Abstract Few studies on the distribution of oral diseases in older people are available in the literature. This study aimed to investigate the prevalence and demographic characteristics of oral and maxillofacial lesions in geriatric patients (age ≥ 60 years). A retrospective descriptive cross-sectional study was performed. Biopsy records were obtained from archives of three Brazilian oral pathology centers over a 20-year period. Data on sex, age, anatomical site, skin color, and histopathological diagnosis were collected and analyzed. Pearson’s chi-square test was used to evaluate differences in the frequency of the different oral and maxillofacial lesion groups. A total of 7,476 biopsy records of older patients were analyzed. Most cases were diagnosed in patients aged 60 to 69 years (n = 4,487; 60.0%). Females were more affected (n = 4,403; 58.9%) with a female-to-male ratio of 1:0.7 (p < 0.001). The tongue (n = 1,196; 16.4%), lower lip (n = 1,005; 13.8%), and buccal mucosa (n = 997; 13.7%) were the most common anatomical sites. Reactive and inflammatory lesions (n = 3,840; 51.3%) were the most prevalent non-neoplastic pathologies (p < 0.001), followed by cysts (n = 475; 6.4%). Malignant neoplasms were more frequent (n = 1,353; 18.1%) than benign neoplasms (n = 512; 6.8%). Fibrous/fibroepithelial hyperplasia (n = 2,042; 53.2%) (p < 0.001) and squamous cell carcinoma (n = 1,191; 88.03%) (p < 0.001) were the most common oral lesions in older adults. Biopsy data allow the accurate characterization of the prevalence of oral and maxillofacial lesions, supporting the development of public health policies that can enable the prevention, early diagnosis, and appropriate treatment of these lesions. Also, they bring valuable information that helps dentists and geriatricians diagnose these diseases.

Abstract Dermoid cysts (DCs) and epidermoid cysts (ECs) are uncommon developmental cysts affecting the oral cavity. This study aims to evaluate patients with oral DCs and ECs and their demographic and clinicopathologic features. A retrospective descriptive cross-sectional study was performed. A total of 105,077 biopsy records of oral and maxillofacial lesions from seven Brazilian oral pathology centers were analyzed. All cases diagnosed as oral DCs and ECs were reviewed, and clinical, demographic, and histopathological data were collected. The series comprised 32 DCs (31.4%) and 70 ECs (68.6%). Most of the DCs occurred on the floor of the mouth (n = 14; 45.2%) of women (n = 17; 53.1%) with a mean age of 34.6 ± 21.6 years. All DCs were lined partially or entirely by stratified squamous epithelium (100%). Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were observed in the fibrous capsule . Most of the ECs affected the labial mucosa (n = 20; 31.7%) of men (n = 39; 56.5%) with a mean age of 48.0±19.8 years. Microscopically, most ECs (n = 68; 97.1%) were lined entirely by stratified squamous epithelium. Two cysts (2.9%) showed areas of respiratory metaplasia. Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were also observed in the fibrous capsule. Conservative surgical excision was the treatment of choice in all cases. Oral DCs and ECs are uncommon and often clinically misdiagnosed lesions. Clinicians should consider DCs and ECs in the differential diagnosis of soft tissue lesions in the oral cavity, mainly located on the floor of the mouth and labial mucosa.

Resumo A mucocele oral (MO) é a lesão mais comum das glândulas salivares menores. O presente estudo teve como objetivo relatar as características clínicas e demográficas de uma grande série de MOs e identificar possíveis variáveis preditivas associadas à taxa de recorrência dessas lesões. Foi realizado um estudo transversal descritivo retrospectivo. Foram analisados 43.754 registros de biópsias de quatro serviços de patologia no Brasil. Todos os casos diagnosticados como MOs foram revisados e dados clínicos e demográficos foram coletados. Participaram do estudo 1.002 mulheres (56,2%) e 782 homens (43,8%), com média de idade de 19,8 ± 16,4 anos (variação: 01-87 anos) e proporção de mulheres para homens de 1,3:1. O lábio inferior (n=1.160; 67,4%) e assoalho da boca (n=172; 10,0%), foram os locais mais acometidos, apresentando-se clinicamente como nódulos (n=978; 79,4%) de superfície lisa (n =428; 77,5%) e coloração normal (n=768, 46,7%). A biópsia excisional foi o tratamento na maioria dos casos (n=1.392; 78,0%). As MOs recorrentes representaram 6,2% de todos os casos diagnosticados (n = 117). As recorrências recorreram mais comumente em pacientes mais jovens (idade < 20 anos) (p < 0,0001), em lesões maiores que 2 cm de diâmetro (p < 0,0001) e naquelas localizadas na superfície ventral da língua (p = 0,0351). Além disso, as taxas de recorrência foram significativamente maiores nos casos tratados com cirurgia a laser do que aqueles com cirurgia convencional utilizando bisturi (p = 0,0005). Pacientes com mucoceles devem ser informados sobre uma possível recorrência, principalmente quando encontrados no lábio ou assoalho bucal de pacientes jovens.

Abstract Oral mucocele (OM) is the most common lesion of minor salivary glands. The present study aimed to report the clinical and demographic features of a large series of OMs and identify possible predictive variables associated with the recurrence rate of these lesions. A retrospective descriptive cross-sectional study was performed. A total of 43,754 biopsy records from four pathology services in Brazil were analyzed. All cases of OMs were reviewed, and clinical and demographic data were collected. The study comprised 1,002 females (56.2%) and 782 males (43.8%), with a mean age of 19.8±16.4 years (range: 01-87 years) and a 1.3:1 female-to-male ratio. The lower lip (n=1,160; 67.4%), and floor of the mouth (n=172; 10.0%), were the most common affected sites, presenting clinically as nodules (n=978; 79.4%) of smooth surface (n=428; 77.5%) and normal color (n=768, 46.7%). Excisional biopsy was the treatment in most cases (n=1,392; 78.0%). Recurrent OMs represented 6.2% of all diagnosed cases (n=117). OMs recurred more commonly in younger patients (aged<20 years) (p<0.0001), in lesions larger than 2 cm in diameter (p<0.0001), and in those located in the ventral tongue (p=0.0351). Also, recurrence rates were higher significantly in cases treated with laser surgery than in those with conventional surgery (p=0.0005). Patients with OMs should be carefully informed of its possible recurrence, especially when found on the ventral tongue of young patients.

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.

ABSTRACT Objective: To compare salivary and serum biochemical levels in patients with chronic renal failure undergoing hemodialysis. Material and Methods: The sample was composed of 57 patients treated in Hemodialysis Reference Centers, from a state of Northeastern Brazilian, with age ≥21 years old with at least 3 months of hemodialysis treatment time. Serum data were obtained from records. Unstimulated and stimulated saliva were collected. Flow rate (mL/min) was measured. Spectrophotometry was performed for the measurement of salivary levels of calcium (570 nm), urea (340 nm), and creatinine (510 nm). Statistical analysis used Mann Whitney and Kruskal-Wallis tests (p<0.05). Results: Unstimulated and stimulated salivary flow rates were 0.43 mL/min and 1.69 mL/min, respectively. There was significant difference (p<0.001) of levels of calcium (5.41 mg/dL and 9.70 mg/dL), urea (118.03 mg/dL and 183.22 mg/dL) and creatinine (0.59 mg/dL and 9.20 mg/dL) between saliva and serum, respectively. Concerning the time of hemodialysis, salivary and serum calcium not exhibited significant association; however, serum urea (p=0.012) and serum creatinine (p=0.025) showed significant association to the time of hemodialysis. Conclusion: Salivary biochemical levels of urea, creatinine and calcium can indicate the presence of a possible chronic renal failure and the saliva demonstrated to be a potential auxiliary biofluid for clinical monitoring renal alterations.

Abstract Regulatory T (Treg) cells can suppress antitumor immune response, but little is known about possible age-related differences in the number of these cells in the microenvironment of oral tongue squamous cell carcinoma (OTSCC). The aim of this study was to determine the number of FoxP3+ Treg cells in the microenvironment of OTSCC in young (≤ 45 years) and older (≥ 60 years) patients, and to correlate the findings with clinicopathological parameters (sex, tumor size/extent, regional lymph node metastasis, clinical staging, and histopathological grade of malignancy). Forty-eight OTSCCs (24 diagnosed in young patients and 24 diagnosed in older patients) were selected. Lymphocytes exhibiting nuclear immunopositivity for FoxP3 were quantified at the tumor invasive front and the results were analyzed statistically using the non-parametric Mann-Whitney test. FoxP3+ lymphocytes were observed in all cases assessed. The number of FoxP3+ lymphocytes in OTSCC tended to be higher in older patients (p = 0.055). Analysis of OTSCC in males and in early clinical stages revealed a higher number of Treg cells in older patients than in young ones (p < 0.05). In older patients, the number of Treg cells tended to be higher in smaller tumors (p = 0.079). Tumors with intense inflammatory infiltrate exhibited a larger number of Treg cells, both in young (p = 0.099) and older patients (p = 0.005). The results suggest a greater participation of Treg cells in immunoinflammatory responses in the microenvironment of OTSCC in older patients, particularly in males and in early stages.

Abstract Objective: To perform an in vitro analysis of antibacterial and antifungal potential of an alcoholic extract from the leaves of Guapira Graciliflora Mart. against oral microorganisms and determine its chemical composition. Material and Methods: A hydroalcoholic extract of the leaves form G. graciliflora was obtained through maceration, vacuum concentration and freeze-drying. Antibacterial and antifungal activities were evaluated against Streptococcus mutans, Streptococcus salivarius, Streptococcus oralis, Streptococcus parasanguinis, Streptococcus mitis and strains of Candida albicans using broth microdilution method. Phytochemical analysis determined the total phenolic compounds, protein concentration and total of sugars present in the extract. Results: G. Graciliflora demonstrated antifungal activity against the LM 11 and LM 410 clinical isolates of C. albicans (MIC 0.5 mg/mL and 2 mg/mL, respectively). The other microorganisms tested were resistant to the extract. The phytochemical analysis revealed 3% proteins, 13% total sugars and 17% phenolic compounds. Conclusion: G. Graciliflora has antifungal activity against clinical strains of C. albicans and exhibits proteins, sugars and phenolic compounds in its chemical composition.

Abstract The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.

Resumo Introdução A queilite actínica e uma condição de natureza inflamatória que acomete o lábio inferior, e é causada pela exposição prolongada e crônica dos lábios à radiação ultravioleta proveniente dos raios solares. Objetivo Identificar as características clínicas e histopatológicas em uma série de 40 casos diagnosticados histopatologicamente como queilite actínica. Além disso, investigar possíveis associações entre estes aspectos. Método Caracterizado como um estudo observacional, transversal, retrospectivo e descritivo. Foram registrados dados a respeito da idade, gênero, ocupação, sintomatologia, histórico de exposição ao sol, uso de proteção solar, tabagismo, cor da pele, aspecto clínico e classificação histopatológica. Os dados foram submetidos ao teste de Qui-Quadrado de Pearson (p<0,05). Resultado Houve uma prevalência do gênero masculino, leucodermas, com faixa etária entre 50 e 60 anos e a ocupação mais presente foi a de agricultor. Da amostra, 85% apresentou histórico de exposição crônica ao sol, onde 50% relatou uso de algum tipo de proteção solar e apenas 25% era tabagista. A principal apresentação clínica foi leucoplasia não ulcerada, e no estudo histopatológico as hiperceratoses foram as mais presentes. Não foi possível correlacionar o grau de alteração tecidual verificada no diagnóstico histopatológico com as variáveis clínicas estudadas (p=0,112). Conclusão Não foi possível correlacionar o grau de alteração tecidual verificada no diagnóstico histopatológico com os aspectos clínicos observados. O aspecto clínico da lesão pode mascarar alterações teciduais em diversos estágios, o que enaltece a importância do diagnóstico precoce.

Abstract Introduction Actinic cheilitis is a inflammatory condition affecting mainly the lower lip and it is caused by chronic and excessive exposure of the lips to the ultraviolet radiation in sunlight. Objective Identifying clinical and histopathologic characteristics in 40 cases histopathologically diagnosed as actinic cheilitis. In addition, to investigate possible associations between these aspects. Method Defined as an observational, transversal, retrospective and descriptive study, it registered data regarding age, gender, occupation, symptomatology, records of sun exposure, frequency of sunblock use, tabagism, skin color, clinical aspect and histopathological classification. The data was submitted to the chi square test of Pearson (p<0.05). Result There was a predominance of male gender, leucodermia, and ages ranging between 50 and 60 years. The most common occupation was farming. From our sample, 85% had history of chronic sun exposure, in which 50% reported the use of some type of sunblock and only 25% were smokers. The main clinical condition was non-ulcerated leukoplakia and in the histopathological study, the hyperkeratosis were more common. A correlation between the degree of tissue alteration verified in the histopathological diagnosis and the studied clinical variables was not established (p=0.112). Conclusion The clinical aspect of the wound can conceal tissue alterations in different stages, emphasizing the importance of a premature diagnosis.

Abstract The immunoexpression of p16, p53, and Bax in oral tongue squamous cell carcinoma (OTSCC) in young and elderly patients is assessed based on clinical and morphological parameters. The sample consists of 60 OTSCC cases: 30 in young (age ≤ 45 years) and 30 in elderly (age ≥ 60 years) patients. Clinical (tumor size, regional node metastasis, distant metastasis, and clinical stage) and morphological (histological grade of malignancy) parameters were evaluated. Immunohistochemical quantitative analysis was performed using anti-p16, anti-p53, and anti-Bax antibodies. None of the evaluated proteins exhibited statistically significant differences between young and elderly patients (p>0.05). There was a significant association of p16 immunoexpression with clinical parameters in elderly patients. There were no associations of p53 and Bax with any of the clinico-morphological parameters. Correlations between p16 and Bax and between p53 and Bax immunoexpression were observed in young patients (r = 0.363; p = 0.048) and in elderly patients (r = 0.433; p = 0.017), respectively. In conclusion, the assessed proteins could not be used to determine differences in the biological behavior of OTSCC between young and elderly patients. Therefore, all proteins activated the pro-apoptotic pathway of OTSCC in both groups.

RESUMO O carcinoma de células escamosas de células fusiformes da língua, é uma variante rara do carcinoma de células escamosas. Este trabalho relata o caso de um paciente do sexo masculino de 64 anos de idade com carcinoma de células escamosas de células fusiformes da língua. Foi feita uma revisão dos aspectos relacionados a etiopatogenia, características clinicopatológicas e imuno-histoquímicas, além do tratamento dessa neoplasia. O paciente procurou atendimento para avaliação de tumefação dolorosa na língua. O exame extraoral revelou linfonodos cervicais submandibulares e cervicais superiores palpáveis. Foi realizada biópsia incisional com base nas hipóteses diagnósticas de carcinoma de células escamosas ou neoplasia maligna de glândula salivar. A análise histopatológica demonstrou proliferação de células fusiformes atípicas, exibindo extenso pleomorfismo. As células tumorais foram positivas para vimentina, p53 e alfa-actina de músculo liso, focalmente positivas para antígeno de membrana epitelial e P63, e negativas para pancitoqueratina (AE1/AE3), CK7, CD138, CD34, CD56 e S-100. O índice de positividade para o Ki-67 foi de aproximadamente 40%. Foi feito o diagnóstico de carcinoma de células escamosas, de células fusiformes, e o paciente foi encaminhado para um serviço de cirurgia de cabeça e pescoço. Na cavidade oral, o carcinoma de células escamosas de células fusiformes da língua, é uma variante agressiva do carcinoma de células escamosas, que geralmente se apresenta como massa exofítica localizada na língua de homens idosos. Devido às suas distintas características histopatológicas, a imuno-histoquímica é uma ferramenta valiosa e útil para estabelecer o diagnóstico de carcinoma de células escamosas de células fusiformes da língua.

ABSTRACT Spindle cell squamous cell carcinoma of the tongue is a rare variant of squamous cell carcinoma. This paper reports the case of a spindle cell squamous cell carcinoma of the tongue, in a 64-year-old male patient, and presents a review of the etiopathogenesis, clinicopathological and immunohistochemical features and treatment of the malignancy. The patient presented for evaluation of a painful swelling on his tongue. Extraoral examination revealed palpable submandibular and superior cervical lymph nodes. Based on the presumptive diagnoses of squamous cell carcinoma or malignant salivary gland neoplasm, an incisional biopsy was performed. Histopathological analysis showed a proliferation of atypical spindle cells, exhibiting extensive pleomorphism. Tumor cells were positive for vimentin, P53 and alpha-smooth muscle actin, focally positive for epithelial membrane antigen and P63, and negative for pan-cytokeratin (AE1/AE3), CK7, CD138, CD34, CD56, and S-100. The positivity index for Ki-67 was approximately 40%. The diagnosis of spindle cell squamous cell carcinoma was established and the patient was referred to a head and neck surgery service. In the oral cavity, spindle cell squamous cell carcinoma of the tongue is an aggressive variant of squamous cell carcinoma, which usually presents as an exophytic mass located on the tongue of elderly males. Due to its distinct histopathological characteristics, immunohistochemistry is a valuable and helpful tool to establish the diagnosis of spindle cell squamous cell carcinoma of the tongue.

RESUMO O tumor neuroectodérmico melanocítico da infância é uma neoplasia rara e de crescimento rápido. Neste estudo, relata-se o caso de uma paciente do sexo feminino de 6 meses de idade, que apresentou tumefação na região anterior de maxila. A reconstrução tomográfica revelou área unilocular hipodensa e expansiva associada ao incisivo central superior direito decíduo. Realizou-se biópsia incisional, considerando as hipóteses diagnósticas de cisto dentígero, tumor odontogênico adenomatoide, tumor neuroectodérmico melanocítico da infância e rabdomiossarcoma. Microscopicamente, a lesão revelou população celular bifásica, consistindo de células pequenas, ovoides, de aparência neuroblástica, e de células epitelioides, contendo melanina. A análise imuno-histoquímica demonstrou que o componente celular contendo melanina era positivo de forma intensa e difusa para HMB-45 e Melan-A, mas levemente positivo para S100. Com base nestes achados, foi estabelecido o diagnóstico definitivo de tumor neuroectodérmico melanocítico da infância. Em seguida, foi realizada a enucleação da lesão com curetagem cuidadosa. Após 2 anos de acompanhamento, não foram verificadas evidências clínicas ou radiográficas de recorrência. O presente caso destaca a importância do diagnóstico precoce e da intervenção terapêutica no momento apropriado, a fim de alcançar um desfecho favorável para o paciente.

ABSTRACT Melanotic neuroectodermal tumor of infancy is a rare and fast-growing neoplasm. In this study, we describe the case of a 6-month-old female patient, who presented swelling in the anterior maxilla. Tomographic reconstruction showed an unilocular hypodense and expansive area associated with the upper right central primary incisor. The presumptive diagnoses were dentigerous cyst, adenomatoid odontogenic tumor, melanotic neuroectodermal tumor of infancy and rhabdomyosarcoma, and an incisional biopsy was performed. Microscopically, the lesion revealed a biphasic cell population, consisting of small, ovoid, neuroblastic-like cells and epithelioid cells containing melanin. Immunohistochemically, the melanocyte-like component was strongly and diffusely positive for HMB-45 and Melan-A, but weakly positive for S100. Based on these findings, definitive diagnosis of melanotic neuroectodermal tumor of infancy was established. Then, enucleation of the lesion was performed by careful curettage. After 2 year follow-up, no clinical or radiographical evidence of recurrence was verified. The present case highlights the importance of early diagnosis and therapeutic intervention at the appropriate time to achieve a favorable outcome for the patient.

RESUMO Os cistos odontogênicos ortoceratinizados são cistos de desenvolvimento de origem odontogênica, de baixa frequência, etiopatogenia desconhecida e baixa taxa de recorrência. Radiograficamente, apresenta-se como uma área radiolúcida em região posterior de mandíbula. O objetivo deste artigo é descrever um caso não usual de cistos odontogênicos ortoceratinizados, que exibia, radiograficamente, focos radiopacos semelhantes à calcificações, no interior da lesão, sugerindo diagnóstico clínico de fibro-odontoma ameloblástico. Após a biópsia incisional e análise microscópica, o diagnóstico conclusivo foi de cistos odontogênicos ortoceratinizados. Observou-se que os focos radiopacos estavam associados, microscopicamente, a presença de uma reação de células gigantes multinucleadas por corpo estranho. O paciente foi tratado cirurgicamente, sob anestesia local, com acesso intrabucal para remoção total da lesão, com o restabelecimento da estética e sem sinais de recidiva após 24 meses. A importância do conhecimento deste tipo de reação dar-se pelo risco de mimetizar uma lesão potencialmente mais agressiva, direcionando a escolha do tratamento da lesão.

ABSTRACT Orthokeratinized odontogenic cysts are developmental odontogenic cysts, presenting with low frequency, low rate of recurrence and their ethiopathogenesis is unknown. Radiographically, they show a radiolucent area in the mandibular posterior region. The aim of this report is to describe an unusual case of orthokeratinized odontogenic cysts, radiographically exhibiting radiopaque areas with an aspect of calcifications in the lesion. Based on this, the clinical hypothesis of ameloblastic fibro-odontoma was suggested. After incisional biopsy and microscopic analysis, the conclusive diagnosis was orthokeratinized odontogenic cysts. The radiopaque foci were observed to be associated with a foreign body reaction. The patient was submitted to surgery under local anesthesia, with intraoral access for complete excision of the lesion and to re-establish esthetics. After follow-up of 24 months there were no signs of recurrence. Knowledge of this type of reaction is important because of the risk that the lesion may mimic a potentially more aggressive lesion, affecting the choice of treatment.

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.

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.