[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-353229-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-353229-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","mutational-profile-of-atypical-fibroxanthoma-and-pleomorphic-dermal-sarcoma-further-expands-the-spectrum-of-genomic-alterations-in-rare-cutaneous-neoplasms-research-findings","Mutational profile of atypical fibroxanthoma and pleomorphic dermal sarcoma further expands the spectrum of genomic alterations in rare cutaneous neoplasms - Research findings","","Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare skin mesenchymal tumors with overlapping clinical and histopathological features, yet PDS shows higher risk of recurrence and metastasis, making precise diagnosis essential. DNA profiling of 32 AFX and PDS samples using a targeted next-generation sequencing panel covering 228 cancer genes confirms frequent mutations in TP53, CDKN2A and NOTCH1 while revealing additional, less common alterations. Integration with published datasets highlights divergent distribution of changes in angiogenic, DNA damage response, and migration/metastasis signaling pathways, offering insights into tumor pathogenesis while maintaining histopathology as the diagnostic gold standard.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/mutational-profile-of-atypical-fibroxanthoma-and-pleomorphic-dermal-sarcoma-further-expands-the-spectrum-of-genomic-alterations-in-rare-cutaneous-neoplasms-research-findings/353229/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/mutational-profile-of-atypical-fibroxanthoma-and-pleomorphic-dermal-sarcoma-further-expands-the-spectrum-of-genomic-alterations-in-rare-cutaneous-neoplasms-research-findings/353229.png","ImageObject",300,407,{"name":42,"@type":43},"Well Done","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why are AFX and PDS difficult to diagnose accurately?","Question",{"text":63,"@type":64},"They share overlapping clinical, histopathological, and immunohistochemical features. Distinguishing infiltrative behavior and related criteria may require deep incisional biopsy, and misclassification can occur when these features are not definitive.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which gene mutations are commonly found across AFX and PDS?",{"text":68,"@type":64},"The study confirms a common pattern of mutations affecting TP53, CDKN2A, and NOTCH1.",{"name":70,"@type":61,"acceptedAnswer":71},"What do the pathway differences between AFX and PDS suggest?",{"text":72,"@type":64},"Integrated analyses show divergent distributions of alterations in angiogenic signaling (KDR, PDGFRB), DNA damage response (ATR), and cellular migration/metastasis (DDR2, CDH1). Although not statistically significant, these differences provide insights into tumor biology.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},353229,1790363520,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},5909892210082,"https://ap-avatar.wpscdn.com/avatar/56001069da27c9f41e8?x-image-process=image/resize,m_fixed,w_180,h_180&k=1789614185077863061","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nMutational profile of atypical fibroxanthoma and pleomorphic dermal sarcoma further expands the spectrum of genomic alterations in rare cutaneous neoplasms  \nElisabetta Caprini3,5􀀍, Giovanni Luca Scaglione4, Claudia Scarponi1, Martina Morelli1, Stefania Madonna1, Carla Marani3, Valeria Sebastiani3, Enrico Scala5, Cristina Albanesi1 & Siavash Rahimi2  \nAtypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare cutaneous mesenchymal tumours sharing clinical and histopathological features. Compared toAFX, PDS hasan increased risk of local recurrence and metastasis. A precise diagnosis is critical to ensure proper clinical management and follow-up. AFX and PDS show a similar genetic background, but also a heterogeneous pattern of different molecular abnormalities still poorly investigated due to the rarity of these tumours. Multiple data from different institutions and geographical areas, facilitate the identification of molecular alteration/s of valuable diagnostic and/or sub-classification power. We investigated the DNA profile of 32 AFX and PDS samples using a custom targeted Next-Generation Sequencing panel including 228 cancer genes. We confirm a common pattern of gene mutations affecting TP53, CDKN2A and NOTCH1. Differences appeared in less frequently detected genes (e.g. TSC2) and in NF2 harbouring novel genetic alterations. Integrating our results with published datasets ofAFX and PDS mutation profiles we observed a divergent distribution of alterations in genes signalling through angiogenic pathway (KDR, PDGFRB), DNA damage response (ATR), cellular migration/metastasis (DDR2, CDH1). These differences do not reach statistical significance, and histopathological evaluation remains the diagnostic gold standard, however, they offer valuable insights into the pathogenesis of these tumours.  \nKeywords Atypical fibroxanthoma, Pleomorphic dermal sarcoma, Next-generation sequencing, NF2, KDR/ PDGFRB, ATR  \nAtypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are morphologically similar mesenchymal neoplasms of the skin, classified in the “Tumours of Uncertain Differentiation” chapter of the 2020 World Health Organization (WHO) classification1,2. Both entities most commonly arise on chronically sun-damaged skin of the head and neck region in elderly male patients, and share overlapping clinical, histopathological, and immunohistochemical features3,4. Immunohistochemical analysis is essential in excluding histological mimickers such as melanoma, cutaneous squamous cell carcinoma, and leiomyosarcoma; tumour cells in AFX and PDS typically lack expression of epithelial, melanocytic, and myogenic markers, however,  \n1Experimental Immunology Laboratory, Fondazione Luigi Maria Monti, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy. 2Department of Histopathology, The Princess Elizabeth Hospital, LeVauquiedor, St Martin GY4 6UU, Guernsey. 3Anatomic Pathology Unit, Fondazione Luigi Maria Monti, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy. 4Bioinformatics Unit, Fondazione Luigi Maria Monti, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy. 5Clinical and Laboratory Molecular Allergy Unit, Fondazione Luigi Maria Monti, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy. 􀀍 email: [e.caprini@idi.it](e.caprini@idi.it)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nsmooth muscle actin may show positivity. Both tumour types consistently demonstrate immunoreactivity for vimentin, CD10, CD68, and α1-antitrypsin5,6. Histological evaluation remains the cornerstone of the differential diagnosis. Unlike AFX, PDS is characterized by infiltrative growth, necrosis, lymphovascular invasion, and/or perineural infiltration, features that require deep incisional biopsy for adequate assessment. Nonetheless, these distinguishing features are not always unequivocal, and well-demarcated AFX les","cbCaia4QKzaW3mp9","https://ap.wps.com/l/cbCaia4QKzaW3mp9","pdf",2289599,11,"English","# Background\n## Clinical and diagnostic challenges\n## Epidemiology and study limitations\n# Methods and study design\n## Targeted NGS panel and cohort\n# Results and molecular findings\n## Common mutation pattern\n## Divergent pathway alterations","[{\"question\":\"Why are AFX and PDS difficult to diagnose accurately?\",\"answer\":\"They share overlapping clinical, histopathological, and immunohistochemical features. Distinguishing infiltrative behavior and related criteria may require deep incisional biopsy, and misclassification can occur when these features are not definitive.\"},{\"question\":\"Which gene mutations are commonly found across AFX and PDS?\",\"answer\":\"The study confirms a common pattern of mutations affecting TP53, CDKN2A, and NOTCH1.\"},{\"question\":\"What do the pathway differences between AFX and PDS suggest?\",\"answer\":\"Integrated analyses show divergent distributions of alterations in angiogenic signaling (KDR, PDGFRB), DNA damage response (ATR), and cellular migration/metastasis (DDR2, CDH1). Although not statistically significant, these differences provide insights into tumor biology.\"}]","Mutational profile of atypical fibroxanthoma and pleomorphic dermal sarcoma further expands the spectrum of genomic alterations in rare cutaneous neoplasms - Research findings | PDF",1790103712,28]