Abstract

Background: Various ancillary methods have been explored to assist in the diagnosis of melanocytic tumors with ambiguous light microscopic features. Recently a gene expression profile (GEP)-based assay has been offered as a commercially available test ("DiffDx-Melanoma"; Castle Biosciences), but published results are limited and experiences in the real world practice of Dermatopathology have been associated with unexpected results.  Methods: Cases were searched for in the consultation practices of two dermatopathologists, when a 2nd opinion was sought about the significance of a positive GEP test, which had been ordered by the submitting pathologists because of some diagnostic uncertainty.  Results: 6 cases were found within a period of 3 months. The lesions occurred on varied anatomical sites. Five cases were interpreted by the consultants as atypical Spitz nevus/tumor, one as deep penetrating nevus. None of these cases met microscopic criteria for melanoma. Cytogenetic testing, which was performed in select cases also supported a benign diagnosis. Conclusion: Our study highlights the potential for false positive results by GEP for melanocytic lesions, particularly with Spitz lesions. These observations per se do not invalidate the test, but they remind pathologists that false positive test results can occur and that the test results need to be correlated with the clinical and histopathologic findings to avoid a misdiagnosis. More studies are needed to determine the value of the GEP test for the diagnosis of melanocytic tumors.