Binary Grading System Research Articles

Is Binary Grading Better Than WHO System for Grading Epithelial Dysplasia? A Systematic Review and Meta-Analysis.

This meta-analysis summarizes the current evidence on the intra- and inter-observer agreement between WHO and the binary grading systems used to assess epithelial dysplasia (ED). A systematic search for observational studies that compared the level of agreement among pathologists between WHO and binary grading systems for ED was conducted using three databases: Medline, Scopus, and EBSCOhost. For the meta-analysis, summary estimations of kappa value (κ) and standard error (SE) were utilized. The pooled analysis of observations by 46 pathologists from a total of eight studies showed better interobserver agreement in the interpretation of ED for the binary system (κ = 0.31; 95% confidence interval [CI], 0.23-0.40) in comparison with the WHO (κ = 0.14; 95% CI, 0.10-0.19). The intra-observer agreement was reported only by five studies and was also found to be higher for the binary system (κ = 0.44; 95% CI, 0.31-0.57) compared to the WHO (κ = 0.25; 95% CI, 0.11-0.39). Our results validate that the binary system has better overall intra-observer and interobserver agreement than the WHO system. Further studies with larger cohorts are mandatory before clinically relevant conclusions are drawn, as evidence remains inadequate.

Evaluating insomnia queries from an artificial intelligence chatbot for patient education.

We evaluated the accuracy of ChatGPT in addressing insomnia-related queries for patient education and assessed ChatGPT's ability to provide varied responses based on differing prompting scenarios. Four identical sets of 20 insomnia-related queries were posed to ChatGPT. Each set differed by the context in which ChatGPT was prompted: no prompt, patient-centered, physician-centered, and with references and statistics. Responses were reviewed by 2 academic sleep surgeons, 1 academic sleep medicine physician, and 2 sleep medicine fellows across 4 domains: clinical accuracy, prompt adherence, referencing, and statistical precision, using a binary grading system. Flesch-Kincaid grade-level scores were calculated to estimate the grade level of the responses, with statistical differences between prompts analyzed via analysis of variance and Tukey's test. Interrater reliability was calculated using Fleiss's kappa. The study revealed significant variations in the Flesch-Kincaid grade-level scores across 4 prompts: unprompted (13.2 ± 2.2), patient-centered (8.1 ± 1.9), physician-centered (15.4 ± 2.8), and with references and statistics (17.3 ± 2.3, P < .001). Despite poor Fleiss kappa scores, indicating low interrater reliability for clinical accuracy and relevance, all evaluators agreed that the majority of ChatGPT's responses were clinically accurate, with the highest variability on Form 4. The responses were also uniformly relevant to the given prompts (100% agreement). Eighty percent of the references ChatGPT cited were verified as both real and relevant, and only 25% of cited statistics were corroborated within referenced articles. ChatGPT can be used to generate clinically accurate responses to insomnia-related inquiries. Alapati R, Campbell D, Molin N, etal. Evaluating insomnia queries from an artificial intelligence chatbot for patient education. J Clin Sleep Med. 2024;20(4):583-594.

Calibration improves the agreement in grading oral epithelial dysplasia-Findings from a National Workshop in Malaysia.

A major pitfall of many of the established oral epithelial dysplasia (OED) grading criteria is their lack of reproducibility and accuracy to predict malignant transformation. The main objective of this study was to determine whether calibration of practicing oral pathologists on OED grading could improve the reproducibility of the WHO 2017 and the binary OED grading systems. A nationwide online exercise was carried out to determine the influence of calibration on the reproducibility of the WHO 2017 and the binary OED grading systems. A significant improvement was observed in the inter-observer agreement for the WHO 2017 OED grading system (K 0.196 vs. 0.448; Kw 0.357 vs. 0.562) after the calibration exercise. The significant difference (p = 0.027) in the level of agreement between those with five or more years and less than 5 years of experience was no more observed (p = 0.426) after the calibration exercise. The percent agreement for binary grading was significantly higher (91.8%) for buccal mucosal lesions as compared to lesions on the tongue after the calibration exercise. This study validates the significance of calibration in improving the reproducibility of OED grading. The nationwide exercise resulted in a statistically significant improvement in the inter-observer agreement for the WHO 2017 OED grading system among a large number of oral pathologists. It is highly recommended that similar exercises should be organized periodically by professional bodies responsible for continuing education among oral pathologists to improve the reliability of OED grading for optimal treatment of oral potentially malignant disorders.

Proposal of Novel Binary Grading Systems for Cervical Squamous Cell Carcinoma.

We compared grading systems and examined associations with tumor stroma and survival in patients with cervical squamous cell carcinoma. Available tumor slides were collected from 10 international institutions. Broders tumor grade, Jesinghaus grade (informed by the pattern of tumor invasion), Silva pattern, and tumor stroma were retrospectively analyzed; associations with overall survival (OS), progression-free survival (PFS), and presence of lymph node metastases were examined. Binary grading systems incorporating tumor stromal changes into Broders and Jesinghaus grading systems were developed. Of 670 cases, 586 were reviewed for original Broders tumor grade, 587 for consensus Broders grade, 587 for Jesinghaus grade, 584 for Silva pattern, and 556 for tumor stroma. Reproducibility among grading systems was poor (κ = 0.365, original Broders/consensus Broders; κ = 0.215, consensus Broders/Jesinghaus). Median follow-up was 5.7 years (range, 0-27.8). PFS rates were 93%, 79%, and 71%, and OS rates were 98%, 86%, and 79% at 1, 5, and 10 years, respectively. On univariable analysis, original Broders ( P < 0.001), consensus Broders ( P < 0.034), and Jesinghaus ( P < 0.013) grades were significant for OS; original Broders grade was significant for PFS ( P = 0.038). Predictive accuracy for OS and PFS were 0.559 and 0.542 (original Broders), 0.542 and 0.525 (consensus Broders), 0.554 and 0.541 (Jesinghaus grade), and 0.512 and 0.515 (Silva pattern), respectively. Broders and Jesinghaus binary tumor grades were significant on univariable analysis for OS and PFS, and predictive value was improved. Jesinghaus tumor grade ( P < 0.001) and both binary systems (Broders, P = 0.007; Jesinghaus, P < 0.001) were associated with the presence of lymph node metastases. Histologic grade has poor reproducibility and limited predictive accuracy for squamous cell carcinoma. The proposed binary grading system offers improved predictive accuracy for survival and the presence of lymph none metastases.

Head-to-head: how many categories for grading urothelial carcinoma?

Tumour grade is a critical prognostic parameter for guiding the management of patients with non-muscle invasive bladder cancer. In 2004, the World Health Organisation (WHO) adopted a binary (low-grade/high-grade) grading system to replace the three-tier (grades 1-3) system used to grade urothelial carcinoma since 1973. However, there is significant global variation in the grading of urothelial carcinoma. Some pathology and clinical guidelines recommend reporting of the WHO 1973 and 2004 grades in parallel, while others require reporting only of the WHO 2004 grade. This variation in pathology practice is clinically significant, because the two grading systems are not readily translatable. Some experts have proposed novel systems for grading urothelial carcinoma that involve splitting of the WHO 1973 and 2004 grade categories. The arguments for and against splitting urothelial carcinomas into two-, three- and four-grade categories are independently discussed by the three authors.

TWO GRADING SYSTEMS FOR ORAL EPITHELIAL DYSPLASIA IN ORAL POTENTIALLY MALIGNANT DISORDERS: A CLINICOPATHOLOGICAL STUDY

Objectives To classify oral epithelial dysplasia (OED), defined by the WHO, and binary grading systems in oral potentially malignant disorders (OPMDs), besides associating sociodemographic and histopathological features of these OPMDs. Study Design Records and slides of 65 cases compatible with clinicopathological diagnoses of OPMDs were evaluated for both classification systems and submitted to bivariate analysis. Results Middle-aged white men, non-smokers, and non-drinkers predominated. Smoking was associated with high-risk lesions by the binary system (p=0.036) and oral leukoplakia (p=0.003). The cases graded as mild-OED and severe-OED by the WHO system (85.7%) were reclassified as low-risk and high-risk respectively by the binary system. By contrast, 61.8% of moderate-OED cases were reclassified as low-risk for malignant transformation. Abnormal variation in cell size and shape, increased number and size of nucleoli, drop-shaped rete ridges, loss of epithelial cell cohesion, and abnormally superficial mitotic figures were statistically significant (p<0.05) in both grading systems. Cytological changes were significant in the WHO system, whereas architectural changes were significant in the binary system. Conclusions These are important histopathological features that should be taken into consideration when grading OED. Smoking was strengthened by the binary system as a risk factor for developing oral leukoplakia and its progression to malignancy. CNPq. To classify oral epithelial dysplasia (OED), defined by the WHO, and binary grading systems in oral potentially malignant disorders (OPMDs), besides associating sociodemographic and histopathological features of these OPMDs. Records and slides of 65 cases compatible with clinicopathological diagnoses of OPMDs were evaluated for both classification systems and submitted to bivariate analysis. Middle-aged white men, non-smokers, and non-drinkers predominated. Smoking was associated with high-risk lesions by the binary system (p=0.036) and oral leukoplakia (p=0.003). The cases graded as mild-OED and severe-OED by the WHO system (85.7%) were reclassified as low-risk and high-risk respectively by the binary system. By contrast, 61.8% of moderate-OED cases were reclassified as low-risk for malignant transformation. Abnormal variation in cell size and shape, increased number and size of nucleoli, drop-shaped rete ridges, loss of epithelial cell cohesion, and abnormally superficial mitotic figures were statistically significant (p<0.05) in both grading systems. Cytological changes were significant in the WHO system, whereas architectural changes were significant in the binary system. These are important histopathological features that should be taken into consideration when grading OED. Smoking was strengthened by the binary system as a risk factor for developing oral leukoplakia and its progression to malignancy. CNPq.

The Significance of International Federation of Gynecology and Obstetrics Grading in Microsatellite Instability-High and POLE-Mutant Endometrioid Endometrial Carcinoma

With the advancement of diagnostic molecular technology and the molecular classification of endometrial endometrioid carcinoma (EEC), it remains to be seen whether conventional International Federation of Gynecology and Obstetrics (FIGO) grading retains clinical significance in certain molecular subtypes of EECs. In this study, we explored the clinical significance of FIGO grading in microsatellite instability-high (MSI-H) and POLE-mutant EECs. A total of 162 cases of MSI-H EECs and 50 cases of POLE-mutant EECs were included in the analysis. Significant differences in tumor mutation burden (TMB), progression-free survival, and disease-specific survival were seen between the MSI-H and POLE-mutant cohorts. Within the MSI-H cohort, there were statistically significant differences in TMB and stage at presentation across FIGO grades, but not survival. Within the POLE-mutant cohort, there was significantly greater TMB with increasing FIGO grade, but there were no significant differences in stage or survival. In both the MSI-H and POLE-mutant cohorts, log-rank survival analysis showed no statistically significant difference in progression-free and disease-specific survival across FIGO grades. Similar findings were also seen when a binary grading system was utilized. Since FIGO grade was not associated with survival, we conclude that the intrinsic biology of these tumors, characterized by their molecular profile, may override the significance of FIGO grading.

Assessment of Interobserver Agreement in the Interpretation of 99mTc-PYP SPECT Imaging of Cardiac Amyloidosis.

Background: Technetium-99m pyrophosphate single photon emission computed tomography (99mTc-PYP SPECT) imaging is widely used to diagnose cardiac amyloidosis, a disease characterized by amyloid protein deposits in the myocardium. The effects of viewing perspectives on interobserver agreement in the interpretation of 99mTc-PYP SPECT images for the diagnosis of cardiac amyloidosis remain unclear. Methods: A retrospective analysis of 32 consecutive patients who underwent 99mTc-PYP imaging for the diagnosis of cardiac amyloidosis at Nagasaki University Hospital between October 2017 and February 2020 was performed. Four evaluators independently reviewed coronal, sagittal, and transaxial images and then all images together and made a categorical diagnosis based on predefined criteria. Interobserver agreement was analyzed using Cohen's Kappa analysis. Results: Kappa coefficient values in the four-grade grading system (grades 0-3) ranged between 0.31 and 0.95, while those in the binary grading system (positive/negative) ranged between 0.88 and 1. The sagittal view showed the highest value in the four-grade grading system (0.95) and the lowest in the binary grading system (0.88). The transaxial view was more likely to show a consistently high kappa value in both the four-grade and binary grading systems. The use of the multiplanar view reduced the number of subjects classified as grade 1. Conclusion: Our study demonstrates that the transaxial view provides the most consistent interpretation of 99mTc-PYP SPECT images for the diagnosis of cardiac amyloidosis. The use of the multiplanar view may also reduce equivocal interpretations, which are graded as grade 1. Further studies with larger sample sizes and a quantitative analysis are needed to confirm the present results.

Implementation of a soft grading system for chemistry in a Moodle plugin

We report a novel approach for grading chemical structure drawings for remote teaching, integrated into the Moodle platform. Typically, existing online platforms use a binary grading system, which often fails to give a nuanced evaluation of the answers given by the students. Therefore, such platforms are unevenly adapted to different disciplines. This is particularly true in the case of chemical structures, where most questions simply cannot be evaluated on a true/false basis. Specifically, a strict comparison of candidate and expected chemical structures is not sufficient when some tolerance is deemed acceptable. To overcome this limitation, we have developed a grading workflow based on the pairwise similarity score of two considered chemical structures. This workflow is implemented as a Moodle plugin, using the Chemdoodle engine for drawing structures and communicating with a REST server to compute the similarity score using molecular descriptors. The plugin (https://github.com/Laboratoire-de-Chemoinformatique/moodle-qtype_molsimilarity) is easily adaptable to any academic user; both embedding and similarity measures can be configured.

A review of the changes in higher education assessment and grading policy during covid-19

The Covid-19 pandemic has not only brought about sociocultural, psychological and economic challenges, but also educational problems that have entailed radical policy changes to allow universities and colleges to fulfil their role. Before the pandemic, the majority of university courses were designed for face-to-face settings; but under the social distancing policies since Covid-19, institutions have had to react quickly, revising their teaching and assessment policies to ensure that education continues for all students and accommodate the new remote reality of education. This paper provides a review of the changes in educational assessment and grading policies of universities around the world in response to the Covid-19 pandemic, where five key themes were identified: covid-19 binary grading system, revised regulations governing the final degree award, relaxed academic progression policies, revised extension, deferral and exceptional circumstances policies, and mark adjustments. This review will serve as a useful summary for institutions to reflect upon and inform planning strategies for subsequent unexpected future events.

Correlation of a New Binary System in Grading of Oral Leukoplakia for Its Prediction of Malignant Transformation - A Retrospective Record-Based Study

Introduction: Oral Leukoplakia is a premalignant lesion with an increased risk of developing oral cancer when the lesion is non-homogeneous. There is a need to validate clinical presentations of a commonly occurring Leukoplakia lesion and its probability of dysplastic changes over some time. Aim: To correlate the Diagnostic accuracy of clinical lesion diagnosed as Leukoplakia and the presence or absence of dysplasia through its histopathological correlation. Materials and Methods: This study gathered data retrospectively during 2016–2021 with an initial diagnosis of oral Leukoplakia. A set of 611 slides were included in the study that was signed out as oral Leukoplakia. We tested the hypothesis that a binary grading system categorizes lesions as “presence” or “absence” of oral epithelial dysplasia. A logistic regression analysis was used in predicting the presence of dysplasia among the various clinical criteria. Results: Most of the mild dysplasia was reported in the buccal mucosa (n = 195; 31.91%), followed by 6 (0.98%) cases in the vestibule. A mean age of 32.33 ± 7.0 was observed for severe dysplasia. A statistically significant relationship between the risk estimates for the clinical diagnosis and dysplasia was noted for all the lesion types. Conclusion: The study concludes that the clinical presentation of a lesion can predict the underlying dysplastic changes, and mixed red and white lesions with growth possess the highest risk of malignant transformations.

Combination of Binary System with Ki67 Immunohistochemical Staining: a Reliable Grading Method for Oral Epithelial Dysplasia.

Oral epithelial dysplasia (OED) is a common potentially malignant lesion of oral cavity that should be managed to prevent likely malignant transformation. Here, we present a combination of binary grading system with complementary immunohistochemical (IHC) staining for Ki67 biomarker to provide a reproducible OED grading system. In this cross-sectional study, seventy out of one hundred OED specimens, which were accompanied by IHC stained microscopic slides for Ki67 antigen were evaluated by four independent oral pathologists. Both three-tier and binary grading systems based on WHO microscopic criteria were employed , blindly in a four-step method with at least two-week interval between each observation. Intra- and inter-observational reliability was assessed using Kappa statistical analysis. OED diagnosis based on binary system showed significant intra-observer reliability comparing to three-tier system without biomarker. Moreover, OED diagnosis based on binary system using Ki67 biomarker showed significant inter-observer reliability comparing to diagnosis in three tier system and based on binary system without Ki67 biomarker showed significant inter-observer reliability comparing to diagnosis based on three-tier system without Ki67. Here, we found that application of IHC staining for Ki67 biomarker in binary system might provide a more reliable grading method for oral pathologist form different educational background.

The clinical utility of contemporary oral epithelial dysplasia grading systems.

Clinical management of oral potentially malignant disorders relies on accurate histopathological assessment of the presence and grade of oral epithelial dysplasia. While adjunctive laboratory tests have provided useful prognostic information, none are in widespread clinical use. This study was performed to assess the clinical utility of two contemporary oral epithelial dysplasia grading systems. Patients were identified from a clinical database. Oral epithelial dysplasia grading was performed by three oral and maxillofacial pathologists blinded to clinical outcome using the WHO 2017 system and a binary classification. The primary outcome measure was the development of oral squamous cell carcinoma, termed 'malignant transformation'. One hundred thirty-one cases satisfied the inclusion criteria, of which 23 underwent malignant transformation. There was substantial inter-rater agreement between the study pathologists for both grading systems, measured using kappa statistics (κ=0.753 - 0.784). However, there was only moderate agreement between the consensus WHO 2017 dysplasia grade for the study against the original grade assigned by a pool of six pathologists in the context of the clinical service (κ=0.491). Higher grade categories correlated with an increased risk of developing cancer using both grading systems. This study demonstrates that the WHO 2017 and binary grading systems are reproducible between calibrated pathologists and that consensus reporting is likely to improve the consistency of grading. The WHO and binary systems were prognostically comparable. We recommend that institutions implement consensus oral epithelial dysplasia grading and prospectively audit the effectiveness of risk stratifying their patients with oral potentially malignant disorders. (249 words).

Binary and WHO dysplasia grading systems for the prediction of malignant transformation of oral leukoplakia and erythroplakia: a systematic review and meta-analysis.

The aim of this systematic review was to examine the evidence of the binary histologic grading system capacity for predicting malignant transformation and to compare it with that of the WHO systems. A systematic review was conducted, using PubMed, EMBASE, LILACS, Web of Science, Scopus, and LIVIVO databases without any language or timeframe restrictions. Studies were included if they compared the binary and the WHO histologic grading systems in the prediction of malignant transformation of oral epithelial dysplasia (OED). The capacity of the WHO and binary grading systems to predict malignant transformation ranged from 16 to 80% and from 5 to 80%, respectively. The pooled malignant transformation rate of lesions classified as severe dysplasia or carcinoma in situ by the WHO grading was 40% (95% confidence interval (CI), 0.02-0.87; I2 = 92%; P = 0.00), while the corresponding value for lesions classified as high-risk by the binary grading system was 31% (95% CI, 0.00-0.84; I2 = 97%; P = 0.00). Overall, there was no significant difference in prognostication accuracy between the WHO and the binary systems (odds ratio = 2.02; 95% CI, 0.88-4.64). Although some studies suggest that the binary system is associated with lower inter-rater variability when grading OED, the evidence remains inconclusive on whether this system is superior to that of the WHO at predicting malignant transformation. The reproducibility of the binary system has the potential to be better for prognostic purposes. However, there is no high-quality evidence to confirm if this advantage may assist clinicians in decision-making.

Grading of Oral Leukoplakia: Can It be Improvised Using Immunohistochemical Markers p63 and CD31.

Introduction:Oral squamous cell carcinoma is usually preceded by potentially malignant disorders (PMDs), the most common being oral leukoplakia. A conservative management protocol is followed for milder dysplastic cases, while severe dysplastic lesions are surgically excised. Several classification systems have been developed based mainly on histopathological features with a lot of inter-observer variations. The present study was done to assess the use of immunohistochemical (IHC) markers in grading leukoplakic lesions in addition to histopathological grading.Aims and Objectives:To grade leukoplakia using different grading systems and assess if IHC markers can aid in categorizing leukoplakia.Materials and Methods:Thirty-five cases of leukoplakia were graded using Ljubljana, 2005 World Health Organization (WHO), and Binary System followed by IHC staining with p63 and CD31.Results and Statistics:Variation was noted in 12 cases while using WHO, 11 using Ljubljana, and 7 using Binary System and was significant on Cohen-Kappa statistics, with the least significant variation noted on Binary System. p63 staining assisted to group doubtful cases and even identify variation in cases graded positively on histopathology. In total, 17 cases stained one-third (mild/low), while 15 cases stained one-half or more (higher grade) epithelial thickness. A weak correlation was observed between all grading systems and p63 on Kendall's Tau-b analysis and the weak correlation was significant for the WHO and binary grading systems. Analyzing p63 and CD31 using Kruskal–Wallis test, an increase in mean vessel density (MVD) was noted for mild/moderate cases but decreased for severe cases.Conclusion:Addressing histological categorization of PMDs assisted by IHC markers to understand the biological behavior of the tissues is currently essential with studies on more markers to assist in the management protocol.

Binary grading may be more appropriate for endometrial cancer

Objective:To elucidate the survival consequences of the prognostic factors for endometrial cancer.Material and Methods:This was a retrospective study of 276 patients diagnosed with endometrial cancer who admitted for staging surgery. The extent of the surgery was determined by clinical staging and preoperative evaluation. The pathology specimens were reassessed by a gynecopathologist. Independent risk factors were revealed for the progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS) utilizing Kaplan-Meier and “Cox” proportional analysis.Results:The median follow up of the patients was 50 months. Of the 29 patients who died, 15 (5.43%) died because of endometrial cancer. Multivariate analysis revealed that independent risk factors for OS and PFS were stage (p=0.002, 0.002, respectively) and grade 3 (G3) histology (p=0.013, 0.015, respectively). Positive peritoneal cytology was an independent risk factor for OS (p=0.024), but not for PFS (p=0.050). Stage (p=0.005) was found to be the only independent risk factor for DSS. Patients with G1 and G2 histology had a similar and more favorable prognosis than patients with G3 histology.Conclusion:Advanced stage, high-grade tumor and the presence of positive peritoneal cytology were ascertained as independent prognostic factors for endometrial cancer. A binary histological grading system could be simpler and as effective as the current three grade system because grade 1 and 2 patients showed similar prognosis.

EVALUATION OF INFLAMMATORY MARKERS IN POTENTIALLY MALIGNANT DISORDERS OF THE ORAL CAVITY

Objective: The aim this study was to evaluate the expression of inflammatory markers in potentially malignant disorders of oral cavity (leukoplakia) and its relationship with the degree of epithelial dysplasia. Study design: Immunohistochemistry was used to identify the number (cells/mm2) of interleukin 17 (IL-17+), neutrophil (CD66 b+), matrix metalloproteinase‐9 (MMP-9+) cells, and neoformed microvessels (CD105+) in the subepithelial region of leukoplakia samples from 31 patients. Evaluation of IL‐17 expression in keratinocytes cells was semiquantitative and performed by assigning scores. Samples of healthy oral mucosa (n = 10) were used as controls. Results: The classification of epithelial dysplasia by the binary grading system totaled 17 samples with high risk and 14 samples with low risk of malignant transformation. Irrespective of the severity of epithelial dysplasia, the counts of inflammatory markers (CD66 b, IL-17, MMP-9, and CD105) were higher in the leukoplakia group compared to controls (P< .05 for all comparisons). In addition, the intraepithelial expression of IL-17 was high in leukoplakia samples (44%) and absent/low in the control group (100%; P< .05). Conclusions: This study showed that potentially malignant disorders of oral cavity are characterized by a high count of inflammatory markers. Objective: The aim this study was to evaluate the expression of inflammatory markers in potentially malignant disorders of oral cavity (leukoplakia) and its relationship with the degree of epithelial dysplasia. Study design: Immunohistochemistry was used to identify the number (cells/mm2) of interleukin 17 (IL-17+), neutrophil (CD66 b+), matrix metalloproteinase‐9 (MMP-9+) cells, and neoformed microvessels (CD105+) in the subepithelial region of leukoplakia samples from 31 patients. Evaluation of IL‐17 expression in keratinocytes cells was semiquantitative and performed by assigning scores. Samples of healthy oral mucosa (n = 10) were used as controls. Results: The classification of epithelial dysplasia by the binary grading system totaled 17 samples with high risk and 14 samples with low risk of malignant transformation. Irrespective of the severity of epithelial dysplasia, the counts of inflammatory markers (CD66 b, IL-17, MMP-9, and CD105) were higher in the leukoplakia group compared to controls (P< .05 for all comparisons). In addition, the intraepithelial expression of IL-17 was high in leukoplakia samples (44%) and absent/low in the control group (100%; P< .05). Conclusions: This study showed that potentially malignant disorders of oral cavity are characterized by a high count of inflammatory markers.

Intra-observer and inter-observer variability in two grading systems for oral epithelial dysplasia: A multi-centre study in India.

The presence and grading of oral epithelial dysplasia (OED) are considered the gold standard for predicting the malignant risk of oral potentially malignant disorders. However, inter-observer and intra-observer agreement in the context of reporting on OED grading has been reputedly considered unreliable. We undertook a multi-centre study of six Indian oral pathologists to assess variations in reporting OED using the World Health Organization (WHO; 2005) system and also the recently introduced binary system. The observer variability was assessed with the use of kappa statistics. The weighted kappa intra-observer agreement scores improved (κw =0.5012) on grouping by two grades as no and mild dysplasia versus moderate and severe dysplasia compared to binary grading system (κ=0.1563) and WHO grading system (κw =0.4297). Poor to fair inter-observer agreement scores were seen between the principal investigator (PI) and the other five observers using the WHO grading system (κ=0.051-0.231; κw =0.145 to 0.361; 35% to 46%) and binary grading system (κ=0.049 to 0.326; 50 to 65%). There is considerable room for improvement in the assessment of OED using either system to help in standardised reporting. The professional pathology organisations in India should take steps to provide external quality assessment in reporting OED among oral and general pathologists who are engaged in routine reporting of head and neck specimens.

Grading systems of oral cavity pre-malignancy: a systematic review and meta-analysis.

Oral potentially malignant disorders (OPMDs) may have varying degrees of oral epithelial dysplasia (OED). Traditional grading schemes separate OED into three-tiers (mild, moderate, and severe). Alternatively, a binary grading system has been previously proposed that stratifies OED into low-risk and high-risk categories based on a quantitative threshold of dysplastic pathologic characteristics. This systematic review evaluates the predictive value of a binary OED grading system and examines agreement between pathologists. This meta-analysis queried 4 databases (PubMed, Ovid-MEDLINE, Cochrane, and SCOPUS) and includes 4 studies evaluating binary OED grading systems. Meta-analysis of proportions and correlations was performed to pool malignant transformation rates (MTR), risk of malignant transformation between OED categories, and measures of interobserver agreement. Pooled analysis of 629 lesions from 4 different studies found a six-time increased odds of malignant transformation in high-risk lesions over low-risk lesions [odds ratio (OR) 6.14, 95% 1.18-15.38]. Reported ORs ranged from 2.8 to 22.4. The overall MTR was 26.8%, with the high-risk and low-risk lesions having MTRs of 57.9% (95% CI 0.386-0.723) and 12.7% (95% CI - 0.210 to 0.438), respectively. Pooled unweighted interobserver kappa values for the binary grading system and three-tiered system were 0.693 (95% CI 0.640-0.740) and 0.388 (95% CI 0.195-0.552), respectively. Binary grading of OED into low-risk and high-risk categories may effectively determine malignant potential, with improved interobserver agreement over three-tiered grading. Improved grading schemes of OED may help guidemanagement (watchful waiting vs. excision) of these OPMDs.

Malignant transformation of oral leukoplakia: a follow-up study.

The main objective of the study was to identify the determinants that contribute to the malignant transformation of oral leukoplakia in a group of patients managed in secondary care. A secondary objective was to compare two dysplasia grading systems to determine their utility in assessing the prognosis. The cohort consisted of 93 patients diagnosed during the period 2009-2013. The variables recorded and analysed included age and sex, clinical presentation (colour) and severity of oral epithelial dysplasia (OED) scored by the WHO (2005) and the binary grading systems. The planned management included excision of high-grade dysplasia and observation of low-grade dysplasia lesions based on the WHO grading system. Patient factors were transcribed from the pathology records and updated using a questionnaire sent out to the whole group of patients. Data were analysed using χ2 test and Kaplan-Meier analysis (P < 0.05). Complete follow-up data were available for 93 patients. Malignant transformation occurred in 7 patients (7.5%) during a mean follow-up period of 30months. Among the surgically excised group (n = 51), a recurrence of oral leukoplakia was noted in 16 patients (31%). WHO OED grading (P = 0.02) and the presence of red areas (P = 0.012) were useful in predicting malignant transformation with severe epithelial dysplastic lesions and red and white mixed lesions showing higher rates. Leukoplakias (7.5%) transformed over a mean follow-up period of 30months. Dysplasia grading and the clinical appearance by colour (mixed white and red) were significant predictors of malignant transformation CLINICAL SIGNIFICANCE: Patients with erythroleukoplakia and those diagnosed with moderate or severe epithelial dysplasia require more intensive interventions as such lesions have a higher risk of developing a malignancy.