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An epidermal nevus is a common birthmark that causes the skin to be a different texture than the rest of the skin. It is often seen at birth or in early childhood., (© 2023 The Society for Pediatric Dermatology.)

Since the late 1970s, the diagnosis and management of dysplastic nevi have been areas fraught with controversy in the fields of dermatology and dermatopathology. Diagnostic uncertainty and lack of standardized nomenclature continue to propagate confusion among clinicians, dermatopathologists, and patients. In part I of this CME review article, we summarize the historical context that gave rise to the debate surrounding dysplastic nevi and review key features for diagnosis, classification, and management, as well as epidemiology. We discuss essentials of clinical criteria, dermoscopic features, histopathologic features, and the diagnostic utility of total body photography and reflectance confocal microscopy in evaluating dysplastic nevi, with emphasis on information available since the last comprehensive review a decade ago., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Paget's disease of the breast is a rare type of cancer that affects the skin of the nipple and usually the areola. At the same time, most patients also have one or more tumors in the immediate vicinity of the focus of mammary Paget's disease. This tumor must be distinguished from normal or atypical Toker cells, and also differentiated from diseases such as Bowen's disease of the nipple and melanocytic lesions of the nipple and areola region, including nipple melanoma and BAP1-inactivated nevus (Wiesner nevus). Currently, there is no routine pathological diagnostic algorithm for these conditions. The aim of the work is to formulate a clear clinical and morphological algorithm for diagnosing Paget's disease of the breast and Toker cells, Bowen's disease of the nipple and areola, as well as melanoma and BAP1-inactivated nevi of the above localizations. Surgical material obtained from patients with Paget's disease of the breast (18), Toker cells of the nipple (2), Bowen's disease of the nipple (6), melanoma of the nipple (1), BAP1-inactivated nevus (1) was studied. The material was examined histologically with hematoxylin and eosin staining, Alcian blue and PAS reaction, as well as immunohistochemically with the following panel of antibodies: CD138, p53, CK8, CK7, HER2/neu, EMA, HMB-45, Melan A, S-100, p63, p16 and BAP1. An easy-to-learn pathoanatomical algorithm for diagnosing Paget's cancer has been developed, which will be especially useful for pathologists who encounter pathology of the nipple and areola in their work.

BACKGROUND Nevus lipomatosus superficialis (NLS) is a rare benign hamartomatous lesion characterized by adipocyte infiltration into the dermal layer of the skin. Clinically, there are 2 types of NLS lesions: the classical type and the solitary type. The solitary type of NLS is significantly more common in women, typically presents after age 30 years, and occurs most often in the inner thighs. This lesion is often mistaken for similar cutaneous lesions, including but not limited to acrochordons, fibrolipoma, neurofibromatosis, and lymphangioma. There is limited information in the literature on unique presentations of this rare lesion. CASE REPORT We present a case of a 26-year-old woman worried about a pedunculated papule in a fluid-filled capsule on her right inner thigh. She reported that the lesion doubled in size within 48 h prior to presentation. The lesion was biopsied in the clinic and pathology showed lobules of adipose cells in the dermis surrounded by collagen fibers and vascularity consistent with a diagnosis of inflamed NLS. Upon follow-up 2 weeks later, there were no signs of recurrence. CONCLUSIONS It was hypothesized that the unique presentation of a fluid-filled capsule surrounding a nevus lipomatosus superficialis occurred acutely following torsion of the pedunculated lesion. In addition to the patient's history of frictional rub between the thighs, histologic signs of lymphocytic infiltration in the dermis and edematous stroma supported the claim of torsional origins. The unique presentation of NLS in a fluid-filled capsule is not often discussed in the literature, and we hope this report will aid providers in identifying such lesions in the clinic.

Skin cancer occurrences increase exponentially worldwide due to the lack of awareness of significant populations and skin specialists. Medical imaging can help with early detection and more accurate diagnosis of skin cancer. The physicians usually follow the manual diagnosis method in their clinics but nonprofessional dermatologists sometimes affect the accuracy of the results. Thus, the automated system is required to assist physicians in diagnosing skin cancer at early stage precisely to decrease the mortality rate. This article presents an automatic skin lesions detection through a microscopic hybrid feature set and machine learning-based classification. The employment of deep features through AlexNet architecture with local optimal-oriented pattern can accurately predict skin lesions. The proposed model is tested on two open-access datasets PAD-UFES-20 and MED-NODE comprising melanoma and nevus images. Experimental results on both datasets exhibit the efficacy of hybrid features with the help of machine learning. Finally, the proposed model achieved 94.7% accuracy using an ensemble classifier. RESEARCH HIGHLIGHTS: The deep features accurately predicted skin lesions through AlexNet architecture with local optimal-oriented pattern. Proposed model is tested on two datasets PAD-UFES-20, MED-NODE comprising melanoma, nevus images and exhibited high accuracy., (© 2022 Wiley Periodicals LLC.)

Background: Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare skin disease characterized by pruritic erythematous scaly plaques distributed along the lines of Blaschko. Two cases of ILVEN with CARD14 mutations and one case with a GJA1 mutation have been previously reported., Objective: To elucidate the genetic cause of a cohort of patients diagnosed based on clinical and histopathological evaluation with ILVEN., Methods: We recruited patients diagnosed with ILVEN based on clinical and histopathological criteria. Exome sequencing of affected skin with or without blood/saliva was performed and germline and somatic pathogenic variants were identified., Results: Five patients were enrolled. All had skin lesions from birth or early childhood. Two patients developed psoriasis vulgaris after the diagnosis of ILVEN. The first had a germline heterozygous CARD14 mutation and a post-zygotic hotspot mutation in KRT10. The histopathologic evaluation did not show epidermolytic hyperkeratosis. The second had a post-zygotic hotspot mutation in HRAS. Her ILVEN became itchy once psoriasis developed. One patient was re-diagnosed with linear porokeratosis based on a germline mutation in PMVK and a post-zygotic second-hit mutation. Two patients were re-diagnosed with congenital hemidysplasia with ichthyosiform nevus and limb defect nevus based on germline NSDHL mutations., Conclusion: ILVEN is a clinical descriptor for a heterogenous group of mosaic inflammatory disorders. Genetic analysis has the potential to more precisely categorize ILVEN and permits pathogenesis-directed therapies in some cases., (© 2022 Wiley Periodicals LLC.)

Background: Histopathological assessment of melanoma and other melanocytic skin lesions can be difficult and can vary between pathologists., Material and Method: Histopathological slides of 196 melanocytic skin lesions from 2009 and 2018-2019 were obtained from the archive of the Department of Pathology at Oslo University Hospital and classified into six diagnostic categories: 1) benign nevus, 2) irregular/dysplastic nevus, i.e. dysplastic nevus with moderate atypia, 3) nevus with severe atypia, i.e. dysplastic nevus with severe atypia, 4) melanoma in situ, 5) superficial spreading or lentiginous melanoma and 6) nodular melanoma. The slides were then examined independently and blindly by three experienced pathologists and categorised in the same way. Interobserver agreement was assessed with Cohen's kappa, and agreement with the original diagnosis was assessed by the proportion of assessments in the same diagnostic category., Results: The kappa values for the assessments from the three pathologists ranged from 0.45 to 0.50. The proportion of reassessments in agreement with the original diagnostic category was 85.7 % (95 % CI 75.7 to 92.1), 29.2 % (19.9 to 40.5), 27.8 % (20.9 to 36.0), 78.3 % (70.4 to 84.5), 81.2 % (73.7 to 86.9) and 93.3 % (82.1 to 97.7), respectively, i.e. highest for nodular melanoma. The proportion of reassessments in which the diagnosis was more serious or less serious than the original diagnosis was higher and lower, respectively, for slides from 2009 than for slides from 2018-2019., Interpretation: The differences between the pathologists' assessments and deviations from the original diagnoses can be explained by poorly reproducible diagnostic criteria, diagnostic entities with overlapping morphology and increasing awareness of early signs of malignancy. Some evolution in diagnostic practice cannot be ruled out.

Background: Melanomas, the most common human malignancy, are primarily diagnosed visually, beginning with an initial clinical screening and followed potentially by dermoscopic analysis, a biopsy, and histopathological examination. We aimed to systematically review the performance and quality of machine learning-based methods in distinguishing melanoma and benign nevus in the relevant literature., Method: Four databases (Web of Science, PubMed, Embase, and the Cochrane library) were searched to retrieve the relevant studies published until March 26, 2022. The Predictive model Deviation Risk Assessment tool (PROBAST) was used to assess the deviation risk of opposing law., Result: This systematic review included thirty researches with 114007 subjects and 71 machine learning models. The convolutional neural network was the main machine learning method. The pooled sensitivity was 85% (95% CI 82-87%), the specificity was 86% (82-88%), and the C -index was 0.87 (0.84-0.90)., Conclusion: The findings of our study showed that ML algorithms had high sensitivity and specificity for distinguishing between melanoma and benign nevi. This suggests that state-of-the-art ML-based algorithms for distinguishing melanoma from benign nevi may be ready for clinical use. However, a large proportion of the earlier published studies had methodological flaws, such as lack of external validation and lack of clinician comparisons. The results of these studies should be interpreted with caution., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Suli Li et al.)

Background: Proteus syndrome is characterized by a progressive segmental or patchy growth of bone, skin, adipose tissue, and central nervous system, associated with a wide range of neoplasms, pulmonary pathology, and thrombotic risk. The main histological findings are diffuse patchy overgrowth of skin and subcutaneous tissue, plantar cerebriform connective tissue nevus, and ossification defects. Case report: We present a patient that met the clinical and histological criteria necessary for the diagnosis of the disease. He required multiple surgical interventions, including amputation of the right foot. Genetic evaluation confirmed an AKT1 mutation. Discussion: CLOVES syndrome, neurofibromatosis 1 or PTEN hamartoma tumor syndrome are partially superimposable entities to Proteus syndrome and may generate diagnostic doubt. Although the clinical criteria and histologic findings are indicative, the diagnostic confirmation of this entity is genetic.

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus (EN) syndrome, featured by co-occurrence of speckled lentiginous nevus (SLN) and nevus sebaceous (NS). The underlying mechanism has not been clarified. Pathogenic mutations in HRAS, KRAS and BRAF gene are recently recognized as the genetic cause of PPK. Here we present a case of Chinese PPK with a mosaic mutation in HRAS gene. Physical examination of the 4-year-old male proband showed NS locating on the scalp, with EN and SLN on trunk and extremities. Except congenital fundus vascular tortuosity, no evidence of extracutaneous abnormalities was found in this case. A rare heterozygous missense c. 181 C>A mosaic mutation in HRAS was identified in samples from NS, EN and pigmented nevus using next-generation sequencing and Sanger sequencing. Meanwhile, no mutation was found in the non-lesion skin, hair follicle, or blood DNA. Recent breakthrough in clinical manifestation, genetic mutation and prognosis of PPK is also reviewed., (© 2022 Japanese Dermatological Association.)

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., Competing Interests: Conflicts of interest None disclosed., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

We explored the capability of low-frequency Electron Paramagnetic Resonance (EPR) to noninvasively detect melanin (a stable semiquinone free radical) in the human skin. As previous in vitro studies on biopsies suggested that the EPR signal from melanin was different when measured in skin melanomas or benign nevi, we conducted a prospective first-in-man clinical EPR study in patients with skin lesions suspicious of melanoma. EPR spectra were obtained using a spectrometer operating at 1 GHz, with a surface coil placed over the area of interest. Two clinical studies were carried out: 1) healthy volunteers (n = 45) presenting different skin phototypes; 2) patients (n = 88) with skin lesions suspicious of melanoma (n = 100) requiring surgical resection. EPR data obtained before surgery were compared with histopathology results. The method was not sensitive enough to measure differences in melanin content due to changes in skin pigmentation. In patients, 92% of the spectra were analyzable. The EPR signal of melanin was significantly higher (p < 0.0001) in melanoma lesions (n = 26) than that in benign atypical nevi (n = 62). A trend toward a higher signal intensity (though not significant) was observed in high Breslow depth melanomas (a marker of skin invasion) than in low Breslow lesions. To date, no naturally occurring free radicals have been detected by low-frequency EPR systems adapted for clinical studies. Here, we demonstrated for the first time the ability of this technology to detect an endogenous free radical, opening new avenues for evaluating clinical EPR as a potential aid in the diagnosis of pigmented skin lesions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Spitzoid melanocytic neoplasms are a diagnostically challenging class of lesions in dermatopathology. Recently, molecular assays and immunohistochemical markers have been explored as ancillary methods to assist in the diagnostic workup. Specifically, preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is a nuclear stain commonly positive in melanomas, but not in nevi. This study investigates PRAME immunoreactivity (≥75% positive nuclear staining in tumor cells) in a set of 59 spitzoid melanocytic neoplasms with known clinical outcomes. We compared PRAME status with (1) the clinical outcomes, (2) the morphologic diagnoses, and (3) the status of TERT promoter mutation. Regarding clinical outcomes, 3 cases developed metastatic disease, of which 2 expressed diffusely positive PRAME staining. Of the 56 cases that did not show evidence of metastasis, 6 expressed diffusely positive PRAME staining. Morphologically, diffusely positive PRAME staining was seen in 7 of 21 cases (33.3%) diagnosed as melanoma and only 1 benign tumor 1 of 38 (2.6%). There were 4 of 8 cases with a TERT promoter mutation which were diffusely PRAME-positive compared with 4 of 51 cases without TERT promoter mutation ( P = 0.001). Our results show a statistically significant correlation between PRAME expression and the diagnosis, outcome, and TERT promoter mutation status of atypical spitzoid melanocytic neoplasms, suggesting immunohistochemistry for PRAME can help support a suspected diagnosis. However, because of occasional false-positive and negative test results, correlation with the clinical and histologic findings as well as results from other tests is needed for the interpretation of diagnostically challenging spitzoid melanocytic neoplasms., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Differential diagnosis of extrafacial flat pigmented lesions with dermoscopic reticular and/or homogeneous pattern is challenging. Dendritic cells upon reflectance confocal microscopy (RCM) still represent a pitfall. This study aims to determine the role of dendritic cells upon RCM in the epidermis and dermo-epidermal junction (DEJ), together with common RCM features for melanoma and nevi, in dermoscopically equivocal extrafacial flat pigmented lesions. A retrospective evaluation of RCM images of melanocytic extrafacial flat pigmented lesions with reticular and/or homogeneous dermoscopic pattern and with histopathological diagnosis, was performed. A multivariate model of RCM features was used to obtain a score of independent risk factors. A total of 698 lesions were included. Increasing patient age, epidermal dendritic cells, many dendritic cells in the DEJ (>30%) and many (>5/mm 2 ) round atypical cells were independent risk factors for melanoma. Edged papillae and melanophages were indicative of nevus. A score based on these features was developed to assist in melanoma differential diagnosis. The RCM observation of abundant (>30%) dendritic cells in the DEJ is highly suggestive of malignity. This independent risk factor should also be considered for improved differential diagnosis of extrafacial melanoma., (© 2022 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

A case of phakomatosis pigmentovascularis (PPV) type III a with a zosteriform distribution of nevus spilus as the main manifestation was reported. A 41-year-old man was born with a zosteriform distribution of pigmented rash on the left half-body, namely upper limb, shoulder and back. Physical examination revealed light brown pigments in a giant zosteriform distribution on the extensor side of the left upper limb and the left shoulder and back, with scattered brown spots and patches of variant sizes on the surface, which are consistent with the appearance of nevus spilus (NS). A relatively small area of dark red patch occurred on the left anterior shoulder, which showed telangiectasia and fading after pressing. It was consistent with the performance of a port-wine stain (PWS). Dermoscopy showed a clearer appearance and localized fusion of blood vessels and pigmented patch. He has no systemic involvement. The patient was diagnosed with phakomatosis pigmentovascularis type Ⅲa. NS and PWS can be treated with lasers if required., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The diagnosis of nodal nevi (NN) is challenging as they mimic melanoma metastases (MM), with a detection rate mostly ranging between 1% and 11% in sentinel lymph node biopsy (SLNB). Herein, we assessed the incidence of NN and the association with the clinical-pathological features of primary melanoma, adopting the updated European Organisation for Research and Treatment of Cancer (EORTC) protocol for SLNB., Methods: All cases of paired melanoma and SLNB were retrospectively evaluated (April 2019-May 2020). Appropriate statistical tests were adopted, with significant variables included in the logistic regression model., Results: 81 patients and a total of 186 lymph nodes (LNs) were included. Eleven patients had only NN and 4 had both NN and MM (18.5%); 29 LNs (15.6%) showed at least one NN and 12 (6.5%) showed more than one NN (a total amount of 43 NN was detected). All NN and none MM stained for p16. NN were associated with age < 60 years (p: 0.042), no ulceration (p: 0.025) and nevus-associated melanoma (NAM) (p: 0.018), with this latter being the only predictor at the logistic regression model (p: 0.022)., Conclusions: The updated EORTC protocol shows a high number of NN and highlights a strong association with NAM., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Becker nevus (BN) is a benign cutaneous smooth muscle hamartoma that presents with a hyperpigmented patch or plaque with or without hypertrichosis.1 BN may be associated with ipsilateral breast hypoplasia or other musculoskeletal abnormalities, an association which has been termed Becker nevus syndrome (BNS).

Nevus lipomatosus cutaneous superficialis (NLCS) is a rare idiopathic cutaneous hamartoma characterized by ectopic clusters of mature adipose tissues in dermis. It is classified into two types. Classical type presenting as multiple lesions with onset at birth or within third decade of life and solitary type with onset between third to sixth decade of life. Here we present a case of 45 years female with adult onset, asymptomatic, grouped, skin colored, soft sessile growth in zosteriform pattern on left buttock. We here intend to report rare case of classical Nevus Lipomatosus Cutaneous Superficialis.

Ichthyosis and deafness syndrome is a group of devastating genodermatoses caused by heterozygous mutations in GJB2, encoding the gap junction protein connexin 26. These syndromes are characterized by severe skin disease, hearing loss, recurrent infections, and cutaneous neoplasms. Cutaneous somatic mutations in the same gene are associated with porokeratotic eccrine ostial dermal duct nevus. Here we report a family in which a parent presented with localized epidermal nevus and his child suffered with hystrix-like ichthyosis with deafness. Histologic examination of the parent's cutaneous lesion revealed verrucous epidermal nevus without features of porokeratotic eccrine ostial dermal duct nevus. Genetic analysis identified the same pathogenic variant, GJB2 c.148G>A (p.D50N), in DNA extracted from the parent's cutaneous lesion and the child's leukocytes, but not in the parent's leukocytes. This study expands the phenotypic heterogeneity of GJB2 mosaic variants in addition to porokeratotic eccrine ostial dermal duct nevus, and emphasizes the importance of molecular diagnosis of mosaic skin diseases considering the risk of severe inherited diseases in the offspring., (© 2021 Japanese Dermatological Association.)

Naevus lipomatosus cutaneous superficialis (NLCS) of Hoffman-Zurhelle is a rare hamartomatous benign condition first described in 1921. Two clinical variants have been described: a classical form of multiple yellow papules that coalesce to form larger plaques with segmental distribution, and a solitary form also known as pedunculated lipofibroma. We present a case of early-stage NLCS with characteristic histopathological and dermoscopic features., (© 2021 British Association of Dermatologists.)

The work-up of melanocytic tumors has undergone significant changes in the last years following the exponential growth of molecular assays. For the practicing pathologist it is often difficult to sort through the myriad of different tests available currently for clinical use. The molecular tests used in melanocytic pathology can be broadly divided into 4 categories: (i) Tests useful in the differential diagnosis of nevus versus melanoma (primarily used as an aid in the diagnosis of histologically ambiguous melanocytic tumors), (ii) Tests that predict prognosis in melanoma, (iii) Tests useful in the classification of melanocytic tumors and (iv) Tests that predict response to systemic therapy in melanoma. This review will present an updated overview of major ancillary tests used in clinical practice., (© 2021 John Wiley & Sons Ltd.)

Background: Cutaneous melanoma accounts for the majority of skin cancer-related deaths. Readily identifiable phenotypic characteristics and total body nevus count (TBNC) >50 are among the most important risk factors for cutaneous melanoma. Implementation of nevus self-count procedures and self-assessment of phenotypic traits as part of skin self-examination could be an excellent screening tool for identifying an at-risk target population., Objectives: Objectives of the study were to assess the skills of a central Italian and eastern Spanish population sample to recognize their skin lesions via the submission of a self-assessment questionnaire and to explore which self-assessment questionnaire item combination best predicts the high-risk condition of TBNC >50., Methods: Patients aged ≥18 years filled a self-assessment questionnaire, autonomously and prior to the dermatological visit. Subsequently, dermatologists performed total body skin examination and reported patients' skin lesions on a separate questionnaire., Results: We reported fair to moderate patient-dermatologist agreement for skin lesion self-assessment. The item number of nevi on the back was the single questionnaire item most accurately predicting TBNC >50. The high-sensitivity and high-specificity classification and regression tree models for the prediction of TBNC >50 displayed different items combinations; the item nevus on the back was always the first and most important predictor in both our models., Conclusions: Patients were partially able to provide correct estimation of their whole-body nevus self-count. The item nevi on the back seems to be the first and most important predictor of TBNC >50 across our models. Delivery of high-sensitivity and high-specificity prediction models based on our questionnaire item combination may help defining a high-risk target population., (© 2022 S. Karger AG, Basel.)

Aim: Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Multiple international studies have described the challenge of providing accurate and reproducible histopathological assessments of melanocytic lesions, highlighting the need for new diagnostic tools including disease-specific biomarkers. Previously, a 38-miRNA signature (MEL38) was identified in melanoma patient plasma and validated as a novel biomarker. In this study, MEL38 expression in solid tissue biopsies representing the benign nevi to metastatic melanoma spectrum is examined. Patients & methods: Nanostring digital gene expression assessment of the MEL38 signature was performed on 308 formalin-fixed paraffin-embedded biopsies of nevi, melanoma in situ and invasive melanoma. Genomic data were interrogated using hierarchical clustering, univariate and multivariate statistical approaches. Classification scores computed from the MEL38 signature were analyzed for their association with demographic data and histopathology results, including MPATH-DX class, AJCC disease stage and tissue subtype. Results: The MEL38 score can stratify higher-risk melanomas (MPATH-Dx class V or more advanced) from lower-risk skin lesions (class I-IV) with an area under the curve of 0.97 (p < 0.001). The genomic score ranges from 0 to 10 and is positively correlated with melanoma progression, with an intraclass correlation coefficient of 0.85 with stage 0-IV disease. Using an optimized classification threshold of ≥2.7 accurately identifies higher-risk melanomas with 89% sensitivity and 94% specificity. Multivariate analysis showed the score to be a significant predictor of malignancy, independent of technical and clinical covariates. Application of the MEL38 signature to Spitz nevi reveals an intrasubtype profile, with elements in common to both nevi and melanoma. Conclusion: Melanoma-specific circulating miRNAs maintain their association with malignancy when measured in the hypothesized tissue of origin. The MEL38 signature is an accurate and reproducible metric of melanoma status, based on changes in miRNA expression that occur as the disease develops and spreads. Inclusion of the MEL38 score into routine practice would provide physicians with previously unavailable, personalized genomic information about their patient's skin lesions. Combining molecular biomarker data with conventional histopathology data may improve diagnostic accuracy, healthcare resource utilization and patient outcomes.

Artificial intelligence (AI) utilizes computer algorithms to carry out tasks with human-like intelligence. Convolutional neural networks, a type of deep learning AI, can classify basal cell carcinoma, seborrheic keratosis, and conventional nevi, highlighting the potential for deep learning algorithms to improve diagnostic workflow in dermatopathology of highly routine diagnoses. Additionally, convolutional neural networks can support the diagnosis of melanoma and may help predict disease outcomes. Capabilities of machine learning in dermatopathology can extend beyond clinical diagnosis to education and research. Intelligent tutoring systems can teach visual diagnoses in inflammatory dermatoses, with measurable cognitive effects on learners. Natural language interfaces can instruct dermatopathology trainees to produce diagnostic reports that capture relevant detail for diagnosis in compliance with guidelines. Furthermore, deep learning can power computation- and population-based research. However, there are many limitations of deep learning that need to be addressed before broad incorporation into clinical practice. The current potential of AI in dermatopathology is to supplement diagnosis, and dermatopathologist guidance is essential for the development of useful deep learning algorithms. Herein, the recent progress of AI in dermatopathology is reviewed with emphasis on how deep learning can influence diagnosis, education, and research., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/objective: Proteus syndrome, caused by a mosaic activating AKT1 variant, typically presents in toddlers with progressive, asymmetric overgrowth of the skin and bones. We aimed to define the spectrum of dermatologic disease in individuals with genetically confirmed Proteus syndrome., Methods: We conducted a retrospective review of records from dermatologic examinations of individuals evaluated at the NIH with a molecular diagnosis of Proteus syndrome. The types, prevalence, and localization of dermatologic findings were assessed., Results: Fifty-one individuals (29 males, 22 females, mean age: 9 years) with clinical features of Proteus syndrome had the mosaic c.49G>A, p.Glu17Lys AKT1 variant. Fifty (98%) had at least one cutaneous feature constituting current clinical diagnostic criteria, including vascular malformations in 42 (82%), epidermal nevus in 41 (80%), volar cerebriform connective tissue nevi in 34 (67%), and adipose dysregulation in 30 (59%). Forty-nine (96%) had at least one dermatologic finding not included within the diagnostic criteria, including confluent volar skin-colored to hypopigmented papules or nodules (n = 33, 65%), papules or nodules on the digits or face (n = 27, 53%), and nonlinear epidermal nevi (n = 15, 29%). Other frequently observed features include nail changes (n = 28, 55%), hyperpigmented macules (n = 27, 53%), patchy dermal hypoplasia (n = 18, 35%), gingival/oral mucosal overgrowth (n = 17, 33%), hypopigmented macules (n = 16, 31%), dental enamel changes (n = 9, 18%), acrochordons (n = 6, 12%), and lingual overgrowth (n = 4, 8%)., Conclusions: The range of mucocutaneous features occurring in Proteus syndrome is broader than previously considered. These observations may assist in earlier diagnosis and management and provide novel insights regarding the pathogenesis of the condition., (© Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Early diagnosis when melanoma is still small and thin is essential for improving mortality and morbidity. However, the diagnosis of small size melanoma might be particularly difficult, not only clinically but also dermoscopically. This study aimed to define clinical and dermatoscopic parameters in the diagnosis of suspicious pigmented cutaneous lesions with a diameter of ≤ 6mm and determine the sensitivity, specificity, positive and negative predictive values as well as the accuracy of each clinical and dermatoscopic criterion. This is a transversal, descriptive and analytical study of dermatoscopic analysis with the gold standard being the pathologic examination obtained from the excisional biopsy of suspicious melanocytic lesions with a diameter of ≤ 6mm. Trunk and limb lesion data from a public health service and a private clinic were prospectively collected from 2011 to 2017 by a unique observer. In total, 481 melanocytic lesions were included, with 73.8% being ≤ 4mm in diameter. Overall, 123 were diagnosed as melanoma, 56.0% in situ and 22.0% as thin melanomas (Breslow index 0.1 to 1.0mm). Melanoma presented symmetry in 53.7% of cases, regular borders in 54.5% and a single color in 60.2%. Regarding evolution, 13.8% of melanomas versus 10.9% of benign lesions (p = 0.116) were new by comparing photos from baseline with photos from the follow-up. The majority of melanomas (65%) were found on the limbs compared to 37.2% of the benign lesions at this location (p<0.001). A multiple logistic regression model adjusted for age, gender and location was created. The independent variables associated with the diagnosis of melanoma ≤ 6mm, adjusted for age, gender and location, were: streaks (adjusted Odds Ratio [aOR] 2.5; 95% CI 1.3-4.7; p = 0.006), and the presence of a structureless area (aOR 2.2, 95% CI 1.2-4.0, p = 0.011). Conversely, a symmetric typical pigment network was a protection variable (aOR 0.4, 95% 0.7-0.9, p = 0.040). In conclusion, dermatoscopic criteria have been identified which help to diagnose cases of small size melanoma. These include streaks and structureless areas that can be taken, particularly in consideration for the diagnosis of this subset of small difficult melanomas., Competing Interests: The authors have declared that no competing interests exist.