the! presence! of! reactive! GCs! favors! NMZL,! while! a! monotonous! proliferation! of! small!
lymphocytes,!plasma!cells,!increased!mast!cells!and!patent!sinuses!characterize!the!LPL.!In!
extranodal!sites,!in!particular!on!bone!marrow!biopsy!(BMB),!LPL!could!mimic!SMZL;!residual!
reactive!GCs,!paratrabecular!neoplastic!aggregates!and!the!prevalence!of!monocytoid!cells!
suggest!a!diagnosis!of!EMZL.!A!prominent!plasma!cell!differentiation!may!be!confusing!since!
none! of! these! entities! have! a! pathognomonic! immunophenotype! and! may! sometimes!
closely! resemble! extramedullary! plasmacytoma.! The! MYD88! L265P! mutation! helps! in! the!
differentiation,!occurring!in!90%!of!LPL!while!it!is!uncommon!in!MZLs.!Differentiation!from!
mantle!cell!lymphoma!(MCL)!has!to!be!considered!in!cases!with!monocytoid!appearance!or!
small! size! of! neoplastic! cells.! An! insidious! pitfall! is! the! leukemic,! non>nodal! MCL! entity,!
presenting! with! PB! and! splenic! involvement! without! lymphadenopathy;! herein,! diagnosis!
relies! upon! BMB.! CLL>like! small! cells! characterize! these! cases,! with! variable! expression! of!
CD5!and!SOX11!negativity.!!
SMZLs!and!SLL>u!share!a!similar!immunophenotype!but!a!different!pattern!of!infiltration!of!
the!splenic!parenchyma.!Differentiation!between!these!entities!becomes!a!challenge!when,!
as! often! happens,! the! spleen! is! not! available.! This! distinction! is! not! feasible! by! BMB!
histopathological! and! immunophenotypic! criteria! alone! and! requires! adequate! integration!
with!morphological,!flow!cytometry!data!on!PB!and!BM,!and!clinical!features.!!
Finally,!the!definition!of!transformation!of!MZL!into!DLBCL!may!be!sometimes!problematic.!
Centroblastic>like! cells! are! more! often! non>GC! type! (63%).! The! current! criteria! require! the!
presence!of!sheets!of!large!cells!to!establish!a!diagnosis!of!DLBCL.!The!actual!problem!relies!
on!cut>off!values!of!large!cells!to!define!a!sheet.!Some!Authors!agree!on!the!presence!of!at!
least!30%!of!large!cells.!B>symptoms,!increased!LDH!levels!and!radiological!correlations!are!
very!helpful!as!well.!!
!
References:(
> Swerdlow! SH,! et! al.! WHO! Classification! of! tumors! of! hematopoieticand! lymphoid! tissues.!
Revised!4th!ed.!IARC!2017.!
> Nakamura! S.,! Ponzoni! M.! Marginal! zone! B>cell! lymphomas:! lessons! from! Western! and!
Eastern!diagnostic!approaches.!Pathology!2020;!52:!15>29!
> Ponzoni!M,!Ferreri!AJ.!Bacteria!associated!with!marginal!zone!lymphomas.!Best!Pract!Res!Clin!
Haematol!2017;30:32>40.!
> Gachard!N,!Parrens!M,!Soubeyran!I,!D!et!al.!IGHV!gene!features!and!MYD88!L265P!mutation!
separate! the! three! marginal! zone! lymphoma! entities! and! Waldenström!
macroglobulinemia/lymphoplasmacytic!lymphomas.!Leukemia!2013;27:183>9.!
> Traverse>Glehen!A,!Baseggio!L,!Bauchu!EC,!et!al.!Splenic!red!pulp!lymphoma!with!numerous!
basophilic! villous! lymphocytes:! a! distinct! clinicopathologic! and! molecular! entity?! Blood!
2008;111:2253>60.!
> Ponzoni! M,! Kanellis! G,! Pouliou! E,! et! al.! Bone! marrow! histopathology! in! the! diagnostic!
evaluation! of! splenic! marginal>zone! and! splenic! diffuse! red! pulp! small! B>cell! lymphoma:! a!
reliable!substitute!for!spleen!histopathology?!Am!J!Surg!Pathol!2012;36:1609>18.!
> Maeshima! AM,! Taniguchi! H,! Toyoda! K,! et! al.! 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.2016;174:923>31.!
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