Histopathological risk assessment in multisite epithelial dysplasia: A meta-analysis.

OBJECTIVE: Histopathological grading of oral epithelial dysplasia (OED) is the current standard for stratifying cancer progression risk but is associated with subjectivity and variability. This problem is not commonly seen regarding the grading of epithelial dysplasia in other sites. This systematic review aims to compare grading systems for oral, anal, penile, and cervical epithelial dysplasia to determine their predictive accuracy for recurrence and malignant transformation (MT) outcomes. METHODS: The review protocol was registered in PROSPERO (CRD42023403035) and was reported according to the PRISMA checklist. A comprehensive search was performed in the main databases and gray literature. The risk of bias in individual studies was analyzed using the Joanna Briggs Institute checklist for each study design. RESULTS: Forty-six studies were deemed eligible and included in this systematic review, of which 45 were included in the quantitative analysis. Meta-analysis revealed that the binary system demonstrated a higher predictive ability for MT/recurrence of OED compared to multilevel systems. Higher predictive accuracy of MT was also observed for binary grading systems in anal intraepithelial neoplasia. CONCLUSIONS: No significant difference was found between the current grading systems of epithelial dysplasia in different body parts. However, binary grading systems have shown better clinical outcomes.

Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

OralEpitheliumDB: A Dataset for Oral Epithelial Dysplasia Image Segmentation and Classification.

Early diagnosis of potentially malignant disorders, such as oral epithelial dysplasia, is the most reliable way to prevent oral cancer. Computational algorithms have been used as an auxiliary tool to aid specialists in this process. Usually, experiments are performed on private data, making it difficult to reproduce the results. There are several public datasets of histological images, but studies focused on oral dysplasia images use inaccessible datasets. This prevents the improvement of algorithms aimed at this lesion. This study introduces an annotated public dataset of oral epithelial dysplasia tissue images. The dataset includes 456 images acquired from 30 mouse tongues. The images were categorized among the lesion grades, with nuclear structures manually marked by a trained specialist and validated by a pathologist. Also, experiments were carried out in order to illustrate the potential of the proposed dataset in classification and segmentation processes commonly explored in the literature. Convolutional neural network (CNN) models for semantic and instance segmentation were employed on the images, which were pre-processed with stain normalization methods. Then, the segmented and non-segmented images were classified with CNN architectures and machine learning algorithms. The data obtained through these processes is available in the dataset. The segmentation stage showed the F1-score value of 0.83, obtained with the U-Net model using the ResNet-50 as a backbone. At the classification stage, the most expressive result was achieved with the Random Forest method, with an accuracy value of 94.22%. The results show that the segmentation contributed to the classification results, but studies are needed for the improvement of these stages of automated diagnosis. The original, gold standard, normalized, and segmented images are publicly available and may be used for the improvement of clinical applications of CAD methods on oral epithelial dysplasia tissue images.

Oral health of an indigenous population in northeastern Brazil: a cross-sectional Study of the Fulni-ô ethnic group

ABSTRACT BACKGROUND: There is a lack of studies evaluating the oral health of traditional indigenous communities in Brazil. OBJECTIVES: Thus, the objective of this study was to describe the oral health characteristics of the indigenous Fulni-ô ethnic group in Northeast Brazil. DESIGN AND SETTING: A cross-sectional observational investigation was conducted within the Project on Atherosclerosis among Indigenous Populations. METHODS: This study included participants of both sexes from the Fulni-ô ethnic group. The participants included in this investigation underwent a comprehensive oral health evaluation by a registered and experienced dentist to assess oral health and identify potentially malignant oral lesions. Participants with suspicious lesions were referred for biopsy. Shapiro-Wilk, Mann-Whitney, and Student's t-tests were used, and measures of central tendency and dispersion were described. Statistical significance was 5%. RESULTS: A total of 104 individuals were included in this study. The prevalence of the use of tobacco derivatives was 94.0%, with similarities between sexes. The prevalence of oral changes in this study population was 84.4%. Fifty-one individuals who underwent oral reassessment were referred for oral lesion biopsy. CONCLUSIONS: This study demonstrated a high prevalence of oral alterations in the Fulni-ô population. Histopathological analyses indicated the presence of mild oral epithelial dysplasia in five cases.

Human Papillomavirus-Associated Oral Epithelial Dysplasia: Report of 5 Illustrative Cases from Latin America.

BACKGROUND: Human papillomavirus-associated oral epithelial dysplasia (HPV-OED) is a distinct oral epithelial disorder characterized by viral cytopathic changes caused by transcriptionally active high-risk HPV. The aim of the present study was to report 5 additional cases from Latin America. METHODS: Clinical data from five patients with HPV-OED were obtained from the archives of three oral pathology services from Brazil and Chile. All cases were submitted to morphological, p16 expression and in situ hybridization (ISH) for HPV analyses. RESULTS: Four patients were male and one patient was female, with a mean age of 55.4 years. Four patients were HIV seropositive and two were smokers. Three cases affected the buccal mucosa and commissure, one of which had an additional plaque in the soft palate, and one case each occurred on the floor of mouth and lower labial mucosa. Most cases presented as well-demarcated white plaques with a verrucous surface. One case presented multiple lesions ranging from normal to white-colored slightly elevated plaques with a cobblestone surface. Peripheral mucosal pigmentation was observed in two cases. All five cases presented with the characteristic microscopic features of HPV-OED, including severe dysplasia with numerous karyorrhectic and apoptotic cells, full-thickness "block positivity" for p16 and high Ki-67 index (> 90%) sharply demarcated from the adjacent non-dysplastic epithelium. Wide-spectrum DNA ISH-HPV was positive in 4 cases. All patients were treated with conservative surgical excision with no signs of recurrence after a mean of 39-month follow-up. CONCLUSION: This represents the first series of HPV-OED from Latin America; most cases presented as well-demarcated papillary white plaques affecting the buccal mucosa and commissure of HIV-positive middle-aged men, two of them exhibiting peripheral pigmentation caused by reactive melanocytes. The typical microscopic findings of HPV-OED were observed in all cases, which also showed strong p16 positivity in a continuous band through the full thickness of the epithelium and high Ki67.

Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor Phenotype.

Oral potentially malignant disorders (OPMD) are clinical presentations that carry an increased risk of cancer development. Currently, epithelial dysplasia grade is based on architectural and cytological epithelial changes and is used to predict the malignant transformation of these lesions. However, predicting which OPMD will progress to a malignant tumor is very challenging. Inflammatory infiltrates can favor cancer development, and recent studies suggest that this association with OPMD lesions may be related to the etiology and/or aggressive clinical behavior of these lesions. Epigenetic changes such as histone modifications may mediate chronic inflammation and also favor tumor cells in immune resistance and evasion. This study aimed to evaluate the relationship between histone acetylation (H3K9ac) and DNA damage in the context of dysplastic lesions with prominent chronic inflammation. Immunofluorescence of "low-risk" and "high-risk" OPMD lesions (n = 24) and inflammatory fibrous hyperplasia (n = 10) as the control group was performed to assess histone acetylation levels and DNA damage through the phosphorylation of H2AX (γH2AX). Cell co-culture assays with PBMCs and oral keratinocyte cell lines (NOK-SI, DOK, and SCC-25) were performed to assess proliferation, adhesion, migration, and epithelial-mesenchymal transition (EMT). Oral dysplastic lesions showed a hypoacetylation of H3K9 and low levels of γH2AX compared to control. The contact of dysplastic oral keratinocytes with PBMCs favored EMT and the loss of cell-cell adhesion. On the other hand, p27 levels increased and cyclin E decreased in DOK, indicating cell cycle arrest. We conclude that the presence of chronic inflammation associated to dysplastic lesions is capable of promoting epigenetic alterations, which in turn can favor the process of malignant transformation.

High density of CD8 T cell and immune imbalance of T lymphocytes subsets are associated with proliferative verrucous leukoplakia.

Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are oral potentially malignant disorders (OPMDs) that microscopically show no or varying degrees of dysplasia. Even sharing clinical and microscopic aspects, PVL shows a more aggressive clinical behaviour, with a malignant transformation rate greater than 40%. Inflammatory infiltrate associated with dysplastic lesions may favour malignant transformation of OPMDs. This study aimed to evaluate the density of T cells and cytokines in dysplastic lesions from OL and PVL patients. Additionally, we evaluated whether soluble products produced in vitro by dysplastic keratinocytes are capable of modulating apoptosis rates and Th phenotype (Th1, Th2, Th17 and Treg) of peripheral blood mononuclear cells. The density of CD3, CD4 and CD8 T cells was assessed by immunohistochemistry. Cytokines and chemokines profile from frozen tissue samples were analysed using the LUMINEX system. Apoptosis rates and Th phenotype modulation were evaluated by flow cytometry. Our results showed an increase in the number of CD8 T cell in the subepithelial region from PVL dysplastic lesions in relation to OL samples. PVL showed increased levels of IL-5 and a decrease in IL-1ß and IFN-γ levels compared to OL. Soluble products of PVL and oral carcinoma cell cultures were able to reduce apoptosis rate and promote an imbalance of Th1/Th2 and Th17/Treg. The high-subepithelial density of CD8 T cells and immune imbalance of T lymphocytes subsets probably play an important role in the pathogenesis of PVL and may explain its more aggressive behaviour in relation to OL.

Oral squamous cell carcinoma arising from chronic traumatic ulcers.

BACKGROUND: A proportion of oral squamous cell carcinoma (OSCC) is preceded by oral potentially malignant disorders (OPMD), and the rest might not be associated with any well-established OPMD. Chronic traumatic ulcer (CTU) has been suggested as a lesion with potential for malignant transformation, but the evidence is inconclusive. OBJECTIVE: The aim of this study was to describe clinicopathological features of non-healing CTU (NHCTU) that later developed to OSCC. MATERIALS AND METHODS: A retrospective cohort study was performed of patients attending the Facultad de Odontología Universidad Nacional de Córdoba (2013-2019). The study included patients with a provisional diagnosis of CTU. CTUs without complete healing after removal of traumatic factors-non healing CTU (NHCTU)-were investigated by biopsy. A detailed description of cases where a malignancy was diagnosed is presented. RESULTS: A total of 107 CTU were included. Of these, 32 CTUs were considered NHCTU and two cases showed histological features of OSCC in the background of NHCTU. In both cases, lesions were found on the lateral tongue. Both were non smoking, non alcohol drinking individuals. Absence of any well-known OPMD was also registered. CONCLUSIONS: The possibility of malignant transformation in a subset of tongue NHCTU should not be underestimated. CLINICAL RELEVANCE: In a subgroup of patients, NHCTU could be considered an OPMD. Although the potential malignant transformation rate is low, these conditions should be always followed up.

Enteropatías congénitas y la implicación diagnóstica en la displasia intestinal o enteropatía en penacho

RESUMEN Introducción: la displasia epitelial intestinal o enteropatía en penacho, es una rara y grave enfermedad debido a mutaciones genéticas, categorizada como enteropatía congénita por defecto del transporte de los enterocitos y su polaridad. Objetivo: Examinar los conocimientos más recientes para la orientación diagnóstica de las enteropatías congénitas en el contexto clínico de las diarreas crónicas intratables del período posnatal y primeros meses de vida. Métodos: Análisis de publicaciones en español e inglés en PubMed, Scimago, ScIELO hasta abril 2021 relacionadas con esta temática. Se usaron los términos diarreas intratables, enteropatías congénitas, displasia epitelial intestinal, enteropatía en penacho y enfermedades para diagnóstico diferencial. Análisis e integración de la información: Se describieron criterios sobre diarreas intratables, enteropatías congénitas; su clasificación. Se revisaron rasgos de la displasia epitelial intestinal y sus manifestaciones de formas clínicas, histopatológicas y mutaciones genéticas, epidemiología, diagnóstico de certeza y diferencial por afecciones debido a defectos congénitos relacionados con el tránsito epitelial y polaridad; tratamiento, pronóstico y actualización sobre trascendencia de las enfermedades raras. Conclusiones: Se revisan los conocimientos más recientes relacionados con enfermedades raras por enteropatías congénitas y en particular sobre la displasia epitelial intestinal o enteropatía en penacho. Se describen sus manifestaciones clínicas, histopatológicas y genéticas. La epidemiología, el tratamiento y sus retos. Se enfatizó en criterios sobre la trascendencia diagnóstica de enfermedades raras relacionadas con enteropatías congénitas.

ABSTRACT Introduction: Intestinal epithelial dysplasia or plume enteropathy is a rare and serious disease due to genetic mutations, categorized as congenital enteropathy due to the defect of enterocyte transport and their polarity. Objective: Examine the most recent knowledge on the diagnostic orientation of congenital enteropathies in the clinical context of intractable chronic diarrhea of the postnatal period and first months of life. Methods: Analysis of publications in Spanish and English in PubMed, Scimago, ScIELO until April 2021 related to this topic. The terms intractable diarrhea, congenital enteropathies, intestinal epithelial dysplasia, plume enteropathy and diseases were used for differential diagnosis. Analysis and integration of information: Criteria on intractable diarrhea, and congenital enteropathies were described; and their classification. Features of intestinal epithelial dysplasia and its manifestations of clinical, histopathological forms and genetic mutations, epidemiology, diagnosis of certainty and differential for conditions due to congenital defects related to epithelial transit and polarity were reviewed; treatment, prognosis and update on the importance of rare diseases. Conclusions: The most recent knowledge related to rare diseases due to congenital enteropathies and in particular about intestinal epithelial dysplasia or plume enteropathy is reviewed. Its clinical, histopathological and genetic manifestations are described, epidemiology, treatment and its challenges. Emphasis was placed on criteria on the diagnostic significance of rare diseases related to congenital enteropathies.

Parámetros histomorfométricos de la mucosa bucal en pacientes portadores de leucoplasia con displasia epitelial / Histomorphometric Parameters of the Buccal Mucosa in Patients with Leukoplakia and Epithelial Dysplasia

RESUMEN Fundamento la leucoplasia es la lesión potencialmente maligna más frecuente en las membranas mucosas de la boca y se puede presentar con diferentes grados de displasia epitelial. El estudio histológico de esta lesión unido a la medición de parámetros morfométricos y estereológicos, permite la mejor comprensión de procesos tanto fisiológicos como patológicos. Objetivo: caracterizar los parámetros histomorfométricos de la mucosa bucal en pacientes portadores de leucoplasia bucal según grado de displasia epitelial. Método: se realizó un estudio de serie de casos, con el objeto de determinar indicadores morfométricos, de lesiones leucoplásicas de la mucosa oral en biopsias de pacientes atendidos en los Servicios de Anatomía Patológica y Maxilofacial del Hospital General Universitario Dr. Gustavo Aldereguía Lima, de la provincia Cienfuegos. La muestra se obtuvo por muestreo intencionado, la cual quedó constituida por 30 láminas histológicas (biopsias), distribuidas en tres grupos de diez láminas por cada grado de displasia epitelial. La variable de estudio fue la caracterización morfométrica de la leucoplasia de la mucosa oral con displasia. Se aplicó estadística descriptiva e inferencial. Resultados: predominaron tres parámetros en la clasificación de la displasia: alteración de los clavos interpapilares, hiperplasia y pérdida de la polaridad de las células basales. Se constató presencia de ortoparaqueratosis, epitelios hiperplásicos e infiltrado inflamatorio del corion, en más de la mitad de los casos. Hubo significación estadística en las relaciones que se establecieron entre la altura o profundidad de las papilas y la densidad relativa de células según grado de displasia epitelial, al aplicar la estadística inferencial. Conclusiones: predominaron tres parámetros en la clasificación de la displasia. Se constató presencia de ortoparaqueratosis, epitelios hiperplásicos e infiltrado inflamatorio del corion, en más de la mitad de los casos.

ABSTRACT Background: leukoplakia is the most frequent potentially malignant lesion in the mucous membranes of the mouth and can present with different degrees of epithelial dysplasia. The histological study of this lesion, together with the measurement of morphometric and stereological parameters, allows a better understanding of both physiological and pathological processes. Objective: to characterize the histomorphometric parameters of the oral mucosa in patients with oral leukoplakia according to the degree of epithelial dysplasia. Method: a case series study was carried out in order to determine morphometric indicators of leukoplastic lesions of the oral mucosa in biopsies of patients treated at the Pathology and Maxillofacial Anatomy services of the Dr. Gustavo Aldereguía Lima General University Hospital, in Cienfuegos province. The sample was obtained by intentional sampling, which was made up of 30 histological slides (biopsies), distributed in three groups of ten slides for each degree of epithelial dysplasia. The study variable was the morphometric characterization of oral mucosal leukoplakia with dysplasia. Descriptive and inferential statistics were applied. Results: three parameters prevailed in the classification of dysplasia: alteration of the interpapillary nails, hyperplasia and loss of polarity of the basal cells. The presence of orthoparakeratosis, hyperplastic epithelia and inflammatory infiltrate of the chorion was confirmed in more than half of the cases. There was statistical significance in the relationships established between the height or depth of the papillae and the relative density of cells according to the degree of epithelial dysplasia, when applying inferential statistics. Conclusions: three parameters predominated in the classification of dysplasia. The presence of orthoparakeratosis, hyperplastic epithelia and inflammatory infiltrate of the chorion was confirmed in more than half of the cases.

Displasia epitelial corneal / Corneal epithelial dysplasia

Las neoplasias intraepiteliales córneo-conjuntival son lesiones premalignas, mal delimitadas, de crecimiento lento y escaso potencial de malignización. Solo el 9 por ciento progresa a carcinoma invasor de células escamosas. Posee varias formas de presentación y tiene múltiples dilataciones vasculares. La displasia epitelial corneal primaria es una forma poco frecuente de neoplasia intraepitelial córnea-epitelial. Se presenta un caso clínico confirmado por estudios anatomopatológicos. En el presente estudio se observó respuesta satisfactoria luego de un mes de tratamiento tópico con 5FU, sin efectos colaterales. El seguimiento durante tres años no ha mostrado signos de recidiva(AU)

Corneal-conjunctival intraepithelial neoplasms are premalignant, poorly demarcated, slow-growing lesions with low malignant potential. Only the 9 percent progresses to invasive squamous cell carcinoma. It appears in several forms and presents multiple vascular dilatations. Primary corneal epithelial dysplasia is a rare form of corneal-epithelial intraepithelial neoplasia. We present a clinical case, confirmed by anatomopathologic studies. In the present study we observed a satisfactory response after one month of topical treatment with 5FU, with no side effects. Follow-up for three years has shown no signs of recurrence(AU)

Identificación y evaluación de lesiones gástricas premalignas asociadas a la infección por Helicobacter pylori / Identification and evaluation of premalignant gastric lesions associated with Helicobacter pylori infection

Introducción: La infección por Helicobacter pylori es la causa principal de enfermedades gastroduodenales (gastritis crónica, úlceras pépticas y cáncer gástrico). En Guatemala existen pocos estudios sobre la prevalencia de H. pylori y su relación con enfermedades gastrointestinales, particularmente con cáncer. Objetivos: Identificar la presencia de lesiones premalignas (atrofia gástrica, metaplasia intestinal y displasia) y su relación con la infección por H. pylori en pacientes de consulta externa en unidades de gastroenterología de dos hospitales nacionales de la ciudad de Guatemala. Métodos: El diagnóstico histopatológico y bacteriológico se realizó por medio de las tinciones de H & E y Giemsa, cultivo e identificación bioquímica, detección de anticuerpos específicos mediante la prueba ELISA, diagnóstico molecular por la amplificación del gen glmM y genotipificación por PCR para identificar los genes VacA y CagA. Se analizaron datos clínico-epidemiológicos de los pacientes, la prevalencia de la infección por H. pylori y la genotipificación de la bacteria. Resultados: En 293 de los pacientes estudiados (83 por ciento) se encontró algún tipo de lesión premaligna; las más frecuentes fueron la atrofia gástrica (70 por ciento), metaplasia intestinal (11 por ciento) y displasia gástrica (2 por ciento). El 17 por ciento de los pacientes no presentó lesiones premalignas. Se halló una prevalencia de infección por H. pylori del 58 por ciento, y el gen cagA se detectó en 118 (57 por ciento) de los pacientes infectados. Conclusiones: La mayoría de los pacientes presentó atrofia gástrica (70 por ciento) y el 43,5 por ciento estaba infectado por H. pylori, principalmente con cepas CagA positivo. Este hecho confirma la importancia del estudio de H. pylori y su relación con cáncer gástrico(AU)

Introduction: Helicobacter pylori infection is the main cause of gastroduodenal diseases (chronic gastritis, peptic ulcer and gastric cancer). In Guatemala few studies have been carried out on the prevalence of H. pylori and its relationship with gastrointestinal diseases, particularly with cancer. Objective: To identify the presence of premalignant lesions (gastric atrophy, intestinal metaplasia and dysplasia) and their relationship with H. pylori infection in outpatients in gastroenterology units in two national hospitals in Guatemala City. Methods: Histopathological and bacteriological diagnostic testings were performed by H & E and Giemsa stain, culture and biochemical identification, detection of specific antibodies by ELISA, molecular diagnosis by glmM gene amplification, and genotypification by PCR to identify vacA and cagA genes. Clinical and epidemiological data from patients, prevalence of H. pylori infection, and bacterium genotypification were analyzed. Results: Among the studied patients, 293 (83 percent) presented some type of premalignant lesion. The most prevalent were gastric atrophy (70 percent), intestinal metaplasia (11 percent), and gastric dysplasia (2 percent). Seventeen percent of the patients did not have any premalignant lesions. The prevalence of H. pylori infection was 58 percent, and cagA gene was identified in 118 (57 percent) of the infected patients. Conclusions: The majority of the patients presented gastric atrophy (70 percent), and 43.5 percent were infected by H. pylori, mainly with positive cagA strains. This finding confirms the importance of studying H. pylori and its relationship with gastric cancer(AU)

Binary and WHO dysplasia grading systems for the prediction of malignant transformation of oral leukoplakia and erythroplakia: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review was to examine the evidence of the binary histologic grading system capacity for predicting malignant transformation and to compare it with that of the WHO systems. MATERIAL AND METHODS: A systematic review was conducted, using PubMed, EMBASE, LILACS, Web of Science, Scopus, and LIVIVO databases without any language or timeframe restrictions. Studies were included if they compared the binary and the WHO histologic grading systems in the prediction of malignant transformation of oral epithelial dysplasia (OED). RESULTS: The capacity of the WHO and binary grading systems to predict malignant transformation ranged from 16 to 80% and from 5 to 80%, respectively. The pooled malignant transformation rate of lesions classified as severe dysplasia or carcinoma in situ by the WHO grading was 40% (95% confidence interval (CI), 0.02-0.87; I2 = 92%; P = 0.00), while the corresponding value for lesions classified as high-risk by the binary grading system was 31% (95% CI, 0.00-0.84; I2 = 97%; P = 0.00). Overall, there was no significant difference in prognostication accuracy between the WHO and the binary systems (odds ratio = 2.02; 95% CI, 0.88-4.64). CONCLUSIONS: Although some studies suggest that the binary system is associated with lower inter-rater variability when grading OED, the evidence remains inconclusive on whether this system is superior to that of the WHO at predicting malignant transformation. CLINICAL RELEVANCE: The reproducibility of the binary system has the potential to be better for prognostic purposes. However, there is no high-quality evidence to confirm if this advantage may assist clinicians in decision-making.

Epithelial Dysplasia in Actinic Cheilitis: Microscopic Study of 70 Cases from Brazil.

To compare two grading systems of epithelial dysplasia-World Health Organization (WHO) and binary system (BS) -in actinic cheilitis (AC). Seventy cases diagnosed as AC in an Oral Pathology Laboratory from Brazil in the last 12 years were retrospectively retrieved, including the demographic data of each patient. All conventionally stained slides were reviewed, and epithelial dysplasia was evaluated by two independent observers using both WHO and BS grading systems. Data correlation was performed using kappa and chi-square tests (p < 0.05). Most patients were white men with a mean age of 57 years old and history of chronic exposure to sunlight. Most of the lesions were clinically described as whitish plaques with irregular surface located in the lower lip semi-mucosa. Most cases were microscopically graded as severe epithelial dysplasia and low-risk by both observers. The interobserver and intraobserver agreement between systems was slight. All reddish lesions were graded as severe epithelial dysplasia, showing an equal distribution between low and high-risk grading. Most ulcerated lesions showed severe epithelial dysplasia but was graded as low-risk of malignant transformation. Statistical significance was observed among the presence of "irregular stratification", severe epithelial dysplasia and high-risk lesions (p < 0.05) likewise among the presence of "loss of polarity of basal cells" and "drop-shaped ridges" (p < 0.05) with high-risk lesions. The absence of "increased mitotic figures", "dyskeratosis" and "keratin pearls" (p < 0.05) were strongly correlated to low-risk lesions. The presence of "hyperchromasia" was statistically significant with severe epithelial dysplasia (p < 0.05) as well the absence of "atypical mitotic figures" with low-risk lesions (p < 0.05). Although there was slight agreement between microscopic grading systems, microscopic analysis indicated that architectural epithelial changes individually may be the more reliable criteria to indicate the risk of malignant transformation in AC in both grading systems.

Histopathological features of photodamage and mast cell infiltrate in actinic cheilitis with different grades of epithelial dysplasia.

BACKGROUND: Actinic cheilitis is induced by chronic exposure to ultraviolet radiation and shows solar elastosis, a feature that has been associated with mast cell infiltrates. This study aimed to investigate the area of solar elastosis, collagen loss, and mast cell infiltrates in a series of actinic cheilitis. METHODS: We evaluated the epithelial dysplasia in 52 cases of actinic cheilitis and the solar elastosis with Weigert's resorcin-fuchsin. Collagen loss was evaluated with Picrosirius red, analyzed under polarized microscopy, and scored from 1 to 3. Elastosis proportionate area (EPA) was calculated with image software. Mast cells were highlighted with toluidine blue stain. RESULTS: EPA varied from 2% to 45%, with a mean of 17.1% in the cases, with no differences among epithelial dysplasia degrees. Most cases presented collagen loss scores of 2 or 3, and higher loss of type I collagen was associated with older age. Mast cell density was higher in severe epithelial dysplasia (P = 0.002) and in high-risk cases (P = 0.01). CONCLUSION: Actinic cheilitis presented variable EPA and marked loss of type I collagen; however, these features were not associated with the degrees of epithelial dysplasia. Besides, mast cell density increased with epithelial dysplasia worsening and this was not associated with elastosis area or collagen loss.

Loss of heterozygosity and immunoexpression of PTEN in oral epithelial dysplasia and squamous cell carcinoma.

INTRODUCTION: Oral epithelial dysplasia (OED) is a risk factor for developing subsequent oral squamous cell carcinoma (OSCC). Loss of heterozygosity (LOH) profiles have been validated as risk predictors of malignant transformation of OED. It is still unclear if Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) allelic loss also occurs in initial stage malignant lesions and if the allelic loss is involved as one of the mechanisms of oral carcinogenesis. Thus, this study objective investigate LOH of PTEN gene and the immunohistochemical expression of the protein in OED and OSCC samples. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded samples of 19 OEDs and 16 OSCCs were included to immunohistochemistry and LOH analysis. Two polymorphic microsatellite markers (AFMA086WG9 and D10S1765) located in chromosome 10 were used in this study for LOH analysis. For immunohistochemical analysis, 5 random fields with 400× magnification were evaluated quantitatively and qualitatively in epithelial and neoplastic cells. RESULTS: AFMA086WG9 marker only demonstrated LOH in OEDs cases (10.5%). D10S1765 marker demonstrated LOH in 57.2% of OEDs and 50% of OSCCs. Higher nuclear immunostaining was detected in cases of OSCCs when compared to OEDs (p < .001) and there was strong cytoplasmic immunoexpression in OSCCs (p < .045). CONCLUSIONS: We provide evidence that the allelic loss of PTEN is present in premalignant oral lesions and OSCCs, however the LOH of PTEN does not seems to influence its protein expression.

Queilitis actínica: Reporte de tres casos y revisión de literatura / Actinic Cheilitis: Report of Three Cases and Review of Literature

RESUMEN La queilitis actínica (QA) es un desorden potencialmente maligno del labio inducido por la exposición crónica a la luz ultravioleta, que afecta principalmente al bermellón del labio inferior de personas adultas y de piel clara. Si no es tratada en forma oportuna puede transformarse en un carcinoma de células escamosas del labio. Histológicamente la QA presenta una serie de alteraciones a nivel epitelial que van desde hiperplasia a displasia; en el tejido conectivo se presentan distintos grados de elastosis actínica acompañada por infiltrado inflamatorio. El objetivo de este trabajo es presentar tres casos de pacientes con QA y analizar sus características clínicas e histopatológicas.

ABSTRACT Actinic cheilitis (AC) is a potentially malignant lip disorder induced by chronic exposure to ultraviolet light, which mainly affects the vermilion of the lower lip of adults and fair skin. If it is not treated in a timely manner it can become a squamous cell carcinoma of the lip. Histologically, AC presents a series of alterations at the epithelial level ranging from hyperplasia to dysplasia; Connective tissue presents different degrees of actinic elastosis accompanied by inflammatory infiltrate. The objective of this work is to present three cases of patients with AC and analyze their clinical and histopathological characteristics.

Subcellular localization and expression of E-cadherin and SNAIL are relevant since early stages of oral carcinogenesis.

The biological process of epithelial-to-mesenchymal transition (EMT) has been studied in oral squamous cell carcinoma (OSCC) metastasis, but it is rarely evaluated at several stages of oral carcinogenesis. This study aimed to analyze the presence of SNAIL and E-cadherin proteins, markers of EMT, in the development and progression of OSCC, evaluating excised specimens of potentially malignant lesions (oral leukoplakia with and without dysplasia-OL and OLD, respectively), tumor tissues (OSCC), metastatic lymph nodes (LN), and normal oral mucosa (NOM) by immunohistochemistry, considering subcellular localization. Additionally, SNAIL and E-cadherin transcripts were evaluated in vitro by qPCR, using SCC-9 cell line in comparison to human keratinocytes (HPEC). There was a significant increase in nuclear expression of SNAIL from NOM to OLD followed by a noticeable decrease in nuclear expression accompanied by increased cytoplasmic expression in OSCC (p<0.05). The E-cadherin cytoplasmic expression was remarkable and statistically significant higher in OSCC and LN, both compared to NOM (p< 0.0001), OL (p<0.01) and OLD (p< 0.0001 and p<0.001, respectively). In vitro, E-cadherin and SNAIL transcripts were lower in SCC-9 compared to HPEC cells, although only the decrease of E-cadherin was statistically significant (p<0.05). Regarding the association of E-cadherin and SNAIL expression with the clinical findings, the analysis revealed an association between the cytoplasmic expression of SNAIL and the invasion pattern (p=0.05) in OSCC. The increased nuclear SNAIL expression may be characteristic of OLD, and the presence of E-cadherin in cell cytoplasm a marker of transformation to malignancy of potentially malignant oral leukoplakias into OSCC.