Early Oral Tongue Research Articles

Histopathologic predictors of recurrence and survival in early T stage oral tongue squamous cell carcinoma.

Recurrence and survival in early T-stage oral tongue squamous cell carcinoma (OTSCC) may be impacted by histopathologic risk factors. This study aims to examine which of these factors predict long-term outcomes of T1 and T2 OTSCC. A retrospective review of T1 and T2 OTSCC patients treated with surgery at a single tertiary care center was conducted. Multivariate regression and Kaplan-Meier survival plots were used to identify predictors of recurrence and compare disease-free survival respectively. 100 consecutive patients were studied. Of these, 51 were staged pT1, 49 pT2, 69 pN0, 10 pN1, and 21 pN2. Multivariate regression analysis revealed that >4 nodes was the strongest predictor of overall recurrence [odds ratio 1.68 (1.23-2.28), p = 0.001], while >4 nodes [odds ratio 1.14 (1.09-1.85), p = 0.008] and pT2 [odds ratio 1.15 (1.01-1.30), p = 0.033] were predictors of local recurrence (R2 = 0.112). Five-year disease-free survival was not significantly impacted by any risk factors except for the number of positive nodes-86% for ≤4 nodes vs. 20% for >4 nodes (p < 0.001)-and pathologic T-stage-90% for pT1 vs. 75% for pT2 (p = 0.035) regardless of adjuvant radiation and/or chemotherapy use. Patients who underwent adjuvant radiation and/or chemotherapy had similar survival to those who did not despite having worse overall tumor prognostic factors. Adding adjuvant therapy may equalize some high-risk histopathologic factors. In the highest risk patients-specifically those with pathologic >4 nodes and pT2 staging-adjuvant therapy should be considered.

The prognostic role of single cell invasion and nuclear diameter in early oral tongue squamous cell carcinoma

BackgroundThe clinical significance of single cell invasion and large nuclear diameter is not well documented in early-stage oral tongue squamous cell carcinoma (OTSCC).MethodsWe used hematoxylin and eosin-stained sections to evaluate the presence of single cell invasion and large nuclei in a multicenter cohort of 311 cases treated for early-stage OTSCC.ResultsSingle cell invasion was associated in multivariable analysis with poor disease-specific survival (DSS) with a hazard ratio (HR) of 2.089 (95% CI 1.224–3.566, P = 0.007), as well as with disease-free survival (DFS) with a HR of 1.666 (95% CI 1.080–2.571, P = 0.021). Furthermore, large nuclei were associated with worse DSS (HR 2.070, 95% CI 1.216–3.523, P = 0.007) and with DFS in multivariable analysis (HR 1.645, 95% CI 1.067–2.538, P = 0.024).ConclusionSingle cell invasion and large nuclei can be utilized for classifying early OTSCC into risk groups.

Regional Nodal Recurence as a Prognostic Factor in Patients Kept on Observation for cT1-T2 Oral Squamous Cell Carcinomas of Tongue: A Meta-Analysis of 11,973 Patients.

The surgical management of the clinically node negative neck in T1-T2 early oral tongue squamous cell carcinoma (OTSCC) has been the topic of debate since few decades. As the occult cervical lymph node metastasis is considered to be the primary prognostic factor in early OTSCC, this meta-analysis has been carried out to find the risk of regional nodal recurrence on patients kept under observation than those who have underwent Elective neck dissection (END). The articles were electronically retrieved from Ovid Medline, PubMed, Cochrane and Scholar for comparison of Observation versus END in early OTSCC. The search strategy identified 35 relevant review articles from April 1979 to April 2020 from different search engines. A total of 11,973 patients from 30 retrospective analyses, 4 prospective and 1 randomized control trials were included in this meta-analysis. Overall test revealed (OR: 13.02 95% CI 1.360-17.154) with t test 2.382 and p value 0.023 which is statistically significant and showed that END significantly reduced the risk of regional nodal recurrence. This meta-analysis finds that there is statistically significant relationship when END was performed which reduced the risk of regional nodal recurrence as seen in patients kept on Observation thereby affecting the Overall survival (OS) rate.

Facial-submental island flap for reconstruction of hemitongue defects in young, middle-aged and elderly patients with early and middle stage oral tongue squamous cell carcinoma

BackgroundThis study evaluated the outcomes of facial-submental artery island flap (FSAIF) for reconstruction of the hemitongue following cancer ablation in patients with early and middle-stage oral tongue squamous cell carcinoma (OTSCC).MethodsIn total, 122 patients with early and middle-stage OTSCC were divided into young, middle-aged, and elderly groups. The Adult Comorbidity Evaluation-27 (ACE-27) index was used to determine the presence of comorbidities. The patients underwent surgical treatment with hemiglossectomy, neck dissection, and hemitongue reconstruction using FSAIF. In addition, stage I (n = 15) and II (n = 69) patients underwent ipsilateral selective neck dissection, whereas those with stage III (n = 38) underwent radical neck dissection. Six patients with T3N1 disease also underwent cobalt-60 adjuvant radiotherapy.ResultsYoung and elderly patients exhibited significant differences in comorbidities, as assessed by the ACE-27 (p < .05). The skin paddles in the young, middle-aged, and elderly patients were 3 × 9 to 4 × 12 cm, 3 × 11 to 4 × 12, and 3 × 10 to 5 × 13 cm in size, respectively. FSAIF failure occurred in four patients (success rate: 96.7%). No significant differences were observed in the skin paddle of the flap or rate of flap failure among the age groups (p > .05). Clavien-Dindo grades I, II, IIIa, IIIb, Iva, and IVb were assigned to 7.1, 36.1, 38.5, 9.8, 4.1, and 4.1% of the patients, respectively, with significant differences seen between the young and elderly patients (p < .05). In total, 52.5% of patients could eat normally, whereas 32.8% required a soft diet. Furthermore, 53.3 and 33.6% of patients achieved normal and intelligible speech, respectively. The aesthetic results were rated as excellent and good in 32.8 and 58.2% of patients, respectively. In total, 68.0% of the patients were alive and exhibited no evidence of disease, while 19.7% were alive with active disease. In addition, 12.3% of patients with stage III OTSCC died due to local recurrence or distant metastases. No differences in swallowing, speech, aesthetic, or survival outcomes were observed among the groups.ConclusionsFSAIF is a simple, safe, and reliable method for reconstructing hemitongue defects following cancer ablation in young, middle-aged, and elderly patients with early and middle-stage OTSCC.

Tertiary lymphoid structures associate with improved survival in early oral tongue cancer

BackgroundThe clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC).MethodsA total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area.ResultsThe presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan–Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09–3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11–2.48; P = 0.014).ConclusionHistological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system.

Long-term outcomes of early stage oral tongue cancer: Main cause of treatment failure and second primary malignancy.

We attempted to investigate the long-term outcomes, prognostic factors, treatment failures, second primary malignancies, and salvage therapies in early (pT1-2N0) oral tongue squamous cell carcinoma (OTSCC). We retrospectively analyzed the medical records of 295 early stage OTSCC patients. Two hundred ninety-five patients were enrolled. The average follow-up period was 64.5months (range, 1-190 months). Five-year recurrence-free survival rate was 84.8% and disease-specific survival rate was 91.2%. On multivariate analysis, only the depth of invasion (DOI) exhibited significant correlations with the disease recurrence. Patient's age and DOI demonstrated a significant association with survival. A total of 53 recurrence and 35 death events occurred, with the main cause of treatment failure being regional or local recurrence. In recurrent cases, the success rate of salvage treatment was 42% at 5 years. During the follow-up period, second primary malignancy occurred in 13 patients, and 8 (61.5%) of those patients were successfully treated. In pT1-2N0 OTSCC, regional or local recurrence is the main recurrence pattern, whereas age and DOI >5 mm are significant prognostic factors related to recurrence and survival. Since several patients experienced second primary malignancies in the head and neck, careful and thorough surveillance may be required to detect second primary lesions. 4.

A change in surgical margin: do wider surgical margins lead to decreased rates of local recurrence in T1 and T2 oral tongue cancer?

The purpose of this study was to assess the impact of a change in macroscopic/surgical margin width upon histological margins and loco-regional failure in early oral tongue squamous cell carcinoma (OTSCC). In 2009, the surgical margin protocol was increased from 10 mm to 15 mm. A retrospective review was performed of all patients who underwent treatment for early OTSCC between 2009 and 2016 with a 15-mm surgical margin (n = 142), and these patients were compared to those treated between 1999 and 2008 with a 10-mm surgical margin (n = 78). There was a significant increase in the rate of clear histological margins (P < 0.001). The rates of close (P = 0.002) and involved (P < 0.001) histological margins decreased significantly. There were significant reductions in local (P < 0.001) and regional (P < 0.001) recurrence rates. This study demonstrated that a surgical margin of 15 mm delivered significantly lower rates of close/involved histological margins and improved local and regional disease recurrence in early OTSCC when compared with a surgical margin of 10 mm.

Role of level IV neck dissection in early tongue cancer

To identify the rate of positive node / skip metastasis at level IV neck node in early carcinoma tongue after elective neck dissection. The records of fifty two patients were retrospectively reviewed from November 2016 to May 2018who underwent wide excision of tongue lesion with elective neck dissection for early tongue cancer. All the metastatic nodes were at the level from I-III. None of the patient had level IV/V neck node metastasis. Supra omohyoid neck dissection is adequate procedure for node negative early oral tongue cancer patients. The inclusion of level IV dissection should be intraoperative decision and should not be aggressive if no disease was found.

Emerging histopathologic markers in early-stage oral tongue cancer: A systematic review and meta-analysis.

Although there are many histopathologic prognosticators, grading of early oral tongue squamous cell carcinoma (OTSCC) is still based on morphological cell differentiation which has low prognostic value. Here we summarize the emerging histopathological markers showing powerful prognostic value, but are not included in pathology reports. Using PubMed, Scopus, Ovid Medline, and Web of Science databases, a systematic literature search was preformed to identify early OTSCC studies that investigated the prognostic significance of hematoxylin–eosin‐based histopathologic markers. Our meta‐analysis showed that tumor budding was associated with overall survival (hazard ratio [HR] 2.32; 95% CI 1.40–3.84; p < 0.01) and disease‐specific survival (DSS) (1.89; 95% CI 1.13–3.15; p = 0.02). Worst pattern of invasion was associated with disease‐free survival (DFS) (1.95; 95% CI 1.04–3.64; p = 0.04). Tumor–stroma ratio was also associated with DFS (1.75, 95% CI 1.24–2.48; p < 0.01) and DSS (1.69; 95% CI 1.19–2.42; p < 0.01). Tumor budding, worst pattern of invasion, and tumor–stroma ratio have a promising prognostic value in early OTSCC. The evaluation and reporting of these markers is cost‐effective and can be incorporated in daily practice.

Subnetwork representation learning for discovering network biomarkers in predicting lymph node metastasis in early oral cancer

Cervical lymph node metastasis is the leading cause of poor prognosis in oral tongue squamous cell carcinoma and also occurs in the early stages. The current clinical diagnosis depends on a physical examination that is not enough to determine whether micrometastasis remains. The transcriptome profiling technique has shown great potential for predicting micrometastasis by capturing the dynamic activation state of genes. However, there are several technical challenges in using transcriptome data to model patient conditions: (1) An Insufficient number of samples compared to the number of genes, (2) Complex dependence between genes that govern the cancer phenotype, and (3) Heterogeneity between patients between cohorts that differ geographically and racially. We developed a computational framework to learn the subnetwork representation of the transcriptome to discover network biomarkers and determine the potential of metastasis in early oral tongue squamous cell carcinoma. Our method achieved high accuracy in predicting the potential of metastasis in two geographically and racially different groups of patients. The robustness of the model and the reproducibility of the discovered network biomarkers show great potential as a tool to diagnose lymph node metastasis in early oral cancer.

Elective neck dissection versus watchful waiting in the management of early tongue cancers with node negative neck: our experience of 68 cases

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Prognosis for tongue squamous cell carcinoma depends upon lymph node metastasis and the treatment plan depends upon the management of cervical lymph node metastasis.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A prospective analysis of early squamous cell carcinoma oral tongue was done February 2017 to February 2020 in previously untreated and biopsy proven patients with T1-2N0 cancer of tongue and patients with clinically negative nodes on the basis of palpation, ultrasound and computerized tomography (CT) and previously untreated and biopsy proven patients with T1-2N0 cancer of oral cavity. After proper work up, patients were divided into two groups. Group 1 (n=35) patients that underwent a surgical excision of primary tumor with 15mm safe margin and selective neck dissection (level I, II, III), group 2 (n=33) patients that underwent surgical excision of primary tumor with 15 mm safe margin and neck observation. All patients with tumor thickness ≥4 mm were included in this group. &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The study included 51 (75%) males and 17(25%) female patients. In this study, recurrence was significantly related to tumor thickness (p&amp;lt;0.05) i.e., &amp;gt;4 mm tumor thickness showed significantly higher local recurrence and nodal recurrences. Also, a significantly higher relationship was seen between nodal recurrence and postoperative close surgical margins (p&amp;lt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Elective neck dissection becomes necessary in patients with T2N0 tumors and tumor thickness of &amp;gt;4 mm as frequency of occult metastasis and recurrence is more in these patients.&lt;/p&gt;

Depth of Invasion as a Predictor of Cervical Nodal Metastasis of Oral Tongue Squamous Cell Carcinoma: Findings From a Tertiary Care Center in Pakistan.

Background and objectiveCervical lymph node metastasis has a significant impact on the survival of patients with oral cavity tumors. The rate of occult neck node metastasis is reported to range from 20 to 40%. The depth of invasion (DOI) has been incorporated in the eighth edition of the American Joint Commission on Cancer (AJCC) staging manual and is an important predictor of cervical lymph node metastasis. In this study, we aimed to identify the occult neck node metastasis rate in early oral tongue squamous cell carcinoma (OTSCC) and correlate it with the DOI.MethodsA retrospective review of all patients presenting to our facility with early-stage OTSCC was performed. Patients with tumor size of ≤4 cm and who underwent elective neck dissection at the time of surgery were included. The study outcomes were the rates of occult neck metastases in T1 and T2 OTSCC and their correlation with the DOI.ResultsThere were 80 patients in total. Occult neck node metastases were seen in 29 (36.25%) patients. Patients with a DOI >5 mm were 1.41 times more likely to have occult neck node metastasis than those with a DOI ≤5 mm.ConclusionOccult neck node metastasis is significantly associated with the DOI. The risk of neck metastasis is higher in patients with a DOI >5 mm.

Clinical outcomes and impact of prognostic factors following adjuvant radiotherapy in oral tongue cancer patients

BackgroundThe purpose of the study was to evaluate survival outcomes in post-operative oral tongue cancer patients undergoing adjuvant radiotherapy (RT) at a tertiary cancer care center and to critically review the impact of various clinical-pathological factors on recurrence and survival. Demographic factors, stage of all the histology proven oral tongue cancer, and treatment details were documented. Overall survival (OS) and recurrence-free survival (RFS) were analyzed along with the potential prognostic factors affecting outcome.ResultsOne hundred forty-four post-operative oral tongue cancer patients referred to our department for adjuvant treatment were evaluated. Median age at presentation was 45 years. Forty-seven patients had pathological early stage disease (stages I and II) and 95 had locally advanced (stages III and IV) disease while post-op details were not present in 2 patients. At a median follow-up of 87 months (60–124) of alive patients, the median RFS for entire cohort was 62 months while median OS was 74 months respectively. Age, perineural invasion (PNI), and grade of the tumor emerged as independent prognostic factors for OS and RFS. Among patients with early stage disease, depth of invasion (DOI), age, and PNI were found as independent prognostic factors for RFS and OS. In locally advanced disease, higher grade, age, and PNI independently impacted the respective survival end points.ConclusionsAge (> 45 years), higher grade, and presence of PNI showed inferior survival outcomes across the sub-groups (early versus locally advanced disease). This may warrant adjuvant treatment intensification. DOI > 10 mm was particularly found to worsen survival in early node negative SCC oral tongue patients.

Trans-lymphatic contrast-enhanced ultrasound with sentinel lymph node biopsy for detecting cervical skip metastasis to lymph nodes in early-stage oral tongue squamous cell carcinoma.

The purpose of this study was to assess whether trans-lymphatic contrast-enhanced ultrasound (CEUS) combined with sentinel lymph node biopsy can be used to assess the status of cervical lymph nodes and skip metastasis in patients with early squamous cell carcinoma (SCC) of the oral tongue. This study included 21 subjects with early oral tongue SCC who received multiple intramucosal peritumoral injections of Sonazoid. CEUS examinations were performed immediately after Sonazoid injection to identify sentinel lymph nodes (SLNs). The SLNs were excised for histological examination to determine if the lymph nodes has metastases. Thirty-five SLNs were detected by CEUS after Sonazoid injection in the subjects. SLNs were identified in 20 of the total 21 subjects. Four participants had metastasis to lymph nodes, and one had skip metastasis in level Ⅲ. In one subject, SLNs were successfully detected in level Ⅳ without skip metastasis. Trans-lymphatic CEUS combined with sentinel lymph node biopsy showed high accuracy for evaluating cervical lymph node status. This could be a reliable approach for detecting cervical skip metastases of lymph nodes in early-stage oral cancer patients.

Prognostic value of tertiary lymphoid structures in early clinical stage oral tongue squamous cell carcinoma.

Tertiary lymphoid structures have been observed in several solid tumors and suggested to be a favorable prognostic factor. However, the prognostic value of tertiary lymphoid structures for early clinical stage (cT1/2N0) oral tongue squamous cell carcinoma (OTSCC) remains unclear. In this study, we aimed to evaluate the prognostic value of tertiary lymphoid structures in cT1/2N0stage OTSCC. Ninety-seven patients with cT1/2N0 stage OTSCC were enrolled in this study. Tertiary lymphoid structures were assessed in paraffin sections with H.E and immunohistochemistry staining. Overall and disease-free survivals were evaluated by the Kaplan-Meier method. Cox proportional hazards regression models were used to assess their prognostic value. Tertiary lymphoid structures can be readily identified in cT1/2N0 stage OTSCC, including early tertiary lymphoid structures, primary follicle-like tertiary lymphoid structures, and secondary follicle-like tertiary lymphoid structures. Its frequency in OTSCC was 76.3% in the cohort. The presence of tertiary lymphoid structures was associated with favorable overall survival (p=0.0176) and disease-free survival (p=0.0183) in early clinical stage OTSCC. Cox regression models showed that tertiary lymphoid structures can serve as an independent prognostic factor for overall survival (HR=0.434, 95% CI=0.212-0.886, p=0.022) and disease-free survival (HR=0.459, 95% CI=0.235-0.897, p=0.023) in early clinical stage OTSCC. The group of low maturity of TLS combined with pN positive had the lowest overall survival (p=0.0094) and disease-free survival (p=0.0028). Tertiary lymphoid structures are frequently observed in OTSCC. It is associated with a favorable prognosis for patients with cT1/2N0 stage OTSCC and may be used to predict immunotherapy sensitivity.

Improving Risk Stratification of Early Oral Tongue Cancer with TNM-Immune (TNM-I) Staging System.

Simple SummarySome patients with early-stage oral tongue cancer suffer from poor survival. The currently used classification requires further improvement to better predict the prognosis. Immune-related parameters (such as assessment of infiltrating lymphocytes) can be used as a modifier for the classification and that can aid in improving the prognostication. We included 290 cases of early-stage oral tongue cancer in this study. Lymphocytes were scored and divided as low or high and incorporated in the traditional tumor-node-metastasis (TNM) classification to form our proposed TNM-Immune staging system. The TNM-Immune staging system allowed for a significant distinction between T1 and T2. The TNM-Immune staging system showed a powerful ability to identify cases with poor survival. TNM-Immune staging forms a step towards a more personalized classification of early-stage oral tongue cancer.Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio (HR) of 2.87 (95% CI 1.92–4.28; p < 0.001); HR of 2.41 (95% CI 1.26–4.60; p = 0.008) for disease-specific survival; and HR of 1.97 (95% CI 1.13–3.43; p = 0.017) for disease-free survival. The TNM-Immune staging system showed a powerful ability to identify cases with worse survival. The immune response is an important player which can be assessed by evaluating TILs, and it can be implemented in the staging criteria of early OTSCC. TNM-Immune staging forms a step towards a more personalized classification of early OTSCC.

NOVEL ADVANCES IN STAGING AND GRADING OF EARLY ORAL TONGUE CANCER: A MULTICENTER STUDY

<h3>Background</h3> Recent research has proposed modifications for the TNM staging and the World Health Organization (WHO) histopathologic grading system of oral cancer. <h3>Objective</h3> (1) To study the significance of different cutoff points of depth of invasion (DOI) in T classification. (2) To study the incorporation of tumor budding to modify the WHO grading system. <h3>Methods</h3> In this multi-institutional study, we included 311 cases treated for early (cT1-2N0M0) oral tongue squamous cell carcinoma at the 5 university hospitals in Finland or at the A.C. Camargo Cancer Centre, São Paulo, Brazil. We suggest using 2 mm DOI to upstage to T2 and 4 mm DOI to upstage to T3. For histopathologic grading, our proposal incorporates tumor budding and defines Grade I as a "well-differentiated cohesive tumor"; grade II as a "moderately differentiated and/or slightly dissociated tumor"; and grade III as a "poorly differentiated and/or dissociated tumor." <h3>Results</h3> There was a significantly improved performance in identification of the high-risk cases for recurrence (hazard ratio [HR] = 2.08; 95% confidence interval [CI], 1.07-4.01; <i>P</i> = .03) and cancer-related mortality (HR = 2.21; 95% CI, 1.05-4.64; <i>P</i> = .036) based on our proposed adjustment of the T stage. Similarly, the proposed histopathologic grade showed worse survival (HR = 3.42; 95% CI, 1.23-9.56; <i>P</i> = .001) and a high rate of recurrence (HR = 1.85; 95% CI, 0.91-3.76; <i>P</i> = .024) for cases having poorly differentiated and/or dissociated tumors. <h3>Conclusions</h3> Our proposed adjustments for staging and grading criteria could improve the risk stratification in early oral tongue squamous cell carcinoma.

Prognostic Role of Tumor-Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma.

Objectives/HypothesisOccult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor‐infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate‐ or high‐grade budding scores was investigated as a prognostic marker for occult neck metastases.Study DesignRetrospective study.MethodsSpecimens from 62 patients with early oral tongue SCC treated with only primary surgery were analyzed by immunohistochemistry for CD4+, CD8+, FoxP3+, and CD45RO+ T cells and CD163+ macrophages. The highest number of each TIL subtype was counted in two areas of parenchyma and stroma in the tumor (Tumor) and peripheral stroma of the invasion margin.ResultsBased on multivariate analysis, a high density of Tumor CD163+ macrophages served as the poorest prognostic factor for regional control (RC) and disease‐free survival (DFS). Patients with both a high density of Tumor CD163+ macrophages and an intermediate‐ or a high‐grade budding score had a poor prognosis for RC according to the log‐rank test.ConclusionsIn summary, each TIL subtype may use different mechanisms during early and advanced stages of oral tongue SCC. A high density of Tumor CD163+ macrophages was determined to be a risk factor for RC and DFS as well as an additional stratification factor for RC in patients with intermediate‐ or high‐grade budding scores. Therefore, identifying TIL subtypes in daily clinical practice can help determine a more successful and individualized therapeutic approach for early oral tongue SCC.Level of EvidenceStep 4 (Level 4) Laryngoscope, 131:2512–2518, 2021

The Potential of MET Immunoreactivity for Prediction of Lymph Node Metastasis in Early Oral Tongue Squamous Cell Carcinoma.

ObjectiveMET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI > 4 mm. The cutoff value used in our institution.MethodsTumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (< 10% uniform positivity) and MET positive (≥ 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM.ResultsForty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (p-value < 0.05).ConclusionMET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DOI ≤ 4 mm, MET positivity could aid in the clinical decision whether regular follow-up, watchful waiting, or END is more appropriate. Realizing that these preliminary results need to be independently validated in a larger patient cohort, we believe that MET positivity could be of added value in the decision making on END in early OTSCC.

Relationship between Thickness of Early Oral Tongue Carcinoma (T1, T2) with Cervical Lymph Node Metastasis

Background: Carcinoma of oral tongue is the most common oral cancer and because of its structure and function is prone for early local and regional spread of cancer. The final outcome of a primary tongue carcinoma patient depends upon various prognostic factors like thickness of tumor, depth of invasion, size of lesion and neck node 67metastasis. Risk of metastasis and spread to neck nodes increases with increase in tumor thickness&#x0D; Methods: This prospective observational study was carried out in the Department of Otolayngology- Head &amp; Neck Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka for 18 months. Thirty patients with early oral tongue carcinoma i.e.T1 &amp; T2 as per UICC and AJC criteria were included in this study by purposive non-randomized sampling technique. Result of the study were expressed as mean, standard deviation (+SD), frequency and percentages. Unpaired Student’s t-test and Pearson’s correlation co-efficient (r) test were performed.&#x0D; Results: Result of the study showed the mean (+SD) thickness of the tumor was 3.62 (+1.46) mm. Minimum thickness 1.1mm and maximum thickness 7.8mm. Only 21 (70%) subjects neck node were metastasized from tongue and mean (+SD) tumor thickness of the positive neck node metastasis was 5.54 (+1.07) mm and negative neck node metastasis was 2.87 (+0.75) mm. This indicated a significant difference between the groups. Pearson’s correlation co-efficient r (+0.981) which indicated tumor thickness was positively correlated with neck node metastasis.&#x0D; Conclusion: Tumor thickness of the early oral carcinoma positively correlated with neck node metastasis. Correlation between thickness and metastatic lymph node can help planning the treatment regimen and indicate the disease prognosis.&#x0D; Bangladesh J Otorhinolaryngol; April 2021; 27(1): 25-35