Diagnostic Utility of PRAME in Rare Melanoma Mimics: A Comparative Analysis Including GNET, MMNST, Epithelioid MPNST, and MITF-Rearranged Melanocytic Tumors.
Ahmed Shah, Jeremiah F Molligan, Carina A Dehner, Jorge Torres-Mora
{"title":"Diagnostic Utility of PRAME in Rare Melanoma Mimics: A Comparative Analysis Including GNET, MMNST, Epithelioid MPNST, and MITF-Rearranged Melanocytic Tumors.","authors":"Ahmed Shah, Jeremiah F Molligan, Carina A Dehner, Jorge Torres-Mora","doi":"10.1111/cup.14849","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Differentiating metastatic melanoma from histologic mimics such as malignant gastrointestinal neuroectodermal tumor (GNET), malignant melanotic nerve sheath tumor (MMNST), and epithelioid malignant peripheral nerve sheath tumor (EMPNST) poses significant diagnostic challenges due to overlapping morphology and immunophenotypes. PRAME is a novel immunohistochemical marker increasingly used to distinguish melanoma from its mimics, but remains underexplored in these rare tumor types.</p><p><strong>Methods: </strong>PRAME immunohistochemistry was performed on four GNETs, seven MMNSTs, 10 EMPNSTs, 16 metastatic melanomas (including eight undifferentiated melanomas), and two MITF-rearranged melanocytic tumors. PRAME expression was scored from 0 to 4+ based on the percentage of tumor nuclei showing moderate to strong staining.</p><p><strong>Results: </strong>All GNETs, MMNSTs, and MITF-rearranged tumors were PRAME-negative. EMPNSTs showed variable expression: six were negative (0-1), one equivocal (2+), and three positive (3-4+). Fifteen of 16 melanomas were PRAME-positive. PRAME scores differed significantly among tumor types (p = 1.99 × 10<sup>-5</sup>). PRAME demonstrated high sensitivity and specificity for distinguishing metastatic melanoma from primary mimickers including GNET and MMNST, but low specificity in EMPNST (71.4%).</p><p><strong>Conclusions: </strong>PRAME reliably distinguishes metastatic melanoma from GNET and MMNST, supporting its use in this differential. However, its reduced specificity in EMPNST limits its standalone diagnostic value in this context, emphasizing the need for a multimodal approach.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":" ","pages":""},"PeriodicalIF":1.1000,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cutaneous Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cup.14849","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Differentiating metastatic melanoma from histologic mimics such as malignant gastrointestinal neuroectodermal tumor (GNET), malignant melanotic nerve sheath tumor (MMNST), and epithelioid malignant peripheral nerve sheath tumor (EMPNST) poses significant diagnostic challenges due to overlapping morphology and immunophenotypes. PRAME is a novel immunohistochemical marker increasingly used to distinguish melanoma from its mimics, but remains underexplored in these rare tumor types.
Methods: PRAME immunohistochemistry was performed on four GNETs, seven MMNSTs, 10 EMPNSTs, 16 metastatic melanomas (including eight undifferentiated melanomas), and two MITF-rearranged melanocytic tumors. PRAME expression was scored from 0 to 4+ based on the percentage of tumor nuclei showing moderate to strong staining.
Results: All GNETs, MMNSTs, and MITF-rearranged tumors were PRAME-negative. EMPNSTs showed variable expression: six were negative (0-1), one equivocal (2+), and three positive (3-4+). Fifteen of 16 melanomas were PRAME-positive. PRAME scores differed significantly among tumor types (p = 1.99 × 10-5). PRAME demonstrated high sensitivity and specificity for distinguishing metastatic melanoma from primary mimickers including GNET and MMNST, but low specificity in EMPNST (71.4%).
Conclusions: PRAME reliably distinguishes metastatic melanoma from GNET and MMNST, supporting its use in this differential. However, its reduced specificity in EMPNST limits its standalone diagnostic value in this context, emphasizing the need for a multimodal approach.
期刊介绍:
Journal of Cutaneous Pathology publishes manuscripts broadly relevant to diseases of the skin and mucosae, with the aims of advancing scientific knowledge regarding dermatopathology and enhancing the communication between clinical practitioners and research scientists. Original scientific manuscripts on diagnostic and experimental cutaneous pathology are especially desirable. Timely, pertinent review articles also will be given high priority. Manuscripts based on light, fluorescence, and electron microscopy, histochemistry, immunology, molecular biology, and genetics, as well as allied sciences, are all welcome, provided their principal focus is on cutaneous pathology. Publication time will be kept as short as possible, ensuring that articles will be quickly available to all interested in this speciality.