DP02: Diagnostic utility of the Pigmented Lesion Assay in an academic setting

P. Shah,¹ L. Fried,¹ J. Stein,¹ T. Liebman,¹ D. Polsky^1,2 and S. Meehan¹

¹New York University Grossman School of Medicine and ²Laura and Isaac Perlmutter Cancer Center, New York City, NY, USA

Current clinical studies of the Pigmented Lesion Assay (PLA; DermTech, La Jolla, CA, USA) are largely supported by DermTech and are thus subject to potential bias. These studies demonstrate a > 99% negative predictive value (NPV) (Ferris LK, Rigel DS, Siegel DM et al. Impact of clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month follow-up of negative test results and utility data from a large US registry study. Dermatol Online J 2019; 25: 13030/qt61w6h7mn), 95% sensitivity, 91% specificity and a 93% positive predictive value (PPV) of a double-positive LINC/PRAME gene expression result (Ferris LK, Gerami P, Skelsey MK et al. Real-world performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions. Melanoma Res 2018; 28: 478–82). We aimed to validate the diagnostic performance of PLA in a real-world study of patients in an academic medical setting. We hypothesized that PLA would have a lower specificity and PPV than previously reported results. We conducted a retrospective cohort study of patients in which the PLA was used to assist the evaluation of a lesion suspicious for melanoma. PLA-positive lesions proceeded to skin biopsy and PLA-negative lesions were managed with follow-up monitoring; PLA-indeterminate lesions (usually due to insufficient sampling) were managed as per the clinical judgement of the dermatologist. PLA lesions with at least 6 months of follow-up were included. PLA sensitivity, specificity, PPV and NPV were evaluated using histopathological examination and follow-up clinical evaluation as ground truth. The study population included 122 cases (57·4% were female). Mean (SD) age was 52·2 (16·3) years. Forty-four patients (36·1%) had a history of melanoma, 38 (31·2%) had a history of keratinocyte cancer, 73 (59·8%) had a history of atypical naevi, 24 (19·7%) had a family history of melanoma and 85 had > 25 naevi on examination (69·7%). Ninety-eight cases (80·3%) were evaluated by pigmented lesion experts. Six cases (4·9%) were melanoma and two (1·6%) were keratinocyte cancers. Fifteen cases (12·2%) had an indeterminate PLA result and 17 cases (13·9%) were lost to follow-up. PLA sensitivity was 80% (n = 4/5), specificity was 82% (n = 71/87), PPV was 20% (n = 4/20) and NPV was 99% (n = 71/72). Double-positive (LINC and PRAME) PPV was 22% (n = 2/9), LINC-only PPV was 11% (n = 1/9) and PRAME-only PPV was 50% (n = 1/2). Median time to follow-up for PLA- lesions was 161 days. In contrast to previously published reports, in an academic medical setting with more high-risk patients for melanoma than typical community settings, PLA performance had lower sensitivity, specificity and double-positive PPV. The NPV is comparable to that previously reported. Study findings are limited by the small case volume. Dermatologists should recognize the potential limitations of PLA use in the evaluation of equivocal lesions for melanoma, including risk for false-positive results, which may require unnecessary biopsies for patients and the costs associated with indeterminate test results.