Dermoscopic features and screening strategies for the detection of small-diameter melanomas.
Abstract Background: Around 70% of cutaneous malignant melanomas (MMs) develop de novo, and small-diameter or 'tiny' lesions are expected to represent the earliest manifestation of most MMs. Aim: To describe the clinical, histopathological and dermoscopic features of tiny MMs, and to investigate the impact of imaging tools, including total body photography (TBP) and sequential digital dermoscopy imaging (SDDI) in their detection. Methods: Consecutive MMs diagnosed over 2 years in a referral centre were retrospectively included. Tiny MMs were defined as MMs with a diameter of ≤ 5 mm on dermoscopy. Dermoscopic features and the performance of four imaging methods were evaluated. Results: Of [...]
BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting
Abstract Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia. Notably, it recommends that pathologists reflexively order BRAF mutation testing whenever a [...]
Multiomic profiling of checkpoint inhibitor-treated melanoma: Identifying predictors of response and resistance, and markers of biological discordance.
Abstract We concurrently examine the whole genome, transcriptome, methylome, and immune cell infiltrates in baseline tumors from 77 patients with advanced cutaneous melanoma treated with anti-PD-1 with or without anti-CTLA-4. We show that high tumor mutation burden (TMB), neoantigen load, expression of IFNγ-related genes, programmed death ligand expression, low PSMB8 methylation (therefore high expression), and T cells in the tumor microenvironment are associated with response to immunotherapy. No specific mutation correlates with therapy response. A multivariable model combining the TMB and IFNγ-related gene expression robustly predicts response (89% sensitivity, 53% specificity, area under the curve [AUC], 0.84); tumors with [...]
BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting.
Abstract Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia. Notably, it recommends that pathologists reflexively order BRAF mutation testing whenever a [...]
Complex melanoma of the scalp: Diagnosis and management aided by confocal microscopy.
Abstract Melanomas of lentigo maligna subtype are a steadily growing problem and frequently represent a clinical challenge. A case is reported of a complex melanoma of the scalp illustrating the critical role of confocal microscopy for optimal diagnosis and management. Read Full Paper
Estimating the potential impact of interventions to reduce over-calling and under-calling of melanoma.
Abstract Background: Pathologists sometimes disagree over the histopathologic diagnosis of melanoma. 'Over-calling' and 'under-calling' of melanoma may harm individuals and healthcare systems. Objectives: To estimate the extent of 'over-calling' and 'under-calling' of melanoma for a population undergoing one excision per person and to model the impact of potential solutions. Methods: In this epidemiological modelling study, we undertook simulations using published data on the prevalence and diagnostic accuracy of melanocytic histopathology in the U.S. Population: We simulated results for 10 000 patients each undergoing excision of one melanocytic lesion, interpreted by one community pathologist. We repeated the simulation using a hypothetical intervention that improves [...]