Goldberg M, Siegel J, Russell B, et al.. A comprehensive diagnostic offering workflow increases the rate of actionable results of the 23- and 35-gene expression profile tests for use as ancillary diagnostic tools for difficult-to-diagnose melanocytic lesions. SKIN The Journal of Cutaneous Medicine. 2021;5(6):s79. doi:10.25251/skin.5.supp.79.
Sequential implementation of a 23- and 35-gene expression profile test may provide additional diagnostic factors for challenging pigmented lesions.
Clinical Pearls
A diagnostic study using archival melanocytic lesions from adults ≥18 years old that were then tested in series by the 23-GEP test and 35-GEP test, if the 23-GEP did not provide definitive results.
After the comprehensive diagnostic offering (CDO), 59.5% of samples were benign and 39.1% were malignant, 1.1% were intermediate and 0.2% were technical failures.
The CDO had a positive predictive value (PPV) of 90.1% and negative predictive value (NPV) of 94.1%.
Discussion:
An average of 1 in 44 Americans develop cutaneous melanoma (CM), a type of skin cancer, in their lifetime, and 7650 Americans are expected to die in 2022 alone from CM. Given morbidity and mortality increase with advancing disease, early detection (and intervention) is paramount. However, pigmented and melanocytic lesions may not always be clear cut based on traditional clinicohistopathologic diagnostic criteria. Several gene-expression profile (GEP) tests have been developed to provide additional data intrinsic to tumor biology, including a 23 and 35-GEP test.
This was a diagnostic study using archival melanocytic lesions from adults ≥18 years old that had previously received a formal diagnosis. These samples, after being reviewed independently by 2 dermatopathologists, were then tested in series, first by the 23-GEP test and, if results were intermediate or “Technical Fail”, then by additional testing with the 35-GEP test.
738 fresh-frozen paraffin-embedded biopsy samples underwent testing. 77.8% of cases had an “actionable” result of benign or malignant after the 23-GEP test with 12.9% having intermediate result and 9.4% being “technical failures”. After additional testing with 35-GEP, an additional 20.9% had actionable results leaving only 1.1% with intermediate results and 0.2% resulting in “technical failure”. Overall, 59.5% of samples were benign and 39.1% were malignant. This test series, termed comprehensive diagnostic offering (CDO) had a sensitivity of 94.7%, specificity of 89.5%, positive predictive value of 90.1% and negative predictive value of 94.1%.
The CDO has demonstrated an ability to provide additional diagnostic information, especially for pigmented and melanocytic lesions that may not meet classical diagnostic criteria. Further testing of the CDO in prospective studies and real-world settings are needed to determine how to properly implement testing for different patient populations, especially patients at high-risk of developing melanomas.
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