Molecular characterization of metastasizing ameloblastoma: A comprehensive review.

Metastasizing ameloblastoma (MA) is a very rare odontogenic tumor with 2% of incidence rate. It exhibits benign histopathological features and malignant intrinsic quality in the form of metastasis which makes it a little more than a pathological curiosity. Various molecular aspects related with malignant behavior have been discussed. Because of this, it provides a diagnostic challenge for clinicians and surgeons. It is an elusive lesion which should be more researched and studied so that definitive diagnostic features can be put forward. The objective of this paper is to review the molecular aspect involved in the pathogenesis of MA which will aid in differentiating non-MA from MA and thus helping in providing proper treatment at an early stage.

Ameloblastoma: current etiopathological concepts and management.

Ameloblastoma is a benign odontogenic tumor of epithelial origin. It is locally aggressive with unlimited growth capacity and has a high potential for malignant transformation as well as metastasis. Ameloblastoma has no established preventive measures although majority of patients are between ages 30 and 60 years. Molecular and genetic factors that promote oncogenic transformation of odontogenic epithelium to ameloblastoma are strongly linked to dysregulation of multiple genes associated with mitogen-activated protein kinase, sonic hedgehog, and WNT/ß-catenin signaling pathways. Treatment of ameloblastoma is focused on surgical resection with a wide margin of normal tissue because of its high propensity for locoregional invasion; but this is often associated with significant patient morbidity. The relatively high recurrence rate of ameloblastoma is influenced by the type of molecular etiological factors, the management approach, and how early the patient presents for treatment. It is expected that further elucidation of molecular factors that orchestrate pathogenesis and recurrence of ameloblastoma will lead to new diagnostic markers and targeted drug therapies for ameloblastoma.

Ameloblastic fibroma in an alpine chamois (Rupicapra rupicapra).

Spontaneous odontogenic tumors are neoplasms characterized by a mixed odontogenic ectomesenchymal and odontogenic epithelial origin; they are rare in both humans and animals. A 3-year-old male Alpine Chamois (Rupicapra rupicapra) was found dead in north-west Italy, and was referred for the necropsy to the Department of Veterinary Sciences of the University of Turin (Italy). At the external examination a 10 × 8 cm, exophytic, red-pink, smooth, firm and ulcerated mass was observed on the inferior lip. Histologically the tumor was characterized by spindle shaped cells arranged in bundles in an abundant hyaline matrix. Multifocal and rare chords of odontogenic epithelium mixed with rare melanocytes that penetrate the neoplasia were visible. Immunohistochemistry showed a clear cytokeratin positivity of epithelial clusters. Macroscopical, histological and immunohistochemical findings were consistent with a diagnosis of locally infiltrative ameloblastic fibroma. To our best knowledge, this is the first report of this tumor in a wild ungulate and in Alpine Chamois.

Reporte de caso: ameloblastoma multiquistico folicular, variante acantomatoso en cuerpo mandibular / Case report:: follicular multicystic ameloblastoma, acanthomatous variationina mandibular body

El ameloblastoma corresponde a una neoplasia poco frecuente, odontogenica, benigna, de carácter local invasivo. Requiere un adecuado diagnóstico en base a la presentación clínica, localización, tamaño, edad y tipo histológico; ya que el tratamiento conlleva gran dificultad. La tasa de recidiva es alta. Se presenta el caso de una paciente femenina adulta, con diagnóstico de ameloblastoma folicular multiquistico acantomatoso localizado en cuerpo de mandíbula sometido a curetaje ante la negativa de resección segmentaria. En control de 6 meses no presentó recidiva.

Ameloblastoma is a rare neoplasia of odontogenic tissue, benign in nature and locally invasive. It requires an appropriate diagnosis based on the clinical presentation, location, size of the lesion, age and histological type, treatment is very difficult, and recurrence being is high. We present the case of an adult female patient, with a diagnosed follicular multicystic ameloblastoma, acanthomatous, located in the mandible body, which was treated with curettage due to refusal of local segmental resection. Six months later, no recurrence was present.

Ameloblastoma: a clinical and therapeutic analysis on six cases / Ameloblastoma: uma análise clínica e terapêutica de seis casos

Ameloblastomas are odontogenic tumors that are locally invasive and slow-growing. Their etiology is still not well defined, but the forms of treatment have been widely discussed because of the possibility of tumor recurrence and postoperative complications. In this study, six patients who were diagnosed with ameloblastoma in the mandibular region and were treated in the Department of Orthopedics and Traumatology of Hospital das Clínicas, Federal University of Goiás, between 1958 and 1963, were evaluated. The radiological, clinical and therapeutic characteristics were evaluated. There was no predominance regarding gender in the sample studied. The symptoms most often presented by the patients were pain and tumor formation. The radiological characteristics with greatest incidence were multilocular lesions and the treatment used for all the patients was radical surgery. There was no recurrence over the minimum follow-up period of one year and six months...

Os ameloblastomas são tumores odontogênicos, localmente invasivos e de crescimento lento. Sua etiologia ainda não foi bem definida e as formas de tratamento são amplamente discutidas, por causa de possíveis recidivas do tumor e complicações pós-operatórias. Neste trabalho, foram avaliados seis pacientes diagnosticados com ameloblastoma na região mandibular e tratados no Departamento de Ortopedia e Traumatologia do HC-UFG, de 1958 a 1963. Foram avaliadas as características radiológicas, clínicas e terapêuticas. Não houve predomínio em relação ao gênero na amostra estudada. Os sintomas mais apresentados pelos pacientes foram dor e tumoração. As características radiológicas de maior incidência são de uma lesão multilocular e o tratamento usado em todos os pacientes foi o cirúrgico radical. A recidiva foi nula em um tempo mínimo de um ano e sete meses de seguimento...

Molecular markers of cell adhesion in ameloblastomas. An update.

Ameloblastoma is the most common odontogenic tumor of epithelial origin, and though it is of a benign nature, it frequently infiltrates the bone, has a high rate of recurrence and could potentially become malignant. Cellular adhesion potentially plays an important role in the manifestation of these characteristics and in the tumor biology of ameloblastomas. Losses of cell-cell and extracellular matrix adhesion and cohesion are among the first events that occur in the invasion and growth of tumors of epithelial origin. The present review includes a description of the molecules that are involved in cell adhesion as reported for various types of ameloblastomas and discusses the possible roles of these molecules in the biological behaviors of this odontogenic tumor. Knowledge of the complex mechanisms in which these molecules play a role is critical for the research and discovery of future therapeutic targets.

Development and growth of adenomatoid odontogenic tumor related to formation and eruption of teeth.

The number of published cases of adenomatoid odontogenic tumor (AOT) has steadily increased, and about half were reported in Asian populations. Although the clinicopathologic profile of AOT has been extensively reported, factual knowledge of its pathogenesis is rudimentary at best, and there is controversy as to precisely which odontogenic epithelium it arises from. AOT is a successional tooth-associated lesion which develops during the mixed dentition. The permanent successor differs from its deciduous predecessor in that it has an eruptive pathway from the dental follicle to the gingiva, the gubernaculum dentis. With this background in mind, the present review focuses mainly on the early development of AOT. We successfully demonstrated a close spatial relationship between AOT and the gubernaculum dentis in a typical case. From further observations of the same AOT in which an enclosed permanent canine showed enamel hypoplasia, it is possible to pinpoint areas around the crown of a developing successional tooth in continuity with the gubernaculum dentis as starting points. In addition, we discuss the unifying histogenetic concept of three clinical variants, namely, pericoronal (follicular), extracoronal (extrafollicular), (see Article note) and peripheral.

Review article: Current concepts of ameloblastoma pathogenesis.

Ameloblastoma is a locally destructive and invasive tumour that can recur despite adequate surgical removal. Molecular studies have offered interesting findings regarding ameloblastoma pathogenesis. In the present review, the following topics are discussed regarding its molecular nature: clonality, cell cycle proliferation, apoptosis, tumour suppressor genes, ameloblastin and other enamel matrix proteins, osteoclastic mechanism and matrix metalloproteinases and other signalling molecules. It is clear from the literature reviewed that translational studies are necessary to identify prognostic markers of ameloblastoma behaviour and to establish new diagnostic tools to the differential diagnosis of unicystic from multicystic ameloblastoma. Finally, molecular biology studies are also important to develop more effective alternative approaches to the treatment of this aggressive odontogenic tumour.

An unsuspected ameloblastoma in the subpontic region of the mandible with consideration of pathogenesis from the radiographic course.

The purpose of this report is to document a case of unsuspected ameloblastoma involving the right man dibular subpontic region in a 38-year-old Cambodian female patient. This lesion was purportedly preceded by multiple radiolucencies which were diagnosed as radicular cysts and treated a few times in the past years by enucleation followed by endodontic therapy of the affected teeth. Bridgework restoration of the partially edentulous area was performed. This case report demonstrates radiographic changes that occurred in the periods before and after the diagnosis of ameloblastoma. The case may represent an example of radicular cysts and ameloblastoma occurring as a collision phenomenon, or the ameloblastoma may have arisen as a result of neoplastic transformation of the lining epithelium in an inflammatory odontogenic epithelial cyst.

[Reconstruction of the head and neck with free osteoseptocutaneous flap in elderly heavy smokers]. / Agir sigara içici yasli hastalarin bas-boyun rekonstrüksiyonunda serbest osteoseptokutan flep uygulamalari.

OBJECTIVES: We evaluated complications of free flap reconstruction following oncological head and neck surgery in elderly patients who smoked heavily. PATIENTS AND METHODS: The study included eight patients (2 females, 6 males; mean age 68.5 years; range 65 to 74 years) over 65 years of age, who smoked heavily (at least 1 pack/day). All cases but one with mandibular ameloblastoma had intraoral squamous cell carcinoma. Two patients underwent reconstruction with free radial forearm osteoseptocutaneous flap following bilateral maxillary resection, and six patients with free fibular osteoseptocutaneous flap following mandibular resection. Postoperative complications, in particular those associated with the donor and recipient sites were evaluated. RESULTS: No partial or total flap loss was observed. Wound healing problems were seen in three patients (37%), which were at the donor site in two patients, and at the recipient site in one patient. Psychogenic disorders were observed in two patients (25%). No other complications were encountered. CONCLUSION: Aside from some recipient- and donor-site-related healing problems, heavy smoking and advanced age cannot be regarded as contraindications for free flap reconstruction.

Ameloblastoma de partes moles: relato de caso e revisão de literatura

Introdução: O ameloblastoma extra-ósseo ou de partes moles é um tumor odontogênico, raro e benigno, idêntico ao ameloblastoma intra-ósseo, mas se desenvolve nos tecidos moles e exibe habitualmente um comportamento clínico brando. O ameloblastoma comumente é intra-ósseo e a maioria das recidivas ocorre no local do tumor primário. O índice de recidiva destes tumores varia de acordo com o tratamento aplicado, com uma taxa de 65% a 75% quando se procede à enucleação ou curetagem do tumor e 5% a 15% quando se realizam ressecções radicais, mas raramente envolvem tecidos moles adjacentes. Em alguns casos de recidiva óssea, o ameblatoma pode também envolver tecidos moles. O ameloblastoma extra-ósseo tende a crescer no tecido mole sem envolvimento ósseo histologicamente comprovado, são geralmente assintomáticos e de crescimento muito lento, têm usualmente uma forma regular, sólida e endurecida com a superfície lisa. Relato do caso: Trata-se de uma de 48 anos, sexo feminino, operada há 20 anos de um ameloblastoma intra-ósseo e que apresenta atualmente recidiva apenas em partes moles. A paciente apresentava uma tumoração submandibular e parafaríngea à esquerda associada a disfagia e dispnéia leve por estreitamento e deslocamento contralateral da coluna aérea da oro e hipofaringe. Feito estudo de imagem com tomografia computadorizada e biópsia que confirmaram o diagnóstico. A paciente foi submetida a tratamento cirúrgico para exérese da tumoração por acesso cervical...

Ameloblastoma associated with the nevoid basal cell carcinoma (Gorlin) syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by a wide range of clinical signs and symptoms. The major criteria for the diagnosis are multiple cutaneous basal cell carcinomas, multiple odontogenic keratocysts of the jaw, palmar and plantar pits, and skeletal abnormalities. Here, we report an unusual case of NBCCS in a 68-year-old woman with late onset of clinical signs and symptoms and with an associated ameloblastoma. Only 4 other cases of this unusual association have been reported.

Ameloblastoma o adamantinoma / Ameloblastoma or adamantinoma

Se relata el caso de un paciente de 26 años de edad, con deformidad facial, que presenta un tumor gingivoyugal posterior derecho con imágenes oteolíticas en los estudios radiológicos simples y en la resonancia magnética, con histopatología e inmunohistoquímica de ameloblastoma. La terapéutica fue quirúrgica con amplio margen. Motiva la presentación la escasa frecuencia de presentación de este tumor.

It is present a ameloblastoma case, tumour of rare case on a patient of 26 years old in who development the process on the maxilla. It is realized a revision of the neoplastic characteristic and it is comment the result of the surgical treatment realized at the patient.

Hamartomatous proliferations of odontogenic epithelium within the jaws: a potential histogenetic source of intraosseous epithelial odontogenic tumors.

BACKGROUND: The jawbone is replete with a vestige of odontogenesis. The overall consensus is that intraosseous remnants of the enamel organ and dental lamina are the only histogenetic option for central epithelial odontogenic tumors. Curiously, incipient tumors or possible precursor conditions of residual odontogenic epithelium have rarely been reported in the literature. METHODS: We microscopically evaluated 39,660 biopsy samples to determine the presence of a tumor-like odontogenic epithelial nodule in the maxilla and mandible. RESULTS: Seven intraosseous specimens that associated with a focal proliferation of odontogenic epithelium were retrieved. Six hamartomatous processes showed four different morphologic patterns comparable with the tumor nests comprising ameloblastoma (n = 1), squamous odontogenic tumor (n=1), calcifying epithelial odontogenic tumor (n=2) and calcifying cystic odontogenic tumor (n=2). Among six lesions, four were the intrafollicular development. The remaining case of interest was multiple hyperplastic clear rests of Malassez in association with an impacted tooth. CONCLUSION: Although it is impossible to predict the fate of these microscopic structures of hamartomatous character, the present case series indicates that any of the dormant embryonic residues of odontogenic epithelium can return to an active state, capable of non-reactive, probably neoplastic proliferation of pathological significance.

Caries dental y ecología bucal, aspectos importantes a considerar / Dental caries and oral ecology, important aspects to be considered: Bibliographic review

La caries dental constituye actualmente la enfermedad más frecuente en el ser humano. Existen algunos elementos de la ecología bucal que pueden favorecer su desarrollo. Se realiza una revisión bibliográfica con el objetivo fundamental de profundizar en los conocimientos teóricos sobre las características del tejido adamantino, aspectos específicos del Streptococcus mutans, papel de la saliva en el medio bucal e influencia de la ingesta de carbohidratos que pueden predisponer a la aparición de caries dental. Se concluye que se debe aumentar la resistencia del esmalte e impedir la adhesión inicial del Streptococcus mutans para prevenir esta enfermedad; la saliva debe ser considerada como un sistema y debemos fomentar la educación nutricional e higiénica de la familia(AU)

Dental caries are nowadays the most frequent disease among human beigns. There are some elements of oral ecology that may favor their development. A bibliographic review is made aimed at going deep into the theoretical knowledge of the characteristics of the adamantine tissue, the specific aspects of Streptococcus mutans, the role of saliva in the oral environment, and the influence of the ingestion of carbohydrates that may predispose the appareance of dental caries. It is concluded that the enamel resistance should be increased and that the initial adhesion of Streptococcus mutans should be impeded to prevent this disease. Saliva should be considered as a system and we should promote the family nutritional and hygiene education(AU)

Does HPV play a role in the etiopathogenesis of ameloblastoma? An immunohistochemical, in situ hybridization and polymerase chain reaction study of 18 cases using laser capture microdissection.

Ameloblastomas are epithelial tumors of odontogenic origin, biologically characterized by local recurrence. Among different etiologic factors, HPV infection has been recently postulated to be somehow involved in ameloblastoma etiopathogenesis. To address this issue, we studied 18 ameloblastomas by means of immunohistochemistry, in situ hybridization (conventional and amplified), polymerase chain reaction and nested-polymerase chain reaction analyses using laser capture microdissection in order to detect the occurrence of HPV in this setting. No evidence of HPV infection was detected by morphological examination, immunohistochemistry, in situ hybridization and conventional polymerase chain reaction, while nested-polymerase chain reaction showed a weak positive band in two cases. However, the subsequent restriction enzyme analysis carried out from the nested-polymerase chain reaction amplification products of these two samples excluded the presence of HPV subtypes 16, 18, 31, 33, 35, 52, and 58. The search for HPV 6 and 11 in the same specimens was also negative. In conclusion, our data do not support an etiopathogenetic evidence for HPV in ameloblastoma.

[Expression of telomerase and p53 in ameloblastoma].

OBJECTIVE: To detect the expression of p53 protein, hTR, and hTERT mRNA in ameloblastoma (AB) and to investigate the clinical biological characteristics of AB. METHODS: We detected hTR and hTERT Mrna in 54 cases of AB by in situ hybridization, and p53 protein by S-P method. RESULTS: The positive ratio of hTR, hTERT mRNA was 2/7 and 1/7 in normal oral mucosa, 81.2%(13/16) and 87.4% (14/16) in odontogenic keratocyst (OKC), 94.4%(51/54) in AB, respectively. There was a significant difference in these three groups (P < 0.001). A strong correlation between hTR and hTERT mRNA was found (rs = 1.000, P < 0.001). p53 protein was expressed in 87.5% (42/49) AB, 44%(11/25) OKC, 33.3%(1/3) normal oral mucosa, respectively. A strong correlation between hTERT mRNA and p53 protein was found (rs = 0.848, P < 0.001). A moderate correlation between hTR mRNA and p53 protein was found (rs = 0.536, P < 0.001). CONCLUSION: The positive ratios of hTR and hTERT were higher than p53 protein in AB. Telomerase activity and p53 expression play an important role in genesis and development of AB.

Aspecto clinicopatológico e inmunohistoquímico en tres casos de ameloblastoma / Clinico-pathologic and immunohistochemical aspects in three ameloblastoma cases

El ameloblastoma es una de las neoplasias odontogénicas más comunes que se presentan en el maxilar inferior con mayor frecuencia, sector posterior, con localización intraósea y periférica (esta última, más rara). Los subtipos histológicos no influencian directamente en el tratamiento ni en el pronóstico porque generalmente se utilizan actos quirúrgicos radicales por la frecuencia de recidiva de los ameloblastomas. Se utilizó en biopsias las técnicas inmunohistoquímicas básicas y Mib-1 (Ki 67 en parafina) para determinar el índice de proliferación celular que indicaría la posible transformación maligna del ameloblastoma o su capacidad de recidiva. En un germen dentario, en estadio de campana, el órgano del esmalte mostró idéntica afinidad inmunohistoquímica con un índice de proliferación celular Mib 1 (Ki 67) de un 1 por ciento (AU)

Genomic organization and localization of mouse Nma/BAMBI: possible implications related to ameloblastoma formation.

Our laboratory has determined the DNA sequence and transcriptional expression pattern of a mouse cDNA clone termed Nma/BAMBI. This clone encodes a highly conserved protein with 89% identity to the human homologue (termed Nma) and 78% similarity to the Xenopus homologue (termed BAMBI) at the predicted amino acid level. Nma/BAMBI encodes a 260-amino-acid transmembrane protein that has homology to the transforming growth factor (TGF) beta type I receptor family. This protein contains an extracellular ligand binding domain, a 24-amino-acid transmembrane domain, and a short intracellular domain that lacks a functional serine/threonine kinase domain. It is believed that Nma/BAMBI is important in the negative regulation of TGF beta signal transduction pathways during development and has implications in tumor progression. We have determined the genomic organization of the mouse Nma/BAMBI gene and confirmed the chromosomal mapping to human chromosome 10 and mouse chromosome 2. Furthermore, we report the production and utilization of an anti-peptide antibody in preliminary immunohistochemical analysis of an ameloblastoma.