PDF(Pubmed)
Abstract：
Appendiceal neuroendocrine tumors (NETs) are common and often are identified as incidental lesions at the time of appendectomy. The guidelines for management are based on tumor size, degree of invasion, and the Ki67 proliferation index. Most small bowel NETs are composed of serotonin-producing EC-cells, but there are multiple other neuroendocrine cell types. In the rectum, there are L-cell tumors that express peptide YY (PYY), glucagon-like peptides (GLPs), and pancreatic polypeptide (PP); they are thought to have a better prognosis than serotonin-producing tumors. We investigated whether the appendix has distinct neuroendocrine tumor types based on cell type and whether that distinction has clinical significance. We collected 135 appendiceal NETs from the pathology archives of UHN Toronto and UHCMC (Cleveland). We analyzed the expression of biomarkers including CDX2, SATB2, PSAP, serotonin, glucagon (that detects GLPs), PYY, and pancreatic polypeptide (PP) and correlated the results with clinicopathologic parameters. Immunohistochemistry identified three types of appendiceal NETs. There were 75 (56%) classified as EC-cell tumors and 37 (27%) classified as L-cell tumors; the remaining 23 (17%) expressed serotonin and one of the L-cell biomarkers and were classified as mixed. EC-cell tumors were significantly larger with more extensive invasion involving the muscularis propria, subserosa, and mesoappendix compared with L-cell tumors. Mixed tumors were intermediate in all of these parameters. Both EC-cell and mixed tumors had lymphatic and/or vascular invasion while L-cell tumors had none. Unlike EC-cell NETs, L-cell tumors were not associated with lymph node metastasis. Tumor type correlated with pT stage and the only patient with distant metastatic disease in this series had an EC-cell tumor. Our study confirms that appendiceal NETs are not a homogeneous tumor population. There are at least three types of appendiceal NET, including EC-cell, L-cell, and mixed tumors. This information is important for surveillance of patients, as monitoring urinary 5HIAA levels is only appropriate for patients with serotonin-producing tumors, whereas measurement of GLPs and/or PP is more appropriate for patients with L-cell tumors. Our data also show that tumor type is of significance with EC-cell tumors exhibiting the most aggressive behavior.
摘要：
阑尾神经内分泌肿瘤（NETs）很常见，通常在阑尾切除术时被确定为偶然病变。管理指南基于肿瘤大小，入侵程度,和Ki67增殖指数。大多数小肠NET由产生5-羟色胺的EC细胞组成，但是还有多种其他神经内分泌细胞类型。在直肠里,有表达肽YY（PYY）的L细胞肿瘤，胰高血糖素样肽（GLPs），和胰腺多肽（PP）；它们被认为比产生5-羟色胺的肿瘤具有更好的预后。我们根据细胞类型调查了阑尾是否有不同的神经内分泌肿瘤类型，以及这种区别是否具有临床意义。我们从UHN多伦多和UHCMC（克利夫兰）的病理档案中收集了135个阑尾NETs。我们分析了生物标志物的表达，包括CDX2，SATB2，PSAP，血清素,胰高血糖素（检测GLPs），PYY,和胰腺多肽（PP），并将结果与临床病理参数相关联。免疫组织化学鉴定出三种类型的阑尾NETs。有75（56％）被分类为EC细胞肿瘤，有37（27％）被分类为L细胞肿瘤；其余23（17％）表达血清素和L细胞生物标志物之一，并被分类为混合。EC细胞肿瘤明显更大，涉及固有肌层的侵袭更广泛，浆膜下,和阑尾膜与L细胞肿瘤相比。混合肿瘤在所有这些参数中处于中间。EC细胞和混合肿瘤均具有淋巴和/或血管浸润，而L细胞肿瘤则没有。与EC-cellNET不同,L细胞肿瘤与淋巴结转移无关。肿瘤类型与pT分期相关，该系列中唯一患有远处转移性疾病的患者患有EC细胞肿瘤。我们的研究证实阑尾NETs不是同质肿瘤群体。至少有三种类型的附录NET，包括EC-cell，L-细胞,和混合肿瘤。这些信息对患者的监测很重要，因为监测尿5HIAA水平仅适用于产生5-羟色胺的肿瘤患者，而GLPs和/或PP的测量更适合L细胞肿瘤患者。我们的数据还表明，肿瘤类型与EC细胞肿瘤表现出最具侵略性的行为有关。
