STEFANO(PILERI((MILAN)(
(
DIAGNOSTICS(
THE(BOUNDARIES(OF(HODGKIN(LYMPHOMA(
(
Stefano( A.( Pileri,( Professor( of( Pathology,( Director( of( the( Haematopathology( Division,( European(
Institute(of(Oncology(>(IEO(IRCCS,(435(Ripamonti(Street,(20121(Milan((Italy)(
!
The! boundaries! of! Hodgkin! lymphoma! (HL)! are! not! always! sharp! and! problems! in! the!
differential!diagnosis!do!exist!for!both!the!lymphocyte!predominant!and!classical!forms.!The!
former!should!be!differentiated!from!T>cell/histiocyte>rich!large!B>cell!lymphoma,!the!latter!
from!diffuse!large!B>cell!lymphoma!(DLBCL).!The!second!situation!is!much!more!frequently!
encountered,!this!having!led!to!the!recognition!of!the!category!of!B>cell,!unclassifiable,!with!
features! intermediate! between! diffuse! large! B>cell! lymphoma! classical! Hodgkin! lymphoma!
(CHL)! in! the! Revised! 4th! Edition! of! the! WHO! Classification! Tissues! (1).! An! example! of! such!
condition!will!be!presented!and!discussed.!
The!case!refers!to!a!26>year>old!male,!who!presented!with!a!bulky!mediastinal!mass!eroding!
the!thoracic!wall!and!supra>diaphragmatic!lymphadenopathies,!the!largest!in!the!right!axilla!
measuring!7!cm>across.!At!PET!scan,!the!SUV!was!homogeneously!high!(maximum!16.9).!The!
right!axillary!lymph!node!was!removed!and!originally!diagnosed!as!CHL,!nodular!sclerosing!
type.! The! case! came! to! our! Division! in! second! opinion.! On! microscopic! examination,! the!
normal! lymph! node! structure! was! obscured! by! a! nodular! growth.! The! nodules! were!
surrounded!by!collagen!bands!developing!from!the!thickened!capsule!and!characterized!by!a!
mixed! cellular! population! consisting! of! small! lymphocytes,! plasmacells,! eosinophils! and!
macrophages.! Within! this! milieu,! there! were! numerous! Hodgkin! and! Reed>Sternberg! cells,!
accounting! for! more! the! 25%! of! the! observed! cellularity! and! often! clustering! to! form!
syncytia! with! central! necrosis.! On! immunohistochemistry,! the! neoplastic! cells! were! partly!
and! weakly! CD30! positive,! CD15! negative,! PAX5! moderately! positive,! CD20,! CD79a,! OCT2,!
BOB1,! CD23,! MAL1,! AND! PD>L1! strongly! and! uniformly! positive.! EBER! 1! /! 2! in( situ!
hybridization! turned! out! negative.! Accordingly,! a! diagnosis! of! B>cell! lymphoma,!
unclassifiable,! with! features! intermediate! between! DLBCL! and! CHL! was! made.! The! patient!
underwent!DA>EPOCH>R!and!went!into!complete!remission.!However,!nine!months!after!the!
completion! of! therapy,! he! relapsed! and! received! R>DAHP! followed! by! autologous! bone>
marrow!transplantation.!Quite!soon,!he!experienced!progression!of!his!disease.!At!the!time!
being,!he!is!receiving!immunotherapy.!The!case!was!studied!by!FISH!and!targeted!NGS.!The!
former!showed!amplification!of!the!PD>L1!locus!at!9p24.1.!The!latter!revealed!mutations!of!
TET2,!EP300!and!NFKB1E!with!a!variant!allele!frequency!(VAF)!>!0.4!(corresponding!to!a!main!
clone)!and!KMT2D,!TNAFAIP3,!NFKB1A,!XPO1,!GNA13,!and!B2M!with!a!VAF!between!0.1!and!
0.3!(thought!to!correspond!to!subclones)>!!
The! present! case! is! illustrative! of! one! of! the! two! conditions! recognized! by! the! WHO!
classification! for! the! diagnosis! of! “B>cell! lymphoma,! unclassifiable,! with! features!
intermediate! between! DLBCL! and! CHL”,! the! other! being! represented! by! the! opposite!
pattern,!i.e.!morphology!consistent!with!PMBL!and!phenotype!characteristic!of!CHL!(1).!The!
term! gray>zone! lymphoma! (GZL)! is! also! frequently! used,! which! however! is! less! restrictive!
than! the! definition! given! by! the! WHO.! In! fact,! it! includes! cases! with! simultaneous! or!
sequential! occurrence! of! CHL! and! PMBL/DLBCL! (2),! the! transition! from! one! pattern! to! the!
other!within!the!same!sample!having!been!reported!in!a!large!series!from!the!LYSA!(3).!This!
SCIENTIFIC PROGRAMME
SESSION I
HODGKIN’S DISEASE
DEBATE I
IS THERE STILL A ROLE
FOR COMBINED MODALITY
THERAPY FOR EARLY
STAGE CHL?
SESSION II
T-CELL LYMPHOMA
ROUNDTABLE I
FUTURE DIRECTIONS IN
T-CELL LYMPHOMA
SESSION III
FOLLICULAR LYMPHOMA
DEBATE II
CAN WE AVOID
CHEMOTHERAPY IN
THE MANAGEMENT OF
FOLLICULAR LYMPHOMA?
SESSION IV
RARE LYMPHOMAS –
MARGINAL ZONE
LYMPHOMA AND
WALDENSTRÖM M
ACROGLOBULINEMIA
ROUNDTABLE II – WHERE
TO GO IN RARE B-CELL
LYMPHOMAS
SESSION V
MANTLE CELL LYMPHOMA
SESSION VI
DIFFUSE LARGE B-CELL
LYMPHOMA
DEBATE III
DO WE STILL NEED ASCT
IN MCL?
SESSION VII
NOVEL THER APEUTIC
CONCEPTS IN B-CELL
LYMPHOMAS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
DISCLOSURES