A N D E R S O N ' S
Atlas of HematologyS E C O N D EDITION
www.medilibros.comSHAUNA C. ANDERSON YOUNG KEILA B. POULSEN
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AND E RS ON ' S
Atlas of Hematology
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A N D E R S O N ' S
Atlas of 5 Hematology jSECOND EDITION
SHAUNA C. ANDERSON YOUNG, PhDProfessor, Department o f Microbiology and Molecular Biology Brigham Young University Provo, Utah
KEILA B. POULSEN, BS, MLS(ASCP)cmH, SHHematology SupervisorEastern Idaho Regional Medical CenterIdaho Falls, Idaho
Acquisitions Editor and Publisher: Christopher JohnsonProduct Manager: Paula C. WilliamsProduction Project Manager: Marian BellusMarketing Manager: Shauna KelleyDesigner: Steve DrudingPrepress Vendor: Aptara, Inc.
Second Edition
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9 8 7 6 5 4 3 2 1
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mRev i ewe r s IMary Lavin-Alcaro, BSClinical Coordinator MLT Department Apollo College Tucson, Arizona
Hassan Aziz, PhDDepartment Head & Associate Professor Medical Technology Department Armstrong Atlantic State University Savannah, Georgia
Carol Becker, MEdProgram Director School o f CLS/School of HT OSF Saint Francis Medical Center Peoria, Illinois
Jimmy Boyd, BS, MS, MHS, CLS(NCA)Assistant Professor of Medical Laboratory
Technology Arkansas State University Beebe, Arkansas
Norma Bryant, BAMLT ProfessorSandhills Community College Pinehurst, North Carolina
Wanda Burrell, MSPHAssistant Professor Health Administration and Science Tennessee State University Nashville, Tennessee
Michelle Butina, MSAssistant Professor Medical Technology Department Armstrong Atlantic State University Savannah, Georgia
Karen Escolas, BS, MS, EdDChairperson MLT Department Farmingdale State College Farmingdale, New York
Debbie Fox, PhDAssistant ProfessorSchool of Arts, Sciences, and Health Professions Our Lady of the Lake College Baton Rouge, Louisiana
Candice Grayson, MA, MT(ASCP)Program Director Medical Laboratory Technology Community College of Baltimore County Baltimore, Maryland
Candy Hill, MEdCLT Program Coordinator Clinical Laboratory Technology Jefferson State Community College Birmingham, Alabama
Lisa Countryman-Jones, MLS(ASCP), CLS(Ca), CPT InstructorMedical Laboratory Technology Program Portland Community College Portland, Oregon
Amy Kapanka, MS, MT(ASCP)SCMLT Program Director Hawkeye Community College Cedar Falls, Iowa
D. Gayle Melberg, MS, MT(ASCP)InstructorMedical Laboratory Technician Program J Sargeant Reynolds Community College Richmond, Virginia
Thuy Pinheiro, MIIAHematology Supervisor De Anza CollegeKaiser Permanente San Jose Medical Center San Jose, California
Bentley Reid, MBA, BS, MT(ASCP)Instructor & Clinical Coordinator Department o f Clinical Lab Science Howard University Washington, District of Columbia
V
VI Reviewers
Catherine Shaffner, MSEducation Coordinator Medical Technology Department Bowling Green State University Bowling Green, Ohio
Becky Socha, MS, MLS(ASCP)cm Clinical Laboratory Sciences University o f Massachusetts Lowell, Massachusetts
Joyce Stone, BSAssistant Program Director Medical Laboratory Science Program University o f New Hampshire Durham, New Hampshire
Dick Y. Teshima, MPH, MT(ASCP)Associate Professor University o f Hawaii at Manoa John A. Burns School o f Medicine Division of Medical Technology Honolulu, Hawaii
P r e f a c eAfter many years of interacting with students, Shauna Anderson Young and Keila Poulsen have produced this adas to accompany the interactive tools, Andersons Electronic Atlas o f Hematology and Andersons Electronic Atlas o f Hematologic Disorders. High-quality images are combined with in-depth descriptive text to create an ideal bench-top tool for the student and practitioner.
The text has two units: Cell Descriptions (or normal hematology) and Hematologic Disorders. The first unit is organized into three parts:
i Hematopoietic cells, including a comparison of some of the commonly confused cells
i Bone marrow cellularity, cells of the reticuloendothelial system, and nonhematopoietic cells
Cytochemical stains
Each cell description includes the cell size, a description of the nucleus and cytoplasm, and a list of associated clinical conditions. A drawing o f the maturation series for each cell type accompanies the high-quality photographs.
The second unit describes hematologic disorders. Each description includes a brief summary of the clinical features, pathology, laboratory features, and a diagnostic scheme. The diagnostic scheme summarizes the relevant laboratory findings that lead to the features of a particular disorder. This unit is also organized into three parts: Red blood cell disorders t White cell disorderst Miscellaneous disorders
The WHO classification of hematopoietic and lymphoid tissue has been incorporated into this adas.
Yes! The atlas can be used to teach any level of hematology. Whether it is used for teaching cell identification or for the diagnosis of disease, it is a valuable learning tool for students in medical laboratory technician or medical laboratory science programs. It is also a great reference for students in nursing and nurse practitioner programs, as well as medical students or residents. Finally, this spiral-bound atlas is an ideal, user-friendly, convenient companion at the microscope and can be used as a retraining resource or as a laboratory reference.
Anderson's Atlas of Hematology, Second Edition, includes additional resources for both instructors and students that are available on the books companion Website at http://thePoint.lww.com/Andersonatlas2e.
$ ORGANIZATION
# IS THIS TEXT FOR YOU?
$ ADDITIONAL RESOURCES
vii
V j Preface
Instructor ResourcesApproved adopting instructors will be given access to the following additional resources:I Image Bank
Student ResourcesStudents who have purchased Andersons Atlas of Hematology, Second Edition, have access to the following additional resources:
Interactive Atlas o f HematologyI Over 900 high-quality imagesI Side-by-side viewing for comparison o f cellsI On/off labeling functionI Over 100 morphology evaluation questions with instant feedback and rationaleI Key terms linked to Stedmans Medical Dictionary
Interactive Atlas o f Hematologic Disorders Over 500 high-quality images Concept applications for each disorder t Image-driven case studies Multiple choice question exam with answer rationale Key terms linked to Stedmans Medical Dictionary
In addition, purchasers o f the text can access the searchable full text online by going to the Andersons Atlas o f Hematology, Second Edition, Website at http://thePoint. lww.com/Andersonatlas2e. See the inside front cover of this text for more details, including the passcode you will need to gain access to the Website.
We would like to thank our families for their support because this project required an incredible time commitment. Our students have always been a source of stimulus and enjoyment. We would like to thank them for their suggestions and our colleagues for their contributions.
Shauna C. Anderson Young Keila B. Poulsen
ix
C o n t e n t sRevieivers v Preface vii Acknowledgments ix
unit i: Cell Descriptions
Section A Blood CellsChapter 1: Red Blood Cells 3 Chapter 2: White Blood Cells 55 Chapter 3: Megakaryocytes 127 Chapter 4: Comparison o f Cells 139
Section B Bone MarrowChapter 1: Cellularity 153Chapter 2: Cells o f the Reticuloendothelial System Chapter 3: Nonhematopoietic Cells 171
Section C CytochemistryChapter 1: Cytochemical Stains 175
165
unit ii: Hematologic Disorders
Section A Red Blood Cell DisordersChapter 1: Erythrocytosis 205Chapter 2: Anemias Due to Disordered Iron Metabolism
or Heme Synthesis 213Chapter 3: Megaloblastic Anemias 229Chapter 4: Hypoproliferative Anemias 237Chapter 5: Hemoglobinopathies 253Chapter 6: Hemolytic Anemias 291Chapter 7: Acute Blood Loss 317Chapter 8: Anemias Associated With Systemic Disorders 321
Section B White Blood Cell DisordersChapter 1: Nonmalignant Leukocyte Disorders 331Chapter 2: French American British (FAB) Classification o f
Leukemia 357Chapter 3: World Health Organization (W H O ) Classification
o f Hematologic Neoplasms 393Chapter 4: Myeloproliferative Neoplasms 395Chapter 5: Myelodysplastic/Myeloproliferative
Neoplasms 415Chapter 6: Myelodysplastic Syndromes/Neoplasms
(MDS) 427
Contents
Chapter 7: Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms 445
Chapter 8: Precursor Lymphoid Neoplasms 499Chapter 9: Mature B-cell Neoplasms 507Chapter 10: Mature T- and NK-cell Neoplasms 533Chapter 11: Hodgkin Lymphoma 541
Section c Miscellaneous DisordersChapter 1: Quantitative Platelet Disorders 545Chapter 2: Hematologic Disease Associated
With Microorganisms 553Chapter 3: Reticuloendothelial System Storage Disorders
Index 583
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Section ABlood Cells
CHAPTER 1
Red Blood Cells
NORMAL MATURATION SERIES
Erythrocyte Series
4 UNIT I Cell Descriptions
Figure IA1-1
Pronormoblast (Rubriblast)
Basophilic Normoblast (Prorubricyte)
Polychromatophilic Normoblast (Rubricyte)
Orthochromic Normoblast (Metarubricyte)
Polychromatophilic Erythrocyte (Reticulocyte)
Mature Red Blood Cell (Mature Erythrocyte)
BLOOD CELLS Red Blood Cells 5
Pronormoblast (Rubriblast)
Size: 14-22 u NucleusShape: Round to slightly oval N /C Ratio: 5:l-8:l Color: Purple-redChromatin: Fine, but granular; parachromatin sparse Nucleoli: 1-2 prominent which may show a bluish tint
CytoplasmColor: Deep blueContents: Golgi, mitochondria, which produce a lighter blue color
(perinuclear halo)
Clinical Conditions Erythroleukemia (FAB-M6a)I Pure erythroid leukemia (FAB-M6b) Acute erythroid leukemia (WHO) Hemolytic disease of the newborn
Basophilic Normoblast (Prorubricyte)
6 UNIT I Cell Descriptions
Figure IA1-3
Size: 12-17u NucleusShape: Round, centered N /C Ratio: 4:l-6:lColor: Purple interspersed with light areas Chromatin: Coarse and somewhat condensed Nucleoli: Usually not visible
CytoplasmColor: Deep blueContents: Golgi may produce a light blue area near the nucleus, many
mitochondria
Clinical ConditionsI Erythroleukemia (FAB-M6a)I Pure erythroid leukemia (FAB-M6b)I Hemolytic disease o f the newbornI Acute erythroid leukemia (WHO)
BLOOD CELLS Red Blood Cells 7
Polychromatophilic Normoblast (Rubricyte)
Size: n -1 4 f i NucleusShape: Round, centered to eccentric N /C Ratio: 1:14:1 Color: Red-purpleChromatin: Coarse and condensed; parachromatin distinct, producing a
checkerboard appearance Nucleoli: None
CytoplasmColor: Bluish-pink to grey-blueContents: Perinuclear halo visible; increased hemoglobin, causing the pink-grey
color; decreased RNA, causing the lighter blue color
Clinical ConditionsI Erythroleukemia (FAB-M6a)I Pure erythroid leukemia (FAB-M6b)I Hemolytic disease o f the newbornI Primary myelofibrosis (PMF)I Chronic myelocytic leukemia (CML)I Hemolytic anemiasI Thalassemia majorI Sickle cell diseaseI Acute erythroid leukemia (WHO)
8 UNIT I Cell Descriptions
Orthochromic Normoblast (Metarubricyte)
^ S * *Figure IA1-5
_ i j ___
Size: 8-12 u NucleusShape: Round, centered to eccentric; may be fragmented or extruding N /C Ratio: l:4-l:2 Color: Blue-purpleChromatin: Condensed and homogeneous (pyknotic)Nucleoli: None
CytoplasmColor: Pink to orange-pink, with a hint of blue Contents: Hemoglobin production increased
Clinical Conditions Erythroleukemia (FAB-M6a)I Pure erythroid leukemia (FAB-M6b) Acute erythroid leukemia (WHO)I Hemolytic disease of the newbornft Myeloproliferative diseasesPMF, CMLI Myelodysplastic syndromest Thalassemia majort Sickle cell disease
BLOOD CELLS Red Blood Cells 9
Polychromatophilic Erythrocyte (Reticulocyte)
Figure IA1-6
Size: 8-11 n NucleusNone
CytoplasmColor: Pink, with a tint of blueContents: Remnants of Golgi and mitochondria, residual RNA (reticulum)
Clinical ConditionsI Increased erythrocyte productionI Hemolytic anemiasI Membrane disordersI Hemolytic disease o f the newborn
10 UNIT I Cell Descriptions
Mature Red Blood Cell (Mature Erythrocyte)
Figure IA1-7
Size: 7-7.5 u NucleusNone
CytoplasmColor: Pink, central pallor about 1/3 of the cell Contents: No mitochondria
MEGALOBLASTIC MATURATION SERIES
Megaloblastic Series
BLOOD CELLS Red Blood Cells
Figure IA1-8
Promegaloblast (Megaloblastic Rubriblast)
Basophilic Megaloblast (Megaloblastic Prorubricyte)
Polychromatophilic Megaloblast (Megaloblastic Rubricyte)
Orthochromic Megaloblast (Megaloblastic Metarubricyte)
Polychromatophilic Megalocyte (Megaloblastic Reticulocyte)
Megalocyte (Oval Macrocyte)
12 UNIT I Cell Descriptions
Promegaloblast (Megaloblastic Rubriblast)
Size: 19-27ii NucleusShape: Round or irregular N /C Ratio: 5:1 Color: PurpleChromatin: Fine and closely meshed Nucleoli: Multiple
CytoplasmColor: Deep blueContents: Nongranular with perinuclear halo
Clinical Conditionst Vitamin B12 deficiencyt Folic acid deficiency Congenital dyserythropoietic anemia I Erythroleukemia (FAB-M6a)t Pure erythroid leukemia (FAB-M6b) Acute erythroid leukemia (WHO)
BLOOD CELLS Red Blood Cells 13
Basophilic Megaloblast (Megaloblastic Prorubricyte)
Figure IA1-10
Size: 17-24 u NucleusShape: Round N /C Ratio: 4:1 Color: PurpleChromatin: Coarser than previous cell but still fine and open Nucleoli: Not visible
CytoplasmColor: Deep blueContents: Faint perinuclear halo
Clinical ConditionsI Vitamin B12 deficiencyt Folic acid deficiency Congenital dyserythropoietic anemia t Erythroleukemia (FAB-M6a) Pure erythroid leukemia (FAB-M6b) Acute erythroid leukemia (WHO)
14 UNIT I Cell Descriptions
Polychromatophilic Megaloblast (Megaloblastic Rubricyte)
Figure IA1-11
Size: 15-20 n NucleusShape: Round and central N /C Ratio: 2:1 Color: PurpleChromatin: Minimal clumping, loosely defined Nucleoli: Not visible
CytoplasmColor: Blue-grey to pink-greyContents: More cytoplasm than in normoblastic cell
Clinical Conditionst Vitamin B12 deficiencyI Folic acid deficiency Congenital dyserythropoietic anemia Erythroleukemia (FAB-M6a)I Pure erythroid leukemia (FAB-M6b) Acute erythroid leukemia (WHO)
BLOOD CELLS Red Blood Cells 15
Orthochromic Megaloblast (Megaloblastic Metarubricyte)
Figure IA1-12
Size: 10-15 x NucleusShape: Round to slightly irregular, central or slightly eccentric N /C Ratio: 1:1Color: Deep purple but still some chromatin structure Chromatin: Clumped, but less than in normoblastic cell Nucleoli: Not visible
CytoplasmColor: Pink, with a hint of blueContents: More cytoplasm than in normoblastic cell
Clinical ConditionsI Vitamin B12 deficiencyI Folic acid deficiencyI Congenital dyserythropoietic anemiaI Erythroleukemia (FAB-M6a)I Pure erythroid leukemia (FAB-M6b)I Acute erythroid leukemia (WHO)
16 UNIT I Cell Descriptions
Polychromatophilic Megalocyte (Megaloblastic Reticulocyte)
Figure IA1-13
_ o * t *0 0 Q*
Size : 9- 1 5 u NucleusNone
CytoplasmColor: Pink, with a hint of blueClinical ConditionsI Vitamin B12 deficiencyI Folic acid deficiencyI Congenital dyserythropoietic anemiaI Erythroleukemia (FAB-M6a)I Pure erythroid leukemia (FAB-M6b)I Acute erythroid leukemia (WHO)
BLOOD CELLS Red Blood Cells 1 7
Megalocyte (Oval Macrocyte)
Size: 9-12 n NucleusNone
CytoplasmColor: Pink, central pallor less distinct Contents: Increased hemoglobin content
Clinical ConditionsI Vitamin B12 deficiencyI Folic acid deficiencyI Congenital dyserythropoietic anemiaI Myelodysplastic syndromesI NewbornI Erythroleukemia (FAB-M6a)I Pure erythroid leukemia (FAB-M6b)I Acute erythroid leukemia (WHO)
IRON-DEFICIENT MATURATION SERIES
Iron-Deficient Series
18 UNIT I Cell Descriptions
Iron-Deficient Pronormoblast (Iron-Deficient Rubriblast)
Iron-Deficient Basophilic Normoblast (Iron-Deficient Prorubricyte)
Iron-Deficient Polychromatophilic Normoblast (Iron-Deficient Rubricyte)
Iron-Deficient Orthochromic Normoblast (Iron-Deficient Metarubricyte)
Iron-Deficient Polychromatophilic Erythrocyte (Reticulocyte)
Figure IA1-15
Iron-Deficient Erythrocyte (Hypochromic/Microcytic)
BLOOD CELLS Red Blood Cells 19
Iron-Deficient Pronormoblast (Iron-Deficient Rubriblast)
Figure IA1-16
iSK
Size: 14-20 i NucleusShape: Irregularly round to slighy oval N /C Ratio: 5:1 Color: Purple-red Chromatin: Fine, but granular Nucleoli: Present, but not distinct
CytoplasmShape: Irregular Color: Deep blueContents: Golgi; mitochondria, which produce a lighter blue perinuclear halo
Clinical ConditionsI Iron deficiency
2 0 UNIT I Cell Descriptions
Iron-Deficient Basophilic Normoblast(Iron-Deficient Prorubricyte)
*i
Figure IA1-17
Size: 10-15)1 NucleusShape: Round, centered N /C Ratio: 5:1Color: Purple, interspersed with light areas Chromatin: Granular to slightly lumpy Nucleoli: Usually not visible
CytoplasmShape: Irregular Color: Deep blueContents: Golgi may produce a light blue area near the nucleus; many
mitochondria
Clinical Conditions
BLOOD CELLS Red Blood Cells 21
Iron-Deficient Polychromatophilic Normoblast(Iron-Deficient Rubricyte)
: fr5 % t*
tin # mFigure IA1-18 t %
Size: 9-12 n NucleusShape: Round N /C Ratio: 2:1 Color: Purple-redChromatin: Lumpy, with lighter parachromatin Nucleoli: None
CytoplasmColor: Bluer than in normoblastic maturation Contents: Lesser amount with shaggy blunt extensions
Clinical Conditionst Iron deficiency
2 2 UNIT I Cell Descriptions
Iron-Deficient Orthochromic Normoblast(Iron-Deficient Metarubricyte)
Figure IAl-19 L
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IO mi
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M L e r
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# 4
Size: 7-11 n NucleusShape: Round N /C Ratio: 1:2 Color: Blue-purpleChromatin: Condensed and homogeneous Nucleoli: None
CytoplasmShape: IrregularColor: Pink, with residual blueness of RNA
Clinical ConditionsIron deficiency
BLOOD CELLS Red Blood Cells 2 3
Iron-Deficient Polychromatophilic Erythrocyte (Reticulocyte)
Figure IA1-20
o.0.|| oo q o
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o ,o V V ? O a - O q _ 9
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Size:
Iron-Deficient Erythrocyte (Hypochromic/Microcytic)
2 4 UNIT I Cell Descriptions
Figure IA1-21
Size:
BLOOD CELLS Red Blood Cells 2 5
DISTRIBUTION
Agglutination
Figure IA1-22
Cell TypeMature red blood cells
DescriptionRandom masses or clusters o f cells
Clinical Conditions Exposure to a variety of antibodies t Hemolytic anemia (autoimmune) Atypical pneumonia Staphylococcal infections Trypanosomiasist Cold agglutinin disease
Rouleaux
2 6 UNIT I Cell Descriptions
Figure IA1-23
Cell TypeMature red blood cell
DescriptionShort or long stacks o f cells (three or four or more) resembling coins;
often a blue-staining background is also present
Clinical ConditionsI HyperproteinemiaI Multiple myelomaI MacroglobulinemiaI Increased fibrinogen (infection, pregnancy)
BLOOD CELLS Red Blood Cells 2 7
SHAPES
Acanthocyte
Cell TypeMature red blood cell
DescriptionSpherical and densely stained cell with 3-12 spicules o f uneven length and width
around the surface
Clinical Conditionst Inherited lipid disorder (abetalipoproteinemia) Alcoholic cirrhosis Malabsorption states t Neonatal hepatitisI Pyruvate kinase deficiency
2 8 UNIT I Cell Descriptions
Codocyte (Target Cell)
Figure IA1-25
Cell TypeMature red blood cell
DescriptionBell shaped, with a thin wall having a greater-than-normal surface membrane:volume
ratio; central area o f hemoglobin, a clear ring, and a peripheral ring of hemoglobin, giving an appearance o f a bulls eye
Clinical Conditions Hemoglobinopathies Thalassemiat Obstructive liver diseaseI Iron deficiency anemia
BLOOD CELLS Red Blood Cells 2 9
Dacryocyte (Teardrop Cell)
Figure IA1-26
Cell TypeMature red blood cell
DescriptionPear-shaped cell with a blunt pointed projection
Clinical Conditionst Extramedullary hematopoiesis (myelofibrosis, myelophthisic anemia) t Megaloblastic anemia I Thalassemia Hypersplenism
3 0 UNIT I Cell Descriptions
Degmacyte (Bite Cell)
S J B LMW
3 r -
P a O A * *Q v a I
* aV3"
.JM
Figure IA1-27
o >o
___________________ ____________
< %
Cell TypeMature red blood cell
DescriptionSemicircular area (denatured and precipitated masses of hemoglobin) of cell
removed by spleen; these cells may show multiple peripheral defects
Clinical Conditions Drug-induced anemias Glucose-6-phosphate dehydrogenase deficiency Thalassemia Unstable hemoglobinopathies
BLOOD CELLS Red Blood Cells 31
Drepanocyte (Sickle Cell)
Figure IA1-28
. cA * i Cell TypeMature red blood cell
DescriptionElongated cell due to polymers o f abnormal hemoglobin; terminal projections,
causing the cell to take on an irregular shape; usually lacks a central pallor
Clinical Conditions Hemoglobinopathies (SS, SC, SD, S-/3 thalassemia)
Echinocyte (Burr Cell)
3 2 UNIT I Cell Descriptions
Figure IA1-29
Cell TypeMature red blood cell
DescriptionCell with evenly distributed, short spicules; the spicules have a blunt end;
retains central pallor
Clinical Conditions Slow drying in high humidity I Renal insufficiencyI Pyruvate kinase deficiencyt Stored blood Severe dehydration Burns
i e f * s .c o r r
Figure IA2-20b
V ^ * t ! S * A i v * -- 8 v i
reMBtj
BLOOD CELLS White Blood Cells
Cell TypeNeutrophil
DescriptionHeterozygous inherited disorder (Pince-Nez)Bilobed or dumbbell-shaped nucleus; clumped, coarse chromatin; normal
cytoplasmic granules Homozygous inherited disorder (Stodtmeister)Round or oval nuclei; dense clumped coarse chromatin; normal cytoplasmic
granules
Clinical ConditionI Pelger-Hutinherited disorder (autosomal dominant)
Pelgeroid Cells
76 UNIT I Cell Descriptions
Figure IA2-21
Cell TypeNeutrophil
DescriptionNucleus resembles Pelger-Hut (round or bilobed); few or no cytoplasmic granules
Clinical Conditionst Myelodysplastic syndromes Acute myelogenous leukemiasdysplastic finding Myelodysplastic/myeloproliferative diseases
BLOOD CELLS White Blood Cells 77
CYTOPLASM IC INCLUSIONS
Alder-Reilly Bodies
i t
Figure IA2-22
Cell TypeNeutrophil, eosinophil, basophil; occasionally lymphocyte and monocyte
DescriptionInherited condition (autosomal recessive)Dense blue cytoplasmic granules consisting o f stored mucopolysaccharides and
sphingomyelin Normal nuclear maturation
Clinical Condition Mucopolysaccharidoses (e.g., Hurlers syndrome, Hunters syndrome)
7 8 UNIT I Cell Descriptions
Auer Rods
Figure IA2-23
Cell TypeMyeloblast and monoblast (rare)
DescriptionReddish-purple, rod-shaped cytoplasmic inclusions Alignment of primary granules
Clinical Conditions Acute myelocytic leukemia without maturation (M l) (FAB) Acute myelocytic leukemia with maturation (M2) (FAB) Acute promyelocytic leukemia (M3) (FAB) Acute myelomonocytic leukemia (M4) (FAB)I Erythroleukemia (M6a) (FAB) Acute myelocytic leukemia with multilineage dysplasia Chronic myelocytic leukemia in blastic transformation AML with t(8;21) (WHO) AML with t(15;17) (WHO)I AML with inv 16 or t (l6 ;l6) (WHO)
BLOOD CELLS White Blood Cells 7 9
Chdiak-Higashi Granules
Figure IA2-24
Cell TypeGranulocyte, lymphocyte, monocyte
DescriptionInherited (autosomal recessive)Many large, greenish primary cytoplasmic granules or many large, reddish-purple
secondary cytoplasmic granules
Clinical ConditionChdiak-Higashi Syndromesevere and often fatal infections in children; complete or partial albinism
Dohle Body
8 0 UNIT I Cell Descriptions
Figure IA2-25
Cell TypeNeutrophil
DescriptionRound or rod-shaped, light-blue cytoplasmic inclusions, often located near cell
membraneInclusions represent ribosomes or rough endoplasmic reticulum
Clinical ConditionsI InfectionsI Drug intoxicationI BurnsI Myelodysplastic syndromes, often seen in the degranulated segmented cellsI May-Hegglin anomalyI PregnancyI Growth factor therapy
BLOOD CELLS White Blood Cells 81
Faggot Cell
Figure IA2-26
Cell TypePromyelocyte
DescriptionGroups or stacks o f cigar-shaped rods in cytoplasm
Clinical Conditions Acute promyelocytic leukemia (M3, M3v) (FAB) AML with t(15;17) (WHO)
8 2 UNIT I Cell Descriptions
May-Hegglin Inclusion
Figure IA2-27
Cell TypeNeutrophil, eosinophil, basophil, monocyte
DescriptionInherited (autosomal dominant)Large, blue, crescent-shaped cytoplasmic inclusions consisting of RNA Resemble large Dohle bodies Presence of enlarged platelets
Clinical ConditionI May-Hegglin anomaly
BLOOD CELLS White Blood Cells 8 3
Microorganisms
Figure IA2-28
Cell TypeNeutrophil, monocyte
DescriptionMicroorganisms in cytoplasm
Clinical ConditionI Microbial infections
8 4 UNIT I Cell Descriptions
Toxic Granulation
Figure IA2-29
J
Cell TypeNeutrophil
DescriptionHeavy, coarse, dark-blue primary cytoplasmic granules Strong peroxidase reactivity
Clinical ConditionsI InfectionsI BumsI Drug intoxicationI InflammationI Growth factor therapy
BLOOD CELLS White Blood Cells 8 5
Vacuolization
Figure IA2-30
Cell TypeNeutrophil, monocyte
DescriptionVacuoles (holes) in cytoplasm
Clinical ConditionsI Severe infectionI Cell degenerationI PhagocytosisI BurnsI Toxins
8 6 UNIT I Cell Descriptions
LE Cell
Figure IA2-31
Cell TypeNeutrophil
DescriptionLarge, spherical body in cytoplasm is homogeneous, has no nuclear structure, and
stains pale purple; nucleus of cell is pushed to periphery and appears to wrap around cytoplasmic inclusion
Clinical Condition Systemic lupus erythematosus
BLOOD CELLS White Blood Cells 8 7
MALIGNANT GRANULOCYTES
Type I Myeloblast (FAB); Agranular Blast (WHO)
Figure IA2-32
Size: 14-18 u NucleusShape: Oval or round N /C Ratio: 6:17:1 Color: Dark purple Chromatin: Fine Nucleoli: 1-3
CytoplasmColor: Light to medium blue Contents: Without azurophilic granules
Clinical Conditions Acute myelocytic leukemia minimally differentiated (MO) (FAB) Acute myelocytic leukemia without maturation (M l) (FAB) Acute myelocytic leukemia with maturation (M2) (FAB) Acute myelomonocytic leukemia (M4) (FAB) t Erythroleukemia (M6a) (FAB)I Myeloproliferative diseasesCML, PMF
Type II Myeloblast (FAB); Granular Blast (WHO)
8 8 UNIT I Cell Descriptions
Figure IA2-33 i : i
Size: 10-18j, NucleusShape: Oval or roundN /C Ratio: Slightly lower than a type IColor: Dark purpleChromatin: Slightly more condensed than a type I Nucleoli: 2-5
CytoplasmColor: Medium blueContents:
BLOOD CELLS White Blood Cells 8 9
Type III Myeloblast (FAB); Granular Blast (WHO)
Figure IA2-34
e
%
Size: 10-18 d NucleusShape: Oval or round N /C Ratio: Lower than a type I Location: Centrally located Color: Dark purpleChromatin: Slightly more condensed than type II Nucleoli: Less visible
CytoplasmColor: Medium blueContents: >20 azurophilic granules but do not obscure the nucleus
Clinical ConditionsI Acute myelocytic leukemia with maturation (M2) (FAB)I AML with t(8;21) (WHO)
9 0 UNIT I Cell Descriptions
Abnormal Promyelocyte
Figure IA2-35a
Figure IA2-35b
O - O
HypergranularType
BLOOD CELLS White Blood Cells 91
Size: 18-25 .i NucleusShape: Round or, more commonly, reniform or bilobed N /C Ratio: 2:1 Color: PurpleChromatin: Relatively fine, becoming coarser Nucleoli: 2-3, varying from visible to indistinct
CytoplasmHypergranular Type:
Color: Intensely basophilicContents: Large red to purple granules; Auer rods may be numerous and
intertwined, giving a haystack appearance (faggot cells); may obscure the nucleus
Microgranular Type:Color: Moderately basophilicContents: Small, indistinct granules that are difficult to see with the light
microscope; Auer rods are often found but not as abundant as those found in the hypergranular type
Clinical Conditions Acute promyelocytic leukemia (M3, M3v) (FAB) AML with t(15;17) (WHO)
ABNORMAL MATURATION
Dysgranulopoiesis
9 2 UNIT I Cell Descriptions
Cell TypeGranulocyte cell line
DescriptionNuclear/cytoplasmic asynchronyCytoplasm shows persistence o f basophilia and may exhibit enlarged granules,
hypogranulation, or agranularity Nuclear asynchrony includes hypersegmentation or hyposegmentation
Clinical ConditionsI Myelodysplastic syndromes I Some leukemias
BLOOD CELLS White Blood Cells 9 3
Giant Myelocytes, Metamyelocytes, and Bands
Metamyelocyte
Band
Myelocyte
Figure IA2-37
Cell TypeMyelocyte, metamyelocyte, band
DescriptionGiant myelocytes are 17-26 U; nucleus is round, oval, or flattened on one side, dark
purple, coarse chromatin, and no visible nucleoli; cytoplasm is pinkish-blue with variable numbers of granules
Giant metamyelocytes are 15-22 L I ; typical dark purple, kidney-shaped nucleus;cytoplasm is pink-blue with pinkish to reddish-blue granules
Giant bands are 14-20 L I ; dark purple nucleus is band shaped; cytoplasm is pink-blue with pinkish-blue granules
Clinical Conditionst Folate deficiency t Vitamin B12 deficiency t Chemotherapy (folate antagonists)
MONOCYTES
Monocyte Maturation Series
9 4 UNIT I Cell Descriptions
BLOOD CELLS White Blood Cells 9 5
Monoblast
Figure IA2-39
Size: 14-20 u NucleusShape: Round or oval N /C Ratio: 3 :l- l :l Color: Light bluish-purple Chromatin: Fine and distinct Nucleoli: 1-5
CytoplasmColor: Blue-gray Contents: No granules
Clinical Conditions Acute myelomonocytic leukemia (M4) (FAB) Acute monoblastic leukemia (M5a) (FAB) Acute monocytic leukemia (M5b) (FAB) Acute myelomonocytic leukemia (WHO) Acute monoblastic and monocytic leukemia (WHO)
Promonocyte
9 6 UNIT I Cell Descriptions
Figure IA2-40
Size: 14-20 u NucleusShape: Oval or indented N /C Ratio: 2 : l- l: l Color: Light bluish-purple Chromatin: Fine reticular pattern Nucleoli: 1-5
CytoplasmColor: Blue-gray, finely granular (ground glass) appearance Contents: Many fine, dustlike, bluish granules; occasional vacuole
Clinical Conditions Acute myelomonocytic leukemia (M4) (FAB) Acute monoblastic leukemia (M5a) (FAB) Acute monocytic leukemia (M5b) (FAB)t Myelodysplastic/myeloproliferative diseaseschronic myelomonocytic leukemia
(CMML) Acute myelomonocytic leukemia (WHO) Acute monoblastic and monocytic leukemia (WHO)
BLOOD CELLS White Blood Cells 9 7
Monocyte
Size: 14-21 1 NucleusShape: Horseshoe shaped or indented; nuclear folding may give the appearance
of brainlike convolutions N /C Ratio: 1:1 Color: Dark purpleChromatin: Fine, delicate strands in linear arrangement with light spaces between
strands Nucleoli: None
CytoplasmColor: Blue-gray, finely granular (ground glass) appearance Contents: Many fine, dustlike, bluish granules; occasional vacuole and blunt
pseudopods
Clinical ConditionsI Myelodysplastic/myeloproliferative diseases CMML, juvenile myelomonocytic
leukemia (JMML)I Myeloproliferative diseases CML (few cases)I Severe infections
LYMPHOCYTES
Lymphocyte Maturation Series
9 8 UNIT I Cell Descriptions
Figure IA2-42
Lymphoblast
Lymphocyte
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BLOOD CELLS White Blood Cells 9 9
Lymphoblast
Figure IA2-43
Size: 10-22 i NucleusShape: Round or oval, centrally or eccentrically placed N /C Ratio: 7:1-4:1 Color: Reddish-purpleChromatin: Fine, lacy pattern to moderately coarse Nucleoli: 1-2 prominent
CytoplasmColor: Moderate to dark blueContents: Smooth, no granules, occasional vacuoles
Clinical Conditions Precursor lymphoblastic leukemia (I.,, U) (FAB) t Burkitt lymphoma (L3) (FAB) Lymphoblastic lymphoma
Mature Lymphocyte
1 0 0 UNIT I Cell Descriptions
Figure IA2-44
Size : 7-15 n NucleusShape: Round or slightly indented, eccentric N /C Ratio: 3:1 Color: Deep purple-blue Chromatin: Course and clumped Nucleoli: None visible
CytoplasmColor: Sky blue to deep blueContents: Scant and usually nongranular; few azurophilic granules may be seen
BLOOD CELLS White Blood Cells 101
REACTIVE LYMPHOCYTES
Reactive Lymphocytes (Atypical Lymphocytes)
Cell TypeLymphocyte
DescriptionCell size ranges from 10-25 fiNucleus can be oval, notched, indented, or elongated One or more large nucleoli may be visibleCytoplasm is often abundant and stains pale to deep blue and darker at periphery;
may be partially indented by adjacent red cells; few lavender granules and/or vacuoles
Clinical ConditionsI Infectious mononucleosisI Other viral diseases including cytomegalovirus, toxoplasmosis, hepatitis, and cat
scratch fever
102 UNIT I Cell Descriptions
Cleaved Cell (Butt Cell)
Figure IA2-46
Cell TypeLymphocyte
DescriptionSmall, mature lymphocyte with cleaved nucleus
Clinical Conditions Pertussis (Whooping cough)I LymphomaI Chronic lymphocytic leukemia
BLOOD CELLS White Blood Cells 1 0 3
Immunoblast
Figure IA2-47
Cell TypeLymphocyte
DescriptionLarge cell (12-25 u) with bluish-purple nucleus and fine chromatin pattern with
several prominent nucleoli Cytoplasm is deep blue
Clinical Conditions Viral and nonviral infections t Immune disorders
Large Granular Lymphocyte
1 0 4 UNIT I Cell Descriptions
Cell TypeLymphocyte
DescriptionLarge cells (14-16 u) with moderate to abundant pale blue cytoplasm Prominent azurophilic granules
Clinical ConditionsI T-gamma lymphoproliferative disease I Large granular lymphocytic leukemia I NK cell leukemia
BLOOD CELLS White Blood Cells 1 0 5
Large Lymphocyte
Figure IA2-49
Cell TypeLymphocyte
DescriptionNucleus is round or oval, may be slightly indented, with coarse chromatin pattern
and no visible nucleoli; moderate, pale-blue cytoplasm with rare purplish-red granules
Clinical ConditionI 10-12% o f lymphocytes is normal
Plasmacytoid Lymphocyte
1 0 6 UNIT I Cell Descriptions
Figure IA2-50
Cell TypeLymphocyte
DescriptionCell is intermediated between small lymphocyte and plasma cell (9-20 |i); nucleus
is centrally to slightly eccentrically located, indented or oval, with a developing perinuclear halo; chromatin strands are heavy or in dense blocks; cytoplasm is intensely basophilic and may contain few vacuoles
Clinical ConditionsI Viral and nonviral infectionsI Immune disordersI Plasma cell myelomaI Waldenstrom macroglobulinemia
MALIGNANT LYMPHOCYTES
Chronic Lymphocytic Leukemia Lymphocyte
BLOOD CELLS White Blood Cells 107
Figure IA2-51
Cell TypeLymphocyte
DescriptionCell size ranges from 10-15Nucleus is round, with an N/C ratio of 7:1-3:1Chromatin is clumped and may show a compartmentalization phenomenonNucleoli are inconspicuous or not visibleCytoplasm is sparse to abundant, clear, and lightly basophilic
Clinical ConditionsI Chronic lymphocytic leukemiaI Prolymphocytic leukemia/chronic lymphocytic leukemia I Prolymphocytic leukemia
108 UNIT I Cell Descriptions
Hairy Cell
Cell TypeLymphocyte
DescriptionScant to abundant agranular, light grayish-blue cytoplasm; numerous, irregular
cytoplasmic projections give a hairlike or ruffled appearance to plasma membrane; nucleus is round or oval and may occasionally appear kidney or hourglass shaped; loose and lacy chromatin pattern with one or two visible nucleoli
Clinical ConditionI Hairy cell leukemia
BLOOD CELLS White Blood Cells 1 0 9
Lt Lymphoblast (FAB)
)
Figure IA2-53
o
o
o
o _ o -
Cell TypeLymphoblast
DescriptionCell size ranges from 10-14 1Nuclear shape is regular or small cleaved and indentedPurple nucleus has a homogeneous and condensed chromatin patternNucleoli are inconspicuous or not visible (0-1)Scanty cytoplasm is moderately basophilic and rarely vacuolated
Clinical ConditionI Precursor lymphoblastic leukemia
110 UNIT I Cell Descriptions
L2 Lymphoblast (FAB)
Figure IA2-54
V O
# M O f lA #o ^ o *
____________________________________________________
Cell TypeLymphoblast
DescriptionCell size ranges from 14-22 i;Nucleus has an irregular or indented shape N/C ratio is average (4:1)Nucleus is purplish-red, with variable heterogeneous chromatin One to two nucleoli are often prominentCytoplasm is variable but occasionally intensely basophilic and rarely vacuolated
Clinical ConditionI Precursor lymphoblastic leukemia
BLOOD CELLS White Blood Cells 111
L3 Lymphoblast (FAB)
Figure IA2-55
Cell TypeLymphoblast
DescriptionCell size ranges from 14-18 /iNucleus is oval to round, purple, and has a finely stippled and homogeneous
chromatin pattern N/C ratio is 5:1-4:1One to two nucleoli are often prominentCytoplasm is intensely basophilic with prominent vacuolization
Clinical ConditionsI Burkitt lymphomaI Acute lymphoblastic leukemia (L3) (FAB)I Burkitt leukemia/lymphoma (WHO)
A
M
112 UNIT I Cell Descriptions
Prolymphocyte
Cell TypeLymphocyte
Size: 10-15 u DescriptionRound, centrally placed nucleus that is reddish-purple, with coarse, clumped
chromatin N/C ratio is 3:1-4:1 One prominent nucleolus Cytoplasm is abundant; light to moderate blue
Clinical Conditions Chronic lymphocytic leukemia (55% prolymphocytes) (FAB) Chronic lymphocytic leukemia/prolymphocytic leukemia (11-55%
prolymphocytes) (FAB) B cell prolymphocytic leukemia (>55% prolymphocytes) (WHO)
BLOOD CELLS White Blood Cells 113
LYMPHOMA CELLS
Lymphoblastic Lymphoma Cell
Figure IA2-57
Cell TypeLymphoblast
DescriptionCell size is variableNucleus is indented or convoluted, with fine chromatin pattern and small,
inconspicuous nucleoli Cytoplasm is scant
Clinical ConditionI Lymphoblastic lymphoma
11 4 UNIT I Cell Descriptions
Reed-Stern berg Cell
Figure IA2-58
A
i H # ,
f t * * t l* >f f r ' r
_______
J f i%m
Cell TypeLymphocytic lineage
DescriptionA large cell (50-100 LI) with an abundance of cytoplasmNucleus is often bilobed or binucleated, with prominent large nucleoli resembling
owl eyes; the two halves o f a binucleated cell often appear as mirror images Not found in peripheral blood; found in lymph nodes
Clinical ConditionI Hodgkin lymphoma
BLOOD CELLS White Blood Cells 1 1 5
Szary Cell
Figure IA2-59
Cell TypeLymphocyte
DescriptionSmall and large cell ranging from 8-30 LLNucleus has brainlike convolutions and is dark purple, with moderately coarse
chromatin; nucleoli are not visible Cytoplasm is scanty and pale to deep blue with occasional vacuoles
Clinical ConditionsI Cutaneous T-cell lymphoma (mycosis fungoides, Szary syndrome)I T4 lymphomas involving the skin
Small Cleaved Lymphoma Cell
116 UNIT I Cell Descriptions
Figure IA2-60
Cell TypeLymphoma cell
DescriptionCell size is 6-12 fi; nucleus is twisted, angulated, and indented, with clumped
chromatin and no nucleoli Cytoplasm is scant to imperceptible
Clinical ConditionI Small cleaved cell lymphoma
BLOOD CELLS White Blood Cells 1 17
Small B Lymphoma Cell
Figure IA2-61
Cell TypeLymphocyte
DescriptionCell is 10-25 //: round nucleus has clumped chromatin and may show a
compartmentalization phenomenon Nucleoli are inconspicuous or not visibleCytoplasm is sparse to abundant and clear and lightly basophilic
Clinical ConditionI Lymphoma
PLASMACYTES
Plasma Cell Series
118 UNIT I Cell Descriptions
M )
Figure IA2-62
Plasmablast
Proplasmacyte
Plasma cell
BLOOD CELLS White Blood Cells 119
Plasmablast
Figure IA2-63
f t
I
Size: 12-15 n NucleusShape: Round N /C Ratio: 5:1-4:1 Color: Purplish-red Chromatin: Fine and linear strands Nucleoli: 1-2
CytoplasmColor: Blue Contents: Nongranular
Clinical Conditionst Plasma cell leukemia I Plasma cell myeloma
1 2 0 UNIT I Cell Descriptions
Proplasmacyte
Size: 12-15 ij. NucleusShape: Round, eccentrically placed N /C Ratio: 5:1-4:1 Color: Purplish-red Chromatin: Moderately clumped Nucleoli: 0-2
CytoplasmColor: Dark blue, prominent light area next to nucleus Contents: Nongranular
Clinical Conditionst Plasma cell leukemiat Plasma cell myeloma Waldenstrom macroglobulinemia Response to infection
BLOOD CELLS White Blood Cells 121
Plasma Cell
Cell TypePlasma cell
DescriptionSize ranges from 9-20Dark purple nucleus is ovoid and eccentrically placed, with a wheel-spoke pattern No nucleoliCytoplasm is abundant and deep blue with a clear area next to the nucleus
Clinical ConditionsI Plasma cell dyscrasias I Response to infections
ABNORMAL PLASMA CELLS AND INCLUSIONS
1 2 2 UNIT I Cell Descriptions
Bilobed Plasma Cell
Figure IA2-66
Cell TypePlasma cell
DescriptionDark purple nucleus is bilobed rather than ovoid Cytoplasm is pale to deeply basophilic
Clinical ConditionI Plasma cell dyscrasias
BLOOD CELLS White Blood Cells 1 2 3
Dutcher Body
Figure IA2-67
Cell TypePlasma cell
DescriptionIntranuclear protein inclusions resulting from membrane-bound cytoplasm in the
nucleus
Clinical ConditionI Plasma cell dyscrasias
Flaming Plasma Cell
1 2 4 UNIT I Cell Descriptions
Figure IA2-68
Cell TypePlasma cell
DescriptionCytoplasmic immunoglobulin (often IgA) accumulating in the peripheral
cytoplasm; stains reddish-purple
Clinical ConditionI Plasma cell dyscrasias
BLOOD CELLS White Blood Cells 1 2 5
Mott Cell (Grape Cell)
Figure IA2-69
Cell TypePlasma cell
DescriptionCytoplasm filled with Russell bodies resembling clusters o f grapes
Clinical ConditionI Plasma cell dyscrasias
1 2 6 UNIT I Cell Descriptions
Russell Bodies
Figure IA2-70
Cell TypePlasma cell
DescriptionIndividual globules of immunoglobulin in cytoplasm, which represent rough
endoplasmic reticulum, smooth endoplasmic reticulum, and Golgi filled with immunoglobulin due to secretory obstruction; globules stain pink or blue depending on pH; if immunoglobulin disappears, colorless vacuoles result
Clinical Condition
5 *
Plasma cell dyscrasias
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CHAPTER 3
Megakaryocytes
127
NORMAL M EGAKARYOCYTIC MATURATION SERIES
Normal Megakaryocytic Series
128 UNIT I Cell Descriptions
BLOOD CELLS Megakaryocytes 129
Megakaryoblast
Figure IA3-2
Size: 20-50 f.i NucleusShape: Round, oval, or kidney shapedN /C Ratio: 5:l-3:lColor: Reddish-purple to purpleChromatin: Fine, distinct strands to dense chromatinNucleoli: Several, often indistinct or maybe more distinct in larger blasts
CytoplasmColor: Moderate to dark blueContents: Blunt cytoplasmic extensions; no granules to fine azurophilic granules
in the larger blasts
Clinical Conditionsft Acute megakaryoblastic leukemia (M7) (FAB) ft Myeloproliferative diseasesCML, PMF ft Myelodysplastic syndromes ft Acute megakaryoblastic leukemia (WHO)
1 3 0 UNIT I Cell Descriptions
Promega ka ryocyte
Size: 20-80 ll NucleusShape: Irregularly indented, with 2-4 lobes N /C Ratio: 1:1 Color: Dark purpleChromatin: Fine; condensed near periphery Nucleoli: Several
CytoplasmColor: Moderate blue to pinkish-blueContents: Few bluish granules; development o f demarcation membrane system
forming small cytoplasmic extensions
Clinical ConditionsI Acute megakaryoblastic leukemia (M7) (FAB)I Myeloproliferative diseases CML, PMF, essential thrombocytosis (ET)I Myelodysplastic syndromesI Acute myelocytic leukemia with multilineage dysplasia I Acute megakaryoblastic leukemia (WHO)
BLOOD CELLS Megakaryocytes
Megakaryocyte
Figure IA3-4
Size: 40-100 .i NucleusShape: Multilobular N /C Ratio: 1:1-1:12 Color: Dark purple Chromatin: Coarse, linear Nucleoli: None
CytoplasmColor: Pinkish-blueContents: Numerous reddish-blue granules
Clinical Conditionst Myeloproliferative diseasesCML, PMF, ET I Myelodysplastic syndromes Acute myelocytic leukemia with multilineage dysplasia
13 2 UNIT I Cell Descriptions
Platelets
Figure IA3-5
Size: 1-4 u NucleusNone
CytoplasmColor: Light blueContents: Small reddish-blue granules
ABNORMAL M EGAKARYOCYTIC CELLS
Giant Platelet
BLOOD CELLS Megakaryocytes 1 33
Figure IA3-6
Cell TypePlatelet
DescriptionPlatelet as large as or larger than erythrocytes or granulocytes; light blue with
small reddish-blue granules or degranulated (pale blue with no granules)
Clinical ConditionsI May-Hegglin syndromeI Myeloproliferative diseasesI SplenectomyI Myelodysplastic syndromes
1 3 4 UNIT I Cell Descriptions
Large Megakaryocyte
Figure IA3-7
Cell TypeMegakaryocyte
DescriptionLarge megakaryocyte with hyperlobulation
Clinical ConditionsI Vitamin B12 deficiencyI Folic acid deficiencyI Myelodysplastic syndromesI Idiopathic thrombocytopenic purpura
BLOOD CELLS Megakaryocytes 1 3 5
Large Mononuclear Megakaryocyte
Figure IA3-8
Cell TypeMegakaryocyte
DescriptionLarge megakaryocyte with a single nucleus
Clinical ConditionsI Myelodysplastic syndromes I Acute megakaryoblastic leukemia (M7) (FAB) I Acute megakaryoblastic leukemia (WHO)
1 3 6 UNIT I Cell Descriptions
Micromegakaryocyte
Figure IA3-9
Cell TypeMegakaryocyte
DescriptionSmall megakaryocyte about the size of a lymphocyteSingle-lobed nucleus resembles medium-sized lymphocyteOne or more platelet fragments attached to nucleus or scant cytoplasm
Clinical Conditions Myeloproliferative diseases t Myelodysplastic syndromes Acute megakaryoblastic leukemia (M7) (FAB) Acute megakaryoblastic leukemia (WFIO)
BLOOD CELLS Megakaryocytes 1 37
Vacuolated Megakaryocyte
Cell TypeMegakaryocyte
DescriptionMegakaryocyte or promegakaryocyte with a single or bilobed nucleus Vacuoles in the basophilic or minimal granule-forming cytoplasm
Clinical ConditionsI Myelodysplastic syndromes Acute megakaryoblastic leukemia (M7) (FAB) Acute megakaryoblastic leukemia (WHO)
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CHAPTER 4
Comparison o f Cells
1 3 9
140 UNIT I Cell Descriptions
Myeloblast, Myelocyte
Myelocyte
Myeloblast
Figure IA4-1
0
MyeloblastFine nuclear chromatinModerate amount of agranular blue cytoplasm N/C ratio higher
MyelocyteModerately clumped deep purple nucleusPresence o f some residual primary granules and the beginning of some secondary
granule formation in the cytoplasm
BLOOD CELLS Comparison of Cells 141
Myeloblast, Promyelocyte, Myelocyte
Promyelocyte
Myelocyte
Myeloblast
Figure IA4-2
MyeloblastHighest N/C ratioFinest nuclear chromatin pattern
PromyelocytePresence o f primary azurophilic granules Cytoplasm is moderate blue color
MyelocyteLowest N/C ratio Muddy gray cytoplasmic color Secondary granules are present Nuclear chromatin is more clumped
14 2 UNIT I Cell Descriptions
Myeloblast, Basophilic Normoblast
MyeloblastFiner nuclear chromatin pattern with visible nucleoli Cytoplasm has a lighter blue color
Basophilic NormoblastNucleus has a more clumped chromatin pattern Cytoplasm has a deeper blue color
BLOOD CELLS Comparison of Cells 1 4 3
Late Polychromatophilic Normoblast, Lymphocyte
Lymphocyte
Polychromatophilic normoblast
Figure IA4-4
Late Polychromatophilic NormoblastNucleus is deep purple and slightly eccentric Nuclear chromatin is intensely condensed Cytoplasm is pink with a bluish tinge
LymphocyteNucleus is pale purple and eccentric Nuclear chromatin is moderately condensed Cytoplasm is light blue and scanty
Monoblast, Promonocyte
1 4 4 UNIT I Cell Descriptions
Monoblast
Promonocyte
Figure IA4-5
MonoblastLarger cellRound nucleus with cleave evident One single nucleoli present Similar cytoplasms
PromonocyteIndented nucleus with a more condensed chromatin pattern
BLOOD CELLS Comparison of Cells 1 4 5
Monoblast, Myeloblast
0 0O O O
Monoblast
a . S *
Figure IA4-6
ivionoDiast
*1Myeloblast
MonoblastMore cytoplasmNucleus has finely dispersed chromatin with a vaguely noticeable cleave
MyeloblastHigher N/C ratio Finer chromatin pattern Smaller cell
1 4 6 UNIT I Cell Descriptions
Monocyte, Reactive Lymphocyte
Reactivelymphocyte
Monocyte
Figure IA4-7
MonocyteCell is largerLower N/C ratioFiner nuclear chromatin pattern
Reactive LymphocyteCell is smallerCondensed nuclear chromatin pattern Higher N/C ratio
BLOOD CELLS Comparison of Cells 1 47
Monocyte, Lymphocyte
Lymphocyte
Monocyte
Figure IA4-8
MonocyteLower N/C ratioFiner, lacy nuclear chromatin pattern Nucleus is indented Larger cell
LymphocyteNucleus is indented Intensely clumped nucleus Higher N/C ratio
Pronormoblast, Myelocyte
148 UNIT I Cell Descriptions
Pronormoblast
Myelocyte
Figure IA4-9
PronormoblastNucleus is large, deep purple, and centrally located Nuclear chromatin is finely stippledCytoplasm is intensely basophilic, with light areas o f mitochondria High N/C ratio
MyelocyteNucleus is light purple and slightly off centerNuclear chromatin is moderately condensed, with a prominent nucleoli (nucleoli
can still be present since this cell can still divide)Cytoplasm is grayish-blue with a hint of pink granulation Lower N/C ratio
BLOOD CELLS Comparison of Cells 1 4 9
Pronormoblast, Promyelocyte
Pronormoblast
Promyelocyte
Figure IA4-10
PronormoblastNucleus is large, deep purple, and centrally located Nuclear chromatin is finely stippledCytoplasm is intensely basophilic light areas o f mitochondria Light area next to the nucleus is the Golgi
PromyelocyteNucleus is purple and eccentrically located Nuclear chromatin is finely condensedCytoplasm has numerous dark, primary granules that have begun to obscure the
nucleus
1 5 0 UNIT I Cell Descriptions
Early Myelocyte, Late Myelocyte
Late
Early
Figure IA4-11
Early MyelocyteNucleus is light purple and slightly off centerNuclear chromatin is moderately condensed, with a prominent nucleoli Cytoplasm is grayish-blue, with a hint o f pink granulation
Late MyelocyteNucleus is purple, oval, and eccentricNuclear chromatin is fairly clumped and has an aggregated pattern with no visible
nucleoliCytoplasm is granulated with pink secondary granules
Metamyelocyte, Neutrophilic Band, Neutrophil
BLOOD CELLS Comparison o f Cells 151
Neutrophil
Metamyelocyte
Band
Figure IA4-12
MetamyelocyteNucleus is deep purple and has a kidney to slightly indented shape Nuclear chromatin is fairly coarse but not as clumped as the band or segmented
neutrophil
Neutrophilic BandNucleus is deep purple and markedly indented to make a band shape Nuclear chromatin is intensely clumped
Segmented NeutrophilNucleus is deep purple and has a segmented shape Nuclear chromatin is coarsely clumpedCytoplasm for all three cells is basically the same and seldom helpful in
differentiating the cells
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Section BBone Marrow
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CHAPTER 1
Cellularity
1 5 4 UNIT I C ell D esc rip tion s
NORMAL CELLULARITY
Normal Adult Cellularity
Description30-80% cellularity
BONE MARROW C e llu la r ity 1 5 5
Normal Elderly Cellularity
Figure IB1-2
Description iedilibros.com20-50% cellularity
1 5 6 UNIT I C ell D esc rip tion s
Normal Adolescent Cellularity
Desertion50-90% cellularity
BONE MARROW C e llu la r ity 1 57
Normal Newborn Cellularity
Figure IB 1-4
X L ,
Adult Hypocellularity
1 5 8 UNIT I C ell D esc rip tion s
Figure IB1-5
Description
BONE MARROW C e llu la r ity 1 5 9
Adult Hypercellularity
Description>50% cellularity
Clinical Conditionst Ineffective hematopoiesis; increased peripheral destruction I Malignancies Reactive processes
Erythropoiesis
1 6 0 UNIT I C e ll D esc rip tion s
t 4 : * * * * h *
'b\ *
?! a '*
t
-0 T V . * ^ V
* i V V v . ' v~i 1 V i * i r r f r V i V 1 . f *
% V * * ' *
Figure IB!-7
7 f 30% of marrow cellularity is erythrocytic
Clinical Conditionst Increased M:E ratiodecreased production o f erythrocytes Decreased M:E ratio increased production of erythrocytes or ineffective
erythropoiesis
BONE MARROW C e llu la r ity 161
Granulopoiesis
Description>40% o f marrow cellularity represents granulopoiesis
Clinical Conditionst Increased M:E ratioincreased granulocyte production Decreased M:E ratio decreased granulocyte production
Lymphopoiesis
1 6 2 UNIT I C e ll D esc rip tion s
Figure IB!-9
Description>20% of marrow cellularity is lymphocytic cells
Clinical ConditionsI Lymphoproliferative disordersI PlasmacytomasI Marrow aplasiasI Chronic lymphocytic leukemia
BONE MARROW C e llu la r ity 163
Megakaryopoiesis
Figure IB1-10
\ Jse> .
^ V-T- V - -
' * *
'
1*7
iV.: * i v
DescriptionUsually see 1-5 megakaryocytes per 1000 cells
Clinical ConditionsI Idiopathic thrombocytopenic purpuraI Myeloproliferative syndromesI Some myelodysplastic syndromes 5 q-syndromeI Acute megakaryoblastic leukemia (M7) (FAB)
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CHAPTER 2
Cells o f the Reticuloendothelial
System
NORMAL CELLS
1 6 6 UNIT I C e ll D esc rip tion s
Macrophage
Size: 7 5-80 u NucleusShape: Egg-shaped, indented, elongatedN /C Ratio: 2:1-1:1Color: PurpleChromatin: Spongy Nucleoli: None
CytoplasmColor: Sky blueContents: Coarse, azure granules; vacuoles; many neutral red bodies scattered
throughout
BONE MARROW Cells o f th e R e tic u lo e n d o th e lia l System 1 67
Size: 20-30 u NucleusShape: Round to oval N /C Ratio: 1:1Color: Purple with reddish hueChromatin: Fine, loosely bound but with areas o f parachromatin Nucleoli: 1 or more
CytoplasmIrregular outlineColor: Pale, blue, often retracted or folded, caused by smearing technique Contents: Reticulin fibers that cause an azurophilic appearance; may contain
phagocytized materials
ABNORMAL CELLS
Gaucher Cell
168 UNIT I Cell Descriptions
Figure IB2-3
>
ly^ll*H!fr^ mtCell TypeMacrophage
Size: 20-80 u DescriptionA pale-staining cell; the cytoplasm is filled with a fibrillar lipid, which gives the
appearance o f crumpled tissue paper or a wrinkled look; the nucleus is small, round, and eccentrically placed
Clinical Conditions Gaucher disease Thalassemia (pseudo-Gaucher cells) Chronic myelocytic leukemia (pseudo-Gaucher cells)
BONE MARROW Cells o f the Reticuloendothelial System 1 6 9
Niemann-Pick Cell
Cell TypeMacrophage
Size: 20-90 u Cell DescriptionPale staining; cytoplasm contains droplets o f sphingomyelin, giving it a globular
appearance; the nucleus is small, round, and eccentrically placed
Clinical ConditionI Niemann-Pick disease
1 7 0 UNIT I C e ll D esc rip tion s
Sea-Blue Histiocyte
Cell TypeHistiocyte
Size: 20-60 u DescriptionCell containing granules that stain a sea-blue or blue-green; nucleus is small,
round, and eccentric, with block chromatin
Clinical ConditionsI Sea-blue histiocytosisI Pseudo-sea-blue histiocytes are seen in the following:
I ThalassemiaI Chronic myelocytic leukemia I Polycythemia vera I Sickle cell anemia I SarcoidosisI Chronic granulomatous disease
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CHAPTER 3
NonhematopoieticCells
171
172 UNIT I C e ll D esc rip tion s
Osteoblast
Size: Frequently Found in Clumps, bu t Each Individual Cell Ranges from 25-50 u NucleusShape: Oval or round; eccentric N /C Ratio: 1:31:4 Color: PurpleChromatin: Finely granular with clumps; some areas of parachromatin Nucleoli: 1-3 present, small, light blue
CytoplasmColor: Pale blue to dark blue with blurred outlines Contents: Round, pink-gray areas (archoplasm)
BONE MARROW N onh e m a to p o ie tic Cells 1 7 3
Osteoclast
Figure IB3-2
Size: Usually >100 u NucleusPolyploid and scattered throughout cell; not interconnectedShape: RoundN /C Ratio: 4:1-2:1-1:1Color: PurpleChromatin: DenseNucleoli: Usually 1-2 present in each nucleus
CytoplasmColor: Light blue to pink, giving a cloudy appearance Contents: Coarse granules
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Section CCytochemistry
CHAPTER 1
Cytochemical Stains
ACID PHOSPHATASE REACTION
With Tartrate Inhibition (TRAP)
1 7 6 UNIT I C ell D esc rip tion s
CYTOCHEMISTRY C ytochem ica l S tains 1 7 7
Cell TypeHairy cells, histiocytes, activated lymphocytes, and activated macrophages
DescriptionAcid phosphatase (isoenzyme 5) is resistant to tartrateHairy cells and histiocytes contain this acid phosphatase, are resistant to inhibition,
and will demonstrate positivity (color is dependent on couplers used)
Clinical ConditionI Hairy cell leukemia
ACID PHOSPHATASE REACTION
Without Tartrate Inhibition
1 78 UNIT I C ell D esc rip tion s
Figure 1C 1-3
Positive
Cell TypeMost nucleated cells o f the hematopoietic system and platelets
DescriptionPositivity is indicated by a diffuse granular red reaction product The red product will disappear or contain only a small amount o f reactivity after
tartrate is added to the reaction Focal positivity may be found in blasts of T-cell ALL
Clinical ConditionsI Some T-cell precursor lymphoblastic leukemia I T-cell prolymphocytic leukemia I T-cell lymphoproliferative disorder I Szary syndrome
f EH
With Fluoride Inhibition
CYTOCHEMISTRY C ytochem ica l Stains 1 7 9
NONSPECIFIC ESTERASE REACTION
Figure IC1-4
Negative for inhibition.
Figure 1C 1-5
# . s
J ** 1 *
H m c o r i K
* 1
", -
^ r iin m
/Positive for inhibition.
1 8 0 UNIT I C e ll D esc rip tion s
Cell TypeMonocytic line
DescriptionMegakaryocytes, histiocytes, and macrophages demonstrate positivity Lymphocytes may have a punctate positivity or foci of positivity for T-cells Monocytes are sensitive to fluoride inhibition and will not show positivity
Clinical ConditionsI Acute myelomonocytic (M4) (FAB) and monocytic (M5) (FAB) leukemias are
inhibited by fluoride I Acute lymphocytic leukemia or leukemias of granulocytic origins are not
inhibited
CYTOCHEMISTRY C ytochem ica l Stains 181
Without Fluoride Inhibition
NONSPECIFIC ESTERASE REACTION
Figure 1C 1-6 Negative
Figure 1C 1-7 Positive
18 2 UNIT I Cell Descriptions
Cell TypeMonocytic line
DescriptionMegakaryocytes, histiocytes, and macrophages demonstrate positivity Lymphocytes may have a punctate positivity or foci of positivity for T-cells Monocytes are sensitive to fluoride inhibition and will not show positivity
Clinical ConditionsI Acute myelomonocytic (M4) (FAB) and monocytic (M5) (FAB) leukemias are
inhibited by fluoride I Acute lymphocytic leukemia or leukemias of granulocytic origins are not
inhibited
CYTOCHEMISTRY Cytochemical Stains 1 8 3
SPECIFIC ESTERASE REACTION
Figure 1C 1-8 Negative
Figure IC1-9 Positive
1 8 4 UNIT I Cell Descriptions
Cell TypeSome myeloblasts, promyelocytes, myelocytes, metamyelocytes, bands, segmented
neutrophils, and abnormal eosinophils
DescriptionEsterases are enzymes that are capable of hydrolyzing the aliphatic and aromatic
ester bonds of the substrate naphthol AS-D chloroacetate Produces a positive reaction, indicated by red to magenta color
Clinical ConditionsI Differentiates granulocytes from lymphocytes and monocytes I Acute myelocytic leukemia without maturation (M l) (FAB)I Acute myelocytic leukemia with maturation (M2) (FAB)I Acute promyelocytic leukemia (M3) (FAB)I Acute myelomonocytic leukemia (M4) (FAB)I Acute myelomonocytic leukemia with abnormal bone marrow eosinophils I AML with recurrent genetic abnormalities (WHO)
AML with t(8;21)AML with t(15;17)AML with inv 16 or t ( l6; l6)
CYTOCHEMISTRY Cytochemical Stains 1 8 5
COMBINED ESTERASE REACTION
Figure IC1-10 Positive
Cell TypeDifferentiation of granulocytic and monocytic series
DescriptionBoth alpha-naphthyl acetate (nonspecific) and naphthyl chloroacetate (specific)
are used as substrates Monocytic series demonstrates positivity with the nonspecific esterase Granulocytic series demonstrates a positive reaction with the specific esterase
(color depends on couplers used)
Clinical ConditionsI Acute myelomonocytic leukemia (M4) (FAB)demonstrates the coexpression of
granulocytic and monocytic enzymes I Acute monoblastic leukemia (M5a) (FAB)I Acute monocytic leukemia (M5b) (FAB)
1 8 6 UNIT I Cell Descriptions
IRON STAINPRUSSIAN BLUE REACTION
Figure IC1-11Negative
Figure IC1-12Positive
CYTOCHEMISTRY Cytochemical Stains 187
Cell TypeErythroblasts, erythrocytes, macrophages, histiocytes
DescriptionIron in the form of hemosiderin is normally present in developing normoblasts
and in the reticuloendothelial cells o f the bone marrow. A Prussian blue color is produced when ferric iron o f hemosiderin reacts with an acid ferrocyanide solution to form ferric ferrocyanide.
Positivity or the presence of iron is indicated by the presence o f blue to blue-green granules
May be used to determine the presence o f iron stores in the marrowMay be used to demonstrate increased numbers of sideroblasts or the presence
of pathologic ferric iron located in mitochondria of the erythroblast (ringed sideroblast)
Clinical ConditionsI Myelodysplastic syndromesI Acute erythroleukemia (M6) (FAB)I ThalassemiasI Intramacrophage iron is decreased in iron deficiency and increased in
hemochromatosis and anemia o f chronic diseases
1 8 8 UNIT I Cell Descriptions
ACID ELUTION (KLEIHAUER-BETKE STAIN)
Cell TypeRed blood cells
DescriptionCells containing hemoglobin F will appear pink to redCells containing no hemoglobin F will have only their outer membrane visible
(ghost cells)
Clinical ConditionsI Hereditary persistence o f fetal hemoglobin I Myelodysplastic syndromesI Some leukemias
CYTOCHEMISTRY Cytochemical Stains 1 89
LEUKOCYTE ALKALINE PHOSPHATASE STAIN
0
Figure IC1-14
Figure IC1-17
Figure IC1-18
1 9 0 UNIT I Cell Descriptions
Cell TypeGranulocyte distinguishes leukemoid reaction from chronic myelogenous leukemia
DescriptionLAP is an enzyme associated with the specific granules Presence of leukocyte alkaline phosphatase activity indicates intracellular
metabolic activityPositivity is indicated by either a ruby red color or a blue-purple color Positivity is quantitated100 consecutive bands or segmented neutrophils are scored using the following
criteria:0 Colorless1 Diffuse positivity; occasional granules2 Diffuse positivity; moderate numbers of granules3 Strong positivity; numerous granules4 Very strong positivity; dark, confluent granules
The scores of the 100 cells are summed
Clinical ConditionsIncreased:
I Leukemoid reaction I Polycythemia vera I Pregnancy I InfectionsI Chronic myelocytic leukemia blast crisisI Myelofibrosis
Decreased:
I Chronic myelogenous leukemiaI Paroxysmal nocturnal hemoglobinuriaI Some myelodysplastic syndromes due to degranulation
NEW METHYLENE BLUE AND BRILLIANT CRESYL BLUE STAINS
CYTOCHEMISTRY Cytochemical Stains 191
Figure IC1-19
Cell TypeRed blood cells
DescriptionSupravital stains commonly used in demonstrating aggregates of RNA in immature
erythrocytes (reticulocytes)Pappenheimer bodies, Howell-Jolly bodies, and Heinz bodies are also stained
Clinical ConditionsI Hemolytic anemiasI Folate deficiencyI Vitamin B12 deficiencyI Glucose-6-phosphate dehydrogenase deficiencyI Hb H diseaseI Myelodysplastic syndromes
PERIODIC ACID-SCHIFF REACTION
1 9 2 UNIT I Cell Descriptions
Figure IC1 Negative
Figure IC1 Positive
20
w w w .m e d ilib ro s ^ c p m c joO 1:4 O
O' O* O O o o
.7 :
21_______
5 % # :) o ft
CYTOCHEMISTRY Cytochemical Stains
Cell TypeNeoplastic erythroblasts, granulocytes, monocytes, lymphoblasts, and
megakaryocytes (most hematopoietic cells in variable quantities)
DescriptionPAS stains glycogenPositivity is indicated by a bright pink colorLymphocytes, granulocytes, monocytes, and megakaryocytes may be positive Normal erythroblasts are negative
Clinical Conditions Acute erythroleukemia (positive)I Thalassemia, iron deficiency, sideroblastic anemia (may be positive)t Burkitt lymphoma cells (negative) (L3) Acute lymphocytic leukemia (may have block positivity) (LI, L2) t Any severe dyserythropoiesis Acute myelomonocytic leukemia with abnormal bone marrow eosinophils
(granules are positive in the abnormal eosinophils)
PEROXIDASE STAIN
1 9 4 UNIT I Cell Descriptions
CYTOCHEMISTRY Cytochemical Stains 1 9 5
Cell TypeMyeloid cellsprimary granules o f the neutrophilic and eosinophilic series,
monocytes are faintly positive
DescriptionMyeloperoxidase is an enzyme capable of oxidizing dye substrates in the presence
o f hydrogen peroxide Positivity is indicated by the presence o f black or red-brown granules (color
depends on the substrate)Positivity is found in some myeloblasts, promyelocytes, myelocytes, metamyelocytes,
neutrophils, eosinophils, and faintly positive in monocytes Early myeloblasts, basophils, plasma cells, and lymphocytic cells and erythroid
cells are negative
Clinical ConditionsI Acute myelocytic leukemia without maturation (M l) (FAB)I Acute myelocytic leukemia with maturation (M2) (FAB)I Acute promyelocytic leukemia (M3) (FAB)I Acute myelomonocytic leukemia (M4) (FAB)I Erythroleukemia (M6a) (FAB)I AML with recurrent genetic abnormalities (WHO)
AML with t(8;21)AML with t(15;17)AML with inv 16 or t ( l6; l6)
SUDAN BLACK B STAIN
1 9 6 UNIT I Cell Descriptions
CYTOCHEMISTRY Cytochemical Stains 19 7
Cell TypeNeutrophilic and eosinophilic cells and their precursors, monocytes are weakly
positive
DescriptionSeparates AML from acute lymphocytic leukemia (ALL)Sudan black B stains lipid particles found in primary and secondary granules, as
well as giving a weak positivity in lysosomal granules found in the monocytic cells
Lymphocytes may rarely have these granulesPositivity is indicated by a brownish-black-colored granule
Clinical ConditionsI Acute myelocytic leukemia without maturation (M l) (FAB)I Acute myelocytic leukemia with maturation (M2) (FAB)I Acute promyelocytic leukemia (M3) (FAB)I Acute myelomonocytic leukemia (M4) (FAB)I Acute monoblastic leukemia (M5a) (FAB) (if myeloblasts are present)I Acute monocytic leukemia (M5b) (FAB) (if myeloblasts are present)I Erythroleukemia (M6a) (FAB) (if myeloblasts are present)I AML with recurrent genetic abnormalities (WHO)
AML with t(8;21)AML with t(15;17)AML with inv 16 or t ( l6; l6)
TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE REACTION
198 UNIT I Cell Descriptions
Figure 1C 1-26Negative
Figure 1C 1-27 Positive
CYTOCHEMISTRY Cytochemical Stains 1 9 9
Cell TypePrimitive lymphocytic cells and neoplastic cells
DescriptionEnzyme (DNA polymerase) found in the nucleusDemonstrated through immunofluorescent or immunoperoxidase procedures Positivity is demonstrated by a lime-green fluorescence or red to brownish-red
staining
Clinical ConditionsI T-cell acute lymphoblastic leukemiaI Precursor B-cell acute lymphocytic leukemiaI Lymphoblastic lymphomaI Chronic myelocytic leukemia with lymphoblastic transformation
TOLUIDINE BLUE STAIN
2 0 0 UNIT I Cell Descriptions
Figure 1C 1-28
Cell TypeBasophils and mast cells
DescriptionReacts with acid mucopolysaccharides (heparan sulfate) to form metachromatic
granulesPositivity is indicated by a red-violet colorMay not be positive in neoplastic disorders involving these cells
Clinical ConditionsI Mast cell diseaseI Basophilic leukemias
CYTOCHEMISTRY Cytochemical Stains 201
RETICULIN STAIN
Cell TypeNew formed collagen
DescriptionThe newly formed collagen is not cross-linked and stains in the biopsy sections
Clinical ConditionsI Elevated numbers of megakaryocytesI Myeloproliferative disordersI Lymphomas (follicular and Hodgkin)I Megakaryocytic leukemiaI Hairy cell leukemia
www.medilibros.com
Hematologic Disorders Section A Red Blood Cell Disorders Section b White Blood Cell Disorders Section c Miscellaneous Disorders
www.medilibros.com
Section ARed Blood Cell Disorders
CHAPTER 1
Erythrocytosis
POLYCYTHEMIA VERA
2 0 6 UNIT II Hematologic Disorders
Figure IIA1-2Bone marrow smear.
RED BLOOD CELL DISORDERS Erythrocytosis 2 0 7
Clinical Features Usually diagnosed in persons aged 55-70 years Slight male predominance Headache, confusion, altered mental status, dizziness, visual changes, tinnitus,
paresthesiast Weight loss, epigastric pain, gout, pruritus, thrombosis, and hemorrhage I Plethora, hypertension, and a mild to moderate degree o f splenomegaly and
hepatomegaly
PathologyI MalignancyI Excessive bone marrow production o f red blood cells and an increase in total
red blood cell volumeI White blood cell and platelet counts may also increase to a lesser extentI Increased blood viscosityI Thrombosis is a complication in more than half o f the casesI Myelofibrosis or acute myeloid leukemia may developI Polycythemic stageI Increased red blood cell massI Spent phase and postpolycythemic myelofibrosis and myeloid metaplasiaI AnemiaI Bone marrow fibrosisI Extramedullary hematopoiesisI Hypersplenism
Laboratory FeaturesWhite Blood Cellst Increased in about two-thirds of patients t Immature forms usually not seen t Eosinophils and basophils may be increased Leukocyte alkaline phosphatase increased in three-quarters of cases
PlateletsI Normal to increased
Red Blood CellsI Hemoglobin level increased I Hematocrit level increased I Red blood cell mass increased
Bone Marrow Hyperplastict Erythroid hyperplasiat Increased megakaryocytes Granulocytic hyperplasiaI Increased reticulin in postpolycythemic myelofibrosis and myeloid metaplasiat Iron stores are often depleted
2 0 8 UNIT II Hematologic Disorders
Traditional Criteria for DiagnosisMeet three major criteria or two major and two minor criteria Major criteria
Increased red blood cell mass SplenomegalyI Normal oxygen level
Minor criteria
> Platelet count >400 X 109/L White blood cell count >12 X 109/L Elevated leukocyte alkaline phosphate level Elevated vitamin B12 level or unbound vitamin B12 binding capacity
World Health Organization Criteria for DiagnosisMajor Criteria
I Hemoglobin greater than 18.5 g/dL in men, 16.5 g/dL in women or other evidence of increased red cell volume
I Presence o f JAK2 V617F or other functionally similar mutation such as JAK2 exon 12 mutation
Minor Criteria
I Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) with prominent erythroid, granulocytic and megakaryocytic proliferation
I Serum erythropoietin level below the reference range for normal I Endogenous erythroid colony formation in vitro
Diagnostic Scheme
RELATIVE POLYCYTHEMIA (G A ISB CK SYNDROME)
RED BLOOD CELL DISORDERS Erythrocytosis 2 0 9
Figure IIA1-3Peripheral blood smear.
Clinical Features Usually occurs in males aged 45-55 years The patients tend to be obese, have hypertension, and are heavy smokers
PathologyI Normal red blood cell mass and clearly decreased plasma volumeI Red blood cell mass at the upper range of normal; plasma volume at the lower
range of normalI Cause o f the low plasma volume is not understood but may be related to a
variety o f causes, including emotional stress, alcoholism, heavy smoking, chronic anxiety, and hypertension
2 1 0 UNIT II Hematologic Disorders
Laboratory FeaturesWhite Blood Cells Not remarkable
Platelets Not remarkable
Red Blood CellsI Hemoglobin level increasedI Hematocrit level increasedI Red blood cell count increasedI Red blood cell mass normalI Plasma volume decreasedI Oxygen pressure normalI Erythropoietin level normal
Diagnostic Scheme
RED BLOOD CELL DISORDERS * Erythrocytosis 211
SECONDARY POLYCYTHEMIA
Figure IIA1-4Peripheral blood smear.
r . i ,
2 1 2 UNIT II Hematologic Disorders
Laboratory FeaturesWhite Blood Cells Not remarkable
Platelets Not remarkable
Red Blood Cellst Hemoglobin level increased I Hematocrit level increased Red blood cell count increased t Red blood cell mass increased Increased erythropoietin Decreased oxygen pressure if due to anoxia; normal oxygen pressure if due to
tumor
Diagnostic Scheme
edilibros.comCHAPTER 2
Anemias Due to Disordered Iron
Metabolism or Hem eSynthesis
2 1 3
ANEMIA OF CH RO N IC DISEASE
2 1 4 UNIT II Hematologic Disorders
Figure IIA2-1APeripheral blood smear.
D o 0 * 0> oO^P-
Figure IIA2-1BPrussian blue stain.
RED BLOOD CELL DISORDERS Anemias Due to Disordered Iron Metabolism or Heme Synthesis 2 1 5
Clinical FeaturesI Those o f the underlying disease: inflammatory, neoplastic, or infectious state
PathologyI Hypoproliferative anemiaI Impaired release o f iron from the reticuloendothelial cells for hemoglobin
synthesis I Decreased red blood cell survival
Laboratory FeaturesWhite Blood Cellst Not consistent depends on the underlying disease
Plateletst Not consistent depends on the underlying disease
Red Blood CellsI Decreased hemoglobin and hematocritI Normocytic/normochromic anemiaI Microcytic/hypochromic anemiaI Reticulocyte count normal to slightly increased
Bone MarrowI Normal to increased hemosiderinI Decreased sideroblastsI Decreased serum iron levelI Normal or decreased total iron binding capacityI Decreased % saturation (usually >15%)I Normal or increased serum ferritin level
2 1 6 UNIT II Hematologic Disorders
Diagnostic Scheme
RDW
J -
TIBC
X
CBC I Peripheral smear j
Platelets Hb& HciVariable Decreased
Normal
Decreased
Increased
www.mc
WBC count Variable
Microcytic/HypochromicNormocytic/Normochromic
MCV
J_Low or normal
Serum iron
Serum ferritin
% saturation Greater than 15%
iTfR level Normal
Decreased
------ 1 , ]Anemia of
chronic disease os.com
ERYTHROPOIETIC PORPHYRIA (GUNTHER'S DISEASE)
RED BLOOD CELL DISORDERS Anemias Due to Disordered Iron Metabolism or Heme Synthesis 2 1 7
Figure IIA2-2Peripheral blood smear.
Clinical Feature!I Rare autosomal recessive disease
Appears in infancy I Urine is pink to reddish-brown Vesicular or bullous eruptions appear on exposed areas of the body Scarring occurs and may lead to severe deformities o f the nose, ears, eyes, and
fingers Teeth fluoresce Hypertrichosis affects the entire body Splenomegaly
PathologyI Decreased tissue uroporphyrinogen III cosynthetase I Hemolytic anemia
Laboratory FeaturesWhite Blood CellsI Not remarkable
PlateletsI Not remarkable
2 1 8 UNIT II Hematologic Disorders
Red Blood Cellst Moderate to severe normocytic/normochromic anemia Polychromatophilia Nucleated red blood cells in the peripheral blood Red blood cells fluoresce Increased reticulocyte count Excessive porphyrin deposits in the red blood cells
Bone Marrow Erythroid hyperplasia Normoblasts fluorescet Ineffective erythropoiesis
ChemistriesI Normal serum iron level I Normal serum ferritin level I Increased unconjugated bilirubin level I Increased urine and fecal urobilinogen levelsI Excessive amounts of uroporphyrin I and coproporphyrin I in urine and feces
Diagnostic Scheme
ERYTHROPOIETIC PROTOPORPHYRIA
RED BLOOD CELL DISORDERS Anemias Due to Disordered Iron Metabolism or Heme Synthesis 2 1 9
Clinical FeaturesI Autosomal dominant or recessive transmissionI Usually begins before teen yearsI Burning, redness, itching, swelling of skinI Photosensitivity is not severeI Relatively mild course
PathologyI Deficiency o f ferrochelatase I Accumulation of protoporphyrin
2 2 0 UNIT II Hematologic Disorders
Laboratory FeaturesWhite Blood Cells Not remarkable
Platelets Not remarkable
Red Blood CellsI No hemolytic anemia I No abnormalitiesI Red blood cells may accumulate protoporphyrins and fluoresce
Bone MarrowI No abnormalitiesI The cytoplasm o f normoblasts fluoresce intensely
Chemistries Increased levels o f protoporphyrin found in red blood cells, plasma, and feces
but not in urine
Diagnostic Scheme
IRON DEFICIENCY ANEMIA
RED BLOOD CELL DISORDERS Anemias Due to Disordered Iron Metabolism or Heme Synthesis 221
f t
Figure IIA2-5Bone marrow smear.
4
2 2 2 UNIT II Hematologic Disorders
Clinical FeaturesI Fatigue, loss of stamina, exercise intolerance I Delayed growth I Lethargy I Dizziness I Pallor I GlossitisI Koilonychia (spoon-nails)I Crave dirt or paint (pica) or ice (pagophagia)
PathologyI Deficient heme synthesis I Ineffective erythropoiesis I Increased iron loss
I Pregnancy I MenstruationI Chronic blood loss from gastrointestinal tract
I Low availability o f iron I Rapid growth period I Defective gastric function I Achlorhydria Gastrectomy
Laboratory FeaturesWhite Blood Cells Not remarkable
PlateletsI Normal or slightly increased
Red Blood CellsI Hemoglobin and hematocrit levels decreased I Microcytic/hypochromic anemia I Reticulocyte count normal or slightly increased I Increased red blood cell distribution width I Pencil- or cigar-shaped red blood cells, codocytes
Bone MarrowI Erythroblastic hyperplasia I Absent hemosiderin I Decreased sideroblasts (
RED BLOOD CELL DISORDERS Anemias Due to Disordered Iron Metabolism or Heme Synthesis 2 2 3
Chemistries Decreased serum iron levelt Increased total iron binding capacity Decreased % saturation (
LEAD INTOXICATION (PLUMBISM)
2 2 4 UNIT II Hematologic Disorders
Figure IIA2-6Peripheral blood smear.
Clinical FeaturesI Abdominal painI ConstipationI VomitingI Muscle weaknessI Lead line on gumsI Skin lesionsI Neurologic dysfunctions
PathologyI Synthesis of heme is impairedI Interference with iron storage in the mitochondria, which may lead to
sideroblastic anemiaI Activity o f most enzymes in heme synthesis is inhibitedI Ineffective erythropoiesis (hemolysis because o f RNA breakdown)
RED BLOOD CELL DISORDERS Anemias Due to Disordered Iron Metabolism or Heme Synthesis 2 2 5
Laboratory FeaturesWhite Blood CellsI Not consistent findings
Plateletst Not remarkable
Red Blood Cellst Microcytic/hypochromic anemia Basophilic stippling Reticulocyte count normal to increased
Bone MarrowI Normal hemosiderin I Basophilic stippling in normoblasts
ChemistriesI Increased free erythrocyte protoporphyrin I Normal serum ferritin level I Increased ^.-aminolevulinic acid levels I Normal porphobilinogen I Increased blood lead levels
Diagnostic Scheme
Platelets Not remarkable
CBC
H b& HctDecreased
RDWNormal
Serum iron studies
Normal
iBlood lead
Increased
-LLead intoxication
_Peripheral smear
WBC count Not remarkable
Normocyt ic/Normochromic Microcytic/Hypochromic
Basophilic stippling
2 2 6 UNIT II Hematologic Disorders
SIDEROBLASTIC ANEMIA
Figure IIA2-7Peripheral blood smear.
Figure IIA2-8Prussian blue stain.
RED BLOOD CELL DISORDERS Anemias Due to Disordered Iron Metabolism or Heme Synthesis 227
Clinical Featurest Hepatosplenomegaly Two classifications:
t Inherited Usually sex linked May be autosomal
Acquired Idiopathic (a type of myelodysplastic syndromerefractory anemia with
ringed sideroblasts [RARS]) Secondary (e.g., drugs)
PathologyI Common features
I Ineffective erythropoiesisI Increased levels of tissue iron (ringed sideroblasts)I Failure o f protoporphyrin and heme synthesis due to abnormal enzyme
activity I Inherited
I Symptoms appear early owing to abnormal heme synthesis enzymes I Idiopathic
I Clonal disorderI Abnormal red blood cell distribution I Abnormal heme synthesis enzymes
I Secondary I Drugs
I Inhibition o f enzymes
Laboratory FeaturesWhite Blood Cellst Normal to decreased
Plateletst Not remarkable
Red Blood CellsI Commonly microcytic/hypochromic anemia I Dimorphismt Increased red blood cell distribution width Reticulocyte count normal or slightly increased Basophilic stipplingt Pappenheimer bodies
Bone Marrowt Erythroid hyperplasia Large numbers of sideroblasts and ringed sideroblasts
228 UNIT II Hematologic Disorders