EMANUELE(ZUCCA((BELLINZONA)(
(
MARGINAL(ZONE(LYMPHOMA(
(
Oncology(Institute(of(Southern(Switzerland,(and(Institute(of(Oncology(Research,(Università(della(
Svizzera(Italiana,(Bellinzona,(Switzerland(
(
The!marginal!zone!B>cell!lymphoma!(MZL)!comprises!the!extranodal!MZL!(EMZL)!of!mucosa>
associated! lymphoid! tissue! (MALT! lymphoma),! the! splenic! (SMZL)! and! the! nodal! MZL!
(NMZL).!MALT!lymphoma!is!a!rare!indolent!non>Hodgkin!lymphoma!originating!from!B>cells!
lymphocytes!of!marginal!zone!of!which!is!the!most!common!subtype!accounting!of!5>8%!of!
all! B>cell! Lymphoma.! MALT! lymphoma! growth! is! driven! by! the! sustained! antigenic!
stimulation! associated! with! chronic! inflammation! processes,! either! infections! or!
autoimmune! disorders,! which! may! contribute! to! B>cell! genetic! damage.! Indeed,! recurrent!
genetic! alterations! (including! the! chromosomal! translocations,! t! (11;18),! t(1;! 14),! and!
t(14;18)!and!mutations!of!the!TNFAIP3!gene)!that!lead!to!constitutive!activation!of!the!NFKB!
pathway! have! been! described! in! MALT! lymphomas.! Along! with! deregulation! of! NFKB,!
trisomies! of! chromosomes! 3! and! 18,! deletions! at! 6q23,! and! deregulation! of! chromatin!
remodeling!genes!are!also!frequent!events!in!all!the!three!MZLs,!which!differ!in!the!presence!
of!recurrent!translocations,!mutations!affecting!the!NOTCH!pathway,!and!the!transcription!
factor!KLF2!or!the!PTPRD!tyrosine!phosphatase.!!
!
The!stomach!is!the!most!common!site,!followed!by!ocular!adnexa,!lung!and!salivary!glands.!
Gastric!MALT!lymphoma!pathogenesis!has!been!incontrovertibly!associated!with!the!chronic!
gastritis!induced!by!Helicobacter(pylori((HP).!HP!eradication!is!the!standard!initial!treatment!
for! gastric! MZL! and! leads! to! a! sustained! lymphoma! regression! in! 75%! of! cases.! Sequential!
gastroscopies!with!multiple!gastric!biopsies!remain!an!essential!follow>up!procedure!and!the!
GELA!histological!score!is!recommended!for!response!evaluation.!!
!
Despite!abundant!literature!showing!that!the!eradication!of!Helicobacter!pylori!can!be!the!
sole! initial! treatment! of! most! patients! with! localized! gastric! MALT! lymphoma,! there! is! no!
consensus! on! the! optimal! treatment! of! patients! with! gastric! involvement! requiring!
subsequent!treatment!or!those!with!extensive!disease.!!
!
Retrospective! series! including! patients! with! various! sites! of! MALT! lymphoma! treated! with!
surgery,!radiotherapy!and!chemotherapy,!alone!or!in!combination,!have!shown!good!disease!
control!and!excellent!cause>specific!and!overall!survival!in!most!patients,!regardless!of!the!
treatment!modality!used.!!
!
In! patients! who! failed! antibiotics! therapy,! intermediate! dose! radiotherapy! can! be! curative!
and! is! the! preferred! option! in! most! cases! of! localized! EMZL.! Systemic! treatment! with!
immunotherapy! or! combination! of! immunochemotherapy! is! indicated! in! patients! with!
symptomatic! disseminated! disease,! contraindication! of! RT! or! suspicion! of! histological!
transformation.!!
The!IELSG19!randomized!trial!of!EMZL!has!demonstrated!a!superior!efficacy!of!Rituximab!in!
combination! with! Chlorambucil! over! Rituximab! or! Chlorambucil! alone! in! terms! of! EFS! and!
PFS.!