Real-World Utility of a Non-Invasive Gene Expression Test to Rule Out Primary Cutaneous Melanoma: A Large US Registry Study

March 2020 | Volume 19 | Issue 3 | Original Article | 257 | Copyright © March 2020


Published online February 18, 2020

Brook Brouha , Laura K. Ferris , Maral K. Skelsey , Gary Peck , Ronald Moy , Zuxu Yao , Burkhard Jansen

aWest Dermatology, La Jolla, CA BDepartment of Dermatology, University of Pittsburgh, Pittsburgh, PA cDepartment of Dermatology, Georgetown University School of Medicine, Washington, DC dDermatologic Surgery Center of Washington, Chevy Chase, MD eRodeoDerm Moy Fincher Chips, Beverly Hills, CA fDermTech, Inc, La Jolla, CA

Abstract
Introduction: The Pigmented Lesion Assay (PLA) is a non-invasive gene expression test that helps clinicians rule out melanoma via a genomics approach that elevates pigmented lesion management beyond what the eye can see. PLA improves care with a negative predictive value of >99% while reducing biopsies by 90% and while reducing cost.

Methods: The registry study described here (53 US dermatology offices, 90 providers, median patient age 48 years, 60.80% female and 39.20% male patients) assesses real-world utility to determine if the PLA changes clinical practice.

Results: Of 3,418 pigmented skin lesions clinically suspicious for melanoma and assessed by PLA, 324 lesions (9.48%) were PLA(+) and 3,094 (90.52%) were negative. A PLA test result is positive if LINC, PRAME, or both target genes are detected; these molecular pathology findings are known to correspond with histopathology findings of in situ or invasive primary melanoma in 7%, 50%, and 93%, respectively. The 9.48% PLA(+) cases consisted of 5.15% LINC only, 1.93% PRAME only, and 2.40% LINC and PRAME double positive cases. Notably, 97.53% of PLA(+) lesions were surgially biopsied, while 99.94% of PLA(-) cases were clinically monitored and not biopsied.

Discussion: These findings demonstrate that community-based clinicians who employ the PLA to improve pigmented lesion management use the test’s results to guide how they practice. Pigmented lesions with PLA(+) test results are subjected to surgical biopsies, whereas PLA(-) lesions are followed clinically and not biopsied.

J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.4766

INTRODUCTION

Efforts to unambiguously assess and adjudicate primary melanocytic skin lesions clinically suspicious of melanoma to rule out melanoma via the existing standard of care of visual assessment and histopathology remains a challenge even for pigmented lesion experts because of inherent limitations of image recognition.1-11 Dermoscopy, confocal microscopy, or computer-aided image analysis of skin lesions can reduce some of these inherent limitations. However, these tools generally do not overcome these issues and challenges continue after biopsy decisions have been made. Histologic evaluation is again guided by image and pattern recognition. Histologic criteria to distinguish between benign and malignant are overlapping and are in nature subjective, affecting the performance of our existing mainstay of establishing diagnoses in pigmented lesion management.4,6 These complexities and issues are highlighted in a large 2017 US study in which Elmore and colleagues assessed the performance of 187 pathologists and dermatopathologists reviewing the histopathology slides of 240 melanocytic lesions including 118 early-stage melanomas.4 From the study, the authors estimate that only 82.8% of all melanocytic skin biopsy diagnoses across a population would be verified by a consensus panel of experts. Furthermore, the accuracy of assigning intermediate melanocytic lesions to the correct one of five mPath categories is low, ranging from 25% to 43%.4 Intra-observer reproducibility showed similarly discouraging discordance.4 Although an increasing number of studies have demonstrated that immunohistochemistry and molecular analysis techniques, such as fluorescence in situ hybridization, comparative genomic hybridization, and messenger ribonucleic acid (RNA) expression profiling of surgically obtained specimens, can help to somewhat enhance our ability to assess melanocytic neoplasms, these approaches fall short of truly impacting pigmented lesion management because of their performance characteristics and because the tests depend