Department of Pathology.
Department of Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA.
Am J Surg Pathol. 2020 May;44(5):617-625. doi: 10.1097/PAS.0000000000001452.
Common variable immunodeficiency (CVID) has a heterogenous clinical presentation and can be challenging to diagnose. Distinct histologic changes have been linked with CVID in several organ systems, which can help identify the correct diagnosis. In this study we review a cohort of hepatic CVID biopsies, to better define the spectrum of histologic and biochemical alterations. We reviewed 26 liver biopsies from 24 patients with CVID, obtained at 4 institutions between 2010 and 2019. Histologic slides were examined, and pathologic, biochemical, and clinical features were recorded. A control cohort of 21 patients with nodular regenerative hyperplasia (NRH) but lacking CVID was also examined. Liver function tests were frequently abnormal, especially alkaline phosphatase (median: 193 IU/L) and aspartate transaminase (median: 56 U/L), elevated in 23 and 17 of 25 biopsies, respectively. Fifteen patients had CVID involvement of other organs. Histologic features of primary biliary cholangitis were present in 2 patients, with florid duct lesions and prominent bile duct injury, in association with positive antimitochondrial antibodies. Among the other 24 biopsies, mild to moderate portal and lobular inflammation were present in 18 and 17 of 24 biopsies, respectively. Overall, 22 of 24 biopsies showed NRH-like changes. Plasma cell were absent. A distinct pattern of pericellular fibrosis was present in 23 of 26 biopsies overall. Involvement ranged from focal centrizonal fibrosis to bridging fibrosis and was accompanied by increased intrasinusoidal lymphocytes in 13 of 24 biopsies. Pericellular fibrosis was identified in 1 of 21 biopsies in the control cohort. Additional findings included granulomatous inflammation or nonhepatocellular foreign body-type multinucleate giant cells, identified in 4 biopsies. Three of 6 examined biopsies also demonstrated focal hepatocellular copper deposition. Hepatic disease in CVID is often associated with elevated alkaline phosphatase and aspartate transaminase and is characterized histologically by the mild nonspecific portal and lobular hepatitis, absence of plasma cells, NRH-like changes, and less commonly, typical histologic features of primary biliary cholangitis. We have also identified a distinctive pattern of delicate pericellular fibrosis that is a helpful clue to the diagnosis of hepatic disease in CVID, especially when accompanied by NRH-like changes.
普通可变免疫缺陷症（CVID）的临床表现多样，诊断具有挑战性。在多个器官系统中，与 CVID 相关的明显组织学改变可以帮助确定正确的诊断。在这项研究中，我们回顾了一组 CVID 肝活检，以更好地定义组织学和生化改变的范围。我们回顾了 2010 年至 2019 年间 4 家机构的 24 名 CVID 患者的 26 例肝活检。检查了组织学切片，并记录了病理、生化和临床特征。还检查了一组 21 例缺乏 CVID 的结节性再生性增生（NRH）患者作为对照。肝功能检查常异常，尤其是碱性磷酸酶（中位数：193IU/L）和天冬氨酸转氨酶（中位数：56U/L），分别在 25 次活检中的 23 次和 17 次升高。15 名患者有其他器官的 CVID 受累。2 名患者存在原发性胆汁性胆管炎的特征性组织学表现，伴有丰富的胆管病变和明显的胆管损伤，同时抗线粒体抗体阳性。在其余 24 例活检中，18 例和 17 例活检分别有轻度至中度门静脉和肝小叶炎症。总的来说，24 例活检中有 22 例显示出 NRH 样改变。浆细胞缺失。26 例活检中有 23 例总体上存在明显的细胞周纤维化模式。这种受累范围从局灶性中心纤维化到桥接纤维化，并伴有 13 例活检中的肝窦内淋巴细胞增多。在对照队列的 21 例活检中仅 1 例存在细胞周纤维化。其他发现包括肉芽肿性炎症或非肝细胞性异物多核巨细胞，在 4 例活检中发现。6 例检查的活检中有 3 例还显示局灶性肝细胞铜沉积。CVID 中的肝脏疾病通常伴有碱性磷酸酶和天冬氨酸转氨酶升高，组织学表现为轻度非特异性门静脉和肝小叶肝炎，无浆细胞，NRH 样改变，以及较少见的原发性胆汁性胆管炎的典型组织学特征。我们还发现了一种独特的细胞周纤维化模式，这是 CVID 肝疾病诊断的一个有用线索，尤其是当伴有 NRH 样改变时。
