Bone Marrow Examination

School of clinical medicine，Ningxia Medical University

Xueyun Liang (梁雪云): Researcher
e-mail：nxmclxy@163.com
Tel.：13895409857
Where
are the blood cells coming from ?

How about it ?
 Cell Lines in Blood Cell Formation

 Genesis of erythrocytes
• Committed cells are proerythroblasts

• Remain in the reticulocyte stage for 1–2 days in

circulation

• Make up about 1–2% of all erythrocytes

 Formation of leukocytes
• Granulocytes form from myeloblasts
• Monoblasts enlarge and for monocytes

 Platelet-forming cells from megakaryoblasts,

break apart into platelets
 COMPONENTS
BM ideally consists of evaluating of these components

 Peripheral blood  Bone marrow tissue section

➢ CBC ➢ Trephine biopsy

➢ Differential count ➢ Clot section
➢ Reticulocyte count
➢ Blood smear morphology

 Bone marrow  Laboratory studies-miscellaneous

➢ aspirate
Morphology ➢ Iron studies
➢ cytochemical stains ➢ B12/folate
➢ Flow cytometric immunophenowping ➢ Hemoglobin electrophoresis
➢ cytogenetic analysis ➢ Immunoelectrophoresis
➢ Molecular biological studies ➢ LDH
➢ Coomb's test
➢ Microbiology culture/serology results
➢ Miscellaneous
Indication For Bone Marrow Evaluation
Evaluation for Primary hernatologic disorder;Staging for
ma|ignancy Hodgkin's disease;Staging for non-Hodgkin's
lymphoma;Metastatic tumor (nonhematopoietic)

Monitoring Post-chemotherapy
therapy Post-bone marrow transplantation
.

Evaluation of Marrow production problem

cytopenias Peripheral destruction; inadequate/ ineffective
marrow release

Culture (fever of unknown origin)

Miscellaneous

Why do we exam bone marrow?

Special aspiration needles are available for
bone marrow aspirations procedure.
 It involves using
a needle to take
a sample

A pathologist of the physician performs the biopsy and

aspiration procedure while the hematology practitioner
prepares the sample for processing.
Position of bone marrow aspiration

• sternum

• anterior iliac crest

• posterior iliac crest

• the medial surface of the
tibia in babies up to the age
of 18months.
 contraindication for bone marrow
aspiration

• Hemorrhage disease due to serious lack of

coagulation factors
• Punctured location has infection or
malformation.
• Be careful when the women with gestation
have bone marrow examination （to
prevent miscarriage）
Dry tap often happens when a marrow is:

fibrotic
□myelosis(leukemia\polycythemia vera )
□myeloproliferative reduce(aplastic
anemia )
□tumor bone marrow infiltration
NEUTROPHIL ALKALINE PHOSPHATASE
STAIN (NAP)

NAP ↑: NAP ↓

➢ Leukemoid
Reaction
➢ Bacterial infections  CML
➢ Polycythemia vera  virual infections
➢ Aplastic anemia  PNH
➢ Acute lymphocytic  AML
leukemia
 AS-D NCE
a -NBE stain
POX stain

NON Specific
PEROXIDASE Specific Esterase Stain
STAIN Esterase Stain ➢ AMOL:
1.Distinguishing the help differential Monoblasts (+)
different types of leukemias inhibited by
acute (1) AML NaF.
leukemia.AML- (2) AMOL/M5 AML:
Positive,AMOL-
(3) ALL Myeloblasts (-)
Faintly positive; ALL or (+) not
– Negative,ALL can
(4) AMMOL /M4
inhibited.
be ruled out in POX
➢ ALL:
positive case. AML
and AMOL can not
Lymphoblasts
be ruled out in POX (-) or (+) not
negative case. inhibited.
2.Distinguishing APL Erythremia
and AMOL Normablast
 Interpretation of Bone Marrow Studies

➢Bone marrow cellularity is best determined on

the bone marrow tissue sections but can be
estimated from the bone marrow aspirate smear
➢The next step in evaluating bone marrow is
determining the distribution of cells within the
marrow.
➢The next step in the evaluation of bone marrow
is assessing myeloid and erythroid development
both quantitatively and qualitatively.
 LEUKEMIA
 Leukemia is an abonormal, uncontrolled proliferation of one or more of
the hemopoietic cells, it is a malignant hemopathy.
 It is a group of clonal and hetergenous maliganancy of hemapoietic
tissue characterized by an overproduction , differentation or
maturation aressted and apoptosis reduced of leukemic cell in the
marrow and impaired production normal blood cells resulting in
grannulocytopenia anemia and thrombocytopenia.
 Leukemic cells present: qualitative change—morphologic-- functional
quatitative abnormality.
 Symptoms

• When there are too many WBC ：Infections

• When there are few RBC: Paleness / Anemia
• When there are few PLT: bleeding
 Leukemias, in general, are defined as malignant neoplasms
of the hematopoietic system arising in the bone marrow.
In a simplistic fashion, it is easiest to classify leukemias based on

1) of disease

• Acute lymphoid
• chronic myeloid
Acute leukemia (AL):
immature,early <6M
Chronic leukemia
(CL):mature,late>1Year
 Classification of leukemias

Acute Chronic
Myeloid Acute Myeloid Chronic Myeloid Leukemia
origin Leukemia 45%(AML) 15%(CML)

Lymphoid Acute Lymphoblastic Chronic Lymphocytic

Leukemia 10%(ALL) Leukemia30% (CLL)
origin
 Blood and Bone Marrow
 Blood:
 A variable WBC count (elevated in most cases) with or without blasts in the
circulation blood. (leukemic leukemia or aleukemic leukemia).
 Normochromic, normocytic anemia with anisocytosis, poikilocytosis and nucleated
red cells.
 Often a severe thrombocytopenia (elevated in early stage of CML).
 Bone marrow aspirate:
 BM is essential to establish the diagnosis and determine the precise cytologic
type. Sometime aspiration is difficult (dry tap or marrow necrosis).
 Abnormal number:
 Morphologic abnormality.
 --Leukemic cells appear to be highly polymorphic
 MICM

MICM Cytogenetics
Molecular biololgy

Immunological

Morphorlogy
 Cytochemical Stain In The AML
PEROXIDASE STAIN ( POX )

(-) (+~++++)
Acute Lymphoblastic M1AMLwithout
Leukemia Al M4, Acute
maturation; M2, AML
myelomonocytic
with maturation;M3,
leukemia
Acute promyelocytic
M5a, Acute
leukemia M4 Acute
monoblastic leukemia
myelomonocytic
leukemia

Specific Esterase Stain NON Specific Esterase Stain

（ a -NBE stain）
 Immunological markers
stem cell: TdT
HLA-DR
CD34
B-cell associated: CD10 CD22,
CD19 CD24,
CD20 CyCD79a

T-cell associated: CD2

CyCD3
CD5
CD7
Myeloid/ monocytic associated: CD33 , CD11 , CD13
CD14 , CD15 , CD117 , MPO
Megakaryoblastic : PPO
CD41 a , b ( Platelet GP Ⅱb / Ⅲa , Ⅱb )
CD61 ( GP Ⅲa )
CD42b ( GPⅠb )
Erythron : glycoprotein A, H
AML subtypes(FAB )& Immunological Markers
Subtypes typical Immunological Markers

M0 CD34, CD33, CD13

M1 MPO, CD34, CD33, CD13
M2 MPO, CD33, CD15, CD13
M3 MPO, CD33, CD13 (HLA-DR
negative)
M4 MPO, CD33, CD15, CD14, CD13
M5 MPO, CD33, CD14, CD13
M6 CD33, Glycoprotein A
M7 CD33,CD41,CD42b,CD61
Cytogenetic Abnormalities in Acute Leukemias

Acute Myeloid Leukemia

Relatively specific
M2 t(8;21)(q22;q22)
M3 t(15;17)(q22;q21)
M4Eo inv(16)(p13q22) or del(16)(q22)
M4,M5 t(8;16)(p11;p13)
M4,M5 t(9;11) (p21;q23)
M2,M4 t(6;9)(p23,q34)
 Acute Myeloid Leukemia
FAB Chromosomal Molecular
Subtype translocation target

M 2b t(8;21) AML 1-MTG8 (ETO)

M 2 or M4 t( 6;9) DEK-CAN
M3 t(15;17) PML-RARα
M 4 E0 inv 16 CBF β-MVHII
M4 or M5 t(8;16) MOZ-CBP
 Acute Lymphoblastic Leukemia, ALL

➢A malignant proliferation of lymphoblasts and prelymphocytes

within the blood and marrow.
➢The onset of symptoms in patients with ALL is usually acute and
rapidly progressive.
➢The clinical manifestations of ALL relate primarily to the
suppression of normal bone marrow elements: weakness,
fatigue, and malaise owing to anemia; fever, infection, and
unresponsiveness to antibiotics owing to leukopenia; and
bleeding owing to thrombocytopenia. Skeletal pain as a result of
marrow expansion is also not an uncommon
 Laboratory Findings--ALL

Blood: Anemia is usual .The total leukocyte count is usually raised with
lymphoblasts present. The granulocyte count is usually reduced. The
PLTcount is usually low.Bone Marrow: The bone marrow is hypercellular
consisting almost entirely of lymphoblasts.
 FAB CLASSEFICATION OF ALL
L1 L2 L3
Size Predominant small cells Heterogeneous, Large cells
intermediate to large
cells

cytoplasm Scant Variable to moderately Moderately abundant

abundant

Nucleoli small/inconspicuous ≥1;prominent to large ≥1;prominent to large

Nuclear chromatin Homogeneous and Heterogeneous with Finely reticular

intermediate reticular some having finely
reticular chromatin

Nuclear shape Regular and round lrregular Regular to round

Basophilic cytoplasm Slight to none Slight to none intense

vacuolation Slight to none Slight to none Prominent; sharply

punched out
ALL can be classified either morphologically or immunologically. FAB morphologic classification of
acute leukemia has designated subtypes FAB-L1,-L2, and -L3,The revised FAB classification of
ALL is based on weighing various criteria: nuclear-to-cytoplasmic ratio, the number of nucleoli,
nuclear membrane irreguiarity, and cell size
 L1
cel
l

L2
cell L3
cell

Bone marrow with Acute lymphoblastic leukemia L3-

primarily L1 blasts Burkitt’s:Leukemia/lymphoma.
and occasional L2 blasts.0
Cytochemical

The lymphoblasts are Sudan

Black and POX negative
( myeloid markers ).

Most cases are non specific

estarase negative (α-NBE
negative).
L1
cel
l

L2
cell
T cell ALL may show ACP stain
positive. PAS stain is often positive.
NAP↑
 This schematic diagram outlines the relationship of the acute and
chronic myeloid and lymphoid leukemias to normal hematopoietic
and lymphoid development.

Thus, referring to Fig,one can rationalize the existence of the various

morphologic subtypes of AML based on whether the granulocytic,
monocytic, erythroid, or megakaryocytic arm of myeloid differentiation is
involved.
Acute Myelogenous Leukemia , AML

The AMLs are a heterogeneous group of

malignancies originating in the hematopoietic,
or myeloid, stem cell. The neoplastic
proliferation seen in AML consists of
myeloblasts or partially differentiated myeloid
cells.
Laboratory Findings
In AML the WBC is elevated in more than half
of patients at the time of diagnosis. pancytopenia
is a constant feature of this leukemia.
As many as 10% of patients will have WBC
counts that are greater than l00.0×109/L with
some patients approaching 500.0×109/L ,Patients
with WBCs greater than 50.0 to 100.0×109/L are
at risk of developing complications owing to
hyperleukocytosis.
FAB（FAB classification ）
F-A- B cooperative group has classified AL on the basis of
the morphologic feature and numbers of blast cells in 1976
 blast
How about quantity?
FAB >30
However, the recent WHO classification, the required percentage of
blasts for diagnosis of AML is decreased to 20%in the bone marrow and
peripheral blood.

WHO > 20
 FAB CLASSIFICATION OF AML
M0 Acute leukemia, undifferentiated; myeloid immunophenotype

M1 Acute myelogenous leukemia(AML)without maturation

M2 AML with maturation
M3 Acute promyelocytic leukemia (APL)
M3v :Hypogranular variant of APL
M4 Acute myelomonocytic leukemia (AMMOL)
M4 e :M4 with eosinophilia
M5 M5a: Acute monoblastic leukemia(AMOL)
M5b:Acute monocytic leukemia
M6 Acute erythroleukemia
M7 Acute megakaryoblastic leukernia(AMKL)

FABgroup on acute leukemia has morphologically subclassified the AMLs into seven major
subtypes: FAB-M1 to FAB-M7.The FAB classification of AML basically relies on the degree of
granulocytic, monocytic, erythroid, and megakaryocytic differentiation
 FAB-MO: minimally differentiated AML
The FAB-M0 group of AML
is myeloid leukemia with
a minimal differentiation
that has a demonstrable
myeloid lineage by
immunophenotyping or
ultrastructural studies.
These AMLs consist of
small-to intermediate-
size leukemic blasts
without any evidence of
granulocytic
differentiation.
Cytochemical staining
with MP0,Sudan black B
(SBB),and nonspecific
esterase(NSE)is
negative.
AML - M0 (minimally differentiated AML)
2-3%(AML)
➢Morphology: Blasts ≥30% (without Auer rods)
➢Cytochemistry: POX, SBB (+) <3%
➢Immunology:MPO+,CD13, CD33, CD14, CD15,
CD11b
➢Cytogenetics and Molecular Biologic
➢Ultrastructure: MPO (+), PPO (-)
 FAB-M1: AML Without Maturation
In these AML s without
maturation, there is
minimal evidence of
cytoplasmic
granulation and
minimal numbers of
Auer rods. The blasts

Type 1 blast cells

are intermediate in
size with finely
reticular chromatin,
small amounts of
grayish-blue
cytoplasm, and
typically one or more
prominent nucleoli
 FAB-M1: AML Without Maturation
BM hypercellular
Myeloid 1)the sum of total blasts is greater than 90% of
the bone marrow cells; Small myeloblasts can be
seen.It characterized by small body ,round nuclei,fine
chromatin,1-2visible nucleoli and pseudopodia. Auer
rods can be seen in few cases.(2)less than 10%of bone
marrow cells shows evidence of granulocytic
differentiation at or beyond the promyelocyrte stage;
Cytochem POX SBB: Positive Myelobalsts >3%.
istry AS-D-NEC (+).
Other CD34+, HLA-DR+, CD33+, CD13+, CD11-,CD15-D,
Cytogenetics: Chromosome inv (3) (p21;q26)
 FAB-M2: AML with Maturation
M2 are the most common
subtype of AML ,These
leukemias show clear
evidence of
differentiation at
blast cells with
or beyond the
Auer rods
promyelocyte
stage, and Auer
rods are
commonly
identified

Auer rods are absolutely specific for a leukemic myelogenous process and
consist of abnormally fused primary granules.Auer rods are needle-to
fusiformlike eosinophilic rods that are found in the cytoplasm of leukemic
myeloid cells and stain red to purple with Wright-Giemsa stain
 FAB-M2: AML with Maturation
BM hypercellular

(1)the sum of myeloblasts is 30% or greater but

less than 90% of the bone marrow cells;
myeloblasts 30-90% (NEC)(2)more than10% of
the bone marrow cells shows evidence of
grannlocytic differentiation; (3) monocytic cells
constitute fewer than 20% of the bone marrow
cells.
Cytochem POX, SBB: +++; AS-D-NCE: ++; α-NAE: (-) (+) not
istry depressed by NaF (sodium fluoride)
Other Chromosome t(8;21) in 90% cases.
Molecular target: AML1-MTG8 (ETO) fusion gene.
 AML M3 (acute Promyelocytic leukemia Faggot cell)

One of the
characteristic
features of
APL are the
so-called
faggot cells,
which are
cells that
contain
multiple Auer
rods that may
be bundled,
intertwined, or
fused together Faggot cells

Auer rods are absolutely specific for a leukemic myelogenous process and
consist of abnormally fused primary granules.Auer rods are needle-to
fusiformlike eosinophilic rods that are found in the cytoplasm of leukemic
myeloid cells and stain red to purple with Wright-Giemsa stain
 FAB-M3: Acute Promyelocytic
Leukemia,APL
BM hypercellular
Pancytopenia in partial cases.
Hyperplasia of abnormal promyelocytes (>30% NEC) in BM.
M3v:micro-granular variant

Cytochem POX, SBB stain:(++)(+); α − NAE: (+) monoblasts depressed by

istry NaF. myeloblasts not depressed by NaF; AS−D−NCE: (++) –
myeloblasts(+)(–) – monoblasts.
Other CD13,CD33
Chromosome t(15:17) )(q22;q12,21)
FAB-M4: Acute Myelomonocytic Leukemia
M4 and FAB-M2 are the
most common AMLs,
together accounting for
approximately two
thirds of all AML cases.
The FAB-M4 subgroup
of AML is probably the
most difficult subgroup Monoblast
of AML in which to
perform a reliable cells
differential count, as
this is a very
heterogeneous-
appearing leukemia.
Both granulocytic and Myeloblast
monocytic cells
differentiation are
present in varying
proportions in the bone
marrow
 FAB-M4: Acute Myelomonocytic Leukemia
BM hypercellular
(1)the sum of all blasts is greater than 30%; (2)the sum of
myeloblasts and granulocytic precursor cells account for
less than 80% of the bone marrow cells;(3)more than
20% of the bone marrow cells are of the monocytic (20%-
80%)lineage as demonstrated by morphology,
Cytochem POX, SBB stain: monoblast (-/±) myeloblast (+)
istry AS-D-NCE [NAS-DCE](++) – myeloblasts (+)(-monoblasts.

Other Abnormalities of chromosome l6,including inversion of

16(p13;q22) or deletion of 16q22, are consistently
identified in this variant.
 Acute myelogenous leukemia M4 with
eosinophilia(M4eos)

A variant of FAB-M4
exists, which has
been called FAB-
M4 with
eosinophiiia(M4eos)
.Criteria for
diagnosis include
the usual diagnostic
criteria for FAB-M4
and an increased
number of atypical
immature bone
marrow eosinophils.
eosinophi
ls
 FAB-M5a: Acute Monoblastic Leukemia and FAB-
M5b:Acute Monocytic Leukemia
FAB-M5a is characterized
by a predominance of
monoblasts that are
large and have
relatively abundant
cytoplasm. Some
azurophilic granules
may be identified in
the cytoplasm that are
MPO negative.
Typically, the nucleus is
displaced to one side
with an ample amount
of cytoplasm wrapping
around the Monoblast and
nucleus.The sole promonocyte
criterion for diagnosis
of FAB-M5a is the
existence of more than
80% monoblasts in the Acute myelogenous leukemia
bone marrow.
M5a.
 Acute myelogenous leukemia M5b.
FAB-M5b, in which more
than 80% of the marrow
cells are monoblasts,
promonocytes, or
monocytes but less than
Promonocyte and
80% of the marrow cells
are monoblasts. In other monocyte
words, FAB-M5b shows
more differentiation than
FAB-M5a. .Nuclear folding
and irregularity are
common in FAB-M5b,and
more azurophilic
granulation is identified
than in FAB-M5a.

Shows round, ellipstical or irregular monoblasts with

indented, folded nuclei. The chromatin is fine reticular with
prominent nucleoli.Cytoplasm is gray – blue.
 FAB-M5a/b: Acute Monoblastic/cytic Leukemia

BM hypercellular
M5a: monoblast >80% (NEC).
M5b: monoblast<80%(NEC)
Cytochem NSE cytochemical stains are positive in the FAB-M5
istry leukemias. Auer rods may be seen in a small
percentage of monoblasts but are certainly much less
frequent than in the granulocytic types of AML.
Other FAB-M5a and FAB-M5b are associated with a high
incidence of exatramedullary infiltration; DIC may also
develop in patients with FAB-M5, second in incidence
only to FAB-M3 among classes of AML. AML-M5a is
more commonly diagnosed in the pediatric age group.
 FAB-M6: Acute Erythroleukemia
(Di Guglielmo’s Syndrome)
Acute erythroleukemia is a relatively
uncommon variant of AML and may have
multiple presenting appearances.
 Acute myelogenous leukemia M6
(erythemic myelosis).

erythroid hyperplasia

One form, which has previously been called erythemic myelosis, is

characterized by bizarre and markedly atypical megablastoid changes
accompanied by extreme erythroid hyperplasia within the bone marrow .
 Acute myelogenous leukemia M6.

erythroblast

myeloblast

In other cases of FAB-M6, the marrow contains more differentiated,

albeit dysplastic, erythroblasts at the time of presentation along with
a definite population of granulocytic cells, including myeloblasts.
 FAB-M6: Acute Erythroleukemia

BM Hyperplasia of myeloid series , erythroid with dysplasia

The following criteria were established by the FAB group
for the diagnosis of erythroleukemia in determining blast
percentage:(1)50% or more of all nucleated bone marrow
cells must be erythroblasts (2) dyserythropoiesis is
prominent;(3) 20% or more of the nonerythroid cells in the
bone marrow are myeloblasts.
Cytochem PAS+
istry

Other Erythremia / Erythroleukemia / Leukemia phase.

 FAB-M7: Acute Megakaryoblastic leukemia
BM Hyperplasia mainly of megakaryoblasts(MKB),
promegakaryocytes and micromegakaryoblasts
The diagnostic criteria for diagnosis includes1）more
than 30% blasts in the bone marrow of
megakaryoblastic
POX, SB, a-NBE : (-) PPO (+) on electronic microscope
Cytochem
MPO (-). Immunophenotyping with monoclonal antibodies
istry reactive with platelet glycoprotein(Gp) IIb/IIIa or Gp
IIIa(CD4land CD61)has provided a more sensitive and
reproducible method of detecting megakaryoblasts.
Other definitive identification of megakaryoblastic involvement
by a platelet peroxidase reaction by electron
microscopy or reactivity with megakaryocyte-speciflc
monoclonal antibodies.
 FAB-M7: Acute Megakaryoblastic leukemia

There is typically scanty basophilic cytoplasm, which may or may not be vacuolated.
Indeed, the degree of basophilia may be comparable with that found in erythroleukmia,
reflecting the close developmental relationship between erythroid and megakaryoblastic
precursors.Very fine granulation can be identified in the cytoplasm of some basts.
Intermediate forms between undifferentiated blasts and definitive micromegakaryocytes
may also be seen
 CLASSIFICATEON OF AML
summery
FAB Diagnostic Criteria
Subtype
M0 No morphologic evidence of differentiation
Negative cytochemical staining with MPO/SBB/NSE
Positivity with myeloid markers (CD13,CD33, etc.)and negative
lymphoid markers

M1 ≥90%blasts in bone marrow

＜10%of marrow showing granulocytic differentiation
＞3%of blasts with MPO or SBB positivity

M2 ≥30%blasts and ＜90%blasts in marrow;

≥10%of marrow showing granulocytic differentiation
≤20%monocytic cells

M3 ≥30%of marrow or abnormal promyelocytes

M3v:Same as M3 except composed of hypogranular variants
FAB Diagnostic Criteria
Subtype
M4 ≥30%blasts
≤80%myeloblasts and granulocytic precursors in marrow
＞20%monocytic cells in marrow (morphology/NSE stain/serum
lysozyme)
M4e :Same as M4 with increased number of atypical/immature
marrow eosinophils
M5 M5a ≥80%monoblasts
M5b ≥80%of monoblasts /promonocytes /monocytes ＜
80%monoblasts in marrow
M6 ≥50%nucleated RBC
Prominent dyserythropoiesis
≥30%rnyeloblasts in nonerythroid cells
M7 ≥30%blasts
Identification of megakaryoblasts by ultrastructurai cytochemistry
or by immunophenotyping
 CHRONIC LYMPHOCYTIC
LEUKEMIA,CLL
➢CLL is a common neoplastic disease
characterized by proliferation of small,
morphologically mature lymphocytes.
➢CLL involves the blood and bone marrow, and
also frequently the lymph nodes, spleen, and
liver.
➢It is a disease with a male predominance and a
median age approximately 65,being rarely seen
in individuals less than 40 years . Most cases of
CLL are of B-cell type
Classification Of Lymphoproliferative Disorders(1)
• Chronic Lymphoproliferative Disorders
• Peripheral B-cell
• Chronic lymphocytic leukemia
• prolymphocytic leukemia
• Hairy-cell leukemia
• Peripheral T-cell
• Chronic lymphocytic leukemia
• prolymphocytic leukemia
• Large grannlar lymphocyte leukemia
• Sezary syndrome
• Adult T-cell leukemia/lymphoma
• Immunoproliferative Disorders
• Plasma cell myelorna
• Plasmacytoma
• Waldenström's macroglobulinemia
• Heavy chain disease
• Benign monoclonal gammopathy
• Amyloidosis
• Malignant Lymphomas
• Non-Hodgkin's lymphoma
• B-cell lymphomas
• T-cell and NK-cell lymphomas
• Hodgkin's disease
• Postransplant lymphoproliferative disorders
• Acute Lymphocytic Leukemia (derived from
precursor B-and T-cells)
• will be discussed in a separate chapter
 CLL - blood count
WBC x 109 /L 150 .0 [4-11]
Hb g/L 98 [120 -16 0 ]
MCV fl 87 [79-9 8 ]
Platelet s x 109 /L 48 [150 -450 ]

Neuts x 109 /L 1.5 [2-7.5]

Lymphs x 10 9 /L 130 .0 [1.5-4]
Monos x 109 /L 0 .5 [0 .2- 0 .8 ]
Eos x 10 9 /L - [0 -0 .7]
Basos x 109 /L - [0 -0 .1]

Smudge cells x 10 9 /L 28.0 [0 ]

Film Comment : appearances suggest CLL

infiltrated by small lymphocytes (>40%) ( PAS++ )
lymphoblasts + prolymphocytes <10%
 Chronic Myelogenous Leukemia, CML

➢Is characterized by an unregulated

proliferation of myeloid elements in the bone
marrow, liver and spleen, leading to marked
leukocytosis and organomegaly.

➢This disease is defined by a molecular marker, the

Philadelphia chromosome (Ph)with the breakpoint
duster region-Abelson murine leukemia virus (BCR-
ABL)fusion gene that results from the translocation
of chromosomes 9and 22[t(9;22) (q34;q11)]
 How to distinguish AML vs CML
from looking at peripheral blood

Myeloid cell CML AML normal

blasts q q
promyelocytes q
myelocytes q
metamyelocytes q
bands q
neutrophils q # q
 The peripheral blood white cell count in leukemia

Whit e Cell Different ial Whit e Cell Count

Count
Acut e Low, normal If high, blast cells
or high predominat e. If normal or low,
can be very few blast s
Chronic High Mat ure cells predominate.
Blast s less t han 10%
 Bone Marrow Finding

➢Marked hypercellularity.
G/E↑↑
➢Hyperplasia of myeloid series with more
matured elements later than myelocytes.
myelocytes and metamyelocytes↑↑

➢Eosinophilia and basophilia may be

present.
Review
 1The reasons of red blood cells
disorder (anemia)
 Blood loss → hemorrhagic anemia
 produce↓
 Insufficient intake or absorption of Fe2+ → iron deficiency anemia（the RBC
diminishes in proportion with Hb.）
 Lack of B12 or intrinsic factor → pernicious anemia
 Destruction of red marrow→ aplastic anemia Rupture of RBC’s → hemolytic anemia
 Destruction, recycling of RBC’s phagocytized in liver, spleen, red marrow, globin
hydrolyzed to amino acids

24
 2 Clinical significance of WBC count
 Neutrophilia is often seen as a consequence of bacterial
infection, drug, marrow damage,an enlarged spleen.
 Eosinophilia are infections by parasites, allergic conditions, and
dermatologic disorder.
 Basophilia is occasionally a clue to the presence of either
chronic myelocytic leukemia or one of the other
myeloproliferative disorders.
 3 The common tests for the diagnosis of anemias

To determine if anemia presents, depending on the lab

findings.The common tests for the diagnosis of anemia are:
 RBC ,Hb, PCV(fllowing)
 3M(MCV MCHC MCH )
 Ret
 Blood smear
 Bone marrow (aspiration biopsy)
 The further laboratory test
 4 The character of different cell lines
during development
 Genesis of erythrocytes
• Committed cells are proerythroblasts
• Remain in the reticulocyte stage for 1–2 days in circulation
• Make up about 1–2% of all erythrocytes
 Formation of leukocytes
• Granulocytes form from myeloblasts
• Monoblasts enlarge and for monocytes

 Platelet-forming cells from megakaryoblasts, break apart into platelets