Ng Chi Sing, Qin Jilong, Kan Chi Hang, Cheng Kristopher T
Department of Pathology, Caritas Medical Center, Kowloon, Hong Kong.
Department of Pathology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Virchows Arch. 2025 Aug 7. doi: 10.1007/s00428-025-04208-0.
The gastrointestinal tract (GIT) is an uncommon destination for metastasis, and the small bowel (SB) is among the more common sites. The SB metastatic carcinoma is often undifferentiated, usually with variable components of rhabdoid tumor cells. Primary lung non-small cell carcinoma (NSCLC) is a commonly implicated source and is often undifferentiated, though other differentiated histotypes may be responsible. Both primary lung and metastatic GIT poorly or undifferentiated carcinomas often show SWI/SNF deficiency especially of SMARCA4 and SMARCA2, singly or co-deficient. We report three such rare cases, in complementation of an earlier larger series, of SB metastatic SMARCA4/A2-deficient undifferentiated carcinoma from lung primary, with full immunophenotypic and genetic workup. We made the novel discovery of the same SMARCA2 mutations in the lung tumors of two of our cases which could have contributed to SMARCA2 deficiency. This contrasts with the conventional belief that SMARCA2 deficiency is mostly related to epigenetic events. It is important to differentiate these metastatic tumors from primary GIT SWI/SNF-deficient undifferentiated carcinomas and possible secondary SB undifferentiated carcinoma from female genital tract (FGT) primary, which are often morphologically difficult to distinguish. The primary GI and secondary FGT carcinomas usually show broader deficiency of SWI/SNF subunits, microsatellite instability-high or mismatch repair protein deficiency. Correlation with clinical and imaging findings is important in making the distinction. As primary NSCLC is a commonly implicated tumor causing SB metastatic undifferentiated carcinoma, discovery of the latter should instigate investigation for possible lung primary which may be helpful for timely introduction of possibly effective therapies such as cisplatin chemotherapy, immunotherapy, and epigenetics or synthetic lethality-based treatment.
胃肠道（GIT）是转移瘤的罕见转移部位，小肠（SB）是较常见的部位之一。小肠转移性癌通常为未分化型，通常伴有横纹肌样瘤细胞的不同成分。原发性肺非小细胞癌（NSCLC）是常见的原发灶，通常为未分化型，不过其他分化型组织学类型也可能是病因。原发性肺癌和转移性GIT低分化或未分化癌通常显示SWI/SNF缺陷，尤其是SMARCA4和SMARCA2单独或共同缺陷。我们报告了3例这样的罕见病例，作为对先前较大系列病例的补充，这些病例为来自肺原发灶的小肠转移性SMARCA4/A2缺陷型未分化癌，并进行了全面的免疫表型和基因检测。我们有了一个新发现，即我们的2例病例的肺肿瘤中存在相同的SMARCA2突变，这可能导致了SMARCA2缺陷。这与传统观念不同，传统观念认为SMARCA2缺陷主要与表观遗传事件有关。将这些转移瘤与原发性GIT SWI/SNF缺陷型未分化癌以及可能来自女性生殖道（FGT）原发灶的继发性小肠未分化癌区分开来很重要，因为它们在形态学上往往难以区分。原发性胃肠道癌和继发性FGT癌通常显示SWI/SNF亚基更广泛的缺陷、微卫星高度不稳定或错配修复蛋白缺陷。与临床和影像学表现相关对于做出区分很重要。由于原发性NSCLC是导致小肠转移性未分化癌的常见肿瘤，发现后者应促使对可能的肺原发灶进行检查，这可能有助于及时引入可能有效的治疗方法，如顺铂化疗、免疫治疗以及基于表观遗传学或合成致死性的治疗。
