Raymond Barnhill

This letter is the authors’ reply to ‘Low-risk lesion, increased-risk patient: separating lesion prognosis from future melanoma risk’ by Baldao-Simó and Podlipnik.

Half of the participants in this randomized online experiment of 1655 Australian adults would prefer to not have a wide local excision (WLE) after a completely excised low-risk melanocytic lesion, if offered this option. Using the term ‘low-risk melanocytic neoplasm’ instead of ‘melanoma in situ’ reduced anxiety and the proportion choosing a WLE. Across all label groups, most participants preferred to attend routine 6-monthly clinic visits for follow-up, most likely reflecting the high prevalence of this in the Australian context.

The past four decades have witnessed a marked increase in melanoma diagnoses, particularly early-stage disease, without proportional decreases in melanoma mortality - a pattern seen across multiple cancer types, termed "overdiagnosis". Overdiagnosis refers to diagnosis of disease that will never cause symptoms or death during a patient’s expected lifetime and requires both the existence of biologically indolent lesions (as are most severely dysplastic nevi, melanomas in situ, and minimally invasive melanomas) and activities leading to their detection (namely, screening). In October 2025, the American Dermatological Association convened leading experts at its annual meeting in Laguna Niguel, California for an unprecedented session titled “The Skin Check of the Future,” bringing together dermatologists, dermatopathologists, and epidemiologists dedicated to melanoma control and technology innovation. The national Melanoma Prevention Working Group contributed additional presentations on skin imaging and artificial intelligence for melanoma early detection and their potential contributions to dermatology workflow. This review synthesizes session presentations and panel discussion, organized around three interconnected themes: the screening conundrum and the critical importance of population risk stratification; the role of pathology in diagnostic uncertainty and emerging approaches to low-risk melanocytic neoplasm relabeling; and the technologies and workflow innovations that may influence future melanoma practice. While robust debate continues about the precise magnitude of overdiagnosis and its implications for individual patient care, this multi-expert synthesis provides a framework for clinicians, researchers, and policymakers to navigate the complex landscape of melanoma detection, while optimizing benefits and minimizing harms across diverse patient populations.

Background: Next‐generation sequencing (NGS) is becoming more commonly used for diagnosis in dermatopathology. It's critical to appraise its efficacy and limitations. Distinguishing benign deep penetrating nevi (DPN) from deep penetrating like‐melanoma (DPN‐M) is a challenging diagnostic scenario even for experienced dermatopathologists. Methods: We sent a two‐phase survey (pre‐and postgenomics) to 32 experienced dermatopathologists to evaluate 39 diagnostically challenging cases from the DPN/WNT‐activated family of melanocytic neoplasms. Results: With NGS data, interobserver agreement improved from 0.41 to 0.51 ( p < 0.0001) in distinguishing DPN‐M from nonmelanoma cases. Overall diagnostic accuracy improved, mostly driven by a 16% increase in accurate diagnosis of DPN‐M. However, in two cases, the inclusion of genomics shifted the majority vote from a correct to an incorrect diagnosis. A total of 218 diagnostic changes occurred between Survey 1 and 2. Among the changes, 132 votes moved toward the correct diagnosis while 86 moved toward an incorrect diagnosis. The shift in voting which resulted in improved diagnostic accuracy was statistically significant ( p = 0.0001). Conclusions: NGS has the potential to improve interobserver agreement and diagnostic accuracy. We provide guidance on the utilization of bioinformatic data to maximize its benefits and improve diagnostic accuracy and interobserver agreement.

The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: ‘Tumours of the nail unit’ and ‘Metastases to skin’, along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.

Allosteric inhibitors of the tyrosine phosphatase Src homology 2 domain–containing protein tyrosine phosphatase 2 (SHP2) hold therapeutic promise in cancers with overactive RAS/ERK signaling, but adaptive resistance to SHP2 inhibitors may limit benefits. Here, we utilized tumor cells that proliferate similarly with or without endogenous SHP2 to explore means to overcome this growth independence from SHP2. We found that SHP2 depletion profoundly altered the output of vascular regulators, cytokines, chemokines, and other factors from SHP2 growth-resistant cancer cells. Tumors derived from inoculation of SHP2-depleted, but SHP2 growth–independent, mouse melanoma and colon carcinoma cell lines displayed a typically subverted architecture, in which proliferative tumor cells surrounding a remodeled vessel formed “vascular islands”, each limited by surrounding hypoxic and dead tumor tissue, where inflammatory blood cells were limited. Although vascular islands generally reflect protected sanctuaries for tumor cells, we found that vascular island–resident, highly proliferative, SHP2-depleted tumor cells acquired an increased sensitivity to blockage of MEK/ERK signaling, resulting in reduced tumor growth. Our results show that the response to targeted therapies in resistant tumor cells was controlled by tumor cell–induced vascular changes and tumor architectural reorganization, providing a compelling approach to elicit tumor responses by exploiting tumor- and endothelium-dependent biochemical changes.

Introduction A diagnosis of melanoma in situ presents negligible risk to a person’s lifespan or physical well-being, but existing terminology makes it difficult for patients to distinguish these from higher risk invasive melanomas. This study aims to explore whether using an alternative label for melanoma in situ may influence patients’ management choices and anxiety levels. Methods and analysis This study is a between-subjects randomised online experiment, using hypothetical scenarios. Following consent, eligible participants will be randomised 1:1:1 to three labels: ‘melanoma in situ’ (control), ‘low-risk melanocytic neoplasm’ (intervention 1) and ‘low-risk melanocytic neoplasm, in situ’ (intervention 2). The required sample size is 1668 people. The co-primary outcomes are (1) choice between no further surgery or further surgery to ensure clear histological margins greater than 5 mm and (2) choice between patient-initiated clinical follow-up when needed (patient-led surveillance) and regular routinely scheduled clinical follow-up (clinician-led surveillance). Secondary outcomes include diagnosis anxiety, perceived risk of invasive melanoma and of dying from melanoma and management choice anxiety (after surgery choice and follow-up choice). We will make pairwise comparisons across the three diagnostic label groups using regression models (univariable and multivariable). Ethics and dissemination The study has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12624000740594). Ethics approval has been received from The University of Sydney Human Research Ethics Committee (2024/HE000019). The results of the study will be published in a peer-reviewed medical journal, and a plain language summary of the findings will be shared on the Wiser Healthcare publication page (https://www.wiserhealthcare.org.au/category/publications/). Trial registration number Australian New Zealand Clinical Trials Registry (ID 386943).

Surgical treatment of liver metastases of uveal melanoma (LMUM) could be proposed for selected patients. This retrospective study examined the prognostic significance of the genetic profiles of liver metastases after LMUM resection. A total of 86 patients treated with resection for LMUM, who underwent genetic analysis of liver metastasis, were included. A multivariable Cox model identified the independent predictors of recurrence-free survival (RFS) and overall survival (OS). The disease-free interval (DFI) and a chromosome 8q surgain (>3 copies) were independent predictors and categorized patients into three risk groups with distinct postoperative prognoses. For the low-, intermediate-, and high-risk scores of recurrence, the median RFS values were 15 months (95% CI: 10–22), 6 months (95% CI: 4–11), and 4 months (95% CI: 2–7), and the median OS values were 86 months (95% CI: 55-NR), 25 months (95% CI: 17–48), and 19 months (95% CI: 12–22), respectively. The predictive accuracy of this scoring system was demonstrated by a mean area under the curve (AUC(t)) of 0.77 (95% CI: 0.65–0.90) for RFS and 0.81 (95% CI: 0.70–0.92) for OS. This novel score, based on a DFI of ≤24 months combined with a chromosome 8q surgain, identifies patients at a high risk of early recurrence and could help clinicians to propose perioperative treatment.