Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 622 W 168th St.VC14-209A, New York, NY, 10032, USA.
Department of Pathology, Mass General Brigham, Boston, MA, USA.
Virchows Arch. 2024 Jan;484(1):61-69. doi: 10.1007/s00428-023-03683-7. Epub 2023 Nov 4.
Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with high mortality. Liver involvement is common (based on elevated liver function tests) with most patients demonstrating acute hepatitis. Liver biopsies are frequently obtained in the setting of suspected HLH for the purpose of identification of erythrophagocytosis, and if present, this finding is thought to suggest or support the diagnosis of HLH. However, there are problems with this approach; in particular, we do not know whether this finding is reproducible or whether it is specific to HLH. Therefore, we conducted a multi-institutional study in which experienced liver pathologists reviewed images taken from liver biopsies from patients with normal liver, acute hepatitis, possible HLH, and clinical HLH to determine if there was agreement about the presence or absence of erythrophagocytosis, and to ascertain whether the finding corresponds to a clinical diagnosis of HLH. Twelve liver pathologists reviewed 141 images in isolation (i.e., no clinical information or diagnosis provided). These came from 32 patients (five normal, 17 acute hepatitis, six HLH, four possible HLH). The pathologists classified each image as negative, equivocal, or positive for erythrophagocytosis. Kappa was .08 (no agreement) for case-level and 0.1 for image-level (1.4% agreement, based on two images which were universally considered negative). There was no difference in the proportion of pathologists who diagnosed erythrophagocytosis among those with different diagnoses at case or image-level (p = 0.82 and p = 0.82, respectively). Thus, erythrophagocytosis is an entirely unreliable histologic parameter in liver, as it is irreproducible and not demonstrably associated with a clinical disease (namely, HLH). Unless and until more reliable guidelines can be established, pathologists should refrain from commenting on the presence or absence of erythrophagocytosis in liver biopsy.
噬血细胞性淋巴组织细胞增生症（HLH）是一种死亡率很高的罕见疾病。肝脏受累很常见（基于肝功能检查升高），大多数患者表现为急性肝炎。在疑似 HLH 的情况下，常进行肝脏活检以确定是否存在红细胞吞噬作用，如果存在，则认为该发现提示或支持 HLH 的诊断。然而，这种方法存在问题；特别是，我们不知道该发现是否具有可重复性，或者它是否特异性地与 HLH 相关。因此，我们进行了一项多机构研究，由经验丰富的肝脏病理学家审查来自正常肝脏、急性肝炎、可能的 HLH 和临床 HLH 患者的肝脏活检的图像，以确定是否存在关于红细胞吞噬作用的存在或不存在的共识，并确定该发现是否与 HLH 的临床诊断相对应。十二位肝脏病理学家独立审查了 141 张图像（即，未提供临床信息或诊断）。这些图像来自 32 名患者（5 名正常，17 名急性肝炎，6 名 HLH，4 名可能的 HLH）。病理学家将每个图像分类为阴性、不确定或阳性的红细胞吞噬作用。病例水平的 Kappa 值为 0.08（无一致性），图像水平的 Kappa 值为 0.1（基于两张被普遍认为是阴性的图像，一致性为 1.4%）。在病例或图像水平上，具有不同诊断的病理学家诊断红细胞吞噬作用的比例没有差异（p = 0.82 和 p = 0.82，分别）。因此，红细胞吞噬作用在肝脏中是一个完全不可靠的组织学参数，因为它是不可重复的，并且不能证明与临床疾病（即 HLH）相关。除非并直到能够建立更可靠的指南，否则病理学家应避免对肝脏活检中红细胞吞噬作用的存在与否发表评论。
