Rate Of Malignant Transformation Research Articles

The Importance of Post-Inflammatory Polyps (PIPs) in Colorectal Cancer Surveillance in Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBDs), encompassing Ulcerative Colitis (UC) and Crohn's Disease (CD), are chronic inflammatory disorders affecting the gastrointestinal tract. The association between IBD and colorectal cancer (CRC) is well-documented. Multiple factors have been identified as contributors to the risk of developing CRC in patients with IBD, including duration of disease, disease extension, family history of CRC, co-existance of primary sclerosing cholangitis (PSC), and potentially the presence of post-inflammatory polyps (PIPs). PIPs, often referred to as pseudopolyps, are polypoid structures that emerge as a result of severe mucosal inflammation. While their presence has been linked to greater disease severity, the role of PIPs in increasing CRC risk remains controversial. Increasing evidence suggests an association between post-inflammatory polyps (PIPs) and the risk of colorectal neoplasia, with PIPs potentially serving as an indicator of this risk through a history of enhanced inflammation. PIPs may also be linked to a distinct patient phenotype, including the presence of other known risk factors. More recent studies suggest that the risk burden (characterized by a high number or by large polyps) may be important. However, the evidence remains inconsistent, with some studies showing no clear association between PIPs and CRC risk after adjusting for other factors, including histological inflammation. In contrast, the data suggest a low rate of malignant transformation of the PIPs themselves. This narrative review aims to summarize the latest evidence regarding the relationship between PIPs and CRC in IBD, with a focus on UC. While some studies suggest that PIPs may serve as markers of higher disease severity and inflammation, their direct contribution to CRC risk remains unclear. Further research is needed to explore the inflammatory and carcinogenic pathways in patients with PIPs to better understand their role in colorectal cancer (CRC) development.

P53 and Ki67 Biomarkers are Predictors for Malignant Transformation in Oral Submucous Fibrosis: A Prospective Study.

Oral submucous fibrosis (OSMF) is a potentially malignant disorder (PMD) characterized by a high rate of malignant transformation (MT). OSMF exhibits atrophic epithelium yet has a high proliferation rate. Both p53 and Ki67 are nuclear proteins associated with cell proliferation, detectable in the early stages of oral cancer (OC). This study aimed to analyze the efficacy of p53 and Ki67 immuno-expression as tools for predicting malignant transformation in OSMF cases. The objective was to correlate the expression of p53 and Ki67 with demographic and chewing habits data. The study group consisted of 60 histopathologically diagnosed cases of OSMF, 60 cases of OC as positive controls, and 60 cases of NOM as negative controls. Immunohistochemistry was performed on neutral-buffered formalin-fixed, paraffin-embedded tissue sections of 3 μm thickness, using ready-to-use anti-human p53 protein (clone DO-7) and monoclonal antibody for Ki67 antigen (clone MIB-1). Statistical analysis was conducted using SPSS software version 21, employing the chi-square test (p < 0.05). The expression of p53 and Ki67 was significantly higher in OSMF samples compared to NOM samples, but lower than in OC samples. When the expression levels of both p53 and Ki67 were correlated with demographic and chewing habits data, the results were statistically significant. The overexpression of p53 and Ki67 may contribute to the progression of MT in OSM. Early detection of these biomarkers is crucial for preventing MT, which also helps reduce the morbidity and mortality of OC. Therefore, both p53 and Ki67 can serve as predictive biomarkers for the early detection of MT in high-risk OSMF patients.

Oncological Outcomes of Patients With Oral Potentially Malignant Disorders

Understanding the clinical course and malignant transformation rate of oral potentially malignant disorders (OPMDs)-including oral leukoplakia, oral erythroplakia, oral submucous fibrosis, and oral lichen planus-is crucial for early detection and improved survival rates in patients with oral cancer. To evaluate the progression of oral cancer from OPMDs using a large US electronic medical database. This retrospective cohort study used data from the University of California, San Francisco's PatientExploreR database between January 1973 and March 2024. Patients with oral leukoplakia, oral erythroplakia, oral submucous fibrosis, and oral lichen planus were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes and keywords. Demographics, tobacco and alcohol use, HIV status, and other known risk factors for oral cancer were recorded to identify factors associated with malignant transformation. Logistic regression and descriptive analyses were used. Diagnosis of oral leukoplakia, oral erythroplakia, oral submucous fibrosis, or oral lichen planus. Incidence of oral cancer, malignant transformation rate, median time to progression, and associations between demographics and risk factors and the development of oral cancer. Among 4 225 251 individuals in the database, 4371 were diagnosed with oral cancer (median [IQR] age, 63 [53-71] years; 2610 [59.9%] male; 0.1% of the cohort), and 110 (2.5%) had a preceding OPMD. Oral leukoplakia was found in 1124 patients, with 94 (8.4%) undergoing malignant transformation (median [IQR] time to progression, 25 [7-129] months). HIV-positive patients with oral leukoplakia were more likely to develop oral cancer (odds ratio, 3.80; 95% CI, 1.35-10.70). Of 22 patients with oral erythroplakia, 11 (50.0%) developed oral cancer (median [IQR] time to progression, 3.7 [0.2-334] months). Those who smoked tobacco with oral erythroplakia showed a higher malignant transformation rate (odds ratio, 3.75; 95% CI, 0.54-26.05). Of the 78 patients with oral submucous fibrosis, 4 (5.1%) underwent malignant transformation (median [IQR] time to progression, 36 [36-48] months). Only 1 patient with oral lichen planus developed oral cancer after 5 years. This cohort study showed that OPMDs have notable but varying propensities to progress to oral cancer. Early detection and monitoring of OPMDs are crucial for improving patient outcomes. However, the risk, etiopathogenesis, and clinical presentation vary for each OPMD and should, therefore, be considered distinct diseases.

Congress of Neurological Surgeons systematic review and evidence-based guidelines for the role of chemotherapy in newly diagnosed WHO Grade II diffuse glioma in adults: update.

It is recommended that chemotherapy be added to radiation therapy in all patients with newly diagnosed high-risk WHO Grade II diffuse glioma to improve overall survival without a decline in neurocognitive function. It is suggested that chemotherapy (temozolomide) be added to RT in all patients with newly diagnosed high-risk WHO Grade II diffuse glioma to improve progression free survival and overall survival. It is suggested that chemotherapy alone should be considered in patients with newly diagnosed WHO Grade II diffuse glioma in cases with 1p/19q co-deletion.New questions and recommendationsTarget populationThese recommendations apply to adult patients diagnosed with WHO Grade II diffuse glioma.QuestionIn adult patients with newly diagnosed WHO grade II diffuse glioma does administration of chemotherapy prior to surgical resection improve extent of resection, provide longer progression free survival and overall survival when compared to chemotherapy alone?RecommendationLevel III: Neo-adjuvant temozolomide may be used in patients with WHO Grade II diffuse gliomas deemed unsafe for resection due to infiltration of eloquent areas or with large contralateral extension as an initial step to improve the extent of resection.There is insufficient evidence to support a recommendation regarding the ability of chemotherapy provided prior to surgical resection to improve progression free survival (PFS) and overall survival (OS).QuestionIn adult patients with newly diagnosed WHO grade II diffuse glioma does the administration of temozolomide increase the rate of malignant transformation when compared to no chemotherapy or other chemotherapy regimens?RecommendationThere is insufficient evidence to support a recommendation against the use of temozolomide for WHO Grade II diffuse gliomas due to concern over increasing the rate of malignant transformation.QuestionIn adult patients with newly diagnosed WHO grade II diffuse glioma does administration of multi-agent chemotherapy improve progression free survival and overall survival when compared to administration of single-agent chemotherapy?RecommendationThere is insufficient evidence to support a recommendation for or against the use of multi-agent chemotherapy to improve progression free survival and overall survival when compared to administration of single-agent chemotherapy in patients with newly diagnosed WHO Grade II diffuse glioma.

Adhesive lipophilic gels delivering rapamycin prevent oral leukoplakia from malignant transformation

Oral leukoplakia (OLK) is the most emblematic oral potentially malignant disorder that may precede the diagnosis of oral squamous cell carcinoma (OSCC) and has an overall malignant transformation rate of 9.8 %. Early intervention is crucial to reduce the malignant transformation rate from OLK to OSCC but the lack of effective local pharmaceutical preparations poses a challenge to clinical management. Rapamycin is speculated to prevent OLK from carcinogenesis and its inherent lipophilicity facilitates its penetration into stratum corneum. Nevertheless, hydrophilic hydrogels frequently encounter challenges when attempting to deliver lipophilic drugs. Furthermore, the oral cavity presents a complex environment defined by oral motor functions, saliva secretion cycles, dynamic fluctuations, and protective barriers comprising mucus and lipid layers. Consequently, addressing issues of muco-penetration and muco-adhesion is imperative for developing an effective drug delivery system aiming at delivering rapamycin to target oral potentially malignant disorders.Here, a dual-function hydrogel drug delivery system integrating adhesion and lipophilicity was successfully developed based on polyvinyl alcohol (PVA) and dioleoyl phosphatidylglycerol (DOPG) via dynamic boronic ester bonds. Rheological experiments based on orthogonal design revealed that PVA-DOPG hydrogels exhibited ideal adhesive strength (around 6 kPa) and could adhere to various surfaces in both dry and wet conditions. PVA-DOPG hydrogels also significantly promoted lipophilic molecules’ penetration into stratum corneum (integrated fluorescence density of 6.95 ± 0.52 × 106 and mean fluorescence depth of 0.96 ± 0.07 mm) of ex-vivo porcine buccal mucosa (p < 0.001). Furthermore, PVA-DOPG hydrogels incorporating rapamycin inhibited malignant transformation of OLK mouse model induced by 4-Nitroquinoline N-oxide (4-NQO), distinct improvements in survival (the neoplasm incidence density at the 40th day is 0.0091) (p < 0.05), decrease in neoplasm incidence density of 36.36 % and inhibition rate in neoplasm volume of 75.04 ± 33.67 % have been demonstrated, suggesting the hydrogels were valuable candidates for potential applications in the management of OLK.

"Navigating the complexities of low-Grade glioma treatment: insights into SBT I-125 and novel assessment tools".

Central nervous system tumors, classified by the WHO into four grades based on their aggressiveness, present significant challenges in treatment, particularly low-grade gliomas (LGGs) which, despite their slower growth, can progress to high-grade gliomas. Lucca B. Palavani and colleagues evaluated the efficacy and safety of SBT I-125 brachytherapy for LGMs in a systematic review and meta-analysis of 20 studies involving 988 patients. The analysis revealed an overall complication rate of 10%, with headaches and cyst formation being the most frequent issues. The five-year progression-free survival (PFS) rate was 66%, while the ten-year PFS rate was 30%, and the rate of malignant transformation was 26%. The mortality rate was 33%. Despite these findings, significant limitations were noted, including data insufficiencies, study heterogeneity, lack of randomized controlled trials, and potential publication bias. Inconsistencies in follow-up durations further hindered the evaluation of long-term efficacy and safety. Recent advancements in automated tumor assessment, such as Cheng et al.'s deep learning-based pipeline, are revolutionizing glioma management by enhancing the accuracy and consistency of tumor volume and RANO measurements. These innovations facilitate improved glioma grading, genetic mutation prediction, surgical planning, real-time intraoperative guidance, and histopathological analysis. Integrating such advanced tools into clinical practice can significantly enhance the precision and efficiency of glioma management. In conclusion, while SBT I-125 brachytherapy shows promise, concerns regarding safety and efficacy underscore the need for further research with standardized methodologies. Incorporating advanced automated assessment tools could improve treatment evaluation and patient outcomes.

Gingival Proliferative Verrucous Leukoplakia and Cancer: A Systematic Review With Meta-Analysis.

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder. Forms that affect only one tissue are poorly studied, especially the exclusively gingival PVL (gPVL), which may have a more increased malignant transformation potential. The aim of the present study was to characterise the gPVL and its risk of malignant transformation to better raise awareness of this specific disorder. The systematic review was performed on PubMed, Scopus, Web of Science and Google Scholar. Only articles reporting primary studies, case reports and case series were included. The meta-analysis was performed for the cancer prevalence, proportion of smokers, age and sex ratio, recurrences of gPVL and mortality. A total of 1298 studies were assessed for eligibility by reading titles and abstracts. Fourteen original articles were included with a total of 58 patients. The malignant transformation rate of gPVL was 47.75%. The mortality was 5.84%. The mean follow-up duration before malignant transformation was 3 years. gPVL seems to have a faster malignant transformation rate than the other forms of PVL. Finding anatomo-pathological or genetic markers could be a line of research to predict gPVL malignant transformation and improve its diagnosis and treatment.

Expression of Programmed Death Ligand 1 and Indoleamine 2,3-Dioxygenase in Oral Lichen Planus and Oral Lichenoid Lesions.

Oral lichen planus (OLP) and oral lichenoid lesions (OLL) are inflammatory T-cell mediated disorders of the oral mucosa (OM). Both are associated with an increased risk of oral squamous cell carcinoma, with OLL possibly having a higher rate of malignant transformation than OLP. Programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO) are immunosuppressive molecules possessing inhibitory effect on T-cells and have been implicated in carcinogenesis. The aim of this study was to examine the expression of PD-L1 and IDO in OLP and OLL. Sixty-eight formalin-fixed, paraffin-embedded tissue samples diagnosed as OLP, compatible with OLP, or OLL were divided into OLP (n = 39) or OLL (n = 29) groups based on both clinical and histopathological diagnostic criteria. Samples of healthy OM (n = 9) served as controls. Samples were immunohistochemically stained for PD-L1 and IDO, and staining distribution and intensity were evaluated. Immunohistochemical expression of PD-L1 was increased in the basal and intermediate layers of epithelium in OLP and in lamina propria in both OLP and OLL compared to controls. OLP and OLL showed increased expression of IDO in epithelium and lamina propria compared to controls. PD-L1 staining intensity in the basal epithelial layer, and IDO staining intensity in lamina propria were increased in OLP compared to OLL. The results indicate that the expression of PD-L1 and IDO increases in OLP and OLL, suggesting that these molecules may play a role in the pathogenesis of both disorders.

Management of Oral Leukoplakia – A Systematic Umbrella Review of Global Evidence

Objective: To summarize the global evidence related to various interventions for treating Oral Leukoplakia. Introduction: Oral leukoplakia is a common oral potentially malignant lesion that precedes the development of oral cancer. The main aim of any treatment is to prevent the malignant transformation. This umbrella review updates the global evidence of different medicinal treatment available for Oral Leukoplakia. Methods: The databases searched were Cochrane database of systematic reviews, JBI Evidence Synthesis, MEDLINE, Web of Science, Scopus. The key terms used were leukoplakia, oral leukoplakias, Proliferative verrucous leukoplakia, interventions, management, chemoprevention, laser, photodynamic, topical agents. JBI Sumari software was used to screen and appraise the articles along with data extraction and data synthesis. Results: A total of 670 citations were identified through the electronic search. Out of which 61 systematic reviews were recognized. Following removal of duplicates, 47 records were retrieved. The full texts of 13 papers were retrieved for further examination with 9 systematic reviews meeting the inclusion criteria and therefore included in this umbrella review. Study overlap calculation was conducted and pooled results showed that the treatments available for oral leukoplakia has little effect on clinical response and malignant transformation rate. Conclusions: Currently we do not have evidence of a treatment that is preventing oral leukoplakia from converting to oral cancer. Treatments such as vitamin A and beta carotene may be effective in reducing clinical size of oral lesions. More long-term studies are required for surgical management, lasers and photodynamic therapy.

Beyond surgical resection: evaluating stereotactic brachytherapy iodine-125 for low-grade gliomas: a systematic review and meta-analysis.

Stereotactic Brachytherapy Iodine-125 (SBT I-125) has been investigated by some studies for the treatment of lowgrade gliomas. We performed a meta-analysis to assess the efficacy and safety of SBT I-125 Brachytherapy for treatment of patients with Low-Grade Gliomas. PubMed, Cochrane, Web of Science, and EMBASE databases were searched for randomized and observational studies. This systematic review and meta-analysis was conducted according to the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. We used relative risk (RR) with 95% confidence intervals and random effects model to compare the effects of I-125 SBT treatment on the interest outcomes. We evaluated heterogeneity using I2 statistics; we considered heterogeneity to be significant if the p-value was less than 0.05 and I2 was higher than 35%. We performed statistical analysis using the software R (version 4.2.3). A total of 20 studies with a cohort of 988 patients with low grade gliomas who received SBT I-125 as a treatment option. The pooled analysis evidenced: (1) Complication rate of 10% (95% CI: 7-12%; I² = 60%); (2) 5-year PFS of 66% (99% CI: 45-86%; I²= 98%); (3) 10-year PFS was 66% (99% CI: 45-86%; I²= 98%); (4) Malignant transformation rate of 26% (95% CI: 8-45%; I²=0); (5) Mortality of 33% (95% CI: 15-51%; I² = 0%). Our systematic review and meta-analysis of SBT I-125 for low-grade gliomas have revealed significant concerns regarding its safety and efficacy. Despite a proportion of patients remaining progression-free, elevated rates of complications and mortality cast doubt on the intervention's reliability. Future research should prioritize long-term follow-up studies, standardized protocols, and comparative effectiveness research.

Malignant Recurrence of Benign Odontogenic Tumors (A Single Center Cross-Sectional Study)

BackgroundDespite their rarity, malignant odontogenic tumors (MOT) represent an important group of oral lesions characterized by their variable clinical presentations and sometimes unexpected biological behavior.ObjectivesThe purpose of this retrospective cross-sectional study was to evaluate the number, types, and frequency of MOT and to investigate the relative rate of malignant transformation in recurrent odontogenic tumors (OT).MethodologyThe records of patients diagnosed with OT in the hospital of the Faculty of Dentistry, Cairo University, were reviewed over 10 years (2013-2022). The OT were investigated for frequency, age, gender, site, and recurrence. The data were recorded and then analyzed using SPSS software version 25.ResultsAmong 5543 oral excisions, 357 cases of them were OT, including 336 benign (94.1%) and 21 malignant neoplasms (5.9%). Among the odontogenic malignancies, 18 lesions (85.7%) appeared de novo, and 3 lesions (14.3%) developed as recurrent of previously classified benign tumors. A high incidence was observed in the middle and old age groups (90.4%) with a median age being 42. Slight male predilection (1.3:1) was noticed. The mandible was the highly affected site but all recurrent cases were diagnosed in the maxilla as ghost cell odontogenic carcinoma (n = 2, 66.6%) and primary intraosseous carcinoma (n = 1, 33.3%).ConclusionRetrospective analysis of the relative frequency of MOT and the documentation of the unusual recurrence of benign OT as a malignancy enhances our understanding of OT behavior and the need for appropriate therapy and clinical follow-up.

Prognostic nomogram for proliferative verrucous leukoplakia

BackgroundProliferative verrucous leukoplakia (PVL) is a special type of leukoplakia characterized by high rate of malignant transformation into oral squamous cell carcinoma (OSCC). This study aimed to analyze the canceration risk and prognostic factors of PVL and establish effective diagnostic and prognostic predictive models. Materials and methodsA total of 467 patients were enrolled, including 170 cases of PVL. The independent risk and prognostic factors of PVL were analyzed by univariable and multivariable logistic regression. Nomogram models were constructed to predict the canceration risk and prognosis of PVL. The predictive power was evaluated by Hosmer–Lemeshow test, receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis. ResultsMultivariable logistic regression analyses identified that canceration risk factors of PVL included sex, lesion sites, clinical presentation, non-smoker and oral epithelial dysplasia (OED). The independent prognostic factors of PVL were sex, clinical presentation, local irritants and OED. Diagnosis and prognostic nomogram models were constructed. The areas under the ROC curve were 0.945 and 0.893, respectively. The calibration plots showed strong agreement between the prediction and observation. Decision curve analysis indicated that the models provided significant clinical benefits for patients. ConclusionOur study established and validated the diagnosis and prognostic predictive nomogram models, which were accurate to predict the canceration risk and prognostic factors of PVL, providing individualized clinical decisions for clinical work.

Clinical Aspects of Oral Cancer and Potentially Malignant Disorders with Special Relevance to South Asia

Abstract Early identification of oral potentially malignant disorders (OPMDs) is utmost important to minimise oral cancer incidence as most oral cancers develop from OPMDs. Leucoplakia and oral submucous fibrosis (OSMF) are the most common OPMDs encountered. Erythroplakia is rare but is more serious as it has a very high malignant transformation rate. Clinical presentation of OPMDs can vary according to the type of the disorder as well as with the aetiological agents. OSMF is much prevalent in South and South Asian countries whereas leucoplakia is prevalent all over the world but with differences in clinical presentation. Identification of OPMD with clinical features at its early change is challenging and may require histopathology through a biopsy for confirmation. This review provides clinical descriptions of the wide range of OPMDs encountered in the oral cavity with emphasis on changes in clinical presentation in different populations.

A Bibliometric and Visualised Analysis of Proliferative Verrucous Leucoplakia From 2003 to 2023

BackgroundProliferative verrucous leucoplakia (PVL) is a rare but slow-growing, aggressive leucoplakia lesion associated with the highest malignant transformation rate in oral potentially malignant disorders (OPMDs). With increasing attention paid to PVL, it is urgent for us to analyse and summarise the publications globally using comprehensive bibliometric studies to help researchers propose possible future research directions and guide them to further conduct relevant studies in the domain. ObjectivesThe purpose of the study was to evaluate global academic productivity, impact, and collaboration of potentially malignant oral disorder PVL utilising bibliometrics based on annual number of publications, countries and regions, institution, authors, journals, citations and co-occurrences of author keywords over the last 20 years. MethodsThis study searched publications pertaining to proliferative verrucous leucoplakia in the Web of Science Core Collection, spanning from 2003 to 2023. Utilizing VOSviewer, R software, Bibliometric online analysis platform, CiteSpace software, and Microsoft Excel, we conducted a bibliometric and visualised analysis of PVL. ResultsThe quantity of pertinent publications in this research domain displays a fluctuating but overall upward trend. In aggregate, there are 148 articles and 61 reviews, encompassing research contributions from 44 countries, 45 institutions, and involving 831 authors. Among these publications, the USA, Spain, and UK emerged as the predominant contributing nations. Predominantly, articles found their publication venue in “Pathology Research and Practice.” Notably, the author with the highest number of publications and most influence is Warnakulasuriya S. The top 3 keywords include “Proliferative Verrucous Leucoplakia,” “Squamous-Cell Carcinoma,” “Oral Leucoplakia,” and “Potentially Malignant Disorders.” ConclusionIn this investigation, statistical analysis and network visualisation were conducted to reveal the research progress, trends, and trending topics on PVL via a thorough bibliometric analysis. We found that current publications comprise mainly case reports, there is a significant research need to explore the molecular mechanisms, specific diagnostic criteria, and effective management options for PVL. Our work should serve as a key reference and a directional guide for future research in this domain.

METB-07. FREQUENCY AND OUTCOMES OF CDKN2A/B LOSS IN PEDIATRIC GLIOMA

Abstract BACKGROUND Chromosome 9p21 deletions involving the tumor-suppressor genes cyclin-dependent kinase 2A and 2B (CDKN2A/B) have been identified as a poor prognostic factor in various cancer types, including adult low-grade gliomas. The frequency and influence of CDKN2A/B hemi- and homozygous deletions in pediatric glioma are less well defined. Herein, we report a single-institution evaluation of the frequency and clinical outcomes of CDKN2A/B loss in pediatric gliomas. METHOD We performed a retrospective, IRB-approved single institutional study, utilizing an existing institutional data registry to identify pediatric patients (age &amp;lt; 21) diagnosed with a glioma who had undergone targeted DNA next generation panel sequencing (Oncopanel) between 2013-2023. IDH1/2-mutant gliomas were excluded. Clinical features, treatment details and outcome data were collected and analyzed. RESULTS Oncopanel was performed on 510 pediatric gliomas. Of these, 372 (72.9%) had low-grade and 138 (27%) had high-grade gliomas. Sixty-six (12.9%) gliomas harbored CDKN2A/B hemi-/homozygous loss; this included 26/372 (7%) low-grade and 40/138 (29%) high-grade gliomas. Homozygous loss was seen in 13/372 (3.5%) low-grade and 26/138 (18.8%) high-grade gliomas. The most common co-alteration with CDKN2A/B loss was BRAFV600E (28/66, 42%), followed by TP53 (8/66, 12%). Median follow-up time of the entire cohort was 3.2 years (range:0.1-36). The 10-year overall survival for pLGGs with CDKN2A/B wildtype and CDKN2A/B homozygous deletion were 95% and 85%, respectively (p=0.03). There was no significant difference in survival of pLGGs with CDKN2A/B wildtype and CDKN2A/B hemizygous deletion. For pHGGs, there was no difference in survival outcomes based on CDKN2A/B status. Further univariate and multivariable analyses are underway. Central pathology review and methylation subtyping to confirm rates of malignant transformation are also ongoing. CONCLUSION CDKN2A/B loss is identified in a subset of both pediatric low- and high-grade gliomas. Our data suggest that homozygous CDKN2A/B loss in pLGG is associated with poorer long-term survival.

Identification of the differentially expressed activated memory CD4+ T-cells-related genes and ceRNAs in oral lichen planus

BackgroundOral lichen planus (OLP) is a common chronic oral mucosal disease with 1.4 % malignant transformation rate, and its etiology especially immune pathogenesis remains unclear. This study was aimed at investigating the immune cells related molecular underlying the pathophysiology of OLP through bioinformatics analysis. MethodsThe dataset GSE52130 obtained from the Gene Expression Omnibus (GEO) database was conducted a comprehensive analysis in this study. The CIBERSORTx was used for investigating immune cells infiltration. The gene set enrichment analysis (GSEA) and gene ontology (GO) enrichment were performed for exploring the biological functions and gene annotation. The protein-protein interactions (PPI) were constructed by STRING database and visualized by Cytoscape software. The cytohubba plugin was utilized for screening hub genes. The receiver operating characteristic (ROC) was performed for evaluating diagnostic value of hub genes. The miRNAs, lncRNAs and drugs were respectively predicted by NetworkAnalyst, miRTarbase, ENCORI, and DGIdb database. ResultsThis study identified 595 differentially expressed genes (DEGs). The GSEA indicated keratinization, innate immune system and biological oxidation were involved in OLP. GO analysis showed extracellular matrix and keratinocyte were mainly enriched. And we found the activated memory CD4+ T cells were lowly infiltrated in OLP. We identified 101 activated memory CD4+ T-cells-related DEGs. Three hub genes (APP, IL1B, TF) were selected. APP and IL1B were significantly up-regulated, whereas TF was down-regulated in OLP. The three hub genes show high diagnostic value in OLP. Additionally, they were involved in MAPK signal, NF-kappaB signal and iron metabolism in OLP. What's more, NEAT1/XIST - miR - 15a - 5p/miR - 155–5p - APP/IL1B signal axis was focused in competing endogenous RNA (ceRNA) network. In addition, 35 drugs were predicted for OLP. ConclusionThree activated memory CD4+ T-cells-related DEGs were identified by integrative analysis. It may provide novel insight into the pathogenesis of OLP and suggest potential therapeutic targets for OLP.

Intralesional nivolumab in oral potentially malignant disorders: A phase 1 pilot study on safety, tolerability, and preliminary efficacy.

6016 Background: Oral Potentially Malignant Disorders (OPMD) encompass a diverse group of oral mucosal diseases, including the prevalent oral leukoplakia (OL), serving as precursors to invasive oral squamous cell carcinoma. OPMD exhibits an annual malignant transformation rate up to 36%. Despite the breadth of research on OPMD the standard-of-care remains surgery or observation. We aim to evaluate the safety and tolerability of intralesional injections of Nivolumab in patients with OPMD. Secondary objectives include assessing objective response rate and pathologic complete response rate. We describe the results of an immune prevention trial designed to avoid systemic toxicities of immunotherapy in patient with pre-malignancy by administrating aPD1 intralesionaly. Methods: Phase 1, single-arm, open-label, dose-escalation pilot study that involves intralesional injections of Nivolumab (index lesion) in patients with high-risk OPMD lesions every 3 weeks (total of 4 doses, 12 weeks). Non-index, non-injected, oral lesion(s) were also documented and monitored. The study includes two dose cohorts (10 mg and 20 mg) to assess maximally tolerated dose with a 3 + 6 dose-escalation design. Adverse events were reported according to NCI CTCAE Version 5.0. Serial biopsies at baseline and up to 8 weeks after treatment were taken to assess efficacy using a composite score (i.e., size and degree of dysplasia) in index lesion. Major response was defined as &gt;80% decrease in score; partial response as 40%-80% decrease. Freshly frozen tumors were subjected to RNA sequencing and gene pathway analysis to identify biomarkers of response or progression. Results: At the time of data analysis, 13 patients have completed treatment (61.5% males), both dose levels were well tolerated. The adverse event grades ranged from grade 1 (i.e. diarrhea, elevated LFT and skin rash) constituting the majority at 80.5% of reported adverse events, grade 2 (i.e. skin rash, cellulitis) at 13.9%, and grade 3 (i.e. hypertension) at 5.6%. Ten patients had multifocal disease. Major response was observed in 22.5% and partial response in 50% of the patients. One patient progressed to invasive SCC in a non-index lesion. RNA sequencing based immune phenotyping revealed increased infiltration of CD8 cytotoxic T cells in index lesions after treatment. Pathway analysis revealed significant alterations in immune pathways including Th1 and Th2 pathways, Natural killer and immunoregulatory pathways. Spatial transcriptome analysis and pharmacokinetics data are pending. Conclusions: Intralesional nivolumab is well tolerated in OPMD with suggested potential biological and clinical activity. A randomized phase II trial to assess cancer free survival is recommended to determine the efficacy in preventing cancer progression. We recommend dose of 20mg for phase II as it was well tolerated. Clinical trial information: NCT05327270 .

Clinical, histopathological characteristics and malignant transformation of proliferative verrucous leukoplakia with 36 patients: a retrospective longitudinal study

BackgroundProliferative verrucous leukoplakia (PVL), distinguished by its malignant transformation rate of 43.87% to 65.8%, stands as the oral potentially malignant disorder with the highest propensity for malignancy. PVL is marked by distinctive heterogeneity regarding the clinical or histopathological characteristics as well as prognostic factors pertinent to this condition. The purpose of this study is to compile and assess the clinicopathological features, malignant transformation, and associated risk factors in patients diagnosed with PVL.MethodsThis study is a hospital-based retrospective longitudinal study of 36 patients diagnosed with PVL from 2013 to 2023. We conducted complete clinical and histopathological evaluations of the patients.ResultsThe cohort comprised 16 males and 20 females, yielding a male-to-female ratio of 1:1.25. The follow-up period ranged from 8 to 125 months, with an average of 47.50 months. The most common clinical type of lesion was the verrucous form (58.33%), and the gingiva was the most common site (44.44%). Each patient had between 2 to 7 lesions, averaging 3.36 per patient. During the follow-up period, twelve patients (33.3%) developed oral cancer, with an average time to malignant transformation of 35.75 months. Kaplan–Meier survival analysis indicated that patients with complaints of pain, roughness, or a rough sensation, with diabetes, and the presence of cytologic atypia histologically showed a higher risk of malignant transformation (p < 0.05). In this study, the rate of malignant transformation in the treatment group (5/23) was lower than that in the untreated group (7/13), however, no statistically significant difference (p = 0.05).ConclusionThe main complaints of pain, roughness, or foreign body sensation, coupled with cytologic atypia histologically are indicative of an increased risk of malignant transformation in PVL. Further research is needed to elucidate the influence of these clinicopathological parameters on the malignant progression of PVL.

Atypical Endometriosis: A Comprehensive Systematic Review of Pathological Patterns and Diagnostic Challenges.

Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is characterized by deviations from the typical microscopic appearance of endometriosis, including cytologic and architectural atypia. AE has been recognized as a potential precursor to endometriosis-associated ovarian cancers (EAOC), particularly endometrioid and clear cell subtypes. AE presents challenges in diagnosis due to its diverse clinical and pathological features, often requiring careful histological evaluation for accurate identification. Architectural AE, defined by localized proliferation of crowded glands with atypical epithelium resembling endometrial neoplasia, and cytologic AE, characterized by nuclear atypia within the epithelial lining of endometriotic cysts, are key subtypes. Immunohistochemical and molecular studies have revealed aberrant expression of markers such as Ki67, COX-2, BAF250a, p53, estrogen receptor, progesterone receptor, and IMP-3. Long-term follow-up studies suggest relatively low recurrence and malignant transformation rates among patients with AE, but uncertainties persist regarding its exact malignancy potential and optimal management strategies. Integration of artificial intelligence and shared molecular aberrations between AE and EAOC may enhance diagnostic accuracy. Continuous interdisciplinary collaboration and ongoing research efforts are crucial for a deeper understanding of the relationship between endometriosis and carcinogenesis, ultimately improving patient care and surveillance.

Benign extra skeletal chondroma of the tongue in a 16-year-old female

Chondromas are tumors that result from chondroid differentiation most frequently occurring in areas where chondrocytes are present. Rarely, they can present in soft tissues, such as the tongue. This case report will review the extra skeletal chondroma found on the posterior tongue of an asymptomatic 16-year-old female. Discussed within this case report will include the importance of histopathological analysis in distinguishing enchondroma versus chondrosarcoma and review the malignant transformation rate. Additionally, it will compare the trends of chondromas found in the oral cavity that have been previously published. This case will highlight the importance of recognizing chondromas in unusual places, such as the origin of soft tissues, and emphasize the importance of early diagnosis, surgical intervention and providing optimal outcomes for young patients.