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


Hurdogan O., Baykal C., Yilmaz İ., Erdem B. Y., Buyukbabani N., Sari S. O.

Journal of Cutaneous Pathology, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1111/cup.70119
  • Dergi Adı: Journal of Cutaneous Pathology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS
  • Anahtar Kelimeler: congenital melanocytic nevus, H3K27me3, malignant melanoma, PRAME, proliferative nodule
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.