Melanoma Epidemiology and Prevention.

The epidemiology of melanoma is complex, and individual risk depends on sun exposure, host factors, and genetic factors, and in their interactions as well. Sun exposure can be classified as intermittent, chronic, or cumulative (overall) exposure, and each appears to have a different effect on type of melanoma. Other environmental factors, such as chemical exposures-either through occupation, atmosphere, or food-may increase risk for melanoma, and this area warrants further study. Host factors that are well known to be important are the numbers and types of nevi and the skin phenotype. Genetic factors are classified as high-penetrant genes, moderate-risk genes, or low-risk genetic polymorphisms. Subtypes of tumors, such as BRAF-mutated tumors, have different risk factors as well as different therapies. Prevention of melanoma has been attempted using various strategies in specific subpopulations, but to date optimal interventions to reduce incidence have not emerged.

IL2 Inducible T-cell Kinase, a Novel Therapeutic Target in Melanoma.

PURPOSE: IL2 inducible T-cell kinase (ITK) promoter CpG sites are hypomethylated in melanomas compared with nevi. The expression of ITK in melanomas, however, has not been established and requires elucidation. EXPERIMENTAL DESIGN: An ITK-specific monoclonal antibody was used to probe sections from deidentified, formalin-fixed paraffin-embedded tumor blocks or cell line arrays and ITK was visualized by IHC. Levels of ITK protein differed among melanoma cell lines and representative lines were transduced with four different lentiviral constructs that each contained an shRNA designed to knockdown ITK mRNA levels. The effects of the selective ITK inhibitor BI 10N on cell lines and mouse models were also determined. RESULTS: ITK protein expression increased with nevus to metastatic melanoma progression. In melanoma cell lines, genetic or pharmacologic inhibition of ITK decreased proliferation and migration and increased the percentage of cells in the G0-G1 phase. Treatment of melanoma-bearing mice with BI 10N reduced growth of ITK-expressing xenografts or established autochthonous (Tyr-Cre/Pten(null)/Braf(V600E)) melanomas. CONCLUSIONS: We conclude that ITK, formerly considered an immune cell-specific protein, is aberrantly expressed in melanoma and promotes tumor development and progression. Our finding that ITK is aberrantly expressed in most metastatic melanomas suggests that inhibitors of ITK may be efficacious for melanoma treatment. The efficacy of a small-molecule ITK inhibitor in the Tyr-Cre/Pten(null)/Braf(V600E) mouse melanoma model supports this possibility.

Examining the efficacy and safety of squaric acid therapy for treatment of recalcitrant warts in children.

The objective of the study was to determine the safety and efficacy of squaric acid dibutyl ester (SADBE) therapy on the treatment of recalcitrant warts in children. This retrospective chart review examined 72 patients treated using SADBE from July 2002 to December 2012. Patients were followed for 6 months to 11 years. Patients were treated at a pediatric dermatology outpatient clinic at the University of North Carolina at Chapel Hill. Seventy-two children with verrucae who failed initial treatment for warts were selected for the study. Full long-term follow-up was obtained in 48 patients. Four patients discontinued the use of SADBE because of adverse effects. The primary study outcome was efficacy of SADBE treatment. Adverse effects, dosages administered, type of wart, other cutaneous disease present, and level of immunosuppression were measured. Forty of 48 (83%) patients in whom treatment outcomes could be obtained reported complete resolution of their warts. Seventy percent of patients used a maximum concentration of 0.4% SADBE and 60% of patients reported no adverse effects. The majority of patients treated with SADBE reported complete resolution of warts. Most patients reported no adverse effects even while receiving doses as high as 2% daily. This study shows that SADBE is a safe and effective treatment for recalcitrant warts in children.

Evaluation of the prognostic significance of follicular extension in actinic keratoses.

OBJECTIVE: To determine the prognostic significance of follicular extension in actinic keratosis. DESIGN: Retrospective, case-controlled study. SETTING: Mount Sinai Dermatopathology Services. PATIENTS/PARTICIPANTS: Out of a randomly selected pool of 1,000 biopsies, 104 cases of actinic keratosis with follicular extension and 104 cases of actinic keratosis without follicular extension were chosen for the study (56.7% male; mean [SD] age, 67.5 [11.8] years; age range, 28-93). MAIN OUTCOME MEASURES: Presence of follicular extension and location of the actinic keratosis. Age and gender of the patient. Number of previously diagnosed squamous cell carcinomas, basal cell carcinomas, and melanomas per patient. RESULTS: Patients with follicular extension of actinic keratosis were 1.8 times more likely to have a previous history of invasive carcinoma than patients without follicular extension. Patients with follicular extension were 11 times more likely to have a previous history of invasive melanoma than patients with actinic keratoses without follicular extension. Patients with follicular extension were more likely to be male, had an older average age, and more often presented with lesions on their leg when compared to patients with actinic keratoses lacking follicular extension. CONCLUSION: Patients presenting with actinic keratoses with follicular extension were more likely to have increased risk factors for skin cancer. These findings have implications for identifying patient factors predictive of progression of actinic keratosis to invasive carcinoma, providing potentially valuable patient screening guidelines.

Leukemia cutis presenting clinically as disseminated herpes zoster in a patient with unrecognized acute promyelocytic leukemia.

A 46-year-old man presented with a two-week history of fatigue, fevers, and multiple nonhealing ulcers on his abdomen and back. He also had several dermatomal plaques clinically consistent with multifocal herpes zoster. Biopsy revealed large atypical myeloid cells dissecting through the dermis as well as marked papillary edema reminiscent of Sweet's syndrome. Blood work revealed an elevated white count (35-10(9) cells/L) with 11 percent blasts. Fluorescence in situ hybridization demonstrated a t(15;17) rearrangement diagnostic of M3 acute nonlymphocytic leukemia/acute promyelocytic leukemia. Chemotherapy was initiated, but the patient became septic and expired within two weeks. Acute promyelocytic leukemia cutis is exceedingly rare with only 24 previously reported cases, all of which occurred following treatment with all-trans retinoic acid, which is thought to induce the dermal tropism. The authors believe this is the first reported case of acute promyelocytic leukemia initially presenting with cutaneous involvement. The case is also notable for the Sweet's-like features of the infiltrate.