Lingual Squamous Cell Carcinoma Research Articles

Prognostic Value of Lymph Node Density in Lingual Squamous Cell Carcinoma

Lymph node density (LND)—the proportion of positive nodes among the total number of resected nodes—has emerged as a reliable prognostic factor in solid tumors. This study aims to assess the importance of LND in lingual squamous cell carcinoma (LSCC) and its prognostic involvement. A retrospective longitudinal study with 62 patients was performed. All patients were diagnosed with LSCC and submitted for tumor resection and neck dissection. Patients were stratified into low (<0.04) and high risk (≥0.04) based on LND. We analyzed the impact of LND on overall survival (OS) and disease-free survival (DFS), as well as the relationship between LND and the pathological staging, the involvement of positive margins, depth of invasion (DOI) and perineural infiltration. This study provides a substantial relationship between lymph node density (LND), overall survival (OS) and disease-free survival (DFS) in lingual squamous cell carcinoma (LSCC). A statistically significant distribution was found between LND, perineural infiltration and pathological staging, whereas no association was found with the rest of the prognostic variables analyzed.

Association of E-cadherin & vimentin expression with clinicopathological parameters in lingual squamous cell carcinomas & their role in incomplete epithelial mesenchymal transition.

Background & objectives:Lingual squamous cell carcinomas (SCC) pose a major public health burden in India. Epithelial-mesenchymal transition (EMT) is the conversion of an epithelial cell to a mesenchymal phenotype at the invasive front (IF) enhancing invasiveness of these cells which may be studied using immunohistochemistry. The objective of this study was to assess the expression of E-cadherin and vimentin at the IF, and their correlation with the histological risk assessment score, clinicopathological parameters and lymph node metastasis.Methods:Thirty consecutive untreated patients diagnosed as lingual SCC who underwent hemiglossectomy over one year formed the study group. The immunohistochemical expression of E-cadherin and vimentin in the periphery as well as the centre of tumour islands was correlated with clinicopathological parameters, Brandwein-Gensler risk assessment score and lymph node metastasis, along with a correlation between the coexpression of two markers at the IF.Results:Loss of E-cadherin expression was seen at IF in 83.3 per cent (25/30) cases. Out of these, 20 per cent (5/25) showed a corresponding gain in vimentin expression (complete epithelial-mesenchymal transition) and 80 per cent (20/25) did not. Overall, 16.6 per cent (5/30) cases showed complete EMT. However, no correlation between E- cadherin and vimentin expression at the IF was found. No statistical significance was found between E-cadherin loss and vimentin gain at the IF, with the various parameters or the risk score.Interpretation & conclusions:The present study suggests that the cells at IF may metastasize even without a gain in vimentin expression (without classical EMT), as cohesive clusters showing incomplete EMT (E-cadh-/Vim-).

Abstract 13127: Cardiac Metastasis of Lingual Squamous Cell Carcinoma, A Systematic Review of Presentation, Management, and Outcomes

Introduction: Cardiac metastasis of lingual squamous cell carcinoma (LSCC) describes a rare oncologic progression of oral disease currently ill-defined by medical literature. In this systematic review, we aim to characterize the presentation, management, and outcomes associated with LSCC cardiac metastases. Methods: A comprehensive search of PubMed, Embase, and Cochrane Library databases was performed from inception until December 2019. Inclusion criteria included a histologically diagnosed LSCC, definitive location of cardiac metastasis, and Oxford evidence level of 4. Duplicate, non-English, animal studies, and non-original research were excluded. Patient demographics, presenting symptomology, imaging findings, interventions, and outcomes were collected and analyzed. Results: Twenty-seven articles containing 31 cases met the outlined inclusion criteria. The average age of patient presentation was 55.6 years, ranging from 23-77 years. Average time from primary cancer diagnosis to identification of cardiac metastasis was 2.2 years, varying from 0.2-11.0 years. Shortness of breath (29.0%) and chest pain (29.0%) were the most common presenting symptoms, while effusion (21.2%) and right ventricular outflow obstruction (18.2%) were the predominant echocardiogram findings. Right sided metastases (76.7%) were identified more commonly than left sided metastases (53.3%) and septal metastases (36.7%). Cardiac metastases most commonly presented within the right ventricle (56.7%), followed by the left ventricle (43.3%) (Figure 1). Surgical resection (80.6%) and radiotherapy (74.2%) were the most frequently utilized interventions. No patients obtained remission with treatment and all patients expired within one year of metastatic diagnosis. Conclusions: Cardiac metastases of LSCC demonstrate ventricular predominance and suggest a poor prognosis. Patients may benefit from palliative measures, rather than invasive intervention.

S1662 A Rare Case of Metastatic Colonic Involvement of Lingual Squamous Cell Carcinoma

S1662 A Rare Case of Metastatic Colonic Involvement of Lingual Squamous Cell Carcinoma

Synergistic Effect of Combined Treatment with Extra Virgin Olive Oil and Doxorubicin on squamous cell carcinoma cell line

Background: In spite of the fact that the medical care has been extremely improved, the survivalrate of patients diagnosed with Squamous cell carcinoma is still decreased . Doxorubicin (DXR)is one of the most effective anti- squamous cell carcinoma drugs. This drug has a dangerous sideeffects. Natural products can lighten the DXR- induced side effects, without compromising itsantitumor efficacy. The consumption of extra virgin olive oil (EVOO ), appeared to be related tofewer malignant tumor occurrences. Aim of the study: The objective of the present study was toevaluate the effect of EVOO when used alone and, more interestingly, when combined with DXR,for 48 hours, on lingual squamous cell carcinoma cell line (SCC25). Materials and methods: SCC25was used in this study, it was divided into four groups. Group I (control), group II (DXR treated),group III (EVOO treated) and group IV (EVOO +DXR treated). Results: there was significantdecrease in MMP-1, VEGFR-2 expressions as well as migration and invasion between the testgroups and the control group. Conclusion: EVOO is a promising anticancer compound when usedalone or in combination with DXR.

Methylene Blue Test in Assessing Disease Free Margins in Lingual Carcinoma Resection

Lingual squamous cell carcinoma is one of the most frequent localization of the oral carcinomas. The tongue neoplasia represents nearly 40% of the oral carcinomas. Recent studies showed an increasing trend of lingual carcinoma in young patients. Several staining tests have been described to early detect the disease. After detection, disease free margins resection will increase the survival rate. This study aims to analyze the methylene blue staining test in achieving disease free resection margins in lingual squamous cell carcinoma.

Staging of squamous cell carcinoma of the tongue: extrinsic lingual muscles and the 8th editions of the American Joint Committee on Cancer/Union for International Cancer Control staging manuals

Our aim was to find out first whether the extrinsic muscles of the tongue are histologically identifiable, and secondly to what degree the use of the new criteria in the 8th editions of the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control (UICC) manuals (which have recognised the importance of depth of invasion of tumour, rather than invasion of the extrinsic muscles of the tongue and extranodal extension), will alter staging of lingual squamous cell carcinoma (SCC). The histological sections from 165 patients who had had primary resection of lingual SCC were reviewed, and one or more extrinsic muscles of the tongue was identified in 100 patients (61%), with the genioglossus seen the most often (in 96). By contrast, the hyoglossus was identified in only eight patients, the styloglossus in two, and the palatoglossus in none. Identification was straightforward only in extensive resections. Applying the criteria from the 8th edition increased the number of pT3 SCC with a simultaneous reduction in pT4a tumours. The number of pN2b SCC was also reduced, but the new category of pN3b meant that overall 53% of tumours were upstaged. The kappa scores for agreement between the two sets of criteria were 0.221 (weighted 0.410) for the pT values, 0.508 (0.713) for pN values (but 0.227, weighted 0.386, if the pN0 values were removed before calculation), and 0.243 (0.514) for overall stage, indicating poor to fair agreement. We conclude that the removal of invasion of extrinsic muscles of the tongue as a criterion for a pT4a SCC is justified, and that many SCC of the tongue will be upstaged as a result of implementation of the 8th editions.

The Characteristic of S100A7 Induction by the Hippo-YAP Pathway in Cervical and Glossopharyngeal Squamous Cell Carcinoma.

S100A7 is expressed in many squamous cell carcinomas (SCCs). Our previous study revealed that S100A7 was dramatically induced in several SCC cells and activation of the Hippo pathway significantly promoted S100A7 in epidermoid carcinoma cells. However, whether the Hippo pathway regulates S100A7 expression in SCCs remains largely unknown. Here, we uncover that S100A7 induction by the Hippo-YAP pathway displays different characteristic in cervical and glossopharyngeal SCC. In well differentiated HCC94 cervical cells and FaDu pharyngeal cells, S100A7 is easily induced by both suspension and dense culture, which is accompanied by an increase in YAP phosphorylation and a decrease in nuclear YAP. Strikingly, these correlations of S100A7 and YAP reverse after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is significantly repressed by nuclear YAP, which is validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Subsequently, we prove that TEAD1 is required for YAP transcriptional repression of S100A7. However, S100A7 is hardly induced in poorly differentiated SiHa cervical cells and NCI-H226 pulmonary cells even in suspension or activation of the Hippo pathway. More importantly, cervical and lingual SCC tissues array analyses show that S100A7 expression displays the positive correlation with pYAP-S127 and the negative correlation with nuclear YAP in the majority of well differentiated but not in poorly differentiated tissues. Collectively, our findings demonstrate that the different induction of S100A7 toward activation of the Hippo pathway mainly depends on the degree of cell differentiation in cervical and glossopharyngeal SCC.

Application of carbon nanoparticles as lymph node tracers in patients with cN0 lingual squamous cell carcinoma un-dergoing neck dissection

This study aimed to investigate the value of carbon nanoparticles as lymph node tracers in neck dissection for cN0 lingual squamous cell carcinoma patients. Ninety-six patients with cN0 lingual squamous cell carcinoma were recruited to undergo surgical treatment were randomly divided into two groups, namely, the carbon nanoparticle-labeled group (the experimental group, 50 cases) and the control group (46 cases). Carbon nanoparticle suspension was injected into the submucosal layer around the site of the primary tumor at three or four points (0.1mL for each point) 12h before surgery. Supraomohyoid neck dissection (SOHND, Levels Ⅰ to Ⅲ) or comprehensive neck dissection (CND, Levels Ⅰto Ⅴ) were performed based on the size and location of the primary tumor. All the lymph nodes were dissected and separated from the ex vivo surgical specimens for histopathological evaluation. The number, size, location, and pathological result of all the lymph nodes were compared between the two groups. Statistical analyses were conducted by SPSS 19.0 software. A total of 1 137 lymph nodes were detected in 31 SOHND patients. The average number of lymph nodes detected in the experimental group was (43.79±19.23) /case, which was significantly higher than that in the control group [(30.82±8.77) /case] (P=0.019). Level Ⅲ covered the largest number of lymph nodes in the two groups. However, the number and proportion of lymph nodes found in Level Ⅱ of the experimental group were significantly higher than those of the control group (P=0.000). A total of 3 938 lymph nodes were detected in 65 CND patients. The average number of lymph nodes detected in the experimental group [(66.67±20.02) /case] was larger than that in the control group [(53.03±20.98) /case] (P=0.026). The difference in the lymph node location between the two groups was not statistically significant (P=0.354). In the two neck dissection methods, both the proportion of minute lymph nodes and the accuracy of the detected lymph nodes in the experimental group were significantly larger than those in the control groups (P=0.000). Compared with the control group, more metastases were proven by the carbon nanoparticle-labeled lymph nodes (P=0.000) in the experimental group. Carbon nanoparticles as lymph node tracers in patients with cN0 lingual squamous cell carcinoma undergoing neck dissection can increase the number of detected lymph nodes, especially the minute nodes. Such nanoparticles can further ensure the thoroughness of neck dissection and the accuracy of clinicopathological stage.

Photomodulation of the osteoclastogenic potential of oral squamous carcinoma cells.

The treatment for oral cancer usually involves surgical excision followed by chemotherapy and/or radiotherapy. The combination of these therapies generally promotes a serious inflammation of the mucosa of the digestive tract, denominated mucositis, which compromises continuity of treatment. Photobiomodulation (PBM) therapy has been used successfully to reduce the oral mucositis, however there is still some controversy regarding the effects of this therapy on unintentionally irradiated tumor cells that may remain after cancer treatment. The aim of this study was to analyze the effect of PBM therapy (using parameters for mucositis) on the modulation of osteoclastogenic potential of a cell line derived from human lingual squamous cell carcinoma (SCC9). Previously irradiated SCC9 cells were co-cultured with human osteoclast precursors. Co-cultures performed with non-irradiated SCC9 cells served as control. After 7, 14 and 21 days the co-cultures were evaluated for the tartrate-resistant acid phosphatase (TRAP) activity, an osteoclastogenic marker. Additionally, the monocultures of SCC9 cells (non-irradiated and irradiated) were analyzed for cell viability/proliferation and for the expression of IL-11 and PTHrP. The irradiation of SCC9 cells with PBM with an energy density of 4J/cm2 decreased the pro-osteoclastogenic potential of those cells. This may represent a potential useful side effect of PBM therapy. PBM (using recommended parameters for mucositis treatment) decreases the osteoclastogenic potential of oral squamous carcinoma cells.

Partial glossectomy in a blue-tongued skink (Tiliqua scincoides) with lingual squamous cell carcinoma.

Partial glossectomy in a blue-tongued skink (Tiliqua scincoides) with lingual squamous cell carcinoma.

Partial Glossectomy in a Blue-Tongued Skink (Tiliqua scincoides) with Lingual Squamous Cell Carcinoma

Abstract A 16-year-old, male, intact blue-tongued skink (Tiliqua scincoides) was evaluated for reluctance to eat, deviation of the tongue, and a pink mass noted in the mouth. On physical examination, a 2–3 cm long by 1 cm wide pink, well-vascularized, friable, cobblestone-textured mass was found adhered to the median raphe on the ventral aspect of the tongue. Surgical debulking was performed and biopsy samples were submitted for histopathology, which revealed a squamous cell carcinoma. Very small numbers of mixed-growth bacteria were also cultured from the sample. A complete blood count revealed toxic heterophils, monocytosis, and basophilia; however, the total white blood cell count was within reference values. A partial glossectomy was performed excising the distal 40% of the tongue, including the mass with 0.5–1 cm gross surgical margins. Histopathologically, the neoplasm was excised with narrow margins of normal tissue, leading to the concern for possible local tumor recurrence and metastasis. The pat...

舌扁平上皮癌に対して舌全摘出術を実施した犬の1例

15歳3ヶ月齢の未去勢雄のミニチュア・ピンシャーが摂食困難を主訴に来院した。口腔内検査にて舌小体付着部正中にSCCを認め、腫瘍の完全切除を目的に舌全摘出術を実施した。術後は胃瘻チューブによる補助的な飲水管理を必要としたが自力採食は可能であり、術後18ヶ月生存した。悪性度が極めて高い舌SCCに対しても舌全摘出術を行うことで局所再発を防ぎ、飼主が満足できるQOLを維持することが可能であった。

Establishment and characterization of human lingual squamous cell carcinoma cell lines designated Nialym derived from metastatic foci of lymph node, and Nialymx derived from transplanted tumor of Nialym cells.

The squamous cell carcinoma cell lines Nialym was successfully established from metastatic foci of lymph nodes from a 48-year-old male Japanese patient with squamous cell carcinoma of the tongue. In addition, the Nialymx cell line was established from a transplanted tumor of Nialym cells in SCID mice. Nialym cells were angular, with neoplastic and pleomorphic features. Two types of Nialym cell were observed by electron microscopy; light cells and dark cells. The dark cells had a number of waved tonofilaments in the cytoplasm, while light cells showed poorly developed organelles. The population doubling times for Nialym and Nialymx cells were approximately, 46 and 42h at the 10th passage. Nialym cells secreted 4.8ng/ml VEGF and 5.9ng/ml HGF, Nialymx cells also secreted 6.7ng/ml VEGF and 4.3ng/ml HGF at the 10th passage for 3days of culture. Histopathological aspects of Nialym and Nialymx cell lines were similar. We believe that these cell lines are valuable tools for elucidating the mechanisms of cancer metastasis and developing immunotherapy and chemotherapy regimens.

長期管理が可能であった犬舌扁平上皮癌の1例

長期管理が可能であった犬舌扁平上皮癌の1例

Is 18F-fluorodeoxyglucose positron emission tomography/computed tomography helpful in the decision-making process for neck dissection in patients with T1-T2 lingual cancer?

Conclusion: The usefulness of addition of positron emission tomography/computed tomography (PET/CT) in decisions as to whether to perform neck dissection in patients with T1-T2 lingual squamous cell carcinoma (SCC) might be limited, but adding the condition of lymph nodes with a maximum standardized uptake value (SUVmax) >4.5 to existing criteria would be helpful. Objectives: The purpose of this study was to investigate the usefulness of PET/CT for performing neck dissection in patients with T1-T2 lingual SCC. Methods: This retrospective review surveyed 19 patients with T1-T2 lingual SCC who underwent neck dissection after meeting one or more of the following criteria: (1) clinically positive nodes; (2) >4 mm thickness; (3) ≥ 3 cm longest diameter of the primary tumor. Focal 18F-fluorodeoxyglucose (FDG) uptake was considered to indicate PET-positive nodes (PET + Ns). The relation between pathologically positive nodes (p + Ns) and PET + Ns was estimated. Results: There were 14 PET + Ns at 12 of 66 levels (18%) in 8 of the 19 (42%) patients. There were also 6 p + Ns (1%) among 412 nodes at 5 cervical lymph node levels (8%) in 5 patients (26%). The sensitivity and specificity for PET/CT were 80% and 64%, respectively. The SUVmax was measured, and receiver operating characteristic (ROC) analysis was undertaken to obtain better accuracy. The sensitivity and specificity were 60% and 100% when the SUVmax cut-off value was set at 4.5.

Establishment of lingual squamous cell carcinoma cell line, cancer stem cell line and the grafted tumor cell line derived from same cancer tissue

Establishment of lingual squamous cell carcinoma cell line, cancer stem cell line and the grafted tumor cell line derived from same cancer tissue

Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) in squamous cell carcinoma of the tongue: markers of nerve invasion?

Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is an independent predictor of poor prognosis. As PNI is not always identified with routine histology, a surrogate marker of PNI would improve detection and better inform treatment planning. The chemokines fractalkine (CX3CL1) and its receptor (CX3CR1) have shown such potential in other cancers, but have yet to be investigated with respect to PNI in oral SCC. Thirty SCCs of the tongue in which PNI was identified histologically, and 30 in which it was not, were stained for fractalkine and fractalkine receptor using polyclonal antibodies and an immunoperoxidase technique. Tumours were assessed as either positive or negative; no attempt was made to subjectively assess staining intensity or extent. Both markers labelled myofibroblasts in the stroma surrounding the tumour, various neural components, leucocytes, endothelium and salivary myoepithelial cells. Fractalkine also labelled salivary ductal epithelium, vascular smooth muscle and 12/30 SCC which showed PNI. Eight of 30 positive SCCs in which PNI was not identified were also positive for this marker. There was no statistically significant association between fractalkine staining and PNI (p = 0.273). No SCC was positive for fractalkine receptor, but immune dendritic cells within tumour islands were strongly positive, as was striated muscle. Neither fractalkine nor fractalkine receptor isa reliable surrogate marker of PNI in lingual SCC.

Ectopic expression of fatty acid binding protein 4 is involved in cell growth of lingual squamous cell carcinoma

Ectopic expression of fatty acid binding protein 4 is involved in cell growth of lingual squamous cell carcinoma

1024PD - Surveillance of Adolescents and Young Adult Patients with Fanconi Anemia (FA): Awareness of Diagnosing Solid Tumors at a Young Age

ABSTRACT Disclosure All authors have declared no conflicts of interest. A great proportion of FA patients reaches adulthood and become at risk for developing secondary malignancies. In 2009, the High Risk and Cancer Prevention Unit (HRCPU) at Hospital Vall d'Hebron started a follow-up program for adolescents and adult patients with FA. The goal was to advocate for prevention measures to reduce cancer risk, and coordinate a multidisciplinary surveillance for different neoplasms. During annual HRCPU visits, FA patients undergo a complete anamnesis and receive health education. The surveillance program includes: hematological follow up with hemograms and bone marrow aspiration; examination for head and neck lesions by an otolaryngologist; detailed examination of the oral cavity by a maxillofacial specialist; semestral gynecologic examinations for women with annual cervical cytology testing and breast examination. Finally, HPV vaccination is encouraged. Since 2009, 14 FA patients have been enrolled in our follow-up program. Overall, 50% were women, and median age was 22 years (14-32). Their mean age at diagnosis of FA was 6.5 years, 57% belonged to FANCA group and 57% underwent a bone marrow transplantation (BMT). Follow up has ranged from 1 month to 3 years, 70% of patients have adhered properly with the program and 83% of women have received HPV vaccination. So far, 4 patients (29%) have been diagnosed with a malignant tumor and another two with a premalignant lesion. Premalignant lesions were found in the oral cavity (hyperplasia with mild dysplasia of the tongue) and gynecological (squamous intraepithelial lesion of the cervix CIN1). From those diagnosed with cancer, two of them had head and neck tumors. One was a lingual squamous cell carcinoma pT2N1M0 diagnosed at 24 years which recurred at 4 years and the patient died at age 30. The patient had received a BMT at age 8. The other one was a squamous cell carcinoma of the epiglottis pT4N1M0 diagnosed at 32 years in a patient with mosaicism. The third and fourth patients have developed several basal cell carcinomas in the jaw and back since age 21 and both had undergone BMT at 7 and 8 years. Head and neck tumors are frequent neoplasms in young adults with FA, regardless prior BMT. We need to reinforce surveillance and prevention strategies to reduce the risk of malignancies in these locations.