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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
Genotype Salient Clinical Features
BL Germinal center B-cell; CD10 expression usually seen
Translocations involving c-myc and Ig loci; usually t(8;14), but also t(2;8) or t(8;22). African (endemic) cases latently infected with EBV
Adolescents or young adults with jaw or extranodal abdominal masses; uncommonly presents as a "leukemia"; aggressive
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 marginal zone lymphoma
Postgerminal center memory B-cell
Trisomy 18, t(11;18), t(1;14); latter create MALT1-IAP2 and BCL10-IgH fusion genes, respectively
Arises at extranodal sites in adults with chronic inflammatory diseases; may remain 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 killer cell (common) or cytotoxic T-cell (rare)
No specific chromosomal abnormality; uniformly EBV associated
Adults with destructive extranodal masses, most commonly sinonasal; often 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
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%
• Classical (CHL)
– 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