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Abstract：
BACKGROUND: SMARCA4, as one of the subunits of the SWI/SNF chromatin remodeling complex, drives SMARCA4-deficient tumors. Gastric SMARCA4-deficient tumors may include gastric SMARCA4-deficient carcinoma and gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Gastric SMARCA4-UT is rare and challenging to diagnose in clinical practice. The present report aims to provide insight into the clinicopathological characteristics and genetic alterations of gastric SMARCA4-UTs.
RESULTS: We retrospectively reported four rare cases of gastric SMARCA4-UTs. All four cases were male, aged between 61 and 82 years. These tumors presented as ulcerated and transmural masses with infiltration, staged as TNM IV in cases 1, 2 and 4, and TNM IIIA in case 3. Pathologically, four cases presented solid architecture with undifferentiated morphology. Cases 2 and 3 showed focal necrosis and focal rhabdoid morphology. Immunohistochemical staining showed negative expression of epithelial markers and deficient expression of SMARCA4. Furthermore, positivity for Syn (cases 1, 2 and 3) and SALL4 (cases 1 and 2) were observed. Mutant p53 expression occurred in four cases, resulting in strong and diffuse staining of p53 expression in cases 1, 2 and 4, and complete loss in case 3. The Ki67 proliferative index exceeded 80%. 25% (1/4, case 4) of cases had mismatch repair deficiency (dMMR). Two available cases (cases 1 and 3) were detected with SMRACA4 gene alterations. The response to neoadjuvant therapy was ineffective in case 1.
CONCLUSIONS: Gastric SMARCA4-UT is a rare entity of gastric cancer with a poor prognosis, predominantly occurs in male patients. The tumors are typically diagnosed at advanced stages and shows a solid architecture with undifferentiated morphology. Negative expression of epithelial markers and complete loss of SMARCA4 immunoexpression are emerging as a useful diagnostic tool for rare gastric SMARCA4-UTs.
RESULTS: We retrospectively reported four rare cases of gastric SMARCA4-UTs. All four cases were male, aged between 61 and 82 years. These tumors presented as ulcerated and transmural masses with infiltration, staged as TNM IV in cases 1, 2 and 4, and TNM IIIA in case 3. Pathologically, four cases presented solid architecture with undifferentiated morphology. Cases 2 and 3 showed focal necrosis and focal rhabdoid morphology. Immunohistochemical staining showed negative expression of epithelial markers and deficient expression of SMARCA4. Furthermore, positivity for Syn (cases 1, 2 and 3) and SALL4 (cases 1 and 2) were observed. Mutant p53 expression occurred in four cases, resulting in strong and diffuse staining of p53 expression in cases 1, 2 and 4, and complete loss in case 3. The Ki67 proliferative index exceeded 80%. 25% (1/4, case 4) of cases had mismatch repair deficiency (dMMR). Two available cases (cases 1 and 3) were detected with SMRACA4 gene alterations. The response to neoadjuvant therapy was ineffective in case 1.
CONCLUSIONS: Gastric SMARCA4-UT is a rare entity of gastric cancer with a poor prognosis, predominantly occurs in male patients. The tumors are typically diagnosed at advanced stages and shows a solid architecture with undifferentiated morphology. Negative expression of epithelial markers and complete loss of SMARCA4 immunoexpression are emerging as a useful diagnostic tool for rare gastric SMARCA4-UTs.
摘要：
背景：SMARCA4，作为SWI/SNF染色质重塑复合物的亚基之一，驱动SMARCA4缺陷型肿瘤。胃SMARCA4缺陷型肿瘤可包括胃SMARCA4缺陷型肿瘤和胃SMARCA4缺陷型未分化肿瘤(SMARCA4-UT)。胃SMARCA4-UT在临床实践中是罕见且具有挑战性的诊断。本报告旨在深入了解胃SMARCA4-UT的临床病理特征和遗传改变。
结果：我们回顾性报道了4例罕见的胃SMARCA4-UTs。四例均为男性,年龄在61至82岁之间。这些肿瘤表现为溃疡和透壁性肿块，伴有浸润，在病例1、2和4中分期为TNMIV，在病例3中分期为TNMIIIA。病理上,4例表现为实体结构，形态未分化。病例2和3显示局灶性坏死和局灶性横纹肌样形态。免疫组织化学染色显示上皮标志物阴性表达和SMARCA4缺陷表达。此外，观察到Syn（病例1、2和3）和SALL4（病例1和2）的阳性。4例突变p53表达，导致在病例1、2和4中p53表达的强和弥漫性染色，在病例3中完全丧失。Ki67增殖指数超过80%。25%(1/4,病例4)的病例存在错配修复缺陷(dMMR)。检测到两个可用的病例（病例1和3）具有SMRACA4基因改变。病例1对新辅助治疗的反应无效。
结论：胃SMARCA4-UT是一种罕见的胃癌，预后不良，主要发生在男性患者。肿瘤通常在晚期诊断,并显示具有未分化形态的固体结构。上皮标志物的阴性表达和SMARCA4免疫表达的完全丧失正在成为罕见胃SMARCA4-UTs的有用诊断工具。
结果：我们回顾性报道了4例罕见的胃SMARCA4-UTs。四例均为男性,年龄在61至82岁之间。这些肿瘤表现为溃疡和透壁性肿块，伴有浸润，在病例1、2和4中分期为TNMIV，在病例3中分期为TNMIIIA。病理上,4例表现为实体结构，形态未分化。病例2和3显示局灶性坏死和局灶性横纹肌样形态。免疫组织化学染色显示上皮标志物阴性表达和SMARCA4缺陷表达。此外，观察到Syn（病例1、2和3）和SALL4（病例1和2）的阳性。4例突变p53表达，导致在病例1、2和4中p53表达的强和弥漫性染色，在病例3中完全丧失。Ki67增殖指数超过80%。25%(1/4,病例4)的病例存在错配修复缺陷(dMMR)。检测到两个可用的病例（病例1和3）具有SMRACA4基因改变。病例1对新辅助治疗的反应无效。
结论：胃SMARCA4-UT是一种罕见的胃癌，预后不良，主要发生在男性患者。肿瘤通常在晚期诊断,并显示具有未分化形态的固体结构。上皮标志物的阴性表达和SMARCA4免疫表达的完全丧失正在成为罕见胃SMARCA4-UTs的有用诊断工具。
