[Circumscribed choroidal hemangioma and non-pigmented choroidal melanoma: clinical, instrumental and molecular genetic features]. / Otgranichennaya gemangioma i bespigmentnaya melanoma khorioidei: kliniko-instrumental'nye i molekulyarno-geneticheskie osobennosti.

Circumscribed choroidal hemangioma (CCH) and early non-pigmented choroidal melanoma (CM) have similar clinical, ultrasound and morphometric features, which in some cases makes their differential diagnosis difficult. There are few studies in the literature devoted to a comparative analysis of the molecular genetic features of CCH and non-pigmented CM, and the results of those studies are contradictory. PURPOSE: This study attempts to develop a method of non-invasive molecular genetic differential diagnostics of CCH and non-pigmented CM. MATERIAL AND METHODS: Based on the results of clinical and instrumental examination methods, 60 patients (60 eyes) with CCH (n=30) and non-pigmented CM (n=30) were included in this prospective study. The control group consisted of 30 individuals without intraocular tumors. Mutations in the GNAQ/GNA11 genes were determined by real-time PCR using the analysis of genomic circulating tumor DNA isolated from peripheral blood plasma. The average follow-up period was 12.1±1.8 months. RESULTS: The study revealed a significant association of mutations in exons 4 and 5 of the GNAQ/GNA11 genes with the presence of non-pigmented CM (27/30; 90%). These mutations were not detected in the group of patients with CCH. Mutations in exons 4 and 5 of the GNAQ/GNA11 genes were also not detected in the control group of healthy individuals. CONCLUSION: This study proposes a method of non-invasive and low-cost differential diagnostics based on molecular genetic analysis and detection of mutations in exons 4 and 5 of the GNAQ and GNA11 genes, which are specific for CM (90%).

Clinical, Morphological and Molecular Features of Spitz tumors.

Spitz tumors represent a heterogeneous group of challenging melanocytic neoplasms, displaying a range of biological behaviors, spanning from benign lesions, Spitz nevi (SN) to Spitz melanomas (SM), with intermediate lesions in between known as atypical Spitz tumors (AST). They are histologically characterized by large epithelioid and/or spindled melanocytes arranged in fascicles or nests, often associated with characteristic epidermal hyperplasia and fibrovascular stromal changes. In the last decade, the detection of mutually exclusive structural rearrangements involving receptor tyrosine kinases ROS1, ALK, NTRK1, NTRK2, NTRK3, RET, MET, serine threonine kinases BRAF and MAP3K8, or HRAS mutation, led to a clinical, morphological and molecular based classification of Spitz tumors. The recognition of some reproducible histological features can help dermatopathologist in assessing these lesions and can provide clues to predict the underlying molecular driver. In this review, we will focus on clinical and morphological findings in molecular Spitz tumor subgroups.

Histopathology of skin melanocytic lesions.

Melanocytic lesions are instable tumors, the genome of which and its changes determinate their morphology and biological properties. Intermediate lesions share histomorphological features of both, nevi and melanoma. Melanocytomas represent a group of them separated on the basis of recent molecular-biological studies. The article summarizes benign, intermediate, malignant and combined melanocytic skin lesions and offers practical recommendations for diagnosis.

Leg skin ulcer with atypical features: vascular wound or advanced melanoma?

BACKGROUND: Leg ulcers have various etiologies, including malignancy, although vascular issues are the most frequent cause. Malignant wounds present diagnostic challenges, with a reported prevalence rate ranging from 0.4% to 23%. This significant variability in reported prevalence appears to be due to the different settings in which data are collected, which suggests potential influence by medical specialty. Consequently, the misdiagnosis of neoplastic ulcers (eg, ulcerated melanoma) as vascular wounds is relatively common, leading to delayed diagnosis, inadequate treatment, and a dramatic worsening of the patient's prognosis. Identifying malignancy in nonresponsive wounds involves recognizing signs such as hypertrophic granulation tissue, bleeding, unusual pigmentation, and raised edges. The appearance of the perilesional skin, together with dermoscopic observation, is also crucial to differentiation. Ultimately, a biopsy may provide valuable diagnostic clarification. CASE REPORT: A case is presented of lower limb melanoma that for years was misdiagnosed as a vascular wound by multiple specialists, with delayed referral to a dermatologist and resulting recognition and diagnosis, at which time nodular satellite metastases were found. Dermoscopy and biopsy confirmed the diagnosis. The disease was already advanced, with in-transit and distant site metastases, and the prognosis was regrettably poor. CONCLUSION: This case underscores the importance of early detection and accurate diagnosis of malignant wounds, emphasizing the need to refer patients with suspicious nonresponsive ulcers to a dermatologist.

Influence of Anatomic Locations of T1b Melanomas and Patient Age on Outcomes.

BACKGROUND: There are no guidelines on when to more strongly recommend sentinel lymph node biopsy (SLNB) for T1b melanomas. OBJECTIVE: To examine whether anatomic locations of T1b melanomas and patient age influence metastases. METHODS: We conducted a retrospective study using data from two hospitals in Los Angeles County from January 2010 through January 2020. RESULTS: Out of 620 patients with primary melanomas, 566 melanomas were staged based on the American Joint Committee on Cancer 8th edition melanoma staging. Forty-one were T1b, of which 13 were located on the face/ear/scalp and 28 were located elsewhere. T1b melanomas located on the face/ear/scalp had an increased risk of lymph node or distant metastasis compared with other anatomic sites (31% vs 3.6%, P=0.028). For all melanomas, the risk of lymph node or distant metastasis decreased with age of 64 years or greater (P<0.001 and P=0.034). For T1b melanomas, the risk of distant metastasis increased with increasing age (P=0.047). LIMITATIONS: Data were from a single county.  Conclusion: T1b melanomas of the face/ear/scalp demonstrated a higher risk of lymph node or distant metastasis and may help guide the recommendation of SLNB, imaging, and surveillance. Younger patients may be more strongly considered for SLNB and older patients with T1b melanomas may warrant imaging.  J Drugs Dermatol. 2024;23(5):306-310. doi:10.36849/JDD.7667.

Malignant melanoma arising in a burn scar.

Secondary malignancies are rare but devastating complications of longstanding burn scars. Squamous cell carcinoma is the most common, followed by basal cell carcinoma and melanomas. There are fewer than 50 total reported cases of malignant melanomas arising in burn scars. We report a case of malignant melanoma arising within a longstanding burn scar confirmed by histology, FISH, and PRAME staining to further characterize melanomas arising in burn scars and to illustrate the diagnostic challenges they present.

[Predicting the effectiveness of organ-preserving treatment of choroidal melanoma using optical coherence tomography data]. / Prognozirovanie effektivnosti organosokhrannogo lecheniya melanomy khorioidei po dannym opticheskoi kogerentnoi tomografii.

Optical coherence tomography (OCT) is currently widely used for the diagnosis of choroidal melanoma (CM), but the problem of predicting the outcomes of planned CM treatment remains unsolved. PURPOSE: This study was conducted to identify OCT signs that adversely affect the outcome of organ-preserving CM treatment. MATERIAL AND METHODS: OCT scan images of 30 patients who underwent organ-preserving treatment and were under observation were selected for this study. Brachytherapy (BT) as monotherapy was performed in 27 patients (in 2 cases - twice, and in 1 case - three times), in one patient - in combination with the previous transpupillary thermotherapy (TTT). Multiple TTT (4 sessions within 4 months) as monotherapy were performed in 2 patients. In 9 cases, a single organ-preserving treatment (BT - 6 patients, TTT - 3 patients) was ineffective. In these cases, the effectiveness of the first stage of organ-preserving treatment was taken into account. RESULTS: Seven signs of an unfavorable prognosis of the performed treatment were identified by analyzis of tomograms and statistical processing of the obtained data. These signs include: the presence of intraretinal edema, detachment of the neuroepithelium (NED) over the tumor, including with a break in the photoreceptors, accumulation of transudate over the tumor, the presence of large cysts, intraretinal cavities and NED near the tumor (secondary retinal detachment). A combination of three or more signs were observed in all cases of inefficiency of the first stage of treatment. Most often, intraretinal edema and NED over the tumor were combined with the accumulation of subretinal transudate and NED near the tumor. The presence of 6 or all 7 signs took place in cases of a negative therapeutic effect after local destruction. CONCLUSION: When planning organ-preserving CM treatment, in addition to biometric parameters, it is necessary to pay special attention to the identification of such morphological signs as NED over and near the tumor, accumulation of transudate under the NED, the presence of intraretinal edema, large intraretinal cysts and cavities.

The Impact of Next-generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Desmoplastic Melanocytic Neoplasms.

Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs). In this study, 20 expert melanoma pathologists rendered a diagnosis on 47 DMNs based on hematoxylin and eosin sections with demographic information. After submitting their diagnosis, the experts were given the same cases, but this time with comprehensive genomic sequencing results, and asked to render a diagnosis again. Identification of desmoplastic melanoma (DM) improved by 7%, and this difference was statistically significant ( P <0.05). In addition, among the 15 melanoma cases, in the pregenomic assessment, only 12 were favored to be DM by the experts, while after genomics, this improved to 14 of the cases being favored to be DM. In fact, some cases resulting in metastatic disease had a substantial increase in the number of experts recognizing them as DM after genomics. The impact of the genomic findings was less dramatic among benign and intermediate-grade desmoplastic tumors (BIDTs). Interobserver agreement also improved, with the Fleiss multirater Kappa being 0.36 before genomics to 0.4 after genomics. NGS has the potential to improve diagnostic accuracy in the assessment of desmoplastic melanocytic tumors. The degree of improvement will be most substantial among pathologists with some background and experience in bioinformatics and melanoma genetics.

Metastatic Melanoma of the Common Bile Duct Presented with Dyspepsia.

Malignant melanoma (MM) is an aggressive tumor that can metastasize to any organ, but biliary tract metastasis is scarce. We describe a very rare case of MM metastasis to the common bile duct (CBD), presented with only dyspeptic symptoms. The patient had mildly elevated alkaline phosphatase and gamma-glutamyl transferase levels. Magnetic resonance cholangiopancreatography demonstrated a dilated common bile duct with a distal stricture. The MM diagnosis was established with the ampulla of Vater biopsy specimens obtained by endoscopic retrograde cholangiopancreatography (ERCP), and the patient's symptoms were resolved after biliary stenting. Both primary CBD cancer and other cancer types like MM that metastasize to CBD can cause obstruction and can be manifested only by dyspeptic symptoms. MM metastasis to CBD can cause obstruction manifested only by dyspeptic symptoms without obstructive jaundice. ERCP can be employed as a promising option for treatment and diagnosis. New-onset dyspeptic symptoms in patients with a history of MM should be investigated thoroughly, especially in the context of biliary metastasis.

The influence of rurality on melanoma diagnosis in Indiana: A retrospective cohort study.

BACKGROUND: Research from across the United States has shown that rurality is associated with worse melanoma outcomes. In Indiana, nearly a quarter of all residents live in rural counties and an estimated 2180 cases of melanoma will be diagnosed in 2023. AIMS: This study examines how geographical location affects the stage of melanoma diagnosis in Indiana, aiming to identify and address rural health disparities to ultimately ensure equitable care. METHODS AND RESULTS: Demographics and disease characteristics of patients diagnosed with melanoma at Indiana University Health from January 2017 to September 2022 were compared using Students t-tests, Wilcoxon tests, chi-squared or Fisher's exact tests. Patients from rural areas presented with more pathological stage T3 melanomas (15.0% vs. 3.5%, p < 0.001) in contrast to their urban counterparts. Additionally, rural patients presented with fewer clinical stage I melanomas (80.8% vs. 89.3%) and more clinical stage II melanomas (19.2% vs. 8.1%), compared to urban patients, with no stage III (p = 0.028). Concerningly, a significantly higher percentage of the rural group (40.7%) had a personal history of BCC compared to the urban group (22.6%) (p = 0.005) and fewer rural patients (78.0%) compared to urban patients (89.4%) received surgical treatment (p = 0.016). CONCLUSION: Patients from rural counties in Indiana have higher pathological and clinical stage melanoma at diagnosis compared to patients from urban counties. Additionally fewer rural patients receive surgical treatment and may be at higher risk of developing subsequent melanomas.

Applications of Data Characteristic AI-Assisted Raman Spectroscopy in Pathological Classification.

Raman spectroscopy has been widely used for label-free biomolecular analysis of cells and tissues for pathological diagnosis in vitro and in vivo. AI technology facilitates disease diagnosis based on Raman spectroscopy, including machine learning (PCA and SVM), manifold learning (UMAP), and deep learning (ResNet and AlexNet). However, it is not clear how to optimize the appropriate AI classification model for different types of Raman spectral data. Here, we selected five representative Raman spectral data sets, including endometrial carcinoma, hepatoma extracellular vesicles, bacteria, melanoma cell, diabetic skin, with different characteristics regarding sample size, spectral data size, Raman shift range, tissue sites, Kullback-Leibler (KL) divergence, and significant Raman shifts (i.e., wavenumbers with significant differences between groups), to explore the performance of different AI models (e.g., PCA-SVM, SVM, UMAP-SVM, ResNet or AlexNet). For data set of large spectral data size, Resnet performed better than PCA-SVM and UMAP. By building data characteristic-assisted AI classification model, we optimized the network parameters (e.g., principal components, activation function, and loss function) of AI model based on data size and KL divergence etc. The accuracy improved from 85.1 to 94.6% for endometrial carcinoma grading, from 77.1 to 90.7% for hepatoma extracellular vesicles detection, from 89.3 to 99.7% for melanoma cell detection, from 88.1 to 97.9% for bacterial identification, from 53.7 to 85.5% for diabetic skin screening, and mean time expense of 5 s.

[COMPREHENSIVE GUIDELINES AND INDICATIONS FOR DIGITAL MONITORING OF PATIENTS AT HIGH-RISK FOR MELANOMA: A POSITION PAPER BY THE ISRAELI ASSOCIATION FOR DERMATOLOGY].

INTRODUCTION: Early detection may lead to reduced morbidity and mortality from melanoma. This study aims to establish guidelines for selecting patients suitable for digital monitoring of skin lesions. METHODS: A literature review was conducted, followed by consensus among experts appointed by the Israeli Dermatology Association. RESULTS: Two effective methods for early melanoma diagnosis were identified: Total-body photography (TBP) and digital dermoscopy. TBP involves capturing clinical images of the entire skin area for long-term monitoring (6-12 months). Digital dermoscopy focuses on close-up images of distinct lesions for short-term monitoring (3-4 months). Various risk factors for melanoma were identified, including genetic and familial factors, as well as demographic and phenotypic characteristics. Based on these risk factors and feasibility of clinical follow-up, a comprehensive list of indications for TBP was developed, categorized into three groups based on the expected level of benefit. Digital dermoscopy surveillance is recommended for patients with flat or slightly raised skin lesions showing dermoscopic features that do not definitively indicate melanoma. DISCUSSION: TBP significantly improves early melanoma detection, enhancing sensitivity and specificity while reducing unnecessary biopsies. However, due to its high cost and limited coverage by the Israeli public health care system, prioritizing patients who would benefit most from TBP is crucial. The compiled list of indications aligns with international recommendations and provides further details within the article.

Prognostic nomograms for predicting long-term overall survival in spindle cell melanoma: a population-based study.

Background: There are few research findings on the survival prognosis of spindle cell melanoma (SCM), which is an unusual kind of melanoma. The purpose of this study was to develop a thorough nomogram for predicting the overall survival (OS) of patients with SCM and to assess its validity by comparing it with the conventional American Joint Committee on Cancer (AJCC) staging system. Methods: The Surveillance, Epidemiology, and End Results database was searched, and 2,015 patients with SCM were selected for the analysis. The patients were randomly divided into training (n = 1,410) and validation (n = 605) cohorts by using R software. Multivariate Cox regression was performed to identify predictive factors. A nomogram was established based on these characteristics to predict OS in SCM. The calibration curve, concordance index (C-index), area under the receiver operating characteristic curve, and decision-curve analysis were utilized to assess the accuracy and reliability of the model. The net reclassification improvement and integrated discrimination improvement were also applied in this model to evaluate its differences with the AJCC model. Results: The developed nomogram suggests that race, AJCC stage, chemotherapy status, regional node examination status, marital status, and sex have the greatest effects on OS in SCM. The nomogram had a higher C-index than the AJCC staging system (0.751 versus 0.633 in the training cohort and 0.747 versus 0.650 in the validation cohort). Calibration plots illustrated that the model was capable of being calibrated. These criteria demonstrated that the nomogram outperforms the AJCC staging system alone. Conclusion: The nomogram developed in this study is sufficiently reliable for forecasting the risk and prognosis of SCM, which may facilitate personalized treatment recommendations in upcoming clinical trials.

Unusual Presentation of Unilateral Choroidal Melanoma with Bilateral Vasculitis in Young Individual: A Case Report and Review of Literature.

Ocular melanoma stands as the predominant primary intraocular malignancy, albeit infrequently exhibiting ipsilateral inflammatory manifestations. In this article, we present an exceptional case involving a middle-aged male who presented with unilateral ocular choroidal melanoma alongside bilateral retinal vasculitis. The patient initially received temporary steroid treatment, followed by brachytherapy, which contributed to the resolution of vasculitis symptoms. The study aims to document the atypical occurrence of bilateral retinal vasculitis, which could potentially masquerade as melanoma, emphasizing the need for heightened vigilance and further investigations when encountering choroidal masses in its presence. Future research endeavors are warranted to better understand the incidence of such occurrences in this context.

Clinical and Histopathological Investigation of Pediatric Melanonychia: A Single-Center Retrospective Case Series.

HYPOTHESIS: The natural history of pediatric melanonychia and the necessity of biopsy for ruling out melanoma are debated in the literature. We hypothesize that there is a low rate of malignant nail pathology among pediatric patients undergoing nail bed biopsy for melanonychia. METHODS: We performed a retrospective chart review of 54 pediatric patients (age <18 years) at a single institution who presented with melanonychia and underwent nail bed biopsy from 2007 to 2022. Data points collected included patient demographics, medical history, physical exam findings, pathology reports, and clinical photos. Univariate and multivariate analyses were performed to assess for risk factors associated with high-risk pathology findings. RESULTS: The average age of melanonychia onset was 5.5 years (SD 4.4). The average age of first biopsy was 7.8 years (SD 4.3). On physical exam, 27 patients had at least four features concerning for melanoma (asymmetry, border irregularity, color heterogeneity, diameter > 1/3 of nail, evolving color, evolving diameter, Hutchinson's sign). The most common pathology diagnoses were melanocytic nevus (35%), atypical intraepidermal melanocytic proliferation (AIMP) with benign features (24%), subungual lentigo (22%), and AIMP with concerning features (17%). There were no cases of melanoma in situ or invasive malignant melanoma. On multivariate regression, the only significant risk factor associated with more concerning pathology (AIMP with concerning features) was the calendar year in which biopsy was performed (coefficient = -0.34, P = 0.016). There was no association between physical exam features and high-risk pathology. Twelve patients had surgical re-excision of the lesion, 6 of which were due to incomplete excision of AIMP with concerning features and 6 of which were due to recurrence. CONCLUSIONS: Our case series did not find any cases of melanoma in situ or malignant melanoma arising from pediatric melanonychia. Atypical intraepidermal melanocytic proliferation with concerning features was associated only with the year in which the biopsy was performed, which may reflect the improved understanding of pediatric melanonychia as often benign despite concerning features on pathology. The decision to perform a nail matrix biopsy in pediatric melanonychia should be based on a collaborative discussion between the patient's parents, dermatologist, and plastic surgeon.

H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma.

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm.