Dermoscopic Features of Melanocytic Nevi in Cardiofaciocutaneous and Costello Syndromes.

Importance: Somatic variants in the RAS/MAPK pathway genes are commonly associated with melanocytic nevi and melanoma, whereas germline variants in these genes are associated with RASopathies, syndromes involving multiple organs, including the skin. Nevi counts may be higher in some RASopathies, but studies on features observed through dermoscopy are limited. Objective: To determine the distinguishing dermoscopic features of melanocytic nevi and how the RAS pathway influences them by comparing nevi in patients with cardiofaciocutaneous syndrome (CFC) and Costello syndrome (CS). Design, Setting, and Participants: In this prospective cohort study, patients with CFC and CS, 2 RASopathies caused by variants in the downstream and upstream components of the RAS/MAPK pathway, were recruited from the international CFC and CS family conferences. Some patients with CFC also elected to participate in a longitudinal follow-up study. Main Outcomes and Measures: The main outcomes were dermoscopic features and, in the longitudinal follow-up study, nevi counts, which were recorded over time. Results: A total of 39 patients, 16 with CFC and 23 with CS, were enrolled (overall cohort: 26 [66.7%] female; median [IQR] age, 13.0 [7.6-22.0] years). The 112 nevi overall frequently displayed an organized dermoscopic pattern (CFC, 61 [84.7%]; CS, 34 [85.0%]) rather than a disorganized pattern (CFC, 6 [8.3%]; CS, 1 [2.5%]). Of the organized nevi, homogenous brown was the most common pattern (CFC, 41 [67.2%]; CS, 22 [64.7%]), followed by reticular (CFC, 11 [18.0%]; CS, 7 [20.6%]) and globular (CFC, 9 [14.8%]; CS, 5 [14.7%]). Pigmented networks occurred in 12 nevi in CFC (16.7%) and 6 nevi in CS (15%; P > .99). Of these, 6 CFC-associated nevi (50%) and no CS-associated nevi had atypical networks (P = .05). Six patients with CFC in the follow-up study developed significantly more nevi within 5 years (median [IQR] increase, 24.5 [10-120] nevi; P = .04). Conclusions and Relevance: In this cohort study, the findings suggest that nevi in patients with CFC and CS commonly display organized homogenous brown dermoscopic patterns, and the number of nevi may significantly increase over time in those with CFC. A disorganized pattern and atypical networks may be more frequent in patients with CFC. Future studies are needed to determine the risk of melanoma in individuals with CFC or CS.

Comparison of S100A8 and PRAME as biomarkers for distinguishing melanoma from melanocytic naevus: a case-control analysis.

BACKGROUND: S100A8 is a melanoma biomarker expressed in the melanoma-associated epidermal keratinocytes, but its diagnostic utility has not been compared with other biomarkers, including PRAME. OBJECTIVES: To compare the utility of S100A8 and PRAME immunohistochemistry (IHC) in the differential diagnosis of melanoma and naevi in a case-control study. METHODS: A previously described cohort of 209 melanomas (case samples) and naevi (control samples) dual-immunostained for S100A8 and PRAME were included. For S100A8, previously reported scores indicating the proportion of tumour-associated epidermis stained (0 = indeterminate; 1 = 0-4%; 2 = 5-25%; 3 = 26-50%; 4 = 51-75%; 5 = > 75%) were utilized. PRAME IHC was reviewed by at least two reviewers and a consensus score assigned, with score indicating the proportion of tumour stained (0 = indeterminate; 1 = 0%; 2 = 1-50%; 3 = > 50%). A positive test was defined as > 50% staining. RESULTS: The area under the receiver operating characteristic curves for S100A8 (0.833) and PRAME (0.874) were not significantly different from each other (P = 0.22). The diagnostic sensitivity and specificity were 42.4% [95% confidence interval (CI) 32.6-52.8%] and 98.2% (95% CI 93.6-99.8%) for S100A8, and 79.8% (95% CI 70.5-87.2%) and 87.3% (95% CI 79.6-92.9%) for PRAME, respectively. A combined test requiring both S100A8 and PRAME IHC positivity had a sensitivity of 39.4% (95% CI 29.7-49.7%) and specificity of 99.1% (95% CI 95.0-100.0%). CONCLUSIONS: S100A8 and PRAME have utility in the diagnostic workup of melanoma, with S100A8 being more specific and PRAME being more sensitive when using this threshold. Our findings suggest that these two immunohistochemical markers may favourably complement one another to improve the detection of melanoma.

Melanocytic neoplasms in neurofibromatosis type 1: a systematic review.

Neurofibromatosis type 1 ( NF1 ) is commonly mutated in melanoma, yet the risk of melanoma in individuals with NF1 is incompletely understood. We performed a systematic review to investigate the risk and characteristics of melanoma and melanocytic nevi in NF1 individuals. PubMed was searched for articles describing NF1 individuals with melanoma, or melanocytic nevi. Those with cutaneous and ocular melanomas were compared to the general population using Surveillance, Epidemiology, and End Results data. Fifty-three articles describing 188 NF1 patients were included (melanoma n  = 82, melanocytic nevi n  = 93, melanocytic nevi, and melanoma n  = 13). Compared to the general population, NF1 patients with cutaneous melanomas had earlier melanoma diagnoses (49.1 vs. 58.6 years, P = 0.012), thicker tumors (3.7 vs. 1.2 mm, P = 0.006), and more frequent disease-specific deaths (27.3% vs. 8.6%, P = 0.005) with shorter survival (12.9 vs. 34.2 months, P = 0.011). Ocular melanomas made up 15.0% of all melanomas in NF1 patients versus 1.5% in the general population ( P < 0.001). In pooling all population-based studies describing melanoma in NF1 populations, NF1 individuals had 2.55 higher odds of having melanoma compared to the general population. A nevus spilus was commonly reported among NF1 individuals with nevi (44.8%, 39/87). Our findings suggest that NF1 individuals may have a higher risk for developing melanomas and tend to have thicker melanomas and worse survival compared to the general population, highlighting the importance of cutaneous and ophthalmologic surveillance in NF1 patients. Our review also supports the association between NF1 and nevus spilus.

SCALP syndrome with a germline heterozygous DOCK6 mutation and somatic mosaic NRAS Q61R mutation.

We present a case of SCALP syndrome, which was diagnosed in a male infant with the characteristic findings of sebaceous nevi, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and giant congenital melanocytic nevi, or pigmented nevi. We identified a germline compound heterozygous DOCK6 mutation and a somatic mosaic NRAS Q61R mutation in the giant congenital melanocytic nevus. This report will increase clinician awareness of SCALP syndrome and augment the literature in characterizing this rare syndrome, including its genetic background.

Pruritic papules after induction chemotherapy with daunorubicin and cytarabine.

We present a 65-year-old woman who developed a diffuse pruritic papular eruption after receiving induction chemotherapy with daunorubicin and cytarabine for newly diagnosed acute myelomonocytic leukemia. The rash improved clinically with triamcinolone treatment and chemotherapy was allowed to continue. This case adds to the growing literature of transient acantholytic dermatosis development in the setting of anti-cancer therapy and emphasizes the importance of clinicopathologic correlation in cutaneous eruptions in cancer patients.

Characteristics of patients with juvenile dermatomyositis from 2001-2021 at a tertiary care center.

BACKGROUND: Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in the pediatric population and can represent a medical emergency. However, many features of JDM remain poorly understood, disease presentation is highly variable, and predictors of disease course have yet to be identified. METHODS: This retrospective chart review included 47 JDM patients seen at a tertiary care center over a 20-year period. Characteristics such as demographics, clinical signs and symptoms, antibody positivity, dermatopathology features, and treatments were recorded. RESULTS: All patients had evidence of cutaneous involvement, whereas 88.4% experienced muscle weakness. Constitutional symptoms and dysphagia were commonly present. The most frequent cutaneous findings were Gottron papules, heliotrope rash, and nailfold changes. Anti-TIF1? was the most prevalent myositis-specific autoantibody. Management involved systemic corticosteroids in nearly all cases. Strikingly, the dermatology department was only involved in the care of four in every ten (19/47) patients. CONCLUSIONS: Prompt recognition of the strikingly reproducible skin findings present in JDM can improve disease outcomes in this population. This study highlights the need for increased education of such pathognomonic findings as well as more multidisciplinary care. In particular, a dermatologist should be involved in the care of patients presenting with muscle weakness and skin changes.

Limited sun safety education in high school curricula: a pilot study and call to action.

Although tanning is widespread, the use of both indoor and outdoor tanning most often begins in adolescence and young adulthood and is more prevalent in adolescents and young adults (AYA) than any other age group. Despite this, information regarding sun safety education in high school curricula is limited. In this pilot study, we sought to characterize the presence of education regarding sun safety in the curricula of US public high schools. Cross-sectional survey administered to random sample stratified by state of public high schools in the US. 31 high schools from 22 states submitted survey responses (Fig. 1). Ten high schools (32.2%) provided curricula regarding sun safety. Southern high schools were less likely to provide sun safety education (p = 0.01). The lack of an association between sociodemographic characteristics of the high school and the provision of sun safety curricula suggests that the lack of sun safety education may be widespread. These findings support a call to action regarding further research to better characterize the efficacy of implementing sun safety education in high school curricula. Educational interventions designed to inform high school students about sun safety present a unique opportunity to intervene in the rising skin cancer rates in the AYA population. As rates of skin cancer in AYA continue to rise, it is vital to develop strategies to implement education regarding sun safety and skin cancer risk factors in high school curricula.

Risk factors and timing of subsequent cutaneous squamous cell carcinoma in patients with cutaneous squamous cell carcinoma: A retrospective cohort study.

BACKGROUND: Information about the frequency and timing of subsequent cutaneous squamous cell carcinoma (cSCC), along with associated risk factors, is limited. However, this information is crucial to guide follow-up care for these patients. OBJECTIVE: To evaluate the risk and timing of subsequent cSCC in patients who presented with an initial diagnosis of cSCC. METHODS: Retrospective review of an institutional review board-approved, single-institution registry of invasive cSCC. All patients had at least 2 primary cSCCs diagnosed on 2 separate dates 2 months apart. RESULTS: A total of 299 primary cSCCs were included. At 6 months from initial cSCC diagnosis, 18.06% (n = 54) of patients developed subsequent cSCC; at 1 year, 31.77% (n = 94); at 3 years, 67.56% (n = 202); and at 5 years, 87.96% (n = 263) developed subsequent cSCC. Risk factors associated with subsequent cSCC include age at initial diagnosis (hazard ratio [HR], 1.02; 95% confidence interval, 1.004-1.027; P = .008), T2 stage (HR, 1.66; 95% CI, 1.07-2.57; P = .025), and poor tumor grade. Tumor grades well, moderate, and unknown have HRs of 0.21 (P < .001), 0.16 (P .001), and 0.25 (P = .001), respectively. CONCLUSIONS: Of patients who develop subsequent cSCC, 18.06% do so within 6 months, and 31.77% do so within 1 year of initial cSCC diagnosis. Patients with advanced age, poor histologic differentiation, and American Joint Committee on Cancer T2 stage are at highest risk. Close clinical follow-up after the initial diagnosis is recommended.