Zoshima Takeshi, Yamada Kazunori, Hara Satoshi, Mizushima Ichiro, Yamagishi Masakazu, Harada Kenichi, Sato Yasuharu, Kawano Mitsuhiro
*Department of Internal Medicine, Division of Rheumatology †Department of Internal Medicine, Division of Cardiology ‡Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa §Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Am J Surg Pathol. 2016 Apr;40(4):495-501. doi: 10.1097/PAS.0000000000000575.
Multicentric Castleman disease is a benign lymphoproliferative disorder with heterogenous clinical symptoms and involves systemic organs in addition to lymph nodes. Elevated serum IgG4 levels and IgG4-positive plasma cell (IgG4+PC) infiltrates have been reported in lymph nodes, lung and skin in some multicentric Castleman disease cases, resembling IgG4-related disease (IgG4-RD) histologically. However, no report has been available regarding IgG4+PC infiltration in the kidneys of multicentric Castleman disease. Here, we report 2 cases of multicentric Castleman disease complicated by IgG4-related disease (IgG4-RD) histologically. However, there has been no report published on PC-rich tubulointerstitial nephritis, lymphadenopathy, with numerous IgG4+PC infiltration, and elevated serum IgG4 levels, mimicking IgG4-RD. The blood examinations revealed systemic inflammation and elevated C-reactive protein and interleukin-6 levels. Corticosteroid therapy was partially effective in both cases, and combination therapy of corticosteroid and tocilizumab was needed in both cases. Moreover, after triple therapy with corticosteroid, rituximab and cyclophosphamide were used in 1 case to tame the severe inflammation. The present cases suggest that if continuously elevated serum C-reactive protein levels and partial corticosteroid responsiveness are encountered, multicentric Castleman disease should be considered rather than IgG4-RD as a differential diagnosis even if serum IgG4 is elevated and IgG4+PCs infiltrate systemic organs.
多中心Castleman病是一种具有异质性临床症状的良性淋巴增殖性疾病,除淋巴结外还累及全身器官。在一些多中心Castleman病病例中,已报道其淋巴结、肺和皮肤中血清IgG4水平升高以及IgG4阳性浆细胞(IgG4+PC)浸润,在组织学上类似于IgG4相关疾病(IgG4-RD)。然而,关于多中心Castleman病肾脏中IgG4+PC浸润尚无报道。在此,我们报告2例组织学上合并IgG4相关疾病(IgG4-RD)的多中心Castleman病病例。然而,尚无关于富含浆细胞的肾小管间质性肾炎、淋巴结病,伴有大量IgG4+PC浸润以及血清IgG4水平升高,酷似IgG4-RD的报道。血液检查显示全身炎症以及C反应蛋白和白细胞介素-6水平升高。皮质类固醇治疗在两例中均部分有效,两例均需要皮质类固醇与托珠单抗联合治疗。此外,在1例中使用皮质类固醇、利妥昔单抗和环磷酰胺三联疗法来控制严重炎症。目前的病例表明,如果遇到血清C反应蛋白水平持续升高以及对皮质类固醇部分反应的情况,即使血清IgG4升高且IgG4+PC浸润全身器官,在鉴别诊断时也应考虑多中心Castleman病而非IgG4-RD。