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Gastroscopy identified a small lesion in the cervical remnant esophagus, and biopsies confirmed squamous cell carcinoma. Whole-exome sequencing showed no comutations between the original primary and other malignancies, while cervical lesions shared many comutations, supporting second primary disease with cervical lymph node metastasis rather than treatable recurrence. Immunochemotherapy reduced lymphadenopathy, but progression occurred after six months, emphasizing regular remnant esophagus surveillance and whole-exome sequencing for treatment decisions.",{"@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/whole-exome-sequencing-in-a-patient-with-a-history-of-esophageal-squamous-cell-carcinoma-to-discriminate-recurrent-disease-from-a-second-primary-tumor/366467/",{"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/whole-exome-sequencing-in-a-patient-with-a-history-of-esophageal-squamous-cell-carcinoma-to-discriminate-recurrent-disease-from-a-second-primary-tumor/366467.png","ImageObject",300,407,{"name":92,"@type":93},"McGucket","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why was whole-exome sequencing important in this case?","Question",{"text":112,"@type":113},"Whole-exome sequencing distinguished whether the new malignancy represented true recurrent disease or a second primary tumor by comparing genetic comutation patterns across time and tumor sites.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What findings confirmed squamous cell carcinoma at both the lesion and lymph nodes?",{"text":117,"@type":113},"Biopsies from the cervical remnant esophageal lesion and cervical lymph nodes confirmed squamous cell carcinoma.",{"name":119,"@type":110,"acceptedAnswer":120},"How did treatment response evolve after immunochemotherapy?",{"text":121,"@type":113},"Significant regression of lymphadenopathy was achieved after two cycles of immunochemotherapy, but six months later PET-CT showed tumor progression with multiple metastases.","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},366467,1790231516,{"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":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":46},1236954412713,"https://us-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Zhang et al. Discover Oncology (2025) 16:1627 [https://doi.org/10.1007/s12672-025-03453-8](https://doi.org/10.1007/s12672-025-03453-8)  \nDiscover Oncology  \nCASE REPORT Open Access  \nWhole-exome sequencing in a patient with a  history of esophageal squamous cell carcinoma to discriminate recurrent disease from a second primary tumor  \nGuoqing Zhang 1, Kaiyuan Li 1, Zheng Ding 1, Jia Zhao 1*, Xue Pan2* and Xiangnan Li 1*  \n*Correspondence: Jia Zhao [fcczhaoj2@zzu.edu.cn](fcczhaoj2@zzu.edu.cn)[ ](fcczhaoj2@zzu.edu.cn)Xue Pan [xuepan321@163.com](xuepan321@163.com)[ ](xuepan321@163.com)Xiangnan Li  \n[lxn-2000@163.com](lxn-2000@163.com)[ ](lxn-2000@163.com)1Department of Thoracic Surgery and Esophageal Surgery, First Affiliated Hospital of Zhengzhou University, No. 1 Jian She Road, Zhengzhou 450052, Henan, China 2School of Nursing and Health, Zhengzhou University, Science Avenue, Zhengzhou 450000, Henan, China  \nAbstract  \nA 52-year-old man who previously underwent McKeown esophagectomy to treat lower thoracic esophageal squamous cell carcinoma (ESCC) and subsequently received radical radiotherapy to treat cervical lymph node malignancy (squamous cell carcinoma on pathology; presumed to be metastasis of the primary tumor) presented with recurrent cervical lymphadenopathy during periodic reexamination. On admission, gastroscopy revealed a 0.5 × 0. 5-cm lesion on the cervical remnant esophagus, and biopsies of both the lesion and cervical lymph nodes confirmed SCC. Whole-exome sequencing revealed that there were no comutations between the tumor samples from the primary ESCC from 2017 and the other malignancies (tumor samples from the remaining ESCC in 2022 and cervical lymph node malignancies on two occasions) . Interestingly, the first and second cervical lymph node malignancies and the tumor in the cervical remnant esophagus shared many comutations, suggesting that the tumor in the cervical remnant esophagus is a second primary tumor with cervical lymph node metastasis and is not amenable to radical radiotherapy. Significant regression of lymphadenopathy was achieved after 2 cycles of immunochemotherapy; however, the patient declined further surgical intervention. Six months later, positron emission tomography–computed tomography (PET–CT) revealed tumor progression with multiple metastases. Herein, we show the importance of regular examination of the remnant esophagus and the significance of whole-exome sequencing for distinguishing the source of malignancy, which could aid in the formulation of appropriate treatment plans.  \nKeywords Whole-exome sequencing, Esophageal squamous cell carcinoma, Remnant esophagus, Cervical lymph node metastasis, Case report  \n1 Background  \nNeoadjuvant chemoradiotherapy and chemotherapy, followed by esophagectomy, have been shown to improve the prognosis of patients with locally advanced esophageal cancer; however, the prevalence of disease recurrence still ranges from 33.7 to 41.9%, and  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http:","cbCait83KS9YvPos","https://ap.wps.com/l/cbCait83KS9YvPos","pdf",1189670,"English","# Abstract\n# 1 Background\n## Recurrence and metastatic patterns\n## Risk of second primary malignancies\n# 2 Case presentation","[{\"question\":\"Why was whole-exome sequencing important in this case?\",\"answer\":\"Whole-exome sequencing distinguished whether the new malignancy represented true recurrent disease or a second primary tumor by comparing genetic comutation patterns across time and tumor sites.\"},{\"question\":\"What findings confirmed squamous cell carcinoma at both the lesion and lymph nodes?\",\"answer\":\"Biopsies from the cervical remnant esophageal lesion and cervical lymph nodes confirmed squamous cell carcinoma.\"},{\"question\":\"How did treatment response evolve after immunochemotherapy?\",\"answer\":\"Significant regression of lymphadenopathy was achieved after two cycles of immunochemotherapy, but six months later PET-CT showed tumor progression with multiple metastases.\"}]","Whole-exome sequencing in a patient with a history of esophageal squamous cell carcinoma to discriminate recurrent disease from a second primary tumor | PDF",1790165690]