Cheng Xiaolin, Chen Shuyue, Jiang Xushui, Li Tao, Zhang Hong, Huang Fengbo, Bao Tianhui
Shexian Branch, Second Affiliated Hospital, Zhejiang University School of Medicine, Huangshan, 245200, China.
Department of Pathology, Shexian People's Hospital, Huangshan, 245200, China.
Diagn Pathol. 2025 Apr 24;20(1):51. doi: 10.1186/s13000-025-01651-0.
Gastric SMARCA4-deficient undifferentiated tumors are rare and have a poor prognosis. We analyzed two cases of gastric SMARCA4-deficient undifferentiated tumors with clinicopathologic characteristics, treatment and flow-up.
Immunohistochemistry was used to evaluate the expression of BRG1 (SAMRCA4), SMARCB1 (INI-1), CKpan, Ki-67, CD3, CD20, CD163, PD-1, and PD-L1 in gastric SMARCA4-deficient undifferentiated tumors. Additionally, the clinical characteristics, imaging features, diagnosis, and treatment were analyzed.
Two elderly male patients (69 and 61 years old) with a large ulcerated mass located in the gastric fundus and cardia. Histologically, the tumor is of low adhesion, diffusely infiltrating lamellar growth, without any percentage of epithelial differentiation zones, and with little stromal component. Tumor cells round, oval, a small amount of irregular shape, easy to see mitotic figures. Some of them had obvious nucleoli, and a few had multiple nucleoli. The cytoplasm varies, and some cells are more abundant. Significant vascular and neural invasion. BRG1(SMARCA4) was absent, INI-1 was present, and Ki-67 proliferation index was highly expressed (≥ 80%). The remaining sarcoma-specific markers were negative. In case 1, the epithelial markers were negative and the PD-L1 combined positive score was 5. In case 2, CKpan was weakly expressed in only a dozen cells, and the PDL1 CPS was 10. The two patients received chemotherapy and anti-PD1 immunotherapy after radical gastrectomy for gastric cancer. The postoperative follow-up time of the two patients was 16 (case 1) and 3 months (case 2), respectively. The general condition was good, no recurrence or metastasis was observed, and the plasma tumor markers were in the normal range.
Large SMARCA4-deficient tumors are more likely to have massive necrosis on the surface, leading to negative biopsy results. This tumor has a diffuse lamellar growth and needs to be differentiated from a variety of tumors with similar morphology, such as lymphoma, malignant melanoma, neuroendocrine carcinoma and undifferentiated sarcoma. The tumor cells were negative or only slightly positive for CKpan increases the difficulty of pathological diagnosis of this disease. However, loss of BRG1 (SMARCA4) expression can confirm the diagnosis. Chemotherapy combined with anti-PD1 treatment may have potential benefits in the management of gastric SMARCA4-deficient undifferentiated tumors. However, given the rarity of these tumors and the limited number of cases in our study, further research with larger cohorts is needed to validate these preliminary results.
胃SMARCA4缺陷型未分化肿瘤罕见，预后较差。我们分析了2例胃SMARCA4缺陷型未分化肿瘤的临床病理特征、治疗及随访情况。
采用免疫组织化学法评估BRG1（SMARCA4）、SMARCB1（INI-1）、广谱细胞角蛋白（CKpan）、Ki-67、CD3、CD20、CD163、程序性死亡受体1（PD-1）和程序性死亡配体1（PD-L1）在胃SMARCA4缺陷型未分化肿瘤中的表达。此外，分析其临床特征及影像学特征、诊断及治疗情况。
2例老年男性患者（分别为69岁和61岁），胃底和贲门处有巨大溃疡型肿块。组织学上，肿瘤黏附性低，呈弥漫性浸润性片状生长，无任何比例的上皮分化区，间质成分少。肿瘤细胞呈圆形、椭圆形，少量呈不规则形，易见核分裂象。部分细胞有明显核仁，少数有多个核仁。细胞质各异，部分细胞较丰富。有明显的血管和神经侵犯。BRG1（SMARCA4）缺失，INI-1存在，Ki-67增殖指数高表达（≥80%）。其余肉瘤特异性标志物均为阴性。病例1中，上皮标志物阴性，PD-L1联合阳性评分5分。病例2中，仅十几个细胞中CKpan弱表达，PD-L1综合阳性评分（CPS）为10分。2例患者均在胃癌根治术后接受化疗及抗PD-1免疫治疗。2例患者术后随访时间分别为16个月（病例1）和3个月（病例2）。一般情况良好，未观察到复发或转移，血浆肿瘤标志物在正常范围内。
SMARCA4缺陷型大肿瘤表面更易出现大片坏死，导致活检结果为阴性。该肿瘤呈弥漫性片状生长，需与多种形态相似的肿瘤鉴别，如淋巴瘤、恶性黑色素瘤、神经内分泌癌及未分化肉瘤。肿瘤细胞CKpan阴性或仅轻度阳性增加了该病病理诊断的难度。然而，BRG1（SMARCA4）表达缺失可确诊。化疗联合抗PD-1治疗可能对胃SMARCA4缺陷型未分化肿瘤的治疗有潜在益处。然而，鉴于这些肿瘤罕见且本研究病例数有限，需要更大样本队列的进一步研究来验证这些初步结果。
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