[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.

Surgery or Not? A Systematic Review of Facial Congenital Melanocytic Nevi Treatment Patterns and Outcomes.

BACKGROUND: Treatment management for congenital melanocytic nevi (CMN) on the face (FCMN) is highly variable and requires a thorough assessment of multiple factors. To date, a systematic review of FCMN treatment is lacking. The purpose of the present study was to elucidate the frequency, variety, and outcomes of treatment modalities for FCMN with different levels of complexity. METHODS: A comprehensive review of Pubmed, Embase, and Google Scholar databases from 1950 to 2022 was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles reporting on FCMN treatment approaches, outcomes, and associated complications were screened and data were extracted according to inclusion criteria. Data were tabulated for thematic analysis of FCMN treatment types, anatomic locations, outcomes, and complications. RESULTS: Of the 561 studies retrieved, 34 met inclusion criteria including 19 surgical treatments, 14 nonsurgical treatments, and one combined surgical and nonsurgical treatment study, totaling 356 patients. The majority of treated FCMN were small-to-medium-sized (56%). Facial CMN treated conservatively were mostly located on the cheek (27%) and/or perinasal region (21%), whereas FCMN treated with surgery were primarily located in the periorbital region (44%) and/or the cheek (17%). Across all treatment cohorts, 22% of patients experienced at least one complication, with 12% of complications experienced by patients treated by surgery. CONCLUSIONS: There is a greater need for standardized FCMN nomenclature that encompasses nevi pattern, dimensions, anatomical coverage, and quantitative measurements of treatment outcome. Future studies should focus on identifying anatomic locations of FCMN that are more prone to complications and determine which treatment approach optimizes outcomes.

Expert Agreement on the Presence and Spatial Localization of Melanocytic Features in Dermoscopy.

Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. In this study, we attempted to evaluate agreement among experts on exemplar images not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least 1 of 31 melanocytic-specific features were submitted by 25 world experts as exemplars. Using a web-based platform that allows for image markup of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with eight achieving excellent agreement (Gwet's AC >0.75) and seven of them being melanoma-specific features. These features were peppering/granularity (0.91), shiny white streaks (0.89), typical pigment network (0.83), blotch irregular (0.82), negative network (0.81), irregular globules (0.78), dotted vessels (0.77), and blue-whitish veil (0.76). By utilizing an exemplar dataset, a good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication, and machine learning experiments.

Perifollicular linear projections: A dermatoscopic criterion for the diagnosis of lentigo maligna on the face.

BACKGROUND: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose. OBJECTIVE: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)" as a diagnostic criterion for LM on the face. METHODS: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis. RESULTS: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles" on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P < .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0]). LIMITATIONS: Retrospective study. CONCLUSION: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model.

[MOCK MOLE: PRODUCING SYNTHETIC IMAGES THAT RECAPITULATE CONFOCAL PATTERNS OF MELANOCYTIC NEVI VIA DEEP-LEARNING MODELS].

INTRODUCTION: Melanocytic nevi present microscopic patterns, which differ in their associated melanoma risk, and can be non-invasively recognized under Reflectance Confocal Microscopy (RCM). AIMS: To train a Generative Adversarial Network (GAN) deep-learning model to produce synthetic images that recapitulate RCM patterns of nevi, enabling reliable classification by human readers and by a Convolutional Neural Network (CNN) computer model. METHODS: A dataset of RCM images of nevi, presenting a uniform pattern, were chosen and classified into one of three patterns - Meshwork, Ring or Clod. Images were used for training a GAN model, which in turn, produced synthetic images recapitulating RCM patterns of nevi. A random sample of synthetic images was classified by two independent human readers and by a CNN model. Human and computer-model classifications were compared. RESULTS: The training set for the GAN model included 1496 RCM images, including 977 images (65.3%) with Meshwork pattern, 261 (17.4%) with Ring and 258 (17.2%) with Clod pattern. The GAN model produced 6000 synthetic RCM-like images. Of these, 302 images were randomly chosen and classified by human readers, including 83 (27.5%) classified as Meshwork, 131 (43.4%) as Ring, and 88 (29.1%) as Clod pattern. Human inter-observer concordance in pattern classification was 91.7%, and human-to-CNN concordance was 87.7%. CONCLUSIONS: We demonstrate feasibility of producing synthetic images, which recapitulate RCM patterns of nevi and can be reproducibly recognized by human readers and by deep-learning models. Synthetic image datasets may allow teaching RCM patterns to novices, training of computer models, and data sharing between research centers.

Diagnostic delay, comorbid hidradenitis suppurativa and the prognostic value of bacterial culture in folliculitis decalvans: A cohort study.

BACKGROUND: Folliculitis decalvans (FD) is a type of primary neutrophilic cicatricial alopecia often leading to irreversible hair loss. Data on its epidemiology, clinical features, outcomes, and prognostic factors are limited. OBJECTIVE: To evaluate a cohort of patients with FD and identify characteristics of severe disease and prognostic factors which impede remission. PATIENTS AND METHODS: This retrospective cohort study included 192 patients diagnosed with FD and followed for at least six months at a tertiary center between 2010 and 2020. RESULTS: There was a diagnostic delay averaging 22.2 (± 29.7) months. Comorbid follicular occlusion disorders were common. Bacterial cultures were positive in 45.6% of the cases, with Staphylococcus (S.) aureus being the most common pathogen. Severe disease was associated with comorbid hidradenitis suppurativa and a positive bacterial culture, particularly S. aureus. 50.7% of patients experienced complete remission: 32% within the first six months of treatment and 18.7% later during follow-up. Relapses were frequent. Negative prognostic factors for achieving remission included younger age and a positive bacterial culture. CONCLUSIONS: There is a need for the education of dermatologists to reduce the diagnostic delay. Screening FD patients for comorbid hidradenitis suppurativa and obtaining bacterial cultures is important for treatment planning.

Reflectance confocal microscopy of facial neoplasms: Follicular involvement as a clue to diagnosis.

BACKGROUND: Facial skin is characterized by high density of follicles. Facial neoplasms may present overlapping clinical and dermoscopic findings. Our goal was to evaluate and compare, via reflectance confocal microscopy (RCM), follicular involvement in facial neoplasms. METHODS: We retrospectively searched our image database, between January 2008 and December 2020, for all facial lesions with (1) a standardized set of clinical, dermoscopic, and RCM images, and (2) a biopsy-proven diagnosis of lentigo maligna/lentigo maligna melanoma (LM/LMM, n = 39), basal cell carcinoma (BCC, n = 51), squamous cell carcinoma in situ (SCCIS, n = 5), actinic keratosis (AK, n = 11), and lichen-planus-like keratosis (LPLK, n = 18). Two readers jointly evaluated the RCM images for a set of predefined features of follicular involvement. RESULTS: Diffuse obliteration of follicles was frequent in BCC (88%), while follicular infiltration by refractile dendritic cells and/or by bright round nucleated cells was common in melanoma (90% and 44%, respectively). Extension of atypical keratinocytes down follicles was more prominent among SCCIS than AK (80% vs. 45%, p = 0.01). In most LPLK (89%), there was follicular sparing. CONCLUSIONS: Evaluation of RCM criteria centering on the follicles can be useful in the differential diagnosis between common facial neoplasms.

Indications for Digital Monitoring of Patients With Multiple Nevi: Recommendations from the International Dermoscopy Society.

Introduction: In patients with multiple nevi, sequential imaging using total body skin photography (TBSP) coupled with digital dermoscopy (DD) documentation reduces unnecessary excisions and improves the early detection of melanoma. Correct patient selection is essential for optimizing the efficacy of this diagnostic approach. Objectives: The purpose of the study was to identify, via expert consensus, the best indications for TBSP and DD follow-up. Methods: This study was performed on behalf of the International Dermoscopy Society (IDS). We attained consensus by using an e-Delphi methodology. The panel of participants included international experts in dermoscopy. In each Delphi round, experts were asked to select from a list of indications for TBSP and DD. Results: Expert consensus was attained after 3 rounds of Delphi. Participants considered a total nevus count of 60 or more nevi or the presence of a CDKN2A mutation sufficient to refer the patient for digital monitoring. Patients with more than 40 nevi were only considered an indication in case of personal history of melanoma or red hair and/or a MC1R mutation or history of organ transplantation. Conclusions: Our recommendations support clinicians in choosing appropriate follow-up regimens for patients with multiple nevi and in applying the time-consuming procedure of sequential imaging more efficiently. Further studies and real-life data are needed to confirm the usefulness of this list of indications in clinical practice.

Predictors of adherence to Narrowband ultraviolet B first-month treatment dosage plan.

BACKGROUND: The adherence to a narrowband ultraviolet B (NB-UVB) treatment plan is derived, in large part, from the patient's skin tolerance to the phototherapy dose. At present, the initial and first-month incremental phototherapy doses are determined prior to treatment initiation based on the patient's Fitzpatrick skin phototyping. OBJECTIVES: To identify variables that predict adherence to NB-UVB first-month treatment dosage plan. METHODS: Charts of 1000 consecutive patients receiving NB-UVB at a hospital-based phototherapy unit were retrospectively analyzed. We included patients receiving NB-UVB for atopic dermatitis, psoriasis, vitiligo, and mycosis fungoides. The first-month NB-UVB treatment plan was determined based on the patient's Fitzpatrick phototype. Adherence to treatment was defined as receiving at least 80% of the planned first-month cumulative dose. We compared adherent vs. non-adherent patient groups for age, sex, Fitzpatrick phototype, presence of freckles, nevus count category, and type of dermatological disease. RESULTS: The study included 817 eligible patients, mean age 40 (2-95) years; 54% men; 32% had Fitzpatrick phototype I-II. Distribution by diagnosis was atopic dermatitis (29%), psoriasis (27%), vitiligo (23%), and mycosis fungoides (21%). Adherence to NB-UVB treatment plan was observed in 71% of patients. Adherence decreased with age, with 7% decrease per year (P = 0.03) and was higher among mycosis fungoides patients (77.3%) compared to all other diagnoses (69.8%; P = 0.02). CONCLUSIONS: Adherence to NB-UVB treatment may be related to age and diagnosis. Fitzpatrick phototype-based first-month treatment plans should be modified accordingly.

Reflectance Confocal Microscopy Findings in a Small-Diameter Invasive Melanoma.

The diagnosis of a small-diameter melanoma may be challenging. We report the case of a 57-year-old man with a small pigmented papular lesion (2.5-mm diameter) that was suspicious on dermoscopy. A more confident differential diagnosis between an atypical nevus and a melanoma was necessary for correct management. Reflectance confocal microscopy (RCM) allowed a confident diagnosis in this lesion, which was an invasive melanoma with 0.3-mm Breslow thickness. This case highlights the benefit of RCM to reach a confident diagnosis and correct management of a small-diameter invasive melanoma.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

BACKGROUND: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. OBJECTIVE: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). METHODS: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. RESULTS: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar ("brush-like") pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. LIMITATIONS: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. CONCLUSION: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar ("brush-like") pattern is a suggestive feature of congenital and congenital-type NMN.

Morphological features of benign pigmented ear lesions: a cross-sectional study.

BACKGROUND: The morphology of benign pigmented lesions on the ears has been scarcely studied. METHODS: We prospectively screened all patients presenting to a pigmented lesion clinic at a tertiary academic hospital, between November 2015 and August 2016, for the presence of benign pigmented ear lesions. Clinical and dermoscopic images were obtained for all lesions. Additionally, we performed a retrospective analysis of reflectance confocal microscopy (RCM) of benign pigmented ear lesions and a retrospective analysis of clinical and dermoscopic findings of biopsy-confirmed ear melanomas. RESULTS: In total, 165 patients (median age 48, 53% female) contributed 708 benign pigmented ear lesions to the study. Participants with multiple body nevi and those with an atypical nevus phenotype (multiple body nevi and ≥ one atypical nevus) had a higher mean number of ear lesions than those without multiple body nevi (4.5 and 5.4 vs. 3.9, P < 0.05). The most common diagnoses were nevus (35%) and solar lentigo (34%), followed by pigmented lentiginous macules (PLM) (27%). Dermoscopically scattered pigmented small globules/dots were observed in 30% of nevi and 17% of PLMs. RCM analysis of 24 ear lesions showed a comparable frequency of RCM-clods between nevi and PLMs. Analysis of 29 ear melanomas revealed larger lesions with more complex dermoscopic patterns. CONCLUSION: Multiple body nevi, and particularly an atypical nevus phenotype, were associated with having more pigmented ear lesions. Based on RCM analysis, PLMs of the ear likely represent small nevi. Ear melanomas tend to be larger and dermoscopically complex compared to ear nevi.

Deep Learning for Basal Cell Carcinoma Detection for Reflectance Confocal Microscopy.

Basal cell carcinoma (BCC) is the most common skin cancer, with over 2 million cases diagnosed annually in the United States. Conventionally, BCC is diagnosed by naked eye examination and dermoscopy. Suspicious lesions are either removed or biopsied for histopathological confirmation, thus lowering the specificity of noninvasive BCC diagnosis. Recently, reflectance confocal microscopy, a noninvasive diagnostic technique that can image skin lesions at cellular level resolution, has shown to improve specificity in BCC diagnosis and reduced the number needed to biopsy by 2-3 times. In this study, we developed and evaluated a deep learning-based artificial intelligence model to automatically detect BCC in reflectance confocal microscopy images. The proposed model achieved an area under the curve for the receiver operator characteristic curve of 89.7% (stack level) and 88.3% (lesion level), a performance on par with that of reflectance confocal microscopy experts. Furthermore, the model achieved an area under the curve of 86.1% on a held-out test set from international collaborators, demonstrating the reproducibility and generalizability of the proposed automated diagnostic approach. These results provide a clear indication that the clinical deployment of decision support systems for the detection of BCC in reflectance confocal microscopy images has the potential for optimizing the evaluation and diagnosis of patients with skin cancer.

Reflectance confocal microscopy terminology glossary for melanocytic skin lesions: A systematic review.

BACKGROUND: There is lack of uniformity in the reflectance confocal microscopy (RCM) terminology for melanocytic lesions. OBJECTIVE: To review published RCM terms for melanocytic lesions and identify redundant, synonymous terms. METHODS: A systematic review of original research articles adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was conducted until August 15, 2018. Two investigators gathered all published RCM terms used to describe melanoma and melanocytic nevi. Synonymous terms were grouped based on similarity in definition and in histopathologic correlation. RESULTS: Out of 156 full-text screened articles, 59 studies met the inclusion criteria. We identified 209 terms; 191 (91.4%) corresponding to high-magnification/cellular-level terms and 18 (8.6%) corresponding to low-magnification/architectural patterns terms. The overall average use frequency of RCM terms was 3.1 times (range, 1-31). By grouping of individual RCM terms based on likely synonymous definitions and by eliminating terms lacking clear definition, the total number of RCM terms could be potentially reduced from 209 to 40 terms (80.8% reduction). LIMITATIONS: Non-English and non-peer-reviewed articles were excluded. CONCLUSIONS: This systematic review of published RCM terms identified significant terminology redundancy. It provides the basis for subsequent terminology consensus on melanocytic neoplasms.

Dermoscopic and clinical predictors of reflectance confocal microscopy patterns of typical nevi on the back and legs: A cross-sectional study.

BACKGROUND: Nevus phenotype is a marker of melanoma risk. In vivo prediction of microscopic pattern is needed to more precisely classify nevi. OBJECTIVE: To identify dermoscopic and clinical predictors of microscopic patterns of typical nevi. METHODS: We used reflectance confocal microscopy (RCM) to classify microscopic patterns of nevi. We prospectively accrued adults presenting for periodic skin screening and imaged, with dermoscopy and RCM, 3 randomly selected nevi from the upper and lower back and lower extremity. RCM patterns were classified into ring, clod, meshwork, and composite types. Logistic regression was used to identify best predictors of RCM pattern. RESULTS: The study included 310 nevi from 112 participants (mean age 44 years; 51 women). Dermoscopic reticular pattern correlated most frequently (59.9%) with RCM ring pattern, dermoscopic globular with RCM composite (56.6%) and RCM clod (35.9%), dermoscopic complex with RCM composite (76.3%), and dermoscopic homogenous with RCM clod (50.8%). Integrating dermoscopic pattern with contour, diameter, color, and anatomic location of nevi improved prediction of microscopic patterns beyond dermoscopy alone. The dermoscopic clinical regression model correctly classified lesions to RCM ring versus RCM clod in 90% and to RCM ring versus RCM composite patterns in 81%. LIMITATIONS: The study was restricted to adults, back and lower extremities, and typical nevi. CONCLUSIONS: Integrating dermoscopic patterns with clinical attributes may improve prediction of microscopic patterns of nevi.

Reflectance confocal microscopy: Principles, basic terminology, clinical indications, limitations, and practical considerations.

Reflectance confocal microscopy (RCM) is a noninvasive imaging tool used for in vivo visualization of the skin. It has been extensively studied for use in the evaluation of equivocal cutaneous neoplasms to decrease the number of biopsy procedures in patients with benign lesions. Furthermore, its applications are broadening to include presurgical cancer margin mapping, tumor recurrence surveillance, monitoring of ablative and noninvasive therapies, and stratification of inflammatory disorders. With the approval of category I Current Procedural Terminology reimbursement codes for RCM image acquisition and interpretation, use of this technology has been increasingly adopted by dermatologists. The first article in this 2-part continuing medical education series highlights basic terminology, principles, clinical applications, limitations, and practical considerations in the clinical use of RCM technology.

Reflectance confocal microscopy: Diagnostic criteria of common benign and malignant neoplasms, dermoscopic and histopathologic correlates of key confocal criteria, and diagnostic algorithms.

Reflectance confocal microscopy (RCM) is a high-resolution, noninvasive tool that is currently approved by the US Food and Drug Administration for obtaining and interpreting images of the skin and cutaneous neoplasms with the goal of decreasing unnecessary biopsy procedures in patients with benign lesions. The second article in this continuing medical education series focuses on identifying key criteria for the diagnosis of common skin cancers-melanoma, basal cell carcinoma, and squamous cell carcinoma. We contrast these findings with RCM features of common benign lesions-melanocytic nevi, solar lentigo, seborrheic keratosis, lichen planus-like keratosis, and sebaceous hyperplasia. We also correlate the dermoscopic and histopathologic findings with the RCM features.