Objective: To investigate the clinicopathological features, immunophenotype and differential diagnoses of SMARCA4-deificient undifferentiated carcinoma (SMARCA4-DUC) of the gastrointestinal tract. Methods: The clinicopathological data and immunohistochemical profiles of nine cases of SMARCA4-DUC of the gastrointestinal tract diagnosed in Fudan University Shanghai Cancer Center, from 2018 to 2021, were analyzed retrospectively. The relevant literature was reviewed. Results: There were seven males and two females with age at presentation ranging from 39 to 74 years (mean 58 years, median 64 years). The tumor occurred in the stomach (6 cases), right hemicolon (2 cases) and duodenum (1 case). The main symptoms included dysphagia, abdominal pain, diarrhea and melena. Five cases were resected, and the tumor sizes ranged from 5.0 to 8.7 cm (mean 6.7 cm). Microscopically, the tumor was composed of sheets of undifferentiated round to epithelioid cells with large vesicular nuclei harboring prominent nucleoli and displaying brisk mitotic activity. Foci of dyscohesive rhabdoid cells were also noted. The tumor cells were generally uniform; however, prominent pleomorphism and spindle cell component was present in one case each. Five cases contained areas of coagulative necrosis, and one case showed myxoid change of the stroma. By immunohistochemistry, eight cases showed complete loss of BRG1 (SMARCA4) and BRM (SMARCA2) expression. Whereas the expression of these two markers was lost in the epithelioid component of one case, it remained in the spindle cell component (mosaic pattern). Apart from one case with partial expression of pan-cytokeratin, all other eight cases showed either limited (<5%, n=5) or totally negative (n=3) staining of pan-cytokeratin. In addition, four cases also expressed CD34, SOX2 and SALL4. Six patients had follow-up data: four died of disease within 1 year. Conclusions: SMARCA4-DUC of the gastrointestinal tract represents a highly aggressive malignancy with poor outcome. Due to lack of cell-specific differentiation, it is not uncommonly misdiagnosed as a wide variety of poorly-differentiated or undifferentiated tumors. Increased recognition of this rare but distinctive entity not only facilitates the diagnosis and differential diagnosis, but also provides important therapeutic and prognostic information for the clinicians.
目的： 探讨胃肠道SMARCA4缺失性未分化癌的临床病理学特征、免疫表型及鉴别诊断。 方法： 回顾性分析2018—2021年复旦大学附属肿瘤医院9例胃肠道SMARCA4缺失性未分化癌的临床资料，总结其病理学特征和免疫表型，并复习相关文献。 结果： 患者中男性7例，女性2例，平均年龄58岁（范围39~74岁）。患者多以消化道症状就诊。肿瘤分别发生于胃（6例）、右半结肠（2例）和十二指肠（1例）。5例行手术治疗，平均最大径6.7 cm（范围5.0~8.7 cm）。镜下观察见片状分布的圆形至上皮样未分化细胞，核仁明显，核分裂象易见，局灶区域瘤细胞呈横纹肌样，并失黏附性。瘤细胞形态相对一致，但1例瘤细胞显示有明显的多形性，1例含有梭形细胞成分。5例肿瘤内可见凝固性坏死，1例间质伴有黏液样变性。免疫组织化学标记显示，8例肿瘤完全失表达BRG1（SMARCA4）和BRM（SMARCA2），1例部分失表达BRG1和BRM。除1例部分表达广谱细胞角蛋白外，其余8例或极少量瘤细胞表达（<5%，5例）或为阴性（3例）。此外，4/7例、4/6例和4/5例还分别表达CD34、SOX2和SALL4。随访6例患者，4例在1年内死亡。 结论： 胃肠道SMARCA4缺失性未分化癌是一种高侵袭性未分化肿瘤，由于瘤细胞缺乏特异性分化，易被误诊为各种类型的差分化或未分化肿瘤。知晓这一特殊类型肿瘤不仅有助于诊断和鉴别诊断，也可为临床治疗和预后判断提供重要信息。.