PDF(Pubmed)
Abstract：
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 de novo 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 cm2. 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.
摘要：
胃肠道间质瘤（GIST）的去分化已经在少数病例中报道，通常在酪氨酸激酶抑制剂（TKI）的压力下治疗。在这里，我们描述了一名32岁中国女性SDH缺乏症的从头去分化GIST。肿瘤位于胃窦的较小曲率上，测量4.1x9.1cm2。微观上,肿瘤由两个不同的形态学群体组成，以多结节生长模式排列的轻度上皮样细胞和以束状或片状结构排列的超色梭形细胞。两个区域显示不同的免疫表型。前者为上皮样GIST,C-KIT阳性表达,DOG-1和CD34，后者表达CKpan和P53，但C-KIT阴性，DOG-1和CD34.然而,两个区域的SDHB染色均为阴性。基因上,下一代测序（NGS）分析显示SDHC突变（p.S48*）在两个组分中，MDM2扩增仅在梭形细胞区域。病变被诊断为SDH缺陷型GIST伴上皮细胞去分化。我们提出P53相关基因改变或KIT非依赖性信号通路的其他替代逃逸机制可能在去分化中起作用。
