Genomic Profiling of Lentigo Maligna within an Interim Registry Analysis​

Abstract

Background:  Pigmented lesion analysis remains a challenging aspect of dermatology. The DermTech Melanoma Test (‘the test’) is a non-invasive genomic test designed to rule-out melanoma. It consists of the pigmented lesion assay, which detects RNA products of Long Intergenic Non-Coding RNA 00518 (LINC00518) and Preferentially Expressed Antigen in Melanoma (PRAME), and an add-on assay for DNA promoter mutations in telomerase reverse transcriptase (TERT).  In previous studies, the test was found to have a negative predictive value ≥99%. This interim analysis of a registry study examines the genomic patterns of the Lentigo Maligna (LM) subtype of melanoma.  

Methods: Between April 2021 and March 2022, multiple geographically diverse sites throughout the US submitted data to a registry to assess real-world use of the test. Approximately 8,000 clinically atypical lesions were tested. After receiving the test result, providers followed their clinical judgement for biopsy decision. Histopathologic diagnoses for biopsied lesions were correlated with test results and all melanomas were sorted into LM subtype vs non-LM subtype. In addition, lesions that were noted to be on sun exposed skin and/or noted to have solar elastosis and called atypical melanocytic hyperplasia were included. 

Results: At the 1-year mark of the registry, there were roughly 8000 unique entries.  Of those, 1003 expressed one or more genomic markers from the DMT and had records available, and 134 (13.2%) were found to be melanoma or melanoma in-situ. More than a third (n=46, 34.3%) of the melanomas were of the Lentigo Maligna sub-type, with 7 of those being Lentigo Maligna Melanoma (LMM). Seven additional lesions were called atypical junctional melanocytic hyperplasia (AJMH) on sun-damaged skin. This group of 53 LM, LMM, and AJMH lesions were all evaluated for correlations to the DMT markers. LINC was the most commonly expressed genomic marker (n=45, 84.9%), with PRAME (n=36, 67.9%) and TERT (n=24, 45.3%) following. Most invasive tumors (LMM) expressed all three markers (n=4) and all 7 expressed LINC. 

Conclusion: While the original validation study included the LM subtype, this interim registry analysis demonstrates real-world use of the DMT in assessing pigmented macules concerning for LM. Over 1/3 of the melanomas reported in the registry were LM subtypes. LINC had a higher correlation with the lentigo maligna subtype of melanoma and was present in all invasive tumors. While AJMH is considered borderline, it may be worthwhile in the clinical context to group AJMH lesions with LM due to similarities in treatment.