PRAME-Positive Eruptive Melanocytic Nevi in the Setting of BRAF-Inhibitors

Preferentially Expressed Antigen in Melanoma (PRAME) is an immunohistochemical marker utilized in the diagnosis of melanocytic neoplasms. While still considered highly specific, both diffuse and variable PRAME immunoreactivity have been demonstrated in benign melanocytic lesions. This phenomenon is widely documented, as well as the phenomenon of eruptive melanocytic nevi (EMN) arising in the context of BRAF-inhibition. We report here a patient on encorafenib who developed numerous new pigmented lesions within 3 weeks of therapy. Initial biopsy suggested evolving melanoma in situ with 70%-75% intraepidermal melanocytes strongly PRAME positive, prompting additional testing. Two subsequent lesions demonstrated only focal PRAME staining and lacked malignant features, leading to the reclassification of the initial lesion as a compound nevus with unusual features. This case underscores that BRAF inhibition may enhance PRAME expression in benign melanocytic nevi, potentially through mechanisms involving mitogen-activated protein kinase (MAPK) activation, altered Erk phosphorylation, or disruption of retinoic acid (RA) signaling. This case also brings awareness to the potential of medication-induced PRAME expression and encourages both dermatologists and dermatopathologists to avoid overdiagnosis as PRAME continues to gain prominence as a diagnostic biomarker.