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Metastasizing ameloblastoma
Int. J. Oral Maxillofac. Surg. 2007; 36: 462–464 doi:10.1016/j.ijom.2006.12.005, available online at http://www.sciencedirect.com
Case Report Clinical Pathology
Metastasizing ameloblastoma
M. Gilijamse1, C. R. Leemans2, H. A. H. Winters3, E. A. J. M. Schulten1, I. van der Waal1
M. Gilijamse, C. R. Leemans, H. A. H. Winters, E. A. J. M. Schulten, I. van der Waal: Metastasizing ameloblastoma. Int. J. Oral Maxillofac. Surg. 2007; 36: 462–464. # 2006 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
1 Department of Oral and Maxillofacial Surgery/Pathology, VU University Medical Center/Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands; 2Department of Otolaryngology, VU University Medical Center, Amsterdam, The Netherlands; 3Department of Plastic and Reconstructive Surgery, VU University Medical Center, Amsterdam, The Netherlands
Abstract. Ameloblastomas are locally invasive tumours of odontogenic origin with a high propensity for local recurrence. Regional and distant metastases are extremely rare. Here is presented a case of a 26-year-old woman with a recurrent ameloblastoma of the mandible and a metastatic lymph node in the homolateral neck.
Accepted for publication 11 December 2006 Available online 1 February 2007
In the most recent World Health Organization (WHO) classification of tumours, a distinction is made between ameloblastoma, metastasizing (malignant) ameloblastoma and ameloblastic carcinoma2. Ameloblastoma is described as a slowly growing, locally invasive, benign tumour with a high propensity for local recurrence if not removed adequately. Metastasizing (malignant) ameloblastoma distinguishes itself from ameloblastoma only by the presence of metastases. There are no specific histological differences compared to ameloblastomas that do not metastasize, and the diagnosis is made on clinical behaviour only. Metastatic deposits are mostly seen in the lung (75%), followed by cervical lymph nodes and spine (each almost 15%)8. Other locations, such as liver, skull, brain, kidney and small bowel, have also been reported, but with lower incidences8,9. Ameloblastic carcinoma is characterized by malignant cytologic features such as atypia in combination with the overall histological pattern of an ameloblastoma, regardless of the presence of metastases. In the WHO classification, two subtypes of ameloblastic carcinoma are recognized: primary type, and secondary or dedifferentiated type in which the
formed. During the submandibular approach of this surgical procedure an enlarged submandibular lymph node with a firm consistency and measuring approximately 1 cm in diameter was encountered. Frozen sections of the lymph node were reported as metastatic tumour consistent with ameloblastoma, without extracapsular spread (Fig. 4). A modified radical neck dissection was then performed with preservation of the internal jugular vein, the spinal accessory nerve and the sternocleidomastoid muscle. Histopathologic analysis of the primary tumour was consistent with the diagnosis of ameloblastoma. The surgical margins were reported to be free of tumour. No signs of cytonuclear polymorphism or mitoses, and no spread through the cortical bone or into the surrounding tissue were observed. Histopathologic examination of the neck dissection specimen did not show any other metastatic lymph nodes. The mandible was reconstructed with a free vascularized osteomyocutaneous fibula graft. The postoperative course was uneventful. Additional work up, consisting of computerized tomography of the lungs, did not show signs of pulmonary metastases. The prosthodontic rehabilitation con-
0901-5027/050462 + 03 $30.00/0
ameloblastic carcinoma has arisen from a pre-existing benign ameloblastoma. Case report
The patient presented for the first time in May 1991 at the age of 12 years. The clinical presentation was that of a gingival swelling distally from tooth 37. The panoramic radiograph showed radiolucency around the impacted 38 (Fig. 1). Under the working diagnosis of a dentigerous cyst, enucleation of the cystic lesion and removal of the wisdom tooth (38) took place. Histopathologic examination showed the lesion to be a multicystic ameloblastoma of the plexiform type (Fig. 2). The patient was followed periodically. In October 1999, the lesion recurred and enucleation was performed. Histopathologic analysis again demonstrated ameloblastoma of the plexiform type. The patient was again followed periodically, at 6month intervals. In February 2005, there were no clinical signs of recurrence, but radiological examination showed the presence of a well-demarcated radiolucency distally from tooth 37 reaching into the mandibular ramus (Fig. 3). This time, a resection of the left mandible was per-
# 2006 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Metastasizing ameloblastoma
Fig. 1. Clinicoradiographic diagnosis of dentigerous cyst of 38.
sisted of insertion of three dental implants in the neo-mandible and a fixed, three-part bridge as superstructure. Further periodical follow up at 16 months postoperatively has not shown signs of locoregional recurrence. A chest radiograph after 1 year’s follow up did not reveal any signs of metastases.
Discussion
Ameloblastomas are rare tumours of odontogenic epithelial origin. The average age at diagnosis of patients with ameloblastoma is 36 years10. Men and women are equally affected with women
Fig. 2. Histopathologic diagnosis of benign ameloblastoma.
463
being approximately 4 years younger than men at the time of first occurrence10. The mandible to maxilla ratio is 5:1, with the molar region of the mandible being most frequently affected10. Ameloblastomas are considered to be benign, although they are locally invasive and have a high propensity for local recurrence. Malignant (metastasizing) ameloblastoma is extremely rare; an occurrence of 2% of all benign ameloblastomas has been reported, but this is probably too high a percentage6. The mean age of the metastasizing ameloblastoma cases described in the literature as reviewed by REICHART & PHILIPSEN was 34.4 years with a range of 5– 74 years9. The female:male ratio for this sample was 1:1.2. As for non-metastasizing ameloblastoma, the majority of cases were localized in the mandible9. The median survival time after the appearance of metastases ranges from 3 months to 5 years5, with the longest reported survival time being 25 years5,8. Most malignant amelolastomas are of the plexiform histopathologic type, but their histologic and cytologic features are not significantly different from those of the non-metastatic type7,9. There are no morphological criteria to predict the biological behaviour of ameloblastomas with respect to their potential for metastatic spread7. Extent of the initial tumour and multiple recurrences and respective surgical interventions seem to contribute to the potential for metastatic spread5,7–9, but not all malignant ameloblastoma cases have a history of repeated surgical intervention1,4. The interval between diagnosis of the primary and development of a metastasis is generally long, with an average of 10–12 years4,7. Lymphatic spread of malignant tumour cells is a well accepted route of metastasis9. However, EISENBERG proposed that the occurrence of ameloblastoma in cervical lymph nodes could be explained by the phenomenon of heterotopia3. This theory states that during embryogenesis odontogenic epithelium becomes entrapped in lymphoid tissue. When this epithelium undergoes benign neoplastic transformation, an ameloblastoma could than develop within a lymph node. This implies that the process could be multifocal. Because of the long interval between diagnosis of the primary tumour and the occurrence of regional or distant metastasis, and the rareness of the phenomenon, the question arises as to whether all ameloblastoma patients should be evaluated routinely for the development of such metastases. GOLDENBERG et al. recommend that patients
464
Gilijamse et al. form a type of neck dissection. Routine postoperative radiotherapy does not seem to be indicated.
References
Fig. 3. Second recurrence of ameloblastoma, 14 years after primary manifestation.
Fig. 4. Cervical lymph-node metastasis of ameloblastoma, plexiform type. No cytological signs of malignancy. (a) Low power view (original magnification 25); (b) detail (original magnification 100).
receive annual chest radiographs to evaluate the most likely site for distant metastasis4. Likewise, annual evaluation of the neck should be considered, together with radiographic examination of the primary site for possible local recurrences.
For operable lung metastasis, surgery seems to be the treatment of choice4,5,7,9, but for non-resectable disease, radiation and/or chemotherapy may play a role5,9. For regional lymph-node involvement, as in this case, it seems appropriate to per-
1. Ameerally P, McGurk M, Shaheen O. Atypical ameloblastoma: report of three cases and a review of the literature. Br J Oral Maxillofac Surg 1996: 34: 235– 239. 2. Barnes L, Eveson JW, Reichart P, Sidransky D, eds: World Health Organization Classification of Tumours. Pathology and Genetics. Head and Neck Tumours. Lyon: International Agency for Research on Cancer (IARC). IARC Press 2005. 3. EISENBERG E. Discussion (response to HOUSTON G, DAVENPORT W, KEATON W, HARRIS S. Malignant (metastatic) ameloblastoma: report of a case. J Oral Maxillofac Surg 1993: 51: 1152–1155). J Oral Maxillofac Surg 1993: 51: 1156–1157. 4. Goldenberg D, Sciubba J, Koch W, Tufano R. Malignant odontogenic tumours: a 22-year experience. Laryngoscope 2004: 114: 1770–1774. 5. Henderson JM, Sonnet JR, Schlesinger C, Ord RA. Pulmonary metastasis of ameloblastoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999: 88: 170–176. 6. Houston G, Davenport W, Keaton W, Harris S. Malignant (metastatic) ameloblastoma: report of a case. J Oral Maxillofac Surg 1993: 51: 1152–1155. 7. Kunze E, Donath K, Luhr HG, Engelhardt W, De Vivie R. Biology of metastasizing ameloblastoma. Pathol Res Pract 1985: 180: 526–535. 8. Laughlin EH. Metastasizing ameloblastoma. Cancer 1989: 64: 776–780. 9. Reichart PA, Philipsen HP. Metastasizing, malignant ameloblastoma. Odontogenic Tumours and Allied Lesions. London: Quintessence Publishing Co. Ltd. 2004: pp. 207–213. 10. Reichart PA, Philipsen HP, Sonner S. Ameloblastoma: biological profile of 3677 cases. Eur J Cancer B Oral Oncol 1995: 31B(2):86–99. Address: I. van der Waal Department of Oral and Maxillofacial Surgery/Oral Pathology VU University Medical Centre (VUMC)/Academic Centre for Dentistry Amsterdam (ACTA) P.O. Box 7057 1007 MB Amsterdam The Netherlands Tel: +31 20 444 4039 Fax: +31 20 444 4046 E-mail: [email protected]
Case Report Clinical Pathology
Metastasizing ameloblastoma
M. Gilijamse1, C. R. Leemans2, H. A. H. Winters3, E. A. J. M. Schulten1, I. van der Waal1
M. Gilijamse, C. R. Leemans, H. A. H. Winters, E. A. J. M. Schulten, I. van der Waal: Metastasizing ameloblastoma. Int. J. Oral Maxillofac. Surg. 2007; 36: 462–464. # 2006 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
1 Department of Oral and Maxillofacial Surgery/Pathology, VU University Medical Center/Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands; 2Department of Otolaryngology, VU University Medical Center, Amsterdam, The Netherlands; 3Department of Plastic and Reconstructive Surgery, VU University Medical Center, Amsterdam, The Netherlands
Abstract. Ameloblastomas are locally invasive tumours of odontogenic origin with a high propensity for local recurrence. Regional and distant metastases are extremely rare. Here is presented a case of a 26-year-old woman with a recurrent ameloblastoma of the mandible and a metastatic lymph node in the homolateral neck.
Accepted for publication 11 December 2006 Available online 1 February 2007
In the most recent World Health Organization (WHO) classification of tumours, a distinction is made between ameloblastoma, metastasizing (malignant) ameloblastoma and ameloblastic carcinoma2. Ameloblastoma is described as a slowly growing, locally invasive, benign tumour with a high propensity for local recurrence if not removed adequately. Metastasizing (malignant) ameloblastoma distinguishes itself from ameloblastoma only by the presence of metastases. There are no specific histological differences compared to ameloblastomas that do not metastasize, and the diagnosis is made on clinical behaviour only. Metastatic deposits are mostly seen in the lung (75%), followed by cervical lymph nodes and spine (each almost 15%)8. Other locations, such as liver, skull, brain, kidney and small bowel, have also been reported, but with lower incidences8,9. Ameloblastic carcinoma is characterized by malignant cytologic features such as atypia in combination with the overall histological pattern of an ameloblastoma, regardless of the presence of metastases. In the WHO classification, two subtypes of ameloblastic carcinoma are recognized: primary type, and secondary or dedifferentiated type in which the
formed. During the submandibular approach of this surgical procedure an enlarged submandibular lymph node with a firm consistency and measuring approximately 1 cm in diameter was encountered. Frozen sections of the lymph node were reported as metastatic tumour consistent with ameloblastoma, without extracapsular spread (Fig. 4). A modified radical neck dissection was then performed with preservation of the internal jugular vein, the spinal accessory nerve and the sternocleidomastoid muscle. Histopathologic analysis of the primary tumour was consistent with the diagnosis of ameloblastoma. The surgical margins were reported to be free of tumour. No signs of cytonuclear polymorphism or mitoses, and no spread through the cortical bone or into the surrounding tissue were observed. Histopathologic examination of the neck dissection specimen did not show any other metastatic lymph nodes. The mandible was reconstructed with a free vascularized osteomyocutaneous fibula graft. The postoperative course was uneventful. Additional work up, consisting of computerized tomography of the lungs, did not show signs of pulmonary metastases. The prosthodontic rehabilitation con-
0901-5027/050462 + 03 $30.00/0
ameloblastic carcinoma has arisen from a pre-existing benign ameloblastoma. Case report
The patient presented for the first time in May 1991 at the age of 12 years. The clinical presentation was that of a gingival swelling distally from tooth 37. The panoramic radiograph showed radiolucency around the impacted 38 (Fig. 1). Under the working diagnosis of a dentigerous cyst, enucleation of the cystic lesion and removal of the wisdom tooth (38) took place. Histopathologic examination showed the lesion to be a multicystic ameloblastoma of the plexiform type (Fig. 2). The patient was followed periodically. In October 1999, the lesion recurred and enucleation was performed. Histopathologic analysis again demonstrated ameloblastoma of the plexiform type. The patient was again followed periodically, at 6month intervals. In February 2005, there were no clinical signs of recurrence, but radiological examination showed the presence of a well-demarcated radiolucency distally from tooth 37 reaching into the mandibular ramus (Fig. 3). This time, a resection of the left mandible was per-
# 2006 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Metastasizing ameloblastoma
Fig. 1. Clinicoradiographic diagnosis of dentigerous cyst of 38.
sisted of insertion of three dental implants in the neo-mandible and a fixed, three-part bridge as superstructure. Further periodical follow up at 16 months postoperatively has not shown signs of locoregional recurrence. A chest radiograph after 1 year’s follow up did not reveal any signs of metastases.
Discussion
Ameloblastomas are rare tumours of odontogenic epithelial origin. The average age at diagnosis of patients with ameloblastoma is 36 years10. Men and women are equally affected with women
Fig. 2. Histopathologic diagnosis of benign ameloblastoma.
463
being approximately 4 years younger than men at the time of first occurrence10. The mandible to maxilla ratio is 5:1, with the molar region of the mandible being most frequently affected10. Ameloblastomas are considered to be benign, although they are locally invasive and have a high propensity for local recurrence. Malignant (metastasizing) ameloblastoma is extremely rare; an occurrence of 2% of all benign ameloblastomas has been reported, but this is probably too high a percentage6. The mean age of the metastasizing ameloblastoma cases described in the literature as reviewed by REICHART & PHILIPSEN was 34.4 years with a range of 5– 74 years9. The female:male ratio for this sample was 1:1.2. As for non-metastasizing ameloblastoma, the majority of cases were localized in the mandible9. The median survival time after the appearance of metastases ranges from 3 months to 5 years5, with the longest reported survival time being 25 years5,8. Most malignant amelolastomas are of the plexiform histopathologic type, but their histologic and cytologic features are not significantly different from those of the non-metastatic type7,9. There are no morphological criteria to predict the biological behaviour of ameloblastomas with respect to their potential for metastatic spread7. Extent of the initial tumour and multiple recurrences and respective surgical interventions seem to contribute to the potential for metastatic spread5,7–9, but not all malignant ameloblastoma cases have a history of repeated surgical intervention1,4. The interval between diagnosis of the primary and development of a metastasis is generally long, with an average of 10–12 years4,7. Lymphatic spread of malignant tumour cells is a well accepted route of metastasis9. However, EISENBERG proposed that the occurrence of ameloblastoma in cervical lymph nodes could be explained by the phenomenon of heterotopia3. This theory states that during embryogenesis odontogenic epithelium becomes entrapped in lymphoid tissue. When this epithelium undergoes benign neoplastic transformation, an ameloblastoma could than develop within a lymph node. This implies that the process could be multifocal. Because of the long interval between diagnosis of the primary tumour and the occurrence of regional or distant metastasis, and the rareness of the phenomenon, the question arises as to whether all ameloblastoma patients should be evaluated routinely for the development of such metastases. GOLDENBERG et al. recommend that patients
464
Gilijamse et al. form a type of neck dissection. Routine postoperative radiotherapy does not seem to be indicated.
References
Fig. 3. Second recurrence of ameloblastoma, 14 years after primary manifestation.
Fig. 4. Cervical lymph-node metastasis of ameloblastoma, plexiform type. No cytological signs of malignancy. (a) Low power view (original magnification 25); (b) detail (original magnification 100).
receive annual chest radiographs to evaluate the most likely site for distant metastasis4. Likewise, annual evaluation of the neck should be considered, together with radiographic examination of the primary site for possible local recurrences.
For operable lung metastasis, surgery seems to be the treatment of choice4,5,7,9, but for non-resectable disease, radiation and/or chemotherapy may play a role5,9. For regional lymph-node involvement, as in this case, it seems appropriate to per-
1. Ameerally P, McGurk M, Shaheen O. Atypical ameloblastoma: report of three cases and a review of the literature. Br J Oral Maxillofac Surg 1996: 34: 235– 239. 2. Barnes L, Eveson JW, Reichart P, Sidransky D, eds: World Health Organization Classification of Tumours. Pathology and Genetics. Head and Neck Tumours. Lyon: International Agency for Research on Cancer (IARC). IARC Press 2005. 3. EISENBERG E. Discussion (response to HOUSTON G, DAVENPORT W, KEATON W, HARRIS S. Malignant (metastatic) ameloblastoma: report of a case. J Oral Maxillofac Surg 1993: 51: 1152–1155). J Oral Maxillofac Surg 1993: 51: 1156–1157. 4. Goldenberg D, Sciubba J, Koch W, Tufano R. Malignant odontogenic tumours: a 22-year experience. Laryngoscope 2004: 114: 1770–1774. 5. Henderson JM, Sonnet JR, Schlesinger C, Ord RA. Pulmonary metastasis of ameloblastoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999: 88: 170–176. 6. Houston G, Davenport W, Keaton W, Harris S. Malignant (metastatic) ameloblastoma: report of a case. J Oral Maxillofac Surg 1993: 51: 1152–1155. 7. Kunze E, Donath K, Luhr HG, Engelhardt W, De Vivie R. Biology of metastasizing ameloblastoma. Pathol Res Pract 1985: 180: 526–535. 8. Laughlin EH. Metastasizing ameloblastoma. Cancer 1989: 64: 776–780. 9. Reichart PA, Philipsen HP. Metastasizing, malignant ameloblastoma. Odontogenic Tumours and Allied Lesions. London: Quintessence Publishing Co. Ltd. 2004: pp. 207–213. 10. Reichart PA, Philipsen HP, Sonner S. Ameloblastoma: biological profile of 3677 cases. Eur J Cancer B Oral Oncol 1995: 31B(2):86–99. Address: I. van der Waal Department of Oral and Maxillofacial Surgery/Oral Pathology VU University Medical Centre (VUMC)/Academic Centre for Dentistry Amsterdam (ACTA) P.O. Box 7057 1007 MB Amsterdam The Netherlands Tel: +31 20 444 4039 Fax: +31 20 444 4046 E-mail: [email protected]