Self-Assessment in Hematology:

Cellular Morphology

Karl S. Theil, M.D.

Staff, Section of Hematopathology
Department of Clinical Pathology
The Cleveland Clinic Foundation

June 7, 2013

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
 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
 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
 Bite Cells

Bite cell Heinz body

Wright-Giemsa stain Supravital stain

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
 Microangiopathic
Hemolytic Anemia
Features:
• Schistocytes
• Polychromasia
• Nucleated RBCs
•  Thrombocytopenia

Autoimmune
Hemolytic Anemia
Features:
• Anemia
• Spherocytes
• Polychromasia
• Nucleated RBCs
• Reticulocytosis
• Positive DAT
 Megaloblastic Anemia

Features:
• Macrocytic anemia
• Pancytopenia
• Hypersegmentation
• Elevated LD
• Megaloblastic
maturation in marrow

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
 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
 Microcytic
Hypochromic Anemias

Iron deficiency anemia

Anemia of chronic disease
Thalassemia minor
Sideroblastic anemia
Lead poisoning
Hemoglobin E trait
 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
 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
 Hemoglobin CC Disease

• Found in 0.02% African-Americans

• A mild-moderate anemia with
microcytosis, target cells, splenomegaly
• Often asymptomatic; pigment gallstones
• Hemoglobin C: b6 Glu Lys
• May occur with other variant Hb and
thalassemia
• Diagnosis by hemoglobin screen
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
 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
 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
H&E stain Congo Red
 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
 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
Microorganisms in Blood Smears

Plasmodium sp.
Babesia sp.
Bacteria (rod, cocci)
Borrelia recurrentis
Fungi (Histoplasma sp.)
Microfilaria
Trypanosomes

Malaria versus Babesiosis

Feature Malaria Babesiosis

Insect vector mosquito tick
Trophozoite rings tetrads
distinctive
Pigment present absent
Gametocyte round or absent
banana-shaped
Extra-erythrocytic absent present
forms
Borreliosis

Features:
• Extracellular
spirochete
• Epidemic relapsing
fever: Louse-borne
• Endemic relapsing
fever: Tick-borne
Disseminated Histoplasmosis

Features:
• Leukopenia often
• Intracellular small
budding yeast in
neutrophils and
monocytes
• Immunocompromised
host
• Serology, culture, PCR

Capnocytophaga sepsis

Features:
• Intracellular fusiform
Gram negative rods
• Association with dog
bite
 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
 Case #6

A 62 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
 Auer Rods

Features:
• Composed of fused
primary granules
• Myeloperoxidase
positive
• May occur in bundles
(APL)
• Found in AML, RAEB-2

Blast Morphology

APL AML

AMoL ALL
 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]
 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]
 Chronic Myelogenous
Leukemia

• Myeloproliferative neoplasm
• Philadelphia chromosome positive
• BCR-ABL1 fusion present
• Neutrophilic leukocytosis with
eosinophilia and basophilia
• Splenomegaly typically present

Karyotype Associations

46,XX[20] Normal female

46,XX,t(9;22)(q34;q11.2)[20]
46,XX,t(15;17)(q24;q21)[20]
45,XX,-7[15]/46,XX[5]
46,XX,del(5)(q13q31)[10]
Chronic myelogenous
leukemia
Acute promyelocytic
leukemia
Myelodysplastic syndrome
Myelodysplastic syndrome
 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
 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
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)

B-cell Lymphoproliferative

Hairy cell Mantle cell B-ALL Monoclonal

B-cell

Flow cytometry allows rapid distinction of these entities

 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
 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
 Giant Platelets

Platelet is larger than normal erythrocyte

Idiopathic thrombocytopenic purpura

Essential thrombocythemia
Certain hereditary platelet disorders

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
 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
 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
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
Spurious Thrombocytopenia

• EDTA-related platelet antibody

Platelet satellitosis
Platelet clumping

• Partially clotted specimen

• Platelet cold agglutinin

 Take Home Point

• Peripheral blood smear review provides

diagnostic information when reviewed in
conjunction with clinical findings.
Thank You!