The combined diagnostic value of 5-hmC and PRAME immunohistochemistry in melanocytic neoplasms

• Published in: Pathology, research and practice Vol. 270; p. 155993
• Main Authors: Yu, Yanhong, Hosseini, Niloufar, Dodington, David, Wood, Kimberly, Ghazarian, Danny, Kamil, Zaid Saeed
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.06.2025
• Subjects: 5-hydroxymethylcytosine; 5-Methylcytosine - analogs & derivatives; Adolescent; Adult; Aged; Antigens, Neoplasm - analysis; Antigens, Neoplasm - metabolism; Biomarkers, Tumor - analysis; Diagnosis, Differential; Dysplastic Nevus Syndrome - diagnosis; Dysplastic Nevus Syndrome - metabolism; Dysplastic Nevus Syndrome - pathology; Female; Humans; Immunohistochemistry; Male; Melanoma; Melanoma - diagnosis; Melanoma - metabolism; Melanoma - pathology; Middle Aged; Nevus; Nevus, Epithelioid and Spindle Cell - diagnosis; Nevus, Epithelioid and Spindle Cell - metabolism; Nevus, Epithelioid and Spindle Cell - pathology; PReferentially expressed Antigen in MElanoma; Retrospective Studies; Skin Neoplasms - diagnosis; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Young Adult; Immunohistochemistry; PReferentially expressed Antigen in MElanoma; 5-hydroxymethylcytosine; Melanoma; Nevus
• DOI: 10.1016/j.prp.2025.155993
• ISSN: 0344-0338; 1618-0631

The diagnosis of melanocytic neoplasms, particularly those with borderline morphologic features, remains a challenging area in dermatopathology. 5-hydroxymethylcytosine (5-hmC) and PRAME (PReferentially expressed Antigen in MElanoma) are recent immunohistochemical markers which have been shown to be valuable in distinguishing benign from malignant melanocytic neoplasms. A retrospective cohort of 144 benign, borderline (Spitz nevi, atypical Spitz tumors and dysplastic nevi) and malignant melanocytic tumors at our institution were analyzed for 5-hmC and PRAME expression by immunohistochemistry. Compared to benign nevi, melanoma cases had higher PRAME expression (p < 0.0001) and lower 5-hmC (p < 0.0001) expression. In receiver operator curve analysis, 5-hmC and PRAME were good discriminators between benign and malignant neoplasms; the area under the curve (AUC) was 0.91 for 5-hmC (p < 0.0001) and 0.94 for PRAME (p < 0.001). Subgroup analysis showed that 5-hmC expression was significantly different between dysplastic nevi and melanoma. The combination of PRAME and 5-hmC significantly improved the predictive ability of these markers (AUC 0.97, p < 0.001). Having both PRAME expression of 4 + (> 75 % lesional cells positive) and 5-hmC of < 0.2 was highly specific for malignancy (98 %) with a sensitivity of 61 %. Utilizing 5-hmC and PRAME in conjunction improves their diagnostic value in distinguishing benign from malignant melanocytic neoplasms.