Dysplastic Lesions Research Articles

Grading Melanocytic Dysplasia: Updated Histopathologic Criteria.

Dr. Martin C. Mihm, Jr.'s innovative work on the dysplastic nevus achieved a milestone in his chapter in the World Health Organisation Classification of Skin Tumours (WHO-C). WHO-C presents a dichotomous classification (high-grade versus low-grade dysplastic nevi) and a quantitative metric to assess melanocytic nuclear enlargement. The Duke classification is a related approach that provides mostly quantitative histopathologic criteria for dysplastic nevi and gives due weight to architectural features as well as cytology. This paper proposes and illustrates updated criteria for scoring and grading melanocytic dysplasia, incorporating some of the definitions and categories of WHO-C, while refining the quantitative and architectural elements of the Duke grading system to facilitate more detailed and precise assessment of dysplastic nevi.

Targeting c-MET for Endoscopic Detection of Dysplastic Lesions Within Barrett's Esophagus Using EMI-137 Fluorescence Imaging.

Esophageal cancer (EC) carries a poor prognosis with 5-year overall survival of less than 20%. Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). The aim of this study was to investigate the ability of EMI-137, a mesenchymal-epithelial transition factor (c-MET)-targeting optical imaging tracer, to detect dysplasia in BE. c-MET expression in human esophageal tissue was investigated using Gene Expression Omnibus (GEO) datasets, tissue microarrays and BE biopsies. EMI-137 was tested in a dual xenograft mouse model bearing OE33 (c-MET high expression) and FLO-1 (c-MET low expression) tumors. Fluorescence molecular endoscopy (FME) was performed in a mouse model of Barrett's-like metaplasia and dysplasia (L2-IL1β). Tumors and organs-of-interest were evaluated through ex vivo fluorescence imaging. MET mRNA expression analyses and c-MET immunostaining confirmed upregulation of c-MET in BE and EAC compared to normal epithelium. There was strong accumulation of EMI-137 in OE33 xenografts 3 h post injection decreasing by more than 50% on co-injection of a 10-fold molar excess of unlabeled EMI-137. The target-to background ratio (TBR) at 3 h p.i. for OE33 and FLO-1 tumors was 10.08 and 1.42, respectively. FME of L2-IL1β mice showed uptake of EMI-137 in dysplastic lesions within BE with a TBR of 1.9 in vivo, and greater than 2 in ex vivo fluorescence imaging. EMI-137 accumulates in dysplastic lesions within BE and in c-MET positive EAC. EMI-137 imaging has potential as a screening and surveillance tool for patients with BE and as a means to detecting dysplasia and EAC.

Can we improve the endoscopic resection of dysplastic lesions in colonic inflammatory bowel diseases?

Can we improve the endoscopic resection of dysplastic lesions in colonic inflammatory bowel diseases?

Endoluminal Approaches for Colorectal Neoplasia in Inflammatory Bowel Disease, A Viable Alternative for Colectomy?

IntroductionEndoscopic resection of visible dysplastic lesions in patients with inflammatory bowel disease (IBD) provides an alternative to colectomy for management. Endoscopic techniques that can be used include endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and a combined hybrid approach of ESD and EMR. These endoscopic treatments may allow organ preservation in patients with IBD. The aim of this study was to evaluate outcomes of endoscopic resection, including EMR, ESD and hybrid ESD/EMR, for the treatment of colorectal dysplasia in patients with IBD. MethodsWe performed a retrospective review of IBD patients who underwent endoscopic resection for colorectal dysplasia at our tertiary care center between 2014 to 2023. Patients were identified through a search of our endoscopy database. Medical records were reviewed to collect data on patient demographics, IBD history, details of endoscopic technique, procedural factors, final pathology results, and outcomes including recurrence of dysplasia. ResultsA total of 50 IBD patients underwent endoscopic resection, including 38 ESD, 11 hybrid ESD/EMR, and 1 EMR. Median age was 62 (IQR: 54-68) years and 34 (68%) were male. Median BMI was 27.6 (IQR: 24.8-31.7). Underlying diagnosis was ulcerative colitis in 33 (66%) and Crohn's disease in 17 (33%). Median disease duration was 27.5 years (IQR 8-30). Polyp locations were distributed as follows: right colon, rectum, left colon, transverse colon, and cecum, with 9 (18%) in each area. Median procedure time was 47.5minutes (IQR: 31.2-73.7). En bloc resection was achieved in 34 (68%) and piecemeal resection in 16 (32%). On pathology, median lesion size was 23.5 (IQR: 20.2-40) mm. High-grade dysplasia was found in 7 (14%) and low-grade dysplasia in 15 (30%). During a median follow-up period of 7.2 years, 18% of patients experienced recurrence. No significant difference in recurrence rates was observed between the ESD and ESD/EMR groups. ConclusionEndoscopic resection, including EMR, ESD and hybrid techniques, enables effective treatment of visible dysplastic lesions as an alternative to colectomy in patients with IBD. In this cohort, favorable short-term outcomes were demonstrated after endoscopic resection.

Ampullectomy of an unusual dysplastic lesion after deroofing of type III choledochocele

Ampullectomy of an unusual dysplastic lesion after deroofing of type III choledochocele

SOX-10 and Melan-A Immunostaining in Areas of Focal Acantholytic Dyskeratosis and Epidermolytic Hyperkeratosis Within Dysplastic Nevi Biopsies: An Observational Study.

Focal acantholytic dyskeratosis (FAD) and epidermolytic hyperkeratosis (EHK) are common incidental epidermal histologic findings within dysplastic nevi biopsies. We evaluate whether areas of FAD and EHK within dysplastic nevi biopsies stain with immunostains used to characterize melanocytic neoplasms. In this case series, a natural language search of histopathology reports from our institution in the past year (2020-2021) identified dysplastic nevus biopsies with concurrent FAD and/or EHK. Tissue samples were examined for positive melanocytic immunostaining with SOX-10 and Melan-A in areas of FAD and EHK. Out of 32 biopsies, 20 of 26 FAD specimens (76.9%) and 2 of 6 EHK specimens (33.3%) showed unexpected suprabasal layer staining with a melanocytic marker that did not correspond to definitively identified melanocytes on the H&E-stained sections. The immunohistochemical staining of FAD and EHK was observed in 2 forms: nonspecific background staining or "true" staining (ie, seemed nuclear on SOX-10 or cytoplasmic on Melan-A). This pilot examination provides evidence that areas of incidental FAD within dysplastic nevi biopsies demonstrate unexpected suprabasal layer staining with melanocytic markers. When dermatopathologists evaluate melanocytic neoplasms with melanocytic markers, it is possible the presence of incidental FAD could lead to over diagnosing pagetoid scatter within these lesions. This study is a proof of concept with mild to moderately dysplastic nevi that do not typically incur the use of melanocytic stains; however, the implication of this unexpected staining pattern would be important when using melanocytic markers on borderline melanocytic neoplasms that have incidental FAD. Close correlation with H&E is imperative to prevent misinterpretation in these cases.

Deep Learning With Optical Coherence Tomography for Melanoma Identification and Risk Prediction.

Malignant melanoma is the most severe skin cancer with a rising incidence rate. Several noninvasive image techniques and computer-aided diagnosis systems have been developed to help find melanoma in its early stages. However, most previous research utilized dermoscopic images to build a diagnosis model, and only a few used prospective datasets. This study develops and evaluates a convolutional neural network (CNN) for melanoma identification and risk prediction using optical coherence tomography (OCT) imaging of mice skin. Longitudinal tests are performed on four animal models: melanoma mice, dysplastic nevus mice, and their respective controls. The CNN classifies melanoma and healthy tissues with high sensitivity (0.99) and specificity (0.98) and also assigns a risk score to each image based on the probability of melanoma presence, which may facilitate early diagnosis and management of melanoma in clinical settings.

Risk of malignancy in patients with Reinke's Edema: evaluation of long-term follow-up results.

Reinke's edema is a benign lesion affecting the subepithelial layer of the vocal cords, often associated with moderate or heavy smoking. Smoking is the most significant risk factor for dysplastic laryngeal lesions, laryngeal carcinomas, and Reinke's edema. Thus, Reinke's edema could potentially be a predisposing factor for laryngeal malignancy in the long term. This study aimed to determine the rate of dysplasia and invasive carcinoma development in the larynx during long-term follow-up of histopathologically confirmed Reinke's edema. Between 2010 and 2019, 28 patients diagnosed with Reinke's edema via microlaryngoscopy and histopathological confirmation were included in this study. Their clinical and pathological data were examined to identify the development of laryngeal dysplasia and malignancy during long-term follow-up. Among the 28 patients, 16 (57%) were female and 12 (43%) were male. A history of smoking was present in 24 (85%) patients. No new pathology was found during long-term follow-up in 21 (75%) patients. None of the patients developed dysplasia or malignancy histopathologically. Seven (25%) patients underwent repeated biopsies during follow-up, and minimal dysplasia was detected in 1 (4%) patient. No invasive carcinoma developed in any patient during long-term follow-up. Despite the high rate of smoking among patients with Reinke's edema, no malignancy developed during long-term follow-up, though there was a low incidence of dysplasia. Therefore, close monitoring of these patients is recommended.

Artificial Intelligence and Colposcopy: Automatic Identification of Vaginal Squamous Cell Carcinoma Precursors

Background/Objectives: While human papillomavirus (HPV) is well known for its role in cervical cancer, it also affects vaginal cancers. Although colposcopy offers a comprehensive examination of the female genital tract, its diagnostic accuracy remains suboptimal. Integrating artificial intelligence (AI) could enhance the cost-effectiveness of colposcopy, but no AI models specifically differentiate low-grade (LSILs) and high-grade (HSILs) squamous intraepithelial lesions in the vagina. This study aims to develop and validate an AI model for the differentiation of HPV-associated dysplastic lesions in this region. Methods: A convolutional neural network (CNN) model was developed to differentiate HSILs from LSILs in vaginoscopy (during colposcopy) still images. The AI model was developed on a dataset of 57,250 frames (90% training/validation [including a 5-fold cross-validation] and 10% testing) obtained from 71 procedures. The model was evaluated based on its sensitivity, specificity, accuracy and area under the receiver operating curve (AUROC). Results: For HSIL/LSIL differentiation in the vagina, during the training/validation phase, the CNN demonstrated a mean sensitivity, specificity and accuracy of 98.7% (IC95% 96.7–100.0%), 99.1% (IC95% 98.1–100.0%), and 98.9% (IC95% 97.9–99.8%), respectively. The mean AUROC was 0.990 ± 0.004. During testing phase, the sensitivity was 99.6% and 99.7% for both specificity and accuracy. Conclusions: This is the first globally developed AI model capable of HSIL/LSIL differentiation in the vaginal region, demonstrating high and robust performance metrics. Its effective application paves the way for AI-powered colposcopic assessment across the entire female genital tract, offering a significant advancement in women’s healthcare worldwide.

Concomitant Cervical and Anal Screening for Human Papilloma Virus (HPV): Worth the Effort or a Waste of Time?

This study represents a follow-up analysis of the AnusGynecology (ANGY) study. This prospective, cross-sectional, single-center study recruited women for concomitant cervical and anal screening of HPV genotypes and cytology during a single appointment. All women with findings of either HPV or any type of dysplastic lesions on anal smears were offered follow-up in a specialized high-resolution anoscopy (HRA) outpatient clinic, representing the study cohort for this follow-up study. Overall, 275 patients (mean age 42 ± 12) were included. Among them, 102 (37%) had cervical high-risk (HR) HPV. In total, HPV was (incidentally) revealed in 91 patients (33%) on anal smears, while any degree of anal squamous intraepithelial lesion (SIL) was found in 30 patients (11%), 6 if which were high-grade SIL (H-SIL). Furthermore, 10 out of 19 biopsies were positive (3 H-SIL lesions). Only half (48/91, 53%) of the women agreed to undergo the recommended specialized follow-up evaluation. Of them, 18 (38%) were diagnosed with dysplastic lesions (9 low grade (L-SIL) and 9 H-SIL, respectively) on biopsies, while the remaining visits revealed no abnormalities. Multivariable analysis revealed cervical HR-HPV infection (OR 4, 95% CI 2.2-7.5) and anal intercourse (OR 3.1, 95% CI 1.7-5.9) as independent risk factors for anal HR-HPV infection. Close follow-up of these women is hence strongly recommended.

Utilizing PRAME Expression and a Meta-Analytic Framework for iSALT to Explore Atypical Late-Onset Nevi of the Elderly and Their Relationship With Lentiginous and Nested Nevoid Melanomas.

In contrast to early-onset dysplastic nevi, late-onset atypical nevi of the elderly are more often precursors to distinctive nevoid melanomas. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry was applied to delineate the nevoid aspect of late-onset oncogenic nevoid pathway. Inducible Skin-Associated Lymphoid Tissue, regulatory T-cell mesenchymal hubs, has emerged as a translational tool and was used to define nevoid oncogenesis within a dynamic meta-analytic pathway. PRAME immunohistochemistry was applied after designating a histopathologic diagnosis. Late-onset atypical nested lentiginous nevus, lentiginous nested melanoma, and hypercellular nested nevoid melanoma were the diagnostic categories. A positive PRAME for melanoma was set at 75% percentage labeling.A wide-ranging published evidence-based database was incorporated to develop a meta-analytic framework for oncogenic nevogenesis. This combined inducible Skin-Associated Lymphoid Tissue incorporating the pleiotropic functions of regulatory T cells regulating immunity and gene regulatory epigenetics as principal modulators. Concordant-negative PRAME expression was present in 64 of 81 (79%) atypical nested lentiginous nevi, concordant-positive PRAME expression occurred in 54 of 75 (72%) nevoid lentiginous and nested melanomas, and 18 of 23 (78%) nevoid hypercellular nested melanomas. PRAME expression confirmed the existence of a late-onset oncogenic nevoid pathway that can be defined by histopathology. Subsequent meta-analysis data linked to the meta-analytic framework revealed that PRAME is an epigenetic surrogate antigen expressed because of repression of retinoic acid receptor signaling, preventing ligand-induced retinoic acid cellular differentiation, growth arrest, and apoptosis, and promoting melanoma growth and survival for melanomas. PRAME is only a single antigen within a highly complex dynamic framework that governs nevoid oncogenesis. Significantly, the retinoic acid/retinoic acid receptor complex has been shown to modulate the immunosuppressive arm of regulatory T cells underpinning immune tolerance and is pertinent to the broad framework but is not linked to PRAME expression in this arm.

Three-Dimensional Total Body Photography, Digital Dermoscopy, and in vivo Reflectance Confocal Microscopy for Follow-Up Assessments of High-Risk Patients for Melanoma: A Prospective, Controlled Study

Plain Language SummaryThe combination of total body photography (TBP) and digital dermoscopy (DD) for the monitoring of patients with high risk for melanoma leads to early detection of melanoma. The aim of the present study was to examine if regular monitoring of patients with high risk for melanoma with 3D-TBP, DD, and confocal microscopy (RCM) leads to a benefit in comparison to a control group (CG). The intervention group (IG) was examined with 3D-TBP at every visit. If necessary, DD and/or RCM were used for diagnosis and/or monitoring of pigmented lesions. The CG was examined clinically with dermoscopy only. A total of 600 patients (324 male and 276 female) were followed up between April 21, 2021, and January 8, 2024. Lesions (n = 166) were monitored with DD and 105 lesions were examined with RCM. The number of lesions that the dermatologists had to cut out to find a melanoma was 2.83, when RCM was used. There were more melanomas (22 vs. 1, p = 0.022) and more nevi excised in the IG (186 vs. 10, p < 0.001), among them more dysplastic nevi (137 vs. 2, p < 0.001). Out of the melanomas diagnosed in the IG, three melanomas were diagnosed with RCM directly, nine melanomas with the combination of 3D-TBP and RCM, and 10 melanomas were diagnosed clinically with dermoscopy only. The follow-up with the combination of 3D-TBP, DD and RCM led to detection of more melanomas in comparison to a CG. RCM led to a reduced NNT for melanocytic lesions.

Matrix-assisted laser desorption/ionization mass spectrometry imaging as a new tool for molecular histopathology in epilepsy surgery.

Epilepsy surgery is a treatment option for patients with seizures that do not respond to pharmacotherapy. The histopathological characterization of the resected tissue has an important prognostic value to define postoperative seizure outcome in these patients. However, the diagnostic classification process based on microscopic assessment remains challenging, particularly in the case of focal cortical dysplasia (FCD). Imaging mass spectrometry is a spatial omics technique that could improve tissue phenotyping and patient stratification by investigating hundreds of biomolecules within a single tissue sample, without the need for target-specific reagents. An insitu proteomic technique called matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is here investigated as a potential new tool to expand conventional diagnosis on standard paraffin brain tissue sections. Unsupervised and region of interest-based MALDI-MSI analyses of sections from 10 FCD type IIb (FCDIIb) cases were performed, and the results were validated by immunohistochemistry. MALDI-MSI identified distinct histopathological features and the boundaries of the dysplastic lesion. The capability to visualize the spatial distribution of well-known diagnostic markers enabling multiplex measurements on single tissue sections was demonstrated. Finally, a fingerprint list of potential discriminant peptides that distinguish FCD core from peri-FCD tissue was generated. This is the first study that explores the potential application of MALDI-MSI in epilepsy postsurgery fixed tissue, by utilizing the well-characterized FCDIIb features as a model. Extending these preliminary analyses to a larger cohort of patients will generate spectral libraries of molecular signatures that discriminate tissue features and will contribute to patient phenotyping.

Skin Biopsies and Diagnostic Outcomes at a Multisite Family Medicine Residency Network.

Physicians other than dermatologists evaluate nearly 60% of all skin diseases, and 22% of these physicians are family physicians. Dermatology education is therefore an important aspect of Family Medicine training. Dermatologic procedural training in Family Medicine residency is not standardized, however, so family physicians graduate with highly variable skills. This study describes the scope and diagnostic outcomes of skin biopsies performed by residents at a multisite Family Medicine residency network in comparison with those performed by attendings at a Family Medicine faculty community practice. We performed a retrospective chart review of patients evaluated at eight Family Medicine residency training sites and one Family Medicine faculty community practice within a regional academic health system between January 2020 and October 2022. Patients with a skin finding who underwent at least one skin biopsy during their visit were included in the study. Among all of the skin findings, the incidence of skin biopsy was 3.6% (258/7104) for residents and 1.8% (175/9917) for attendings (P < 0.001). Family Medicine residents performed fewer shave biopsies (57.8% vs 77.7%, P < 0.001) and more punch biopsies (25.6% vs 11.4%, P < 0.001) compared with attendings. Most biopsies performed by residents and attendings were benign, although residents biopsied significantly more benign (79.1% vs 64.6%, P < 0.001) and malignant lesions (11.2% vs 5.7%, P = 0.049). Attendings biopsied significantly more low-to-moderate-grade dysplastic (22.3% vs 5.0%, P < 0.001) and high-grade atypical lesions (4.0% vs 0.8%, P = 0.034). Family Medicine residents at this residency network receive training in a variety of skin biopsy types. Distinct skin biopsy practices and outcomes between residents and attendings may reflect differences in patient populations, clinical expertise, and dermatology referral patterns.

The expression of immune checkpoint proteins PD-L1 and TIM3 in mouse and human head and neck squamous cell carcinoma.

The aim of this study was to examine the expression of programmed death-ligand 1 (PD-L1) and of T cell immunoglobulin and mucin domain-containing protein (TIM3) in oral epithelial dysplasia and head and neck squamous cell carcinoma (HNSCC). Mouse HNSCC was induced with 4-nitroquinoline-1 oxide (4NQO). Oral epithelial dysplastic lesions, carcinoma in situ and HNSCC lesions were stained with anti-PD-L1 and TIM3 antibodies. The expression of PD-L1 and TIM3 in tumor cells and immune cells was semiquantitatively measured and compared. In parallel, human dysplasia and HNSCC were stained with anti-PD-L1 and anti-TIM3. The expression pattern of PD-L1+ and TIM3+ cells was further compared. In human and mouse samples both PD-L1 and TIM3 were found to be expressed in neoplastic and immune cells in HNSCC, but not in dysplasia. There was no significant difference in PD-L1 and TIM3 expression between metastatic and nonmetastatic HNSCC. We conclude that the 4NQO-induced mouse HNSCC model may be an excellent preclinical model for immune checkpoint therapy.

Prevalence of cervical dysplastic lesions in cervical smears from Baghdad city: a single centre study.

To assess the association of demographic and clinical features of patients with clinicopathological markers in cases of abnormal Pap smear. The retrospective study was conducted from July 2020 to June 2021 at Al-Elwiya Maternity Teaching Hospital, Baghdad, Iraq, and comprised data from January 2019 to June 2020 of women who underwent Pap-smear. Data was retrieved for patients' age, marital status, smoking status, clinical symptoms at presentation, findings of clinical and cytological examinations, as well as follow-up or human papillomavirus testing data where applicable. Data was analysed using SPSS 26. Of the 560 women with mean age 40.42±10.211 years, 26(4.6%) were attending the hospital for routine check-ups/screening, and 12(2.1%) for follow-up screening with previous abnormal Pap-tests, while the rest had been referred for medical consultation. The most common diagnosis was negative for intraepithelial lesion or malignancy 403(72%) Cervical epithelial abnormalities were seen in 136(24.3%) cases, and, of them, 12(8.8%) returned for follow-up. Epithelial abnormalities had a significant association with age, clinical presentation, and clinical examination results (p<0.05), while it had a non-significant relation with marital and smoking statuses (p>0.05). The majority of subjects were referred cases, with routine cervical screening being <5%. Increasing public awareness about the importance of cervical screening and follow-up is essential.

Abstract C123: Exploring the cancer phenotype of a potential CDKN2A founder variant, c.146T&amp;gt;C (p.Ile49Thr), in Hispanic/Latinos of predominately Mexican ancestry

Abstract BACKGROUND: CDKN2A germline pathogenic/likely pathogenic variants (PVs) cause familial atypical multiple mole melanoma syndrome, which increases melanoma (MEL) and pancreatic cancer (PC) risk. The interpretation of genetic test results can be complicated by discordant variant classifications. CDKN2A c.146T&amp;gt;C (ClinVar ID:127523) is such a variant and is classified as likely pathogenic at some laboratories and as uncertain at others. Furthermore, the variant frequency in Hispanic/Latinos (H/Ls) is higher than typically expected for a PV in CDKN2A and some functional studies support that it is a PV. METHODS: Genetic counseling databases at various institutions were queried for demographic, personal and family cancer history data for individuals with known PVs in CDKN2A, with c.146T&amp;gt;C, and c.–2G&amp;gt;A (ClinVar ID:141245), a benign CDKN2A variant (BV) seen in H/Ls to serve as a comparator. The association between personal and/or family history of PC and/or MEL and demographic/clinical characteristics was tested using Fischer exact test, Chi-square test, and post-hoc test with ANOVA. Odds ratios were calculated with multinomial logistic regression. RESULTS: Overall, 219 individuals were identified; 109 with c.146T&amp;gt;C, 60 with other CDKN2A PVs, and 50 with the BV; 82% were female, 76% H/L, and 70% had a personal cancer history – 18% (n=27) had MEL and 10% (n=16) had PC. By variant group, 99% (c.146T&amp;gt;C) and 96% (BV) were H/L; 85% and 84% of Mexican ancestry, respectively. MEL was reported in 38% (n=22) of other PVs, 5% (n=5) of c.146T&amp;gt;C, and not at all in the BV group. Those with c.146T&amp;gt;C were 92% less likely to have MEL than other CDKN2A PVs (p&amp;lt;0.001), with no difference in mean age at diagnosis, 32y vs. 40y, respectively (p=0.71). Seven (12%) of other PVs had PC compared to 6% (n=7) of c.146T&amp;gt;C and 4% (n=2) of the BV. While this difference was not significant (p=0.27), the mean age at diagnosis in c.146T&amp;gt;C was significantly younger than other PVs (32y vs. 71y; p=0.02). When including family history, those with c.146T&amp;gt;C were 80% less likely to have a personal AND family history of MEL than other PVs (p&amp;lt;0.001), but the odds of having both a personal AND family history of PC was not significantly different (p=0.52). CONCLUSION: In the largest CDKN2A c.146T&amp;gt;C study (n=109) to date, MEL was significantly less frequent in individuals with this variant compared to other PVs CDKN2A. A similar, non-significant, trend was seen for PC. Notably, individuals with c.146T&amp;gt;C who developed PC presented at a significantly younger age than individuals with other CDKN2A PVs. The presence of c.146T&amp;gt;C in H/Ls of mostly Mexican ancestry suggests it may be a founder variant. While more research is needed to further refine cancer penetrance and associations, the conservative approach is to manage c.146T&amp;gt;C as per CDKN2A PV guidelines. Given the frequency of this variant in genomic databases, clarifying clinical impact is vital for risk- appropriate management and to reduce existing cancer disparities faced by many H/Ls. Citation Format: Daisy Hernandez, Ashlie Browning, Amber Gemmell, Karlena Lara-Otero, Mariana Niell-Swiller, Kathyrn A. Mraz, Amie Blanco, Yvonne Cardona, Emmeline Chang, Jacob Comeaux, Julie O. Culver, James M. Ford, Natalia Gutierrez, Daniella Kamara, Beth Y. Karlan, Ming Li, Jacqueline Mersch, Qi Nie, Maria L. Wei, Charité N. Ricker. Exploring the cancer phenotype of a potential CDKN2A founder variant, c.146T&amp;gt;C (p.Ile49Thr), in Hispanic/Latinos of predominately Mexican ancestry [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C123.

A Cross-Sectional Study on Oral Potentially Malignant Disorders: Diagnostic Challenges in Early Detection of Dysplasia and the Role of Velscope.

The oral cancer burden has become a global challenge in the present scenario. Early diagnosis of oral potentially malignant disorders (OPMDs) with dysplasia is crucial to increasing the overall survival rate of the patients. Efficient chairside techniques are much needed to enhance diagnostic efficacy at early stages. This study evaluates the effectiveness of Velscope in detecting dysplastic lesions and analyzes the impact of lifestyle factors on the prevalence and progression of oral potentially malignant disorders among 40 participants. A cross-sectional study was conducted with 40 participants diagnosed with OPMDs. Participants underwent a Velscope examination followed by incisional biopsy and histopathological evaluation. Data on lifestyle factors such as tobacco, alcohol, pan, and gutka use were collected through self-reported questionnaires. Data were analyzed to assess Velscope efficacy and correlations between lifestyle risk factors and lesion sites. Statistical analysis was performed using SPSS statistics for Windows (version 26.0, IBM Corp., Armonk, NY). The significance level was fixed at 5% (α=0.05). The data analysis of the study revealed that Velscope showed a sensitivity of 88.89% and a specificity of 46.15% (p = 0.013). The positive predictive value (PPV) of the Velscope was 77.42%, and the negative predictive value (NPV) was 66.67%. Overall, the diagnostic accuracy of the Velscope in this study was 75.0%. Cohen's kappa of 0.381 indicated moderate agreement with biopsy results. Biopsy results showed no statistically significant correlation was found between dysplasia and lesion site, gender, smoking, alcohol, or pan use except for gutka users, who had a significantly higher rate of dysplasia (p = 0.027). Velscope demonstrated high sensitivity but moderate specificity in detecting dysplasia, emphasizing its role as an adjunctive tool in early detection and delineation of oral lesions in conjunction with biopsies for accurate diagnosis. The higher rate of positive results for dysplasia among gutka users suggests that focused public health interventions are needed to address significant lifestyle risk factors, which in turn could reduce malignant transformations in OPMDs.

Melanoma in situ and low risk pT1a melanoma: Need for new diagnostic terminology

Melanoma incidence has risen rapidly, at least until recently, while mortality has changed only a little, a phenomenon suggestive of overdiagnosis, which can be defined as the diagnosis as “melanoma” of a lesion that would not have had the competence to cause death or symptoms even if it had not been excised. Overdiagnosis has been attributed to efforts at early diagnosis (“overdetection”), and to changes in criteria resulting in diagnosis as melanoma of lesions previously termed nevi (“overdefinition”). In terms of overdefinition, there is evidence that criteria for the histopathologic diagnosis of melanoma has changed over a period of approximately two decades. Specialization may play a role in overdefinition; research has shown that when pathologists interpret the same lesion, dermatopathologists are more likely to diagnose low stage (AJCC T1a) melanomas and general/surgical pathologists are more likely to diagnose atypical nevi. An important subset that contributes to overdiagnosis is those melanomas that lack the property of tumorigenic vertical growth phase, thus lacking metastatic competence, and perhaps not warranting diagnosis as overt melanomas. Studies have defined subsets of patients with very low stage lesions diagnosed as melanomas in which observed survival has been 100%. In the past, many of these lesions would have been diagnosed as nevi, constituting overdefinition. Other key characteristics for very low risk (or no risk) lesions that are currently termed invasive “melanomas” include low Breslow thickness, Clark's level II invasion, absence of mitoses, and clinically, lack of observed or experienced dynamic changes. We propose a provisional terminology for diagnosing extremely low risk subgroups as “Melanocytic neoplasms of low malignant potential”, aimed at reducing the negative personal and social effects of a cancer diagnosis for patients whose health and wellbeing are in reality not affected by an overdiagnosed “melanoma”. With additional confirmation and appropriate consensus, it is likely that some of these subgroups can be reclassified as atypical or dysplastic nevi.

PRAME Immunohistochemistry in Thin Melanomas Compared to Melanocytic Nevi.

PRAME (PReferentially expressed Antigen in Melanoma) immunohistochemistry has proven helpful in distinguishing malignant from benign melanocytic tumors. We studied PRAME IHC expression in 46 thin melanomas and 39 melanocytic nevi, mostly dysplastic nevi. Twenty-six percent (26.09%) of the melanomas showed diffuse PRAME staining in over 76% of the tumor cells (4+), and 34.78% of the melanomas showed PRAME expression in over 51% of the tumor cells (3+ or 4+), while 8% were entirely negative for PRAME. No melanocytic nevi were PRAME 4+ or 3+. More than half of the nevi (64%) were entirely negative for PRAME staining, and 36% of the nevi showed staining expression in 1-25% (1+) or 26-50% of the cells (2+). No nevi were stained with a color intensity of 3, while 16.67% of the melanomas were stained with this color intensity. Most nevi (78.57%) were stained with an intensity of 1. With a lower positivity threshold, sensitivity increases with still reasonable specificity. The best accuracy was obtained for the 2+ positivity threshold. In conclusion, PRAME staining helps distinguish thin melanomas from dysplastic nevi. However, the threshold of positivity should be lowered in order not to miss thin melanomas.