Clinicopathologic Features of PRAME-Positive Common Melanocytic Nevi: A Case-Control Study

Preferentially Expressed Antigen in Melanoma (PRAME) immunohistochemistry has been found to be relatively sensitive and specific for the diagnosis of melanoma, although the detection of PRAME positivity in some melanocytic nevi is a significant limitation. This study was designed to investigate the features of common melanocytic nevi showing PRAME staining, encountered in routine community practice. We reviewed all pathology reports on common melanocytic nevi seen in routine practice for a 1-month period and found that 7.1% of nevi stained with PRAME were considered positive by the original reporting pathologist. A total of 41 PRAME-positive nevi (representing 4.7% of nevi) and a control group of 43 PRAME-negative nevi collected during the same period were identified. The histologic features were reviewed, and the diagnosis and PRAME staining were recorded in a masked fashion by 3 dermatopathologists. Our results suggest that caution is warranted in the interpretation of PRAME in the assessment of small lentiginous melanocytic nevi with a low level of suspicion for melanoma, because these are not infrequently PRAME positive. We found a statistically significant association between the presence of solar elastosis and lentiginous growth pattern, and PRAME status (P < 0.01). When comparing the original diagnosis with the reviewer's diagnosis, the original diagnosis was severely atypical in 54% of PRAME-positive cases, while only 7% were considered to show severe atypia on review masked to PRAME status (P < 0.001). There was no such discrepancy among PRAME-negative cases (9% vs. 19%, considered severely atypical). This finding provides evidence of a "PRAME bias" in the interpretation of melanocytic lesions with no or mild atypia, whereby such lesions are classified as severely atypical when PRAME is positive, likely with the intention of prompting re-excision.