d'Amore E S, Manivel J C, Pettinato G, Niehans G A, Snover D C
Department of Laboratory Medicine and Pathology, University of Minnesota Hospital, Minneapolis.
Hum Pathol. 1991 Mar;22(3):276-86. doi: 10.1016/0046-8177(91)90162-i.
Six cases of intestinal ganglioneuromatosis (GN) included in this study reveal the occurrence of two morphologic patterns. Transmural GN was characterized by neural hyperplasia in all layers of the bowel wall with predominant involvement of the myenteric plexus. It was found in three patients affected by multiple endocrine neoplasia IIb. Mucosal GN, having predominant involvement of the mucosa without concomitant hyperplasia of the myenteric plexus, was associated with von Recklinghausen's disease, adenocarcinoma of the colon, and multiple adenomas with megacolon in one case each. Clinicopathologic correlations and review of the literature suggest that mucosal GN might represent a distinct entity with a lower morbidity rate than the transmural variant. Immunohistochemical stains reveal considerable heterogeneity. S-100 protein, neuron-specific enolase, and synapto-physin immunostaining followed the distribution of the nervous hyperplasia in the different intestinal layers as identified morphologically and allowed precise determination of the proliferating cells. Increased reactivity for vasoactive intestinal polypeptide, opioid peptides leu-enkephalin and met-enkephalin, and substance P was present in all cases with transmural involvement; mucosal GN showed normal reactivity for opioid peptides and focal increased staining for substance P (one case) and vasoactive intestinal polypeptide (two cases) in the lamina propria. Mild increased immunoreactivity for tyrosine hydroxylase was present in the myenteric plexus of four out of four cases. Histochemical determination of acetylcholinesterase, performed in one case of transmural type, demonstrated hyperplasia of parasympathetic fibers and neurons. Electron microscopic study of another case suggested the presence of several neurotransmitters. These results indicate that the physiopathology of GN is related to a complex hyperplasia of several peptidergic, cholinergic, and probably adrenergic nerve fibers instead of a selective overgrowth of one type of nerve fiber.
本研究纳入的6例肠道神经节瘤病（GN）呈现出两种形态学模式。透壁性GN的特征是肠壁各层神经增生，主要累及肌间神经丛。在3例患有多发性内分泌肿瘤IIb型的患者中发现了这种情况。黏膜性GN主要累及黏膜，肌间神经丛无伴随增生，分别与冯雷克林霍增氏病、结肠癌以及1例伴有巨结肠的多发性腺瘤相关。临床病理相关性分析及文献回顾表明，黏膜性GN可能是一种独特的实体，其发病率低于透壁性变体。免疫组织化学染色显示出相当大的异质性。S-100蛋白、神经元特异性烯醇化酶和突触素免疫染色遵循不同肠层神经增生的分布情况，这在形态学上已得到确认，并且能够精确确定增殖细胞。在所有透壁受累的病例中，血管活性肠肽、阿片肽亮脑啡肽和甲硫脑啡肽以及P物质的反应性均增强；黏膜性GN对阿片肽显示正常反应性，固有层中P物质（1例）和血管活性肠肽（2例）呈局灶性染色增加。4例中有4例的肌间神经丛中酪氨酸羟化酶免疫反应性轻度增强。在1例透壁型病例中进行了乙酰胆碱酯酶的组织化学测定，结果显示副交感神经纤维和神经元增生。对另一例病例的电子显微镜研究表明存在几种神经递质。这些结果表明，GN的生理病理学与几种肽能、胆碱能以及可能的肾上腺素能神经纤维的复杂增生有关，而不是某一种神经纤维的选择性过度生长。
