Department of Pathology, Queen Elizabeth Hospital, Hong Kong.
Adv Anat Pathol. 2010 Sep;17(5):303-32. doi: 10.1097/PAP.0b013e3181ee63ce.
An elevated serum titer of immunoglobulin G4 (IgG4), the least common (3% to 6%) of the 4 subclasses of IgG, is a surrogate marker for the recently characterized IgG4-related sclerosing disease. The syndrome affects predominantly middle-aged and elderly patients, with male predominance. The patients present with symptoms referable to the involvement of 1 or more sites, usually in the form of mass lesions. The prototype is IgG4-related sclerosing pancreatitis (also known as autoimmune pancreatitis), most commonly presenting as painless obstructive jaundice with or without a pancreatic mass. Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, but practically any organ-site can be affected, such as retroperitoneum, aorta, mediastinum, soft tissue, skin, central nervous system, breast, kidney, prostate, upper aerodigestive tract, and lung. The patients usually have a good general condition, with no fever or constitutional symptoms. Common laboratory findings include raised serum globulin, IgG, IgG4, and IgE, whereas lactate dehydrogenase is usually not raised. Some patients have low titers of autoantibodies (such as antinuclear antibodies and rheumatoid factor). The disease often shows excellent response to steroid therapy. The natural history is characterized by the development of multiple sites of involvement with time, sometimes after many years. However, the disease can remain localized to 1 site in occasional patients. The main pathologic findings in various extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, accompanied by atrophy and loss of the specialized structures of the involved tissue (such as secretory acini in pancreas, salivary gland, or lacrimal gland). The relative predominance of the lymphoplasmacytic and sclerotic components results in 3 histologic patterns: pseudolymphomatous, mixed, and sclerosing. Immunostaining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). The lymph nodes show multicentric Castleman disease-like features, reactive follicular hyperplasia, interfollicular expansion, or progressive transformation of germinal centers, with the unifying feature being an increase in IgG4+ plasma cells on immunostaining. The nature and pathogenesis of IgG4-related sclerosing disease are still elusive. Occasionally, the disease can be complicated by the development of malignant lymphoma and possibly carcinoma.
血清免疫球蛋白 G4（IgG4）浓度升高是新近被描述的 IgG4 相关硬化性疾病的替代标志物，而 IgG4 是 IgG 的四个亚型中最少见的（3%至 6%）。该综合征主要影响中老年患者，以男性为主。患者表现为 1 个或多个部位受累的症状，通常表现为肿块病变。其典型表现为 IgG4 相关硬化性胰腺炎（也称为自身免疫性胰腺炎），最常见的表现为无痛性阻塞性黄疸，伴或不伴胰腺肿块。其他常见受累部位为肝胆道、唾液腺、眼眶和淋巴结，但实际上任何器官部位都可能受累，如腹膜后腔、主动脉、纵隔、软组织、皮肤、中枢神经系统、乳腺、肾脏、前列腺、上呼吸道和肺。患者通常一般情况良好，无发热或全身症状。常见的实验室检查结果包括血清球蛋白、IgG、IgG4 和 IgE 升高，而乳酸脱氢酶通常不升高。部分患者有低滴度的自身抗体（如抗核抗体和类风湿因子）。该疾病通常对类固醇治疗有良好的反应。随着时间的推移，疾病的特征是多部位受累的发展，有时在多年后。然而，在一些患者中，疾病可能仍然局限于 1 个部位。各种结外部位的主要病理发现包括淋巴浆细胞浸润、淋巴滤泡形成、硬化和闭塞性静脉炎，伴有受累组织的萎缩和特定结构的丧失（如胰腺、唾液腺或泪腺的分泌腺）。淋巴浆细胞和硬化成分的相对优势导致 3 种组织学模式：假淋巴瘤样、混合和硬化。免疫组化显示受累组织中 IgG4+细胞增多（>高倍镜视野 50 个，IgG4/IgG 比值>40%）。淋巴结显示多中心 Castleman 病样特征、反应性滤泡增生、滤泡间扩张或生发中心进行性转化，其统一特征是免疫组化显示 IgG4+浆细胞增多。IgG4 相关硬化性疾病的性质和发病机制仍不清楚。偶尔，疾病可并发恶性淋巴瘤和可能的癌。
