Errisa Devi Fauzi

Diggs, Sturm, Bell

The Morphology of
Human Blood Cells

Sabah Sallah, MD
Associate Professor of Medicine

Ann Bell, MS, SH (ASCP)

Emeritus Professor of Clinical Laboratory Sciences
Emeritus Assistant Professor, Department of Medicine

University of Tennessee Health Science Center

Department of Medicine
Division of Hematology
Memphis, Tennessee

Photomicrographs digitized and paintings edited by

John Silver, DVM, MCS, Multimedia Laboratory Coordinator
Health Sciences Library and Biocommunications Center
University of Tennessee Health Science Center

Sixth Edition

a ABBOTT DIAGNOSTICS
A DIVISION OF ABBOTT LABORATORIES

Copyright © 2003, 1985, 1984, 1978, 1975, 1970 by Abbott Laboratories. All rights reserved. Printed in the United States of America.
No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic,
mechanical, photocopying, recording or otherwise, without the prior permission of the publisher.

Errisa Devi Fauzi

 Preface
This atlas, which portrays the morphologic characteristics of
normal and pathologic cells in blood and bone marrow, is
published for the use of medical students, student medical
technologists, veterinary students, and other health science
students who are learning to identify the various types of
blood cells. This monograph also is an aid for teachers of
morphological hematology and for technologists who are
responsible for the examination of smears by manual or
automated methods. A knowledge of morphology is also
useful for residents in clinical and anatomic pathology, pedi-
atrics, and medicine.
Major emphasis is placed on the anatomical characteris-
tics of individual cells in the various stages of their matura-
tion as revealed by light microscopy, employing
oil-immersion objective. Unless otherwise stated, the cells
that are described and visually pictured by the artist, Dorothy
Sturm, are those present in thin, air-exposed, dried smears or
marrow imprints that have been stained by Wright stain.
The procedure was to select an ideally prepared stained
smear of fresh blood or aspirate of bone marrow without
admixture with an anticoagulant and without fixation except
by air drying and by methyl alcohol in the stain and then to
locate a typical cell in the thin portion of a smear. Dorothy, a
skilled artist, as well as a biologically trained scientist, painted
the various colors and structures of the cells as she viewed
them. Watercolors were employed for the color plates.
It is impossible to portray by means of a relatively few
cells all the infinite variations of nuclear and cytoplasmic
structures of normal and pathologic cells. Once selected, the
cell was painted as that individual cell appeared.
The original paintings by Dorothy Sturm are stored in
the archival room of the National Museum of Science and
Medicine in Washington, D.C. and were digitized by Dr.
Michael Rhode, curator at the Museum. The digitized pic-
tures were sent to the UTHSC Library, Multimedia
Laboratory, in Memphis.
In this edition photomicrographs of similar cells as por-
trayed by the artist's drawings are added. The microscopic
identification and enumeration of cells in stained smears is
of value as a screening procedure to detect normality as well
as an aid in the diagnosis and differential diagnosis of vari-
ous diseases, the establishment of prognosis, the indications
for treatment, the response to therapy, and as a safeguard
against drug toxicity.
Errisa Devi Fauzi
ii
The reader is referred to textbooks of hematology (a few
listed in references) for a discussion of etiologic factors, the
clinical and anatomical manifestations, and the treatment of
various diseases of blood and blood-forming organs.
Appreciation is expressed to individuals who assisted in
various ways in the preparation of this atlas. From the
University of Tennessee Department of Medicine, Division
of Hematology: Dr. Alvin Mauer, Emeritus Professor of
Medicine and Pediatrics; Dr. Harvey Niell, Professor of
Medicine; Dr. Marion Dugdale, Professor of Medicine; Dr.
Carolyn Chesney, Professor of Medicine; Dr. Patricia
Adams-Graves, Associate Professor of Medicine; Mrs. Janie
F. Gardner, MS, H(ASCP), Instructor and Education
Coordinator; Mrs. Loretta Pitts, administrative secretary
an and Mrs. Deanye Rowe, secretary.
Dr. Charles Handorf, Associate Professor of Pathology,
UTHSC, gave editorial advise to the authors. Dr. David
Armbruster, Associate Professor in the UTHSC Library,
guided the authors in the format of this work.
Mrs. Alice Diggs Sullivan created seven figures for this
atlas. This edition of the atlas would not have been possible
without the photographic skill of Mr. Thurman Hobson,
Mrs. Sandy Peters, and Mr. Jim Wallace of the Photographic
Section of UTHSC.
Dr. Frank White, hematopathologist at Methodist
Health Care System in Memphis, gave editorial advice and
smears for photomicrography.
The authors wish to thank Mr. Eugene Nichols, head of
Professional Relations, and Mr. Donald Wright, BS, MT
(ASCP)SH, U.S. Scientific Affairs Manager for Abbott
Laboratories, for their great interest, splendid cooperation,
and desire to produce an atlas of blood cells for anyone
interested in studying, teaching, or responsible for morpho-
logic hematology. Ms. Maret Thorpe, graphic designer for
Abbott, deserves much credit for her design of the atlas in
the most current manner. Ms. Cathy Mongeau of Abbott
created the special cover for this work.
Sabah Sallah, MD, Associate Professor of Medicine
Ann Bell, MS, SH(ASCP), CLSPH(NCA),
Professor Emeritus of Clinical Laboratory Sciences,
Assistant Professor Emeritus, Department of Medicine
University of Tennessee Health Science Center (UTHSC)
Department of Medicine,
Division of Hematology,
Memphis, Tennessee
Preface ii
Tables and Figures iii-v
1. Hematopoiesis '.' 1
Myelopoiesis 1
Erythropoiesis 6
Megakaryopoiesis 7
Lymphopoiesis 9
2. Other Bone Marrow Cells 12
Macrophage 12
Mast Cell 12
Fat Cell 13
Osteoblast and Osteoclast 13
Endothelial Cell 14
Fibroblast 15
3. Erythrocyte Morphological Abnormalities : 15
Anisocytosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Poikilocytosis 15
Hemoglobin Concentration 16
Inclusions 16
4. Disorders of Iron Metabolism , 18
Iron Deficiency Anemia 18
Sideroblastic Anemia 19
5. Megaloblastic Anemia 19
Physical Examination 20
Laboratory Findings 20
6. Aplastic Anemia 20
7. Hemoglobinopathies 21
The Thalassemias 21
Sickle Cell Disorders 22
Hemoglobin C Diseases 23
Hemoglobin E 23
8. Hereditary Erythrocyte Membrane Abnormalities 24
Hereditary Elliptocytosis 24
Hereditary Pyropoikilocytosis 24
Hereditary Spherocytosis 24
Hereditary Stomatocytosis 24
9. Microangiopathic Hemolytic Anemias 25
Thrombotic Thrombocytopehic Purpura and Hemolytic Uremic Syndrome 25
Hemolytic Anemia due to Thermal Injury and Venoms : .. 25 .

Errisa Devi Fauzi

iii
 10. leukocyte Morphological Abnormalities 25
Acquired Leukocyte Abnormalities 25
Hereditary Leukocyte Anomalies 26

11. Chronic Myeloproliferative Disorders 27

Chronic Myelogenous Leukemia 27
Polycythemia Vera 28
Essential Thrombocythemia 29
Idiopathic Myelofibrosis 29

12. Acute Myelogenous leukemia 30

The Morphologic (FAB) Classification of AML 30
Presentation of AML 30
Laboratory Findings 30
Therapy 31

13. Myelodysplastic Syndromes 31

Presentation of MDS 31
Laboratory Findings-Morphologic (FAB) Classification ofMDS 31
Treatment : 31

14. lymphoproliferative Disorders 32

Hodgkin's Disesase 32
Non-Hodgkin's Lymphoma 32
Chronic Lymphocytic Leukemia 33
Hairy-Cell Leukemia 33
Multiple Myeloma 34
Sezary Syndrome 34

15. Acute lymphoblastic leukemia ; 35

Presentation of ALL-Immunologic and Morphologic (FAB) Classifications 35
Laboratory Studies 35
Treatment. 35

16. Infectious Disease In Hematology 36

Infectious Mononucleosis 36
Malaria 36
Babesiosis 36
Ehrlichiosis 36
Histoplasmosis 37
Leishmaniasis 37
Parvovirus B 19 37
References 37
Plates and Photomicrographs 38-115
Origin and Development of Blood CelIS 116-117
Index 118-121

Errisa Devi Fauzi

iv
Tables and Figures

Tables
1. Peripheral Blood Cells: Normal Adult Values 1
2. Bone Marrow Cells: Normal Adult Values 1
3. Normal Mean Corpuscular Values and RDW 19
4. Phenotypes and Genotypes of (X- Thalassemia 21
5. Morphologic (FAB) Classification of Acute Myelogenous Leukemia 30
6. Morphologic (FAB) Classification of Myelodysplastic Syndromes 31
7. Immunologic Classification of Adult Acute Lymphoblastic Leukemia 35
8. Morphologic (FAB) Classification of Acute Lymphoblastic Leukemia 35

Figures
1. Proliferation and Differentiation of Hematopoietic Cells 2
2. Terminology Based on Indentation of Nuclei 3
3. Neutrophilic Band and Segmented Cells 4
4. Differentiation and Cell Markers of Lymphocytes 10
5. Osteoblast vs. Plasmacyte 14
6. Osteoclast vs. Megakaryocyte 14
7. Red Blood Cell Inclusions 17
8. Cabot Rings 17
9. Hereditary Stomatocytosis, Blood Smear 24
10. Plasma Cell Myeloma, Bone Marrow 34
11. Histoplasma capsulatum in Peripheral Blood Cells 37

Errisa Devi Fauzi

v
1 Hematopoiesis
Hematopoiesis or formation of blood elements is a complex
process that includes proliferation, differentiation and mat-
uration. Transition from the early cell in the bone marrow to
the more mature cell in the peripheral blood is best charac-
terized as a sequence of interaction between three function-
al compartments (FIG. 1). The stem cell compartment is
made of pluripotential or multipotential cells that are mitot-
ically quiescent but highly self-renewing cells. Because of the
low frequency in the bone marrow nucleated cell popula-
tion, it has been difficult to fully characterize the stem cell
on morphological and biological levels. Multipotential stem
cells can be recognized by the expression of the CD34 anti-
gen but lack of other antigen expressions. The stem cell has
the very important capacity of giving rise to all blood cells.
Cells in the progenitor compartment are derived from
the stem cell but demonstrate very little self-renewing
capacity. However, progenitor cells have the ability to differ-
entiate along one lineage and are mitotically more active
than the stem cell. Committed progenitor cells are best
defined functionally based on the capacity to form colonies
in in vitro assays.
Transition to the precursor cell compartment is charac-
terized by the acquisition of certain nuclear and cytoplasmic
morphologic features that distinguish each lineage of
hematopoietic cells. These cells make up most cells in the
bone marrow but lack any self-renewal capacity. This is
compensated by the large number of precursor cells which
provide an amplifier of all hematopoietic cells. The steps of
loss of self-renewal, differentiation, commitment, and pro-
liferation are very tightly regulated by several cytokines,
growth factors, complex of receptor systems, and by the
microenvironment in which the hematopoietic elements
exist.
eosinophils, basophils, and monocytes. The earliest cell in
the myelocytic series is the myeloblast. Maturation of the
myelocytic series of cells stained with Wright stain is char-
acterized by the development of azurophilic or primary
granules (in the promyelocyte) and later the formation of
secondary granules (in the myelocyte) that differ in their
affinity for various dyes. The cells which have granules with
an affinity for blue or basic dye in Wright stain are called
basophils. Cells with granules that stain reddish-orange with
the acid dye eosin are called eosinophils. Cells that do not
stain intensely with either dye are called neutrophils. As the
cells begin to mature, the nuclei of these three cell lines
undergo progressive changes from round to indented to
band and to segmented forms (FIG. 2). These three cell lines
have similar patterns of proliferation, differentiation, matu-
ration, storage in the marrow, and then appearance in
peripheral blood. Normal values for blood and marrow cells
are given in Tables 1 and 2.
Myeloblast
A myeloblast is an immature cell (10-18 urn) which may
occasionally be found in normal bone marrow (0-1 %) but
is not observed in normal peripheral blood. It has a large
round or slightly oval nucleus that stains predominantly
purplish red in Wright stain. The interlaced chromatin
strands are fine, delicate, and evenly stained. One or two
nucleoli are usually demonstrable. There is a small to mod-
erate amount of bluish nongranular cytoplasm which stains
unevenly and may rarely appear lighter near the nucleus
than at the periphery. A myeloblast does not have granules
Table 2. Bone Marrow Cells: Normal Adult Values
BONE MARROW CELLS NORMAL ADULT VALUES

Myeloblast o - 1 %
Myelopoiesis Promyelocyte 1 - 5
N. myelocyte 2 - 10
In the bone marrow a hematopoietic stem cell becomes
N. metamyelocyte 5 - 15
committed to form progenitor myeloid and monocytic cells
N. band 10 - 40
which eventually lead to the formation of neutrophils,
N. segmented 10 - 30
Eosinophil o - 3
Table 1. Peripheral Blood Cells: Normal Adult Values Basophil o - 1
PERIPHERAL NORMAL ADULT VALUES Lymphocyte 5 - 15
BLOOD CELLS PERCENT PER CU MM Plasmacyte o - 1
N. band 5 50 50 Monocyte o - 2
N. segmented 50 - 70 2,500 7,000 Proerythroblast o -
Eosinophil 1 3 50 300 Basophilicerythroblast 1 - 4
Basophil 0 0 100 Polychromatophilicerythroblast 10 - 20
Lymphocyte 20 - 40 1,000 - 4,000 Orthochromatic erythroblast 5 - 10
Monocyte 6 50 600 Myeloid:Erythroid(M:E)ratio 4:1

Errisa Devi Fauzi

The M~rphology of Human Blood Cells

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(PLATES 1-3,74). The myeloblast divides and gives rise to
the promyelocyte which then gives rise to the myelocyte and
eventually to a mature neutrophil.
Promyelocyte
A cell ceases to be a myeloblast when it develops primary
granules and it is then called a promyelocyte (progranulo-
cyte). The primary granules are azurophilic or dark blue and
most are round. They increase in numbers during this stage.
Granules may be visible above the nucleus and in the deep
blue cytoplasm. A few of these granules may persist
throughout the maturation sequence (PLATES 1-3,74).
The nucleus is round and large in relation to the cyto-
plasm. The chromatin is slightly coarser than in the
myeloblast. Nucleoli may be visible but are often indistinct
and less prominent as the promyelocyte develops. There are
no secondary granules in the promyelocyte. The cytoplasm
is dark blue with a relatively light area adjacent to the nucle-
us. The cell margins are smooth. The size of the cell may be
variable (12-20 urn) but the promyelocyte is often slightly
larger than the myeloblast. Promyelocytes are not seen in
normal peripheral blood. In normal adult bone marrow
there are about 1% to 5% promyelocytes.
A promyelocyte becomes a myelocyte with the forma-
tion of the secondary or specific granules. These granules
differentiate so that the cells can be identified as neutrophil,
eosinophil, or basophil myelocytes.
Myelocyte
An early neutrophil that has developed specific granules is
now called a myelocyte. The specific granules present iden-
tify the myelocyte as a neutrophilic, eosinophilic, or baso-
philic myelocyte.
The first sign of neutrophil differentiation is the devel-
opment in the cytoplasm of a small, relatively light island of
ill-defined specific pinkish neutrophilic granules adjacent to
the nucleus. This light area of secondary granules has been
called "the dawn of neutrophilia." The cell is now identified
as a neutrophilic myelocyte. Some of the prominent
azurophilic primary granules of the promyelocyte are also
still present (PLATE 9).
Myelocyte Metamyelocyte
Figure 2. Terminology Based on Indentation
Errisa Devi Fauzi
The Morphology of Human Blood Cells
As the azurophilic granules become less prominent, the
neutrophilic granules predominate. Neutrophilic (N.) rnye-
locytes are usually smaller (12-18 umj'than progranulocytes
and have relatively more cytoplasm (PLATES 1-3,74).
The nuclei are round, oval, or flattened on one side. The
chromatin strands are coarse or thickened and unevenly
stained. The myelocyte is the last cell of the neutrophilic
sequence which is capable of mitotic division. The later
stages differentiate but do not divide. There are approxi-
mately 2% to 10% N. myelocytes in normal.bone marrow.
Myelocytes are not present in normal blood. When the
nucleus of a myelocyte begins to have an indentation, the
cell is called a metamyelocyte.
Metamyelocyte
A N. metamyelocyte has a slightly indented or bean-shaped
nucleus and small pinkish secondary granules (PLATES 1-3,
9, 74). The indentation of the nucleus is less than half the
width of the hypothetical round nucleus. The nuclear chro-
matin is moderately dense with some clumping at the periph-
ery of the nucleus. These cells are slightly smaller (10-18 urn)
than myelocytes and have relatively smaller nuclei and less
well-defined chromatin structure. The cytoplasm contains
mostly secondary granules but there remain a few primary
granules. There are approximately 5% to 15% N. metamyelo-
cytes in normal bone marrrow but N. metamyelocytes are
extremely rare in normal peripheral blood.
As the metamyelocyte matures, the nuclear indentation
becomes more marked until a stage is reached in which
the indentation is greater than half the width of the hypo-
thetical round nucleus. The cell is now identified as a neu-
trophil band.
Band
A N. band (or nonsegmented cell) is slightly smaller or the
same size as a metamyelocyte. The nucleus is indented to
more than half the distance from the farthest nuclear margin.
The nucleus is coarse and clumpy and may be in the shape of a
horseshoe, sausage, or the letters C or U. If the nucleus
appears lobulated, the filament between the lobes must be
wide enough to have two distinct parallel dark margins with
Band Segmented
of Nuclei
3
The Morphology of Human Blood Cells
nuclear chromatin material in between; then the cell is classi-
fied as a band. Small extensions or appendages of the nucleus
may be seen but the cell is still classified as a band if a thin seg-
ment or filament is not present (PLATES 1-4,74, FIGS. 2,3).
(In case of doubt the cell should be identified as a segmented
cell.) The arms of the band may show concentrated areas of
chromatin at each pole. Cytoplasm is abundant with pale
shades of pink and blue and contains a large number of fine
lilac (specific) granules.
In normal bone marrow of adults there are 10% to 40%
N. bands. Band forms constitute 1% to 5% of the white cells
in the peripheral blood of healthy adult individuals. An
increase in non segmented forms along with other immature
neutrophils is known as a "shift to the left" or a shift to
immaturity and is an indicator of an abnormal response.
Segmented
The nucleus' of an N. segmented cell in a smear stained with
Wright stain has a dark purplish color and is separated into
definite lobes with a thin segment or filament connecting
the lobes. The segment may not be visible if the lobes are
superimposed on each other. If the margin of a superim-
posed lobe can be traced as a continuing line from one side
of the lobe to the other side, it is assumed that a filament
is present even though it is not visible. The light pink
cytoplasm has numerous small pink or specific neutrophilic
granules and also a few primary azurophilic granules
(PLATES 174,74). The mature neutrophilic segmented cell
(l0-15 urn) is about twice the size of an erythrocyte.
There are 10% to 30% N. segmented cells in normal
adult bone marrow. The N. segmented cell is the most fre-
quently occurring cell in normal blood of adults. N. seg-
mented cells of healthy older children and adults are from
50% to 70% (average 60%) in the blood. Approximately 5%
of the segmented cells have one lobe, 35% two lobes, 41%
three lobes, 17% four lobes, and 2% with 5 lobes, and an
extremely rare sixth lobe.
Neutrophilic Band Cells
Neutrophilic Segmented Cells
Figure 3. Neutrophilic
Errisa Devi Fauzi
4
The transition between band and segmented neu-
trophil is gradual. Some cells are borderline and difficult to
distinguish from each other. In differentiating between seg-
mented and nonsegmented (band) nuclei, do not restrict
evaluation to any single morphological characteristic but
combine the features including parallel sides, width of the
connecting link, visibility of chromatin between the mar-
gins, and superimposed lobes. In case of doubt, place the cell
in the mature segmented category which is the most likely to
be correct.
Segmented cells are increased in acute infections,
inflammatory processes, intoxication, acute hemorrhage,
acute hemolysis, vigorous exercise, malignant neoplasms,
and myeloproliferative diseases. Leukopenia with neutrope-
nia may be observed in infections; certain hematologic
conditions such as pernicious anemia and aplastic anemia;
anaphylactoid shock; following hemodialysis, drugs, chemi-
calor physical agents; and after excessive intake of alcohol.
Eosinophil
Eosinophils are derived from progenitor myeloid cells. The
earliest recognizable cell-eosinophilic myelocyte-has a
few dark bluish primary granules characteristic of the pro-
granulocyte intermingled with the secondary specific red-
dish granules of the eosinophil. As the eosinophils pass
through their various developmental stages (metamyelo-
cyte, band, segmented), the bluish granules disappear as the
relatively large spherical granules with affinity for the acid
dye eosin in Wright stain fill the cytoplasm. Mature
eosinophils are 10-15 urn in size.
Eosinophils are recognized easily by the large, spherical
granules which have a bright reddish-orange color in an
excellent stain (PLATES 1-4, 18,74). The granules are uni-
form in size and usually they are evenly distributed in the
cell and fill the cytoplasm. Rarely do they overlie the nucle-
us. On focusing up and down, highlights on individual
granules can be brought out and may reveal the granules as
Band and Segmented Cells

little circles. Often this spherical shape permits identifica-
tion of the cell when the stain is unsatisfactory.
Eosinophils can be identified in moist preparations
without stain because the granules are distinct, round, and
relatively large. In an electron photomicrograph each
granule contains a rectangular or crystalline-like core sur-
rounded by a matrix that is less electron dense. The core
contains mostly major basic protein with the matrix con-
taining other proteins.
In a normal peripheral blood smear, eosinophils are
about the size of neutrophils (10-15 urn) and have a band or
two-lobed nucleus. They usually make up 1% to 3% of the
leukocytes in peripheral blood and bone marrow of normal
individuals. Since the percentage of these cells is usually low
in bone marrow, no useful clinical purpose is served by rou-
tinely separating the eosinophils into their various myelo-
cyte, metamyelocyte, band, and segmented categories. On
the other hand, in situations in which the eosinophils are
greatly increased, an analysis of the incidence of the various
stages is indicated.
There is a relative and absolute eosinophilia in associa-
tion with the invasion, migration, and encystment of animal
(metazoal) parasites. Other diseases and conditions charac-
terized by an increase in eosinophils include allergy,
bronchial asthma, pulmonary infiltrates, hay fever, extensive
skin diseases, recovery from bacterial and other infections,
idiopathic eosinophilic syndrome, chronic myelocytic
leukemia, myelomonocytic leukemia with eosinophils, neo-
plastic malignancy, following radiation, and miscellaneous
disorders. Eosinophilia may be observed in patients with
acquired immune deficiency syndrome (AIDS).
Eosinophils have a diurnal variation with lowest level in
the morning and highest at night. Mild eosinophilia is con-
sidered to be 5% to 15% and is often associated with aller-
gy; marked eosinophilia greater than 50% may be associat-
ed with parasitic infestation.
Basophil
Basophils are derived from myeloid progenitor cells in the
bone marrow. These cells are distinguished by the numer-
ous, unevenly distributed deep purplish-blue to black dis-
tinct granules that fill the cytoplasm and which overlie the
nucleus (PLATES 1-4, 46, 74). The granules stand out in
sharp contrast to the light pinkish color of the cytoplasm.
The granules vary in size from 0.2 to 1.0 !lm and have an
affinity for the basic dye in Wright stain. The basophilic
granules yield negative or very weak peroxidase, Sudan
black, and alkaline phosphatase reactions. Some basophils
react positively when periodic acid Schiff (PAS) stain is
used. The granules in basophils are membrane-bound sacks
containing secretory products including heparin, histamine,
major basic protein (as eosinophils do), and other cherni-
cals. They are not lysosomes (as are neutrophilic granules)
that contain digestive enzymes. When properly stimulated,
the granules eject the chemicals contained in their storage
areas (exocytosis). The nucleus has a round, indented, band,
Errisa Devi Fauzi
The Morphology of Human Blood Cells
or segmented shape and is inconspicuous because of the
large dark staining granules. The number of basophils is 0-
1 per 100 white blood cells in peripheral blood of healthy
individuals. In normal bone marrow of adults the number
of basophils is less than 1 per 100 nucleated cells. There are
so few in peripheral blood and bone marrow that there .is no
clinical advantage in placing the cells in separate stages.
Basophils in blood or tissue range in size from 10 to 15 urn,
They are about the size of neutrophils in the same or close-
ly adjacent microscopic fields. Basophils differ from neu-
trophils in that they are not phagocytic.
The relative and absolute number of basophils in
peripheral blood of chronic myelocytic leukemia and in the
terminal blast transformation of chronic myelocytic
leukemia are increased. Blood basophilia and basophilic
progenitors are poor prognostic indicators in chronic mye-
locytic leukemia. The most striking increase in basophils in
peripheral blood and bone marrow occurs as a manifesta-
tion of basophilic leukemia. Basophilia may be observed in
myxedema, ulcerative colitis, chronic sinusitis, smallpox,
chickenpox, and after the injection of foreign protein.
Monoblast
Monoblasts are derived from myelocytic-monocytic pro-
genitor cells in the bone marrow. Differentiation of a
monoblast from a myeloblast on morphology alone is diffi-
cult and almost impossible unless there are mature mono-
cytic cells nearby on the smear. A monoblast is able to form
mature colonies of mononuclear phagocytes in in vitro agar
culture. A monoblast has a large early nucleus with one or
two nucleoli, fine linear chromatin, small indentations (or
nuclear creases), basophilic cytoplasm with no granules, and
measures about 16 urn in diameter (PLATES 10,49,50,74).
Monoblasts and promonocytes are identifiable in condi-
tions in which there is marked proliferation of cells of the
monocytic type such as monoblastic leukemia or in
myelomonocytic leukemia.
Promonocyte
A promonocyte may be slightly larger in diameter than a
monoblast. The nucleus is indented, has fine chromatin, and
often a nucleolus. The cytoplasm is basophilic, has a few fine
granules varying in size, and may have cytoplasmic projec-
tions which relate to its property of motility (PLATES 10,
49, 50, 74). Peroxidase stain, monocytic esterase stain, and
lysozyme are usually positive. The identification of early
mononuclear cells is based on the indented and folded
nuclei and the association with more mature monocytes
having blunt pseudopods, fine granules, or vacuoles.
Monocyte
The mature monocyte in blood and bone marrow varies in
size (12-20 urn) and shape. The cell has a large nucleus
which is often convoluted or indented. The nuclear chro-
matin is delicate and somewhat linear. The abundant cyto-
plasm contains numerous fine, bluish granules which give a
5
The Morphology of Human Blood Cells
ground-glass appearance to the cytoplasm (PLATES 4, 7-10,
74). Vacuoles may also be present in the cytoplasm. There
are 1% to 6% monocytes in normal peripheral blood.
Monocytes in peripheral blood are slightly larger than
neutrophils and their diameter is three to four times that of
erythrocytes in the same microscopic field. The shape of a
monocyte is variable. These cells may be round or oval and
may have blunt pseudopods which indicate their slow motili-
ty. Monocytes generally have a large amount of dull gray·
blue cytoplasm contrasted with the pinkish color of the cyto-
plasm of neutrophils in adjacent fields. The nucleus of a
monocyte may be round, kidney-shaped, oval or deeply
indented, and usually centrally located. One of the most dis-
tinctive and diagnostic features of the nucleus is the presence
of convolutions. Another feature of the nucleus of a mono-
cyte is the tendency to be loose with light spaces in between
chromatin strands, thus giving a delicate, linear pattern in
contrast to the lymphocyte with its clumped chromatin.
The lilac or light purple granules in the gray-blue cyto-
plasm are usually fine,' small, numerous, lightly stained, and
evenly distributed giving a ground-glass appearance. In
addition to the small granules there may be varying num-
bers of prominent granules. Vacuoles are often present.
Monocytes often have pseudopods which extend slowly
from the cytoplasm as cells move in random fashion. As
these cells grow, they are transformed into macrophages
which are too large to pass readily through capillaries.
Extremely large mononuclear phagocytes are not seen in
blood smears of normal individuals but they are demonstra-
ble in bone marrow and in body fluids other than blood.
Monocytes are phagocytic leukocytes of the blood
which, together with macrophages and neutrophilic leuko-
cytes, playa major role as a first line of defense against path-
ogenic organisms and foreign cells. Mononuclear
phagocytes ,in the lung ingest and degrade pathogenic
organisms. Phagocytic cells of varying size and mobility
remove from the circulating blood injured and dead cells,
microorganisms, cell fragments, insoluble particles, and
ingest and degrade noxious external agents.
Monocytes may be increased in certain chronic bacterial
infections (such as tuberculosis, subacute bacterial endo-
carditis, syphilis, brucellosis), during recovery from acute
infections, agranulocytosis, protozoal infections (malaria,
babesiosis, ehrlichiosis, trypanosomiasis, histoplasmosis),
lymphoma, monocytic leukemia, myelomonocytic leukemia,
chronic myelocytic leukemia, lipid storage diseases, malig-
nancy, multiple myeloma, collagen vascular disease (lupus
erythematosus and rheumatoid arthritis), granulomatous
disease, and chronic steroid therapy.
Erythropoiesis
Erythropoiesis is the term used to describe the process in
which red blood cells are produced in the bone marrow.
This process of erythropoiesis results in a constant red cell
Errisa Devi Fauzi
6
mass in the .body, The late phase of erythropoiesis is con-
trolled by the hormone erythropoietin which is the regula-
tor of red cell production. Erythroblasts in the marrow are
produced by immature erythroid cells called erythroid pro-
genitor cells which cannot be identified by morphology.
However, progenitor cells are able to form in vitro colonies
of erythroblasts.
Involved in erythropoiesis are the precursor red cells at
the earliest maturation stage (proerythroblast) and at the
end is the mature circulating erythrocyte (Fl). This mass of
erythroid cells has been termed the erythron to emphasize
the unity of erythrocytic cells as a tissue beginning with the
committed progenitor cells and their precursors.
Erythropoiesis occurs in the marrow over a period of
about 5 days through successive morphologic alterations
from the proerythroblast (the earliest erythroid precursor)
to the orthochromatic erythroblast followed by a nonnucle-
ated polychromatophilic erythrocyte and then by a mature
erythrocyte (PLATE 11). The maturation of the various
stages is noted by increasing condensation of the nuclear
chromatin, disappearance of nucleoli, and changing of the
deep blue color of the immature cytoplasm with its high
ribonucleic acid (RNA) content to the reddish color indicat-
ing hemoglobin. During the early maturation period, mito-
chondria, Golgi apparatus, and polyribosomes are devel-
oped. Genes related to hemoglobin synthesis are activated,
and in the cytoplasm of the later developmental stages, there
is increasing hemoglobin synthesis. Three or four mitotic
divisions occur in the early phases, but in the late phase, the
cells are unable to divide.
The main functions of erythrocytes are to transport
oxygen to the tissues and to return carbon dioxide to the
lungs from the tissues. This gaseous exchange within the
erythrocyte is accomplished by the oxygen-carrying protein,
hemoglobin. The presence of hemoglobin usually is not vis-
ible as a reddish color in normal nucleated red cells until the
polychromatophilic erythroblast stage. In addition to hemo-
globin, mature nucleated erythrocytes are differentiated
from the proerythroblast by the coarsening of the chromatin
pattern and absent nucleoli. The cytoplasm color changes as
the cell matures and there is increasing concentration of
hemoglobin and decreasing RNA. The predominant color of
the. cytoplasm is blue but there is a reddish tinge due to the
presence of hemoglobin. Normal bone marrow contains
enzymes for the production of energy and for maintenance
of hemoglobin in the reduced state.
Proerythroblast .
The earliest cell of the erythrocytic sequence, the proery-
throblast, is similar to "blasts" in the other series. The
proerythroblast is the largest cell (14-19 urn) in the erythro-
cytic series. Nucleoli are usually prominent. The nuclear
chromatin strands are linear and distinct. The cytoplasm
stains a deep blue (PLATES 11,36,74)' In normal bone mar-
row of adults there are 0% to 1% proerythroblasts.

Basophilic Erythroblast
The basophilic erythroblast is smaller (12-17 urn) than the
proerythroblast. This cell is differentiated from the proery-
throblast by the coarsening of the chromatin pattern and ill-
defined or absent nucleoli. The cytoplasm color changes as
the cell matures and .there is increasing concentration of
hemoglobin and decreasing RNA. The predominant color of
the cytoplasm is deep blue but there is a reddish tinge due to
the presence of hemoglobin (PLATES 11,36,74). In normal
bone marrow there are 1-4% basophilic erythroblasts.
Polychromatophilic Erythroblast
Polychromatophilic erythroblasts are smaller (12-16 urn)
than basophilic erythroblasts, have relatively more cyto-
plasm, and contain varying mixtures of red and blue stains
in the cytoplasm. There is an increasing amount of hemo-
globin giving a more reddish color to the cytoplasm. The
nuclear chromatin is thickened and irregularly condensed
and nucleoli are no longer visible (PLATES 11, 36, 74).
There are 10% to 20% polychromatophilic erythroblasts in
normal bone marrow.
Orthochromatic Erythroblast
The orthochromatic erythroblast has a predominantly red-
dish cytoplasm due to increasing hemoglobin concentration.
This cell is smaller than the polychromatophilic erythroblast
and has a nonlinear clumped chromatin structure or a solid
blue-black degenerated nucleus. (PLATES 11,36, 74.) Nude-
ated red cells with fragmented or partially extruded nuclei are
classified as orthochromatic erythroblasts. In normal bone
marrow there are 5% to 10% orthochromatic erythroblasts.
The nucleus is extruded from the orthochromatic erythro-
blast in the marrow, leaving a polychromatophilic erythro-
cyte. The nucleus is phagocytized by a macrophage.
Polychromatophilic Erythrocyte
Polychromatophilic erythrocytes usually have lost their
nuclei but still maintain some of their bluish color due to
the presence of ribosomes. They are larger than mature red
cells. Polychromatophilic erythrocytes, when stained with a
supravital stain such as new methylene blue, reveal a gran-
ulofilamentous network that has been called reticulum and
thus the name reticulocyte (PLATES 11,32,36,74). This cell
is released in 1 to 2 days from the marrow and circulates in
the peripheral blood and spleen for 1 to 2 days before
maturing into an erythrocyte.
Erythrocyte
Normal erythrocytes are biconcave discs 7.2 to 7.9 urn in
diameter and 1.5 to 2.5 urn thick, which appear in stained
smears as circular objects with distinct and smooth margins
(PLATE 4). In the central portion of the erythrocyte where
the cellis thinnest the intensity of the stain is less than at the
thicker marginal area. This is the normal area of central pal-
lor. Erythrocytes in normal blood should be uniform in size,
shape, and color content and have no inclusions such as
Errisa Devi Fauzi
The Morphology of Human Blood Cells
stippling or nucleated red cells. The diameter of a red cell
may be measured by comparing the red cell with the nucle-
us of a small lymphocyte in the same or adjacent field.
Every blood smear examination should include an eval-
uation of the erythrocytes according to size, shape, color con-
tent, and inclusions. The morphology of the red blood cells
should be evaluated in the area of the smear where the ery-
throcytes are close together but not overlapping and not at
the "feather end" of the smear. At the end of the smear the red
cells are flattened out and do not reveal normal central pallor.
Nucleated Red Cells Clustered
Around Macrophage
Macrophages that have acquired iron from ingested red
blood cells and erythrocyte fragments serve as feeder or
nursing cells to nucleated red cells that cluster around their
margins (PLATE 17). There is intimate intercellular contact
between the satellite nucleated erythrocytes and the
macrophage; the macrophage supplies the nutrients, such as
ferritin, to the surrounding nucleated cells, a process similar
to nursing.
Comparison of Basophilic Erythroblasts,
Lymphocytes, and Plasmacytes
Basophilic erythroblasts, lymphocytes, and plasmacytes
have in common a round nucleus without lobulations and a
blue, nongranular cytoplasm (PLATE 12). Immature eryth-
rocytes and plasma cells may have mixtures of red and blue
in their cytoplasm, which gives them an intense royal-blue
color. Lymphocytes, as well as plasmacytes, may have bubbly
or foamy cytoplasm.
Basophilic erythroblasts do not have' a bubbly cyto-
plasm, seldom contain vacuoles, and usually have smooth
margins. They have less cytoplasm than plasma cells, the
perinuclear clear zone is less striking, and the nuclei are not
eccentric as are the nuclei of plasmacytes.
Lymphocytes have a narrow rim of blue cytoplasm, a
small perinuclear clear zone is present, and the nucleus is not
as eccentric as the plasma cell. Reddish color of the cyto-
plasm occasionally seen in plasma cells and in immature
nucleated red cells is not present.
Features which favor the diagnosis of the cellas a plas-
ma cell are the relatively large amount of cytoplasm, eccen-
tric nucleus, relatively large light area next to the nucleus,
vacuoles, fibrillar structure, and frayed edges.
In many individual cells, the similarity between these
cells is so close that differentiation cannot be made on mor-
phologic grounds alone. Often it is necessary to classify the.
atypical cell by association with the predominant cell or by
arbitrarily placing it in the column that it most closely
resembles.
Megakaryopoiesis
The hematopoietic stem cell forms progenitor cells commit-
ted to produce the megakaryocytic series in which the
7
The Morphology of Human Blood Cells
cytoplasm later fragments to form circulating blood
platelets (PLATES 14, 15,74). Megakaryopoiesis takes place
primarily in the bone marrow. Megakaryocytic cells do not
have the capacity for self-renewal. They are maintained by a
continuing flow of progenitor cells from the stem cell com-
partment, which become committed to form megakary-
ocytes. Progenitors for the megakaryocytic lineage are
indistinguishable from other undifferentiated cells in the
marrow but in semisolid media they are able to grow into
mature megakaryocytes with the appropriate growth factors
(such as interleukins 3 and 6, and granulocyte-macrophage
colony stimulating factor-Glvl-Cxf').
Cells of the megakaryocytic system are unique in that
the nucleus undergoes multiple mitotic divisions but there is
no cytoplasmic separation. Thus a giant polyploid nucleus is
produced. All of the nuclei in a given cell replicate at the
Same time producing 2, 4, 8,16, or rarely 32 nuclei. The mul-
tiple nuclei remain attached to each other and are often
superimposed, giving a lobular appearance to a single poly-
ploid nucleus.
The cytoplasm matures by progressively increasing in
size and granularity but there is no division of the cyto-
plasm. The maturation of the megakaryocyte culminates in
platelet differentiation and liberation. Platelet.masses usual-
ly appear at the margins of the megakaryocyte in the fourto
eight nucleated stages of development. In some cells platelets
may form in cells with single or double nuclei.
Megakaryoblast
The megakaryoblast is a moderately large cell with one or
two nuclei in a round nucleus and with blue nongranular
cytoplasm (PLATES 14, 15,74). Nucleoli are often demon-
strable. The cytoplasm may have blunt pseudopods or blebs
(suggesting early platelet formation) which stain bluish. The
nucleus begins to indent with lobes starting to form and the
nucleus increases in size. A megakaryoblast has a high
nuclear to cytoplasmic ratio and may be greater than 15 Jlm
in diameter.
Promegakaryocyte and Megakaryocyte
Promegakaryocytes and megakaryocytes are larger than
megakaryoblasts (25 to 60 urn in diameter). When the
basophilic cytoplasm becomes filled with azurophilic gran-
ules, the cell is called a promegakaryocyte (or granulated
megakaryocyte). The number oflobes also increases in mul-
tiples of two (PLATE 14; 15, 74). The lobulated nucleus
helps to distinguish the megakaryocyte from the osteoclast
which has many separated nuclei. The numerous
azurophilic granules begin to aggregate into platelets and the
cell is then identified as a megakaryocyte (with platelets).
The time of differentiation of the stem cell to production of
the megakaryocyte with platelets averages about 10 days.
Megakaryocytes in the more advanced stages of matu-
ration are slowly ameboid. They extend portions of their
cytoplasm through the basement membranes and between
the 'endothelial cells of the sinusoids of the bone marrow.
Errisa Devi Fauzi
From these cytoplasmic protrusions, the differentiated and
membrane-bound platelets separate and are swept into the
flowing blood stream. Other megakaryocytes escape into the
vascular channels of the marrow and are transported to the
lungs where they lodge in the terminal pulmonary arterioles
and alveolar capillaries. They may also be found in other
major organs, such as the spleen.
From these sites, they continue to differentiate and to
liberate portions of their cytoplasm in the form of platelets.
The mechanism of liberation of platelets is somewhat con-
troversial. The naked nuclei disintegrate or are phagocytized
by macrophages. Estimates of the number of platelets pro-
duced by one megakaryocyte vary from several hundred to
thousands. In bone marrow smears and in sections of mar-
row tissue from normal individuals, the megakaryocyte con-
stitutes 1 to 4 per 1,000 nucleated cells and most are in the
later stage of maturation.
When platelet production is accelerated, megakary-
ocytes increase in both volume and number. When there is
accelerated platelet destruction causing various forms of
thrombocytopenia, the morphology of megakaryocytes is
abnormal with degenerating megakaryocytes and cells that
do not appear to produce platelets. Occasionally a marrow
cell(s) may be seen within a megakaryocyte in normal mar-
row, in association with blood loss, and with a variety-of
neoplastic disorders.
In myelofibrosis, megakaryocytes may have a role in
this abnormality by stimulating fibroblast proliferation and
collagen secretion. Intact small megakaryoblasts (or micro-
megakaryoblasts), fragments of megakaryocytes, and naked
nuclei are occasionally demonstrable in smears of peripheral
blood from patients with myeloproliferative diseases such as
myelofibrosis, megakaryocytic leukemia, polycythemia vera,
chronic myelogenous leukemia, and myelodysplasia.
Micromegakaryoblasts are small cells, have a blast
nucleus and blunt cytoplasmic blebs (which represent early
platelet formation), and are found in small numbers in
peripheral blood of megakaryocytic (or megakaryoblastic)
leukemia (PLATES 54,55). Small and large megakaryoblasts
are observed in the bone marrow which is difficult or almost
impossible to obtain because of increase in reticulin fibrosis.
The diagnosis depends on the immunologic demonstration
of platelet glycoprotein Ib or IIb/IIIa within the blast cells.
Megakaryoblasts stain positively with a-naphthyl-acetate
esterase.
Platelet
Platelets (thrombocytes) are fragments of cytoplasm from
megakaryocytes in the bone marrow. In films of blood from
normal individuals the diameters of single platelets vary from
1 to 4 urn (PLATE 4). However, in various diseases the size
may range from barely visible structures to masses larger
than red cells or leukocytes (PLATE73). There also may be a
slight to marked decrease in platelets in other disease states.
The platelet is made up of a variable number of small
reddish-blue granules which tend to aggregate in the center

of a minimal amount of blue cytoplasm. The number of
platelets per oil immersion field varies from 7 to 15 in the
thin portions of the blood smear where erythrocytes and
leukocytes are evaluated. The number of platelets in the
average oil immersion field multiplied by 20 gives the
approximate number of platelets per 109/L (or by 20,000 =
number of platelets per cu mm). At least 10 oil immersion
fields should be counted and the average number per field
calculated. If platelets are decreased, then 50 to 100 oil
immersion fields should be counted and averaged. No report
of a blood smear examination is complete unless the num-
ber of platelets per oil field is stated and any abnormalities
described. Platelets may appear as satellites (PLATE 73)
around the cytoplasmic margins of neutrophils when the
blood film is made from anticoagulated blood, particularly
ethylene diaminetetraacetic acid (EDTA).
Lymphopoiesis
Lymphocytes are the cornerstones of the immune system.
They are divided into B cells responsible for humoral immu-
nity (production of antibodies or immunoglobulins) and T
lymphocytes which mediate cellular immunity. The use of
monoclonal antibodies in the laboratory investigation of
blood cell components has changed our understanding of
lymphocytes and their benign and malignant disorders. The
reagents used in these studies can identify the expression of
certain antigens on leukocytes at different stages of matura-
tion and differentiation. Using a combination of molecular,
biochemical, and flow cytometric techniques, the molecules
recognized by these antibodies have been grouped in clusters,
thereby enabling the recognition of certain antigens by clus-
ter designation (CD) (FIG. 4). Several of these CDs playa
crucial role in the recognition and interaction with antigens,
proliferation, cell signaling, adhesion, and activation. B- and
T-lineage-associated cell-surface molecules are now the basis
for classification of most, if not all, lymphoid diseases.
The bone marrow is the primary site of myeloid and
B lymphocyte development. The earlier Band T cells (lym-
phoid stem cells) are characterized by the intranuclear
expression of the enzyme terminal deoxynucleotidyl trans-
ferase (TdT) and surface expression of the stem cell antigen
CD34. Models of human B-cell maturation and differentia-
tion are based on flow cytometric analysis and studies of
leukemic B-cell precursors. The most immature B-cell
precursor is called pro-B and expresses the CD19 antigen on
its surface.
The first identifiable stage of B-cell maturation occurs
as the cell begins the process of producing immunoglobulin.
Cells that express cytoplasmic !l heavy chain protein and
surface antigen CD20 are called pre-B cells. These cells also
express the CD10 antigen, otherwise called common acute
lymphoblastic leukemia antigen (CALLA). This is an impor-
tant but nonlineage specific marker that is useful in the
classification of acute lymphoblastic leukemias. Immuno-
globulin is the unique marker of B-lineage cells, and its
Errisa Devi Fauzi
The Morphology of Human Blood .Cells
expression in the cytoplasm or surface depends on a com-
plex but orderly series of gene arrangements at the heavy
and light chain loci.
Surface expression of a complete IgM molecule and loss
of CD 10 defines the first stage of transition from pre- B to B
cell. In addition to surface IgM, the mature B cell acquires
CD21 and CD22 antigens. It is important to remember that
the microenvironment of the bone marrow is crucial for B
lymphopoiesis. Stromal cells are a primary source of
cytokines that influence the process of B-cell development.
Normal T lymphopoiesis involves a series of steps that
parallel that of the B cell. However, the process of differenti-
ation and maturation of T cells takes place in the thymus,
not in the bone marrow as for B cells. The earliest identifi-
able immature precursor of T cells in the thymus expresses
the CD7 marker along with the CD34 on the cell mem-
brane. These immature precursors then generate a progeny
characterized by expresssion of CD2+/CD5+ and cytoplas-
mic CD3. Subsequently, CD4 and CD8 antigens are
expressed on the surface of thymocytes.
A more unique marker of the T-cell lineage is called T-
cell receptor (TCR). Analogous to the immunoglobulin
heavy and light molecules, the genes that encode TCR pro-
tein undergo a process of rearrangement. Cells that are dou-
ble positive for CD4/CD8 and expressing TCR soon pass
from the thymic cortex to the medulla and become com-
mitted either to positive CD4 helper or cytotoxic CD8 T
cells. Single positive T cells expressing an intact TCR on the
cell surface accompanied by the CD3 complex leave the thy-
mus and populate lymphoid tissues such as the spleen and
lymph nodes. The development of T cells is regulated by
stromal and other supporting cells in the thymus and is
mediated through secretion of different cytokines.
Interaction between T and B cells is critical for the reg-
ulation of a normal immune response. Such interaction
takes place through cell-surface receptors and is initiated by
certain signals. Signaling triggers a cascade of events includ-
ing cellular and molecular changes which eventually gener-
ate an effective immune response. Examples of this type of
collaboration between the Band T cells are the interaction
between the major histocompatibility antigen (MHC) class
II molecules and CD4 on T cells which is essential for T-cell
activation. Of similar importance is the interaction between
the surface immunoglobulin molecule and CD28 on T cells
which generates signals that up-regulate T-cell surface
expression of other cytokine receptors and ligands.
Lymphoblast
Lymphoblasts are 8-12 Ilm in diameter, are round or slight-
ly oval in shape, and have a large round nucleus with one
distinct nucleolus or two nucleoli (PLATES 10, 58-60, 74).
The nuclear chromatin strands are thin, delicate, evenly
stained, and deep purplish-blue. The nongranular cyto-
plasm is blue, may be moderate or scanty in amount, and has
a paranuclear clear zone. Lymphoblasts are not seen in
smears of normal adults. The nuclei become progressively
The Morphology-of Human Blood Cells

Pluripotent Hematopoietic Stem Cell

Pluripotent Stem Cell

Myeloid Restricted
Precursor

Lymphoid Restricted
Precursor

HLA- DR
CD 34
C019

Thymus

HLA- DR
C019·
COlO

CD 34
CD 7

Prothymocyte

HLA- DR
C019
CD 20
CD 22
CD 7
CD 2
CD 5
CD 4
CD 8
Pre-B Cell

+---- Antigen

IgM
CD 7
HLA - DR
CD3 TCR
CD19
CD 2. CD8
CD 20
CD 5
CD 22

Mature T Cell Mature T Cell Mature B Cell

Figure 4. Differentiation and Cell Markers of lymphocytes

Errisa Devi Fauzi

10

smaller as the cells mature. Differentiation of cells in the
lymphocytic maturation sequence is based principally on
differences in nuclear structure.
Prolymphocyte
Prolymphocytes are somewhat smaller and have less distinct
nucleoli than lymphoblasts (PLATES 10,58,74). The chro-
matin structure is intermediate between lymphoblasts and
mature lymphocytes. Pro lymphocytes are not seen in normal
adults but occasionally are observed in children. There is a
rare acute leukemia in which prolymphocytes are increased
and this is called prolymphocyticleukemia (PLATE 60).
Lymphocyte
Mature lymphocytes are usually small, have a round nucle-
us with dense chromatin and a rim of blue nongranular
cytoplasm (PLATES 4-6, 9,10,74). The nucleus in relation to
the cytoplasm is large and occupies about 90% of the cell
area. The diameter of small lymphocytes ranges from 7 to 10
flm. The size of the nucleus of small lymphocytes is compa-
rable to the diameter of normal red cells in the same or
nearby microscopic fields.
Small lymphocytes usually have a round shape and
smooth cytoplasmic margins. A lymphocyte may occasion-
ally have a spindle shape with oval and eccentrically located
nuclei. Nucleoli that may be present are not visible by light
microscopy because they are obscured by dense chromatin
but are visible by electron microscopy. The fact that nucleoli
are present in some small lymphocytes is proof of metabol-
ic activity and the capacity for these cells for growth and
replication. The color of the cytoplasm of lymphocytes is
blue but the intensity of the blue varies from light blue to
darker blue in different cells. The color is evenly distributed
in some cells and uneven in other cells. There may be a small
paranuclear clear zone.
Lymphocytes are the second most frequently occurring
leukocytes in the peripheral blood. In older children and
adults lymphocytes constitute from 20% to 40% of the
leukocytes in peripheral blood smears. The total number of
lymphocytes in the blood of individuals in good health
varies from 1.5 to 4.0 x 109L. During the first few years oflife
while children are developing immunity to infectious agents
and other foreign environmental factors, lymphocytes make
up from 30% to 70% of the white cells in peripheral blood.
A few larger lymphocytes (9-15 flm in diameter) may
be observed in normal individuals. The nucleus of a large
lymphocyte in contrast to the nucleus of a small lymphocyte
may be increased in size and slightly indented. The
basophilic chromatin is condensed.
The margins oflarge lymphocytes are often indented by
erythrocytes producing serrated, scalloped, or holly leaf
shapes. The abundant cytoplasm stains varying shades of
light blue and may contain a few unevenly distributed gran-
ules which are reddish-violet (or azurophilic) and are easily
countable. These granules are peroxidase and Sudan Black
negative and acid phosphatase positive. It is not necessary to
Errisa Devi Fauzi
The Morphology of Human Blood Cells
report the number of so-called "large"lymphocytes separate-
ly from the "small" lymphocytes unless there is a striking
increase in large lymphocytes. Large reactive lymphocytes are
characteristic of infectious mononucleosis (PLATES 65-66).
Lymphocytosis occurs in acute viral illnesses such as
infectious mononucleosis and pertussis; certain chronic
infections, e.g., tuberculosis; mumps and German measles;
neutropenic states; and hairy cell leukemia. Lymphoblasts
are observed in acute lymphoblastic leukemia and in the
lymphoblastic crisis of chronic myelocytic leukemia.
Mature small lymphocytes are increased in peripheral
blood of chronic lymphocytic leukemia (CLL) in adults
(PLATE 60). Smudges or disintegrated lymphocytes are also
features of CLL.
Plasma Cell
Plasma cells were first thought to constitute a separate cell
line but now they are considered to be the progeny of B
lymphocytes. Plasma cells constitute about 1% of nucleated
cells of normal bone marrow but are not seen in the periph-
eral blood smears of healthy adults.
Plasmacytes are usually round or oval and have slightly
irregular margins, particularly in the marrow where they are
torn in the process of aspiration. The cytoplasm is nongran-
ular and always stains a dark blue (described as cornflower
blue or larkspur blue) at the periphery of the cell (PLATES
10, 12, 74). The cytoplasm adjacent to the nucleus is rela-
tively pale with a paranuclear clear zone containing the
Golgi apparatus. In many plasma cells there are one or more
vacuoles in the cytoplasm.
The nuclei of mature plasma cells are relatively small,
oval, or round and eccentrically placed. The nucleus is small
in relation to cell size and is made up of dense masses of
chromatin. In marrow tissue fixed in formaldehyde, there
may be nuclear artifacts in plasma cells characterized by the
tendency of the chromatin to clump and to adhere to the
nuclear membrane, giving the visual impression of a "clock
face" nuclei or the "spokes of a wheel:' This nuclear artifact
is not observed in bone marrow smears made directly from
the marrow puncture and without a fixative.
Lymphocytes may have deep blue cytoplasm and some-
what resemble plasma cells. Such cells are called plasma-
cytoid lymphocytes and they are observed in viral infection
(e.g., infectious mononucleosis, viral hepatitis, AIDS) and in
immunologic diseases with hypergammaglobulinemia and
in plasma cell dyscrasias. Plasma cells are observed in aller-
gic states, serum sickness, chronic bacterial and fungal infec-
tion, toxoplasmosis, and multiple myeloma.
Plasma cells manufacture immunoglobulins. These
cells may be seen in the marrow clustered around
macrophages (PLATE 17). Antigenic material processed by
macrophages is transferred to the plasma cells which in turn
manufacture immune globulins. This proteinaceous materi-
al is usually in the form of round red globules called Russell
bodies but may be colorless or reveal other pastel colors
(PLATE 63). The globules may fill the cytoplasm, giving the
11
The Morphology of Human Blood Cells
appearance of a bunch of grapes (called grape, berry or
morula cells). Rarely "flame" plasma cells may be found in
which the red color is diffusely distributed throughout the
cytoplasm (PLATE 13). The proteinaceous material may
crystallize and produce elongated or needle-like structures
which may be colorless or stain various shades of red.
Plasmablast
In multiple myeloma plasmablasts are increased in the bone
marrow with some large cells having two, three, or more
nuclei which may vary in size (PLATE 63). Nucleoli are
prominent in the blasts and visible in proplasmacytes. The
nucleus of these early cells is eccentrically placed. There is an
2 Other Bone Marrow Cells
Macrophage
Macrophages, as the name implies, are large cells which
phagocytize actively. Macrophages (phagocytic histiocytes)
serve as the tissue phase of the mononuclear phagocytic sys-
tem. These cells are a heterogeneous group of cells and orig-
inate in the bone marrow from progenitor cells that eventu-
ally form blood monocytes which function as phagocytic
cells in the blood. Some of these motile macrophages
squirm between endothelial lining cells of blood vessels and
through basement membranes of vascular channels into
connective tissue spaces where their growth continues; they
differentiate into macrophages in response to local condi-
tions in many organs in the body.
The diameters of macrophages are two to five times
those of neutrophils in the same microscopic fields. The
cytoplasm is abundant, may have blunt pseudopods, stains
light blue, and has a fine reticular structure and numerous
granules of varying sizes (PLATE 16, 17). Vacuoles are some-
times demonstrable in the cytoplasm. The nuclei are rela-
tively small in relation to the cytoplasm and are round, oval,
or slightly indented. The chromatin pattern is linear.
Nucleoli may be demonstrable. Phagocytized objects that
may be revealed in digestive vacuoles include intact red cells,
leukocytes, cell fragments, platelets, hemosiderin, bacteria,
fungi, protozoa, and crystals.
Cells of the monocytic phagocytic system are distrib-
uted widely throughout the body. Monocytes and
macrophages are demonstrable in all types of body fluids
including blood, urine, sputum, saliva, tears, cerebrospinal
fluid, mucous secretions from the nose and facial sinuses,
12
Errisa Devi Fauzi
abundance of basophilic cytoplasm with a paranuclear clear
zone present. Rarely there may be cytoplasmic inclusions
such as reddish round bodies (PLATE 63), crystalline rod-
like structures, and round globules.
Rouleaux of red cells (PLATE 63) is a common finding
in marrow and blood smears in myeloma and is due to the
increase in globulins which coat the red cells in myeloma. A
bluish background to the smear may be observed due to
increase in proteinaceous material which stains bluish.
Rarely a plasma cell may be found in the blood smear of
myeloma. An increase in plasma cells in blood is called plas-
ma cell leukemia.
and synovial fluids. Macrophages are in various tissues:
lung, spleen, lymph nodes, bowel, liver, brain, peritoneal
cavity, and kidney. Hepatic macrophages (Kupffer cells) are
interspersed with endothelial-lining cells in the sinusoids
of the liver and are responsible for clearing activated coagu-
1ation factors. If this filtering function fails during DIC or
fibrinolysis, it would be harmful to the patient. The sputum
of patients with congestive heart failure and stasis of blood
in pulmonary vessels contains macrophages laden with
hemosiderin. There is a constant influx of monocytes into
tissue in order to maintain a stable number of macrophages.
Macrophages do not re-enter the blood again but leave the
tissue and probably have a steady death rate.
Mast Cell
Mast cells are thought to be derived from a hematopoietic
precursor cell in the bone marrow and do not differentiate
into mature granulocytes. Mast cells normally mature in con-
nective tissue and are found in the supporting connective tis-
sue underlying epithelium. A small number of mast cells are
noted in particles of marrow stroma.
Mast cells appear to be round, oval, or elongated in
bone marrow or spindle-shaped in tissue. The nucleus can
be small, round or oval. Nucleoli apparently are absent from
normal mast cells. The cytoplasm is filled with intensely
stained violet-blue to blue-black granules, which are rela-
tively. round and approximately the same size. They fre-
quently overlie the margins of the pale nucleus or may
partially or completely obscure the nucleus (PLATE 18).

Mast cells are widely scattered in various organs includ-
ing bone marrow. They are not usually encountered while
performing a differential count of several hundred cells in
the bone marrow. Mast cells may be relatively increased and
conspicuous in conditions associated with aplastic anemia
and myelosclerosis. Mast cells may proliferate in urticaria
pigmentosa and mastocytosis. Mast cells rarely appear in
peripheral blood except in mast cell leukemia.
Mast cells and blood basophils are closely related in
their chemical characteristics and in their functions. The
granules of mast cells and basophils contain histamine and
heparin. Blood basophils as well as mast cells participate in
a similar manner in acute and delayed allergic reactions
since they have high affinity receptors for IgE. Basophils are
smaller than mast cells and contain fewer granules than
mast cells. Basophils differentiate and mature in the bone
marrow like neutrophils do and they circulate in the blood.
Mast cells do not circulate in the blood but are found in
'connective tissue. The exact nature of the relationship of
basophils and mast cells is still not completely understood.
According to ultrastructural studies blood basophils are
round but may have various shapes in tissue. Mast cells
may appear round, oval, or spindle-shaped in tissue. The
nucleus of a basophil is usually multilobed whereas mast
cells can be round or lobed. Ribosomes, Golgi apparatus,
and rough endoplasmic reticulum are scarce in basophils
and mast cells. Both cells have membrane-bound electron-
dense granules.
Fat Cell
Fat cells are seldom seen in thin smears of bone marrow, for
they are ruptured in the process of aspiration. When spread
on a slide, the contained globules of fat tend to escape and
leave the stroma and cell membranes as unidentifiable
debris. In thicker portions of the marrow smears, individual
fat cells or groups of fat cells (lipocytes) can be seen,
surrounded by other marrow cells.
Mature fat cells are large round cells (50 to 80 Jlm in
diameter), comparable in size to megakaryocytes and osteo-
clasts in diameter (PLATE 19). The small round or oval
nuclei are located eccentrically, presumably pushed to one
side by the pressure of globules of fat in the cytoplasm. The
chromatin structure in many of the nuclei is linear. Often
there is a globular body in the nucleus thought to be fatty
material in the process of manufacture. The globules of fat
in the cytoplasm are of varying size and are chromophobic
or stain a light blue or pink. The fat globules have smooth
margins. The globules compress each other, producing
irregular shapes. The lipid masses are separated in compart-
ments by cytoplasmic material which appears as delicate
blue lines. The fixed character of the cells is revealed by mul-
tiple fibrils which extend outward from the cell margins and
interface with the fibers of fibrocytes and endothelial cells.
The lipid material in fat cells has an affinity for various
Sudan dyes.
Errisa Devi Fauzi
The Morphology of Human Blood Cells
Osteoblast and Osteoclast
Bone cells identified as osteoblasts and osteoclasts do not
take part in hematopoiesis. Osteoblasts are responsible for
formation and maintenance of bone. The function of osteo-
clasts is the destruction and resorption of bone. The coop-
erative roles of these two cells is essential to remodeling of
bone in growth and repair. These cells are not common in
normal adult bone marrow but osteoblasts are seen more
frequently in early childhood.
Osteoblast
An osteoblast is a moderately large cell with ample cyto-
plasm and relatively small, round, and eccentrically placed
nucleus (PLATES 20,21). An osteoblast is descended from a
fibroblast. An osteoblast may be traumatized in the process
of aspiration and smearing and often has irregular shapes
and cytoplasmic streamers. The cells may have comet or tad-
pole shapes. The nucleus may be partially extruded or may
rest outside the cell, like a small round head on a round
body. The nuclear chromatin strands and the nuclear mar-
gins are well defmed. Usually there is a distinct nucleolus
which takes a predominantly blue color in contrast to pur-
ple-red stain of the chromatin. The basic color of the abun-
dant cytoplasm is blue. Wavy fibrils are often visible at the
periphery. Throughout the cytoplasm, there are small spher-
ical bodies which are colorless and give to the cytoplasm a
bubbly appearance. Within the cytoplasm, there is a promi-
nent round or oval zone which takes a lighter stain than the
rest of the cytoplasm. This area is usually away from the
nucleus but may be adjacent to the nucleus.
Osteoblasts morphologically resemble plasma cells, for
both have eccentric nuclei and irregular shapes, pointed
cytoplasmic protrusions, blue cytoplasm, chromophobic
areas within the cytoplasm, cytoplasmic fibrils and vacuoles.
Osteoblasts as a class are larger than normal plasma cells.
The relatively unstained cytoplasmic zone of the plasma cell
is adjacent to the nucleus and partially surrounds the nucle-
us as a collar, whereas the clear zone of the osteoblast is often
distinctly separate from the nuclear margin and when adja-
cent to the nucleus does not surround or enclose the nucle-
us (FIG. 5) The protein secretions of plasma cells sometimes
impart a reddish background color which is not demonstra-
ble in osteoblasts.
Osteoblasts in marrow smears often appear in groups
or aggregates in specimens from young children. A clump of
osteoblasts may simulate a clump of tumor cells; however,
the margins of cells in a malignant cluster are indistinct and
one cannot tell where one cell begins and the other ends.
Malignant cells are crowded and distorted. The size of
tumor cells and the color and structure of the nuclei tend to
be quite variable, whereas in osteoblasts the cells are more
orderly and uniform in size and chromatin structure. Light-
staining areas in the cytoplasm away from the nucleus are
characteristic of osteoblasts and are seldom demonstrable in
malignant cells.
13
The Morphology of Human Blood Cells

Chromophobic Area

Away from Nucleus Near Nucleus

Osteoblast Plasmacyte

Figure 5. Osteoblast vs. Plasmacyte

Osteoclast broom-like fringe aids in resorption of bone. Os teo clasts

Osteo clasts are professional phagocytes which resorb bone.
An osteoclast is a giant multinucleated cell which is formed
by fusion of precursor cells descended from marrow
macrophage progenitor cells. The osteoclast is a very large
(30-100 urn), irregularly shaped, and elongated cell with
multiple round nuclei which are approximately the same
size and appear benign in morphology (PLATES 20, 21). The
number of nuclei is quite variable (from 2 to 50 nuclei). The
nuclei are separate and are distributed somewhat evenly
within the cytoplasm. In contrast to the separate nuclei of
the osteoclast the megakaryocyte has a lobulated nucleus
(FIG. 6). The nuclear chromatin of the osteoclast stains dark
purple and is usually condensed; a single blue nucleolus is
usually visible in each nucleus.
The abundant grayish-blue cytoplasm on Wright stain
contains numerous azurophilic granules containing acid
phosphatase. In thin marrow smears it is possible to demon-
strate a ruffled cytoplasmic border or fringe consisting of
diaphanous veils or fingerlike cytoplasmic protrusions. This
are usually demonstrable in areas where bone is in
the process of demineralization and resorption such as in
multiple myeloma.
Endothelial Cell
Endothelial cells form a monolayer lining the inner surface
of all blood vessels and lymphatic vessels and maintain vas-
cular integrity by providing collagen, elastin, basement
membrane, and fibronectin to the subendothelial connec-
tive tissue. If the lining of the endothelium is damaged the
result is hemorrhage or an alteration in hemostasis.
Endothelial cells synthesize collagen, von Willebrand factor,
antithrombin III, tissue factor, and other proteins necessary
for blood coagulation. These cells remove platelet aggrega-
tion agents and vasoactive material from the blood.
In a marrow smear a fragment of a small intact vascu-
lar channel, the lumen of which is bounded by elongated
nongranular endothelial cells, can be observed rarely. These

Separated Attached
Osteoclast Megakaryocyte

Figure 6. Osteoclast vs. Megakaryocyte

Errisa Devi Fauzi
14

cells may be mistaken for malignant cells. In the process of
performing a venipuncture the point of the needle may
scrape the vessel wall and collect single or several endothe-
lial cells (PLATE 22) which are deposited on the smear. If the
first drop of blood from a small puncture wound of the fin-
ger is used to make a blood smear, an endothelial cell may
also be found on the smear.
Fibroblast
Fibroblasts are elongated cells with cytoplasmic processes
and are found in connective tissue. Collagen is synthesized
3 Erythrocyte Morphological Abnormalities
A normal human erythrocyte is normal in size (7.2-7.9 urn),
shape, and hemoglobin concentration; has no inclusions;
and is without a nucleus. (See earlier discussion of normal
erythrocytes under Erythropoiesis.)
Anisocytosis
Anisocytosis (Gr. anisos-unequal, uneven) is the term used
to describe variation in size of erythrocytes.
Macrocyte
Macrocyte is a red cell with a diameter larger (>8.0 urn)
than a normal erythrocyte (PLATES 24,36,37,39) and also
larger than the nucleus of a small lymphocyte; a macrocyte
is well hemoglobinized and usually lacks central pallor. Oval
macrocytes are observed in megaloblastic anemia and
round macrocytes are usually found in liver disease.
Microcyte
A microcyte is a red cell smaller (<6 urn) than a normal red
cell (7.2-7.9 urn) and also smaller than the nucleus of a small
lymphocyte (PLATES 24,36,37). A microcyte has increased
central pallor because of decreased hemoglobin concentra-
tion. Microcytes are characteristic of iron deficiency anemia
and thalassemia.
Poikilocytosis
Poikilocytosis (Gr. poikilo-varied) is the name given to any
variation in shape of the red cell (PLATE 23). Common
shape variations in erythrocytes are given below together
with associated disease states.
Errisa Devi Fauzi
The Morphology of Human Blood Cells
by fibroblasts and types I and III collagen are the main ele-
ments of the fibrosis in myelofibrosis and increase as the
disease continues. There is an infiltration of fibroblasts
along with lymphocytes, plasmacytes, and monocytes in
chronic inflammation. Clinical investigations indicate that
fibroblasts do not have their origin with hematopoietic tis-
sue and do not have the chromosome abnormalities that are
in hematopoietic cells. In the hematopoietic microenviron-
ment of the marrow fibroblasts, endothelial cells, fat cells,
and macrophages are grouped together to form a stromal
cell network and create a surface for hematopoietic stem
cells to proliferate and mature.
Acanthocyte
Acanthocyte (spur, thorn, or spiculated cells) has about 5 to
10 spicules of varying length and diameter and is irregular
in spacing and thickness (Gr. akantha-a thorn, prickle;
kytos-cell). Spur cells are seen in patients with alcoholic
liver disease, postsplenectomy, and abetalipoproteinemia
(PLATES 23, 26).
Bite Cell
A bite cell has approximately a half circle taken from the
edge of the red cell probably due to pitting of a Heinz body
by the spleen. Bite cells are found in patients with G-6-PD
deficiency (PLATE 26) and after dapsone.
Echinocyte
Echinocyte (burr cell) has about 10-30 short spicules or pro-
jections which are evenly spaced over the surface of the cell
and mostly uniform in size (PLATES 23, 26). Echinocytes
(Gr. echinos-spiny, prickly) are seen in uremia, pyruvate
kinase deficiency, bleeding ulcer, and carcinoma of stomach.
Helmet Cell
A helmet cell resembles a football helmet, loses part of its
membrane as it squeezes through fibrin strands in arteri-
oles, and has two or three pointed ends (PLATES 23, 25).
Helmet cells are classic findings in microangiopathic
hemolytic anemia (MAHA).
Keratocyte
Keratocyte (Gr. keras-horn) is a horn-like cell with a rup-
tured membrane and blunt extensions and is found in dis-
seminated intravascular coagulation (DIC) and vascular
prosthesis.
15
The Morphology of Human Blood Cells
Leptocyte
Leptocyte (Gr.leptos-slender, thin), a thin cell with a small
rim of hemoglobin at cell periphery and a large area of cen-
tral pallor, is observed in microcytic anemia (PLATE 24),
thalassemia, and obstructive liver disease.
Rouleaux
The word rouleaux (Fr. roll) identifies aggregates of eryth-
rocytes resembling a stack of coins (PLATE 63). Rouleaux
formation is usually seen in patients with myeloma, para-
proteinemia, and macroglobulinemia.
Schistocyte
Schistocyte (Gr. schistos-split) is an injured red cell such as
a helmet, fragment, or triangular cell with two or three
pointed ends (PLATES 23,25). Schistocytes are characteris-
tic of MAHA (microangiopathic hemolytic anemia) which
includes DIC (disseminated intrasvascular coagulation),
TTP (thrombotic thrombocytopenic purpura), malignant
hypertension and heart valve prosthesis (PLATE 25, Parts I,
2), burn patients, and pyropoikilocytosis (PLATE 31).
Sickle Cell
Sickle cell (drepanocyte: Gr. drepane-sickle; kytos-cell) is
a thin elongated erythrocyte with a point at each end, no
central pallor, and with "1", "V", "S" shapes due to polymer-
ization of sickle hemoglobin (PLATES 23, 27). Sickle cells
are observed in Hb SS, Hb S-thalassemia, Hb SC, Hb C
Harlem, Hb Memphis/S, and Hb SD-Punjab.
Spherocyte
Spherocyte (Gr. sphaira-sphere or globe) a spherical cell
with dense appearance (no central pallor) due to thickness
of the cell and often decreased diameter (PLATES 23, 26,
29). Spherocytes are encountered in hereditary spherocyto-
sis, acquired hemolytic anemia, after transfusion, burns,
venoms, chemical injury, and immunohemolytic anemia.
Stomatocyte
Stomatocyte (Gr. stoma, mouth) has a mouth or cup-like
area of central pallor instead of a circular area of pallor
(PLATE 23) and is seen in hereditary stomatocytosis
(FIG. 9), alcoholism, cirrhosis, and obstructive liver disease.
Target Cell
Target cell resembles a target with a central spot of hemo-
globin pigment surrounded by a pale area and then a
peripheral rim of hemoglobin (PLATES 23, 27) and is com-
mon in Hb SS, Hb CC, Hb SC, thalassemia, Hb S-
thalassemia, liver disease, and postsplenectomy.
Teardrop Cell
Teardrop cells (PLATE 23) are found in a variety of disor-
ders such as megaloblastic anemia (PLATES 24, 37, 39),
myelofibrosis (PLATE 31), and myelodysplasia (PLATE 56).
Errisa Devi Fauzi
16
Hemoglobin Concentration
In the normal human erythrocyte, hemoglobin should be
evenly distributed except in the small central area which
stains relatively pale compared with the periphery (indicat-
ing its biconcave shape).
Anisochromia (Gr. aniso-uneven, unequal + Gr.
chroma-color) represents variation in the color of erythro-
cytes due to unequal hemoglobin content. An increased pale
central area with only a small thin peripheral rim of hemo-
globin reflects poor hemoglobinization and is designated as
hypochromia (PLATE24). Macrocytes may lack normal cen-
tral pallor and are well filled with hemoglobin (PLATE24).
Small, dense cells or spherocytes (PLATES23, 26, 29) lack
central pallor because of the thickness of the cell.
Inclusions
Basophilic Stippling
Basophilic stippling in an erythrocyte is composed of pre-
cipitation of ribosomes of varying size and number that
form during drying of the smear and staining. With Wright
stain the stippling stains a deep blue (PLATE 32; FIG. 7).
Stippled cells are present in lead or other heavy-metal intox-
ication, nutritional deficiencies, and after the use of cytotox-
ic drugs.
Cabot Ring
Cabot ring is usually seen as a dark blue ring but it may
appear as blue granules in a linear array rather than as a
complete ring (PLATES 33, 39; FIG. 8). It probably origi-
nates from spindle material in abnormal mitosis. This
thread-like inclusion may be found in reticulocytes and in
erythrocytes in a Wright-stained smear of megaloblastic
anemia. The Cabot ring may also appear as a figure-eight
form. It may be seen along with stippling in an erythrocyte
or in the cytoplasm of a nucleated red blood cell.
Heinz Body
Heinz bodies represent denatured hemoglobin and are seen
as round, blue precipitates or inclusions in erythrocytes after
supervital staining with crystal violet (PLATE 35; FIG. 7).
They are observed after the administration of drugs such as
phenylhydrazine and primaquine; the drugs result in oxida-
tive denaturation of hemoglobin. The same inclusion bod-
ies are seen in G-6-PD deficient individuals or when an
unstable hemoglobin, such as Hemoglobin Zurich, is pres-
ent. Heinz bodies are not stained with Wright or Giemsa
stains as are Howell-Jolly bodies and Pappenheimer bodies.
Howell-Jolly Body
Howell-Jolly body is a small, round, dense nuclear fragment
composed of DNA and may be observed in an erythrocyte
in a Wright-stained smear (PLATES 33, 39; FIG. 7) and in a
 The Morphology of Human Blood Cells

SUPRAVITAL STAIN WRIGHT STAIN

Reticulum
(Reticulocyte)

Basophilic
0 RNA

Stippling RNA
(Reticulocyte)

Howell-
Jolly Body
0 0 00 DNA

CJ 0 0 0
Iron
Siderotic (Pappenheimer
Granule bodies)

Heinz Body
() 0 0 0 Denatured
Globin

Figure 7. Red Blood Cell Inclusions

.•
(i) CY •
.

Q.
. I _M

"._'

Figure 8. Cabot Rings

Errisa Devi Fauzi

17
The Morphology of Human Blood Cells
reticulocyte in a supravital stain. It is about 0.5 urn in diam-
eter. Usually only one Howell-Jolly body is present in an ery-
throcyte. Normally, these nuclear remnants are pitted from
erythrocytes during passage through the spleen. Howell-
Jolly bodies are observed in sickle cell anemia, megaloblastic
anemia, other hemolytic anemias, and in the blood of
splenectomized patients.
Pappenheimer Bodies
Pappenheimer bodies in red cells are siderotic granules that
stain as basophilic granules with Wright stain. A few are usu-
ally found near the periphery of the red cell but are not dis-
tributed throughout the cell as is stippling. Pappenheimer
bodies stain positively for iron in a Pruss ian blue iron stain
(PLATE 34; FIG. 7) and are identified as siderocytes.
Polychromatophilic Erythrocyte
(reticulocyte)
Polychromatophilic erythrocytes have a bluish hue in a
Wright stain smear and are usually larger than a normal red
cell (PLATE 32; FIG. 7). Polychromasia represents ribosomal
material. A polychromatophilic erythrocyte leaves the mar-
row and enters the circulation containing a small number of
ribosomes and other cytoplasmic organelles. When a drop
of blood is mixed with drops of new methylene blue, these
organelles aggregate and appear as a granuloftlamentous
pattern or reticulum in an erythrocyte; hence the name
4 Disorders of Iron Metabolism
Iron Deficiency Anemia
Iron deficiency anemia (IDA) results from depletion of iron
storage caused by either increased requirements or excessive
loss. Gastrointestinal blood loss and increased demands
for iron during human growth and at pregnancy are the
most common causes leading to IDA. Iron deficiency is the
most common type of anemia worldwide. It is most com-
mon in young children, menstruating females, and elderly
individuals.
Clinical Description
Patients with IDA may be asymptomatic with only abnor-
mal laboratory studies or may present with fatigue,
weakness, dizziness, and headache. Physical signs specific for
Errisa Devi Fauzi
18
reticulocyte (PLATE 32) is derived. The reticulocyte matures
in the circulation in about 2 days and becomes a mature ery-
throcyte. Most cells identified as reticulocytes have lost their
nuclei, but a rare orthochromatic erythroblast with gran-
ulofilarnentous material may be observed. Normal adult
blood contains less than 2% reticulocytes. An increase in
reticulocytes is observed in hemolytic anemia (e.g., sickle
cell anemia) and after treatment for nutritional deficiencies.
Decreased reticulocytes are found in hypoplastic states.
Ringed Sideroblast
A ringed sideroblast is an erythroblast with Prussian blue
positive iron granules that form a partial or full ring around
the nucleus (PLATE 34). Ringed sideroblasts are typical of
sideroblastic anemia.
Sideroblast
A sideroblast is a nucleated red cell that contains one or
more Prussian blue positive (iron-containing) granules in
marrow of normal individuals (PLATE 34). Sideroblasts are
increased in marrow smears of sideroblastic anemia.
Siderocyte
A siderocyte is a mature red cell containing siderotic gran-
ules when the smear is stained with Prussian blue iron stain
(PLATE 34).
IDA, such as koilonychia and blue sclerae, are more com-
mon in severe cases and malnutrition states. Tachycardia
and pallor are common and occasionally glossitis and angu-
lar stomatitis may be present.
Laboratory Findings
The diagnosis of IDA requires careful evaluation of the
peripheral blood smear and the iron studies. It should be
remembered that by the time IDA is manifested clinically,
iron storage has almost been completely depleted. The inad-
equate supply of iron to red blood cells leads eventually to
IDA. The peripheral blood smear in patients with IDA usu-
ally reveals small erythrocytes (microcytes) with increased
central pallor due to the lack of hemoglobin in individual
red cells (PLATE 24). If the anemia is severe, the degree of

pallor is greater and red cells may appear as rings. Besides
microcytes, elliptical forms and other irregular shapes are
observed. The platelet count is often markedly increased.
The bone marrow reveals an erythroid hyperplasia. Late ery-
throblasts may be small and have scanty blue cytoplasm
with ragged borders (PLATES 36, 37). The MCV and MCH
values are reduced and the MCHC is decreased in severe
anemia (TABLE 3). The RDW is almost always elevated in
patients with iron deficiency anemia (TABLE 3) and it is
among the earliest indices to become abnormal.
Iron studies are required to confirm the diagnosis of
IDA. Serum ferritin which reflects iron storage is low to
absent and iron-binding capacity is typically increased in
patients with IDA. Transferrin saturation usually declines to
<16% in IDA, while it is expected to be >20% in patients
with anemia of chronic disease. Other microcytic anemias
such as thalassemias can be differentiated from IDA by care-
ful history and examination of peripheral blood film and by
other tests, such as iron studies, hemoglobin electrophoresis,
and Hb A2 determination.
It should be remembered that the cause of iron deficien-
cy should be investigated meticulously except in obvious con-
ditions, such as excessive menstruation or pregnancy. A
source of blood loss should be determined and the presence
of gastrointestinal tumors should be carefully evaluated.
Table 3. Normal Mean Corpuscular Values and ROW
Me VALUES. ROW RANGE
MCV(Mean corpuscular volume) 88 ± 8 fl
MCH(Mean corpuscular hemoglobin) 30 ± 3 pg
MCHC(Mean corpuscular hemoglobin
concentration) 34.4 ± 1.1 g/dl
RDW(Red cell distribution width) reflects
the variabilityof red cell size and is based on
width of the red blood cellvolume 11.5t014.5
5 Megaloblastic Anemia
The megaloblastic anemias are a group of disorders due to
impaired DNA synthesis and characterized by similar mor-
phologic abnormalities of the hematopoietic cells. The
defect in DNA synthesis is a common feature that leads to
pancytopenia and other laboratory and clinical manifesta-
tions of these disorders. The arrest in DNA but not RNA
synthesis causes asynchrony between nuclear and cytoplas-
mic cellular components. With repeated divisions this defect
becomes exaggerated and generates large cells with short life
Errisa Devi Fauzi
The Morphology of Human Blood Cells
Sideroblastic Anemia
The sideroblastic anemias are a group of disorders charac-
terized by variable degrees of anemia. The diagnosis is con-
firmed by the presence of excess iron in the form of ringed
sideroblasts in the bone marrow smear stained with
Prussian blue stain (PLATE 34). Common to all sideroblas-
tic anemias is the impaired biosynthesis of heme in the ery-
throid cells in the bone marrow. The inherited form of
sideroblastic anemia is rare. This form has an x-linked pat-
tern of inheritance with the underlying defect being in the
gene encoding for the enzyme 3-aminolevulinic acid (ALA)
synthetase. This enzyme is a rate-limiting step in the heme
synthetic pathway. The anemia in patients with ALA syn-
thetase deficiency may present early in infancy, but milder
defects may not be manifested until midlife. The anemia is
usually microcytic and hypochromic. Serum iron, ferritin,
and transferrin saturation are increased. Other blood counts
are usually normal. .
Acquired sideroblastic anemia is much more common
than the hereditary form and can be either idiopathic or sec-
ondary to other conditions. Alcohol consumption is the most
common cause for sideroblastic anemia in adults. Refractory
anemia with ringed sideroblasts is a disorder related to the
myelodysplastic syndromes encountered in many individuals
above 50 years. Anemia usually develops slowly but some
patients may require regular support with blood transfu-
sions. The diagnosis of acquired sideroblastic anemia
requires that at least 15% of all erythroblasts in the marrow
aspirate are ringed sideroblasts. Other common findings in
bone marrow are erythroid hyperplasia and dyserythro-
poiesis. A specimen for cytogenetic analysis should be
obtained from all patients with sideroblastic anemia.
span. Because proliferating cells are affected by this defect,
the manifestations of megaloblastic anemias are not restrict-
ed to hematopoietic cells but involve almost all organs.
The most common causes of megaloblastic anemias are
deficiencies of two vitamins essential for DNA synthesis:
vitamin B12 (cobalamin) and folate. Although a score of
pathogenic mechanisms can be responsible for vitamin B12
deficiency, lack of absorption from the gastric mucosa is the
most common cause in the United States. Anemia caused by
19
The Morphology of Human Blood Cells
atrophy of the gastric mucosa and defective binding with the
intrinsic factor necessary for cobalamin absorption is
referred to as pernicious anemia. However, the underlying
mechanism is immune-mediated and not malignancy as the
term may imply. The most common causes of megaloblastic
anemia from folic acid deficiency are unbalanced diet and
increased requirement as in pregnancy or in hemolytic ane-
mia. Also folic acid deficiency commonly occurs in patients
with malabsorption such as celiac disease.
Physical Examination
Physical examination of patients with megaloblastic anemia
reveals pallor and tachycardia. Occasionally icterus second-
ary to hyperbilirubinemia may be present. Patients with
severe deficiency of cobalamin or folate may present with
hepatomegaly, skin pigmentation, and tender beefy tongue.
Neurologic signs indicating involvement of the posterior,
pyramidal, and spinocerebellar tracts are characteristic of
B12 but not folate deficiency.
6 Aplastic Anemia
The term aplastic anemia is used to describe peripheral
blood pancytopenia in association with hypocellular bone
marrow. All blood lineages are usually affected and
hematopoietic cell elements are replaced by fatty infiltra-
tions in the bone marrow. By definition, no malignant cells
are present in the bone marrow of patients with aplastic
anemia. The disease can be inherited as in Fanconi's anemia
or dyskeratosis congenita or most commonly occurs sec-
ondary to exposure to radiation, cytotoxic agents, and cer-
tain medications, such as chloramphenicol. Infections with
hepatitis viruses and parvovirus B19 (PLATE 71) are rela-
tively common causes for aplastic anemia in certain regions
of the world.
The manifestations of aplastic anemia stem from the
deficiency in hematopoietic cells. Patients with severe
thrombocytopenia may present with recurrent bleeding
episodes requiring platelet transfusion. Anemia is common
and red blood cell transfusions are often needed to maintain
adequate levels of hemoglobin. Surprisingly, severe or recur-
rent infections are not a common feature of aplastic anemia
despite depressed neutrophil counts. Pancytopenia is
Errisa Devi Fauzi
20
Laboratory Findings
Examination of the peripheral blood smear reveals two
important findings: neutrophil hypersegmentation (>5
lobes-PLATES 39,40) and oval macrocytes (PLATES24, 39).
The macrocytes are well filled with hemoglobin and central
pallor is absent or slightly decreased. Pear-shaped or tear-
drop erythrocytes may also be found. The MCV is > 105 fl in
the majority of patients and low white cell count and
decreased platelets are common. The RDW is most often
increased.
The bone marrow is megaloblastic and cellular.
Megaloblasts are large and may show karyorrhexis or
nuclear fragmentation. Asynchronism in maturation is evi-
dent in the later stages of erythroblast development as the
cytoplasm appears more mature than the nucleus which
appears immature (PLATES 36-39). N. myelocytes,
metamyelocytes, and bands often have a large nucleus and
are larger in size than normal cells. Hypersegmented neu-
trophils are present. Once the diagnosis of megaloblastic
anemia is confirmed, a search for the cause of B12 or folic
acid deficiencies should be conducted.
characteristic although the lymphocyte count in some
patients may be normal. No particular erythrocyte morpho-
logic abnormalities are seen but some degree of anisocytosis
is common.
The bone marrow is hypocellular and megakaryocytes
are reduced or absent. The normal hematopoietic elements
are replaced by fatty spaces and normal lymphocytes; plas-
ma cells and macrophages can be found in normal distribu-
tion. Patchy areas of normal hematopoietic cells can be seen
occasionally in the bone marrow trephine biopsy. Careful
evaluation of the bone marrow and peripheral blood is nec-
essary to exclude the presence of blastic or dysplastic cells.
Investigation of patients with aplastic anemia should
include acid serum lysis test and sucrose lysis test to rule out
paroxysmal nocturnal hemoglobinemia, measurement of
B12 and folate, and viral studies. Evaluation for cytogenetic
abnormalities should be carried out in all patients diag-
nosed with aplastic anemia. Complete evaluation is crucial
to determine the etiology of the disease and subsequently
the prognosis of patients.
7 Hemoglobinopathies
The Thalassemias
The thalassemias are the most common group of hereditary
anemias. The word thalassemia is a Greek term translated
into "anemia of the sea" denoting its prevalence in the
Mediterranean basin. Thalassemia is caused by defective
synthesis of one or more of the chains that form normal
hemoglobin.
Normal polypeptide hemoglobin tetramers are formed
by two a-chains and two ~-chains interlocked together. A
minor component of adult hemoglobin is formed by a com-
bination of a chains with y chains to form fetal hemoglobin
(Hb F). Adult hemoglobin is a mixture of97% Hb A (a2~2)'
2-3% Hb ~ (a282), and approximately 1% Hb F (a2y 2)'
Genetic defects that cause reduced or absent production of
one or more globin chains of Hb A have two major conse-
quences. First, decreased synthesis of hemoglobin tetramers
is manifested as microcytic and hypochromic anemia charac-
teristic of most thalassemia syndromes. Second, because of
the imbalance in production of hemoglobin subunits, a pro-
portion of globin chains remains free or unpaired. Free glo-
bin chains are insoluble and lack the oxygen-carrying
capacity of normal hemoglobin. The accumulation of these
unmatched chains has a detrimental effect on red blood cells
manifested as excessive intramedullary hemolysis, which is
the principle cause of morbidity in thalassemia patients.
a-Thalassemia Syndromes
The a-globin chains are encoded by two pairs of genes (hap-
lorypes) located on the short arm of chromosome 16.
Therefore, o-thalassemia is classified into four syndromes
based on whether the inherited defect is in one or more of
the four a-globin genes. Most thalassernias are caused by
large gene deletions in the a-globin genes. The nomencla-
ture of o.-thaiassemias is depicted in Table 4. Mutations that
affect one a gene only (silent carrier) have little or no clini-
cal impact. In most cases, the hematologic indices are within
the normal limit.
ti-Th al assemia-Z (silent carrier) is common in
Southeast Asia and the Melanesia. The diagnosis is suspect-
ed based on family studies of an a-thalassemia proband
since the Hb A) and Hb F are normal in these individuals.
In ex-Thalassemia-J (minor), two genes are affected.
The genotypes and subsequently the clinical expression vary
depending on the site and type of mutation. In Asians, the
defect usually affects the genes on the same chromosome
(-Iaa.) while in African Americans and in Mediterraneans,
the genotype is (-exl-ex). Individuals with a-thalassemia
minor are usually asymptomatic; microcytosis and
hypochromia are discovered on review of blood film. This
type of anemia should be differentiated from iron deficiency
anemia by the presence of' a more severe decrease in MCV
Errisa Devi Fauzi
and MCH and the minimal degree of decline in hemoglobin
level. Poikilocytosis and target cells are a constant finding in
the blood smear of patients with a-thalassemia.
Confirmation of the diagnosis of cc-thalassemia-Z requires
molecular or DNA testing.
Hemoglobin H disease lacks three a genes (TABLE4) and
is associated with variable degrees of anemia. The disease is
more common in Asians than Mediterraneans and occurs
very rarely in African Americans. Accumulation of Hb H
leads to damage and hemolysis of red blood cells.
Hemoglobin H precipitate is detected as inclusion bodies
when red blood cells are incubated with supravital oxidizing
stains such as 1% brilliant cresyl blue. Hemoglobin H com-
prises approximately 5-30% of hemoglobin and the rest
being mostly Hb A, reduced amount of Hb A2, and traces of
Hb Bart's. Mild to moderate anemia and splenomegaly are
common findings in individuals with Hb H disease.
Hydrops fetalis with Hb Bart's occurs as a result of the
absence of all four a genes (TABLE 4). The predominant
hemoglobin in the affected fetuses is Hb Bart's (yz). A minor
hemoglobin component is formed by Hb Portland 1 (~2 Y2)
and Hb H. Hemoglobin Bart's has high oxygen affinity and
lacks the normal cooperativity leading to diminished oxygen
unloading to various tissues. Affected infants are described
as hydropic due to generalized edema caused by congestive
heart failure and low albumin. Hypochromia and microcy-
tosis are severe and the blood smear usually reveals target
cells and nucleated red cells. The diagnosis is made by Hb
electrophoresis and women suspected of carrying a hydrop-
ic fetus should undergo amniocentesis in order to obtain
DNA studies or globin synthesis evaluation. Prenatal diag-
nosis of Hb Bart's is effective in reducing the morbidity and
mortality of both the mother and the fetus.
Table 4. Phenotypes and Genotypes of
a-Tha lassemia
NUMBER OF a
PHENOTYPE GENOTYPE AFFECTED GENES
Normal a aaJaa o
a-Thalassemia-2 -cuoo.
(Silent carrier)
a-Thalassemia-1 -/aaor 2
(Minor) -cd-o.
+I«:
Hb H disease 3
Hb Bart's hydrops fetalis -/- 4
~-Thalassemia Syndromes
The ~-globin chain production is encoded by two genes locat-
ed on chromosome 11. Decreased or absence of ~-chain syn-
thesis caused by the types of mutation in the ~-globin genes
leads to the different clinical syndromes of ~-thalassemia.
21
The Morphology of Human Blood Cells
Most types of ~-thalassemia are caused by point mutations
affecting one or more than one base in the globin gene.
Homozygous ~O-thalassemia or thalassemia major
(Cooley's anemia) results from the absence of synthesis of any
~-globin chains. Red blood cells are incapable of proteolysing
the excess of unpaired a-globin chains. Aggregates of a-
chains form inclusion bodies which are damaging to red cell
membrane and lead to destruction of these cells either in the
bone marrow (ineffective erythropoiesis) or in the spleen.
Absence of ~-globin chains also causes the red cells to be
microcytic and hypochromic. The ineffective erythropoiesis
and hemolysis combined with the decreased oxygen-carrying
capacity of red cells provides stimulus for production of more
red blood cells through the release of erythropoietin.
In response to the increasing demands for red cell produc-
tion, the bone marrow undergoes massive expansion which
accounts for the thalassemia facies, thinning and pathologic
fractures of vertebrae and long bones. Hemolytic anemia
results in massive splenomegaly and congestive heart failure.
The anemia is manifested gradually during the first two years
of life. This occurs because of the switch from Hb F produc-
tion to Hb A during this period. Anemia is severe and hemo-
globin levels of 2 to 3 g/dL are not unusual. Marked
anisocytosis and poikilocytosis with hypochromia are pres-
ent. The peripheral blood smear reveals striking abnormali-
ties of red cells including hypochromia, target cells,
leptocytes, nucleated red cells, and basophilic stippling
(PLATE29). The predominant hemoglobin is Hb F with vari-
able amounts ofHb A and Hb ~.
~+ -thalassemia minor is characterized by a hypo-
chromic microcytic blood picture but the patient is usually
without symptoms. This syndrome is often discovered acci-
dentally during examination for symptoms not related to
thalassemia. There is mild anemia or no anemia (10-15
gm/dl). MCV and MCH are low but red cell count is high.
The RDW is usually normal in ~-thalassemia minor com-
pared with an elevated RDW in iron deficiency anemia.
Reticulocytes may be slightly increased. Hemoglobin elec-
trophoresis shows a predominance of Hb A. Hb ~ is
increased (3.5-8%). Hb F is normal or minimally increased.
Morphologic alterations of peripheral red blood cells
include microcytes, target cells, occasional poikilocytes,
hypochromia, and basophilic stippling (PLATE 30). The
bone marrow shows slight erythroid hyperplasia. Body iron
content is normal unless iron therapy has been given.
Sickle Cell Disorders
Sickle Cell Anemia
Laboratory findings in newborns with sickle cell anemia
(Hb SS) are characterized as a mild hemolytic anemia by 10
to 12 weeks of age and it remains throughout the life of the
patient. In adults the hemoglobin range is 6.0-9 g/dl; the
MCV (90± fl) and MCHC (34± %) are often in the normal
range. The reticulocyte count is around 10% (range 5-25%).
Errisa Devi Fauzi
22
Peripheral blood smears of Hb SS show a varying num-
ber of sickle cells. Erythrocytes that are identified as sickle
cells in Wright-stained smears have undergone transforma-
tion slowly as a result of hemoglobin polymerization, thus
causing their membranes to lose elasticity and become per-
manently sickled (irreversible sickle cells). Sickled red cells
are thin, elongated erythrocytes with a point at each end;
they have no central pallor; they may have oat, crescent, "1",
"V;' and "S" shape (PLATES 23, 27). The blood smear also
has numerous target cells, elliptocytes, and other odd
shapes. Orthochromatic erythroblasts are often present in
small numbers. Howell-Jolly bodies are observed in young
and older adults as the result of asplenia. Pappenheimer
bodies (siderocytes in an iron stain) are sometimes present.
The white blood cell count is usually in the range of 12
to 15 x 109/L in steady-state conditions. The hyperplastic
bone marrow in Hb SS is characterized by an increase in
orthochromatic and polychromatophilic erythroblasts. The
platelet count is increased.
The diagnosis of sickle cell anemia is confirmed by high
performance liquid chromatography (HPLC) or by cellulose
acetate electrophoresis. Various hemoglobins are precisely
separated and quantitated by HPLC using ion exchange high
performance liquid chromatography and reported as per-
centages. In a patient with Hb SS electrophoresis shows one
band in the S position, which compares with the control S
band at pH 8.6. Valine is substituted for glutamic acid in the
B6 position. Only the hemoglobin variants with this substi-
tution undergo sickling. There is no Hb A in the elec-
trophoretic pattern unless the patient has been transfused.
Hb F may be present in varying amounts. Hb ~ is normal
unless the patient also has Hb S-~ thalassemia.
Clinical features of Hb SS include dactylitis, acute pain,
acute chest syndrome, and loss of splenic function during the
first years oflife. Vaso-occlusive episodes may begin to appear
between 6 and 12 months in about half of the babies, before 6
years in most children, and by a few in late childhood. Other
acute vaso-occlusive events include stroke, priapism, and
hematologic crisis (aplastic, hemolytic, megaloblastic) in
children less than 5 years of age. Chronic problems include
damage to kidney, central nervous sytem, bones and joints,
lung, liver, and gastrointestinal system; leg ulcers and preg-
nancy problems also occur. Infections can be fatal complica-
tions in children with sickle cell anemia at about 1year of age.
Sickle Cell Trait
Sickle cell trait (Hb AS), the heterozygous state for Hb S
gene, is found in about 8% of African Americans.
Individuals with the sickle cell trait (Hb AS) have no anemia
and the red cell morphology on the blood smear is normal.
Under normal conditions clinical or hematological manifes-
tations of hemoglobin S are rare in sickle cell trait individu-
als. The red blood cells contain more Hb A than Hb S. In
cellulose acetate electrophoresis at pH 8.6 there are two
bands which demonstrate more Hb A than Hb S.

Erythrocytes containing sickle cell hemoglobin (Hb S)
undergo shape alterations when deoxygenated in moist
preparations of blood mixed with reducing agents such as
sodium metabisulfite. The soluble sickle cell hemoglobin
when deoxygenated becomes insoluble and polymerizes in
the form of elongated and pointed crystal-like structures.
These linear polymers distort the elastic membrane, produc-
ing multipointed, "holly-leaf" shapes (PLATE 28). Cells
assuming this shape are capable of immediately reverting to
the disc shape when reoxygenated. Such cells are known as
reversible sickle cells. There are also rapid solubility tests that
identify the presence of Hb S. Hb A is present and Hb F is
usually normal in individuals with sickle cell trait.
Hemoglobin SC
Clinical features of hemoglobin SC (Hb SC) are similar to
Hb SS but a little less severe. Symptoms are rare in the first
year of life and most individuals are asymptomatic for the
first decade. The most common symptom is abdominal or
skeletal pain similar to crises in Hb SS. Spleen is enlarged in
approximately two-thirds of children and may persist into
adult life. Retinopathy is more severe and more common in
Hb SC than SS disease. Aseptic necrosis of femoral head is
reported to be frequent.
Hematology findings show that anemia is mild or does
not exist. Reticulocytes are slightly increased. White cell
count and platelet count are normal. Many target cells are
present on the blood smear. Crystals of Hb SC (PLATES 23,
27) distort a few of the erythrocytes by forming a pyramid-
like elongated projection of condensed aggregates of hemo-
globin. Several small crystals form in a red cell giving a
quartz-like appearance to the cell. A red cell may have an
elongated crystal-like aggregate of dense hemoglobin at each
end leaving a hemoglobin-free central area. A rare sickle cell
may be found. The diagnosis ofHb SC is confirmed by HPLC
or by hemoglobin electrophoresis. Using electrophoresis
with an alkaline buffer one band will be in the S position and
one band in the C position compared with the control hemo-
globin hemolysates.
Hemoglobin C Diseases
Hemoglobin CC
Hemoglobin CC (Hb CC) is a mild disease that may be
detected in newborn screening programs for a hemoglo-
binopathy. Enlargement of the spleen is a feature in most
individuals.
Anemia is mildly to moderately severe. Hematocrit is
around 33%. Hemoglobin level varies from 8 to 12 g/dl,
Reticulocyte counts are slightly elevated from 2-6%.
Morphology of erythrocytes is abnormal with numerous tar-
get cells, microcytes, occasional spherocyte, and a few hemo-
globin C crystals (PLATES 23, 27). Erythrocyte survival is
shortened and there is evidence of splenic sequestration.
Errisa Devi Fauzi
The Morphology of Human Blood Cells
A Hb C crystal is elongated with pyramid-shaped ends
and is well filled with hemoglobin. The crystal may be seen
within the pale membrane of the cell or it may be free.
Occasionally there may be more than one small C crystal
within the cell membrane. Red cells with Hb C are more
rigid than normal. After splenectomy the crystals are fre-
quent. Crystals may also be seen in reticulocyte preparations
and in moist preparations. Incubation with 3% sodium
chloride enhances the crystallization of Hb C. The disease
may remain undetected unless the erythrocytes on the blood
smear are carefully examined.
The diagnosis is made by HPLC or by electrophoretic
analysis of hemoglobin at pH 8.6 with the major fraction
being Hb C. Glutamic acid in the sixth position from the N
terminal of the beta chain has been replaced by lysine. There
is no Hb S. Hb F may be slightly increased. Hb C moves elec-
trophoretically in the same position as Hb ~, Hb E and
Hb 0 Arab at alkaline pH and it can be separated from other
hemoglobins by acid agar gel electrophoresis. Hb A2 may be
slightly increased by column chromatography.
Hemoglobin AC Trait
Hemoglobin AC trait (Hb AC), the heterogyzous state of
Hb C, has fewer target cells than Hb CC and hemoglobin C
crystals have not been observed on the blood smear.
Hemoglobin is usually in the low range of normal. Red cell
survival may be decreased. Reticulocyte count is not
increased. With alkaline hemoglobin electrophoresis about
30-40% is Hb C and about 50-60% is Hb A. There may be
a slight increase in Hb A2 by column chromatography. Hb C
cannot be separated from Hb A2 except by acid agar gel elec-
trophoresis.
Hemoglobin E
Hemoglobin E (Hb E) is a frequent hemoglobin variant in
South East Asia and it is found in the United States as the
result of the influx of refugees. Heterozygous (Hb AE)
patients are healthy individuals and do not have anemia.
Morphology of red cells is similar to ~-thalassemia minor
with microcytes and target cells. Electrophoresis shows 25-
30% Hb E with the remainder being Hb A. MCV average is
73 fl; MCH is low; MCHC is almost normal.
Homozygous Hb E (Hb EE) has a mild anemia without
many symptoms. Numerous microcytes and target cells are
on peripheral blood smear. Average MCV is 67 fl, MCH is
low, and MCHC is almost normal.
Hemoglobin E is commonly associated with ~o_
thalassemia major. Microcytic hypochromia anemia with
target cells, fragments, leptocytes, bite cells, and spherical
cells is present. Hb E-~O-thalassemia (PLATE 30) resembles
thalassemia major clinically as well as hematologically
(MCV 55 to 65 fl). Hb E migrates with Hb C and Hb A2 on
alkaline hemoglobin electrophoresis. To separate Hb E from
Hb C HPLC or agar gel electrophoresis at acid pH should
be performed.
23
 8 Hereditary Erythrocyte
Membrane Abnormalities
Hereditary Elliptocytosis
Hereditary elliptocytosis (HE) syndromes are a group of
RBC disorders that are characterized by the presence of
elliptocytes (ovalocytes) in the peripheral blood film and by
a varied clinical presentation. The majority of individuals
with HE do not have anemia and red cell survival is normal.
Heterozygosity for HE is not associated with splenomegaly.
The blood film contains 25% to almost 100% elliptocytes
(PLATES 23,29).
Homozygous HE patients with chronic hemolysis have
a moderate to severe hemolytic anemia (Hb 9-12 g/dl) and
decreased red cell life span. Reticulocytes are increased. The
blood film of these patients contains not only elliptocytes
but also poikilocytes and some microspherocytes.
Splenomegaly and gall bladder disease may be present in
homozygotes.
HE disorders are caused by intrinsic membrane protein
abnormalities which lead to altered membrane function,
change in shape, and sometimes hemolysis. Primary defect
in HE is in the membrane cytoskeleton involving spectrin
and less frequently protein 4.1. In most HE patients spectrin
is normal quantitatively but abnormal in structure. Normal
red blood cells have 90% spectrin in the form of tetramers,
whereas spectrin from HE is present in dimers.
Hereditary Pyropoikilocytosis
Hereditary pyropoikilocytosis (HPP) is a severe hereditary
hemolytic anemia which is very similar clinically to homozy-
gous HE and demonstrates extreme micropoikilocytosis and
thermal instability of red cells (PLATE 31). HPP results from
a double heterozygous state for n-spectrin mutant and defec-
tive synthesis of spectrin. HPP was first thought to be a sepa-
rate disorder but now it is considered a subtype of common
HE; HE and HPP can exist in the same family.
In HPP red cell morphology includes extreme poikilocy-
tosis, microspherocytes, microelliptocytes, cell fragments,
and membrane budding. MCV is very low «65 fl); MCHC is
normal; osmotic fragility is increased. Reticulocytes are
increased. Normal red cells fragment at temperatures greater
than 49°C but HPP erythrocytes show striking membrane
instability at 45-46°C; this susceptibility of HPP red cells to
heat injury is the result of thermal instabilityofHPP spectrin.
Hereditary Spherocytosis
Hereditary spherocytosis (HS) is a hemolytic disorder that is
characterized by anemia, spherocytes, jaundice, and
splenomegaly. HS is inherited as an autosomal dominant
trait. The primary pathologic feature of HS is a combined
Errisa Devi Fauzi
24
deficiency of the cytoskeletal support proteins, usually spec-
trin and ankyrin. This results in a loss of part of the poorly
supported lipid bi-layer causing a transformation of cell
shape from normal to spheroid. The deformability of
spherocytes is decreased compared with the normal disc-
shaped red cells which have a larger membrane surface area.
The microspherocyte is smaller than a normal red cell, is
dense, and lacks central pallor (PLATES 23, 26,29).
Patients with HS usually present with decreased hema-
tocrit, increase in reticulocytes, increased MCHC (second-
ary to mild cell dehydration), microspherocytes on tlle
blood smear, hyperbilirubinemia, and an abnormal osmotic
fragility test. MeV is usually normal.
The number of spherocytes varies greatly in each
patient but is fairly uniform in size and density. In severe HS
there may also be odd-shaped red cells as well as sphero-
cytes. The bone marrow is characterized by an erythroblas-
tic hyperplasia (late erythroblasts).
Hereditary Stomatocytosis
Erythrocytes with a central slit instead of a circular area of
pallor are called stomatocytes (Gr. stoma, mouth) (PLATE
23; FIG. 9). Hereditary stomatocytosis (HSt) or hereditary
hydrocytosis includes a group of autosomal dominant
hemolytic anemias which are characterized by erythrocyte
overhydration and macrocytosis. In some cases this disorder
is clinically silent with no or little anemia. Most patients
with anemia and jaundice have mild symptoms and no ther-
apy is required. Reticulocytes are moderately increased.
MCV is often elevated but the MCHC is normal. The num-
ber of stomatocytes is variable (10% to 50%). The osmotic
fragility is increased. The anemia is rarely severe enough to
require transfusion. Splenomegaly may be observed in
severe anemia. The hemolytic anemia of HSt improves after
splenectomy in most patients.
Fig. 9. Hereditary Stomatocytosis-blood smear
9 Microangiopathic Hemolytic Anemias
Thrombotic Thrombocytopenic
Purpura and Hemolytic Uremic
Syndrome
The microangiopathic hemolytic anemias (MAHA) are a
diverse group of disorders characterized by anemia with
schistocytes and thrombocytopenia. The most common of
these disorders are thrombotic thrombocytopenic purpura
(TTP) and the hemolytic uremic syndrome (HUS).
The etiology of thrombotic thrombocytopenic purpura
remains unclear; however, recent evidence suggests that an
antibody against the protease that cleaves von Willebrand
multimers into smaller multimers is present in some
patients. Some of these released multimers have high affini-
ty to platelets causing their aggregation.
Certain toxins released by Shigella or E. coli strains have
been strongly implicated in the pathogenesis of hemolytic
uremic syndrome. Severe thrombocytopenia and intravas-
cular hemolysis with many fragmented red blood cells or
schistocytes on peripheral blood smear are characteristic of
both disorders (PLATES 23,25 Parts 1 and 2).
Clinical Presentation
Fever and neurologic symptoms are common findings and
renal failure is usually more severe in patients with HUS.
Widespread microvascular thrombi and occlusive lesions in
the brain, lungs, kidney, heart, and virtually all other organs
can be demonstrated in the majority of patients who died
from TIP. Both TTP and HUS are considered true
10 Leukocyte Morphological Abnormalities
Acquired Leukocyte
Abnormalities
Structural abnormalities that are visible by light microscopy
in the cytoplasm and nucleus of neutrophils are useful in the
differential diagnosis of various diseases and conditions.
Auer Rods
Auer rods (or Auer bodies) are elongated, narrow (about 1.5
urn long and 0.5 urn wide), purplish-red, rod-like inclusions
Errisa Devi Fauzi
hematologic emergencies requiring immediate attention and
appropriate care.
Laboratory Features
The diagnosis can be made only by reviewing the peripheral
blood smear and correlating the microscopic with the clinical
and laboratory findings. This procedure is essential in all
patients referred with thrombocytopenia or anemia.
Schistocytes (helmet, fragmented, triangular cells), polychro-
masia, and nucleated red blood cells are present in all patients
with TTP and HUS (PLATES 23, 25 Parts 1 and 2). Other lab-
oratory findings include reticulocytosis, very high LDH, and
high indirect bilirubin. Once the diagnosis is confirmed plas-
ma exchange should be initiated without any delay.
Hemolytic Anemia due to
Thermal Injury and Venoms
Acquired hemolytic anemia has been observed after exten-
sive thermal burns. Schistocytes, spherocytes, echinocytes,
and fragmented cells are observed on the blood smear with
intravascular hemolysis (PLATE 31). Increased osmotic and
mechanical fragility of the erythrocytes is noted. The sever-
ity of the hemolytic anemia is related to the body surface
affected and results partly from the direct effects of heat
on erythrocytes.
The bite of the brown recluse spider (Loxosceles reclusa)
is associated with a hemolytic anemia with spherocytes and
fragmented cells (PLATE 26).
that are demonstrable in the cytoplasm of blasts (PLATE 47)
in about one-third of the patients with acute myelocytic
leukemia (AML). Auer rods represent a fusion of primary
granules. Auer rods are present in approximately 1% to 10%
of blast cells and a diligent search must be made for them.
Usually there is only one Auer rod in a blast. In acute
promyelocytic leukemia multiple Auer rods may be found in
promyelocytes in the bone marrow. Auer rods stain posi-
tively with myeloperoxidase, Sudan black, and acid phos-
phatase indicating that they represent granular material.
25
The Morphology of Human Blood Cells
They are not demonstrable in blast cells of lymphocytic,
plasmacytic, erythroblastic, and megakaryocytic leukemias.
Degenerated Neutrophils
Degenerated neutrophils are cells with a round degenerated
nucleus and granular cytoplasm and are found in smears
made from old (several hours or more) anticoagulated
blood (PLATE 40). These cells may be mistakenly identified
as nucleated red cells with possible stippling. They actually
are old neutrophils in which the lobes of the nuclei have
degenerated into one (or more) round dark-staining nucle-
us. Similar degenerated cells may be seen in other old body
fluids, e.g., cerebrospinal, peritoneal, and pleural fluids.
Dahle Bodies
Dohle bodies are faintly visible, round, oval, or irregularly
shaped blue inclusions that are found near the periphery of
the cytoplasm of neutrophils (PLATE 40) in infection. These
small (diameter 1-3 um) indistinct bodies represent aggre-
gates of rough endoplasmic reticulum by electron
microscopy. They may be easily overlooked but since they
are a sign of infection a careful search for their presence
should be made.
Dohle bodies were first described in patients with
scarlet fever. They are associated with severe or systemic
infections, severe burns, exposure to cytotoxic agents,
myelodysplasia, toxemia of pregnancy, and plant and animal
poisons. They are often accompanied by toxic granulation
and cytoplasmic vacuoles. Similar basophilic inclusions are
observed in the hereditary anomaly May-Hegglin
(PLATE 43) but they are usually larger and have more
sharply defined borders.
Hypersegmented Neutrophils
Normal segmented neutrophils have two to four lobes with
a few five lobes. Hypersegmented neutrophils have six or
more lobes (PLATES 39,40) along with many five lobes and
are characteristic observations in smears of blood of
patients with megaloblastic anemia and related vitamin
Bl2-folic acid deficiences. One of the first hematologic
abnormalities to appear in megaloblastic anemia is neu-
trophil hypersegmentation and it persists for two or more
weeks after specific therapy has begun. Hypersegmentation
of neutrophils may rarely be inherited.
Toxic Granules
Toxic granules are prominent purplish or blue-black gran-
ules (PLATE 40) that are often demonstrable in neutrophil
cytoplasm (particularly segmented and band neutrophils)
with severe infections and other toxic states. Toxic granules
vary in size, shape, distribution, and color. These granules
resemble the primary granules of promyelocytes and early
neutrophilic myelocytes and may indicate a disturbance in
neutrophil maturation with persistence of the primary
granules in the mature neutrophils. Toxic granules are
myeloperoxidase positive.
Errisa Devi Fauzi
26
Vacuoles
Vacuoles are observed in the cytoplasm of leukocytes, par-
ticularly neutrophils and monocytes, and are manifestations
of degenerative changes; this finding may suggest sepsis.
Vacuoles may also appear in neutrophils and monocytes in
blood films made from old anticoagulated blood
(PLATE 40).
Hereditary Leukocyte Anomalies
Pelger-Huet Anomaly
Pelger-Huet anomaly, a hereditary and benign anomaly, is
characterized by hypolobulation of the nuclei of the mature
neutrophils (PLATE 41) or the failure to develop normal
nuclear lobes in segmented cells during terminal differenti-
ation. The nuclear chromatin in neutrophils is coarse and
clumped. In the heterozygous form the nuclei may have
dumbbell or peanut-shaped nuclei or two smooth round
lobes connected by a short filament (spectacle-like or pince-
nez). In the homozygous form, the nuclei of most of the
neutrophils are round (PLATE 41) The granules are similar
to normal neutrophil granules. The neutrophils appear to
function normally and to phagocytize and destroy microor-
ganisms. Hypolobulated neutrophils of Pelger- Huet must be
distinguished from the typical neutrophil bands which
occur with infection.
The white blood cell count and differential count are
normal in Pelger-Huet, These hypolobulated cells survive
normally in circulation. They display a shift toward maturi-
ty (with three, four, or five lobes) when there is a deficiency
of vitamin B12 or folic acid. After treatment the Pelger
peanut shape and spectacle-like nuclei reappear.
Pelger-Huet anomaly is inherited as a heterozygous
autosomal dominant trait and is not associated with any dis-
ease state or with any other congenital abnormality. Pseudo-
Pelger-Huet cells with morphologic changes like those just
described have been observed with acute or chronic myelo-
cytic leukemia, myelodysplasia, and myelofibrosis.
Occasionally they have been noted in association with
leukemoid reaction secondary to metastasis in bone mar-
row, agranulocytosis, multiple myeloma, drug sensitivity,
malaria, myxedema, or acute enteritis. The nucleus of pseu-
do-Pelger cells are more often roundish or oblong rather
than bilobed or pince-nez; they appear transiently in these
disorders; they may indicate the clinical onset of one of
these disorders in advance of the disease.
May-Hegglin Anomaly
May-Hegglin anomaly, a rare and dominantly inherited dis-
order, is characterized by large (2 to 5 urn) basophilic inclu-
sions in the cytoplasm of neutrophils, eosinophils, basophils,
and monocytes (PLATE 43), by thrombocytopenia, and by
giant platelets (PLATE 73) which often have few granules.
Inclusions in these cells are similar to Dohle bodies in infec-
tious states but are larger, more prominent, often spindle-

shaped, discrete, sometimes elongated, and present in many
cells. Inclusions consist of RNA and apparently are derived
from rough endoplasmic reticulum. These inclusions do not
stain with Sudan black or periodic acid Schiff.
Laboratory tests in patients with May- Hegglin anomaly
reveal poor clot retraction, prolonged bleeding time, short
survival of platelets, and variable results in platelet function
tests. Occasionally abnormal bleeding, easy bruising, and
epistaxis may occur in these patients.
Chediak-Higashi Syndrome
Chediak-Higashi (CH) syndrome (or anomaly) is a rare
autosomal recessive disorder characterized by the presence
of large lysosome-like granules in granulocytes, lympho-
cytes and monocytes in the peripheral blood, early granulo-
cytes in the bone marrow, and melanocytes in hair strands
(PLATE 42). These large abnormal lysosomal granules have
been reported to be formed by progressive fusion of
azurophilic and specific granules during maturation.
Patients have an increased susceptibility to infection which
may be due to decreased bactericidal activity and degranu-
lation of neutrophils.
Neutrophils have numerous large lysosomal granules
which are peroxidase positive. Lymphocytes and plasma
cells may have one large abnormal red-staining granule.
Monocytes have abnormal granules resulting from granule
fusion. Similar large lysosomal granules have been observed
11 Chronic Myeloproliferative Disorders
The chronic myeloproliferative syndromes are a diverse
group of neoplastic disorders characterized by proliferation
of one or more of the hematopoietic stem cell compart-
ments. The hallmark of chronic myeloproliferative disorders
(MPD) is the clonal expansion of one or multiple cell line-
ages within the bone marrow and at extramedullary sites.
These disorders include
• Chronic Myelogenous Leukemia
• Polycythemia Vera
• Essential Thrombocythemia
• Idiopathic Myelofibrosis
Chronic Myelogenous Leukemia
Chronic myelogenous leukemia (CML) or chronic granulo-
cytic leukemia is an acquired clonal disease originating from
malignant transformation that occurs at the stem cell level.
Errisa Devi Fauzi
The Morphology of Human Blood Cells
in renal tubular cells, fibroblasts, vascular epithelium,
neurons in the central nervous system, and ocular pigment.
Patients with CH have partial ocular and cutaneous
albinism, pale silvery hair, light skin, and photophobia. These
patients may develop an accelerated phase with fever, lym-
phadenopathy, hepatosplenomegaly, anemia, neutropenia,
and thrombocytopenia. Consideration to use bone marrow
transplantation has been suggested as a possible treatment.
Alder-Reilly Anomaly
Alder-Reilly anomaly is characterized by large dark blue or
lilac granules in the cytoplasm of neutrophils and more
commonly in bone marrow (PLATE 44). Lymphocytes and
monocytes may have similar inclusions. Eosinophils and
basophils have large granules. The abnormal granules are
observed in a group of metabolic disorders named
mucopolysaccharidoses, particularly in association with
Hurler's and Hunter's syndromes. They can be confused
with toxic granules seen in infectious states. This rare anom-
aly is inherited as a recessive trait and apparently does not
interfere with leukocyte function.
The defect in these diseases is the incomplete degrada-
tion of the protein-carbohydrate complexes which are
known as mucopolysaccharides, each of which have differ-
ent enzymatic deficiencies. Alder-Reilly inclusions are com-
posed of deposits of acid mucopolysaccharides throughout
tissues giving rise to various symptoms.
Although the disorder is described as myeloid, all cell line-
ages are usually involved. The natural course of CML
includes a long chronic and rather indolent phase that
transforms sooner or later into an accelerated phase charac-
terized by increasing blasts in the peripheral blood and bone
marrow. Finally, the disease evolves into a blastic phase
which represents a true transformation into acute leukemia.
Cytogenetic Abnormality
A distinctive cytogenetic abnormality involving an unequal
reciprocal translocation between chromosomes 9 and 22
t(9,22) called the Philadelphia (Ph) chromosome is consis-
tently found in patients with CML. The abnormality is usu-
ally present in 90% to 100% of metaphases in the bone mar-
row of newly diagnosed patients. During formation of the
Ph chromosome, a proto-oncogene called abl on the long
arm of chromosome 9 is detached and translocated onto the
27
The Morphology of Human Blood Cells
breakpoint cluster region (bcr) of chromosome 22 creating
a chimeric bcr-abl gene. The complete function of this
chimeric gene is not well understood and it is thought that
the bcr-abl fusion gene generates a hyperactive tyrosine
kinase that signals uncontrolled proliferation of the affected
cells. Because of the increased evidence linking CML to the
Ph chromosome, the disease is currently defined by the
presence of cytogenetic translocation t(9,22) or by the pres-
ence of the rearrangement bcr-abl on DNA analysis. It is
important to remember that the Ph chromosome is also the
most common karyotypic abnormality found in adult
patients with acute lymphoblastic leukemia. Progression of
CML to the blastic phase may be associated with the acqui-
sition of new cytogenetic anomalies.
Clinical Description
The annual incidence of CML in the United States is
approximately 4,000 new cases which account for about
20% of all leukemias. The median age at the time of diag-
nosis is 60 years. However, recently, an increasing number of
young patients have been diagnosed in our institution and
other centers in the United States.
In the chronic phase, patients with CML may be asymp-
tomatic presenting only with an elevated granulocyte count
discovered on routine laboratory tests. Patients with white
cell count (WEC) above 30,000 usually report symptoms
such as fatigue, malaise, and low grade fever. With WBC
exceeding 80,000, patients may complain of abdominal dis-
tention or discomfort secondary to an enlarged spleen.
Weight loss and bone pain may be prominent complaints by
some patients, especially with very high WEe. Splenomegaly
is possibly the most common physical finding, being detected
in more than 90% of patients. The liver is palpable in approx-
imately 50% of patients in the chronic phase.
Hematology Findings
Hematologic findings of CML include a neutrophilic leukocy-
tosis (20 to 500x1Q9/1) with all stages of neutrophil matura-
tion: myeloblast (±3%); progranulocyte (±4%); myelocyte,
metamyelocyte, band (±40%), segmented (± 35%) (PLATES
45,46). An absolute basophilia is an important blood finding
and often precedes clinical manifestations. Eosinophilia may
be noted. Occasional monocytes may be present. Leukocyte
alkaline phosphatase stain of mature neutrophils is decreased
in CML (PLATES 46, 48, Part 2). Thrombocytosis is present in
about half of the cases; the platelets may be large. Occasional
megakaryocyte fragments may be observed. There is a nor-
mocytic normochromic anemia at diagnosis. Minimal aniso-
cytosis and poikilocytosis with an occasional nucleated RBC
are frequently observed. The bone marrow is markedly hyper-
cellular with neutrophilic precursors from myeloblast to seg-
mented neutrophiL Usually there are no more than 5%
myeloblasts. Basophils and eosinophils are often increased.
Megakaryocytes may be increased. Erythroid precursors are
found in normal, increased, or decreased numbers. Myeloid-
erythroid ratio is increased.
Errisa Devi Fauzi
28
Blast Crisis of CML
CML is predestined to transform to acute or blastic phase
which may be preceded by an accelerated phase. Patients
with accelerated or blastic phase usually complain of fever,
sweats, weight loss, bone pain, and increasing tenderness at
the splenic area. The average time for transformation to
acute phase is 4 years; however, metamorphosis can occur as
early as 2 years and as late as 10 years after the initial diag-
nosis. Observations in the blood during blast transforma-
tion reveal excess blasts and promyelocytes which may out-
number the myelocytes and metamyelocytes. In approxi-
mately 70% of CML patients the blastic transformation is of
myeloid lineage while in 30% the predominantly malignant
cell has lymphoblastic morphology (PLATE 46).
Treatment
The initial goal of treatment should aim at relieving symp-
toms and controlling the high cell count. This is usually
achieved by using hydroxyurea, a drug that inhibits DNA
synthesis. Combination of interferon-a, a biologic response
modifier, and cytosine-arabinoside are considered the best
treatment available for management of CML. Treatment
with this combination yields better results than hydroxyurea
and may prolong survival of patients in the chronic phase.
Interferon-a alone or in combination with cytosine-arabi-
noside may also lead to clonal remission (normalization of
the cytogenetic defect) in approximately 20-30% of patients.
Although chemotherapy can improve the quality of life, it
does not cure the disease. Bone marrow transplantation
from an HLA-match sibling provides the only curative treat-
ment for CML. Recently a tyrosine kinase inhibitor
(Gleevec) has been approved and is considered now the first
line of treatment in the majority of patients with CML.
Polycythemia Vera
Polycythemia vera (PV) is a clonal hematologic malignancy
characterized by increased proliferation of all hematopoiet-
ic elements within the bone marrow. As in the case of CML,
the clinical course of PV evolves gradually over several years
and many patients are expected to have normal survival if
appropriate measures are taken to control the production of
their red cell mass. Several factors including radiation, occu-
pational exposures, and hereditary defects have been impli-
cated in the pathogenesis of PV
Clinical Features
The clinical features of PV are the direct result of excessive
production of blood cells. The diagnosis may be an inciden-
tal finding of increased red blood cells in an asymptomatic
patient on a routine office visit. Excessive increase in ery-
throcyte count may cause symptoms such as headache,
dizziness, blurred vision, and puritis. These symptoms are
referred to as hyperviscosity syndrome. Physical examina-
tion usually reveals conjunctival plethora, hepatomegaly,
and splenomegaly. Thrombosis is a common problem in
 The Morphology of Human Blood Cells

patients with PV presenting as deep venou thrombosis of conditions may reach lOOOxl09/1; however, this increase
lower extremities, peripheral vascular di ea e, and cere- rarely causes thromboembolic phenomena.
brovascular accidents.
Treatment
Laboratory Results Treatment of ET aims at reducing the platelet counts in
Laboratory results include elevated red blood cells with symptomatic patients. Recently, Anegrelide, a drug that
hematocrit approaching 80% or higher in some patients. inhibits megakaryopoiesis, has been approved for the treat-
Leukocytosis and increased platelet numbers are observed in ment of ET. The drug has almost replaced other and more
more than 50% of patients with PY. Examination of periph- toxic treatments such as hydroxyurea. The prognosis of
eral blood usually reveals anisopoikilocytosis, polychroma- patients with ET is usually very good, provided that the
sia, and megathrombocytes and some early granulocytes. platelet counts are well controlled.
Elevated blood cell mass, normal plasma volume, and nor-
mal arterial oxygen aturation usually differentiate between
PV and other causes of erythrocytosis.
Idiopathic Myelofibrosis
It i estimated that 10% of patients with PV undergo Idiopathic myelofibrosis is a clonal myeloproliferative disor-
evolution to myelofibrosis. This phase is characterized by der characterized by the presence of splenomegaly, leuko-
increasing splenomegaly, excessive reticulin in the bone erythroblastic blood picture, excessive teardrop erythro-
marrow, and a leukoerythroblastic picture in peripheral cytes, marrow fibrosis, and extramedullary hematopoiesis.
blood. Transformation to acute myeloid leukemia occurs in The hematopoietic abnormality in myelofibrosis arises from
approximately 9% of patients with PY. a defect at the stem cell level. However, it should be empha-
sized that mesenchymal cells and fibroblasts are not part of
Treatment the malignant clone and that marrow fibrosis is considered
Treatment of PV aims at reducing blood cell mass in symp- secondary or reactive. The cause of fibrosis in this disease is
tomatic patients by phlebotomy or other therapeutic a matter of some debate. Dysregulation in the synthesis of
modalities. collagen, excessive release of growth factors, and abnormal-
itie of platelet activation have been implicated as po sible
source of marrow fibro is.
Essential Thrombocythemia
Es ential thrombocythemia (ET) is defined by the presence Presentation
of platelet counts in exces of 600xl09/l, megakaryocytic Like other myeloproliferative di orders, patients with
hyperplasia, splenomegaly, and absence of Ph chromosome. myelofibrosis may be asymptomatic and the diagnosis may
The disease is considered a clonal hematopoietic neoplasm be sought after detection of enlarged spleen on routine
originating at" the level of the stem cell. physical examination or because of an abnormal blood pic-
ture. The most common symptoms are fatigue, fever,
Clinical Features abdominal discomfort, weight loss, and night sweats.
The average age of patients at the time of diagnosis of ET is Moderate to massive splenomegaly is present in approxi-
55 years. Increased platelet counts may be an incidental mately 90% of patients. The spleen has the extraordinary
finding or patients may present with bleeding or thrombot- ability of accommodating a large blood volume and increas-
ic problem. Splenomegaly can be found in approximately ing growth of hematopoietic elements.
40% of patients with ET.
Hematology Findings
Laboratory Examination Peripheral blood examination in myelofibrosis is character-
Peripheral blood examination usually reveal the presence ized by a leukoerythroblastic picture (nucleated red cells and
of anisopoikiiocytosis, thrombocytosis (PLATE 57), imma- immature myeloid elements), teardrop cells (PLATES 3],57),
ture myeloid precursors, nucleated red cells, and large giant platelets (PLATE 73) and megakaryocytic fragments.
platelets. In most patients, the bone marrow i hypercellular Anemia is a constant feature of myelofibrosis and is caused by
with increased megakaryocytes. Most patients with ET have ineffective erythropoiesis, hemolysis and hemodilution
abnormal platelet functions which may explain the bleeding caused by increased blood volume. The platelets are usually
and thrombotic manifestations of this disease. Essential increased while leukopenia and leukocytosis are common
thrombocythemia should be differentiated from other dis- findings in myelofibrosis. The bone marrow is inaspirable in
orders that cause increase in platelet counts. Secondary the majority of patients. Marrow biopsy usually reveals fibro-
thrombocytosis can be present in patient with iron defi- sis with patches of cellularity and increased megakaryocytes.
ciency anemia, chronic inflammatory di ease such as
Crohn's disea e and rheumatoid arthritis, some chronic Treatment
infections, and in patients with underlying malignancy such Treatment options range from watchful follow-up and
as lung or colon cancer. The platelet counts in these transfusion support to bone marrow transplantation.

Errisa Devi Fauzi

29
 12 Acute Myelogenous Leukemia
Acute myelogenous leukemia (AML) is a malignant clonal
disorder characterized by discordance between proliferation
and differentiation: the leukemic cell lineage retains the abil-
ity to proliferate but differentiation to mature cells is com-
promised. The result is excessive accumulation of immature
cells and inhibition of well differentiated hematopoietic
elements. Exposure to radiation, hydrocarbons, and
chemotherapeutic agents appears to increase the risk of
AML. Several genetic abnormalities including mutations in
growth factor receptors and defects in the normal control
mechanisms of the cell cycle have been described in patients
with acute leukemia.
The FAB Classification of AML
Acute myelogenous leukemia is a heterogeneous group of
hematologic malignancies that are classified according to
the predominant malignant cell type. The French American
British (FAB) Cooperative Group developed in 1976 a clas-
sification system (TABLE 5) that was based on marrow and
blood morphology and cytochemical staining. Immuno-
phenotypic markers of leukemic cells (phenotyping) are
used to establish the lineage in cases of poorly differentiated
leukemias. The FAB classification defines groups (MI-M7)
of AML based on the percentage of maturing cells beyond
the myeloblast stage. The FAB classification did not include
criteria such as cytogenetic abnormalities, response to ther-
apy, and prognosis. However, it remains the most accepted
classification system of acute myelogenous leukemias.
Presentation of AML
All leukemia subtypes share similar clinical characteristics.
However, certain features such as involvement of the skin
and gums are more common in the M4 and M5 subtypes.
Similarly, disseminated intravascular coagulation (DIC) is a
constant feature of M3, but can occur in any variant of AML.
Presenting symptoms of AML include fatigue, weakness,
Laboratory Findings
The diagnosis of acute leukemia becomes apparent after
evaluating the patient and examining the peripheral blood
smear. Blasts or immature cells are usually present in the
majority of patients with AML, but in a very few patients, no
circulating blast cells can be found. The presence of an Auer
rod in a blast aids in the diagnosis of AML. Multiple Auer
rods are observed in a few early cells in AML M3 (PLATE
47). The diagnosis of AML is established when more than
30% of nonerythroid cells in the marrow are myeloid blasts.
The bone marrow in acute leukemia is typically hypercellu-
lar. It is essential to obtain enough material from the bone
marrow for cytogenetic analysis and flow cytometric studies.
The most important cytogenetic abnormalities
observed in patients with AML include translocations of
chromosomes 8,11 in M2; 15, 17 in patients with M3; and
inversion of chromosome 16 in M4 with eosinophils.
The evaluation of the patient with AML should include
screening coagulation tests, fibrinogen, and D-dimer to rule
out the presence of DIe. Appropriate measures should be
taken to manage these patients since chemotherapy can
exacerbate DIC leading to excessive morbidity.
It is important to perform histochemical stains in every
patient being evaluated for acute leukemia. The majority of
AML blasts stain positively (PLATE48) for myeloperoxidase
(MPO), while as a general rule, lymphoblasts are MPO neg-
ative but stain positively for terminal deoxynucleotidyl
transferase (TdT). Other stains used to differentiate
myeloblasts from lymphoblasts are the Sudan black and
esterase stains. Sudan black (PLATE 48) and granulocyte
esterase stains are positive in Ml through M4 and negative
Table 5. Morphologic (FAB) Classification
of Acute Myelogenous Leukemia (AML)
SUBTYPE DESCRIPTION

fever, weight loss, petechiae, and easy bruising. Physical MI: Acute myeloblastic leukemia without maturation
examination usually reveals pallor, tachycardia, ecchymosis, (Plate 47)
and petechiae. The spleen may be palpable in a few patients. M2: Acute myeloblastic leukemia with maturation
Cutaneous leukemia infiltrates the gums causing gingival (Plate 47)
hyperplasia and signs of leptomeningeal leukemia can be
M3: Acute promyelocytic leukemia (Plate 47)
seen in some patients. Anemia and thrombocytopenia are
M4: Acute myelomonocytic leukemia (Plate 49)
constant features of AML. Approximately 50% of patients
M4EO: Acute myelomonocytic leukemia with eosinophilia
with AML present with high white cell counts. The presence
of blasts in excess of 80xl09 cells/I is a worrisome sign and M5: Acute monocytic leukemia (Plates 49,50)
warrants prophylaxis for tumor lysis syndrome and meas- M6: Acute erythroleukemia (or erythroblastic) leukemia
ures to reduce the blast load. Very low white cell count is (Plates 51- 53)
seen in 25-35% of patients with AML, and pancytopenia is a M7: Acute megakaryocytic (or megakaryoblastic) leukemia
common presenting feature of this disease. (Plates 54, 55)

Errisa Devi Fauzi

30
 The Morphology of Human Blood CeUs

in Iymphoblasts. Monocytic esterase stain is positive in M4 normal hematopoiesis. However, induction alone does. not
and M5 and negative in Iymphoblasts. guarantee the eradication of leukemia even in the absence of
morphologic evidence of leukemia. This concept provides
rationale for further treatment with chemotherapy usually
Therapy referred to as consolidation. Bone marrow transplantation
Treatment of AML aims at inducing and maintammg plays an important role in the treatment of AML. Patients
durable remission. Remission is defined as circulating neu- who relapse within a short period after achieving remission
trophils > 1.5xl09/1, platelets> 100xl09/1, absence of blasts in and patients with unfavorable prognostic factors are consid-
peripheral blood, and a bone marrow cellularity >20% with ered as candidates for the procedure. Approximately 25% of
<5% blasts. Combination chemotherapy is always used in patients with AML are expected to be alive more than five
the induction phase of treatment of AML. The goal of years after initial diagnosis.
induction is to reduce the leukemic burden and restore

13 Myelodysplastic Syndromes
The term myelodysplastic syndrome (M DS) is used to Single or complex cytogenetic abnormalities are found in the
describe biJineage or trilineage morphologic dysplastic majority of patients with MDS. They often involve chromo-
changes in the bone marrow. By definition, MDS is a clonal somes 5, 7, and 8 alone or in combination with other defects.
disorder that affects all hematopoietic cell lines. The majori-
ty of patients with MDS are destined to transform into acute
leukemia. Myelodysplastic syndromes appearing without
Treatment
obvious explanation or cause are called de IlOVO, while those Treatment of MDS includes support with red blood cell or
developing after exposure to chemicals, radiation, or platelet transfusions for patients with refractory anemia or
chemotherapeutic agents are called secondary MDS. thrombocytopenia. Aggressive antibiotic therapy should be
administered to patients with neutropenic fever. Growth
factors to maintain appropriate levels of red cells, neu-
Presentation of MDS trophils, and platelets have recently become available to help
The majority of patients affected with MDS are above 60 support patients with MDS. These measures, however, do
years of age. Patients usually present with refractory anemia, not alter the course of these patients but provide temporary
fatigue, and fever secondary to neutropenic infections. control of the symptoms. Presently, only patients younger
Thrombocytopenia is common in patients with MDS and than 55 years of age can potentially be cured by matched-
may lead to frequent transfusions to prevent or treat bleed- sibling bone marrow transplantation.
ing episodes. Splenomegaly occurs in approximately 10-20%
of patients diagnosed with MDS. Table 6. Morphologic (FAB) Classification of
Myelodysplastic Syndromes (Plate 56)

Laboratory Findings BONE

MARROW
PERIPHERAL
BLOOD PROGRESSION
MDS SUBTYPES BLASTS ('Yo) BLASTS ('Yo) TO AML ('Yo)
The morphologic abnormalities in M DS include ringed
sideroblasts in the bone marrow of patients with refractory Refractory anemia (RA) ~5 ~1 8
anemia, bizarre nuclear shapes, frequent mitosis, and inter- Refractory anemia with <5 <1 12
nuclear bridging (PLATE 56). Hypogranulated granulocytes ringed sideroblasts (RARS)
and hyposegmented leukocytes with abnormal chromatin
Refractory anemia with 5-20 ~5 44
condensation (pseudo-Pelger-Huet) are common observa-
excess blasts (RAEB)
tions (PLAfE 56). Micromegakaryocytes and other dysmor-
phic megakaryocytes can be seen in all types of MDS but Chronic myelomonocytic <20 <5 4
especially the 5q-syndrome. Because of the variation in mor- leukemia (CMML)
phologic appearances, risks for transformation to acute Refractory anemia with 21-30 ~5 60
leukemia, and prognosis, the myelodysplastic syndromes excess blasts in
have been classified into five categories depicted in Table 6. transformation (RAEB-T)

Errisa Devi Fauzi

31
 14 Lymphoproliferative Disorders
The lymphoproliferative disorders (LPD) are a heteroge-
neous group of diseases characterized by malignant and
excessive growth of cells of the lymphocytic lineage. These
disorders are classified based on their morphologic appear-
ance, extent of involvement of the bone marrow versus
peripheral blood and, most importantly, the stage of matu-
ration of the malignant lymphocyte. A list of the most com-
mon LPDs include
• Hodgkin's Disease
• Non-Hodgkin's Lymphoma
• Chronic Lymphocytic Leukemia (PLATES 58,60)
• Hairy Cell Leukemia (PLATES 60-62)
• Multiple Myeloma (PLATE 63)
• Sezary Syndrome (PLATE 64)
Hodgkins Disease
Hodgkin's disease (HD) is a lymphoid malignancy of uncer-
tain etiology that has unique differences from other LPDs.
Certain types of cells called Reed-Sternberg cells and their
variants are central to making the diagnosis of HD.
Hodgkin's disease has a bimodal pattern of incidence occur-
ring at ages between 20-30 years with a second peak in indi-
viduals above 60 years. The disease has a predictable pattern
of involvement of the lymph nodes and mediastinum.
Unlike other malignancies, HD in the majority of patients is
considered a curable neoplasm.
Clinical Presentation
Patients with HD present with lymphadenopathy involving,
in decreasing frequency, the mediastinum, left and right
sides of neck, left and right axillae, and left and right hilar
inguinal lymph nodes. Bulky lymphadenopathy may cause
local symptoms due to compression of the adjacent organs.
The spleen is the most common organ involved below the
diaphragm and is an important determinant of the thera-
peutic approach of HD.
Histology
Hodgkin's disease is a rather complex entity from a
histopathological point of view. Based on the degree of
fibrosis or sclerosis and the predominance of lymphocytic
elements, Lukes and associates classified HD into four major
histopathological types: (1) nodular sclerosis, (2) lympho-
cyte predominance, (3) lymphocyte depletion, and
(4) mixed cellularity. In most reports from the United States
and Europe, nodular sclerosis followed by mixed cellularity
are the most frequent types of HD. Reed-Sternberg cells or
their variants are seen in variable frequencies among the
different types of HD. Patients infected with the human
Errisa Devi Fauzi
32
immunodeficiency virus are more likely to develop the
mixed cellularity type and to follow a more aggressive clini-
cal course. The diagnosis of HD should be established by an
excisional lymph node biopsy examined by an expert
hematopathologist.
Staging
Staging of Hodgkin's disease and non-Hodgkin's lymphoma
is as important as establishing the diagnosis. Staging aims at'
defining the extent of the tumor and provides therapeutic
and prognostic directions for the physician. Staging consists
of detailed clinical and physical examination with, special
interest in constitutional complaints (B symptoms) such
as fever, night sweats, and weight loss, and documentation
with measurement of all areas of lymphadenopathy, spleen,
and liver.
Laboratory Studies and Other Procedures
Laboratory studies should include complete blood count
with differential, liver, and renal function tests. Radiological
studies include chest radiograph and computed tomography
scan (CT scan) of the chest and upper and lower abdomen.
Gallium scan is obtained to evaluate bulky lymphade-
nopathy.
Lymphangiography has been largely replaced by CT
scan or other less invasive testing modalities. Bone marrow
biopsy is necessary to evaluate the extent of disease and
involvement of bone marrow. Biopsy of other extra nodal
areas is indicated as dictated by the clinical picture.
Treatment
Treatment of HD requires full understanding of the disease
in any given patient. Treatment decisions should be made in
the context of multimodality approach and after consulta-
tion with an expert pathologist, radiotherapist, radiologist,
and under the guidance of a hematologist familiar with the
treatment of the disease.
Non-Hodgkin's Lymphoma
The non-Hodgkin's lymphomas (NHL) are a complex of
disorders with a variable histologic and clinical presentation.
The histopathologic classification of these disorders has
undergone several modifications over the past years. Most
recent classification systems rely on a combination of
cytologic and immunophenotypic features of the neoplastic
cells. This information is often complemented by molecular
and cytogenetic data and by clinical correlation with the dis-
ease course and degree of aggressiveness. The World Health
Organization (WHO) has recently adopted a classification

sy tern that subdivides HLs into B- and T-cell neoplasms
based on flow cytometric and other immunophenotypic
markers.
The clinicaL presentation of patients with NHL cannot
be distinguished from HD or other lymphoproliferative dis-
orders. The presence of B symptoms varies among the dif-
ferent types of NHL. Involvement of the skin and other
extra nodal areas is more common in patients with T-cell
but can occur in alJ types ofNHL. The diagnosis and staging
of NHL follows the same guidelines as for HO. Every effort
should be made to obtain sufficient material for hi topatho-
logic, flow cytometric, and molecular studies. Excisional
lymph node biopsy remains the preferred method of diag-
nosis of HL ince it provides information on all the archi-
tecture of the node. Su picious areas on physical examina-
tion or on imaging studies should be biopsied to evaluate
possible extra nodal disease. Accurate staging is of utmost
importance in all Iymphoproliferative disorders, but espe-
cially HD and NHL. The stage of disease usually determines
the therapeutic strategies and provides valuable prognostic
information. With few exceptions, treatment of NH L entails
the administration of a combination of chemotherapeutic
agents with periodic assessment and restaging studies to
confirm the response tarus of the patients. Radiotherapy
and treatment of the nervous system may be included based
on the clinical presentation.
Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is the rno t common
type of leukemia in Western countries. About 10,000 new
cases are diagnosed every year in the United States. The dis-
ease is less common in Asian countries such as Japan and
China. The etiology of CLL is unknown and several viruses
have been implicated in the pathogenesis of the disease
without sufficient supporting evidence. A genetic predispo-
sition is supported by the finding of clusters of CLL in some
families. However, the precise mechanism for this predispo-
sition i still unknown. The disease is characterized by pro-
gressive accumulation of lymphocytes arrested in late stages
of their differentiation with no apparent increase in their
role of proliferation. Approximately 95% of CLL in the
United tates are of the B-celJ phenotype. Leukemic cells in
CLL usually stain for COS, CD19, and C020. T-cell and CD
negative CLL are usually more aggressive than B-CLL.
Presentation
Patients with CLL usually complain of fatigue, weakness,
night sweats, and weight loss. At times, the diagnosis is made
incidentally in patients with high lymphocyte count but no
symptoms. Lymphadenopathy is the most common physical
finding and splenomegaly is common in patients with CLL.
Laboratory Results
The diagnosis of CLL is considered in the presence of >5x
109/1lymphocyte count that i sustained over at least a 4-week
Errisa Devi Fauzi
The Morphology of Human Blood Cells
period. The diagnosis is facilitated by immunophenotypic
studies showing monoclonal B-phenotype with low breis of
surface immunoglobulin. The diagnosis can also be made in
the pre ence of >30% lymphocytes in a normal cellular or
hypercellular bone marrow. The lymphocyte count in
patients with CLL usually ranges between 5 to SOOx109/1. The
lymphocytes appear morphologically mature, usually small
with the nucleus occupying the entire cell (PLATES 58,60).
The nuclear chromatin i usually dense and clumped. The
leukemic lymphocytes may become deformed upon prepara-
tion of films. Thi oval deformity is recognized as smudge
cells on a peripheral blood smear. The hemoglobin level and
platelet count vary considerably among patient with CLL.
Hemoglobin <11 g1dL and platelets <100xJ09/1 indicate
more advanced disease. Autoimmune hematologic compli-
cation such as autoimmune hemolytic anemia and immune
thrombocytopenia are common in patients with CLL.
Hypogammaglobulinemia is common in CLL and con-
tributes to the immunodeficiency state of these patients.
Treatment
Patients with CLL should be evaluated carefu.lly to deter-
mine or predict the clinical course of the disease. Patients
with only increased lymphocyte count without symptoms
or autoimmune phenomena should be watched periodical-
ly.The disease in the e patients may follow a very chronic or
indolent course without any specific treatment. Patients
with systemic symptoms and patients with massive or bulky
lymphadenopathy as well as those with autoimmune com-
plications should be offered treatment. Patients with rapid-
ly increasing lymphocyte count are also candidates for
immediate treatment. The treatment of choice is the purine
analog fludarabine with or without prednisone. Special
attention should be given to treatment of opportunistic
infections. Aggressive transformation to Richter's syndrome
and prolymphocytic leukemia can occur in approximately
10% of cases.
Hairy-Cell Leukemia
Description of Hairy Cells
Hairy-cell leukemia (HCL) is a rare Iyrnphoproliferative dis-
order characterized by the pre ence of hairy cells which are
lymphocytes with prominent cytoplasmic projections
(PLATES60- 62) that infiltrate the bone marrow and spleen.
Morphologically, hairy cells are mononuclear cells that vary
in cell size and nuclear shape. The nucleus may be either
centrally or eccentrically located. The cell usuaLly has a fine
reticu.lar appearance and the nuclear shape may be round,
ovoid, indented, or convoluted. The bone marrow is often
inaspirable. Bone marrow biopsy usually shows diffuse or
focal infiltration by hairy cells and a mixture of small lym-
phocytes and mast cells. The cells are separated by a network
of fibrils giving them a pattern referred to as "fried-egg"
appearance. Hairy cell stain strongly positive for tartrate-
33
The Morphology of Human Blood Cells
resistant acid phosphatase (TRAP). Approximately 90% of
patients with HCL demonstrate TRAP positivity (PLATE
62) which can be an additional diagnostic tool in combina-
tion with the morphologic appearance of cells. Immuno-
phenotypic analysis usually demonstrates the presence of
CDllc and CD25 positive cells.
Presentation
Patients with HCL present with fatigue, weakness, and occa-
sionally left upper quadrant tenderness. The majority of
patients present with anemia, thrombocytopenia, and neu-
tropenia. Infections with typical and atypical organisms are
common and need to be treated aggressively. The diagnosis
of HCL should be considered in all patients with pancy-
topenia. HCL should also be differentiated from low-grade
lymphoma and other lymphoproliferative disorders.
Treatment
The treatment of choice for patients with HCL is the purine
analog 2-chlorodeoxyadenosine.
Multiple Myeloma
Multiple myeloma (MM) is the most common plasma cell
disorder. The disease is characterized by the increased pro-
liferation of a clone of plasma cells in the bone marrow
(PLATE 63; FIG. 10). These malignant cells produce exces-
sive amounts of a monoclonal immunoglobulin. The dis-
ease comprises approximately 10% of all hematologic
malignancies with peak incidence during the seventh decade
of life.
Presentation
Bone pain is the most common complaint in patients with
MM. Back pain is very common and some patients may
experience vertebral collapse or pathologic fractures.
Fig. 10. Plasma Cell Myeloma, Bone Marrow
Errisa Devi Fauzi
34
Laboratory Studies
The majority of patients with MM have anemia at the time
of diagnosis. The malignant clone secretes monoclonal pro-
tein, which can be detected on serum protein electrophore-
sis in more than 80% of patients. Immunoelectrophoresis
and immunofixation of the serum should be ordered in all
patients with MM. Combined, these methods reveal a
monoclonal problem in >95% of patients. The presence of
abnormal protein should also be checked in the urine of
patients suspected with the disease. The presence of mono-
clonal protein in the urine is referred to as Bence Jones pro-
tein. Renal involvement and hypercalcemia are common
and should be investigated in all patients with MM.
Radiological studies usually reveal the presence of lytic
lesions along several skeletal areas.
Diagnosis
The diagnosis of MM is made by a combination of studies
including bone marrow aspiration and biopsy showing
> 10% plasmablasts, monoclonal protein in the serum or
urine, and lytic bone lesions. Rouleaux of erythrocytes in
blood and marrow smears is due to an increase in immuno-
globulins which coat the cells.
Plasma cells have been observed in peripheral blood in
a few cases, particularly in the last stages of myeloma. When
plasmablasts predominate, the condition is called plasma
cell leukemia. A bluish background to the smears may be
observed due to an increase in protein material which
stains blue.
Treatment
The most common agents in the treatment of patients with
multiple myeloma are corticosteroids, alkylators and anthra-
cyclines.
Sezary Syndrome
Sezary syndrome, a cutaneous T-cell lymphoma, has a vary-
ing number of circulating atypical lymphoid cells in the
peripheral blood (PLATE 64). The nucleus of these atypical
lymphoid cells is often cerebriform (or convoluted) and has
a swirled chromatin pattern. Vacuoles may appear around
the periphery of the cytoplasm. Patients with this syndrome .
have pruritis, generalized exfoliative erythroderma, and
other features of mycosis fungo ides.
15 Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a malignant disor-
der that arises from genetic damage that leads to dysregulat-
ed growth of a single progenitor cell. The incidence of ALL
reaches a peak between 2 and 7 years of age representing
approximately 80% of acute leukemia in children less than
15 years of age. The current classification of ALL relies on
the immunologic features of the leukemic cell and is deter-
mined by the presence of surface immunoglobulin and
T-cell receptor expression. Table 7 depicts current immuno-
logical classifications of ALL and their frequency. The
immunologic classification has largely replaced the FAB
morphologic classification of ALL (TABLE 8).
very poor prognosis and should be considered for bone
marrow transplantation from a matched sibling if available.
Other laboratory findings that should be evaluated in all
patients with suspicion of acute leukemia include serum
uric acid, lactate dehydrogenous (LDH), calcium, APIT, PT,
and fibrinogen. Lumbar puncture should be performed on
all patients newly diagnosed with ALL.
Treatment
Treatment of ALL includes an induction phase to achieve
remission and consolidation followed by maintenance
chemotherapy for a total duration of two years.

Presentation of ALL
The onset of ALL is usually acute with symptoms of fatigue, Table 7. Immunologic Classification of Adult Acute
malaise, fever, and night sweats. Bone pain, lymphadenopa- Lymphoblastic Leukemia
thy, and hepatosplenomegaly are common and reflect the
LINEAGE CELL SURFACE MARKER FREQUENCY
presence of uncontrolled growth of abnormal cells in the
B cell
bone marrow and lymphoid organs. Involvement of the
central nervous system occurs in about 5% of children and Early pre-B-ALL C019+, TdT+, HLA-OR 12
15% of adults at the time of diagnosis of ALL. Testicular Common-ALL C019+, TdT+, COl 0+, HLA-OR 50
leukemia can occur as an isolated relapse in patients with
bone marrow remission. Pre-B-ALL Cytoplasmic Ig+, TdT+, C019+ 10
C010+

Laboratory Studies Mature B cell-ALL C019+, HLA-OR+,surface Ig+ 4

CO 10'"
Approximately 50% of patients with ALL present with ele-
vated white cell counts. Patients with leukocyte count above Tcell

50x109/1 have a poor prognosis and higher likelihood of EarlyT-ALL 8

involvement of the central nervous system. A subset of
patient may present with pancytopenia and no identifiable
blasts in the peripheral blood. Bone marrow aspiration and
biopsy invariably reveal the presence of blasts (PLATE 58,
59) suggestive of acute leukemia. The presence of >5% blast
cells is suggestive of the diagnosis, although in most cases
>50% lymphoblasts are present in the bone marrow. Lym-
phoblasts usually stain positively for TdT, but a proportion
of ALL may be TdT negative. lmmunophenotyping is very
important in ALL since it is used for classification and for
prognostic indications and sometimes to determine the type
of treatment to be administered. Differentiating B- from T-
cell ALL is very important at initial evaluation and prior to
treatment. Cytogenetic and molecular studies provide valu-
able information to determine the therapeutic intervention
and the prognostic features of new patients with ALL.
Approximately 20% of adult ALL patients have the translo-
cation (9,22) by cytogenetic analysis. These patients have
Mature T cell-ALL TdT+, C03+, C07+, C01+, C02+ 16
Table 8. Morphologic (FAB) Classification of Acute
Lymphoblastic Leukemia (Plate 59)
DESCRIPTION
Small blasts: High nuclear to cytoplasmic ratio, homogeneous
but condensed nuclear chromatin, no or indis-
tinct nucleoli, scanty cytoplasm (L1)
Larger blasts: Irregular membrane, homogeneous with fine
nuclear chromatin, one or more nucleoli,
moderately abundant blue cytoplasm (L2)
Large blasts: Round to oval nucleus, fine nuclear chromatin,
prominent nucleoli, intense blue cytoplasm,
often vacuolated (L3)

Errisa Devi Fauzi

35
 16 Infectious Disease In Hematology
Infectious Mononucleosis
Clinical Features
Infectious mononucleosis (IM) is a viral infection that usu-
ally affects young adults. In developing countries infections
occur in very young children. Clinical features include irreg-
ular fever, severe pharyngitis, adenopathy, and splen-
omegaly. Typical laboratory findings include an absolute
lymphocytosis with atypical lymphocytes (10% or more)
and rising titers against the Epstein-Barr virus (EBV). The
EBV infects epithelial cells of the oropharynx as well as the
small, resting B-Iymphocytes. These virus-containing B-
cells account for a small number of atypical cells in the
blood smear during the early phase of the disease.
Reactive Lymphocytes
The characteristic feature of IM is the pleomorphism of the
lymphocytic cells in the blood film. Besides normal lympho-
cytes and monocytes there are also large reactive (atypical)
lymphocytic cells (PLATES 65, 66) that are not found in nor-
mal blood. The nucleus may be oval, kidney-shaped, or irreg-
ularly shaped; there may be a barely visible nucleolus; the
chromatin pattern is not as dense or clumped as in a small
normal lymphocyte. The cytoplasm demonstrates varying
shades of basophilia, may have "holly leaf edges" when
indented by surrounding red cells, and also may have a few
distinct reddish granules. Some cells may show a somewhat
royal blue cytoplasm (similar to that seen in plasma cells).
These reactive cells show a great variety of cell types in con-
trast to the repetitious type of pathologic cells in acute
leukemia. Phenotypically these cells are classified as Tvlym-
phocytes. The hemoglobin levels are normal usually and
severe thrombocytopenia is very rare. The bone marrow
reveals no particular abnormalities. The serologic test for 1M
is called the heterophil antibody test because the sera of
patients with IM have agglutinins against sheep red cells.
Malaria
Malaria is an acute or chronic protozoan disease in humans
caused by Plasmodium (P) vivax, P [alciparum, P malariae,
and P ovale (PLATES 67, 68, Parts 1,2). Malarial sporozoites
are transmitted to humans by the bite of an infected female
Anopheles mosquito. Sporozoites invade the liver and rup-
ture of infected liver cells releases merozoites into the circu-
lation. Merozoites then invade the interior of the erythro-
cyte and are nourished by the cell's contents. Malaria also
can be transmitted by transfusion.
Errisa Devi Fauzi
36
The prominent clinical features are recurring paroxys-
mal chills and fever (as high as 105 to 106 F) associated
0 0
with headache, vomiting, and malaise. Paroxysms seem to
occur regularly every 32-72 hours depending on the type
of malaria.
The diagnosis of malaria can be made by careful exam-
ination of the erythrocytes on a Wright-Giemsa stained
blood smear or on thick drop preparations stained with
Giemsa. The chance of finding the parasites is greatest dur-
ing the febrile episodes. Erythrocytes of P [alciparum may
contain multiple rings and banana-shaped gametocytes
(PLATES 67, 68). The diagnosis of malaria may be delayed
because malaria has not been suspected. This delay maybe
dangerous for patients with P [alciparum because of the
early mortality rate. P vivax is characterized by enlarged red
cells containing Schuffner's dots and 12 to 16 merozoites in
the late schizont stage (PLATES 67,68). The red cells in P
malariae are not enlarged; there are no Schuffner's dots; the
parasite assumes an elongated or band form in the tropho-
zoite stages; the schizont stage has 6 to 10 merozoites in a
rosette form around a central mass of pigment (PLATES 67,
68). P ovale erythrocytes are oval and enlarged, contain dis-
tinct red dots, have 4 to 12 merozoites in the schizont stages,
have ragged margins, and pigment is scanty (PLATE 67).
Babesiosis
Babesia is an intraerythrocytic protozoan parasite that nor-
mally parasitizes rodents and cattle but is transmitted to
humans by the bite of the deer tick and also by blood trans-
fusion from asymptomatic carriers. Babesiosis is particular-
ly dangerous for splenectomized or irnmunocompromised
patients. The protozoan can be demonstrated by finding
small ring-shaped organisms (1.0to 3.5 mm in diameter) or
tetrad forms in erythrocytes on a Wright-Giemsa stained
blood smear. Babesia rings are similar to the rings of P [al-
ciparum. The babesia rings may also appear in aggregates
outside of red cells; malarial rings appear within the red cell
(PLATE 68-2). The diagnosis can be confirmed by an indi-
rect immunofluorescence antibody test on the serum.
Babesiosis has a gradual onset with malaise, fatigue,
anorexia, fever, sweats, muscle and joint pain. Hemolytic
anemia may be seen in some patients with babesia.
Ehrlichiosis
Ehrlichiae, small intracellular bacteria, are transmitted by
ticks to humans and they grow as a cluster (morulae) in a
cytoplasmic vacuole in neutrophils, monocytes, and
macrophages. E. phagocytophila is found in the cytoplasm of
 The Morphology of Human Blood Cells

neutrophils (PLATE 69) while E. chaffeensis is found in
monocytes and macrophages. Thrombocytopenia and
leukopenia with left shift in neutrophils and mild to moder-
ate increase in hepatic transaminases are noted in most
patients. Patients infected with Ehrlichiae may present with
flu-like symptoms, headache, confusion, anorexia, nausea,
vomiting, diarrhea, and abdominal pain. Occasionally
patients may present with adult respiratory syndrome and
acute renal failure. Ehrlichiae can be detected by careful
examination of peripheral blood smears for presence of
intracellular aggregates (morulae) of small bacteria in neu-
trophils or monocytes. The diagnosis can be confirmed by
rising antibody immunofluorescence titer or by polymerase
chain reaction. Since there is the potential for severe or fatal
outcome, early diagnosis and therapy are vital.
characteristic of this organsim (PLATE 70), which may be
observed in marrow macrophages. Culture of the marrow
provides a sensitive test for disseminated leishmaniasis in
AIDS patients.
Parvovirus B 19
Parvovirus B19, a DNA virus, may cause depression of ery-
thropoiesis and lead to erythroid aplasia. Progenitor cells
and precursor cells are infected and their growth inhibited.
This results in extremely large proerythroblasts which are
observed in a bone marrow smear (PLATE 71). Parvovirus
infection may depress marrow activity in sickle cell anemia
and cause an aplastic crisis. The hematopoietic precursor
cells become infected with parvovirus in HIV infection and
severe neutropenia and sometimes pancytopenia occurs.

Histoplasmosis
Histoplasma capsulatum, an intracellular fungus, may be
observed in neutrophils and monocytes often at the feather
ends of a peripheral blood smear (stained with Wright-
Giemsa) in immunocompromised patients with HIV infec-
tion (FIG.l1). Histoplasma organisms are quite variable in
size (2-5 urn) and shape. They do not have a true capsule.
Histoplasma capsulatum can be seen in macrophages in a
bone marrow smear in patients with AIDS (PLATE 70) who
are exposed to the organism.

Leishmaniasis
Leishman-Donovan bodies are oval inclusions with a nucle-
us and a rod of extra nuclear DNA (called a kinetoplast).
The leishman bodies are about 2-3 urn across and are Fig. 11. Histoplasma capsulatum in peripheral blood cells

References

1. Beutler E, Lichtman MA, Coller BS, Kipps T), Seligsohn See Figure 8.1, page 147, in Volume 1. The cells of the
U: Williams Hematology, 5th ed, 2001, McGraw-Hill, blood, lymphoid organs, and their precursors in the
Inc, New York, NY. bone marrow.

2. Damier IS, Walker DH: Tick-borne ehrlichiosis. Lancet 5. Markell ER, John DT, Krotoski WA: Markell & Voge's
Infectious Disease, April 2001, 21-28. Medical Parasitology, 8th ed, 1999, WB Saunders,
Philadelphia, PA;Malaria 90-122; Babesia 172-175.
3. land! JH: Blood: Textbook of Hematology. 2nd ed, 1998,
Little, Brown & Co, Boston, MA.
4. Lee GR, Foerster l, Lukens J, et al.: Wintrobe's Clinical
Hematology, 10th ed, 1999, Vols 1 & 2, Williams and
Wilkins, Baltimore, MD.

Errisa Devi Fauzi

37
 Color Plates

Cell Drawings by Dorothy Sturm

Photomicrographs by Ann Bell

Smears were given for photomicrographs by the following individuals and institutions:
Dr. Luther Burkett
Dr. Marion Dugdale
Mrs. Janie Gardner, MS, H(ASCP)
Ms. Rachel Lehman, MT(ASCP)
Dr. Alvin Mauer
Mrs. Ioye Thomas, MT(ASCP)
Dr. Frank White
Centers for Disease Control, Atlanta, GA
LeBonheur Children's Medical Center, Memphis, TN
St. Jude Children's Research Hospital, Memphis, TN

Note: The photomicrographs are from the University of Tennessee Division of

Hematology teaching file, which was started more than twenty-five years ago. Stains and
staining techniques have changed during this period of time and, hence, cell colors may
vary and drawing paper used by the artist has darkened.

Errisa Devi Fauzi

38
 Plate 1. Myelocytic (Granulocytic) System

1A. Myeloblast

1B. Promyelocyte
(Progranulocyte)

1C. Basophilic myelocyte 1G. Neutrophilic 1K. Eosinophilic

myelocyte myelocyte

1D. Basophilic metamyelocyte 1H. Neutrophilic 1L. Eosinophilic

metamyelocyte metamyelocyte

1E. Basophilic band 11. Neutrophilic band 1M. Eosinophilic band

• .~-
.

1F. Basophilic segmented 1J. Neutrophilic segmented 1N. Eosinophilic

segmented

Errisa Devi Fauzi

39
 Plate 2. Myelocytic Cells-Normal Bone Marrow

•
10

2A. 2B. 2(,

2D. 2E.

Plate 2. 1. Myeloblast, 2. Promyelocyte, 3. N. Myelocyte, 4. N. Metamyelocyte,S. N. Band, 6. N. segmented, 7. Eosinophil, 8. Monocyte,

9 Polychromatophilic erythroblast, 10. Orthochromatic erythroblast, 11. Neutrophil-questionable stage

O.~4
a
2F. Basophil 2G. Eosinophilic myelocyte

2H. Myeloblast 21. Promyelocyte

Errisa Devi Fauzi

40
 Plate 3. Myelocytic Cells-Normal Bone Marrow

3A. 3(.

3B.

3D. 3E.

3F. 3G.

3H. 31.

Plate3. 1. Myeloblast, 2. Promyelocyte, 3. N. Myelocyte, 4. N. Metamyelocyte,S. N. band, 6. N. segmented, 7. Eosinophilic metamyelocyte,

8. Basophil, 9. Monocyte, 10. Polychromatophilic erythroblast, 11. Orthochromatic erythroblast, 12. Lymphocyte, 13. Plasma cell, 14. Smudge
Errisa Devi Fauzi
41
 Plate 4. Cell Types Found on Peripheral Blood Smears from Normal Individuals

4A. Erythrocytes 4F Monocyte with gray blue cytoplasm, coarse linear chromatin,
4B. Large lymphocyte with purplish-red (azurophil) granules blunt pseudopods
and deeply indented by adjacent erythrocytes 4G. Platelets (thrombocytes)
4(, Neutrophilic segmented 4H. Lymphocyte
40. Eosinophilic segmented 41. Neutrophilic band
4E. Neutrophilic segmented 4J. Basophil

The arrangement is arbitrary and the number of leukocytes in relation to erythrocytes and thrombocytes is greater than would occur in an actual
microscopic field.

Errisa Devi Fauzi

42
 Plate 5. Lymphocytes

SA. 5maillymphocyte 58, Lymphocyte of 5(, Lymphocyte with

intermediate size indented nucleus

5D. Lymphocyte of 5E. Lymphocyte with pointed SF. Spindle-shaped

intermediate size cytoplasmic projections (frayed lymphocyte with
cytoplasm) indented nucleus

SG. Large lymphocyte with SH. Large lymphocyte SI. Large lymphocyte with
indented nucleus and pointed purplish-red (azurophilic )
cytoplasmic projections granules

:-,

SJ. Large lymphocyte with 5K. Large lymphocyte with purplish- SL. Large lymphocyte
irregular cytoplasmic contours red (azurophilic) granules and with with purplish-red
indentations caused by pressure of (azurophilic) granules
erythrocytes

Errisa Devi Fauzi

43
 Plate 6. Lymphocytes from Normal Peripheral Blood Smears

Small lymphocyte; large lymphocyte 68. Small lymphocyte; large lymphocyte

with holly-leaf edges with azurophilic granules

6C. Lymphocyte, large 6D. Lymphocyte with 6E. Large lymphocyte

azurophilic granules

6F. Lymphocyte, intermediate size; small 6G. Large lymphocyte with indented
lymphocyte nucleus, azurophilic granules;
lymphocyte

6H. Lymphocyte with azurophilic 61. Large lymphocyte with azurophilic

granules; N. segmented granules; N. segmented

(Azurophilic granules in lymphocytes are countable)

Errisa Devi Fauzi

44
 Plate 7. Monocytes

7A Monocyte with "ground-glass" 7B. Monocyte with blue granular 7C. Monocyte with
appearance. evenly distributed fine cytoplasm. lobulation of nucleus prominent granules and
granules. occasional azuroph,lic with linear chromatin deeply indented nucleus
granules. and vacuoles In cytoplasm

70. Monocyte without nuclear 7E. Monocyte with gray-blue 7F. Monocyte with gray-blue
indentations cytoplasm. band type of nucleus. cytoplasm. blunt pseudopods.
linear chromatin. blunt and multilobulated nucleus
pseudopods. and fine granules

7G. Monocyte with segmented- 7H. Monocyte with multiple blunt 71.Monocyte with vacuoles.
type nucleus nongranular pseudopods. nuclear nongranular ectoplasm, and
indentations. and folds granular endoplasm

Errisa Devi Fauzi

45
 Plate 8. Monocytes from Normal Blood Smears

SA. Monocyte; SB. Monocytes sc Monocyte;

N. segmented N. segmented

SO. Monocytes SE. Monocyte with SF. Monocytes

phagocytized RBC

SG. Monocyte; lymphocyte SH. N. segmented; monocyte SI. Monocyte (top); lymphocyte with
azure granules

Errisa Devi Fauzi

46
 Plate 9. Comparative Morphology: Early Neutrophils, Monocytes, Lymphocytes

9A. N. myelocyte with mixture 98. Monocyte with nuclear fold 9(, Large lymphocyte with
of neutrophilic and dark scalloped shape and absence
reddish-purple granules of folds in nucleus

9D. N. metamyelocyte with 9E. Monocyte with gray-blue 9F. Large lymphocyte with
light-pink cytoplasmic color cytoplasm, prominent granules, nongranular cytoplasm
and neutrophilic granules brain-like convolutions in nucleus
and linear chromatin strands

9G. N. myelocyte 9H. Typical monocyte with lobu- 91. Large lymphocyte with purplish-
lated nucleus, gray-blue granular red (azurophilic) granules and lumpy
cytoplasm, and blunt pseudopods nuclear structure

Errisa Devi Fauzi

47
 Plate 10. Lymphocytic, Monocytic, Plasmacytic Systems

10A. Lymphoblast 10B. Monoblast 10C. Plasmablast

100. Prolymphocyte 10E. Promonocyte 10F. Proplasmacyte

10G. Lymphocyte with 10H. Monocyte 101. Plasmacyte

clumped chromatin

Errisa Devi Fauzi

48
 Plate 11. Erythroblastic System

c
o F

11 A. Proerythroblast 11 E. Polychromatophilic erythrocyte

11 B. Basophilic erythroblast 11 F. Eryth rocyte
11C Polychromatophilic erythroblast
11 D. Orthochromatic erythroblast

Erythroblasts in Normal Bone Marrow

11 G. Proerythroblasts (2), N. segmented, 11H. Proerythroblasts (2), polychromatophilic and

N. myelocyte, N. metamyelocyte, orthochromatic erythroblasts, N. band, N. segmented,
orthochromatic erythroblast and smudge

111. Basophilic erythroblasts 11J. Polychromatophilic (4) and

basophilic erythroblasts

11 K. Lymphocyte, orthochromatic 11 L. Basophilic (center), polychro- 11M. Orthochromatic erythroblast,

erythroblast, basophilic erythroblast matophilic, and orthochromatic lymphocyte (right)
erythroblasts; smudge

Errisa Devi Fauzi

49
 Plate 12. Comparative Morphology: Plasmacytes, Lymphocytes, Nucleated Red Cells

D F

12A. Plasmacyte with intense-blue cytoplasm, eccentric nucleus, 12D. Lymphocyte with foamy cytoplasm and frayed (hair-like)
clear zone, vacuoles, irregular shape (marrow) margins
12B. Plasmacyte with foamy and fibrillar reddish-blue cytoplasm 12E. Basophilic erythroblast with reddish-blue cytoplasm
(marrow) (marrow)
12(, Lymphocyte with slightly indented nucleus, unevenly 12F. Polychromatophilic erythroblast with reddish cytoplasm
stained bluish cytoplasm (marrow)

Plasma Cell, Lymphocytes, Immature Nucleated Red Cells

from Bone Marrow and Blood Smears

12G. Plasma cell (marrow) 12H. Lymphocyte; large lymphocyte 121. Polychromatophilic erythroblasts
(blood) with reddish cytoplasm in meqaloblastic
anemia (marrow); nuclear fragment in
one cell

Errisa Devi Fauzi

50
 Plate 13. Plasma Cell Variants on Bone Marrow Smears

13A. Plasma cell with globular bodies

(Mott cell)
138. Plasma cell with globular bodies (Mott cell)

13C. Plasma cell showing reticular cytoplasmic 13D. Plasma cell with globular bodies in nucleus,
structure reticular cytoplasmic structure, shaggy margins,
and red secretions

13E. Plasma cell with red cytoplasmic 13F. Plasma cell with "flame"
border red cytoplasm and two nuclei

13G. Plasma cell with globular bodies 13H. Plasma cells with globular bodies
(Mott cell) (Mott cells)

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51
 Plate 14. Megakaryocytic System

A B

E F

14A. Magakaryoblast with single oval nucleus, nucleoli, 14D. Megakaryocyte with lobulated nucleus and platelets
and bluish foamy marginal cytoplasmic blebs 14E. Megakaryocytic nucleus with attached platelets
14B. Promegakaryocyte with two nuclei, granular blue 14F. Platelets
cytoplasm, and marginal bubbly cytoplasmic blebs
14(, Megakaryocyte with lobulated nucleus, granular
cytoplasm, and without platelets
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52
 Plate 15. Megakaryocytes on Normal Bone Marrow Smears

1SA. Megakaryoblast 1S8. Megakaryoblast 1SC. Promegakaryocyte

1SD. Promegakaryocyte 1SE. Megakaryocyte with 1SF. Granular megakaryocytes without platelets
lobulated nucleus, granular
cytoplasm surrounded by
vacuoles, and no platelets

1SG. Granular megakaryocytes without 1SH. Megakaryocyte with lobulated 1SI. Megakaryocyte with lobulated
platelets nucleus and platelets nucleus and platelets

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53
 Plate 16. Macrophages on Bone Marrow Smears

..

16A. Macrophage with reticular cytoplasm, 16B. Macrophage with phagocytized

vacuoles, and phagocytized particles erythrocytes and dark-staining particles

...

16C. Macrophage with phagocytized 16D. Macrophage with phagocytized

hemosiderin in cytoplasm particles and vacuoles

16E. Macrophage with vacuoles and phagocytized malarial pigment

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54
 Plate 17. Macrophages on Bone Marrow Smears

17 A. Macrophage with engulfed neutrophil; 178. Macrophage with engulfed red cells
macrophage with hemosiderin

17(, Macrophage with pigment 170. Macrophage with blue pigment

17E. Macrophages with cystine crystals

17F. Plasmacytes around macrophage 17G. Late erythroblasts around macrophage

Errisa Devi Fauzi

55
 Plate 18. Early Eosinophils and Mast Cells on Bone Marrow Smears

18A. Early eosinophil with nucleoli and tapering 18B. Mast cell (formerly called tissue
cytoplasmic extensions (formerly called tissue eosinophil) basophil)

18C Eosinophilic myelocyte with 18D. Eosinophilic myelocyte

cytoplasmic extensions

18E. Mast cell 18F. Mast cell

18G. Mast cell 18H. Mast cell

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56
 Plate 19. Fat Cells on Bone Marrow Smears

19A. Fat cell with small round nucleus, linear chromatin,
globular body in nucleus, ample cytoplasm with lipoid globules,
wrinkled membrane, reticular stroma, fibrillar marginal
structures, and surrounded by erythrocytes.
[
19B. Fat cell showing cytoplasmic lipoid bodies separated by
reticular structures. Mature erythrocytes surround fat cell.

19C. Fat cell 19D. Fat cell

19E. Fat cell 19F. Fat cell

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57
 Plate 20. Osteoblasts and Osteoclast on Bone Marrow Smears

20A. Osteoblast with prominent light zone in
cytoplasm located away from nucleus
20B. Osteoblast with oval eccentric nucleus,
distinct linear chromatin and nucleolus, blue
bubbly cytoplasm with prominent light zone
adjacent to nucleus, and fibrillar marginal
structures

20(, Osteoclast: Large multinucleated cell with

uneven number of separated oval nuclei with nucleoli,
blue granules, and frayed cytoplasmic margins

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58
 Plate 21. Osteoblasts and Osteoclasts on Bone Marrow Smears

21 A. Osteoblasts 21 B. Osteoblasts 21 C. Osteoblasts

21 D. Aggregate of osteoblasts 21 E. Osteoclast

21 F. Osteoclast 21 G. Osteoclasts 21 H. Osteoclast

Errisa Devi Fauzi

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 Plate 22. Endothelial Cells

22A. Endothelial cells 228. Endothelial cell

22(, Endothelial cells 220. Endothelial cells

22E. Endothelial cell 22F. Endothelial cells

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 Plate 23. Shapes of Red Cells

Normal Crenated Burr (echinocyte)

Target Spherocyte
Oat (sickle cell)

Sickled SC crystal CC crystal

Elliptocyte (ovalocyte) Stomatocyte Folded cell

Marginal achromia (blister) Helmet Pinched

Teardrop, pear, pointed Filamented Triangular

Poikilospherocyte Aca nthocyte Small fragments

(small, dark, irregular) (thorn, spur, spiculated)

"Schistocyte" refers to hel met,

triangular, and small fragments.

Errisa Devi Fauzi

Membranous ghost Crescent (Semilunar) 61
 Plate 24. Erythrocyte Morphology on Blood Smears in Nutritional Anemias

24A. Iron deficiency anemia 24B. Normal erythrocytes 24C. Megaloblastic anemia

24D. Iron deficiency anemia: (red cells: 24E. Normal erythrocytes 24F. Megaloblastic anemia: (red cells:
microcytic and smaller than nucleus of large and oval; two teardrop cells);
a small lymphocyte; hypochromic) hyperlobulated N. segmented

24G. Iron deficiency anemia after 24H. Iron deficiency anemia after 241. Megaloblastic anemia (red cells:
transfusion (two populations of iron therapy (two populations of oval and larger than nucleus of small
red cells) red cells) lymphocyte; two teardrop cells)

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62
 Plate 25, Part 1. Erythrocyte Morphology on Blood Smears
in Microangiopathic Hemolytic Anemias

25A. Thrombotic thrombo- 25B. Chronic nephritis 25(, Sickle cell anemia with
cytopenic purpura (TIP) with hypertension schistocytes in some cases of
pulmonary embolism

e ·0 "iii07 - '1

,~~~
9 .@::.4 <i.
~f\,
q,C~ ~C?

25D. TIP 25E. Chronic nephritis with hypertension

" ., ~ ~
".,.._

25F. Sickle cell anemia with schistocytes

in some cases of pulmonary embolism

25G. TIP 25H. Chronic nephritis with hypertension 251. Sickle cell anemia with schistocytes
in some cases of pulmonary embolism

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63
 Plate 25, Part 2. Erythrocyte Morphology on Blood Smears in
Microangiopathic Hemolytic Anemia Due to Heart Valve Dysfunction

Patient 1 Patient 1 Patient 2

• V"V

••
.. ~'

. 0> .'.,

Patient 3
• ~:

_ .....
'

Patient 3

1('111
~

Patient 4 Patient S Patients

Morphology in five patients

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64
 Plate 26. Anemias with Abnormal Erythrocyte Morphology on Blood Smears

26A. Spur cell anemia 26B. Erythrocytes in paroxysmal 26C. Microangiopathic

nocturnal hemoglobinuria hemolytic anemia following
liver transplant

26D. Erythrocytes in 26E. Erythrocytes in 26F. Echinocytes (burr cells) in

Hemoglobin Zurich after G-6-PD deficiency pyruvate kinase deficiency
sulfonamides

26G. Hemolytic anemia (bite 26H. Hemolytic anemia 261. Spherocytic anemia due
cells) after dapsone (spherocytes) due to bite of to Clostridium perfringens
Loxosceles rec/usa

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65
 Plate 27. Erythrocyte Morphology on Blood Smears in Sickle Cell Anemia,
Sickle Cell-Hemoglobin C, Hemoglobin CC

27 A Sickle cell anemia (Hb SS) 278. Sickle ceil-hemoglobin C 27C. Hemoglobin CC (Hb CC)
(Hb SC)

~
27D. Hemoglobin SS 27E. Hemoglobin SC 27F. Hemoglobin CC

27G. Hemoglobin SS 27H. Hemoglobin SC 271. Hemoglobin CC after

splenectomy

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66
 Plate 28. Moist Unstained Preparations of Blood from Patients with
Sickle Cell Trait and Sickle Cell Anemia

28A. Moist unstained preparation of blood from a patient with sickle cell trait showing
reversible elongated multipointed red cells.

28B. 28(,

28B and 28(, Moist unstained preparations of drop of blood from patient with sickle cell anemia mixed with drop
of sodium meta bisulfite solution showing irreversible elongated sickle cells and a few multi pointed erythrocytes

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67
 Plate 29. Erythrocyte Morphology on Blood Smears in Hereditary Spherocytosis,
Elliptocytosis, and Thalassemia Major

29A. Hereditary spherocytosis 29B. Hereditary elliptocytosis 29C. Thalassemia major

(Cooley's anemia)

.......
29D. Hereditary spherocytOSIS 29E. Hereditary elliptocytosis 29F. Thalassemia major (Cooley's anemia):
late erythroblast, Howell-Jolly body

,..•...
l1li.
,. ~

"'_ A
291. Thalassemia major (Cooley's anemia):
orthochromatic erythroblasts (4),
Howell-Jolly body

29G. Hereditary spherocytosis 29H. Hereditary elliptocytosis with

hemolytic anemia

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68
 Plate 30. Erythrocyte Morphology on Blood Smears from Patients
with Thalassemia Minor

30A. ~+-thalassemia minor 30B. ~+-thalassemia minor-Fetal Hb 4.2% 30(, ~+-thalassemia minor: target cell
with stippling (arrow)

30D. ~+-thalassemia minor 30E. ~+-thalassemia minor-Fetal Hb 4.2% 30F. ~+-thalassemia minor

30G. W-thalassemia minor 30H. Hemoglobin E-~O-thalassemia 301. Alpha-thalassemia 1

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69
 Plate 31. Erythrocyte Morphology on Blood Smears from Patients with Burns,
Hereditary Pyropoikilocytosis, and Myelofibrosis

31 A. Erythrocytes in severely 31 B. Hereditary pyropoikilocytosis 31 C. Myelofibrosis

burned patient

310. Severely burned patient 31 E. Hereditary pyropoi kilocytosis before 31 F. Myelofibrosis

incubation of blood

.......
31 G. Severely burned patient 31 H. Hereditary pyropoikilocytosis after 311. Myelofibrosis
60 minutes at 45° C Incubation

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70
 Plate 32. Stippled Erythrocytes, Polychromatophilic Erythrocytes, and Reticulocytes
32A Selected stippled
erythrocytes in a Wright-stained
blood smear from a patient with
lead poisoning
32D. Stippled cells in Wright-
stained smear from lead poisoning
32G. Stippled red blood
cell; lymphocyte
32B. Selected polychromatophilic
erythrocytes in a blood smear,
Wright stain
32E. Polychromatophilic erythrocytes
(arrows) In a Wright-stained smear of
thrombotic thrombocytopenic purpura
32H. Polychromatophilic
erythrocytes (arrows) in a Wright-
stained smear of hemolytic anemia
Errisa Devi Fauzi
32(, Selected reticulocytes
containing granulofllamentous
structures in a smear from blood
mixed with new methylene blue
stain. Polychromatophilic red cells
and stippled cells stain as reticulocytes
in this preparation.
32F. Reticulocytes increased In a new
methylene blue preparation of blood
from sickle ceil-thalassemia
(Sturm)
321. Reticulocytes increased in
hemolytic anemia
71
 Plate 33. Erythrocytes with Inclusions

33A. Orthochromatic 33B. Stippled orthochromatic 33(, Erythrocyte 33D. Thrombocyte on red
erythroblast with partial erythroblast with Howell-Jolly containing malarial ring cell (Note clear area aroun<
extrusion of portion of body and Cabot rings platelet indicating it is on
nucleus top of cell)

33E. Howell-Jolly bodies in erythrocytes 33F Cabot rings in erythrocytes; stippling and
Howell-Jolly body in one red cell with Cabot ring

33G. Cabot ring 33H. Cabot ring, stippling, Howell- 331. Malarial ring (left) versus platelet
Jolly body on red cell (right)

.a..
..
33J. Cabot ring in orthochromatic 33K. Howell-Jolly bodies 33L. Plasmodium falciparum rings in
erythroblast red cells

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72
 Plate 34. Erythrocytes with Siderotic Granules

/
34A. Wright stain showing one orthochromatic
erythroblast and multiple erythrocytes with Pappenheimer
bodies (or siderotic granules in iron stain). The granules
vary in number, size, shape, and color, and are unevenly
distributed.
34B. Prussian blue stain for iron showing one
orthochromatic erythroblast with siderotic granules
(ringed sideroblast) and erythrocytes containing siderotic
granules. The nucleus of the erythroblast stains red with
safran in. (Howell-Jolly bodies, Heinz bodies, and stippling
do not give a blue color with iron stain).

Erythrocyte Morphology in Blood and Marrow Smears from Sideroblastic Anemia

,) '<t~
ft •

..
34(, Erythrocytes with Pappenheimer 34D. Erythroblasts with siderotic granules 34E. Ringed sideroblasts in Prussian
bodies in Wright stain (blood) (top) and ringed side rob lasts in Prussian blue iron stain (marrow)
blue iron stain (marrow)

34F. Erythrocytes with Pappenheimer 34G. Erythroblasts with siderotic granules 34H. Ringed sideroblasts in Prussian
bodies in Wright stain (blood) in Prussian blue iron stain (marrow) blue iron stain (marrow)

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73
 Plate 35. Erythrocytes with Heinz Bodies

Erythrocytes in a moist preparation after four hour incubation with acetyl-phenylhydrazine followed by staining with crystal violet

35A. Normal blood with one to four Heinz bodies in most 35B. Erythrocytes from a patient with G-6-PD deficiency.
erythrocytes Majority of red cells have five or more Heinz bodies.

, •
~# ~ .. ~
'" .. • •
• • lit
,..."
.,
A

-~i~"4" ..... ...,.

~~
'"
•
• .... .'
-
•
35C. Heinz body preparation of normal 35D. Heinz body preparation of erythrocytes in
erythrocytes Hemoglobin Zurich

35E. Heinz body preparation of normal erythrocytes 35F. Heinz body preparation of erythrocytes
in G-6-PD deficiency

Errisa Devi Fauzi

74
 Plate 36. Erythrocytic Sequence in Bone Marrow: Megaloblastic Anemia,
Normal Marrow, and Iron Deficiency Anemia

Left column: Megaloblastic Anemia Middle column: Normal Right column: Iron
in B12 and Folic acid deficiencies Erythroblast Sequence Deficiency Anemia (IDA)

Promegaloblast Proerythroblast Proerythrobast (small)

Basophilic megaloblast Basophilic erythroblast Basophilic erythroblast (small)

Polychromatophilic Polychromatophilic Polychromatophilic

rneqaloblast erythroblast erythroblast

Orthochromatic megaloblast Orthochromatic erythroblast Orthochromatic erythroblast

Polychromatophilic macrocyte Polychromatophilic erythrocyte Polychromatophilic

erythrocyte

Macrocyte Norma I eryth rocyte Hypochromic microcyte

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75
 Plate 37. Comparison of Erythrocyte Morphology in Blood and Bone Marrow:
Iron Deficiency Anemia and Megaloblastic Anemia

o
6P o.
37 A. Iron deficiency anemia with microcytic 37B. Iron deficiency anemia with three late
hypochromic erythrocytes (blood) erythroblasts (iron-deficient) having minimal
bluish cytoplasm (marrow)

37(, D. Iron deficiency anemia with numerous late erythroblasts (iron-deficient) having minimal bluish cytoplasm (marrow)

37E. Megaloblastic anemia with large oval and 37F Megaloblastic anemia with large oval and
round macrocytes and pear-shaped erythrocytes round macrocytes and one orthochromatic
(blood) megaloblast (blood)

37G. Megaloblastic anemia with three basophilic 37H. Megaloblastic anemia with promegaloblasts and
megaloblasts (marrow) basophilic megaloblasts (marrow)
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76
 Plate 38. Pathological Erythroblasts in Bone Marrow of Megaloblastic Anemia

38A. Polychromatophilic 38B. Polychromatophilic 38(, Basophilic megaloblast

megaloblast with two nuclei megaloblast with fragmentation with asynchronism between
of nucleus (karyorrhexis) nuclear structure and
cytoplasmic color

380. Basophilic megaloblast 38E. Basophilic megaloblast; 38F Orthochromatic

with nuclear fragments; asynchronism asynchronism megaloblast with degenerated
nucleus and stippling

38G. Polychromatophilic erythrocyte (top), 38H. Promegaloblast, basophilic and orthochromatic

polychromatophilic and basophilic megaloblasts megaloblasts, plasma cell (lower left)

•
•

381. Basophilic megaloblast showing asynchronism 38J. Giant orthochromatic megaloblast with
Howell-Jolly bodies
Errisa Devi Fauzi
77
 Plate 39, Part 1. Pathological Erythroblasts and Erythrocytes in Bone Marrow
of Megaloblastic Anemia

Selected nucleated and nonnucleated red cells in bone marrow smears of patients with untreated megaloblastic anemia.
There is asynchronism between nucleus and cytoplasm with the nucleus less mature than the cytoplasm. Identification of
nucleated cells is based primarily on chromatin configuration and not on cytoplasmic coloration. Anisocytosis,
poikilocytosis, and anisochromia may be observed in nonnucleated erythrocytes.

39A. Orthochromatic megaloblast showing karyorrhexis 390. Polychromatophilic megaloblast with asynchronism
and asynchronism 39P. Microcytic poikilocyte
39B. Orthochromatic megaloblast with Howell-Jolly bodies 390. Promegaloblast
39(, Teardrop erythrocyte 39R. Macrocyte with Howell-Jolly bodies
39D. Basophilic megaloblast with asynchronism 39S. Mitotic figure
39E. Stippled oval macrocyte 39T Orthochromatic megaloblast with one
39F Cabot ring in oval macrocyte Howell-Jolly body
39G. Polychromatophilic macrocyte 39U. Oval macrocyte
39H. Lobulated megaloblastic neutrophil 39V Basophilic megaloblast
391. Orthochromatic megaloblast showing karyorrhexis 39W Basophilic erythroblast
and Howell-Jolly bodies
39J. Promegaloblast with multiple nucleoli
39K. Hypersegmented neutrophil
39L. Pear-shaped erythrocyte
39M. Polychromatophilic megaloblast
39N. Orthochromatic meqaloblast with beginning
nuclear extrusion

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78
Plate 39, Part 2. Pathological Erythroblasts and Erythrocytes in Bone Marrow
of Megaloblastic Anemia

Errisa Devi Fauzi

79
 Plate 40. Pathological leukocytes

40A. N. segmented with 40B. N. segmented with 40C. N. metamyelocyte with 40D. Degenerated round
tOXICgranules vacuoles and toxic granules toxic granules neutrophil nucleus (old EDTA
blood); toxic granules

40E. Degenerated neutrophil 40F. Hyperlobulated neutrophil 40G. N. segmented with 40H. Monocyte with
nucleus (old EDTA blood) engulfed dark nuclear mass phagocytized nuclear mass
(LE cell)*

401. N. myelocyte, 40J. N. segmented cells with 40K. Degenerated neutrophils (old EDTA blood)
metamyelocyte, ?segmented toxic granules
with toxic granules (marrow)

40L. Vacuoles in neutrophils 40M. Dahle bodies in 40N. Monocyte with 400. Dahle body, toxic
neutrophil phagocytized red cell granules in N. segmented

*40G. Neutrophil which contains a phagocytized reddish-purple nuclear mass from another leukocyte following a special technique which is no
longer used as an aid in diagnosis. This cell was designated as a so-called "LE cell" since it was observed in patients with lupus erythematosus.

Errisa Devi Fauzi

80
 Plate 41. Cell Types on Blood Smears of Patients with Pelqer-Huet Anomaly

This hereditary anomaly is characterized by hypolobulation of the nuclei of neutrophils. The chromatin structure of the
granulocytes with round or indented nucleus is that of mature cells. The size, chromatin structure, and phagocytic function
of these cells are normal.

41 A Slightly indented nucleus 41 B_ Nucleus with closely 41 C. Round nucleus 41 D_ "Peanut" -shaped nucleus
("peanut" shaped) approximated round lobes
(pince-nez or spectaclelike)

41 E_ Two "peanut"-shaped nuclei 41 F. Pince-nez nucleus: slightly 41 G_ "Peanut" -shaped nucleus; slightly
indented nucleus indented nucleus (bottom)

41 H_ Pseudo-Pelger cell 411. Pseudo-Pelger cell 41J Pelger-Huet cell with

in myelodysplasia in myelodysplasia pince-nez nucleus

Note: Pseudo-Pelger cells are observed in myelodysplasia and other myeloid dyscrasias.

Errisa Devi Fauzi

81
 Plate 42. Cell Types from Patients with Chediak-Hiqashi Anomaly

Leukocytes in smears of peripheral blood or of bone marrow from patients with Chediak-Hiqashi anomaly showing
abnormal and giant Iysosomes in the cytoplasm.

42A Lymphocyte (blood)

42(, Promyelocyte (marrow)

42B. Mitotic figure of promyelocyte (marrow)

42D. Eosinophil-large granules 42E. Basophil-large granules (blood) 42F. Neutrophil segmented (blood)
(blood)

42G. Lymphocytes, N. segmented (blood) 42H. Lymphocyte (blood) 421. Neutrophil (blood) 42J Basophil (blood)

42K. Mitotic figure (marrow) 42L. Eosinophilic myelocyte (marrow)

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82
 Plate 43. Cell Types on a Blood Smear from a Patient with May-Hegglin Anomaly

Each leukocyte has one (or two) large bluish, elongated, irregularly shaped Dohle-like body

'E

43A. Monocyte with Dahle-like bodies

..
43D. Neutrophils with Dahle-like bodies
43B. Eosinophil with Dohle-like body 43E. Large abnormal platelets
43(, Basophil with Dahle-like body
The number of cells in drawing is greater than occurs in a single oil-immersion field. Note shape variation in erythrocytes of
this patient. The platelets are large and abnormal.

43F. Neutrophil with Dohle-like 43G. Neutrophil with Dohle-like 43H. Neutrophil with Dohle-Iike
body (arrow); large platelets body (arrows); large platelets body (arrows); large platelets

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83
 Plate 44. Cell Types on Blood and Marrow Smears from a Patient with Alder-Reilly Anomaly

44A. Neutrophilic myelocyte (marrow) 44B. Neutrophilic metamyelocyte (marrow) 44(, Neutrophilic band (marrow)

44D. Neutrophilic segmented (blood) 44E. Basophil (blood) 44F. Eosinophil (blood)

44G. Two neutrophils (blood) 44H. Two neutrophils (blood)

441. Lymphocyte, N. segmented, and

basophil (blood)

. The cytoplasm of neutrophils and basophils in blood or bone marrow of patients with Alder-Reilly anomaly contain
multiple deep blue or lilac, round granules in blood and marrow smears. Eosinophil granules are large.

Errisa Devi Fauzi

84
 Plate 45. Selected Cells from Blood and Marrow Smears of Patients with Acute and
Chronic Myelogenous (Myelocytic) Leukemia
45A. Myeloblast with prominent
nucleoli, well-defined chromatin
structure, blue cytoplasm with
no granules
45D. Atypical promyelocyte
with a few dark granules
..
"'..
',.
45G. Atypical early neutrophil
(simulating a monocyte) with
indented nucleus, intermediate
nuclear chromatin structure,
nonspecific granules and
pale cytoplasm
45C. Myeloblast
with Auer rod
458. Megakaryoblast with dark
coarse nuclear chromatin
structure and blunt vacuolated
blebs (marrow)
45E. Atypical promyelocyte 45F. Atypical promyelocyte
with prominent purple with fine and coarse granules
granules (marrow)
45H. Progranulocyte variant 451. Macrocytic polyploid neutrophil
with abundant granular
cytoplasm and irregular
margin (marrow) (formerly
called Ferrata cell)
Errisa Devi Fauzi
85
 Plate 46. Chronic Myelogenous (Myelocytic) Leukemia (CML), Peripheral Blood,
Wright stain, and Leukocyte Alkaline Phosphatase (LAP) stain

46A Myeloid cells in CML (see cell 46B. Myeloid cells in CML 46C. Myeloid cells in CML
numbers below)

.. 0
__
0 ~
460. Myeloid cells in CML 46E. Myeloid cells in CML 46F. CML, Leukocyte alkaline
phosphatase stain (N segmented and
band are negative)

46G. Pseudo-Pelger cells in CML 46H. CML in AML blast crisis with 461. CML in ALL blast crisis with
increase in basophils increase in early lymphoid cells

Identification of cells:
1. Myeloblast, 2. Promyelocyte, 3. N. myelocyte, 4. N. metamyelocyte, 5. N. band, 6. N. segmented, 7. Eosinophil, 8. Basophil,
9. Pseudo-Pelger neutrophil, 10. Early lymphoid cell (lymphoblast)

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86
 Plate 47. Acute Myelogenous (Myelocytic) leukemia (AMl): (FAB) M1, M2, M3

Acute myelogenous leukemia: M 1 without maturation; M2 with some maturation;

M3 acute pro myelocytic leukemia

47 A. Myeloblasts, MI (blood)

47B. Myeloblasts-positive Sudan 47(, Myeloblasts with Auer rod

Black stain, Ml (blood) (arrow), M 1 (blood)

•
47D. Myeloblast, promyelocyte, 47E. Promyelocytes and myelocyte, 47F. Positive myeloperoxidase stain,
M2 (blood) M2 (marrow) M2 (marrow)

47G. Hypergranular promyelocytes, 47H. Auer rods In early myelocytic 471. Promyelocyte with multiple
M3 (marrow) cells, M3 (marrow) Auer rods, M3 (marrow)

Note: 47 A and 47B from same patient; D-F same patient; G-I same patient
Errisa Devi Fauzi
87
 Plate 48. Cytochemical Stains, Part 1

1'--
' ..
Myeloperoxidase Stain: The two upper cells (48A) are myeloperoxidase negative (lymphocytes); the two
lower cells (48B) are myeloperoxidase positive (neutrophils). The red cells are laked and appear as
shadow forms. This stain is of aid in differentiating early cells of the myelocytic and monocytic systems
from cells of the lymphocytic system .

• l

48C. Positive myeloperoxidase stain, AML, M 1 (blood) 48D. Positive myeloperoxidase stain, AML,
Ml (marrow)

48E. Blasts: negative myeloperoxidase stain-ALL (L2) 48F. Large Blasts: negative myeloperoxidase stain-ALL
marrow (positive neutrophil in center right serves as (L3) marrow (positive neutrophil myelocyte in lower
quality control for adequate stain) center serves as control for adequate stain)

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88
 Plate 48. Cytochemical Stains, Part 2

Periodic Acid Schiff (PAS) Stain: Reaction for the detection of intracellular glycogen

48G. PAS positive Iymphocyte- 48H. Negative PASreaction- 481. Strongly positive PASreaction-
Sezary cell (blood) lymphocyte (normal blood) segmented neutrophil (blood)

Sudan Black Stain: For the detection of lipids

48J Positive reaction-immature 48K. Negative reaction- 48L. Strongly positive reaction-
granulocyte (blood) lymphocyte (blood) N. segmented (blood)

Leukocyte Alkaline Phosphatase (LAP) Stain: For detection of LAP in neutrophils

48M. Positive (2+) reaction- 48N. Negative reaction- 480. Strongly positive (4+) reaction-
neutrophil segmented (blood) neutrophil segmented in CML neutrophil segmented (blood)

48P. Positive PASstain: (lymphoblasts)-ALL, 48Q Positive Sudan Black stain in AML Ml (blood)
L3 (marrow)

48R. Positive LAP stain in myelofibrosis (blood) 48S. Negative LAP stain in CML (blood)
Errisa Devi Fauzi
89
 Plate 49. Acute Myelogenous leukemia (AMl) (FAB): M4 and MS

Acute myelomonocytic leukemia: M4; Acute monocytic leukemia M5

49A. M4 (blood) 49B. M4 (blood) 49C. M4 (blood)

49D. M5: monoblasts (marrow) 49E. M5: monoblasts (marrow) 49F. M5: positive monocytic
esterase stain (marrow)

~
49G. M5: monoblasts (marrow) 49H. M5: monocytes (blood) 491. M5: monocytes and promonocytes
(marrow)

Identification of Cells: 1. Monocyte; 2. Promonocyte; 3. Blast with Auer rod; 4. N. Myelocyte; 5. Basophil; 6. Eosinophil

Note: 49A, 49B same patient; 49D, 49G same patient; 49H, 491 same patient
Errisa Devi Fauzi
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 Plate 50. Selected Cells from Patients with Acute Monocytic Leukemia: (FAB) M5

SOA. Monoblast: prominent nucleoli, SOB. Monoblast: prominent SOc. Monocyte:

indented nucleus, blunt pseudopods nucleoli phagocytized red cell

SOD. Promonocyte nuclear folds, SOE. Promonocyte: two nuclear SOF. Monocyte: deeply indented
foamy cytoplasm lobes, nucleoli, prominent nucleus, fine granular cytoplasm
granules, clear ectoplasm

SOG. Monocyte: transparent folded SOH. Monocyte: folded nucleus, 501. Promonocyte: nucleoli;
nucleus, granules in cytoplasm linear chromatin, distinct granules, vacuoles in cytoplasm
elongated shape

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91
 Plate 51. Selected Cells from Blood Smear of Acute Erythroleukemia: (FAB) M6

51 A. Macrocytic polychromatophilic 51 B. Macrocytic basophilic 51 C. Macrocytic basophilic

erythroblast with three nuclei erythroblast with two nuclei erythroblast with asynchronism
and asynchronism

51 D. Macrocytic orthochromatic 51 E. Nuclear fragmentation in 51 F. Macrocytic orthochromatic

erythroblast with five nuclei an erythroblast erythroblast with asynchronism

6(7) __

51 G. M6 (See cells below) 51 H. M6 (See cells below) 511. M6 (See cells below)

Identification of cells: 1. Proerythroblasts often with vacuoles; 2. Promyelocyte; 3. Pseudo-Pelger neutrophil;

4. Orthochromatic erythroblast; 5. Mitotic figure; 6. Polychromatophilic erythroblast
Asynchronism nucleus less mature than cytoplasm

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92
 Plate 52. Selected Erythroblasts from Bone Marrow Smears of
Acute Erythroleukemia: (FAB) M6

52B. Macrocytic proerythroblast: nucleoli and

prominent cytoplasmic vacuolization
52A Macrocytic proerythroblast: nucleoli and small
vacuoles in cytoplasm

52(, Macrocytic basophilic erythroblast: two large nuclei S2D. Macrocytic polychromatophilic erythroblast: four
nuclei of different sizes; asynchronism

52E. Giant late erythroblast: multiple nuclei, fragmentation S2F. Large basophilic erythroblast: three nuclei
of nuclei and Howell-Jolly bodies

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93
 Plate 53. Pathological Erythroblasts from Bone Marrow Smears
of Acute Erythroleukemia: (FAB) M6

53A. Large basophilic erythroblast 53B. Basophilic erythroblast: two nuclei 53C. Proerythroblast: two nuclei

53D. Large polychromatophilic 53E. Macrocytic proerythroblast: 53F. Giant polychromatophilic

erythroblast: three nuclei four nuclei erythroblast: multiple nuclei;
nuclear fragments

53G. Prussian blue iron stain: 53H. Periodic Acid Schiff stain: 531. Periodic Acid Schiff stain: positive
ringed sideroblasts positive polychromatophilic erythroblast lobulated polychromatophilic erythroblast

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94
 Plate 54. Micromegakaryoblasts in Blood and Marrow Smears
of Megakaryoblastic Crisis of CML

Selected cells from patient with megakaryoblastic crisis of chronic myelogenous leukemia. Variant forms of micro-
megakaryoblasts. Nuclei are usually small and single but one cell has two nuclei. In most cells, granular cytoplasmic
blebs (which represent early platelet formation) are noted.

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95
 Plate 55. Megakaryoblasts in Blood and Marrow Smears of
Acute Megakaryoblastic (Megakaryocytic) Leukemia: (FAB) M7

55A. Micromegakaryoblasts (blood) 55B. Megakaryoblasts (marrow) SSe. Megakaryoblast with

cytoplasmic blebs; mitotic
figure (marrow)

_ .

......
55D. Micromegakaryoblast; large SSE. Megakaryoblast with 55F. Megakaryoblast with
platelet (blood) blebs (marrow) blebs (marrow)

SSG. Megakaryoblast with 55H. Megakaryoblast with 551. Megakaryoblast with blebs
blebs (marrow) platelets (marrow) (top left); micromegakaryoblast
(marrow)

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96
 Plate 56. Myelodysplasia: Peripheral Blood (PB) and Bone Marrow (BM)

L.
56A Refractory anemia (RA), (PB): 56B. RA, PB poikilocytosis, 56C. RA, PB: poikilocytosis,
anisocytosis, poikilocytosis, anisocytosis, anisochromia anisocytosis, anisochromia
anisochromia

56D. Prussian blue iron stain: 56E. RARS, BM: erythroblastic 56F. Proerythroblasts with
ringed sideroblasts, macrophage hyperplasia: orthochromatic, vacuoles, basophilic, and
with hemosiderin, RARS, BM polychromatic erythroblasts; and polychromatic erythroblasts..
two nuclei in 2 cells RARS BM

56G. Pseudo-Pelger neutrophils 56H. RAEB Three myeloblasts, 561. CMML: Two atypical
(right); N. metamyelocytes (left), 2 basophils, BM vacuolated monocytes, PB
MDS BM

Myelodysplasia categories: RA: Refractory anemia; RARS: Refractory anemia with ringed sideroblasts; RAEB: Refractory
anemia with excess blasts; CMML: Chronic myelomonocytic leukemia. 56D and 56E from same patient.

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97
 Plate 57. Myelofibrosis; Essential Thrombocytosis (ET): Blood Smears
- Q
,
57 A. Myelofibrosis: teardrop
and oval erythrocytes
57E. Myelofibrosis: N.
myelocytes (2), promyelocyte
(17) N. segmented
571. ET:Micromegakaryocyte,
increased platelets
98
57B. Myelofibrosis: teardrop
erythrocytes, anisocytosis
57F. Myelofibrosis: leukocyte
alkaline phosphatase stain:
positive, 2+, 3+, 4+
57J. ET:thrombocytosis, six
lobed N. segmented
Errisa Devi Fauzi
57(, Myelofibrosis: teardrop,
oval and odd shapes
'"'
d· .
57G. MyelofibrosIs: myeloblast
(top); megakaryoblast; large
platelets: one giant platelet
57K. ET thrombocytosis
57D. Myelofibrosis:
anisocytosis, poikilocytosis;
large platelets
57H. Myelofibrosis: giant
platelet, large platelets
57L. Essential thrombocytosis
 Plate 58. Selected Cells in Acute lymphoblastic leukemia (All) and
Chronic lymphocytic leukemia (Cll)

58A. Lymphoblast with

nucleolus, ALL 58e. Prolymphocyte with
58B. Lymphoblast with indistinct nucleolus, ALL
prominent nucleoli, ALL

58D. Prolymphocyte: intermediate S8E. Prolymphocyte: double nuclei, 58F. Atypical early lymphocyte:
chromatin structure, rippled immature nuclear chromatin, ALL clumping of nuclear chromatin,
cytoplasm, ALL purplish-red nongranular
cytoplasm, ALL

58G. Prolymphocyte 58H. Atypical 581. lymphocyte with 58J. Smudge (frequent in Cll)
with deep nuclear cleft, lymphocyte with nuclear fragment, CLl
ALL nuclear lobulation,
CLL

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 Plate 59. Acute Lymphoblastic Leukemia (ALL): (FAB) Peripheral Blood (PB), Bone Marrow
(BM), Cerebrospinal Fluid «(SF); Prolymphytic Leukemia

59A ALL, PB. Small 59B. ALL, PB. Larger 59(, ALL, BM. Large 59D. T cell ALL, PB.
Iymphoblasts: little cytoplasm, Iymphoblasts with nucleoli, Iymphoblasts (~ lineage) with Lymphocytic cells with
no or faint nucleoli, thrombocytopenia (L2) vacuoles and nucleoli (L3) prominent azure granules
thrombocytopenia (L1)

59E. ALL, BM. Small 59F. ALL, BM. Larger 59G. ALL, BM. Large 59H. All, BM. Acid
Iymphoblasts: no or indistinct Iymphoblasts with nucleoli (L2) Iymphoblasts (~ lineage) with phosphatase positive stain

,
nucleoli, little cytoplasm (L1) vacuoles and nucleoli (L3)

591. PAS positive stain, BM. 59!. ALL, (SF. Larger 59K. ALL, BM. Large 59L. Prolymphocytic leukemia,
Small Iymphoblasts (L1) Iymphoblasts with nucleoli (L2) Iymphoblasts (~ lineage) with PB. Large Iymphoblasts
vacuoles and nucleoli (L3) with nucleoli

Note: 59A, 59E, 591 from same patient; 59B, 59F, 59J from same patient; 59(, 59K from same patient

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100
 Plate 60. Chronic Lymphocytic Leukemia (CLL): Peripheral Blood (PB)
and Bone Marrow (BM); Prolymphocytic Leukemia (PLL)

60A cu. lymphocytes (5), smudge 60B. Cll: many lymphocytes, smudge 60C Comparison: hairy cell (top),
cells (3), platelet (1), PB cell, no platelets, PB prolymphocyte (PlL), lymphocyte, PB

600. cu. lymphocytes, Iymphoblasts 60E. Cll: lymphocytes, lymphoblast 60F Cll lymphocytes, Iymphoblasts,
(2), smudge cells (2), BM (I), BM smudge cell, BM

60G, Cll lymphocytes, Iymphoblasts 60H. Cll numerous small 601. PlL big prolymphocyte with
(2), BM lymphoid cells, N. band, nucleolus, PB
orthochromatic erythroblast, BM

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101
 Plate 61. Hairy Cell Leukemia: Peripheral Blood

Selected cells in peripheral blood smears from a patient with hairy cell leukemia. These cells have veillike cytoplasmic
extrusions and delicate threadlike filaments. Hairy cells tend to push neighboring cells away or aside, leaving clear
spaces around the hairy cell. One cell has prominent azure granules and a few hairlike projections.

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102
 Plate 62. Hairy Cell Leukemia: Peripheral Blood (PB) and Bone Marrow (BM)

;;.a..
62A. Hairy cells, PB 62B. Hairy cells, PB 62C. Comparison: hairy cell (top),
prolymphocytes, lymphocyte, PB

62D. Hairy cells, 6 lobed 62E. Tartrate resistant acid phosphatase 62F. Hairy cell, BM
N. segmented, PB stain: positive hairy cells, PB

62G. Hairy cells-one cell with 62H. Hairy cells, BM 621. Hairy cells, BM
cytoplasmic extension, BM

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103
 Plate 63. Pathological Plasma Cells; Plasma Cell Myeloma, Bone Marrow (BM)

63C. Plasma cell: red-

staining globules (Russell
63A. Proplasmacyte: three early bodies)
nuclei and reticular cytoplasm

63D. Flame type of plasma cell 63B. Plasma cell: nebulous 63E. Plasma cell: eccentric
cytoplasmic margin, multiple nucleus, red staining crystaline
globules, pink-staining secretory bodies and globules, reticulated
material cytoplasm

63F Plasma cell myeloma, BM 63G. Plasma cell myeloma, BM (artifact on cell at top left)
(artifact, p. 104)

,JiIil
63H. Plasma cell myeloma, BM note nucleoli in 3 cells 631. (a) Rouleaux of erythrocytes, blood,
(myeloma); vs (b) Agglutination

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104
 Plate 64. Selected Cells from Blood Smears of Sezary Syndrome

64A. Vacuolated atypical
immature lymphocyte:
indented nucleus, swirled
chromatin pattern, nucleoli:
Sezary cell
64B. Vacuolated atypical
early lymphocyte distinct
chromatin pattern:
Sezary cell
64C. Atypical lymphocyte 64D. Atypical lymphocyte
of intermediate size: with nuclear folds: Sezary cell
brainlike (cerebriform)
convolutions and granules:
Sezary cell

64E. Sezary cell 64F. Sezary cell 64G. Sezary cell 64H. Sezary cell

641. Sezary cell with nuclear convolutions and 64J. PASpositive Sezery cell
nuclear fragment

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105
 Plate 65. Selected Cells from Blood Smears of Patients with Infectious Mononucleosis

65A. Primitive plasma-like cell 65B. Early plasma-like cell: 65(, Early plasma-like cell:
indented nucleus indented nucleus

65D. Large reactive lymphocyte: 65E. Large lymphocyte: 65F. Atypical monocyte; fine and
unevenly stained bluish cytoplasm vacuolated periphery coarse granules, pseudopods

65G. Large lymphocyte; azure 65H. Large lymphocyte: 651. Atypical monocyte
granules, scalloped borders (indented prominent azurophilic granules
by red cells)

65J. Reactive lymphocytes 65K. Reactive lymphocytes, 65L. Reactive lymphocytes

normal small lymphocyte

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106
 Plate 66. Reactive lymphocytes-Peripheral Blood

In this color plate leukocytes other than lymphocytes have been left out. Selected lymphocytes reacting to
antigenic stimuli and showing heterogeneous forms have been portrayed in increased numbers in order to reveal
the marked variation in size and shape and in nucleus and cytoplasmic characteristics. Note large cells with
prominent basophilic cytoplasm, granules in one cell and indentation of some lymphocytes by red cells. Red cells
and platelets are normal.

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107
 Plate 67. Malarial Parasites, Peripheral Blood (Wright-Giemsa stain)

Plasmodium Plasmodium Plasmodium Plasmodium

falciparum vivax malariae o vale

Early ring

,
Late ring

Early trophozoite
.. .If· ,..

••

Late trophozoite

Immature schizont I

Mature schizont

Macrogametocyte

Microgametocyte

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108
 Plate 68, Part 1. Malarial Parasites, Peripheral Blood Smear (Wright-Giemsa
stain); Thick Drop (Giemsa stain)

68A. Plasmodium falciparum 68B. P falciparum 68C. P falciparum 68D. P falciparum thick drop-
rings (Wright-Giemsa stain) gametocytes gametocyte many rings (Giemsa stain)

« •

68E. P vivax rings 68F. P vivax ring, 68G. P vivax mature schizont 68H. P vivax thick drop-
immature schizont trophozoites, schizonts
(Giemsa stain)

681. P malariae ring 68J. P malariae trophozoite 68K. P malariae trophozoite 68L. P malariae
("band" form) mature schizont

68M. P malariae mature schizont 68N. Platelet on RBC (left) 680. P vivax trophozoites 68P. P vivax trophozoites
vs Ring in RBC (right)

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109
 Plate 68, Part 2. Protozoan Parasites: Babesia microti; Plasmodium falciparum

68, Part 2 A. Babesia microti, intracellular and 68, Part 2 B. Plasmodium falciparum, ring forms (one to
extracellular parasites four parasites per cell)

~
68, Part 2 C. Babesia microti rings 68, Part 2 D. Plasmodium falciparum rings

68, Part 2 E. Babesia microti tetrad form and rings 68 Part 2 F. Plasmodium falciparum rings

Errisa Devi Fauzi

110
 Plate 69. Infections in Hematology-Peripheral Blood

69A. Ehrlichia phagocytophiJa in 69B. Ehrlichia phagocytophila

neutrophil (Wright stain) in neutrophil

69C. Ehrlichia caffenesis in monocyte 69D. Ehrlichia phagocytophila

In neutrophil

69E. Staphylococci in a neutrophil from 69F. Meningococci in a monocyte

a burn patient (Wright stain) (Wright stain)

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111
 Plate 70. Histoplasma, leishmania, Microfilariae in Blood and Marrow Smears

.....

'.

. ...

70A. Macrophage with phagocytized Histoplasma 70B. Macrophage with Leishmania donovani (marrow)
capsula tum (marrow)

~_.._~
70C. Histoplasma capsula tum in neutrophils at 700. Macrophage with amastiogotes of
feather end of blood smear Leishmania species

70E. Histoplasma capsula tum in 70F. Macrophage with amastiogotes of

macrophage---bone marrow Leishmania species

70G. H]. »plestn» capsula tum in 70H. Microfilaria in thick drop of blood
disinteqrai 'g cell-blood

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112
Plate 71. Giant Proerythroblasts in Bone Marrow from Patient with Parvovirus B19

Giant proerythroblasts with basophilic cytoplasm containing vacuoles in bone marrow smear stained with
Wright stain are characteristic of Parvovirus B19. Note large nuclear inclusions (viral).

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113
 PLate 72. Lipid Histiocytes: Bone Marrow Smears

72A. Gaucher cell 72B. Nieman-Pick cell

72(, Gaucher cell 72D. Nieman-Pick cell

72E. Two Gaucher cells 72F. Three Nieman-Pick cells

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114
 Plate 73. Platelets on Blood Smears

73A. Platelets-idiopathic 73B. Platelets-May-Hegglin 73C. Platelets-myelofibrosis

thrombocytopenic purpura (ITP) anomaly

...

..- I

73D. Large elongated platelet-ITP 73E. Platelets-May-Hegglin 73F. Platelets-myelofibrosis

anomaly

73G. Giant platelet syndrome 73H. Giant platelet syndrome

731. Platelet satellitosis (EDTA blood smear)

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115
 Plate 74. Origin and Development of Blood Cells-S1Wvvv

/
Myeloblast
Monoblast

Basophilic myelocyte Neutrophilic myelocyte Eosinophilic myelocyte

Promonocyte

Basophilic metamyelocyte Neutrophilic metamyelocyte Eosinophilic metamyelocyte

Basophilic band Neutrophilic band Eosinophilic band

Basophilic segmented Neutrophilic segmented Eosinophilic segmented Monocyte

Errisa Devi Fauzi S1:A.vvYv
116
-------- MegaKaryob\ast
proerythroblast
Plasmablast

Basophi\iC erythroblast

prop\aS

POlychromatophiliC erythroblast

MegaKaryocyte without platelets

orthOchromatic erythroblast

POlychromatophiliC erythrocyte

MegaKaryoCyte with platelets

£rythrocyte

Platelets

Errisa Devi Fauzi

 Index

Figures are indicated by a bold face "F" and the figure number, followed by the page number in parentheses.
Plates are indicated by a bold face "P" and the plate number.
Tables are indicated by a bold face "T" and the table number, followed by the page number in parentheses.

Acanthocyte (spur, thorn) 15, P23, P26 Cabot ring 16, F8 (17), P33, P39 (Parts 1"2)
Acid phosphatase stain P59 CALLA (Common acute lymphoblastic antigen) 9
Acute erythroleukemia P52, P53 CD (Cluster designation) Markers 9, F4 (10)
Acute lymphoblastic leukemia (ALL) 35, P58-P59 Chediak-Higashi anomaly 27, P42
Acute megakaryocytic leukemia P45, P55 Chronic lymphocytic leukemia (CLL) 33, P58, P60
Acute myelogenous leukemia 30,31, P45, P47-P55 Chronic myelogenous leukemia (CML) 27, P45-P46
Acute myelomonocytic leukemia (AML) P30, P49 Classification of ALL 35, P58-P59
Alder-Reilly Anomaly 27, P44 Classification of AML 30, P45, P47-P55
Anemia Classification ofMDS 31, P56, T6 (31)
aplastic 20 Clostridium perfringens 26
heart valve dysfunction P25 (Part 2) Cooley's anemia 22, P29
hemolytic due to burns, venoms 25, P31 Crescent body (semilunar body) P23
hemolytic uremic syndrome 25
iron deficiency IS, P24, P36-P37 Degenerated neutrophil 26, P40
megaloblastic 19, P36-P39 (Parts 1-2) Dahle body 26, P40, P43
microangiopathic hemolytic anemias 25, Drepanocyte (sickle cell) 16
P25 (Parts 1-2)
sickle cell 22, P23, P27-P28 Echinocyte 15, P23, P26
sideroblastic 19, P34 Ehrlichiosis 36, P69
Thalassemia major 22, P29 Electrophoresis Hb 22, 23
Thalassemia minor 21, P30 Elliptocyte 24, P23, P29
Thrombotic thrombocytopenic purpura 25, Elliptocytosis 24, P23, P29
P25 (Part 1) Endothelial cell 14, P22
Anisocytosis 15 Eosinophil 1,4, Fl (2), PI-P4, PIS, P74, Tl (1), T2 (1)
Aplastic anemia 20 band 4, FI (2), PI-P2, P74
Auerrod(body) 30,P45,P47 metamyelocyte 4, FI (2), PI-P3, P18, P74
myelocyte 4, FI (2), PI-P2, PI8, P74
B cell 9, Fl (2), F4 (10) segmented 4, Fl (2), PI, P4, P74
Babesiosis 36, P68 (Part 2) Erythrocyte
Band neutrophil 1-3, Fl (2), PI-P3, P74, Tl-T2 (1) acanthocyte (spur, thorn) 15, P23
Basophil 1,2,5, Fl (2), PI-P4, P46, P74, Tl-T2 (1) basophilic erythroblast 7, FI (2), Pll, P36, P74,
band 5, Fl (2), PI, P74 Tl (1)
metamyelocyte 5, Fl (2), PI, P74 basophilic stippling 16, F7 (17), P32
myelocyte 5, Fl (2), PI, P74 bite 15, P26
segmented 5, Fl (2), PI, P74 blister (marginal achromia) P23
Basophilic erythroblast 1,7, FI (2), F7 (17), Pll, P36, P74, burn patient 25, P3I
T2 (1) burr 15,P23,P26
Basophilic stippling 16, F7 (17), P32 Cabot ring in 16, F8 (17), P33, P39 (Part 1)
Bite cell 15, P26 crenated P23
Blister cell P23 crescent (semilunar body) P23
Blood cells, normal values Tl (1) crystals (Hb SS, SC, CC) 23, P23, P27
Bone cells 13, P20-P2I echinocyte 15, P23, P26
Bone marrow cells, normal values T2 (1) elliptocyte 24, P23, P29
Burned patients, erythrocytes in 25, P31 filamented P23
Burr cell 15, P23, P26 folded P23
fragment (schistocyte) 16,25, P23, P25 (Parts 1-2)

Errisa Devi Fauzi

118
 The Morphology of Human Blood Cells

helmet 15, P23, P25 (Parts 1-2) Gaucher cell P72

Heinz body 16, F7 (17), P35 G-6-PD Deficiency 15, P26
Howell-Jollybody 16, F7 (17), P33, P39 (Parts 1-2) Granule(s)
hypochromic 16, P24, P37 primary 1,3
inclusions in 7, F7 (17), P32-P35 secondary I, 3
keratocyte 15 siderotic (iron-containing) 18, P34
leptocyte 16, P24
macrocyte 15, P24, P36-P37, P39 (Parts 1-2) Hairy cell leukemia 33, P60-P62
malaria in 36, P67-P68 Heinz body 16, F7 (17), P35
membranous ghost P23 Helmet cell 15, P23, P25 (Parts 1-2)
microcyte 15,18, P24, P36-P37, P39 (Parts 1-2) Hematopoiesis I, FI (2)
normal 7, 15, P23-P24 Hematopoietic stem cell I, FI (2), F4 (lO)
orthochromatic erythroblast 7, FI (2), PI I, P36, P74, Hemoglobin A 22,23
T2 (1) Hemoglobin A2 23
oval (ovalocyte, elliptocyte) 24, P23, P29 Hemoglobin AC 23
pear 20, P23 Hemoglobin AE 23
pinched (pinchered) P23 Hemoglobin AS 22, P28
poikilospherocyte P23 Hemoglobin ~o thalassemia 22, P29
polychromasia 18 Hemoglobin ~+ thalassemia 22, P30
polychromatophilic erythroblast 7, FI (2), PI I, P36, Hemoglobin Bart's 21, T4 (21)
P74, TI (1) Hemoglobin concentration 16
polychromatophilic erythrocyte 7, 18, FI (2), Pll, Hemoglobin CC 23, P27
P32,P36,P74 Hemoglobin E 23
proerythroblast 6, FI (2), Pll, P36, P74, T2 (1) Hemoglobin E-~-thalassemia 23, P30
ringed sideroblast 18, P34 Hemoglobin electrophoresis 22,23
rouleaux 16,34, P63 Hemoglobin H 21
schistocyte (fragment) 16,25, P23, P25 (Part 1) Hemoglobin 0 23
semilunar body (crescent) P23 Hemoglobin SC 23, P23, P27
sickle cell (drepanocyte) 16,22, P23, P27, P28 Hemoglobin 55 23, P23, P27-P28
sideroblast 18, P34 Hemoglobin Zurich P26
siderocyte 18, P34, F7 (17) Hereditary elliptocytosis 24, P23, P29
siderotic granules in 18, F7 (17), P34 Hereditary pyropoikilocytosis 24, P31
spherocyte 16, P23, P26, P29 Hereditary spherocytosis 24, P23, P29
stippled 16, F7 (17), P32 Hereditary stomatocytosis 24, F9 (24), P23
stomatocyte 16, F9 (24), P23 Histioplasma capsulatum 37, FII (37), P70
target 16, P23, P27, P29-P30 Histoplasmosis 37, P70
teardrop 16, P23, P24, P39 (Parts 1-2), P56-P57 HLA-DR 10
triangular 16, P23, P25 (Part 1) Hodgkin's disease 32
venoms, on 25, P26 Howell-Jolly body 16, F7 (17), P33, P39 (Parts 1-2)
Erythropoiesis 2,6, Fl (2), Pll, P36 Hydrops fetalis 21, T4 (21)
Esterase stains Hyperlobulated neutrophil P24, P39-P40
monocytic 31
myelocytic 30 Immunologic classification of adult ALL 35, T7 (35)
Inclusions in erythrocytes 16, P33
FAB classification of ALL 35, P58-P59, T8 (35) Infectious mononucleosis 36, P65-P66
FAB classification of AML 30, P45, P47-P55, T5 (30) Iron deficiency anemia 18, P24, P36-P37
FAB classification ofMDS 31, P56, T6 (31) Iron Stain P34, P53-P56
Fat cell (lipocyte) 13, PI9 Iron studies 19
Ferrata cell P45
Fibroblast 15 Keratocyte 15
Folic acid deficiency 19, P24, P36-P39 (Parts 1-2)
Fragmented cell (schistocyte) 16,24,25, P23
Errisa Devi Fauzi
119
The Morphology of Human Blood Cells

L.E. cell P40 Microcyte 8,15,18, P24, P36-P37

Leishmaniasis 37, P70 Micromegakaryoblasts 8, P54-P55
Leptocyte 16 Monoblast 5, Fl (2), PI~, P49-P50, P74, T2 (2), T5 (30)
Leukemia Monocyte 5, FI (2), P4, P7-IO, P74, Tl-T2 (1)
basophilic 5 Monocytic leukemia 6,30, P49-P50, T5 (30)
erythroleukemia (erythroblastic) P51-P53, T5 (30) Myeloblast 1, FI (2), PI-P3, P45-P47, P74
hairy cell 33, P60-P62 Myelocyte
lymphoblastic, acute 35, P58, P59, T7-T8 (35) basophilic 1,5, FI (2), PI-P3, P74
lymphocytic, chronic 33, P58, P60 eosinophilic 1,4, FI (2), PI-P3, P74
megakaryoblastic, acute 30, P54-P55 neutrophilic 1,3, FI (2), PI-P3, P74
monocytic, acute 30, P49-P50 Myelodysplastic syndrome 31, P56
myelocytic, chronic 27, P45-P46 Myelofibrosis 29, P57, P73
myelogenous, acute 30, P45, P47-P55, T5 (30) Myelogenous leukemia P45-P48
myelogenous, chronic 27, P45-P46 acute 30, P45-P55, T5 (30)
myelomonocytic, acute 30, P49 chronic 27, P45-P46, P48
myelomonocytic with eosinophilia 30 Myeloid: Erythroid ratio I, T2 (1)
plasma cell 34 Myeloma 34, FlO (34), P63
promyelocytic 30, P47, T5 (30) Myeloperoxidase stain (MPO) 30, P48 (Part 1)
prolymphocytic 11, P59-P60 Myelopoiesis 1, FI (2)
Leukocyte alkaline phosphatase (LAP) stain 28, P46,
P48 (Part 2) Neiman-Pick disease P72
Lipocyte (fat cell) 13, P19 Neutrophilic
Lymphoblast 9,35, PlO, P58-P59 band 1-3, FI (2), F2 (3), PI-P4, P74, Tl-T2 (1)
Lymphocyte Tl- T2 (1) degenerated 26, P40
B cell 9, Fl (2), F4 (10) hypersegmented 26, P39-P40
cell markers 9, F4 (10) hyposegmented (Pelger-Huet) 26, P4I
reactive 36, P65"-P66 metamyelocyte 1-3, Fl (2), F2 (3), PI-P3, P74, T2 (1)
T cell 9, Fl (2), F4 (10) myelocyte 1-3, FI (2), F2 (3), PI-P3, P74, T2 (1)
Lymphopoiesis 9, Fl (2), F4 (10) segmented 1-4, FI (2), F2 (3), F3 (4), PI, P74,
Tl-T2 (1)
Macrocyte 15,20, P24, P37-P39 (Parts 1-2) Non-Hodgkin's lymphoma 32
Macrophage 12, PI6-PI7, P56 Normal values
Malaria 36, P67-P68 (Parts 1-2) bone marrow 1, T2 (1)
Mast cell 12, P18 peripheral blood 1, Tl (1)
May Hegglin anomaly 26, P43 MeH 19
Mean corpuscular hemoglobin (MeH) 19,22 MeHe 19,22
Mean corpuscular values 19,20 MeV 19,20,22
Mean corpuscular hemoglobin concentration (MeHe) RDW 19,20,22
19,22
Mean corpuscular volume (MeV) 19,20,22 Orthochromatic erythroblast 7, Fl (2), Pll, P36, P74, T2
Megakaryoblast 8, Fl (2), PI4-PI5, P74 Osteoblast 13, F5 (14), P20-P21
Megakaryocyte 8, Fl (2), PI4-PI5, P74 Osteoclast 14, F6 (14), P20-P21
Megaloblastic anemia 19, P36-P39 (Parts 1-2)
Metamyelocyte Pappenheimer body (siderocyte) 18, F7 (17), P34
basophilic 1,5, FI (2), PI-P3, P74 Parvovirus B19 37, P71
eosinophilic 1,4, Fl (2), PI-P3, P74 Pelger-Huet anomaly 26, P41
neutrophilic I, Fl (2), F2 (3),3, F3 (4), PI-P3, P74, Periodic Acid Schiff (PAS) stain P48 (Part 2), P53,
T2 (1) P59,P64
Microangiopathic hemolytic anemia (MAHA) 25,
P25 (Parts 1-2)

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Peroxidase stain 30, P48 (Part 1) Sickle cell trait (Hb AS) 22, P28
Plasmablast 12, PI0, P63, P74 Sideroblast-ringed 18,19, P34
Plasma cell (Plasmacyte) II, PI0, P74 Sideroblastic anemia 19, P34
Plasma cell leukemia 12 Siderocyte 18, F7 (17), P34
Plasmodium Smudge cell 33, P60
falciparum 36, P67-P68 (Parts 1-2) Spherocyte 16,24, P23, P26, P29
malariae 36, P67-P68 (Part 1) Spherocytosis, hereditary 24, P29
ovale 36, P67 Spider bite on RBC 25, P26
vivax 36, P67-P68 (Part 1) Spur cell P26
Platelet (thrombocyte) 8, Fl (2), P4, P14-P15, P73, P74 Stem cell l , Fl (2), F4 (10)
Pluripotent stem cell F4 (10) Stem cell compartment 1
Poikilocytosis 15 Stippled red blood cell 16, F7 (17), P32
Polychromasia 18 Stomatocyte 16,24, F9 (24), P23
Polychromatophilic erythroblast 7, Fl (2), Pll, P36, P74 Stomatocytosis, hereditary 16,24, F9 (24), P23
. Polychromatophilic erythrocyte 7, 18, Fl (2), Pll, P32, Sudan black B stain 30, P47, P48 (Part 2)
P36,P74
Polycythemia vera 27,28 Target cell 16,21,22, P23, P27
Precursor compartment I, Fl (2) Tartrate-resistant acid phosphatase (TRAP) 33,34, P62
Pre-B cell 9, Fl (2), F4 (10) T cell 9, Fl (2), F4 (10)
Pre-T cell Fl (2) T-cell receptor (TCR) 9, 10
Pro-B cell 9, F4 (10) Terminal deoxynucleotidyl transferose (TdT) 9,30, F4 (10)
Pro-Tcell F4(10) Teardrop cell 16, P23-P24, P37, P39 (Parts 1-2)
Proerythroblast 6, Fl (2), Pll, P36, P74, T2 (1) Thalassemia
Progenitor compartment I, Fl (2) alpha 21
Prolymphocyte II, PI0, P58-P60, P74 beta 21,23
Promegakaryocyte 8, Fl (2), P14-P15, P74 major 21,22, P29, P30
Promonocyte 5, Fl (2), PIO, P49-P50, P74, T2 (2), T5 (30) minor 21,22, P30
Promyelocyte (progranulocyte) 3, Fl (2), PI-P3, P46-P47, Thermal injury to RBC 25, P31
P74 Thrombocyte (platelet) satellitosis P73
Proplasmacyte 12, PI0, P74 Thrombocythemia, essential 29, P57
Prothymocyte F4 (10) Thrombotic thrombocytopenic purpura (TTP) 25,
Prussian blue iron stain on P25 (Part 1)
erythrocytes P34, P53, P56 Thymocyte F4 (10)
macrophage P56 Thymus Fl (2), F4 (10)
Pseudo-Pelger Huet cell 31, P56 Tissue basophil P18
Pyropoikilocytosis, hereditary 24, P31 Tissue eosinophil P18
Toxic granules 26, P40
Red cell distribution width (RDW) 19,20, T3 (19)
Reactive lymphocyte 36, P65-66 Venoms on erythrocytes 25, P26
Reticulocyte 18, F7 (17), P32 Vitamin B12, Folic Acid deficiency 19, P36-P39 (Parts 1-2)
Ringed sideroblast 18, 19, P34
Rouleaux 12,34, P63
Russell body (plasma cell) II, P63

Satellitosis (platelets around neutrophil) 9, P73

Schistocyte 16,25, P23, P25 (Parts 1-2)
SemilunarIcrescent) body P23
Sezary syndrome 34, P48, P64
Sickle cell 22, P23, P27, P28
Sickle cell anemia (Hb SS) 22, P23, P27-P28
Sickle cell-hemoglobin SC disease (Hb SC) 23, P23, P27

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