Regmi Aayushma, Parra Ourania, Ma Weijie, LeBlanc Robert E, Sriharan Aravindhan, Momtahen Shabnam, Cloutier Jeffrey M, Yan Shaofeng, Linos Konstantinos
Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH; and.
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, NY.
Am J Dermatopathol. 2025 Aug 28. doi: 10.1097/DAD.0000000000003018.
The 23-gene expression signature (GES) assay (myPath Melanoma) is a well-established molecular test for analyzing challenging melanocytic lesions, alongside fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) array. However, routine use of these tests is often limited by high costs, long turnaround times, significant tissue requirements, and limited accessibility. This study aimed to evaluate the diagnostic concordance of PRAME immunohistochemistry (IHC) and the GES assay in difficult melanocytic lesions to determine whether PRAME IHC, widely available in pathology laboratories, could serve as a surrogate for GES. In addition, we correlated these methods with SNP array and FISH analyses, where available, to assess their diagnostic value in challenging melanocytic lesions.
We conducted a single-institution retrospective analysis of 56 diagnostically ambiguous melanocytic lesions that underwent ancillary GES testing. All 56 cases were evaluated for PRAME IHC, while 35 had FISH results, 16 had SNP array results, and 3 had both FISH and SNP results. Two board-certified dermatopathologists independently reviewed hematoxylin and eosin (H&E)-stained slides, PRAME IHC slides, and other available immunostains, along with GES results, FISH, and/or SNP array results, classifying each lesion as benign or malignant.
Fifty-six cutaneous melanocytic lesions with challenging histopathologic features were evaluated. Diagnostically ambiguous categories included dysplastic nevi versus melanoma (29 cases, 51.8%), spitzoid lesions (19 cases, 33.9%), nevoid lesions (7 cases, 12.5%), and blue nevus-like lesions (1 case, 1.8%). Of these, 38 cases (67.9%) were ultimately classified as benign, while 18 cases (32.1%) were classified as malignant.PRAME IHC showed a significant association with malignancy, with an 83.9% concordance rate (χ2 = 21.37, P = 0.0001), accurately classifying 47 out of 56 cases. GES demonstrated an 82.1% concordance rate (χ2 = 18.68, P = 0.0001), accurately classifying 46 out of 56 cases. FISH showed a 77.1% agreement with the final diagnosis (χ2 = 7.63, P = 0.005), correctly categorizing 27 out of 35 cases. Although the number of cases were relatively small, SNP array analysis correctly identified all 16 cases (χ2 = 16, P = 0.0001).
This study supports PRAME IHC as a useful surrogate for the GES assay in the evaluation of challenging melanocytic lesions. PRAME IHC offers a cost-efficient, accessible, and practical ancillary tool that can be rapidly integrated into routine clinical practice for diagnostically ambiguous melanocytic lesions.
23基因表达特征（GES）检测（myPath黑色素瘤检测）是一种成熟的分子检测方法，可用于分析具有挑战性的黑素细胞性病变，与荧光原位杂交（FISH）和单核苷酸多态性（SNP）阵列检测并列。然而，这些检测方法的常规使用常常受到高成本、周转时间长、组织需求量大以及可及性有限的限制。本研究旨在评估PRAME免疫组化（IHC）与GES检测在疑难黑素细胞性病变中的诊断一致性，以确定在病理实验室广泛可用的PRAME IHC是否可作为GES的替代方法。此外，我们将这些方法与SNP阵列和FISH分析（如有）相关联，以评估它们在疑难黑素细胞性病变中的诊断价值。
我们对56例接受辅助GES检测的诊断不明确的黑素细胞性病变进行了单机构回顾性分析。所有56例病例均进行了PRAME IHC评估，其中35例有FISH结果，16例有SNP阵列结果，3例同时有FISH和SNP结果。两名获得委员会认证的皮肤病理学家独立审查苏木精和伊红（H&E）染色切片、PRAME IHC切片及其他可用免疫染色，以及GES结果、FISH和/或SNP阵列结果，将每个病变分类为良性或恶性。
评估了56例具有挑战性组织病理学特征的皮肤黑素细胞性病变。诊断不明确的类别包括发育异常痣与黑色素瘤（29例，51.8%）、Spitz样病变（19例，33.9%）、痣样病变（7例，12.5%）和蓝痣样病变（1例，1.8%）。其中，38例（67.9%）最终被分类为良性，18例（32.1%）被分类为恶性。PRAME IHC与恶性肿瘤有显著相关性，一致率为83.9%（χ2 = 21.37，P = 0.0001），56例中有47例分类准确。GES的一致率为82.1%（χ2 = 18.68，P = 0.0001），56例中有46例分类准确。FISH与最终诊断的一致率为77.1%（χ2 = 7.63，P = 0.005），35例中有27例分类正确。虽然病例数相对较少，但SNP阵列分析正确识别了所有16例（χ2 = 16，P = 0.0001）。
本研究支持PRAME IHC作为GES检测在评估疑难黑素细胞性病变中的有用替代方法。PRAME IHC提供了一种经济高效、可及且实用的辅助工具，可迅速纳入对诊断不明确的黑素细胞性病变的常规临床实践中。
