The Leukemias

Classification (FAB):
According to course of disease
Acute
Sub-acute
Chronic
According to cell type
Myelocytic, Monocytic, Erythrocytic
Lymphocytic, Plasmacytic

According to Blood picture

Leukemic
Subleukemic
Aleukemic

The Leukemias
Predisposing factors
Signs and Symptoms:
Pallor
Anorexia
Palpitation

The Leukemias
Acute Leukemias
AML
ALL
Criteria
Auer rods

The Myeloid Leukemias

Acute Myelogenous Leukemia
myeloPOD, esterases
Contain auer rods
Classification
Sub-classification

Morphology
Cytochemistry
Cytogenetic abnormalities

Acute Myelogenous Leukemias

M0 - Myeloblastic leukemia minimally

differentiated
Criteria for diagnosis:

Nongranular blasts; less than 3% of blasts are

myeloperoxidase positive by enzyme
cytochemistry; blasts express myeloid but not
classic lymphocyte antigens; blasts may
aberrantly express some lymphocyte antigens

Acute Myelogenous Leukemias

M1 Myeloblastic leukemia without

maturation
Criteria for diagnosis:

At least 90% of nonerythroid cells are

myeloblasts;
At least 3% of blasts must be positive for
myeloperoxidase or Sudan black B

PBS: very immature cells, usually round

with few granules or Auer rods; little

maturation beyond myeloblast stage

Acute Myelogenous Leukemias

M2 Myeloblastic leukemia with maturation
Criteria for diagnosis:
20-89% of nonerythroid cells are myeloblasts

PBS

Full range of myeloid maturation through

granulocytes; Auer rods usually present; maturing
neutrophils, erythroid and megakaryocyte precursors
may have dysplastic changes; 70% of patients have
Auer rods
Enzyme cytochemistry

myeloperoxidase or Sudan black B

Acute Myelogenous Leukemias

M3 Hypergranular promyelocytic

leukemia
DIC

Criteria for diagnosis

Most cells (>50%) are abnormal promyelocytes with
heavy cytoplasmic granulation, often with reniform
nucleus; cells with multiple Auer bodies usually
present
Microscopic: most cells hypergranular

promyelocytes with heavy red/purple

cytoplasmic granulation

M3 Hypergranular promyelocytic
leukemia

Acute Myelogenous Leukemias

M4 - Myelomonocytic leukemia
Often with markedly elevated WBC,

organomegaly, lymphadenopathy and other

tissue infiltration (monocytes infiltrate)
Criteria for diagnosis:

Myeloblasts and monoblasts are 20% or more of

nonerythroid cells

60% of patients have Auer rods in myeloblasts

M4 - Myelomonocytic leukemia

Acute Myelogenous Leukemias

M5 - Monocytic leukemia
Older patients, high incidence of organomegaly,

lymphadenopathy, tissue infiltration

(monocytes infiltrate)
Criteria for diagnosis: 80% or more
nonerythroid bone marrow cells are monocyte
lineage
Types:

M5a
M5b

Enzyme cytochemistry

M5 - Monocytic leukemia

Acute Myelogenous Leukemias

M6 - Erythroleukemia
Criteria for diagnosis:

50% or more nucleated bone marrow cells are

erythroblasts
20% or more of nonerythroid cells are
myeloblasts
Dyserythropoiesis is prominent

Enzyme cytochemistry

Acute Myelogenous Leukemias

M7 - Megakaryocytic leukemia
Associated with marrow fibrosis due to

megakaryoblast secretion of fibrogenic

cytokines
Peripheral blood often contains
micromegakaryocytes and atypical platelets
Criteria for diagnosis:

20% or more blasts are present in bone marrow

Megakaryoblasts are medium/large cells with dense
chromatin, blue vacuolated cytoplasm, fine granules,
cytoplasmic projections resembling platelets

M7 - Megakaryocytic leukemia

The Lymphocyte Leukemias

Acute Lymphoblastic Leukemias
85% B cell
15% T cell
Risk factors

Acute Lymphoblastic Leukemias

FAB classification
ALL-L1: small uniform cells
ALL-L2: large varied cells

ALL-L3: large varied cells with vacuoles

(bubble-like features)
Kids: 80% L1, 10-20% L2, <5% L3
Adults: 35% L1, 60% L2, <5% L3

Acute Lymphoblastic Leukemias

WHO classification system:
ALL (includes former L1/L2)
Burkitts (former L3)

pre-B ALL
pre-T ALL
Biphenotypic acute leukemia

The Chronic Leukemias

Chronic Granulocytic Leukemia
Chronic Myelogenous Leukemia

Chronic Eosinophilic Leukemia

Chronic Myelomonocytic

Leukemia
Ph1

is absent

Chronic Lymphocytic Leukemia

Other WBC Dyscrasias

Hairy cell Leukemia
Aka Leukemic reticuloendotheliosis
Hairy cells: 12-20 microns, round to oval

nucleus, cytoplasm has fine filamentous

projections arising from membrane
Multiple Myeloma
Plasma cells with varying degrees of
maturation

Other WBC Dyscrasias

Lymphoma
Malignant tumors of lymphoid tissues

Types:
Hodgkins Lymphoma
Reed-Sternberg Cells
Non-Hodgkins Lymphoma
Other Lymphomas:
Sezary Syndrome
Burkitts Lymphoma

HISTORICAL PERSPECTIVE

Thomas Hodgkin
(1798-1866)
Thomas Hodgkin
published in 1832 the
first description of
lymphoma, specifically of
the form named after
him, Hodgkin's
lymphoma.
Name Hodgkin's Disease
proposed in 1865 by
Wiks.

Rationale for Classification

WHO classification of tumours of the

haematopoietic and lymphoid tissues 4th

edition, 2008
Classification is a language of medicine
Consensus on definitions and terminologies
For clinical practice and investigation

Development of Classification
First, recognising that the underlying causes of the

neoplasm are often unknown and may vary. So, we use

morphology, immunophenotype, genetic features, and
clinical features to define diseases.
Second principle is that classification relies on building a
consensus among as many experts as possible on the
definition and nomenclature of the disease.
Third, while pathologists must take primary responsibility
for developing a primary classification, involvement of
clinicians is essential to ensure its usefulness and
acceptance in daily practice.

WHO classification (4th Edition- 2008) of

myeloid neoplasms and acute leukemia
Myeloproliferative neoplasms (MPN)
Myeloid and lymphoid neoplasms associated with
eosinophilia and abnormalities of PDGFRA, PDGFRB,
or FGFR1

Myelodysplastic/myeloproliferative neoplasms
(MDS/MPN)
Myelodysplastic syndrome (MDS)
Acute myeloid leukemia and related neoplasms
Acute leukemias of ambiguous lineage

B lymphoblastic leukemia/lymphoma
T lymphoblastic leukemia/lymphoma

WHO classification of myeloid neoplasms and acute leukemia

WHO classification of myeloid neoplasms and acute leukemia

WHO classification of myeloid neoplasms and acute leukemia

WHO classification of myeloid neoplasms and acute leukemia

Components of Classification
System
Clinical Features
Morphology
Cytochemistry
Immunophenotyping

Cytogentic or Molecular Genetics

Clinical Features

Role of Morphology

Role of Morphology

Role of Cytochemistry

Role of Immunophenotyping

Genetics in Acute Leukemias

Genetics for Classification

Algorithmic Approach

Summary..

Conceptualizing lymphoma and its

Classification
neoplasms of lymphoid origin, typically causing

lymphadenopathy
leukemia vs lymphoma (extent of BM involvement)
lymphomas as clonal expansions of cells at certain
developmental stages

ALL

CLL

Lymphomas

MM

nave
B-lymphocytes

Lymphoid
progenitor

AML
Hematopoietic
stem cell

Myeloid
progenitor

Plasma
cells
T-lymphocytes

Myeloproliferative disorders
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells

B-cell development
CLL

stem
cell

lymphoid
progenitor

mature
naive
B-cell

germinal
center
B-cell

MM

progenitor-B

ALL

memory
B-cell

pre-B
immature
B-cell

DLBCL,
FL, HL

plasma cell

A practical way to think of lymphoma

Category

NonHodgkin
lymphoma

Survival of
untreated
patients

Curability

To treat or
not to treat

Indolent

Years

Generally
not
curable

Generally defer
Rx if
asymptomatic

Aggressive

Months

Curable in
some

Treat

Very

Weeks

Curable in
some

Treat

Variable
months to
years

Curable in
most

Treat

aggressive
Hodgkin
lymphoma

All types

Classification
Biologically rational
classification

Clinically useful
classification

Diseases that have distinct

morphology
immunophenotype
genetic features
clinical features

Diseases that have distinct

clinical features
natural history
prognosis
treatment

Sources
Blood
D. Arber, Stanford University
Algorithmic approach to Leukemias
S. Zaidi
UC Davis Health system