title: High prevalence of splenic marginal zone lymphoma among patients with acquired C1 inhibitor deficiency.
abstract: 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.
authors.affiliation: Department of Biomedical and Clinical Sciences Luigi Sacco, Luigi Sacco Hospital Milan, University of Milan, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Castelli
authors.affiliation: Department of Biomedical and Clinical Sciences Luigi Sacco, Luigi Sacco Hospital Milan, University of Milan, Milan, Italy.
authors.forename: Maddalena Alessandra
authors.initials: MA
authors.lastname: Wu
authors.affiliation: Department of Biomedical and Clinical Sciences Luigi Sacco, Luigi Sacco Hospital Milan, University of Milan, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Arquati
authors.affiliation: Department of Biomedical and Clinical Sciences Luigi Sacco, Luigi Sacco Hospital Milan, University of Milan, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanichelli
authors.affiliation: Department of Biomedical and Clinical Sciences Luigi Sacco, Luigi Sacco Hospital Milan, University of Milan, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Suffritti
authors.affiliation: Division of Haematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Department of Biomedical and Clinical Sciences Luigi Sacco, Luigi Sacco Hospital Milan, University of Milan, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cicardi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000799:Angioedema / Q000209:etiology; D054179:Angioedemas, Hereditary / Q000150:complications*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D013160:Splenic Neoplasms / Q000188:drug therapy / Q000209:etiology*
keywords: Non Hodgkin Lymphoma; Splenic marginal zone lymphomas; acquired angioedema; antigen-driven lymphomagenesis; indolent non-follicular NHL