Epidemiological Features of 4777 Cysts and Odontogenic Tumors Based on the 2022 WHO Classification.

OBJECTIVE: The epidemiology of cysts and odontogenic tumors is important for differential diagnosis and treatment strategies. We aimed to describe the epidemiological features of cysts and odontogenic tumors in the Chilean population using the current WHO classification. MATERIALS AND METHODS: We reviewed 22,914 biopsy requests received between January 1984 and September 2023 at the oral pathology department, School of Dentistry, Universidad Mayor, Santiago, Chile. Patients diagnosed with cysts of the jaws and odontogenic tumors were selected and information regarding age, sex, and location was recorded. RESULTS: 4226 (18.4%) were cysts, and 551 (2.4%) were odontogenic tumors, ranging from 2 to 97 years old. Males represented 54.4% and females 45.7% of the total sample. The most prevalent cysts were radicular cysts (58.6%), dentigerous cysts (17.9%), and odontogenic keratocysts (13.3%). The most prevalent odontogenic tumors were odontomas (40.1%) and conventional ameloblastoma (17.6%). CONCLUSIONS: Our study was the first retrospective analysis to determine the epidemiological features of both cysts and odontogenic tumors together, based on the 2022 WHO classification. This is relevant as it offers a potential basis for comprehensive comparisons of the epidemiological features of these entities, which could contribute to an accurate differential diagnosis, therefore, leading to more effective therapeutic interventions.

Tomographic Evaluation of the Odontogenic Maxillary Myxoma. Case Report and Literature Review / Evaluación tomográfica del mixoma odontogénico en maxilar superior. Reporte de caso y revisión de la literatura

Odontogenic myxoma (OM) is a slow-growing, painless, aggressive and non-metastatic central jaw tumor of mesenchymal origin. Radiographically, it can vary from a unilocular radiolucent lesion to a multilocular lesion with well-defined or diffuse margins. The aim of this paper is to recognize the radiographic and tomographic characteristics of OM in a patient who attended the Dental Clinic of the Faculty of Dentistry of the Universidad Nacional Mayor de San Marcos in Lima-Peru. Case presentation: 86 year old male patient, who in the panoramic radiography indicated for his oral rehabilitation, a unilocular radiolucent image was found in the anterosuperior area with partially defined limits, corticalized edges and oval shape. In the volumetric tomography there was evidence of thinning and erosion of both bone tables, thinning of the floor of the nasal cavity. The radiolucent image seems to havean extension close to the alveolar ridge.In adition, there was an effacement of the cortices of the nasopalatine duct. The lesion was enucleated and an anatomopathological examination was performed. Diagnosis was odontogenic myxoma. The patient was evaluated at one year and six months with satisfactory results. The wide variety of radiographic characteristics of odontogenic myxoma leads us to think of a large number of differential diagnoses, being the histological evaluation together with the imaging analysis the ones that provide a definitive diagnosis. Although the anterosuperior area is the least common for its presentation, radiolucent images in this area should be considered as possible odontogenic myxomas, since this condition is more frequent in latín race.

El mixoma odontogénico (MO) es un tumor mandibular central de origen mesenquimal, de crecimiento lento, indoloro, agresivo y no metastásico. Radiográficamente, puede variar desde una lesión unilocular radiolúcida a una lesión multilocular con márgenes bien definidos o difusos. El objetivo de este trabajo es reconocer las características radiográficas y tomográficas del MO en un paciente que acudió a la Clínica Odontológica de la Facultad de Odontología de la Universidad Nacional Mayor de San Marcos en Lima-Perú. Presentación del caso: Paciente masculino de 86 años, en la radiografía panorámica indicada para rehabilitación oral, se encontró una imagen radiolúcida unilocular en la zona anterosuperior con límites parcialmente definidos, bordes corticalizados y forma ovalada. En la tomografía volumétrica se evidenció adelgazamiento y erosión de ambas tablas óseas, adelgazamiento del piso de la cavidad nasal, la imagen radiolúcida parece tener una extensión cercana a la cresta alveolar. Además, había un adelzamiento de las corticales del conducto nasopalatino. La lesión fue enucleada y se realizó un examen anatomopatológico. El diagnóstico fue mixoma odontogénico. La paciente fue evaluada al año y a los seis meses con resultados satisfactorios. La gran variedad de características radiográficas del mixoma odontogénico nos lleva a pensar en un gran número de diagnósticos diferenciales, siendo la evaluación histológica junto con el análisis de imagen los que proporcionan un diagnóstico definitivo. Aunque el área anterosuperior es la menos común para su presentación, las imágenes radiolúcidas en esta área deben ser consideradas como posibles mixomas odontogénicos, ya que esta condición es más frecuente en la raza latina.

Queratoquiste: Expresión clínica mandibular atípica en un caso clínico

El queratoquiste odontogénico constituye del 3 a 11% de los quistes odontogénicos. Se presenta desde la infancia hasta la vejez con mayor incidencia en hombres. La mandíbula está involucrada en el 60% al 80% de los casos, con una frecuencia en cuerpo y rama. Las lesiones de menor tamaño suelen ser asintomáticos, diagnosticados por examen radiográfico, no obstante, las lesiones más grandes pueden estar asociadas con dolor y aumento de volumen. Radiográficamente se observan lesiones uniloculares o multiloculares radiolúcidas de bordes nítidos, corticalizados, asociado a un diente retenido. Se presenta caso clínico de paciente género masculino de 30 años de edad, que exhibe una expresión atípica. Manifestándose como una doble lesión de queratoquistes odontogénicos independientes entre sí, localizados en rama y cuerpo mandibular derecha, tratado en el Servicio de Cirugía Maxilofacial del Hospital San José, Santiago de Chile. Se describe diagnóstico y tratamiento quirúrgico realizado. El interés clínico del caso es la presencia de dos lesiones independientes entre sí, con el mismo diagnóstico. Presentación que nos parece fundamental reportar en la literatura científica debido a su alto alcance e impacto.

The odontogenic keratocyst represents 3 to 11% of all odontogenic cysts. It occurs from childhood to old age with a higher incidence in men. The mandible is involved in 60% to 80% of cases, with a frequency in the body and ramus. Smaller lesions are usually asymptomatic and diagnosed by radiographic examination. However, larger lesions may be associated with pain and increased volume. Radiographically, radiolucent unilocular or multilocular lesions with sharp, corticalized edges are observed, associated with an impacted tooth. A clinical case of a 30-year-old male patient, who exhibits an atypical expression, is presented. A double lesion of odontogenic keratocysts independent of each other appears, located in the right mandibular ramus and body, treated in the Maxillofacial Surgery Service of the San José Hospital, Santiago de Chile. Diagnosis and surgical treatment performed are described. The clinical interest of the case is the presence of two lesions independent of each other, with the same diagnosis. It seems fundamental to us to report it in the scientific literature due to its high scope and impact.

Podoplanin immunoexpression in odontogenic lesions: a systematic review, meta-analysis, and integrated bioinformatic analysis.

BACKGROUND: Podoplanin (PDPN) is a transmembrane glycoprotein implicated in the pathogenesis of odontogenic lesions (OL). It is localized at the membrane and cytoplasmic level, and its interaction with other proteins could trigger cell proliferation, invasion and migration. The main objective of this systematic review is to explore the immunoexpression pattern of podoplanin in OL. In addition, as secondary objectives, we aimed to compare the immunostaining intensity of PDPN in OL, to analyze its interaction networks by bioinformatic analysis and to highlight its importance as a potential diagnostic marker useful in the pathogenesis of OL. METHODS: The protocol was developed following PRISMA and Cochrane guidelines. The digital search was performed in the databases: PubMed/MEDLINE, ScienceDirect, Scopus, Web of Science and Google Schoolar from August 15, 2010 to June 15, 2023. We included cross-sectional and cohort studies that will analyze the pattern of PDPN immunoexpression in OL. Two investigators independently searched for eligible articles, selected titles and abstracts, analyzed full text, conducted data collection, and performed assessment of study quality and risk of bias. In addition, part of the results were summarized through a random-effects meta-analysis. STRING database was used for protein-protein interaction analysis. RESULTS: Twenty-nine relevant studies were included. The ages of the subjects ranged from 2 to 89 years, with a mean age of 33.41 years. Twenty-two point two percent were female, 21.4% were male, and in 56.4% the gender of the participants was not specified. A total of 1,337 OL samples were analyzed for PDPN immunoexpression pattern. Ninety-four (7.03%) were dental follicles and germs, 715 (53.47%) were odontogenic cysts, and 528 (39.49%) were odontogenic tumors. Meta-analysis indicated that the immunostaining intensity was significantly stronger in odontogenic keratocysts compared to dentigerous cysts (SMD=3.3(CI=1.85-4.82, p=0.000*). Furthermore, bioinformatic analysis revealed that PECAM-1, TNFRF10B, MSN, EZR and RDX interact directly with PDPN and their expression in OL was demonstrated. CONCLUSIONS: The results of the present systematic review support the unique immunoexpression of PDPN as a potential useful diagnostic marker in the pathogenesis of OL.

Primordial Odontogenic Tumor: A Review of the Literature and Report of Three New Patients.

The primordial odontogenic tumor (POT) is a rare mixed odontogenic tumor composed of mesenchymal cells, columnar odontogenic epithelium, and fibromyxoid stroma affecting the posterior mandible of children and adolescents. Herein, we report 3 patients with POT and the clinicopathological features of POT previously reported in the literature. A 12-year-old, 19-year-old, and 4-year-old patient presented an asymptomatic swelling in the posterior maxilla and posterior mandible. Imaging exams revealed radiolucent lesions associated with unerupted teeth. The lesions were surgically removed, and the histopathological examination revealed spindle-to-ovoid mesenchymal cells in a fibromyxoid stroma surfaced by columnar odontogenic epithelial cells with reverse nuclear polarization. Deposition of mineralized tissue was observed. The final diagnosis was POT, and patients did not exhibit signs of recurrence. POT should be included in the differential diagnoses of intraosseous lesions in the posterior mandible in pediatric patients.

Unravelling the mystery of the central dentinogenic ghost cell tumor- a rare case report and recurrent insights.

Dentinogenic ghost cell tumor (DGCT) is a rare benign neoplasm form of calcifying odontogenic cyst (COC) characterized by ghost cells. Although benign, it presents an aggressive behavior. DGCT accounts for 2% to 14% of all COCs and less than 0.5% of all odontogenic tumors. It is a benign odontogenic tumor despite its local invasion and the likelihood of recurrence. To detect recurrence, central DGCT patients must be monitored long-term. We present the case of a 51-year-old male who reported pain in the right upper back tooth region. On examination, a soft to firm, bright red swelling was present in the buccal vestibule and gingival margin of the maxillary right first and second molar, which extended up to the palate. Histopathological analysis confirmed the diagnosis of a DGCT, which occurred in a previously treated calcifying odontogenic cyst. The case is reported here, along with a review of the literature update of such recurred instances in the past.

Clinicopathologic and imaging features of odontogenic myxomas: a multi-institutional study.

PURPOSE: This study aims to report clinicopathologic and imaging features of odontogenic myxomas (OM), highlighting uncommon findings. METHODS: Clinicopathologic and imaging data of OMs diagnosed in the five Brazilian diagnostic pathology centers were collected and analyzed. RESULTS: The series comprised 42 females (68.9%) and 19 males (31.1%), with a 2.2:1 female-to-male ratio and a mean age of 34.5±15.4 years (range: 4-80). Clinically, most OMs presented as painless intraoral swelling (n = 36; 70.6%) in the mandible (n=37; 59.7%). Multilocular lesions (n=30; 83.3%) were more common than unilocular lesions (n=6; 16.7%). There was no statistically significant difference between the average size of unilocular and multilocular OMs (p=0.2431). The borders of OMs were mainly well-defined (n=24; 66.7%) with different degrees of cortication. Only seven tumors caused tooth resorption (15.9%), while 24 (54.5%) caused tooth displacement. Cortical bone perforation was observed in 12 (38.7%) cases. Morphologically, OMs were characterized mainly by stellate or spindle-shaped cells in a myxoid background (n=53; 85.5%). Surgical resection was the most common treatment modality (n=15; 65.2%), followed by conservative surgery (n=8; 34.8%). Outcomes were available in 20 cases (32.3%). Seven of these patients had local recurrence (35%). Enucleation was the treatment with the highest recurrence rate (4/7; 57.1%). CONCLUSIONS: OM has a predilection for the posterior region of the jaws of female adults. Despite their bland morphological appearance, they displayed diverse imaging features. Clinicians must include the OM in the differential diagnosis of osteolytic lesions of the jaws. A long follow-up is needed to monitor possible recurrences.

CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions.

BACKGROUND: Odontogenic lesions constitute a heterogeneous group of lesions. CLIC4 protein regulates different cellular processes, including epithelial-mesenchymal transition and fibroblast-myofibroblast transdifferentiation. This study analyzed CLIC4, E-cadherin, Vimentin, and α-SMA immunoexpression in epithelial odontogenic lesions that exhibit different biological behavior. METHODS: It analyzed the immunoexpression of CLIC4, E-cadherin, and Vimentin in the epithelial cells, as well as CLIC4 and α-SMA in the mesenchymal cells, of ameloblastoma (AM) (n = 16), odontogenic keratocyst (OKC) (n = 20), and adenomatoid odontogenic tumor (AOT) (n = 8). Immunoexpressions were categorized as score 0 (0% positive cells), 1 (< 25%), 2 (≥ 25% - < 50%), 3 (≥ 50% - < 75%), or 4 (≥ 75%). RESULTS: Cytoplasmic CLIC4 immunoexpression was higher in AM and AOT (p < 0.001) epithelial cells. Nuclear-cytoplasmic CLIC4 was higher in OKC's epithelial lining (p < 0.001). Membrane (p = 0.012) and membrane-cytoplasmic (p < 0.001) E-cadherin immunoexpression were higher in OKC, while cytoplasmic E-cadherin expression was higher in AM and AOT (p < 0.001). Vimentin immunoexpression was higher in AM and AOT (p < 0.001). Stromal CLIC4 was higher in AM and OKC (p = 0.008). Similarly, α-SMA immunoexpression was higher in AM and OKC (p = 0.037). Correlations in these proteins' immunoexpression were observed in AM and OKC (p < 0.05). CONCLUSIONS: CLIC4 seems to regulate the epithelial-mesenchymal transition, modifying E-cadherin and Vimentin expression. In mesenchymal cells, CLIC4 may play a role in fibroblast-myofibroblast transdifferentiation. CLIC4 may be associated with epithelial odontogenic lesions with aggressive biological behavior.

Tumor odontogénico epitelial calcificante en la rama mandibular. Informe de un caso clínico basado en una actualización bibliográfica / Calcifying epithelial odontogenic tumor in the mandibular ramus. A case report based on a literature update

Objetivo: Presentar un caso clínico de un tumor odon- togénico epitelial calcificante (TOEC), así como una revisión de la literatura disponible sobre esta neoplasia para contribuir al análisis del mejor método de tratamiento de la patología. Caso clínico: Se presenta el caso de una paciente mujer de 35 años con un tumor odontogénico epitelial calcifican- te que recibió tratamiento de enucleación quirúrgica con una evolución favorable y seguimiento de 5 años por medio de evaluación clínica y radiológica. La elección terapéutica se basó en el resultado de un análisis exhaustivo de la literatura para determinar el mejor abordaje de la neoplasia (AU)

Aim: To present a clinical case of a calcifying epithelial odontogenic tumor (CEOT), as well as a review of the availa- ble literature on this neoplasia to contribute to the analysis of the best treatment method for the pathology. Clinical case: The case of a 35-year-old patient with a calcifying epithelial odontogenic tumor who received surgical enucleation treatment with a favorable evolution and 5-year follow-up through clinical and radiological evaluation is pre- sented. The therapeutic choice was based on the result of an exhaustive analysis of the literature to determine the best ap- proach to the neoplasia (AU))

Fibroma ameloblástico mandibular: caso clínico / Fibroblastic fibroma mandibular: a clinical case

El fibroma ameloblástico (FA) se describe como una neoplasia benigna de origen odontogénico mixto que suele presentarse entre la primera y segunda década de vida, frecuentemente en los molares permanentes inferiores. Por lo general es asintomático, pero las lesiones de gran tamaño suelen acompañarse con dolor e inflamación. Su tratamiento por lo regular es conservador. Se describe el caso de un fibroma ameloblástico en un paciente de 13 años de edad, que involucraba cuerpo y ángulo mandibular izquierdo, tratado de manera conservadora, se realiza extirpación del tumor, regeneración ósea guiada y rehabilitación con implante dental (AU)

Ameloblastic fibroma (AF) is described as a benign neoplasm of mixed odontogenic origin that usually presents between the first and second decade of life, frequently in lower permanent molars. It is usually asymptomatic, but large lesions are usually accompanied by pain and inflammation. His treatment is generally conservative. The clinical case of an ameloblastic fibroma in a 13-year-old patient is described, involving the left mandibular body and angle, treated conservatively, tumor removal, guided bone regeneration and rehabilitation with dental implants are performed (AU)

Does YAP influence cell proliferation and apoptosis in benign epithelial odontogenic lesions?

OBJECTIVE: To analyze the immunohistochemical expression of YAP and its correlation with markers involved in cell proliferation and apoptosis in benign epithelial odontogenic lesions. STUDY DESIGN: The sample consisted of 95 cases of odontogenic lesions (25 dentigerous cysts, 30 non-syndromic odontogenic keratocysts, 30 conventional ameloblastomas, and 10 unicystic ameloblastomas) and 10 dental follicles used as normal odontogenic tissue. The histological sections were submitted to immunohistochemistry with YAP, cyclin D1, Ki-67, and Bcl-2 antibodies. Immunoexpression was analyzed qualitatively and quantitatively using an adapted method. The collected data were analyzed descriptively and statistically (p ≤ 0.05). RESULTS: The highest YAP expression was observed in odontogenic keratocysts, followed by unicystic ameloblastomas and conventional ameloblastomas, which exhibited moderate immunoreactivity predominantly in peripheral cells. Furthermore, significant differences in YAP immunoexpression were observed between the groups analyzed, with significant positive correlations between YAP and cyclin D1 in dentigerous cysts and unicystic ameloblastomas and between YAP and Ki-67 in unicystic ameloblastomas (p < 0.05). However, there were no statistically significant correlations between YAP and Bcl-2 immunoexpression in the groups studied. CONCLUSION: YAP may influence epithelial cell proliferation in odontogenic cysts and tumors, suggesting its possible participation in the progression of the odontogenic lesions studied.

Epidemiological and Clinicopathological Analysis of Odontogenic Tumors: A 20-Year Study

ABSTRACT Objective: To perform the epidemiological and clinicopathological analyses of odontogenic tumors in Kerman for 20 years. Material and Methods: The present study investigated collected records from pathology departments of the Faculty of Dentistry, Bahonar, and Shafa teaching-medical hospitals for 20 years. Data on odontogenic tumors was recorded based on age, sex, and tumor location in the information forms. The statistical t-test and the Kappa coefficient computer codes were utilized for data analysis. Results: 38 samples of odontogenic tumors were considered in the present study. The mean age of participants was 31.7± 10.3 years. The frequency of tumors was higher in women (63.2%) and in the lower jaw) 78.9%). Among various tumors, ameloblastoma (63.1%) and odontoma (18.4%) were the most common tumors, respectively. The correlation between clinical and histopathologic diagnoses was 71.8% using the kappa coefficient. Conclusion: Ameloblastoma is the most common odontogenic tumor. The incidence of lesions was higher in the mandible, and odontogenic tumors were higher in women. Since the diagnosis of odontogenic tumors is based on radiographic and histologic appearances, clinical physicians and pathologists should collaborate for the definitive diagnosis of the disease.

Prevalence of BRAF p.V600E and Detection Methods in Benign Mixed and Malignant Odontogenic Tumors: A Systematic Review.

BACKGROUND: The BRAF p.V600E genetic variant facilitates the pathogenesis of various tumors by triggering tumor proliferation and progression. The aim of this study was to analyze the prevalence of BRAF p.V600E in benign mixed epithelial and mesenchymal and malignant odontogenic tumors. In addition, we discussed the different detection methods used to assess for aberrant BRAF. METHODS: This systematic review followed the PRISMA guidelines and was registered in Prospero (CRD42023445689). A comprehensive search of the PubMed/MEDLINE, Scopus, Web of Science, and Embase electronic databases was performed to answer the question "What is the prevalence of the BRAF p.V600E mutation in benign mixed and malignant odontogenic tumors?" The methodological quality of the selected studies was assessed using the JBI's Critical Appraisal Tool. RESULTS: Initially, 387 records were identified, but only 11 articles met the inclusion criteria. A total of 70 patients with benign mixed epithelial and mesenchymal odontogenic tumors and 63 with malignant odontogenic tumors were included in the analysis. We found that the BRAF p.V600E mutation had a prevalence of 31.42% in mixed tumors and 26.98% in malignant odontogenic tumors. Moreover, immunohistochemistry showed high concordance with DNA-based molecular methods. CONCLUSION: In general, the BRAF p.V600E variant exhibited a prominent prevalence in mixed and malignant odontogenic tumors. However, most of the findings are based on small cohorts of patients and further studies with larger cohorts are needed.

Fibro-odontoma Ameloblástico: Revisión de la Literatura a Propósito de un Caso

El fibro-odontoma ameloblástico (FOA) es una neoplasia odontogénica benigna poco frecuente que afecta a los huesos maxilares. Posee un componente de tejido epitelial y ectomesénquima, por lo que hasta hace un tiempo era incluido dentro de la clasificación de tumores odontogénicos de origen mixto. Actualmente estas lesiones no están incorporadas en la última clasificación de los tumores odontogénicos y huesos maxilofaciales de la organización mundial de la salud y son consideradas como un odontoma en desarrollo. Clínicamente se presenta con mayor frecuencia en mandíbula y asociado a la falta de erupción de un diente. Presentamos el caso clínico de un niño de 6 años de edad que acudió a nuestro servicio maxilofacial por la no erupción de un diente temporal mandibular. El cuadro clínico y las investigaciones confirmaron la hipótesis diagnóstica de FOA con una impactación del segundo molar temporal inferior izquierdo hacia el margen basilar mandibular y el germen dentario del premolar por sobre la corona del diente retenido.

Ameloblastic fibro-odontoma (AFO) is a rare benign odontogenic neoplasm that affects the maxillary bones. It possesses both an epithelial and ectomesenchymal component, for which it was previously included in the classification of mixed odontogenic tumors. The AFO is currently not included in the latest classification of odontogenic and maxillofacial bone tumors, and is considered a developing odontoma. Clinically, it predominantly manifests in the mandible, in frequent association with the lack of eruption of a tooth. In this article, the authors present a case of a 6 year old boy with the query of an unerupted primary mandibular tooth. Both the clinical examination and the subsequent investigation confirmed the diagnostic hypothesis of an AFO with subsequent impaction of the primary left mandibular second molar, which was displaced against the base of the mandible, and the tooth germ for the left mandibular second premolar positionedover the crown of the retained tooth.

Squamous Odontogenic Tumor in the Posterior Region of Maxilla.

Squamous odontogenic tumor (SOT) is a rare benign but locally infiltrative tumor often misdiagnosed as other entities, such as ameloblastoma and squamous cell carcinoma, due to overlapping morphological findings. We document here the clinicopathological and imaging findings of an aggressive intraosseous SOT in the posterior left region of the maxilla in a 25-year-old male patient. On intraoral examination, the tumor extended from the region of the left lateral incisor to the upper left premolar and was covered by reddish mucosa, with discrete areas of ulceration. Imaging exams revealed an osteolytic lesion causing thinning, erosion, and buccal and lingual cortical plate perforation associated with an impacted canine. Microscopically, the tumor showed a proliferation of islands of well-differentiated squamous epithelium in a variably collagenized background. The peripheral cells of the islands were flat or slightly cuboidal and did not exhibit nuclei with peripheral palisade and reverse polarization. The diagnosis of SOT was rendered. The patient underwent surgical resection and has been under clinical follow-up for approximately 12 months with no signs of recurrence. A careful morphological evaluation is essential to avoid misdiagnosis and ensure a satisfactory treatment approach.

Deep learning applied to the histopathological diagnosis of ameloblastomas and ameloblastic carcinomas.

BACKGROUND: Odontogenic tumors (OT) are composed of heterogeneous lesions, which can be benign or malignant, with different behavior and histology. Within this classification, ameloblastoma and ameloblastic carcinoma (AC) represent a diagnostic challenge in daily histopathological practice due to their similar characteristics and the limitations that incisional biopsies represent. From these premises, we wanted to test the usefulness of models based on artificial intelligence (AI) in the field of oral and maxillofacial pathology for differential diagnosis. The main advantages of integrating Machine Learning (ML) with microscopic and radiographic imaging is the ability to significantly reduce intra-and inter observer variability and improve diagnostic objectivity and reproducibility. METHODS: Thirty Digitized slides were collected from different diagnostic centers of oral pathology in Brazil. After performing manual annotation in the region of interest, the images were segmented and fragmented into small patches. In the supervised learning methodology for image classification, three models (ResNet50, DenseNet, and VGG16) were focus of investigation to provide the probability of an image being classified as class0 (i.e., ameloblastoma) or class1 (i.e., Ameloblastic carcinoma). RESULTS: The training and validation metrics did not show convergence, characterizing overfitting. However, the test results were satisfactory, with an average for ResNet50 of 0.75, 0.71, 0.84, 0.65, and 0.77 for accuracy, precision, sensitivity, specificity, and F1-score, respectively. CONCLUSIONS: The models demonstrated a strong potential of learning, but lack of generalization ability. The models learn fast, reaching a training accuracy of 98%. The evaluation process showed instability in validation; however, acceptable performance in the testing process, which may be due to the small data set. This first investigation opens an opportunity for expanding collaboration to incorporate more complementary data; as well as, developing and evaluating new alternative models.

Conservative treatment of ameloblastoma: report of 2 cases and review of the literature / Tratamiento conservador de ameloblastoma: reporte de 2 casos y revisión de la literatura

Introduction: ameloblastomas correspond to one of the most prevalent odontogenic tumors in developing countries, they are mainly located in the mandible, and their treatment has been widely discussed over the years, using radical or conservative treatments depending on different variables. Clinical case: we present two cases of patients with ameloblastoma who underwent conservative treatment without the use of adjuvant therapy, obtaining satisfactory results at 36 and 48 months. Discussion: due to a possible recurrence with conservative treatment, radical management has been suggested, however, the choice of treatment should be based on a series of clinical, histological, and radiographic characteristics.

Introducción: Los ameloblastomas corresponden a uno de los tumores odontogénicos más prevalentes en los países en desarrollo, se ubican principalmente en la mandíbula, y su tratamiento ha sido ampliamente discutido a lo largo de los años, utilizando tratamientos radicales o conservadores dependiendo de distintas variables. Caso clínico: se presentan dos casos de pacientes con un ameloblastoma a quienes se les realizó tratamiento conservador sin uso de terapia coadyuvante, obteniendo resultados satisfactorios a los 36 y 48 meses. Discusión: Debido a una posible recurrencia con un tratamiento conservador, se ha sugerido manejo radical, sin embargo, la elección de tratamiento debe ser en base a una serie de características clínicas, histológicas y radiográficas.

Imunoexpressão de clic4, α-sma, e-caderina e vimentina em lesões odontogênicas epitelias benígnas / Immunoexpression of clic4, α-sma, e-cadherin and vimentin in benign epithelial odontogenic lesions

As lesões odontogênicas epiteliais benignas constituem um grupo heterogêneo de lesões. A proteína CLIC4 atua na regulação dos processos de parada de crescimento e apoptose, participando também do processo de transdiferenciação dos fibroblastos em miofibroblastos que passam a expressar α-SMA. Além disso, a expressão de CLIC4 pode interferir no processo de transição epitélio-mesenquima (TEM) em neoplasias. Este trabalho avaliou a imunoexpressão de CLIC4, α-SMA, E-caderina e Vimentina em ameloblastomas (AM) (n = 16), ceratocistos odontogênicos (n = 20) e tumores odontogênicos adenomatóides (TOA) (n = 8). A análise da expressão imunoistoquímica das proteínas CLIC4, E-caderina e vimentina no componente epitelial das lesões e de CLIC4 e α-SMA no tecido conjuntivo foi realizada de forma semi-quantitativa por um avaliador previamente calibrado. A expressão no componente epitelial de CLIC4 foi analisada separadamente no núcleo e no citoplasma, bem como a marcação de E-caderina que foi avaliada na membrana e no citoplasma. As comparações dos percentuais de imunorreatividade em relação aos grupos estudados foram realizadas por meio dos testes não paramétricos de Kruskal-Wallis e Mann-Whitney. Possíveis correlações entre a expressão de CLIC4, α-SMA, E-caderina e Vimentina foram avaliadas por meio do teste de correlação de Spearman. O nível de significância foi estabelecido em 5% (p < 0,05). Foram observados diferentes padrões de marcação entre os grupos analisados, observando-se que a imunoexpressão exclusivamente citoplasmática da CLIC4 no componente epitelial dos AM (p < 0,001) e TOA (p < 0,001) foi significativamente superior a dos CO, não demonstrarando significância estatística entre os AM e TOA. A imunoexpressão (nuclear e citoplasmática) da CLIC4 no revestimento epitelial CO foi significativamente superior à encontrada no componente epitelial dos AM (p < 0,001) e dos TOA (p < 0,001). A imunoexpressão estromal de CLIC4 foi significativamente superior nos AM (p = 0,009) e CO (p = 0,004) quando comparados aos TOA. A imunoexpressao de α-SMA significativamente maior em AM (p = 0,016) e CO (p = 0,034) quando comparados aos TOA. Para a imunoexpressão membranar da E-caderina em CO foi significativamente superior em comparação à encontrada nos AM (p = 0,009) e nos TOA (p = 0,024). Foi observada maior imunoexpressão de E-caderina (membranar e citoplasmática) nos COs, quando comparados aos AM (p < 0,001) e aos TOAs (p < 0,001). A expressão de Ecaderina citoplasmática foi significativamente maior nos AM e TOA (p < 0,001) quando comparados aos CO. Observou-se diferença estatisticamente significativa na imunoexpressão de vimentina entre os casos de AM e os casos de TOA (p = 0,038) e CO (p < 0,001), bem como entre o TOA e CO (p < 0,001). As correlações testadas entre os escores das proteínas estudadas evidenciou que no grupo dos AM foi possível evidenciar moderada correlação positiva e estatisticamente significativa (r = 0,527; p = 0,036) entre a expressão citoplasmática da CLIC4 e a expressão citoplasmática da E-caderina. Também foi verificada fraca correlação negativa e estatisticamente significativa (r = -0,499; p = 0,049) entre a expressão núcleo-citoplasmática da CLIC4 e a expressão citoplasmática da E-caderina nos AM. Além disso, uma moderada correlação positiva e estatisticamente significativa entre a expressão estromal da CLIC4 e a expressão da α-SMA nos AM (r = 0,648; p = 0,007) e nos CO (r = 0,541; p = 0,014). Foi observada forte correlação negativa e estatisticamente significativa (r = -0,813; p < 0,001) entre a expressão da E-caderina e a expressão da vimentina nos AM. Os resultados deste estudo sugerem um potencial envolvimento de CLIC4 no processo de transdiferenciação de miofibroblastos, e que a presença destas células é mais frequentemente associada a lesões de comportamento biológico mais agressivo como os AM e CO, além de uma possível atuação desta proteína na regulação do ciclo celular e na TEM nas lesões estudadas (AU).

Benign epithelial odontogenic lesions constitute a heterogeneous group of lesions. the CLIC4 protein acts in the regulation of growth arrest and apoptosis processes, also participating in the process of transdifferentiation of fibroblasts Into myofibroblasts that begin to express α-SMA. Furthermore, CLIC4 expression can interfere with the epithelialmesenchymal transition (EMT) process in neoplasms. This work evaluated the immunoexpression of CLIC4, α-SMA, e-cadherin and vimentin in ameloblastomas (AM) (n = 16), odontogenic keratocysts (OK) (n = 20) and adenomatoid odontogenic tumors (AOT) (n = 8). The analysis of the immunohistochemical expression of the proteins CLIC4, ecadherin and vimentin in the epithelial component of the lesions and of CLIC4 and α-SMA in the connective tissue was carried out in a semi-quantitative way by a previously calibrated evaluator. Expression in the epithelial component of CLIC4 was analyzed separately in the nucleus and cytoplasm, as well as e-cadherin labeling, which was evaluated in the membrane and cytoplasm. Comparisons of the percentages of immunoreactivity in relation to the studied groups were carried out using the nonparametric kruskal-wallis and mann-whitney tests. Possible correlations between the expression of CLIC4, α-SMA, e-cadherin and vimentin were evaluated using the spearman correlation test. The significance level was set at 5% (p < 0.05). Different staining patterns were observed between the groups analyzed, observing that the exclusively cytoplasmic immunoexpression of CLIC4 in the epithelial component of AM (p < 0.001) and AOT (p < 0.001) was significantly higher than that of OK, not demonstrating statistical significance between the AM and AOT. The immunoexpression (nuclear and cytoplasmic) of CLIC4 in the co epithelial lining was significantly higher than that found in the epithelial component of AM (p < 0.001) and AOT (p < 0.001). Stromal CLIC4 immunoexpression was significantly higher in AM (p = 0.009) and OK (p = 0.004) when compared to AOT. The immunoexpression of α-SMA is significantly higher in AM (p = 0.016) and OK (p = 0.034) when compared to AOT. For e-cadherin membrane immunoexpression in co was significantly higher compared to that found in AM (p = 0.009) and AOT (p = 0.024). Greater immunoexpression of e-cadherin (membrane and cytoplasmic) was observed in OK, when compared to AM (p < 0.001) and AOT (p < 0.001). Cytoplasmic ecadherin expression was significantly higher in AM and AOT (p < 0.001) when compared to OK. A statistically significant difference in vimentin immunoexpression was observed between cases of AM and cases of AOT (p = 0.038) and OK (p < 0.001), as well as between AOT and OK (p < 0.001). The correlations tested between the scores of the proteins studied showed that in the am group it was possible to demonstrate a moderate positive and statistically significant correlation (r = 0.527; p = 0.036) between the cytoplasmic expression of clic4 and the cytoplasmic expression of e-cadherin. A weak and statistically significant negative correlation (r = -0.499; p = 0.049) was also found between the nucleus-cytoplasmic expression of clic4 and the cytoplasmic expression of e- cadherin in AM. Furthermore, a moderate positive and statistically significant correlation between the stromal expression of CLIC4 and the expression of α-SMA in AM (r = 0.648; p = 0.007) and OK (r = 0.541; p = 0.014). Additionally, a strong negative and statistically significant correlation (r = -0.813; p < 0.001) was observed between the expression of ecadherin and the expression of vimentin in AM. The results of this study suggest a potential involvement of CLIC4 in the myofibroblast transdifferentiation process, and that the presence of these cells is more frequently associated with lesions with more aggressive biological behavior such as AM and OK, in addition to a possible role of this protein in the regulation of cell cycle and EMT in the lesions studied (AU).

Does BRAF V600E mutation affect recurrence rate of ameloblastomas? Systematic review and meta-analysis.

OBJECTIVE: The objective of this systematic review with meta-analysis was to critically evaluate the available data on the association of the BRAF V600E mutation and recurrence rate of ameloblastomas. MATERIALS AND METHODS: This systematic review was registered in Prospero (CRD42020183645) and performed based on the PRISMA statement. A comprehensive search in PubMed, Web of Science, Scopus and Cochrane Library databases was performed in order to answer the question "Does BRAF V600E mutation affect recurrence rate of ameloblastomas?" Methodological quality and risk of bias of the selected studies were assessed with JBI Critical Appraise Tool. Meta-analysis of quantitative data was conducted with RevMan 5.3 and Jamovi 2.3. RESULTS: The initial search identified 302 articles, and 21 met the inclusion criteria. A total of 855 subjects with ameloblastoma were included in the analysis. The pooled measures for frequency of BRAF V600E mutation was 65.30% (95% CI: 0.56-0.75; p < .001; I2 = 90.85%; τ = 0.205; p < .001), and the pooled recurrence rate was 25.30% (95% CI: 0.19-0.31; p < .001; I2 = 79.44%; τ = 0.118; p < .001). No differences in recurrence rate were observed between the BRAF V600E and wild type BRAF ameloblastomas, with a pooled Odds Ratio of 0.93 (95% CI: 0.56-1.54; p = .78; I2 = 31%; p = .09). CONCLUSIONS: BRAF V600E mutation is a frequent event in ameloblastomas, but does not increase nor reduce its recurrence rate, and thus have a limited value in predicting its prognosis.