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.

[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.

Analyses of VEGFC/VEGF-D expressions, density and endothelial lymphatic proliferation in salivary gland neoplasms.

OBJECTIVE: The aim of this study was to assess vascular endothelial growth factor C (VEGF-C) and VEGF-D expressions, tumor lymphatic density (D2-40) and endothelial lymphatic proliferation (D2-40/Ki-67 double labeling) in a series of salivary gland neoplasm cases. MATERIALS AND METHODS: Twenty pleomorphic adenomas (PA), 20 adenoid cystic carcinomas (ACC) and 20 mucoepidermoid carcinomas (MEC) were assessed, as well as 10 normal minor salivary gland (SG) tissues for comparison. RESULTS: All cases presented positive VEGF-C expression in the peritumoral and intratumoral regions, and no differences in immunoexpression were detected between groups. However, the ACC group presented a significant difference in VEGF-C immunoexpression according to the predominant histological pattern. Most cases presented poor VEGF-D labeling in the peritumoral and intratumoral regions. Concerning peritumoral, intratumoral and total lymphatic endothelial density, the assessed groups revealed an increasing gradient, with lower values for PA, followed by MEC and ACC. CONCLUSION: No correlation was detected between VEGF-C and VEGF-D immunoexpression in relation to lymphatic tumor density and endothelial lymphatic proliferation. Western blotting (WB) revealed no difference between VEGF-C and VEGF-D expression among the lesions, corroborating the immunohistochemistry findings.

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.

A Brazilian multicentre study of 2,497 isolated cases of odontogenic keratocysts.

We present the frequency of cases of isolated odontogenic keratocysts submitted to microscopic examination at 10 Brazilian referral centres in Oral and Maxillofacial Pathology. In a retrospective (1953-2017) analysis, data on clinicoradiographic features and treatment of these lesions were collected and analysed descriptively. Among the 258,867 cases retrieved, 2,497 (0.96%) were isolated odontogenic keratocysts. In summary, an overview of individuals affected with isolated odontogenic keratocysts is reported herein. This lesion showed predilection for the posterior mandible of young adult men.

The occurrence and pattern of head and neck sarcomas: a comprehensive cancer center experience.

PURPOSE: This study aimed to analyze the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas diagnosed in a reference center in the Brazilian Northeast. MATERIALS AND METHODS: This retrospective cohort study reviewed the clinical records of patients with head and neck sarcomas. Epidemiologic data consisted in clinical location, age, gender, histopathological diagnosis, clinical TNM staging and treatment. Outcome variables were local recurrence and survival. The statistical analyses were performed by a binary logistic regression analysis. The survival analysis was assessed through the Kaplan-Meier curve. RESULTS: Sixty-nine patients with head and neck sarcomas (male 39; female 30) were analyzed. The most common histologic subtypes were rhabdomyosarcoma, dermatofibrosarcoma, and pleomorphic sarcoma. The mean age of the patients at the time of diagnosis was 38.1 years old. A total of 31 patient died (sarcoma-related death) up to the end of the follow-up, with a mean follow-up rate of 1.63 years. A multivariate analysis revealed that anatomical site, treatment modality, histopathological diagnosis, and clinical stage of the disease were associated with specific survival, reaching statistical significance. CONCLUSION: This study demonstrates the impact of important clinical-pathological parameters on the overall prognosis of head and neck sarcomas.

Neoplasms and non-neoplastic pathologies in the oral and maxillofacial regions in children and adolescents of a Brazilian population.

BACKGROUND: Few studies regarding the distribution of pediatric oral diseases are available. Thus, the aim of this study was to investigate the incidence and demographic profile of neoplasms and non-neoplastic lesions among children and adolescents (0-19 years old). METHODS: A retrospective descriptive cross-sectional study was performed and data regarding gender, age, anatomical location, and histopathological diagnosis were collected and categorized. Biopsy records were obtained from the archives of a Brazilian referral center between 1980 and 2016. RESULTS: A total of 2.114 pediatric patient biopsy records were analyzed, where most cases were diagnosed in patients aged 10 to 19 years old (80.7%). Females were more affected (n = 1180) and the lip (n = 507) was the most common anatomical site. Reactive and inflammatory lesions (n = 942) were the most prevalent non-neoplastic pathologies, followed by cysts (n = 308). Benign neoplasms were the most frequent among neoplasms (n = 346) and malignant cases were very rare (n = 11). CONCLUSIONS: An increase in the prevalence of lesions in the second decade of life was observed, where reactive and inflammatory lesions, cysts, and benign neoplasms were most frequent. CLINICAL RELEVANCE: Biopsy data allows for the real characterization of the incidence of oral and maxillofacial lesions and, thus, permits Brazilian dentists and pediatricians to diagnose these diseases.

Odontogenic myxoma: A 63-year retrospective multicenter study of 85 cases in a Brazil population and a review of 999 cases from literature.

BACKGROUND: Odontogenic myxoma (OM) is an uncommon neoplasm of the jaws. Considering the importance of defining the relative incidence and demographic profile of these lesions in South America, the aim of this study was to analyze the clinical and imagiological features of OM from three South American oral pathology services and to discuss these findings in light of the literature. METHODS: Data regarding age, gender, anatomic site, and imagiological features from 85 cases of OM were collected. Additionally, we did a review of OM studies published in three electronic databases. RESULTS: Among 63 450 oral biopsies, 1178 (1.85%) were odontogenic tumors (World Health Organization - 2017), of which 85 (7.21%) met the criteria of OM. The mean age was 30.7 years (range: 10-61 years; SD: 12.22). Forty-five (52.9%) cases occurred in females and 40 (47.1%) in males (ratio: 1:1.12). Maxilla was affected in 44 cases (53%) and mandible in 39 (47%). Of the 41 informed cases (48.2%), all of them were radiolucent lesions. The literature review indicated a majority of mean ages in third decade and a predilection for females, mandible, and multilocular radiolucent lesions. CONCLUSIONS: The features of OM samples have strong similarity to that reported in studies from other continents. It is possible to infer that geographic variation does not help to explain some differences observed in the clinical features of OM.

Differential expression of cyclooxygenase-2 and cyclin D1 in salivary gland tumors.

PURPOSE: Salivary gland tumors are complex and have a great histomorphological diversity; more than 30 histological subtypes are currently described and the study of proteins that help understand and differentiate these tumors is essential. We aimed to analyze the immunoexpression of cyclooxygenase-2 (COX-2) and cyclin D1 proteins in pleomorphic adenomas (PA), mucoepidermoid carcinomas (MEC) and adenoid cystic carcinomas (AdCC) of salivary glands. METHODS: A total of 38 PA, 12 AdCC and 12 MEC underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were analyzed semi-quantitatively. For statistical analysis, a significance level was set at p ≤ 0.05. RESULTS: Overall, these tumors were more prevalent in women (n = 37). The mean age of these patients was 58-year-old and the parotid gland was the most affected anatomic site (n = 33). All cases of AdCC and MEC showed immunopositivity to cyclin D1; however, 39.5% of the PAs were negative (p < 0.001). Regarding COX-2 immunoexpression, we observed that all cases of CME were positive, whereas 60.5% of the PA and 75% of the CAC analyzed were completely negative (p = 0.042). CONCLUSIONS: The overexpression of COX-2, observed only in MEC, emphasizes that salivary gland tumors have different profiles. Cyclin D1 is more immunoexpressed in malignant tumors. Together, these immunohistochemical findings may be useful in differentiating the studied tumors.

Cripto-1 is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland.

INTRODUCTION: Cripto-1 is a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family. Besides being critical for early embryonic development, Cripto-1 is also associated with the development and behavior of several cancers. OBJECTIVE: We analyzed the immunoexpression of Cripto-1 in normal salivary glands (NSGs), pleomorphic adenomas (PAs), and carcinoma ex pleomorphic adenomas (CaExPAs) of salivary glands. METHODS: A total of 12 NSGs, 16 PAs and 12 CaExPAs underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were evaluated semiquantitatively (scores 0-3). For statistical analysis, Mann-Whitney and Kruskal-Wallis tests were performed and a significance level of p ≤ 0.05 was established. RESULTS: Most CaExPAs (n = 10) were strong positive (score 3) for Cripto-1, and only three cases of PAs and two specimens of NSGs exhibited some expression (score 1), being statistically significant these findings (p < 0.001). No difference between the expression of this protein in tumors of major and minor salivary glands was observed. Overexpression was found mainly in cases of CaExPAs with invasive growth (n = 8) when compared to those without capsular invasion (intracapsular pattern) (p = 0.036). Patients with or without lymph node metastasis showed no difference (p = 0.294). CONCLUSION: The results revealed a significantly higher expression of Cripto-1 in CaExPA compared to PA and NSG, suggesting this protein is possibly deregulated in PA malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior (invasive growth) in salivary gland tumors.

Apurinic/apyrimidinic endonuclease 1 (APE1) is overexpressed in malignant transformation of salivary gland pleomorphic adenoma.

DNA repair systems play a critical role in protecting the human genome against cumulative damage. The apurinic/apyrimidinic endonuclease 1 is a protein involved in DNA base excision repair and its expression still needs to be investigated in salivary gland tumors. The objective of this study is to analyze the immunoexpression of apurinic/apyrimidinic endonuclease 1 in pleomorphic adenomas and carcinomas ex pleomorphic adenomas of the salivary glands. A total of 33 pleomorphic adenomas and 16 carcinomas ex pleomorphic adenomas of the salivary glands underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were analyzed quantitatively. For statistical analysis, Mann-Whitney test was performed and a significance level was set at p ≤ 0.05. All analyzed tumors (n = 49) were positive for apurinic/apyrimidinic endonuclease 1. However, there was a higher median expression in carcinomas ex pleomorphic adenomas (p < 0.001). There was no difference between this protein immunoexpression and tumors of major or minor salivary gland. Overexpression was found mainly in cases of carcinomas ex pleomorphic adenomas with lymph node metastasis (p = 0.002) and invasive growth (p = 0.003), when compared to cases without metastasis and without capsular invasion (intracapsular pattern). Our findings revealed that apurinic/apyrimidinic endonuclease 1 is downregulated in pleomorphic adenomas and overexpressed in carcinomas ex pleomorphic adenomas, suggesting that this protein is possibly deregulated in pleomorphic adenoma malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior in carcinomas ex pleomorphic adenomas, which suggests that this protein may represent a prognostic biomarker in the studied salivary gland tumors.

Clinicopathological and cell proliferation evaluation of ameloblastomas and keratocystic odontogenic tumors: a 10 year retrospective study.

Odontogenic tumors (OTs) are important lesions of the gnathic bones due to their clinicopathological heterogeneity and variable biological behavior; therefore, epidemiological studies are needed to outline the incidence and behavior of these tumors. To evaluate the incidence and epidemiological profile of ameloblastoma (AMB) and keratocystic odontogenic tumor (KCOT) from an oral pathology service, and correlate morphological findings of these tumors with the immunoexpression of a cellular proliferation marker (Ki-67), a retrospective study (2002-2012) was conducted to characterize demographic, clinical, radiological, and morphological data of AMBs and KCOTs. Then, a representative sample composed of 49 cases of each tumor was selected to perform immunohistochemical (IHC) analysis of Ki-67 through the streptavidin biotin peroxidase technique. For statistical analysis, we used Fisher's exact test (p < 0.05). A total of 279 OTs were found in the service, in which 91 (32.6%) were AMB and 98 (35 %) were KCOT. Most cases occurred in white women, and the average age of patients with AMB and KCOT was 32 and 33 years, respectively. The maxilla-mandible ratio was 1:6 and 1:3.6 for AMB and KCOT, respectively. Regarding IHC analysis, AMB and KCOT had similar levels of cellular proliferation. However, KCOTs with intense inflammation showed higher Ki-67 expression (p < 0.001). Recurrent cases had similar Ki-67 immunoexpression. The demographic profile of the studied tumors corroborates with data reported in the literature, and the levels of cellular proliferation were similar in both tumors, although the inflammation seems to induce a differential proliferative behavior in KCOT.

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.

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.

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.

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.

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.

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.

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.