g.fraternali orcioni

IRCCS Azienda Ospedaliera Universitaria “San Martino” – ISTIstituto Nazionale Per La Ricerca Sul Cancro, Genova
U.O.C. Anatomia Patologica Ospedaliera e Universitaria
Linfoma diffuso a grandi cellule B
aspetti immunomorfologici e parametri prognostici
Savona 6/11/2015
Dr. Giulio Fraternali Orcioni
DLBCL, centroblastic
DLBCL, multilobated
DLBCL, immunoblastic
+ plasma cell differentiation
Rare cytologic variants
Epithelioid
Clear cell
Signet Ring
Rosettes
Hans CP, Blood
2004
CD10
BCL6
MUM1
CD10
BCL6
MUM1
GC
Activated
Non-GC
Chang CC, Am J
Surg Pathol 2004
CD138
GC
Act-GC
Activated
Non-GC
1 activation
antigen
CONTROL
R-CHOP
IPI
•• Control
Control (CHOP,
(CHOP, CHOEP,
CHOEP, VACOP,
VACOP, MACOB-B,
MACOB-B, EPOCH,
EPOCH, CNOP).
CNOP).
Immunohistochemically
Immunohistochemically defined
defined GC
GC phenotype
phenotype predicts
predicts significantly
significantly better
better
overall
overall (OS)
(OS) and
and failure-free
failure-free survival
survival (FFS)
(FFS) than
than the
the non-GC
non-GC group.
group.
•• R-CHOP.
R-CHOP. Immunohistochemically
Immunohistochemically defined
defined GC
GC phenotype
phenotype not
not predictive
predictive of
of
outcome.
outcome.
•• IPI
IPI separates
separates the
the high-risk
high-risk patients
patients from
from lowlow- and
and intermediate-risk
intermediate-risk groups.
groups.
•• We
We conclude
conclude that
that rituximab
rituximab in
in combination
combination with
with chemotherapy
chemotherapy seems
seems to
to
eliminate
eliminate the
the prognostic
prognostic value
value of
of immunohistochemically
immunohistochemically defined
defined GCGC- and
and
non-GC
non-GC phenotypes
phenotypes in
in DLBCL.
DLBCL.
WHO 2008
“The immunophenotypic subgrouping (GCB vs. non‐GCB) does not currently determine therapy”.
“The use of immunohistochemical panels to assign prognostic groups does not currently have a role in routine clinical practice”.
J Clin Oncol 2006;24:961-8
J Clin Oncol 2006;24:4135-42
Ann Hematol 2004;83:414-9
BCL-2 + : Fattore prognostico negativo nei DLBCL,
sia GC and ACT-type
Leuk Lymphoma 2004;45:1017
Clin Cancer Res 2003;9:2133-9
Blood 2002; 99: 1136-43
Leuk Lymphoma
2001;42:1089-98
Leuk Lymphoma 1999;34:4552
J Clin Oncol 1996;14:2131-8
Report immunomorfologico :
Linfoma di derivazione dai linfociti B periferici a grandi cellule diffuso (WHO
2008)
Immunoistochimica cellule neoplastiche : CD20 +, CD79alfa, CD5, CD10, bcl2, bcl-6, CD23, Ciclina D1, IRF-4/MUM-1. Ki67 pari a circa il ….
Studi relativi ad anomalie di MYC, BCL2 and BCL6 in DLBCL
•Kramer, Blood 1998
•Kawasaki, Leuk&Lymph 2001
•Nakamura, Mod Pathol 2002
•AU, Leukemia 2004
•Kusumoto, AJSP 2004
•Haralambieva, AJSP 2005
•McClure, AJSP 2005
•Le Gouill, Haematologica 2007
•Salaverria, Haematologica 2008
•Yoon, Histopathology 2008
•Klapper, Leukemia 2008
•Mead, Blood 2008
•Copie-Bergman, JCO 2009
•Tomita, Haematologica 2009
•Stasik, Haematologica 2009
•Johnson, Blood 2009
•Shustik, Haematologica 2010
•Cuccuini, Blood 2012
Il risconto di ogni anomalia , ma specialmente la traslocazione di MYC o BCL2, e particolarmente MYC+BCL2 (double hit) identifica un high risk DLBCL
Quesito operativo : quando fare la FISH ? Linfomi di derivazione dai linfociti B periferici aggressivi : approccio diagnostico
Morfologia
Fenotipo
MIB
Diagnosi
FISH
BL
BL
BL/DLBCL
DLBCL
CD10 +
BCL2 BCL6 +
CD10+
BCL2 +
BCL6 +
CD10+, BCL2BCL6 +
any
>95%
>95%
>95%
< 70%
BL
DLBCL
Any but
BCL2 ++
>70% < 95%
DLBCL
opzionale
necessaria
necessaria
raccomandata
BL
BL
BL
H.R.
MYC + altri
H.R.
H.R.
H.R.
BCL2
H.R.
H.R.
H.R.
BCL6
DLBCL
DLBCL
DLBCL
MYC singolo