伊马替尼治疗后具有不寻常表型的胃肠道间质瘤：1例报告及ETV1 mRNA原位杂交的诊断效用
Gastrointestinal stromal tumor of unusual phenotype after imatinib treatment: A case report and diagnostic utility of ETV1 mRNA in situ hybridization.
作者信息
Jung Minsun, Park Sung-Hye, Jeon Yoon Kyung, Won Jae-Kyung, Yang Han-Kwang, Kim Woo Ho
机构信息
Department of Pathology Department of Surgery, Seoul National University Hospital Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
出版信息
Medicine (Baltimore). 2017 Dec;96(49):e9031. doi: 10.1097/MD.0000000000009031.
RATIONALE
Gastrointestinal stromal tumor (GIST) is the most common tumor of mesenchymal origin in gastrointestinal tract. Immunohistochemical (IHC) staining combined with a typical morphology is used for the diagnosis of GIST. Typically, IHC staining for v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene (KIT) and discovered on GIST-1(DOG1) is positive in almost all GISTs. However, imatinib mesylate, a specific inhibitor of KIT tyrosine kinase, frequently involves changes in the morphology and IHC staining of GIST, impeding the diagnosis. Recently, in situ hybridization (ISH) for E26 transformation-specific sequence variant 1 (ETV1) mRNA was introduced as a useful marker to diagnose GIST.
PATIENT CONCERNS
We report 2 cases of gastric GIST, which expressed unusual phenotypes after imatinib therapy.
DIAGNOSES
The first patient was found to have a gastric subepithelial tumor in gastroduodenoscopy done for regular checkup. In biopsy of the tumor, it showed homogenous spindle cells that were positive to standard IHC markers for GIST. The second patient visited our hospital because of a palpable mass in the abdomen. In abdominal computed tomography (CT), a tumor arising from the stomach was found. A needle biopsy was done and the patient was diagnosed of gastric GIST because the biopsy showed spindle cells positive to typical IHC markers for GIST. After imatinib treatment, in both patients, the resected tumors were composed of heterogeneous spindle cells negative to KIT, DOG1, and CD34 IHC staining, which was unusual for GIST. However, ISH for ETV1 mRNA done for both biopsied and resected tumors was positive, even after imatinib treatment. A molecular analysis found a mutation in exon 11 of KIT gene before and after imatinib therapy in both patients, confirming the diagnosis of GIST.
INTERVENTIONS
Both patients took neoadjuvant imatinib treatment, and afterwards, underwent a surgical resection.
OUTCOMES
The patients remain on imatinib treatment and no progression or recurrence has been detected to date.
LESSONS
ISH for ETV1 mRNA is a useful technique in diagnosing GIST when IHC with KIT, DOG1, or CD34 fail to stain positive after imatinib therapy.
原理
胃肠道间质瘤（GIST）是胃肠道最常见的间叶源性肿瘤。免疫组织化学（IHC）染色结合典型形态学用于GIST的诊断。通常，几乎所有GIST中针对v-kit Hardy-Zuckerman 4猫肉瘤病毒癌基因（KIT）和在GIST-1（DOG1）上发现的免疫组织化学染色均为阳性。然而，甲磺酸伊马替尼作为KIT酪氨酸激酶的特异性抑制剂，常导致GIST的形态学和免疫组织化学染色发生变化，从而妨碍诊断。最近，E26转化特异性序列变异体1（ETV1）mRNA的原位杂交（ISH）被引入作为诊断GIST的有用标志物。
患者情况
我们报告2例胃GIST病例，其在伊马替尼治疗后表现出不寻常的表型。
诊断
首例患者在定期体检的胃镜检查中发现胃黏膜下肿瘤。肿瘤活检显示为均匀的梭形细胞，对GIST的标准免疫组织化学标志物呈阳性。第二例患者因腹部可触及肿块就诊我院。腹部计算机断层扫描（CT）发现胃来源的肿瘤。进行了针吸活检，活检显示梭形细胞对GIST的典型免疫组织化学标志物呈阳性，该患者被诊断为胃GIST。伊马替尼治疗后，两名患者切除的肿瘤均由异质性梭形细胞组成，对KIT、DOG1和CD34免疫组织化学染色呈阴性，这在GIST中并不常见。然而，对活检和切除肿瘤进行的ETV1 mRNA原位杂交在伊马替尼治疗后仍为阳性。分子分析发现两名患者在伊马替尼治疗前后KIT基因第11外显子均有突变，证实为GIST诊断。
干预措施
两名患者均接受了新辅助伊马替尼治疗，随后接受了手术切除。
结果
患者继续接受伊马替尼治疗，迄今为止未检测到进展或复发。
经验教训
当伊马替尼治疗后KIT、DOG1或CD34免疫组织化学染色未能呈阳性时，ETV1 mRNA原位杂交是诊断GIST的有用技术。
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