Malignant ameloblastoma metastasis to the lung: a case report Giselle Segnini Senra, MSc,a Andresa Costa Pereira, MSc,a Lucio Murilo dos Santos, PhD,b Yasmin Rodarte Carvalho, PhD,b and Adriana Aigotti Haberbeck Brandão, PhD,b São Paulo, Brazil SÃO PAULO STATE UNIVERSITY (UNESP)
Ameloblastoma is an odontogenic tumor, usually benign, which rarely metastasizes to distant organs. The case of a 27-year-old white woman is described, who presented a metastatic pulmonary ameloblastoma 7 years after the removal of a mandibular ameloblastoma. She presented no pulmonary symptoms, but a lung nodule was found in a chest x-ray during a routine check-up for job admission. Computed tomography (CT) revealed a 2-cm well-defined solitary round nodule without calcifications, leading to the hypothesis of a metastatic tumor. Clinical and CT investigation confirmed no ameloblastoma recurrence in the jaw and no other primary tumor. The diagnosis of metastatic ameloblastoma was confirmed by microscopic evaluation of the pulmonary nodule. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:e42-e46)
A 27-year-old white woman, with no history of habitual drinking or smoking, presented a pulmonary nodule in chest radiographs realized during a routine check-up for job admission conducted by a physician. A thoracic computed tomography (CT) scan confirmed the lesion in the right lung (Fig. 1). The image showed a 2-cm well-defined solitary round nodule without calcifications. The absence of calcification and the patient’s clinical history discarded the hypothesis of tuberculosis and other granulomatous processes. The age and sex of the patient, as well as the linear and well-circumscribed limits of the lesion were not compatible with bronchogenic carcinoma. Because of the low prevalence of benign pulmonary tumors and the radiographic characteristics, the hypothesis of a metastatic tumor was considered. A primary tumor was investigated and although one was not found, lobectomy was indicated. A review of the patient’s clinical history showed that, at 19 years old, she had presented buccal and lingual expansion of the posterior mandible (Fig. 2) in the second molar region, with a radiographic aspect suggestive of ameloblastoma. The incisional biopsy showed a plexiform-type ameloblastoma (Fig. 3, A). Later, the patient underwent a hemimandibulectomy, a
PhD student, Department of Biosciences and Oral Diagnosis, School of Dentistry of São José dos Campos, São Paulo State University (UNESP), São Paulo, Brazil. b Professor, Department of Biosciences and Oral Diagnosis, School of Dentistry of São José dos Campos, São Paulo State University (UNESP), São Paulo, Brazil. Received for publication Aug 3, 2007; returned for revision Sep 11, 2007; accepted for publication Sep 12, 2007. 1079-2104/$ - see front matter © 2008 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2007.09.006
with tumor-free margins, and reconstruction of the mandibular body, as previously reported.1 The diagnosis of a plexiform-type ameloblastoma was confirmed (Fig. 3, B). Given the past history of ameloblastoma, the clinical diagnosis of the current lung nodule had to include metastasizing ameloblastoma and, subsequently, a partial pulmonary lobectomy was performed (Fig. 4). DIAGNOSIS Histopathological evaluation confirmed the diagnosis of a metastasizing ameloblastoma in the lung. A well-differentiated tumor was revealed, characterized by peripheral columnar cells, similar to ameloblasts, in peripheral palisading orientation, showing nuclear polarization away from the basement membrane and connective tissue surrounding the epithelial nests (Figs. 5 and 6). Numerous areas were filled by cells with clear and poorly defined cytoplasm that resembled stellate reticulum of the enamel organ, with a central area of loosely arranged cells (Fig. 7). The fibroblastic stroma presented an inflammatory infiltrate, rich in mononuclear cells, dispersed among collagen fibers. Occasionally, the stroma presented a dense aspect and in other areas, a loose aspect. No hyperchromatic nuclei, mitotic figures, or other signs of malignancy were observed. Based on these results, the lesion from the right lung presented no features that were distinct from the ameloblastoma originally diagnosed in the jaw. MANAGEMENT In the 2 years following the partial pulmonary lobectomy, no additional lesion has been found in the lungs. Furthermore, no evidence of local mandibular recurrence of the ameloblastoma has been observed.
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Fig. 3. Histological aspect of the incisional biopsy (A) and the hemimandibulectomy (B). Both pictures show a plexiform-type ameloblastoma, with cells similar to ameloblasts and areas of loosely arranged cells that resemble stellate reticulum of the enamel organ (hematoxylin and eosin [H&E], original magnification ⫻200). Fig. 1. A thoracic computed tomography scan showing a well-defined nodule in the right lung ( ).
Fig. 4. Macroscopic aspect of the partial pulmonary lobectomy.
Fig. 2. Computed tomography scan presenting buccal and lingual expansion of the posterior mandible ( ).
DISCUSSION Ameloblastoma is an uncommon disease that represents 1% of all cysts and tumors diagnosed in the jaws.2 Ameloblastoma of the jaws is most often considered by clinicians to be a benign tumor,3,4 with a distressing tendency to exhibit locally aggressive behavior and local recurrence in 50% to 72% of cases. However, some of these can be reclassified as malignant when metastases occur.5 The 2005 World Health Organization (WHO) Classification of Odontogenic Tumors6 places metastasizing ameloblastoma under the general
grouping of odontogenic carcinomas, along with ameloblastic carcinoma. The typical WHO description of a metastasizing (malignant) ameloblastoma is an ameloblastoma that metastasizes in spite of a benign histological appearance.6 Many factors have been associated with the likelihood of developing metastases, including the duration of tumor presence, extent of initial disease, multiple surgical procedures, or radiation therapy.7-9 Metastasizing ameloblastoma is a rare tumor and it is known to occur in roughly 2% to 5% of cases.8 However, even in patients without the characteristic history of multiple recurrences and operations, ameloblastoma may appear as a metastatic lesion, usually in the lungs, many years after treatment of the primary tumor.4 Malignancies in ameloblastoma have been separated into 2 categories: metastasizing (malignant) ameloblas-
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Fig. 5. Low-power view of the pulmonary metastasis microscopic aspects (H&E, ⫻100).
Fig. 6. Pulmonary metastasis well-differentiated tumor, characterized by peripheral columnar cells, similar to ameloblasts, in peripheral palisading orientation, showing nuclear polarization away from the basement membrane and connective tissue surrounding the epithelial nests (H&E, ⫻200).
toma and ameloblastic carcinoma (primary type). Ameloblastic carcinoma portrays histologically malignant features in both the primary and metastatic sites,5,10 along with a pattern that resembles an ameloblastoma.8 Despite the distinct patterns between the 2 categories, some authors do not distinguish malignant ameloblastoma from ameloblastic carcinoma.11,12 Therefore, the correct number of cases of these lesions reported in the literature up to now is questionable. According to Ciment and Ciment,8 up to 2002, fewer than 45 cases of ameloblastoma presenting metastasis have been reported.
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Fig. 7. Area in the pulmonary metastasis filled by cells with clear and poorly defined cytoplasm that resembles stellate reticulum of the enamel organ, with a central area of loosely arranged cells (H&E, ⫻400).
Campbell et al.3 reported a malignant ameloblastoma metastasis in the lung. The original lesion in the jaw showed typical features of well-differentiated follicular ameloblastoma; however, the lesion from the lung retained typical histological features of ameloblastoma in certain areas, while other areas were relatively undifferentiated. Hayakawa et al.10 described a metastatic malignant ameloblastoma case in both kidneys. The patient’s history showed a previous hemimandibulectomy and lung metastatic lesion surgery, with the diagnosis of malignant ameloblastoma. In their patient, the metastatic lesions in the kidneys showed histological malignant transformation. However, the lesions in the mandible and lung showed benign features. Most ameloblastoma metastases occur in the lungs, accounting for over 80% of reported cases,13 followed by regional lymph nodes, vertebrae, and, less frequently, the skull, liver, parotid gland, diaphragm, and brain.5,8,9,13 The mode of spread of malignant ameloblastoma has not been clearly defined. Three routes are commonly mentioned: hematogenous, lymphatic, and by aspiration.7 Vorzimer and Perla14 observed tumor casts within the bronchi and bronchioli, which led investigators to believe that the metastatic mechanism was by aspiration.4,7,15 Some controversies are apparent when reviewing the literature, because pulmonary metastatic lesions are most commonly found bilaterally, presenting multiple nodules, which supports the theory of hematogenous spread.7,15 Since there have been several reports of extrapulmonary spread, clearly metastases also occur by the hematogenous or lymphatic route,16
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possibly due to disruption of the tumor and vessels during surgical resection.5 In contrast, according to Kunze et al.,15 the pulmonary capillaries evidently provide an effective barrier for ameloblastoma cells and prevent further dissemination into the systemic circulation, since only some patients develop additional extrapulmonary metastases. The most important element in the treatment and management of metastatic ameloblastoma is adequate treatment of the primary lesion. Multiple surgeries significantly increase the risk of metastases7 and curettage opens pathways for dissemination of the tumor to adjacent structures.17 Therefore, en-bloc resection is the method of choice, using a 10- to 15-mm safety margin of normal bone, wherever possible,17 like the procedure performed in the present case during the primary tumor resection. Isolated and discrete lung metastases, particularly in the lung periphery,3 have been treated by open thoracotomy and wedge resection,16 or even by lobotomy, depending on the number of lesions and their location.7 Significant resection, with preservation of as much viable lung tissue as possible, has been the treatment of choice, since this is the only way to offer a significant disease-free interval. Chemotherapy has occasionally been used, with variable results, in limited cases presenting only a reduction in the size of the tumor3,7; however, in most cases, it produced no effective improvement. Radiotherapy is recommended for inoperable metastatic deposits, but the response is unpredictable8,13 and, consequently, radiotherapy should be used only for palliative care.7 This case showed a metastasizing (malignant) ameloblastoma about 7 years after the primary tumor diagnosis and resection, while the median disease-free interval of previously reported metastatic ameloblastoma cases was 9 years.13 However, it is important to note that this metastatic lesion was found incidentally, since the patient presented no symptoms in reference to her tumor. In the case reported by Campbell et al.,3 the metastatic pulmonary ameloblastoma was resected 25 years after the removal of an apparently benign primary ameloblastoma of the jaw. Hayakawa et al.10 stated that the patient presented a well-differentiated lesion in the lung and an undifferentiated lesion in the kidneys, 2 and 5 years after hemimandibulectomy, respectively. In their report they cite other cases regarding patients similar to ours, who presented late pulmonary metastases with no evidence of local recurrence. These data may lead us to question the follow-up of such cases. Histological and cytological patterns of both primary and metastatic lesions may be not significantly different in cases presenting metastasis occurrence and in non-
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metastasizing ameloblastomas,6,13 making it difficult to predict when or if metastases will occur. Thus, it is important to consider that the absence of atypical histological features in the primary tumor does not preclude the possibility of metastases occurrence. Given these facts, periodic follow-up, including complete pulmonary and jaw investigation for a long period of time, is imperative. Treatment of pulmonary metastases has been disappointing and the best results are found with surgical removal of operable lesions,3 which can prolong life expectancy or may even be curative, especially regarding solitary metastasis, such as in this case. Finally, we would like to emphasize how important it is to maintain contact with these patients, providing routine monitoring of their health status and the potential for early detection of asymptomatic lung dissemination. REFERENCES 1. Murilo-Santos L, Sá-Lima JR, Morais LC. Ameloblastoma– Revisão da literatura e relato de caso. BCI – Revista Brasileira de Cirurgia e Implantodontia 2000;7(28):18-21. 2. Waldron C. Odontogenic cysts and tumors. In: Neville BW, Damm DD, Allen CM, Bouquot JE, editors. Oral and maxillofacial pathology. Philadelphia: WB Saunders; 2002. p. 589-704. 3. Campbell D, Jeffrey RR, Wallis F, Hulks G, Kerr KM. Metastatic pulmonary ameloblastoma. An unusual case. Br J Oral Maxillofac Surg 2003;41(3):194-6. 4. Clay RP, Weiland LH, Jackson IT. Ameloblastoma metastatic to the lung. Ann Plast Surg 1989;22(2):160-2. 5. Verneuil A, Sapp P, Huang C, Abemayor E. Malignant ameloblastoma: classification, diagnostic, and therapeutic challenges. Am J Otolaryngol 2002;23(1):44-8. 6. Barnes L, Eveson JW, Reichart P, Sidransky D, World Health Organization Classification of Tumours. Pathology and genetics of head and neck tumours. Odontogenic Tumours. Lyon: IARC Press; 2005. p. 283-328. 7. Henderson JM, Sonnet JR, Schlesinger C, Ord R. Pulmonary metastasis of ameloblastoma: case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88(2):170-6. 8. Ciment LM, Ciment AJ. Malignant ameloblastoma metastatic to the lungs 29 years after primary resection—a case report. Chest 2002;121(4):1359-61. 9. Zwahlen RA, Vogt P, Fischer FS, Grätz KW. Case report: myocardial metastasis of a maxillary malignant ameloblastoma. J Oral Maxillofac Surg 2003;61(6):731-4. 10. Hayakawa K, Hayashi E, Aoyagi T, Hata M, Kuramoto C, Tonogi M, et al. Metastatic malignant ameloblastoma of the kidneys. Int J Urol 2004;11(6):424-6. 11. Mosqueda-Taylor A, Meneses-Garcia A, Ruiz-Godoy-Rivera LM, Luna-Ortiz K. Malignant odontogenic tumors. A retrospective study of seven cases. Med Oral 2003;8(2):110-21. 12. Kuramoto C, Morisaki S, Tonogi M, Yamane G, Tanaka Y. A case of malignant ameloblastoma that metastasized throughout the body. Oral Surg Oral Med Oral Pathol 2003;95(4): 429.
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13. Laughlin EH. Metastasizing ameloblastoma. Cancer 1989;64(3): 776-80. 14. Vorzimer J, Perla D. An instance of adamantinoma of the jaw with metastasis of the right lung. Am J Pathol 1932;8: 445-53. 15. Kunze E, Donath K, Luhr HG, Engelhardt W, De Vivie R. Biology of metastasizing ameloblastoma. Path Res Pract 1985; 180(5):526-35. 16. Newman L, Howells GL, Coghlan K.M, DiBiase A, Williams DM. Malignant ameloblastoma revisited. Br J Oral Maxillofac Surg 1995;33(1):47-50.
17. Zwahlen RA, Grätz KW. Maxillary ameloblastomas: a review of the literature and of a 15-year database. J Craniomaxillofac Surg 2002;30(5):273-9. Reprint requests: Giselle Segnini Senra, MSc Faculdade de Odontologia de São José dos Campos - UNESP Departamento de Biociências e Diagnóstico Bucal Av. Engenheiro Francisco José Longo, 777 12245-000 – São José dos Campos, SP [email protected]