Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Am J Surg Pathol. 2012 May;36(5):732-6. doi: 10.1097/PAS.0b013e31824b1dff.
Primary biliary cirrhosis (PBC) is characterized by chronic nonsuppurative destructive cholangitis, which is considered to be a cell-mediated immune reaction. Antigen-presenting cells, including Langerhans cells and dendritic cells, have been found in portal tracts and in bile duct epithelium and may play a role in the pathogenesis of PBC, but the importance of identifying these cells for diagnosing PBC has not been studied yet. In this study, we sought to evaluate the importance of identifying Langerhans cells using a CD1a immunostain in the diagnosis of PBC. Liver biopsies from adult patients diagnosed with PBC (n=60), primary sclerosing cholangitis (n=29), obstructive cholangitis (n=13), chronic viral hepatitis B or C (n=19), autoimmune hepatitis (AIH, n=15), acute cellular rejection (n=11), and chronic rejection (n=10) at our institution were retrospectively reviewed. An immunohistochemical stain for CD1a was used to detect Langerhans cells, and the distribution of CD1a-positive Langerhans cell infiltrate was recorded as lobular, portal with bile duct sparing, and intraepithelial. Intraepithelial Langerhans cells were identified in 58% of PBC including antimitochondrial antibody-negative PBC and PBC-AIH overlap cases, 14% of primary sclerosing cholangitis, 15% of obstructive cholangitis, 9% of acute cellular rejection, 6% of AIH, and no cases of chronic viral hepatitis or chronic rejection. The number of intraepithelial Langerhans cells was significantly higher in PBC than in other conditions, with the mean number of CD1a-positive intraepithelial Langerhans cells per bile duct in PBC calculated as 2.2 compared with <1 per duct for the other control cases. Thirty-three of 60 (55%) PBC cases showed at least one bile duct containing ≥2 CD1a-positive Langerhans cells. This was statistically significant (P<0.01) when compared with control groups. The overall sensitivity and specificity of using ≥2 CD1a-positive Langerhans cells per bile duct as the diagnostic criteria for PBC were 55% and 96%. Given the heterogenous nature of liver involvement by PBC, a review of cases with morphologic features of duct damage yielded an increased sensitivity (79%) with no reduction in specificity. In conclusion, the detection of a Langerhans cell infiltrate of ≥2 cells by CD1a in a given bile duct on needle biopsy may be a valuable tool in the diagnosis of PBC.
原发性胆汁性肝硬化（PBC）的特征是慢性非化脓性破坏性胆管炎，被认为是一种细胞介导的免疫反应。已在门脉区和胆管上皮中发现了抗原呈递细胞，包括朗格汉斯细胞和树突状细胞，它们可能在 PBC 的发病机制中发挥作用，但尚未研究鉴定这些细胞对诊断 PBC 的重要性。在这项研究中，我们试图评估使用 CD1a 免疫染色鉴定朗格汉斯细胞在 PBC 诊断中的重要性。我们回顾性分析了我院诊断为 PBC（n=60）、原发性硬化性胆管炎（n=29）、梗阻性胆管炎（n=13）、慢性乙型或丙型病毒性肝炎（n=19）、自身免疫性肝炎（AIH，n=15）、急性细胞性排斥（n=11）和慢性排斥（n=10）的成年患者的肝活检标本。使用 CD1a 免疫组织化学染色来检测朗格汉斯细胞，并记录 CD1a 阳性朗格汉斯细胞浸润的分布为小叶内、门脉伴胆管保留和上皮内。在包括抗线粒体抗体阴性 PBC 和 PBC-AIH 重叠病例在内的 58%的 PBC 中，发现了上皮内朗格汉斯细胞，在 14%的原发性硬化性胆管炎、15%的梗阻性胆管炎、9%的急性细胞性排斥、6%的 AIH 中未发现，而在慢性病毒性肝炎或慢性排斥中未发现。上皮内朗格汉斯细胞的数量在 PBC 中明显高于其他情况，PBC 中每根胆管内 CD1a 阳性上皮内朗格汉斯细胞的平均值为 2.2，而其他对照组每根胆管内<1。60 例 PBC 中有 33 例（55%）至少有一根胆管含有≥2 个 CD1a 阳性朗格汉斯细胞。与对照组相比，这具有统计学意义（P<0.01）。使用每根胆管内≥2 个 CD1a 阳性朗格汉斯细胞作为 PBC 的诊断标准，其总体敏感性和特异性分别为 55%和 96%。鉴于 PBC 肝脏受累的异质性，对具有胆管损伤形态特征的病例进行回顾性分析可提高敏感性（79%），而特异性无降低。总之，在针吸活检中，在给定的胆管中通过 CD1a 检测到≥2 个朗格汉斯细胞浸润可能是诊断 PBC 的有用工具。
