Novel developments in the pathogenesis and diagnosis of extranodal marginal zone lymphoma

Thieblemont C (2005) Clinical presentation and management of marginal zone lymphomas. Hematology Am Soc Hematol Educ Program 307–313. https://doi.org/10.1182/asheducation-2005.1.307 Du MQ (2016) MALT lymphoma: a paradigm of NF-kappaB dysregulation. Semin Cancer Biol 39:49–60. https://doi.org/10.1016/j.semcancer.2016.07.003 Zucca E, Bertoni F, Vannata B, Cavalli F (2014) Emerging role of infectious etiologies in the pathogenesis of marginal zone B-cell lymphomas. Clin Cancer Res: Off J Am Assoc Cancer Res 20(20):5207–5216. https://doi.org/10.1158/1078-0432.CCR-14-0496 Olszewski AJ, Castillo JJ (2013) Survival of patients with marginal zone lymphoma: analysis of the surveillance, epidemiology, and end results database. Cancer 119(3):629–638. https://doi.org/10.1002/cncr.27773 Meyer AH, Stroux A, Lerch K, Eucker J, Eitle J, Hohloch K, Andrzejak M, Possinger K, Dorken B, Pezzutto A, Scholz CW (2014) Transformation and additional malignancies are leading risk factors for an adverse course of disease in marginal zone lymphoma. Ann Oncol: Off J Eur Soc Med Oncol/ESMO 25(1):210–215. https://doi.org/10.1093/annonc/mdt507 Sretenovic M, Colovic M, Jankovic G, Suvajdzic N, Mihaljevic B, Colovic N, Todorovic M, Atkinson HD (2009) More than a third of non-gastric malt lymphomas are disseminated at diagnosis: a single center survey. Eur J Haematol 82(5):373–380. https://doi.org/10.1111/j.1600-0609.2009.01217.x Thieblemont C, Berger F, Dumontet C, Moullet I, Bouafia F, Felman P, Salles G, Coiffier B (2000) Mucosa-associated lymphoid tissue lymphoma is a disseminated disease in one third of 158 patients analyzed. Blood 95(3):802–806 Bertoni F, Cazzaniga G, Bosshard G, Roggero E, Barbazza R, De Boni M, Capella C, Pedrinis E, Cavalli F, Biondi A, Zucca E (1997) Immunoglobulin heavy chain diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process. Br J Haematol 97(4):830–836 Craig VJ, Arnold I, Gerke C, Huynh MQ, Wundisch T, Neubauer A, Renner C, Falkow S, Muller A (2010) Gastric MALT lymphoma B cells express polyreactive, somatically mutated immunoglobulins. Blood 115(3):581–591. https://doi.org/10.1182/blood-2009-06-228015 Wohrer S, Troch M, Streubel B, Zwerina J, Skrabs C, Formanek M, Hauff W, Hoffmann M, Mullauer L, Chott A, Raderer M (2007) MALT lymphoma in patients with autoimmune diseases: a comparative analysis of characteristics and clinical course. Leukemia 21(8):1812–1818. https://doi.org/10.1038/sj.leu.2404782 Ekstrom Smedby K, Vajdic CM, Falster M, Engels EA, Martinez-Maza O, Turner J, Hjalgrim H, Vineis P, Seniori Costantini A, Bracci PM, Holly EA, Willett E, Spinelli JJ, La Vecchia C, Zheng T, Becker N, De Sanjose S, Chiu BC, Dal Maso L, Cocco P, Maynadie M, Foretova L, Staines A, Brennan P, Davis S, Severson R, Cerhan JR, Breen EC, Birmann B, Grulich AE, Cozen W (2008) Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. Blood 111(8):4029–4038. https://doi.org/10.1182/blood-2007-10-119974 Luminari S, Cesaretti M, Marcheselli L, Rashid I, Madrigali S, Maiorana A, Federico M (2010) Decreasing incidence of gastric MALT lymphomas in the era of anti-Helicobacter pylori interventions: results from a population-based study on extranodal marginal zone lymphomas. Ann Oncol: Off J Eur Soc Med Oncol/ESMO 21(4):855–859. https://doi.org/10.1093/annonc/mdp402 Hussell T, Isaacson PG, Crabtree JE, Spencer J (1993) The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet 342(8871):571–574 Munari F, Lonardi S, Cassatella MA, Doglioni C, Cangi MG, Amedei A, Facchetti F, Eishi Y, Rugge M, Fassan M, de Bernard M, D'Elios MM, Vermi W (2011) Tumor-associated macrophages as major source of APRIL in gastric MALT lymphoma. Blood 117(24):6612–6616. https://doi.org/10.1182/blood-2010-06-293266 Wang HP, Zhu YL, Shao W (2013) Role of Helicobacter pylori virulence factor cytotoxin-associated gene A in gastric mucosa-associated lymphoid tissue lymphoma. World J Gastroenterol 19(45):8219–8226. https://doi.org/10.3748/wjg.v19.i45.8219 Tohidpour A (2016) CagA-mediated pathogenesis of Helicobacter pylori. Microb Pathog 93:44–55. https://doi.org/10.1016/j.micpath.2016.01.005 Lin WC, Tsai HF, Kuo SH, Wu MS, Lin CW, Hsu PI, Cheng AL, Hsu PN (2010) Translocation of Helicobacter pylori CagA into human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma. Cancer Res 70(14):5740–5748. https://doi.org/10.1158/0008-5472.CAN-09-4690 Selbach M, Moese S, Hauck CR, Meyer TF, Backert S (2002) Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo. J Biol Chem 277(9):6775–6778. https://doi.org/10.1074/jbc.C100754200 Poppe M, Feller SM, Romer G, Wessler S (2007) Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility. Oncogene 26(24):3462–3472. https://doi.org/10.1038/sj.onc.1210139 Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M, Hatakeyama M (2002) SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 295(5555):683–686. https://doi.org/10.1126/science.1067147 Zhu Y, Wang C, Huang J, Ge Z, Dong Q, Zhong X, Su Y, Zheng S (2007) The Helicobacter pylori virulence factor CagA promotes Erk1/2-mediated bad phosphorylation in lymphocytes: a mechanism of CagA-inhibited lymphocyte apoptosis. Cell Microbiol 9(4):952–961. https://doi.org/10.1111/j.1462-5822.2006.00843.x Kuo SH, Chen LT, Lin CW, Yeh KH, Shun CT, Tzeng YS, Liou JM, Wu MS, Hsu PN, Cheng AL (2016) Expressions of the CagA protein and CagA-signaling molecules predict H. pylori-dependence of early-stage gastric DLBCL. Blood. https://doi.org/10.1182/blood-2016-04-713719 Buti L, Spooner E, Van der Veen AG, Rappuoli R, Covacci A, Ploegh HL (2011) Helicobacter pylori cytotoxin-associated gene A (CagA) subverts the apoptosis-stimulating protein of p53 (ASPP2) tumor suppressor pathway of the host. Proc Natl Acad Sci U S A 108(22):9238–9243. https://doi.org/10.1073/pnas.1106200108 Umehara S, Higashi H, Ohnishi N, Asaka M, Hatakeyama M (2003) Effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma. Oncogene 22(51):8337–8342. https://doi.org/10.1038/sj.onc.1207028 Ohmae T, Hirata Y, Maeda S, Shibata W, Yanai A, Ogura K, Yoshida H, Kawabe T, Omata M (2005) Helicobacter pylori activates NF-kappaB via the alternative pathway in B lymphocytes. J Immunol 175(11):7162–7169 Haesebrouck F, Pasmans F, Flahou B, Smet A, Vandamme P, Ducatelle R (2011) Non-Helicobacter pylori Helicobacter species in the human gastric mucosa: a proposal to introduce the terms H. heilmannii sensu lato and sensu stricto. Helicobacter 16(4):339–340. https://doi.org/10.1111/j.1523-5378.2011.00849.x Bento-Miranda M, Figueiredo C (2014) Helicobacter heilmannii sensu lato: an overview of the infection in humans. World J Gastroenterol 20(47):17779–17787. https://doi.org/10.3748/wjg.v20.i47.17779 Stolte M, Bayerdorffer E, Morgner A, Alpen B, Wundisch T, Thiede C, Neubauer A (2002) Helicobacter and gastric MALT lymphoma. Gut 50(Suppl 3):III19–III24 Ferreri AJ, Guidoboni M, Ponzoni M, De Conciliis C, Dell’Oro S, Fleischhauer K, Caggiari L, Lettini AA, Dal Cin E, Ieri R, Freschi M, Villa E, Boiocchi M, Dolcetti R (2004) Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 96(8):586–594 Ferreri AJ, Ponzoni M, Guidoboni M, Resti AG, Politi LS, Cortelazzo S, Demeter J, Zallio F, Palmas A, Muti G, Dognini GP, Pasini E, Lettini AA, Sacchetti F, De Conciliis C, Doglioni C, Dolcetti R (2006) Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a multicenter prospective trial. J Natl Cancer Inst 98(19):1375–1382. https://doi.org/10.1093/jnci/djj373 Chanudet E, Zhou Y, Bacon CM, Wotherspoon AC, Muller-Hermelink HK, Adam P, Dong HY, de Jong D, Li Y, Wei R, Gong X, Wu Q, Ranaldi R, Goteri G, Pileri SA, Ye H, Hamoudi RA, Liu H, Radford J, Du MQ (2006) Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions. J Pathol 209(3):344–351. https://doi.org/10.1002/path.1984 Daibata M, Nemoto Y, Togitani K, Fukushima A, Ueno H, Ouchi K, Fukushi H, Imai S, Taguchi H (2006) Absence of Chlamydia psittaci in ocular adnexal lymphoma from Japanese patients. Br J Haematol 132(5):651–652. https://doi.org/10.1111/j.1365-2141.2005.05943.x Rosado MF, Byrne GE Jr, Ding F, Fields KA, Ruiz P, Dubovy SR, Walker GR, Markoe A, Lossos IS (2006) Ocular adnexal lymphoma: a clinicopathologic study of a large cohort of patients with no evidence for an association with Chlamydia psittaci. Blood 107(2):467–472. https://doi.org/10.1182/blood-2005-06-2332 Husain A, Roberts D, Pro B, McLaughlin P, Esmaeli B (2007) Meta-analyses of the association between Chlamydia psittaci and ocular adnexal lymphoma and the response of ocular adnexal lymphoma to antibiotics. Cancer 110(4):809–815. https://doi.org/10.1002/cncr.22843 Ponzoni M, Ferreri AJ, Guidoboni M, Lettini AA, Cangi MG, Pasini E, Sacchi L, Pecciarini L, Grassi S, Dal Cin E, Stefano R, Magnino S, Dolcetti R, Doglioni C (2008) Chlamydia infection and lymphomas: association beyond ocular adnexal lymphomas highlighted by multiple detection methods. Clin Cancer Res: Off J Am Assoc Cancer Res 14(18):5794–5800. https://doi.org/10.1158/1078-0432.CCR-08-0676 Dingle KE, Van Den Braak N, Colles FM, Price LJ, Woodward DL, Rodgers FG, Endtz HP, Van Belkum A, Maiden MC (2001) Sequence typing confirms that Campylobacter jejuni strains associated with Guillain-Barre and Miller-Fisher syndromes are of diverse genetic lineage, serotype, and flagella type. J Clin Microbiol 39(9):3346–3349 Lecuit M, Abachin E, Martin A, Poyart C, Pochart P, Suarez F, Bengoufa D, Feuillard J, Lavergne A, Gordon JI, Berche P, Guillevin L, Lortholary O (2004) Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med 350(3):239–248. https://doi.org/10.1056/NEJMoa031887 Ben-Ayed F, Halphen M, Najjar T, Boussene H, Jaafoura H, Bouguerra A, Ben Salah N, Mourali N, Ayed K, Ben Khalifa H et al (1989) Treatment of alpha chain disease. Results of a prospective study in 21 Tunisian patients by the Tunisian-French Intestinal Lymphoma Study Group. Cancer 63(7):1251–1256 Goodlad JR, Davidson MM, Hollowood K, Ling C, MacKenzie C, Christie I, Batstone PJ, Ho-Yen DO (2000) Primary cutaneous B-cell lymphoma and Borrelia burgdorferi infection in patients from the highlands of Scotland. Am J Surg Pathol 24(9):1279–1285 Cerroni L, Zochling N, Putz B, Kerl H (1997) Infection by Borrelia burgdorferi and cutaneous B-cell lymphoma. J Cutan Pathol 24(8):457–461 Ponzoni M, Ferreri AJ, Mappa S, Pasini E, Govi S, Facchetti F, Fanoni D, Tucci A, Vino A, Doglioni C, Berti E, Dolcetti R (2011) Prevalence of Borrelia burgdorferi infection in a series of 98 primary cutaneous lymphomas. Oncologist 16(11):1582–1588. https://doi.org/10.1634/theoncologist.2011-0108 de la Fouchardiere A, Vandenesch F, Berger F (2003) Borrelia-associated primary cutaneous MALT lymphoma in a nonendemic region. Am J Surg Pathol 27(5):702–703 Adam P, Czapiewski P, Colak S, Kosmidis P, Tousseyn T, Sagaert X, Boudova L, Okon K, Morresi-Hauf A, Agostinelli C, Pileri S, Pruneri G, Martinelli G, Du MQ, Fend F (2014) Prevalence of Achromobacter xylosoxidans in pulmonary mucosa-associated lymphoid tissue lymphoma in different regions of Europe. Br J Haematol 164(6):804–810. https://doi.org/10.1111/bjh.12703 Luppi M, Longo G, Ferrari MG, Ferrara L, Marasca R, Barozzi P, Morselli M, Emilia G, Torelli G (1996) Additional neoplasms and HCV infection in low-grade lymphoma of MALT type. Br J Haematol 94(2):373–375 Michot JM, Canioni D, Driss H, Alric L, Cacoub P, Suarez F, Sibon D, Thieblemont C, Dupuis J, Terrier B, Feray C, Tilly H, Pol S, Leblond V, Settegrana C, Rabiega P, Barthe Y, Hendel-Chavez H, Nguyen-Khac F, Merle-Beral H, Berger F, Molina T, Charlotte F, Carrat F, Davi F, Hermine O, Besson C, Group AH-L-CS (2015) Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B-cell non-Hodgkin lymphomas, ANRS HC-13 lympho-C study. Am J Hematol 90(3):197–203. https://doi.org/10.1002/ajh.23889 Marcucci F, Mele A (2011) Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities. Blood 117(6):1792–1798. https://doi.org/10.1182/blood-2010-06-275818 Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM (2000) Clinical evolution, and morbidity and mortality of primary Sjogren’s syndrome. Semin Arthritis Rheum 29(5):296–304 Papageorgiou A, Voulgarelis M, Tzioufas AG (2015) Clinical picture, outcome and predictive factors of lymphoma in Sjgren syndrome. Autoimmun Rev 14(7):641–649. https://doi.org/10.1016/j.autrev.2015.03.004 Ambrosetti A, Zanotti R, Pattaro C, Lenzi L, Chilosi M, Caramaschi P, Arcaini L, Pasini F, Biasi D, Orlandi E, D'Adda M, Lucioni M, Pizzolo G (2004) Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection. Br J Haematol 126(1):43–49. https://doi.org/10.1111/j.1365-2141.2004.04993.x Brito-Zeron P, Kostov B, Fraile G, Caravia-Duran D, Maure B, Rascon FJ, Zamora M, Casanovas A, Lopez-Dupla M, Ripoll M, Pinilla B, Fonseca E, Akasbi M, de la Red G, Duarte-Millan MA, Fanlo P, Guisado-Vasco P, Perez-Alvarez R, Chamorro AJ, Morcillo C, Jimenez-Heredia I, Sanchez-Berna I, Lopez-Guillermo A, Ramos-Casals M, GEAS-SEMI SSSG (2017) Characterization and risk estimate of cancer in patients with primary Sjogren syndrome. J Hematol Oncol 10(1):90. https://doi.org/10.1186/s13045-017-0464-5 Streubel B, Huber D, Wohrer S, Chott A, Raderer M (2004) Frequency of chromosomal aberrations involving MALT1 in mucosa-associated lymphoid tissue lymphoma in patients with Sjogren’s syndrome. Clin Cancer R: Off J Am Assoc Cancer Res 10(2):476–480 Papageorgiou A, Mavragani CP, Nezos A, Zintzaras E, Quartuccio L, De Vita S, Koutsilieris M, Tzioufas AG, Moutsopoulos HM, Voulgarelis M (2015) A BAFF receptor His159Tyr mutation in Sjogren’s syndrome-related lymphoproliferation. Arthritis Rheumatol 67(10):2732–2741. https://doi.org/10.1002/art.39231 Nocturne G, Boudaoud S, Miceli-Richard C, Viengchareun S, Lazure T, Nititham J, Taylor KE, Ma A, Busato F, Melki J, Lessard CJ, Sivils KL, Dubost JJ, Hachulla E, Gottenberg JE, Lombes M, Tost J, Criswell LA, Mariette X (2013) Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjogren's syndrome. Blood 122(25):4068–4076. https://doi.org/10.1182/blood-2013-05-503383 Ellis GL (2007) Lymphoid lesions of salivary glands: malignant and benign. Med Oral Patol Oral Cir Bucal 12(7):E479–E485 Carbone A, Gloghini A, Ferlito A (2000) Pathological features of lymphoid proliferations of the salivary glands: lymphoepithelial sialadenitis versus low-grade B-cell lymphoma of the malt type. Ann Otology Rhinol Laryngol 109(12 Pt 1):1170–1175 Pedersen RK, Pedersen NT (1996) Primary non-Hodgkin’s lymphoma of the thyroid gland: a population based study. Histopathology 28(1):25–32 Ahmed R, Al-Shaikh S, Akhtar M (2012) Hashimoto thyroiditis: a century later. Adv Anat Pathol 19(3):181–186. https://doi.org/10.1097/PAP.0b013e3182534868 Chistiakov DA (2005) Immunogenetics of Hashimoto’s thyroiditis. J Autoimmune Dis 2(1):1. https://doi.org/10.1186/1740-2557-2-1 Streubel B, Simonitsch-Klupp I, Mullauer L, Lamprecht A, Huber D, Siebert R, Stolte M, Trautinger F, Lukas J, Puspok A, Formanek M, Assanasen T, Muller-Hermelink HK, Cerroni L, Raderer M, Chott A (2004) Variable frequencies of MALT lymphoma-associated genetic aberrations in MALT lymphomas of different sites. Leukemia 18(10):1722–1726. https://doi.org/10.1038/sj.leu.2403501 Brynes RK, Almaguer PD, Leathery KE, McCourty A, Arber DA, Medeiros LJ, Nathwani BN (1996) Numerical cytogenetic abnormalities of chromosomes 3, 7, and 12 in marginal zone B-cell lymphomas. Mod Pathol 9(10):995–1000 Wotherspoon AC, Finn TM, Isaacson PG (1995) Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. Blood 85(8):2000–2004 Hoeve MA, Gisbertz IA, Schouten HC, Schuuring E, Bot FJ, Hermans J, Hopman A, Kluin PM, Arends JW, van Krieken JH (1999) Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy. Leukemia 13(5):799–807 Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer MJ (1999) Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell 96(1):35–45 Streubel B, Lamprecht A, Dierlamm J, Cerroni L, Stolte M, Ott G, Raderer M, Chott A (2003) T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood 101(6):2335–2339. https://doi.org/10.1182/blood-2002-09-2963 Auer IA, Gascoyne RD, Connors JM, Cotter FE, Greiner TC, Sanger WG, Horsman DE (1997) t(11;18)(q21;q21) is the most common translocation in MALT lymphomas. Ann Oncol 8(10):979–985 Ott G, Katzenberger T, Greiner A, Kalla J, Rosenwald A, Heinrich U, Ott MM, Muller-Hermelink HK (1997) The t(11;18)(q21;q21) chromosome translocation is a frequent and specific aberration in low-grade but not high-grade malignant non-Hodgkin’s lymphomas of the mucosa-associated lymphoid tissue (MALT-) type. Cancer Res 57(18):3944–3948 Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott A (2005) T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. Leukemia 19(4):652–658. https://doi.org/10.1038/sj.leu.2403644 Wlodarska I, Veyt E, De Paepe P, Vandenberghe P, Nooijen P, Theate I, Michaux L, Sagaert X, Marynen P, Hagemeijer A, De Wolf-Peeters C (2005) FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations. Leukemia 19(8):1299–1305. https://doi.org/10.1038/sj.leu.2403813 Liu H, Ye H, Ruskone-Fourmestraux A, De Jong D, Pileri S, Thiede C, Lavergne A, Boot H, Caletti G, Wundisch T, Molina T, Taal BG, Elena S, Thomas T, Zinzani PL, Neubauer A, Stolte M, Hamoudi RA, Dogan A, Isaacson PG, Du MQ (2002) T(11;18) is a marker for all stage gastric MALT lymphomas that will not respond to H. pylori eradication. Gastroenterology 122(5):1286–1294 Liu H, Ruskon-Fourmestraux A, Lavergne-Slove A, Ye H, Molina T, Bouhnik Y, Hamoudi RA, Diss TC, Dogan A, Megraud F, Rambaud JC, Du MQ, Isaacson PG (2001) Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy. Lancet 357(9249):39–40. https://doi.org/10.1016/S0140-6736(00)03571-6 Du MQ (2011) MALT lymphoma: many roads lead to nuclear factor-kappab activation. Histopathology 58(1):26–38. https://doi.org/10.1111/j.1365-2559.2010.03699.x van Keimpema M, Gruneberg LJ, Mokry M, van Boxtel R, Koster J, Coffer PJ, Pals ST, Spaargaren M (2014) FOXP1 directly represses transcription of proapoptotic genes and cooperates with NF-kappaB to promote survival of human B cells. Blood 124(23):3431–3440. https://doi.org/10.1182/blood-2014-01-553412 Green MR, Gandhi MK, Courtney MJ, Marlton P, Griffiths L (2009) Relative abundance of full-length and truncated FOXP1 isoforms is associated with differential NFkappaB activity in follicular lymphoma. Leuk Res 33(12):1699–1702. https://doi.org/10.1016/j.leukres.2009.05.004 Goatly A, Bacon CM, Nakamura S, Ye H, Kim I, Brown PJ, Ruskone-Fourmestraux A, Cervera P, Streubel B, Banham AH, Du MQ (2008) FOXP1 abnormalities in lymphoma: translocation breakpoint mapping reveals insights into deregulated transcriptional control. Mod Pathol 21(7):902–911. https://doi.org/10.1038/modpathol.2008.74 Rouhigharabaei L, Finalet Ferreiro J, Tousseyn T, van der Krogt JA, Put N, Haralambieva E, Graux C, Maes B, Vicente C, Vandenberghe P, Cools J, Wlodarska I (2014) Non-IG aberrations of FOXP1 in B-cell malignancies lead to an aberrant expression of N-truncated isoforms of FOXP1. PLoS One 9(1):e85851. https://doi.org/10.1371/journal.pone.0085851 Ye H, Remstein ED, Bacon CM, Nicholson AG, Dogan A, Du MQ (2008) Chromosomal translocations involving BCL6 in MALT lymphoma. Haematologica 93(1):145–146. https://doi.org/10.3324/haematol.11927 Ansell SM, Akasaka T, McPhail E, Manske M, Braggio E, Price-Troska T, Ziesmer S, Secreto F, Fonseca R, Gupta M, Law M, Witzig TE, Dyer MJ, Dogan A, Cerhan JR, Novak AJ (2012) t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth. Blood 120(19):3949–3957. https://doi.org/10.1182/blood-2011-11-389908 Baens M, Finalet Ferreiro J, Tousseyn T, Urbankova H, Michaux L, de Leval L, Dierickx D, Wolter P, Sagaert X, Vandenberghe P, De Wolf-Peeters C, Wlodarska I (2012) t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34. Haematologica 97(2):184–188. https://doi.org/10.3324/haematol.2011.052639 Vinatzer U, Gollinger M, Mullauer L, Raderer M, Chott A, Streubel B (2008) Mucosa-associated lymphoid tissue lymphoma: novel translocations including rearrangements of ODZ2, JMJD2C, and CNN3. Clin Cancer Res: Off J Am Assoc Cancer Res 14(20):6426–6431. https://doi.org/10.1158/1078-0432.CCR-08-0702 Kim WS, Honma K, Karnan S, Tagawa H, Kim YD, Oh YL, Seto M, Ko YH (2007) Genome-wide array-based comparative genomic hybridization of ocular marginal zone B cell lymphoma: comparison with pulmonary and nodal marginal zone B cell lymphoma. Genes, Chromosom Cancer 46(8):776–783. https://doi.org/10.1002/gcc.20463 Honma K, Tsuzuki S, Nakagawa M, Karnan S, Aizawa Y, Kim WS, Kim YD, Ko YH, Seto M (2008) TNFAIP3 is the target gene of chromosome band 6q23.3-q24.1 loss in ocular adnexal marginal zone B cell lymphoma. Genes Chromosom Cancer 47(1):1–7. https://doi.org/10.1002/gcc.20499 Chanudet E, Ye H, Ferry J, Bacon CM, Adam P, Muller-Hermelink HK, Radford J, Pileri SA, Ichimura K, Collins VP, Hamoudi RA, Nicholson AG, Wotherspoon AC, Isaacson PG, Du MQ (2009) A20 deletion is associated with copy number gain at the TNFA/B/C locus and occurs preferentially in translocation-negative MALT lymphoma of the ocular adnexa and salivary glands. J Pathol 217(3):420–430. https://doi.org/10.1002/path.2466 Kwee I, Rancoita PM, Rinaldi A, Ferreri AJ, Bhagat G, Gascoyne RD, Canzonieri V, Gaidano G, Doglioni C, Zucca E, Ponzoni M, Bertoni F (2011) Genomic profiles of MALT lymphomas: variability across anatomical sites. Haematologica 96(7):1064–1066. https://doi.org/10.3324/haematol.2011.040402 Go JH, Yang WI, Ree HJ (2001) Mutational analysis of the 5′ noncoding region of the bcl-6 gene in primary gastric lymphomas. Mod Pathol 14(5):410–414. https://doi.org/10.1038/modpathol.3880327 Deutsch AJ, Fruhwirth M, Aigelsreiter A, Cerroni L, Neumeister P (2009) Primary cutaneous marginal zone B-cell lymphomas are targeted by aberrant somatic hypermutation. J Investig Dermatol 129(2):476–479. https://doi.org/10.1038/jid.2008.243 Deutsch AJ, Aigelsreiter A, Staber PB, Beham A, Linkesch W, Guelly C, Brezinschek RI, Fruhwirth M, Emberger W, Buettner M, Beham-Schmid C, Neumeister P (2007) MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation. Blood 109(8):3500–3504. https://doi.org/10.1182/blood-2006-06-030494 Yan Q, Wang M, Moody S, Xue X, Huang Y, Bi Y, Du MQ (2013) Distinct involvement of NF-kappaB regulators by somatic mutation in ocular adnexal malt lymphoma. Br J Haematol 160(6):851–854. https://doi.org/10.1111/bjh.12162 Li ZM, Rinaldi A, Cavalli A, Mensah AA, Ponzoni M, Gascoyne RD, Bhagat G, Zucca E, Bertoni F (2012) MYD88 somatic mutations in MALT lymphomas. Br J Haematol 158(5):662–664. https://doi.org/10.1111/j.1365-2141.2012.09176.x Johansson P, Klein-Hitpass L, Grabellus F, Arnold G, Klapper W, Pfortner R, Duhrsen U, Eckstein A, Durig J, Kuppers R (2016) Recurrent mutations in NF-kappaB pathway components, KMT2D, and NOTCH1/2 in ocular adnexal MALT-type marginal zone lymphomas. Oncotarget. https://doi.org/10.18632/oncotarget.11548 Du MQ, Peng H, Liu H, Hamoudi RA, Diss TC, Willis TG, Ye H, Dogan A, Wotherspoon AC, Dyer MJ, Isaacson PG (2000) BCL10 gene mutation in lymphoma. Blood 95(12):3885–3890 Jung H, Yoo HY, Lee SH, Shin S, Kim SC, Lee S, Joung JG, Nam JY, Ryu D, Yun JW, Choi JK, Ghosh A, Kim KK, Kim SJ, Kim WS, Park WY, Ko YH (2017) The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP. Oncotarget 8(10):17038–17049. https://doi.org/10.18632/oncotarget.14928 Oeckinghaus A, Ghosh S (2009) The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 1(4):a000034. https://doi.org/10.1101/cshperspect.a000034 Motshwene PG, Moncrieffe MC, Grossmann JG, Kao C, Ayaluru M, Sandercock AM, Robinson CV, Latz E, Gay NJ (2009) An oligomeric signaling platform formed by the Toll-like receptor signal transducers MyD88 and IRAK-4. J Biol Chem 284(37):25404–25411. https://doi.org/10.1074/jbc.M109.022392 Rosebeck S, Rehman AO, Lucas PC, McAllister-Lucas LM (2011) From MALT lymphoma to the CBM signalosome: three decades of discovery. Cell Cycle 10(15):2485–2496. https://doi.org/10.4161/cc.10.15.16923 Kanayama A, Seth RB, Sun L, Ea CK, Hong M, Shaito A, Chiu YH, Deng L, Chen ZJ (2004) TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Mol Cell 15(4):535–548. https://doi.org/10.1016/j.molcel.2004.08.008 Jaworski M, Thome M (2016) The paracaspase MALT1: biological function and potential for therapeutic inhibition. Cell Mol Life Sci: CMLS 73(3):459–473. https://doi.org/10.1007/s00018-015-2059-z Afonina IS, Elton L, Carpentier I, Beyaert R (2015) MALT1—a universal soldier: multiple strategies to ensure NF-kappaB activation and target gene expression. FEBS J 282(17):3286–3297. https://doi.org/10.1111/febs.13325 Chanudet E, Huang Y, Ichimura K, Dong G, Hamoudi RA, Radford J, Wotherspoon AC, Isaacson PG, Ferry J, Du MQ (2010) A20 is targeted by promoter methylation, deletion and inactivating mutation in MALT lymphoma. Leukemia 24(2):483–487. https://doi.org/10.1038/leu.2009.234 Elton L, Carpentier I, Staal J, Driege Y, Haegman M, Beyaert R (2016) MALT1 cleaves the E3 ubiquitin ligase HOIL-1 in activated T cells, generating a dominant negative inhibitor of LUBAC-induced NF-kappaB signaling. FEBS J 283(3):403–412. https://doi.org/10.1111/febs.13597 Klein T, Fung SY, Renner F, Blank MA, Dufour A, Kang S, Bolger-Munro M, Scurll JM, Priatel JJ, Schweigler P, Melkko S, Gold MR, Viner RI, Regnier CH, Turvey SE, Overall CM (2015) The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-kappaB signalling. Nat Commun 6:8777. https://doi.org/10.1038/ncomms9777 Rosebeck S, Lim MS, Elenitoba-Johnson KS, McAllister-Lucas LM, Lucas PC (2016) API2-MALT1 oncoprotein promotes lymphomagenesis via unique program of substrate ubiquitination and proteolysis. World J Biol Chem 7(1):128–137. https://doi.org/10.4331/wjbc.v7.i1.128 Stoffel A, Le Beau MM (2001) The API2/MALT1 fusion product may lead to germinal center B cell lymphomas by suppression of apoptosis. Human Hered 51(1-2):1–7 Dierlamm J, Baens M, Wlodarska I, Stefanova-Ouzounova M, Hernandez JM, Hossfeld DK, De Wolf-Peeters C, Hagemeijer A, Van den Berghe H, Marynen P (1999) The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas. Blood 93(11):3601–3609 Rosebeck S, Madden L, Jin X, Gu S, Apel IJ, Appert A, Hamoudi RA, Noels H, Sagaert X, Van Loo P, Baens M, Du MQ, Lucas PC, McAllister-Lucas LM (2011) Cleavage of NIK by the API2-MALT1 fusion oncoprotein leads to noncanonical NF-kappaB activation. Science 331(6016):468–472. https://doi.org/10.1126/science.1198946 Nie Z, Du MQ, McAllister-Lucas LM, Lucas PC, Bailey NG, Hogaboam CM, Lim MS, Elenitoba-Johnson KS (2015) Conversion of the LIMA1 tumour suppressor into an oncogenic LMO-like protein by API2-MALT1 in MALT lymphoma. Nat Commun 6:5908. https://doi.org/10.1038/ncomms6908 Conconi A, Franceschetti S, Aprile von Hohenstaufen K, Margiotta-Casaluci G, Stathis A, Moccia AA, Bertoni F, Ramponi A, Mazzucchelli L, Cavalli F, Gaidano G, Zucca E (2015) Histologic transformation in marginal zone lymphomasdagger. Ann Oncol 26(11):2329–2335. https://doi.org/10.1093/annonc/mdv368 Zucca E, Conconi A, Pedrinis E, Cortelazzo S, Motta T, Gospodarowicz MK, Patterson BJ, Ferreri AJ, Ponzoni M, Devizzi L, Giardini R, Pinotti G, Capella C, Zinzani PL, Pileri S, Lopez-Guillermo A, Campo E, Ambrosetti A, Baldini L, Cavalli F, International Extranodal Lymphoma Study G (2003) Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood 101(7):2489–2495. https://doi.org/10.1182/blood-2002-04-1279 Maeshima AM, Taniguchi H, Toyoda K, Yamauchi N, Makita S, Fukuhara S, Munakata W, Maruyama D, Kobayashi Y, Tobinai K (2016) Clinicopathological features of histological transformation from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue to diffuse large B-cell lymphoma: an analysis of 467 patients. Br J Haematol 174(6):923–931. https://doi.org/10.1111/bjh.14153 Schreuder MI, Hoeve MA, Hebeda KM, Verdijk MA, Ligtenberg MJ, Bot FJ, Chott A, van Krieken JH (2003) Mutual exclusion of t(11;18)(q21;q21) and numerical chromosomal aberrations in the development of different types of primary gastric lymphomas. Br J Haematol 123(4):590–599 Starostik P, Patzner J, Greiner A, Schwarz S, Kalla J, Ott G, Muller-Hermelink HK (2002) Gastric marginal zone B-cell lymphomas of MALT type develop along 2 distinct pathogenetic pathways. Blood 99(1):3–9 Toracchio S, Ota H, de Jong D, Wotherspoon A, Rugge M, Graham DY, Samani A, El-Zimaity HM (2009) Translocation t(11;18)(q21;q21) in gastric B-cell lymphomas. Cancer Sci 100(5):881–887. https://doi.org/10.1111/j.1349-7006.2009.01128.x Huang X, Zhang Z, Liu H, Ye H, Chuang SS, Wang J, Lin S, Gao Z, Du MQ (2003) t(11;18)(q21;q21) in gastric MALT lymphoma and diffuse large B-cell lymphoma of Chinese patients. Hematol J 4(5):342–345. https://doi.org/10.1038/sj.thj.6200295 Du M, Peng H, Singh N, Isaacson PG, Pan L (1995) The accumulation of p53 abnormalities is associated with progression of mucosa-associated lymphoid tissue lymphoma. Blood 86(12):4587–4593 Neumeister P, Hoefler G, Beham-Schmid C, Schmidt H, Apfelbeck U, Schaider H, Linkesch W, Sill H (1997) Deletion analysis of the p16 tumor suppressor gene in gastrointestinal mucosa-associated lymphoid tissue lymphomas. Gastroenterology 112(6):1871–1875 Chen YW, Liang AC, Au WY, Chu KM, Wong KY, Hu X, Lu L, Tang JC, Chan KW, Beh SL, Kwong YL, Liang RH, Srivastava G (2003) Multiple BCL6 translocation partners in individual cases of gastric lymphoma. Blood 102(5):1931–1932; author reply 1932. https://doi.org/10.1182/blood-2003-06-1786 Liang R, Chan WP, Kwong YL, Xu WS, Srivastava G, Ho FC (1997) High incidence of BCL-6 gene rearrangement in diffuse large B-cell lymphoma of primary gastric origin. Cancer Genet Cytogenet 97(2):114–118 Flossbach L, Antoneag E, Buck M, Siebert R, Mattfeldt T, Moller P, Barth TF (2011) BCL6 gene rearrangement and protein expression are associated with large cell presentation of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Int J Cancer 129(1):70–77. https://doi.org/10.1002/ijc.25663 Sonoki T, Harder L, Horsman DE, Karran L, Taniguchi I, Willis TG, Gesk S, Steinemann D, Zucca E, Schlegelberger B, Sole F, Mungall AJ, Gascoyne RD, Siebert R, Dyer MJ (2001) Cyclin D3 is a target gene of t(6;14)(p21.1;q32.3) of mature B-cell malignancies. Blood 98(9):2837–2844 Huang W, Guo L, Liu H, Zheng B, Ying J, Lv N (2014) C-MYC overexpression predicts aggressive transformation and a poor outcome in mucosa-associated lymphoid tissue lymphomas. Int J Clin Exp Pathol 7(9):5634–5644 Sagaert X, de Paepe P, Libbrecht L, Vanhentenrijk V, Verhoef G, Thomas J, Wlodarska I, De Wolf-Peeters C (2006) Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 24(16):2490–2497. https://doi.org/10.1200/JCO.2006.05.6150 Deutsch AJ, Steinbauer E, Hofmann NA, Strunk D, Gerlza T, Beham-Schmid C, Schaider H, Neumeister P (2013) Chemokine receptors in gastric MALT lymphoma: loss of CXCR4 and upregulation of CXCR7 is associated with progression to diffuse large B-cell lymphoma. Mod Pathol 26(2):182–194. https://doi.org/10.1038/modpathol.2012.134 Kanellis G, Roncador G, Arribas A, Mollejo M, Montes-Moreno S, Maestre L, Campos-Martin Y, Rios Gonzalez JL, Martinez-Torrecuadrada JL, Sanchez-Verde L, Pajares R, Cigudosa JC, Martin MC, Piris MA (2009) Identification of MNDA as a new marker for nodal marginal zone lymphoma. Leukemia 23(10):1847–1857. https://doi.org/10.1038/leu.2009.108 Metcalf RA, Monabati A, Vyas M, Roncador G, Gualco G, Bacchi CE, Younes SF, Natkunam Y, Freud AG (2014) Myeloid cell nuclear differentiation antigen is expressed in a subset of marginal zone lymphomas and is useful in the differential diagnosis with follicular lymphoma. Hum Pathol 45(8):1730–1736. https://doi.org/10.1016/j.humpath.2014.04.004 Falini B, Agostinelli C, Bigerna B, Pucciarini A, Pacini R, Tabarrini A, Falcinelli F, Piccioli M, Paulli M, Gambacorta M, Ponzoni M, Tiacci E, Ascani S, Martelli MP, Dalla Favera R, Stein H, Pileri SA (2012) IRTA1 is selectively expressed in nodal and extranodal marginal zone lymphomas. Histopathology 61(5):930–941. https://doi.org/10.1111/j.1365-2559.2012.04289.x Ikeda JI, Kohara M, Tsuruta Y, Nojima S, Tahara S, Ohshima K, Kurashige M, Wada N, Morii E (2017) Immunohistochemical analysis of the novel marginal zone B-cell marker IRTA1 in malignant lymphoma. Hum Pathol 59:70–79. https://doi.org/10.1016/j.humpath.2016.09.011 Ye H, Gong L, Liu H, Hamoudi RA, Shirali S, Ho L, Chott A, Streubel B, Siebert R, Gesk S, Martin-Subero JI, Radford JA, Banerjee S, Nicholson AG, Ranaldi R, Remstein ED, Gao Z, Zheng J, Isaacson PG, Dogan A, Du MQ (2005) MALT lymphoma with t(14;18)(q32;q21)/IGH-MALT1 is characterized by strong cytoplasmic MALT1 and BCL10 expression. J Pathol 205(3):293–301. https://doi.org/10.1002/path.1715 Sagaert X, Laurent M, Baens M, Wlodarska I, De Wolf-Peeters C (2006) MALT1 and BCL10 aberrations in MALT lymphomas and their effect on the expression of BCL10 in the tumour cells. Mod Pathol 19(2):225–232. https://doi.org/10.1038/modpathol.3800523 van Krieken JH, Langerak AW, Macintyre EA, Kneba M, Hodges E, Sanz RG, Morgan GJ, Parreira A, Molina TJ, Cabecadas J, Gaulard P, Jasani B, Garcia JF, Ott M, Hannsmann ML, Berger F, Hummel M, Davi F, Bruggemann M, Lavender FL, Schuuring E, Evans PA, White H, Salles G, Groenen PJ, Gameiro P, Pott C, Dongen JJ (2007) Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia 21(2):201–206. https://doi.org/10.1038/sj.leu.2404467 Evans PA, Pott C, Groenen PJ, Salles G, Davi F, Berger F, Garcia JF, van Krieken JH, Pals S, Kluin P, Schuuring E, Spaargaren M, Boone E, Gonzalez D, Martinez B, Villuendas R, Gameiro P, Diss TC, Mills K, Morgan GJ, Carter GI, Milner BJ, Pearson D, Hummel M, Jung W, Ott M, Canioni D, Beldjord K, Bastard C, Delfau-Larue MH, van Dongen JJ, Molina TJ, Cabecadas J (2007) Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia 21(2):207–214. https://doi.org/10.1038/sj.leu.2404479 van Maldegem F, Wormhoudt TA, Mulder MM, Oud ME, Schilder-Tol E, Musler AR, Aten J, Saeed P, Kersten MJ, Pals ST, van Noesel CJ, Bende RJ (2012) Chlamydia psittaci-negative ocular adnexal marginal zone B-cell lymphomas have biased VH4-34 immunoglobulin gene expression and proliferate in a distinct inflammatory environment. Leukemia 26(7):1647–1653. https://doi.org/10.1038/leu.2012.28 Miklos JA, Swerdlow SH, Bahler DW (2000) Salivary gland mucosa-associated lymphoid tissue lymphoma immunoglobulin V(H) genes show frequent use of V1-69 with distinctive CDR3 features. Blood 95(12):3878–3884 Michaeli M, Tabibian-Keissar H, Schiby G, Shahaf G, Pickman Y, Hazanov L, Rosenblatt K, Dunn-Walters DK, Barshack I, Mehr R (2014) Immunoglobulin gene repertoire diversification and selection in the stomach—from gastritis to gastric lymphomas. Front Immunol 5:264. https://doi.org/10.3389/fimmu.2014.00264 Schreuder MI, Hoefnagel JJ, Jansen PM, van Krieken JH, Willemze R, Hebeda KM (2005) FISH analysis of MALT lymphoma-specific translocations and aneuploidy in primary cutaneous marginal zone lymphoma. J Pathol 205(3):302–310. https://doi.org/10.1002/path.1711 Ventura RA, Martin-Subero JI, Jones M, McParland J, Gesk S, Mason DY, Siebert R (2006) FISH analysis for the detection of lymphoma-associated chromosomal abnormalities in routine paraffin-embedded tissue. J Mol Diagn: JMD 8(2):141–151. https://doi.org/10.2353/jmoldx.2006.050083 Dierlamm J, Baens M, Stefanova-Ouzounova M, Hinz K, Wlodarska I, Maes B, Steyls A, Driessen A, Verhoef G, Gaulard P, Hagemeijer A, Hossfeld DK, De Wolf-Peeters C, Marynen P (2000) Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLT specific probes. Blood 96(6):2215–2218 Remstein ED, Kurtin PJ, James CD, Wang XY, Meyer RG, Dewald GW (2002) Mucosa-associated lymphoid tissue lymphomas with t(11;18)(q21;q21) and mucosa-associated lymphoid tissue lymphomas with aneuploidy develop along different pathogenetic pathways. Am J Pathol 161(1):63–71. https://doi.org/10.1016/S0002-9440(10)64157-0 Inagaki H, Okabe M, Seto M, Nakamura S, Ueda R, Eimoto T (2001) API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphoma: multiplex RT-PCR detection using formalin-fixed paraffin-embedded specimens. Am J Pathol 158(2):699–706. https://doi.org/10.1016/S0002-9440(10)64012-6 Schreuder MI, Hoeve MA, Groothuis L, Boot H, Boerrigter LH, de Jong D, Veenendaal RA, Jansen JH, van Krieken JH (2005) Monitoring gastric lymphoma in peripheral blood by quantitative IgH allele-specific oligonucleotide real-time PCR and API2-MALT1 PCR. Br J Haematol 131(5):619–623. https://doi.org/10.1111/j.1365-2141.2005.05807.x Ferreri AJ, Govi S, Pasini E, Mappa S, Bertoni F, Zaja F, Montalban C, Stelitano C, Cabrera ME, Giordano Resti A, Politi LS, Doglioni C, Cavalli F, Zucca E, Ponzoni M, Dolcetti R (2012) Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial. J Clin Oncol Off J Am Soc Clin Oncol 30(24):2988–2994. https://doi.org/10.1200/JCO.2011.41.4466 Wundisch T, Thiede C, Morgner A, Dempfle A, Gunther A, Liu H, Ye H, Du MQ, Kim TD, Bayerdorffer E, Stolte M, Neubauer A (2005) Long-term follow-up of gastric MALT lymphoma after Helicobacter pylori eradication. J Clin Oncol: Off J Am Soci Clin Oncol 23(31):8018–8024. https://doi.org/10.1200/JCO.2005.02.3903 Zullo A, Hassan C, Cristofari F, Andriani A, De Francesco V, Ierardi E, Tomao S, Stolte M, Morini S, Vaira D (2010) Effects of Helicobacter pylori eradication on early stage gastric mucosa-associated lymphoid tissue lymphoma. Clin Gastroenterol Hepatol 8(2):105–110. https://doi.org/10.1016/j.cgh.2009.07.017 Nakamura S, Sugiyama T, Matsumoto T, Iijima K, Ono S, Tajika M, Tari A, Kitadai Y, Matsumoto H, Nagaya T, Kamoshida T, Watanabe N, Chiba T, Origasa H, Asaka M, Group JGS (2012) Long-term clinical outcome of gastric MALT lymphoma after eradication of Helicobacter pylori: a multicentre cohort follow-up study of 420 patients in Japan. Gut 61(4):507–513. https://doi.org/10.1136/gutjnl-2011-300495 Gong EJ, Ahn JY, Jung HY, Park H, Ko YB, Na HK, Jung KW, Kim DH, Lee JH, Choi KD, Song HJ, Lee GH, Kim JH (2016) Helicobacter pylori eradication therapy is effective as the initial treatment for patients with H. pylori -negative and disseminated gastric mucosa-associated lymphoid tissue lymphoma. Gut Liver. https://doi.org/10.5009/gnl15510 Raderer M, Jager G, Brugger S, Puspok A, Fiebiger W, Drach J, Wotherspoon A, Chott A (2003) Rituximab for treatment of advanced extranodal marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue lymphoma. Oncology 65(4):306–310 Kiesewetter B, Troch M, Dolak W, Mullauer L, Lukas J, Zielinski CC, Raderer M (2013) A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma). Haematologica 98(3):353–356. https://doi.org/10.3324/haematol.2012.065995 ZuccaE, ConconiA, MartinelliG, BouabdallahR, TucciA, VitoloU, MartelliM, PettengellR, SallesG, SebbanC, GuillermoAL, PinottiG, DevizziL, MorschhauserF, TillyH, TorriV, HohausS, FerreriAJ, ZacheeP, BoslyA, HaiounC, StelitanoC, BelleiM, PonzoniM, Copie-BergmanC, JackA, CampoE, MazzucchelliL, CavalliF, JohnsonP, ThieblemontC (2017) Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. Journal of Clinical Oncology: official journal of the American Society of Clinical Oncology:JCO2016706994. doi:https://doi.org/10.1200/JCO.2016.70.6994 Kiesewetter B, Willenbacher E, Willenbacher W, Egle A, Neumeister P, Voskova D, Mayerhoefer ME, Simonitsch-Klupp I, Melchardt T, Greil R, Raderer M (2016) A phase II study of rituximab plus lenalidomide for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). Blood. https://doi.org/10.1182/blood-2016-06-720599 Rosenthal A, Dueck AC, Ansell S, Gano K, Conley C, Nowakowski GS, Camoriano J, Leis JF, Mikhael JR, Keith Stewart A, Inwards D, Dingli D, Kumar S, Noel P, Gertz M, Porrata L, Russell S, Colgan J, Fonseca R, Habermann TM, Kapoor P, Buadi F, Leung N, Tiedemann R, Witzig TE, Reeder C (2017) A phase 2 study of lenalidomide, rituximab, cyclophosphamide, and dexamethasone (LR-CD) for untreated low-grade non-Hodgkin lymphoma requiring therapy. Am J Hematol 92(5):467–472. https://doi.org/10.1002/ajh.24693 Conconi A, Raderer M, Franceschetti S, Devizzi L, Ferreri AJ, Magagnoli M, Arcaini L, Zinzani PL, Martinelli G, Vitolo U, Kiesewetter B, Porro E, Stathis A, Gaidano G, Cavalli F, Zucca E (2014) Clinical activity of everolimus in relapsed/refractory marginal zone B-cell lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group. Br J Haematol 166(1):69–76. https://doi.org/10.1111/bjh.12845 Chen R, Frankel P, Popplewell L, Siddiqi T, Ruel N, Rotter A, Thomas SH, Mott M, Nathwani N, Htut M, Nademanee A, Forman SJ, Kirschbaum M (2015) A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma. Haematologica 100(3):357–362. https://doi.org/10.3324/haematol.2014.117473 Kirschbaum MH, Goldman BH, Zain JM, Cook JR, Rimsza LM, Forman SJ, Fisher RI (2012) A phase 2 study of vorinostat for treatment of relapsed or refractory Hodgkin lymphoma: Southwest Oncology Group Study S0517. Leuk Lymphoma 53(2):259–262. https://doi.org/10.3109/10428194.2011.608448 Conconi A, Martinelli G, Lopez-Guillermo A, Zinzani PL, Ferreri AJ, Rigacci L, Devizzi L, Vitolo U, Luminari S, Cavalli F, Zucca E, International Extranodal Lymphoma Study G (2011) Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG). Ann Oncol 22(3):689–695. https://doi.org/10.1093/annonc/mdq416 Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH (2013) Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol: Off J Am Soc Clin Oncol 31(1):88–94. https://doi.org/10.1200/JCO.2012.42.7906 Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, Collins GP, Ma S, Coleman M, Peles S, Smith S, Barrientos JC, Smith A, Munneke B, Dimery I, Beaupre DM, Chen R (2017) Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood 129(16):2224–2232. https://doi.org/10.1182/blood-2016-10-747345 Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA (2014) PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med 370(11):1008–1018. https://doi.org/10.1056/NEJMoa1314583 Ferch U, Kloo B, Gewies A, Pfander V, Duwel M, Peschel C, Krappmann D, Ruland J (2009) Inhibition of MALT1 protease activity is selectively toxic for activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 206(11):2313–2320. https://doi.org/10.1084/jem.20091167 Fontan L, Yang C, Kabaleeswaran V, Volpon L, Osborne MJ, Beltran E, Garcia M, Cerchietti L, Shaknovich R, Yang SN, Fang F, Gascoyne RD, Martinez-Climent JA, Glickman JF, Borden K, Wu H, Melnick A (2012) MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivo. Cancer Cell 22(6):812–824. https://doi.org/10.1016/j.ccr.2012.11.003 Nagel D, Spranger S, Vincendeau M, Grau M, Raffegerst S, Kloo B, Hlahla D, Neuenschwander M, Peter von Kries J, Hadian K, Dorken B, Lenz P, Lenz G, Schendel DJ, Krappmann D (2012) Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL. Cancer Cell 22(6):825–837. https://doi.org/10.1016/j.ccr.2012.11.002