Longitudinal Analysis Reveals Dynamic Changes in Histopathologic Features in Responders to Neoadjuvant Treatment in a Stage III BRAF-Mutant Melanoma Cohort.
Abstract Despite advances in systemic therapies, cutaneous melanoma remains a highly deadly disease. Patients with high-risk stage III melanoma have a significant likelihood of recurrence following surgery. Although adjuvant immunotherapy has been the standard of care, recent evidence demonstrates that neoadjuvant immunotherapy is more effective for higher-risk stage III patients, showing superior survival outcomes compared with adjuvant immunotherapy. This has led to an immediate paradigm shift in clinical practice toward neoadjuvant therapy for this cohort. The NeoTrio clinical trial assessed the efficacy of sequential or combination BRAF-targeted therapy with anti-programmed cell death-1 in the neoadjuvant setting. However, research on [...]
Global Applicability of a Risk Prediction Tool for Sentinel Node Positivity in Patients With Primary Cutaneous Melanoma.
Abstract Importance: The Melanoma Institute Australia (MIA) sentinel node (SN) metastasis risk calculator provides estimates of positivity for individual patients based on 6 standard clinicopathological parameters and the full 6-parameter model has been externally validated previously using US data. However, given its geographically widespread use, further validation is required to ensure its applicability to other populations. Objective: To further externally validate the MIA SN metastasis risk calculator and increase its precision by refinement of the 95% CIs. Design, setting, and participants: A retrospective multicenter cohort study was carried out using data from 4 continents, including the national Danish Melanoma Database and cancer [...]
Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma.
Abstract Background: Patients with resected American Joint Committee on Cancer eighth edition (AJCC v8) stage IIIA melanoma have been underrepresented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted therapy and immunotherapy in this population is unclear. Patients and methods: In this multicentre, retrospective study, patients with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab [anti-programmed cell death protein 1 (PD-1)], BRAF/MEK-targeted therapy dabrafenib + trametinib (TT) or no adjuvant treatment [observation (OBS)] were included. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and toxicity rates were examined. Results: A total of 628 patients from 34 centres [...]
Molecular Analysis of Cutaneous Sarcomatoid Neoplasms Frequently Identifies Melanoma Driver Variants.
Abstract Primary cutaneous neoplasms that lack definitive histologic and immunophenotypic evidence of differentiation are a heterogeneous group of tumors with diverse prognoses and management options. These include undifferentiated and dedifferentiated melanoma (UM/DM), atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma (PDS), and sarcomatoid squamous cell carcinoma. Diagnosis requires careful correlation between the clinicopathologic and molecular features, and the finding of a MAPK pathway variant commonly associated with melanoma may support the diagnosis of melanoma over other tumors in this group. To examine the frequency of typical melanoma-associated MAPK pathway-related variants (BRAF, NRAS, KIT, GNAQ, GNA11) among a cohort of primary cutaneous [...]
Shifts in Cutaneous Melanocytic Tumor Diagnostic Terminology: Melanocytoma, MPATH-Dx V2.0 and the WHO Skin5.
Abstract In this Special Issue of the Journal of Cutaneous Pathology in memory of Dr. Martin C. Mihm, Jr, we highlight his many contributions over more than 50 years to the catalog of specific melanocytic tumor terminology. Dr. Mihm was an active participant in the International Melanoma Pathology Study Group (IMPSG). Discussions led to proposed recommendations for changes in the terminology of melanocytic tumors and their standardized diagnostic reporting. Histopathological reports of melanocytic tumors provide critical information that guides patient counseling and therapy. Importantly the pathology report must relay whether the melanocytic tumor is benign, intermediate, or malignant, and [...]
Management of Local Skin Reactions Caused by 5-FU 4% Cream for the Treatment of Actinic Keratosis: A Delphi Consensus.
Abstract Introduction: Treatments such as 4% 5-fluorouracil (5-FU) cream have demonstrated strong efficacy in lesion clearance of actinic keratosis; however, local skin reactions (LSR) during treatment remain a significant challenge, potentially affecting patient adherence. Objective: We sought to build consensus on management of LSR associated with 4% 5-FU using the Delphi methodology. Methods: Twenty-eight expert dermatologists participated in a 3-round Delphi process. Experts evaluated LSR management strategies, including emollients, antibiotics, steroids, and treatment discontinuation. Agreement levels were measured using a 7-point Likert scale. Consensus was categorized as high if >80% of votes were within the 5-7 rating range and low when >25% [...]
Reconsidering the surgical approach in cutaneous melanoma: does wide local excision after a complete diagnostic excision reduce the risk of recurrence?
Abstract Objectives: This study examines whether wide local excision (WLE) after complete diagnostic excision improves recurrence-free survival (RFS) in clinical stage I/II primary cutaneous melanoma. Background: Since the 1950s, melanoma treatment has included a two-step surgical approach, involving diagnostic excision followed by WLE. WLE aims to achieve locoregional disease control by eliminating potential microsatellites and, thus, minimising the risk of locoregional recurrence and melanoma-related death. However, its impact on RFS is unclear, while it adds morbidity and costs. Methods: This retrospective nationwide cohort study analysed pathology reports of a Dutch population-based cohort of newly diagnosed invasive cutaneous melanoma patients who underwent a [...]
External validation of a model to predict recurrence-free and melanoma-specific survival for patients with melanoma after sentinel node biopsy.
Abstract Background: Recently, a model to predict 5-year recurrence-free survival (RFS) and melanoma-specific survival (MSS) after sentinel lymph node biopsy (SLNB) was published. The aim of this study was to validate that model in a large independent international cohort. Methods: The database of the Sentinel Lymph Node Working Group (SLNWG) was analysed for patients with malignant melanoma who underwent SLNB. Patients with clinical stage III melanoma, a history of other malignancies, or receiving concomitant systemic therapies during follow-up were excluded. The model's predictive performance was evaluated using discrimination and calibration metrics in the eligible cohort. Decision curve analysis was performed to [...]
Absolute Risk of Developing a Second Primary Cancer After a First Primary Melanoma: An Australian Population-Based Cohort Study.
Abstract Understanding the absolute risk of developing a second primary cancer is important to guide patient surveillance and education. We aimed to examine the cumulative incidence and factors associated with development of a second primary cancer (melanoma versus other) after diagnosis of a first primary melanoma (invasive or in situ). We analysed a population-based study cohort of 154,695 people diagnosed with a first primary melanoma in New South Wales, Australia, between 1982-2019. The cohort was followed for future cancer incidence and vital status for a median of 7.0 years. We used Fine-Gray models to account for death as a [...]
Global Burden of Cutaneous Melanoma in 2020 and Projections to 2040
Abstract Importance: Despite many cases being preventable, cutaneous melanoma remains the most serious skin cancer worldwide. Understanding the scale and profile of the disease is vital to concentrate and reinforce global prevention efforts. Objective: To examine global patterns of cutaneous melanoma in 2020 and to provide projected estimates of cases and deaths by 2040. Design, setting, and participants: This population-based study used the GLOBOCAN 2020 database for global epidemiological assessment of new cases and deaths due to invasive melanoma. Main outcomes and measures: Age-standardized incidence and mortality rates were calculated per 100 000 person-years by country, world region, and 4-tier level of human [...]