Signalling by senescent melanocytes hyperactivates hair growth.

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma.

DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA hydroxylases. Here, we report that "loss of 5-hmC" is an epigenetic hallmark of melanoma, with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of the 5-hmC landscape in the melanoma epigenome. We show that downregulation of isocitrate dehydrogenase 2 (IDH2) and TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy.

Mosaic RASopathies concept: different skin lesions, same systemic manifestations?

BACKGROUND: Cutaneous epidermal nevi are genotypically diverse mosaic disorders. Pathogenic hotspot variants in HRAS, KRAS, and less frequently, NRAS and BRAF may cause isolated keratinocytic epidermal nevi and sebaceous nevi or several different syndromes when associated with extracutaneous anomalies. Therefore, some authors suggest the concept of mosaic RASopathies to group these different disorders. METHODS: In this paper, we describe three new cases of syndromic epidermal nevi caused by mosaic HRAS variants: one associating an extensive keratinocytic epidermal nevus with hypomastia, another with extensive mucosal involvement and a third combining a small sebaceous nevus with seizures and intellectual deficiency. Moreover, we performed extensive literature of all cases of syndromic epidermal nevi and related disorders with confirmed pathogenic postzygotic variants in HRAS, KRAS, NRAS or BRAF. RESULTS: Most patients presented with bone, ophthalmological or neurological anomalies. Rhabdomyosarcoma, urothelial cell carcinoma and pubertas praecox are also repeatedly reported. KRAS pathogenic variants are involved in 50% of the cases, especially in sebaceous nevi, oculoectodermal syndrome and encephalocraniocutaneous lipomatosis. They are frequently associated with eye and brain anomalies. Pathogenic variants in HRAS are rather present in syndromic keratinocytic epidermal nevi and phacomatosis pigmentokeratotica. CONCLUSION: This review delineates genotype/phenotype correlations of syndromic epidermal nevi with somatic RAS and BRAF pathogenic variants and may help improve their follow-up.

Lipid fingerprint-based histology accurately classifies nevus, primary melanoma, and metastatic melanoma samples.

Probably, the most important factor for the survival of a melanoma patient is early detection and precise diagnosis. Although in most cases these tasks are readily carried out by pathologists and dermatologists, there are still difficult cases in which no consensus among experts is achieved. To deal with such cases, new methodologies are required. Following this motivation, we explore here the use of lipid imaging mass spectrometry as a complementary tool for the aid in the diagnosis. Thus, 53 samples (15 nevus, 24 primary melanomas, and 14 metastasis) were explored with the aid of a mass spectrometer, using negative polarity. The rich lipid fingerprint obtained from the samples allowed us to set up an artificial intelligence-based classification model that achieved 100% of specificity and precision both in training and validation data sets. A deeper analysis of the image data shows that the technique reports important information on the tumor microenvironment that may give invaluable insights in the prognosis of the lesion, with the correct interpretation.

Transcriptome Analysis Identifies Oncogenic Tissue Remodeling during Progression from Common Nevi to Early Melanoma.

Early detection and treatment of melanoma, the most aggressive skin cancer, improves the median 5-year survival rate of patients from 25% to 99%. Melanoma development involves a stepwise process during which genetic changes drive histologic alterations within nevi and surrounding tissue. Herein, a comprehensive analysis of publicly available gene expression data sets of melanoma, common or congenital nevi (CN), and dysplastic nevi (DN), assessed molecular and genetic pathways leading to early melanoma. The results demonstrate several pathways reflective of ongoing local structural tissue remodeling activity likely involved during the transition from benign to early-stage melanoma. These processes include the gene expression of cancer-associated fibroblasts, collagens, extracellular matrix, and integrins, which assist early melanoma development and the immune surveillance that plays a substantial role at this early stage. Furthermore, genes up-regulated in DN were also overexpressed in melanoma tissue, supporting the notion that DN may serve as a transitional phase toward oncogenesis. CN collected from healthy individuals exhibited different gene signatures compared with histologically benign nevi tissue located adjacent to melanoma (adjacent nevi). Finally, the expression profile of microdissected adjacent nevi tissue was more similar to melanoma compared with CN, revealing the melanoma influence on this annexed tissue.

Nevus lipomatosus superficialis: A series of six cases.

Nevus lipomatosus still imposes diagnostic, categorization, and etiologic challenges. Even though an intradermal adipose tissue is a histopathologic prerequisite, the lesions are clinically divided into classic multiple forms and a solitary variant, which some consider a separate so-called lipofibroma clinicopathologic entity. This further complicates the true prevalence, classification and etiopathogenesis of nevus lipomatosus. Case reports and series studies have reflected either consistent or variable and sometimes conflicting clinicopathologic findings. A few have reported electron microscopic findings. Immunohistochemistry is lacking. We report two multiple and four solitary forms of nevus lipomatosus in six patients, highlighting their salient histopathologic features and immunohistochemical profile. Both forms showed intradermal groups of perivascular S100+ lipogenic and CD34+ mesenchymal cells intermixed with scattered CD1a+ and FXIIIa+ dendrocytes, CD3 lymphocytic and CD117 mast cells in a fibromyxoid milieu. Epidermal nevoid and comedonal follicular alterations, attenuated dermal connective tissue and adnexal structures were variably present in both forms. We compared our findings with seven series of studies reporting classic and solitary forms. Both forms showed similar histopathologic findings, comparable clinicopathologic features, predominantly pelvic, and shoulder girdle distribution patterns in bimodal age onsets. Even though some lipomatous skin lesions clinically and histopathologically overlap with nevus lipomatosus, certain findings are helpful distinguishing features. Small intradermal islands of lipocytic fibroplasia have characteristic perivascular milieu that may function as a niche of preadipose CD34 mesenchymal stem cells. They are most likely represented in the dermis of the pelvic and shoulder areas in certain individuals prone to maintain these embryonic reservoirs, which are clinically manifested at different ages. Some may have unifocal or multifocal residues reflecting multiple and solitary forms.

Giant congenital fibroblastic connective tissue nevus associated with vascular anomalies.

We described an unusual combination of fibroblastic connective nevus (FCTN) already present at birth with underlying vascular anomalies. Overall, the lesion appeared as a large purplish-brown mass in the groin region up to the third of the right thigh, with partial spontaneous regression during the first three months of life. The FCTN observed exhibited several unusual characteristics: it was congenital, large in size, and located in the lower limbs. Finally, it represented the first case described in which an FCTN arose in association with vascular anomalies.

Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence.

The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are hallmarks of cancer and chronic circadian rhythm disruption predisposes individuals to tumour development. This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBα (also known as NR1D1) and REV-ERBß (also known as NR1D2), are essential components of the circadian clock. Here we show that two agonists of REV-ERBs-SR9009 and SR9011-are specifically lethal to cancer cells and oncogene-induced senescent cells, including melanocytic naevi, and have no effect on the viability of normal cells or tissues. The anticancer activity of SR9009 and SR9011 affects a number of oncogenic drivers (such as HRAS, BRAF, PIK3CA and others) and persists in the absence of p53 and under hypoxic conditions. The regulation of autophagy and de novo lipogenesis by SR9009 and SR9011 has a critical role in evoking an apoptotic response in malignant cells. Notably, the selective anticancer properties of these REV-ERB agonists impair glioblastoma growth in vivo and improve survival without causing overt toxicity in mice. These results indicate that pharmacological modulation of circadian regulators is an effective antitumour strategy, identifying a class of anticancer agents with a wide therapeutic window. We propose that REV-ERB agonists are inhibitors of autophagy and de novo lipogenesis, with selective activity towards malignant and benign neoplasms.

Clinical and Dermoscopic Insights Into Scalp Nevi in Chinese Children.

BACKGROUND: The presence of scalp nevi in children frequently causes apprehension, leading physicians and parents to consider unnecessary biopsies or excisions of scalp nevi in children. There are limited data on the dermoscopic characteristics of scalp nevi in Chinese children. OBJECTIVE: The aim of this study was to comprehensively analyze the clinical and dermoscopic features of scalp nevi in this specific population of Chinese pediatric patients, with a focus on a single pediatric dermatologic surgery practice. METHODS: This retrospective cohort study investigated patients who underwent surgical excision of scalp nevi. All patients underwent dermoscopy with photographic documentation. RESULTS: Seventy-two scalp nevi in 56 Chinese children were included. Notably, no melanoma cases were detected. The parietal region (35, 48.6%) was the most frequently affected anatomical site. Clinical asymmetry was more prevalent in nevi with a diameter exceeding 6 mm ( p < .05). The predominant dermoscopic pattern observed was the globular pattern (50, 69.4%) while an intriguing rarity of a reverse-eclipse pattern (1, 1.4%). CONCLUSION: This study revealed that scalp nevi in Chinese children usually did not exhibit concerning behavior. Increasing awareness of the clinical characteristics, dermoscopic features, and the natural progression of scalp nevi in children can potentially help reduce unnecessary surgical interventions.

Cutaneous Horn Presentation in Porokeratotic Eccrine Ostial and Dermal Duct Nevus. A Brief Review and Case Report.

ABSTRACT: Porokeratotic eccrine ostial and dermal duct nevus is a rare adnexal hamartoma characterized by the presence of a cornoid lamella exclusively overlying eccrine acrosyringia. Different clinical presentations have been reported in the literature. Here, we report a case of a 6-year-old girl diagnosed with porokeratotic eccrine ostial and dermal duct nevus confirmed by histopathologic study. Atypical lesions are described as whitish, warty-looking neoformations located in the anterolateral region of the right hip (cutaneous horn).

PRAME and Historical Immunohistochemical Antibodies Ki-67, P16, and HMB-45 in Ambiguous Melanocytic Tumors.

ABSTRACT: Ambiguous melanocytic lesions/tumors (AMLs) can be simply described as melanocytic neoplasms that cannot be differentiated as either a melanoma or a nevus. Preferentially expressed antigen in melanoma (PRAME) is a novel antibody that can help differentiate between nevi and melanomas. However, its usefulness remains controversial in AMLs. The aim of this study was to demonstrate the importance of PRAME and diagnostic auxiliary antibodies (Ki-67, p16, HMB-45) in the diagnosis of melanocytic lesions, especially in AMLs. This study included 52 ambiguous melanocytic lesions, 40 nevi, and 40 melanomas. All immunohistochemical studies were performed automatically using the Universal Alkaline Phosphatase Red Detection Kit. Different analytic approaches were used for each antibody based on the literature. Statistically, the multinomial forward stepwise elimination logistic regression analysis was used to create a statistical model to predict the diagnosis of melanocytic lesions based on clinical, morphological, and immunohistochemical data. PRAME positivity was very strong and diffuse in the melanoma group and statistically significantly higher than that of the AML and nevus groups. There was no statistically significant difference between the nevus and AML groups. The Ki-67 proliferation index and HMB-45 staining pattern provided valuable indications for distinguishing between these 3 groups. The P16 antibody was limited in supporting the differential diagnosis. Our statistical model showed that a high mitosis count, central pagetoid spread, and PRAME positivity increased the probability of melanoma against an AML diagnosis. This study showed the advantages of evaluating the PRAME antibody together with morphological features and other immunohistochemical markers (Ki-67 and HMB-45) in the differential diagnosis of melanocytic lesions.

What Is Nevus Simplex?

Nevus simplex, also called a "salmon patch" or "stork bite," is a special mark that some babies are born with. It is very common and doesn't hurt.

¿Qué son los nevos simples?

Los nevos simples, también conocidos como "parches de salmón" o "marcas de la cigüeña", son marcas de nacimiento especial en algunos recién nacidos. Son muy comunes y no causan dolor.

Epidermal nevi and epidermolytic hyperkeratosis: A review of cases, highlighting indications for biopsy and genetics referral.

Epidermal nevi are common benign cutaneous hamartomas that may rarely demonstrate histopathologic evidence of epidermolytic hyperkeratosis (EHK), representing cutaneous mosaicism for pathogenic keratin variants. Rarely, individuals with linear epidermal nevi transmit to their children the inherited form of EHK, also known as epidermolytic ichthyosis, characterized by generalized erythema, blistering, and scaling at birth evolving to widespread hyperkeratosis. We present an updated review of reported cases of linear epidermal nevi with EHK exhibiting transmission of epidermolytic ichthyosis to guide important considerations in the care of individuals with epidermal nevi. Clinical characteristics of linear epidermal nevi do not reliably predict the presence of EHK. All reported cases of transmission to offspring have occurred in individuals with linear epidermal nevi involving more than one anatomic area suggesting increased reproductive risk with involvement of two or more anatomic sites. Therefore, genetics consultation is recommended for these individuals with biopsy-confirmed EHK. For individuals with smaller areas of epidermal nevus involvement, the implications are less well known, though genetics consultation may still be considered for those interested in further discussion of general reproductive risk.

Rate of Benign and Malignant Secondary Tumors Associated With Nevus Sebaceous: A Systematic Review and Meta-Analysis.

BACKGROUND: Nevus sebaceous (NS) is a rare congenital skin lesion affecting approximately 0.3% of all newborns. Although benign, NS lesions can harbor malignant secondary tumors. The published rate of development of these malignant tumors varies. This meta-analysis aimed to identify the rate of malignant and benign secondary neoplasms occurring in NS. METHODS: A literature search was conducted using PubMed, Embase, and Web of Science from inception to April 2023. Eligible studies reported incidence or risk of secondary neoplasms in patients with NS. Two independent reviewers screened studies, extracted data, and assessed the quality of included studies. The primary outcome was the pooled incidence of secondary neoplasms. Studies with sample sizes greater than 50 patients were eligible for meta-analysis using the random-effects model. RESULTS: Twenty-eight studies were identified, 22 of which were eligible for meta-analysis. The overall rate of secondary neoplasms was 12.8% (95% confidence interval [Cl], 9.2%-17.6%). The rates of development of malignant and benign tumors were 2.4% (95% CI, 1.4%-4.1%) and 10.3% (95% CI, 7.5%-13.9%), respectively. The rate of development of basal cell carcinoma was 1.7% (95% CI, 0.9%-3.2%), whereas the rate of the development of syringocystadenoma papilliferum was 3.6% (95% CI, 2.5%-5.3%) and that if trichoblastoma was 2.6% (95% CI, 1.7%-3.8%). CONCLUSIONS: Although the rate of development of malignant tumors within a primary NS lesion is low, it is not negligible. Prophylactic early excision remains a viable approach to prevent secondary malignant neoplasms, address cosmetic and functional complications, and preempt the need for complex reconstruction in the future. We propose that resection of NS lesions in childhood remains a reasonable first-line option in the appropriate patient keeping in mind that it may leave an undesirable scar.

Thickness of melanocytes in giant congenital melanocytic nevus for complete surgical excision: clinicopathological evaluation of 117 lesions according to the area and size.

BACKGROUND: Giant congenital melanocytic nevi (GCMN) are usually defined as nevi that exceed 20 cm in maximal diameter or 15% of the total body surface area. There have been reports of life-long malignant change risks arising from GCMN, leading to surgical excision of GCMN. This study aims to evaluate the thickness of melanocytes based on clinical factors in order to provide objective information for the complete resection of the lesion. METHODS: Overall, 75 patients diagnosed with GCMN between 2000 and 2021 were included, and their clinical records were collected retrospectively. 117 pathologic slides obtained during excision were reviewed to measure nevus thickness. Clinical factors were assessed with a generalized estimated equation model for association with nevus thickness. RESULTS: The thickness of nevus was significantly associated with the location and size. Nevus thickness was more superficial in the distal extremity than in the head and trunk (P = 0.003 [head]; P < 0.001 [trunk]; P = 0.091 [Proximal extremity]). Nevi sized 60 cm or more were significantly deeper than those measuring 20-29.9 cm (P = 0.035). An interaction between size and location existed (P < 0.001). Trunk and distal extremity lesions consistently exhibited uniform thickness regardless of lesion size, whereas head and proximal extremity lesions showed variations in thickness based on lesion size. CONCLUSION: GCMNs have differences in thickness according to location and size. Therefore, it is necessary to devise an approach optimized for each patient to treat GCMN. In the study, it was emphasized that the thickness of GCMN is correlated with clinical factors, specifically the location and size of the nevus. Consequently, these findings underscore the need for individualized treatment plans for effective surgical intervention.

Reduction of overfitting on the highly imbalanced ISIC-2019 skin dataset using deep learning frameworks.

BACKGROUND: With the rapid growth of Deep Neural Networks (DNN) and Computer-Aided Diagnosis (CAD), more significant works have been analysed for cancer related diseases. Skin cancer is the most hazardous type of cancer that cannot be diagnosed in the early stages. OBJECTIVE: The diagnosis of skin cancer is becoming a challenge to dermatologists as an abnormal lesion looks like an ordinary nevus at the initial stages. Therefore, early identification of lesions (origin of skin cancer) is essential and helpful for treating skin cancer patients effectively. The enormous development of automated skin cancer diagnosis systems significantly supports dermatologists. METHODS: This paper performs a classification of skin cancer by utilising various deep-learning frameworks after resolving the class Imbalance problem in the ISIC-2019 dataset. A fine-tuned ResNet-50 model is used to evaluate the performance of original data, augmented data, and after by adding the focal loss. Focal loss is the best technique to solve overfitting problems by assigning weights to hard misclassified images. RESULTS: Finally, augmented data with focal loss is given a good classification performance with 98.85% accuracy, 95.52% precision, and 95.93% recall. Matthews Correlation coefficient (MCC) is the best metric to evaluate the quality of multi-class images. It has given outstanding performance by using augmented data and focal loss.

Clinical features and management of eyelid margin nevi.

PURPOSE: Acquired melanocytic nevi are common eyelid lesions; however, their clinical presentation is not well documented. METHODS: In this retrospective study, clinical records were reviewed in patients evaluated between 2005 and 2022. RESULTS: Eyelid margin nevi (n = 150) were more commonly excised in female (78%) and Caucasian (86%) patients. Change in appearance/size were frequent presenting complaints, and 17% experienced ocular symptoms. Referring diagnosis included other benign lesions (11.3%), and concern for malignancy (16.7%). Many individuals (38.7%) noted their lesion for ≤5 years. Nevi were distributed across the 4 margins (9% peripunctal), and 88% had a regular base. Visible pigmentation was more common in non-Caucasians (95.2%) than Caucasians (41.1%). Lashes grew through 60.7% of nevi and were often misdirected.Nevi were treated with superficial excision and cauterization. Histologic subtypes included: dermal (86.6%), compound (9.4%), blue (2.7%), junctional (0.7%), lentiginous dysplastic (0.7%). An irregular base (p=0.042) and pigmentation (p=0.056) were more common in compound than dermal nevi. Lash line quality and appearance were improved in the majority of patients returning for follow-up, although postoperative trichiasis, marginal erythema, and residual pigmentation were observed. CONCLUSIONS: Melanocytic nevi commonly involve the eyelid margins and have a variety of presentations and appearances. Existing nevi can change, and new lesions appear throughout adulthood. Stable, benign appearing nevi can be observed. Shave excision provides a diagnosis and improved appearance for symptomatic or suspicious lesions, with few serious complications. Malignant transformation is rare, although evidence for recurrence warrants further evaluation.

Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study. / Cambios en la dermatoscopia digital en lesiones melanocíticas en 368 pacientes con diagnóstico de síndrome de nevus atípicos y su asociación con el desarrollo de melanoma: estudio de cohorte.

BACKGROUND AND OBJECTIVE: Atypical 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 METHODS: We 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. RESULTS: A 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). CONCLUSIONS: The 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.

[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 OBJECTIVE: Atypical 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 METHODS: We 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. RESULTS: A 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). CONCLUSIONS: The 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.