lingula). Endobronchial biopsies were obtained from the 2 sides. Histopathologic examination of biopsy specimens showed metastatic tumor with confirmed origin of the primary mandibular tumor. The type displayed was a follicular pattern with tumor islands showing peripheral and central cystic degeneration (Fig 6). The immediate next step was to perform brain and abdominal CT scans to complete tumor staging. CT findings were unremarkable for metastatic disease. The patient was discharged on the third hospital day and his cough resolved spontaneously without therapy. The lung tumor was not operable because of extensive mediastinal lymphadenopathy, and no chemotherapy or other palliative therapy was performed. The health
status of the present patient remained stable at 11-month follow-up. He has presented dyspnea only on exertion but has lacked any other symptoms.
Discussion Ameloblastoma occurs in all areas of the jaws, but 80% of cases arise in the mandible.5,6 Only 2% to 4.5% of ameloblastomas metastasize.13,14 Vorzimer and Perla15 first reported lung metastasis of an ameloblastoma in 1932. The rarity of metastases makes every effort to establish risk factors difficult. Metastasis can occur as soon as a few months after the appearance of the primary site or as late as 31 years after initial treatment.1,12 The mechanism of the development of the metastatic focus has been widely discussed. It seems that most investigators have concluded that
FIGURE 5. Fiberoptic bronchoscopic images show complete obstruction of the left upper bronchus (right, arrow) and right upper bronchus (left, arrow). Georgakas et al. Mandibular Ameloblastoma/Pulmonary Metastasis. J Oral Maxillofac Surg 2012.
MANDIBULAR AMELOBLASTOMA/PULMONARY METASTASIS
FIGURE 6. Microscopic image from histologic specimen shows a follicular pattern with tumor islands indicating peripheral and central cystic degeneration (hematoxylin and eosin stain; original magnification, ⫻200). Note the respiratory epithelium (arrow). Georgakas et al. Mandibular Ameloblastoma/Pulmonary Metastasis. J Oral Maxillofac Surg 2012.
there are 3 separate routes by which neoplastic cells can find their way to the metastatic focus: 1) the hematogenous route; 2) the lymphogenous route; 3) and metastasis by aspiration. Cases of metastases to cervical lymph nodes, the spine, liver, diaphragm, brain, base of the skull, orbit, bone, kidney, small bowel, and skin have been reported in the literature, suggesting that blood-borne and lymph-borne metastases of ameloblastomas are well documented.7 Metastasis to the lungs is more common, probably because spread to the lungs can easily occur because of aspiration and implantation of neoplastic cells during surgery, but it can also occur by hematogenous spread. In the present case, these metastases were intraluminal, so the possible mechanism could be malignant cell aspiration during oral surgical excision. Multiple surgical excisions of extensive ameloblastoma recurrences increase the possibility of inhalation of neoplastic cells during operative procedures. The hypercalcemia might be explained by a parathormone-like substance secreted by the neoplasm.4 The most common clinical symptoms caused by endobronchial metastases are those attributed to obstruction of airflow, including cough, sputum, and dyspnea, and often accompanied by signs of recurrent respiratory infections or bronchiectasis. Physical examination, spirometric results, chest radiograph, and CT scan of the thorax are reported to be helpful in establishing the diagnosis. Fiberoptic bronchoscopy is the most valuable method of final diagnosis,
because the histologic specimens taken by biopsy are usually sufficient to indicate the type of tumor. There is no universally accepted mode of treatment of lung metastases. The lack of a significant number of cases precludes the development of an effective treatment protocol. All treatment modalities have been tested, with very variable results. Surgical wedge excision, whenever possible, seems to be the treatment of choice, although recurrences are not infrequent.1,6,9 Multiple nodules are also amenable to surgical resection, if adequate pulmonary reserve is preserved. Tumors at the periphery of the lung may have the best prognosis because wedge excision is possible.6 It has to be stated that resection of lung metastasis is not a radical treatment and that recurrence or appearance of a new focus must be expected and treated surgically if adequate pulmonary reserves exist. Chemotherapy is not useful as a radical treatment but may be used as a palliative treatment when the patient has insufficient pulmonary reserve or in combination with surgery because in some cases it is effective in decreasing tumor size, thus facilitating surgical excision. Adriamycin, cyclophosphamide, and cisplatin have been used in variable schemes without very promising results.6,16 Radiotherapy has also been applied, but results are controversial and associated with high recurrence rates.7 Simple follow-up is another viable option because these tumors grow very slowly and usually remain asymptomatic.
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Prognosis is considered poor. Henderson et al1 reported that median survival after detection of metastases is approximately 2 years. However, Sheppard et al9 reviewed 29 cases of lung metastases and concluded that median survival was much longer when surgical resection was performed (6.6 years) than when other treatment modalities or simple follow-up were chosen. The mean survival for patients who received no treatment and for patients who were treated with multiagent chemotherapy was 1.1 years. Radiotherapy alone was performed in only 1 patient who survived 5 years.9 Radiotherapy offers unpredictable results and is not recommended as a viable treatment option.8 If the tumor cannot be resected because of its size and extent or because of inability to preserve adequate viable lung tissue, palliative therapy may be chosen; although there is no evidence to support that it improves prognosis.1 However, some investigators have reported prolonged survival without applying any treatment.7,9 In the present case, the tumor extended to the mediastinum and could not be excised. In conclusion, pulmonary metastases from ameloblastoma are rare, but must be considered in the differential diagnosis in patients with such a history who manifest persistent symptoms from the respiratory system.
2. 3. 4.
5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.
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literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88:170, 1999 Reid-Nicholson M, Teague D, White B, et al: Fine needle aspiration findings in malignant ameloblastoma: A case report and differential diagnosis. Diagn Cytopathol 37:586, 2009 Gold L: Biologic behavior of ameloblastoma. Oral Maxillofac Surg Clin North Am 3:21, 1991 Inoue N, Shimojyo M, Iwai H, et al: Malignant ameloblastoma with pulmonary metastasis and hypercalcemia. Report of an autopsy case and review of the literature. Am J Clin Pathol 90:474, 1988 Kessler HP: Intraosseous ameloblastoma. Oral Maxillofac Surg Clin North Am 16:309, 2004 Campbell D, Jeffrey RR, Wallis F, et al: Metastatic pulmonary ameloblastoma. An unusual case. Br J Oral Maxillofac Surg 41:194, 2003 Hasim FW, Poon CC, Smith AC: Prolonged survival with confirmed metastatic pulmonary ameloblastoma. Int J Oral Maxillofac Surg 36:953, 2007 Ciment LM, Ciment AJ: Malignant ameloblastoma metastatic to the lungs 29 years after primary resection: A case report. Chest 121:1359, 2002 Sheppard BC, Temeck BK, Tauenberger JK, et al: Pulmonary metastatic disease in ameloblastoma. Chest 104:1933, 1993 Houston G, Davenport W, Keaton W, et al: Metastatic ameloblastoma: Report of a case. J Oral Maxillofac Surg 51:1152, 1993 Yoon HJ, Hong SP, Lee JI, et al: Ameloblastic carcinoma: An analysis of 6 cases with review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 108:904, 2009 Ricard AS, Majoufre-Lefebvre C, Siberchicot F, et al: A multirecurrent ameloblastoma metastatic to the lung. Rev Stomatol Chir Maxillofac 111:98, 2010 Laughlin EH: Metastasizing ameloblastoma. Cancer 64:776, 1989 Ameloblastoma RHBG: A survey of 379 cases from the literature. Arch Pathol 23:831, 1937 Vorzimer J, Perla D: An instance of adamantinoma of the jaw with metastases to the right lung. Am J Pathol 8:445, 1932 Ramadas K, Jose C, Subhashini J, et al: Pulmonary metastases from ameloblastoma of the mandible treated with cisplatin, adriamycin and cyclophosphamide. Cancer 66:1475, 1990