Malignant Epithelial Odontogenic Tumor Research Articles

Ameloblastoma of the Mandible With Carcinoma Transformation in a Young Adult.

Ameloblastic carcinoma (AC) is a rare and aggressive malignant epithelial odontogenic tumor making up less than 1% of malignant head and neck tumors. The majority of cases occur in the mandible with a minority occurring in the maxilla. Most occur de novo, while rare cases of AC have resulted from transformation from ameloblastoma. Here, we present a case in which a 30-year-old man presented with proptosis and a recurrent right temporal mass, which had been previously diagnosed as ameloblastoma on surgical pathology. CT findings demonstrated local invasion, and he was subsequently taken to the operating room for right craniotomy, infratemporal and middle cranial fossa tumor resection, and right modified radical neck dissection with reconstruction. Final pathology, which included areas of early focal necrosis, loss of peripheral palisading, and hyperchromatism, confirmed the diagnosis of ameloblastoma with transformation to AC. We further discuss radiologic and histopathological signs of this rare tumor, as well as recommended treatment modalities.

THREE CASES OF AMELOBLASTIC CARCINOMA WITH REVIEW OF CLINICAL, RADIOGRAPHIC AND HISTOPATHOLOGIC FEATURES

<h3>Introduction</h3> Ameloblastic carcinoma (AC) is a rare malignant primary epithelial odontogenic tumor demonstrat- ing histologic features of ameloblastoma with signs of overt malignancy. In this case series, we describe the clinical, radiographic and histologic features of 3 cases of AC. <h3>Methods</h3> Three cases of AC were identified from the University of Florida Oral Pathology Biopsy archives. Clinical data and original slides were retrospectively analyzed. Immuno- histochemical (IHC) stains for cytokeratin 19 (CK19) was performed on all cases to demonstrate odontogenic epithe- lial origin. <h3>Results</h3> All cases of AC in this series occurred in elderly males, with two presenting in the mandible and one in maxilla. Radiographically, all presented as ill-defined radiolucencies and demonstrated cortical expansion, consistent with features of malignancy. The first case involved a 60-year-old male with an erosive soft tissue mass along the anterior mandible between teeth #27 and #28 and corresponding radiolucent lesion on films. The second case occurred in a 75-year-old male presenting with gingival swelling and an expansile radiolucent lesion in the right maxilla, extending from tooth #3 to #7. The third case was seen in a 75-year-old male displaying a large oste- olytic lesion of the mandibular ramus surrounded by a bulky soft tissue mass extending deep into the right lateral and medial pterygoid muscles. Histologically, all cases revealed large sheets of interconnecting islands and strands of malignant cells displaying peripheral palisading, reverse nuclear polarity and apical vacuolization. In addition, the malignant islands exhibited central necrosis and neoplastic cells showed significant hyperchromatism with nu- clear pleomorphism. IHC staining with CK19 were strongly positive in two cases and focally positive in one case. <h3>Conclusion</h3> This case series documents 3 cases of a rare odontogenic malignancy and highlights the importance of including this entity in a differential diagnosis of aggressive lesions of the jaws, especially in older patients.

Challenges in the diagnostics and treatment of ectopic ameloblastic carcinoma: a case report

Ameloblastic carcinoma (AC) is a rare and aggressive malignant epithelial odontogenic tumor, most commonly located in the mandible or maxilla. An extremely rare extragnathic localization of AC with no connection to the jaws, ectopic ameloblastic carcinoma (EAC), has so far been described only three times. This report presents a 64-year-old male with skull base ameloblastic carcinoma and offers a review of diagnostic and treatment challenges related to EAC. Because of its rarity and histological similarity to other tumors, EAC is often misdiagnosed. This is why we established a pathohistological and immunohistochemical profile of EAC that differentiates it from histologically similar tumors. The most frequently used EAC treatment is radical surgical resection, but the majority of reviewed reports described local recurrence. Taking into consideration new scientific discoveries on the molecular pathogenesis of ameloblastoma, we are the first to have performed BRAF mutation analysis in an EAC patient. BRAF inhibitors offer promising results in the treatment of BRAF-positive ameloblastomas and should continue to be researched in AC and EAC patients. Finally, EAC should be considered in differential diagnosis of head and neck tumors outside the jaws.

EVALUATION OF SOX2 AS A POTENTIAL STEM CELL MARKER IN BENIGN AND MALIGNANT ODONTOGENIC TUMORS

INTRODUCTION: Odontogenic tumors (OTs) constitute a wide range of lesions derived from the tooth forming apparatus and its remnants. These tumors are generally benign, yet some are aggressive and have locally invasive behavior with a high rate of recurrence and some are malignant. Tumor stem cells (TSCs) are a unique subpopulation of cells that possess the ability to initiate a neoplasm and sustain self-renewal. Epithelial stem cell (ESC) markers such as sex-determining region Y (SRY)-box 2 (SOX2) are capable of identifying these stem cells which are expressed during the early stages of tooth development. OBJECTIVES: To evaluate immunohistochemically the expression of the stem cell proliferating marker SOX2 in benign and malignant epithelial odontogenic tumors. MATERIAL AND METHODS: Immunohistochemical (IHC) study using the SOX2 antibody was done on 30 surgical specimens of benign and malignant epithelial OTs as study group and 5 normal tooth germ tissues as a control group. RESULTS: Malignant OTs biopsies showed intense immune-reactivity to SOX2, while aggressive benign OTs showed medium immunereactivity with variable intensity. Totally benign tumors were immune-negative. The IHC staining intensity was directly proportional to the state of malignancy of odontogenic tumors. The difference in the expression of SOX2 in malignant and benign OTs was statistically significant. However, the difference in the expression of SOX2 in OTs and control group was not statistically significant in mean of area percent, while it was statistically significant in mean of optical density. CONCLUSIONS: SOX2 is highly expressed in malignant OTs biopsies. Medium immune-reactivity with variable intensities is seen in aggressive benign OTs.

CLEAR CELL AMELOBLASTIC CARCINOMA. A CASE REPORT

Objective To report a case of ameloblastic carcinoma with onset in the lower jaw, showing histological traits as well as immunological profile with molecular markers expression and tumor proliferation. Ameloblastic carcinoma (AC) is a malignant epithelial odontogenic tumor combining ameloblastoma's histological features with malignant cytological traits. We hereby present the case report of a 62 year old female who was referred to the Oral Medicine Clinic, Faculty of Dentistry, National Autonomous University of Mexico (UNAM): The patient exhibited a swollen area in the anterior section of the lower jaw with destruction of cortical bone and displacement of anterior teeth; lesion was a nodular and ulcerated mass. Radiographic imaging revealed a poorly circumscribed radiolucent lesion in the anterior section of the mandible. Histological examination of a biopsy specimen revealed a lesion with proliferation of polygonal and cylindrical cells arranged in an hypercellular solid mass, with presence of abundant mitotic figures as well as some areas with necrosis. Some hyalinization areas in connective tissue were found along with islands of abundant glycogen-rich cells, positive to PAS. Neoplastic cells were nuclear for beta-catenin amelogenin and 40% for ki67 Discussion AC is an aggressive, malignant neoplasm with onset in the jaws, it can arise de novo or be secondary to the malignant transformation of a pre-existing ameloblastoma. Presence of clear cells is extremely rare; immunohistochemical analysis confirmed presence of glycogen. Metaplasia of clear cells n this tumor has not been reported as prognostic factor, nevertheless, it is and indicator of the lesion's morphological diversity. Conclusion Reports of ameloblastic carcinoma with clear cells are rare, nevertheless, long-term follow-up of ameloblastoma is of the utmost importance bearing in mind that these are aggressive tumors with high recurrence to malignify.

Clear cell odontogenic carcinoma: a rare jaw tumor. a review of 107 cases

Background: Clear cell odontogenic carcinoma (CCOC) is a rare intraosseous carcinoma, characterized as a malignant epithelial odontogenic tumor occurring primarily in the posterior mandible of women in their fifth and sixth decades.

Ameloblastic carcinoma of the mandible: A case report and review of the literature

Aim: The purpose of this paper was to report an additional case of ameloblastic carcinoma of the left hemi-mandible and to review and analyze clinical, radiological and histopathologic features, treatment modalities and prognosis. Presentation of case: A 70 year old malepatient presented to Maxillofacial Department for a painful swelling of the left cheek. An ameloblastic carcinoma of the left hemi-mandible was diagnosed. He underwent radical surgical intervention comprising hemimandibulectomy, supraomohyoid neck dissection, and fibula free-flap reconstruction. Postoperative radiotherapy was employed. Discussion: Ameloblastic carcinoma of the mandible is a rare aggressive tumor with a poor prognosis. It can be seen in different ages. The most common symptom is a rapidly progressing painful swelling. It is defined as a malignant epithelial odontogenic tumor that retains the features of ameloblastic differentiation with cytologic features of malignancy. Non therapeutic consensus is established. However, wide surgical excision with radiotherapy is the most common treatment. Conclusion: Diagnosis of ameloblastic carcinoma at early stage and close periodic screening for metastasis are necessary to improve patient prognosis.

Correlation between ploidy status using flow cytometry and nucleolar organizer regions in benign and malignant epithelial odontogenic tumors

ObjectiveDifferentiation between the aggressive benign odontogenic tumors and their malignant counterparts is controversial and difficult. While flow cytometry (FCM) allowed DNA analysis in neoplasia, argyrophilic organizer regions (AgNORs) number and/or size in a nucleus are correlated with the ribosomal gene activity and therefore with cellular proliferation. The aim of this research was to study the diagnostic accuracy of FCM and AgNORs staining in differentiating between benign and malignant epithelial odontogenic tumors and to correlate between these two interventions. DesignSixteen benign cases [8 cases of ameloblastoma (AB) and 8 cases of keratocystic odontogenic tumor (KCOT)] and 13 malignant epithelial odontogenic tumors [8 cases of ameloblastic carcinoma (ABC) and 5 cases of clear cell odontogenic carcinoma(CCOC)] were included in the current study. For FCM analysis, a single cell suspension from Formalin fixed paraffin-embedded (FFPE) tumors was prepared according to a modified method described by Hedley (1989) and AgNORs staining were performed in accordance to the Ploton protocol (1986). Analysis of AgNORs was performed using both quantitative and qualitative methods. ResultsThe work revealed that all the examined tumors were diploid, except for 40% of CCOC cases. The S-phase fraction (SPF) value, AgNORs count and AgNORs area/cell showed statistically significant difference on comparing benign and malignant groups. A weak positive correlation was observed between SPF and AgNORs count. ConclusionThe SPF value was considered to be more sensitive and specific in differentiation between aggressive benign and malignant epithelial odontogenic tumors in comparison to AgNORs counting.

Abstract 702: BRAF V600E mutation in benign and malignant epithelial odontogenic tumors

Abstract The classification of ameloblastoma in multicystic or unicystic variants is associated with its clinical behaviour. Recently, BRAF and SMO mutations have been reported in ameloblastomas. However, it is not clear if such mutations are shared by the multi- and unicystic variants of ameloblastoma or by odontogenic carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin-embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas, were included. The BRAFV600E mutation was assessed by real-time PCR with a specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation was assessed by Sanger sequencing. Fourteen out of 17 (82%) ameloblastomas showed the BRAFV600E mutation, specifically, 5/6 (83%) unicystic, 7/9 (78%) multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected in 4/11 (36%) malignant tumours, specifically, 3/8 (38%) ameloblastic carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E mutation was less frequent in odontogenic carcinomas than in ameloblastomas. In ameloblastomas, this mutation occurred at similar proportions in cases from the mandible and maxilla, as well as among unicystic, multicystic and desmoplastic variants, suggesting that there is no difference in their molecular pathogenesis. Our findings support the possibility for personalised, molecular targeted therapy for ameloblastomas and ameloblastic carcinomas harbouring the BRAFV600E mutation. Supported by: FAPEMIG (Fundação de Amparo à Pesquisa de Minas Gerais), CNPq (National Council for Scientific and Technological Development) and CAPES (Coordination for Improvement of Higher Education Personnel), Brazil Citation Format: Marina Goncalves Diniz, Carolina Cavalieri Gomes, Bruna Viana Antonini Guimaraes, Alessandra Pires Duarte, Ricardo Santiago Gomez. BRAF V600E mutation in benign and malignant epithelial odontogenic tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 702. doi:10.1158/1538-7445.AM2015-702

Ameloblastic Carcinoma of the Mandible: A Case Report

Ameloblastic carcinoma is a rare malignant epithelial odontogenic tumor that combines the histological features of ameloblastoma and cytological atypia, irrespective of the presence or absence of metastasis. A 36-year-old female presented with a 4-month history of a painful, ulcerated swelling in the posterior left mandible. Radiographic examination showed a unilocular radiolucency with cortical bone rupture. The preliminary diagnosis of ameloblastoma prompted an incisional biopsy. Histopathological examination revealed islands and cords of odontogenic epithelium with peripheral palisading columnar cells exhibiting reverse nuclear polarization. Stellate reticulum-like tissue was present in the center of the islands. In their vicinity, islands of cells with pleomorphism, hyperchromatism, nuclear atypia, focal necrosis, and frequent mitotic figures were identified. Immunohistochemical analysis revealed positivity for alpha-smooth muscle actin within the epithelial islands. The definitive diagnosis was ameloblastic carcinoma. The patient was referred to a head and neck surgical service.

Identification of Proteins With Increased Levels in Ameloblastic Carcinoma

The comparative proteomic approach by a combination of 2-dimensional electrophoresis and matrix-assisted laser desorption-ionization-time of flight mass spectrometry (MS) analysis is an attractive strategy for the discovery of cancer biomarkers and therapeutic targets. The identification of protein biomarkers associated with ameloblastic carcinoma (AC), a malignant epithelial odontogenic tumor, will potentially improve the diagnostic and prognostic accuracy for this malignant neoplasm. The aim of the present study was to identify highly expressed proteins in AC that could be considered as potential biomarkers. The protein profile of an AC was compared with the protein profiles of 3 cases of benign ameloblastoma. Proteins that showed increased levels in AC were identified using MS, and the augmented amount of some of these proteins in the malignant lesion was confirmed by Western blot or immunohistochemistry. We detected a total of 782 spots in the protein profile of AC, and 19 of them, showing elevated levels compared with benign ameloblastoma, were identified using MS. These proteins have been implicated in several cellular functions, such as cell structure, metabolism, stress response, and signal transduction. The increased expression of the identified proteins and the minor expression of some proteins that might inhibit tumor progression could be involved in the evolution from a benign lesion to carcinoma.

Ameloblastic carcinoma: Secondary dedifferentiated carcinoma of the mandible: Report of a rare entity with a brief review

Epithelial odontogenic tumors arise from odontogenic epithelial structures. Malignant epithelial odontogenic tumors are extremely rare. Ameloblastic carcinomas may present denovo, ex ameloblastoma or ex odontogenic cyst. Most ameloblastic carcinomas are presumed to present denovo. To date less than 45 cases of ameloblastoma with metastasis have been reported. It occurs primarily in the mandible in a wide range of age groups; no sex or race predilection has been noted. It may present as a cystic lesion with benign clinical features or as a large tissue mass with ulceration, significant bone resorption, and tooth mobility. The lesion is usually found unexpectedly after an incisional biopsy or the removal of a cyst. Histologic features of ameloblastic carcinoma shows tumor cells that resemble the cells seen in ameloblastoma, but they show cytologic atypia. Moreover, they lack the characteristic arrangement seen in ameloblastoma. The clinical course of ameloblastic carcinoma is typically aggressive, with extensive local destruction. Here we describe a rare case of ameloblastic carcinoma (secondary dedifferentiated carcinoma) of mandible in a 40-year-old female patient. Ameloblastic carcinoma: Secondary dedifferentiated carcinoma of the mandible.

Ameloblastic Carcinoma

Ameloblastic carcinoma (AC) is a rare aggressive malignant epithelial odontogenic tumor of the maxillofacial skeleton with a distinct predilection in the mandible. It may appear de novo or originate from a pre-existing ameloblastoma or odontogenic cyst. It exhibits cytological features of ameloblastoma and carcinoma. It may present as a cystic lesion with benign clinical features or as a large tissue mass with ulceration, significant bone resorption and tooth mobility. The clinical course of ameloblastic carcinoma is typically aggressive, with extensive local destruction. Direct extension of the tumour, lymph node involvement and metastasis to various sites has been reported. Wide local excision is the treatment of choice. Regional lymph node dissection should be considered and performed selectively. Radiotherapy and chemotherapy have limited role in the treatment of ameloblastic carcinomas. Close periodic reassessment of the patient is mandatory.

Nucleolar Organizing Regions and α-Smooth Muscle Actin Expression in a Case of Ameloblastic Carcinoma

Ameloblastic carcinoma is a rare lesion of odontogenic origin. It is defined as a malignant epithelial odontogenic tumor that histologically has retained the features of ameloblastic differentiation and also exhibits cytologic features of malignancy, like atypia and mitotic activity. Although this lesion represents a separate entity, differentiating it from ameloblastoma has been often challenging to pathologists. In this case study reporting a case of ameloblastic carcinoma, we have attempted to verify the previous findings on the use of Argyrophilic nucleolar organizing regions (AgNORs) and immunohistochemical staining for the alpha-smooth muscle actin (alpha-SMA) in differentiating ameloblastic carcinoma from ameloblastoma. It was observed that AgNORs was found to be almost twice in ameloblastic carcinoma as it was in ameloblastoma. A difference between the two lesions in the pattern of expression of alpha-SMA was also observed, with alpha-SMA being expressed in the odontogenic epithelium and the stroma of ameloblastic carcinoma whereas, in the case of ameloblastoma, it was found only in the stromal part. These findings suggest that AgNORs and alpha-SMA expression may be used as adjuncts to the routine histopathologic examination to differentiate ameloblastic carcinoma and ameloblastoma.

Maligne odontogene Tumoren

Malignant odontogenic tumors are extremely rare. As with benign odontogenic tumors, malignant epithelial odontogenic tumors or odontogenic carcinomas are distinguished from the even rarer mesenchymal ones, the odontogenic sarcomas. The existence of odontogenic carcinosarcomas is not yet acknowledged by the World Health Organization. Odontogenic carcinomas comprise ameloblastic carcinoma (AmCa), primary intraosseous carcinoma (PIOC), clear cell odontogenic carcinoma, odontogenic ghost cell carcinoma (OGCC), and the special case of metastasizing ameloblastoma. Odontogenic sarcomas consist of ameloblastic fibrosarcoma and ameloblastic fibrodentinosarcoma and fibroodontosarcoma. Whereas metastasizing ameloblastoma can be diagnosed only after having metastasized, all other malignant odontogenic tumors present with atypia, increased cellularity and mitoses, and invasion. Odontogenic sarcomas are regarded as low-grade tumors that rarely metastasize. Odontogenic carcinomas, however, especially AmCa, OGCC, and PIOC, are more aggressive, with a 5-year survival rate of about 70% for AmCa and OGCC and a 3-year survival rate of about 37% for PIOC. Radical surgery, eventually in combination with radiotherapy, is the treatment of choice.

Ameloblastic Carcinoma Arising from Anterior Skull Base

Ameloblastic carcinoma (AC) is an aggressive malignant epithelial odontogenic tumor. It may appear de novo or originate from a pre-existing ameloblastoma or odontogenic cyst. To our knowledge, an AC that originates from the anterior skull base has not been reported before in the English literature. We report a case of an AC that originated from the anterior skull base and invaded the dura of the anterior fossa and discuss its clinical course and treatment.

Expression profiling of ameloblastic carcinoma.

Ameloblastic carcinoma (AC) is a malignant epithelial odontogenic tumor that histologically retains the features of ameloblastic differentiation and exhibits cytological features of malignancy in the primary or recurrent tumor. It may develop within a preexisting ameloblastoma or arise de novo or from an odontogenic cyst. Expression profiling by DNA microarray is a new molecular technology that allows the analysis of cell and tissue gene expression. By using DNA microarrays containing 19,200 genes, several genes whose expression was significantly upregulated or downregulated were identified in a case of AC. The differentially expressed genes cover a broad range of functional activities: 1) transcription, 2) signaling transduction, 3) cell cycle regulation, 4) apoptosis control, and 5) differentiation. The data reported are, to our knowledge, the first genetic portrait of an AC. No final conclusion can be drawn; however, this portrait will be useful in investigating the biological behavior and in identifying possible gene targets for cancer therapy when more cases of this rare tumor are reported and compared.

Revision of the 1992 edition of the WHO histological typing of odontogenic tumors. A suggestion

The WHO classification of odontogenic tumors (1992, OT) was revised. The following main changes were proposed: (1) OT are not only "related to" odontogenic tissues but are derived from these; (2) the stroma of the epithelial tumor group (1.1.1) is of a fibrous nature and does not contain any ectomesenchymal component; (3) subtypes of ameloblastomas have to be differentiated (intra-, extraosseous, desmoplastic, unicystic); (4) eponyms are no longer used in the revised classification; (5) the AOT is reclassified as an epithelial OT; (6) a neoplastic and non-neoplastic line of the ameloblastic fibroma and ameloblastic fibrodentinoma is proposed; (7) the calcifying ghost cell odontogenic tumor is included in the classification; (8) the simple and the WHO type of odontogenic fibroma are included in the classification; (9) the classification of malignant OT is adapted from Eversole (1999) with a few changes. In particular, ameloblastic carcinoma is differentiated from malignant ( metastasizing) ameloblastoma; (10) the term carcinoma in intraosseous (peripheral) ameloblastoma is introduced. Also, the malignant epithelial odontogenic ghost cell tumor is termed calcifying ghost cell odontogenic carcinoma; (11) the clear cell odontogenic tumor is termed clear cell odontogenic carcinoma; (12) the so-called pseudocysts are termed "cavities" (aneurysmal bone cavity, simple bone cavity, lingual and buccal mandibular bone cavity, focal marrow-containing jaw cavity).