Lymphocytic Host Response Research Articles

New histological risk grading system for prediction of lymph node metastasis in patients with penile cancer

AbstractInguinal lymph node surgery is a standard treatment for penile cancer patients with intermediate or high risk for lymph node metastasis (LNM) according to European Association of Urology (EAU) risk grading. We are proposing a more objective histological prognostic grading system for inguinal LNM in these patients. We assessed worst pattern of invasion, lymphocytic host response, lymphovascular invasion, and perineural invasion in a population-based cohort of 306 penile cancer patients. Patients were classified into low, intermediate, and high risk for inguinal LNM. There was a significant association both between risk groups and pT stage (p < 0.001) and between risk groups and LNM. Univariate logistic regression showed 25.43 times higher odds of LNM for patients in the intermediate risk group compared with the low risk group (odds ratio (OR) 25.43; 95% confidence interval (CI): 5.94–108.97) and a 177.13 times higher odds in the high risk group compared to the low risk group (OR 177.13; 95% CI: 40.09–782.51). When comparing our histological risk grading with the EAU grading, we found a higher sensitivity, of 51.28% (95% CI: 45.68–56.88) versus 37.09% (95% CI: 31.68–42.50), as well as a higher area under the curve (0.86; 95% CI: 0.81–0.89; versus 0.65; 95% CI: 0.58–0.71) with our grading system. While our grading classified 111 patients as low risk, only 31 were considered low risk for LNM according to the EAU risk classification. The new histological risk grading system shows a higher sensitivity and includes a higher number of patients in the low risk group in whom lymph node surgery could be avoided, reducing morbidity and costs.

Protocol for assessment and correlation of Brandwein-Gensler criteria with P53 immunoexpression in oral squamous cell carcinoma: A retrospective study

Introduction: The commonest type of malignancy in the head and neck region is oral squamous cell carcinoma (OSCC). Brandwein provided a risk model that includes scores for the following three factors: worst invasion pattern, lymphocytic host response and perineural invasion. This risk model accounts for overall survival and local recurrence. p53 is considered to be one of the most significant prognostic markers. Objectives: To assess and correlate Brandwein-Gensler criteria with p53 immunoexpression in oral squamous cell carcinoma. Methods: In this study, a total of 80 samples will be included from histopathologically diagnosed OSCC patients will be taken for the study. H&E-stained slides of all cases will be evaluated using Brandwein-Gensler criteria and then immunostaining will be done for p53 immunoexpression. A correlation between Brandwein-Gensler criteria and p53 immunoexpression will be determined. The present study will assess and correlate Brandwein-Gensler criteria with p53 immunoexpression. If the Brandwein-Gensler criteria score increases, the intensity of p53 immunoexpression will also increase. Conclusions: We hypothesize that Brandwein-Gensler criteria may be significantly correlated with p53 immunoexpression in OSCC.

Lymphocytic Host Response and other Prognostic Factors in Early Stage Squamous Cell Carcinoma of Tongue: Retrospective Analysis from a Tertiary Cancer Center.

Aswin Anapathoor NagarajanIntroduction The tongue is the most common site of malignancy in the oral cavity, and squamous cell carcinoma is the commonest histology. The prognosis remains unfavorable despite treatment, resulting in higher mortality rates. Early stage carcinoma of the tongue is a distinct entity and is primarily treated with either surgery or radiotherapy. Various factors have been implicated in the prognosis of early stage tongue carcinomas. The main objective of this study is to access whether the lymphocytic host response (LHR) and other prognostic factors influence the survival. Patients and Methods The data of 129 patients with Stage I and Stage II (T1-2, N0) tongue cancer treated in our institute from January 2012 to December 2016 were retrospectively abstracted from the hospital case records. The various clinical and pathological factors were recorded. The Kaplan-Meier model was used for survival analysis. The disease-free survival (DFS) and the overall survival (OS) with respect to stage and LHR were calculated. Results On multivariate analysis, site of lesion, comorbidities, habits, grade of the tumor, perineural infiltration (PNI) did not influence the survival. The main factor which was found to be significant in DFS was LHR. The DFS was better for the patients who had lymphocytic infiltration of ≥ 70% (strong LHR) when compared with <70%(weak LHR) ( p = 0.037). The OS with respect to stage ( p = 0.608) and LHR ( p = 0.164) was not found to be statistically significant. Conclusion The patients with weak LHR had less DFS when compared with patients with strong LHR. Larger studies are needed to evaluate whether adding adjuvant therapy may benefit the patients with weak LHR in early stage tongue cancer.

Emerging insights of NK cells immunosurveillance in histomorphologic prognostic indicators of oral squamous cell carcinoma.

IFN-gamma and natural killer (NK) cells have been considered the most effective cells in the combat of cancer, contributing to better prognosis and longer survival. The aim of the study was to analyze and correlate the CD 57 immunopositive NK cell-mediated Interferon-γ pathway in regulating immune mechanisms in Oral Squamous Cell Carcinoma. The study sample was composed of a total of 40 cases of histopathologically confirmed cases of Oral Squamous cell carcinoma (OSCC). Clinical data such as age, gender, habit history, signs and symptoms, and TNM staging were obtained for each case. The biopsy specimens of the cases obtained were fixed with 10% neutral buffered formalin and processed and embedded in paraffin wax. 3-4 μ thick sections were taken for hematoxylin and eosin staining and immunohistochemistry procedure. A saliva sample was collected from each patient and stored at 20 degree Celsius for estimation of salivary interferon-gamma levels using the sandwich ELISA technique. CD 57 NK cells quantitative assessment was significantly associated with tumor budding, cell nest size, the pattern of invasion, lymphocytic host response, NK cell morphology, Depth of invasion, and Tumor thickness. The ratio of CD 57 immunopositive NK cells to salivary IFN-γ levels showed a significant association with histopathological grades, tumor size, and lymph node status. Adoptive cellular transfer therapy with NK cells has been advocated in both experimental models and clinical trials in treating hematopoietic malignancies. The strategy is based on reviving the patient innate immune surveillance and control of tumor invasion by the infusion of activated NK cells. The IFN-gamma and NK cell infiltration in oral squamous cell carcinoma might show a distinctive tumor microenvironment with a favorable local cytotoxic immune response against neoplastic cells.

Histological risk score and its role in predicting recurrence in early-stage oral squamous cell carcinomas.

Oral squamous cell carcinoma (OSCC) comprises more than 90% of oral cancers and is the most common carcinoma affecting the oral cavity. Early stage T1/T2 OSCC have a heterogeneous prognosis and a significant number of patients develop loco regional recurrence (LRR) and have reduced disease free survival (DFS) with increased disease related mortality. To assess the impact of the three parameters used in Brandwein-Gensler risk model along with lympho-vascular invasion (LVI), depth of invasion (DOI) and lymph node metastases in predicting LRR in early stage OSCC. This was a retrospective study on early stage T1/2 OSCC patients over a period of 2 years who received treatment by surgical resection and had follow-up data. LRR was assessed based on recurrence of OSCC at the initial site or in regional lymph nodes. Out of 1135 OSCC cases during our study period a total of 207 cases befitted our inclusion criteria. Recurrence was noted in 113 (54.6%) cases. Univariate analysis identified LVI (P < 0.00001), DOI (P < 0.00001), nodal involvement (P < 0.00001), worst pattern of invasion (WPOI) (P < 0.00001), lymphocytic host response (LHR) (P = 0.004), perineural invasion (PNI) (P = 0.012) as strong statistically significant risk factors for LRR. Adequate assessment of simple parameters on routine H and E by incorporating Brandwein-Gensler histological risk scoring model at the initial presentation can help prognosticate and predict LRR and select patients for post-surgical adjuvant therapy.

Histopathological prognosticators and their clinicopathological correlation in oral squamous cell carcinomas of the tongue.

Tongue carcinomas account for 25%-40% of intraoral squamous cell carcinomas (OSCCs). Although TNM staging systems is an international standard for cancer reporting, prognosis evaluation, and treatment planning, multiple histopathological risk assessment predictors such as tumor thickness (TT), tumor shape, tumor growth pattern, and invasive malignancy grading scoring systems have been studied and should form a basis for prediction and prognostication of such aggressive carcinomas. To evaluate and characterize the histomorphological prognostic indicators in OSCCs of tongue and compare it with OSCCs of other anatomic sites within the oral cavity. Furthermore, to elucidate the significance of histopathological indicators in predicting prognosis of tongue squamous cell carcinomas (SCCs). Forty SCC cases with 20 each of tongue and 20 from other intraoral sites were retrieved from department archives. Clinical data and staging were obtained for each case. Histomorphological parameters including pattern of invasion (POI), tumor budding (TB), depth of invasion (DOI), TT, lymphocytic host response, tumor-associated tissue eosinophilia (TATE), vascular invasion, perineural invasion (PNI), and muscular invasion were assessed. The results were statistically evaluated. TB, DOI, and sarcolemmal spread were significant histologic predictors in tongue SCC. Upon correlation of histomorphological parameters with clinical staging, TT, POI, and TATE were observed to be significantly correlated (P ≤ 0.05). The histomorphological risk assessment model may serve as important addition to the existing prognosticators and may be used as a prognostic index to help plan and individualize treatment protocol in cases with aggressive high-risk disease for whom the use of multimodality treatment seems beneficial.

Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging

Different aspects of intra-tumor heterogeneity (ITH), which are associated with the development of cancer and its response to treatment, have postulated prognostic value. Here we searched for potential association between phenotypic ITH analyzed by mass spectrometry imaging (MSI) and prognosis of head and neck cancer. The study involved tissue specimens resected from 77 patients with locally advanced oral squamous cell carcinoma, including 37 patients where matched samples of primary tumor and synchronous lymph node metastases were analyzed. A 3-year follow-up was available for all patients which enabled their separation into two groups: with no evidence of disease (NED, n = 41) and with progressive disease (PD, n = 36). After on-tissue trypsin digestion, peptide maps of all cancer regions were segmented using an unsupervised approach to reveal their intrinsic heterogeneity. We found that intra-tumor similarity of spectra was higher in the PD group and diversity of clusters identified during image segmentation was higher in the NED group, which indicated a higher level of ITH in patients with more favorable outcomes. Signature of molecular components that correlated with long-term outcomes could be associated with proteins involved in the immune functions. Furthermore, a positive correlation between ITH and histopathological lymphocytic host response was observed. Hence, we proposed that a higher level of ITH revealed by MSI in cancers with a better prognosis could reflect the presence of heterotypic components of tumor microenvironment such as infiltrating immune cells enhancing the response to the treatment.

INTRA-ORAL AND LOWER LIP SQUAMOUS CELL CARCINOMA: A COMPARATIVE ANALYSIS OF THE LYMPHOCYTIC HOST RESPONSE

Objectives To compare the effect of lymphocytic host response (LHR) in the prognosis of patients with tongue and/or floor of mouth squamous cell carcinoma (TFMSCC) and with lower lip squamous cell carcinoma (LLSCC). Study Design Records and slides from 179 patients were evaluated according to the histopathologic risk assessment (HRA) to LHR and submitted to bivariate (chi-square) and survival (Kaplan-Meier and log-rank) analyses. Results White male smokers at initial cTNM were the most affected, in both the TFMSCC and LLSCC. Tumors with strong LHR (61.9%) predominated and were classified as intermediate risk (56.9%) by AHR for TFMSCC and LLSCC. Associations between dense continuous band of LHR and smoking (P = .019), tumors located in the tongue or lower lip (P ≤ .0001), initial pTNM (P ≤ .0001), no recurrence (P = .021), moderately differentiated tumors (P = .001), and intermediate risk by AHR (P ≤ .0001) were observed. Patients with weak LHR had poor overall survival (OS) (P ≤ .0001) and disease-free survival (DFS) (P = .002). Conclusions For both lower lip cancer and intraoral cancer, the presence of a strong LHR demonstrates a favorable effect for OS and DFS and proved to be an important prognostic factor for these patients. To compare the effect of lymphocytic host response (LHR) in the prognosis of patients with tongue and/or floor of mouth squamous cell carcinoma (TFMSCC) and with lower lip squamous cell carcinoma (LLSCC). Records and slides from 179 patients were evaluated according to the histopathologic risk assessment (HRA) to LHR and submitted to bivariate (chi-square) and survival (Kaplan-Meier and log-rank) analyses. White male smokers at initial cTNM were the most affected, in both the TFMSCC and LLSCC. Tumors with strong LHR (61.9%) predominated and were classified as intermediate risk (56.9%) by AHR for TFMSCC and LLSCC. Associations between dense continuous band of LHR and smoking (P = .019), tumors located in the tongue or lower lip (P ≤ .0001), initial pTNM (P ≤ .0001), no recurrence (P = .021), moderately differentiated tumors (P = .001), and intermediate risk by AHR (P ≤ .0001) were observed. Patients with weak LHR had poor overall survival (OS) (P ≤ .0001) and disease-free survival (DFS) (P = .002). For both lower lip cancer and intraoral cancer, the presence of a strong LHR demonstrates a favorable effect for OS and DFS and proved to be an important prognostic factor for these patients.

High tumor budding activity may predict poor prognosis in laryngeal squamous cell carcinomas.

Laryngeal squamous cell carcinoma (SCC) which is the most common carcinoma of the respiratory system after lung carcinomas is graded by the World Health Organization (WHO) into three groups as grades 1, 2, and 3. This system does not correlate with the prognosis and has a low reproducibility among the pathologists. Searching for a new grading system, in this study, we investigated the relationship between tumor budding and histomorphological parameters and survival status. We examined the new grading system based on cell nest size and tumor budding. Partial and total laryngectomy materials of 130 patients diagnosed as laryngeal SCC between 2012 and 2018 in our clinic were evaluated retrospectively by two pathologists. Tumor budding activity and cell nests were scored and a new score was obtained by summing the scores. According to the scores obtained, a new grading system was created. There was a statistically significant difference between the tumor budding activity and the overall and disease-free survival times of the groups. The overall and disease-free survival time of the patients with high tumor budding significantly reduced. Tumor budding was found to be low in the presence of an intense lymphocytic host response (P < 0.05). There was no relationship between the new grade system and cell nest size and life expectancy (P > 0.05). Tumor budding provides significant clues in predicting the life expectancy of the patients. Therefore, tumor budding might be a component of new grading systems and should take place in pathology reports.

Evaluation of the Relationship Between the Invasive Front of Oral Squamous Cell Carcinoma and Clinicopathological Parameters.

Background & Objective:The present study investigated the relationship between invasive front (IF) of tumors and clinicopathological parameters including stage, grade, nodal involvement, lymphocytic host response (LHR), recurrence, overall survival (OS), and disease-free survival (DFS).Methods:A total of 87 oral squamous cell carcinoma (OSCC) biopsies were evaluated. Clinical stage, grading, nodal involvement, time of recurrence, OS, and DFS were assessed. The number of tumor budding cells in the IF was measured by two pathologists with an optic microscope. IF was graded to low risk (<5) and high risk (>5), according to the counting of tumor budding as a single cancer cell or cluster cells. Also, LHR was reported in the IF as mild, moderate, and severe.Results:IF was reported in 43.7% of patients as a low-risk group and 49.4% as a high-risk group. LHR was also mild in 31%, moderate in 25.3%, and severe in 43.7% of the patients. Most of the patients were in stage IV (31%) and grade 1 (60.9%). The high risk IF group had a significant statistical relationship with stage (P=0.001), grade (P=0.039), five years OS (P=0.03), five years DSF (P=0.01), and lymph node involvement (P=0.007). The relation between LHR and stage of disease was significant (P=0.034).Conclusion:Considering the essential role of histopathological reports in the treatment plan of patients and the relationship between IF and clinical parameters, IF evaluation in routine histopathological examinations, especially in the early stages of OSCC, seems to be necessary.

Histologic evaluation of host immune microenvironment and its prognostic significance in oral tongue squamous cell carcinoma: a comparative study on lymphocytic host response (LHR) and tumor infiltrating lymphocytes (TILs)

BackgroundHost immune microenvironment is a key component of anti-tumoral immune response, influencing tumor progression, regression, and treatment responses. There is a need for simple and reliable histologic measurements of host immune response in routine histopathologic diagnosis. MethodsThe prognostic value of lymphocytic host response (LHR), a qualitative histologic grading scheme, was compared to stromal/intratumoral TIL (sTIL/iTIL) percentage, a quantitative measurement in a retrospective study of 329 patients with oral tongue squamous cell carcinoma (OTSCC) of 4 cm or less in size. ResultsHigh sTIL predicted improved distant recurrence free survival on univariate survival analysis and was an independent prognostic factor for better overall survival on multivariate analysis. LHR and iTIL were not associated with the risk of nodal metastasis or outcome. ConclusionssTIL appears to be a superior quantitative histologic measurement for the host immune microenvironment compared with the qualitative LHR grading scheme. sTIL is an independent prognostic factor for overall survival in OTSCC.

IMPACT OF THE LYMPHOCYTIC HOST RESPONSE ON THE PROGNOSIS OF THE ORAL SQUAMOUS CELL CARCINOMA

The Risk Model (RM) is a histopathological classification based on the worst pattern of invasion (WPOI), lymphocytic host response (LHR), and perineural invasion (PNI) to establish the patient’s risk score. Objective: To analyze the effect of the LHR in the RM in patients with tongue and floor of mouth carcinomas (TFSCCs). Study design: Records and slides from 308 patients diagnosed with TFSCCs and surgically treated were characterized according to the RM and analyzed by bivariate (x²) and survival (Kaplan-Meier) analysis; the data contained sociodemographic, clinical, pathologic, and follow-up information. Results: Males aged between 41 and 60 years, with a smoking and drinking history and tumors of the tongue (clinical II and pathologic IV stages) were the most affected. Tumors with strong LHR (47.7%) predominated and classified as intermediate-risk (50.6%) by RM. Associations between strong LHR and tumors located in the tongue (P

Reframing Histological Risk Assessment of Oral Squamous Cell Carcinoma in the Era of UICC 8th Edition TNM Staging

ObjectivesTo assess whether application of the risk model originally proposed by Brandwein-Gensler, influences survival and disease progression in patients treated for oral squamous cell carcinoma (OSCCs)Materials and MethodsTumours from 134 T1 and T2 OSCC resections (7th edition) were scored independently by 3 histopathologists according to worst pattern of invasion (WPOI), lymphocytic host response (LHR) and perineural invasion (PNI) and categorised according to risk score. Local recurrence, locoregional recurrence, disease progression and overall survival were study endpoints. Interobserver variability of pathologist scoring was also assessed.ResultsSeventy-two patients (54%) were classified with low or intermediate risk and 62 (46%) patients were ‘high risk’. The inter-observer agreement was in moderate to strong agreement with the consensus scores (k range = 0.45–0.82). There was statistical significance between distant metastasis and ‘high risk’ tumours. Thirty tumours were upstaged to T3 in the 8th edition TNM staging, of which 83% had high risk scores. Overall risk score and TNM8 T stage has significant correlation with overall survival in comparison to the TNM 7 T stage.Conclusion‘High risk’ tumours were significantly associated with distant metastasis possibly due to the greater likelihood of aggressive features such as WPOI and PNI. Primary tumours are more likely to express high risk features with increasing T stage. None of the patients classified as ‘low risk’ died perhaps suggesting these tumours represent a rare variant of OSCC with excellent prognosis.

Machine Learning Predicts Lymph Node Metastasis in Early-Stage Oral Tongue Squamous Cell Carcinoma

Early-stage oral tongue squamous cell cancer (OTSCC) has a rate of metastasis to the cervical lymph nodes of 20 to 50%. This study aimed to build and validate 4 machine learning (ML) models to predict the occurrence of lymph node metastasis before and after surgery for early-stage (cT1N0 to cT2N0) OTSCC. We designed a retrospective cross-sectional study and reviewed the clinical and pathologic records of patients with early-stage OTSCC. The sample was composed of 2 groups with different node status (positive or negative) and was randomly split into training (70%) and testing (30%) sets. Four common ML algorithms-logistic regression, random forest, support vector machine, and naive Bayes-were used to predict pathologic nodal metastasis of early-stage OTSCC. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to assess the performance of these models and conventional methods including depth of invasion (DOI), neutrophil-to-lymphocyte ratio (NLR), and tumor budding. A total of 145 patients (56 with positive and 89 with negative lymph nodes) were included in this study. The performance of ML models was significantly superior to that of conventional prediction methods. The random forest model performed best (AUC, 0.786; sensitivity, 85%; specificity, 75%) and exceeded the performance of NLR (AUC, 0.539; sensitivity, 53.6%; specificity, 53.9%; P=.003).When DOI, worst pattern of invasion, lymphocytic host response, and tumor budding were added to model analysis according to patients' postoperative pathologic records, the support vector machine model performed best (AUC, 0.956; sensitivity, 100%; specificity, 87.5%) and was superior to univariate assessment of tumor budding (AUC, 0.830; sensitivity, 80.9%; specificity, 87.5%, P=.002), DOI (AUC, 0.613; sensitivity, 91.1%; specificity, 31.5%; P<.001), and NLR. ML shows a better performance in predicting lymph node metastasis of early-stage OTSCC than conventional prediction methods of DOI, NLR, or tumor budding.

Correlative study of tumor budding, mode of invasion and lymphocytic host response with known clinicopathological prognostic factors in oral squamous cell carcinoma.

Background:Oral squamous cell carcinoma (OSCC) is a significant public health problem in India, accounting to 30% of all cancers with a worrying rise in incidence and related mortality. Invasive tumor front (ITF) of OSCC has been an area of histopathologic research interest, where parameters like tumor budding (TB), mode of invasion (MOI) and lymphocytic host response (LHR) are being evaluated extensively.Objectives:The aim is to study and evaluate the possible association of ITF histological parameters such as TB, LHR and MOI with known clinicopathological prognostic factors in cases of OSCC.Subjects and Methods:We reviewed and analyzed 69 cases of OSCC for routine clinicopathological parameters, TB, MOI and LHR for any significant correlation (P < 0.05 by Chi-square test) with each other and with outcome in cases where follow-up was available.Results:TB correlated significantly with histological grade, worst pattern of invasion (WPOI), Lymphnodal involvement (LNI), Lymphovascular invasion (LVI), Perineural invasion (PNI) and age; MOI correlated with WPOI, LNI, LVI and PNI; and LHR significantly correlated with WPOI, PNI, Tumor size (pT) and outcome. TB showed a strong correlation with MOI (P < 0.001) and LHR; and no significant association was noted between LHR and MOI. Among all the clinicopathological parameters, depth of invasion, pT, WPOI, PNI and LHR showed significant correlation with outcome.Conclusion:TB, MOI and LHR showed good correlation with established parameters and as they are easy and helps in prognostication, they should be included in routine histopathological reporting guidelines.

Worst pattern of invasion - type 4 (WPOI-4) and Lymphocyte host response should be mandatory reporting criteria for oral cavity squamous cell carcinoma: A re-look at the American Joint Committee of Cancer (AJCC) minimum dataset.

A proportion of early-stage node-negative oral squamous carcinoma patients fail despite complete surgical resection. Adjuvant treatment in early oral cancer is controversial and is often individualized based on stage, depth, and margin status. We reviewed various histological markers in pT1/T2N0 cases, resected upfront with elective nodal dissection, with an emphasis on tumor-tissue interface characteristics of the worst pattern of invasion (WPOI), tumor cell nest size (sCNS), budding and lymphocytic host response (LHR), to assess their prognostic significance. Archived blocks of 95 cases were reviewed. Tumor stage, grade, size, depth of invasion, lymphovascular, and perineural invasion, WPOI, LHR, sCNS, and tumor bud (single cells or <5 cell clusters) score were recorded. Prognostic significance was statistically analyzed using SPSS software version 20. Depth of invasion (P = 0.008), WPOI- 4 and 5 (P = 0.033), sCNS (<5 cells) at tumor interface (P = 0.010), high bud count (≥3 buds/40 × hpf) (P = 0.021) and poor LHR (P = 0.019) correlated significantly with poor disease-free survival on univariate analysis. However, on multivariate analysis only LHR and WPOI-4 (that is presence of small cell nests or buds) were significant, with high hazard ratio of 4.351 (95% CI 1.290-14.676, P = 0.018) and 5.019 (95% CI 1.212-20.789, P = 0.026), respectively. We propose mandatory reporting of WPOI-4 at the tumor interface and absence of LHR, as significant markers of poor prognosis in early-stage oral cavity squamous carcinoma.

Validation of the Brandwein Gensler Risk Model in Patients of Oral Cavity Squamous Cell Carcinoma in North India.

India has one of the highest incidences of oral squamous cell carcinoma (OSCC), with 75,000-80,000 new cases a year. The outcome in early oral cancer is better, but a significant proportion (12-14%) of these patients still relapses and dies due to locoregional or distant recurrences. Several clinicopathological and molecular factors have been used to prognosticate and predict outcomes in these patients of OSCC. The present study aims to validate Brandwein Gensler (BG) risk predictive model in surgically treated OSCC patients in a tertiary care centre in North India. All oral cavity cancer patients, treated in the Department of Surgical Oncology, King George's Medical University, between 2013 and 2017, were reviewed. Patients with histologically diagnosed OSCC, aged > 18years undergoing primary surgical resection were included in the study. The final histopathological evaluation was done by a dedicated pathologist to categorize patients according to BG model risk categories. This model comprises of three factors, lymphocytic host response, perineural invasion and worst pattern of invasion, scored by the method described by Brandwein Gensler et al. The sum of these scores is used to define low, moderate and high risk categories. The study, conducted during 2013-2017, included 149 patients. Median age was 45years (range 25-75years). Tobacco use was noted in 143 patients. Buccal mucosa was the most common site (51%). Surgical margins were clear (> 5mm) in 97.9% cases. Postoperative radiotherapy was given in 47.7% patients. Locoregional recurrences (LRR) (primary site and neck) were documented in 17 of the 149 patients (11.4%). There was no synchronous or metachronous distant metastasis noted in any of the study patients. Six patients had disease specific mortality. Among the 17 patients with LRR, majority (11) belonged to the high risk category of the BG risk model. Adjuvant radiotherapy had been administered in 10 of these 11 recurrent patients belonging to the high risk category. The Brandwein Gensler risk model is predictive of locoregional recurrences (p = 0.02) for OSCC undergoing primary surgery. It can be used to devise strategies to prevent recurrences or identification of recurrences at an earlier point for salvage. The benefit of further escalation of adjuvant therapy in the high risk category needs further studies, as 90% patients in this group recurred despite complete adjuvant treatment.

Machine learning application for prediction of locoregional recurrences in early oral tongue cancer: a Web-based prognostic tool

Estimation of risk of recurrence in early-stage oral tongue squamous cell carcinoma (OTSCC) remains a challenge in the field of head and neck oncology. We examined the use of artificial neural networks (ANNs) to predict recurrences in early-stage OTSCC. A Web-based tool available for public use was also developed. A feedforward neural network was trained for prediction of locoregional recurrences in early OTSCC. The trained network was used to evaluate several prognostic parameters (age, gender, T stage, WHO histologic grade, depth of invasion, tumor budding, worst pattern of invasion, perineural invasion, and lymphocytic host response). Our neural network model identified tumor budding and depth of invasion as the most important prognosticators to predict locoregional recurrence. The accuracy of the neural network was 92.7%, which was higher than that of the logistic regression model (86.5%). Our online tool provided 88.2% accuracy, 71.2% sensitivity, and 98.9% specificity. In conclusion, ANN seems to offer a unique decision-making support predicting recurrences and thus adding value for the management of early OTSCC. To the best of our knowledge, this is the first study that applied ANN for prediction of recurrence in early OTSCC and provided a Web-based tool.

PLAQUE-TYPE LICHEN PLANUS OR LEUKOPLAKIA WITH LYMPHOCYTIC HOST RESPONSE?

Introduction Oral epithelial dysplasia (OED) and oral squamous cell carcinomas (SCCAs) often exhibit a lymphocytic host response (LHR) present as a band at the epithelium-connective tissue interface. Because these are often diagnosed as dysplasia with lichenoid mucositis or lichenoid dysplasia, clinicians assume that such lesions represent dysplasia or SCCA arising within lesions of oral lichen planus (OLP). If the clinical lesion is a solitary plaque, the diagnosis of plaque-type OLP may be made. Lichenoid lymphocytic reactions are not specific to OLP and may be seen in drug-induced, contact hypersensitivity reactions and other conditions. The objective of this study is to review cases of leukoplakia with a lichenoid LHR. Materials and Methods Cases diagnosed as OED with lichenoid features or lichenoid mucositis that represented biopsies from solitary white lesions were identified from the files of one laboratory from January 2013 to December 2018. Results There were 13 males and 11 females (1.2:1 male to female ratio), and the median age was 61 (range 37– 90). All lesions were unilateral and the two most common locations were the tongue (12 cases, 50.0%) and the gingiva (5 cases, 20.8%). Hyperkeratosis and/or parakeratosis and epithelial atrophy was present in 23 (95.8 %) and 10 cases (41.6%) respectively while degeneration of the basal cells was present in 7 cases (29.1%) only. OED was present in 13 (54.1%) of the cases (5 mild, 5 moderate, 2 severe, and 1 carcinoma-in-situ); 36.3% of the cases that showed epithelial atrophy also showed OED. A lymphocytic band was present in 24 cases (100%). Conclusion These lichenoid lesions were solitary plaques located most commonly on the tongue and gingiva, common sites for leukoplakia with 54.1% exhibiting OED. As such, these lesions more likely represent leukoplakia with a LHR rather than OLP. Clinicopathologic correlation is essential for accurate diagnosis.

The histologic risk model is a useful and inexpensive tool to assess risk of recurrence and death in stage I or II squamous cell carcinoma of tongue and floor of mouth

AbstractSurgery is the mainstay of treatment for low-stage (stage I/II, ie, T1N0/T2N0) squamous cell carcinoma of oral cavity. However, a significant percentage of low-stage squamous cell carcinoma of oral cavity will develop local recurrence and disease-related mortality. In this study, we stratified 64 patients with low-stage of oral tongue and floor of mouth patients into high-, intermediate- and low-risk categories based on existing histologic risk model. The classification of these risk categories was based on presence or absence of perineural invasion and evaluation of tumor–host junction for worst pattern of invasion and lymphocytic host response. We correlated risk category and other variables with recurrence and death. In a univariate model, high-risk category tumors had a significantly higher rate of recurrence and death due to recurrence compared with low/intermediate-risk categories (P=0.000 and P=0.047, respectively). Controlling for margin status and T-stage, high-risk category had a 12.4 odds ratio of later recurrence when compared with low/intermediate-risk categories, with a P-value of 0.001. In conclusion, we found low-stage oral cavity squamous cell carcinoma patients with high-risk category have a significantly higher risk for recurrence when compared with patients in the low- or intermediate-risk category, even when controlling for margin status and T-stage. These patients may be suitable candidates for adjuvant treatment to decrease morbidity and mortality associated with a recurrence. Our results indicate that the histologic risk model is a useful and simple tool to assess risk of recurrence in stage I or II squamous cell carcinoma of oral cavity.