Dysplastic Lesions Research Articles

Association between continuous cessation or reduction of drinking alcohol and improvement of multiple dysplastic lesions in patients with esophageal squamous cell carcinoma after endoscopic resection.

Multiple development of squamous cell carcinoma (SCC) in the upper aerodigestive tract has been explained by the 'field cancerization phenomenon' associated with alcohol drinking. Squamous dysplastic lesion is clinically visualised as a Lugol-voiding lesion (LVL) by chromoendoscopy. Whether cessation or reduction of alcohol drinking improves multiple LVL and reduces the risk of field cancerization has not been elucidated. We analysed 330 patients with newly diagnosed superficial esophageal SCC (ESCC) enrolled in the cohort study. The grade of LVL was assessed in all patients every 6months. We instructed the patients to stop smoking and drinking and recorded their drinking and smoking status every 6months. Among 330 patients, we excluded 98 with no LVL or no drinking habit. Of the remaining 232 patients, 158 continuously ceased or reduced their drinking habit. Patients who ceased or reduced their drinking habit significantly showed improvement in the grade of LVL. Multivariate analysis showed that continuous cessation or reduction of drinking habit improved the grade of LVL (hazard ratio [HR] = 8.5, 95% confidence interval [CI] 1.7-153.8, p = 0.0053). Higher grade of LVL carried a high risk of multiple ESCC and head and neck SCC (HNSCC) (HR = 3.7, 95% CI 2.2-6.4, p < 0.0001). Improvement in LVL significantly decreased the risk of multiple ESCC and HNSCC (HR = 0.2, 95% CI 0.04-0.7, p = 0.009). This is the first report indicating that field cancerization was reversible and cessation or reduction of drinking alcohol could prevent multiple squamous dysplastic lesion and multiple ESCC and HNSCC development. UMIN000001676.

PRAME Immunohistochemistry for Distinguishing Vulvar and Vaginal Melanoma From Benign Melanocytic Nevi.

Vulvovaginal melanoma (VVM) is a rare but deadly disease, accounting for 5% of all vulvar malignancies, with a 5-yr survival rate of only 47% for all stages of the disease. VVM is a distinct subset of melanoma, with a unique genomic profile and underlying pathogenesis unassociated with sun exposure. Distinguishing these rare malignancies from very common pigmented lesions of the vulva and vagina is challenging as histologic features often overlap between entities. PReferentially expressed Antigen in MElanoma (PRAME) is a melanoma-associated protein, and immunohistochemistry (IHC) for PRAME distinguishes cutaneous, oral mucosal, and retinal melanoma from atypical nevi. Given the biological differences between VVM and cutaneous melanoma, the utility of PRAME IHC for the diagnosis of VVM is unknown. We accrued a cohort of 20 VVM and 21 benign vulvar melanocytic nevi. We found that nuclear PRAME IHC staining with 4+ intensity was present in 85% of the VVM and 0% of the nevi. With the assistance of PRAME IHC, we found evidence of close or positive margin involvement in 3 of 10 cases where margins were originally diagnosed as negative for melanoma in situ. Our study is the first to assess PRAME IHC in a cohort of VVM cases and provides confidence for using PRAME IHC to assist with diagnosis and margin assessment in this rare disease.

Translated article] Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study

Background and objectiveAtypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. Material and methodsWe conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. ResultsA total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P<.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). ConclusionsThe main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network.

Dye Chromoendoscopy Outperforms High-Definition White Light Endoscopy in Dysplasia Detection for Patients With Inflammatory Bowel Disease: An Updated Meta-Analysis of Randomized Controlled Trials.

Whether dye spray chromoendoscopy (DCE) adds value in surveillance colonoscopy with high-definition (HD) scopes remains controversial. This updated meta-analysis compares dysplasia detection using DCE and high-definition white light endoscopy (HD-WLE) in patients with inflammatory bowel disease (IBD) undergoing surveillance colonoscopy. A comprehensive search was performed for randomized controlled trials (RCT) comparing HD-WLE and DCE in patients with IBD. The primary outcome was to compare the proportion of patients with at least 1 dysplastic lesion detected by DCE vs HD-WLE. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using the random-effects model, with I2 > 60% indicating substantial heterogeneity. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence (CoE). Six RCT involving 978 patients were analyzed (DCE = 479 vs HD-WLE = 499 patients). DCE detected significantly more patients with dysplasia than HD-WLE (18.8% vs 9.4%), OR 1.94 (95% CI 1.21-3.11, I2 = 28%, P = 0.006, high CoE). This remained significant after excluding 2 RCT published as abstracts. A sensitivity analysis excluding a noninferiority RCT with a single experienced operator eliminated the results' heterogeneity, OR 2.46 (95% CI 1.56-3.90, I2 = 0%). Although high-grade dysplasia detection was numerically higher in the DCE group (2.8% vs 1.1%), the difference was statistically insignificant, OR 2.21 (95% CI 0.64-7.62, I2 = 0%, low CoE). Our updated meta-analysis supports DCE as a superior strategy in overall dysplasia detection in IBD, even with HD scopes. When expertise is available, DCE should be considered for surveillance colonoscopy in patients with high-risk IBD, with the acknowledgment that virtual chromoendoscopy shows equivalence in recent studies. Further multicenter trials with multiple endoscopists with varying expertise levels and longer-term outcome data showing a reduction in cancer or cancer-related death are needed.

Cervical cancer screening in Doukoula- the far north region of Cameroon

With a morbidity of 600,000 cases and 375,000 lethal cases per year, cervical cancer (CC) is the second most prevalent gynecological cancer all over the world. Because of the absence of a widespread preventative campaign, CC has a significant impact in developing countries. An acceptable, efficient, and cost-effective screening technique in low-income nations is the visual inspection of the cervix with acetic acid and Lugol's iodine. By conducting a CC screening exercise in Doukoula, we hope to ignite the culture of CC screening campaigns in the Kar-Hay health district in the extreme north of Cameroon. Methods: Doukoula District Hospital hosted a one-week CC screening and treatment exercise from the 3rd of November 2021 to the 9th of November 2021. Treatments for dysplastic lesions included thermal coagulation and LEEP. To improve cervix visibility, a MobileODT colposcopic gadget was used. Results: 306 women in all agreed to take part in the study. A screening uptake of 82% was achieved, with 251 of them completing the process. 7 (2.8%) declared being HIV positive. The mean age of this study was 37.33. We had 31 cases of dysplasia (12.75%) and 1 case of cervical cancer (0.4%). Out of 251 participants, only 3 (1.2%) had undergone CC screening, and just one had received an HPV vaccination in the past. Five CIN-1 cases, aged 25 years and below, did not receive any treatment. The 11 cases of CIN 1 aged over 25 years and the 13 CIN 2 cases were eligible for thermotherapy. The two CIN-3 cases had a LEEP, and a sample was taken for pathology analysis. 20 presented themselves for treatment. The total uptake for treatment was 76.72%. Conclusion: Despite growing recognition that cervical cancer is a disease that can be prevented, relatively little is being done to increase vaccine, screening, and treatment rates. While waiting for the development of efficient national screening systems, the use of a “see and treat” screening strategy is a reasonable method of approach for the prevention of CC in low-income countries.

Evaluation of BIRC6 Expression in Oral Squamous Cell Carcinoma, Epithelial Dysplasia, Lichen Planus with and without Dysplasia, and Hyperkeratosis

Background: BIRC6, regarded as the pivotal member of the inhibitor of the apoptosis (IAP) family, has been linked to the development of different types of cancer in humans. The objective of this study was to examine the expression of BIRC6 in various oral conditions, including OLP with dysplasia (OLPD), hyperkeratosis (HK), OLP, epithelial dysplasia (ED), and oral squamous cell carcinoma (OSCC), to investigate its potential involvement in the development of OSCC and the pathogenesis and malignant transformation of OLP, which is known as a precancerous condition. Methods: In this retrospective cross-sectional study, 99 cases, consisting of 19 cases of OSCC, 21 cases of ED, 23 cases of OLP, 20 cases of OLPD, and 16 cases of HK as the control group, were investigated regarding BIRC6 expression by immunohistochemical staining. After that, the immunohistochemical expression of BIRC6 in the epithelial compartment was analyzed. Statistical analysis was performed to investigate the relationship between the expression of BIRC6 and clinicopathological variables. The statistical analysis of the data involved the use of one-way ANOVA, post hoc Tukey, Kruskal–Wallis, Chi-square, Spearman’s correlation, and Mann–Whitney tests. The significance level was set at p &lt; 0.05. Results: Positive BIRC6 staining was found in 91.7% of the subjects of OLP, 88.1% of HK, 86.1% of ED, 93% of OLPD, and 94.7% of OSCC. OSCC showed the highest BIRC6 expression (p = 0.00). The average total staining score was remarkably greater in OSCC and dysplastic lesions compared with HK (p = 0.00, p = 0.00). Conclusions: While the current study suggested that BIRC6 may play a role in the tumorigenesis of OSCC, its role in the malignant transformation of OLP has yet to be definitively established.

The divisive dysplastic nevus: Searching for concordance in discord.

The divisive dysplastic nevus: Searching for concordance in discord.

Validation of a new optical diagnosis training module to improve dysplasia characterization in inflammatory bowel disease: a multicenter international study

Background and aimsInflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aim to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPTIC-IBD. MethodsWe designed a web-based learning module that includes surveillance principles, optical diagnostic methods, approach to characterization, classifications of colonic lesions, utilizing still images and videos. We invited gastroenterologists from Canada, Italy, and the UK, with a wide range of experience. Participants reviewed 24 educational videos of IBD colonic lesions, predicted histology, and rated their confidence. The primary endpoint was to improve accuracy in detecting dysplastic lesions following training on the platform. Furthermore, participants were randomized 1:1 to get additional training or not, with a final assessment occurring after 60 days. Diagnostic performance for dysplasia and rater confidence were measured. ResultsOne hundred seventeen participants completed the study and were assessed for the primary endpoint. Diagnostic accuracy improved from 70.8% to 75.0% (p 0.002) following training, with the greatest improvements seen in less experienced endoscopists. Improvements in both accuracy and confidence were sustained after 2 months of assessment, although the group randomized to receive additional training did not improve further. Similarly, participants’ confidence in characterizing lesions significantly improved between pre- and post-course (p<0.001), and it was sustained after 2 months of assessment. ConclusionsThe OPTIC-IBD training module demonstrated that an online platform could improve participants’ accuracy and confidence in the optical diagnosis of dysplasia in patients with IBD. The training platform can be widely available and improve endoscopic care for people with IBD. Clinicaltrials.gov NCT04924543.

IDH1-mutated Crohn's disease-associated small bowel adenocarcinomas: Distinctive pathological features and association with MGMT methylation and serrated-type dysplasia.

Patients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD-SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1-mutated CrD-SBAs. An international multicentre series of surgically resected CrD-SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6-methylguanine-DNA methyltransferase (MGMT) and long interspersed nuclear element-1 (LINE-1) methylation were compared between IDH1-mutated and IDH1 wild-type CrD-SBAs. Ten (20%) of the 49 CrD-SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild-type cases, IDH1-mutated CrD-SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1-mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non-conventional subtype (two serrated dysplastic lesions and one goblet cell-deficient dysplasia). In particular, non-conventional serrated dysplasia was significantly associated with IDH1-mutated CrD-SBAs (P = 0.029). No significant cancer-specific survival difference between IDH1-mutated CrD-SBA patients and IDH1 wild-type CrD-SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16-1.89; P = 0.313). IDH1-mutated CrD-SBAs, which represent approximately one-fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1-mutated non-conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD-SBAs.

Melanoma Skin Cancer Detection using SVM and CNN

In the field of cancer detection and prevention, doctors and patients are facing numerous challenges when it comes to cancer prediction. Melanoma skin cancer is a deadly type of skin cancer with a multitude of variants spread across the world. Traditional methods involved manual inspection followed by various tests of samples. This time-consuming work and inaccurate predictions sometimes risk the overall health of the patient. The two aspects of solving skin cancer detection problems utilising both conventional image-processing techniques and methods based on machine learning and deep learning are elaborated in this article. It gives a review of current skin cancer detection techniques, weighs the benefits and drawbacks of those techniques, and introduces some relevant cancer datasets. The proposed method focuses mainly on Melanoma skin cancer detection and its previous stages (Common Nevus and Atypical Nevus). The methods being proposed employ a blend of colour, texture, and shape characteristics to derive distinguishing attributes from the images. Using CNN (convolutional neural networks) and SVM (support vector machine) algorithms to identify the type of skin cancer the patient is affected with and achieved an accuracy of 92% and 95% respectively.

Publication Trends and Hot Topics in Dysplastic Nevus Research: A 30-Year Bibliometric Analysis.

Dysplastic nevi are pigmented lesions that exhibit clinical and histological features of both common nevi and melanoma. In recent years, there has been an increase in publications on dysplastic nevi. Bibliometric analysis is a method of evaluating trends in large number of publications and identifying popular topics. The objective of this study is to provide an overview of the landscape of publications related to dysplastic nevi, visualize trends and identify popular topics in the literature. Thomson Reuters' Web of Science database was searched with the following query in title, abstract or keywords: TS = ("dysplastic nevus" OR "clark nevus" OR "atypical nevus" OR "dysplastic nevi" OR "clark nevi" OR "atypical nevi"). Time span was set to 1992-2022. Document type was set to Article. Titles, authors, abstracts, institutions, countries, journals, references, and the citation information were recorded. Although the number of publications has declined over time, the USA remains the leading contributor to published articles. Key clusters of frequently used keywords were identified. The Journal of the American Academy of Dermatology had the highest number of published titles. Country and journal analysis were supplemented by co-citation and co-cited reference cluster analysis. Burst analyses revealed authors like Kittler, Argenziano, and Gandini as significant contributors, with their works receiving strong citation bursts extending until the end of the study period. This bibliometric analysis revealed trends and interest pockets in the literature pertaining to dysplastic nevi and melanoma. This study aids in understanding the current research landscape and highlights potential future directions in this field.

Possibilities of fluorescence diagnostics in detecting multicentric focies of cervical dysplasia

Colposcopy allows the examiner to localize potential lesions, assess the severity of the lesion, and obtain a colposcopic guided biopsy. This method has limited sensitivity and specificity, raising serious concerns about the possibility of missing cervical dysplasia. Fluorescent methods for diagnosing precancerous diseases of the cervix and early forms of cancer have an extremely high sensitivity, reaching 90%. The presented results of the study allow us to fully declare the high information content of fluorescent colposcopy in identifying dysplastic lesions on the cervix.

Cervical cancer in Region Skåne, Sweden 2017-2020 after the implementation of primary HPV screening: A quality assurance audit.

Primary human papilloma virus (HPV) screening to detect cervical cancer and dysplastic lesions was implemented in Region Skåne 2017 for women aged 30-70. The aim of this study was to characterize the screening history of women diagnosed with cervical cancer to evaluate the performance of the screening program, as well as to assess the cancer treatments given and shortcomings in the follow-up of women with cervical dysplasia. We performed a quality assurance audit. The data was collected from the National Cervical Cancer Prevention Registry, Region Skåne Labmedicin database and the Melior Journal system in 2017-2020. We identified 247 women diagnosed with invasive cervical cancer in Region Skåne in 2017-2020. Of these, 35 (14.2%) had a screening history over at least two screening rounds before diagnosis. There were 25 (10.1%) women diagnosed with cervical cancer in between screening intervals, i.e., interval cancer. The most common screening history in women with cervical cancer was irregular screening (143, 57.9%), followed by women being above screening age (44, 17.8%). HPV was detected in 96% of the cases, either in cervical cytology or in the tumor tissue. The screening program detected the disease in 96 (38.9%) of the patients, 149 (60.3%) were diagnosed through symptoms and two (0.80%) as a result of incidental findings. The most powerful tool in the prevention of cervical cancer is screening program attendance. Prolongation with HPV screening among elderly women will also reduce the incidence of cervical cancer. Today, such cancers are usually discovered when symptoms appear.

Staining Intensity of P16INK4a and Ki-67 Determine the Grade of Cervical Lesion: An Experience from Single Tertiary Care Centre

Background: Various non-neoplastic and neoplastic lesions occur in cervix. HPV infection plays a major role in genesis of cervical lesions. Although most HPV infections are cleared out, infections with high risk HPVs may persist resulting in cervical dysplastic lesions. Using p16, a surrogate marker for HPV infection and Ki-67, a proliferation marker, along with histopathology, help improve the diagnostic accuracy of these lesions. The aim of the study was to evaluate the expression of p16 and Ki-67 in cervical lesions and association of their staining intensity with the histologic grading. Also to determine the predictive value of these markers in association with the cervical lesions. Methodology: A cross sectional study was carried out in 122 cases which were diagnosed histopathologically and then evaluated for the immunohistochemical expression of p16 and Ki-67 and their staining intensities. Results: The dysplastic lesions comprised of 83.7% cases [29.5% LSIL, 5.7% HSIL, 43.5% SCC and 4.9% adenocarcinoma] and 16.3% had non dysplastic lesions. p16 and Ki-67 expression were seen in 64.7% and 68% cases respectively. The intensity of p16 and Ki-67 expression was scored according to Galgano et al (2010). An increasing intensity of p16 and Ki-67 expression with higher grades of the cervical lesions was noted and this association was found to be statistically significant. (χ2 = 43.46 and p value &lt; 0.0001). Conclusion: Though histopathology is the gold standard, the role of p16 and Ki-67 have emerged as useful adjuncts in detecting the true nature of the cervical lesions. They aid in the proper diagnosis, classification and distinction from non-dysplastic lesions, helping the clinicians in taking prompt action for management of the cases.

Canine elbow realignment osteotomy for treatment of axial humeroradial or humeroulnar incongruency in four dogs

AbstractCanine elbow incongruity is a condition that may be associated with the development of dysplastic lesions of the elbow; namely, medial coronoid process disease, osteochondrosis of the humeral condyle and ununited anconeal process. Axial elbow incongruity (either short radius or short ulna syndrome) may predispose to the development of elbow osteoarthritis. Surgical correction of incongruity has previously been described in an effort to improve lameness and mitigate progression of osteoarthritis, although a system by which to achieve measured and precise adjustment of congruity of both the radius and ulna has been lacking. This case series describes use of a novel acute correction surgery, canine elbow realignment osteotomy for correction of axial elbow incongruency in four dogs.

Mitochondrial DNA content as a biomarker for oral carcinogenesis: correlation with clinicopathologic parameters.

Mitochondrial genome (mtDNA) exhibits greater vulnerability to mutations and/or copy number variations than nuclear counterpart (nDNA) in both normal and cancer cells due to oxidative stress generated by inflammation, viral infections, physical, mechanical, and chemical load. The study was designed to evaluate the mtDNA content in oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). Various parameters were analyzed including its variation with human papillomavirus (HPV) during oral carcinogenesis. The present cross-sectional study comprised of two hundred patients (100 OPMDs and 100 OSCCs) and 100 healthy controls. PCR amplifications were done for mtDNA content and HPV in OPMDs and OSCC using real-time and conventional PCR respectively. The relative mtDNA content was assessed quantitatively and it was observed that mtDNA was greater in OSCC (7.60±0.94) followed by OPMDs (5.93±0.92) and controls (5.37±0.95). It showed a positive linear correlation with habits and increasing histopathological grades. Total HPV-positive study groups showed higher mtDNA content (7.06±1.64) than HPV-negative counterparts (6.21±1.29). An elevated mutant mtDNA may be attributed to increased free radicals and selective cell clonal proliferation in test groups. Moreover, sustained HPV infection enhances tumorigenesis through mitochondria mediated apoptosis. Since, mtDNA content is directly linked to oxidative DNA damage, these quantifications might serve as a surrogate measure for invasiveness in dysplastic lesions and typify their malignant potential.

Minichromosome maintenance protein 5 - a promising prognostic marker of oral epithelial dysplasias and oral squamous cell carcinomas.

Early diagnosis is the single most effective means of reducing the mortality rate of oral cancer. This study was undertaken to assess the expression of minichromosome maintenance protein 5 (MCM5) in oral epithelial dysplasias and oral squamous cell carcinomas (OSCCs) and to evaluate their possible role as a biomarker for early diagnosis and prognosis of OSCC. A retrospective cross-sectional study. The study was conducted to assess the expression of MCM5 immunohistochemically in the tissue samples of oral epithelial dysplasias (n = 27) and OSCCs (n = 30) diagnosed between 2014 and 2019. The difference in the mean nuclear labelling index (LI) between the groups and the subgroups was analysed statistically using the Kruskal-Wallis test and the post hoc test, and the Dunn-Bonferroni multiple comparison analysis was conducted for pairwise comparison between the four main groups and the subgroups. The association between mean MCM5 LI and clinicopathological parameters was analysed using Spearman's rank correlation coefficient. A progressive increase in the nuclear expression of MCM5 protein (P-value <0.001) was noticed from normal oral mucosa through oral epithelial hyperplasia and oral epithelial dysplasia to OSCC. A significant correlation was also observed between the mean nuclear MCM5 LI of OSCC and TNM staging (R2 = 0.268, P = 0.029). Our findings suggest that MCM5 may be of great value in assessing the malignant potential of dysplastic lesions and may serve as biomarker of utility in the early diagnosis and prognosis of OSCC.

Clinical, Morphologic, and Molecular Features of Benign and Intermediate-grade Melanocytic Tumors With Activating Mutations in MAP2K1.

Activating mutations in MAP2K1 can be seen in benign and intermediate-grade melanocytic neoplasms with spitzoid morphology. We analyzed the clinical, histopathologic, and genetic features for 16 cases of benign and intermediate-grade melanocytic tumors harboring activating MAP2K1 mutations. We compared them to Spitz neoplasms with characteristic Spitz fusions or HRAS mutation. We also compared the mutational pattern of benign and intermediate-grade MAP2K1 -mutated neoplasms and melanomas with activating MAP2K1 mutations. Among the 16 cases, the favored morphologic diagnosis was Spitz nevus (8/16), atypical Spitz tumors (6/16), and deep penetrating nevus (2/16). The 2 most common architectural patterns seen included a plaque-like silhouette with fibroplasia around the rete reminiscent of a dysplastic nevus (n=7) or a wedge-shaped or nodular pattern with the plexiform arrangement of the nests aggregating around the adnexa or neurovascular bundle (n=8). The cases with dysplastic architecture and spitzoid cytology resembled dysplastic Spitz nevi. Compared with true Spitz neoplasms, MAP2K1 -mutated neoplasms occurred in older age groups and had more frequent pagetosis and a lower average mitotic count. The most common type of mutation in the benign and intermediate-grade cases in the literature involves an in-frame deletion, while, in melanomas, missense mutations are predominant. Benign and intermediate-grade melanocytic neoplasms with activating mutations in MAP2K1 can have morphologic overlap with Spitz neoplasms. A significant proportion of melanomas also have activating MAP2K1 mutations. In-frame deletions are predominantly seen in the benign and intermediate-grade cases, and missense mutations are predominantly seen in melanomas.

Standardized Computer-Assisted Analysis of 5-hmC Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas.

5-Hydroxymethylcytosine (5-hmC) is an important intermediate of DNA demethylation. Hypomethylation of DNA is frequent in cancer, resulting in deregulation of 5-hmC levels in melanoma. However, the interpretation of the intensity and distribution of 5-hmC immunoreactivity is not very standardized, which makes its interpretation difficult. In this study, 5-hmC-stained histological slides of superficial spreading melanomas (SSM) and dysplastic compound nevi (DN) were digitized and analyzed using the digital pathology and image platform QuPath. Receiver operating characteristic/area under the curve (ROCAUC) and t-tests were performed. A p-value of <0.05 was used for statistical significance, and a ROCAUC score of >0.8 was considered a "good" result. In total, 92 5-hmC-stained specimens were analyzed, including 42 SSM (45.7%) and 50 DN (54.3%). The mean of 5-hmC-positive cells/mm2 for the epidermis and dermo-epidermal junction and the entire lesion differed significantly between DN and SSM (p = 0.002 and p = 0.006, respectively) and showed a trend towards higher immunoreactivity in the dermal component (p = 0.069). The ROCAUC of 5-hmC-positive cells of the epidermis and dermo-epidermal junction was 0.79, for the dermis 0.74, and for the entire lesion 0.76. These results show that the assessment of the epidermal with junctional expression of 5-hmC is slightly superior to dermal immunoreactivity in distinguishing between DN and SSM.

Concordance of Dye-Spraying Chromoendoscopy and Virtual Chromoendoscopy for Colonic Dysplasia Detection in Longstanding Inflammatory Bowel Disease.

In the past, dye-spraying chromoendoscopy was the technique of choice for colonic surveillance in patients with long-standing extensive inflammatory bowel disease. Recent evidence suggests that virtual chromoendoscopy is an equally acceptable technique. Eleven gastroenterologists were given a survey with 20 pairs of pictures from inflammatory bowel disease surveillance colonoscopies (10 with nondysplastic lesions, 5 with dysplastic lesions, and 5 with no lesions). Each pair contained the same image captured during colonoscopy using indigo carmine and narrow-band imaging. For each picture, the gastroenterologist assessed the presence/absence of lesion and, when a lesion was identified, assessed the presence/absence of dysplasia and delineated its margins. To compare lesion and dysplasia detection between techniques, sensitivity, specificity, and interobserver agreement were calculated. The chi-square test was used to assess the accuracy of margins delineation. When assessing lesion and dysplasia detection, similar sensitivity and specificity values were obtained for both techniques. Interobserver agreement analysis revealed that dye-spraying chromoendoscopy and virtual chromoendoscopy had a moderate agreement in lesion detection but, for dysplasia detection, dye-spraying chromoendoscopy had a slight agreement [K = 0.11 (0.03-0.18), P < .01] and virtual chromoendoscopy a fair agreement [K = 0.30 (0.22-0.37), P < .01]. Margin delineation was similar between techniques. Sensitivity and specificity for lesion and dysplasia detection, as well as the accuracy of margins delineation, were similar between dye-spraying chromoendoscopy and virtual chromoendoscopy. Interobserver agreement for dysplasia detection was suboptimal in both techniques; however, it was superior when using virtual chromoendoscopy. These findings suggest that virtual chromoendoscopy constitutes a valid alternative for dysplasia screening in inflammatory bowel disease.