Unusual Microsatellite-Instable Mixed Neuroendocrine and Non-neuroendocrine Neoplasm - A Clinicopathological Inspection and Literature Review

Sep 24, 2026

Mixed neuroendocrine and non-endocrine neoplasms (MiNENs) remain difficult to diagnose and manage because knowledge of their pathobiology, molecular drivers, and treatment strategies is incomplete. Microsatellite instability (MSI) influences carcinogenesis, yet MSI mechanisms in MiNENs are seldom reported. 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.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

Definitions and biology of MiNENs

Diagnostic challenges

Clinical importance of timely diagnosis

Unusual Microsatellite-Instable Mixed Neuroendocrine and Non-neuroendocrine Neoplasm: A Clinicopathological Inspection and Literature Review Cancer Control Volume 30: 1–8 © The Author(s) 2023 Article reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions) [DOI: 10.1177/10732748231160992](DOI: 10.1177/10732748231160992)[ ](DOI: 10.1177/10732748231160992)[journals.sagepub.com/home/ccx](journals.sagepub.com/home/ccx) Daniela Pereira, MD 1, Daley White, BA2 􀀁, Michael Mortellaro, MD3, and Kun Jiang, MD, PhD3,4 􀀁 Abstract Background: Mixed neuroendocrine and non-endocrine neoplasms (MiNENs) are challenging to diagnose and manage clinically. The current understanding of MiNENs’ pathobiology, molecular mechanisms, and management is incomplete. Though microsatellite 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. Loss 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. Conclusion: 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. Keywords minen, microsatellite, instability, gastrointestinal, mismatch Introduction Gastrointestinal 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 1 Anatomic Pathology, Instituto Portuguˆes de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal 2Biomedical Library, Mofﬁtt Cancer Center, Tampa, FL, USA 3Morsani College of Medicine University of South Florida, Tampa, FL, USA 4Anatomic Pathology, Mofﬁtt Cancer Center, Tampa, FL, USA Corresponding Author: Kun Jiang, Department of Anatomic Pathology, Mofﬁtt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA. Email: kun.jiang@mofﬁ[tt.org](tt.org) Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-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, reproduction 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)). MiNENs 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

FAQs

What makes mixed neuroendocrine and non-endocrine neoplasms (MiNENs) clinically challenging?

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.

What MSI-related findings were reported in the unusual colonic MiNEN case?

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.

How was treatment handled and what was the patient outcome?

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.

Sep 24, 2026

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