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Novel Molecular Test Contributes to Definitive Diagnosis in Melanoma

Kelly Goff, MD
Published: Thursday, Feb 12, 2015

Dr. Sancy LeachmanSancy Leachman, MD


With a need to make more definitive diagnoses of melanocytic lesions, the Myriad myPath Melanoma molecular diagnostic test has been reported as a tool to calculate melanoma diagnostic scores (MDS) and help practitioners differentiate between benign and malignant lesions, according to results from a prospective study. 

“In the validation study, Myriad myPath Melanoma was shown to differentiate malignant melanoma from benign skin lesions using traditional dermatopathology as a gold standard. This represents a significant contribution toward making a prompt and accurate diagnosis of potentially fatal melanoma,” said coauthor Sancy Leachman, MD, PhD, chair of the Department of Dermatology at the Oregon Health & Science University School of Medicine and director of the Melanoma Research Program at the Knight Cancer Institute.
Reducing the number of indeterminate diagnoses is highly desirable for patients and their doctors. “Patients and physicians with an indeterminate biopsy result face the challenging clinical question of whether to treat the lesion as melanoma or risk not treating a potentially fatal cancer,” said Loren Clarke, MD, study coauthor and vice president of Medical Affairs of Dermatology at Myriad Genetics.1

Numerous studies have shown that the diagnosis for melanoma can be difficult for practitioners and discordance often occurs, even among experienced dermatopathologists. 

“There are approximately 1.5 million biopsies done in [the United States] alone for atypical moles in an effort to exclude the possibility of melanoma each year. We estimate...that approximately 15% of those, maybe more, are indeterminate or difficult to diagnose,” said Clarke.2

The current standard for diagnosis is histopathologic analysis. The 5-year survival rate for stage 1 melanoma is approximately 97%. Misdiagnosis, however, can lead to inadequate treatment, with possible spread of the disease and increased stage. The 5-year survival rate for stage 4 disease is approximately 15% to 25%.3

“Unfortunately, some melanomas mimic benign skin lesions, making them very difficult to diagnose, and an uncertain result is confusing for patients and clinicians. What we need is a new tool to help us make a more definitive diagnosis,” said Leachman.4

Knowledge of genetic expression of melanocytic lesions significantly reduced the number of indeterminate diagnoses made by dermatopathologists, according to results from a prospective study on the utility of the Myriad myPath Melanoma molecular diagnostic test, presented in November at the 2014 American Society of Dermatopathology Annual Meeting in Chicago, IL.5

The Myriad myPath Melanoma molecular diagnostic test is a molecular assay that analyzes gene expression of the lesion. Prior research, using quantitative reverse transcription polymerase chain reaction (qRT-PCR), identified a 23-gene expression signature of melanocytic lesions. This gene signature includes genes that regulate cell differentiation, immune function, and cellular housekeeping.

Using the gene signature, a MDS was calculated and used to differentiate between benign and malignant lesions. The MDS was shown to discriminate between benign nevi and malignant melanoma with 93% specificity and 89% sensitivity (P = 2 × 10-63).6

The clinical utility of the MDS was further validated by the current study. Melanocytic lesions were submitted by dermatopathologists with a questionnaire regarding diagnosis, diagnostic confidence, and recommended medical management. Prior to myPath testing of the 687 lesions, 14.8% had an indiscriminate diagnosis and 17.2% had lower diagnostic confidence. The lesions then underwent qRT-PCR and an MDS was calculated for each lesion.

The MDS was given to the submitting dermatopathologist, who was asked to complete a posttest questionnaire. The answers given on the questionnaire showed that, with the additional gene expression information, 76.5% of indeterminate diagnoses were revised to more definitive ones. Most revisions (58.8%) downgraded the diagnosis to benign. After receiving the MDS, dermatopathologists recommended less invasive management in 23.5% of the cases and more invasive management in 11.6% of the cases.

The researchers noted that this test should be incorporated into the current diagnostic approach. “These data strongly support the integration of the Myriad myPath Melanoma test into clinical practice to personalize and improve patient care,” said Clarke. “The Myriad myPath Melanoma test objectively answers a vital clinical question for physicians: does my patient have malignant melanoma that requires aggressive intervention or a harmless skin lesion that should be monitored?” 

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Evolving Roles for Targeted Melanoma Therapies: Assessing Rapid Progress in the Field and Looking Toward Future CombinationsFeb 28, 20191.5
Advances in™ Melanoma: Exploring BRAF/MEK in Adjuvant and Neoadjuvant SettingsSep 28, 20191.5
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