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Squamous cell carcinoma (SCC) of the tongue rarely metastasizes to the lingual lymph nodes (LLNs), which are inconstant nodes and often situated outside the areas of basic tongue tumor surgery. The current study evaluated the clinicopathological features and prognostic impact of LLN metastasis (LLNM), compared to that of cervical lymph node metastasis, in patients with tongue SCC. A total of 608 patients underwent radical surgery for tongue SCC at our department between January 2001 and December 2016. During neck dissection, we scrutinized and resected lateral LLNs, when present. Of the 128 patients with lymph node metastasis, 107 had cervical lymph node metastasis and 21 had both cervical lymph node metastasis and LLNM. Univariate analysis demonstrated that LLNM was significantly associated with the adverse features of cervical lymph node metastasis. The 5-year disease-specific survival (5y-DSS) was significantly lower in patients with LLNMs than in those without LLNMs (49.0% vs. 88.4%, P < 0.01). Moreover, Cox proportional hazards model analyses revealed that cervical lymph node metastasis at level IV or V and LLNM were independent prognostic factors for 5y-DSS. LLNM has a strong negative impact on survival in patients with tongue SCC. An advanced status of cervical lymph node metastasis may predict LLNM. [ABSTRACT FROM AUTHOR]

Background: Floor of the mouth (FOM) squamous cell carcinoma (SCC) accounts for approximately 10% of all oral SCCs. FOM SCC can be classified into the anterior and posterior types according to their site of origin, but few studies have compared these types. This study sought to clarify differences in clinicopathological characteristics between these two types. Methods: A total of 1,220 patients with oral SCC were treated at our department from January 2001 to December 2015. Among these patients, 62 had FOM SCC. The FOM SCCs were classified into two groups: the anterior type and the posterior type. The anterior and posterior types were defined by the boundary connecting the spaces between the canine and the first premolar bilaterally. We retrospectively compared the sex, age, smoking and drinking history, clinical stage, treatment, histopathological diagnosis, multiple primary cancers, and outcomes of the two groups. Results: Among the 62 patients, 32 had the anterior type, while 30 had the posterior type. The anterior type was found more significantly in men (p = 0.01) and individuals with a smoking history than the posterior type (p = 0.04). pN2–3 cervical lymph node metastasis was significantly more common in the anterior type than in the posterior type (p = 0.01). The median depth of invasion in the anterior type was 4 mm. Multivariate analysis showed that the anterior type was an independent risk factor for multiple primary cancer development in FOM SCC (p = 0.02). The cumulative 10-year disease-specific survival rates of the anterior and posterior types were 92.8 and 95.0%, respectively, while the overall survival rates were 65.4 and 95.0%, respectively. In the anterior type FOM SCC, a lower overall survival rate was associated with multiple primary cancers and smoking-related diseases. Conclusion: Smoking cessation and adequate systemic screening for multiple primary cancers are needed to improve the prognosis of FOM SCC, particularly the anterior type. [ABSTRACT FROM AUTHOR]

Background: Burning mouth syndrome (BMS) is a common condition of predominant oral pain without evident cause, that maxillofacial surgeons and otolaryngologists often refer to psychiatrists as somatic symptom disorder. In very rare cases, its typical burning symptom mimics those of other diseases in which serious fatal comorbidities may be missed. We encountered three rare cases of oral squamous cell carcinoma (OSCC) with the first symptom of burning tongue. Case Presentation: Case 1: A 68-year-old woman had burning pain on the left lingual margin for 8 years. Antidepressant treatment was not efficacious. Cytology and biopsy revealed OSCC. Case 2: A 70-year-old man had burning sensation and paralysis of the tongue for 6 months. Magnetic resonance imaging (MRI) revealed a 37 × 23-mm mass under the floor of the mouth and enlargement of lymph nodes on both sides. Case 3: A 90-year-old man had burning sensation of the tongue for 1 year. MRI revealed a 12 × 12-mm mass on the mandible with bone absorption. Conclusion: This case series suggests that psychiatrists must always be careful in regarding BMS as somatic symptom disorder and be cautious of the possibility of OSCC, especially in elderly patients. [ABSTRACT FROM AUTHOR]

Background: Primary intraosseous carcinoma (PIOC), NOS is an odontogenic carcinoma with unknown etiology. Its diagnosis may be used when central jaw carcinoma cannot be categorized as any other type of carcinoma. Further information on this extremely rare tumor is needed to improve our understanding and evaluate the classification of odontogenic carcinomas. Case presentation: We herein presented two patients with PIOC, NOS with different clinical and histopathological features and analyzed gene mutations in these patients using next-generation sequencing (NGS). The typical PIOC, NOS case had many histopathological similarities to oral squamous cell carcinoma (OSCC), including the missense point mutations of TP53 Glu285Val, KDR Gln472His, and APC Pro1433Leu, which are similar to those in other cancers; however, no mutations were detected in the other patient with an atypical presentation of PIOC, NOS, which was derived from a precursor cystic lesion with similarities to both ameloblastic carcinoma and OSCC. Conclusions: Genetic analysis suggested that these two PIOC, NOS cases have different features and can be subcategorized. [ABSTRACT FROM AUTHOR]

Previous studies have revealed several genes involved in the carcinogenesis of oral cancer. However, the detailed mechanisms underlying this process are poorly understood. Previously, we established a database cataloging the transcriptional progression profile of oral carcinogenesis and identified several candidate genes with continuously increasing or decreasing expression, which specifically promote the transition of oral premalignant lesions to invasive carcinomas. In this study, using our microarray database, we attempted to determine significant genes that may contribute to metabolic alterations during oral carcinogenesis. After performing a literature survey, we focused on 15 candidate genes associated with glucose metabolism changes, particularly the tri-carboxylic acid cycle, and investigated the mRNA-expression status of these genes with our database. Only the solute carrier family 2 member 1 gene (also known as GLUT1), showed significantly increased mRNA expression during oral tumorigenesis. Immunohistochemical analysis confirmed that GLUT1 protein expression significantly increased during oral carcinogenesis. In addition, tumors with high expression of this protein significantly correlated with nodal status (P=0.002). Kaplan-Meier survival curves clearly demonstrated the adverse impact of high GLUT1 protein expression on disease-free survival (P=0.004). GLUT1 mRNA and protein expression increased in the order of normal mucosal tissues, epithelial dysplastic lesions and invasive carcinomas. Therefore, metabolic alterations, especially in glucose metabolism, occurred at the very early stage of development of oral malignancies. In addition, GLUT1 played a significant role in oral cancer, acquiring a malignant phenotype. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the risk factors associated with cervical lymph node metastasis (CLNM) in patients with buccal mucosa squamous cell carcinoma (BMSCC). This retrospective study included patients with primary BMSCC who underwent surgery at the Department of Oral and Maxillofacial Surgical Oncology of Tokyo Medical and Dental University (Tokyo, Japan) between January 2008 and December 2017. The following data were collected and analyzed: Sex, age, primary lesion subsite, tumor/node/metastasis stage, clinical growth patterns, tumor differentiation, lymphovascular and perineural invasion, mode of invasion, pathological depth of invasion, extent of tumor invasion, and clinical outcome of patients with BMSCC. Multivariate analysis was performed to identify the possible risk factors for CLNM. A total of 75 patients were included in the present study, among whom 30 (40%) were found to have histological CLNM. Of the 33 patients with buccinator muscle infiltration by the tumor, 24 (72.7%) had CLNM. Multiple logistic regression analysis revealed that buccinator muscle invasion was the most significant predictive risk factor for CLNM in BMSCC. The present study found that tumor invasion of the buccinator muscle was the most significant predictive risk factor for CLNM in BMSCC. Therefore, elective neck dissection should be performed if buccinator muscle invasion is identified in patients with BMSCC. [ABSTRACT FROM AUTHOR]

Pigmented oral squamous cell carcinoma (POSCC) is a rare and underrecognized pathological variant of oral squamous cell carcinoma (OSCC). The current study aimed to evaluate the clinicopathological characteristics, treatment outcomes and prognosis of patients with POSCC and to investigate its oncological properties using immunohistochemical studies. A total of 1,512 patients were pathologically diagnosed with squamous cell carcinoma of the oral cavity, and were treated at the Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University between January 2001 and December 2018. A total of 25 patients had POSCC and underwent radical surgery. Of these 25 patients, 23 presented with early T stage disease. Additionally, 22 patients were negative for cervical lymph nodes metastasis. Only one patient had local recurrence. The 5-year disease-free and disease-specific survival rates were 86.6 and 95.8%, respectively. Immunohistochemically, a high percentage of POSCC exhibited low p53 and Ki-67, preserved E-cadherin or negative vimentin expression. The results suggested that POSCC tends to exhibit non-aggressive oncological behavior and demonstrates a good prognosis. [ABSTRACT FROM AUTHOR]

Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction. [Copyright &y& Elsevier]

Objectives: In patients with advanced oral squamous cell carcinoma (OSCC), surgical treatment is often administered in combination with radiotherapy-based postoperative adjuvant therapy. The aim of the present study was to determine the most appropriate dose by comparing patient outcomes between doses of 50- and 66-Gy for postoperative cervical irradiation.Materials and Methods: This retrospective study included patients who underwent postoperative cervical irradiation following neck dissection for OSCC with lymph nodes metastases, and their primary lesions were controlled. They were divided into the 50- and 66-Gy irradiation groups and were examined for sex, age, primary lesion site, tumor/node/metastasis stage, initial treatment for primary cancer, neck dissection procedure, number of metastatic lymph nodes, presence or absence of extranodal extension (ENE), concomitant anticancer agents, and therapeutic outcomes.Results: A total of 78 patients met the clinical criteria for study enrollment. The 50- and 66-Gy postoperative cervical irradiation groups included 40 and 38 patients, with neck dissection performed at 45 and 38 sites, respectively. Cervical control rate was 97.5% and 97.3% in the 50- and 66-Gy irradiation groups (p = 0.74). The cumulative disease-specific 5-year survival rate was 85.6% and 88.3%, respectively, with no significant difference (p = 0.64).Conclusion: The findings of our study indicate that the irradiation dose of 50 Gy is appropriate for postoperative cervical irradiation in patients with OSCC. [ABSTRACT FROM AUTHOR]