No abstract

Background: Strategies to non-invasively detect cutaneous melanoma generally focus on differentiating melanoma from non-melanoma lesions. However, given the variabilities in practice and lack of guidelines, it is important for clinicians to understand how such strategies and technologies perform on borderline lesions of uncertain clinical behavior. Objective: To evaluate LINC and PRAME gene expression and the presence of somatic mutations in BRAF, NRAS, and/or TERT in severely dysplastic nevi (SDN) and to assess, how combining gene expression and mutation analyses may impact test performance.Materials and Methods: One hundred three eligible skin lesions clinically suspicious for melanoma were non-invasively sampled via adhesive patches to enable genomic analyses. Afterward, these same lesions were immediately surgically biopsied to enable comparisons of genomic analyses with histopathologic diagnoses rendered by a panel of three dermatopathologists.  Twenty-three of these lesions analyzed were deemed borderline lesions of SDN histology by at least one dermatopathologist. RNA-based gene expression positivity by Pigmented Lesion Assay (PLA) analysis was defined by detectable levels of LINC and/or PRAME. DNA-based mutation positivity was defined as detection of somatic mutations in BRAF (non-V600E), NRAS, and/or the TERT promoter. Results: Adding TERT mutation analyses to PLA gene expression increases the test’s sensitivity to rule out melanoma from 93% to 97% in this study.  In addition, 61% of PLA positive lesions that were not diagnosed as melanoma were found to have severe histologic atypia. PLA-positive lesions histopathologically diagnosed as melanomas harbored TERT mutations in 70% of cases while both SDN and non-melanoma lesions including nevi without severe histologic atypia harbored TERT mutations in 4% of cases.  BRAF non-V600E and NRAS mutations were only found in the melanoma group and adding these mutations did not further enhance the test’s sensitivity. Conclusions and Relevance: PLA positivity increases with histologic atypia of pigmented skin lesions. Combining TERT mutation analyses with melanoma-associated gene expression provides additional genetic information to further non-invasively risk-stratify pigmented lesions.  These findings furthermore support that pigmented lesions exist on a spectrum of genomic atypia that may prove useful in identifying borderline lesions beyond their morphological appearance.

New-onset psoriasis in patients receiving tumor necrosis factor inhibitors is well recognized in children and adults. We describe three children who underwent cardiac transplantation and developed an analogous form of paradoxic eczema occurring 2-48 months after starting systemic tacrolimus, a drug widely used topically to treat eczema. Anecdotal reports and our experience suggest that tacrolimus taper with alternative systemic antirejection immunosuppressant may lead to skin clearance.Pending additional insight, treatment should include optimizing skin barrier function, minimizing microbial and allergic triggers, and coordinating care to choose the besttolerated systemic immunosuppressant regimen at the lowest effective dose.eczema, genetic disease/mechanism, immunodeficiency, systemic therapy, topical therapy | INTRODUCTIONParadoxic psoriasis triggered by tumor necrosis factor (TNF) inhibitors has been reported in children and adults. 1 We report an analogous form of eczema occurring in children who underwent cardiac transplantation taking systemic antirejection therapy featuring the calcineurin inhibitor tacrolimus. Tacrolimus is used systemically to prevent solid organ rejection but also topically to control atopic dermatitis. Several reports have associated systemic tacrolimus with food allergy, asthma, eosinophilia, 2-4 and, paradoxically, eczema. 5-7One proposed mechanism for tacrolimus-associated atopy is sup- | Patient 1Patient 1 underwent cardiac transplantation at 1 month of age for pulmonary atresia with intact intraventricular septum, hypoplastic right heart, and right ventricle-dependent coronary arteries. He was started on systemic immunosuppression with oral tacrolimus (0.14 mg/kg/d, adjusted to goal serum trough 8-10 ng/mL) and mycophenolate mofetil (10-15 mg/kg/d), followed by worsening eczema that prompted dermatology evaluation at 10 months (Table 1). His history and examination were remarkable for recurrent cutaneous and extracutaneous infections, developmental and language delay, and dysmorphic features, including bilateral hair whorls, high arched palate, and notched superior helices suggestive of DiGeorge-velocardiofacial syndrome (DGS-VCFS), although fluorescence in situ hybridization (FISH) testing was negative. Recurrent otitis media and sinusitis were controlled using daily cefdinir prophylaxis.Bland emollients, bleach baths, ketoconazole shampoo, and intermittent mometasone 0.1% ointment improved his skin but did not mitigate frequent flares. Serial surveillance skin and throat cultures identified colonization with group A Streptococcus (GAS) and methicillin-resistant Staphylococcus aureus, addressed with tonsillectomy and adenoidectomy at age 29 months. His skin disease stabilized for 16 months with adjunctive pimecrolimus 1% cream, monthly mupirocin decolonization, and ciclopirox shampoo, but subsequently worsened, requiring hospitalization for intensive skin care. Herpes simplex

No abstract

No abstract