Department of Laboratory Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Am J Surg Pathol. 2010 Jan;34(1):88-94. doi: 10.1097/PAS.0b013e3181c6c09a.
Sclerosing cholangitis can be primary (PSC) or secondary. One unusual cause of secondary sclerosing cholangitis is the newly recognized entity of IgG4-associated cholangitis. The prevalence and significance of IgG4 plasma cells in patients, who are clinically and radiologically classified as PSC, however, are unknown. Clinical information and histology of liver explants of 98 consecutive liver transplants performed for PSC were reviewed. IgG4 immunohistochemical stain was performed on sections from hilar areas that contained large bile ducts and corresponding cholecystectomy specimens (available in 74 cases). Serum IgG4 levels were measured in stored serum from 81 cases. Tissue IgG4 positivity (>or=10 IgG4+ plasma cells/high power field) was correlated with clinical features (age, sex, presence of inflammatory bowel disease and cholangiocarcinoma, pancreatogram, PSC duration, PSC recurrence after transplant, and number of acute rejection episodes) and histologic findings (periductal lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis) in the liver explants. Twenty-three (23%) liver explants showed periductal infiltration with IgG4+ plasma cells. Eighteen cases (22%) had elevated serum IgG4 levels, including 8 without tissue IgG4 positivity. All cases showed dense periductal fibrosis; none had storiform fibrosis or obliterative phlebitis. IgG4 positivity in the liver strongly correlated with moderate-to-marked periductal lymphoplasmacytic inflammation (P=0.002). Clinically, IgG4 positivity in tissue, but not in serum, was correlated with shorter PSC duration before transplant and higher risk of recurrence after transplant. Nearly one quarter of explanted livers that carry a clinical diagnosis of PSC contain increased IgG4+ periductal plasma cell infiltrates and positive serum IgG4 levels. However, none of the explants show histologic features diagnostic of IgG4-associated cholangitis. PSC with tissue IgG4 positivity has a more aggressive clinical course manifested by shorter time to transplant and a higher likelihood of recurrence than IgG4 negative PSC.
原发性硬化性胆管炎（PSC）可分为原发性和继发性。继发性硬化性胆管炎的一个不常见病因是新发现的 IgG4 相关胆管炎实体。然而，临床上和影像学上被归类为 PSC 的患者 IgG4 浆细胞的患病率和意义尚不清楚。对 98 例连续行肝移植的 PSC 患者的临床资料和肝活检组织学进行了回顾性分析。对包含大胆管的肝门区和相应胆囊切除术标本（74 例中有）进行 IgG4 免疫组化染色。对 81 例病例的储存血清进行 IgG4 血清水平检测。组织 IgG4 阳性（≥10 IgG4+浆细胞/高倍视野）与临床特征（年龄、性别、炎症性肠病和胆管癌的存在、胰胆管造影、PSC 病程、移植后 PSC 复发和急性排斥反应发作次数）和肝活检组织学发现（胆管周围淋巴浆细胞浸润、席纹状纤维化和闭塞性静脉炎）相关。23 例（23%）肝活检标本显示胆管周围有 IgG4+浆细胞浸润。18 例（22%）有升高的 IgG4 血清水平，包括 8 例组织 IgG4 阳性。所有病例均显示致密的胆管周围纤维化；无一例有席纹状纤维化或闭塞性静脉炎。肝组织 IgG4 阳性与中度至显著的胆管周围淋巴浆细胞炎症强烈相关（P=0.002）。临床上，组织 IgG4 阳性，但血清 IgG4 阴性，与移植前 PSC 病程较短和移植后复发风险较高相关。近四分之一的携带 PSC 临床诊断的肝移植标本中含有增加的 IgG4+胆管周围浆细胞浸润和阳性 IgG4 血清水平。然而，没有一个标本显示出 IgG4 相关胆管炎的组织学特征。组织 IgG4 阳性的 PSC 具有更具侵袭性的临床病程，表现为移植时间更短和复发可能性更高。
