Is epithelial-mesenchymal transition related to the biological behavior of salivary gland neoplasms?

OBJECTIVE: To evaluate and compare the expression of E-cadherin, Snail1 and Twist1 in pleomorphic adenomas (PAs), adenoid cystic carcinomas (AdCCa) and carcinoma ex-pleomorphic adenomas (CaexPA) of salivary glands, as well as investigate possible associations with clinicopathological parameters. STUDY DESIGN: E-cadherin, Snail1 and Twist1 antibody immunostaining were analyzed semiquantitatively in 20 PAs, 20 AdCCas and 10 CaexPAs. Cases were classified as low and high expression for analysis of the association with clinicopathological parameters. RESULTS: Compared to PAs, AdCCas and CaexPAs exhibited higher nuclear expression of Snail1 (p = 0.021 and p = 0.028, respectively) and Twist1 (p = 0.009 and p = 0.001). Membranous and cytoplasmic expression of E-cadherin were positively correlated in PAs, AdCCas and CaexPAs (r = 0.645, p = 0.002; r = 0.824, p < 0.001; r = 0.677, p = 0.031). In PAs, positive correlation was found between nuclear expression of Snail1 and membrane expression of E-cadherin (r = 0.634; p = 0.003), as well as between nuclear expression of Snail1 and Twist1 (r = 0.580; p = 0.007). Negative correlations were detected between membrane expression of E-cadherin and cytoplasmic expression of Snail1 in AdCCas (r = - 0.489; p = 0.029). CONCLUSIONS: E-cadherin, Twist1, and Snail1 may participate in modulating events related to cell differentiation and adhesion in PAs and to biological behavior in AdCCas and CaexPAs, which indicates the involvement of EMT in these processes. Furthermore, the expression of these proteins in these carcinomas may reflect the plasticity feature of EMT.

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.

Malignant salivary gland tumors: agreement between fine needle aspiration biopsy, incisional biopsy and final histopathological diagnostic / Tumores malignos de glándulas salivales: concordancia entre biopsia por aspiración con aguja fina, biopsia incisional y diagnóstico histopatológico final

Background: Incisional biopsy is indicated for intraoral tumors, but it is a contraindicated surgical procedure formajor salivary glands. To avoid complications and facilitate diagnosis, fine needle aspiration biopsy (FNAB) is atype of biopsy widely used for preoperative diagnosis in these glands.Material and Methods: The aim of this study was to analyze the agreement between the diagnosis by FNAB (ma-jor glands), incisional biopsy (minor glands) and histopathological analysis of the surgical specimen in salivarygland tumors from a database (medical records) of patients treated in a cancer treatment reference center in theNortheast region of Brazil.Results: The sample consisted of 110 cases, being 86 of them malignant tumors in major salivary glands (parotidgland=73; submandibular gland=13) and 24 cases in minor salivary glands (palate). The female gender was themost affected (57.3%), especially in patients over 60 years (42.7%). In the TNM classification, 41.8% of the caseswere in T2 at the time of diagnosis, with most of the regional lymph nodes in N0 (85.5%) and 87.3% of the casesin M0. FNAB was able to identify malignant neoplasms in 68.6% of the cases (n=59), while incisional biopsy inpalatal tumors obtained agreement of 75% of the cases (n=18). The analysis revealed that tumors classified as T3-T4 (p=0.012) showed greater agreement between pre- and post-surgical diagnosis.(AU)

Immunohistochemical comparative analysis of tumor stem cell biomarkers in pleomorphic adenoma, adenoid cystic carcinoma and mucoepidermoid carcinoma of salivary glands.

OBJECTIVE: This study aimed to compare the immunoexpression profile of tumor stem cell (TSC) biomarkers CD44, aldehyde dehydrogenase 1 (ALDH1), OCT4, and SOX2 in salivary gland tumors (SGTs). STUDY DESIGN: Sixty tissue specimens of SGTs, including 20 pleomorphic adenomas, 20 adenoid cystic carcinomas (ACCs), and 20 mucoepidermoid carcinomas, in addition to 4 samples of normal glandular tissue, were subjected to immunohistochemistry. The expression of the biomarkers in the parenchyma and stroma was evaluated. Data were analyzed statistically by nonparametric tests (P < .05). RESULTS: Higher parenchymal expression of ALDH1, OCT4, and SOX2 was observed in pleomorphic adenomas, ACCs, and mucoepidermoid carcinomas, respectively. Most ACCs did not express ALDH1. Higher immunoexpression of ALDH1 in major SGTs (P = .021) and of OCT4 in minor SGTs (P = .011) was found. Immunoexpression of SOX2 was related to lesions without myoepithelial differentiation (P < .001) and malignant behavior (P = .002). Furthermore, OCT4 was related to myoepithelial differentiation (P = .009). CD44 expression was related to a better prognosis. Stromal immunoexpressions of CD44, ALDH1, and OCT4 were higher in malignant SGTs. CONCLUSIONS: Our findings suggest the participation of TSCs in the pathogenesis of SGTs. We emphasize the need for further investigations into the presence and role of TSCs in the stroma of these lesions.

Mucocutaneous diseases with manifestations in the head and neck region: 24 years of experience in a Dermatology service

Background: This study aimed to evaluate the clinicopathological features of mucocutaneous diseases with manifestation in the head and neck region. Material and methods: A retrospective analysis of a dermatology reference center database was carried out. Over 24 years. Clinicopathological data were collected from medical records and the data was analyzed by descriptive statistics. Results: A total of 11.538 medical records were analyzed, being 152 cases of mucocutaneous diseases with manifestations in the head and neck region. Cutaneous lupus erythematosus was the most prevalent diagnosis (66.4%). Face (44.1%), females (79.6%), and patients with 45 years mean age were the most common features. In the oral cavity, the most affected region was the buccal mucosa (37.5%). Conclusions: Mucocutaneous diseases with head and neck manifestation were rare in the sample analyzed (1.3%), with cutaneous lupus erythematosus and lichen planus being the most common lesions in this region. (AU)

[COVID-19 in Brazil: trends, challenges, and perspectives after 18 months of the pandemicCOVID-19 en Brasil: tendencias, desafíos y perspectivas después de 18 meses de pandemia]. / COVID-19 no Brasil: tendências, desafios e perspectivas após 18 meses de pandemia.

Objective: To analyze the incidence and mortality trends from COVID-19 in Brazil as well as in federation units and their capitals. Method: An ecological study was performed using COVID-19 incidence and mortality data covering the period from 25 February 2020 (first case recorded in Brazil) to 31 July 2021. Data were grouped by month for calculation of crude rates (by 100 000 population) and assessment of time trends in federation units and capitals. Significant changes in time trends were analyzed by joinpoint regression. Results: Two waves of new cases and deaths were identified. The highest incidence rates were recorded in the states of Amapá, Rio Grande do Norte, Rondônia, and Roraima. The states of Amazonas and Rondônia had the highest mortality rates. In general, incidence and mortality rates were worse in the second wave. In the first wave, the mean number of months until the onset of reduction in new cases was higher in capitals, whereas in the second wave the onset of reduction in new cases took longer in the federation units. The decline in mortality began earlier in capital cities in both waves. Conclusion: The regional differences detected underscore the notion that COVID-19 incidence and mortality are associated with political, geographic, cultural, social, and economic factors.

Objetivo: Analizar las tendencias de la incidencia de COVID-19 y la mortalidad por esta enfermedad en Brasil (unidades federativas y capitales). Método: Se realizó un estudio ecológico con datos sobre incidencia de COVID-19 y la mortalidad por esta enfermedad en el período comprendido entre el 25 de febrero del 2020 (fecha del primer caso notificado en Brasil) y el 31 de julio del 2021. Los datos se agruparon por mes para calcular las tasas brutas (por 100 000 habitantes) y evaluar las tendencias temporales observadas en las unidades federativas y sus capitales. Las modificaciones significativas en las tendencias temporales se analizaron con el método de regresión de punto de inflexión (joinpoint). Resultados: Se identificaron dos olas de casos nuevos y muertes. Las unidades federativas con las mayores tasas de incidencia fueron Amapá, Rio Grande do Norte, Rondônia y Roraima; Amazonas y Rondônia tuvieron las mayores tasas de mortalidad. En general, la incidencia y la mortalidad fueron peores en la segunda ola. En la primera ola, el promedio de meses transcurridos hasta que empezó a reducirse el número de casos nuevos fue mayor en las capitales, mientras que, en la segunda ola, fue mayor en los estados. En ambas olas, el número de muertes se redujo en menos tiempo en las capitales. Conclusión: La heterogeneidad regional detectada refuerza la idea de que la incidencia de la COVID-19 y la mortalidad por esta enfermedad guardan relación con factores políticos, geográficos, culturales, sociales y económicos.

COVID-19 no Brasil: tendências, desafios e perspectivas após 18 meses de pandemia

[RESUMO]. Objetivo. Analisar as tendências de incidência e mortalidade por COVID-19 no Brasil, nas unidades da fede- ração e nas capitais. Método. Realizou-se um estudo ecológico com dados de incidência e de mortalidade por COVID-19 referen- tes ao período de 25 de fevereiro de 2020 (primeiro caso notificado no Brasil) a 31 de julho de 2021. Os dados foram agrupados por mês para cálculo das taxas brutas (por 100 000 habitantes) e avaliação das tendências temporais das unidades da federação e de suas capitais. As modificações significativas nas tendências tem- porais foram analisadas pelo método de regressão por joinpoint. Resultados. Foram identificadas duas ondas de novos casos e óbitos. As unidades da federação com as maiores taxas de incidência foram Amapá, Rio Grande do Norte, Rondônia e Roraima; Amazonas e Rondônia tiveram as maiores taxas de mortalidade. Em geral, as taxas de incidência e mortalidade foram piores na segunda onda. Na primeira onda, a média de meses até o início de uma redução de casos novos foi maior nas capitais, enquanto na segunda onda, o início da redução demorou mais nos estados. Quanto aos óbitos, as capitais necessitaram de menos tempo para apresentar redução tanto na primeira quanto na segunda onda. Conclusão. A heterogeneidade regional detectada reforça a ideia de que a incidência e a mortalidade por COVID-19 estão associadas a fatores políticos, geográficos, culturais, sociais e econômicos.

[ABSTRACT]. Objective. To analyze the incidence and mortality trends from COVID-19 in Brazil as well as in federation units and their capitals. Method. An ecological study was performed using COVID-19 incidence and mortality data covering the period from 25 February 2020 (first case recorded in Brazil) to 31 July 2021. Data were grouped by month for calculation of crude rates (by 100 000 population) and assessment of time trends in federation units and capitals. Significant changes in time trends were analyzed by joinpoint regression. Results. Two waves of new cases and deaths were identified. The highest incidence rates were recorded in the states of Amapá, Rio Grande do Norte, Rondônia, and Roraima. The states of Amazonas and Rondônia had the highest mortality rates. In general, incidence and mortality rates were worse in the second wave. In the first wave, the mean number of months until the onset of reduction in new cases was higher in capitals, whe- reas in the second wave the onset of reduction in new cases took longer in the federation units. The decline in mortality began earlier in capital cities in both waves. Conclusion. The regional differences detected underscore the notion that COVID-19 incidence and mortality are associated with political, geographic, cultural, social, and economic factors.

[RESUMEN]. Objetivo. Analizar las tendencias de la incidencia de COVID-19 y la mortalidad por esta enfermedad en Brasil (unidades federativas y capitales). Método. Se realizó un estudio ecológico con datos sobre incidencia de COVID-19 y la mortalidad por esta enfermedad en el período comprendido entre el 25 de febrero del 2020 (fecha del primer caso notificado en Brasil) y el 31 de julio del 2021. Los datos se agruparon por mes para calcular las tasas brutas (por 100 000 habitantes) y evaluar las tendencias temporales observadas en las unidades federativas y sus capitales. Las modificaciones significativas en las tendencias temporales se analizaron con el método de regresión de punto de inflexión (joinpoint). Resultados. Se identificaron dos olas de casos nuevos y muertes. Las unidades federativas con las mayores tasas de incidencia fueron Amapá, Rio Grande do Norte, Rondônia y Roraima; Amazonas y Rondônia tuvieron las mayores tasas de mortalidad. En general, la incidencia y la mortalidad fueron peores en la segunda ola. En la primera ola, el promedio de meses transcurridos hasta que empezó a reducirse el número de casos nuevos fue mayor en las capitales, mientras que, en la segunda ola, fue mayor en los estados. En ambas olas, el número de muertes se redujo en menos tiempo en las capitales. Conclusión. La heterogeneidad regional detectada refuerza la idea de que la incidencia de la COVID-19 y la mortalidad por esta enfermedad guardan relación con factores políticos, geográficos, culturales, sociales y económicos.

Expression of a Tumor Stem Cell Marker (Aldehyde Dehydrogenase 1-ALDH1) in Benign Epithelial Odontogenic Lesions.

The morphological diversity and different biological behaviors of human lesions has been attributed to the presence of cells with stem cell (SC) characteristics. Among SC markers, ALDH1 has been used in studies investigating different neoplasms and high expression of this marker was associated with clinicopathological features and prognosis in some groups. The aim of this study was to analyze the presence and distribution of SCs based on the expression of ALDH1 in epithelial odontogenic cysts and tumors. The sample consisted of 80 cases (20 dentigerous cysts (DCs), 20 odontogenic keratocysts (OKCs), 20 ameloblastomas (AMs), and 20 adenomatoid odontogenic tumors (AOTs). An immunoreactivity score was obtained from the percentage of positive cells and intensity of immunostaining. A level of 5% (p < 0.05) was adopted for the statistical tests. Immunoexpression of ALDH1 was observed in cytoplasm and nucleus-cytoplasm. The median scores indicated significantly higher expression in OKCs and DCs compared to AMs (p < 0.0001) and AOTs (p < 0.0001). In the tumor stroma and cystic capsule, immunoreactivity was detected in all odontogenic cysts studied and in 85% and 90% of AMs and AOTs, respectively. The expression of ALDH1 suggests the presence of SCs in the odontogenic lesions studied. Epithelial immunoexpression was higher in odontogenic cysts than in odontogenic tumors.

ALDH1 expression and potential clinical implications in chronic inflammatory periapical lesions.

Aldehyde dehydrogenase 1 (ALDH-1) is a marker of stem cells in a variety of diseases, but its role in individuals with chronic inflammatory periapical lesions remains unknown. The aim of this study was to investigate the presence of cells with a stem cell profile based on the immunoexpression of ALDH-1 in periapical granulomas (PGs) and radicular cysts (RCs). A total of 51 cases of periapical lesions (25 PGs and 26 RCs) were subjected to immunohistochemical study. The anti-ALDH-1 antibody was applied using the immunoperoxidase technique. An immunoexpression score (intensity vs. percentage of cells) was used, with the cases being classified as low expression (score: 0 to 4) and high expression (score: 6 to 9). The Chi-square test was used with a 5% level of significance. Immunoexpression of ALDH-1 was detected in all cases of PGs and RCs. In PG cases, the expression was diffuse in connective tissue cells, with most cases exhibiting high expression (n = 18; 69.2%), while in RC cases the expression revealed focal distribution in cells of the capsule and epithelial cells of the cystic lining, with most cases classified as low expression (n = 18; 72%). Significant differences in the expression scores of ALDH-1 were observed in PGs (p = 0.003). The variable expression of ALDH-1 suggests the presence of cells with stem cell profiles in PGs and RCs. These findings suggest that periapical tissues infiltrated by chronic inflammation can recruit important cells for the repair or evolution of periapical lesions.

COVID-19 no Brasil: tendências, desafios e perspectivas após 18 meses de pandemia / COVID-19 in Brazil: trends, challenges, and perspectives after 18 months of the pandemic / COVID-19 en Brasil: tendencias, desafíos y perspectivas después de 18 meses de pandemia

RESUMO Objetivo. Analisar as tendências de incidência e mortalidade por COVID-19 no Brasil, nas unidades da federação e nas capitais. Método. Realizou-se um estudo ecológico com dados de incidência e de mortalidade por COVID-19 referentes ao período de 25 de fevereiro de 2020 (primeiro caso notificado no Brasil) a 31 de julho de 2021. Os dados foram agrupados por mês para cálculo das taxas brutas (por 100 000 habitantes) e avaliação das tendências temporais das unidades da federação e de suas capitais. As modificações significativas nas tendências temporais foram analisadas pelo método de regressão por joinpoint. Resultados. Foram identificadas duas ondas de novos casos e óbitos. As unidades da federação com as maiores taxas de incidência foram Amapá, Rio Grande do Norte, Rondônia e Roraima; Amazonas e Rondônia tiveram as maiores taxas de mortalidade. Em geral, as taxas de incidência e mortalidade foram piores na segunda onda. Na primeira onda, a média de meses até o início de uma redução de casos novos foi maior nas capitais, enquanto na segunda onda, o início da redução demorou mais nos estados. Quanto aos óbitos, as capitais necessitaram de menos tempo para apresentar redução tanto na primeira quanto na segunda onda. Conclusão. A heterogeneidade regional detectada reforça a ideia de que a incidência e a mortalidade por COVID-19 estão associadas a fatores políticos, geográficos, culturais, sociais e econômicos.

ABSTRACT Objective. To analyze the incidence and mortality trends from COVID-19 in Brazil as well as in federation units and their capitals. Method. An ecological study was performed using COVID-19 incidence and mortality data covering the period from 25 February 2020 (first case recorded in Brazil) to 31 July 2021. Data were grouped by month for calculation of crude rates (by 100 000 population) and assessment of time trends in federation units and capitals. Significant changes in time trends were analyzed by joinpoint regression. Results. Two waves of new cases and deaths were identified. The highest incidence rates were recorded in the states of Amapá, Rio Grande do Norte, Rondônia, and Roraima. The states of Amazonas and Rondônia had the highest mortality rates. In general, incidence and mortality rates were worse in the second wave. In the first wave, the mean number of months until the onset of reduction in new cases was higher in capitals, whereas in the second wave the onset of reduction in new cases took longer in the federation units. The decline in mortality began earlier in capital cities in both waves. Conclusion. The regional differences detected underscore the notion that COVID-19 incidence and mortality are associated with political, geographic, cultural, social, and economic factors.

RESUMEN Objetivo. Analizar las tendencias de la incidencia de COVID-19 y la mortalidad por esta enfermedad en Brasil (unidades federativas y capitales). Método. Se realizó un estudio ecológico con datos sobre incidencia de COVID-19 y la mortalidad por esta enfermedad en el período comprendido entre el 25 de febrero del 2020 (fecha del primer caso notificado en Brasil) y el 31 de julio del 2021. Los datos se agruparon por mes para calcular las tasas brutas (por 100 000 habitantes) y evaluar las tendencias temporales observadas en las unidades federativas y sus capitales. Las modificaciones significativas en las tendencias temporales se analizaron con el método de regresión de punto de inflexión (joinpoint). Resultados. Se identificaron dos olas de casos nuevos y muertes. Las unidades federativas con las mayores tasas de incidencia fueron Amapá, Rio Grande do Norte, Rondônia y Roraima; Amazonas y Rondônia tuvieron las mayores tasas de mortalidad. En general, la incidencia y la mortalidad fueron peores en la segunda ola. En la primera ola, el promedio de meses transcurridos hasta que empezó a reducirse el número de casos nuevos fue mayor en las capitales, mientras que, en la segunda ola, fue mayor en los estados. En ambas olas, el número de muertes se redujo en menos tiempo en las capitales. Conclusión. La heterogeneidad regional detectada refuerza la idea de que la incidencia de la COVID-19 y la mortalidad por esta enfermedad guardan relación con factores políticos, geográficos, culturales, sociales y económicos.

ALDH1 expression and potential clinical implications in chronic inflammatory periapical lesions

Abstract: Aldehyde dehydrogenase 1 (ALDH-1) is a marker of stem cells in a variety of diseases, but its role in individuals with chronic inflammatory periapical lesions remains unknown. The aim of this study was to investigate the presence of cells with a stem cell profile based on the immunoexpression of ALDH-1 in periapical granulomas (PGs) and radicular cysts (RCs). A total of 51 cases of periapical lesions (25 PGs and 26 RCs) were subjected to immunohistochemical study. The anti-ALDH-1 antibody was applied using the immunoperoxidase technique. An immunoexpression score (intensity vs. percentage of cells) was used, with the cases being classified as low expression (score: 0 to 4) and high expression (score: 6 to 9). The Chi-square test was used with a 5% level of significance. Immunoexpression of ALDH-1 was detected in all cases of PGs and RCs. In PG cases, the expression was diffuse in connective tissue cells, with most cases exhibiting high expression (n = 18; 69.2%), while in RC cases the expression revealed focal distribution in cells of the capsule and epithelial cells of the cystic lining, with most cases classified as low expression (n = 18; 72%). Significant differences in the expression scores of ALDH-1 were observed in PGs (p = 0.003). The variable expression of ALDH-1 suggests the presence of cells with stem cell profiles in PGs and RCs. These findings suggest that periapical tissues infiltrated by chronic inflammation can recruit important cells for the repair or evolution of periapical lesions.

Morphological analysis and immunohistochemical expression in restorations with self-adhesive resin: A randomized split-mouth design-controlled study.

BACKGROUND: To evaluate the morphology and immunohistochemical expression of MMP-9, TIMP-3, COL-I, TNF-alfa and COX-2 in the dentinopulp complex of restorations with self adhesive composite (Vertise Flow/Kerr) compared with conventional resin composite with self-etching adhesive (Filtek Z250/3M ESPE and Clearfil SE Bond/Kuraray-Noritake). MATERIAL AND METHODS: A randomized, controlled, double-blind, split-mouth, two-arm clinical trial was conducted. Twenty-seven volunteers with third molars indicated for extraction received two deep class I restorations, one with each material. The morphology and immunohistochemical expression were measured at 15 days after the restorative procesures. The data were submitted to the Fisher`s Exct test (α=0.05). RESULTS: Through morphological analysis, a slight disorganization of the odontoblastic layer was visualized, along with a slight inflammatory infiltrate in the VERT and CSEB groups (p< 0.05). In immunohistochemical analysis, TNF-alpha, MMP-9, TIMP-3 and COX-2 demonstrated more cases of positive pulp labeling. CONCLUSIONS: Self-adhesive resin composite and conventional resin composite with a self-etching bonding agent promoted slight alterations in the dentin-pulp complex, indicating a repair ability and reversibility of the inflammatory process against aggressions of the adhesive restorative procedure. Key words:Immunohistochemistry, inflammation, randomized clinical trial, self-adhering composite, dentistry.

Incidence and profile of benign epithelial tumors of salivary glands from a single center in Northeast of Brazil

BACKGROUND: Benign tumors of the salivary glands are a group of lesions with varied histopathological and clinical spectrum. The aim was to determine the incidence and clinicopathological characteristics of benign salivary gland neoplasms diagnosed between 2007 and 2016 in a single center located in northeastern Brazil. MATERIAL AND METHODS: Records regarding sex, age, anatomical location, histopathological subtype and treatment were retrieved, and data were analyzed using the Stata/IC software (version 12.0). RESULTS: There were above 7,100 cases of neoplasms in the head and neck region, of which 403 corresponded to salivary gland neoplasms. Of these, 238 (59%) were benign, being pleomorphic adenoma (PA) the most frequent neoplasm (n=178; 74.8%), followed by Warthin's tumor (WT) (n=23; 9.7%). Overall, most cases occurred in females (n=136; 57.1%) and age ranged from 11 to 83 years. The parotid gland (n=188; 79%) was the most common anatomical site, and all patients were treated by surgical excision. Of the cases diagnosed as PA, malignant transformation to carcinoma ex-pleomorphic adenoma (CAEXPA) occurred in 7 (3.9%) cases. CONCLUSIONS: The present study confirmed the clinical and demographic profile of benign salivary gland neoplasms, which contributes to the continuous knowledge of current data about these lesions

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A rare case of a metastatic giant cell-rich osteosarcoma of the mandible: Update and differential diagnostic considerations.

A metastatic giant cell-rich osteosarcoma (GCRO) to the jaws is an exceedingly rare neoplasm. To date, fewer than 10 cases have been reported in the English language literature. In this article, we describe an additional case of a metastatic GCRO that presented the diagnostic challenge of a painless mass in the posterior mandible of a 19-year-old girl who exhibited rapid and aggressive local growth. The lesion was confirmed radiologically as an ill-defined expansive osteolytic mass showing cortical perforation. Microscopically, the presence of osteoclast-like giant cells permeated with atypical oval and rounded mesenchymal cells in a fibrovascular stroma, cellular atypia, and scarce osteoid formation were observed. Immunohistochemistry revealed the Ki-67 proliferative index in 50% of positive cells, positivity for vimentin and CD68, as well as scarce positivity for CDK4. The patient's medical history involved a GCRO in the proximal ulna. This report highlights the aggressive behavior of GCRO and its high capacity for metastasis to different parts of the body. Clinicians, pathologists, and surgeons should be aware of the giant cell-rich variant of osteosarcoma of the jaws, an imminent "wolf in a sheep's skin", because its indolent but unrelenting growth and dissemination, with radiographic and histologic characteristics that may represent a diagnostic pitfall regarding aggressive central giant cell lesions of the jaws.

Prognostic Factors and Survival in Adenoid Cystic Carcinoma of the Head and Neck: A Retrospective Clinical and Histopathological Analysis of Patients Seen at a Cancer Center.

Adenoid cystic carcinoma (AdCC) is a rare malignancy that accounts for approximately 1% of all head and neck cancers. This neoplasm is characterized by slow but often relentless growth and dissemination. Our aim was to retrospectively evaluate the clinical-pathological features of patients diagnosed with head and neck AdCC and to identify possible prognostic factors. This retrospective observational study analyzed 87 cases of AdCC of the head and neck. Clinical parameters (tumor size, lymph node and distant metastasis, clinical stage, and survival) were obtained from the records. Survival curves were constructed using the Kaplan-Meier method. A p value ≤ 0.05 was considered significant. There was a slight predominance of cases diagnosed in female patients (54%). The mean age at diagnosis was 51.5 years. Analysis using Cox's proportional hazards model considering 10-year disease-specific survival identified histologic pattern and presence of perineural invasion as independent prognostic variables. Primary tumor size and distant metastasis were prognostic predictors of 5- and 10-year disease-free survival. Detailed analysis of the association between clinical-pathological parameters and prognosis can assist professionals with cancer treatment planning and adequate patient management. Considering the long-term aggressive behavior of AdCC, rigorous patient follow-up is important to identify possible locoregional or distant recurrences.

DNA base excision repair and nucleotide excision repair proteins in malignant salivary gland tumors.

OBJECTIVE: To analyze the immunohistochemical expression of the base excision repair (BER) proteins apurinic/apyrimidinic endonuclease 1 (APE1) and X-ray repair cross-complementing protein 1 (XRCC1) and nucleotide excision repair (NER) protein xeroderma pigmentosum group F (XPF) in malignant salivary gland tumors (MSGTs). DESIGN: Sixty-two cases of MSGTs were selected, including 14 acinic cell carcinomas (AcCC), 15 polymorphous adenocarcinomas (PAC), 16 adenoid cystic carcinomas (ACC), and 17 mucoepidermoid carcinomas (MEC). The specimens were submitted to quantitative immunohistochemical analysis. RESULTS: All MSGTs exhibited nuclear or nucleo-cytoplasmic immunostaining of APE1, XRCC1 and XPF, with a high percentage of positive cells (median = 78.31, 70.48 and 75.46, respectively). XRCC1 expression was higher in PAC compared to MEC (p = 0.032). Nuclear APE1 immunostaining was significantly higher than nucleo-cytoplasmic expression in the selected MSGTs (p < 0.0001). APE1 expression was significantly associated with T1-T2 tumors in ACC (p = 0.006). Increased expression of XPF was associated with age older than 60 years in MEC (p = 0.015) and with ACC involving the minor salivary gland (p = 0.012), while a lower expression was found in AcCC and ACC patients treated by surgery combined with adjuvant therapy (p = 0.036 and p = 0.020, respectively). Low expression of XRCC1 in the nucleus (p = 0.028) and concomitant expression of this protein in the nucleus/cytoplasm were associated with a lower overall 5-year survival rate (p = 0.017). CONCLUSIONS: This study showed that BER and NER proteins evaluated are highly expressed in the MSGTs studied, indicating mechanisms of genotoxic control in these tumors. In addition, the dysregulation of XRCC1 expression was a prognostic predictor in MSGTs analyzed.

Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma

Abstract Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.

Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma.

Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.

Increased expression of ALDH-1 is associated with clinical parameters of salivary glands neoplasms.

The enzyme aldehyde dehydrogenase-1 (ALDH-1) is a known putative tumour stem cells (TSC) marker, and these cells are implicated in carcinogenesis and progression of human neoplasms. We aimed to evaluate ALDH-1 expression in benign and malignant salivary gland neoplasms and its clinicopathological and prognostic significance. Expression of ALDH-1 was investigated by immunohistochemistry and confirmed by Western Blot analysis in 154 salivary gland neoplasms (103 malignant and 51 benign neoplasms). The expression was identified in the parenchyma of malignant (n = 88; 85.6%) and benign (100%) neoplasms. Overall, expression in the parenchyma varied considerably and was not associated with clinical parameters in most malignant neoplasms, however, a high expression in mucoepidermoid carcinomas (MEC) was associated with advanced pathological TNM stage (p = 0.047). The presence of ALDH-1 in stromal cells of malignant neoplasms (n = 67; 65.0%) was associated with lymph node metastasis (p = 0.032), tumour recurrence (p = 0.006) and death (p = 0.013). Overall and disease-free survival in 5 and 10 years was lower in patients with diagnosis of adenoid cystic carcinoma, tumour recurrence, advanced staging, and presence of ALDH-1 in the stroma. When adjusted by multivariate analysis, advanced staging and stromal expression were independent prognostic factors affecting disease-free survival. Our findings provide evidence that cells characterized as TSC in the parenchyma and stroma are differentially present among the different types of neoplasms studied and may be related to tumourigenesis, biological behaviour and persistence capacity of malignant tumours of the salivary gland.

Teratocarcinoma-derived growth factor-1 (Cripto-1) is overexpressed in epithelial odontogenic lesions displaying more aggressive behaviour.

PURPOSE: Cripto-1 also known as teratoma-derived growth factor 1 (TDGF-1) belongs to the EGF-CFC family of growth factor-like molecules. Cripto-1 is involved with embryonic development and not expressed in adult tissue, but some tumours are accompanied by reactivation. METHODS: The aim of this study was to evaluate the immunohistochemical expression of Cripto-1 in most common odontogenic cysts and tumours. Thirty ameloblastomas, 30 keratocysts, 30 dentigerous cysts and two ameloblastic carcinomas were evaluated using the polymeric immunoperoxidase technique. Immunohistochemical expressions were analysed by the IRS (immunoreactive score). Statistical analyses were performed by the Kruskal-Wallis and Mann-Whitney tests (p ≤ 0.05). RESULTS: Age ranged from 9 to 75 years old, with a prevalence of females (n = 49/53.3%). The mandible was the most affected anatomical site (n = 69/75.0%). Cripto-1 immunoexpression was observed in all ameloblastoma, keratocyst and ameloblastic carcinoma cases, although nine dentigerous cyst cases (30%) were negative. Expression scores were higher in ameloblastoma, keratocyst and ameloblastic carcinoma cases (median ranging from 8 to 11) when compared with dentigerous cyst cases (median of 2), with a statistically significant difference (p < 0.001). CONCLUSIONS: Cripto-1 is critically important in the progression of several tumours since it is related to significant cell survival and differentiation pathways. The high expression of Cripto-1 in more aggressive odontogenic lesions suggests that this molecule may be involved in the activation of important pathways related to the etiopathogenesis of these lesions.