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This work describes an unusual colonic MSI-MiNEN in an 89-year-old woman and reviews relevant literature, integrating pathology, immunohistochemistry, and sequencing to connect MSI findings with clinical response and outcome.",{"@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/unusual-microsatellite-instable-mixed-neuroendocrine-and-non-neuroendocrine-neoplasm-a-clinicopathological-inspection-and-literature-review/386737/",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/unusual-microsatellite-instable-mixed-neuroendocrine-and-non-neuroendocrine-neoplasm-a-clinicopathological-inspection-and-literature-review/386737.png","ImageObject",300,407,{"name":42,"@type":43},"pixelkiddo","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-06","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What makes mixed neuroendocrine and non-endocrine neoplasms (MiNENs) clinically challenging?","Question",{"text":63,"@type":64},"MiNENs are rare and heterogeneous, with incomplete understanding of their pathobiology, molecular mechanisms, and management. Their diagnosis is further hindered by unusual morphology/immunoprofiles and limited biopsy material.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What MSI-related findings were reported in the unusual colonic MiNEN case?",{"text":68,"@type":64},"Loss of MLH1 and PMS2 mismatch repair proteins was detected in tumor cells. INSM1 staining highlighted about 50% of the tumor, and next-generation sequencing identified multiple carcinogenic mutations.",{"name":70,"@type":61,"acceptedAnswer":71},"How was treatment handled and what was the patient outcome?",{"text":72,"@type":64},"Surgical resection was aborted due to advanced stage and adhesion to adjacent organs, and immunotherapy was initiated. 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The current understanding of MiNENs’ pathobiology, molecular mechanisms, and management is incomplete. Though  \nmicrosatellite instability (MSI) is known to impact carcinogenesis, reports examining MSI mechanisms for MiNENs are rare. Methods: We report an unusual colonic MSI-MiNEN uncovered in an 89-year-old woman and the review of the literature. Results: Pathologic inspection revealed a high-grade carcinoma composed of tumor cells with neuroendocrine histologic traits and immunophenotype intermixed with mucin-containing signet ring–like cells arranged in nested and micronodular patterns.  \nLoss of MLH1 and PMS2 mismatch repair proteins was detected in tumor cells. INSM1 immunostaining highlighted about 50% of the tumour, further reinforcing the MiNEN diagnosis. Next-generation sequencing identified multiple carcinogenic mutations. Because of the advanced stage of the tumor and its adhesion to the adjacent organs, surgical resection was aborted; immunotherapy was initiated. The tumor is in remission 30 months following initiation of treatment, and the patient remains asymptomatic.  \nConclusion: This unique MSI MiNEN was characterized by its immunohistochemical and molecular signatures and illustrated how correctly diagnosing MSI can strongly improve a patient’s outcomes.  \nKeywords  \nminen, microsatellite, instability, gastrointestinal, mismatch  \nIntroduction  \nGastrointestinal tract mixed neuroendocrine and non-endocrine neoplasms (MiNENs) are a conceptual category of epithelial neoplasms in which both neuroendocrine and nonneuroendocrine components are present, with each component being histologically and immunophenotypically recognizable and constituting at least 30% of the neoplasm.1 The molecular mechanisms affecting the initiation and progression of MiNENs have not been fully understood, but it has been discovered that the disease outcome is predominantly determined by the proliferative potential of the neuroendocrine component.2  \n1 Anatomic Pathology, Instituto Portuguˆes de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal  \n2Biomedical Library, Moffitt Cancer Center, Tampa, FL, USA  \n3Morsani College of Medicine University of South Florida, Tampa, FL, USA 4Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA  \nCorresponding Author:  \nKun Jiang, Department of Anatomic Pathology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA.  \nEmail: kun.jiang@moffi[tt.org](tt.org)  \nCreative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons  \nAttribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use,  \nreproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ([https://us.sagepub.com/en-us/nam/open-access-at-sage](https://us.sagepub.com/en-us/nam/open-access-at-sage)).  \nMiNENs constitute a great pathologic and clinical challenge because of their rarity and heterogeneity. Pathologically, the neuroendocrine component can range from a low-grade well-differentiated neuroendocrine tumor to a high-grade neuroendocrine carcinoma (NEC), such as a large-cell or small-cell NEC","cbCaik73SSCZDFLP","https://ap.wps.com/l/cbCaik73SSCZDFLP","pdf",2155204,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction\n## Definitions and biology of MiNENs\n## Diagnostic challenges\n## Clinical importance of timely diagnosis","[{\"question\":\"What makes mixed neuroendocrine and non-endocrine neoplasms (MiNENs) clinically challenging?\",\"answer\":\"MiNENs are rare and heterogeneous, with incomplete understanding of their pathobiology, molecular mechanisms, and management. Their diagnosis is further hindered by unusual morphology/immunoprofiles and limited biopsy material.\"},{\"question\":\"What MSI-related findings were reported in the unusual colonic MiNEN case?\",\"answer\":\"Loss of MLH1 and PMS2 mismatch repair proteins was detected in tumor cells. INSM1 staining highlighted about 50% of the tumor, and next-generation sequencing identified multiple carcinogenic mutations.\"},{\"question\":\"How was treatment handled and what was the patient outcome?\",\"answer\":\"Surgical resection was aborted due to advanced stage and adhesion to adjacent organs, and immunotherapy was initiated. Remission persisted for 30 months after treatment initiation, with the patient remaining asymptomatic.\"}]","Unusual Microsatellite-Instable Mixed Neuroendocrine and Non-neuroendocrine Neoplasm - A Clinicopathological Inspection and Literature Review | PDF",1790275535]