New insights into the role of the oral leukoplakia microenvironment in malignant transformation.

Oral leukoplakia is the most frequent and potentially malignant lesion of the oral cavity. Although dysplasia grading remains the main factor for risk assessment, challenges persist in determining the exact risk of transformation, and the literature has focused on studying alternative biomarkers. The interaction between dysplastic epithelial cells and the microenvironment starts early, and the communication is mainly mediated by lymphocytes, inflammatory factors, fibroblasts, and the extracellular matrix, leading to dysplastic progression. Leukoplakia-infiltrating leukocytes (LILs) and leukoplakia-associated fibroblasts (LAFs) play crucial roles in the dysplastic microenvironment. The immune response is related to intraepithelial T lymphocyte infiltration, mechanisms of immunosuppression coordinated by regulatory T cells, M2 macrophage polarization, and increased numbers of Langerhans cells; in contrast, fibroblastic and extracellular matrix factors are associated with increased numbers of pro-tumorigenic myofibroblasts, increased expression of metalloproteinases vs. decreased expression of TIMPs, and increased expression of chemokines and other inflammatory mediators. The microenvironment offers insights into the progression of leukoplakia to carcinoma, and understanding the complexity of the oral microenvironment in potentially malignant diseases aids in determining the risk of malignant transformation and proposing new therapeutic alternatives.

Granuloma piogénico oral de comportamiento agresivo: Reporte de un caso

El granuloma piogénico es una lesión vascular reactiva benigna del tejido blando que surge en respuesta a irritantes crónicos de bajo grado. Rara vez crece más de 2 cm de diámetro y por lo general, no provoca cambios en el hueso alveolar. Presentamos un caso inusual de granuloma piógeno en una mujer de 19 años, de extenso tamaño y comportamiento agresivo, asociado a resorción ósea severa, movilidad dentaria, hemorragia, anemia ferropénica y recurrencias.

Pyogenic granuloma is a benign reactive vascular lesion of the soft tissue that arises in response to chronic low-grade irritants. It rarely grows more than 2 cm in diameter and usually does not cause changes in the alveolar bone. We present the case of a 19-year-old woman with an unusual pyogenic granuloma of extensive size and aggressive behavior, associated with severe bone resorption, tooth mobility, hemorrhage, iron deficiency anemia and recurrences.

Whole-exome sequencing of oral epithelial dysplasia samples reveals an association with new genes.

The genetic basis of oral epithelial (OED) is unknown, and there is no reliable method for evaluating the risk of malignant transformation. Somatic mutations are responsible for the transformation of dysplastic mucosa to invasive cancer. In addition, these genomic variations could represent objective markers of the potential for malignant transformation. We performed whole-exome sequencing of 10 OED samples from Brazilian and Chilean patients. Using public genetic repositories, we identified 41 deleterious variants that could produce high-impact changes in the amino acid structures of 38 genes. In addition, the variants were filtered according to normal skin and Native American genome profiles. Finally, 13 genes harboring 15 variants were found to be exclusively related to OED. High-grade epithelial dysplasia samples showed a tendency to accumulate highly deleterious variants. We observed that 62% of 13 OED genes identified in our study were also found in head and neck squamous cell carcinoma. Among the shared genes, eight were not identified in oral squamous cell carcinoma. To our knowledge, we have described for the first time 13 genes that are found in OED in a Latin American population, of which five genes have already been observed in oral squamous cell carcinoma. Through this study, we identified genes that may be related to basal biological functions in OED.

Proliferative verrucous leukoplakia mimicking oral lichen planus: case report and literature review

This report presents the clinical, microscopic and immunohistochemical aspects of a case of proliferative verrucous leukoplakia (PVL) mimicking oral lichen planus (OLP) in a 66-year-old woman. We also review the literature reporting cases of PVL mimicking OLP, where we found a higher prevalence in women who do not consume tobacco or alcohol. The initial manifestation of lichenoid areas was around the age of 59, with the diagnosis of PVL being established on average 6 years later, while malignant transformation occurred in 8 of the 22 cases at an average of 3.7 years after the final diagnosis of PVL. We emphasize the need for a close follow-up of any patient presenting white lesions of the oral mucosa. Lesions that are clinically and microscopically compatible with lichenoid reactions or OLP must be investigated and differentiated from PVL, which has a worse prognosis.

Este relato apresenta os aspectos clínicos, microscópicos e imuno-histoquímicos de um caso de leucoplasia verrucosa proliferativa (LPV) mimetizando líquen plano oral (LPO) em uma paciente do sexo feminino de 66 anos. Também revisamos a literatura relatando casos de LPV mimetizando LPO, onde encontramos maior prevalência em mulheres que não consomem tabaco ou álcool, com manifestação inicial de áreas liquenoides por volta dos 59 anos, sendo estabelecido o diagnóstico de LPV em média 6 anos depois, enquanto a transformação maligna ocorreu em 8 dos 22 casos em média 3,7 anos após o diagnóstico final de LPV. Ressaltamos a necessidade de acompanhamento rigoroso de qualquer paciente que apresente lesões brancas da mucosa oral, devendo ser investigadas lesões clinicamente e microscopicamente compatíveis com reações liquenóides ou LPO e diferenciadas da LPV, que tem pior prognóstico

Este reporte presenta los aspectos clínicos, microscópicos e inmunohistoquímicos de un caso de leucoplasia verrugosa proliferativa (LVP) simulando liquen plano oral (LPO) en una paciente de 66 años. También revisamos la literatura reportando casos de LVP simulando LPO, donde encontramos una mayor prevalencia en mujeres que no consumen tabaco ni alcohol, con una manifestación inicial de áreas liquenoides alrededor de los 59 años, estableciéndose el diagnóstico de LVP en promedio 6 años después, mientras que la transformación maligna ocurrió en 8 de los 22 casos en un promedio de 3,7 años después del diagnóstico final de LVP. Resaltamos la necesidad de un seguimiento estrecho de todo paciente que presente lesiones blanquecinas de la mucosa oral, que las lesiones clínica y microscópicamente compatibles con reacciones liquenoides o LPO deben ser investigadas y diferenciadas de la LVP, que tienen peor pronóstico.

Whole-exome sequencing of oral epithelial dysplasia samples reveals an association with new genes

Abstract The genetic basis of oral epithelial (OED) is unknown, and there is no reliable method for evaluating the risk of malignant transformation. Somatic mutations are responsible for the transformation of dysplastic mucosa to invasive cancer. In addition, these genomic variations could represent objective markers of the potential for malignant transformation. We performed whole-exome sequencing of 10 OED samples from Brazilian and Chilean patients. Using public genetic repositories, we identified 41 deleterious variants that could produce high-impact changes in the amino acid structures of 38 genes. In addition, the variants were filtered according to normal skin and Native American genome profiles. Finally, 13 genes harboring 15 variants were found to be exclusively related to OED. High-grade epithelial dysplasia samples showed a tendency to accumulate highly deleterious variants. We observed that 62% of 13 OED genes identified in our study were also found in head and neck squamous cell carcinoma. Among the shared genes, eight were not identified in oral squamous cell carcinoma. To our knowledge, we have described for the first time 13 genes that are found in OED in a Latin American population, of which five genes have already been observed in oral squamous cell carcinoma. Through this study, we identified genes that may be related to basal biological functions in OED.

Diversity of clinical, radiographic and genealogical findings in 41 families with amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in the clinical presentation; according to Witkop, AI can be categorized into 14 subtypes, which makes its diagnosis extremely complex. OBJECTIVE: This study aimed to describe and determine the frequency of clinical and radiographic features and inheritance patterns found in 41 Chilean families diagnosed with diverse types of AI. MATERIAL AND METHODS: We analyzed the clinical records, photographs, pedigrees and radiographs of 121 individuals recruited between 2003 and 2016. All of the information was included in a database that was analyzed using the application Stata 14. RESULTS: The 72 affected individuals had average age of 16 years, and no sex association with the presence of AI was found. The most frequent clinical subtypes were as follows: 43% hypomature, 25% hypoplastic, 21% hypomature/hypoplastic, 7% hypocalcified and 4% hypocalcified/hypoplastic. The number of severely affected teeth was 22, which occurred in the patients with hypocalcified and hypocalcified/hypoplasic AI who presented the highest number of damaged teeth. Caries and periodontal disease were found in 47 and 32% of the patients, respectively. Malocclusions were observed in 43% of the individuals with AI, with open bite being the most frequent. Radiographically, the thickness of the enamel decreased in 51% of the patients, and 80% showed decreased radiopacity of the enamel compared to that of dentin. Autosomal dominant inheritance pattern was found in 37% of the families with hypoplastic AI, and autosomal recessive pattern was present in 56% of the other clinical subtypes, but more frequently in those affected with hypomature and hypocalcified AI. CONCLUSION: Of the five clinical subtypes, autosomal recessive hypomature, autosomal dominant hypoplastic and autosomal recessive hypomature/hypoplastic AI were the most prevalent subtypes in this group.

Diversity of clinical, radiographic and genealogical findings in 41 families with amelogenesis imperfecta

Abstract Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in the clinical presentation; according to Witkop, AI can be categorized into 14 subtypes, which makes its diagnosis extremely complex. Objective: This study aimed to describe and determine the frequency of clinical and radiographic features and inheritance patterns found in 41 Chilean families diagnosed with diverse types of AI. Material and Methods: We analyzed the clinical records, photographs, pedigrees and radiographs of 121 individuals recruited between 2003 and 2016. All of the information was included in a database that was analyzed using the application Stata 14. Results: The 72 affected individuals had average age of 16 years, and no sex association with the presence of AI was found. The most frequent clinical subtypes were as follows: 43% hypomature, 25% hypoplastic, 21% hypomature/hypoplastic, 7% hypocalcified and 4% hypocalcified/hypoplastic. The number of severely affected teeth was 22, which occurred in the patients with hypocalcified and hypocalcified/hypoplasic AI who presented the highest number of damaged teeth. Caries and periodontal disease were found in 47 and 32% of the patients, respectively. Malocclusions were observed in 43% of the individuals with AI, with open bite being the most frequent. Radiographically, the thickness of the enamel decreased in 51% of the patients, and 80% showed decreased radiopacity of the enamel compared to that of dentin. Autosomal dominant inheritance pattern was found in 37% of the families with hypoplastic AI, and autosomal recessive pattern was present in 56% of the other clinical subtypes, but more frequently in those affected with hypomature and hypocalcified AI. Conclusion: Of the five clinical subtypes, autosomal recessive hypomature, autosomal dominant hypoplastic and autosomal recessive hypomature/hypoplastic AI were the most prevalent subtypes in this group.

Sobrevida de carcinoma oral de células escamosas: reporte de la Universidad de Chile / Survival of oral squamous cell carcinoma: report of the University of Chile

RESUMEN: El carcinoma oral de células escamosas es la neoplasia maligna más frecuente en la cavidad oral. Sin embargo, los estudios sobre supervivencia general en pacientes con cáncer oral son escasos en Chile. Objetivo: Determinar las características sociodemográficas y la supervivencia general de pacientes diagnosticados con carcinoma en labio y cavidad oral en el Servicio de Anatomía Patológica de la Facultad de Odontología, Universidad de Chile. Material y métodos: Se seleccionaron los casos de carcinoma oral de células escamosas diagnosticados entre los años 2000-2012. Se incluyeron sólo los primeros diagnósticos y las recidivas fueron excluidas. Resultados: De 134 casos registrados, 120 cumplían los criterios de inclusión. El 60% correspondió a hombres (razón hombre-mujer 1,3:1) y la media de edad fue 63 años. La supervivencia general a dos años fue 48,3% y a cinco años 33,9% según estimación de Kaplan-Meier. Se detectó una mayor supervivencia en el grupo de pacientes que tenían menos de 55 años (p<0,05). 79,2% de los casos fallecidos registra como causa de muerte cáncer oral. Conclusiones: El mayor porcentaje de personas diagnosticadas fueron hombres y adultos mayores. La supervivencia general a cinco años fue menor a lo determinado en reportes nacionales previos. Los adultos de 55 años y mayores presentaron una menor supervivencia general.

ABSTRACT: Oral squamous cell carcinoma is the most common malignant neoplasm of oral cavity. Research about general survival rates in patients with oral cancer is limited in Chile. Objective: To determine the sociodemographic characteristics and general survival of patients diagnosed with lip and oral carcinoma in the Pathological Anatomy Service at the School of Dentistry, University of Chile. Material and methods: All cases of oral squamous cell carcinoma selected were diagnosed between the years 2000 and 2012. All cases included in this study corresponded to the first diagnosis and tumor recurrence was excluded. Results: The 134 registered cases, 120 were selected with inclusion criteria. 60% were men (male and female ratio of 1.3: 1) and median age 63 year-old. Overall survival at two years was 48.3% and at five years 33.9%, according to Kaplan-Meier estimate. A higher survival was detected in the group of patients younger than 55 years old (p <0.05). In 79.2% of dead patients, the cause of death was registered as oral cancer. Conclusions: The highest percentage of patients diagnosed was men and elders. Five-year survival was lower than previously reported in national reports. Adults aged 55 years and older had a lower overall survival.

Ameloblastoma with adenoid features: A series of eight cases.

BACKGROUND: Ameloblastoma with adenoid features are characterized by the presence of duct-like structures formed from the parenchyma of the tumor. This study was conducted to report a series of eight ameloblastomas with adenoid features, highlighting their clinicopathological and immunohistochemical aspects. MATERIAL AND METHODS: Out of 71 cases of ameloblastomas, this study classified 8 cases as ameloblastomas with adenoid features. Clinicopathological data and immunohistochemistry for CK7, CK14, CK19, IMP3, p53 and Ki-67 were evaluated. RESULTS: From those cases of ameloblastoma exhibiting adenoid features, there were 4 women and 4 men, with mean age of 39 years. Most cases affected the mandible and all presented radiographically as a radiolucency. The predominant histopathological features were pseudoducts, squamous metaplasia, nuclear hyperchromatism, clear cells, whorled aspect of epithelial structures, cribriform growth pattern, proliferation of spindle cells and extracellular eosinophilic material. Immunohistochemical analysis showed high expression for CK14 (n = 6) and CK19 (n = 3) and all cases (n = 8) were negative for p53, IMP3 and CK7. In addition, all samples (n = 8) showed low expression for Ki-67. CONCLUSIONS: The similarities between the histopathological and immunohistochemical features of eight cases described in the present study and those described in previous studies support the possibility that these lesions are adenoid ameloblastomas. In addition, the immunohistochemical results of CK14, CK19, p53 and Ki-67 did not differ from those of conventional ameloblastomas.

A retrospective analysis of reactive hyperplastic lesions of the oral cavity: study of 1149 cases diagnosed between 2000 and 2011, Chile.

UNLABELLED: The aim of this study was to determine the relative frequency and distribution of reactive hyperplastic lesions (RHL) of the oral mucosa at the Oral Pathology Institute of the School of Dentistry at the University of Chile. This was a retrospective study of 1149 biopsies with histopathological diagnosis of RHL, performed between 2000 and 2011. The RHL were classified in 4 groups: fibrous hyperplasia (FH), pyogenic granuloma (PG), peripheral giant-cell granuloma (PGCG) and peripheral ossifying fibroma (POF). RESULTS: the most frequent RHL was FH (71. 1%), followed by PG (21.1%), PGCG (5 %) and POF (2.9%). RHLs were more frequent in women (70.7%). The most highly affected age group was the 50- to 59-year-olds (22%). The most frequent location for RHL was maxilla (24.7%), followed by cheek (20.6%), tongue (19.4%) and jaw (18.5%). The most prevalent RHL diagnosis was FH. The most frequently affected sex was female, the most frequent age range was 50-59 years, and the most frequent location, maxilla.

A retrospective analysis of reactive hyperplastic lesions of the oral cavity: study of 1149 cases diagnosed between 2000 and 2011, Chile / Análisis retrospectivo de lesiones reaccionales hiperplásicas en mucosa oral: estudio de 1149 casos diagnosticados entre el 2000–2011 en chile

El objetivo de este estudio fue determinar la frecuencia relativa y distribución de lesiones reaccionales hiperplásicas (LRH) de la mucosa oral, presentes en el registro de biopsias del Servicio de Anatomía Patológica de la Facultad de Odontología, Universidad de Chile. Este estudio de tipo retrospectivo consistió en 1149 biopsias con diagnóstico histopatológico de LRH, entre los años 2000-2011. Las LRH se clasificaron en 5 grupos: Hiperplasia fibrosa (HF), granuloma piogénico (GP), granuloma periférico de células gigantes (GPCG) y fibroma osificante periférico(FOP). Los datos de edad y sexo de los sujetos, y de localización y tipo de lesión, fueron obtenidos del registro de biopsias de cada caso. De las LRH, la lesión más frecuente fue HF (71,1 por ciento), seguido de GP (21,1 por ciento), GPCG (5 por ciento) y FOP (2,9 por ciento) respectivamente. Las biopsias de LRH fueron mas frecuentes en mujeres (70,7 por ciento). El rango etario más afectado fue el de 50 a 59 años (22 por ciento). La localización de mayor frecuencia de LRH fue el maxilar superior (24,7 por ciento), seguida de mejilla (20,6 por ciento), lengua (19,4 por ciento), mandíbula (18,5 por ciento), labio inferior (9,9 por ciento) y labio superior (6,7 por ciento). En este estudio, de las LRH el diagnóstico más prevalente fue FH. El sexo más afectado fue el femenino, el rango etario el de 50 a 59 años y la ubicación más frecuente, maxilar superior. Estos resultados en general son concordantes con lo descrito en otros países.

The aim of this study was to determine the relative frequency and distribution of reactive hyperplastic lesions (RHL) of the oral mucosa at the Oral Pathology Institute of the School of Dentistry at the University of Chile. This was a retrospective study of 1149 biopsies with histopathological diagnosis of RHL, performed between 2000 and 2011. The RHL were classified in 4 groups: fibrous hyperplasia (FH), pyogenic granuloma (PG), peripheral giant-cell granuloma (PGCG) and peripheral ossifying fibroma (POF). Results: the most frequent RHL was FH (71. 1%), followed by PG (21.1%), PGCG (5 %) and POF (2.9%). RHLs were more frequent in women (70.7%). The most highly affected age group was the 50- to 59-year-olds (22%). The most frequent location for RHL was maxilla (24.7%), followed by cheek (20.6%), tongue (19.4%) and jaw (18.5%). The most prevalent RHL diagnosis was FH. Themost frequently affected sex was female, the most frequent agerange was 50-59 years, and the most frequent location, maxilla.