Oral Mucosal Melanoma: A Case Report and Literature Review

ABSTRACT: Oral mucosal melanoma is an unusual and aggressive malignant tumor that mainly affects the palate of men aged between 50 and 60 years. We present a literature review focusing on the etiopathogenesis and the clinicopathologic features of this entity. In addition, we reported a rare case of an oral mucosal melanoma arising in the left cheek of a 60-yea r- old man. Computed tomography scan revealed infiltration of the tumor to other anatomic structures including the maxillary sinus, the zygomatic bone and the pterygoid processes. Based on its extension, the lesion was considered inoperable and treatment with three-dimensional conformal radiation therapy was proposed but the patient only attended to the first session and died from cancer progression 6 months after the diagnosis. This paper reinforces the importance of inclusion of this malignant tumor in the differential diagnosis of pigmented lesions of the oral mucosa.

RESUMEN: El melanoma de la mucosa oral es un tumor maligno inusual y agresivo que afecta principalmente al paladar de hombres de entre 50 y 60 años. Presentamos una revisión bibliográfica centrada en la etiopatogenia y las características clínico-patológicas de esta entidad. Además, reportamos un caso raro de melanoma de la mucosa oral que surgió en la mejilla izquierda de un hombre de 60 años. La tomografía computarizada reveló la infiltración del tumor a otras estructuras anatómicas, incluido el seno maxilar, el hueso cigomático y los procesos pterigoideos. En base a su extensión, la lesión se consideró inoperable y se propuso tratamiento con radioterapia conformada tridimensional pero el paciente solo asistió a la primera sesión y falleció por progresión del cáncer 6 meses después del diagnóstico. Este trabajo refuerza la importancia de la inclusión de este tumor maligno en el diagnóstico diferencial de las lesiones pigmentadas de la mucosa oral.

Beta adrenergic receptor activation inhibits oral cancer migration and invasiveness.

OBJECTIVE: The aim of this study was to verify ß2-AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of this receptor in migration and invasion of these neoplastic cells. DESIGN: SCC-9 and SCC-25 cells were investigated for gene and protein expression of ß2-AR. Cell migration and invasion were analyzed by wound healing assay and transwell invasion camera system. Different concentrations (0.1, 1 and 10 µM) of norepinephrine were used to stimulate, and 1 µM propranolol was used to block the beta-adrenergic receptors on cancer cells. Differences in median values of SCC-9 and SCC-25 and ß2-AR protein expression were analyzed by Friedman test and in case of significant differences; pairwise comparisons were performed using Bonferroni correction. RESULTS: The results showed that the ß2-AR gene and protein expression were observed in both oral cancer cell lines. The concentration of 10 µM of norepinephrine significantly inhibited (p ≤ 0.05) migration of SCC-9 and SCC-25 cell lines. Furthermore, there was a significant reduction (p ≤ 0.05) in the effect of norepinephrine on cell migration when the ß2-AR was inhibited by propranolol. The blockade by propranolol showed a tendency to reverse the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. CONCLUSIONS: The use of beta-adrenergic receptor agonists could become an adjuvant therapeutic target in the treatment of this malignancy.

Correlation of Beta-2 Adrenergic Receptor Expression in Tumor-Free Surgical Margin and at the Invasive Front of Oral Squamous Cell Carcinoma.

Background. The beta-2 adrenergic receptor is expressed by neoplastic cells and is correlated with a wide spectrum of tumor cell mechanisms including proliferation, apoptosis, angiogenesis, migration, and metastasis. Objectives. The present study aimed to analyze the expression of the beta-2 adrenergic receptor (ß2-AR) in tumor-free surgical margins of oral squamous cell carcinomas (OSCC) and at the invasive front. Sixty-two patients diagnosed with OSCC, confirmed by biopsy, were selected for the study. The clinicopathological data and clinical follow-up were obtained from medical records and their association with ß2-AR expression was verified by the chi-square test or Fischer's exact test. To verify the correlation of ß2-AR expression in tumor-free surgical margins and at the invasive front of OSCCs, Pearson's correlation coefficient test was applied. Results. The expression of ß2-AR presented a statistically significant correlation between the tumor-free surgical margins and the invasive front of OSCC (r = 0.383; p = 0.002). The immunohistochemical distribution of ß2-AR at the invasive front of OSCC was also statistically significant associated with alcohol (p = 0.038), simultaneous alcohol and tobacco consumption (p = 0.010), and T stage (p = 0.014). Conclusions. The correlation of ß2-AR expression in OSCC and tumor-free surgical margins suggests a role of this receptor in tumor progression and its expression in normal oral epithelium seems to be constitutive.

Correlation of Beta-2 Adrenergic Receptor Expression inTumor-Free Surgical Margin and at the Invasive Front ofOral Squamous Cell Carcinoma

Background. The beta-2 adrenergic receptor is expressed by neoplastic cells and is correlated with a wide spectrum of tumor cell mechanisms including proliferation, apoptosis, angiogenesis, migration, and metastasis. Objectives. The present study aimed to analyze the expression of the beta-2 adrenergic receptor (ß2-AR) in tumor-free surgical margins of oral squamous cell carcinomas (OSCC) and at the invasive front. Sixty-two patients diagnosed with OSCC, confirmed by biopsy, were selected for the study. The clinicopathological data and clinical follow-up were obtained from medical records and their association with ß2-AR expression was verified by the chi-square test or Fischer's exact test. To verify the correlation of ß2-AR expression in tumor-free surgical margins and at the invasive front of OSCCs, Pearson's correlation coefficient test was applied. Results. The expression of ß2-AR presented a statistically significant correlation between the tumor-free surgical margins and the invasive front of OSCC (r = 0.383; p = 0.002). The immunohistochemical distribution of ß2-AR at the invasive front of OSCC was also statistically significant associated with alcohol (p = 0.038), simultaneous alcohol and tobacco consumption (p = 0.010), and T stage (p = 0.014). Conclusions. The correlation of ß2-AR expression in OSCC and tumor-free surgical margins suggests a role of this receptor in tumor progression and its expression in normal oral epithelium seems to be constitutive

Migração e invasão do câncer de boca via ativação de receptor beta 2 adrenérgico por mediador do estresse / Cell migration and invasion of oral cancer via activation of beta 2 adrenergic receptor by stress mediator

A ativação do receptor beta 2 adrenérgico (β2-AR), pelos mediadores químicos do estresse, pode induzir efeitos estimuladores ou inibidores na migração e invasão celular, dependendo do tipo de tumor maligno. A importância deste receptor na evolução do câncer de boca não está totalmente esclarecida. O objetivo deste estudo foi verificar a expressão do β2-AR em linhagens de carcinomas espinocelular de boca (SCC-9 e SCC-25), e investigar o papel da ativação deste receptor pela norepinefrina e de seu bloqueio por um antagonista na migração e invasão destas células neoplásicas. As células SCC-9 e SCC-25 foram investigadas quanto à expressão gênica e proteica do β2-AR, respectivamente, pelo RT-qPCR e pelo Western blot. A migração e a invasão celular foram analisadas pelo ensaio de cicatrização de feridas e pelo sistema de câmeras de invasão Transwell, respectivamente. Diferentes concentrações (0,1; 1 e 10μM) de norepinefrina foram utilizadas para estimular e 1μM de propranolol foi empregado para bloquear os receptores beta adrenérgicos nas células neoplásicas. As diferenças das médias obtidas nos experimentos de invasão e migração de SCC-9 e SCC-25 e da expressão proteica do β2-AR, foram comparadas pelo teste t de Student com nível de significância de 5%. Os resultados mostraram que a expressão gênica e proteica do β2-AR foi verificada em ambas as linhagens de câncer de boca. A concentração de 10μM de norepinefrina inibiu, significativamente (p≤0,05), a migração e invasão celular de SCC-9 e SCC-25, sendo este efeito mais acentuado nas células SCC-25. Além disso, houve uma redução significativa (p≤0,05) do efeito da norepinefrina na migração celular quando os β2-AR foram inibidos pelo propranolol. Adicionalmente, o bloqueio dos β-ARs pelo propranolol reverteu parcialmente o efeito da norepinefrina na capacidade invasiva de SCC-9 e SCC-25. Estes resultados comprovam que a norepinefrina, via ativação do β2-AR, reduziu a migração e a invasão das...

The activation of beta 2 adrenergic receptor (β2-AR), by chemical mediators of stress, can induce stimulatory or inhibitory effects on cell migration and invasion, depending on the type of malignancy. The importance of this receptor in the oral cancer outcome is not fully understood. The aim of this study was to verify β2- AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of activation of this receptor by norepinephrine and its blockade by an antagonist in migration and invasion of these neoplastic cells. SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR, respectively, by RT-qPCR and Western blot. The cell migration and invasion were analyzed by wound healing assay and Transwell invasion camera system, respectively. Different concentrations (0.1, 1 and 10μM) of norepinephrine were used to stimulate and 1μM propranolol was used to block the beta adrenergic receptors on cancer cells. Differences in mean values of the invasion and migration assays of SCC-9 and SCC-25 and β2-AR protein expression were compared by the Student t test with 5% significance level. The results showed that β2-AR gene and protein expression was verified in both oral cancer cell lines. The concentration of 10μM of norepinephrine inhibited significantly (p≤0.05), cell migration and invasion of SCC-9 and SCC-25, being the most pronounced effect in SCC-25 cells. Furthermore, there was a significant reduction (p≤0.05) of norepinephrine effect on cell migration when the β2-AR was inhibited by propranolol. In addition, blockade of β-ARs by propranolol partially reversed the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. These results show that norepinephrine via β2-AR activation, reduced the migration and invasion of oral squamous cell carcinoma cells and, therefore, the use of beta-adrenergic receptors agonists could become an adjuvant therapeutic target in the treatment of this malignancy.

Migração e invasão do câncer de boca via ativação de receptor beta 2 adrenérgico por mediador do estresse / Cell migration and invasion of oral cancer via activation of beta 2 adrenergic receptor by stress mediator

A ativação do receptor beta 2 adrenérgico (β2-AR), pelos mediadores químicos do estresse, pode induzir efeitos estimuladores ou inibidores na migração e invasão celular, dependendo do tipo de tumor maligno. A importância deste receptor na evolução do câncer de boca não está totalmente esclarecida. O objetivo deste estudo foi verificar a expressão do β2-AR em linhagens de carcinomas espinocelular de boca (SCC-9 e SCC-25), e investigar o papel da ativação deste receptor pela norepinefrina e de seu bloqueio por um antagonista na migração e invasão destas células neoplásicas. As células SCC-9 e SCC-25 foram investigadas quanto à expressão gênica e proteica do β2-AR, respectivamente, pelo RT-qPCR e pelo Western blot. A migração e a invasão celular foram analisadas pelo ensaio de cicatrização de feridas e pelo sistema de câmeras de invasão Transwell, respectivamente. Diferentes concentrações (0,1; 1 e 10μM) de norepinefrina foram utilizadas para estimular e 1μM de propranolol foi empregado para bloquear os receptores beta adrenérgicos nas células neoplásicas. As diferenças das médias obtidas nos experimentos de invasão e migração de SCC-9 e SCC-25 e da expressão proteica do β2-AR, foram comparadas pelo teste t de Student com nível de significância de 5%. Os resultados mostraram que a expressão gênica e proteica do β2-AR foi verificada em ambas as linhagens de câncer de boca. A concentração de 10μM de norepinefrina inibiu, significativamente (p≤0,05), a migração e invasão celular de SCC-9 e SCC-25, sendo este efeito mais acentuado nas células SCC-25. Além disso, houve uma redução significativa (p≤0,05) do efeito da norepinefrina na migração celular quando os β2-AR foram inibidos pelo propranolol. Adicionalmente, o bloqueio dos β-ARs pelo propranolol reverteu parcialmente o efeito da norepinefrina na capacidade invasiva de SCC-9 e SCC-25. Estes resultados comprovam que a norepinefrina, via ativação do β2-AR, reduziu a migração e a invasão das...

The activation of beta 2 adrenergic receptor (β2-AR), by chemical mediators of stress, can induce stimulatory or inhibitory effects on cell migration and invasion, depending on the type of malignancy. The importance of this receptor in the oral cancer outcome is not fully understood. The aim of this study was to verify β2- AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of activation of this receptor by norepinephrine and its blockade by an antagonist in migration and invasion of these neoplastic cells. SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR, respectively, by RT-qPCR and Western blot. The cell migration and invasion were analyzed by wound healing assay and Transwell invasion camera system, respectively. Different concentrations (0.1, 1 and 10μM) of norepinephrine were used to stimulate and 1μM propranolol was used to block the beta adrenergic receptors on cancer cells. Differences in mean values of the invasion and migration assays of SCC-9 and SCC-25 and β2-AR protein expression were compared by the Student t test with 5% significance level. The results showed that β2-AR gene and protein expression was verified in both oral cancer cell lines. The concentration of 10μM of norepinephrine inhibited significantly (p≤0.05), cell migration and invasion of SCC-9 and SCC-25, being the most pronounced effect in SCC-25 cells. Furthermore, there was a significant reduction (p≤0.05) of norepinephrine effect on cell migration when the β2-AR was inhibited by propranolol. In addition, blockade of β-ARs by propranolol partially reversed the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. These results show that norepinephrine via β2-AR activation, reduced the migration and invasion of oral squamous cell carcinoma cells and, therefore, the use of beta-adrenergic receptors agonists could become an adjuvant therapeutic target in the treatment of this malignancy...

Hyperplastic dental follicle: a case report and literature review.

Hyperplastic dental follicle is an odontogenic hamartomatous lesion associated with delayed or tooth eruption failure in young patients. The occurrence of this pericoronal dental lesion may be single or multiple and it seems to be more frequent than literature has reported. We present a literature review focusing on the etiopathogenesis and clinicopathological features of this hamartomatous lesion in young patients. In addition, we reported a case of hyperplastic dental follicle causing delayed tooth eruption of 14-year-old male patient. Microscopic analyses based on routine staining and immunohistochemistry were used to discuss the cells found in pericoronal follicle. This paper reinforces the importance of association between clinical history and radiographic features with microscopic pericoronal follicle examination for diagnosis of this hamartomatous lesion.

Squamous cell carcinoma arising from inverted schneiderian papilloma: a case report with oral involvement.

Inverted Schneiderian papilloma is an uncommon benign tumor that presents tendency to recur and propensity to be associated with malignancy in approximately 10% of the cases. Some of these lesions are isolated in the maxillary sinus, and predominantly affect white males with mean age of 50 years. We report a case of squamous cell carcinoma arising from inverted Schneiderian papilloma in the maxillary sinus extending to the mouth. The patient was submitted to extraction of a maxillary molar tooth four months before the exacerbation of the symptoms of nasal airway obstruction and facial enlargement. Computed tomography scan revealed a sinonasal mass causing opacification of the right maxillary sinus with destruction of the lateral nasal wall and maxillary sinus floor. The patient was referred to an oncology center for treatment and died from tumor progression one year after the cancer was diagnosed. The intention of this report is to alert dentists to include the inverted Schneiderian papilloma, either associated with squamous cell carcinoma, or not, in the differential diagnosis of maxillary sinus tumors with aggressive behavior, which may extend to the oral cavity or involve roots of teeth.

VEGF-C expression in oral cancer by neurotransmitter-induced activation of beta-adrenergic receptors.

The aim of this study was to investigate the expression of vascular endothelial growth factor type C (VEGF-C) in oral squamous cell carcinoma (OSCC) cell lines through norepinephrine-induced activation of beta-adrenergic receptors. Human OSCC cell lines (SCC-9 and SCC-25) expressing beta-adrenergic receptors were stimulated with different concentrations of norepinephrine (0.1, 1, and 10 µM) and 1 µM of propranolol, and analyzed after 1, 6, and 24 h. VEGF-C gene expression and VEGF-C production in the cell supernatant were evaluated by real-time PCR and by ELISA, respectively. The results showed that beta-adrenergic receptor stimulation by different concentrations of norepinephrine or blocking by propranolol did not markedly alter VEGF-C expression by SCC-9 and SCC-25 cells. VEGF-C protein levels produced by oral malignant cell lines after stimulation with different norepinephrine concentrations or blocking with propranolol was statistically similar (p > 0.05) to those of the control group (nonstimulated OSCC cell lines). Our findings suggest that stimulation of beta-adrenergic receptors by means of norepinephrine does not seem to modulate the VEGF-C expression in OSCC cell lines. These findings reinforce the need for further studies in order to understand the responsiveness of oral cancer to beta-adrenergic receptor stimulation or blockage, especially with regard to VEGF-C production.

Bilateral osteoporotic bone marrow defects of the mandible: a case report.

Osteoporotic bone marrow defect of the jaws has been reported as a poorly demarcated radiolucency that affect mainly posterior mandible of middle-aged woman. The incidence of this condition is not exactly established and its pathogenesis remains unknown. An additional unusual case of osteoporotic bone marrow defects occurring bilaterally in the mandibular edentulous regions of a 32-year-old white woman is presented reinforcing its diagnostic criteria and histopathological findings.

Prognostic significance of beta-2 adrenergic receptor in oral squamous cell carcinoma.

The aim of this study was to evaluate the expression of ß2-adrenergic receptor (ß2-AR) in oral squamous cell carcinoma (OSCC) and to investigate the correlations between expression level and clinical characteristics, outcome, and patient prognosis. A total of 106 OSCC patients underwent surgical treatment at the A.C. Camargo Cancer Hospital, São Paulo, Brazil, were analyzed for clinicopathological data, treatment, tumor outcome, prognosis and immunohistochemical expression of ß2-AR. The ß2-AR expression was statistically analyzed relative to clinicopathological variables and survival using the Chi-square test, Kaplan-Meier curves and Cox regression model. Most OSCC (72.6%) exhibited malignant cells with strong cytoplasmatic and membranous ß2-AR expression. ß2-AR expression was significantly associated with alcohol (p = 0.021), simultaneous consumption of alcohol and tobacco (p = 0.014) and T stage (p = 0.07). In addition, OSCC patients who exhibited strong ß2-AR expression demonstrated a higher rate of overall survival (p = 0.001) and cancer specific survival (p = 0.004) compared to patients with weak/negative ß2-AR expression. The Cox regression model demonstrated that strong ß2-AR expression was an independent favorable prognostic factor for OSCC patients. These results suggest that the strong malignant cell ß2-AR expression is a favorable prognostic factor for OSCC patients and could be used as a target for new anti-neoplastic pharmacological strategies.

Expressão de receptor beta-2 adrenérgico em carcinoma espinocelular de boca e sua associação com a evolução clínica tumoral / Expression of beta-2 adrenergic receptor in oral squamous cell carcinoma and its association with tumor clinical outcome

Os hormônios produzidos durante o estresse e seus receptores específicos têm sido amplamente envolvidos com a progressão do câncer. O objetivo deste estudo foi avaliar a expressão dos receptores β2 adrenérgicos pelas células malignas de carcinomas espinocelulares de boca (CEC) e sua correlação com as a características clínicas, evolução e o prognóstico dos pacientes. Um total de 106 pacientes portadores de CEC de boca em estádios clínicos II, III e IV, tratados no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital de Câncer A.C. Camargo, São Paulo, Brasil, no período de 1970 a 2000, foram analisados quanto aos dados demográficos, história clínica, localização e extensão do tumor, classificação pelo sistema TNM-UICC, tratamento e evolução tumoral. Analisaram-se também as características histopatológicas, índice de malignidade tumoral e a expressão imuno-histoquímica do receptor β2 adrenérgico pelas células malignas no front de invasão tumoral. A associação da expressão do receptor β2 adrenérgico e as variáveis clínicas ou microscópicas foi calculada pelo teste do qui quadrado ou teste exato de Fisher. As probabilidades de sobrevida global e específica por câncer em 5 e 10 anos foram calculadas pelo estimador produto-limite de Kaplan-Meier, comparadas pelo test de long-rank e pelo modelo de regressão múltiplo de Cox. A expressão do receptor β2 adrenérgico foi detectada na membrana e no citoplasma das células malignas da maioria dos CECs de boca (72,6%) e, significativamente associada ao etilismo (p=0,021), tabagismo e etilismo simultâneo (p=0,014) e estadiamento T (p=0,07). Os pacientes cujos tumores demonstraram expressão positiva do receptor β2 adrenérgico apresentaram maiores taxas de sobrevida global (p=0,001) e específica por câncer (p=0,004), quando comparadas aquelas dos pacientes com tumores com ausência da expressão desta proteína. Esses resultados sugerem que a expressão do receptor β2 adrenérgico...

The stress related hormones and their specific receptors have been widely involved with cancer progression. The aim of this study was to evaluate the expression of β2 adrenergic receptor by malignant cells in oral squamous cell carcinoma (OSCC) and its correlation with clinical characteristics, outcome and patients prognosis. A total of 106 patients with OSCC in clinical stages II, III and IV submitted to surgical treatment at the Head and Neck Surgery and Otorhinolaryngology Department, of the Cancer Hospital A.C. Camargo, São Paulo, Brazil, from 1970 to 2000, were analyzed for demographics data, clinical history, location, tumor extension, stage by the TNM-UICC, treatment and tumor outcome. In addition, we investigated the morphologic features, the histopathological malignant index and the immunohistochemical expression of β2 adrenergic receptor by malignant cells of the invasive front of tumor. Chi-square test or Fishers exact test was used to analyze the association among β2 adrenergic receptor expression and the clinical or morphologic variables. The probability of overall and cancer specific survival in 5 and 10 years were calculated by Kaplan-Meier method and the prognostic value of the clinical and morphologic variables was obtained by Cox regression model. Most of OSCCs (72,6%) showed the β2 adrenergic receptor expression in cytoplasm and cell membrane of malignant cells. In OSCC, positive β2 adrenergic receptor expression was significantly associated with alcoholism (p=0.021), simultaneous consumption of alcohol and tobacco (p=0.014) and T stage (p=0.07). OSCC patients with positive expression of β2 adrenergic receptor showed higher rates of overall survival (p=0.001) and cancer specific (p=0.004) than those patients with tumors without expression of this protein. These results suggest that the β2 adrenergic receptor expression by malignant cells in the invasive front of tumor is a favorable prognostic factor in patients with OSCC and can be used...