Leukopenia, leukocytosis

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Leukopenia, leukocytosis
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Follicular hyperplasia
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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

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Etiology and pathogenetic factors in white cell
neoplasia

• Chromosomal translocations and oncogenes
• Inherited genetic factors
• Virus
• Environmental agents
• Iatrogenic factors

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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

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Histology of a lymph node
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Secondary Lymphoid Follicle (B-cell)

• Interfollicular
• zone (T-cell)
• Mantle zone
• Germinal
• center
• Dark zone
• Light zone
• Centrocyte
• Centroblast

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Development of Lymphocytes
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Normal Counterpart of B-cell Neoplasms
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Lymphoma Classification

• Revised European-American Classification of
  Lymphoid Neoplasms (REAL) proposed by ILSG in
  1994
• World Health Organization (WHO) classification
• Why classification?

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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

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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)
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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 ?/d T-cell lymphoma
Adult T-cell leukemia/lymphoma
NK/T-cell lymphoma, nasal type
NK-cell leukemia
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V. Hodgkin Lymphoma
Classical subtypes
Nodular sclerosis (NS)
Mixed cellularity (MC)
Lymphocyte-rich (LRC)
Lymphocyte depletion (LD)
Lymphocyte predominance (LP)
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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(814), but also t(28) or t(822). African (endemic) cases latently infected with EBV Adolescents or young adults with jaw or extranodal abdominal masses uncommonly presents as a "leukemia" aggressive
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SLL/CLL
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Prolymphocyte
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CLL
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SLL/CLL
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FL
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Centrocyte centroblast
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FL (spleen)
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Bcl-2 expression in reactive and neoplastic
follicles
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DLBCL
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DLBCL (spleen)
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BL
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BL
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LPL
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MCL
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MCL
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Mucosa-associated lymphoid tissue (MALT)
type-lymphoma
Extranodal marginal zone lymphoma Postgerminal center memory B-cell Trisomy 18, t(1118), t(114) latter create MALT1-IAP2 and BCL10-IgH fusion genes, respectively Arises at extranodal sites in adults with chronic inflammatory diseases may remain localized indolent
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Mature B cell lymphomas

• Epidemiology
• Median age 6th7th decades
• Mediastinal large B-cell lymphoma 37
• Burkitt lymphoma 30
• In children
• Burkitt lymphoma (BL)
• Diffuse large B-cell lymphoma (DLBCL)
• MgtF mantle cell lymphoma
• FgtM mediastinal large B-cell lymphoma

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Risk factors

• Abnormality of the immune system
• Immunodeficiency (HIV, recipient of
  transplantation)
• BL, DLBCL
• Autoimmune disease
• MALT lymphoma

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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)

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Genetics

• Mantle cell lymphoma (MCL)
• t(1114) Cyclin D1/Bcl-1
• Follicular lymphoma (FL)
• t(1418) Bcl-2
• Burkitt lymphoma (BL)
• t(814), t(28), t(822) c-myc
• MALT lymphoma
• t(1118) API-2

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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

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Clinical features and survival

• Indolent incurable
• SLL/CLL, FL median survival gt 5 yrs
• Indolent curable
• MALT lymphoma
• Incurable aggressive
• MCL median survival 3 yrs
• Aggressive but curable
• DLBCL (40 cure rate), BL

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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

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Etiology

• Virus
• EBV
• NK/T-cell lymphoma
• NK/T-cell leukemia
• HTLV-1
• Adult T-cell leukemia/lymphoma
• unknown

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PTCL, unspecified
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ALCL-hallmark (horseshoe) cells
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ALK expression in ALCL
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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
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Reed-Sternberg (RS) cell
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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

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Mononuclear variant of RS cell
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Lacunar variant
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Lymphohistiocytic (LH) variant
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Subclassification

• Nodular lymphocyte predominant (NLPHL)
• 5 of all HL
• 3050 y/o male
• Most stage I/II
• Develop slowly
• Frequent relapses
• Responsive to Tx
• Rarely being fatal
• 10 yr survival rate gt90

• Classical (CHL)
• 95 of all HL
• 1535 late adult
• Neck, mediastinum
• 55 stage I/II
• 40 systemic symptoms
• EBV association
• Curable in the majority
• 5 yr survival gt85

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NS type
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MC type
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NLP type
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Signals mediate cross-talk between RS and
surrounding normal cells
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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
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THANK YOU
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HCL
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HCL