The significance of radiologic main duct dilatation in pancreatic intraductal papillary mucinous neoplasms.

Utility of p53, p16, and MTAP Immunohistochemistry in Oral Epithelial Dysplasia With Concurrent Candidiasis: A Novel Pattern-based Approach.

BMP5 mediates macrophage-driven Oral leukoplakia carcinogenesis.

Oral Submucous Fibrosis (OSF) is a chronic, progressive, potentially malignant disorder associated with areca-nut exposure, characterized by persistent inflammation, extracellular matrix accumulation, and fibrotic restriction of oral function. This review highlights how fibrosis-driven vascular compromise and sustained hypoxia generate a tumor-promoting microenvironment that underlies malignant transformation. Dysregulated fibroblast activation, abnormal matrix remodeling, impaired angiogenesis, and chronic inflammatory signaling collectively promote stromal stiffness, oxidative stress, epithelial instability, and EMT-like changes. These interconnected angio-fibrotic and hypoxic mechanisms facilitate progression from fibrosis to epithelial dysplasia and ultimately oral squamous cell carcinoma. Understanding this pathogenic network provides a framework for early risk stratification and supports development of targeted anti-fibrotic and anti-angiogenic therapeutic strategies in OSF.

Quantitative evaluation and comparison of Cyclin D1 expression in various histological grades of oral epithelial dysplasia. A total of 66 instances of oral epithelial dysplasia were included, with a histological diagnosis, consisting of 22 cases for each of the three histopathological grades. These cases were evaluated for cyclin D1 expression using immunohistochemistry techniques. To compare the average number of positive cells among the three groups with epithelial dysplasia, the Tukey's multiple posthoc method and the one-way ANOVA test were utilized. A P value of 0.05 or less was considered statistically significant. The expression of Cyclin D1 protein has been shown to vary significantly across mild, moderate, and severe epithelial dysplasia, with the group exhibiting severe oral epithelial dysplasia (OED) showing the highest average levels of expression. The overproduction of cyclin D1 in individuals with severe epithelial dysplasia suggests that it could serve as a precursor to the onset of oral cancer. Cyclin D1 may act as a potential predictive marker for malignant transformation.

Background: Oral leukoplakia (OL) with oral epithelial dysplasia (OED) carries an increased risk of malignant transformation and typically requires active management and long-term surveillance. Surgical excision remains the gold standard, yet recurrence is common and morbidity may be substantial, particularly in extensive or multifocal disease. Photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has emerged as a minimally invasive alternative. However, its effectiveness in dysplastic OL has not been quantified systematically. Methods: A systematic review and meta-analysis were conducted according to a prospectively registered protocol (PROSPERO: CRD420251249586) and reported in line with PRISMA 2020. PubMed, Scopus, and Web of Science were searched from inception to 15 December 2025 for clinical studies evaluating ALA-PDT as primary treatment for OL with histopathologically confirmed OED. Single-arm prospective or retrospective studies reporting clinical response were eligible. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Pooled overall response rate (ORR) and complete response (CR) were estimated as proportions using random-effects models. Recurrence and malignant transformation were summarized as incidence rates per 100 person-years. Results: Six single-arm clinical studies including 109 patients with dysplastic oral leukoplakia treated with 5-ALA-mediated photodynamic therapy were eligible for quantitative synthesis. The pooled overall response rate was 0.85 (95% CI 0.74-0.93), whereas the pooled complete response rate reached 0.34 (95% CI 0.18-0.53), with moderate to substantial heterogeneity. Recurrence and malignant transformation outcomes were limited and analyzed descriptively, suggesting low but persistent long-term risk. The overall certainty of the evidence was rated as very low according to GRADE. Conclusions: 5-ALA-mediated photodynamic therapy appears to be an effective and minimally invasive treatment option for oral leukoplakia with epithelial dysplasia; however, the very low certainty of evidence, lack of standardized protocols, and persistent risk of recurrence and malignant transformation highlight the need for well-designed controlled studies and long-term clinical surveillance.

Aspartame, a widely used artificial sweetener, has attracted increasing attention for its potential systemic and oral toxicity. However, the molecular mechanisms by which it induces oral diseases remain largely unexplored. This study aims to investigate the potential molecular mechanisms of oral leukoplakia (OLK) induced by aspartame. This study conducted an integrative analysis of multiple gene expression datasets associated with OLK, combining network toxicology, Mendelian randomization, machine learning, and molecular dynamics simulations to investigate the interactions between aspartame and disease-related target genes. Subsequently, preliminary validation was conducted using clinical OLK tissues, cell lines, and C57BL/6 mice, respectively. A total of 27 candidate genes were identified as potential molecular targets linking aspartame exposure to the pathogenesis of OLK. Among them, ITGAV, PLAU, MMP16, and NOS3 were recognized as core genes with the highest diagnostic value. These genes were significantly upregulated in OLK tissues and represented key regulatory nodes associated with extracellular matrix remodeling, oxidative stress, angiogenesis, and epithelial dysplasia. Molecular simulations suggested potential interactions between aspartame and these target genes. Both in vitro and in vivo experiments further confirmed that aspartame exposure markedly upregulated the expression of these genes and was accompanied by histopathological alterations indicative of epithelial dysplasia. This study presents an exploratory, integrative analysis identifying molecular features potentially linking aspartame exposure with OLK-associated epithelial phenotypes. The findings support the generation of testable hypotheses regarding ITGAV-, PLAU-, MMP16-, and NOS3-related pathways but do not establish exposure-response relationships or causal mechanisms. Further studies incorporating physiologically relevant dosing, pharmacokinetic validation, appropriate metabolic controls, and pathway-specific interventions are required to determine the biological relevance of these observations to real-world oral exposure.

NOTCH1 is associated with various tumors, including oral squamous cell carcinoma (OSCC), with a complex role depending on cellular contexts. Our aim was to analyze the expression of NOTCH1, several stem cell markers, and selected microRNAs in preneoplastic lesion of the oral cavity, oral epithelial dysplasia (OAD). Our study included formalin-fixed paraffin-embedded biopsy samples of 36 cases of OAD and 15 cases of normal oral mucosa. Expression of NOTCH1, stem cell markers (AGR2, KLF4, NANOG, OCT4, SOX2), and miR-27a, miR-34a, miR-128, miR-145, miR-150, and miR-335 was analyzed by quantitative PCR (qPCR). Expression of NOTCH1 protein was analyzed by immunohistochemistry. In OAD compared to normal mucosa, we found a significant increase in mRNA levels of NOTCH1, stem cell markers AGR2, NANOG, OCT4, and SOX2, and miR-150 and miR-128. NOTCH1 mRNA positively correlated with all five stem cell markers' mRNA levels and miR-150. Immunohistochemistry showed variable expression patterns of NOTCH1 in OAD and normal mucosa. Our results support the role of NOTCH1 in early phases of OSCC development, with a potential contributory role in stemness, in association with AGR2, NANOG, OCT4, and SOX2, miR-150 and miR-128. These results support a complex role of NOTCH1 in carcinoma development, i.e., from oncogenic to tumor suppressor roles and stemness maintenance, not only in invasive OSCC but also in its precursor-OED.

Identifying Malignant Transformation Risk of Dysplastic Oral Lesions Using the S100A7 Biomarker Signature-Based Assay.

Inflammaging is considered a driver of age-associated pathology across tissues. Similarly, intestinal permeability is a feature of ageing and underlies a range of inflammatory and age-related diseases. Increased intestinal permeability has been described as both a cause and a consequence of inflammation. Both intestinal permeability and inflammation are closely associated with microbial dysbiosis, epithelial dysplasia and mortality but dissecting the complex interplay between these phenotypes remains challenging. Here we genetically induce intestinal immune activation in Drosophila and stratify animals by their intestinal barrier status using the Smurf assay. We demonstrate that intestinal barrier failure has a distinct impact on the microbiota. Further, immune activation, both within the intestine and systemically, drives intestinal barrier failure and mortality even in the absence of the microbiota. Importantly, immune-induced intestinal barrier failure takes time to develop and is closely associated with the onset of mortality. Our work adds to building evidence that the impact of intestinal permeability on the microbiota and on animal health needs to be considered independently of its relationship with inflammation.

Background: Candida species are among the most common oral fungal pathogens. Oral Candida infection may obscure the presence of tongue cancer, resulting in delayed diagnosis. Method: Retrospective clinical case review. Results: A 59-year-old man had a white plaque on the left ventral surface of his tongue, noted during a routine dental visit. The plaque was painless and could not be removed by scraping. An incisional biopsy specimen showed hyperplastic candidiasis, and Candida albicans was recovered in culture. The plaque did not resolve despite antifungal treatment. A repeat tongue biopsy at 14 months after the initial biopsy showed mild to moderate epithelial dysplasia and papillary squamous cell carcinoma without invasion (squamous cell carcinoma in situ). Treatment included surgical excision of the carcinoma with wide margins. Follow-up at 7 years showed no recurrence. Conclusions: This case suggests that a high index of suspicion for malignancy is warranted in patients with oral candidal lesions that persist beyond 14 days of systemic antifungal therapy. Close monitoring and repeat biopsy may help minimize delays in cancer diagnosis and treatment.

Evaluating MCM3 Expression as a Diagnostic and Prognostic Marker in Oral Epithelial Dysplasia and OSCC: A Systematic Review

Proliferative verrucous leukoplakia (PVL) is a rare yet aggressive oral potentially malignant disease (OPMD) with the greatest rate of malignant transformation. Its pathophysiology is poorly understood despite much histopathological and molecular research. Particularly, Telomerase reverse transcriptase (TERT) promoter mutations at C228T and C250T have been linked to many epithelial malignancies; however, their significance in PVL is yet unknown in the Indian population. The aim of this study was to assess frequency of TERT promoter mutations (C228T, C250T) and rs2853669 single nucleotide polymorphism (SNP) in PVL, oral leukoplakia (OL), oral squamous cell carcinoma (OSCC) and healthy controls. 120 fresh frozen tissue specimens (30 each of OL, PVL, OSCC and controls) were tested for presence of C228T and C250T mutation in TERT promoter gene region and SNP at rs2853669, using Sanger sequencing on genomic DNA. TERT C228T mutation was found in 6.7%, 0% and 20% cases in PVL, OL and OSCC group (p = 0.03) respectively. TERT C250T mutation was present only in OSCC group (6.7% cases). None of the two mutations were present in controls. Both the mutations were mutually exclusive of each other. A significant association was found between rs2853669 SNP and epithelial dysplasia in OL, specifically with CC genotype (p = 0.04). Molecular signature of PVL shows limited evidence of TERT promoter mutations. The findings of this study suggest that the genetic underpinnings of PVL are distinct from those commonly observed in other forms of cancerous lesions.

Objective: To find out immunohistochemical (IHC) profile of cytokeratin 13 and 17 expression in oral premalignant and malignant epithelial lesions. Methodology: This descriptive cross-sectional study was conducted at, pathology department of Liaquat University of medical and health science Jamshoro from January 2017 to June 2019. Excisional biopsy samples of patients of all age groups, both gender with complain of oral mucosal epithelial lesions were enrolled. Oral mucosal biopsies were fixed in 10% formalin, routinely processed, and stained with H&E for histopathological diagnosis. Immunohistochemistry for Cytokeratin 13 and 17 was performed on paraffin sections after deparaffinization and blocking of endogenous peroxidase activity. Tissue sections were kept moist throughout the procedure and mounted on FLEX IHC slides. All the relevant pathological and clinical data were recorded using study proforma and analyzed by SPSS version 20. Results: Patient’s mean age was 40.45+11.94 years and males were in majority 63.4%. Buccal mucosa, cheek and tongue were most common sites of biopsy, 32.8%, 21.6% and 31.3% respectively. CK13 was positive among 73 cases. CK17 was positive among 96 cases. Leukoplakia, sub mucous fibrosis, ulcers were significantly associated with CK13 p=0.003, while leukoplakia and squamous cell carcinoma were significantly associated with CK 17 p=0.001. Results: A total of 139 cases were included. The mean age of patients was 40.45 ± 11.94 years. Males constituted the majority (63.4%). The most common biopsy sites were buccal mucosa (32.8%), cheek (21.6%), and tongue (31.3%). Most patients (78.4%) reported symptoms for 1 to 3 months. Leukoplakia was the most frequent oral lesion, observed in 22.3% of cases. CK13 positivity was observed in 73 cases, while CK17 was positive in 96 cases. CK13 expression was significantly associated with leukoplakia, submucous fibrosis, and ulcers (p = 0.003). CK17 expression showed significant association with leukoplakia and squamous cell carcinoma (SCC) (p = 0.001). Histologically, dysplasia was significantly associated with positive CK13 expression, whereas SCC was significantly associated with CK17 expression, both with statistically significant p-values. Conclusion: CK13 is a useful immunohistochemical marker for epithelial dysplasia, while CK17 serves as a reliable diagnostic marker for squamous cell carcinoma. CK13 expression was significantly higher in cases of leukoplakia, submucous fibrosis, ulcers, and epithelial dysplasia. CK17 was more frequently expressed in cases of leukoplakia and SCC.

Immunohistochemical evaluation of Yes-associated protein1 (YAP1) expression in oral leukoplakia and squamous cell carcinoma: Implications for prognosis.

Objective: This study aimed to evaluate serum and salivary podoplanin (PDPN) levels in patients with oral cancer (OC) and oral leukoplakia (OL) and to investigate their potential role as diagnostic biomarkers in distinguishing between these conditions. Materials and Method: Ninety participants were enrolled: 30 healthy controls, 30 patients with OL, and 30 patients with histopathologically confirmed OC. All cases were recruited from the Department of Otorhinolaryngology, Cerrahpaşa Medical Faculty and Istanbul Atlas University Hospital. Demographic characteristics, comorbidities, and biochemical parameters were recorded. Serum and salivary PDPN levels were measured using the ELISA method. Results: Serum PDPN levels were significantly higher in the OC group (3.25 ± 0.80 ng/mL) compared with both OL (1.85 ± 0.56 ng/mL) and controls (0.98 ± 0.42 ng/mL) (p < 0.001). Salivary PDPN levels showed a similar pattern, being highest in OC (2.65 ± 0.75 ng/mL), followed by leukoplakia (1.40 ± 0.45 ng/mL), and controls (0.72 ± 0.30 ng/mL) (p < 0.001). Importantly, both serum and salivary PDPN concentrations increased progressively with increasing epithelial dysplasia severity among patients with OL (one-way ANOVA, p < 0.001). ROC analysis demonstrated excellent diagnostic accuracy for OC: AUC = 0.976 for serum PDPN (cut-off: 2.0 ng/mL; sensitivity 93.3%, specificity 100%) and AUC = 0.987 for salivary PDPN (cut-off 1.24 ng/mL; sensitivity 93.3%, specificity 95%). Conclusions: Serum and salivary PDPN levels were significantly elevated in patients with OC and demonstrated excellent diagnostic performance in distinguishing malignant lesions from OL and healthy controls. The observed stepwise increase in PDPN levels with dysplasia severity further supports its role in malignant transformation. Notably, salivary PDPN represents a non-invasive, practical, and reproducible biomarker that may aid in early detection and risk stratification of high-risk oral premalignant lesions. PDPN assessment could therefore complement clinical and histopathological evaluation, although larger prospective studies are warranted to validate its diagnostic and prognostic utility.

Osteopontin expression in oral potentially malignant disorders and squamous cell carcinoma: association with early invasion but not with dysplastic grade.

Eosinophilic ulcer of the oral mucosa is a rare and benign condition that clinically mimics oral malignancy due to its alarming features such as indurated, everted margins and prolonged persistence. This case report discusses a 70-year-old female who presented with a chronic non-healing ulcer on the right lateral border of the tongue, which had been present for three months and caused discomfort during speech and mastication. Ultrasonography showed no neck lymph node involvement. A biopsy of the lesion demonstrated a dense eosinophilic infiltrate without evidence of malignancy. To confirm the diagnosis and ensure complete excision, a wide local excision with adequate margins was performed. Histopathological analysis of the excised tissue confirmed the diagnosis of eosinophilic ulcer, revealing stratified squamous epithelium with surface ulceration, a dense inflammatory infiltrate rich in eosinophils, neutrophils, and plasma cells, and no evidence of malignancy or epithelial dysplasia. Postoperative recovery was uneventful, with no recurrence noted during follow-up. Eosinophilic ulcers are commonly misdiagnosed due to their resemblance to malignant lesions. Although the aetiopathogenesis remains unclear, trauma is a suspected contributing factor. In this case report, an intricate tooth bite was identified as the contributing causative factor. Surgical excision is considered the treatment of choice, with excellent prognosis and low recurrence rates. This case emphasises the critical role of histopathological examination in differentiating benign ulcers from malignant lesions, thus preventing overtreatment. Eosinophilic ulcer should be considered in the differential diagnosis of chronic oral ulcers, especially when typical risk factors for malignancy are absent.

Association of Oral Epithelial Dysplasia with Sociodemographic and Clinical Characteristics in Individuals with Oral Lichen Planus and Oral Lichenoid Lesion

Oral leukoplakia (OL) is the most prevalent oral potentially malignant disorder worldwide. Its diagnosis is clinical and based on excluding all other white patches of the oral cavity, which can be challenging and time-consuming. In recent years, artificial intelligence (AI) has emerged as a promising tool to overcome these limitations, yet a comprehensive overview of the existing evidence is still lacking. This scoping review surveys the current landscape of artificial intelligence applications for diagnosing oral leukoplakia, both clinically and histopathologically. A comprehensive search was conducted in PubMed, Scopus, Web of Science, and OVID for studies on the use of artificial intelligence for the diagnosis of oral leukoplakia. No date/language restrictions were applied. Two reviewers screened articles and extracted data into predefined tables. Ten studies were included. Early research used spectroscopy-based models, while recent work employed deep learning for clinical and histopathological image analysis. Most models achieved moderate-to-high diagnostic performance, with sensitivity, specificity and accuracy values above 80%. Overall, models allowed differentiating oral leukoplakia from normal oral mucosa, oral squamous cell carcinoma, and proliferative verrucous leukoplakia, with stronger performance in advanced lesions. Furthermore, artificial intelligence showed promise in grading oral epithelial dysplasia severity in histological samples, occasionally outperforming oral pathologists. While current evidence remains preliminary, artificial intelligence shows promise as an adjunct tool for oral leukoplakia diagnosis. However, standardized reporting, inclusion of lesions within datasets, and multicenter validation in large and diverse cohorts are still needed to ensure generalizability and further clinical validation.