胃肠道髓样癌是腺癌的一种罕见的组织学亚型。由于非壶腹小肠髓样癌 (SB-MC) 的特征较差，我们旨在分析其临床病理学和免疫组织化学特征，并将其与非髓样小肠腺癌 (NM-SBA) 进行比较。通过意大利小肠癌协会收集的手术切除的 SBA被分类为 SB-MC（≥50% 的肿瘤满足 MC 典型组织学标准的癌）或 NM-SBAs。在 SB-MC 和 NM-SBA 中对细胞角蛋白 (CK)7、CK20、CDX2、程序性死亡配体 1 (PD-L1) 和错配修复蛋白进行免疫组织化学分析。还通过原位杂交测试了 SB-MC 的 CK8/18、突触素、SMARCB1、SMARCA2、SMARCA4 和 ARID1A 以及 Epstein-Barr 病毒 (EBV) 编码的 RNA。在 MLH1 缺陷病例中评估 MLH1 启动子甲基化状态。鉴定出 11 个 SB-MC 和 149 个 NM-SBA。 1 例 (9%) SB-MC 为 EBV 阳性，而 10 例 (91%) 则存在错配修复缺陷 (dMMR)。在所有测试的八个 dMMR SB-MC 中均发现 MLH1 启动子高甲基化。在两个 (18%) SB-MC 中发现开关/蔗糖不可发酵缺陷，两者均伴有 ARID1A 的孤立缺失。与 NM-SBAs 相比，SB-MCs 与乳糜泻相关 (P < 0.001)、更高的 dMMR 发生率 (P < 0.001)，以及肿瘤比例评分和综合阳性评分的 PD-L1 阳性率 (P < 0.001)两者），CK20 表达率较低（P = 0.024）。生存分析显示，与 NM-SBA 病例相比，SB-MC 患者的预后更好 (P = 0.02)。SB-MC 代表一种独特的组织学亚型，与 NM-SBA 相比具有独特的特征，包括与乳糜泻、dMMR、PD 的相关性-L1 表达，以及更好的预后。© 2024 作者。组织病理学由约翰·威利出版

Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB-MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM-SBAs).Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB-MCs (carcinomas with ≥50% of tumour fulfilling the typical histologic criteria of MC) or NM-SBAs. Immunohistochemistry for cytokeratin (CK)7, CK20, CDX2, programmed death-ligand 1 (PD-L1) and mismatch repair proteins was performed in both SB-MCs and NM-SBAs. SB-MCs were also tested for CK8/18, synaptophysin, SMARCB1, SMARCA2, SMARCA4, and ARID1A and for Epstein-Barr virus (EBV)-encoded RNAs by in-situ hybridization. MLH1 promoter methylation status was evaluated in MLH1-deficient cases. Eleven SB-MCs and 149 NM-SBAs were identified. One (9%) SB-MC was EBV-positive, while 10 (91%) harboured mismatch repair deficiency (dMMR). MLH1 promoter hypermethylation was found in all eight dMMR SB-MCs tested. Switch/sucrose nonfermentable deficiency was seen in two (18%) SB-MCs, both with isolated loss of ARID1A. Compared with NM-SBAs, SB-MCs exhibited an association with coeliac disease (P < 0.001), higher rates of dMMR (P < 0.001), and PD-L1 positivity by both tumour proportion score and combined positive score (P < 0.001 for both), and a lower rate of CK20 expression (P = 0.024). Survival analysis revealed a better prognosis of SB-MC patients compared to NM-SBA cases (P = 0.02).SB-MCs represent a distinct histologic subtype, with peculiar features compared to NM-SBAs, including association with coeliac disease, dMMR, PD-L1 expression, and better prognosis.© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.