Medical Oncology

, 35:118 | Cite as

Splenic marginal zone lymphomas in acquired C1-inhibitor deficiency: clinical and molecular characterization

  • Matteo Sbattella
  • Andrea Zanichelli
  • Paolo Ghia
  • Valter Gattei
  • Chiara Suffritti
  • Thomas Teatini
  • Marco Cicardi
  • Roberto CastelliEmail author
Short Communication


Angioedema due to acquired deficiency of the inhibitor of the first component of complement (C1-INH) is a rare disease known as acquired angioedema (AAE). About 70% of patients with AEE display autoantibodies to C1-INH, the remaining patients have no antibodies to C1-INH. The clinical features of C1-INH deficiency include recurrent, self-limiting local swellings involving the skin, the gastrointestinal tract, and the upper respiratory tract. Swelling is due to accumulation of bradykinin released from high molecular weight kininogen. Patients with angioedema due to acquired C1 inhibitor deficiency (AEE) often have an associated lymphoproliferative disease including Non-Hodgkin Lymphomas (NHL). Among AAE patients with NHL, splenic marginal zone lymphoma (SMZL) has a higher prevalence (66%) compared to general population (2%) In the present study, we focused on patients with SMZL in AAE. We found 24 AAE patients with NHL and, among them 15 SMZL (62.5% of all NHL). We found NOTCH 2 activation in 4 /15 patients (26.6%) with SMZL, while no patients carried MYD 88 or BIRC3 mutations. Restricted immunoglobulin gene repertoire analysis showed that the IGHV1-2*04 allele was found to be over-represented in the group of patients with or without lymphoproliferative disease presenting with autoantibodies to C1-INH (41 of 55 (75%) of patients; p value 0.011) when compared to the control group of patients with AEE without antibodies to C1-INH, (7 of 27 (26%) of patients). Immunophenotyping failed to demonstrate the presence of autoreactive clones against C1-inhibitor. Taken together, these findings suggest a role for antigenic stimulation in the pathogenesis of lymphomas associated with AEE.


Acquired angioedema (AAE) Lymphoproliferative disease Splenic marginal zone lymphoma (SMZL) NOTCH2 mutation Restricted immunoglobulin gene repertoire analysis 


Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individuals participants included in the study.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biomedical and Clinical Sciences Luigi SaccoUniversity of Milan, Luigi Sacco Hospital MilanMilanItaly
  2. 2.Division of Experimental OncologyUniversity Vita-Salute San Raffaele and IRCCS San Raffaele Scientific Institute MilanMilanItaly
  3. 3.Clinical and Experimental Onco-Hematology UnitCRO Aviano National Cancer Institute IRCCSAvianoItaly

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