Cell proliferation is associated with intensity of tumor budding in oral squamous cell carcinoma.

BACKGROUND: Tumor budding is a morphological marker of cancer invasion, defined as the presence of isolated or small clusters of neoplastic cells at the tumor invasive front. This study aimed to evaluate the association between intensity of tumor budding and cell proliferation in oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemistry was employed in 163 OSCC samples to detect the cell proliferation marker Ki-67 and multicytokeratin (to identify OSCC cells in tumor budding evaluation). The Mann-Whitney test was used to evaluate differences in the cell proliferation index between samples with high-intensity tumor budding and samples with low-intensity or no tumor budding. In samples with high-intensity tumor budding, the Wilcoxon test was used to evaluate differences in the cell proliferation index between the budding area and the area outside the budding. The chi-square test assessed the association between cell proliferation index and intensity of tumor budding. RESULTS: The cell proliferation index was higher in samples with high-intensity tumor budding than in samples with low-intensity or no tumor budding (P < .05). Tumors with high-intensity tumor budding showed a higher cell proliferation index in the budding area than in the area outside the budding (P < .05). Finally, samples showing high-intensity tumor budding were associated with high cell proliferation index (P < .05). CONCLUSION: Cell proliferation is positively associated with intensity of tumor budding in OSCC. Moreover, in tumors showing high-intensity tumor budding, the budding area is the location of higher cell proliferation. These findings reinforce the hypothesis that tumor budding is associated with the biological behavior of OSCC.

Reproducibility, repeatability, and level of difficulty of two methods for tumor budding evaluation in oral squamous cell carcinoma.

BACKGROUND: This study aimed to analyze the reproducibility, repeatability, and level of difficulty of two methods for tumor budding evaluation in oral squamous cell carcinoma (OSCC): staining by hematoxylin and eosin (HE) and immunostaining for multicytokeratin. METHODS: The evaluation of tumor budding was performed by three examiners in 103 samples of OSCC, using the two methods. A Likert-type scale was used to measure the difficulty in the assessment. The interexaminer agreement (reproducibility) was estimated using Fleiss's kappa and the intra-examiner agreement (repeatability) was estimated using Cohen's kappa. The agreement between the two methods was evaluated using Cohen's Kappa. The Friedman test was used to compare the three examiners' perceived levels of difficulty of assessment. The Wilcoxon test was used to compare the level of difficulty of the evaluation between the two methods. RESULTS: Reproducibility by the immunostaining method for multicytokeratin was substantial, being higher than the only fair agreement by the HE. Repeatability by the HE ranged from moderate to substantial among examiners, regardless of the examiner's experience. Repeatability by the immunostaining method for multicytokeratin did not vary among examiners, showing almost perfect agreement. The agreement between the two methods ranged from fair to moderate among examiners, being lower in the less experienced examiner. All the examiners presented greater difficulty in the evaluation by the HE. CONCLUSION: In view of the unsatisfactory agreement between the two methods of tumor budding evaluation in OSCC, it is recommended that this evaluation should be performed by the immunostaining method for multicytokeratin, considering its higher reproducibility, greater replicability, and lower difficulty compared to the HE.

Laminin-5 gamma 2 chain expression is associated with intensity of tumor budding and density of stromal myofibroblasts in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide. Laminin-5 gamma 2 chain (laminin-5 γ2) is a protein associated to a migratory phenotype in epithelial neoplastic cells. Stromal myofibroblasts also play a significant role in tumor invasion, due to its ability to modify the extracellular matrix. Tumor budding is a morphologic marker of tumor invasion. The aim of this study was to evaluate the expression of laminin-5 γ2 in OSCC and its association with intensity of tumor budding and density of stromal myofibroblasts. METHODS: Paraffin-embedded archival samples of 57 OSCC patients were evaluated. Immunohistochemistry was employed to detect laminin-5 γ2, alpha smooth muscle actin (marker of stromal myofibroblasts), and multicytokeratin (to identify OSCC cells in tumor budding evaluation). Laminin-5 γ2 expression and its association with intensity of tumor budding and density of stromal myofibroblasts were analyzed. Association among intensity of tumor budding and density of stromal myofibroblasts was also evaluated. RESULTS: Higher laminin-5 γ2 expression was associated with high-intensity tumor budding (P < 0.05) and with higher density of stromal myofibroblasts (P < 0.05). Moreover, high-intensity tumor budding was associated with higher density of stromal myofibroblasts (P < 0.05). CONCLUSIONS: In OSCC, higher laminin-5 γ2 expression is associated with high-intensity tumor budding and with higher density of stromal myofibroblasts, suggesting that this expression is related to the establishment of an invasive phenotype of neoplastic cells and a permissive environment for tumor invasion in this neoplasia.

Immunolocalization of Cancer Stem Cells Marker ALDH1 and its Association with Tumor Budding in Oral Squamous Cell Carcinoma.

Tumor budding is a prognostic marker for oral squamous cell carcinoma (OSCC) characterized by the presence of isolated or small clusters of neoplastic cells at the tumor invasive front. Aldehyde dehydrogenase-1 (ALDH1) is associated with tumorigenesis, linked to treatment resistance and shown to identify cancer stem cells (CSC)-like cells. This study aimed to evaluate the expression of ALDH1 and its association with tumor budding in OSCC. Immunohistochemistry was employed in 163 OSCC samples to identify pancytokeratin (AE1/AE3) and ALDH1. While pancytokeratin (AE1/AE3) identified squamous tumor buds, the CSC-like cells were identified using ALDH1. A Chi square test was used to evaluate association between ALDH1 expression and tumor budding, while McNemar's test was used to identify differences in ALDH1 expression between the budding area and the area outside the budding. A positive expression of ALDH1 was observed in 47.24% of the samples and in 70% of anatomic locations affected. No association was observed between ALDH1 expression and tumor budding (p > 0.05). In tumors with high-intensity tumor budding, ALDH1 expression was higher in the budding area than in the area outside the budding (p < 0.05). The finding that tumor bud cells in OSCC show phenotypic characteristics of CSC-like cells reinforces the relevance of tumor budding in determining the biological behavior of this malignant neoplasm. Moreover, the presence of CSC-like cells in nearly half of evaluated samples of OSCC and in most of the affected anatomic locations is in accordance with the CSC model of oral carcinogenesis.

Excisional Biopsy of the Pyogenic Granuloma in Very High-Risk Patient.

Oral surgery to remove pyogenic granuloma in a high-risk patient is reported. A 47-year-old man with gastroesophageal reflux disease, diabetes mellitus II, dyslipidemia, and chronic coronary insufficiency (myocardial infarction within 2 years) with episodes of unstable angina was submitted to an excisional biopsy of hemorrhagic lesion in the lingual right mandibular gingiva. During dental treatment, the arterial blood pressure, oxygen saturation, heart rate, and electrocardiogram were monitored. Local anesthesia was performed with 0.45 ml of 3% prilocaine with 0.03 IU/ml felypressin. The anticoagulant therapy was not interrupted. No local or systemic complications were noticed during or after the surgery.

Microvascular density and tumor budding in oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant head and neck tumor, excluding the nonmelanoma skin cancer. Despite recent advances in the diagnosis and treatment, the disease's mortality rate is nonetheless high. The presence of isolated neoplastic cells or small clusters of up to four cells at the tumor's invasive front, named tumor budding, is associated with a worse prognosis in OSCC. Angiogenesis has also been recognized as a determining factor in the progression of malignancies and in the development of metastases. Several studies have investigated the assessment of microvascular density (MVD) as a potential prognostic factor in OSCC. This study aimed to evaluate, in OSCC, differences in MVD between tumors with high-intensity tumor budding and tumors with low-intensity or no tumor budding. In samples with high-intensity tumor budding, differences in MVD between the budding area and the area outside the budding were also evaluated. Moreover, the study assessed differences in MVD concerning clinicopathological characteristics such as sex, age, tobacco smoking, tumor location and tumor size. Material and methods: One hundred and fifty [150] samples of OSCC were subjected to immunohistochemistry to assess the intensity of tumor budding (by immunostaining for multi-cytokeratin) and MVD (by immunostaining for CD34 and CD105, independently). The data were treated using descriptive and analytical statistics. (AU)

Oral Lichen Sclerosus: A Rare Case Report and Review of the Literature.

Lichen sclerosus (LS) is a chronic inflammatory mucocutaneous disease that often affects the anogenital area and causes significant discomfort and morbidity. Oral mucosal lesions in LS are extremely rare and might be associated with genital and/or skin manifestations. As a unique manifestation of LS, oral lesions are even more rare, with only 20 cases reported in English-language literature. In reviewing that literature in this paper, we present the case of a 44-year-old white man who sought dental assistance with a complaint of a white spot on his upper lip. Extraoral clinical examination revealed a slight white macule on the left upper lip vermilion next to the labial commissure. Intraoral examination revealed that the macule was approximately 3.5 × 2.0 cm, extended to the upper left labial mucosa, and presented an ivory-white color. Following an incisional biopsy and microscopy, the lesion was shown to be covered by a stratified squamous epithelium showing hyperkeratosis and atrophy. The superficial lamina propria revealed a well-marked band of subepithelial hyalinization and, below it, a band-like mononuclear inflammatory infiltrate. Sections stained by Verhoeff's technique revealed a scantiness of elastic fibers in the superficial lamina propria. The diagnosis of LS was then established. The patient was referred for dermatologic evaluation, which identified no skin or genital lesions, and no treatment was employed. After 6 years, no significant changes in clinical features were observed. Altogether, this rare case makes an important contribution to knowledge on this uncommon condition.

Oral Congenital Melanocytic Nevus: A Rare Case Report and Review of the Literature.

Melanocytic nevi are congenital or acquired benign proliferations of cells of melanocytic origin. Oral congenital melanocytic nevi are rare, and only a few cases have been reported in the literature. The purpose of this study is to present the clinical, histological and immunohistochemical features of an oral congenital melanocytic nevus in a 16-year-old female with an 11-year follow-up and to review the pertinent literature. The reported case is the fifth well-documented case report of oral congenital melanocytic nevus in the English literature and the first with a long period of follow-up, thereby making it an important contribution to the knowledge regarding this uncommon oral mucosa lesion.