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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：混合性神经内分泌和非内分泌肿瘤（MiNENs）在临床诊断和治疗方面具有挑战性。目前对MINENs病理生物学的理解，分子机制，管理是不完整的。尽管已知微卫星不稳定性（MSI）会影响致癌作用，检查MINENs的MSI机制的报告很少见。
方法：我们报告了一个在89岁女性中发现的不寻常的结肠MSI-MINEN，并对文献进行了综述。
结果：病理检查发现，由具有神经内分泌组织学特征和免疫表型的肿瘤细胞与巢状和微结节状排列的含粘蛋白的印戒样细胞混合组成的高级别癌。在肿瘤细胞中检测到MLH1和PMS2错配修复蛋白的缺失。INSM1免疫染色突出显示了约50％的肿瘤，进一步加强MiNEN诊断。下一代测序鉴定了多种致癌突变。由于肿瘤的晚期和与邻近器官的粘附，手术切除中止;免疫疗法开始.肿瘤在开始治疗30个月后缓解，患者仍然无症状。
结论：这种独特的MSIMiNEN以其免疫组织化学和分子特征为特征，并说明了如何正确诊断MSI可以大大改善患者的预后。
方法：我们报告了一个在89岁女性中发现的不寻常的结肠MSI-MINEN，并对文献进行了综述。
结果：病理检查发现，由具有神经内分泌组织学特征和免疫表型的肿瘤细胞与巢状和微结节状排列的含粘蛋白的印戒样细胞混合组成的高级别癌。
结论：这种独特的MSIMiNEN以其免疫组织化学和分子特征为特征，并说明了如何正确诊断MSI可以大大改善患者的预后。
