Hirota Seiichi
Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Transl Gastroenterol Hepatol. 2018 May 12;3:27. doi: 10.21037/tgh.2018.04.01. eCollection 2018.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal (GI) tract. GISTs account for approximately 80% of the clinically relevant GI mesenchymal tumors. Although most GISTs show spindle cell morphology, 10-15% of GISTs show pure epithelioid configuration. Therefore, not only spindle cell tumors but also epithelioid cell ones developing in the GI tract are subject to the differential diagnoses of GISTs. GISTs are basically positive for KIT, a receptor tyrosine kinase (RTK) encoded by protooncogene c, by immunohistochemistry, but approximately 5% of GISTs are only weakly or barely positive for KIT. Since almost all spindle cell type GISTs are strongly and diffusely positive for KIT regardless of different genetic subtypes, diagnosis of the spindle cell type GISTs is not difficult. On the other hand, epithelioid cell type GISTs show different staining patterns of KIT in different genetic backgrounds. Approximately half of the epithelioid cell type GISTs with platelet-derived growth factor receptor alpha () gene mutation might show weak or undetectable staining of KIT. On the other hand, almost all GISTs are negative for desmin, which is a positive marker for mature smooth muscle cells, and S100 protein, which is a Schwann cell marker. Smooth muscle tumors such as leiomyomas and leiomyosarcomas, which usually show the spindle cell morphology, consist of approximately 10% of the clinically relevant GI mesenchymal tumors and are almost positive for desmin and negative for KIT and S100 protein. Schwannomas which nearly always show the spindle cell pattern, comprise up to 5% of the GI mesenchymal tumors, and almost all of them are positive for S100 protein and negative for KIT and desmin. Thus, most GI mesenchymal tumors are differentially diagnosed by immunohistochemistry (IHC) of KIT, desmin and S100 protein. However, mesenchymal tumors such as desmoids, solitary fibrous tumors (SFTs), inflammatory myofibroblastic tumors (IMTs), perivascular epithelioid cell tumors (PEComas), inflammatory fibroid polyps (IFPs), rarely develop in the GI tract, and have to be correctly diagnosed through detection of specific immunohistochemical markers and/or unique genetic aberrations.
胃肠道间质瘤（GISTs）是胃肠道（GI）中最常见的间叶性肿瘤。GISTs约占临床相关胃肠道间叶性肿瘤的80%。尽管大多数GISTs表现为梭形细胞形态，但10% - 15%的GISTs表现为纯上皮样结构。因此，不仅胃肠道中发生的梭形细胞瘤，而且上皮样细胞瘤都需要进行GISTs的鉴别诊断。通过免疫组织化学检测，GISTs通常对由原癌基因c编码的受体酪氨酸激酶（RTK）KIT呈阳性，但约5%的GISTs对KIT仅呈弱阳性或几乎为阴性。由于几乎所有梭形细胞型GISTs无论基因亚型如何，对KIT均呈强阳性且弥漫性阳性，所以梭形细胞型GISTs的诊断并不困难。另一方面，上皮样细胞型GISTs在不同基因背景下KIT染色模式不同。约一半具有血小板衍生生长因子受体α（）基因突变的上皮样细胞型GISTs可能对KIT呈弱阳性或检测不到染色。另一方面，几乎所有GISTs对结蛋白（成熟平滑肌细胞的阳性标志物）和S100蛋白（雪旺细胞标志物）均为阴性。通常表现为梭形细胞形态的平滑肌瘤和平滑肌肉瘤等平滑肌肿瘤，约占临床相关胃肠道间叶性肿瘤的10%，对结蛋白几乎呈阳性，对KIT和S100蛋白呈阴性。几乎总是表现为梭形细胞模式的神经鞘瘤，占胃肠道间叶性肿瘤的比例高达5%，几乎所有神经鞘瘤对S100蛋白呈阳性，对KIT和结蛋白呈阴性。因此，大多数胃肠道间叶性肿瘤通过KIT、结蛋白和S100蛋白的免疫组织化学（IHC）进行鉴别诊断。然而，诸如硬纤维瘤、孤立性纤维性肿瘤（SFTs）、炎性肌成纤维细胞瘤（IMTs）、血管周上皮样细胞肿瘤（PEComas）、炎性纤维性息肉（IFPs）等间叶性肿瘤很少在胃肠道中发生，必须通过检测特定的免疫组织化学标志物和/或独特的基因畸变来正确诊断。
