The Development and Evaluation of a Convolutional Neural Network for Cutaneous Melanoma Detection in Whole Slide Images.

Context.—: The current melanoma staging system does not account for 26% of the variance seen in melanoma-specific survival, therefore our ability to predict patient outcome is not fully elucidated. Morphology may be of greater significance than in other solid tumors, with Breslow thickness remaining the strongest prognostic indicator despite being subject to high levels of interobserver variation.

Variation in the practice of wide local excision for melanoma in Ireland and the UK: a questionnaire survey.

Background: Wide local excision (WLE) is standard practice in the management of melanoma, but no national or international guidelines exist regarding its technique.

Objectives: To assess variation in the practice of WLE and to explore the effect of clinicians' specialty and grade on such variation.

Methods: This was an international, anonymized, cross-sectional study.

Ulcerated melanoma: Systems biology evidence of inflammatory imbalance towards pro-tumourigenicity.

Microscopic ulceration is an independent predictor of melanoma death. Here, we used systems biology to query the role of host and tumour-specific processes in defining the phenotype. Albumin level as a measure of systemic inflammation was predictive of fewer tumour-infiltrating lymphocytes and poorer survival in the Leeds Melanoma Cohort.

A machine learning approach to automatic detection of irregularity in skin lesion border using dermoscopic images.

Skin lesion border irregularity is considered an important clinical feature for the early diagnosis of melanoma, representing the B feature in the ABCD rule. In this article we propose an automated approach for skin lesion border irregularity detection. The approach involves extracting the skin lesion from the image, detecting the skin lesion border, measuring the border irregularity, training a Convolutional Neural Network and Gaussian naive Bayes ensemble, to the automatic detection of border irregularity, which results in an objective decision on whether the skin lesion border is considered regular or irregular.

Towards the automatic detection of skin lesion shape asymmetry, color variegation and diameter in dermoscopic images.

Asymmetry, color variegation and diameter are considered strong indicators of malignant melanoma. The subjectivity inherent in the first two features and the fact that 10% of melanomas tend to be missed in the early diagnosis due to having a diameter less than 6mm, deem it necessary to develop an objective computer vision system to evaluate these criteria and aid in the early detection of melanoma which could eventually lead to a higher 5-year survival rate. This paper proposes an approach for evaluating the three criteria objectively, whereby we develop a measure to find asymmetry with the aid of a decision tree which we train on the extracted asymmetry measures and then use to predict the asymmetry of new skin lesion images.

Vitamin D-VDR Signaling Inhibits Wnt/β-Catenin-Mediated Melanoma Progression and Promotes Antitumor Immunity.

1α,25-Dihydroxyvitamin D3 signals via the vitamin D receptor (VDR). Higher serum vitamin D is associated with thinner primary melanoma and better outcome, although a causal mechanism has not been established. As patients with melanoma commonly avoid sun exposure, and consequent vitamin D deficiency might worsen outcomes, we interrogated 703 primary melanoma transcriptomes to understand the role of vitamin D-VDR signaling and replicated the findings in The Cancer Genome Atlas metastases.

Transcriptomic Analysis Reveals Prognostic Molecular Signatures of Stage I Melanoma.

Purpose: Previously identified transcriptomic signatures have been based on primary and metastatic melanomas with relatively few American Joint Committee on Cancer (AJCC) stage I tumors, given difficulties in sampling small tumors. The advent of adjuvant therapies has highlighted the need for better prognostic and predictive biomarkers, especially for AJCC stage I and stage II disease.

Experimental Design: A total of 687 primary melanoma transcriptomes were generated from the Leeds Melanoma Cohort (LMC).

Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide.

Background: The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a hereditary tumor syndrome caused by germline pathogenic variants in BAP1 encoding a tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic tumors. However, the full spectrum of tumors associated with the syndrome is yet to be determined. Improved understanding of the BAP1-TPDS is crucial for appropriate clinical management of BAP1 germline variant carriers and their families, including genetic counseling and surveillance for new tumors.

β-Catenin-mediated immune evasion pathway frequently operates in primary cutaneous melanomas.

Immunotherapy prolongs survival in only a subset of melanoma patients, highlighting the need to better understand the driver tumor microenvironment. We conducted bioinformatic analyses of 703 transcriptomes to probe the immune landscape of primary cutaneous melanomas in a population-ascertained cohort. We identified and validated 6 immunologically distinct subgroups, with the largest having the lowest immune scores and the poorest survival.

A population-based analysis of germline BAP1 mutations in melanoma.

Germline mutation of the BRCA1 associated protein-1 (BAP1) gene has been linked to uveal melanoma, mesothelioma, meningioma, renal cell carcinoma and basal cell carcinoma. Germline variants have also been found in familial cutaneous melanoma pedigrees, but their contribution to sporadic melanoma has not been fully assessed. We sequenced BAP1 in 1,977 melanoma cases and 754 controls and used deubiquitinase assays, a pedigree analysis, and a histopathological review to assess the consequences of the mutations found.

Which symptoms are linked to a delayed presentation among melanoma patients? A retrospective study.

Background: The incidence of melanoma is rising. Early detection is associated with a more favourable outcome. The factors that influence the timing of a patient's presentation for medical assessment are not fully understood.