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Chronic solar ultraviolet radiation (sUVR) exposure leads to an increased incidence of non-melanoma skin cancer (NMSC) development, particularly when accumulated over decades. Workers in certain industries, such as construction, agriculture, postal workers, and the military, are at higher risk due to cumulative sUVR exposure in their line of work. By assessing the relationship between sUVR exposure in outdoor workers and their skin cancer risk and defining methods of prevention, clinicians can offer focused sun protection counseling to this unique population. PubMed was used to perform a literature review to address the following research questions: 1. How is ultraviolet radiation measured? 2. What is the modern utility of the ultraviolet index in modifying sun protection behaviors in outdoor industry workers? 3. What is the risk of non-melanoma skin cancer development in individuals working in outdoor occupations? 4. What is the prevalence of skin cancer among outdoor workers? 5. Is the number of nevi and solar lentigines elevated among individuals employed in outdoor occupations? The literature suggests that individuals in outdoor occupations are exposed to UV levels that often surpass safety limits for occupational UVR exposure, increasing their risk of developing skin cancer and precursor and pigmented lesions. Individuals in high-risk occupations experience significantly higher levels of sUVR exposure than their indoor worker counterparts, increasing their risk of malignant cutaneous transformation. Accordingly, these individuals must be counseled on effective solar protection methods, and employers should advocate for actionable change., (© 2023 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Numerous epidemiologic studies have reported positive associations between higher nevus counts and internal cancers. Whether this association represents a true relationship or is due to bias or confounding by factors associated with both nevus counts and cancer remains unclear. We used germline genetic variants for nevus count to test whether this phenotypic trait is a risk-marker for cancer. We calculated polygenic risk scores (PRS) for nevus counts using individual-level data in the UK Biobank (n = 394 306) and QSkin cohort (n = 17 427). The association between the nevus PRS and each cancer site was assessed using logistic regression adjusted for the effects of age, sex and the first five principal components. In both cohorts, those in the highest nevus PRS quartile had higher risks of melanoma than those in the lowest quartile (UK Biobank odds ratio [OR] 1.42, 95% confidence interval [CI]: 1.29-1.55; QSkin OR 1.58, 95% CI: 1.29-1.94). We also observed increases in risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) associated with higher nevus PRS quartiles (BCC UK Biobank OR 1.38, 95% CI: 1.33-1.44; QSkin OR 1.20, 95% CI: 1.05-1.38 and SCC UK Biobank OR 1.41, 95% CI: 1.28-1.55; QSkin OR 1.44, 95% CI: 1.19-1.77). We found no consistent evidence that nevus count PRS were associated with risks of developing internal cancers. We infer that associations between nevus counts and internal cancers reported in earlier observational studies arose because of unmeasured confounding or other biases., (© 2021 UICC.)

Palmoplantar keratodermas (PPKs) are characterized by thickness of stratum corneum and epidermal hyperkeratosis localized in palms and soles. PPKs can be epidermolytic (EPPK) or non epidermolytic (NEPPK). Specific mutations of keratin 16 (K16) and keratin 1 (K1) have been associated to EPPK, and NEPPK. Cases of mosaicism in PPKs due to somatic keratin mutations have also been described in scientific literature. We evaluated a patient presenting hyperkeratosis localized monolaterally in the right palmar area, characterized by linear yellowish hyperkeratotic lesions following the Blaschko lines. No other relatives of the patient showed any dermatological disease. Light and confocal histological analysis confirmed the presence of epidermolityic hyperkeratosis. Genetic analysis performed demonstrates the heterozygous deletion NM_006121.4:r.274_472del for a total of 198 nucleotides, in KRT1 cDNA obtained by a palmar lesional skin biopsy, corresponding to the protein mutation NP_006112.3:p.Gly71_Gly137del. DNA extracted from peripheral blood lymphocytes did not display the presence of the mutation. These results suggest a somatic mutation causing an alteration in K1 N-terminal variable domain (V1). The deleted sequence involves the ISIS subdomain, containing a lysine residue already described as fundamental for epidermal transglutaminases in the crosslinking of IF cytoskeleton. Moreover, a computational analysis of the wild-type and V1-mutated K1/K10 keratin dimers, suggests an unusual interaction between these keratin filaments. The mutation taster in silico analysis also returned a high probability for a deleterious mutation. These data demonstrate once again the importance of the head domain (V1) of K1 in the formation of a functional keratinocyte cytoskeleton. Moreover, this is a further demonstration of the presence of somatic mutations arising in later stages of the embryogenesis, generating a mosaic phenotype.

Background/aim: Differences in risk factors for melanoma between young adults (18-39 years) and middle-aged (40-60 years) are not well documented. In this study, we aimed to determine differences in risk factors and characteristics of melanoma between these groups., Patients and Methods: This retrospective study is a review on 330 patients, including 250 middle-aged and 80 young adults, during the period 2006-2016 in the Tampere university hospital, in Finland., Results: Forty-one per cent of middle-aged and 47% of young adults were defined as higher-risk patients. High nevus count was the most common host risk factor in both groups. Young were more likely to have a family history of melanoma. Middle-aged had more often excessive intermittent sun exposure and a history of sunburn. Host risk characteristics were less commonly associated with thicker melanomas., Conclusion: A high number of patients have host risk factors for melanoma. Several differences exist in risk factors and characteristics of melanomas between young adults and middle-aged patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Melanoma rates have increased in populations that are mainly European. The main etiologic factor is ultraviolet radiation, from the sun as well as artificial tanning devices. Host factors such as skin color, number of nevi, hair and eye color and tanning ability are critical factors in modifying an individual's response to the sun. Genetic factors interact with host factors and environmental factors to increase risk. This review summarizes our current knowledge of environment and genetics on melanoma risk and on gene-environment interaction.

Importance: Nevi are a risk factor for melanoma and other forms of skin cancer, and many of the same factors confer risk for both. Understanding childhood nevus development may provide clues to possible causes and prevention of melanoma., Objectives: To describe nevus acquisition from the ages of 3 to 16 years among white youths and evaluate variation by sex, Hispanic ethnicity, and body sites that are chronically vs intermittently exposed to the sun., Design, Setting, and Participants: This annual longitudinal observational cohort study of nevus development was conducted between June 1, 2001, and October 31, 2014, among 1085 Colorado youths. Data analysis was conducted between February 1, 2015, and August 31, 2017., Main Outcomes and Measures: Total nevus counts on all body sites and on sites chronically and intermittently exposed to the sun separately., Results: A total of 557 girls and 528 boys (150 [13.8%] Hispanic participants) born in 1998 were included in this study. Median total body nevus counts increased linearly among non-Hispanic white boys and girls between the age of 3 years (boys, 6.31; 95% CI, 5.66-7.03; and girls, 6.61; 95% CI, 5.96-7.33) and the age of 16 years (boys, 81.30; 95% CI, 75.95-87.03; and girls, 77.58; 95% CI, 72.68-82.81). Median total body nevus counts were lower among Hispanic white children (boys aged 16 years, 51.45; 95% CI, 44.01-60.15; and girls aged 16 years, 53.75; 95% CI, 45.40-63.62) compared with non-Hispanic white children, but they followed a largely linear trend that varied by sex. Nevus counts on body sites chronically exposed to the sun increased over time but leveled off by the age of 16 years. Nevus counts on sites intermittently exposed to the sun followed a strong linear pattern through the age of 16 years. Hispanic white boys and girls had similar nevus counts on sites intermittently exposed to the sun through the age of 10 years, but increases thereafter were steeper for girls, with nevus counts surpassing those of boys aged 11 to 16 years., Conclusions and Relevance: Youths are at risk for nevus development beginning in early childhood and continuing through midadolescence. Patterns of nevus acquisition differ between boys and girls, Hispanic and non-Hispanic white youths, and body sites that are chronically exposed to the sun and body sites that are intermittently exposed to the sun. Exposure to UV light during this period should be reduced, particularly on body sites intermittently exposed to the sun, where nevi accumulate through midadolescence in all children. Increased attention to sun protection appears to be merited for boys, in general, because they accumulated more nevi overall, and for girls, specifically, during the adolescent years.

Background: The plantar cerebriform connective tissue nevus (CCTN) is the most common and problematic cutaneous manifestation of Proteus syndrome., Objective: To gain insights into CCTN pathogenesis and natural history., Methods: The size and location of plantar CCTN was measured on 152 images from 22 individuals with Proteus syndrome by 2 independent, blinded reviewers. Average measures of plantar CCTN were transformed into a linear mixed model to estimate proportionate change in size with age., Results: Median patient age was 6.9 years at study onset. The intraclass correlation coefficient between 2 blinded reviewers was 0.946 for CCTN single measures. The CCTN relative area increased with age in children (n = 18, P < .0001) by 5.6% per year. Confluent papules and nodules extending beyond the boundaries of CCTNs were gradually replaced by typical CCTN over time. The location of CCTN in different individuals overlapped near the ball of the foot. A positive relationship between CCTN growth rate and AKT1 mutant allele frequency was observed (0.62, P = .10, n = 8)., Limitations: This was a retrospective review using photographs., Conclusion: CCTN growth is affected by age and extent of the CCTN precursor lesion. Monitoring of CCTN size might prove useful for evaluating drug response in the treatment of Proteus syndrome., (Published by Elsevier Inc.)

Introduction: Severe cutaneous adverse drug reactions (SCARs) are not uncommon and potentially lifethreatening. Our objective is to study the patient characteristics, the pattern of implicated drugs and treatment outcome among patients with SCARs., Methods: A 10-year retrospective analysis of SCARs cases in Penang General Hospital was carried out from January 2006 to December 2015. Data collection is based on the Malaysian Adverse Drug Reactions Advisory Committee registry and dermatology clinic records., Results: A total of 189 cases of SCARs were encountered (F:M ratio; 1.2:1.0; mean age of 45 year). The commonest manifestation was Stevens-Johnson Syndrome [SJS] (55.0%), followed by toxic epidermal necrolysis [TEN] (23.8%), drug rash with eosinophilia and systemic symptoms [DRESS] (12.7%), acute generalised exanthematous pustulosis [AGEP] (4.8%), SJS/TEN overlap syndrome (2.6%) and generalised bullous fixed drug eruptions [GBFDE] (1.1%). Mean time to onset for TEN/SJS/Overlap syndrome was 10.5±13 days; AGEP, three days; GBFDE, 2.5±0.7 days, and DRESS, 29.4±5.7 days. The most common drugs implicated were antibiotics (33.3%), followed by allopurinol (18.9%) and anticonvulsant (18.4%). Out of 154 cases of SJS/TEN/overlap syndrome, allopurinol was the commonest causative agents (20.1%). In DRESS, allopurinol accounts for 45.8% of the cases. The mortality rate in SJS, TEN and DRESS were 1.9%, 13.3% and 12.5% respectively. No mortality was observed in AGEP and GBFDE., Conclusion: The commonest manifestations of SCARs in our setting were SJS, TEN and DRESS. Allopurinol was the most common culprit. Thus, judicious allopurinol use is advocated and pre-emptive genetic screening for HLAB *5801 should be considered.

Objectives: The incidence and mortality of melanoma are increased in organ transplant recipients. Multiple acquired common and dysplastic nevi are risk factors for melanoma. A new or changing nevus may suggest melanoma. Strategies used by transplant dermatologists to monitor nevi are unknown. Herein, we aimed to assess the methods used by transplant dermatologists for monitoring multiple acquired common nevi, dysplastic nevi, and new or changing nevi., Materials and Methods: A questionnaire was e-mailed to 63 members of the Skin Care in Organ Transplant Patients, Europe., Results: Thirty-eight (92.7%) of 41 responders reported that they instruct their patients to perform regular self-skin examinations. Of 41 responders, 41.5% prescribed screening every 6 months, 36.6% prescribed it every 12 months, 12.2% prescribed it every 3 months, and 9.7% performed screening without regular intervals. Regarding type of examination, 80.5% performed full-body skin examinations with the naked eye, 70.7% performed dermoscopy of clinically suspicious nevi, 53.6% offered dermoscopic photography of dermoscopically suspicious nevi, 36.6% provided close-up photography of clinically suspicious nevi, 34.1% performed baseline total body photography, and 24.4% conducted dermoscopy of all nevi. We also found that 7.3%, 4.9%, and 4.9% performed only full-body skin examination with the naked eye, only dermoscopy of clinically suspicious nevi, and only dermoscopy of all nevi, respectively., Conclusions: Dedicated transplant dermatologists perform a wide variety of nevi screening procedures in organ transplant recipients. Transplant dermatologists should include sequential digital dermoscopic imaging in their armamentarium to follow organ transplant recipients with melanocytic lesions. A combination of techniques is advisable for detecting early posttransplant melanomas.

Acral melanoma is distinct from melanoma of other cutaneous sites, yet there is considerable variation within this category. To better define this variation, we assessed melanomas occurring on dorsal (n = 21), volar (n = 9), and subungual/interdigital (n = 13) acral skin as well as acral nevi (n = 24) for clinical, histologic, and molecular features. Melanomas on dorsal acral surfaces demonstrated clear differences compared with volar and subungual/interdigital melanomas. The latter two groups exhibited significantly less frequent BRAF mutations (P = 0.01), were significantly less likely to have the superficial spreading histologic subtype (P = 0.01), occurred in older patients (P = 0.05), and had more frequent involvement in non-Caucasians (P = 0.01). These differences can be explained by differing levels of UV exposure. Subungual/interdigital melanomas had the most diverse group of oncogenic mutations including PIK3CA (2/13), STK11 (2/13), EGFR (1/13), FGFR3 (1/13), and PTPN11 (1/13). In addition, subungual/interdigital melanomas had a significantly higher frequency of copy number aberrations (67%) than other subgroups (P = 0.02), particularly in CDK4 and cyclin D1, and were less likely to have BRAF mutations or a superficial spreading histologic subtype (P = 0.05) compared with volar acral melanomas. Although based on a limited sample size, differences between volar and subungual/interdigital melanomas in our study may be the result of differing levels of UV exposure., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies and/or scoliosis syndrome is a PIK3CA-related overgrowth spectrum presenting with congenital, asymmetric, disproportionate overgrowth associated with dysregulated adipose tissue, enlarged bony structures, and mixed primarily truncal vascular malformations. We present this case to raise awareness that very thin body habitus (lipoatrophy) contrasting with areas of overgrowth can be an important clinical feature of this syndrome and, if not recognized, can lead to unnecessary investigations., (© 2017 Wiley Periodicals, Inc.)

Background: Incidence rates have increased considerably worldwide for both differentiated thyroid cancer and cutaneous melanoma, and two-way associations between these neoplasms have been described. Whether melanoma risk factors are associated with thyroid cancer risk remains unknown., Methods: Using Cox regression modeling, we prospectively analyzed the relationship between self-reported pigmentary traits, baseline residential ultraviolet (UV) exposure, and thyroid cancer risk in 86,960 women from the E3N cohort, followed-up over 1990-2008 through biennial questionnaires. We assessed associations of pigmentary traits and UV exposure with personal history of benign thyroid diseases using logistic regression modeling. All statistical tests were two sided., Results: In models adjusted for age and thyroid cancer risk factors, number of nevi was positively associated with thyroid cancer risk ("very many" vs. "none": hazards ratio [HR] = 1.7, 95% confidence interval [CI] = 1.0, 2.8; Ptrend = 0.01), independently of residential UV exposure or iodine intake. Risk was inversely associated with latitude and positively associated with mean daily UV level at baseline (HRs for the fourth vs. first quartile of latitude and spring/summer UVB level = 0.7, 95% CI = 0.5, 0.9; Ptrend = 0.03, and HR = 1.9, 95% CI = 1.4, 2.7; Ptrend = 0.02, respectively); associations were restricted to women with dietary iodine below the median intake. Number of nevi and UV level were also associated with personal histories of dysthyroidism and of goiter/nodules, although more weakly so., Conclusions: Our results suggest that number of nevi and residential UV exposure are associated with the risks of thyroid cancer and benign conditions. They point to novel pathways in thyroid cancer or melanoma etiologies and warrant replication.

Importance: Patients with tuberous sclerosis complex (TSC) frequently develop collagenous connective tissue nevi. The prototypical lesion is a large shagreen patch located on the lower back, but some patients only manifest small collagenomas or have lesions elsewhere on the body. The ability to recognize these variable presentations can be important for the diagnosis of TSC., Objective: To describe the clinical characteristics of connective tissue nevi on the trunk and extremities of patients with tuberous sclerosis complex., Design, Setting, and Participants: A retrospective analysis of patient medical records and skin photography was performed; 104 adult patients with TSC were enrolled in an observational cohort study that was enriched for those with pulmonary lymphangioleiomyomatosis, and was therefore composed mostly of women (99 women, 5 men). All patients included were examined at the National Institutes of Health (NIH) in Bethesda, Maryland, from 1998 to 2013. Connective tissue nevi were categorized per anatomic location and size. Lesions less than 1 cm in diameter were termed collagenomas. Shagreen patches were characterized as small (1 to <4 cm), medium (4 to <8 cm), and large (≥8 cm)., Main Outcome and Measures: Frequency, anatomic location, size, and histological appearance of connective tissue nevi in patients with TSC., Results: Overall, 58 of 104 patients (median [range] age, 42 [19-70] years) with TSC (56%) had at least 1 connective tissue nevus on the trunk or thighs; of these, 28 of 58 patients (48%) had a solitary lesion, and 30 of 58 patients (52%) had 2 or more lesions. Overall, 120 lesions from 55 patients were classified by size; 46 lesions (38%) were collagenomas; 39 lesions (32%) were small shagreen patches; 21 lesions (18%), medium shagreen patches; and 14 lesions (12%), large shagreen patches. The distribution of lesions was 9% (n = 11), upper back; 29% (n = 35), middle back; 51% (n = 61), lower back; and 11% (n = 13), other locations. All 26 shagreen patches that were analyzed histopathologically had coarse collagen fibers and 24 of 26 stained with Miller elastic stain had decreased elastic fibers. On immunoblot analysis, fibroblasts grown from shagreen patches expressed higher levels of phosphorylated ribosomal protein S6 than paired fibroblasts from normal-appearing skin., Conclusions and Relevance: Tuberous sclerosis complex-related connective tissue nevi are not limited to the lower back, and occasionally present on the central or upper back, buttocks, or thighs. Elastic fibers are typically decreased. Recognition of these variable presentations can be important for TSC diagnosis.

Skin changes have been described in myotonic dystrophy type 1 (DM1). However, whether and in which way skin is a target of specific disease alterations in DM1 and DM2 has not been yet clarified. This study aims to explore cutaneous features of DM1 and DM2 patients. Skin examination was performed in 60 DM1, 15 DM2, and 103 control, unselected patients by means of dermoscopy. It revealed quantitative and qualitative abnormalities of nevi and typical signs of premature aging in both DM1 and DM2 patients, with a significantly higher frequency of dysplastic nevi, alopecia, xerosis and seborrheic dermatitis. Twenty-eight nevi were excised in DM patients and none showed histological features of melanoma, although 12 of them were diagnosed as dysplastic and the remaining 16 presented histological irregularity in melanin distribution. In DM1 patients, the number of nevi correlated with CTG expansion size, whereas the presence of dysplastic nevi and xerosis inversely correlated with vitamin D levels. DM1 and DM2 patients display a high frequency of skin abnormalities, the most common of which correlate with genotype severity and serum vitamin D levels. Skin examination is highly informative in these patients and reveals features suggestive of premature aging and impaired vitamin D homeostasis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Epidermal nevus syndrome (ENS), also known as Solomon syndrome, is a rare neurocutaneous disorder defined by mosaicism. Epidermal nevus syndrome may be associated with a variety of systemic findings, several of which have been described in the literature, including but not limited to central nervous system abnormalities and internal malignancies. There is a paucity of reports of patients with both epidermal nevi and papillary transitional cell bladder carcinoma in the literature. We present a rare case of systematized epidermal nevi associated with development of papillary transitional cell bladder carcinoma in a young woman. Patients diagnosed with generalized epidermal nevi should have workup for possible associated central nervous system, musculoskeletal, genitourinary abnormalities, and internal malignancies. The association of epidermal nevi and transitional cell bladder carcinoma may be linked to a mutation in the fibroblast growth factor receptor 3 gene, FGFR 3 , but a clear link has yet to be substantiated and additional molecular studies are needed.

Purpose: To investigate sex differences and the effect of other variables on the association between obesity and choroidal nevus in the US adult population., Methods: The study population of this cross-sectional study included 5575 subjects aged ≥40 years from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES) who underwent retinal imaging. Primary predictor variables were body mass index (BMI) when the subject was 25 years old ("former BMI") and BMI at time of NHANES participation ("current BMI"). Body mass index was classified "elevated" (≥25 kg/m2) versus "normal" (<25 kg/m2). The main outcome measure was choroidal nevus in either eye on retinal imaging. Subgroup analysis was stratified by sex and race., Results: The mean age of the study population was 56.4 years, with 47.3% male and 52.7% female subjects. The prevalence of choroidal nevus was 4.7% overall. Former elevated BMI was associated with choroidal nevus in the overall population (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.06-1.71, P = 0.01) and males (OR: 1.43, CI: 1.03-1.99, P = 0.03). Current elevated BMI was associated with choroidal nevus in the overall population (OR: 1.37, CI: 1.02-1.85, P = 0.04); females (OR: 1.72, CI: 1.11-2.68, P = 0.02), and postmenopausal females (OR: 1.94, CI: 1.23-3.06, P = 0.006)., Conclusions: Choroidal nevus is associated with former and current obesity. Sex and postmenopausal status differences in this association could provide insight into the demographics of patients at risk for developing choroidal nevus.

Nevus sebaceus (NS) and Becker's nevus (BN) are two variants of epidermal nevi. NS clinically presents as a yellowish-orange, hairless plaque on the scalp, face, or neck, while BN presents as a tan-to-brown hyperpigmented, sometimes hypertrichotic, plaque typically on the chest and shoulder. Histologically, NS displays mature or nearly mature sebaceus glands as well as acanthosis and fibroplasia of the papillary dermis. BN shows variable papillomatosis, acanthosis, and hyperkeratosis, with hyperpigmentation of the basal/suprabasal layer. While the genetic basis of NS is thought to be due to post-zygotic mutations in the Harvey rat sarcoma viral oncogene homolog (HRAS)/Kristen rat sarcoma viral oncogene homolog (KRAS) genes, the genetic basis of BN is relatively unknown and is implicated with paradominant inheritance. In some patients, NS and BN can each be associated with additional cutaneous and extra-cutaneous anomalies, ranging from benign or malignant tumors to multiple organ irregularities. Due to the wide range of possible associations, treatment for NS and BN is devised on a case-by-case basis. In this article, we review the features, etiology, and diagnosis/management of NS and BN, with a focus on associations. We also report a patient who concomitantly presents with both lesions.

Nevus anemicus (NA) is a cutaneous anomaly characterized by pale, well-defined patches with limited vascularization after rubbing. They are largely known to be associated with neurofibromatosis 1 (NF1) and have received little attention in the literature until recently. We sought to characterize the prevalence and clinical features of patients with NA and NF1. We conducted an observational prospective study of 99 children with NF1 at the Hospital Niño Jesús, Madrid, Spain, from January 1, 2012, through July 31, 2013, and reviewed three other series of patients with NF1 and NA recently reported. The prevalence of NA in children with NF1 ranged from 8.8% to 51%, being much more prevalent at younger ages. Prospective studies yielded a higher prevalence than retrospective studies. NA was located most commonly on the trunk, particularly on the anterior chest wall, and was often multiple. Patients with segmental NF1 or isolated café au lait spots rarely had NA, and NA was absent in other genodermatoses. The collection of data was not homogeneous in all studies. NA has a high prevalence in individuals with NF1 patients but seems to be absent in connection with other genodermatoses, therefore its presence can assist in the diagnosis of suspected cases of NF1. The subtle clinical appearance of NA makes its detection difficult, and physicians involved in the care of children with NF1 must be aware of its possible presence and significance., (© 2015 Wiley Periodicals, Inc.)

"Eruptive nevi" is a phenomenon characterized by a rapid appearance of multiple melanocytic nevi. It is mainly developed in three groups of patients: those with systemic immunosuppression, bullous cutaneous disorders, and a melanocytic stimulation drug. We report on the case of an 11-year-old boy who was diagnosed with acute lymphoblastic leukemia. A few months after the beginning of the chemotherapy, he developed multiple pigmented lesions over the skin. Eruptive nevi syndrome has been described in the literature in 29 cases in the context of severe bullous disease and in immunosuppression. Nevi most often appear on the trunk and extremities, notably on the feet in the context of immunosuppression. They are localized in areas of bullous lesions in bullous diseases. Due to an increased melanocytic stimulation in eruptive nevi patients, long-term surveillance of individuals who have developed eruptive nevi is required, and increased sun prevention should be suggested., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Sports-related acquired connective tissue nevus or "athlete's nodule" has been reported under a variety of different names. The lesion develops in response to activity causing chronic or repetitive low-grade pressure or irritation activity, which is often a component of athletic training. A case of "athlete's nodule" in a figure skater has been reported. Our case demonstrates the typical histopathologic findings of deposition of normal-appearing collagen bundles arranged haphazardly within the dermis as described in previous reports. Additionally, results of CD34, colloidal iron, and elastic tissue staining have been described. The macular clinical presentation with the absence of significant epidermal change is a unique presentation of athletic nodule. It is the goal of the authors to create increased awareness among pathologists and clinicians in identifying these lesions and to expand the clinical presentation to include nonprotuberant lesions.

Cutaneous melanoma is epidemiologically linked to ultraviolet radiation (UVR), but the molecular mechanisms by which UVR drives melanomagenesis remain unclear. The most common somatic mutation in melanoma is a V600E substitution in BRAF, which is an early event. To investigate how UVR accelerates oncogenic BRAF-driven melanomagenesis, we used a BRAF(V600E) mouse model. In mice expressing BRAF(V600E) in their melanocytes, a single dose of UVR that mimicked mild sunburn in humans induced clonal expansion of the melanocytes, and repeated doses of UVR increased melanoma burden. Here we show that sunscreen (UVA superior, UVB sun protection factor (SPF) 50) delayed the onset of UVR-driven melanoma, but only provided partial protection. The UVR-exposed tumours showed increased numbers of single nucleotide variants and we observed mutations (H39Y, S124F, R245C, R270C, C272G) in the Trp53 tumour suppressor in approximately 40% of cases. TP53 is an accepted UVR target in human non-melanoma skin cancer, but is not thought to have a major role in melanoma. However, we show that, in mice, mutant Trp53 accelerated BRAF(V600E)-driven melanomagenesis, and that TP53 mutations are linked to evidence of UVR-induced DNA damage in human melanoma. Thus, we provide mechanistic insight into epidemiological data linking UVR to acquired naevi in humans. Furthermore, we identify TP53/Trp53 as a UVR-target gene that cooperates with BRAF(V600E) to induce melanoma, providing molecular insight into how UVR accelerates melanomagenesis. Our study validates public health campaigns that promote sunscreen protection for individuals at risk of melanoma.

We report a neonate who presented at birth with multiple, scattered, white macerated plaques. Punch biopsy confirmed epidermal nevi. At 3 months of age the patient presented with infantile spasms and, after full evaluation, was diagnosed with tuberous sclerosis complex (TSC). We suggest that physicians consider TSC in a neonate with epidermal nevi inconsistent with any described epidermal nevus syndrome., (Published 2012. This article is a U.S. Government work and is in the public domain in the USA.)

Importance: The diagnosis of neurofibromatosis type 1 (NF1) is based on 7 clinical criteria. However, they are of limited value before the age of 2 years. Juvenile xanthogranuloma (JXG) and nevus anemicus (NA) are commonly observed in children with NF1 and may be useful diagnostic clues., Objectives: To evaluate the frequency of JXG and NA, to describe their clinical features, and to determine their diagnostic value in patients with NF1., Design, Setting, and Participants: Retrospective medical record review of outpatients seen between January 1, 2005, and December 31, 2011. University hospital dermatology department affiliated with the French NF1 referral center network. Patients with NF1 diagnosed by at least 2 National Institutes of Health criteria and examined at our department., Main Outcomes and Measures: Percentage of patients with NF1 who had JXG or NA categorized into 4 age groups., Results: Among 72 patients with NF1 (median age, 15.4 years), 23 had JXG (10%) or NA (25%). Both lesions were more frequent (55%) in those younger than 2 years (JXG, 30%; NA, 35%). Most JXG lesions were multiple and resolved spontaneously. Cephalic and genital involvement was frequent. No patient with JXG developed chronic myelomonocytic leukemia. Nevus anemicus was present on the neck and upper chest in 72% of cases. Among 10 patients (14%) who had only 1 diagnostic criterion at first visit, including 9 younger than 2 years, JXG or NA was present in 8 (80%)., Conclusions and Relevance: We found a high frequency of JXG and NA in patients with NF1, especially in children younger than 2 years with fewer than 2 diagnostic criteria. Hence, JXG and NA appear helpful in improving early diagnosis of NF1 in young children and infants.

Background: Children with multiple café-au-lait macules (CALMs) may be followed for years before a second National Institutes of Health clinical criterion of neurofibromatosis type 1 (NF1) develops to confirm the diagnosis., Objective: We sought to assess the prevalence of nevus anemicus (NA) in NF1 and its association with neuro-ophthalmologic complications., Methods: This was a prospective multicenter case-control study of 210 consecutive patients with multiple CALMs. Patients with NF1 were matched for age, sex, and center with control subjects. We documented the number, location, and morphologic appearance of NA; dermatologic features of NF1; magnetic resonance imaging results; and family history., Results: In all, 77 (51%) patients with NF1 had NA compared with 6 (2%) control subjects. NA was not detected in 26 patients with other genodermatoses associated with CALMs. Patients with NF1 and NA were younger than those without NA (median age: 17 years) (P = .002). NA was mostly localized to the upper anterior aspect of the chest. NA was not significantly linked with other clinical manifestations of NF1, including optic glioma and unidentified bright objects., Limitations: A potential referral bias associated with tertiary care centers is a limitation., Conclusions: NA appears to have a high prevalence and specificity in NF1 and might serve as a marker for NF1 in children with multiple CALMs., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Nevus lipomatosus superficialis (NLS) is a unique developmental anomaly or nevoid form of lipoma characterized by the ectopic presence of mature adipocytes in reticular dermis. The condition is rare; apart frrom isolated case reports, there are no large case series dealing with the clinicoepidemiologic characteristics and posttreatment long-term follow-up in patients with NLS and little published information on treatment outcome., Objective: To study the clinicoepidemiologic characteristics and long-term posttreatment follow-up in patients with NLS., Methods: This was an 11-year retrospective study analyzing disease characteristics and treatment outcome in eight patients with NLS., Results: There were eight (six males, two females) patients with NLS, of whom three were children. The classic variant of NLS was the predominant presentation. One patient demonstrated a combination of both classic and solitary variants. Most patients, especially those with solitary variants, were commonly misdiagnosed before presenting to us. Four patients, including two with the solitary variant, one each with the classic and the combined type, underwent surgical resection without any recurrence over 8 years of follow-up., Conclusions: The rare nature of the disorder, which is commonly misdiagnosed, and the absence of long-term follow-up data prompted us to share our experience about NLS to increase its awareness among health care providers.

Anemic nevus (AN) is a congenital-vascular anomaly of the skin. Although it is a benign and asymptomatic lesion, it could be a frequent 'cutaneous finding' in neurofibromatosis type 1 (NF1). We performed a retrospective analysis to detect the prevalence of AN in all children with a presumptive diagnosis of NF1 treated in our center., (Copyright © 2013 S. Karger AG, Basel.)

Objective: To investigate risk factors for lentigo maligna melanoma (LMM) compared with superficial spreading melanoma (SSM)., Design: Population-based case-control study in Queensland, Australia., Setting: General community., Participants: Population-based sample of 49 patients with LMM and 141 with SSM (in situ or invasive) aged 14 to 86 years at diagnosis in 1979 and 1980 and 232 control subjects. Response rates were 97.1% in cases and 91.8% in controls., Main Outcome Measures: Risks of both subtypes in relation to phenotypic and environmental factors, estimated by multinomial logistic regression., Results: The number of solar lentigines was the strongest determinant for LMM (odds ratio [OR], 15.93; P < .001 for trend) and significantly weaker for SSM (4.61; P < .001 for trend; P = .04 for homogeneity). Skin cancer history was significantly associated with LMM (OR, 2.84) but not with SSM (1.33; P = .07 for homogeneity). In contrast, the number of nevi was the strongest determinant for SSM (OR, 23.22; P < .001 for trend) while significantly weaker for LMM (3.60; P = .02 for trend; P < .001 for homogeneity). Multiple lifetime sunburns almost tripled the risk for SSM, whereas no association was detected with LMM (P = .04 for homogeneity). Shared risk factors for both subtypes were the number of solar keratoses (P < .001 for trend for both) and sun-sensitive complexion (ie, light eye/hair colors, sunburn propensity, and freckling) (2-fold to 5-fold increased risks)., Conclusions: A propensity to lentigines is a stronger predictor of LMM, whereas high nevus propensity is a stronger predictor of SSM. Skin cancer history appears to determine LMM risk only, whereas the number of lifetime sunburns determines SSM only. Prevention strategies could be tailored differently given these distinctive points of difference.

Acne rarely presents in segmental patterns, which are encountered only in cutaneous mosaicism. We report herein two cases of segmentally arranged acne and systematically review the literature on the topic. Beside already known mosaic conditions which may show primary lesions typical of acne, i.e. nevus comedonicus, Happle-Tinschert syndrome, acne superimposed on epidermal nevi and mosaic Apert syndrome, we introduce the possibility that acne itself may present in a mosaic form. As from the extremely small casuistics retrieved, segmental acne is not present at birth, follows Blaschko lines, is polymorphous in nature and occurs on locations typical of common acne., (Copyright © 2012 S. Karger AG, Basel.)

The purpose of this article is to improve the general practitioner's knowledge about nevi and to teach how to evaluate the risk of a lesion during a medical visit. The most frequent kind of nevi will be defined, as well as their transformation risk. Different melanoma risk factors and the semiology that can alert the practitioner will be defined. A set of the most frequently asked questions about nevi will be answered.

A 55-year-old man presented with a pigmented skin tumor on the left thorax but refused excision. At the 2-month follow-up a change was evident and the patient agreed to excision. This example emphasizes the importance of regular monitoring since this was the only way to prevent an atypical growth from becoming malignant.

Epidermolysis bullosa (EB) nevi are large, eruptive, asymmetrical, often irregularly pigmented melanocytic lesions. Such nevi may give rise to small satellite nevi surrounding the primary nevus, and thus frequently manifest clinical features suggestive of melanoma. They usually arise in sites of previous bullae or erosions. At least twice a year all persisting wounds and EB nevi should be evaluated with a low threshold for histopathologic examination if warranted. Our practice is to punch biopsy EB nevi showing dermoscopic features of concern as well as dermoscopically featureless lesions. Given the skin fragility and potentially impaired wound healing in EB patients, we avoid prophylactic total excision of large EB nevi, but rather use the dermoscope to select appropriate sites for punch biopsies within giant EB nevi.

Objective: To examine the relationship between tanning and nevus development in very-light-skinned children., Design: Prospective cohort nested within a randomized controlled trial. Skin examinations in 3 consecutive years (2004, 2005, and 2006) included full-body counts of nevi, skin color and tanning measurement using colorimetry, and hair and eye color evaluation by comparison with charts. Telephone interviews of parents provided sun exposure, sun protection, and sunburn history., Setting: Large managed-care organization and private pediatric offices in the Denver, Colorado, metropolitan area., Participants: A total of 131 very-light-skinned white children without red hair and 444 darker-skinned white children without red hair born in Colorado in 1998., Main Outcome Measures: Full-body nevus counts at ages 6 to 8 years., Results: Among very-light-skinned white children, geometric mean numbers of nevi for minimally tanned children were 14.8 at age 6 years; 18.8 at age 7 years; and 22.3 at age 8 years. Mean numbers of nevi for tanned children were 21.2 at age 6 years; 27.9 at age 7 years; and 31.9 at age 8 years. Differences in nevus counts between untanned and tanned children were statistically significant at all ages (P < .05 for all comparisons). The relationship between tanning and number of nevi was independent of the child's hair and eye color, parent-reported sun exposure, and skin phototype. Among darker-skinned white children, there was no relationship between tanning and nevi., Conclusions: Very-light-skinned children who tan (based on objective measurement) develop more nevi than children who do not tan. These results suggest that light-skinned children who develop tans may be increasing their risk for developing melanoma later in life.

Background: Malignant melanoma is becoming an increasingly important problem in public health as incidence rates have been increasing continuously in Caucasian populations. Childhood and adolescence is an important time of life for the formation and evolution of nevi, and the presence of a higher number of nevi in early life could predict a major risk of developing melanoma., Objectives: (1) To determine the number of nevi and the dermoscopic pattern predominance in children of our population. (2) To relate it to constitutional and environmental factors., Methods: Clinical and dermoscopic examinations were performed in 180 children aged 1-15 years. A questionnaire including topics such as past history of sunburns, tanning ability, tendency to sunburn, history of sunlight exposure, use of sunscreens, tendency to freckle and family history of cancer was completed in a face-to-face interview with the parents. On clinical examination, we evaluated hair color, eye color, number of nevi and the presence of nevi in specific locations. All melanocytic lesions were examined dermoscopically, and all patterns were registered as present or absent. We also registered the predominant dermoscopic pattern of the child, defined as being present in more than 40% of all of the individual's nevi., Results: The mean number of moles was 17.5. Male gender, past history of sunburns, facial freckling and family history of breast cancer were independent risk factors for having a higher number of nevi. We found that 61.1% of children had nevi on the face and neck, 17.2% on the buttocks, 11.7% on the scalp, 19.4% had acral nevi and 31.7% had congenital nevi. We found the presence of nevi in some of these locations to be a risk factor for having a higher number of nevi. The most frequent dominant dermoscopic pattern found in our population was the globular type. Interestingly, we found that the homogeneous pattern predominates in the youngest children, the reticular pattern predominates in adolescents and the dominant globular pattern is constant among all ages evaluated., Conclusion: This is the first study clinically and dermoscopically characterizing nevi in children from our population, and evaluating constitutional and environmental risk factors., (2008 S. Karger AG, Basel)

A large number of melanocytic nevi is the strongest known risk factor for melanoma in whites, but its relationship to sun exposure overseas among young white women living in temperate climates is unclear. A total of 754 white English women aged 18-46 years were recruited into a cross-sectional study in 1997-2000 to investigate the effect of ultraviolet exposures on numbers of nevi and atypical nevi, and on skin aging as measured by microtopography. Having ever holidayed in hotter countries was associated with a greater age- and phenotype-adjusted mean number of whole-body nevi (percent increase=74; 95% confidence interval: 24, 144; P=0.001), particularly for holidays taken at ages 18-29 years and for counts of the trunk and lower limbs. Having ever lived overseas was not associated with nevus counts, but was inversely associated with number of atypical nevi (P=0.02). Skin aging was not associated with residence or holidays abroad. The association of holidays overseas with an increased nevus count in young white women, which was stronger in the anatomical sites intermittently exposed to sunlight, supports the hypothesis that intermittent sun exposure is of relevance in the etiology of nevi and, hence, melanoma. The findings are of public health relevance given the growing popularity of foreign holidays.

It is now well established that a subpopulation of tumor stem cells (TSCs) are present within cancer tissues. This suggests that tumors evolve from stem cells; however, the exact cell of tumor origin, the potential role of dedifferentiation, and the role of plasticity in tumor development are largely unknown. A model cancer for the study of the oncologic process is melanoma. The developmental biology of melanocytes is relatively well understood, the cells pigment as they differentiate making them easy to identify, and benign and malignant tumors develop on the skin surface allowing direct observation of growth features, early detection, and removal. This ready access to early-stage tumors will facilitate study of the early oncologic processes and the role of tissue stem cells. Melanomas, like other cancers, include a subpopulation of TSCs. These TSCs have access to embryologic developmental programs, including the capacity to differentiate along multiple cell lineages. For example, melanomas can activate germ-cell pathways with major implications for TSC self-renewal through the activation of telomerase and genomic instability through the collision of meiotic and mitotic pathways (meiomitosis). The TSC model is still evolving, but the existence of TSCs has significant ramifications for tumor development, diagnosis, prognosis, and treatment of melanoma and other cancers.

Atypical moles can be distinguished visually by clinical features of size greater than 6 mm in diameter, color variegation, indistinct borders, and textured surface. All patients who have atypical moles should be counselled about sun avoidance, screening of family members, and regular skin checks at least once per year. Total body photography and dermoscopy can aid in regular skin monitoring for changes in atypical moles and the emergence of new lesions. The presence of multiple atypical moles increases the risk of melanoma. The greatest risk of melanoma is in patients who have more than 50 atypical moles and two or more family members with melanoma (familial atypical mole and melanoma syndrome). Atypical moles should be removed when they have features suggestive of malignant transformation. Elliptical excision is the preferred removal technique. Removing all atypical moles is neither necessary nor cost effective.