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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. [ABSTRACT FROM AUTHOR]

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Most somatic mutations in I BRAF i and I NRAS i oncogenes result in the activation of the mitogen-activated protein kinase (MAPK) pathway and have a role in the development of both benign melanocytic tumours, such as acquired and congenital naevi,[[1]] and melanoma.[3] Dermoscopic features associated with melanomas harbouring I BRAF i mutations have been reported,[[4]] but limited data are available concerning I NRAS i melanomas.[6] The objective was to report the dermoscopic characteristics of melanoma according to mutational status and investigate possible associations between dermoscopic phenotype and genotype. I BRAF i melanomas were mostly superficial spreading melanomas (50.0%), with trunk localization (39.5%), while I NRAS i melanomas were mostly found on the limbs (38.1%). In summary, the results confirm that peppering and blue-white veil were present more frequently in I BRAF- i and I NRAS i -mutated melanomas compared to WT melanomas, while the presence of pseudopods and radial projections was found more frequently only in melanomas with a I BRAF i mutation. [Extracted from the article]

Background: In phase 1-2 trials in patients with resectable, macroscopic stage III melanoma, neoadjuvant immunotherapy was more efficacious than adjuvant immunotherapy., Methods: In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma to two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery or surgery followed by 12 cycles of adjuvant nivolumab. Only patients in the neoadjuvant group with a partial response or nonresponse received adjuvant treatment. The primary end point was event-free survival., Results: A total of 423 patients underwent randomization. At a median follow-up of 9.9 months, the estimated 12-month event-free survival was 83.7% (99.9% confidence interval [CI], 73.8 to 94.8) in the neoadjuvant group and 57.2% (99.9% CI, 45.1 to 72.7) in the adjuvant group. The difference in restricted mean survival time was 8.00 months (99.9% CI, 4.94 to 11.05; P<0.001; hazard ratio for progression, recurrence, or death, 0.32; 99.9% CI, 0.15 to 0.66). In the neoadjuvant group, 59.0% of patients had a major pathological response, 8.0% had a partial response, 26.4% had a nonresponse (>50% residual viable tumor), and 2.4% had progression; in 4.2%, surgery had not yet been performed or was omitted. The estimated 12-month recurrence-free survival was 95.1% in patients in the neoadjuvant group who had a major pathological response, 76.1% among those with a partial response, and 57.0% among those with a nonresponse. Adverse events of grade 3 or higher that were related to systemic treatment occurred in 29.7% of patients in the neoadjuvant group and in 14.7% in the adjuvant group., Conclusions: Among patients with resectable, macroscopic stage III melanoma, neoadjuvant ipilimumab plus nivolumab followed by surgery and response-driven adjuvant therapy resulted in longer event-free survival than surgery followed by adjuvant nivolumab. (Funded by Bristol Myers Squibb and others; NADINA ClinicalTrials.gov number, NCT04949113.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Only a fraction of patients with metastatic melanoma derive durable benefit from approved treatments. The clinical impact of personalized medicine strategies for melanoma, apart from BRAF, NRAS, or CKIT targeting, has rarely been reported., Materials and Methods: By means of the Group of Cutaneous Oncology of the French Society of Dermatology, we retrospectively included all patients with advanced melanoma aged 18 years and older for whom molecular testing identified one or more actionable molecular alterations and who accordingly received molecularly matched therapy. We excluded patients with only BRAF, NRAS, or CKIT alterations and patients who received molecularly matched therapy for less than 15 days., Results: We included 26 patients with a median follow-up of 8 months (1-54), a median age of 63 years (24-89), and a sex ratio of 2.7. These patients had been heavily pretreated, and 64% had elevated LDH levels. The disease control rate was 38%, with 4 cases of partial response (overall response rate: 15%) and 6 of stable disease for at least 6 months. The median duration of treatment was 3.1 months (0.9-13.5). Among patients with disease control, the median duration of control was 6.6 months (2.6-13.5) and 3 cases were ongoing at the end of the study. Patients with controlled disease had GNA11, MAP2K1, FYCO1-RAF1, HRAS, ATM, CCND1, MDM2/CDK4, and CDKN2A/NRAS alterations., Conclusions: High-throughput sequencing followed by matched targeted therapy is a promising approach for patients with advanced melanoma refractory to approved treatments., (© The Author(s) 2024. Published by Oxford University Press.)

Competing Interests: Declaration of interests We declare no competing interests.

The need for reliable biomarkers to predict clinical benefit from anti-PD1 treatment in metastatic melanoma (MM) patients remains unmet. Several parameters have been considered in the tumor environment or the blood, but none has yet achieved sufficient accuracy for routine clinical practice. Whole blood samples from MM patients receiving second-line anti-PD1 treatment (NCT02626065), collected longitudinally, were analyzed by flow cytometry to assess the immune cell subsets absolute numbers, the expression of immune checkpoints or ligands on T cells and the functionality of innate immune cells and T cells. Clinical response was assessed according to Progression-Free Survival (PFS) status at one-year following initiation of anti-PD1 (responders: PFS > 1 year; non-responders: PFS ≤ 1 year). At baseline, several phenotypic and functional alterations in blood immune cells were observed in MM patients compared to healthy donors, but only the proportion of polyfunctional memory CD4+ T cells was associated with response to anti-PD1. Under treatment, a decreased frequency of HVEM on CD4+ and CD8+ T cells after 3 months of treatment identified responding patients, whereas its receptor BTLA was not modulated. Both reduced proportion of CD69-expressing CD4+ and CD8+ T cells and increased number of polyfunctional blood memory T cells after 3 months of treatment were associated with response to anti-PD1. Of upmost importance, the combination of changes of all these markers accurately discriminated between responding and non-responding patients. These results suggest that drugs targeting HVEM/BTLA pathway may be of interest to improve anti-PD1 efficacy., Competing Interests: SD received institutional research grants from MSD, BMS and Pierre Fabre companies., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)