Akanksha Nagarkar, Jackson Turbeville, Molly A. Hinshaw, Philip E. LeBoit, Jeffrey Gagan, Mark Raffeld, Kenneth Aldape, Niharika Shah, Frederic G. Barr, Liqiang Xi, Ina Lee, Christina K. Ferrone, Svetlana D. Pack, Rosandra Kaplan, Mary Frances Wedekind Malone, Marielle Yohe, Michael R. Sargen
{"title":"Large Congenital Melanocytic Nevus With LMNA::NTRK1 Fusion: Expanding Targeted Therapy Options for Congenital Nevi and Melanoma","authors":"Akanksha Nagarkar, Jackson Turbeville, Molly A. Hinshaw, Philip E. LeBoit, Jeffrey Gagan, Mark Raffeld, Kenneth Aldape, Niharika Shah, Frederic G. Barr, Liqiang Xi, Ina Lee, Christina K. Ferrone, Svetlana D. Pack, Rosandra Kaplan, Mary Frances Wedekind Malone, Marielle Yohe, Michael R. Sargen","doi":"10.1111/cup.14822","DOIUrl":null,"url":null,"abstract":"<p>Large congenital melanocytic nevi/nevus (LCMN) are caused by genetic events that activate the mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) pathway. Individuals with LCMN are prone to developing aggressive melanomas during childhood. Targeted therapies are needed to treat this form of melanoma and manage LCMN symptoms such as pruritus and pain, which significantly impact quality of life. Here, we present the first case of an LCMN with an <i>NTRK</i> fusion driver event. The patient presented with an atypical proliferative nodule arising in the background nevus. RNA sequencing of the proliferative nodule with background nevus identified a pathogenic <i>LMNA::NTRK1</i> fusion. The fusion resulted in constitutive expression of TrkA, demonstrated by strong cytoplasmic pan-TRK staining, along with activation of the MAPK/ERK pathway, as indicated by positive nuclear and cytoplasmic staining for phosphorylated ERK. The background nevus beneath the proliferative nodule also expressed pan-TRK and phosphorylated ERK, suggesting that the <i>NTRK1</i> fusion occurred prior to the formation of the proliferative nodule. This case broadens the spectrum of driver events for LCMN and suggests that screening for <i>TRK</i> fusions in LCMN should be considered when systemic therapy is being considered for melanoma or symptom management.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 8","pages":"523-527"},"PeriodicalIF":1.1000,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.14822","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cutaneous Pathology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cup.14822","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
Large congenital melanocytic nevi/nevus (LCMN) are caused by genetic events that activate the mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) pathway. Individuals with LCMN are prone to developing aggressive melanomas during childhood. Targeted therapies are needed to treat this form of melanoma and manage LCMN symptoms such as pruritus and pain, which significantly impact quality of life. Here, we present the first case of an LCMN with an NTRK fusion driver event. The patient presented with an atypical proliferative nodule arising in the background nevus. RNA sequencing of the proliferative nodule with background nevus identified a pathogenic LMNA::NTRK1 fusion. The fusion resulted in constitutive expression of TrkA, demonstrated by strong cytoplasmic pan-TRK staining, along with activation of the MAPK/ERK pathway, as indicated by positive nuclear and cytoplasmic staining for phosphorylated ERK. The background nevus beneath the proliferative nodule also expressed pan-TRK and phosphorylated ERK, suggesting that the NTRK1 fusion occurred prior to the formation of the proliferative nodule. This case broadens the spectrum of driver events for LCMN and suggests that screening for TRK fusions in LCMN should be considered when systemic therapy is being considered for melanoma or symptom management.
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.