[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-377598-105":59,"doc-detail-377598-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","germline-testing-of-mismatch-repair-genes-is-needed-in-the-initial-evaluation-of-patients-with-muir-torre-syndrome-associated-cutaneous-sebaceous-neoplasms-case-series","Germline Testing of Mismatch Repair Genes Is Needed in the Initial Evaluation of Patients With Muir-Torre Syndrome-Associated Cutaneous Sebaceous Neoplasms - Case Series","","Muir-Torre syndrome, a Lynch syndrome subtype, is defined by germline mutations in mismatch repair genes (e.g., MLH1, MSH2, MSH6, PMS2) leading to microsatellite instability and at least one malignancy plus one sebaceous neoplasm (adenoma, epithelioma, or carcinoma). Germline risk can precede, coexist with, or follow syndrome-associated cancer, and sequencing of normal tissues enables detection. Tumor immunohistochemistry, microsatellite instability, and next-generation sequencing assess malignancies and sebaceous lesions, but cannot reliably distinguish somatic from germline changes and may yield false negatives. A Mayo risk score may not identify which patients need germline testing; three cases show missed germline alterations and support germline mismatch repair gene testing in initial evaluation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/germline-testing-of-mismatch-repair-genes-is-needed-in-the-initial-evaluation-of-patients-with-muir-torre-syndrome-associated-cutaneous-sebaceous-neoplasms-case-series/377598/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/germline-testing-of-mismatch-repair-genes-is-needed-in-the-initial-evaluation-of-patients-with-muir-torre-syndrome-associated-cutaneous-sebaceous-neoplasms-case-series/377598.png","ImageObject",300,407,{"name":92,"@type":93},"acoobca","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is germline testing recommended in patients with even a single Muir-Torre syndrome-associated sebaceous neoplasm?","Question",{"text":112,"@type":113},"Because tumor immunohistochemistry and microsatellite stability testing can miss germline alterations. Germline testing helps identify mismatch repair gene mutations that guide genetic counseling and cancer screening.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What kinds of mismatch repair gene mutations are involved in Muir-Torre syndrome?",{"text":117,"@type":113},"The syndrome is associated with germline mutations in mismatch repair genes such as MLH1, MSH2, MSH6, and PMS2, which lead to microsatellite instability.",{"name":119,"@type":110,"acceptedAnswer":120},"How can current tumor-based tests fail to identify germline alterations?",{"text":121,"@type":113},"Immunohistochemistry and microsatellite instability assessments cannot reliably differentiate somatic versus germline changes and may produce false negatives.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},377598,1790293360,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},3985747870733,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Open Access Case  \nReport DOI: 10.7759/cureus.33975  \nReview began 01/10/2023  \nReview ended 01/11/2023  \nPublished 01/19/2023  \n© Copyright 2023  \nCohen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0. , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited.  \nGermline Testing of Mismatch Repair Genes Is Needed in the Initial Evaluation of Patients With Muir-Torre Syndrome-Associated Cutaneous Sebaceous Neoplasms: A Case Series  \nPhilip R. Cohen 1 , Razelle Kurzrock 2, 3  \n1. Dermatology, University of California, Davis Medical Center, Sacramento, USA 2. Medicine, Medical College of Wisconsin Cancer Center and Genome Sciences and Precision Medicine Center, Milwaukee, USA 3. Oncology, Worldwide Innovative Networking (WIN) Consortium, Villejuif, FRA  \nCorresponding author: Philip R. Cohen, [mitehead@gmail.com](mitehead@gmail.com)  \nAbstract  \nMuir-Torre syndrome, a subtype of Lynch syndrome, is characterized by a germline mutation of one or more mismatch repair genes such as MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), MutS Homolog 6 (MSH6), and PMS1 Homolog 2, mismatch repair system component (PMS2) resulting in microsatellite instability and at least one malignancy and a minimum of one syndrome-associated sebaceous neoplasm such as a sebaceous adenoma, epithelioma, or carcinoma. The syndrome has an autosomal dominant mode of inheritance detectable with germline sequencing of normal body elements such as blood, saliva, or normal skin for a mismatch repair gene mutation. Sebaceous neoplasms can occur before, concurrent with, or following Muir-Torre syndrome-related cancer. Immunohistochemistry, microsatellite instability testing, and next-generation sequencing of tumor tissue can evaluate malignancies such as colorectal and endometrial cancer and sebaceous neoplasms for somatic mismatch repair gene defects. However, these tests cannot differentiate somatic (acquired) versus germline alterations, and immunohistochemistry and microsatellite stability assessment can produce false negatives. Finally, the Mayo Muir-Torre syndrome risk score algorithm cannot always reliably determine which patient with a new sebaceous neoplasm should have germline testing.  \nWe report three men who presented with a Muir-Torre syndrome-associated sebaceous neoplasm: a 67-yearold male with no personal or family history of cancer who presented with a chest sebaceous carcinoma with MSH2 and MSH6 gene expression loss on immunohistochemistry and a Mayo Muir-Torre syndrome risk score of 0 who declined germline testing; a 74-year-old male with Janus kinase 2 (JAK2)-related myelodysplastic syndrome, yet no history of a Lynch syndrome-associated cancer, who developed a sebaceous epithelioma on his leg with PMS2 gene expression loss by immunohistochemistry and, although Mayo Muir-Torre syndrome risk score was only 1 (suggests no likelihood of a Lynch syndrome germline mismatch repair gene mutation), germline testing demonstrated a PMS2 alteration; and a 59-year-old male with a germlineconfirmed MLH1-associated Lynch syndrome and a prior colon carcinoma, who developed a sebaceous adenoma on his nostril that unexpectedly demonstrated preservation of normal MLH1 staining (reflecting a false negative) by immunohistochemistry. In summary, these cases are consistent with the literature suggesting that tumor immunohistochemistry and microsatellite stability testing can miss germline alterations. Hence, we recommend that the initial evaluation of a patient with even a single new Muir-Torre syndrome-associated sebaceous neoplasm should include germline mismatch repair gene mutation testing. Finding a mismatch repair gene germline mutation should prompt genetic counseling, initial and future cancer screening recommendations, and germline testing of family members.  \nCategories: Dermatology, Pathology, Oncology  \nKeywords","cbCaimBstidxoVWU","https://ap.wps.com/l/cbCaimBstidxoVWU","pdf",3497876,21,"English","# Abstract\n## Immunohistochemistry and microsatellite testing limitations\n## Case series findings and recommendations","[{\"question\":\"Why is germline testing recommended in patients with even a single Muir-Torre syndrome-associated sebaceous neoplasm?\",\"answer\":\"Because tumor immunohistochemistry and microsatellite stability testing can miss germline alterations. Germline testing helps identify mismatch repair gene mutations that guide genetic counseling and cancer screening.\"},{\"question\":\"What kinds of mismatch repair gene mutations are involved in Muir-Torre syndrome?\",\"answer\":\"The syndrome is associated with germline mutations in mismatch repair genes such as MLH1, MSH2, MSH6, and PMS2, which lead to microsatellite instability.\"},{\"question\":\"How can current tumor-based tests fail to identify germline alterations?\",\"answer\":\"Immunohistochemistry and microsatellite instability assessments cannot reliably differentiate somatic versus germline changes and may produce false negatives.\"}]","Germline Testing of Mismatch Repair Genes Is Needed in the Initial Evaluation of Patients With Muir-Torre Syndrome-Associated Cutaneous Sebaceous Neoplasms - Case Series | PDF",1790226170,53]