The Impact of Next-Generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Deep Penetrating Melanocytic Neoplasms

Background: Next-generation sequencing (NGS) is becoming more commonly used for diagnosis in dermatopathology. It's critical to appraise its efficacy and limitations. Distinguishing benign deep penetrating nevi (DPN) from deep penetrating like-melanoma (DPN-M) is a challenging diagnostic scenario even for experienced dermatopathologists. Methods: We sent a two-phase survey (pre-and postgenomics) to 32 experienced dermatopathologists to evaluate 39 diagnostically challenging cases from the DPN/WNT-activated family of melanocytic neoplasms. Results: With NGS data, interobserver agreement improved from 0.41 to 0.51 (p < 0.0001) in distinguishing DPN-M from nonmelanoma cases. Overall diagnostic accuracy improved, mostly driven by a 16% increase in accurate diagnosis of DPN-M. However, in two cases, the inclusion of genomics shifted the majority vote from a correct to an incorrect diagnosis. A total of 218 diagnostic changes occurred between Survey 1 and 2. Among the changes, 132 votes moved toward the correct diagnosis while 86 moved toward an incorrect diagnosis. The shift in voting which resulted in improved diagnostic accuracy was statistically significant (p = 0.0001). Conclusions: NGS has the potential to improve interobserver agreement and diagnostic accuracy. We provide guidance on the utilization of bioinformatic data to maximize its benefits and improve diagnostic accuracy and interobserver agreement.