Association of Incident Amelanotic Melanoma With Phenotypic Characteristics, MC1R Status, and Prior Amelanotic Melanoma.

Importance: We previously reported that survival is poorer from histopathologically amelanotic than pigmented melanoma because of more advanced stage at diagnosis. Identifying patients at risk of amelanotic melanoma might enable earlier diagnosis and improved survival; however, the phenotypic characteristics and underlying genetics associated with amelanotic melanoma are unknown. Objective: To determine whether phenotypic characteristics, carriage of MC1R variants, and history of amelanotic melanoma are associated with histopathologically amelanotic melanoma. Design, Setting, and Participants: The Genes, Environment, and Melanoma (GEM) study is an international cohort study that enrolled patients with incident primary cutaneous melanomas from population-based and hospital-based cancer registries (1998 to 2003). The GEM participants included here were 2387 patients with data for phenotypes, MC1R genotype, and primary melanomas scored for histopathologic pigmentation. Of these 2387 patients with incident melanomas scored for pigmentation, 527 had prior primary melanomas also scored for pigmentation. Main Outcomes and Measures: Associations of phenotypic characteristics (freckles, nevi, phenotypic index) and MC1R status with incident amelanotic melanomas were evaluated using logistic regression models adjusted for age, sex, study center, and primary status (single or multiple primary melanoma); odds ratios (ORs) and 95% CIs are reported. Association of histopathologic pigmentation between incident and prior melanomas was analyzed using an exact logistic regression model. Results: This study included 2387 patients (1065 women, 1322 men; mean [SD] age at diagnosis, 58.3 [16.1] years) and 2917 primary melanomas. In a multivariable model including phenotypic characteristics, absence of back nevi, presence of many freckles, and a sun-sensitive phenotypic index were independently associated with amelanotic melanoma. Carriage of MC1R variants was associated with amelanotic melanoma but lost statistical significance in a model with phenotype. Further, patients with incident primary amelanotic melanomas were more likely to have had a prior primary amelanotic melanoma (OR, 4.62; 95% CI, 1.25-14.13) than those with incident primary pigmented melanomas. Conclusions and Relevance: Absence of back nevi, presence of many freckles, a sun-sensitive phenotypic index, and prior amelanotic melanoma increase odds for development of amelanotic melanoma. An increased index of suspicion for melanoma in presenting nonpigmented lesions and more careful examination for signs of amelanotic melanoma during periodic skin examination in patients at increased odds of amelanotic melanoma might lead to earlier diagnosis and improved survival.

Comparison of clinicopathologic features and survival of histopathologically amelanotic and pigmented melanomas: a population-based study.

IMPORTANCE Previous studies have reported that histopathologically amelanotic melanoma is associated with poorer survival than pigmented melanoma; however, small numbers of amelanotic melanomas, selected populations, lack of centralized pathologic review, or no adjustment for stage limit the interpretation or generalization of results from prior studies.OBJECTIVE To compare melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented melanoma in a large international population-based study.DESIGN, SETTING, AND PARTICIPANTS Survival analysis with a median follow-up of 7.6 years.The study population comprised 2995 patients with 3486 invasive primary melanomas centrally scored for histologic pigmentation from the Genes, Environment, and Melanoma(GEM) Study, which enrolled incident cases of melanoma diagnosed in 1998 through 2003 from international population-based cancer registries.MAIN OUTCOMES AND MEASURES Clinicopathologic predictors and melanoma-specific survival of histologically amelanotic and pigmented melanoma were compared using generalized estimating equations and Cox regression models, respectively.RESULTS Of 3467 melanomas, 275 (8%) were histopathologically amelanotic. Female sex,nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a coexisting nevus were independently associated with amelanotic melanoma (each P < .05). Amelanotic melanoma was generally ofa higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis (odds ratios[ORs] [95%CIs] between 2.9 [1.8-4.6] and 11.1 [5.8-21.2] for tumor stages between T1b and T3b and ORs [95%CIs] of 24.6 [13.6-44.4] for T4a and 29.1 [15.5-54.9] for T4b relative to T1a;P value for trend, <.001) than pigmented melanoma. Hazard of death from melanoma was higher for amelanotic than for pigmented melanoma (hazard ratio [HR], 2.0; 95%CI, 1.4-3.0)(P < .001), adjusted for age, sex, anatomic site, and study design variables, but survival did not differ once AJCC tumor stage was also taken into account (HR, 0.8; 95%CI, 0.5-1.2)(P = .36).CONCLUSIONS AND RELEVANCE At the population level, survival after diagnosis of amelanotic melanoma is poorer than after pigmented melanoma because of its more advanced stage at diagnosis. It is probable that amelanotic melanomas present at more advanced tumor stages because they are difficult to diagnose. The association of amelanotic melanoma with presence of mitoses independently of Breslow thickness and other clinicopathologic characteristics suggests that amelanotic melanomas might also grow faster than pigmented melanomas. New strategies for early diagnosis and investigation of the biological properties of amelanotic melanoma are warranted.

Benchmarking US Department of Veterans Affairs dermatologic services: results from a national survey.

BACKGROUND: How well Department of Veterans Affairs (VA) dermatology services provide clinical care, medical education, and innovative research is a largely unexplored topic in the literature. OBJECTIVE: We sought to benchmark VA dermatology services by surveying VA dermatologists about their environment, resources, and the pros and cons of working in the VA. METHODS: Printed surveys were mailed to VA dermatologists and responses were compiled and analyzed. RESULTS: Of 105 dermatology services surveyed, 48% returned surveys completed by board-certified dermatologists (n = 50); 20 surveys completed by nondermatologists were excluded from the analysis. Most services trained dermatology residents (72%) and medical students (80%). One third of services reported significant research involvement. Qualitative analysis revealed the academic environment, patient population, and decreased business management responsibilities as the 3 most commonly cited advantages to VA employment. The most commonly listed disadvantages included low salaries, bureaucracy, and lack of resources. LIMITATIONS: The survey data were self-reported and not independently verified. Not all services returned the survey. CONCLUSIONS: Outpatient VA dermatology services accomplish significant primary care and preventive services (eg, sun safety counseling, skin cancer screening, and treatment). However, the small number of dedicated dermatology services, their irregular geographic distribution, and the lack of staffing and resources may adversely affect optimal patient care. Dermatologist responses regarding the positive and negative aspects of working in the VA system may lead to improved management strategies to better retain and recruit dermatologists to provide patient care, medical education, and medical research despite dramatically lower dermatologist salaries within the VA system compared with private practice.

Systemic treatment of pediatric atopic dermatitis with azathioprine and mycophenolate mofetil.

Severe forms of atopic dermatitis (AD) cause significant morbidity in vulnerable pediatric populations and necessitate treatment with systemic therapy. The existing literature concerning the treatment of severe pediatric AD with azathioprine (AZ) and mycophenolate mofetil (MM) is sparse. The purpose of this case series is to examine the use of these two drugs in the treatment of severe pediatric AD. Medical records of 28 pediatric patients with AD from the University of North Carolina at Chapel Hill pediatric dermatology clinic treated using these two drugs were analyzed for laboratory values, thiopurine methyltransferase (TPMT) levels, symptoms, infections, and other relevant data. Patients were also contacted via the telephone to ascertain outcomes and any missing data. Treatment outcomes were scored into three categories: significant improvement, some improvement, and no improvement. AZ dosing was correlated to TPMT levels successfully, with comparable levels of improvement in the heterozygous and homozygous wild-type groups. Absolute eosinophil count corresponded to AD activity and treatment response across both treatment modalities in 18 of 26 (69%) patients. Seventeen of 28 (61%) patients treated with AZ and eight of 12 (66%) treated with MM reported significant improvement. We had lower rates of laboratory abnormalities and side effects with MM than with AZ but similar rates of cutaneous infections. Treatment outcomes did not appear to differ with race, sex, or TPMT level. We experienced success with AZ and MM in the treatment of severe pediatric AD. Coordinating treatment to each patient's unique morbidities is the best way to choose systemic treatments.