Melanoma arising in a nevus of Ito: novel genetic mutations and a review of the literature on cutaneous malignant transformation of dermal melanocytosis.

Dermal melanocytosis refers to a spectrum of benign melanocytic proliferations that includes Mongolian spot, nevus of Ota and nevus of Ito. These lesions most commonly occur in persons of Asian or African descent and are often present at birth or develop during childhood. Very rarely, dermal melanocytoses undergo malignant transformation. There have been only 13 reports in the literature of primary cutaneous melanoma arising in dermal melanocytoses. We report a case of a Chinese woman with melanoma arising in a congenital nevus of Ito. We performed targeted next-generation sequencing of the tumor which revealed mutations of GNAQ and BAP1, suggesting that alterations in these two genes led to malignant transformation of the nevus of Ito. We also provide a summary of reports in the literature regarding primary cutaneous melanoma arising in the context of dermal melanocytosis.

Merkel cell carcinoma, version 1.2014.

Merkel cell carcinoma is a rare, aggressive cutaneous tumor that combines the local recurrence rates of infiltrative nonmelanoma skin cancer with the regional and distant metastatic rates of thick melanoma. The NCCN Guidelines for Merkel Cell Carcinoma provide recommendations on the diagnosis and management of this aggressive disease based on clinical evidence and expert consensus. This version includes revisions regarding the use of PET/CT imaging and the addition of a new section on the principles of pathology to provide guidance on the analysis, interpretation, and reporting of pathology results.

Dermatofibrosarcoma protuberans, version 1.2014.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor characterized by a relatively high risk of local recurrence and low risk of metastasis. The NCCN Guidelines for DFSP provide multidisciplinary recommendations on the management of patients with this rare disease. These NCCN Guidelines Insights highlight the addition of the Principles of Pathology section, which provides recommendations on the pathologic assessment of DFSP. Because DFSP can mimic other lesions, immunohistochemical studies are often required to establish diagnosis. Cytogenetic testing for the characteristic translocation t(17;22)(q22;q13) can also be valuable in the differential diagnosis of DFSP with other histologically similar tumors.

Skin cancer education and early detection at the beach: a randomized trial of dermatologist examination and biometric feedback.

BACKGROUND: There are limited data on the effectiveness of skin cancer prevention education and early detection programs at beaches. OBJECTIVES: We evaluate 4 strategies for addressing skin cancer prevention in beach settings. METHODS: This prospective study at 4 beaches included 4 intervention conditions: (1) education only; (2) education plus biometric feedback; (3) education plus dermatologist skin examination; or (4) education plus biometric feedback and dermatologist skin examination. Outcomes included sun protection behaviors, sunburns, and skin self-examinations. RESULTS: There was a significant increase in hat wearing, sunscreen use, and a reduction in sunburns in the education plus biometric feedback group (odds ratio = 1.97, 1.94, and 1.07, respectively), and greater improvements in knowing what to look for in skin-self examinations (odds ratio = 1.13); there were no differences in frequency of self-examinations. Skin examinations plus biometric feedback led to greater reductions in sunburns. The dermatologist examinations identified atypical moles in 28% of participants. LIMITATIONS: Inclusion of only one beach per condition, use of self-report data, and a limited intervention period are limitations. CONCLUSIONS: Education and biometric feedback may be more effective than education alone for impacting sun protective attitudes and behaviors in beachgoing, high-risk populations.

Lentigo maligna (melanoma in situ) treated with imiquimod cream 5%: 12 case reports.

Lentigo maligna (LM) is an in situ variant of melanoma. Although LM has the potential for invasion, it often has a greatly protracted radial growth phase and may remain indolent for years. The current standard of care is surgical excision, but this often results in substantial morbidity; thus, nonsurgical approaches continue to be investigated. Imiquimod cream 5% is an immunomodulatory agent that previously has been reported to successfully eradicate LM. We evaluated the treatment course of topical imiquimod in 12 patients with LM. Data from patients with biopsy-proven LM were collected retrospectively, reviewed, and summarized. Patients ranged in age from 54 to 83 years. Most patients chose imiquimod cream as their initial form of treatment; however, other patients had a history of LM recurrence after excision or had positive histologic margins at the time of excision. Initial application regimens varied from 2 to 7 times weekly. The average duration of treatment was 15.7 weeks but ranged from 7 to 44 weeks. Results of posttreatment biopsies of the most clinically suspicious areas in 6 patients showed histologic clearance; 2 patients demonstrated single atypical melanocytes and 4 patients demonstrated clinical clearance without histologic confirmation. These findings suggest that imiquimod cream 5% may be an effective alternative treatment for LM.

Using Appearance-Based Messages to Increase Sun Protection in Adolescent Young Adult Cancer Survivors: A Pilot Study of Ultraviolet Light Photography.

Despite risk for secondary skin cancers, many adolescent and young adult (AYA) cancer survivors do not practice recommended sun protection (SP). Ultraviolet light photography (UVP), which demonstrates the negative impact of sun exposure on physical appearance, has been shown to increase SP in community AYA samples. This study of 58 AYA cancer survivors demonstrates that UVP is acceptable and not distressing to this population. Follow-up data on 23 AYAs demonstrated that those given UVP significantly improve their SP behaviors, while those receiving standard educational materials do not. Results demonstrate UVP is a promising tool for increasing SP in AYA survivors.

Methotrexate-induced bullous acral erythema in a child.

Chemotherapy induced acral erythema (CIAE) is an uncommon and dramatic reaction to high-dose chemotherapy. It is characterized by symmetrical, well-demarcated, painful erythema of the palms and soles which may progress to bullae formation and desquamation. Prompt recognition and discrimination from more serious conditions such as graft-vs-host disease or toxic epidermal necrolysis is essential. This paper describes the case of a 12-year-old boy who developed CIAE after high-dose methotrexate treatment and discusses the important clinical, histopathological, and therapeutic features of this condition.

Targeted next-generation sequencing reveals high frequency of mutations in epigenetic regulators across treatment-naïve patient melanomas.

BACKGROUND: Recent developments in genomic sequencing have advanced our understanding of the mutations underlying human malignancy. Melanoma is a prototype of an aggressive, genetically heterogeneous cancer notorious for its biologic plasticity and predilection towards developing resistance to targeted therapies. Evidence is rapidly accumulating that dysregulated epigenetic mechanisms (DNA methylation/demethylation, histone modification, non-coding RNAs) may play a central role in the pathogenesis of melanoma. Therefore, we sought to characterize the frequency and nature of mutations in epigenetic regulators in clinical, treatment-naïve, patient melanoma specimens obtained from one academic institution. RESULTS: Targeted next-generation sequencing for 275 known and investigative cancer genes (of which 41 genes, or 14.9 %, encoded an epigenetic regulator) of 38 treatment-naïve patient melanoma samples revealed that 22.3 % (165 of 740) of all non-silent mutations affected an epigenetic regulator. The most frequently mutated genes were BRAF, MECOM, NRAS, TP53, MLL2, and CDKN2A. Of the 40 most commonly mutated genes, 12 (30.0 %) encoded epigenetic regulators, including genes encoding enzymes involved in histone modification (MECOM, MLL2, SETD2), chromatin remodeling (ARID1B, ARID2), and DNA methylation and demethylation (TET2, IDH1). Among the 38 patient melanoma samples, 35 (92.1 %) harbored at least one mutation in an epigenetic regulator. The genes with the highest number of total UVB-signature mutations encoded epigenetic regulators, including MLL2 (100 %, 16 of 16) and MECOM (82.6 %, 19 of 23). Moreover, on average, epigenetic genes harbored a significantly greater number of UVB-signature mutations per gene than non-epigenetic genes (3.7 versus 2.4, respectively; p = 0.01). Bioinformatics analysis of The Cancer Genome Atlas (TCGA) melanoma mutation dataset also revealed a frequency of mutations in the 41 epigenetic genes comparable to that found within our cohort of patient melanoma samples. CONCLUSIONS: Our study identified a high prevalence of somatic mutations in genes encoding epigenetic regulators, including those involved in DNA demethylation, histone modification, chromatin remodeling, and microRNA processing. Moreover, UVB-signature mutations were found more commonly among epigenetic genes than in non-epigenetic genes. Taken together, these findings further implicate epigenetic mechanisms, particularly those involving the chromatin-remodeling enzyme MECOM/EVI1 and histone-modifying enzyme MLL2, in the pathobiology of melanoma.

Poison ivy: an underreported cause of erythema multiforme.

The relationship between herpes simplex virus (HSV) and erythema multiforme (EM) has been well described. Many authors contend that EM (excluding Stevens-Johnson syndrome and toxic epidermal necrolysis) occurs almost exclusively as a response to HSV infection. During the past year, however, we have observed several cases of EM complicating severe Rhus allergic contact dermatitis. Although this association has been previously documented, the paucity of cases in the literature, along with our experience, suggests that this is an underreported phenomenon. We describe 4 of our cases.

Sun exposure in young adult cancer survivors on and off the beach: results from Project REACH.

BACKGROUND: Although cancer survivors are at risk for future skin cancers, many do not practice recommended sun protection. Studies have demonstrated poor adherence to specific behaviors (e.g., sunscreen, artificial tanning) during sunbathing, but less is known about survivors' typical amount of sun exposure during activities other than sunbathing. METHODS: We conducted a mailed survey of 153 adults (median age = 26.1) diagnosed with a non-skin cancer before age 30. Information on recent sunbathing and incidental sun exposures, protective behaviors, and perceived vulnerability was collected. Analyses focused on characterizing survivors with the lowest levels of recommended sun protection. RESULTS: Twenty-nine percent of participants exhibited low sun protection adherence during sunbathing and 31% during incidental exposure. Younger age was associated with low adherence, but this difference was significant only for sunbathing (OR=0.4; 95% CI, 0.2-0.9). Women were more likely than men to have low adherence during sunbathing (34.0% vs. 20.3%; OR = 2.44; 95% CI, 1.1-5.5). Survivors treated with radiation did not differ on exposures, adherence, or perceived vulnerability to the sun, despite feeling more susceptible to skin cancers (p = 0.03). CONCLUSIONS: Despite known skin cancer risks, many young cancer survivors receive significant sun exposure. Assessment of sunbathing alone fails to capture sun exposure behaviors, particularly in men. Survivors treated with radiation may recognize their increased risk of skin cancer, but not the role of sun protection in modifying that risk.

Patient follow-up after participating in a beach-based skin cancer screening program.

Many skin cancer screenings occur in non-traditional community settings, with the beach being an important setting due to beachgoers being at high risk for skin cancer. This study is a secondary analysis of data from a randomized trial of a skin cancer intervention in which participants (n = 312) had a full-body skin examination by a clinician and received a presumptive diagnosis (abnormal finding, no abnormal finding). Participants' pursuit of follow-up was assessed post-intervention (n = 283). Analyses examined: (1) participant's recall of screening results; and (2) whether cognitive and behavioral variables were associated with follow-up being as advised. Just 12% of participants (36/312) did not correctly recall the results of their skin examination. One-third (33%, 93/283) of participants' follow-up was classified as being not as advised (recommend follow-up not pursued, unadvised follow-up pursued). Among participants whose follow-up was not as advised, 71% (66/93) did not seek recommended care. None of the measured behavioral and cognitive variables were significantly associated with recall of screening examination results or whether follow-up was as advised. Research is needed to determine what factors are associated with follow-up being as advised and to develop messages that increase receipt of advised follow-up care.