Hematopoiesis

Erythropoiesis
1. Pronormoblast
(Rubriblast)
 14 to 20 µm in
diameter
 Deeply basophilic
cytoplasm, non-
granular
 N/C ratio is about 8:1
 Fine chromatin pattern
 Usually 1 to 2 nucleoli
Erythropoiesis
2. Basophilic Normoblast
(Prorubricyte)
 12 to 17 µm in
diamater
 Intensely basophilic
cytoplas
 N/C ratio is about 6:1
 Chromatin pattern is
slightly coarser
 Nucleoli are usually not
visible
Erythropoiesis
3. Polychromatophilic
Normoblast
(Rubricyte)
 10 to 15 µm in
diameter
 Blue-gray to pink-gray
cytoplasm due to start
of hemoglobin
production
 N/C ratio approx 4:1
 Chromatin is coarse
and clumped
Erythropoiesis
4. Orthochromic
Normoblast
(Metarubricyte)
 7 to 12 µm in diameter
 Pink cytoplasm
 N/C ratio is about 1:2
 Small pyknotic nucleus
Erythropoiesis
5. Reticulocyte
 7 to 10 µm in diamter
 Pink to slight pinkish
gray cytoplasm with
fine basophilic
reticulum of RNA, Reticulocytes, Wright stain

which only stains with

supravital stain

Reticulocytes, Supravital stain

Erythropoiesis
6. Mature Red Blood
Cell
 6 to 8 µm in diameter
 Pink in color
 Non-nucleated, round
biconcave cell
Granulopoiesis
1. Myeloblast
 15 to 20 µm in
diameter
 Cytoplasm moderately
blue in color,
nongranular
 N/C ratio of 4:1
 Fine chromatin pattern
 Contains 2 to 5
nucleoli
Granulopoiesis
2. Promyelocyte
 15 to 21 µm in
diameter
 Pale blue cytoplasm,
containing few to many
large blue to reddish
purple nonspecific
(primary) granules
 N/C ration of 3:1 to 2:1
 Chromatin slightly
coarser
 2 or 3 nucleoli present
Granulopoiesis
3. Myelocyte
 12 to 18 µm in diameter
 Small, specific
(secondary) granules
begin to appear
 N/C ratio is 1:1
 Chromatin becomes
coarser and more
condensed
 Shows no nucleoli
 Neutrophil myelocyte
 Eosinophil myelocyte
 Basophil myelocyte
Granulopoiesis
4. Metamyelocyte (Juvenile)
 10 to 15 µm in diameter
 Indented or kidney
shaped nucleus
 Chromatin pattern is
coarse and stains dark
purple
 Neutrophil metamyelocyte
 Eosinophil metamyeocyte
 Basophil metamyelocyte
Granulopoiesis
5. Band
 9 to 15 µm in diameter
 Elongated or band-
shaped nucleus
 Chromatin pattern is
coarse and clumped
Granulopoiesis
6. Segmented Neutrophil
 9 to 15 µm in diameter
 Pink to rose-violet
specific granules
 Normally 2 to 5 lobes
connected by thin
nuclear filaments
 Coarse, clumped
chromatin pattern
Granulopoiesis
 Eosinophil
 9 to 15 µm in diameter
 Reddish-orange
granules
 Nucleus usually has two
lobes
 Coarse, clumped
chromatin pattern
Granulopoiesis
 Basophil
 10 to 16 µm in diameter
 Contains specific dark
purple to blue-black
granules
 Generally unsegmented
or bilobed nucleus,
rarely has three or four
lobes
Monopoiesis
1. Monoblast 2. Promonocyte
 12 to 20 µm in  14 to 18 µm in diamter
diameter  Blue-gray cytoplasm
 Moderately basophilic  N/C ratio is 3:1 to 2:1
to blue-gray cytoplasm,  Fine chromatin pattern
nongranular
 1 to 5 nucleoli
 N/C ratio is 4:1 to 3:1
 Fine chromatin
 1 to 2 nucleoli
Monopoiesis
3. Monocyte
 14 to 20 µm in diameter
 Blue-gray cytoplasm
 Many fine azurophilic
granules giving a ground-
glass appearance
 Nucleus is round, kidney-
shaped or may show
slight lobulation, may be
folded over on top of
itself thus showing
brainlike convolutions
Megakaryopoiesis
1. Megakaryoblast
 20 to 50 µm in
diameter
 Cytoplasm in varying
shades of blue
 N/C ratio is about 10:1
 Fine chromatin pattern
 Multiple nucleoli
2. Promegakaryocyte
 20 to 60 µm in
diameter
 N/C ratio is 4:1 to 7:1
 Irregularly shaped
nucleus, may even
show slight lobulation
 Chromatin becomes
more coarse
 Multiple nucleoli
Megakaryopoiesis
3. Granular megakaryocyte
 30 to 90 µm in diameter
 Very fine and diffusely
granular cytoplasm
 N/C ratio is 2:1 to 1:1
 Multiple nuclei may be
visible or the nucleus
may show multi-
lobulation
 No nucleoli are visible
4. Mature megakaryocyte
 40 to 120 µm in diameter
 Contains coarse clumps
of granules aggregating
into little bundles, which
bud off from the
periphery to become
platelets
 N/C ratio is less than 1:1
 Multiple nuclei are
present
Megakaryopoiesis
5. Platelet
(Thrombocyte)
 1 to 4 µm in diameter
 Light blue to purple
cytoplasm, very
granular
Lymphopoiesis
1. Lymphoblast
 10 to 18 µm in
diameter
 Moderate to dark blue
cytoplasm
 N/C ratio is 4:1
 Chromatin is coarse
 1 to 2 distinct nucleoli
2. Prolymphocyte
 Size may be the same
as the lymphoblast or
smaller
 Moderate to dark blue
cytoplasm
 Round, oval or slightly
indented nucleus
 1 to 2 nucleoli
 Chromatin pattern is
more clumped
Lymphopoiesis
3. Mature Lymphocyte
 Small (8 to 10 µm dia.)
 Med (10 to 12 µm dia.)
 Large (12 to 16 µm dia.)
 Blue cytoplasm

 Round or oval nucleus

 No nucleoli are visible

Plasma cells
1. Plasmablast
2. Proplasmacyte
3. Plasmacyte/Plasma cell
 8 to 20 µm in diameter
 Deeply basophilic
cytoplasm
 Large well-defined hof
next to nucleus
 Eccentrically located
nucleus
 Chromatin patter is
condensed and coarse
 No nucleoli are visible
Myeloproliferative
Disorders
Myeloproliferative Disorders
 Group of acquired, malignant disorders that
develop from the proliferation of abnormal
pluripotential stem cell

 The stem cell differentiates into the

granulocytic, megakaryocytic, and erythroid
cell lines
Myeloproliferative Disorders
The disorders include:
 Chronic myelogenous leukemia

 Myelofibrosis with myeloid metaplasia

 Essential thrombocythemia

 Polycythemia vera
Chronic Myelogenous
Leukemia (CML)
 Stem cell disorder affecting the granulocytic,
monocytic, erythrocytic and megakaryocytic
cell lines

 Primarily a disease of adults, occurring

between the ages of 30 and 50

 Accounts for about 20% of all the leukemias

Chronic Myelogenous
Leukemia (CML)
 Exams and tests

 CBC
 Bone marrow aspiration
 Leukocyte alkaline phosphatase (LAP)
 Testing for the presence of the Philadelphia
chromosome
Chronic Myelogenous
Leukemia (CML)
 CBC
 WBC count: 50,000 to 30,000/uL
 <10% myeloblasts are present in peripheral
blood, and there is a complete spectrum of
granulocytic cells from the myeloblasts to the
mature neutrophil with a predominance of
neutrophil and myelocytes
 Eosinophils and basophils are increased
 Percentage of monocytes may also show an
increase
Chronic Myelogenous
Leukemia (CML)
 CBC

 Mild normochromic anemia

 Platelet count is usually increased, and large from

of the platelets may be present, as well as the
megakaryocyte fragment
Chronic Myelogenous
Leukemia (CML)

High-power microscopic view of a blood smear from a

person with classical CML shows predominantly normal-
Hypercellular bone marrow
appearing cells with intermediate maturity characteristic of CML
Chronic Myelogenous
Leukemia (CML)
 Leukocyte alkaline phosphatase (LAP) stain

 LAP is decreased or absent in this disorder

Chronic Myelogenous
Leukemia (CML)
 Bone marrow aspiration

 Hypercellular and shows an increased number of

myeloid cells, with a slightly higher percentage of
immature granulocytes than is present in
peripheral blood, and megakaryocytes are more
numerous than usual

 Myeloid-erythroid (M:E) ratio can be as high as

25:1
Chronic Myelogenous
Leukemia (CML)
 Philadelphia chromosome
 In 90% of the cases, one arm of the chromosome
pair number 22 is found to be translocated to
chromosome 9 (Philadelphia chromosome)
 Occurs in the eryhroid, granulocytic, monocytic
and megakaryocytic cells
 Patients with this disorders who are negative for
the Philadelphia chromosome usually have a
poorer prognosis and do not respond particularly
well to chemotherapy
Myelofibrosis
 Idiopathic myelofibrosis or agnogenic myeloid
metaplasia
 Characterized by fibrosis and granulocytic
hyperplasia of the bone marrow, with
granulocytic and megakaryocytic proliferation
in the liver and spleen
 It is generally found in the middle aged or
elderly people
Myelofibrosis
 Exam and tests

 CBC

 Leukocyte alkaline phosphatase (LAP) stain

 Bone marrow biopsy

Myelofibrosis
 CBC
 Normocytic normochromic anemia

 Stained blood smear characteristically shows

teardrop-shaped red cells

 Presence of nucleated red cells

 Polychromatophilia is present, and the

reticulocyte count is increased
Myelofibrosis
 CBC
 White blood cell count is variable but is increased
in the majority of patients
 Immature granulocytes are generally present on
the stained blood smear and the number of
basophils is often increased
 Dwarf megakaryocytes or small megakaryoblasts
are present in small numbers in peripheral blood
 Platelet count is increased in about 50% of the
cases at diagnosis but decreases below normal
as the disease progresses
Myelofibrosis

Teardrop cells (dacrocytes)

Myelofibrosis
 Leukocyte alkaline phosphatase (LAP) stain

 LAP is increased in the majority of cases but may

be normal or decreased
Myelofibrosis
 Bone marrow biopsy
 BM is usually hypocellular and the collagen
content is increased
 However, in the early stages of the disease, the
marrow may be hypercellular and contain an
increased number of megakaryocytes, some of
which are abnormal
 Marrow generally becomes fibrotic with the
abundance of reticulin fibers
Essential Thrombocythemia
 Characterized by
excessive proliferation of
cells of the
megakaryocytic lineage
 Platelet count usually to
levels greater than 1
million/µL
 Platelets appear large
and morphologically
abnormal
 Platelets are functionally
abnormal
Polycythemia vera
 Chronic myeloproliferatve disease of
unknown origin that is found in patients over
60 years of age

 It is characterized by the excessive

proliferation of the erythroid, granulocytic and
megakaryocytic cell lines
Polycythemia vera
 Exams and tests

 CBC

 Bone marrow biopsy

Polycythemia vera
 CBC
 Disease is characterized by an absolute increase
in the red blood cells, white blood cells and
platelets
 Red blood cell count, hemoglobin, hematocrit,
white blood cell count and platelet count are
increased
 Peripheral blood smear shows normocytic
normochromic red blood cells, moderate
anisocytosis, and slight polychromatophilia
Polycythemia vera
 Reticulocyte count generally shows slight
elevation, although not usually over 4%

 ESR is usually decreased

 LAP is usually increased, which aids in the

distinguishing polycythemia vera from other
types of erythrocytosis
Polycythemia vera
 Bone marrow biopsy
 Hypercellular showing an overall increase in the
granulocytic, erythroid, and megakaryocytic cells
 Distribution, morphology and maturation of the
marrow cells are normal
 Bone marrow iron stores are decreased or absent
from unknown blood losses and excessive
erythropoiesis
Lymphoproliferative
Disorders
Lymphoproliferative Disorders
 Conditions characterized by unregulated
growth and proliferation of cells of the
lymphoid lineage

 Acute Lymphoproliferative Disorders

 Chronic Lymphoproliefrative Disorders

Chronic Lymphocytic
Leukemia
 Majority of cases appear to involved the B
lymphocytes, T lymphocytes is less involved
 More than twice as common in men as in
women
 Lymphadenopathy, fatigue, weight loss,
splenomegaly, and hepatomegaly are
common clinical features
Chronic Lymphocytic
Leukemia
RAI CLASSIFICATION

0 Bone marrow and blood lymphocytosis

only
I Lymphocytosis with enlarged lymph nodes

II Lymphocytosis with enlarged spleen and/or

liver
III Lymphocytosis with anemia (hb<11g/dL)

IV Lymphocytosis with thrombocytopenia

(platelets <100,000/mm3)
Chronic Lymphocytic
Leukemia
 WBC count is usually 20,000 to 200,000/µL with
peripheral blood smear showing 60 to 95%
lymphocytes

 Lymphoblasts are generally absent from the

peripheral blood but a rare prolymphocyte may
sometimes be found.

 Large number of smudge cells are usually seen on

the Wright stained smear
Chronic Lymphocytic
Leukemia
 Normocytic, normochromic anemia generally
develops as the disease progress

 Platelet count is usually normal or shows only a

slight decrease

 Bone marrow is hypercellular, and the

predominant cell is the small mature lymphocyte
Chronic Lymphocytic
Leukemia

Smudge cells
Hairy Cell Leukemia
 Leukemic reticuloendotheliosis
 Characterized by the presence of variable
numbers of distinct type of cell called “hairy”
cells in the blood and bone marrow
 Monoclonal antibody studies show these cells
to be of lymphocytic origin and show
characteristic of B lymphocytes
 Acid phosphatase stain using tartaric acid will
be positive
Hairy Cell Leukemia
Hairy Cell Leukemia
 Usually there is pancytopenia or depression of
all cell lines in most patients upon presentation,
but the white blood cell count may be increased
depending on the number of cells in peripheral
blood
 Generally a mild normocytic normochromic
anemia
 Platelet count is usually decreased below
 50, 000/µL, and the white cell count below
3,000/µL, with no pervious therapy
Lymphomas
 Malignant neoplasms of the lymphoid organs
characterized by neoplastic growth of cells
committed toward lymphoid differentiation
 Tumors primarily affect lymphoid tissues,
particularly lymph nodes and spleen, but may
involve other lymphoreticular sites, including
the liver, gastrointestinal tract,
nasopharyngeal tissues, and the lungs
Non-Hodgkin’s Lymphoma
 Proliferations of malignant lymphocytes that are
arrested at certain stages of maturation
 Primarily neoplasms of the B-cell lymphocytes and
occur predominantly in the middle and older age
groups
 The exact cause of non-Hodgkin’s lymphoma is not
known, but in 60% of the cases there is evidence of
chromosomal damage that account for the
unregulated growth of lymphocytes
 Chemicals, ionizing radiation and viruses may play a
role in initiating this damage
Hodgkin’s Lymphoma
 Malignant lymphoma, but has a different
histologic appearance in that the cells
reacting to the neoplasm usually predominate
rather than the neoplastic cells themselves
 Hallmark of the disease is the Reed-
Sternberg cell, which is a large binucleated or
multinucleated cell, with each nucleus
bearing a very large nucleolus
Hodgkin’s Lymphoma

Reed-Sternberg cell
Hodgkin’s Lymphoma
 Hematologic findings early in course:

 Mild normochromic, normocytic anemia

 Moderate leukocytosis with eosinophilia to 10%

 Normal or increased platelet count

 Increased ESR
Hodgkin’s Lymphoma
 Hematologic findings later in disease:

 Lymphopenia

 More severe anemia

 Thrombocytopenia
Acute Lymphoblastic
Leukemia
 L1
 Lymphoblasts are small
and homogenous, with
scanty cytoplasm and
inconspicuous nucleoli;
the nucleus is large and
irregular in shape

 Most common type

(84%) of childhood ALL
Acute Lymphoblastic
Leukemia
 L2
 Lymphoblasts are larger
and variable in size with
basophilic cytoplasm,
and nuclei are clefted
with nucleoli present

 Accounts for 14% of the

cases of childhood ALL,
and includes 64% of the
adult type of ALL
Acute Lymphoblastic
Leukemia
 L3, Burkitt-type
 Lymphoblast is large, but
vary little in size;
cytoplasm is moderate in
quantity and deeply
basophilic, often with
prominent vacuoles

 Accounts for only about

2% of the cases of ALL