Melanoma in situ and low-risk pT1a melanoma: Need for new diagnostic terminology.

The incidence of melanoma has risen rapidly, at least until recently, while the mortality rate has changed only a little, a phenomenon suggestive of overdiagnosis, which can be defined as the diagnosis as "melanoma" of a lesion that would not have had the competence to cause death or symptoms even if it had not been excised. Overdiagnosis has been attributed to efforts at early diagnosis ("overdetection") and to changes in criteria resulting in diagnosis as melanoma of lesions previously termed nevi ("overdefinition"). In terms of overdefinition, there is evidence that criteria for the histopathologic diagnosis of melanoma have changed over a period of approximately two decades.

MPATH-Dx version 2.0 schema for melanocytic lesions: A robust tool for standardized diagnostic reporting.

The new revised MPATH-Dx (version 2.0) reporting schema for melanocytic lesions is presented. Principal changes include the simplification of the previous five-class version 1.

International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

Background: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms.

Objectives: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping.

The Impact of Next-generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Desmoplastic Melanocytic Neoplasms.

Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs).

Immunohistochemistry for Diagnosing Melanoma in Older Adults.

Importance: Pathologic assessment to diagnose skin biopsies, especially for cutaneous melanoma, can be challenging, and immunohistochemistry (IHC) staining has the potential to aid decision-making. Currently, the temporal trends regarding the use of IHC for the examination of skin biopsies on a national level have not been described.

Objective: To illustrate trends in the use of IHC for the examination of skin biopsies in melanoma diagnoses.

Dermatologist-like explainable AI enhances trust and confidence in diagnosing melanoma.

Artificial intelligence (AI) systems have been shown to help dermatologists diagnose melanoma more accurately, however they lack transparency, hindering user acceptance. Explainable AI (XAI) methods can help to increase transparency, yet often lack precise, domain-specific explanations. Moreover, the impact of XAI methods on dermatologists' decisions has not yet been evaluated.

Implementing the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis: Long-term effect of a simple educational intervention.

Background: A standardized pathology management tool for melanocytic skin lesions may improve patient care by simplifying interpretation and categorization of the diverse terminology currently extant.

Objective: To assess an online educational intervention that teaches dermatopathologists to use the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx), a schema collapsing multiple diagnostic terms into 5 classes ranging from benign to invasive melanoma.

Methods: Practicing dermatopathologists ( 149) from 40 US states participated in a 2-year educational intervention study (71% response rate).

Diagnostic error, uncertainty, and overdiagnosis in melanoma.

Diagnostic error can be defined as deviation from a gold standard diagnosis, typically defined in terms of expert opinion, although sometimes in terms of unexpected events that might occur in follow-up (such as progression and death from disease). Although diagnostic error does exist for melanoma, deviations from gold standard diagnosis, certainly among appropriately trained and experienced practitioners, are likely to be the result of uncertainty and lack of specific criteria, and differences of opinion, rather than lack of diagnostic skills. In this review, the concept of diagnostic error will be considered in relation to diagnostic uncertainty, and the concept of overdiagnosis in melanoma will be presented and discussed.

Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions: A Consensus Statement.

Importance: A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.

Objective: To revise the MPATH-Dx version 1.

Prognostic modeling of cutaneous melanoma stage I patients using cancer registry data identifies subsets with very-low melanoma mortality.

Background: Evidence exists that escalating melanoma incidence is due in part to overdiagnosis, the diagnosis of lesions that will not lead to symptoms or death. The authors aimed to characterize subsets of melanoma patients with very-low risk of death that may be contributing to overdiagnosis.

Methods: Melanoma patients diagnosed in 2010 and 2011 with stage I lesions ≤1.

Monitoring Angiotropic Extravascular Migratory Metastasis In Vitro.

The mechanism of cancer cell migration from the primary tumor toward secondary sites is not fully understood. In addition to intravascular cellular migration, angiotropic extravascular migratory metastasis (EVMM) has been recognized as a metastatic pathway involving tumor cells crawling along the abluminal vascular surface to distant sites. A very simple in vitro 3D assay is described here, which is based on a previous in vitro angiogenesis assay.

Targeted Long-Read Bisulfite Sequencing Identifies Differences in the Promoter Methylation Profiles between Wild-Type and Mutant Cancer Cells.

Background: TERT promoter methylation, located several hundred base pairs upstream of the transcriptional start site, is cancer specific and correlates with increased TERT mRNA expression and poorer patient outcome. Promoter methylation, however, is not mutually exclusive to TERT activating genetic alterations, as predicted for functionally redundant mechanisms. To annotate the altered patterns of TERT promoter methylation and their relationship with gene expression, we applied a Pacific Biosciences-based, long-read, bisulfite-sequencing technology and compared the differences in the methylation marks between wild-type and mutant cancers in an allele-specific manner.

Effect of Prior Diagnoses on Dermatopathologists' Interpretations of Melanocytic Lesions: A Randomized Controlled Trial.

Importance: Medical second opinions are common, although little is known about the best processes for obtaining them. This study assesses whether knowledge of a prior physician's diagnosis influences consulting physicians' diagnoses.

Objective: To measure the extent to which dermatopathologists' diagnoses are influenced by prior diagnostic information from another dermatopathologist.

Dermatopathologist Perceptions of Overdiagnosis of Melanocytic Skin Lesions and Association With Diagnostic Behaviors.

Importance: Despite evidence of overdiagnosis of in situ and invasive melanoma, neither the perceptions of practicing dermatopathologists about overdiagnosis nor possible associations between perceptions of overdiagnosis and diagnostic practices have been studied.

Objective: To examine practicing US dermatopathologists' perceptions of melanoma overdiagnosis as a public health issue, and to associate diagnostic behaviors of dermatopathologists with perceptions of melanoma overdiagnosis.

Design, Setting, And Participants: This survey study included 115 board-certified and/or fellowship-trained dermatopathologists and their diagnostic interpretations on a set of 18 skin biopsy cases (5 slide sets comprising 90 melanocytic skin lesions).

Histopathological diagnosis of cutaneous melanocytic lesions: blinded and nonblinded second opinions offer similar improvement in diagnostic accuracy.

Background: Previous studies of second opinions in the diagnosis of melanocytic skin lesions have examined blinded second opinions, which do not reflect usual clinical practice. The current study, conducted in the USA, investigated both blinded and nonblinded second opinions for their impact on diagnostic accuracy.

Methods: In total, 100 melanocytic skin biopsy cases, ranging from benign to invasive melanoma, were interpreted by 74 dermatopathologists.

Vessel co-option and angiotropic extravascular migratory metastasis: a continuum of tumour growth and spread?

Two fields of cancer research have emerged dealing with the biology of tumour cells localised to the abluminal vascular surface: vessel co-option (VCo), a non-angiogenic mode of tumour growth and angiotropic extravascular migratory metastasis (EVMM), a non-hematogenous mode of tumour migration and metastasis. VCo is a mechanism by which tumour cells gain access to a blood supply by spreading along existing blood vessels in order to grow locally. Angiotropic EVMM involves "pericytic mimicry" (PM), which is characterised by tumour cells continuously migrating in the place of pericytes distantly along abluminal vascular surfaces.

Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms.

Atypical Spitzoid melanocytic tumors are diagnostically challenging. Many studies have suggested various genomic markers to improve classification and prognostication. We aimed to assess whether next-generation sequencing studies using the Tempus xO assay assessing mutations in 1711 cancer-related genes and performing whole transcriptome mRNA sequencing for structural alterations could improve diagnostic agreement and accuracy in assessing neoplasms with Spitzoid histologic features.

Skin cancer classification via convolutional neural networks: systematic review of studies involving human experts.

Background: Multiple studies have compared the performance of artificial intelligence (AI)-based models for automated skin cancer classification to human experts, thus setting the cornerstone for a successful translation of AI-based tools into clinicopathological practice.

Objective: The objective of the study was to systematically analyse the current state of research on reader studies involving melanoma and to assess their potential clinical relevance by evaluating three main aspects: test set characteristics (holdout/out-of-distribution data set, composition), test setting (experimental/clinical, inclusion of metadata) and representativeness of participating clinicians.

Methods: PubMed, Medline and ScienceDirect were screened for peer-reviewed studies published between 2017 and 2021 and dealing with AI-based skin cancer classification involving melanoma.

Characterization of multiple diagnostic terms in melanocytic skin lesion pathology reports.

Background: Histopathologically ambiguous melanocytic lesions lead some pathologists to list multiple diagnostic considerations in the pathology report. The frequency and circumstance of multiple diagnostic considerations remain poorly characterized.

Methods: Two hundred and forty skin biopsy samples were interpreted by 187 pathologists (8976 independent diagnoses) and classified according to a diagnostic/treatment stratification (MPATH-Dx).

Histopathologic synoptic reporting of invasive melanoma: How reliable are the data?

Background: Synoptic reporting is recommended by many guideline committees to encourage the thorough histologic documentation necessary for optimal management of patients with melanoma.

Methods: One hundred fifty-one pathologists from 40 US states interpreted 41 invasive melanoma cases. For each synoptic reporting factor, the authors identified cases with "complete agreement" (all participants recorded the same value) versus any disagreement.

Visualizing Pericyte Mimicry of Angiotropic Melanoma by Direct Labeling of the Angioarchitecture.

In addition to intravascular dissemination, angiotropic melanoma cells have the propensity to spread along the external surface of blood vessels in a pericytic location, or pericytic mimicry. Such continuous migration without intravasation has been termed "extravascular migratory metastasis" or EVMM. In order to visualize this mechanism of tumor propagation, we used a murine brain melanoma model utilizing green fluorescent human melanoma cells and red fluorescent lectin-tagged murine vessels.