Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 277e278
Contents lists available at ScienceDirect
Journal of Cranio-Maxillo-Facial Surgery journal homepage: www.jcmfs.com
Letter to the Editor
Longest survival of lung metastatic ameloblastoma with a rare cause of malignant hypercalcemia Keywords: Ameloblastoma Odontogenic tumour Malignant hypercalcemia Hypercalcemia
To the editor, Ameloblastoma is the second most common benign odontogenic tumour of the mandible, representing approximately 1% of all mandibular tumours and cysts (Eckardt et al., 2009). Although ameloblastomas have a very high local recurrence rate, the incidence of distant metastases is very rare, constituting less than 2% of ameloblastomas (Henderson et al., 1999). Ameloblastomas frequently metastasize to the lungs bilaterally via a hematogenous route. Treatment of metastasizing (malignant) ameloblastoma should be a combination of close observation, thoracotomy with wedge resections or experimental chemotherapeutic combinations. This letter presents a case of longest survival of metastatic ameloblastoma to the lungs with co-incident hypercalcemia, which is rarely seen. In December 2007, a 48 year-old-male patient presented to our clinic with chronic cough and fatigue. A mandibular ameloblastoma had been resected 8 months previously. The pathology had revealed malignant epithelial tumour with nest cells associated with squamous differentiation and with a positive anterior surgical margin. 8 months after surgery, thoracoabdominal computed tomography (CT) revealed metastatic nodular lesions, the largest being 1.5 cm in the middle lobe of right lung. Right inferior lobectomy and wedge resection of the nodules were performed. A histopathological examination of the mass showed a well differentiation malignant epithelial neoplasm which was composed of strands of peripheral columnar cells demonstrating palisading orientation, consistent with the diagnosis of metastatic ameloblastoma. The patient was treated conservatively because he refused further treatment and there was no data demonstrating the benefits of chemotherapy after metastasectomy. 2 months after metastasectomy, no metastases were found in an F-18 fluorodeoxyglucose (18-FDG) positron emission tomography/CT. The patient failed to attend for follow up. 46 months after metastasectomy the patient was readmitted with polyuria and polydipsia laboratory results showed an elevated calcium level of 16.8 mg/dl (normal range; 8.6e10.2 mg/dl), with normal renal function and low levels of parathyroid hormone and calcitriol. Thoracoabdominal CT revealed
multiple metastatic lesions in both lungs. Whole body bone scintigraphy failed to demonstrate metastases in the skeletal system. The patient was treated with zoledronic acid and serum calcium level decreased to 10.2 mg/dl. It was decided to treat the patient with carboplatin and paclitaxel combination chemotherapy but the patient did not accept treatment. So has been treated with 4 mg/ 21d zoledronic acid regularly for 26 months without any chemotherapy to date. Hypercalcemia can occur in up to 20e 30 percent of cases with cancer (Roodman, 2004). Malignant hypercalcemia signifies poor prognosis and more than half of the patients die in a short time with a median 4 month overall survival (Ralston et al., 1990). Malignant hypercalcemia mostly occurs by the three mechanisms; osteolytic metastases with local release of cytokines (including osteoclast activating factors); tumour secretion of parathyroid hormone-related protein (PTHrP); and tumour production of 1,25-dihydroxyvitamin D (calcitriol) (Roodman, 2004). Although mechanisms of hypercalcemia associated with certain types of malignancy are well-known the exact mechanism of hypercalcemia associated with ameloblastoma is not known. There are only 27 well-documented cases of metastatic ameloblastomas reported in the literature and lung is the most common site. There is no proven efficacy of standard single agent or combination chemotherapy for palliation of unresectable metastatic ameloblastoma (Van Dam et al., 2010). Despite metastases, some patients of metastatic ameloblastoma could survive without any treatment (Hasim et al., 2007) for long periods. Metastatic ameloblastoma with hypercalcemia is a very rare condition, first reported in 1981 by Madiedo and colleagues (Madiedo et al., 1981). In our case, no relation was found between hypercalcemia and serum PTH/calcitriol levels. The mechanism of hypercalcemia in our case was likely to be tumour secretion of PTHrP. No bone metastases were found. As a result hypercalcemia is an uncommon process in ameloblastoma and must always be considered by the practitioner. In conclusion, metastases and hypercalcemia are rare situations during the course of ameloblastoma and patients can live longer than other malignant hypercalcemia situations without any treatment as in our case. Conflict of interest The authors declare that they have no conflict of interest. References Eckardt AM, Kokemuller H, Flemming P, Schultze A: Recurrent ameloblastoma following osseous reconstructionea review of twenty years. J Craniomaxillofac Surg 37: 36e41, 2009
1010-5182/$ e see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery. All rights reserved. http://dx.doi.org/10.1016/j.jcms.2013.11.011
278
Letter to the Editor / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 277e278
Hasim FW, Poon CC, Smith AC: Prolonged survival with confirmed metastatic pulmonary ameloblastoma. Int J Oral Maxillofac Surg 36: 953e955, 2007 Henderson JM, Sonnet JR, Schlesinger C, Ord RA: Pulmonary metastasis of ameloblastoma: case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88: 170e176, 1999 Madiedo G, Choi H, Kleinman JG: Ameloblastoma of the maxilla with distant metastases and hypercalcemia. Am J Clin Pathol 75: 585e591, 1981 Ralston SH, Gallacher SJ, Patel U, Campbell J, Boyle IT: Cancer-associated hypercalcemia: morbidity and mortality. Clinical experience in 126 treated patients. Ann Intern Med 112: 499e504, 1990 Roodman GD: Mechanisms of bone metastasis. N Engl J Med 350: 1655e1664, 2004 Van Dam SD, Unni KK, Keller EE: Metastasizing (malignant) ameloblastoma: review of a unique histopathologic entity and report of Mayo Clinic experience. J Oral Maxillofac Surg 68: 2962e2974, 2010
Yusuf Açıkgöz Ankara Numune Education and Research Hospital, Department of Internal Medicine, Ankara, Turkey
Mehmet Ali Nahit Sendur*, Nuriye Yıldırım Özdemir Ankara Numune Education and Research Hospital, Department of Medical Oncology, Ankara, Turkey Sercan Aksoy Hacettepe University Cancer Institute, Department of Medical Oncology, Ankara, Turkey Dogan Uncu, Nurullah Zengin Ankara Numune Education and Research Hospital, Department of Medical Oncology, Ankara, Turkey * Corresponding author. Ankara Numune Education and Research Hospital, Department of Medical Oncology, 06100 Sihhiye, Ankara, Turkey. Tel.: þ90 312 508 4600; fax: þ90 312 311 2778. E-mail address: [email protected] (M.A.N. Sendur).
12 August 2013
Contents lists available at ScienceDirect
Journal of Cranio-Maxillo-Facial Surgery journal homepage: www.jcmfs.com
Letter to the Editor
Longest survival of lung metastatic ameloblastoma with a rare cause of malignant hypercalcemia Keywords: Ameloblastoma Odontogenic tumour Malignant hypercalcemia Hypercalcemia
To the editor, Ameloblastoma is the second most common benign odontogenic tumour of the mandible, representing approximately 1% of all mandibular tumours and cysts (Eckardt et al., 2009). Although ameloblastomas have a very high local recurrence rate, the incidence of distant metastases is very rare, constituting less than 2% of ameloblastomas (Henderson et al., 1999). Ameloblastomas frequently metastasize to the lungs bilaterally via a hematogenous route. Treatment of metastasizing (malignant) ameloblastoma should be a combination of close observation, thoracotomy with wedge resections or experimental chemotherapeutic combinations. This letter presents a case of longest survival of metastatic ameloblastoma to the lungs with co-incident hypercalcemia, which is rarely seen. In December 2007, a 48 year-old-male patient presented to our clinic with chronic cough and fatigue. A mandibular ameloblastoma had been resected 8 months previously. The pathology had revealed malignant epithelial tumour with nest cells associated with squamous differentiation and with a positive anterior surgical margin. 8 months after surgery, thoracoabdominal computed tomography (CT) revealed metastatic nodular lesions, the largest being 1.5 cm in the middle lobe of right lung. Right inferior lobectomy and wedge resection of the nodules were performed. A histopathological examination of the mass showed a well differentiation malignant epithelial neoplasm which was composed of strands of peripheral columnar cells demonstrating palisading orientation, consistent with the diagnosis of metastatic ameloblastoma. The patient was treated conservatively because he refused further treatment and there was no data demonstrating the benefits of chemotherapy after metastasectomy. 2 months after metastasectomy, no metastases were found in an F-18 fluorodeoxyglucose (18-FDG) positron emission tomography/CT. The patient failed to attend for follow up. 46 months after metastasectomy the patient was readmitted with polyuria and polydipsia laboratory results showed an elevated calcium level of 16.8 mg/dl (normal range; 8.6e10.2 mg/dl), with normal renal function and low levels of parathyroid hormone and calcitriol. Thoracoabdominal CT revealed
multiple metastatic lesions in both lungs. Whole body bone scintigraphy failed to demonstrate metastases in the skeletal system. The patient was treated with zoledronic acid and serum calcium level decreased to 10.2 mg/dl. It was decided to treat the patient with carboplatin and paclitaxel combination chemotherapy but the patient did not accept treatment. So has been treated with 4 mg/ 21d zoledronic acid regularly for 26 months without any chemotherapy to date. Hypercalcemia can occur in up to 20e 30 percent of cases with cancer (Roodman, 2004). Malignant hypercalcemia signifies poor prognosis and more than half of the patients die in a short time with a median 4 month overall survival (Ralston et al., 1990). Malignant hypercalcemia mostly occurs by the three mechanisms; osteolytic metastases with local release of cytokines (including osteoclast activating factors); tumour secretion of parathyroid hormone-related protein (PTHrP); and tumour production of 1,25-dihydroxyvitamin D (calcitriol) (Roodman, 2004). Although mechanisms of hypercalcemia associated with certain types of malignancy are well-known the exact mechanism of hypercalcemia associated with ameloblastoma is not known. There are only 27 well-documented cases of metastatic ameloblastomas reported in the literature and lung is the most common site. There is no proven efficacy of standard single agent or combination chemotherapy for palliation of unresectable metastatic ameloblastoma (Van Dam et al., 2010). Despite metastases, some patients of metastatic ameloblastoma could survive without any treatment (Hasim et al., 2007) for long periods. Metastatic ameloblastoma with hypercalcemia is a very rare condition, first reported in 1981 by Madiedo and colleagues (Madiedo et al., 1981). In our case, no relation was found between hypercalcemia and serum PTH/calcitriol levels. The mechanism of hypercalcemia in our case was likely to be tumour secretion of PTHrP. No bone metastases were found. As a result hypercalcemia is an uncommon process in ameloblastoma and must always be considered by the practitioner. In conclusion, metastases and hypercalcemia are rare situations during the course of ameloblastoma and patients can live longer than other malignant hypercalcemia situations without any treatment as in our case. Conflict of interest The authors declare that they have no conflict of interest. References Eckardt AM, Kokemuller H, Flemming P, Schultze A: Recurrent ameloblastoma following osseous reconstructionea review of twenty years. J Craniomaxillofac Surg 37: 36e41, 2009
1010-5182/$ e see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery. All rights reserved. http://dx.doi.org/10.1016/j.jcms.2013.11.011
278
Letter to the Editor / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 277e278
Hasim FW, Poon CC, Smith AC: Prolonged survival with confirmed metastatic pulmonary ameloblastoma. Int J Oral Maxillofac Surg 36: 953e955, 2007 Henderson JM, Sonnet JR, Schlesinger C, Ord RA: Pulmonary metastasis of ameloblastoma: case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88: 170e176, 1999 Madiedo G, Choi H, Kleinman JG: Ameloblastoma of the maxilla with distant metastases and hypercalcemia. Am J Clin Pathol 75: 585e591, 1981 Ralston SH, Gallacher SJ, Patel U, Campbell J, Boyle IT: Cancer-associated hypercalcemia: morbidity and mortality. Clinical experience in 126 treated patients. Ann Intern Med 112: 499e504, 1990 Roodman GD: Mechanisms of bone metastasis. N Engl J Med 350: 1655e1664, 2004 Van Dam SD, Unni KK, Keller EE: Metastasizing (malignant) ameloblastoma: review of a unique histopathologic entity and report of Mayo Clinic experience. J Oral Maxillofac Surg 68: 2962e2974, 2010
Yusuf Açıkgöz Ankara Numune Education and Research Hospital, Department of Internal Medicine, Ankara, Turkey
Mehmet Ali Nahit Sendur*, Nuriye Yıldırım Özdemir Ankara Numune Education and Research Hospital, Department of Medical Oncology, Ankara, Turkey Sercan Aksoy Hacettepe University Cancer Institute, Department of Medical Oncology, Ankara, Turkey Dogan Uncu, Nurullah Zengin Ankara Numune Education and Research Hospital, Department of Medical Oncology, Ankara, Turkey * Corresponding author. Ankara Numune Education and Research Hospital, Department of Medical Oncology, 06100 Sihhiye, Ankara, Turkey. Tel.: þ90 312 508 4600; fax: þ90 312 311 2778. E-mail address: [email protected] (M.A.N. Sendur).
12 August 2013
