The impact of next generation sequencing studies on the diagnosis of BAP1 inactivated melanocytic tumors.
Abstract BAP1 inactivated melanocytic tumors (BIMTs) are recognized for their potential for significant morphologic atypia including nuclear atypia, expansile growth, and mitotic activity, making it difficult to form firm morphologic criteria for malignancy. Next generation sequencing (NGS) is becoming increasingly utilized in melanocytic pathology. We conducted a two-phase survey with 26 dermatopathologists from the International Melanoma Pathology Study Group to assess the impact of NGS on diagnostic accuracy and interobserver agreement in 31 BIMTs. After NGS results, interobserver agreement improved from fair on Survey 1 (κ = 0.348) to moderate on Survey 2 (κ = 0.441). Respondents were 1.7 [...]
The Impact of Next-Generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Deep Penetrating Melanocytic Neoplasms
Abstract 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. [...]
GLUT1 expression, lymphocyte distribution and CD3+ T-cell metabolic subsets as predictive markers of response to immunotherapy in advanced melanoma
Abstract Background: Glycolysis, commonly used by malignant tumors for energy production, results in acidification of the tumor microenvironment (TME) through the secretion and accumulation of lactic acid. Acidosis is a potent inhibitor of immune cell function and may therefore affect T-cell infiltration and the efficacy of immunotherapy. This study aimed to characterize the metabolic tumor microenvironment and its association with lymphocyte distribution in patients with advanced melanoma treated with immune checkpoint blockade (ICB) therapies. Methods: Pre-treatment formalin-fixed, paraffin-embedded metastatic melanoma specimens from 45 patients treated with anti-PD-1 ± anti-CTLA-4 ICB were included in this study. Patients with progression-free survival (PFS) ≥ [...]
The Prognostic Significance of Tumoral Melanosis
Abstract Background: Tumoral melanosis (TM) is a histological term to describe a nodular aggregation of macrophages containing melanin pigment (melanophages) that is devoid of viable melanocytes. It is most often identified in skin, where it may be appreciated clinically as a pigmented lesion; however, it can also be found in other organs such as lymph nodes. The presence of TM is usually thought to signify the presence of a regressed melanoma or other pigmented tumor. Until recently, it was a relatively uncommon finding; however, with the use of effective systemic therapies against melanoma, its occurrence in histological specimens is more [...]
Predictive Performance of the Clinicopathologic Gene Expression Profile (CP-GEP) in Identifying Cutaneous Melanoma Patients for Whom Sentinel Lymph Node Biopsy is Unnecessary: A Systematic Review and Meta-Analysis
Abstract Context & aim: Sentinel lymph node biopsy (SLNB) is an invasive procedure that detects microscopic nodal metastasis, crucial for accurate staging and optimal management. In melanoma, most patients who undergo the procedure have no sentinel lymph node (SLN) metastasis detected. The CP-GEP model (Merlin Assay) was developed to identify patients who do not have SLN metastases and who may therefore safely forgo SLNB, based upon clinicopathologic and gene expression features of the primary tumour. While the Merlin Assay has been validated by independent cohorts with relatively moderate sample sizes, this meta-analysis aims to assess the overall predictive performance of [...]
A multimodal vision foundation model for clinical dermatology.
Abstract Diagnosing and treating skin diseases require advanced visual skills across domains and the ability to synthesize information from multiple imaging modalities. While current deep learning models excel at specific tasks such as skin cancer diagnosis from dermoscopic images, they struggle to meet the complex, multimodal requirements of clinical practice. Here we introduce PanDerm, a multimodal dermatology foundation model pretrained through self-supervised learning on over 2 million real-world skin disease images from 11 clinical institutions across 4 imaging modalities. We evaluated PanDerm on 28 diverse benchmarks, including skin cancer screening, risk stratification, differential diagnosis of common and rare skin [...]
In vivo reflectance confocal microscopy role for early to advanced lentigo maligna melanoma spectrum: A systematic review and pooled analysis.
Abstract Background: Lentigo maligna (LM) is a growing problem worldwide and the main type of melanoma in situ in some Caucasian populations. It presents as a spectrum from atypical intraepidermal melanocytic proliferation (AIMP) to invasive lentigo maligna melanoma (LMM). Accurate diagnosis and staging are crucial for determining appropriate management strategies. Objectives: To assess the role of in vivo reflectance confocal microscopy (RCM) in differentiating early and advanced stages of lentigo maligna. Methods: A systematic search was conducted on Medline, PubMed, Scopus, Web of Science, Proquest Central, Embase, Cochrane and Google Scholar. References of included and excluded studies were reviewed for additional sources. [...]
Multiomic profiling of checkpoint inhibitor-treated melanoma: Identifying predictors of response and resistance, and markers of biological discordance.
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Impact of alternative diagnostic labels for melanoma in situ on management choices and psychological outcomes: protocol for an online randomised study.
Abstract 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 [...]
In vivo reflectance confocal microscopy role for early to advanced lentigo maligna melanoma spectrum: A systematic review and pooled analysis.
Abstract Background: Lentigo maligna (LM) is a growing problem worldwide and the main type of melanoma in situ in some Caucasian populations. It presents as a spectrum from atypical intraepidermal melanocytic proliferation (AIMP) to invasive lentigo maligna melanoma (LMM). Accurate diagnosis and staging are crucial for determining appropriate management strategies. Objectives: To assess the role of in vivo reflectance confocal microscopy (RCM) in differentiating early and advanced stages of lentigo maligna. Methods: A systematic search was conducted on Medline, PubMed, Scopus, Web of Science, Proquest Central, Embase, Cochrane and Google Scholar. References of included and excluded studies were reviewed for additional sources. [...]