Persistent response to vemurafenib in metastatic ameloblastoma with BRAF mutation: a case report.

BACKGROUND: Ameloblastomas are uncommon locally aggressive tumors of odontogenic epithelium that rarely metastasize. Currently, there is no standard of care for the metastatic forms. Several studies have shown that ameloblastomas frequently have a BRAF mutation. CASE PRESENTATION: We report a case of a 33-year-old Caucasian woman with ameloblastoma diagnosed 30 years ago who developed lung metastasis 19 years ago. Systemic oral treatment with vemurafenib, a BRAF inhibitor, was initiated 28 months ago within the AcSé French basket clinical trial of vemurafenib. CONCLUSIONS: The patient has shown a durable clinical, functional, and radiographic partial response with vemurafenib. These observations suggest the possibility of introducing neoadjuvant and/or adjuvant targeted therapy in locally advanced ameloblastoma to improve outcome. BRAF inhibition has proved to be an efficient strategy in patients with a BRAF-mutated ameloblastoma.

MAID chemotherapy regimen as a treatment strategy for metastatic malignant ameloblastoma: A case report.

RATIONALE: Ameloblastoma is generally characterized as a benign tumor originating in odontogenic epithelium. However, few cases of metastatic malignant ameloblastoma have also been reported. Due to the low incidence of malignant ameloblastoma, there is no established treatment regimen. To explore effective treatment for malignant ameloblastoma, we reported this case study. PATIENTS CONCERNS: This report described a case of a 28-year-old malignant ameloblastoma female patient with multiple metastasis (brain and lung). DIAGNOSES: The patient presented ameloblastoma of the left mandible in 2012. Three years later, local recurrence and brain metastasis was observed during a follow-up examination. Five years later, malignant ameloblastoma was detected by imaging and immunohistochemistry in the bilateral multiple pulmonary nodules and mediastinal lymph nodes. INTERVENTIONS: The patient was initially treated with tumor resection. Three years later after local recurrence and brain metastasis, she was accepted the extensive mandibulectomy supplemented with brain stereotactic body radiotherapy (SBRT). When diagnosed with pulmonary metastasis, the patient received combined chemotherapy regimen of MAID (mesna, adriamycin, ifosfamide and dacarbazine) for 6 cycles. OUTCOMES: The efficacy evaluation was partial remission (PR) after the 6 cycles of MAID. The last patient follow-up was July 24th 2018, and no evidence of progression was observed. The progression-free survival (PFS) of the patient was more than 9 months. LESSONS: Surgical resection is the optimal treatment for locally recurrent ameloblastoma. SBRT may be an effective treatment for unresectable oligometastasis of malignant ameloblastoma. Finally, combined chemotherapy of MAID showed encouraging effects in the management of metastatic malignant ameloblastoma.

Mandible ameloblastoma with lung metastasis: a rare case report.

BACKGROUND: The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-facial region. Although the histopathological manifestation of ameloblastoma is benign, it has unique biological behavior, for example local invasion and recurrence repeatedly. A few case of ameloblastoma was locally aggressive growth, and rarely metastasis to other tissue, for example the lungs, lymph nodes, and spine. CASE REPORT: A 64-year-old Chinese man, diagnosed with metastatic ameloblastoma, was treated with palliative chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin for six cycles, and radiotherapy for 50 Gy after the last cycle chemotherapy. During the surveillance CT scan after the therapy, the tissues of the tumor were nearly complete response. CONCLUSION: The purpose of this study was to report a case of a patient with a right mandible ameloblastoma that recurred repeatedly and metastasized into bilateral lung. After the chemotherapy and radiotherapy, the tissues of the tumor were nearly complete response. This case is interesting because it investigated the diagnosis and treatment of the malignancy ameloblastoma, as this may help diagnose and treatment for clinician to the metastatic ameloblastoma.

Ameloblastic Carcinoma.

BACKGROUND: Ameloblastic carcinoma secondary type is an extremely rare and aggressive odontogenic neoplasm that exhibits histological features of malignancy in primary and metastatic sites. It arises through carcinomatous de-differentiation of a pre-existing ameloblastoma or odontogenic cyst, typically following repeated treatments and recurrences of the benign precursor neoplasm. Identification of an ameloblastic carcinoma, secondary type presenting with histologic features of malignant transformation from an earlier untreated benign lesion remains a rarity. Herein, we report 1 such case. CASE REPORT: A 66-year-old man was referred for management of a newly diagnosed ameloblastic carcinoma. He underwent radical surgical intervention comprising hemimandibulectomy, supraomohyoid neck dissection, and free-flap reconstruction. Final histologic analysis demonstrated features suggestive of carcinomatous de-differentiation for a consensus diagnosis of ameloblastic carcinoma, secondary type (de-differentiated) intraosseous. CONCLUSIONS: Ameloblastic carcinoma, secondary type represents a rare and challenging histologic diagnosis. Radical surgical resection with adequate hard and soft tissue margins is essential for curative management of localized disease.

Malignant ameloblastoma (metastatic ameloblastoma) in the lung: 3 cases of misdiagnosis as primary lung tumor with a unique growth pattern.

Malignant ameloblastoma (metastatic ameloblastoma, MA) is currently defined as a distinct pathologic entity, MA, despite its histologically benign appearance. According to the new criteria, the histological and clinical features of MA are more homogenous. Here, we report three cases of histologically confirmed pulmonary MA. Two of the three patients complained of chest pain as the primary symptom, and the other case was detected upon the evaluation of pulmonary nodules found during a health examination after a local recurrence of mandible ameloblastoma. All three patients were female with an average age of 48 years. The intervals between the primary ameloblastoma and metastasis to the lung were 14 years, 19 years and 10 years, averaging 14.3 years. Prior to metastasis to the lung, only one patient experienced local recurrences, at 5 and 19 years after the primary tumor resection, while the other two patients both remained disease-free. Computed tomography (CT) or X-ray evaluation demonstrated multiple bilateral lung nodules ranging in size from several millimeters up to 2 cm. Histologically, the pulmonary metastatic tumors showed a unique growth pattern: the tumor cells grew among the interstitial alveoli but did not appear to destructively infiltrate the surrounding tissue. Immunohistochemically, the MA cells expressed squamous differentiation markers, such as CK10/13 and p63, while the alveolar epithelial cells stained for TTF1 and PE10. In this paper, we discuss the clinical behavior, differential diagnosis and unique growth pattern of pulmonary MA.

A single cervical lymph node metastasis of malignant ameloblastoma.

INTRODUCTION: Cervical node metastasis of malignant ameloblastoma is extremely rare. Because of its rarity, there is no standard treatment modality in a single lymph node metastasis in malignant ameloblastoma. MATERIALS AND METHODS: Eleven patients of malignant ameloblastoma involving a single cervical lymph node metastasis and one new case were reviewed. Neck treatment was classified into neck dissection and simple excision. Local nodal recurrence, distant metastasis and follow-up periods were investigated. RESULTS: Eight patients were treated with neck dissection (group A) and four patients underwent a simple node excision (group B). Two patients in group A experienced multiple organ metastases such as liver and lung seven months and 13 years after neck dissection respectively. The other patients showed no recurrence and metastasis. In group B, there was no report of a regional neck recurrence and distant metastasis during follow-up of 1-7 years. CONCLUSION: Multiple nodes metastasis requires a radical neck dissection; however, simple excision with close follow-up may be used in a single node metastasis in malignant ameloblastoma.

Metastasizing Ameloblastoma - a perennial pathological enigma? Report of a case and review of literature.

The Ameloblastoma is a slow growing locally invasive odontogenic epithelial neoplasm with a high recurrence rate and a low tendency to metastasize. Metastasis in Ameloblastoma was first described by Simmons and Emura in the 1920s. Slootweg and Muller proposed the term Malignant Ameloblastoma to describe a well-differentiated ameloblastoma that metastasizes but maintains the characteristic cytologic features of the original tumour and the term Ameloblastic Carcinoma to an ameloblastoma with malignant cytological features. About 2% of ameloblastomas undergo metastasis. So far there have only been two cases of Metastasizing Ameloblastoma reported from the Indian Subcontinent. We present the case of a 22-year-old male Indian patient, who presented with a diffuse swelling in the left posterior mandible. Radiographs revealed a multilocular radiolucency in the left mandible. On histopathological examination, the lesion was diagnosed as follicular ameloblastoma. Four years later the patient presented with a swelling in the left submandibular region. Histological examination revealed metastatic ameloblastoma within the cervical lymph node.

Metastasizing Ameloblastoma With Localized Interstitial Spread in the Lung: Report of Two Cases.

Ameloblastoma is a locally aggressive, epithelial odontogenic tumor involving mandibles and maxillas. Distant metastasis is a very rare condition and is designated as metastasizing (malignant) ameloblastoma despite its benign histological appearance. Up to now, only 27 well-documented cases of metastasizing ameloblastomas are reported in the literature, and lung is the most commonly involved organ. In previous reports of pulmonary metastasizing ameloblastomas, there was little description of the histopathologic finding. Here, the authors report 2 cases of pulmonary metastasizing ameloblastomas with special emphasis on their interesting, interstitial spread along alveolar septa, resulting in a unique 2-cell pattern under microscopic examination. Pulmonary metastasizing ameloblastoma may pose difficulty in diagnosis if the pathologist is not aware of patient's clinical history of ameloblastoma.

A novel technique for ventral orbital stabilization: the masseter muscle flap.

Loss of the caudal maxilla and ventral orbit after tumor resections can have negative functional and esthetic influences on the eye involved. This article reports on a case of a caudal maxillary acanthomatous ameloblastoma involving the ventral orbit that was resected and stabilized with a masseter muscle flap. The masseter muscle flap was generated from the superficial belly of the masseter muscle in order to close a defect in the orbital rim, created by a caudal maxillectomy. None of the published complications such as enophthalmos, excessive lacrimation, globe deviation, or strabismus were noted, 8 months following the procedure. The only clinical sign present at the time of re-evaluation was mild lacrimation. The authors propose the use of a masseter muscle flap as a viable technique in stabilizing the ventral orbit after caudal maxillectomy and ventral orbitectomy, preventing the complications associated with this surgery.

Ameloblastoma with varied sites of metastasis: report of two cases and literature review.

OBJECTIVE: We report two rare cases of lung metastasis from maxillary ameloblastoma, in order to review its risk and analyse the types of metastases that can present with this disease. METHODS: A 40-year-old male with multiple recurrences and a 46-year-old female, who had undergone successful surgical treatment of a maxillary ameloblastoma, presented with metastatic lesions. The primary tumour and metastases were benign in both patients. We reviewed and analysed 20 cases of the same condition reported in recent years. RESULTS: Our initial treatment for the primary maxillary lesion was performed more than 10 years before the pulmonary lesions presented. Due to the aggressive nature of this tumour, metastases in the lungs and cervical lymph nodes (male patient) were confirmed. CONCLUSION: These cases presented a diagnostic challenge due to the multiple and varied sites of recurrence, which indicate the natural behaviour of this tumour. Different routes of metastasis can occur, including implanting, haematogenous, and lymphatic spread. CT-guided percutaneous transthoracic lung biopsy is an important method to confirm metastatic ameloblastoma.

The variability and complexity of ameloblastoma: carcinoma ex ameloblastoma or primary ameloblastic carcinoma.

Ameloblastoma is characterized by slow-growing, local invasiveness and high incidence of local recurrence. It usually presents with a benign histological appearance. However, ameloblastoma occasionally demonstrates a clinical course that is characteristic of malignant transformation. Here, we present a case of ameloblastoma with an aggressive clinical course, including multiple recurrences, a short disease-free interval, pulmonary metastasis and extensive skull-base infiltration. With a careful re-evaluation of the histology and cytology of the specimens of primary and recurrent ameloblastoma in 2006 and 2007, malignant transformation was observed and carcinoma ex ameloblastoma was ultimately diagnosed.

Malignant ameloblastoma metastasis to the neck--radiological and pathohistological dilemma.

INTRODUCTION: Ameloblastomas are odontogenic epithelial, locally invasive tumors of slow growth and mostly of benign behavior. Their frequency is low (they account for 1% of all head and neck tumors and about 11% of tumors of dental origin). Malignant variations of ameloblastoma are malignant ameloblastoma and ameloblastic carcinoma. They constitute less than 1% of all ameloblastomas. We presented a case of malignant ameloblastoma of the mandible with neck metastasis. CASE REPORT: A patient, aged 72, presented with the following symptoms: pain in the lower jaw, swelling in the left submandibular area and difficult mouth opening. The patient was admitted to the Department of Oral and Maxillofacial Surgery, Clinical Center of Montenegro, two months after he had noticed the symptoms. Panoramic radiography (OPG) showed that both jaws were partially toothless with terminal stage of periodontitis of the remaining teeth. Also, OPG showed sharply limited semicircular defect in the retromolar region and along the front edge of the mandible rami. Conventional histopathologic examination of the neck masses showed malignant ameloblastoma which contained central fields of squamous differentiation. Immunoreactivity of several markers was determined using immunohistochemical analyses. After these diagnostic methods a definite histopathology diagnosis was made: Ameloblastoma metastaticum in textus fibroadiposus regio colli (typus acanthomatosus). CONCLUSION: It is not possible to distinguish conventional, ie intraosseous, ameloblastoma from malignant ameloblastoma according to histopathologic features. It is necessary to pay special attention, especially in elderly patients, and to carry out further clinical, radiological and pathohistological diagnostic procedures, such as immunohistochemical analysis. A timely and correct diagnosis and treatment of malignant ameloblastoma require a multidisciplinary approach.

Pulmonary metastases from an Ameloblastoma: case report and review of the literature.

Ameloblastomas have a high recurrence rate, and because of their biological tendency towards local invasion are considered borderline tumours. Despite this, reports of metastasis of these tumours are rare. This report presents a patient with mandibular ameloblastoma that recurred 29 years after surgery and metastasized to both lungs. Because of the large range of the area of metastasis, complete surgical resection of the tumours was impossible. After confirming the diagnosis by biopsy of the pulmonary lesions the pulmonary metastases were not treated actively. Observation over 4 years showed no obvious change in the lung metastasis. Recent cases are summarized and analyzed in this paper, with respect to its occurrence, pathological types, methods of treatment and other related aspects.

Malignant ameloblastoma: concurrent presentation of primary and distant disease and review of the literature.

Malignant ameloblastoma is a rare tumor of odontogenic origin with a metastatic focus. Distant metastatic disease is found most commonly in the lungs. A review of the literature shows that most cases of malignant ameloblastoma involve a disease-free period from primary tumor extirpation to the discovery of metastasis. This report describes the case of a 56-year-old man presenting with ameloblastoma of the maxilla and a solitary pulmonary metastasis concurrently. This represents a rare case in which there is a simultaneous diagnosis of primary ameloblastoma and a metastatic lesion. Appropriate workup for ameloblastoma includes surveillance for metastatic disease. Surgical resection of primary and distant disease is recommended. Chemotherapy and radiation may play a role in palliation when resection of metastatic disease is not feasible.

Management of recurrent ameloblastoma of the jaws; a 40-year single institution experience.

Ameloblastoma is a histologically almost always benign odontogenic tumor with a high rate of recurrence if not removed completely. Therefore, radical surgery is the treatment of choice of a primary ameloblastoma. Of 18 patients with a recurrent ameloblastoma, previously treated by enucleation, radical surgery was deemed impossible in three because of the extent of the tumor or because of a poor general condition of the patient. Of the remaining 15 patients three refused to undergo radical surgery and have been treated for their recurrence by enucleation again. In none of the twelve remaining patients treated by radical surgery a recurrence was observed in a mean follow-up period of 10.5 years. In one of these patients a metastatic cervical lymph node was detected during the primary reconstruction of the mandibular defect. The absence of recurrences in patients treated by radical surgery should be looked at with some reservation, since recurrences may still show up after 10.5 years. The three patients who refused radical surgery all developed one or more new recurrences.

Metastasizing (malignant) ameloblastoma: review of a unique histopathologic entity and report of Mayo Clinic experience.

PURPOSE: To provide a comprehensive review of metastasizing (malignant) ameloblastoma, establish a new baseline of valid cases using histologic criteria and minimum documentation, and report 3 cases from the Mayo Clinic files. PATIENTS AND METHODS: Ninety-eight original reports of "metastasizing," "malignant," or "atypical" ameloblastoma were reviewed. The following data were gathered for reports that demonstrated well-differentiated ameloblastoma at the metastatic site: gender, ethnicity, age at time of primary tumor diagnosis, histologic pattern of primary tumor, anatomic sites of primary and metastatic tumors, interval from diagnosis of primary to diagnosis of metastasis, number of recurrences preceding metastasis, treatment responses to radiation and/or chemotherapy, presence of hypercalcemia, and length of survival after metastasis. RESULTS: Twenty-seven valid reports of metastasizing (malignant) ameloblastoma were identified; 81% originated in the mandible, recurring on average 4 times before metastasis. Lungs were the initial site of metastasis in 78% of reports, of which 71% were bilateral. The average time from diagnosis of primary to metastasis was 18 years. Over half of the patients were alive and had survived an average of 10 years since diagnosis of metastasis. Those patients who had succumbed to their disease had an average survival time of 3 years after diagnosis of metastasis. CONCLUSIONS: Metastasis of well-differentiated ameloblastoma occurs more rarely than previously believed. Metastasis to the lungs bilaterally, by the hematogenous route, usually follows multiple failed attempts at primary tumor control. The absence of malignant cytologic transformation correlates with relatively indolent metastatic site growth. Treatment of metastasizing (malignant) ameloblastoma should include close observation, thoracotomy with wedge resections, or experimental chemotherapeutic combinations.