Pathology of the Liver in Familial Hemophagocytic Lymphohistiocytosis
Pathology of the Liver in Familial Hemophagocytic Lymphohistiocytosis
复制标题
DOI：
10.1097/pas.0b013e3181dbbb17
复制
发表时间：
2010-06-01
影响因子：
5.6
通讯作者：
Perez-Atayde, Antonio R.
中科院分区：
文献类型：
--
作者：
Chen, Jey-Hsin;Fleming, Mark D.;Perez-Atayde, Antonio R.
家族性噬血细胞淋巴组织细胞增多症是一种罕见的、进展迅速的疾病，其特征是免疫系统的激活导致淋巴细胞和组织细胞的系统性增殖。这种疾病在遗传上是异质性的，至少映射到4个基因座，包括编码穿孔素的基因，穿孔素是一种对T淋巴细胞和自然杀伤(NK)细胞的细胞毒性和调节功能至关重要的蛋白质。肝功能障碍通常发生在临床病程的早期，但肝脏的病理特征并不是很好。对19例(男11例，女7例，不明原因1例，年龄12d~11mo，中位数3mo)FHL的临床病史、实验室资料和病理资料(25例肝脏标本)进行了复习。所有病例均行常规和免疫组织化学染色，并进行穿孔素基因测序。所有标本均可见CD3(+)、CD8(+)、颗粒酶B+淋巴细胞与CD68(+)、CD1a-组织细胞混合的门状和窦状浸润，表现为吞噬血细胞。门静脉和中央静脉内皮炎及淋巴细胞介导的胆管损伤。门静脉窦淋巴组织细胞和内皮炎的程度由轻到重不等，并与临床严重程度相关。在一些标本中，以组织细胞为主，在另一些标本中，有广泛的肝细胞巨细胞转化。相应地，观察到4种组织病理类型：(1)慢性肝炎样，(2)白血病样，(3)组织细胞储存障碍样，(4)新生儿巨细胞肝炎样。2例50delT缺失纯合子婴儿无穿孔素免疫反应细胞，1例缺失错义突变复合杂合子婴儿穿孔素表达明显降低，1例穿孔素错义突变婴儿穿孔素表达完整。认识肝脏的形态变化和浸润液的免疫表型特征对于快速诊断和及时治疗至关重要。
Familial hemophagocytic lymphohistiocytosis is a rare, rapidly progressive disorder characterized by an activation of the immune system resulting in a systemic proliferation of lymphocytes and histiocytes. The disease is genetically heterogeneous and maps to at least 4 loci including the gene encoding perforin, a protein critical for the cytotoxic and regulatory functions of T lymphocytes and natural killer (NK) cells. Hepatic dysfunction often occurs early in the clinical course, but the pathology of the liver is not well characterized. The clinical history, laboratory data, and pathologic material (25 hepatic specimens) from 19 children (11 boys, 7 girls, 1 unknown, 12 d to 11mo of age, median 3 mo) with FHL were reviewed. Routine and immunohistochemical stains were carried out in all cases, and perforin gene sequencing in a subset. Common to all specimens was a portal and sinusoidal infiltrate of CD3(+), CD8(+), granzyme B+ lymphocytes admixed with CD68(+), CD1a- histiocytes that exhibited hemophagocytosis. There was endothelialitis of portal and central veins and lymphocyte-mediated bile duct injury. The degree of portal and sinusoidal lymphohistiocytic infiltrate and endothelialitis varied from mild to marked and correlated with clinical severity. In some specimens, histiocytic cells predominated and in others, there was extensive hepatocellular giant cell transformation. Accordingly, 4 histopathologic patterns were observed: (1) chronic hepatitis-like, (2) leukemia-like, (3) histiocytic storage disorder-like, and (4) neonatal giant cell hepatitis-like. Two siblings homozygous for a 50delT nucleotide deletion had no perforin immunoreactive cells, 1 compound heterozygote for a deletion and missense mutation had cells with markedly diminished perforin expression, and 1 infant hemizygous for a perforin missense mutation had intact expression. Recognizing the morphologic changes in the liver and the immunophenotypic features of the infiltrate are critical for a rapid diagnosis and a prompt institution of treatment.