Oral manifestations of amyloidosis and the diagnostic applicability of oral tissue biopsy.

BACKGROUND: Amyloidosis exhibits a variable spectrum of systemic signs and oral manifestations that can be difficult to diagnose. This study aimed to characterize the clinical, demographic, and microscopic features of amyloidosis in the oral cavity. METHODS: This collaborative study involved three Brazilian oral pathology centers and described cases with a confirmed diagnosis of amyloidosis on available oral tissue biopsies. Clinical data were obtained from medical records. H&E, Congo-red, and immunohistochemically stained slides were analyzed. RESULTS: Twenty-six oral biopsies from 23 individuals (65.2% males; mean age: 59.6 years) were included. Oral involvement was the first sign of the disease in 67.0% of cases. Two patients had no clinical manifestation in the oral mucosa, although the histological analysis confirmed amyloid deposition. Amyloid deposits were distributed in perivascular (88.0%), periacinar and periductal (80.0%), perineurial (80.0%), endoneurial (33.3%), perimuscular (88.2%), intramuscular (94.1%), and subepithelial (35.3%) sites as well as around fat cells (100.0%). Mild/moderate inflammation was found in 65.4% of cases and 23.1% had giant cells. CONCLUSIONS: Amyloid deposits were consistently found in oral tissues, exhibiting distinct deposition patterns. Oral biopsy is less invasive than internal organ biopsy and enables the reliable identification of amyloid deposits even in the absence of oral manifestations. These findings corroborate the relevance of oral biopsy for the diagnosis of amyloidosis.

Palatal Stent Following Tumor Ablative Surgery.

Mucoepidermoid carcinoma is one of the most prevalent malignant tumors of the salivary glands. Resection of this tumor can result in postsurgical morbidity, affecting the patient's quality of life and normal oral functioning. This study aimed to present a successful case of postsurgical rehabilitation following mucoepidermoid carcinoma resection in the palate. Following tumor ablative surgery, the 32-year-old patient experienced impairments in both speech and feeding due to the surgical wound. A protective stent that covered the entire extent of the palate and teeth was made. This esthetic device was fabricated in a single session and provided sealing and protection of the surgical site, ensuring comfort, functionality, and, consequently, a higher quality of life during the postoperative period. The simplicity and low cost of the custom palatal stent make it applicable for use in a diverse range of postsurgical oncology patients, providing protection for surgical wounds and reducing postoperative morbidity.

Subgemmal neurogenous plaque: a series of six cases and a literature overview.

The study aims to describe six subgemmal neurogenous plaque (SNP) cases and compile the previously available data on SNP. Searches on PubMed, Web of Science, Embase, Scopus, and a two-step study selection were performed to compile data from case reports/series of SNP published in English literature. Our six patients (range 29-63 years) had SNP in the posterior lateral border of the tongue. Four of them were associated with lymphoepithelial cysts. A total of 15 studies, comprising 116 patients, were included in this overview. There was a slight predilection for female patients (56.0%) in the 5th (22.4%) and the 7th (23.9%) decades. The lateral border of the tongue (66.4%) was the most common anatomical location. The major manifestation was nodule/papule. Histologically, the presence of taste buds (n = 40/ 34.5%), superficial neural plexus (n = 32/ 27.6%), deep nerve fascicles (n = 32/ 27.6%), ganglion cells (n = 41/ 35.3%), and lymphoid tissue (n = 22/ 19.0%) was mainly reported. Surgical removal was the primary approach, with a low recurrence rate. Although largely unknown, SNP is a regular and likely frequent structure located in the tongue. The findings emphasize the importance of describing clinicopathological patterns of SNP as a differential diagnosis of neural lesions that affect the tongue.

Mast cells in oral lichen planus and oral lichenoid lesions related to dental amalgam contact.

The aim of this study was to analyze the expression of mast cell markers toluidine blue, c-kit, and tryptase and presence of mononuclear inflammatory cells in oral lichen planus (OLP) and oral lichenoid lesions related to dental amalgam. Nineteen specimens of OLP, OLLC, and healthy oral mucosa were selected. Mononuclear inflammatory cells were analyzed. Histochemical and immunohistochemical analyses were performed using toluidine blue, anti-c-kit and anti-tryptase reagents, and the results were quantified in areas A and B of connective tissue. Mast cells of all OLP and OLLC samples were positive for toluidine blue, c-kit, and tryptase. The density of toluidine blue+, c-kit+ and tryptase+ mast cells was higher in tissue with OLP and OLLC compared with healthy controls (p < 0.05). No difference was noted in mast cells density between OLP and OLLC (p > 0.05). The density of tryptase+ mast cells was higher in the subepithelial region (area A) than the region below it (Area B) in OLLC (p = 0.047). The mononuclear inflammatory cell density was higher in OLLC compared to OLP, but without statistical significance (p > 0.05). A positive statistical correlation was found between mononuclear immune cells and density of c-kit+ and tryptase+ mast cells in OLP (r = 0.943 and r = 0.886, respectively). Our data demonstrate that the etiopathogenesis process of OLP and OLLC modulates the expansion and degranulation of mast cells; mast cells density, however, was similar between OLP and OLLC. The distribution of mast cells appears to vary along the lamina propria.

EZH2 immunoexpression in pleomorphic adenoma and adenoid cystic carcinoma and clinicopathological features.

The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy.

Can predictive factors determine the time to treatment initiation for oral and oropharyngeal cancer? A classification and regression tree analysis.

This ecological study aimed to identify the factors with the greatest power to discriminate the proportion of oral and oropharyngeal cancer (OOC) records with time to treatment initiation (TTI) within 30 days of diagnosis in Brazilian municipalities. A descriptive analysis was performed on the variables grouped into five dimensions related to patient characteristics, access to health services, support for cancer diagnosis, human resources, and socioeconomic characteristics of 3,218 Brazilian municipalities that registered at least one case of OOC in 2019. The Classification and Regression Trees (CART) technique was adopted to identify the explanatory variables with greater discriminatory power for the TTI response variable. There was a higher median percentage of records in the age group of 60 years or older. The median percentage of records with stage III and IV of the disease was 46.97%, and of records with chemotherapy, radiation, or both as the first treatment was 50%. The median percentage of people with private dental and health insurance was low. Up to 75% had no cancer diagnostic support services, and up to 50% of the municipalities had no specialist dentists. Most municipalities (49.4%) started treatment after more than 30 days. In the CART analysis, treatment with chemotherapy, radiotherapy, or both explained the highest TTI in all municipalities, and it was the most relevant for predicting TTI. The final model also included anatomical sites in the oral cavity and oropharynx and the number of computed tomography services per 100,000. There is a need to expand the availability of oncology services and human resources specialized in diagnosing and treating OOC in Brazilian municipalities for a timely TTI of OOC.

EZH2 immunoexpression in pleomorphic adenoma and adenoid cystic carcinoma and clinicopathological features

Abstract The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy.

Mast cells in oral lichen planus and oral lichenoid lesions related to dental amalgam contact

Abstract The aim of this study was to analyze the expression of mast cell markers toluidine blue, c-kit, and tryptase and presence of mononuclear inflammatory cells in oral lichen planus (OLP) and oral lichenoid lesions related to dental amalgam. Nineteen specimens of OLP, OLLC, and healthy oral mucosa were selected. Mononuclear inflammatory cells were analyzed. Histochemical and immunohistochemical analyses were performed using toluidine blue, anti-c-kit and anti-tryptase reagents, and the results were quantified in areas A and B of connective tissue. Mast cells of all OLP and OLLC samples were positive for toluidine blue, c-kit, and tryptase. The density of toluidine blue+, c-kit+ and tryptase+ mast cells was higher in tissue with OLP and OLLC compared with healthy controls (p < 0.05). No difference was noted in mast cells density between OLP and OLLC (p > 0.05). The density of tryptase+ mast cells was higher in the subepithelial region (area A) than the region below it (Area B) in OLLC (p = 0.047). The mononuclear inflammatory cell density was higher in OLLC compared to OLP, but without statistical significance (p > 0.05). A positive statistical correlation was found between mononuclear immune cells and density of c-kit+ and tryptase+ mast cells in OLP (r = 0.943 and r = 0.886, respectively). Our data demonstrate that the etiopathogenesis process of OLP and OLLC modulates the expansion and degranulation of mast cells; mast cells density, however, was similar between OLP and OLLC. The distribution of mast cells appears to vary along the lamina propria.

Effects of tobacco on the DNA of smokers and non-smokers affected by OSCC: systematic review and meta-analysis

Abstract Scientific evidence about genetic and molecular changes in oral squamous cell carcinoma (OSCC) among smokers and non-smokers is inconclusive. This systematic review and meta-analysis assessed the effects of tobacco on the DNA of individuals with OSCC based on protein mutations. Electronic searches were conducted on PubMed, Ovid, Web of Science, and Scopus to identify observational studies published up to January/2022. The Joanna Briggs Institute tool was used for the critical appraisal of studies. The certainty of the evidence was evaluated. Twenty-three studies assessing 4,060 individuals (2,967 smokers vs. 1,093 non-smokers) were included in this review. Fifteen groups of proteins/genes were investigated. Analysis of the quality of articles revealed low risk of bias in most studies. The certainty of the evidence was very low. The meta-analysis confirmed no significant difference between smokers and non-smokers with respect to damage to GSTM1 (OR: 0.60; 95%CI: 0.30-1.18), GSTT1 (OR: 1.18; 95%CI:0.49-2.83), hydrolase proteins (Ku70 and Ku80) (OR: 0.74; 95%CI: 0.18-3.05), and transferase proteins (GSTM1, GSTT1, GSTM3) (OR: 0.74; 95%CI: 0.47-1.18). Most of the studies included showed that smokers are more likely to exhibit genetic instability. However, the meta-analysis revealed that smokers do not necessarily have more genetic alterations in the DNA than non-smokers.

DNA damage-related proteins in smokers and non-smokers with oral cancer

Abstract: Tobacco smoking involves a high risk of human malignancies, including oral cancer, because it contains multiple carcinogens that cause genetic instability. Thus, a worse prognosis would be expected for cancer patients who are smokers. The aim of this study was to assess the DNA damage response through the expression of checkpoint kinase 2 (CHK2), H2A histone family member X (H2AX), and P53 among smokers and non-smokers with oral squamous cell carcinoma (OSCC). Associations between immunoexpression of proteins and clinicopathological data and histopathological grading were also analyzed. A total of 35 individuals (18 non-smokers and 17 smokers) with OSCC of the tongue and/or floor of the mouth were included. Immunohistochemistry for H2AX was conducted for the identification of double-strand breaks, CHK2, and P53 to evaluate the expression of this protein in cell cycle regulation. The sample consisted of 22 males and 13 females, with a mean age of 63.9±11.8 years. OSCC of non-smokers were well-differentiated tumors in 50% of the cases, and those of smokers were equally distributed into moderately differentiated and poorly differentiated tumors (35.3% each). Overall, 31 (88.6%) cases were CHK2-positive, 27 (77.1%) were H2AX-positive, and 23 (65.7%) were P53-positive, with no difference between smokers and non-smokers (p > 0.05). No association was found between proteins and clinicopathologic data (p > 0.05). Similarities in CHK2, H2AX, and P53 immunohistochemical staining patterns were observed between smokers and non-smokers, and immunoexpression was not associated with clinicopathological parameters. However, the findings indicated consistent expression of these proteins in OSCC.

Salivary molecules of bone remodeling and tissue repair after head and neck radiotherapy

Abstract Head and neck radiotherapy causes quantitative and qualitative changes in saliva. The objective of this case-control study was to evaluate the salivary biomarkers associated with bone remodeling and tissue repair in patients submitted to radiotherapy for head and neck cancer treatment, compared with non-irradiated individuals. Total unstimulated saliva was collected for ELISA assay analysis of receptor activator for nuclear factor κ B (RANK) and its ligand (RANK-L), osteoprotegerin, matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2, vascular endothelial growth factor, and epidermal growth factor. Statistics were performed, and revealed that salivary RANK (p = 0.0304), RANK-L (p = 0.0005), matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2 (p = 0.0067), vascular endothelial growth factor (p = 0.0060), and epidermal growth factor (p < 0.0001) were reduced in patients, compared with the control group. Osteoprotegerin did not differ between the groups (p = 0.3765). Salivary biomarkers did not differ according to radiotherapy completion time (p > 0.05). In conclusion, the lower output of the salivary molecules - essential for bone remodeling and tissue repair - may disrupt tissue homeostasis and play a role in the pathogenesis of the radiotherapy-induced deleterious effects in the oral cavity.

Chronic inflammatory periapical diseases: a Brazilian multicenter study of 10, 381 cases and literature review

Abstract The aim of this study was to investigate the epidemiological and clinical characteristics of chronic inflammatory periapical diseases in different regions of Brazil and to compare with data from the literature. A multicenter study was carried out in four Brazilian referral centers in oral diagnosis. Histopathological records were reviewed, and all cases diagnosed microscopically as periapical granuloma, radicular cyst, and periapical abscess were included. Demographic and clinical data were collected. Descriptive statistics and Pearson's chi-square test were performed. A total of 10,381 cases of chronic inflammatory periapical diseases were found (13.8% of 74,931 archived specimens) over a period of 65 years. Radicular cysts were the most common lesion (59.9%). Women (56.1%) with a mean age of 37.01 years old (range 13 to 100 ± 14.42) and people of white skin color (59.2%) were the most affected individuals by chronic inflammatory periapical diseases. The lesions were generally asymptomatic (28.1%), located in the maxilla (60.1%), and posterior region (49.8%). The radicular cysts were larger when compared to periapical granulomas (p < 0.001). The disagreement between the clinical and histopathological diagnoses was higher when the final diagnosis was a periapical granuloma (p < 0.001). Chronic inflammatory periapical diseases continue to be common lesions affecting mainly adults. This should be a consequence of the burden of untreated caries in permanent teeth. Women are more affected and radicular cyst was the most common lesion.

Diagnosing acquired syphilis through oral lesions: the 12 year experience of an Oral Medicine Center / Diagnosticando sífilis adquirida através de lesões orais: a experiência de 12 anos de um Centro de Medicina Oral

Abstract Introduction: A resurgence of syphilis in Brazil has been reported in recent years. Objective: With this in mind, the present study sought to investigate the frequency, demographics, and clinical characteristics of patients with acquired syphilis with oral involvement who received medical care at an Oral Medicine Reference Center in a Brazilian Public Hospital. Methods: A retrospective study, spanning a period of 12 years, was performed to identify changing trends in syphilis over time. Medical records from all patients diagnosed with acquired syphilis who received medical care at the Hospital's Oral Medicine Clinic from 2005 to 2016 were reviewed, and the demographic and clinical data were collected. Results: A total of 85 patients had been diagnosed with acquired syphilis, with a significant increase in the number of cases over the past 5 years. Patients ranged from 16 to 76 years of age, with a peak in the third and fourth decades. Forty-eight cases affected males (56.5%), while 37 cases affected females (43.5%). Most of the oral lesions appeared as unique ulcers or plaques, with the lips and tongue representing the most affected sites. All cases were positive for Venereal Disease Research Laboratory or Fluorescent Treponemal Antibody Absorption, and treatment was performed with Penicillin G benzathine in most cases (84.7%). Conclusion: The frequency of oral syphilis has been rising over time and oral lesions may well represent a diagnostic clue; therefore, oral health professionals must be made aware and properly trained in an attempt to develop a high degree of clinical suspicion in the diagnosis of syphilis.

Resumo Introdução: Um ressurgimento da sífilis no Brasil tem sido relatado nos últimos anos. Objetivo: Investigar a frequência, as características demográficas e clínicas dos pacientes com sífilis adquirida com envolvimento oral que receberam atendimento médico em um centro de referência em medicina oral em um hospital público brasileiro. Método: Estudo retrospectivo, abrangeu 12 anos, feito para identificar tendências de mudança na sífilis. Registros médicos de todos os pacientes diagnosticados com sífilis adquirida que receberam atendimento médico na clínica de medicina oral do hospital de 2005 a 2016 foram revisados e os dados demográficos e clínicos foram coletados. Resultados: Foram diagnosticas 85 pacientes com sífilis adquirida, com um aumento significativo no número de casos nos últimos 5 anos. A idade dos pacientes variou de 16 a 76 anos, com pico na terceira e quarta décadas; 48 casos eram do sexo masculino (56,5%) e 37 do sexo feminino (43,5%). A maioria das lesões orais apareceu como úlceras ou placas únicas, os lábios e a língua representaram os locais mais afetados. Todos os casos foram positivos para Venereal Disease Research Laboratory e Fluorescent Treponemal Antibody Absorption Test e o tratamento foi feito com penicilina G benzatina na maioria dos casos (84,7%). Conclusão: A frequência da sífilis oral tem aumentado com o tempo e as lesões orais podem representar uma pista diagnóstica; portanto, os profissionais de saúde bucal devem ser conscientizados e devidamente treinados na tentativa de desenvolver um alto grau de suspeição clínica no diagnóstico da sífilis.

Advanced carcinoma of the oropharynx: survival analysis comparing two treatment modalities

Abstract About 92,000 new cases of oropharynx carcinoma are expected to occur annually worldwide. There is no consensus about the best therapy for these advanced tumors. The objective of the present study was to evaluate overall and disease-free survival rates of patients with advanced oropharynx squamous cell carcinoma, comparing surgery + radiotherapy with chemotherapy + radiotherapy. Medical records of patients were reviewed. Previously treated tumors were excluded. Clinical, demographic and microscopic information was collected, and p16 staining was performed. Kaplan-Meier survival curves were plotted. Forty-seven cases were included, 41 men and 6 women, having a mean age of 56.3 years. Most patients were smokers (85.1%) and consumed alcohol (74.5%). Patients were stage III (21.3%) or IV (78.7%). Most lesions affected the base of the tongue (36.2%). Of the 23 cases available for p16 testing, 3 were positive (13.0%). There was no difference between the overall and the disease-free survival rates for the two treatment modalities (p>0.05), even when only resectable tumors were compared. Seventeen cases experienced recurrence (36.2%); 16 (34.0%) patients remained alive without disease; 15 (31.9%) died due to disease; 9 (19.2%) were recurrent at the last follow-up. The two treatment protocols were equally efficient in treating advanced oropharynx squamous cell carcinoma, since both promoted similar overall and disease-free survival rates. The results and interpretations related herein mostly regard "conventional" oropharyngeal squamous cell carcinomas, as opposed to HPV-associated tumors.

Oral Cancer: Socio-Spatial Analysis of a Brazilian Sample / Câncer Bucal: Análise Socioespacial de uma Amostra Brasileira / Cáncer Oral: Análisis Socioespacial de una Muestra Brasileña

Introduction:Socio-spatial measures are largely used in health research, but it is still unusual in oral cancer investigation. Objective: This study aims to describe the sociodemographic and clinical features of oral cancer and analyze the spatial distribution of the disease in relation to the neighborhood socioeconomic status including availability of health care centers.Method: Sociodemographic, clinical and histopathologic data were collected from patients treated from 2005 to 2015. Descriptive data analyses of all variables were performed. The spatial analysis was carried out through the program R. Geographic distribution of patients' home addresses was analyzed using Ripley's K function and Kernel maps. The socio-spatial vulnerability was defined by household income and home adequacy. Results: Of the 127 patients included, the majority were males (76.4%), Caucasian or Brown (82.7%), married (35.4%), with low educational level (71.6%) and mean age of 59.5 years. Cases were distributed in clusters characterized by lower median income and inadequate sanitary conditions. Primary health care centers were homogeneously distributed throughout the city. Conclusion: These oral cancer cases are concentrated in regions under relatively low socioeconomic conditions, and despite the homogeneous distribution of primary health care centers, it is not enough to promote access for patients and oral cancer remains being diagnosed late

Introdução: Medidas socioespaciais são amplamente utilizadas na pesquisa em saúde, mas ainda pouco exploradas em relação ao câncer de boca.Objetivo: Descrever as características sociodemográficas e clínicas do câncer de boca e analisar a distribuição espacial da doença em relação ao status socioeconômico do bairro, incluindo a disponibilidade de centros de saúde. Método: Foram coletados dados sociodemográficos, clínicos e histopatológicos dos pacientes atendidos no período de 2005 a 2015. Foram realizadas análises descritivas dos dados de todas as variáveis. A análise espacial foi realizada por meio do programa R. A distribuição geográfica dos endereços residenciais dos pacientes foi analisada usando a função K de Ripley e mapas de Kernel. A vulnerabilidade socioespacial foi definida pela renda familiar e adequação do domicílio. Resultados: Dos 127 pacientes incluídos, a maioria era do sexo masculino (76,4%), branca ou parda (82,7%), casada (35,4%), com baixa escolaridade (71,6%) e idade média de 59,5 anos. Os casos foram distribuídos em grupos caracterizados por menor renda mediana e condições sanitárias inadequadas. Conclusão: Os casos de câncer oral estão concentrados em regiões de baixa condição econômica. Embora os centros de atenção primária à saúde tenham sido homogeneamente distribuídos por toda a cidade, isso não é suficiente para promover o acesso dos pacientes e o câncer de boca continua sendo diagnosticado tardiamente.

Introducción: Las medidas socioespaciales son ampliamente utilizadas en las investigaciones relacionadas con la salud, sin embargo, existen pocos estudios en relación con el cáncer oral. Objetivo: Describir las características sociodemográficas y clínicas del cáncer oral y analizar la distribución espacial de la enfermedad en relación con el estado socioeconómico del vecindario, la disponibilidad de centros de salud. Método: Se recogieron datos sociodemográficos, clínicos e histopatológicos de pacientes tratados entre 2005 y 2015. Se realizaron análisis descriptivos de los datos para todas las variables. El análisis espacial se realizó utilizando el programa R. La distribución geográfica de las direcciones de los hogares de los pacientes se analizó utilizando la función K de Ripley y los mapas de Kernel. La vulnerabilidad socioespacial se definió por el ingreso familiar y la adecuación del hogar. Resultados: De los 127 pacientes incluidos, la mayoría eran hombres (76.4%), blancos o morenos (82.7%), casados (35.4%), con baja educación (71.6%) y edad promedio 59,5 años. Los casos se distribuyeron en grupos caracterizados por ingresos medios más bajos y condiciones sanitarias inadecuadas. Los centros de atención primaria de salud se distribuyeron de manera homogénea en toda la ciudad. Conclusión: Estos casos de cáncer están concentrados en regiones con condiciones socioeconómicas relativamente mas bajas. A pesar de la distribución de la atención primaria, esta no suficiente para promover el acceso de los pacientes a ella y su diagnóstico continúa siendo tardío.

Cytokines and chemokines associated with Treg/Th17 response in chronic inflammatory periapical disease

Abstract Cytokines and chemokines have a fundamental role in the maintenance of inflammation and bone response, which culminate in the development of chronic periapical lesions. Regulatory (Treg) and Th17 cytokines play a key role in regulating the immune response involved in this process. The aim of this study was to investigate the role of Treg and Th17 cells in chronic inflammatory periapical disease, by comparing the expression of the immunoregulatory mediators TGF-β, IL-10, CCL4, and the proinflammatory IL-17 and CCL20 in the periapical tissue of teeth with pulp necrosis, with and without associated chronic lesions. Eighty-six periapical tissue samples were obtained from human teeth. The samples were divided into three groups: pulp necrosis with a periapical lesion (n=26); pulp necrosis without a periapical lesion (n=30), and control (n=30). All samples were submitted to histopathological analysis and cytokine and chemokine measurement through ELISA. Statistical analyses were done with Kruskal-Wallis and Mann-Whitney tests and Spearman correlation. The group with pulp necrosis and a periapical lesion showed a higher expression of CCL4 and TGF-β in comparison with pulp necrosis without a lesion. CCL20 was higher in the group with a periapical lesion when compared to the control. In all groups there was a weak positive correlation between IL-17/CCL20, IL-10/CCL4, and IL-17/TGF-β. Both types of cytokines, pro-inflammatory and immunoregulatory, occur simultaneously in periapical tissue. However, a rise in immunosuppressive cytokines and chemokines (CCL4 and TGF-β) in periapical lesions suggests a role of these cytokines in stable periapical disease.

Tumor-associated macrophages (TAMs): clinical-pathological parameters in squamous cell carcinomas of the lower lip

Abstract The objective of this study was to analyze the presence of tumor-associated macrophage (TAM) subpopulations M1 and M2 in squamous cell carcinoma of the lower lip (SCCLL) by immunohistochemitry, and to evaluate the possible role of these subtypes in the development of regional lymph node metastasis and their association with clinical and pathological parameters. Forty-two cases of SCCLL were divided into two groups (21 with and 21 without regional lymph node metastasis). The histopathological grade of malignancy was determined and the material was submitted to double staining with anti-CD68/anti-CD163 and anti-CD68/anti-HLA-DR monoclonal antibodies. The results were analyzed statistically using the Wilcoxon signed-rank and Spearman correlation tests. The M1 and M2 subpopulations were observed in all cases studied. No significant difference was observed between the quantities of M1 and M2 TAMs regarding tumor size (p > 0.05). A significantly larger number of M2 compared to M1 TAMs was observed in tumors without regional lymph node metastasis, tumors in early stages, and low-grade tumors (p < 0.05). No significant difference between the numbers of M1 and M2 TAMs was observed in tumors with regional lymph node metastasis, tumors in advanced stages, and high-grade tumors (p > 0.05). There was a positive weak correlation between M1 and M2 TAMs (r = 0.361; p = 0.019). The results suggest a more important role of M2 TAMs in early stages than advanced stages of lip carcinogenesis. The progression of SCCLL does not seem to be related to an imbalance of macrophage polarization in the microenvironment of these tumors.

Immunohistochemical analysis of FoxP3+ regulatory T cells in lower lip squamous cell carcinomas

Abstract: The aim of this study was to determine the number of FoxP3+ regulatory T (Treg) cells in the microenvironment of lower lip squamous cell carcinomas (LLSCCs) and to correlate the findings with clinicopathological parameters (tumor size/extent, regional lymph node metastasis, clinical stage, and histopathological grade of malignancy). Fifty cases of LLSCC were selected. Lymphocytes exhibiting nuclear immunostaining for FoxP3 were quantified in 10 microscopic fields at the deep invasive front of LLSCCs. The results were analyzed statistically using the nonparametric Mann-Whitney test and Fisher's exact test. FoxP3+ lymphocytes were observed in all cases studied. The number of these cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (p > 0.05). Low-grade tumors contained a larger number of FoxP3+ lymphocytes than high-grade tumors (p = 0.019). Tumors with an intense inflammatory infiltrate exhibited a larger number of Treg cells (p = 0.035). On the other hand, the number of FoxP3+ lymphocytes was smaller in tumors arranged in small cell clusters (p = 0.003). No significant differences in the number of FoxP3+ lymphocytes were observed according to the degree of keratinization (p = 0.525) or nuclear pleomorphism (p = 0.343). The results suggest the participation of Treg cells in immune and inflammatory responses in the microenvironment of LLSCCs. These cells may play a more important role in early stages rather than in advanced stages of lip carcinogenesis.