Composite gangliocytoma/neuroma and neuroendocrine tumor: a clinicopathologic, immunohistochemical, and molecular genetic study of 11 cases.

IF 3.1 3区 医学 Q1 PATHOLOGY
M Lisa Zhang, David M Meredith, Andrew M Bellizzi, Jonathan A Nowak, David J Papke
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引用次数: 0

Abstract

Composite gangliocytoma/neuroma and neuroendocrine tumor (CoGNET, previously "gangliocytic paraganglioma"), is a rare tumor type of uncertain pathogenesis in the ampulla/periampullary duodenum. Here, we present 11 CoGNETs in 6 females (55%) and 5 males (median age: 55 years; range: 28-69 years), all in the ampulla or duodenum. Tumors were triphasic with variable proportions of (1) neuroendocrine nests, (2) spindle cell nerve sheath regions, and (3) ganglion-like cells. By immunohistochemistry, ganglion-like cells expressed broad-spectrum keratins, somatostatin, NFP, and islet-1, and they lacked expression of PHOX2B. Neuroendocrine nests diffusely expressed ARX, islet-1, pancreatic polypeptide, and somatostatin, and they lacked expression of CDX2 and PDX1. Spindle cells expressed NFP and S-100. Targeted DNA sequencing of four tumors demonstrated 15q loss in two and multiple copy number alterations in one. Whole-exome DNA sequencing of five tumors showed borderline evidence of an NF1 frameshift mutation in one. Clinical follow-up was available for 8 patients (73%; median length: 7.0 years; range: 1.3 months-13.9 years). One Whipple resection showed regional lymph node metastases in a patient who remained disease-free 12.3 years later. No patients experienced recurrence or metastasis following surgery. The expression pattern of endocrine hormones and transcription factors distinguished CoGNET from other pancreatic and duodenal neuroendocrine tumor subtypes. The ganglion-like cells expressed keratins and not PHOX2B, demonstrating immunophenotypic divergence from true ganglion cells. Therefore, we propose that alternative nomenclature "gangliocytoid neuroendocrine neoplasm" or "composite gangliocytoid neuroendocrine neoplasm" be considered. The relative lack of pathogenic mutations raises the possibility that these tumors might harbor epigenetic drivers.

神经节细胞瘤/神经瘤及神经内分泌肿瘤:11例临床病理、免疫组织化学及分子遗传学研究
复合神经节细胞瘤/神经瘤和神经内分泌肿瘤(CoGNET,以前称为神经节细胞副神经节瘤)是一种罕见的发生于壶腹/壶腹周围十二指肠的肿瘤类型,发病机制不确定。在这里,我们报告了6名女性(55%)和5名男性(中位年龄:55岁;年龄范围:28-69岁),均在壶腹或十二指肠。肿瘤为三期,有不同比例的(1)神经内分泌巢,(2)梭形细胞神经鞘区,(3)神经节样细胞。免疫组化发现,神经节样细胞表达广谱角蛋白、生长抑素、NFP和胰岛素-1,缺乏PHOX2B的表达。神经内分泌巢弥漫表达ARX、胰岛-1、胰腺多肽和生长抑素,缺乏CDX2和PDX1的表达。梭形细胞表达NFP和S-100。4个肿瘤的靶向DNA测序显示,其中2个肿瘤出现15q缺失,1个肿瘤出现多个拷贝数改变。五个肿瘤的全外显子组DNA测序显示其中一个肿瘤存在NF1移码突变的边缘证据。临床随访8例(73%;中位寿命:7.0年;范围:1.3个月-13.9年)。一例惠普尔切除术显示,12.3年后无病的患者出现了局部淋巴结转移。手术后无复发或转移。内分泌激素和转录因子的表达模式将CoGNET与其他胰腺和十二指肠神经内分泌肿瘤亚型区分开来。神经节样细胞表达角蛋白而不是PHOX2B,显示出与真正神经节细胞的免疫表型差异。因此,我们建议考虑“神经节细胞样神经内分泌肿瘤”或“复合神经节细胞样神经内分泌肿瘤”的替代命名。致病突变的相对缺乏增加了这些肿瘤可能包含表观遗传驱动因素的可能性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Virchows Archiv
Virchows Archiv 医学-病理学
CiteScore
7.40
自引率
2.90%
发文量
204
审稿时长
4-8 weeks
期刊介绍: Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.
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