Diagnostic Utility of <scp>PRAME</scp> and <scp>H3K27me3</scp> in Distinguishing Malignant Melanoma From Proliferative Nodules on Congenital Melanocytic Nevi

BACKGROUND: Malignant melanoma (MM) and proliferative nodules (PN) may arise in large/giant congenital melanocytic nevi (LCMN/GCMN), posing clinical and pathological challenges in differential diagnosis. We investigated immunohistochemical expression of PRAME and H3K27me3 in MMs and PNs in LCMN/GCMN, examining their potential utility. METHODS: Three MMs and six PNs arising in LCMN/GCMN were subjected to immunohistochemical analyses. PRAME staining was scored as percentage of positive cells and H3K27me3 as follows: score0 = no staining; score1 = 1%-25%; score2 = 26%-50%; score3 = 51%-75%; score4 = 76%-100% staining in tumor cells. BRAF, NRAS, KIT, GNAQ, GNA11, and TERT mutations were tested by polymerase chain reaction-based direct Sanger sequencing for 3 MMs. RESULTS: Mean age was 6.2 (0-24), 33.6% were male. All MM cases were metastatic and two died of disease. CMN components were negative for PRAME in all cases, whereas 3 MMs and 1 PN were positive (> 90%). MMs showed loss of H3K27me3 expression, whereas expression was retained in all PNs. Two cases showed NRAS mutations in both MM and nevus components. CONCLUSION: Combined use of PRAME and H3K27me3 can be utilized to discriminate MM from PN arising in LCMN/GCMN if validated on larger cohorts.