Malignant peripheral nerve sheath tumor (MPNST) is a rare neurogenic malignant tumor. MPNST has aty-pical clinical symptoms and imaging presentations, difficult diagnosis, a high degree of malignancy, and poor prognosis. It usually occurs in the trunk, approximately 20% in the head and neck, and rarely in the mouth. This paper reports a case of MPNST of the tongue. A summary of the clinical features, diagnosis, and treatment of MPNST is presented in combination with a literature review to provide a reference for the diagnosis and treatment of this disease.
Humans ; Nerve Sheath Neoplasms/pathology* ; Neurofibrosarcoma ; Tongue/pathology*

Tongue squamous cell carcinoma is highly malignant and has a poor prognosis. In this study, we aimed to combine whole-genome sequencing, whole-genome methylation, and whole-transcriptome analyses to understand the molecular mechanisms of tongue squamous cell carcinoma better. Oral tongue squamous cell carcinoma and adjacent normal tissues from five patients with tongue squamous cell carcinoma were included as five paired samples. After multi-omics sequencing, differentially methylated intervals, methylated loop sites, methylated promoters, and transcripts were screened for variation in all paired samples. Correlations were analyzed to determine biological processes in tongue squamous cell carcinoma. We found five mutated methylation promoters that were significantly associated with mRNA and lncRNA expression levels. Functional annotation of these transcripts revealed their involvement in triggering the mitogen-activated protein kinase cascade, which is associated with cancer progression and the development of drug resistance during treatment. The prognostic signature models constructed based on WDR81 and HNRNPH1 and combined clinical phenotype-gene prognostic signature models showed high predictive efficacy and can be applied to predict patient prognostic risk in clinical settings. We identified biological processes in tongue squamous cell carcinoma that are initiated by mutations in the methylation promoter and are associated with the expression levels of specific mRNAs and lncRNAs. Collectively, changes in transcript levels affect the prognosis of tongue squamous cell carcinoma patients.
Humans ; Biomarkers, Tumor ; Nerve Tissue Proteins ; Prognosis ; Squamous Cell Carcinoma of Head and Neck/pathology* ; Tongue Neoplasms/pathology*

In contrast to the well-established genomic 5-methylcytosine (5mC), the existence of N⁶-methyladenine (6 mA) in eukaryotic genomes was discovered only recently. Initial studies found that it was actively regulated in cancer cells, suggesting its involvement in the process of carcinogenesis. However, the contribution of 6 mA in tongue squamous cell carcinoma (TSCC) still remains uncharacterized. In this study, a pan-cancer type analysis was first performed, which revealed enhanced 6 mA metabolism in diverse cancer types. The study was then focused on the regulation of 6 mA metabolism, as well as its effects on TSCC cells. To these aspects, genome 6 mA level was found greatly increased in TSCC tissues and cultured cells. By knocking down 6 mA methylases N6AMT1 and METTL4, the level of genomic 6 mA was decreased in TSCC cells. This led to suppressed colony formation and cell migration. By contrast, knockdown of 6 mA demethylase ALKBH1 resulted in an increased 6 mA level, enhanced colony formation, and cell migration. Further study suggested that regulation of the NF-κB pathway might contribute to the enhanced migration of TSCC cells. Therefore, in the case of TSCC, we have shown that genomic 6 mA modification is involved in the proliferation and migration of cancer cells.
AlkB Homolog 1, Histone H2a Dioxygenase/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Site-Specific DNA-Methyltransferase (Adenine-Specific)/metabolism* ; Tongue Neoplasms/metabolism*

Carcinoma, Merkel Cell/pathology* ; Humans ; Skin Neoplasms/pathology* ; Tongue ; Tongue Diseases

OBJECTIVE: To examine the correlation of CCBE1 expression in adjacent tissues of tongue squamous cell carcinoma (TSCC) with pericancerous lymphatic vessel proliferation, cervical lymph node metastasis and survival outcomes of the patients. METHODS: Lymphatic vessel density was quantified in pericancerous tissue sections of 44 cases of cT_1-2N₀ TSCC using D2-40 as the lymphatic vessel endothelial marker for calibration and counting of the lymphatic vessels. Of these 44 cases, 22 showed a relatively low lymphatic vessel density (group A) and the other 22 had a high lymphatic vessel density (group B), and the expression levels of CCBE1 in the adjacent tissues determined using immunohistochemistry, immunofluorescence assay and Western blotting were compared between the two groups. The expression level of CCBE1 was also measured in another 90 patients with TSCC using immunohistochemistry, and all the patients were followed up for their survival outcomes. RESULTS: Immunohistochemistry and Western blotting showed a significantly lower rate of high CCBE1 expression in group A than in group B (P < 0.05). Immunofluorescence assay showed co-localization of CCBE1 and D2-40 in the adjacent tissues of TSCC. In the 90 TSCC patients with complete follow-up data, a high expression of CCBE1 was found to correlate with lymph node metastasis and a poor 5-year survival outcomes of the patients (P < 0.05). CONCLUSION A high expression of CCBE1 in the adjacent tissues of TSCC is closely related with pericancerous lymphatic vessel proliferation, cervical lymph node metastasis and a poor 5-year survival of the patients, suggesting the value of CCBE1 as a potential prognostic predictor for TSCC.
Humans ; Tongue Neoplasms/pathology* ; Carcinoma, Squamous Cell/metabolism* ; Lymphatic Metastasis ; Prognosis ; Lymphatic Vessels/pathology* ; Cell Proliferation ; Tongue/pathology* ; Calcium-Binding Proteins/metabolism* ; Tumor Suppressor Proteins/metabolism*

OBJECTIVES: Occult cervical lymph node metastasis is the most important reason for recurrence of early-stage tongue cancer and oropharyngeal cancer. Cervical sentinel lymph node (SLN) biopsy may help to identify them. Pigment dyes and radionuclide were used to label SLN. Both of them had shortage. This study aims to investigate the application and clinical value of indocyanine green fluorescence imaging in cervical SLN biopsy for patients with early-stage tongue cancer and oropharyngeal cancer. METHODS: Retrospective analysis was conducted on 23 patients with early tongue cancer and oropharyngeal cancer, who received surgical treatment and used indocyanine green as a tracer to find SLN in Hunan Cancer Hospital from April to October 2021. The detection rate of SLN was calculated and the distribution of SLN in different regions of the neck was analyzed. RESULTS: SLN was successfully identified in 22 of 23 patients, with a detection rate of 95.65%. Among these 22 patients, 3 patients were found to have cancer metastasis, and the rate of occult lymph node metastasis was 13.63%. No pathologically positive lymph nodes were detected in SLN-negative patients, and thus the positive predictive rate was 100%. For patients with primary lesions located in the anterior 2/3 of the tongue, the constituent ratios of SLN in neck area I, II, III, and IV were 15.15%, 71.72%, 13.13%, and 0, respectively. For patients with primary lesions located in base of the tongue, the constituent ratios of SLN in neck area I, II, III, and IV were 0, 44.44%, 44.44%, and 11.12%, respectively. CONCLUSIONS Indocyanine green fluorescence imaging has a high detection rate with accurate positive prediction in the anterior cervical SLN biopsy in patients with early-stage tongue cancer and oropharyngeal cancer. Meanwhile, it can also reflect the lymphatic drainage of tumors located at different primary sites, which has high clinical value.
Humans ; Sentinel Lymph Node Biopsy/methods* ; Indocyanine Green ; Lymphatic Metastasis/pathology* ; Tongue Neoplasms/surgery* ; Retrospective Studies ; Lymph Nodes/pathology* ; Oropharyngeal Neoplasms/surgery* ; Tongue

To screen for additional treatment targets against tongue cancer, we evaluated the contributions of extracellular signal-related kinase (ERK), AKT and ezrin in cancer development. Immunohistochemical staining showed that ERK and ezrin expressions were significantly higher in invasive squamous cell carcinoma than in carcinoma in situ. To investigate the roles of ERK and ezrin in cancer development, we used the non-woven silica fibre sheet Cellbed with a structure resembling the loose connective tissue morphology in a novel 3D culture system. We confirmed that the 3D system using Cellbed accurately mimicked cancer cell morphology in vivo. Furthermore, cell projections were much more apparent in 3D-cultured tongue cancer cell lines than in 2D cultures. Typically, under conventional 2D culture conditions, F-actin and cortactin are colocalized in the form of puncta within cells. However, in the 3D-cultured cells, colocalization was mainly observed at the cell margins, including the projections. Projections containing F-actin and cortactin colocalization were predicted to be invadopodia. Although suppressing ezrin expression with small interfering RNA transfection caused no marked changes in morphology, cell projection formation was decreased, and the tumour thickness in vertical sections after 3D culture was markedly decreased after suppressing ERK activity because both the invasion ability and proliferation were inhibited. An association between cortactin activation as well as ERK activity and invadopodia formation was detected. Our novel 3D culture systems using Cellbed™ are simple and useful for in vitro studies before conducting animal experiments. ERK contributes to tongue cancer development by increasing both cancer cell proliferation and migration via cortactin activation.
Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Culture Techniques ; methods ; Cell Movement ; Cell Proliferation ; Cytoskeletal Proteins ; metabolism ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Neoplasm Invasiveness ; pathology ; Phosphorylation ; Podosomes ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Silicon Dioxide ; Tongue Neoplasms ; metabolism ; pathology ; Tumor Cells, Cultured

OBJECTIVETo investigate the expression of LRG-1 in clinical specimens and Tca8113 cell line of tongue carcinoma and analyze the relationship between LRG-1 expression and the clinicopathological parameters.

METHODSLRG-1 expression was detected in 40 tongue squamous cell carcinoma (TSCC) tissues and paired normal adjacent tissues, 20 atypical hyperplasia tissues of the tongue, and 20 tissues of tongue cancer in situ using immunohistochemical method. The expression of LRG-1 in Tca8113 cell line was detected using flow cytometry. The expression of LRG-1 was also detected in human TSCC tissues and Tca8113 cells with Western blotting. The effect of LRG-1 on the proliferation of HUVECs was determined using MTT assay, and its effect on angiogenesis was evaluated with Matrigel tube formation assays.

RESULTSHuman TSCC tissues had a significantly higher rate of positive expression for LRG-1 (85%, 34/40) than the adjacent tissues (10%, 4/40), invasive tongue cancer (30%, 6/20), and tongue cancer in situ (50%, 10/20) (P<0.05). LRG-1 expression was correlated with the degree of tumor differentiation, clinical stage and lymph node metastasis of the tumor (P<0.05) but not with the patients' age or gender. In the in vitro experiment, LRG-1 promoted HUVEC proliferation and angiogenesis.

CONCLUSIONAbnormal LRG-1 expression is present in the human TSCC tissue and Tca8113 cells. LRG-1 can promote HUVEC proliferation and angiogenesis in vitro, suggesting its possible role in promoting tumor angiogenesis.

Carcinoma, Squamous Cell ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Glycoproteins ; genetics ; metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Lymphatic Metastasis ; Tongue ; metabolism ; pathology ; Tongue Neoplasms ; genetics ; metabolism

OBJECTIVETo study the effects of RhoA down-regulation by RNA interference on the invasion of tongue carcinoma Tca8113 and SCC-4.

METHODSDetermination of the human RhoA sequence as well as the design and constructionof a short specific small interfering RNAs (siRNA) were performed. The siRNA of RhoA gene was transfected into humantongue squamous cell carcinoma Tca8113 and SCC-4 cells line by Lipofectamine 2000. Quantitative real-time polymerasechain reaction was used to examine the mRNA expressionlevels of RhoA. Protein expressions of mRNA, galectin-3,and matrix metalloproteinase (MMP)-9 were evaluated byWestern blot. Transwell invasion assay was performed toassess the invasion ability of tongue carcinoma.

RESULTSRhoA expressions in Tca8113 and SCC-4 cells were reducedsignificantly after transfection of RhoA-siRNA. Protein levels f galectin-3 and MVP-9 were also down-regulated significantly. Invasion ability was inhibited as well.

CONCLUSIONRhoA-siRNA can effectively inhibit RhoA expression in Tca8113 and SCC-4 cells. The invasion ability of tongue carcinoma cells decreased with down-regulation of the protein expressions of galectin-3 and MMP-9, indicating that RhoA-siRNA can inhibit invasion of tongue carcinoma. Results show that RhoA may play an important role in the processes of invasion and metastasis of tongue carcinoma.

Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Down-Regulation ; Galectin 3 ; metabolism ; Gene Silencing ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Tongue Neoplasms ; genetics ; metabolism ; pathology ; Transfection

OBJECTIVE: To repair the postoperative tissue detect of the base of tongue cancer in advanced patients. METHOD: There were 30 patients of medium-high differentiation squamous cell carcinoma(SCC) included in this study. According to the TNM staging of AJCC 2002, there were 4 cases of T2N1M0, 7 of T3N1M0, 10 of T3N2M0, 4 of T4N1M0 and 5 of T4N2M0. Surgical approach of the primary lesion: 12 with transhyoidpharyngotomy approach and 18 with mandibulotomy approach. All cases accepted radiotherapy 4-6 weeks after surgery. RESULT: Twenty-five cases were reconstructed with pedicle pectoralis major myocutaneous flaps, and all them survived. Among them, 1 flap was partial split with surrounding tissue spontaneously, and another flap had partial tissue necrosis, however, both flaps grew well with dressing and other local treatment. Other 5 cases were reconstructed with free anterolateral myocutaneous flaps. Among them, 1 flap had partial tissue necrosis, but had a secondary healing after removing necrotic tissue via mouth approach. All 18 patients of larynx-preservation had tracheal tube pulled out. The 3-year survival rate was 68% and the local control rate was 87%. CONCLUSION Pedicle pectoralis major myocutaneous flaps and free anterolateral myocutaneous flaps were alternative donor area for repairing postoperative tissue defect of the base of tongue; The former was preferred, and the latter was concealed so as to be a kind of effective method, which need adept technique of microsurgery.
Carcinoma, Squamous Cell ; surgery ; Free Tissue Flaps ; Humans ; Larynx ; Myocutaneous Flap ; Neoplasm Staging ; Otorhinolaryngologic Surgical Procedures ; methods ; Reconstructive Surgical Procedures ; methods ; Survival Rate ; Tongue ; pathology ; surgery ; Tongue Neoplasms ; surgery