Kelly C. Nelson

Clinicopathologic study of 85 cases of melanoma of the female genitalia

BACKGROUND Melanoma of the female genitalia has poor overall prognosis. OBJECTIVE AND METHODS To examine prognostic factors influencing survival, the Duke Melanoma and Tumor Registry Databases were queried for patients who had received their clinical care at Duke University Medical Center, with a diagnosis of melanoma of the female genitalia, including vulva, vagina, and cervix, between 1970 and 2009. From this group, any available histopathologic specimens were procured for further review. RESULTS Eighty-five patients were identified. The median follow-up time was 8.8 years with 60% of the patients experiencing melanoma-related mortality at last follow-up. Survival rates at 1, 5, and 10 years were 85%, 51%, and 30%, respectively. The available histopathologic specimens from 36 cases were reviewed by a dermatopathologist (M.A.S.). Fifteen of 36 cases were notable for the presence of atypical melanocytic hyperplasia adjacent to the primary melanoma. Breslow depth, lymph node status, systemic therapy, and surgery were also examined for differences in survival distributions using the log-rank test. In general, survival was inversely correlated with Breslow depth, extent of nodal involvement, and provision of systemic therapy. A higher survival rate was observed among those who received wide local excision. Log-rank test demonstrated that survival between different decades of diagnosis was not significantly different. LIMITATIONS Because of its small sample size, this study may be underpowered. CONCLUSION Despite new treatments developed and attempted, there is no evidence that survival has improved over the past 40 years. In summary, patients with thinner melanomas amenable to surgical resection had a better prognosis than those with more extensive, metastatic disease at presentation.

Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi: Pigmented Lesion Subcommittee consensus statement.

IMPORTANCE The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few data to guide the process. Management recommendations for DN with positive histologic margins were developed by the Delphi method to achieve consensus among members of the Pigmented Lesion Subcommittee (PLS) of the Melanoma Prevention Working Group (MPWG) after reviewing the current evidence. OBJECTIVES To outline key issues related to the management of CAN/DN: (1) biopsies of CAN and how positive margins arise, (2) whether incompletely excised DN evolve into melanoma, (3) current data on the outcomes of DN with positive histologic margins, (4) consensus recommendations, and (5) a proposal for future studies, including a large-scale study to help guide the management of DN with positive margins. EVIDENCE REVIEW The literature, including recent studies examining management and outcomes of DN with positive margins between 2009 to 2014, was reviewed. FINDINGS A consensus statement by the PLS of the MPWG following review of the literature, group discussions, and a structured Delphi method consensus. CONCLUSIONS AND RELEVANCE This consensus statement reviews the complexities of management of CAN/DN. A review of the literature and 2 rounds of a structured Delphi consensus resulted in the following recommendations: (1) mildly and moderately DN with clear margins do not need to be reexcised, (2) mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than reexcised, and (3) observation may be a reasonable option for management of moderately DN with positive histologic margins without clinically apparent residual pigmentation; however, more data are needed to make definitive recommendations in this clinical scenario.

Skin cancer screening: recommendations for data-driven screening guidelines and a review of the US Preventive Services Task Force controversy

Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Forces 2016 Draft Recommendation Statement on skin cancer screening.

Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract

BACKGROUND The genetic heterogeneity of melanomas and melanocytic nevi of the female genital tract is poorly understood. OBJECTIVE We aim to characterize the frequency of mutations of the following genes: BRAF, NRAS, KIT, GNA11, and GNAQ in female genital tract melanomas. We also characterize the frequency of BRAF mutations in female genital tract melanomas compared with melanocytic nevi. METHODS Mutational screening was performed on the following female genital tract melanocytic neoplasms: 25 melanomas, 7 benign melanocytic nevi, and 4 atypical melanocytic nevi. RESULTS Of the 25 female genital tract melanoma specimens queried, KIT mutations were detected in 4 (16.0%), NRAS mutations in 4 (16.0%), and BRAF mutations in 2 (8.0%) samples. Two of the tumors with KIT mutations harbored double mutations in the same exon. No GNAQ or GNA11 mutations were identified among 11 melanomas screened. BRAF V600E mutations were detected in 7 of 7 benign melanocytic genital nevi (100%) and 3 of 4 atypical genital nevi (75%). LIMITATIONS Our study is limited by the small sample size of this rare subset of melanomas. CONCLUSION KIT, NRAS, and BRAF mutations are found in a subset of female genital tract melanomas. Screening for oncogenic mutations is important for developing and applying clinical therapies for melanomas of the female genital tract.

Evaluation of 39 cases of pediatric cutaneous head and neck melanoma

BACKGROUND Studies examining head and neck (H&N) melanoma in the pediatric population are scarce. OBJECTIVE The goal of this study is to describe pediatric H&N melanoma with the intent of increasing understanding of the course of disease. METHODS The Duke Melanoma Database and Duke Tumor Registry Database were searched for patients with a diagnosis of melanoma occurring on the H&N before age 18 years, with exclusion of ocular/mucosal/aerodigestive melanomas. RESULTS Queries yielded 39 Caucasian pediatric patients, 24 (61.5%) of them male. The mean age at diagnosis was 14.2 years (15 years, median). The primary sites were represented as follows: cutaneous auricular (1/39, 2.6%), facial (15/39, 38.5%), and scalp/neck (23/39, 59%). The follow-up time ranged from 2 months to 23 years with a median of 9.9 years (95% confidence interval: 6.2-13 years). At the time of follow-up, there were 12 (12/39, 30.8%) melanoma-associated deaths. The anatomic distribution of primary melanoma for these 12 patients follows: 4 (33.3%) facial and 8 (66.7%) scalp/neck. Histologic data revealed 24 (61.5%) tumors classified as superficial spreading melanoma with nodular melanoma (12.8%) a distant second. The mean Breslow depth for patients with melanoma-related mortality was 2.4 mm, compared with 1.8 mm for those who were alive at last follow-up. LIMITATIONS Small sample size limited this study. CONCLUSION This study found that the majority (59%) of H&N melanomas presented as scalp or neck lesions with a predilection for adolescents and boys. Those who experienced melanoma-related mortality had thicker lesions. Superficial spreading melanoma was the most common subtype.

Regional Squamous Cell Carcinomas Following Systemic Sorafenib Therapy and Isolated Limb Infusion for Regionally Advanced Metastatic Melanoma of the Limb

had carbamazepine-induced Stevens-Johnson syndrome. J Formos Med Assoc. 2007;106(12):1032-1037. 4. Chung WH, Hung SI, Chen YT. Human leukocyte antigens and drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2007;7(4):317-323. 5. Ferrell PB Jr, McLeod HL. Carbamazepine, HLA-B*1502 and risk of StevensJohnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics. 2008;9(10):1543-1546.

Patient safety and quality care.

This whole journey began with a very busy day in my procedure clinic; at this point in time, Duke Dermatology was in the midst of a very active growth period. Several new dermatologists, including myself, had joined the faculty over the previous 2 years, and our nursing support structure was in the process of growing in parallel to keep pace. As a result, clinics not infrequently were relatively understaffed with nursing team members. On this particular day, two patients had been added to my schedule with fairly short notice; I had a new resident working with me; and we had no dedicated nursing support. I saw two patients that day for spot check of concerning lesions; I’ll call them Mr. Ear and Mr. Chest. Mr. Ear had a raised keratotic papule on his left ear; Mr. Chest had a stuckon–appearing thin plaque on his right upper chest that was partially avulsed. Mr. Ear was concerned that his spot might be a small squamous cell skin cancer; I agreed. Mr. Chest was worried that his spot might be a melanoma; I greatly favored a traumatized seborrheic keratosis. The resident and I were in and out of examination rooms several times to gather procedural supplies, generate

Regressed melanocytic nevi secondary to pembrolizumab therapy: An emerging melanocytic dermatologic effect from immune checkpoint antibody blockade

Immune checkpoint antibody blockade is an emerging therapeutic option for treating certain cancers including melanoma. This therapy is associated with dermatologic and systemic toxicities, some of which are more severe than others and may require withholding therapy.

Management Strategies of Academic Pigmented Lesion Clinic Directors in the United States

of patients had a good response and 15% had an excellent response. There was a statistically significant difference between the groups (P 1⁄4 .024) with regard to satisfaction, with 40% of patients in group 3 expressing excellent satisfaction (Table I). Different treatment options for vitiligo, acting either on proliferation of melanocytes or suppression of immune response, have been used. Recent procedures, including needling, have shown acceptable degrees of repigmentation in limited types of vitiligo. In a comparison of the results of needling plus a topical steroid with NB-UVB and an examination of the additional value of a using combination of both modalities in acrofacial vitiligo, needling yielded a good-to-excellent response in 45% of cases, whereas combining needling with NB-UVB raised that percentage to 70%. The overall incidence of side effects was minimal, except for pain, which can be minimized by using topical anesthetics before sessions. In conclusion, the addition of needling to NB-UVB is a reasonable combination therapy for patients with resistant vitiligo and is well tolerated.

Chemoprevention agents for melanoma: a path forward into phase 3 clinical trials

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.