摘要： 研究背景 IgG4 相关性疾病为新近定义的自身免疫性疾病类型，主要临床特征为多器官受累和血清IgG4 水平升高。可发生于垂体，且部分患者表现为孤立性鞍区肿物和（或）垂体柄增粗，由于缺乏特征性影像学表现，若无血清IgG4 水平异常之证据，术前明确诊断困难且易误诊为垂体腺瘤。方法与结果 男性患者，47 岁，临床主要表现为四肢乏力、性功能减退；血清睾酮、皮质醇、卵泡刺激素和黄体生成素均低于正常值范围。头部MRI显示鞍内、鞍上巨大肿物，增强后病灶均匀强化。临床拟诊为垂体腺瘤，手术大部分切除。光学显微镜观察肿物主要为腺垂体，腺泡萎缩、数目减少，间质内可见大量淋巴浆细胞浸润，伴广泛性纤维组织增生、玻璃样变，未见明确的垂体腺瘤结构；边缘可见多灶性合体样细胞巢团，但胞核异型性不明显。免疫组织化学染色，淋巴浆细胞并非肿瘤性单克隆性增生，但IgG4阳性浆细胞数目> 30 个/高倍视野且IgG4+/IgG+ > 40%。合体样细胞巢团波形蛋白、上皮膜抗原和孕激素受体表达阳性；血清IgG4 为2.93 g/L。明确诊断为IgG4 相关性垂体炎伴鞍区脑膜反应。术后予泼尼松35 mg/d 持续治疗2 周，减至30 mg/d 维持治疗，临床症状明显改善，血清IgG4 降至正常水平，鞍区肿物体积明显缩小。结论 IgG4相关性垂体炎缺乏特征性影像学表现，其组织学与非特异性炎症性病变相似，术前明确诊断和鉴别诊断困难。血清IgG4水平升高是明确诊断的重要线索和依据。

关键词: 免疫球蛋白G, 垂体, 自身免疫疾病, 病理学, 免疫组织化学

Abstract: Background  Immunoglobulin G4 (IgG4)-related disease is a recently characterized autoimmune disease entity marked by elevated serum IgG4 levels and tissue infiltration by IgG4-positive plasma cells in multiple involved organs. Hypophysitis is a rare inflammatory disorder and IgG4-related sclerosing disease involving the ituitary alone is especially rare. Imaging studies may reveal a mass lesion in the sellar area or a thickening of pituitary stalk, mimicking a pituitary tumor. Due to its rarity and non-specific appearance in radiological examination, it is a diagnostic challenge for clinicians and histopathologists to differentiate solitary IgG4-related hypophysitis from other pituitary lesions. The aim of this study is to summarize the clinicopathological features of unusual IgG4-related hypophysitis and discuss the differential diagnosis of histologically similar inflammatory lesions in pituitary. Methods The clinical manifestation of a patient with solitary IgG4-related hypophysitis was presented retrospectively. Resected mass was routinely paraffin-embedded and stained with Hematoxylin and Eosin. Dako EnVision immunohistochemical staining system was used to detect the tumor antigen expressions, including vimentin (Vim), S-100 protein (S-100), pan cytokeratin (PCK), epithelial membrane antigen (EMA), CD3, CD20, CD68, CD1a, κ-light chain, λ-light chain and progestrone receptor (PR).  Results  A 47-year-old male patient presented with 1-year history of mild limb weakness and hyposexuality. Laboratory examination revealed hypopituitarism with low levels of serum testosterone, cortisol, luteinizing hormone (LH) and follicle stimulating hormone (FSH), although his serum IgG4 level was high. MRI of the pituitary gland revealed a mass lesion in the sellar area with T₁WI mild hyperintense and homogeneous enhancement after gadolinium administration. The patient underwent a transsphenoidal mass resection of the pituitary gland. Histological examination showed bland appearing spindle cell proliferation in the sclerotic background with marked infiltration of lymphocytes, plasma cells, as well as multiple foci of meningothelial-like nodules at the periphery of tissues. Immunohistochemical staining showed that the lymphocytes were positive for CD3 and CD20. Plasma cells were distinct and the number of κ and λ-light chains was the same. There were more than 30 IgG4-positive plasma cells per high power field (HPF), which accounted for greater than 40% of the IgG-positive plasma cells. The meningothelial-like nodules were positive for Vim, EMA and PR, but negative for CD68, S-100 and CD1a. A final histological diagnosis of IgG4-related hypophysitis with meningothelial reaction was made. The patient took prednisolone orally at 35 mg/d for 2 weeks, and the symptoms of limb weakness and hyposexuality showed improvement. The mass lesion of pituitary gland demonstrated a reduction in size. The prednisolone therapy was continued at a dose of 30 mg/d to prevent recurrence of IgG4-related disease.  Conclusions  IgG4-related hypophysitis is a rare disease of central nervous system with good response to corticosteroid treatment. Due to the relative paucity of reported cases and similarities in histological findings, it may be difficult to differentiate IgG4-related disease from other pituitary lesions with prominent inflammatory cell infiltration and stromal fibrosis. Thorough inspection under the microscopy and more importantly elevated serum IgG4 level are necessary for correct diagnosis.

Key words: Immunoglobulin G, Pituitary gland, Autoimmune diseases, Pathology, Immunohistochemistry