Andrew E. Werchniak

Drug-Associated Dermatomyositis Following Ipilimumab Therapy: A Novel Immune-Mediated Adverse Event Associated With Cytotoxic T-Lymphocyte Antigen 4 Blockade

IMPORTANCE Ipilimumab, a human monoclonal antibody targeted against cytotoxic T-lymphocyte antigen 4, has shown promise in the treatment of metastatic melanoma. However, given its mechanism of action, immune-related adverse effects have been reported with this therapy. Despite increasing reports of immune-related adverse effects related to ipilimumab therapy, dermatomyositis associated with this agent has not previously been reported. OBSERVATIONS We describe a woman undergoing treatment with ipilimumab for metastatic melanoma who developed classic cutaneous findings of dermatomyositis along with proximal muscle weakness and elevated muscle enzymes. CONCLUSIONS AND RELEVANCE This case adds to the expanding literature regarding immune-related adverse events associated with ipilimumab. To our knowledge, drug-induced dermatomyositis from ipilimumab has not previously been reported. Physicians should be aware of these potential immune-related adverse events and consider drug-associated dermatomyositis in the differential diagnosis in patients receiving ipilimumab who present with a cutaneous eruption or muscle weakness.

Photodynamic therapy for multiple eruptive keratoacanthomas associated with vemurafenib treatment for metastatic melanoma.

BACKGROUND The development of keratoacanthomas (KAs) and well-differentiated squamous cell carcinomas (SCCs) is a known adverse effect of novel BRAF inhibitors such as vemurafenib. With multiple such neoplasms often arising after BRAF inhibitor therapy, surgical excision is often impractical. OBSERVATIONS We describe a patient with stage IV melanoma who received the BRAF inhibitor vemurafenib (recently approved by the US Food and Drug Administration) as part of a clinical trial and developed numerous diffuse, pathology-proven KAs and SCCs. The high number of lesions across a broad area precluded surgical treatment; instead, a noninvasive field approach using photodynamic therapy (PDT) was initiated. Compared with untreated tumors, most lesions demonstrated significant clinical regression following successive cycles of PDT. CONCLUSIONS Given vemurafenibs recent approval by the US Food and Drug Administration, we provide a timely case report on the effective use of PDT in the treatment of BRAF inhibitor-associated KAs and SCCs. Although further studies are needed to better understand the biological processes of these secondary neoplasms, our observation provides an alternative noninvasive solution for improving the quality of life for patients receiving BRAF inhibitor therapy.

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

BackgroundAlthough 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.MethodsWe 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.ResultsTwenty-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).ConclusionsDespite 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.

Risk stratification in extramammary Paget disease.

Extramammary Paget disease (EMPD) is an uncommon intraepithelial adenocarcinoma that involves body sites with apocrine glands such as the genital, perineal and perianal regions. Risk stratification and treatment planning for EMPD can be challenging. This review presents important prognostic information in EMPD to assist physicians with risk stratification of patients with EMPD. The best‐understood prognostic factors are depth of invasion and involvement of extracutaneous sites. Tumours that invade into the reticular dermis or have a depth of > 1 mm are associated with poorer prognosis. Additionally, tumours spreading outside the skin into lymph nodes or other tissues are higher risk. There is an emerging understanding of the importance of tumour genetics in risk stratification, and we review the data on Ki‐67, cyclin D1, Mucin 5AC and E‐cadherin. There is less evidence supporting the importance of lesion site and patient age in risk stratification. This succinct review will be helpful in clinical practice and in EMPD research.

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.

Multiple Tense Bullae Localized to the Right Breast in a Woman in Her Seventies

Awoman in her 70s presented with a 1-month history of multiple tense bullae on the right breast associated with worsening erythema and tenderness. Four months prior, she had completed radiation therapy (RT) to this site (total energy dose, 50 Gy [to convert to rad,multiplyby 100]) for treatmentof invasiveductal breast carcinoma.Shewas initially treatedwithdicloxacillin sodiumforpossible bullous impetigo after a culture demonstrated Staphylococcus aureus but was then hospitalized for administration of broadspectrum intravenous antibiotics after demonstrating no clinical improvement. On physical examination, thereweremultiple tense 0.5to 3-cm bullae localized to the right breast (Figure, A and B). The bullae, aswell asmultiple erosions and surrounding erythema, occurredwithin thepreviously irradiated site, as demarcatedby radiation tattoos (Figure, A). There was no involvement of mucosal membranes. Punch biopsies were performed (Figure, C and D). What is your diagnosis?

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.

Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (SCC) is the second most common cutaneous malignancy in the USA, accounting for 20% of non-melanoma skin cancers. Among Caucasians, it is the second most common cancer overall. Although the great majority of cases are cured by surgery or other treatments, deaths from SCC may be nearly as common as those from melanoma. Identification of patients at risk for untoward outcomes as well as clarity regarding appropriate staging and management, particularly of high-risk tumors, is imperative. This chapter discusses the current state of knowledge regarding the pathophysiology leading to cutaneous SCC, risk factors for its development, and the clinical spectrum of squamous dysplasia with particular attention given to high-risk and invasive disease. It provides an in-depth discussion of the available data regarding surgical and non-surgical management of cutaneous SCC, particularly of high-risk tumors.

Developing Healthy Sun Habits for Life: Challenges and Opportunities

O VER THE PAST SEVERAL YEARS, AN INCREASing emphasis has been placed on the need for the development of a healthy lifestyle in the pursuit of long-term good health. This generally has included a focus on proper diet and exercise. Indeed, a large amount of media attention has been dedicated to strategies for creating such a lifestyle. Given the potential morbidity and mortality from skin cancer and the strong evidence pointing to excessive sun exposure as a strong risk factor, it is clear that developing good sun protection habits should be an important component of healthy living. But precisely which individuals should be specifically targeted? In which situations? And how is this best accomplished? Three articles in this issue of the Archives contribute to this important discussion with insights into risk stratification. These articles also highlight many of the challenges surrounding the behavioral changes that need to take place for significant public health benefits to be realized.