European Federation of Cytology Societies
4tu Annual Tutorial in Cytopathology
Trieste, June 66-10, 2011
Fine needle cytology of lymph nodes:
Non‐‐neoplastic condictions
Non
Pio Zeppa MD,
MD PhD
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli, “Federico II” Naples, Italy
Why cytology for lymph nodes?
Why cytology for lymph nodes?
REACTIVE !!
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Why cytology for lymph nodes?
Peri‐carotideal lymph node, the surgeon refused to perform the excision, US guided FNC: NHL
Diffuse spleen enlargement
Deep cervical node: suspect NHL, FNC: metastasis high D
i l d
t NHL FNC
t t i hi h
respiratory tract, nasopharyngeal carcinoma, RX therapy No surgery !
patient F. S.:
ti t F S
fourth relapse from MCL !
t(11;14)(q13;q32)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Why cytology for lymphoma?
y y
gy
y p
 1,5 million of new cases in the world
 Doubled incidence in the last 20 yrs
Doubled incidence in the last 20 yrs
 200.000 patients and 15.000 new cases yrs, in Italy
 Increased n. of complete remissions and prolonged survivals
p
p
g
 30% of patients will develop recurrences
 30% will develop non‐lymphomatous swellings
 Non‐invasive procedures do not produce definitive diagnoses
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Wh
Why cytology for lymphoma?
t l
f l
h
?
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Lymph‐nodal cytology and ancillary techniques
y p
y
gy
y
q
Hodgkin’s disease
immunocytochemistry
metastases
large‐cell
large
cell NHL
NHL
reactive? small ‐
reactive?
small
medium‐cell NHL?
Diff Quik
FISH
flow
cytometry
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
PCR
others
From Zajicek to flow cytometry
Colorado M, et al: Simultaneous cytomorphologic and multiparametric flow cytometric analysis onlymph node samples is faster than and as valid as histopathologic study y
y p
p
p
g
y
todiagnose most non‐Hodgkin lymphomas. Am J Clin Pathol. 2010; 133:81.
Katz RL et al.: Fine‐needle aspiration cytology of peripheral T‐cell lymphoma. A cytologic, immunologic, and cytometric study. Am J Clin Pathol. 1989; 9:120. Dunphy CH, Katz RL et al: Leukemic lymphadenopathy: diagnosis by fine needle aspiration. Hematol Pathol. 1989; 3:35. Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
“GATING”
N
Normal
l lymph
l
h node
d histology
hi l
Reactive hyperplasia (BRH)
Reactive hyperplasia (BRH)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
non-specific hyperplasia with follicular centre expansion
Non-specific hyperplasia with follicular centre expansion: smears show numerous centrocytes
and centroblasts with two or more eccentrical nucleoli intermingled with small mature
lymphocytes with slightly lengthened nuclei and cytoplasmic “tales”, plasma cells and
immunoblasts.
non-specific hyperplasia with follicular centre expansion
Cy: numerous centrocytes and centroblasts
intermingled with a variable number of small
lymphocytes. Differential diagnosis with a NHL is
often pointed out.
FC :T and B-cell populations , a follicular centre cell population which co-expresses CD19/CD10 and
balanced expression of kappa and lambda light chains
non-specific hyperplasia with interfollicular expansion
Non specific hyperplasia with interfollicular expansion: the smear shows a prevalence of mature
lymphocytes with large nucleolated immunoblasts and plasma cells.
non-specific hyperplasia with interfollicular expansion
FC in non specific hyperplasia with interfollicular expansion may shows a prevalence of T-lymphocytes
(CD5) with CD2/3/7 co-expression.
Viral and post-vaccinial
 FNC show
h
smallll lymphocytes
l
h
t
and
d numerous centrocytes
t
t
and
d
centroblasts intermingled with small mature lymphocytes, plasma
cells and immunoblasts. Capillary structures, phagocyting histiocytes
and eosinophils may also be present.
 Differential diagnosis: follicular lymphoma (see NHL).
Mononucleosis
 FNC shows normal cell type constituents including centrocytes and
centroblasts. Numerous immunoblasts with large nucleoli and a rim
of blue cytoplasm are present. Macrophages and capillary structures
may be present.
 Differential diagnosis: Hodgkin lymphoma (see HL).
Histiocytosis
 This is mainly observed in lymph nodes draining inflamed tissues or
organs or cancer. Corresponding smears may show histiocytes,
small lymphocytes and macrophages with engulfed cytoplasm.
 Differential
diagnosis:
Sinus
histiocytosis
with
massive
lymphadenopathy.
Suppurative lymphadenitis
 This condition can be observed in lymph nodes draining bacterial
infections. Smears show of granulocytes and a variable amount of
lymphocytes in a necrotic background. Attention should be paid
because metastatic squamous cell carcinoma and rarely HL, may
show a prevalent necrotico-suppurative background.
Granulomatous lymphadenitis
 Granulomatous
G
l
t
l
lymphadenitis
h d iti may be
b determined
d t
i d by
b severall infective
i f ti
agents or by different pathological processes, sarcoidosis and
tuberculosis being the most frequent. Granulomatous lymphadenitis
may also occur along hematological diseases or after chemotherapy
or radiotherapy. Smears show epithelioid cells and/or multinucleated
giant cells, either isolated or in a granulomatous arrangement in a
lymphoid background.
T
Toxoplasmosis
l
i
Reactive lymph node with toxoplasmosis:Small groups of epitheliod cells intermingled with
lymphocytes.
FC sub‐classification of small/medium cell size NHL
phenotype
LpcL
SLL
MCL
FCL
MZL/
MALT
SNCL
PTCL
NK
k:λ>4:1 or <1:3
+
+
+
+
+
+/-
-
-
CD19/CD5+
-
+
+
-
-
-
-
-
CD19/CD10+
-
-
-
+
-
+
-
-
CD19/CD23+
+/-
+
-
-
-
-
-
-
CD19/FMC7+
+/-
-
+
+/-
-
-
-
-
CD19/CD38+
+
-
-
-
-
-
-
-
b l 2+/CD10
bcl-2+/CD10
-
-
-
+
-
-
-
-
CD4+/CD8- , CD4-/CD8+
-
-
-
-
-
-
+
-
CD3+, CD5+, CD19-
-
-
-
-
-
-
+
-
CD2/CD3+CD7- or
CD2/CD7+CD3-
-
-
-
-
-
-
+
-
CD3+/- CD56+ CD19-
-
-
-
-
-
-
-
+
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Cytology, phenotype (FC), IGH quantitative assessment (PCR), IGH integrity evaluation (FISH) of lymphoid cells
IGH probe, split signal
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
 IGH (14q32) is the most frequently involved in different translocations of B‐cell NHL
tt (14;18)(q32;q21) in FL
(14;18)(q32;q21) in FL and a subset of DLBCL
and a subset of DLBCL
t (11;14)(q13;q32) in MCL
t (q14;q32) in 60 % in MM with different chromosomal partners
t (9;14)(p13;q32) in 50% of LPCL and some cases of MZL
t (8;14)(q24;q32) in 100% of BL
 The The IGH FISH DNA probe, split signal, is a mixture of two fluorochrome:
IGH FISH DNA probe, split signal, is a mixture of two fluorochrome:
the green labelled DNA probe that binds to a 612 kb telomeric segment, and
the red labelled that binds to a 460 kb centromeric segment, to the IGH breakpoint
 Therefore IGH FISH DNA probe
probe, split signal should detect any breakage involving the IGH locus
at chromosome 14q32.
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Indirect FC markers of malignancy
g
y
CD5/CD19 co‐expression
/
p
g
CD19/CD10 co‐expression in >50% of the gated cells
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Chronic lymphatic leukemia/small lymphocytic lymphoma (CLL/SLL)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Lymphoplasmacytoid Lymphoma (LPCL)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Mantle cell lymphoma (MCL)
Mantle cell lymphoma (MCL)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Mantle cell lymphoma
Mantle cell lymphoma
Cyclin D1/bcl-1
t(11;14)(q13;q32)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Follicular lymphoma (FL)
Follicular lymphoma (FL)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
bcl 2 in follicular lymphoma
bcl‐2 in follicular lymphoma
 Laane E et al.: Flow cytometric immunophenotyping including Bcl‐2 detection on fine needle aspirates in the diagnosis of reactive lymphadenopathy and non‐Hodgkin's lymphoma Cytometry B Clin Cytom 2005;64:34
lymphoma. Cytometry B Clin Cytom. 2005;64:34. Bcl‐2 quantification might be useful using antisense oligonucleotides
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
FL with dim or not expressed light chains
t(14;18)(q32;q21)
p
T(
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Marginal zone B‐cell lymphoma (MZL)
zone B cell lymphoma (MZL)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Extranodal B‐cell lymphoma of mucosa associated l mphoid tiss e (MALT l mphoma)
lymphoid tissue (MALT lymphoma)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Diffuse large B‐cell
Diffuse large B
cell lymphoma
lymphoma
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Burkitt lymphoma (BL)
Burkitt lymphoma (BL)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Peripheral T cell lymphoma (PTL)
Peripheral T‐cell lymphoma (PTL)
CD45 Ro
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Peripheral T cell lymphoma (PTL)
Peripheral T‐cell lymphoma (PTL)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Peripheral T cell lymphoma (PTL)
Peripheral T‐cell lymphoma (PTL)
CD45Ro
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
NK ll l
NK‐cell lymphoma/leukemia
h
/l k i
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Pitfalls and shortcomings !
Pitfalls and shortcomings !
Hodgkin Lymphoma
anaplastic large cell lymphoma
CD30
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
F, 57‐yrs, FNC of 50 mm nodule in the left thyroidal area
,
y ,
y
Cytological diagnosis:
y
g
g
T‐cell lymphoproliferative process
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Hi t l i l di
Histological diagnosis: benign type B1 ectopic thymoma
i b i t
B1 t i th
CD45Ro
CK-pan
CK
pan
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Thymic lymphocytes:
y
y p y
•mature “polyclonal” T‐cells profile: (CD2+,CD3+,CD5+,CD7+)
•CD10+ in an immature T‐cell subsets
•maturation: CD4‐ CD8‐ in the cortex, continues as CD4+ CD8+,
reaches maturation as CD4+ CD8‐ or CD4‐ CD8+ in the medulla.
CD4+/CD8+ is a specific feature of intrathymic T‐cells
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
 40 yrs old female, HIV positive with right ‐ cervical swelling. The patient suffered from a FL, since 2 yrs, last chemotherapy 10 months before
 US: 2,5 cm large lymph node, oval with hilus preservation
US: 2 5 cm large lymph node oval with hilus preservation
 FC: CD5:10%, CD19:49%, CD23: 10%, FMC7: 0%, CD10:40%, CD10/19:40%, lambda light chains 40%, kappa light chains 0%.
Cytological FC diagnosis: FL
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Final histological diagnosis: reactive hyperplasia with Fi
l hi t l i l di
i
ti h
l i ith
florid follicular proliferation!
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Incidence, phenotypical and molecular data of non-lymphomatous,
clonal B-cell
B cell population: a review of the literature
Author/year
organ
sample
Berthold F, 1989
lymph node
histology
Matsubayashi S, 1990
thyroid
FNA
Cartagena N, 1992
lymph node
Jordan RC, 1996
n. of cases
1
clinical background
light chain restriction
FC‐ICC‐IHH ( pos./total)
IgH clonality PCR (pos./total)
follow‐up
Herpes virus 6
NP
+ (1/1)*
negative
15
Hashimoto thyroiditis
FC/ + (7/15)
NP
NR
FNA
86
NP
ICC/ + (1/86)
NP
NR
minor salivary glands
histology
50
Sjogren’s syndrome
NP
+ (4/50)
NR
Zhou XG, 1999
lymph node tonsils
histology
9
NR
NP
+ (9/9)
negative
Saxena A, 2000
stomach
histology
20
Helicobacter pylori gastritis
NP
+ (10/20)
negative
Kussik SJ, 2004
lymph node
histology and FNA
6
5 negative,1 HIV
FC/ + (6/6)*
+ (3/6)
negative
Chen H, 2006
thyroid
histology and FNA
21
Hashimoto thyroiditis
FC/ + (18/21)
‐
negative
Venkatraman L, 2006
lymph node
FNA
26
NHL, reactive, HIV (1case)
ICC+ (1‐HIV/26)
+ (1/26)
negative
Bangerter M, 2007
lymph node
FNA
131
NR
FC+ (3/131)
NP
negative
Nam‐Cha SH, 2008
lymph node
histology
8
Castleman’s, LES, EBV, HIV (1 case)
IHH/+ (8/8)*
+ (3/8)
6 negative, 2 developed NHL
Bhargava P, 2008
lymph node
FNA
1
HIV
FC/+ ‐
negative
Zeppa P, 2009
thyroid
FNA
34
Hashimoto thyroiditis
FC/+ (5/34)
‐
negative
Fan HB, 2009
liver
histology
40
HCV hepatitis
‐
+ (4/40)
negative
FUTURE PERSPECTIVES
FUTURE PERSPECTIVES
New antibodies for diagnosis
New antibodies for diagnosis
 Schniederjan SD et al.: A novel flow cytometric antibody panel for distinguishing Burkitt lymphoma fromCD10+ diffuse large B‐cell lymphoma. Am J Clin Pathol. 2010 133 718
2010;133:718.
 ……expression of CD44 and CD54 differs significantly between BL and CD10+ DLBCL…..
between BL and CD10
DLBCL…..

Leshchenko et al.: Genomewide DNA methylation analysis reveals novel targets for drug development in mantle cell lymphoma. Blood. 2010;116:1025.
…….CD37 surface expression in 93% MCL. CD37 f
i i 93% MCL
FUTURE PERSPECTIVES
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
N H d ki l
h
l
l
ib di
Non Hodgkin lymphoma, monoclonal antibodies
and Flow Cytometry
 Monoclonal antibodies have a direct action against IgG constant regions and a cross‐fire effect (radio conjugated)
 Flow cytometry may quantify the target cells by the evaluation of antigen co‐
expression and their numerical evaluation
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
FUTURE PERSPECTIVES
FUTURE PERSPECTIVES
Högerkorp CM et al.: Identification of uniquely expressed transcription factors in highly Högerkorp
CM et al : Identification of uniquely expressed transcription factors in highly
purified B‐cell lymphoma samples. Am J Hematol. 2010;85:418.
Andréasson U et al.: Identification of molecular targets associated with transformed diffuse Andréasson
U et al : Identification of molecular targets associated with transformed diffuse
large B cell lymphoma using highly purified tumor cells. Am J Hematol. 2009;84:803.
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
acknowledgments
 Prof. L. Palombini
 Prof. A. Vetrani
 Prof. G. Troncone
 Dr. I. Cozzolino
Dr I Cozzolino







Dr. A. Iaccarino
Dr C Frangella
Dr. C. Frangella
Dr. U. Malapelle
Dr. F. Plaitano
Dr. M. Russo
Dr. M. Salatiello
Dr. L.V. Sosa Fernandez
www.eurocytology.eu
y
gy
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
mantle cell l mphoma and mTOR gene acti ation
mantle cell lymphoma and mTOR gene activation
Farnesyltransferase (Rapamicyn):
 hampers the progression G1‐S inhibiting the transduction of mTOR,
 reduces cyclin D2‐
d
l D3 and increases CDk and p27
d C k d  p27 may be evaluated on FNC samples by FC or ICC
P27/kip1
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
lymphoplasmacytic lymphoma
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
why cytology for lymphomas?
h
t l
f l
h
?
 Lymphomas are an increasing pathology: 60.000 new cases per year in USA
 30% of these patients will develop recurrences
 30% develop non
30% develop non‐lymphomatous swellings
lymphomatous swellings
 Non‐invasive procedures do not produce definitive diagnoses*
*Zinzani PL, et al.: Histological verification of positive positron emission tomography findings in the follow‐up of p
patients with mediastinal lymphoma. Haematologica. 2007; 92(6):771‐777.
y p
g
7; 9 ( ) 77 777
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
palpable
l bl
FNC/FC
lymph node 148
iimpalpable
l bl
us/ct guided
lymph node 98
thyroid
13
spleen
20
suspicious 10
parotid
15
liver
2
BRH
135
breast
4
small bowel 1
NHL
70
soft tissue
5
soft tissue
NHLr
77
Total
185
Total
1
122
inadequate 15
Total
307
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Follicular lymphoma (FL)
Follicular lymphoma (FL)
new drugs for non‐Hodgkin lymphomas
DRUG
PATHOGENETIC
TARGET
MECHANISM
TARGET
Antisense oligonucleotides
(Bcl-2 antisense) G3139
Bcl-2 over expression
– chemotherapy
resistance
Inhibition of target gene
Follicular lymphoma
Anti ubiquitin proteasome
(Bortezomib)
NF-kB over
expression – p21,
p21 p27
degradation
Anti ubiquitin proteasome action –
p21 p27 restoration
p21,
Myeloma,
Mantle Marginal
Mantle,
Marginal, Small
lymphocytic lymphoma
Protease inhibitors
mTOR gene activation
–progression G1 - S
Transduction inhibition of mTOR – cyclin D2,
D3 reduction – CDK, p27 increase
Mantle cell lymphoma
Monoclonal antibodies
(unconjugated and radioconjugated):
anti CD20 (Rituximab)
anti CD22(Epratuxumab)
anti HLA-DR(Apolizumab)
Clonal expansion of
lymphocytes
Direct action against IgG constant region
region,
cross-fire effect (radioconjugated)
Follicular lymphoma
Histone deacetylase inhibitors
depsipepside, hydroxamic acids
(TSA,SAHA)
3q27 translocation –
bcl-6 over expression
Bcl-6 gene deacetylation
Diffuse large B-cell
lymphoma
Farnesyltransferase (Rapamicyn)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
new drugs for non‐Hodgkin lymphomas
DRUG
PATHOGENETIC TARGET
MECHANISM
TARGET
Antisense oligonucleotides
(Bcl-2 antisense) G3139
Bcl-2 over expression –
chemotherapy resistance
Inhibition of target gene
Follicular lymphoma
Anti ubiquitin proteasome
(Bortezomib)
NF-kB over expression –
p21, p27 degradation
Anti ubiquitin proteasome action – p21, p27
restoration
Myeloma,
Mantle, Marginal, Small
y p
y lymphoma
y p
lymphocytic
Farnesyltransferase,
(Rapamicyn)
mTOR gene activation –
progression G1 - S
Transduction Inhibition of mTOR – cyclin
D2,D3 riduction – CDK, P27 increase
Mantle cell lymphoma
Monoclonal antibodies
((unconjugated
j
t d and
d
radioconjugated):
anti CD20 (Rituximab)
anti CD22 (Epratuxumab) anti
HLA-DR (Apolizumab)
Clonal expansion of
l
lymphocytes
h
t
Direct action against IgG constant region,
cross-fire
fi effect
ff t (radio
( di conjugated)
j
t d)
Follicular lymphoma
Histone deacetylase
inhibitors:depsipepside,
hydroxamic acids (TSA,
SAHA)
3q27 translocation – bcl-6
over expression
Bcl-6 gene deacetylation
Diffuse large B-cell lymphoma
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
marginal zone B-cell lymphoma
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Diffuse large B‐cell lymphoma (DLBCL)
therapy of non Hodgkin lymphomas
therapy of non Hodgkin lymphomas
Future
Past
Leukeran
Present
 Protease inhibitors: Farnesyl transferase
 Antisense oligonucleotides: Bcl‐2 antisense
 “watch and wait” (indolent)
 Monoclonal antibodies:
 Chemotherapeutic agents:
COP, Fludarabina, Antraciclina (low grade). CHOP (high grade)
 Monoclonal antibody:
Rituximab (antiCD20) Unconjugates: Rituximab (anti ‐ CD20), Epratuxumab (anti‐ CD22), Apolizumab, (anti‐
CD52)
Radioconjugates: Iodine 131 anti‐CD20
Radioconjugates: Iodine 131 anti
CD20, 90
90‐Yttrium
Yttrium anti‐CD20
 Histone deacetylase inhibitors:
depsipepside hydroxamic acids (TSA SAHA)
depsipepside, hydroxamic acids (TSA, SAHA)
 Vaccines
 Bone marrow transplantation
p
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
new drugs for non‐Hodgkin
new drugs for non
Hodgkin lymphomas
lymphomas
•Antifolate: Pralatrexate,
PTL
•Heat Shock Protein Inhibitors DLBCL
•Antiangiogenetic
Aggressive NHL
15th Congress of the European Hematology
Association, Barcelona June 2010
Monoclonal antibodies bi-specific T-cell
engager (BiTE) (Blimatumomab)
 Lymphomas are the most complex and heterogeneous set of human malignancies
 Lymphomas comprise some of the fastest (Burkitt, lymphoblastic) and slowest growing (small lymphocytic, follicular low grade) malignancies
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Anaplastic large cell lymphoma (ALCL)
NHL in pleural effusion
NHL i l
NHL in pleural effusion
l ff i
mantle cell lymphoma (MCL)
MCL “small boxes”
MCL
C n.o.s.
.o.s.
MCL “centrocytic”
MCL Ki67
Chronic lymphatic leukemia/small lymphocytic Ch
i l
h i l k i /
ll l
h
i
lymphoma (CLL/SLL)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Chronic lymphatic leukemia/small lymphocytic lymphoma Chronic
lymphatic leukemia/small lymphocytic lymphoma
(CLL/SLL)
ICC of SLL/CLL on cytospins
showing negativity for
lambda and positivity for
kappa light chains
(peroxidase/anti peroxidase
immunostain)
lambda
kappa
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Lymphoplasmacytoid Lymphoma (LPCL)
Lymphoplasmacytoid Lymphoma (LPCL)
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT
Diffuse large B‐cell lymphoma (DLBCL)
Diffuse large B‐cell lymphoma (DLBCL)
 GCB (germinal center B)
 ABC (peripheral B cell)
ABC (peripheral B cell)
 5‐years overall survival
GCB
76%
ABC
24%
Alizadeh AA et al: Distinct types of diffuse large B‐
cell lymphoma identified by gene expression profiling. Nature 2000; 3;403:503. fl
Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli “Federico II” IT