Castelli Roberto, Wu Maddalena Alessandra, Arquati Massimo, Zanichelli Andrea, Suffritti Chiara, Rossi Davide, Cicardi Marco
Department of Biomedical and Clinical Sciences Luigi Sacco, Luigi Sacco Hospital Milan, University of Milan, Milan, Italy.
Division of Haematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
Br J Haematol. 2016 Mar;172(6):902-8. doi: 10.1111/bjh.13908. Epub 2016 Jan 5.
Marginal zone lymphoma represents about 10% of all non-Hodgkin lymphomas (NHLs). 33% of patients with acquired angioedema (AAE) due to acquired C1-inhibitor (C1-INH) deficiency (C1-INH-AAE) have or will develop NHLs. C1-INH-AAE is a rare condition. We report the follow-up of 72 C1-INH-AAE patients, followed for a median of 15 years (range 1-24). Median age was 71 (range 64-79) years; median age at onset of angioedema symptoms was 57·5 (range 50-66) years and it was 63 [range 45-80) years at diagnosis]. Twenty patients were diagnosed with low-grade non-follicular B-cell lymphomas (75% were splenic MZL), one with follicular and three with high-grade lymphomas (two diffuse large B-cell lymphomas and one mantle cell lymphoma). Fifteen NHLs were diagnosed at onset of AAE or thereafter (3 months to 7 years), eight had already been diagnosed at onset of angioedema. Two of 24 patients remain on watchful wait. Thirthen of 24 received chemotherapy, two received rituximab. Three underwent splenectomy. All 18 patients receiving therapy for NHL experienced post-treatment reduction in AAE symptoms. Our study suggests that clonal B-cell proliferation is the pathology underlying AAE leading to production of C1-INH-neutralizing autoantibodies and to NHLs. The post-germinal centre origin of NHL suggests that immune stimulation may contribute to lymphomagenesis.
边缘区淋巴瘤约占所有非霍奇金淋巴瘤（NHL）的10%。33%因获得性C1抑制物（C1-INH）缺乏导致获得性血管性水肿（AAE）（C1-INH-AAE）的患者患有或将会发生NHL。C1-INH-AAE是一种罕见疾病。我们报告了72例C1-INH-AAE患者的随访情况，随访时间中位数为15年（范围1 - 24年）。年龄中位数为71岁（范围64 - 79岁）；血管性水肿症状出现时的年龄中位数为57.5岁（范围50 - 66岁），诊断时为63岁（范围45 - 80岁）。20例患者被诊断为低级别非滤泡性B细胞淋巴瘤（75%为脾边缘区淋巴瘤），1例为滤泡性淋巴瘤，3例为高级别淋巴瘤（2例弥漫性大B细胞淋巴瘤和1例套细胞淋巴瘤）。15例NHL在AAE发病时或之后（3个月至7年）被诊断出来，8例在血管性水肿发病时就已被诊断。24例患者中有2例仍在观察等待。24例中有13例接受了化疗，2例接受了利妥昔单抗治疗。3例接受了脾切除术。所有18例接受NHL治疗的患者在治疗后AAE症状减轻。我们的研究表明，克隆性B细胞增殖是AAE的病理基础，导致产生C1-INH中和性自身抗体并引发NHL。NHL生发中心后起源提示免疫刺激可能促成淋巴瘤发生。
