Clear Cell Myoepithelial Carcinoma of the Upper Lip -A Rare Case Report.

Myoepithelial carcinomas are quite infrequent neoplasms and coupled with their diverse morphological appearance are interesting as far as diagnosis and management is concerned. They account for less than 1% of all salivary gland tumors. The variable morphologic appearance of myoepithelial carcinoma leads to a wide differential diagnosis, including primary salivary gland tumors and metastatic tumors. The prognosis of these tumors is not fair as they are locally aggressive and approximately one third of the patients die of the pathology. We report a case of clear cell variant of myoepithelial carcinoma in an unusual location, i.e. the upper lip. The treatment carried out was wide surgical resection. The patient was followed up for 2 years and was symptom free. The clear cell variant of myoepithelial carcinoma is extremely rare and only about 51 cases of this variant affecting the salivary glands have been reported worldwide so far.

Moesin Involvement in Oral Carcinogenesis of the Lower Lip.

BACKGROUND/AIM: This study analyzed moesin immunoexpression in 91 lip squamous cell carcinomas and its influence in patients' prognosis. MATERIALS AND METHODS: Moesin immunoexpression was evaluated at the invasive tumor front by a semi-quantitative score method. The association of moesin with the clinicopathological variables was analyzed by the Chi-square test, the survival rates were calculated by Kaplan-Meier and the survival curves compared using the log-rank test. RESULTS: The expression of moesin was strong at the invasive tumor front and weak/negative in differentiated cells such as keratin pearls. There was no association between moesin expression and the clinicopathological variables, but there was a tendency for patients with lip cancer and strong moesin expression to have lower 5- and 10-year overall and disease-free survival rates. CONCLUSION: Our results confirm the participation of moesin in oral carcinogenesis and suggest that this protein can influence the survival rates of patients with lip squamous cell carcinoma.

Rhabdomyoma of the Lip: A Case Report With Review of the Literature.

Rhabdomyoma (RM) is a rare benign mesenchymal tumor associated with skeletal muscle differentiation. We report a case of adult-type RM occurring in the lower lip of a 48-year-old man, clinically suspicious for squamous cell carcinoma. Only 3 cases of adult-type RM have been described in the literature in this anatomical site. The histologic differential diagnoses with other lesions are presented, with emphasis on immunohistochemical aspects.

Neglected giant spinocellular carcinoma of the lower lip.

Although squamous cell carcinoma (SCC) is the most common type of lip cancer worldwide, its giant form is extremely rare, due to its easy detection and early diagnosis. The survival rate is good if early eradication is performed, as 5-year survival accounts for approximately 80-90%. We present a rare variant of giant form of SCC on the lower lip in a 70-year-old patient, which had been neglected for many years, due to social disadvantages and absence of any resources for adequate medical help, until the tumor caused total inability of administration of food and drink. The recent diagnostic and therapeutic options are considered. Despite well-known etiologic factors regarding squamous cell carcinoma and the newest prognostic factors on tumor differentiation, such as ß-catenin abnormal expression, the negative influence of the demographic characteristics of the patient were also in focus. Certain outcast ways of living should be considered as potential risk factors for the development of giant forms of SCC. In addition, an improvement of the quality of life of these patients results as being critical for the prevention of various of risk factors, as well as improving the survival rate in general.

Expression of glucose transporters 1 and 3 in metastatic and non-metastatic lower lip squamous cell carcinoma.

This study aimed to evaluate the immunoexpression of glucose transporters 1 (GLUT-1) and 3 (GLUT-3) in metastatic and non-metastatic lower lip squamous cell carcinoma (LLSCC). Twenty LLSCCs with regional nodal metastasis and 20 LLSCCs without metastasis were selected. The distribution of staining and the percentage of GLUT-1 and GLUT-3 staining in each tumor core and at the deep invasive front were assessed. Most tumors (70%) exhibited peripheral staining for GLUT-1 in nests, sheets and islands of neoplastic cells, whereas predominantly central staining was observed for GLUT-3 (72.5%). A high percentage of GLUT-1-positive cells was observed at the deep invasive front and in the tumor core of metastatic and non-metastatic tumors (p>0.05). The percentage of GLUT-1-positive cells was much higher than that of GLUT-3-positive cells both in the deep invasive front (p<0.001) and in the tumor core (p<0.001) of LLSCCs. No significant differences in the percentage of GLUT-1- and GLUT-3-positive cells were observed according to nodal metastasis, clinical stage or histological grade of malignancy (p>0.05). In conclusion, the results of the present study suggest an important role of GLUT-1 in glucose uptake in LLSCCs, although this protein does not seem to be involved in the progression of these tumors. On the other hand, GLUT-3 expression may represent a secondary glucose uptake mechanism in LLSCCs.

Ki-67, TGF-ß1, and elastin content are significantly altered in lip carcinogenesis.

Epithelial changes observed in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC) have been studied using different markers in order to observe diagnostic and prognostic factors for both lesions. The aim of the present study was to analyze Ki-67, TGF-ß1, and elastin content in AC and LLSCC to determine the possible role of these proteins in lip carcinogenesis. Medical records of 29 cases of AC and 53 cases of LLSCC were analyzed. Lesions were classified according histological pattern and submitted to immunostaining for Ki-67, TGF-ß1, and elastin. Different percentages of Ki-67-positive cells were found in AC depending on the degree of epithelial dysplasia (p < 0.01). An association was also found between the percentage of Ki-67-positive cells and tumor grade in LLSCC (p < 0.01). An inverse correlation was found between Ki-67 and TGF-ß1 in AC and LLSCC (p < 0.01). Elastosis was thinner and more discontinuous in LLSCC in comparison to AC, and this difference in the elastin immunolabeling pattern was statistically significant between groups (p < 0.01). The present findings indicate that changes in Ki-67 and TGF-ß1 content contribute to lip carcinogenesis. Furthermore, elastin content reflects changes in the extracellular matrix in both AC and LLSCC.

Canalicular adenoma immunoprofile: a case report.

OBJECTIVES: To report a case of canalicular adenoma (CA) and discuss the use of immunohistochemistry to better address the diagnosis given some unusual characteristics in this patient. BACKGROUND: CA is an uncommon benign neoplasm that can develop in minor salivary gland duct tissues throughout the oral cavity. At histology, it shares several features with other salivary tumors. Immunohistochemistry can be useful in the differential diagnosis. MATERIALS AND METHODS: The clinical presentation consisted in a nodule on the left upper lip of an 85-year-old man. The patient's main complaint was upper denture instability secondary to soft tissue changes. The nodule was excised under local anesthesia and underwent histological and immunohistochemical examination to rule out any malignancy. RESULTS: Histological findings, cytokeratin positivity and the absence of any reactivity to specific markers of myoepithelial differentiation confirmed the epithelial nature of the lesion. CONCLUSION: The histological diagnosis of benign salivary tumors such as CA can be confirmed by immunohistochemistry.

Relationship between the epithelial expression of hMLH1, MDM2, and p63 and lower lip carcinogenesis.

OBJECTIVES: To evaluate the relationship between the epithelial expression of hMLH1, MDM2, and p63 in lower lip carcinogenesis, comparing the immunostaining of these proteins in cases of actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC). STUDY DESIGN: Forty cases of AC and 40 cases of SCC were studied, both lesions were of lower lip. Histological sections of 3 µm were submitted to immunoperoxidase method, and 1000 cells were counted for immunohistochemical analysis of lesions. The results were analyzed quantitatively, and expression was compared by the Mann-Whitney, Student t-test, or one-way ANOVA, adopting a level of significance of 5%. RESULTS: A higher percentage of epithelial cells expressing hMLH1 was observed in cases of AC without dysplasia or mild dysplasia (721.23 ± 88.116), whereas fewer positive cells were observed in lower lip SSCs (255.03 ± 199.47) when compared to the AC group (P < 0.001). Immunoexpression of MDM2 was higher in SCCs of the lower lip compared with AC (P = 0.019). For p63 protein, the expression was higher in AC than in SCC (P = 0.045). CONCLUSION: The present results showed changes in the immunoexpression of hMLH1, MDM2, and p63 in epithelial cells from premalignant and malignant lip disease, supporting the hypothesis that these alterations are related to the process of lower lip carcinogenesis.

STAG2 expression in oral cancer and potentially malignant lesions.

Oral cancer is a world health problem, and one of the highest incidence rates of oral cancer worldwide occurs in Brazil. STAG2 is part of the cohesin complex which is responsible for sister chromatid cohesion. STAG2 loss of expression was reported in a range of tumors, and STAG2 loss was found to cause chromosomal instability and aneuploidy in cancer cells. On the basis of these findings, we investigated STAG2 expression in oral cancer and potentially malignant lesions. We investigated STAG2 immunoexpression in oral cancer, lip cancer, oral leukoplakia, and actinic cheilitis, including complete clinical information. Normal oral mucosa samples were included as normal controls. STAG2 protein was highly expressed in all samples. We further tested STAG2 expression in gastric adenocarcinomas and glioblastomas, as these tumor types were previously shown to lose STAG2 expression. We found homogenous expression of STAG2 by these tumor cells. Our results suggest that STAG2 loss of expression is not a common event in oral carcinogenesis.

Expression of laminin-5 and integrins in actinic cheilitis and superficially invasive squamous cell carcinomas of the lip.

The progression of carcinogenesis entails the detachment of cells, invasion and migration of neoplastic cells. Alterations in epithelial adhesion and basement membrane proteins might mediate the early stages of carcinogenesis. This study investigated the expression of adhesion molecules and the basement membrane protein laminin-5 in actinic cheilitis (AC) and incipient squamous cell carcinoma of the lower lip to understand early photocarcinogenesis. Ln-5γ2 chain as well as α3, ß1 subunits of α3ß1 heterodimer and ß4 subunit of integrin α6ß4 were evaluated by immunohistochemistry in 16 cases of AC and 16 cases of superficially invasive squamous cell carcinoma (SISCC). Most AC cases showed reduced expression of ß1, ß4 and α3 integrins, and SISCCs lacked ß1, ß4 and α3 integrins in the invasive front. AC cases were negative for the Ln-5γ2 chain. Five cases of SISCC (31%) showed heterogeneous Ln-5γ2 chain expression in the invasive front of the tumor. Integrin ß1, ß4 and α3 expression is lost during the early stages of lip carcinogenesis. Expression of Ln-5γ2 in the invasive front in cases and its correlation with tumor progression suggest that it mediates the acquisition of the migrating and invading epithelial cell phenotype.

Mucosa-associated lymphatic tissue lymphoma of the lower lip in a child.

Mucosa-associated lymphatic tissue lymphoma of the lip in a child is a very rare clinical entity whose cause is poorly understood. We describe an 11-year-old boy who presented with a 5-month history of an asymptomatic nodule on the lower lip with the clinical appearance of a benign mucocele. After surgical excision of the lower lip lesion, lymphocyte phenotypic analysis and histologic examination of the specimen disclosed an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphatic tissue type of the buccal minor salivary glands. Mucosa-associated lymphatic tissue lymphoma of the lip may clinically resemble a large mucocele. To prevent a delayed detection of lip mucosa-associated lymphatic tissue lymphoma, an incisional biopsy of large mucous cysts of the oral mucosa before marsupialization is recommended.

Evaluation of MMP-1, MMP-10, TIMP-1, a-SMA and TGF-b1 in angiofibromas of tuberous sclerosis.

AIM: Tuberous sclerosis is a neurocutaneous syndrome characterized by affect multiple organs such as brain, kidneys, heart, eyes, lungs and skin. The aim of this study was to analyze the pattern of immunolocalization of markers MMP-1, MMP-10, TIMP-1, α-SMA and TGF-ß1 in oral and facial angiofibromas in individuals affected by tuberous sclerosis. METHODS: Microscopical analyses on hematoxilin-eosin and immunohistochemistry reactions were performed to analyze the previously cited biological markers pattern in orofacial angiofibromas. RESULTS: Reactivity was observed for MMP-1, MMP-10 and TGF-ß1, in addition to negative for TIMP-1 and α-SMA, except perivascular and epithelial staining for this. Concerning the intensity, a strong marking for MMP-1 in the basal layer of the epithelium, and a slight positivity in the suprabasal layers predominated. MMP-10 was slightly expressed in all epithelial layers. The connective tissue showed slight to moderate reactivity for MMP-1 and MMP-10. TIMP-1 demonstrated slight to moderate marking in the various layers of a single lesion and to TGF-ß1 expression showed varied in intensity staining both between lesions and between tissue layers. CONCLUSION: MMP-1, MMP-10 and TGF-ß1 exhibited reactivity in oral and cutaneous angiofibromas with heterogeneous distribution patterns among both tissue elements analyzed in the intensity of marking the same among the specimens. TIMP-1 showed reactivity predominantly negative in the specimens analyzed and α-SMA presented restricted to epithelial and perivascular regions of these lesions.

Immunohistochemical expression of E-cadherin and CD44v6 in squamous cell carcinomas of the lower lip and tongue.

This study analyzed the immunohistochemical expression of E-cadherin and CD44v6 in 15 squamous cell carcinomas (SCCs) of lower lip and 15 SCCs of tongue in order to verify a possible association between these proteins and the anatomic location of the lesion, nodal metastasis and histological grading of malignancy. The pattern of expression and number of immunopositive cells were evaluated. The results were analyzed with the Fisher's exact test, Mann-Whitney test and Spearman's Correlation Coefficient (r). using the SPSS software 10.0 for Windows. Statistical significance was set at 5% determined for a p-value<0.05 for all tests. There was no significant difference (p>0.05) in the pattern of expression and number of immunopositive cells for E-cadherin and CD44v6, regarding the anatomical location and nodal metastasis. For the histological grading, low score SCCs showed higher immunopositivity for E-cadherin and CD44v6, both for the pattern of expression and number of immunopositive cells (p<0.05). There was a negative correlation between the total score of malignancy and the pattern of expression and number of immunopositive cells for E-cadherin and CD44v6 (p<0.05). In conclusion, SCCs of the lower lip and tongue did not reveal significant differences in the expression of E-cadherin and CD44v6. The expression of these adhesion molecules revealed association only with tumor histological grading of malignancy. Therefore, these results suggest that E-cadherin and CD44v6 may not help elucidating the differences between the biological behavior of SCCs of the lower lip and tongue.

Changes in immunoexpression of E-cadherin and beta-catenin in oral squamous cell carcinoma with and without nodal metastasis.

The aim of this study is to analyze the immunohistochemical expression of E-cadherin and beta-catenin in oral squamous cell carcinoma to better understand the biological behavior of this lesion. The sample consisted of 15 cases of the tongue and 15 of the lower lip. The pattern and intensity of the labeling and the analysis of the percentage of tumor cells immunopositive in membrane for E-cadherin and beta-catenin were related to the anatomic location of the lesion, the presence or absence of nodal metastasis, and the histological gradation of malignancy in the tumor invasion front. The presence or absence of cytoplasmic and nuclear labeling was also recorded. The membrane expression for E-cadherin and beta-catenin predominately displayed a heterogeneous pattern in the carcinomas studied. No significant difference was observed between the expression pattern and the quantity of cells immunopositive for E-cadherin and beta-catenin and the anatomic location of the lesion or the presence or absence of nodal metastasis. However, a statistically significant difference was found between the reduced expressio\n of these proteins and the high malignancy score. The reduced immunoexpression of these proteins in the membrane may be related to the high degree of cell indifferentiation in cases of oral squamous cell carcinoma with high scores.

Immunohistochemical expression of E-cadherin and CD44v6 in squamous cell carcinomas of the lower lip and tongue

This study analyzed the immunohistochemical expression of E-cadherin and CD44v6 in 15 squamous cell carcinomas (SCCs) of lower lip and 15 SCCs of tongue in order to verify a possible association between these proteins and the anatomic location of the lesion, nodal metastasis and histological grading of malignancy. The pattern of expression and number of immunopositive cells were evaluated. The results were analyzed with the Fisher's exact test, Mann-Whitney test and Spearman's Correlation Coefficient (r). using the SPSS software 10.0 for Windows. Statistical significance was set at 5 percent determined for a p-value<0.05 for all tests. There was no significant difference (p>0.05) in the pattern of expression and number of immunopositive cells for E-cadherin and CD44v6, regarding the anatomical location and nodal metastasis. For the histological grading, low score SCCs showed higher immunopositivity for E-cadherin and CD44v6, both for the pattern of expression and number of immunopositive cells (p<0.05). There was a negative correlation between the total score of malignancy and the pattern of expression and number of immunopositive cells for E-cadherin and CD44v6 (p<0.05). In conclusion, SCCs of the lower lip and tongue did not reveal significant differences in the expression of E-cadherin and CD44v6. The expression of these adhesion molecules revealed association only with tumor histological grading of malignancy. Therefore, these results suggest that E-cadherin and CD44v6 may not help elucidating the differences between the biological behavior of SCCs of the lower lip and tongue.

Este estudo analisou a expressão imuno-histoquímica de E-caderina e CD44v6 em 15 carcinomas de células escamosas (CCEs) de lábio inferior e em 15 CCEs de língua, com o intuito de identificar possíveis associações entre a expressão destas proteínas e a localização anatômica da lesão, ocorrência de metástase nodal e gradação histológica de malignidade. Foram avaliados o padrão de expressão e o número de células imunopositivas. Os resultados foram analisados pelo teste exato de Fisher, teste de Mann-Withney e coeficiente de correlação de Spearman (r), utilizando o software SPSS 10.0 para Windows. Para todos os testes, a significância estatística foi determinada em 5 por cento, para um valor de p<0,05. Os resultados revelaram não haver diferença significativa no padrão de expressão e na quantidade de células imunopositivas para E-caderina e CD44v6 em relação à localização anatômica e metástase nodal (p>0,05). Para a gradação histológica de malignidade, os CCEs de baixo escore revelaram maior imunopositividade para E-caderina e CD44v6, tanto para o padrão de expressão quanto para o número de células imunopositivas (p<0,05). Observou-se correlação negativa entre o escore total de malignidade e o padrão de expressão e a quantidade de células imunopositivas para E-caderina e CD44v6 (p<0,05). Em conclusão, CCEs de lábio inferior e língua não revelaram diferenças significativas na expressão de E-caderina e CD44v6. A expressão destas moléculas de adesão revelou associação apenas com gradação histológica de malignidade dos CCEs. Dessa forma, os resultados sugerem que E-caderina e CD44v6 podem não ser capazes de elucidar as diferenças existentes no comportamento biológico de CCEs de lábio inferior e língua.

[Prognostic molecular markers in oral and lip squamous cell carcinoma--evaluation of expression and its significance]. / Ekspresja niektórych molekularnych markerów immunohistochemicznych i ocena ich znaczenia prognostycznego w rakach plaskonablonkowych jamy ustnej i wargi.

INTRODUCTION: Head and neck cancer treatment optimization and individualization has become possible due to the implementation of the prognostic and predictive molecular markers in diagnostics. AIM: The aim of this study was an attempt to determine which of the investigated molecular markers may have prognostic and predictive value in head and neck cancers. MATERIALS AND METHODS: The paraffin blocks from 47 patients with oral and lip squamous cell carcinoma (SCC) after surgical treatment in the Institute of Oncology in Gliwice in the period of 1998-2002 were investigated. For immunohistochemical studies the DAKO monoclonal antibodies were used: p53, Ki67, Cyclin D1, Cathepsin B and Cox2-Cayman Chemical antibody. Staining reactions were evaluated at 400x magnification. The average percent of staining cells was estimated in every case in the groups of patients with (N+) and without (No) node metastases. The results were subsequently juxtaposed with selected clinical and histological parameters. Statistical analysis was performed with Mann-Whitney and Kruskal-Wallis tests and the log rank test with a significance level of 0.05 (p = 0,05). RESULTS: Significantly higher expression of Ki67 in N+ patients (p = 0,010) were recorded, although average staining in the group of treated and the group of unhealed patients was statistically insignificant. Cathepsin B expression (<20% and > 20%) was correlated with 3 year-long survival and a slight higher average staining (33,5%) in unhealed in comparison with treated patients (29,0%) was notified. Everage expression of p53 in unhealed patients (33,1%) was slightly higher than in treated ones (28,4%). Weaker Cyclin D1 expression (<10%) correlated with higher disease free survival. Average Cycline D1 staining in the groups of unhealed patients (19,6%) was higher than in the treated ones (12,0%). There were no significant differences in COX-2 staining in correlation with clinical and histological parameters. CONCLUSIONS: Lower expression of Cyclin D1 and Cathepsin B in neoplastic cells correlated with higher percentage of disease free survival what suggests the prognostic value of these markers. Higher proliferation activity of primary tumor neoplastic cells correlated with node metastases what may has the predictive value in the course of the disease.The different markers expressions observed in the different oral cavity localizations confirm the necessity to select patients for further investigations with respect to uniform disease changes topography.