Self-Assessment in Hematology:
Cellular Morphology
Karl S. Theil, M.D.
Staff, Section of Hematopathology
Department of Laboratory Medicine
Cleveland Clinic
Objectives
• Recognize “classic” morphologic features
used to diagnose blood and marrow disorders
• Discuss the use of ancillary laboratory tests
in hematology diagnosis
Format
• Ten single answer, multiple choice questions
• First view question, examine image, then
answer question using audience response
system
• Discuss correct and incorrect choices
Intensive Review of Internal Medicine
Case #1
• A 56 year old woman developed
anemia while being treated for
rheumatoid arthritis
• The most likely diagnosis is
A. Microangiopathic hemolytic anemia
B. Autoimmune hemolytic anemia
C. Heinz body hemolytic anemia
D. Megaloblastic anemia
E. Anemia of chronic disease
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Intensive Review of Internal Medicine
Case #1
• A 56 year old woman developed
anemia while being treated for
rheumatoid arthritis
• The most likely diagnosis is
A. Microangiopathic hemolytic anemia
B. Autoimmune hemolytic anemia
C. Heinz body hemolytic anemia
D. Megaloblastic anemia
E. Anemia of chronic disease
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Intensive Review of Internal Medicine
Bite Cells
Bite cell
Wright-Giemsa stain
Heinz body
Supravital stain
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Heinz Body Hemolytic Anemias
• Red cell enzymopathies
̶
G6PD deficiency
• Exposure to oxidant drugs
̶
4,4’ diaminodiphenylsulfone (Dapsone)
• Chemical poisoning
̶
Naphthalene
• Unstable hemoglobin variants
̶
Hb Köln, Hb Zurich, Hb Hammersmith
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Microangiopathic
Hemolytic Anemia
Features:
–
–
–
–
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Schistocytes
Polychromasia
Nucleated RBCs
 Thrombocytopenia
Autoimmune
Hemolytic Anemia
Features:
–
–
–
–
–
–
Anemia
Spherocytes
Polychromasia
Nucleated RBCs
Reticulocytosis
Positive DAT
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Megaloblastic Anemia
Features:
–
–
–
–
–
Macrocytic anemia
Pancytopenia
Hypersegmentation
Elevated LD
Megaloblastic
maturation in marrow
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Case #2
• A 36 year old African-American woman
presented with fatigue. A CBC showed:
Hgb: 7.3 g/dL, MCV: 59.8 fL, and RDW: 20.3%
• The most likely diagnosis is
A.
Iron deficiency anemia
B.
Anemia of chronic disease
C.
Thalassemia minor
D.
Sideroblastic anemia
E.
Hemoglobin E trait
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Intensive Review of Internal Medicine
Case #2
• A 36 year old African-American woman
presented with fatigue. A CBC showed:
Hgb: 7.3 g/dL, MCV: 59.8 fL, and RDW: 20.3%
• The most likely diagnosis is
A.
Iron deficiency anemia
B.
Anemia of chronic disease
C.
Thalassemia minor
D.
Sideroblastic anemia
E.
Hemoglobin E trait
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Microcytic Hypochromic
Anemias
• Iron deficiency anemia
• Anemia of chronic disease
• Thalassemia minor
• Sideroblastic anemia
• Lead poisoning
• Hemoglobin E trait
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Case #3
• An 83 year old man presents with
anemia. Hgb: 7.3 g/dL; MCV: 76.8 fL;
RDW: 15.8%
• The most likely diagnosis is
A. Hemoglobin AC
B. Hemoglobin CC
C. Hemoglobin SC
D. Hemoglobin AS
E. Hemoglobin SS
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Intensive Review of Internal Medicine
Case #3
• An 83 year old man presents with
anemia. Hgb: 7.3 g/dL; MCV: 76.8 fL;
RDW: 15.8%
• The most likely diagnosis is
A. Hemoglobin AC
B. Hemoglobin CC
C. Hemoglobin SC
D. Hemoglobin AS
E. Hemoglobin SS
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Hemoglobin CC Disease
• Found in 0.02% African-Americans
• A mild-moderate anemia with
microcytosis, target cells, splenomegaly
• Often asymptomatic; pigment gallstones
• Hemoglobin C: b 6 Glu  Lys
• May occur with other variant Hb and
thalassemia
• Diagnosis by hemoglobin screen
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Hb SC Disease
Hb SS Disease
Case #4
• A 53 year old man developed painful
enlarging skin ulcers on the plantar
surface of his foot in association with
winter weather
• The most likely diagnosis is
A. Rouleaux
B. Cold agglutinin disease
C. Amyloidosis
D. Cryoglobulinemia
E. Artifact
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Intensive Review of Internal Medicine
Case #4
• A 53 year old man developed painful
enlarging skin ulcers on the plantar
surface of his foot in association with
winter weather
• The most likely diagnosis is
A. Rouleaux
B. Cold agglutinin disease
C. Amyloidosis
D. Cryoglobulinemia
E. Artifact
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Cryoglobulinemia
• Protein that precipitates in cold,
dissolves when warmed- specimen
collection critical
• Appears as amorphous pale blue
extracellular material in peripheral smear
• Typically immunoglobulin: IgM, IgG
or IgA
• Classified as Types I, II and III
• Not always symptomatic
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H&E stain
Congo Red
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Case #5
• A 58 year old male presented to the ER
with fever and chills
• The most likely diagnosis is
A. Malaria
B. Babesiosis
C. Borreliosis
D. Disseminated Histoplasmosis
E. Capnocytophaga sepsis
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Intensive Review of Internal Medicine
Case #5
• A 58 year old male presented to the ER
with fever and chills
• The most likely diagnosis is
A. Malaria
B. Babesiosis
C. Borreliosis
D. Disseminated Histoplasmosis
E. Capnocytophaga sepsis
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Intensive Review of Internal Medicine
Microorganisms in Blood Smears
• Plasmodium sp.
• Babesia sp.
• Bacteria (rod, cocci)
• Borrelia recurrentis
• Fungi (Histoplasma sp.)
• Microfilaria
• Trypanosomes
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Malaria versus Babesiosis
Feature
Malaria
Babesiosis
Insect vector
mosquito
tick
Trophozoite
rings
tetrads
distinctive
Pigment
present
absent
Gametocyte
round or
banana-shaped
absent
Extra-erythrocytic
forms
absent
present
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Borreliosis
Features:
– Extracellular
spirochete
– Epidemic relapsing
fever: Louse-borne
– Endemic relapsing
fever: Tick-borne
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Disseminated Histoplasmosis
Features:
– Leukopenia often
– Intracellular small
budding yeast in
neutrophils and
monocytes
– Immunocompromised
host
– Serology, culture,
PCR
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Capnocytophaga sepsis
Features:
– Intracellular fusiform
Gram negative rods
– Association with
dog bite
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Case #6
• A 45 year old man presented with
fatigue and leukocytosis and anemia
• The most likely diagnosis is
A. Acute myeloid leukemia
B. Chronic myelogenous leukemia
C. Chronic myelomonocytic leukemia
D. Refractory anemia with excess blasts-1
E. Atypical chronic myeloid leukemia
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Intensive Review of Internal Medicine
Case #6
• A 45 year old man presented with
fatigue and leukocytosis and anemia
• The most likely diagnosis is
A. Acute myeloid leukemia
B. Chronic myelogenous leukemia
C. Chronic myelomonocytic leukemia
D. Refractory anemia with excess blasts-1
E. Atypical chronic myeloid leukemia
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Auer Rods
Features:
– Composed of fused
primary granules
– Myeloperoxidase
positive
– May occur in
bundles (APL)
– Found in AML,
RAEB-2
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Blast Morphology
APL
AML
AMoL
ALL
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Case #7
• A 32 year old woman with WBC:
450 x 103/uL, Hgb: 12 g/dL, and
platelets: 229 x 103/uL
• The most likely karyotype is
A. 46,XX[20]
B. 46,XX,t(9;22)(q34;q11.2)[20]
C. 46,XX,t(15;17)(q24;q21)[20]
D. 45,XX,-7[15]/46,XX[5]
E. 46,XX,del(5)(q13q31)[10]/46,XX[10]
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Intensive Review of Internal Medicine
Case #7
• A 32 year old woman with WBC:
450 x 103/uL, Hgb: 12 g/dL, and
platelets: 229 x 103/uL
• The most likely karyotype is
A. 46,XX[20]
B. 46,XX,t(9;22)(q34;q11.2)[20]
C. 46,XX,t(15;17)(q24;q21)[20]
D. 45,XX,-7[15]/46,XX[5]
E. 46,XX,del(5)(q13q31)[10]/46,XX[10]
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Chronic Myelogenous Leukemia
• Myeloproliferative neoplasm
• Philadelphia chromosome positive
• BCR-ABL1 fusion present
• Neutrophilic leukocytosis with
eosinophilia and basophilia
• Splenomegaly typically present
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Karyotype Associations
46,XX[20]
Normal female
46,XX,t(9;22)(q34;q11.2)[20]
Chronic myelogenous
leukemia
46,XX,t(15;17)(q24;q21)[20]
Acute promyelocytic
leukemia
45,XX,-7[15]/46,XX[5]
Myelodysplastic
syndrome
46,XX,del(5)(q13q31)[10]
Myelodysplastic
syndrome
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Case #8
• A 64 year old man presented with
WBC: 24,000/uL, Hgb: 13.7 g/dL and
Platelets: 345,000/uL. Physical exam
showed mild splenomegaly
• The most likely diagnosis is
A. Monoclonal B-cell lymphocytosis
B. Chronic lymphocytic leukemia
C. Hairy cell leukemia
D. Mantle cell lymphoma
E. B-lymphoblastic leukemia
Intensive Review of Internal Medicine
Intensive Review of Internal Medicine
Case #8
• A 64 year old man presented with
WBC: 24,000/uL, Hgb: 13.7 g/dL and
Platelets: 345,000/uL. Physical exam
showed mild splenomegaly
• The most likely diagnosis is
A. Monoclonal B-cell lymphocytosis
B. Chronic lymphocytic leukemia
C. Hairy cell leukemia
D. Mantle cell lymphoma
E. B-lymphoblastic leukemia
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Chronic Lymphocytic Leukemia
• Clonal B-cell lymphocytosis >5,000 cells/uL
• Often smudge cells
• CD19+, CD5+, CD23+, CD20+, CD79b• Dim surface immunoglobulin (k or l)
• Adverse prognosis: CD38+, ZAP-70+
• Genetic markers: +12, del(13q), del(11q),
del(17p)
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B-cell Lymphoproliferative
Hairy cell
Mantle cell
B-ALL
Monoclonal
B-cell
Flow cytometry allows rapid distinction of these entities
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Case #9
• A 46 year old woman was evaluated for
persistent thrombocytopenia following
splenectomy. Ristocetin-induced platelet
aggregation was normal
• The most likely diagnosis is
A.
Chronic idiopathic thrombocytopenic purpura
B.
Thrombotic thrombocytopenic purpura
C.
Gray platelet syndrome
D.
Bernard-Soulier syndrome
E.
May-Hegglin anomaly
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Case #9
• A 46 year old woman was evaluated for
persistent thrombocytopenia following
splenectomy. Ristocetin-induced platelet
aggregation was normal
• The most likely diagnosis is
A.
Chronic idiopathic thrombocytopenic purpura
B.
Thrombotic thrombocytopenic purpura
C.
Gray platelet syndrome
D.
Bernard-Soulier syndrome
E.
May-Hegglin anomaly
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Giant Platelets
• Platelet is larger than normal erythrocyte
• Idiopathic thrombocytopenic purpura
• Essential thrombocythemia
• Certain hereditary platelet disorders
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Macrothrombocytopenias
• MYH9-related disorders
̶
Rare; autosomal dominant
 neutrophil inclusions
Mild bleeding disorder
̶
̶
• Bernard-Soulier syndrome
̶
̶
̶
̶
Rare defect of GPIb/IX/V receptor
Autosomal recessive
Mucocutaneous bleeding
Absent ristocetin aggregation
• Gray platelet syndrome
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Case #10
• A 24 year old male presents with acute
onset of fever and obtundation. Hgb: 7.9
g/dL. Platelets: 23,000/uL. BUN: 63; Cr: 2.8.
PT, APTT, and fibrinogen were normal
• The most likely diagnosis is
A. Idiopathic thrombocytopenic purpura
B. Thrombotic thrombocytopenic purpura
C. Disseminated intravascular coagulation
D. Acute promyelocytic leukemia
E. Spurious thrombocytopenia
Intensive Review of Internal Medicine
Intensive Review of Internal Medicine
Case #10
• A 24 year old male presents with acute
onset of fever and obtundation. Hgb: 7.9
g/dL. Platelets: 23,000/uL. BUN: 63; Cr: 2.8.
PT, APTT, and fibrinogen were normal
• The most likely diagnosis is
A. Idiopathic thrombocytopenic purpura
B. Thrombotic thrombocytopenic purpura
C. Disseminated intravascular coagulation
D. Acute promyelocytic leukemia
E. Spurious thrombocytopenia
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Intensive Review of Internal Medicine
Microangiopathic Hemolytic
Anemia
• Disseminated intravascular coagulation
• Thrombotic thrombocytopenic purpura
• Hemolytic uremic syndrome
• Heart valve disease
• Vasculitis
• Metastatic carcinoma
• Drugs (mitomycin C, cyclosporine)
• Severe burns
• Malignant hypertension
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Spurious Thrombocytopenia
• EDTA-related platelet antibody
̶
̶
Platelet satellitosis
Platelet clumping
• Partially clotted specimen
• Platelet cold agglutinin
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Take Home Point
Peripheral blood smear review provides
diagnostic information when reviewed in
conjunction with clinical findings.
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Thank You!
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