Departments of Pathology and Immunology.
Internal Medicine, Washington University School of Medicine, Saint Louis, MO.
Am J Surg Pathol. 2020 Aug;44(8):1137-1142. doi: 10.1097/PAS.0000000000001484.
Intestinal inertia is a severe form of gut dysmotility that may require surgical resection. Loss of myenteric ganglion cells has been proposed as a possible etiology. Preclinical models have also suggested that virus infection-associated ganglionitis may be an alternative pathogenic factor. We determined to the extent intestinal inertia is associated with the lack of myenteric ganglion cells or ganglionitis using resection specimens from 27 intestinal inertia and 28 colon cancer patients. A hot spot approach with 5 HPFs was used for quantifying inflammatory cells. CD3, CD8, and CD20 immunohistochemistry was used to quantify T and B lymphocytes, along with subtyping the T-lymphocyte population by CD8. None of the intestinal inertia nor control cases showed the absence of myenteric ganglion cells. A total of 15 (55.6%) of the intestinal inertia cases showed inflammatory cell infiltration in the myenteric ganglion cells, compared with only 1 of 28 (3.6%) control cases (P<0.0001 by Fisher exact test). The inertia cases with inflammatory infiltrates were all associated predominantly with lymphocytes, including 3 cases (11.1%) with concurrent eosinophil infiltration, and 1 case (3.7%) with concurrent neutrophil infiltration. Furthermore, all 15 inertia cases with myenteric lymphocytic ganglionitis were associated with T lymphocytes (100%), including 1 case with a subset of concurrent B lymphocytes. The average CD3 count was 3.8 cells/HPF. CD8 immunohistochemical stain showed positive staining in 12 of the 15 cases (80%) with CD8-positive cells ranging from 1 to 8/HPF. In contrast, the only control case with lymphocytic ganglionitis showed mixed B and T lymphocytes and eosinophils. The high prevalence of T-lymphocyte infiltration in the myenteric ganglion in intestinal inertia cases suggests a possible pathogenic role.
肠动力障碍是一种严重的肠道动力障碍，可能需要手术切除。有人提出，肠神经元缺失可能是其病因之一。临床前模型还表明，病毒感染相关性节炎可能是另一种致病因素。我们通过对 27 例肠动力障碍和 28 例结肠癌患者的切除标本进行研究，旨在确定肠动力障碍与肠神经元缺失或节炎的相关性。我们使用 5 个高倍视野（HPFs）热点法来定量炎症细胞。我们使用 CD3、CD8 和 CD20 免疫组化来定量 T 和 B 淋巴细胞，并通过 CD8 对 T 淋巴细胞进行亚型分类。在所有肠动力障碍和对照病例中均未发现肠神经元缺失。与 28 例对照病例（3.6%）相比，15 例（55.6%）肠动力障碍病例的肌间神经节细胞中存在炎症细胞浸润（Fisher 确切检验，P<0.0001）。具有炎症浸润的肠动力障碍病例均主要与淋巴细胞有关，包括 3 例（11.1%）合并嗜酸性粒细胞浸润，1 例（3.7%）合并中性粒细胞浸润。此外，所有 15 例肌间淋巴细胞性节炎肠动力障碍病例均与 T 淋巴细胞有关（100%），包括 1 例伴有并发 B 淋巴细胞。平均 CD3 计数为 3.8 个/HPF。CD8 免疫组化染色显示，15 例病例中有 12 例（80%）阳性，CD8 阳性细胞范围为 1 至 8/HPF。相比之下，唯一的伴有淋巴细胞性节炎的对照病例表现为混合性 B 和 T 淋巴细胞以及嗜酸性粒细胞。肠动力障碍病例的肌间神经节中 T 淋巴细胞浸润率较高，提示可能存在致病作用。
