TGFß signaling pathway in salivary gland tumors.

OBJECTIVE: Pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) are the most prevalent salivary gland tumors. Their pathogenesis has been recently associated with complex molecular cascades, including the TGFß signaling pathway. The aim of this study was to evaluate the expression of genes associated with the TGFß signaling pathway (TGFB1, ITGB6, SMAD2, SMAD4, FBN1, LTBP1, and c-MYC) to map possible downstream alterations in the TGFß cascade. DESIGN: Thirteen PA, 17 MEC, 13 ACC, and 10 non-neoplastic salivary gland samples were analyzed by real-time RT-PCR. RESULTS: Cases of PA presented increased TGFB1, LTPB1, c-MYC, and FBN1 expressions, whereas SMAD2 expression was decreased when compared to non-neoplastic tissue. MEC patients displayed increased expressions of TGFB1, ITGB6, FBN1, and c-MYC and decreased expressions of SMAD2 and SMAD4. ACC cases exhibited elevated expressions of the investigated genes except TGFB1. The present results suggest that decreased expression of SMAD2 and SMAD4 does not impede the transcriptional regulation of c-MYC, especially in PA and MEC. Increased expressions of ITGB6, TGFB1, LTBP1, and FBN1 appear to be related to the regulation of the TGFß signaling pathway in these tumors. Additionally, we observed a higher expression of SMAD4 in ACC and a raised expression of ITGB6 and lowered expression of SMAD2 in MEC. CONCLUSIONS: Our study demonstrated the differential expression of TGFß cascade members in salivary gland tumors such as SMAD2/SMAD4 and c-MYC as well as the participation of ITGB6, TGFB1, LTBP1, and FBN1, contributing to the understanding of the mechanisms involved in tumor progression.

DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas.

Oral cavity squamous cell carcinoma (OSCC) is a complex and dynamic disease characterized by clinicopathological and molecular heterogeneity. Spatial and temporal heterogeneity of cell subpopulations has been associated with cancer progression and implicated in the prognosis and therapy response. Emerging evidence indicates that aberrant epigenetic profiles in OSCC may foster an immunosuppressive tumor microenvironment by modulating the expression of immune-related long non-coding RNAs (lncRNAs). DNA methylation analysis was performed in 46 matched OSCC and normal adjacent tissue samples using a genome-wide platform (Infinium HumanMethylation450 BeadChip). Reference-based computational deconvolution (MethylCIBERSORT) was applied to infer the immune cell composition of the bulk samples. The expression levels of genes encoding immune markers and differentially methylated lncRNAs were investigated using The Cancer Genome Atlas dataset. OSCC specimens presented distinct immune cell composition, including the enrichment of monocyte lineage cells, natural killer cells, cytotoxic T-lymphocytes, regulatory T-lymphocytes, and neutrophils. In contrast, B-lymphocytes, effector T-lymphocytes, and fibroblasts were diminished in tumor samples. The hypomethylation of three immune-associated lncRNAs (MEG3, MIR155HG, and WFDC21P) at individual CpG sites was confirmed by bisulfite-pyrosequencing. Also, the upregulation of a set of immune markers (FOXP3, GZMB, IL10, IL2RA, TGFB, IFNG, TDO2, IDO1, and HIF1A) was detected. The immune cell composition, immune markers alteration, and dysregulation of immune-associated lncRNAs reinforce the impact of the immune microenvironment in OSCC. These concurrent factors contribute to tumor heterogeneity, suggesting that epi-immunotherapy could be an efficient alternative to treat OSCC.

Exuberant clear cell odontogenic carcinoma of the mandible harboring EWSR1 rearrangement: Report of a rare case and a literature review.

Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumour (MOT) that mainly affects the mandible, with a slight female predominance in adult patients. In this study, we described an exuberant CCOC in mandible of a 22-year-female patient. On radiographic examination, a radiolucent lesion in the region of tooth 36 to 44 with tooth displacement and alveolar cortical resorption was observed. Histopathological study revealed a malignant neoplasm of the odontogenic epithelium, composed of PAS-positive clear cells and immunoreactivity for CK5, CK7, CK19, p63. The Ki-67 index was low (<10 %). Fluorescent in situ hybridization revealed EWSR1 gene rearrangement. The diagnosis of CCOC was established and the patient was referred for surgical treatment.

Collagen-chitosan-hydroxyapatite composite scaffolds for bone repair in ovariectomized rats.

Lesions with bone loss may require autologous grafts, which are considered the gold standard; however, natural or synthetic biomaterials are alternatives that can be used in clinical situations that require support for bone neoformation. Collagen and hydroxyapatite have been used for bone repair based on the concept of biomimetics, which can be combined with chitosan, forming a scaffold for cell adhesion and growth. However, osteoporosis caused by gonadal hormone deficiency can thus compromise the expected results of the osseointegration of scaffolds. The aim of this study was to investigate the osteoregenerative capacity of collagen (Co)/chitosan (Ch)/hydroxyapatite (Ha) scaffolds in rats with hormone deficiency caused by experimental bilateral ovariectomy. Forty-two rats were divided into non-ovariectomized (NO) and ovariectomized (O) groups, divided into three subgroups: control (empty defect) and two subgroups receiving collagen/chitosan/hydroxyapatite scaffolds prepared using different methods of hydroxyapatite incorporation, in situ (CoChHa1) and ex situ (CoChHa2). The defect areas were submitted to macroscopic, radiological, and histomorphometric analysis. No inflammatory processes were found in the tibial defect area that would indicate immune rejection of the scaffolds, thus confirming the biocompatibility of the biomaterials. Bone formation starting from the margins of the bone defect were observed in all rats, with a greater volume in the NO groups, particularly the group receiving CoChHa2. Less bone formation was found in the O subgroups when compared to the NO. In conclusion, collagen/chitosan/hydroxyapatite scaffolds stimulate bone growth in vivo but abnormal conditions of bone fragility caused by gonadal hormone deficiency may have delayed the bone repair process.

Oncologic outcomes of microscopic tumor cut-through in locally advanced oral squamous cell carcinoma

Introduction: The gold standard treatment of oral cavity squamous cell carcinoma (OCSCC) is surgical resection; however, standardization of the margins and the role of frozen section are still debatable. Microscopic tumor cut-thought (MTCT) occurs when the surgeon has an initial positive frozen section margin that is cleared with further resection to negative. Objective: This study aims to determine the impact of MTCT on local recurrence and disease-specific survival in patients with locally advanced T3-T4 OCSCC and compare it with other clinicopathological variables. Methods: A retrospective database analysis of patients diagnosed with locally advanced T3-T4 OCSCC surgically treated and submitted to intraoperative frozen section guiding the margin status. Survival was analyzed using the Kaplan-Meier estimator followed by the Cox model for multivariate analysis. Results: We analyzed 475 patients who met inclusion criteria: MTCT occurred in 29 patients (6.11%) and local recurrence was observed in 131 patients (27.6%). MTCT had an impact on univariate (HR 2.205; 95% CI 1.243 ­ 3.914; p=0.007) and multivariate (HR 1.851; 95% CI 1.285 ­ 2.666; p=0.001) analyses. Similar results were found for disease-specific survival: univariate (HZ 1.669; 95% CI 1.056 ­ 2.635; p=0.028) and multivariate (HZ 1.307; 95% CI 0.816 ­ 2.092; p=0.265) analyses. A total of 231 patients (48.6%) had died of cancer by the end of follow-up. The best predictor for compromised frozen sections was tumor depth of invasion. Conclusion: Even after negative final margins, MTCT is an important factor associated with poorer outcome, and treatment intensification should be considered in these patients.

Intraoperative assessment of surgical margins using ‟en face" frozen sections in the management of cutaneous carcinomas

Abstract Background: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative ‟en face" freezing technique evaluates all peripheral and deep margins. Objective: To report the results of the ‟en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. Methods: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. Results: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative ‟en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. Study limitations: Not having a minimum follow-up time of 5 years for all patients. Conclusion: The ‟en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.

Characterization of BRAF mutation in patients older than 45 years with well-differentiated thyroid carcinoma / Caracterização da mutação em BRAF em pacientes acima de 45 anos com carcinoma bem diferenciado de tireoide

Abstract Introduction: Papillary thyroid carcinoma is the most frequent endocrine neoplasia and its incidence has tripled over the past 35years. Although papillary thyroid carcinoma carries a good prognosis, 10%-30% of patients still develop recurrence and metastasis. Some clinical and genetic features are associated with worse prognosis. The most frequent mutation is the BRAF p.V600E, which has been associated with many clinical features of poor prognosis. However, many studies have produced controversial results without any association between BRAF mutation and clinicopathological features of poor prognosis. Objective: Since the prognostic value of BRAF mutations remains controversial, this study aims to investigate the importance of this mutation in therapeutic decisions for papillary thyroid carcinoma. Methods: Therefore, we evaluated whether the presence of BRAF mutation is associated with features of poor prognosis in 85 patients with papillary thyroid carcinoma older than 45years treated at A.C. Camargo Cancer Center, from 1980 to 2007. BRAF mutation was evaluated by pyrosequencing. Statistical analysis was performed using SPSS. Results: The mean age of patients was 54 years (range: 45 - 77 years), 73 were women (85.8%) and 12 were men (14.2%). Among them, 39 cases (45.9%) presented extrathyroidal extension and 11 cases had recurrent disease. BRAF mutation was detected in 57 (67%) patients. No significant association was observed between BRAF mutation and gender (p =0.743), age (p = 0.236), N-stage (p =0.423), vascular and perineural infiltration (p =0.085 or multifocality (p = 1.0). Although not statistically significant, the majority of patients with recurrent disease were BRAF positive (9 out of 11) (p =0.325). Patients affected by BRAF mutation are associated with tumors larger than 1 cm (p =0.034) and with extrathyroidal extension (p =0.033). Conclusion: Although BRAF testing is widely available, there are no consistent data to support improvement in outcomes from incorporating it into therapeutic decision for thyroid cancer.

Resumo Introdução: O carcinoma papilífero de tireoide é a neoplasia endócrina mais frequente e sua incidência triplicou nos últimos 35 anos. Embora o carcinoma papilífero de tireoide tenha um bom prognóstico, 1% a 30% dos pacientes desenvolvem recorrência e metástase. Algumas características clínicas e genéticas estão associadas a um pior prognóstico. A mutação mais frequente é a BRAF p.V600E, a qual tem sido associada a muitas características clínicas de pior prognóstico. No entanto, muitos estudos apresentam resultados controversos, sem qualquer associação entre a mutação em BRAF e características clinicopatológicas de pior prognóstico. Objetivo: Uma vez que o valor prognóstico das mutações em BRAF permanece controverso, investigar a importância dessa mutação em decisões terapêuticas para o carcinoma papilífero de tireoide. Método: Foi avaliada a associação da mutação em BRAF com características de pior prognóstico em 85 pacientes com carcinoma papilífero de tireoide acima de 45 anos tratados no A.C. Camargo Cancer Center, de 1980 a 2007. A mutação em BRAF foi avaliada por pirossequenciamento. A análise estatística foi feita com o software SPSS. Resultados: A média de idade dos pacientes foi de 54 anos (variação de 45 - 77), 73 eram mulheres (85,8%) e 12 eram homens (14,2%). Entre eles, 39 casos (45,9%) apresentaram extensão extratireoidiana e 11, doença recorrente. A mutação em BRAF foi detectada em 57 (67%) pacientes. Não foi observada associação significante entre mutação em BRAF e sexo (p = 0,743), idade (p = 0,236), estágio N (p = 0,423), infiltração vascular e perineural (p = 0,085) ou multi-focalidade (p = 1,0). Apesar de não apresentar associação estatística, a maioria dos pacientes com doença recorrente foi positiva para BRAF (9 em 11) (p = 0,325). Os pacientes afetados pela mutação em BRAF estão associados a tumores maiores do que 1 cm (p = 0,034) e com extensão extratireoidiana (p = 0,033). Conclusão: Embora a mutação em BRAF seja amplamente avaliada, não há dados consistentes que demonstrem uma melhor sobrevida ou benefício clínico ao incorporá-la à decisão terapêutica para o câncer de tireoide.

Intraoperative assessment of surgical margins using "en face" frozen sections in the management of cutaneous carcinomas.

BACKGROUND: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative "en face" freezing technique evaluates all peripheral and deep margins. OBJECTIVE: To report the results of the "en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. METHODS: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. RESULTS: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative "en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. STUDY LIMITATIONS: Not having a minimum follow-up time of 5 years for all patients. CONCLUSION: The "en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.

Polypodium leucotomos targets multiple aspects of oral carcinogenesis and it is a potential antitumor phytotherapy against tongue cancer growth.

Introduction: Oral cancer refers to malignant tumors, of which 90% are squamous cell carcinomas (OSCCs). These malignancies exhibit rapid progression, poor prognosis, and often mutilating therapeutical approaches. The determination of a prophylactic and/or therapeutic antitumor role of the polyphenolic extract Polypodium leucotomos(PL) would be relevant in developing new tools for prevention and treatment. Methods: We aimed to determine the antitumor effect of PL by treating OSCC cell lines with PL metabolites and evaluating its action during OSCC progression in vivo. Results: PL treatment successfully impaired cell cycling and proliferation, migration, and invasion, enhanced apoptosis, and modulated macrophage polarization associated with the tumoral immune-inflammatory response of tongue cancer cell lines (TSCC). PL treatment significantly decreased the expression of MMP1 (p < 0.01) and MMP2 (p < 0.001), and increased the expression of TIMP1 (p < 0.001) and TIMP2 (p < 0.0001) in these cells. The mesenchymal-epithelial transition phenotype was promoted in cells treated with PL, through upregulation of E-CAD (p < 0.001) and reduction of N-CAD (p < 0.05). PL restrained OSCC progression in vivo by inhibiting tumor volume growth and decreasing the number of severe dysplasia lesions and squamous cell carcinomas. Ki-67 was significantly higher expressed in tongue tissues of animals not treated with PL(p < 0.05), and a notable reduction in Bcl2 (p < 0.05) and Pcna (p < 0.05) cell proliferation-associated genes was found in dysplastic lesions and TSCCs of PL-treated mice. Finally, N-cad(Cdh2), Vim, and Twist were significantly reduced in tongue tissues treated with PL. Conclusion: PL significantly decreased OSCC carcinogenic processes in vitro and inhibited tumor progression in vivo. PL also appears to contribute to the modulation of immune-inflammatory oral tumor-associated responses. Taken together, these results suggest that PL plays an important antitumor role in processes associated with oral carcinogenesis and may be a potential phytotherapeutic target for the prevention and/or adjuvant treatment of TSCCs.

The impact of worst pattern of invasion on the extension of surgical margins in oral squamous cell carcinoma.

BACKGROUND: To evaluate margins for oral carcinoma according to types of invasion front. METHODS: Retrospective cohort of 772 patients with worst pattern of invasion (WPOI) graded 1-5. Local recurrence was the outcome of interest. RESULTS: Local recurrences occurred in 164 patients (21.2%) and was affected by WPOI type 4/5, margin distance, perineural invasion, and adjuvant radiotherapy. In patients with WPOI types 1/2/3, a cutoff of 1.7 mm was considered ideal margin extent and in patients with WPOI types 4/5, the cutoff was 7.8 mm. Patients below these thresholds had a significantly higher incidence of local recurrence. CONCLUSIONS: Different WPOI determine the ideal extent of surgical margins as 1.7 mm for patients with types 1-3, and 7.8 mm in patients with types 4/5.

Pigmented lesion on the face: which is the chance of being melanoma using reflectance confocal microscopy features?

Facial melanoma presents itself as a brownish macula, being difficult to differentiate it from benign pigmented lesions of the face on clinical examination. Reflectance confocal microscopy (RCM) assists in diagnosing facial lesions in which dermoscopy has limitations, allowing to increase the diagnostic accuracy. The study aimed to analyze the RCM features of pigmented isolated lesions of the face for diagnosing melanoma. Also, we sought to establish the chance of a pigmented lesion on the face being a melanoma using RCM criteria. In this retrospective and prospective study, 105 clinical pigmented lesions on the face underwent RCM, and cytoarchitectural features in the epidermis, the dermo-epidermal junction (DEJ), and dermis were described. For statistical analysis, the exact chi-square test was applied to the RCM criteria. The odds ratio was estimated using univariate logistic regression. Finally, we used the multiple logistic regression method for creating a nomogram to predict the chance of a lesion being a melanoma. After univariate and multivariate logistic regression, atypical round nucleated cells within the epidermis, pagetoid spread, and follicular dendritic cells presented as statistically significant features. Then, a complex nomogram was created to give the chance of a pigmented lesion on the face being a melanoma. The presence of these three features resulted in a 98% probability for melanoma. This study allowed to estimate the diagnosis of melanoma on the face, using RCM, practicable and feasible in the daily routine, through the presence of some RCM nomogram criteria.

Characterization of BRAF mutation in patients older than 45 years with well-differentiated thyroid carcinoma.

INTRODUCTION: Papillary thyroid carcinoma is the most frequent endocrine neoplasia and its incidence has tripled over the past 35 years. Although papillary thyroid carcinoma carries a good prognosis, 10%-30% of patients still develop recurrence and metastasis. Some clinical and genetic features are associated with worse prognosis. The most frequent mutation is the BRAF p.V600E, which has been associated with many clinical features of poor prognosis. However, many studies have produced controversial results without any association between BRAF mutation and clinicopathological features of poor prognosis. OBJECTIVE: Since the prognostic value of BRAF mutations remains controversial, this study aims to investigate the importance of this mutation in therapeutic decisions for papillary thyroid carcinoma. METHODS: Therefore, we evaluated whether the presence of BRAF mutation is associated with features of poor prognosis in 85 patients with papillary thyroid carcinoma older than 45 years treated at A.C. Camargo Cancer Center, from 1980 to 2007. BRAF mutation was evaluated by pyrosequencing. Statistical analysis was performed using SPSS. RESULTS: The mean age of patients was 54 years (range: 45 - 77 years), 73 were women (85.8%) and 12 were men (14.2%). Among them, 39 cases (45.9%) presented extrathyroidal extension and 11 cases had recurrent disease. BRAF mutation was detected in 57 (67%) patients. No significant association was observed between BRAF mutation and gender (p  = 0.743), age (p  = 0.236), N-stage (p  = 0.423), vascular and perineural infiltration (p  = 0.085 or multifocality (p  = 1.0). Although not statistically significant, the majority of patients with recurrent disease were BRAF positive (9 out of 11) (p  = 0.325). Patients affected by BRAF mutation are associated with tumors larger than 1 cm (p  = 0.034) and with extrathyroidal extension (p  = 0.033). CONCLUSION: Although BRAF testing is widely available, there are no consistent data to support improvement in outcomes from incorporating it into therapeutic decision for thyroid cancer.

Malignant pleural mesothelioma: an update.

Malignant mesotheliomas are rare types of cancers that affect the mesothelial surfaces, usually the pleura and peritoneum. They are associated with asbestos exposure, but due to a latency period of more than 30 years and difficult diagnosis, most cases are not detected until they reach advanced stages. Treatment options for this tumor type are very limited and survival ranges from 12 to 36 months. This review discusses the molecular physiopathology, current diagnosis, and latest therapeutic options for this disease.

Germline variants in DNA repair genes are associated with young-onset head and neck cancer.

The genetic predisposition to head and neck carcinomas (HNSCC) and how the known risk factors (papillomavirus infection, alcohol, and tobacco consumption) contribute to the early-onset disease are barely explored. Although HNSCC at early onset is rare, its frequency is increasing in recent years. Germline and somatic variants were assessed to build a comprehensive genetic influence pattern in HNSCC predisposition and patient outcome. Whole-exome sequencing was performed in 45 oral and oropharynx carcinomas paired with normal samples of young adults (≤49 years). We found FANCG, CDKN2A, and TPP germline variants previously associated with HNSCC risk. At least one germline variant in DNA repair pathway genes was detected in 67% of cases. Germline and somatic variants (including copy number variations) in FAT1 gene were identified in 9 patients (20%) and 12 tumors (30%), respectively. Somatic variants were found in HNSCC associated genes, such as TP53, CDKN2A, and PIK3CA. To date, 55 of 521 cases from the large cohort of TCGA presented < 49 years old. A comparison between the somatic alterations of TCGA-HNSCC at early onset and our dataset revealed strong similarities. Protein-protein interaction analysis between somatic and germline altered genes revealed a central role of TP53. Altogether, germline alterations in DNA repair genes potentially contribute to an increased risk of developing HNSCC at early-onset, while FAT1 could impact the prognosis.

Master Regulators of Epithelial-Mesenchymal Transition and WNT Signaling Pathways in Juvenile Nasopharyngeal Angiofibromas.

Juvenile nasopharyngeal angiofibroma (JNA) is a rare fibrovascular benign tumor showing an invasive growth pattern and affecting mainly male adolescents. We investigated the role of epithelial-mesenchymal transition (EMT) and WNT signaling pathways in JNA. Gene expression profiles using nine JNA paired with four inferior nasal turbinate samples were interrogated using a customized 2.3K microarray platform containing genes mainly involved in EMT and WNT/PI3K pathways. The expression of selected genes (BCL2, CAV1, CD74, COL4A2, FZD7, ING1, LAMB1, and RAC2) and proteins (BCL2, CAV1, CD74, FZD7, RAF1, WNT5A, and WNT5B) was investigated by RT-qPCR (28 cases) and immunohistochemistry (40 cases), respectively. Among 104 differentially expressed genes, we found a significantly increased expression of COL4A2 and LAMB1 and a decreased expression of BCL2 and RAC2 by RT-qPCR. The immunohistochemistry analysis revealed a low expression of BCL2 and a negative to moderate expression of FZD7 in most samples, while increased CAV1 and RAF1 expression were detected. Moderate to strong CD74 protein expression was observed in endothelial and inflammatory cells. A significant number of JNAs (78%) presented reduced WNT5A and increased WNT5B expression. Overall, the transcript and protein profile indicated the involvement of EMT and WNT pathways in JNA. These candidates are promising druggable targets for treating JNA.

Intratumoral lymphatic vascular density is an independent factor for disease-free and overall survival in advanced stage oral squamous cell carcinoma.

OBJECTIVE: The presence of lymphatic and blood vessels in oral squamous cell carcinoma (OSCC) should play a key role in progression and dissemination. This study aimed to evaluate the correlation between the lymphatic and blood vessel densities with prognostic outcomes in advanced stage OSCC. STUDY DESIGN: Immunohistochemical reactions for D-240, CD34, and CD105 were performed in 88 advanced stage OSCC cases located at the oral tongue and the floor of the mouth. The lymphatic vascular density (LVD), blood vascular density (BVD), and neoformed vascular density (NVD) were assessed by counting positive reactions in 4 hotspot areas, both intratumoral (IT) and peritumoral (PT), at high magnification (× 40). RESULTS: High IT LVD was associated with extracapsular spread of lymph node metastasis (P = .03). Recurrence rates were correlated with IT LVD (P < .0001), IT BVD (P = .036), and IT NVD (P = .047), and overall survival was associated with high IT LVD (P = .0016) and IT NVD (P = .009). Yet, IT LVD was an independent factor for disease-free survival and for overall survival based on the Cox proportional hazards model. CONCLUSIONS: Our results suggest that high IT LVD has a strong impact on survival outcomes in advanced stage OSCC.

A rare case of Ewing sarcoma metastasis to the oral cavity.

Ewing sarcoma in the head and neck is rare, and metastasis from other bones to the mandible accounts for 0.7% of cases. This report presents a case of oral metastasis in a 24-year-old male patient diagnosed with Ewing sarcoma of the femur (p53 gene mutation and EWSR1-ERG fusion). The chief complaint was numbness in the mandible and pain for 1 month and a hardened, ulcerated exophytic lesion in the right retromolar region. Imaging exams revealed an unspecified thinning of the cortical bone of the inferior alveolar canal in the right mandibular ramus, associated with erosion of the alveolar bone. Histopathological analysis confirmed metastasis of Ewing sarcoma. The patient presented an aggressive disease progression and died 1 month after the oral diagnosis. It is important to recognize the signs and symptoms compatible with rare clinical outcomes, leading to an early diagnosis that can improve patients' quality of life and survival.