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The authors highlight diagnostic dilemmas in vulvar oncology, emphasizing histopathologic pitfalls, potential marker overlap, and the resulting need for precise interpretation. They propose 3D bio-printed full-thickness skin models and vulva-specific CRISPR editing guidelines to improve preclinical validation, surgical planning, and safe application in dermatologic oncology.",{"@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/crisprs-cutaneous-comeback-edited-keratinocyte-hyperplasias-mimicking-extramammary-pagets-disease-in-rare-vulvar-squamous-cell-carcinoma/439861/",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/crisprs-cutaneous-comeback-edited-keratinocyte-hyperplasias-mimicking-extramammary-pagets-disease-in-rare-vulvar-squamous-cell-carcinoma/439861.png","ImageObject",300,407,{"name":42,"@type":43},"supergirl","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-28","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",5,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What CRISPR-related post-editing phenomenon is discussed in the letter?","Question",{"text":63,"@type":64},"The letter describes pagetoid spread of keratinocyte hyperplasia that mimics extramammary Paget’s disease (EMPD) in rare cases of vulvar squamous cell carcinoma.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Why does this mimicry create a diagnostic dilemma?",{"text":68,"@type":64},"Because edited keratinocyte hyperplasias resemble EMPD, lacking glandular components, overlap of immune and molecular markers can mislead pathologists without context-specific knowledge.",{"name":70,"@type":61,"acceptedAnswer":71},"How do the authors suggest improving diagnosis and translational validation?",{"text":72,"@type":64},"They propose developing 3D bio-printed full-thickness human skin models and creating vulva-specific CRISPR editing guidelines, incorporating standard histopathologic criteria and interdisciplinary 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mimickingextramammary Paget’s disease in rarevulvar squamous cell carcinoma  \nPakeeza Saif, MBBSa , Muhammad Talha, MBBSa , Mahnoor Fatima, MBBSb,*, Muammar Hassan, MBBSa ,Abdullah Imtiaz, MBBSc  \nTo the Editor,  \nCRISPR gene editing has made significant advancesin treat -ments and research applications concerned with cutaneousdisorders. Evidence from recent research has demonstrateda novel postediting phenomenon: pagetoid spread of keratino -  \ncyte hyperplasia mimicking extramammary Paget’s disease  \n(EMPD), exhibited in rare cases of vulvar squamous cell carci -noma, notably without any glandular component. This com -plex histopathologic mimicry serves as a major diagnosticdilemma in vulvar oncology, creating complications for bothclinical management and pathological interpretation [1,2] . Thisis inline with the TITAN Guidelines on the need for transpar -ency in AI use in health care [3] .  \nCurrently, the number of research studies is relatively fewregarding pseudoinvasive cutaneous changes due to CRISPR,including CRISPR-induced pagetoid hyperplasia. Fewer than 98publications have currently studied this specific CRISPR-induceddermatologic pseudoinvasion phenomenon, reflecting the evidencegap, with serious implications for precise histopathologic diagno -sisand ultimately forthe optimization of therapy. However, asgene-editing techniques are becoming an integral part of thedermatology field, it becomes imperative to understand andanticipate these types of pseudoinvasive morphologies[4] .  \nThree-dimensional (3D) bio-printed human skin models providepreclinical platforms specifically designed to examine CRISPRedit -ing results on the keratinocyte behavior and skin architecturedirectly. These models allow episcopical real-time posteditdynamics to be simulatedin detail, aiding the process of differentiat -ing true neoplastic invasion from hyperplastic mimicry caused by  \naDepartment of Medicine, King Edward Medical University, Lahore, Pakistan,bDepartment of Medicine, Shaheed Ziaur Rahman Medical College, RajshahiMedical University, Rajshahi, Bangladesh and cDepartment of Medicine, WahMedical College, Wah Cantt, Pakistan  \nSponsorships or competing interests that maybe relevant to content are disclosedatthe end of this article.  \n*Corresponding author. Address: Department of Medicine, Ladies hostel, ShaheedZiaur Rahman Medical College, Rajshahi Medical University, Bogura 5800,Bangladesh. E-mail: mahnoorzahid786@gmail.com (M. Fatima).  \nCopyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is anopen access article distributed under the Creative Commons Attribution License 4.0(CCBY), which permits unrestricted use, distribution, and reproduction in any medium,provided the original work is properly cited.  \nAnnals of Medicine & Surgery (2026) 88:943–944Received 23 September 2025; Accepted 27 October 2025Published online 11 November 2025http://dx.doi.org/10.1097/MS9.0000000000004279  \ngene editing, thereby reducing themisdiagnosis risk considerably.Because of the complex structure of vulvar skin andthe peculiarmicro-environment, the design and development of vulva-specificmodeling and diagnostic parameters has become criticallyessential[5] .  \nThe histopathological pitfalls associated with edited keratinocytehyperplasias are emphasized by their resemblance to EMPD,a vulvar cancer with distinct glandular features lacking in postedithyperplasias. Without context-specific knowledge of CRISPR edit -ing effects on epidermal and adnexal cells, the overlap of immuneand molecular markers can lead to errors in diagnosis by patholo -gists. Knowledge of these editing-induced changes is paramount toappropriate surgical and medical management of vulvar squamousneoplasms[1,2] .  \nThis perspective illuminates a unique dimension within thediscourse of dermatological gene editing, as it documentsCRISPR-induced histopathological effects in ke","cbCaibxU0tUyOW4V","https://ap.wps.com/l/cbCaibxU0tUyOW4V","pdf",169625,"English","# Letter to the Editor\n## CRISPR-induced pagetoid keratinocyte hyperplasia mimicking EMPD\n## Diagnostic dilemmas in vulvar oncology\n## Proposed 3D bio-printed skin models and guideline needs\n## Ethical approval, consent, funding, and declarations","[{\"question\":\"What CRISPR-related post-editing phenomenon is discussed in the letter?\",\"answer\":\"The letter describes pagetoid spread of keratinocyte hyperplasia that mimics extramammary Paget’s disease (EMPD) in rare cases of vulvar squamous cell carcinoma.\"},{\"question\":\"Why does this mimicry create a diagnostic dilemma?\",\"answer\":\"Because edited keratinocyte hyperplasias resemble EMPD, lacking glandular components, overlap of immune and molecular markers can mislead pathologists without context-specific knowledge.\"},{\"question\":\"How do the authors suggest improving diagnosis and translational validation?\",\"answer\":\"They propose developing 3D bio-printed full-thickness human skin models and creating vulva-specific CRISPR editing guidelines, incorporating standard histopathologic criteria and interdisciplinary collaboration.\"}]","CRISPR’s cutaneous comeback: edited keratinocyte hyperplasias mimicking extramammary Paget’s disease in rare vulvar squamous cell carcinoma | PDF",1790690433]