Diagnostic utility of combining PRAME and HMB-45 stains in primary melanocytic tumors

• Published in: Annals of diagnostic pathology Vol. 67; p. 152211
• Main Authors: Rasic, Dusan, Korsgaard, Niels, Marcussen, Niels, Precht Jensen, Eva Magrethe
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2023
• Subjects: Antibodies, Monoclonal; Antigens, Neoplasm; Coloring Agents; Diagnosis, Differential; Dysplastic Nevus Syndrome - diagnosis; Dysplastic Nevus Syndrome - pathology; HMB-45; Humans; Immunohistochemistry; Melanocytic tumor; Melanoma - diagnosis; Melanoma - pathology; Nevus - pathology; PRAME; Skin Neoplasms - diagnosis; Skin Neoplasms - pathology; Staining and Labeling; Immunohistochemistry; HMB-45; PRAME; Melanocytic tumor
• ISSN: 1092-9134; 1532-8198
• DOI: 10.1016/j.anndiagpath.2023.152211

Pathologists face ongoing challenges distinguishing between benign and malignant melanocytic tumors. PRAME (PReferentially expressed Antigen in Melanoma) has a demonstrated value distinguishing between these types of lesions. However, the sensitivity of single immunohistochemistry is variable. HMB-45 is another valuable marker, but on its own, has a limited ability in setting of primary melanocytic tumors. This study sought to evaluate the diagnostic potential of a dual panel combining PRAME and HMB-45 in the assessment of primary melanocytic tumors.
259 tumors, of which 141 were benign nevi, 31 dysplastic nevi (either low- or high grade dysplasia), and further 87 malignant melanomas, were retrieved from the department's archives and assessed by two experienced dermatopathologists. New sections were stained with PRAME and HMB-45, respectively. For PRAME, a nuclear, and for HMB-45, a cytoplasmic staining, was considered positive and scored as described in the literature on a scale from 0 to 4+. Only dermal component was assessed on HMB-45 stain.
PRAME was diffusely expressed in only 1 benign nevus, with focal expression in further 28 compared to 22 diffusely and 103 focally HMB-45-positive benign nevi. 5 high-grade dysplastic nevi showed diffuse PRAME expression in epidermal component, with varying degree of positivity in adjacent dermal compartment, and further 8 dysplastic nevi showed only focal expression. HMB-45 was diffusely expressed in only 2, with focal expression in 23, and no apparent positivity in remaining 6 dysplastic nevi. In invasive melanoma group, PRAME stained >75 % cells in 64/87 tumors, however, 10/87 melanomas were completely negative. HMB-45 was captured diffusely in 49/87 melanomas, 32 showed patchy expression, and 6 tumors were blank negative. Diffuse 4+ PRAME positivity showed superior sensitivity and specificity of 73,6 % and 96,5 %, respectively, compared to HMB-45, 56,3 % and 86,0 %, respectively. No nevi showed double 4+ positivity, however, the sensitivity for double positivity was only 49,4 %.
Our results confirm the superiority of PRAME over HMB-45 in the differential diagnosis of melanocytic tumors. However, combined staining can significantly increase specificity, rendering a benign diagnosis more unlikely in a double 4+ diffuse positivity setting.
•PRAME is superior to HMB-45 in diagnostic of melanocytic tumors.•Benign melanocytic tumors are rarely or not at all diffusely positive in both PRAME and HMB-45.•Dysplastic nevi are more often PRAME-positive than common nevi.