High Risk Of Malignant Transformation Research Articles

STUDI KASUS: OSTEOCHONDROMA SCAPULA DAN TIBIA FIBULA PADA REMAJA USIA 14 TAHUN

Multiple Hereditary Exostoses (MHE) is an autosomal dominant inherited genetic condition characterized by multiple exostoses (or osteochondromas). Genetic analysis had identified a certain type of mutated Exostosin genes, can potentially cause exostoses. A 14 years old boy referred to our hospital with a chronic hard palpable lump on his left back and right lower limb in the past 10 years, and was gradually increased in size. Laboratory test which consists of complete blood count, urinalysis, and renal function test were normal. A radiographic examination of the related skeleton demonstrated multiple osteochondromas of scapula and tibia fibula. As a consequence of mutations in the Exostosin 1 and Exostosin 2 genes, chondrocytes exhibiting shortened Heparan Sulfate chains are present in this region. In the later stages, these cells develop exostoses. Multiple Hereditary Exostoses may involve different bone locations and could be diagnosed using various medical imaging modalities, however plain radiography x-ray was already sufficient enough to conclude the abnormality. Sessile lesions were much more common than pedunculated in Multiple Hereditary Exostoses, however Sessile lesions bear a higher risk of malignant transformation into chondrosarcoma. Upon early detection, the prognosis for patients who have chondrosarcoma was favorable. Multiple Hereditary Exostoses is a rare bone disorder marked by the development of non-cancerous tumors near the growth plates of bones. This condition can greatly affect an individual's quality of life, resulting in restricted mobility, skeletal abnormalities, ongoing pain, inhibited growth, and the risk of the exostoses becoming malignant.

SOX2-induced IL1α-mediated immune suppression drives epithelial dysplasia malignant transformation.

Squamous cell carcinomas (SCC) are often preceded by potentially malignant precursor lesions, most of which remain benign. The terminal exhaustion phenotypes of effector T-cells and the accumulation of myeloid-derived suppressor cells (MDSC) have been thoroughly characterized in established SCC. However, it is unclear what precancerous lesions harbor a bona fide high risk for malignant transformation and how precancerous epithelial dysplasia drives the immune system to the point of no return. Here we show that expression of SRY-box transcription factor 2 (SOX2) in precancerous lesions imparts an irreversible risk that recruits suppressive myeloid cells by promoting the release of CCL2. We developed a unique genetically engineered mouse model (GEMM) to recapitulate the malignant transformation of epithelial dysplasia to SCC in the oral mucosa with high histologic and phenotypic fidelity. Using a combination of longitudinal human specimens and the Sox2-GEMM, we found that the myeloid cells in precancerous epithelial dysplasia exhibit a distinctive dichotomous profile featuring high levels of IL-1α-SLC2A1 and low levels of type-I interferon (IFN-I) signatures, which occurs before SCC emerges histologically. Brief priming of myeloid cells with IL-1α desensitizes them to IFN-I agonists and makes myeloid-derived suppressor cells (MDSC) even more suppressive of T-cell activation. Mechanistically, IL-1 activation represses the expression of DHHC3/7 enzymes, which are responsible for the palmitoylation of stimulator of interferon genes (STING). Early blockade of IL1 signaling using pharmacologic and genetic approaches similarly reduces MDSC and SLC2A1 high myeloid cells, suppresses epithelial dysplasia transformation, and extends survival. This work establishes a previously unrecognized SOX2-CCL2-IL1 pathway that leads to irreversible immune escape when precancerous epithelial lesions transform.

Human Papillomavirus Genotype Attribution and Integration in High-Grade Vaginal Intraepithelial Neoplasia.

The aim of the study was to investigate the distribution and association between human papillomavirus (HPV) genotypes and integration as well as their correlation with cervical lesions. Two hundred seven patients diagnosed with high-grade vaginal intraepithelial neoplasia (HG-VaIN) were recruited from the Women's Hospital School of Medicine Zhejiang University between 2015 and 2021 and assayed for HPV genotyping. HPV integration sequencing analysis was conducted using tissues from 53 patients with HG-VaIN and 4 patients with invasive vaginal carcinoma (IVC), along with paired cervical lesion specimens. A total of 207 patients with HG-VaIN were categorized as having cervical lesions unrelated to HG-VaIN (group A, 71 patients, 34.30%) or cervical lesion-related HG-VaIN (group B, 136 patients, 65.70%). With an average follow-up of 42.19 months, 12 of 153 patients progressed to IVC and were all from group B. HPV16 infection and the presence of cervical lesions were the 2 main factors associated with disease progression, with cervical lesion coexistence being an independent factor. Compared with group A (5/20, 25%), group B (17/33, 51.52%) showed a higher rate of HPV integration, as demonstrated using HPV integration sequencing analysis, with HPV16 being the most integrated genotype (72.73%). The integration analysis of 4 patients with IVC paired with cervical lesion specimens showed that 3 of the 4 pairs exhibited the same HPV infection and integration sites, indicating a high degree of homology in HPV integration between cervical lesions and HG-VaIN-induced IVC. Patients with HG-VaIN associated with cervical lesions exhibited a higher risk of malignant transformation, necessitating more proactive treatment approaches.

Premalignant lesions of the oral cavity: a narrative review of factors and mechanisms of transformation into cancer.

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer. The development and progression of OSCC are closely linked to various aetiological factors. Early signs of OSCC may manifest as oral lesions, genetic abnormalities, and chronic inflammation. Lesions with dysplastic features have a high risk of malignant transformation into OSCC. Moreover, dysplastic lesions are characteristic of many oral potentially malignant disorders (OPMDs). Currently, there is no unified standard of treatment for OPMD patients, due to the variability in risk factors and mechanisms of transformation. Therefore, it is essential to detect and manage OPMDs at an early stage in order to prevent their malignant transformation into OSCC. This necessitates analysing OPMD mechanisms to identify objective markers for predicting the risk of malignant transformation. The aim of this review was to describe the process of OPMD transformation into OSCC under the influence of environmental, immune, microbiome, and molecular factors.

Therapeutic Strategies in Neurocutaneous Melanocytosis.

Neurocutaneous melanocytosis (NCM) is a rare, congenital condition primarily affecting children, characterized by large or giant congenital melanocytic nevi (L/GCMN) on the skin and pigmented lesions in the brain. The presence of pigmented lesions in the brain often leads to neurological symptoms like headaches, seizures, and hydrocephalus, typically manifesting before age two. Melanocytic lesions in the brain can range from benign melanocytosis to malignant melanoma. NCM is nearly always fatal if symptomatic, with a high risk of malignant transformation. Patients with larger skin nevi with neurological involvement tend to have a greater lifetime risk of malignancy. There is no specific treatment, and current therapies focus on palliative care, including surgery, radiation, and chemotherapy. Malignant transformation into melanoma requires aggressive treatments like surgery, radiation, and chemotherapy. Despite these approaches, outcomes remain poor, with no definitive cure for NCM. This study aims to review and critically evaluate the current therapeutic strategies for NCM while also exploring prospective avenues for developing specific and effective treatments. It aims to highlight recent advancements in the molecular understanding of NCM and examine how these insights may inform the development of novel therapeutic approaches. Additionally, the study will address the significant unmet medical needs associated with this rare and often fatal condition, emphasizing the importance of continued research and innovation in its management.

Evaluation of Feulgen Reaction for Quantitative DNA Analysis in Oral Leukoplakia: Insights into Malignant Transformation Risk

ABSTRACT Background: Oral leukoplakia is a potentially malignant disorder with a significant risk of transformation into oral squamous cell carcinoma. The Feulgen reaction, a DNA-specific staining technique, has been widely used for the quantitative analysis of DNA content in various tissues. Materials and Methods: A total of 50 patients diagnosed with oral leukoplakia were selected for the study. Biopsy samples were obtained from the lesions, and the Feulgen reaction was performed to stain the DNA. Quantitative DNA analysis was conducted using image cytometry, measuring the integrated optical density (IOD) of Feulgen-stained nuclei. The samples were categorized based on their DNA content into diploid, aneuploid, and tetraploid groups. Statistical analysis was performed to assess the correlation between DNA content and the histopathological grading of the lesions. Results: Out of the 50 samples, 30% (n = 15) exhibited diploid DNA content, 50% (n = 25) were aneuploid, and 20% (n = 10) were tetraploid. A significant correlation was found between aneuploid DNA content and higher grades of dysplasia (P < 0.05). The mean IOD values for diploid, aneuploid, and tetraploid samples were 1.2, 2.8, and 3.5, respectively. Patients with aneuploid DNA content demonstrated a higher risk of malignant transformation compared to those with diploid DNA content. Conclusion: The Feulgen reaction, combined with quantitative DNA analysis, is a valuable tool in assessing the malignant transformation risk in oral leukoplakia. The presence of aneuploidy in these lesions is significantly associated with higher dysplastic changes and an increased risk of progression to oral cancer. Further studies with larger sample sizes are recommended to validate these findings and to establish the Feulgen reaction as a standard predictive marker in clinical practice.

HIF-1Α IN SALIVA: A PROMISING BIOMARKER FOR EARLY DIAGNOSIS OF ORAL SUBMUCOUS FIBROSIS AND ITS MALIGNANT POTENTIAL

Oral submucous fibrosis (OSF) is a chronic condition with a high risk of transforming into oral squamous cell carcinoma (OSCC). Identifying reliable biomarkers for early diagnosis and monitoring of OSF is crucial for malignancy prevention. Objective: This study evaluates the expression of Hypoxia Inducible Factor-1α (HIF-1α) in saliva as a potential biomarker for OSF. Methods: Study was a cross-sectional study conducted in Karachi. The study was completed in 6 months from July 2023 to December 2023 and Sixty-five OSF patients participated in the study, providing saliva samples analyzed for HIF-1α expression using immunohistochemically (IHC). Clinic pathological features, including age, gender, body mass index (BMI), and etiological factors (tobacco, smoking, areca nut), were documented. Relationships between clinical symptoms (burning sensation, pain, ulceration, and dry mouth), fibrosis severity, and HIF-1α staining intensity in blood vessels and fibroblasts were assessed. Results: The study population included 68.3% males and 31.7% females, with a mean age of 32.56±4.12 years. Tobacco use (47.7%) was the most common etiology. HIF-1α expression was significantly elevated in fibroblasts compared to blood vessels, with mild staining in 54.2% of blood vessels and 49.8% of fibroblasts. Increased HIF-1α expression correlated with more severe OSF symptoms, indicating a higher risk of malignant transformation. Conclusion: HIF-1α is a promising biomarker for early diagnosis and assessment of malignant potential in OSF. Early detection and monitoring could improve clinical management and reduce OSCC risk, warranting further research for validation and therapeutic targeting.

Ferroptosis Induction Enhances Photodynamic Therapy Efficacy for OLK

Oral leukoplakia (OLK) is the most representative oral potentially malignant disorder, with a high risk of malignant transformation and unclear mechanisms of occurrence. Recently, photodynamic therapy (PDT) has exhibited great potential in the treatment of OLK. However, the efficacy of PDT is difficult to predict and varies from person to person. Ferroptosis-related pathways are upregulated in many cancers, and ferroptosis induction is considered to be a potential synergistic strategy for various antitumor therapies, but its role in OLK treatment remains unclear. This study aimed to determine whether ferroptosis induction can enhance the efficacy of PDT in OLK treatment. Our study revealed that solute carrier family 7 member 11 (SLC7A11), a component of a crucial amino acid transporter and a key negative regulator of ferroptosis, was found to be highly expressed in OLK patients with no response to PDT. 5-Aminolevulinic acid (ALA)-PDT is known to cause apoptosis and necrosis, but ferroptosis also occurred under ALA-PDT in OLK cells in our study. Using erastin to induce ferroptosis enhanced the efficacy of ALA-PDT on OLK cells by disrupting the antioxidant system and further elevating intracellular reactive oxygen species levels, leading to increased apoptosis. Furthermore, this combined modality also enhanced the efficacy of ALA-PDT on 4-nitroquinoline-1-oxide (4NQO)–induced OLK lesions in mice. In summary, ferroptosis induction may serve as a potential strategy to enhance the efficacy of ALA-PDT for OLK treatment.

A complete course of photodynamic therapy reduced the risk of malignant transformation of oral leukoplakia

BackgroundPhotodynamic therapy (PDT) has shown good short-term efficacy in the treatment of oral leukoplakia (OLK). However, the malignant transformation of OLK was seldom evaluated in most PDT studies. Therefore, this study evaluated the effect of PDT on the risk of malignant transformation of OLK. MethodsKaplan-Meier survival analysis, COX regression, and sensitivity analysis were used to evaluate the effects of PDT on the risk of malignant transformation of OLK. Subgroup analyses were performed to explore the role of PDT in OLK patients with different clinical characteristics. ResultsOLK patients with older age (HR=1.032, P = 0.018) and non-homogeneous lesion (HR=2.104, P = 0.044) had higher risk of malignant transformation. Patients who had finished a complete course of PDT (HR=0.305, P = 0.006) had a significant lower risk of malignant transformation, while those who hadn't finished a complete course of PDT (HR=0.692, P = 0.352) cannot be considered to have such a protective effect. In the subgroup analyses, complete PDT course showed a significant protective effect on malignant transformation of OLK in patients with female sex, no smoking or drinking habits, non-homogeneous lesions, lesions on oral mucosa outside the dangerous region, and any grade of epithelial dysplasia. ConclusionsA complete course of PDT could significantly reduce the risk of malignant transformation of OLK, especially in those patients with risk factors of malignant transformation.

The Evaluation of Tumor Budding in Oral Squamous Cell Carcinoma Arising in the Background of Oral Submucous Fibrosis.

Background and objective Oral submucous fibrosis (OSMF) is a common and potentially malignant disorder with a high risk of malignant transformation to oral squamous cell carcinoma (OSCC). Tumor budding is a scattered pattern of invasion and is related to the aggressive behavior of malignant tumors, increased depth of invasion, higher clinical staging, size, and grade of the tumor. The present study aimed to evaluate tumor budding in OSCCarising in the background of OSMF. Materials and methods A total of 120 patients with OSCC (30 each of OSCC arising in the background of OSMF, well-differentiated, moderately differentiated, and poorly differentiated OSCC) were included in the study. Hematoxylin and eosin (H&E)-stained sections were evaluated for the presence of tumor buds at the invasive front of the tumor. Kappa statistics and chi-square tests were employed to statistically compare the results by using IBM SPSS Statistics 23 software (IBM Corp., Armonk, NY). A p-value of less than or equal to 0.05 was considered statistically significant. Results The mean age of the occurrence of OSCC arising in the background of OSMF was 45.3 ±7.62 years. A progressive increase in the tumor buds was noted in OSCC arising in the background of OSMF, well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (WDSCC), and poorly differentiated squamous cell carcinoma (PDSCC). The chi-square test showed no significant difference between OSCC in the setting of OSMF and WDSCC (p=0.604) groups; however, a significant difference was noted with MDSCC (p=0.001) and PDSCC (p=0.000) groups. Conclusions OSCC arising in the background of OSMF shows lower tumor budding at the invasive front of the tumor. This histopathological parameter can be easily identified in the H&E sections and is fairly reproducible. Hence, reporting the presence of tumor budding will help in predicting the prognosis of these patients.

β-catenin, PAX2, and PTEN Aberrancy Across the Spectrum of Endometrioid Ovarian Lesions.

Endometriosis is a common condition, with the ovary being the most common anatomic site. Endometriosis-particularly in the ovary-is associated with a risk of malignant progression, with a histologic spectrum of lesions from benign to malignant. Recently, a panel of 3 markers consisting of β-catenin, PAX2, and PTEN has been described as a potentially useful diagnostic adjunct in the diagnosis of intrauterine endometrioid neoplasia, where aberrancy for one or more of the markers is strongly associated with neoplasia. Here, we applied the panel to ovarian endometrioid lesions, including endometriosis, endometriosis with flat cytologic atypia, endometrioid borderline tumors, and endometrioid adenocarcinoma (n=85 cases in total). The incidence of aberrancy for the 3 markers increased along this putative neoplastic spectrum, arguing for a role of each of the markers in the neoplastic transformation of ovarian endometriosis. Just 1/32 (3%) of cases of nonatypical endometriosis was marker-aberrant, and this case was aberrant only for PAX2. One of 5 cases (20%) of endometriosis with atypia was marker-aberrant (both PAX2 and PTEN), supporting prior findings that some cases of flat atypia may represent bona fide precursor lesions. Of 19 endometrioid borderline tumors, 10 (53%) were aberrant for one or more markers, with PAX2 being the most frequently aberrant. Of 29 endometrioid adenocarcinomas, 28 (96.6%) were aberrant for at least 1 marker, with PAX2 again the most frequently aberrant. Patterns of aberrancy were well-preserved in areas of nonatypical endometriosis adjacent to borderline tumor or adenocarcinoma, supporting a biological origin in a common marker-aberrant precursor. The findings show that the biomarker panel could be of some diagnostic utility in the characterization of ovarian endometrioid neoplasia, such as in the diagnosis of endometrioid borderline tumor, distinguishing endometrioid from nonendometrioid lesions, or in identifying other types of early precursors at a higher risk of malignant transformation.

Liver Transplantation for Adenomatosis: A Single-Center Experience

Liver adenomatosis is characterized by multiple adenomas diffusely distributed throughout the liver parenchyma. Studies addressing liver transplantation for those cases are scarce, and the criteria used to indicate transplantation are still debatable. To report a single-center experience of liver transplantation for diffuse adenomatosis. Single-center retrospective study involving all adult patients who underwent liver transplantation due to adenomatosis from January/2010 to June/2023. A total of 13 patients were identified, corresponding to 0.89% of liver transplants performed during the study period. The mean age was 33 ± 6.55 years, and most of them were female (n = 9, 69.23%). There were 12 transplants with deceased donors and 1 with a right lobe from a living donor. The most frequent reason to preclude liver resection was multiple and large unresectable adenomas in patients without previous liver disease (n = 8, 61.58%), followed by underlying liver disease (Abernethy Malformation, n = 3, 23.07%) and recurrence after liver resection (n = 2, 15.38%). The indications for liver transplantation were high risk of malignant transformation (n = 7, 53.84%), increasing size and number of nodules (n = 3, 23.07%), confirmed malignant transformation (n = 2, 15.38%), and hemorrhage (n = 2, 15.38%). There was 1 perioperative death due to primary non-function. Another patient died during follow-up because of COVID-19. Liver adenomatosis is a rare indication for liver transplantation, with acceptable post-transplant outcomes. Unresectable adenomas with high-risk or confirmed malignant transformation are the main indications for transplant. Reasons for unresectability involve underlying liver disease, multiple and large high-risk nodules, and recurrence after previous resection.

Efficacy and safety of the vebreltinib in patients with previously treated, secondary glioblastoma/IDH mutant glioblastoma with PTPRZ1-METFUsion GENe (FUGEN): A randomised, multicentre, open-label, phase II/III trial.

2003 Background: Although gliomas with mutated IDH have an improved prognosis compared to gliomas with wild-type IDH, IDH-mutant gliomas carry a high risk of malignant transformation from low-grade gliomas into high-grade gliomas within 10 years, resulting in poor prognosis. However, effective targeted drugs for high-grade gliomas are still lacking. Here, we report data from the FUGEN study of Vebreltinib, the first completed phase II/III trial of sGBM / IDH mutant glioblastoma patients with previously treated, PTPRZ1-MET Fusion gene positive. Methods: In this open-label, phase II/III trial, we randomly assigned, in a 1:1 ratio, 84 patients with Histologically confirmed secondary GBM or IDH-mutant GBM to receive twice-daily oral vebreltinib in 300 mg dose or the investigator's choice of chemotherapy (temozolomide [100-150 mg/m2/day, 7days on followed by 7 days off ] or cis-platinum [80-100 mg/m2 for 3 days] combined with etoposide [100mg/m2/day for 3 days]) every 28 days. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). Results: 42 patients of the vebreltinib group and 39 patients of the chemotherapy group were included in the full analysis set. After a median follow-up of 4.44 months, the median OS in the vebreltinib group and chemotherapy group was 6.31 months (95% CI, 4.44-8.77) and 3.38 months (95% CI, 2.37-4.27), respectively. The HR for OS was 0.52 (90% CI, 0.32-0.85; P = 0.009). The median PFS in the vebreltinib group and chemotherapy group was 1.87 months (95% CI, 1.41-2.76) and 1.05 months (95% CI, 0.95-1.77), respectively. The HR for PFS was 0.54 (95% CI, 0.33-0.88; P = 0.014). No significant differences were observed in ORR (9.5% vs. 2.6%) for the vebreltinib group and chemotherapy group. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the vebreltinib group, as compared with 12.2% of those in the chemotherapy group. No treatment-related deaths were observed. Conclusions: These results of the FUGEN trail support the use of vebreltinib as the first target therapy in patients with previously treated, PTPRZ1-MET fusion gene positive, secondary glioblastoma / IDH-mutant glioblastoma, and shed light on a novel therapeutic pathway in the landscape of IDH-mutant high-grade gliomas. Clinical Trials Information: NCT06105619 and ChiCTR2300077783 Research Funding:Beijing Pearl Biotechnology Co., Ltd. and Avistone Biotechnology Limited. Clinical trial information: NCT06105619 .

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.

Leukoplakia with Diverse Grades of Epithelial Dysplasia – A Case Series and Review of Literature with Updated Management Protocol

Oral leukoplakia is considered the most potentially malignant disorder of the oral cavity, with a high risk of malignant transformation. Based on the clinical manifestation, it has been classified as a homogeneous and non-homogeneous variant. It has been considered predominantly a white lesion of the oral cavity that cannot be classified under any other definable lesions. Leukoplakia is a term used to describe the lesion clinically. There are various components responsible for the threatening change of oral leukoplakia. The clinical diagnosis of leukoplakia is confirmed by histopathology, which commonly indicates intense epithelial dysplasia. This manuscript describes a series of cases diagnosed clinically as leukoplakia and their grades of epithelial dysplasia, a Review of literature about etiology and the key pathogenesis behind it, risk determinants for malignant transformation, chair side investigation for epithelial dysplasia, and updated management protocol.

Knowledge About the Importance of Early Diagnosis and Treatment of Oral Potentially Malignant Disorders Among the South Indian Population: An Institutional Retrospective Study.

The significant malignant transformation rates of oral potentially malignant disorders (OPMDs) demand early diagnosis and proper management of OPMDs not only to reduce symptoms but also to prevent their aggressive outcomes. This retrospective study aimed to quantify the need for patient-related awareness in identifying OPMDs by quantitatively evaluating the association between the type of referral in OPMD cases. This study also aims to analyze the association between gender and types of referral in OPMDs. The sample size of n=1577 (500-leukoplakia, 500-oral submucous fibrosis (OSMF), 500-lichen planus, 77-lichenoid reaction) was considered in the present retrospective study. Data regarding the sample cases were extracted from the common patient database of the Saveetha Dental College and Hospitals from June 2019 to February 2024. Random sampling method was used, and the OPMDs were categorized into two groups based on the chief complaint as self-referred and specialist-referred cases. The segregated data were tabulated in Microsoft Excel (Microsoft® Corp., Redmond, WA) and then exported to IBMSPSSStatistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York, United States) for statistical analysis. Pearson's chi-square test was conducted to analyze the association of referral type, OPMDs, and gender. Out of 1577 OPMD cases, 929 (58.9%) were specialist-referral cases and 648 (41.1%) were self-referral cases. Among OPMDs, lichen planus was the most self-referred 310 (62%) and leukoplakia was the most specialist-referred 470 (78.6%) category. This study found a statistically significant correlation between the type of referrals and the type of OPMDs (p=0.000). Self-referral was more commonly observed in females (23.3%) than males (17.8%) in general and among all categories of OPMDs except lichenoid reactions. This observation was also statistically significant (p=0.000). Conclusion: Among OPMDs selected in the present study, lichen planus and OSMF were more self-referred and leukoplakia cases were mostly specialist-referred. This study highlights the need of detecting less symptomatic lesions, such as leukoplakia, which has a high risk of malignant transformation. The lack of awareness about the identification of OPMDs among patients can result in delayed diagnosis and treatment, which may further result in progression to aggressive outcomes.

Дифференциальная диагностика невусов и меланом хориоидеи по данным ОКТ

The article presents the study results of 64 patients with suspicious (progressive) nevi (n = 42) and initial choroid melanomas (n = 22, of which n = 3 had anamnesis of choroid nevus). Ultrasound examination, digital photoregistration of the fundus and OCT were done for all patients. According to the OCT data it was possible to identify diagnostic criteria that help distinguish of suspicious nevi including those with a high risk of malignant transformation from initial choroid melanomas. First of all these are the preservation of the Bruch membrane and the presence of druses. While malignant transformation of suspicious nevi was characterized by shape asymmetry of the enlarged “choroidal complex”, dilation of large choroidal vessels around the nevus, the presence of RPE detachment and the presence of hyperreflective intraretinal inclusions. Criteria of initial choroid melanomas were violation of the integrity of the Bruch membrane, rounded cavities in the inner layers of the choroid, deposits at the level of RPE, edema and/or rupture of the photoreceptor layer. Keywords: suspicious choroid nevus, choroid melanoma, OCT

Proliferative verrucous leukoplakia: a general dental practitioner-focused clinical review

Proliferative verrucous leukoplakia (PVL) is a distinct type of oral leukoplakia which has the potential to enlarge or develop into new areas of leukoplakia coupled with areas of a warty surface texture. PVL is usually diagnosed from the fifth decade onwards and is more common in female patients. The most frequent sites involved tend to be gingivae, followed by buccal mucosa and lateral border of tongue. It is one of the oral potentially malignant conditions with a high risk of malignant transformation. It is important for general dental practitioners (GDPs) to identify such lesions to facilitate referral for further investigation and diagnosis. Management is challenging with long-term monitoring and surgical excision when appropriate; however, PVL tends to recur following surgical excision. This article provides an up-to-date review tailored for GDPs on the present knowledge of PVL and illustrates the management challenges with clinical cases.

Diagnosis of differentiated dysplasia as a variant of oral epithelial dysplasia.

The World Health Organization's definition of oral epithelial dysplasia includes differentiated dysplasia, which is defined by purely architectural abnormalities of oral mucosa without cytological changes. We analysed differentiated dysplasia's frequency, progression risk and correlation with oral brush cytology. Cytoarchitectural criteria and expression patterns of keratin 13/17 and ki67 were studied in oral biopsies clinically diagnosed with leukoplakia. Biopsies were assessed for dysplasia and its grade. Available brush cytology findings were obtained from clinical records. We included 159 biopsies from 112 patients (33% differentiated dysplasia; 27% keratosis without dysplasia; oral epithelial dysplasia with atypia of mild, moderate and severe degree including invasive cancers in 9%, 8% and 7%, respectively). Keratin 13 loss and keratin 17 gain were higher in differentiated-dysplasia cases (p < 0.0001), which had the highest hypergranulosis frequency. Keratin 17 expression was associated with higher malignant-transformation rates (p = 0.0028). The transformation rate and time were comparable between dysplasia with atypia and differentiated-dysplasia cases, which had higher progression rates and shorter time periods than keratosis cases without dysplasia (p = 0.08). Cytology prior to differentiated dysplasia all indicated normal oral mucosa. Keratin 17 but not oral brush cytology can help identify patients with differentiated dysplasia with higher risk for malignant transformation.

Temporal epidemiological profile of oral potentially malignant disorders in southern Brazil.

The study aimed to investigate oral potentially malignant disorders (OPMDs) diagnosed in an Oral Pathology service in southern Brazil over a span of 56 years and to assess the factors influencing their severity and outcomes. A retrospective analysis of histopathological records from 1965 to 2021 was performed. Lesions diagnosed as leukoplakia, erythroplakia, leukoerythroplakia, or actinic cheilitis were included. Data on age, sex, race, tobacco smoking, alcohol drinking, clinical characteristics, biopsy type, and histopathological diagnosis were collected. Among 32.698 histopathological reports, 2.10% were classified as OPMD. The study included 689 specimens from 602 patients, with a predominance of cases affecting men aged over 51 years, particularly in anatomical sites considered of low risk. White lesions, with leukoplakia as the most common clinical diagnosis were observed. Over time, there was an increase in the incidence of OPMDs among females and in high-risk anatomical sites. The mean follow-up period was 30.28 ± 29.86 months, during which 9.6% of cases exhibited malignant transformation. Lesions diagnosed as leukoerythroplakia and those presenting epithelial dysplasia exhibited a higher risk of malignant transformation, particularly when located in high-risk sites. This underscores the importance of identifying clinical and microscopic features, as well as lesion's anatomical location, as crucial factors in determining the risk of malignant transformation. These findings provide valuable insights for clinicians managing OPMDs and contribute to the improvement of oral cancer prevention.