Intraoperative dermoscopy features of subungual squamous cell carcinoma: a study of 53 cases.

BACKGROUND: Subungual squamous cell carcinoma (SU-SCC) is the most common malignant tumour of the nail unit. Intraoperative nail dermoscopy has been described only for pigmented tumours, onychomatricoma and glomus tumours. AIM: To establish a description of intraoperative dermoscopic features of SU-SCC. METHODS: A single-centre retrospective cohort of 53 SU-SCC cases over a 5-year period was reviewed by six examiners who individually scored 31 intraoperative dermoscopic features as present or absent. For each feature, the frequency and interobserver agreement was evaluated, then the data were compared and a consensus was reached. RESULTS: No feature had perfect or substantial interobserver agreement. Regarding anatomy and architecture, most tumours involved both the nail bed and nail matrix (n = 34, 64.2%) and had nonparallel lateral side edges (n = 36, 67.9%). Regarding vascular features, several different patterns were found: dotted vessels (n = 49, 92.5%), irregular vessels (n = 47, 88.7%), curved vessels (n = 46, 86.8%), sagittal vessels (n = 45, 84.9%), milky-red areas (n = 42, 79.2%), linear and regular vessels (n = 30, 56.6%), coiled and hairpin vessels (n = 23, 43.4%), and arborizing vessels (n = 16, 30.2%). Pigmented dermoscopy structures included dotted purpura, grey granulation and splinter haemorrhages, which were found in 49 (20.8%), 9 (17%) and 9 (17%) cases, respectively. Other dermoscopic signs were pink background, translucent structureless area, whitish scaly areas, distal plug, yellowish scales and dots, and 'digitiform' proximal edge, which were found in 49 (84.9%), 49 (84.9%), 43 (81.1%), 37 (69.8%), 28 (52.8%) and 22 (41.5%) cases, respectively. CONCLUSION: Analysis of this first large series of SU-SCC studied by intraoperative dermoscopy suggests that it gives useful information to better approach the diagnosis and to target biopsies.

Cutaneous adverse events: a predictor of tumour response under anti-PD-1 therapy for metastatic melanoma, a cohort analysis of 189 patients.

INTRODUCTION: Cutaneous adverse events (AEs) are the most prevalent toxicity under checkpoint inhibitors in clinical trials. In 'real-life' conditions of use, skin toxicities under anti-PD-1 have not been described to date in a large cohort. The objective of this study was to determine the clinical features of skin toxicities in patients with advanced melanoma receiving anti-PD-1 therapy under 'real-life' conditions of use. Secondary objectives were to evaluate the characteristics of patients with skin toxicities and to analyse associated extra-cutaneous toxicities, progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: Advanced melanoma patients treated with nivolumab or pembrolizumab between August 2014 and October 2017 were included. Patients lost to follow-up or receiving anti-PD-1 as part of a clinical trial were excluded. RESULTS: One hundred and eighty-nine patients with metastatic melanoma (with 109 men (57.7%) were included. Cutaneous AE occurred in 39 patients (20.6%). The three most prevalent cutaneous AEs were skin eruption (macular-papular or eczematous) (n = 18, 9.5%), vitiligo (n = 16; 8.5%) and isolated pruritus (n = 5, 2.6%). Grade 3-4 skin toxicity was diagnosed in five patients (2.6%). Atopy (28.2% vs. 12.0%; P = 0.024), hypereosinophilia (20.5% vs. 8.7%; P = 0.046), thyroiditis (17.9% vs. 4.7%; P = 0.011) and renal toxicity (15.4% vs. 4%; P = 0.019) were significantly associated with cutaneous AE. Patients with skin eruption (log-rank = 0.001), vitiligo (log-rank = 0.001) and any type of cutaneous AE (log-rank < 0.001) had a better overall survival. CONCLUSIONS: Cutaneous AEs are frequent and often manageable toxicity and were a predictor of tumour response in melanoma patients under anti-PD-1 therapy in this cohort.

Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma.

BACKGROUND: Anti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in advanced melanoma. To date, no prospective data are available to give the best sequence of treatment. The objective of this study was to evaluate in real-life the efficacy of anti-PD-1 after BRAFi, ipilimumab, or chemotherapy failure. METHODS: This was a single institution cohort analysis in patients treated with anti-PD-1 right after BRAFi, ipilimumab, or chemotherapy failure. Melanoma evolution after anti-PD-1 initiation was analyzed in BRAF-mutated and BRAF wild-type patients. The efficacy of treatment was evaluated by Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS). RESULTS: Seventy-four patients were included: 33 wild-type and 41 BRAF-mutated melanoma. ORR to anti-PD-1 was significantly lower in BRAF-mutated patients (12.2% vs. 45.5%, p = 0.002). After anti-PD-1 initiation, the median PFS and OS was significantly shorter in the BRAF mutated group (2 vs. 5 months and 7 vs. 20 months, p = 0.001). The hazard ratio for disease progression was of 2.3 (95%CI:1.3-3.9; p = 0.003) and 2.5 (95%CI:1.3-4.5; p = 0.005) for death. Thirty-nine percent of BRAF-mutated-patients died within 3 months after anti-PD-1 initiation. Rapid death (≤3 months) was significantly higher in BRAF-mutated patients (55.2% vs. 20.0%, p = 0.014). DISCUSSION: This is the largest series of unselected patients treated in real-life with anti-PD-1 as second-or-higher line of treatment. Anti-PD-1 was less effective in BRAF-mutated cases as a majority of patients presented aggressive tumor evolution after BRAFi discontinuation. These data are consistent with previous studies suggesting a negative impact of BRAFi prior to immunotherapy.

Overview of the use of dermoscopy in academic and non-academic hospital centres in France: a nationwide survey.

BACKGROUND: Dermoscopy is acknowledged to improve the diagnostic accuracy of melanoma by several concordant meta-analyses. However, the use of dermoscopy was not considered as a high level of evidence diagnostic tool by French Health Authorities. However, as shown in Australian, American and in our recent surveys, dermoscopy is used by most of dermatologists in private practice. OBJECTIVES: To analyse the use, beliefs, teaching given and research produced in dermoscopy in dermatology departments of French hospitals. METHODS: A questionnaire about the use, available equipment, teaching activities and published research on dermoscopy was mailed to all chairmen of dermatology departments in French both academic and non-academic hospitals. RESULTS: Seventy-six of 110 mailed questionnaires were returned. The majority of centres claimed to use dermoscopy (97.5%), but it seemed heterogeneous among practitioners according to their age and position. The use of dermoscopy was four times higher in non-academic centres (P = 0.015). Centres located in the south east of France were higher users comparing with others (P = 0.004). Earlier detection of melanoma was the most important advantage reported. Excessive training time was the most important reported disadvantage. Twenty-five percent of centres had dedicated clinics for pigmented lesions. Few centres (14.5%) run formal dermoscopy training programs. Most centres (74.7%) declared a use of dermoscopy for the diagnosis of non-tumoral diseases. CONCLUSIONS: This is the first European study evaluating the use of dermoscopy among hospital. Despite a large use, dermoscopy-dedicated teaching and research time appeared to be insufficient.

Nodular progression of lentigo malignant melanoma during a treatment with tocilizumab: cause or coincidence?

Tocilizumab is an anti-interleukin (IL)-6 receptor monoclonal antibody, used since 2010 for the treatment of severe rheumatoid arthritis (RA). It is known to induce infection, similarly to other biotherapies which modulate immune response and cytokines. Few cases of malignancy, however, have as yet been reported. We describe here the case of a patient with severe RA, previously treated with prednisolone, methotrexate, leflunomide, etanercept, and rituximab, who, after 8 months of treatment with tocilizumab, developed rapidly progressive nodular melanoma on a preexisting pigmented lesion on her left cheek. Recently, another case of nodular melanoma under tocilizumab has been published. The possible causative role of tocilizumab and other immunomodulatory agents in the development of this malignancy is discussed. Based on the present case, dermatologic screening is recommended before initiation of tocilizumab.