Transcript 投影片 1 - tcu.edu.tw

Leukopenia, leukocytosis
Follicular hyperplasia
NEOPLASTIC PROLIFERATIONS
OF WHITE CELLS
• Lymphoid neoplasms
– The phenotype of the tumor cells resembles
that of normal counterparts
• Myeloid neoplasms
– Origin of hematopoietic stem cells that give
rise to cells of the myeloid lineage
• Histiocytoses
– Proliferative lesions of macrophages and
dendritic cells
Etiology and pathogenetic
factors in white cell neoplasia
• Chromosomal translocations and
oncogenes
• Inherited genetic factors
• Virus
• Environmental agents
• Iatrogenic factors
Definition of lymphoid
neoplasms
• Lymphoma
– Lymphoid neoplasms present
predominantly as solid masses
• Leukemia (lymphoid leukemia)
– Lymphoid neoplasms involve mainly in
bone marrow and usually in peripheral
blood
Histology of a lymph node
Secondary Lymphoid Follicle (B-cell)
Interfollicular
zone (T-cell)
Mantle zone
Germinal
center
Dark zone
Light zone
Centrocyte
Centroblast
Development of Lymphocytes
Normal Counterpart of B-cell Neoplasms
Lymphoma Classification
• “Revised European-American
Classification of Lymphoid Neoplasms”
(REAL) proposed by ILSG in 1994
• World Health Organization (WHO)
classification
• Why classification?
Three major categories of
lymphoid neoplasms
• B cell lymphomas
– Precursor vs. peripheral
• T and NK cell lymphomas
– Precursor vs. peripheral
• Hodgkin lymphoma (HL)
• Lymphoma vs. leukemia
– Small lymphocyte, lymphoblast, Burkitt
The WHO Classification of the Lymphoid Neoplasms
I. Precursor B-Cell Neoplasms
Precursor-B lymphoblastic leukemia/lymphoma
II. Peripheral B-Cell Neoplasms
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
B-cell prolymphocytic leukemia
Lymphoplasmacytic lymphoma (LPL)
Splenic and nodal marginal zone lymphomas
Extranodal marginal zone lymphoma
Mantle cell lymphoma (MCL)
Follicular lymphoma (FL)
Marginal zone lymphoma (MZL)
Hairy cell leukemia
Plasmacytoma/plasma cell myeloma
Diffuse large B-cell lymphoma (DLBCL)
Burkitt lymphoma (BL)
III. Precursor T-Cell Neoplasms
Precursor-T lymphoblastic leukemia/lymphoma
IV. Peripheral T-Cell and NK-Cell Neoplasms
T-cell prolymphocytic leukemia
Large granular lymphocytic leukemia
Mycosis fungoides/Sézary syndrome
Peripheral T-cell lymphoma, unspecified (PTCL, NOS)
Anaplastic large cell lymphoma (ALCL)
Angioimmunoblastic T-cell lymphoma
Enteropathy-associated T-cell lymphoma
Panniculitis-like T-cell lymphoma
Hepatosplenic γ/δ T-cell lymphoma
Adult T-cell leukemia/lymphoma
NK/T-cell lymphoma, nasal type
NK-cell leukemia
V. Hodgkin Lymphoma
Classical subtypes
Nodular sclerosis (NS)
Mixed cellularity (MC)
Lymphocyte-rich (LRC)
Lymphocyte depletion (LD)
Lymphocyte predominance (LP)
Summary of Major Types of
Lymphoid Neoplasms
Diagnosis Cell of
Origin
BL
Genotype
Salient Clinical
Features
Germinal
Translocations
Adolescents or young
center Binvolving c-myc
adults with jaw or
cell;
and Ig loci;
extranodal
CD10
usually t(8;14),
abdominal masses;
expressi
but also t(2;8) or
uncommonly
on
t(8;22). African
presents as a
usually
(endemic)
"leukemia";
seen
cases latently
aggressive
infected with
EBV
SLL/CLL
Prolymphocyte
CLL
SLL/CLL
FL
Centrocyte & centroblast
FL (spleen)
Bcl-2 expression in reactive and
neoplastic follicles
DLBCL
DLBCL (spleen)
BL
BL
LPL
MCL
MCL
Mucosa-associated lymphoid
tissue (MALT) type-lymphoma
Extranodal Postgermin
marginal
al center
zone
memory
lympho
B-cell
ma
Trisomy 18,
Arises at
t(11;18),
extranodal
t(1;14); latter
sites in
create
adults with
MALT1-IAP2
chronic
and BCL10inflammatory
IgH fusion
diseases;
genes,
may remain
respectively
localized;
indolent
Mature B cell lymphomas
• Epidemiology
– Median age: 6th~7th decades
• Mediastinal large B-cell lymphoma: 37
• Burkitt lymphoma: 30
– In children
• Burkitt lymphoma (BL)
• Diffuse large B-cell lymphoma (DLBCL)
– M>F: mantle cell lymphoma
– F>M: mediastinal large B-cell lymphoma
Risk factors
• Abnormality of the immune system
– Immunodeficiency (HIV, recipient of
transplantation)
• BL, DLBCL
– Autoimmune disease
• MALT lymphoma
Etiology-- Infectious agents
• EBV
– BL (100% in endemic, 40% in others)
– lymphomas in immunosuppressed patients
• HHV8
– primary effusion lymphoma
• Hepatitis C virus
– lymphoplasmacytic lymphoma
• Bacteria
– MALT lymphoma (stomach, skin, intestine)
Genetics
• Mantle cell lymphoma (MCL)
– t(11;14): Cyclin D1/Bcl-1
• Follicular lymphoma (FL)
– t(14;18): Bcl-2
• Burkitt lymphoma (BL)
– t(8;14), t(2;8), t(8;22): c-myc
• MALT lymphoma
– t(11;18): API-2
Clinical Presentations
• Predominantly disseminated (leukemia)
– SLL/CLL, LPL, hairy cell leukemia (HCL),
splenic marginal zone lymphoma, myeloma
• Primary extranodal
– MALT lymphoma
• Predominantly nodal
– Follicular lymphoma, mantle cell lymphoma,
nodal marginal zone lymphoma
Clinical features and survival
• Indolent & incurable
– SLL/CLL, FL: median survival > 5 yrs
• Indolent & curable
– MALT lymphoma
• Incurable & aggressive
– MCL: median survival 3 yrs
• Aggressive but curable
– DLBCL (40% cure rate), BL
Mature T- and NK-cell
neoplasms
• Incidence
– 12% in the Western world
• Peripheral T-cell lymphoma, unspecified (PTCL-U)
• Anaplastic large cell lymphoma (ALCL)
– 39% in Taiwan
• Nasal and nasal-type NK/T-cell lymphoma
• Why?
– Lower B lymphoma, virus, racial
predisposition
Etiology
• Virus
– EBV
• NK/T-cell lymphoma
• NK/T-cell leukemia
– HTLV-1
• Adult T-cell leukemia/lymphoma
• unknown
PTCL, unspecified
ALCL-hallmark (horseshoe) cells
ALK expression in ALCL
Nasal type NK/T-cell lymphoma
Natural
No specific
Adults with
killer cell
chromosomal
destructive
(common)
abnormality;
extranodal
or
uniformly
masses, most
cytotoxic
EBV
commonly
T-cell
associated
sinonasal; often
(rare)
accompanied by
hemophagocytic
syndrome;
aggressive
Reed-Sternberg (RS) cell
Characteristics
•
•
•
•
About 30% of all lymphomas
Usually arise in cervical lymph nodes
The majority in young adults
Typically localized at presentation
• Scattered tumor cells in a background of
inflammatory cells
• The tumor cells are usually ringed by T-cells in
a rosette-like manner
Mononuclear variant of RS cell
Lacunar variant
Lymphohistiocytic (L&H) variant
Subclassification
• Nodular lymphocyte
• Classical (CHL)
predominant (NLPHL)
–
–
–
–
–
–
–
–
5% of all HL
30~50 y/o male
Most stage I/II
Develop slowly
Frequent relapses
Responsive to Tx
Rarely being fatal
10 yr survival rate
>90%
–
–
–
–
–
95% of all HL
15~35 & late adult
Neck, mediastinum
55% stage I/II
40% systemic
symptoms
– EBV association
– Curable in the majority
– 5 yr survival >85%
NS type
MC type
NLP type
Signals mediate cross-talk between RS
and surrounding normal cells
Clinical Differences Between Hodgkin
and Non-Hodgkin Lymphomas
Hodgkin Lymphoma
Non-Hodgkin Lymphoma
More often localized to a
single axial group of
nodes (cervical,
mediastinal, para-aortic)
More frequent involvement
of multiple peripheral
nodes
Orderly spread by contiguity
Noncontiguous spread
Mesenteric nodes and
Waldeyer ring rarely
involved
Waldeyer ring and
mesenteric nodes
commonly involved
Extranodal involvement
uncommon
Extranodal involvement
common
THANK YOU
HCL
HCL