Immunohistochemical evaluation of HLA-G and FoxP3+ T regulatory cells in oral cavity and lower lip squamous cell carcinomas

Abstract: Human Leukocyte Antigen G (HLA-G) is a molecule involved in the tumor immunosuppression and also in the generation of regulatory T (Treg) cells, thus leading to evasion to the immune system host, and consequently, contributing to tumor progression in several cancers. The aim of this study was to evaluate the immunoexpression of HLA-G by tumor cells and FoxP3+ Treg cells in 25 oral tongue squamous cell carcinomas (SCCs) and 25 lower lip SCCs and analyze their relationship with clinical parameters. HLA-G expression was higher in oral tongue SCCs than in lower lip SCCs. In oral tongue SCCs and lower lip SCCs, no association between HLA-G expression and clinical parameters (tumor size, lymph node status, distant metastasis, and clinical stage) was verified (P>0.05). FoxP3+ Treg cells were detected along the tumor invasive front in all cases of oral tongue and lower lip SCCs. In oral tongue SCC cases, the number of Treg 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). A significant positive correlation was found between the expression of HLA-G by neoplastic cells and Treg cells in lower lip SCCs (p = 0.008). Our findings suggest the involvement of HLA-G and Treg cells in the modulation of immune responses in oral tongue and lower lip SCCs. This interaction between HLA-G and Treg cells may represent an evasion mechanism in these malignancies.

Immunoexpression of human leukocyte antigen-DR in actinic cheilitis and lower lip squamous cell carcinoma

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.

Valor prognóstico da imunoexpressão de podoplanina e de CD44v6 na recidiva locorregional dos pacientes com câncer de lábio / Prognostic value of podoplanin and CD44v6 immunoexpressions on locoregional recurrence of the patients with lip cancer

O objetivo deste estudo consistiu em avaliar a expressão imuno-histoquímica da podoplanina e do CD44v6 pelas células malignas, verificando a associação destas proteínas com as variáveis clínicas, microscópicas, com o índice histopatológico de malignidade e com a sobrevivência livre de doença de 91 pacientes portadores de carcinomas espinocelulares (CEC) de lábio inferior, tratados no Centro de Tratamento e Pesquisa do Hospital do Câncer A.C.Camargo, São Paulo. Os tumores foram corados, separadamente, com os anticorpos anti-podoplanina e anti-CD44v6, sendo avaliada a imunoexpressão destas proteínas pelas células neoplásicas, no front de invasão tumoral, por meio de um método semi-quantitativo de escores. A associação da expressão da podoplanina e do CD44v6 com as variáveis demográficas, clínicas e microscópicas foi feita pelo teste do qui-quadrado ou exato de Fisher. As taxas de sobrevivência livre de doença, acumuladas em cinco e dez anos, foram calculadas pelo teste de Kaplan-Meier e a influência das variáveis clínicas e microscópicas no prognóstico avaliadas pelo modelo de regressão de Cox. A correlação entre a podoplanina e o CD44v6 foi analisada pelo teste de Spearman. Em todos os testes estatísticos utilizou-se um nível de significância de 5%. Os resultados mostraram uma predominância da forte expressão membranosa e citoplasmática da podoplanina pelas células malignas. Verificou-se uma associação significativa da podoplanina citoplasmática com a recidiva locorregional (p=0,028) e da podoplanina membranosa com o índice histopatológico de malignidade tumoral (p=0,026). O CD44v6 foi fortemente expresso pelas células neoplásicas de 95,4% dos CECs e significativamente, associado com o estadiamento clínico T (p=0,034). Não houve correlação entre a podoplanina e o CD44v6 nos CECs de lábio inferior. A forte expressão de podoplanina membranosa (p=0,016) e citoplasmática (p=0,030) pelas células malignas foi fator de prognóstico favorável independente na sobrevivência livre de doença. Concluímos que a podoplanina e o CD44v6 são fortemente expressos pelas células neoplásicas e que a forte imunoexpressão membranosa e citoplasmática da podoplanina pode auxiliar na identificação do risco de recidiva locorregional nos pacientes portadores de carcinoma espinocelular de lábio inferior.(AU)

The aim of this study was evalute the podoplanin and CD44v6 immunohistochemical expression by malignant cells and its association with the clinical and microscopic variables, tumor histopathological grading and disease-free survival of 91 patients with lip squamous cell carcinomas (SCC), submitted to surgical treatment at Research and Treatment Center of the Cancer Hospital A.C. Camargo, São Paulo. The tumors were stained separately, with the antibodies anti-podoplanin and anti-CD44v6, and the immunoexpression of these proteins, by the neoplastic cells in the invasion front, was evaluated by a semi-quantitative scores method. Chi-square test or Fishers exact test was used to analyze the association of podoplanin and CD44v6 expression with demographic, clinical, and microscopic variables. Disease-free survival in five and ten years, were calculated by the Kaplan-Meier method and the influence of clinical and microscopic variables on prognosis were evaluated by the Cox regression model. The correlation between podoplanin and CD44v6 expression was analyzed by Spearman's test and a significance level of 5% was used in all statistical tests. The results showed a predominance of strong membranous and cytoplasmic podoplanin expression by malignant cells. An association between cytoplasmic podoplanin and locorregional recurrence (p=0,028) and membranous podoplanin with tumor histopathological grading (p=0,026). CD44v6 was strongly expressed in 95.4% of the SCCs neoplastic cells and significantly associated with the clinical staging T (p=0,034). There was no correlation between podoplanin and CD44v6 expression in the lower lip SCC. The strong expression of membranous (p=0.016) and cytoplasmic (p=0.030) podoplanin by malignant cells was a favorable independent prognostic factor in disease-free survival. Concluding, the podoplanin and CD44v6 are strongly expressed by neoplastic cells and the strong membranous and cytoplasmic immunoexpression of podoplanin can help the identification of locoregional recurrence risk in patients with squamous cell carcinoma of the lower lip.(AU)

Plasmoacanthoma

Abstract Plasmoacanthoma is an extremely rare verrucous tumor located on periorificial regions characterized by dense dermal plasmacytic infiltrates. Some authors classify it as a form of reactive plasma cell proliferation which represents a heterogeneous spectrum of mucocutaneous disorders. These plasma cell proliferations have been considered to be a benign immunologic inflammatory reaction to known or unknown stimuli. However, the etiology of plasmoacanthoma remains highly speculative. We report the case of a 40-year-old woman who presented with a lobulated warty lesion affecting the lower lip. Biopsy from the lesion was compatible with plasmoacanthoma, which remains an underreported disease in the dermatology literature.

Lymphangiogenesis and angiogenesis in oral cavity and lower lip squamous cell carcinoma / Linfangiogênese e angiogênese em carcinomas de células escamosas de lábio inferior e da cavidade oral

ABSTRACT INTRODUCTION: Tumors of the lip and oral cavity differ in various aspects; therefore a clarification of the distinctions among these sites may help to better understand the biologic behavior of neoplasms occurring in these locations. OBJECTIVE: Considering that angiogenesis and lymphangiogenesis are two major elements that can influence various aspects of tumor biology, we aimed to compare these factors between squamous cell carcinoma of the lower lip and oral cavity. METHODS: A total of 84 primary squamous cell carcinomas including 45 oral and 39 lower lip tumors were selected and immunohistochemically stained with monoclonal antibody against D2-40 and CD105. Mean microvessel density was assessed in tumoral tissue, while lymphatic vessel density was calculated in both neoplastic tissue and invasion front. Data were statistically analyzed using t-test and p-values of <0.05 were considered significant. RESULTS: We found a mean microvessel density ± standard deviation of 31.94 ± 18.9 in oral cavity and 27.54 ± 20.8 in lower lip squamous cell carcinomas, with no significant difference (p = 0.32). Mean lymphatic vessel density ± standard deviation was 13.05 ± 8.2 and 16.57 ± 10.79 in of oral cavity and lower lip neoplastic tissue, respectively. The corresponding values were 9.94 ± 5.59 and 12.50 ± 7.8 in the invasive front. Significant differences were not observed in either of the lymphatic vessel density variables between the two sites. CONCLUSION: According to our results, it seems that the search for additional factors other than those related to the vasculature should continue, to help clarify the differences in biologic behavior between lower lip and oral cavity squamous cell carcinomas.

Resumo Introdução: Os tumores de lábio e da cavidade oral diferem em vários aspectos; portanto, o conhecimento das diferenças entre eles pode ajudar na melhor compreensão do comportamento biológico das neoplasias que ocorrem nesses locais. Objetivo: Considerando que a angiogênese e a linfangiogênese são dois elementos importantes que podem influenciar diversos aspectos da biologia dos tumores, objetivamos comparar esses fatores entre o carcinoma de células escamosas (CCE) de lábio inferior e da cavidade oral. Método: No total, foram selecionados 84 CCEs primários (45 tumores da cavidade oral e 39 tumores de lábio). Esses tumores foram corados por processo imunohistoquímico com anticorpo monoclonal anti-D2-40 e CD105. Avaliamos a densidade média de microvasos (DMV) no tecido tumoral, enquanto que a densidade vascular linfática (DVL) foi calculada tanto no tecido neoplásico como no front de invasão. Os dados foram estatisticamente analisados com o uso do teste t e valores de p < 0,05 foram considerados significantes. Resultados: Chegamos a uma média para DMV ± DP de 31,94 ± 18,9 para CCEs na cavidade oral e de 27,54 ± 20,8 no lábio inferior, sem diferença significante (p = 0,32). As médias para DVL ± DP foram de 13,05 ± 8,2 e 16,57 ± 10,79 no tecido neoplásico da cavidade oral e lábio inferior, respectivamente. Os valores correspondentes foram 9,94 ± 5,59 e 12,50 ± 7,8 no front invasivo. Não foram observadas diferenças significantes nas duas variáveis DVL entre os dois locais. Conclusão: De acordo com os nossos resultados, a pesquisa por fatores adicionais, além daqueles relacionados à vasculatura, deve ter continuidade, para auxiliar no esclarecimento das diferenças do comportamento biológico entre CCEs no lábio inferior e na cavidade oral.

Immunoexpression of cleaved caspase-3 shows lower apoptotic area indices in lip carcinomas than in intraoral cancer

ABSTRACT Objective This study aimed to evaluate apoptosis by assessing cleaved caspase-3 immunoexpression in hyperplastic, potentially malignant disorder (PMD), and malignant tumors in intraoral and lower lip sites. Material and Methods A retrospective study using paraffin blocks with tissues from patients with inflammatory fibrous hyperplasia (IFH), actinic cheilitis, oral leukoplakia, lower lip and intraoral squamous cell carcinoma (SCC) was performed. The tissues were evaluated by immunohistochemical analysis with anti-cleaved caspase-3 antibody. Apoptotic area index was then correlated with lesion type. Results From 120 lesions assessed, 55 (46%) were cleaved caspase-3-positive. The SCC samples (n=40) had the highest apoptotic area indices (n=35; 87.5%). Significant differences were detected between SCCs and PMDs (p=0.0003), as well as SCCs and IFHs (p=0.001), regarding caspase-3 immunopositivity. Carcinomas of the lower lip had lower apoptotic area indices than intraoral cancer (p=0.0015). Conclusions Cleaved caspase-3 immunoexpression showed differences in oral SCCs and PMDs and demonstrated a distinct role of apoptosis in carcinogenesis of intraoral and lower lip cancer. In future, the expression of cleaved caspase-3 with other target molecules in oral cancer may be helpful in delineating the prognosis and treatment of these tumors.

Avaliação da expressão de ß-catenina e ciclina D1 como biomarcadores preditivos para o câncer de lábio / Evaluation of ß-catenin and cyclin D1 expression as predictive biomarkers for lip cancer

Um dos objetivos da pesquisa científica, atualmente, é encontrar biomarcadores que possam auxiliar na definição da probabilidade de progressão das lesões orais displásicas, e ainda sejam capazes de identificar os principais agentes moleculares envolvidos na carcinogênese de um determinado tipo de tumor. Assim, o objetivo deste estudo foi investigar a expressão de ß-catenina, ciclina D1 e Ki-67 em 15 espécimes de epitélio oral normal, 45 queilites actínicas displásicas e em 30 carcinomas espinocelulares de lábio. Essa amostra foi constituída por pacientes tratados na Faculdade de Medicina de Botucatu (Brasil) e no Hospital Clínico San Cecílio de Granada (Espanha). O grau de displasia epitelial e de diferenciação tumoral foi classificado com base nos critérios definidos pela Organização Mundial da Saúde. A avaliação dos biomarcadores foi realizada por meio da técnica imunohistoquímica, dividindo a espessura do epitélio em quatro compartimentos (basal, suprabasal, terço médio e terço superior) para o grupo controle e para as queilites actínicas e em três compartimentos (basal, suprabasal e região interna) para o grupo dos carcinomas espinocelulares de lábio. Para a comparação da média de expressão de cada marcador, nas diferentes localizações do epitélio foi utilizado o teste estatístico de Kruskal-Wallis. Para a correlação da expressão dos três marcadores entre os grupos foi utilizada a correlação de Spearman, com nível de significância de 5%. Os resultados demonstraram uma perda discreta da expressão membranosa de ß-catenina na camada basal das queilites actínicas com displasia epitelial intensa (Cis) e nos carcinomas espinocelulares de lábio, assim como uma expressão citoplasmática e nuclear, discreta e diretamente proporcional à desorganização epitelial nas camadas basal e suprabasal das queilites actínicas e carcinomas espinocelulares de lábio. Notou-se também um aumento da expressão de ciclina D1 e Ki-67 na camada basal à medida que aumentava a desorganização epitelial. Houve uma associação estatisticamente significativa da expressão de ciclina D1 e Ki-67 na camada suprabasal do grupo controle (p=0,030) e das queilites actínicas (p=0,001) e ainda na região interna dos carcinomas espinocelulares de lábio (p=0,000). Não houve correlação significativa entre as expressões nucleares de ß-catenina e de ciclina D1. Nossos resultados reforçam que a ß-catenina, a ciclina D1 e o Ki-67, podem ser utilizados como biomarcadores preditivos para o câncer de lábio. Além disso, sugerem que a ß-catenina e a ciclina D1 participam da carcinogênese labial, em eventos independentes da via de sinalização/Wnt.(AU)

One of the goals of scientific research today is to find predictive biomarkers that can help define the probability of progression of dysplastic oral lesions, and are still able to identify key molecular agents involved in the carcinogenesis of a particular type of tumor. The objective of this study was to investigate ß-catenin, cyclin D1 and Ki-67 expression in 15 specimens of normal oral epithelium, 45 dysplastic actinic cheilitis and 30 squamous cell carcinoma of the lip. This sample consisted of patients treated at the Botucatu Medicine School (Brazil) and the Clinical Hospital San Cecilio of Granada (Spain). The degree of epithelial dysplasia and tumor differentiation was classified based on the criteria defined by the World Health Organization. The evaluation of biomarkers was performed by immunohistochemical technique, dividing the thickness of the epithelium into four compartments (basal, suprabasal, middle third and upper third) for the control group and actinic cheilitis and three compartments (basal, suprabasal and inner region) to the group of squamous cell carcinoma of the lip. For comparing the average expression of each marker in different locations of the epithelium we used the statistical test of Kruskal-Wallis. For the correlation of the three markers expression between the groups was used Spearman, with 5% significance level. The results showed a slight loss of membranous expression of ß-catenin in the basal layer of actinic cheilitis with severe epithelial dysplasia (Cis) and squamous cell carcinoma of the lip, and a cytoplasmic and nuclear expression, slight and directly proportional to the epithelial disorganization in layers basal and suprabasal of actinic cheilitis and squamous cell carcinoma of the lip. It was also noted an increase in expression of cyclin D1 and Ki-67 in the basal layer as increased epithelial disorganization. There was a statistically significant association of cyclin expression D1 and Ki-67 in the suprabasal layer of the control group (p=0.030) and actinic cheilitis (p=0.001) and also in the inner region of squamous cell carcinoma of the lip (p=0.000). There was no significant correlation between the nuclear expression of ß-catenin and cyclin D1. Our results emphasize that ß-catenin, cyclin D1 and Ki-67 can be used as predictive biomarkers for lip cancer. Moreover, they suggest that ß-catenin and cyclin D1 acts on the lip carcinogenesis, in independent events signaling pathway/Wnt.(AU)

Accuracy of clinical diagnosis for the identification of potentially malignant disorders and malignant lip lesions

Abstract: The aim of this study was to assess the accuracy of clinical diagnosis for lip lesions based on sensitivity and specificity. The retrospective analysis focused on the detection of lesions caused by potentially malignant disorders (PMDs) and malignant lesions (n = 1195). All cases were classified as benign, PMD, and malignant lesions. Concordance between diagnoses based on clinical examination and those based on histopathological analysis was assessed, and accuracy for the identification of PMD and malignant lesions was calculated. Histopathological analysis revealed 44 lesion types; PMD and malignant lesions comprised 8.3% of all cases. Compared with histopathological analysis, clinical examination showed 97.4% accuracy for the identification of non-malignant and potentially malignant/malignant cases. Degrees of specific sensitivity ranged from 34% to 77% for different lesions, and were highest for autoimmune (77%) and reactive (72%) lesions. Positive and negative predictive values for the identification of PMD and malignant lesions were 81.9% and 98.9%, respectively. Clinical examination showed a high degree of accuracy for the detection of PMD and malignant lip lesions, indicating good reliability.

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.

Carcinoma invasor con compromiso completo de labio inferior. Técnica de reconstrucción de WebsterSchuchardt / Invasive carcinoma with full commitment to lower lip. Technique Webster Schuchardt reconstruction

La reconstrucción del labio inferior es una práctica compleja y que requiere la restitución de la mucosa, músculos y piel. Se ha descripto una gran variedad de procedimientos; sin embargo, se debe adaptar cada técnica al caso. Se presenta una paciente con carcinoma espinocelular invasor que compromete la totalidad del labio inferior. Se decidió efectuar la reconstrucción con técnica de Webster y modifi cada por Schuchardt para compensar en la parte del mentón. Se muestran detalles técnicos así como los resultados funcionales y estéticos obtenidos

Reconstruction of the lower lip is a complex practice that requires to restore the mucosa, the muscles and the skin. There are a variety of procedures, however, each technique must be adapted to each case. We present a young patient with invasive squamous cell carcinoma that involves the entire lower lip. We decided to perform the Webster Technique reconstruction modifi ed by Schuchardt (chin fl ap). Technical details, functional and aesthetic results obtained are shown

Clinical and Histological Features of Multifocal Canalicular Adenomas of the Upper Lip

Canalicular adenoma (CA) is an uncommon benign salivary gland tumor that mostly occurs in the upper lip. Despite its benign nature, some patients may present multiple nodules and also microscopic growth that can be multifocal with foci of tumor within the adjacent gland. Microscopically, CA can be mistaken for a polymorphous low-grade adenocarcinoma (PLGA) or basal cell adenoma (BCA), and immunohistochemistry can be helpful in differentiating them. Two cases of canalicular adenoma showing tumor foci within the adjacent gland are described. Both cases occurred in the upper lip of white females aged 72 and 79 years. In addition to the histological multifocal aspect, one of the patients presented bi-lateral nodules. Histological examination of both lesions revealed interconnecting and branching canal-like structures composed by uniform columnar and sometimes cuboidal cells, partially encapsulated. Immunohistochemical analysis showed intense expression of cytokeratins (CK) 7, a weak reaction to CK14 and a negative reaction to vimentin. Upon the diagnosis of CA the lesions were excised. In conclusion, it is important to properly diagnose CA and differentiate its multifocal aspect from a malignant behavior.

O adenoma canalicular (AC) é uma rara neoplasia benigna de glândula salivar que ocorre com maior frequência em lábio superior. Apesar de sua natureza benigna, alguns pacientes podem apresentar múltiplos nódulos, além de apresentar microscopicamente um crescimento multifocal com focos de neoplasia na glândula adjacente. Microscopicamente, AC pode ser confundido com adenocarcinoma polimorfo de baixo grau ou adenoma de células basais, sendo a imunohistoquímica útil na diferenciação entre eles. Dois casos de AC com focos de neoplasia dentro da glândula são descritos. Ambos os casos ocorreram em lábio superior de dois indivíduos do sexo feminino com 72 e 79 anos de idade. Além do aspecto histológico multifocal, um dos pacientes apresentou nódulos bilaterais. A análise histológica dos dois casos revelou estruturas canaliculares interligadas, compostas por células colunares uniformes e cuboidais, parcialmente encapsuladas. A análise imunohistoquímica mostrou intensa marcação de citoqueratina (CK) 7, uma fraca expressão para CK14, e reação negativa para vmentina. Após o diagnóstico as lesões foram excisionadas. Conclusão: É importante o correto diagnóstico do AC e a diferenciação do aspecto multifocal de um comportamento maligno.

[Squamous cell carcinoma of the lip: a report of 30 cases]

Squamous cell carcinoma [SCC] is one of the most common malignant tumors of the lips [90%]. The prognosis of these SCC seems to be poor thus here periorificial localization. To present the epidemiological, clinical, pathological, therapeutic features and out come of SCC of the lips. We conducted a retrospective study performed in the dermatology department of the La Rabta hospital of Tunis over a 11-year-period [2000-2010] recording patients with histologically confirmed SCC of lips. Thirty patients were included [26 men and 4 women] with an average age of 63 years. The most frequent risk factors were smoking and chronic sunlight exposure. The occurrence of the labial SCC on a precursor lesion was noted in 11 cases. It occurred more frequently on the lower lip [80%]. Tumor was ulcero-vegetant in 21 patients. Twenty patients had a commune SCC, 19 of them were well-differentiated. Surgery was indicated in 18 cases and 10 patients were treated by exclusive radiotherapy. Lymph nodes metastases were noted in 2 cases. No visceral metastasis was observed. During the period of follow-up [20.12 months], two patients died. The diagnosis of SCC of the lips is late and the treatment often mutilating. The improvement of the prognosis depends not only on the early diagnosis and the treatment of the precursors, but also on the photo protection and alcohol and smoking eviction

Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects / Queilite actínica e carcinoma espinocelular do lábio: aspectos clínicos, histopatológicos e imunogenéticos

Actinic cheilitis is the main precancerous lesion of the lip. Squamous cell carcinoma of the lip is reported together with oral carcinomas in the Brazilian official statistics. Overall, they account for 40% of the head and neck carcinomas. In general, physicians and dentists know little about what causes oral tumor development and progression. Tumor suppressor genes and cell proliferation regulatory proteins play a role in the progression of actinic cheilitis to squamous cell carcinoma and in its biological behavior. Knowledge on prognostic and diagnostic markers has a positive impact on the follow-up of these patients.

Queilite actínica é a principal lesão pré-neoplásica do lábio. O carcinoma espinocelular do lábio é incluído nas estatísticas brasileiras junto com os cânceres de boca e, em conjunto, somam 40% dos cânceres de cabeça e pescoço. Há certo desconhecimento médico e odontológico em geral quanto aos fatores relacionados à carcinogênese e à progressão de tumores de boca. Genes de supressão tumoral e proteínas regulatórias de proliferação celular exercem papel na evolução da queilite actínica para carcinoma espinocelular e no comportamento biológico deste. O conhecimento de marcadores de diagnóstico e prognóstico e sua investigação têm utilidade no acompanhamento de tais pacientes.

Carcinoma de células escamosas labial em paciente jovem / Squamous cell carcinoma labial in young patient

O Carcinoma de células escamosas de lábio é uma neoplasia de origem epitelial que acomete, preferencialmente, homens, com idade superior a 50 anos, com fototipo de pele baixo, história de fotoexposição no passado, tabagistas e etilistas. Apresenta-se, mais comumente, no lábio inferior. O diagnóstico é feito através de história clínica, exame físico, biópsia e exame histopatológico. O tratamento de escolha é a cirurgia com a ressecção completa da lesão, a reconstrução labial e o esvaziamento cervical em casos indicados. Em virtude da elevada mortalidade, torna-se fundamental o diagnóstico e o tratamento precoces. Este trabalho tem por objetivo relatar o caso de um paciente do sexo masculino, de 21 anos, sem fatores de risco associados, mas que desenvolveu o carcinoma de células escamosas em lábio inferior.

Squamous Cell Carcinoma of lip is a cancer of epithelial origin that affects mainly men, aged over 50 years, with low skin phototype, history of sun exposure in the past, smokers and alcoholics. It presents more commonly in the lower lip. Diagnosis is done by clinical history, physical examination, biopsy and histopathology test. The treatment of choice is surgery with complete resection of the lesion, a lip reconstruction and the neck´s lymph node dissection dissection in indicated cases. Due to high mortality, early diagnosis and treatment are crucial for good prognosis. This paper aims to report the case of a male patient of 21 years old without risk factors who developed squamous cell carcinoma on the lower lip.

E-cadherin and c-Met expression in actinic cheilits and lip squamous cell carcinoma

Objective: The aim of this study was to assess epithelial expression of E-cadherin and c-Met in normal lip, in actinic cheilitis and lip squamous cell carcinoma. Study Design: Biopsies of normal lip vermillion (NL, n=18), actinic cheilitis (AC, n=37), and lip SCC (n=22) were processed for E-cadherin and c-Met immunodetection. Epithelial and tumor cell expression was scored for each sample considering staining intensity and percentage. Results: E-cadherin expression was significantly reduced in AC and lip SCC as compared to normal lip (P<0.05), with a significant reduction in lip SCC as compared to AC (P=0.003). Expression of c-Met was significantly higher in AC and lip SCC as compared to NL (P<0.05), with a significant increase in lip SCC as compared to AC (P<0.0001). Conclusion: The results showed that epithelial E-cadherin expression is reduced and c-Met expression is increased as lip carcinogenesis progresses, suggesting that these proteins may be useful markers of malignant transformation.

Oral and oropharyngeal squamous cell carcinoma in our population: the clinic-pathological and morphological description of 153 cases / Carcinoma de células escamosas oral y orofaríngeo en nuestra población: descripción clínico-patológica y morfológica de 153 casos

Oral cavity and oropharynx are one of the commonest sites for cancers in our population due to a high prevalence of tobacco use, especially chewing, in our country. The objective of this study was to prospectively assess the clinico-pathological and morphological aspects of the patients presenting to us with these malignancies. We studied 153 patients with oral and oropharyngeal squamous cell carcinoma who were managed in the department of otolaryngology and head and neck surgery between January 2006 and December 2007 at Maulana Azad Medical College and associated hospitals in New Delhi. There were 127 male patients (83 percent) and 26 females (17 percent) with ages ranging from 22 years to 70 years. One hundred and eleven patients (73 percent) presented with oral cavity and 42 patients (27 percent) with oropharyngeal carcinomas. Most common site of presentation in the oral cavity was the buccal mucosa, whereas, base of tongue was the commonest site in the oropharynx. Amongst the oral cavity cancers, 51 each (46 percent each) were well differentiated and moderately differentiated, whereas, 9 (8 percent) were poorly differentiated cancers. However, amongst the oropharyngeal cancers, 27 (64 percent) were moderately differentiated and 15 (36 percent) were poorly differentiated. Overall, 73 patients presented with lymphadenopathy on presentation, out of which, 44 patients were those with oral cavity and 29 with oropharyngeal cancers. There was a significant correlation between the site (i.e. oral cavity or orophaynx) and lymphadenopathy on presentation. Fifty nine patients (39 percent) presented to us with early stage disease (i.e. stage I and II), whereas, 94 patients (61 percent) presented with late stage disease (i.e. stage III and IV). There was a significant correlation between the site (i.e. oral cavity or oropharynx) and stage at presentation.

En nuestro país, la cavidad oral y orofaringe son los sitios más comunmente afectados por cáncer, debido a la alta prevalencia del consumo de tabaco, especialmente, el tabaco de mascar. El objetivo de este estudio fue evaluar prospectivamente los aspectos clínico-patológicos y morfológicos de los pacientes que acuden con estas malignidades. Se estudiaron 153 pacientes con carcinoma de células escamosas de la cavidad oral y orofaringe que fueron tratados en el Servicio de Otorrinolaringología y Cirugía de Cabeza y Cuello entre enero del 2006 y diciembre del 2007 en Maulana Azad Medical College y hospitales asociados en Nueva Delhi. Se evaluaron pacientes de ambos sexos, 127 hombres (83 por ciento) y 26 mujeres (17 por ciento) con edades entre 22 a 70 años. Ciento once pacientes (73 por ciento) presentaron carcinoma de la cavidad oral y 42 (27 por ciento) carcinomas de la orofaringe. El sitio más común de presentación en la cavidad oral fue la mucosa bucal, mientras que la base de la lengua fue el sitio más común de la orofaringe. Entre los cánceres de la cavidad oral, 51 (46 por ciento cada uno) estaban bien diferenciados y moderadamente diferenciados, mientras que 9 (8 por ciento) fueron escazamente diferenciado. Sin embargo, entre los cánceres de la orofaringe, 27 (64 por ciento) fueron moderadamente diferenciados y 15 (36 por ciento) fueron pobremente diferenciados. En total, 73 pacientes se presentaron con adenopatías, de los cuales, 44 pacientes fueron en la cavidad oral y 29 en la orofaringe. Se observó una correlación significativa entre el sitio (es decir, la cavidad oral u orofaringe) y la presentación de adenopatías. Cincuenta y nueve pacientes (39 por ciento) se presentaron con enfermedad en estadio temprano (estadios I y II), mientras que 94 pacientes (61 por ciento) se presentaron con enfermedad en estadio tardío (etapas III y IV). Se observó una correlación significativa entre el sitio (cavidad oral u orofaringe) y la etapa en la presentación.

Morphology of collagen fibers and elastic system fibers in actinic cheilitis.

Background: Actinic cheilitis (AC) is a premalignant condition intimately related to exposure of the lips to sun rays. Aim: The objective of this study was to evaluate the elastic and collagen fibers in the lamina propria of AC. The degree of epithelial atypia was correlated with the quantity of elastic and collagen fibers. Materials and Methods: Fifty-one cases were investigated. One slide was stained with hematoxylin-eosin for the evaluation of atypia, the second was stained with Weigert's resorcin-fuchsin for the assessment of elastic fibers, and the third slide was stained with Mallory's trichrome for the analysis of collagen fibers. Results: Ordinal logistic regression analysis revealed a significant correlation between the presence of atypia and collagen fibers (P<0.05). Conclusions: It was concluded that there seems to be a reduction in the quantity of collagen fibers in cases of moderate and severe atypia. No correlation was observed between the degradation of elastic system fibers and the grade of dysplasia.

FGF-2, TGFâ-1, PDGF-A and respective receptors expression in pleomorphic adenoma myoepithelial cells: an in vivo and in vitro study

Myoepithelial cells have an important role in salivary gland tumor development, contributing to a low grade of aggressiveness of these tumors. Normal myoepithelial cells are known by their suppressor function presenting increased expression of extracellular matrix genes and protease inhibitors. The importance of stromal cells and growth factors during tumor initiation and progression has been highlighted by recent literature. Many tumors result from the alteration of paracrine growth factors pathways. Growth factors mediate a wide variety of biological processes such as development, tissue repair and tumorigenesis, and also contribute to cellular proliferation and transformation in neoplastic cells. OBJECTIVES: This study evaluated the expression of fibroblast growth factor-2 (FGF-2), transforming growth factor â-1 (TGFâ-1), platelet-derived growth factor-A (PDGF-A) and their respective receptors (FGFR-1, FGFR-2, TGFâR-II and PDGFR-á) in myoepithelial cells from pleomorphic adenomas (PA) by in vivo and in vitro experiments. MATERIAL AND METHODS: Serial sections were obtained from paraffin-embedded PA samples obtained from the school's files. Myoepithelial cells were obtained from explants of PA tumors provided by surgery from different donors. Immunohistochemistry, cell culture and immunofluorescence assays were used to evaluate growth factor expression. RESULTS: The present findings demonstrated that myoepithelial cells from PA were mainly positive to FGF-2 and FGFR-1 by immunohistochemistry and immunofluorescence. PDGF-A and PDGFR-á had moderate expression by immunohistochemistry and presented punctated deposits throughout cytoplasm of myoepithelial cells. FGFR-2, TGFâ-1 and TGFâR-II were negative in all samples. CONCLUSIONS: These data suggested that FGF-2 compared to the other studied growth factors has an important role in PA benign myoepithelial cells, probably contributing to proliferation of ...