PHILIPPE&GAULARD&(CRÉTEIL)
PERIPHERAL(T?CELL(LYMPHOMAS:(DIAGNOSIS(AND(REFINEMENT(THROUGH(
UNDERSTANDING(
!
Department(of(Pathology,(Hôpital(Henri(Mondor,(Créteil,(France(
!
Peripheral!T>cell!lymphomas!(PTCLs)!are!heterogeneous!and!uncommon!malignancies!which!
are!characterized!by!a!usually!poor!outcome!with!current!treatment!strategies.!Till!recently,!
with! the! exception! of! ALK>positive! anaplastic! large! cell! lymphoma! (ALCL),! PTCLs! lacked!
specific,! entity>defining,! genetic! alterations.! In! addition,! the! cell! derivation! of! most! PTCL!
entities!is!still!incompletely!understood.!Consequently,!their!pathological!diagnosis!is!often!
challenging,! with! significant! overlaps! across! distinct! entities! and! a! relatively! poor! inter>
observer!reproducibility.!However,!in!the!recent!years,!significant!advances!have!occurred!in!
their!classification,!which!have!led!to!revisions!in!the!currently!updated!(2017)!classification!
with!a!better!definition!of!several!entities!and!introduction!of!new!provisional!entities.!Many!
of!these!changes!are!the!results!of!recent!transcriptomic!or!genomic!studies!having!defined!
the!molecular!signature!and!the!genetic!landscape!of!most!PTCL!entities.!
Among!nodal(PTCLs,!those!with!a!TFH!phenotype,!as!defined!by!the!expression!of!at!least!2!
–better!three!or!more!>!!TFH>associated!molecules!(i.e.!CD10,!ICOS,!PD1,!BCL6,!CXCL13..),!are!
now! grouped! into! a! category! designated! “Nodal! T>cell! lymphomas! with! T>follicular! helper!
(TFH)! phenotype”.! This! umbrella! category! >! likely! the! most! prevalent! in! most! countries! >!
includes! angioimmunoblastic! T>cell! lymphoma,! follicular! T>cell! lymphoma,! and! other! nodal!
PTCL! with! a! TFH! phenotype.! These! lymphomas! show! clinical,! pathological! and! genetic!
overlapping! features,! especially! recurrent! genetic! abnormalities! such! as! mutations! in!
epigenetic! modifiers! (TET2,( DNMT3A,( IDH2),! in! the! RHOA! (G17V)! GTPase! and! in! T>cell!
receptor! related! genes! (including! mutations/fusions! involving! CD28)! some! of! which! could!
potentially!impact!therapy.!Several!studies!have!shown!that!the!cooperation!between!TET2!
loss! of! function! and! RHOA( G17V! mutations! drives! AITL>like! disease! in! mice.! This! group! of!
nodal!PTCL!with!a!TFH!phenotype!may!be!accompanied!with!B>blasts!with!Reed>Sternberg>
like!features!which!can!be!misleading!for!Hodgkin!lymphoma.!!
Besides!the!well>characterized!ALK>positive!ALCL!category!defined!by!the!rearrangement!of!
the!ALK!gene!resulting!in!ALK!expression,!ALCL!ALK>negative!is!now!recognized!as!a!definite!
entity! that! includes! genetic! subsets! that! may! have! prognostic! implications.! Especially,! a!
subset!with!6p25!rearrangements!at!IRF4/DUSP22!locus!seems!to!have!distinct!biology!and!
may!have!a!good!outcome.!Among!ALCL!ALK>negative,!a!novel!entity!occurring!as!an!effusion!
between! the! implant! itself! and! the! surrounding! fibrous! capsule! (seroma)! or! as! a! mass!
adjacent! to! the! breast! implant,! is! now! incorporated! as! “Breast! implant–associated! ALCL”:!
this! subtype! usually! associates! with! an! excellent! outcome! and! shows! a! distinct! genetic!
landscape.! Although! CD30! expression! is! a! feature! of! ALCL,! it! is! noteworthy! that! CD30! is!
found! in! a! variable! proportion! of! lymphoma! cells! in! several! other! entities,! including! PTCL,!
not! otherwise! specified! (PTCL>NOS),! enteropathy>associated! T>cell! lymphoma! (EATL),! and!
extranodal!NK/T>cell!lymphoma,!nasal>type,!a!feature!that!can!be!of!therapeutic!relevance.!!
The! remaining! PTCL>NOS! category! is! now! less! prevalent! when! excluding! the! subset! with! a!
TFH!phenotype.!This!category!“by!default”!is!heterogeneous!both!at!pathological!and!clinical!
grounds.!Gene!expression!studies!have!shown!that!they!display!a!global!signature!close!to!
that! of! activated! T>lymphocytes,! and! identified! discrete! subtypes! characterized! by!
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