Gong Qi-Xing, Ding Ying, Zhang Wei-Ming, Zhang Jia-Wen, Zhang Zhi-Hong
Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Oncol. 2023 Sep 14;13:1233561. doi: 10.3389/fonc.2023.1233561. eCollection 2023.
The dedifferentiation of the gastrointestinal stromal tumors (GISTs) has been reported in a small number of cases, usually under the pressure of the tyrosine kinase inhibitor (TKI) treatment. Herein, we described a dedifferentiated GIST with the SDH deficiency in a 32-year-old Chinese woman. The tumor was located on the lesser curvature of the gastric antrum, measuring 4.1x9.1 cm. Microscopically, the tumor was composed of 2 distinct morphological populations, mild epithelioid cells arranged in the multinodular growth pattern and hyperchromatic spindle cells arranged in the fascicular or sheet-like architecture. The two zones showed different immunophenotypes. The former proved to be an epithelioid GIST with the positive expression for C-KIT, DOG-1, and CD34, and the latter expressed the CKpan and P53, but negative for the C-KIT, DOG-1, and CD34. However, the SDHB staining was negative in both areas. Genetically, the next-generation sequencing (NGS) analysis showed the SDHC mutation (p.S48*) in both components and the MDM2 amplification was only in the spindle cell area. The lesion was diagnosed as the SDH-deficient GIST with the epithelial cell dedifferentiation. We proposed that the P53 associated gene alteration or other alternative escape mechanisms for the KIT-independent signaling pathways might play a role in the dedifferentiation.
少数胃肠道间质瘤（GISTs）会发生去分化，通常是在酪氨酸激酶抑制剂（TKI）治疗的压力下。在此，我们描述了一名32岁中国女性的伴有琥珀酸脱氢酶（SDH）缺陷的去分化GIST。肿瘤位于胃窦小弯侧，大小为4.1×9.1厘米。显微镜下，肿瘤由两种不同形态的细胞群组成，轻度上皮样细胞呈多结节生长模式，深染的梭形细胞呈束状或片状结构排列。这两个区域显示出不同的免疫表型。前者被证明是上皮样GIST，C-KIT、DOG-1和CD34呈阳性表达，后者表达细胞角蛋白广谱（CKpan）和P53，但C-KIT、DOG-1和CD34呈阴性。然而，两个区域的SDHB染色均为阴性。基因方面，二代测序（NGS）分析显示两个成分中均存在SDHC突变（p.S48*），且MDM2扩增仅存在于梭形细胞区域。该病变被诊断为伴有上皮细胞去分化的SDH缺陷型GIST。我们认为P53相关基因改变或其他KIT非依赖性信号通路的替代逃逸机制可能在去分化过程中起作用。
