Hematology Flashcards
1
Q
Hereditary spherocytosis: Incidence (2).
A
United States: 1 in 5000.
Northern Europe: 1 in 1000.
2
Q
Hereditary spherocytosis: Possible clinical manifestations (4).
A
All patients: Anemia.
Infants: Jaundice.
Adults: Gallstones, splenomegaly.
3
Q
Hereditary spherocytosis: Complete blood count (3).
A
Elevated MCHC.
Normal MCV, MCH.
Reticulocytosis.
4
Q
Hereditary spherocytosis: Tests of stability of red cells.
A
Increased osmotic fragility.
Increased autohemolysis.
5
Q
Hereditary spherocytosis: Other laboratory findings (2).
A
Increased unconjugated bilirubin.
Increased LDH.
6
Q
Hereditary elliptocytosis: Incidence (2).
A
United States: 1 in 2500.
Parts of Africa: 1 in 100.
7
Q
Hereditary elliptocytosis: Clinical manifestations.
A
Mild disease.
8
Q
Hereditary elliptocytosis:
A. Inheritance.
B. Molecular defect.
A
A. Autosomal dominant.
B. The α chain of spectrin.
9
Q
Hereditary elliptocytosis: Types.
A
Common: Found in Africans; includes hereditary pyropoikilocytosis.
Spherocytic: Double heterozygosity of HE and HS.
Stomatocytic: Found in Malaysians.
10
Q
Hereditary elliptocytosis, stomatocytic type:
A. Synonym.
B. Molecular defect.
C. Evolutionary advantage.
A
A. Southeast Asian ovalocytosis.
B. Band 3.
C. Protection against Plasmodium vivax.
11
Q
Glucose-6-phosphate dehydrogenase deficiency: Examples of oxidative stress (6).
A
Fava beans.
Methylene blue.
Sulfa drugs.
Primiquine.
Infections.
Nitrofurantoin.
12
Q
Glucose-6-phosphate dehydrogenase deficiency: Peripheral smear.
A
Heinz bodies (revealed by supravital stain).
13
Q
Glucose-6-phosphate dehydrogenase deficiency: Inheritance.
A
X-linked recessive.
14
Q
Pyruvate kinase deficiency:
A. Effect on cell.
B. Clinical presentation.
C. Laboratory findings.
A
A. Cannot produce enough ATP; cannot maintain ion pumps.
B. Chronic hemolysis of variable severity.
C. Echinocytosis; evidence of extravascular hemolysis.
15
Q
Pyruvate kinase deficiency:
A. Epidemiology.
B. Inheritance.
A
A. Occurs worldwide.
B. Autosomal recessive.
16
Q
Hemoglobin chains:
A. Hb A.
B. Hb A₂.
C. Hb F.
A
A. α₂β₂.
Β. α₂δ₂.
C. α₂γ₂.
17
Q
Chains of early fetal hemoglobins.
A
Hb Gower 1: ζ₂ε₂.
Hb Gower 2: α₂ε₂.
18
Q
Hemoglobin S:
A. Mutation.
B. Incidence of trait in the United States.
A
A. β₆ Glu to Val.
B. 8% in blacks.
19
Q
Sickle-cell trait: Hemoglobins.
A
Hb A: 50-65%.
Hb S: 35-45%.
Hb A₂: Less than 3%.
20
Q
Sickle-cell trait:
A. Peripheral smear.
B. Screening tests.
A
A. Normal.
B. Positive metabisulfite and dithionate tests.
21
Q
Sickle-cell trait: Renal complications (4).
A
Hematuria.
Isosthenuria.
Papillary necrosis.
Renal medullary carcinoma.
22
Q
Sickle-cell trait: Other possible complications (2).
A
Hypoxia-induced splenic infarct.
Exercise-induced rhabdomyolysis.
23
Q
Sickle-cell disease: Lifespan of red cells.
A
17 days.
24
Q
Sickle-cell disease: Hemoglobins.
A
Hb S: More than 80%.
Hb F: 1-20%.
Hb A: 0%.
Hb A₂: 1-4%.
25
Sickle-cell disease: Onset of symptoms.
Occurs at 6 months of age, when Hb S is 50% of total hemoglobin.
26
Sickle-cell disease: Effect of Hb F.
Prevents polymerization of Hb S.
27
SC disease:
A. Clinical severity.
B. Hemoglobins.
A. Worse than sickle-cell trait but not as bad as sickle-cell disease.
B. Hb S makes a little more than half of total hemoglobin; Hb C makes up the rest.
28
Sickle-cell trait/α thalassemia: Percentage of Hb S (2).
One mutated α gene: 30-35% Hb S.
Two mutated α genes: 25-30% Hb S.
29
Sickle-cell trait/β thalassemia:
A. Percentage of Hb S.
B. Clinical severity.
A. Usually more than 50%.
B. May be severe.
30
Hemoglobin C: Mutation.
β₆ Glu to Lys.
31
Hemoglobin C trait:
A. Peripheral smear.
B. Clinical severity.
A. Target cells.
B. Generally asymptomatic.
32
Hemoglobin C disease: Hemoglobins.
Hb C: 90%.
Hb F: 7%.
Hb A: 0%.
Hb A₂: 3%.
33
Hemoglobin C disease:
A. Peripheral smear.
B. Clinical severity.
A. Target cells; rod-shaped or hexagonal crystals.
B. Mild hemolytic anemia; splenomegaly.
34
Hemoglobin E: Mutation.
β₂₆ Glu to Lys.
35
Hemoglobin E:
A. Peripheral smear and CBC.
B. Clinical severity.
A. Target cells, thalassemic indices.
B. Mild anemia unless there is concurrent β thalassemia.
36
Hemoglobins D and G:
A. Clinical severity.
B. Defect.
A. Asymptomatic.
B. Hb D: Defect in β chain; Hb G: Defect in α chain.
37
Hemoglobins D and G:
A. Gel electrophoresis.
B. Identification.
A. Both run with Hb S on alkaline gel but not on citrate gel.
B. Negative metabisulfite, dithionate tests.
38
Hemoglobin Lepore: Epidemiology.
Found in Italy and other Mediterranean lands.
39
Hemoglobin Lepore: Identification (4).
Makes up 15% of total hemoglobin.
Thalassemic indices.
Runs with Hb S on alkaline gel.
Negative metabisulfite, dithionate tests.
40
Hemoglobin Lepore: Mutation.
Fusion of genes for δ and β chains.
41
Hemoglobin Constant Spring:
A. Epidemiology.
B. CBC.
A. More common in Southeast Asia.
B. Thalassemic indices.
42
Hemoglobin Constant Spring: Mutation.
Loss of stop codon in the gene for the α chain results in an abnormally long transcript.
43
pH of ___ gel.
A. cellulose-acetate
B. citrate
A. 8.6.
B. 6.2.
44
Cellulose-acetate gel: Layout.
+
A
F
S D G Lepore
A₂ C E O
(carbonic anhydrase)
(origin)
−
45
Citrate gel: Layout.
+
C
S
(origin)
A D A₂ G E O
F
−
46
Causes of shift of the hemoglobin-oxygen dissociation curve to the right.
Acidosis.
Hyperthermia.
Increased 2,3-DPG.
Hemoglobin with low affinity for oxygen.
47
Clinical features of a hemoglobin with ___ affinity for oxygen.
A. low
B. high
A. Anemia, cyanosis.
B. Erythrocytosis.
48
Unstable hemoglobins:
A. Definition.
B. Peripheral smear.
C. Examples.
A. Easily oxidized.
B. Heinz bodies, bite cells.
C. Hb Köln, Hb Hammersmith, Hb Ann Arbor.
49
Methemoglobin:
A. Synonym.
B. Definition.
C. Importance.
A. Hemiglobin.
B. Hemoglobin that contains ferric iron.
C. Cannot carry oxygen.
50
Methemoglobin: Amount in normal blood.
No more than 1.5%.
51
Methemoglobin: Inherited causes of abnormal levels (2).
Deficiency of methemoglobin reductase.
Abnormal hemoglobin that resists the reductase.
52
Methemoglobin: Acquired causes of abnormal levels (4).
Nitrites.
Phenacetin.
Quinones.
Sulfonamides.
53
Methemoglobin: Level at which cyanosis appears.
At 1.5 g/dL or about 10% of total hemoglobin.
54
Methemoglobin:
A. Detection.
B. Treatment.
A. Co-oximetry.
B. Methylene blue.
55
Sulfhemoglobin: Peripheral smear.
Heinz bodies.
56
Sulfhemoglobin:
A. Amount in normal blood.
B. Causes of increase.
A. No more than 1%.
B. Sulfonamides; bacteremia with Clostridium perfringens.
57
Sulfhemoglobin: Level at which cyanosis appears.
At 0.5 g/dL or about 3-4% of total hemoglobin.
58
Tetramers in thalassemia:
A. Significance.
B. In α thalassemia.
C. In β thalassemia.
A. May precipitate and shorten the life span of the red cell.
B. β₄, γ₄.
C. α₄.
59
Thalassemia: Formula for distinguishing from iron-deficiency anemia.
MCV ÷ RBC
− Less than 13: Probable thalassemia.
− More than 15: Probable iron deficiency.
60
Thalassemia: Peripheral smear (3).
Target cells.
Microcytosis.
Basophilic stippling.
61
β-Thalassemia:
A. Chromosome.
B. Type of mutation.
A. 11.
B. Point mutation.
62
β-Thalassemia: Alleles.
β+: Some β chains are produced.
β⁰: No β chains.
63
β-Thalassemia: Age at presentation.
6 to 9 months.
64
β-Thalassemia: Hemoglobins in homozygotes.
Hb F: 50-95%.
Hb A: Very low or absent.
Hb A₂: Normal or increased.
65
β-Thalassemia: Difference between major and intermedia.
Major: Transfusion dependent.
66
δβ-Thalassemia: Definition.
Mutation involving the δ and β genes.
67
δβ-Thalassemia: Hemoglobins.
Hb F: 5-20%.
Hb A: Decreased.
Hb A₂: Normal.
68
δβ-Thalassemia vs. Hb Lepore on hemoglobin electrophoresis.
Hb Lepore runs with Hb S on alkaline gel and makes up no more than 15% of total hemoglobin.
69
α-Thalassemia:
A. Chromosome.
B. Typical mutation.
A. 16.
B. Large deletion.
70
α-Thalassemia 1 haplotype:
A. Synonym.
B. Definition.
C. Epidemiology.
A. α⁰.
B. Deletion of both genes from the chromosome.
C. Asians.
71
α-Thalassemia 2 haplotype:
A. Synonym.
B. Definition.
C. Epidemiology.
A. α+.
B. Deletion of one gene from the chromosome.
C. Blacks.
72
α-Thalassemia, silent carrier:
A. Genotype.
B. CBC and peripheral smear.
A. -α/αα.
B. Normal.
73
α-Thalassemia trait:
A. Genotype.
B. CBC and peripheral smear.
A. -α/-α or --/αα.
B. Thalassemia indices and morphology.
74
Hemoglobin H disease:
A. Genotype.
B. CBC and peripheral smear.
C. Abnormal hemoglobin.
A. --/-α or --/αCSα.
B. Thalassemic indices and morphology; Heinz bodies.
C. Hb H = β₄.
75
Hemoglobin Barts disease:
A. Genotype.
B. Peripheral smear.
C. Abnormal hemoglobin.
A. --/--.
B. Hypochromia; nucleated RBCs.
C. Hb Barts = γ₄.
76
α-Thalassemia: Migration of abnormal hemoglobins.
Both Hb H and Hb Barts are fast migrators.
77
α-Thalassemia: Age at presentation.
Birth.
78
α-Thalassemia: Population at risk for Hb H disease and Hb Barts disease.
Asians, because of the relative frequency of the α⁰ haplotype.
79
How ___-thalassemia affects the concentration of Hb S (or Hb C, etc.).
A. α.
B. β.
A. Decrease.
B. Increase.
80
Hemoglobin F: Normal percentage at different ages (4).
Birth: 30-40%.
6 months: Less than 10%.
1 years: Less than 5%.
2 years: Less than 1%.
81
Hereditary persistence of hemoglobin F: Recognition.
Hereditary: Pancellular.
Acquired: Heterocellular.
82
Combined sickle-cell disease and hereditary persistence of hemoglobin F:
A. Frequency.
B. Percentage of Hb F.
C. Clinical features.
A. About 1 in 100 with sickle-cell disease.
B. About 25%.
C. No anemia, no vaso-occlusive episodes.
83
Combined sickle-cell disease and hereditary persistence of hemoglobin F vs. combined sickle-cell disease and β-thalassemia.
On electrophoresis, both diseases show a mixture of Hb S, Hb F, and Hb A₂.
Combined sickle-cell disease and β-thalassemia is clinically more severe.
84
Acquired causes of elevated hemoglobin F (6).
Anemias: Megaloblastic, aplastic, Fanconi's.
Leukemias: JMML, acute erythrocytic.
Paroxysmal nocturnal hemoglobinuria.
85
Warm autoimmune hemolytic anemia:
A. Specificity of antibody.
B. Detection.
A. Broad reactivity with Rh antigens.
B. Positive DAT with anti-IgG or polyspecific reagent; all cell react in the AHG phase.
86
Warm autoimmune hemolytic anemia:
A. Location of hemolysis.
B. Peripheral smear.
A. Extravascular.
B. Spherocytes.
87
Warm autoimmune hemolytic anemia: Causes (5).
Idiopathic.
Thymoma.
Collagen-vascular diseases.
Hematological malignancy (esp. CLL/SLL).
Inherited immunodeficiencies.
88
Cold-agglutinin disease:
A. Isotype of antibody.
B. Detection.
A. IgM.
B. Positive DAT with anti-C3; cells react in the IS and AHG phases.
89
Cold-agglutinin disease: Specificities of the antibody.
Anti-I, anti-i, anti-H, anti-IH, anti-Pr.
90
Cold-agglutinin disease: Causes.
Anti-I: Mycoplasma pneumoniae, lymphoma.
Anti-i: Infectious mononucleosis.
91
Cold-agglutinin disease: How to determine the specificity of the antibody.
Reaction with (type O) cord blood but not with adult blood: Anti-i.
Reaction with adult blood but not with cord blood: Anti-I.
Reaction with type O blood only: Anti-H.
Reaction with type O and type A₂ blood only: Anti-IH.
Reaction with all types of blood only: Anti-Pr.
92
Cold agglutinins: Other tests for specificity of the antibody.
Anti-H and anti-IH are neutralized by saliva.
Pr antigen is destroyed by enzymes.
93
Cold agglutinins: Characteristics of benign ones (2).
Reactivity at 4-22⁰C (best at 4⁰C).
Titer at 4⁰C is less than 1 : 64.
94
Cold agglutinins: Characteristics of pathologic ones (3).
Broad thermal amplitude.
Titer at 4⁰C is more than 1 : 1000.
Spontaneous agglutination at room temperature.
95
Cold agglutinins: Characteristics of idiopathic ones (3).
Chronic.
Monoclonal IgM.
Often affects elderly patients.
96
Paroxysmal cold hemoglobinuria: Clinical associations (2).
Classic: Adult with syphilis.
Modern: Child with viral infection or otitis media.
97
Paroxysmal cold hemoglobinuria:
A. Peripheral smear.
B. Treatment.
A. Neutrophils with ingested red cells (rare).
B. Keep the patient warm and transfuse warmed blood as needed.
98
Paroxysmal cold hemoglobinuria:
A. Antibody.
B. Detection of the antibody.
A. Cold-reacting IgG anti-P.
B. Blood kept at 4⁰C for 30 minutes and then at 37⁰C for 30 minutes undergoes hemolysis.
99
Cryoglobulins: How to isolate them.
Let drawn blood clot at 37⁰C; centrifuge it at 37⁰C.
Chill the serum at 4⁰C for 3 days; centrifuge it at 4⁰C.
100
Cryoglobulinemia:
A. Histology.
B. Peripheral smear.
A. Vasculitis.
B. Cloudy, pale purple aggregates of protein.
101
Paroxysmal nocturnal hemoglobinuria:
A. Gene and chromosome.
B. Mutant protein.
C. LAP score.
A. PIG-A on the X chromosome.
B. GPI (glycosyl phosphatidylinositol) anchors.
C. Decreased.
102
Paroxysmal nocturnal hemoglobinuria: Secondarily affected proteins (5).
CD59 (MIRL).
CD55 (DAF).
CD16, CD48.
Acetylcholinesterase.
103
Paroxysmal nocturnal hemoglobinuria: Cause of the hemoglobinuria.
Loss of protection against complement-mediated destruction.
104
Paroxysmal nocturnal hemoglobinuria: Clinical consequences (6).
Early: Chronic hemolytic anemia.
Later: Thrombocytopenia, leukopenia.
Possible: Aplastic anemia, AML, thrombosis.
105
Paroxysmal nocturnal hemoglobinuria: Relation to aplastic anemia.
Either disease can lead to the other.
106
Paroxysmal nocturnal hemoglobinuria: Diagnostic tests.
Insensitive: Sucrose lysis, acidified serum (Ham's).
Preferred: Flow cytometry.
107
Paroxysmal nocturnal hemoglobinuria: Principle of diagnosis by flow cytometry.
FLAER (fluorescent aerolysin derived from Aeromonas hydrophila) binds specifically to GPI anchors.
108
Paroxysmal nocturnal hemoglobinuria: Typical flow-cytometric plots for
A. Neutrophils.
B. Monocytes.
C. Erythrocytes.
A. CD24 vs. FLAER.
B. CD14 vs. FLAER.
C. CD135 vs. CD59 or CD55.
109
Paroxysmal nocturnal hemoglobinuria: Flow-cytometry classification of red blood cells.
Type I: Normal expression of CD59 (or CD55).
Type II: Partial expression.
Type III: No expression.
110
Paroxysmal nocturnal hemoglobinuria: Use of flow cytometry to predict morbidity.
Hemolysis and thrombosis are likely if
− More than 20% of red blood cells are of type III and/or
− More than 50% of neutrophils are abnormal.
111
Iron-deficiency anemia:
A. Total iron-binding capacity.
B. Iron saturation.
C. Zinc protoporphyrin.
A,C. Increased.
B. Decreased.
112
Causes of increased soluble transferrin receptors in the serum (4).
Iron-deficiency anemia.
Hemolytic anemia.
Hemorrhage.
Polycythemia.
113
Causes of increased zinc protoporphyrin and free erythrocyte protoporphyrin (3).
Iron-deficiency anemia.
Lead toxicity.
Anemia of chronic disease.
114
Folate: Purpose.
Cofactor in the transfer of methyl groups, e.g. to dUMP to form dTMP for the synthesis of DNA.
115
Folate: Absorption.
Occurs in the proximal small intestine.
116
B₁₂: Purpose.
Essential in the conversion of methylfolate to active tetrahydrofolate.
117
B₁₂: Absorption.
Stomach: Carried by R factor.
Duodenum: Freed from R factor and bound to gastric-derived intrinsic factor.
Ileum: Absorbed by the enterocytes and bound to transcobalamins I and II for export into the bloodstream.
118
How can pancreatic insufficiency cause megaloblastic anemia?
Release of B₁₂ from R factor depends on pancreatic enzymes.
119
Drugs that can cause megaloblastic anemia.
Methotrexate: Folate deficiency.
Phenytoin: B₁₂ deficiency.
120
Folate deficiency: Laboratory findings (5).
Increased LDH.
Increased unconjugated bilirubin.
Increased forminoglutamic acid.
Decreased serum folate.
Decreased red-cell folate.
121
B₁₂ deficiency: Laboratory findings (6).
Increased LDH.
Increased unconjugated bilirubin.
Increased urinary methylmalonic acid.
Decreased red-cell folate (in ⅔ of cases).
Normal serum folate.
Decreased serum B₁₂.
122
Serum B₁₂: Causes of spurious abnormalities.
Falsely low serum B₁₂: HIV infection.
Falsely high: Liver disease, renal insufficiency, myeloproliferative neoplasms.
123
B₁₂ deficiency: Other laboratory findings (2).
Even mild B₁₂ deficiency causes increased
− Serum methylmalonic acid.
− Serum homocysteine.
124
Assay for antibodies to intrinsic factor.
Sensitive and specific for pernicious anemia.
125
Anemia of chronic disease:
A. Serum iron.
B. Total iron-binding capacity.
C. Percent saturation of transferrin.
D. Soluble transferrin receptors.
A. Low or normal.
B. Low or normal (?)
C. Greater than 15%.
D. Normal.
126
Sideroblastic anemia: Peripheral smear (4).
Hypochromia.
Microcytosis, normocytosis, or macrocytosis.
Biphasic population of red cells.
Pappenheimer bodies.
127
Sideroblastic anemia: Bone marrow (3).
Erythroid hyperplasia.
Increased iron stores.
Ringed sideroblasts.
128
Sideroblastic anemia: Laboratory findings (3).
Increased
− Serum iron.
− Ferritin.
− Percent saturation of transferrin.
129
Acquired sideroblastic anemia: Causes (5).
Myelodysplasia.
Irradiation.
Copper deficiency.
Alcohol abuse.
Drugs: isoniazid, chloramphenicol, chemotherapy.
130
Inherited sideroblastic anemia:
A. Most common gene and its location.
B. Treatment.
A. ALAS2 on the X chromosome.
B. Large doses of pyridoxine (B₆).
131
Pearson's syndrome:
A. Clinical manifestations.
B. Mutation.
A. Sideroblastic anemia, pancreatic insufficiency.
B. Microdeletion in mitochondrial DNA.
132
Congenital dyserythropoietic anemia, type II:
A. Synonym.
B. Inheritance.
A. Hereditary erythroid multinucleation with positive acidified serum.
B. Autosomal recessive.
133
Congenital dyserythropoietic anemia, type II: Morphology.
Dysplastic erythroid precursors with frequent internuclear bridges.
134
Congenital dyserythropoietic anemias: Antigen.
Overexpression of the i antigen.
135
Fanconi's anemia:
A. Inheritance.
B. Hematological features (3).
A. Autosomal recessive.
B. Aplastic anemia, MDS, AML (esp. monocytic or monoblastic),
136
Fanconi's anemia: Harbingers of pancytopenia.
Macrocytic anemia.
Thrombocytopenia.
137
Fanconi's anemia: Other manifestations (6).
Short stature.
Café-au-lait spots.
Renal abnormalities.
Elevated hemoglobin F.
Absent thumbs or radii.
Microcephaly.
138
Fanconi's anemia: Genes.
FANCA.
FANCC.
FANCG.
139
Fanconi's anemia: Epidemiology.
Highest incidence is in white South Africans.
140
Fanconi's anemia: Diagnosis.
Expose cultured cells to DNA-cross-linking agents (e.g. mitomycin C, cisplatin, diepoxybutane) and look for chromosomal breakage.
141
Diamond-Blackfan syndrome:
A. Synonym.
B. Bone marrow.
C. Other abnormalities of red cells.
A. Congenital pure red-cell aplasia.
B. Few or no erythroid precursors.
C. Increased expression of i antigen, increased Hb F, increased adenosine deaminase.
142
Diamond-Blackfan syndrome:
A. Inheritance.
B. Gene and its location.
A. Autosomal dominant.
B. DBA1 (RPS19) on 19q13.2.
143
β-Thalassemia: Hemoglobins in heterozygotes.
Hb A: Decreased.
Hb F: Increased.
Hb A₂: Increased unless there is also iron deficiency.
144
Diamond-Blackfan syndrome: Non-hematological abnormalities (3).
Short stature.
Anomalies of thumbs or radii.
Cardiac septal defects.
145
Diamond-Blackfan syndrome: Treatment.
Corticosteroids help 75% of children.
146
Acquired pure red-cell aplasia: Causes (5).
Thymoma.
Collagen-vascular diseases.
Drugs.
Parvovirus B19.
Large-granular-lymphocytic leukemias.
147
Transient erythrocytopenia of childhood: Clinical features.
Self-limited.
Affects previously healthy children aged 1 to 4 years.
148
Congenital amegakaryocytic thrombocytopenia:
A. Bone marrow.
B. Course.
A. No megakaryocytes.
B. Thrombocytopenia progressing to pancytopenia by 10 years of age.
149
Congenital amegakaryocytic thrombocytopenia:
A. Inheritance.
B. Gene and its location.
A. Autosomal recessive.
B. MPL (thrombopoietin receptor) on 1p34.
150
Kostmann's syndrome:
A. Course.
B. Inheritance.
C. Gene and its location.
A. Neutropenia, possibly manifesting as omphalitis, progressing to pancytopenia or to leukemia.
B. Autosomal dominant.
C. ELA2 (neutrophil elastase) on 19p13.
151
Cyclic neutropenia: Synonym.
Benign familial neutropenia.
152
Cyclic neutropenia:
A. Clinical presentation.
B. Neutrophil count.
C. Affected gene and its location.
A. Fever, ulcers, and other inflammations during periods of neutropenia.
B. Ranges from nil to normal over about 21 days.
C. ELA2 on 19p13.
153
Dyskeratosis congenita: Clinical features (6).
Aplastic anemia.
Reticulated skin pigmentation.
Nail dystrophy.
Oral leukoplakia.
Lacrimal-duct atresia.
Testicular atrophy.
154
Dyskeratosis congenita: Gene and its location.
DKC1 on Xq28.
155
Shwachman-Diamond syndrome: Clinical features (5).
Aplastic anemia.
Pancreatic exocrine insufficiency.
Short stature.
Severe combined immunodeficiency.
Reticular dysgenesis.
156
Shwachman-Diamond syndrome:
A. Inheritance.
B. Gene and its location.
A. Autosomal recessive.
B. SBDS on 7q11.
157
Percentage of cases of plastic anemia caused by ___.
A. drugs or toxins
B. viral hepatitis
C. unknown agent
A. 10%.
B. 5%.
C. 70%.
158
Aplastic anemia: Mimics (5).
Hairy-cell leukemia.
Hypoplastic MDS.
Hypoplastic AML.
Paroxysmal nocturnal hemoglobinuria.
Leukemia of T-cytotoxic LGLs.
159
Intravascular hemolysis: Causes (6).
Complement.
Oxidative stress.
Microangiopathic hemolytic anemia.
Mechanical destruction.
Infections.
Toxins.
160
Extravascular hemolysis: Causes.
Anything not included among the causes of intravascular hemolysis.
161
Intravascular hemolysis: Laboratory findings (5).
Schistocytes.
Increased LDH.
Decreased haptoglobin.
Increased free hemoglobin.
Hemosiderinuria.
162
Extravascular hemolysis: Laboratory findings (5).
Microspherocytes.
Increased LDH.
Increased unconjugated bilirubin.
Normal or decreased haptoglobin.
Increased urinary urobilinogen.
163
Acanthocyte:
A. Synonym.
B. Morphology.
C. Associations (3).
A. Spur cell.
B. Projections have blunt, bulbous ends and are unevenly distributed.
C. Liver disease, abetalipoproteinemia, McLeod phenotype.
164
Basophilic stippling: Composition.
Clumps of ribosomes (RNA).
165
Basophilic stippling: Associations (7).
Thalassemia.
Hemolytic anemia.
Arsenic toxicity.
Lead toxicity.
Megaloblastic anemia.
Alcohol abuse.
5'-Nucleotidase deficiency.
166
Teardrop cells: Clinical associations (3).
Myelophthisis.
Megaloblastic anemia.
Thalassemia.
167
Echinocyte:
A. Synonym.
B. Morphology.
A. Burr cell.
B. Projections are sharp and evenly distributed.
168
Echinocyte: Associations (5).
Gastric ulcer.
Uremia.
Pyruvate kinase deficiency.
Splenectomy.
Artifact.
169
Elliptocyte: Morphology.
Red cell is twice as long as it is wide.
170
Elliptocyte: Associations (4).
Deficiency of folate or of B₁₂.
Iron deficiency.
Myelodysplasia.
Elliptocytosis, hereditary.
171
Howell-Jolly body: Composition.
DNA (nuclear remnant).
172
Cabot ring:
A. Morphology.
B. Association.
A. Pink or red-purple ring or figure-of-eight.
B. Disorders of erythropoiesis.
173
Macrocytosis: Associations.
Round macrocytosis: Liver disease, hypothyroidism, myelodysplasia.
Oval macrocytosis: Deficiency of folate or of B₁₂.
174
Pappenheimer bodies:
A. Morphology.
B. Composition.
C. Associations (3).
A. Larger and more irregular than basophilic stippling.
B. Iron-containing mitochondria.
C. Sideroblastic anemia, asplenia, myelodysplasia.
175
Rouleaux: Causes.
Monoclonal protein.
Marked hyperfibrinogenemia.
176
Schistocytes in healthy adults.
A. Frequency.
B. As a percentage of RBCs.
A. 58%.
B. 0.05%.
177
Stomatocyte: Associations (5).
Stomatocytosis, hereditary.
Alcohol abuse.
Rh-null phenotype.
Phenytoin.
Artifact.
178
Target cells: Associations (3).
Thalassemia.
Abnormal hemoglobins such as Hb C, Hb E.
Liver disease.
179
Workup of anemia: First step.
Determine whether the anemia is
− Hyperregenerative (high reticulocyte count).
− Hyporegenerative (low or normal reticulocyte count).
180
Hyperregenerative normocytic anemia: Differential diagnosis.
Hemorrhage vs. hemolysis.
181
Hyporegenerative normocytic anemia: Workup.
Step 1. Is there bi- or pancytopenia?
− Yes: MDS vs. marrow infiltration vs. aplastic anemia.
− No: Step 2.
Step 2. Is the cause anemia of chronic disease; renal failure; early deficiency of Fe, folate, or B₁₂; drugs?
− No: MDS vs. pure red-cell aplasia vs. PNH.
182
Hyperregenerative microcytic anemia: Workup.
Step 1. Are there spherocytes?
− Yes: Step 2.
− No: Inherited defect in membrane or enzyme.
Step 2: Is the DAT positive?
− Yes: Immune-mediated hemolytic anemia.
− No: Hereditary spherocytosis.
183
Hyporegenerative microcytic anemia: Workup.
Step 1: Obtain iron studies (serum iron, ferritin, percent saturation of transferrin).
− Low: Iron-deficiency anemia.
− Normal: Step 2.
Step 2: Is hemoglobin electrophoresis abnormal (e.g. Hb C, Hb E, thalassemia)?
− No: Anemia of chronic disease or sideroblastic anemia.
184
Hyperregenerative macrocytic anemia: Differential diagnosis.
Hemorrhage vs. hemolysis.
185
Hyporegenerative macrocytic anemia: Workup
Step 1. Is the MCV greater than 115, or are there hyperlobate neutrophils?
− Yes: Step 2.
− No: Step 3.
Step 2. Studies of B₁₂ and folate.
− Low: Deficiency of B₁₂ and folate.
− Normal: Step 3.
Step 3. Is the cause hypothyroidism, liver disease, alcohol abuse, drugs (MTX, thioguanines, antiretrovirals), early deficiency of B₁₂ and folate, or Down's syndrome?
− No: Probable MDS.
186
Paraneoplastic erythrocytosis:
A. Solid neoplasms that cause it (4).
B. Mechanism.
A. HCC, RCC, epithelioid hemangioblastoma, uterine leiomyoma.
B. Secretion of erythropoietin.
187
Reactive neutrophilia: Usual upper limit.
30,000 per μL.
188
Reactive neutrophilia: Pharmacological causes (3).
Corticosteroids.
GM-CSF.
Epinephrine.
189
Reactive neutrophilia: Physiologic causes.
Exercise.
Pregnancy.
190
Reactive lymphocytosis: Leading causes.
Viral infection.
Toxoplasmosis.
191
Transient stress lymphocytosis:
A. Proliferating cells.
B. Morphology of predominant cell type.
A. B cells, T cells, NK cells.
B. Small, eccentric, indented nucleus; cytoplasm may contain granules.
192
Persistent polyclonal B lymphocytosis:
A. Typical patient.
B. Typical HLA type.
A. Young female smoker.
B. DR7.
193
Persistent polyclonal B lymphocytosis:
A. Morphology.
B. Additional laboratory finding.
A. Small, eccentric, indented or bilobate nucleus; much pale cytoplasm.
B. Polyclonal hypergammaglobulinemia.
194
Reider cells:
A. Morphology.
B. Association.
A. Mature small lymphocytes with cleft nuclei.
B. Reactive lymphocytosis in children (classically associated with pertussis).
195
Age at which absolute lymphocytosis must be considered suspicious for neoplasm.
40 years and older.
196
Reactive monocytosis: Causes (4).
Chronic infections (e.g. tuberculosis, listeriosis).
Collagen-vascular diseases.
Recovery from neutropenia.
Solid tumors.
197
Leading cause of reactive eosinophilia:
A. In the United States.
B. Worldwide.
A. Allergy.
B. Helminths.
198
Paraneoplastic reactive eosinophilia: Causes (3).
Hodgkin's lymphoma.
T-cell neoplasms.
Colonic carcinoma.
199
Reactive eosinophilia: Systemic inflammatory causes.
Eosinophilic cellulitis (Wells' syndrome).
Eosinophilic fasciitis (Shulman's syndrome).
Eosinophilic pneumonia (Löffler's syndrome).
Eosinophilic vasculitis (Churg-Strauss syndrome).
200
Reactive eosinophilia: Other causes (2).
Collagen-vascular diseases.
Inflammatory bowel disease.
201
Neutropenia:
A. Mechanisms (3).
B. Leading cause.
A. Increased destruction, decreased production, splenic sequestration.
B. Drugs.
202
Neutropenia: Causative drugs (9).
Methimazole.
Carbimazole.
Propylthiouracil.
Penicillins.
Chloramphenicol.
Sulfasalazine.
Carbamazepine.
Valproic acid.
Procainamide.
203
Autoimmune neutropenia:
A. Causes (3).
B. Syndrome.
A. SLE or rheumatoid arthritis in adults; usually idiopathic in children.
B. Felty's syndrome: Rheumatoid arthritis, neutropenia, splenomegaly.
204
Neutropenia: Infectious causes (5).
Typhoid fever.
Tularemia.
Brucellosis.
Rickettsial infections.
Overwhelming sepsis in infants and in the elderly.
205
Neutropenia: Causes of decreased production (3).
Drugs.
Inherited neutropenias.
Leukemias of large granular lymphocytes.
206
Lymphopenia:
A. Autoimmune cause.
B. Infectious causes.
A. Systemic lupus erythematosus.
B. HIV, SARS.
207
Lymphopenia: Causative drugs.
Steroids.
Rituximab.
208
Lymphopenia: Congenital causes (3).
Bruton's X-linked agammaglobulinemia.
Combined variable immunodeficiency.
DiGeorge's syndrome.
209
Deficiency of which type of lymphocyte is most likely to affect the total lymphocyte count?
The T lymphocyte.
210
Monocytopenia: Causes (3).
Hairy-cell leukemia.
Steroids.
Onset of neutropenia.
211
Pseudothrombocytopenia:
A. Cause.
B. Frequency.
C. Resolution.
A. EDTA.
B. 1% of hospitalized patients.
C. Collect a new sample in citrate or in acid-citrate-dextrose.
212
Thrombocytopenia: Causes of large or variably sized platelets (3).
May-Hegglin anomaly.
Bernard-Soulier syndrome.
ITP.
213
Thrombocytopenia: Meaning of schistocytes.
Microangiopathic hemolytic anemia: TTP, HUS, DIC, or HELLP.
214
Thrombocytopenia: Inherited causes with giant platelets (6).
May-Hegglin anomaly and other MYH9 syndromes.
Bernard-Soulier syndrome.
Gray-platelet syndrome.
DiGeorge's syndrome.
Microthrombocytopenias (Mediterranean and X-linked).
215
Thrombocytopenia: Inherited causes with small platelets.
Wiscott-Aldrich syndrome.
Congenital amegakaryocytic thrombocytopenia.
Thrombocytopenia−absent radii syndrome.
Glanzmann's thrombasthenia.
216
Thrombocytopenia: Causes in neonates (5).
Aneuploidies: +13, +18, +21, -X.
Maternal ITP.
Inherited causes.
Neonatal alloimmune thrombocytopenia.
TORCH infections.
217
Thrombocytopenia in children:
A. Leading cause and how to recognize it.
B. How to recognize a different cause.
A. ITP responds rapidly to steroids.
B. Inherited thrombocytopenias respond poorly to steroids but well to platelet transfusions.
218
Thrombocytopenia: Main causes in adults.
Drugs.
ITP.
Splenic sequestration.
219
Thrombocytopenia: Causative drugs (6).
Antibiotics.
Antiarrhythmics.
Alcohol.
Abciximab.
Heparin.
Thiazides.
220
Thrombocytopenia: How quinidine may cause it.
Induction of antibodies against GP IX.
221
Thrombocytopenia: Targets of antibodies in ITP (4).
GP IIIa.
GP IIb.
GP Ib.
GP V.
222
Thrombocytopenia: Principles of diagnosis of ITP (3).
Usually a diagnosis of exclusion.
Best test is trial of immunomodulation.
Tests for anti-platelet antibodies are nonspecific and usually not readily available.
223
Thrombocytopenia: ___ causes in adults.
A. Infectious
B. Neoplastic
C. Autoimmune
A. HIV, HCV, H. pylori.
B. MDS, B-cell neoplasms.
C. Antiphospholipid syndrome.
224
Thrombotic thrombocytopenic purpura: Pentad.
Fever.
Thrombocytopenia.
Microangiopathic hemolytic anemia.
Neurological dysfunction.
Renal dysfunction.
225
Thrombotic thrombocytopenic purpura:
A. Peripheral smear.
B. Laboratory finding.
A. Many schistocytes.
B. Very high serum LDH.
226
Thrombotic thrombocytopenic purpura: Causes of sporadic form (4).
Idiopathic.
Pregnancy.
Ticlopidine.
Antibodies to ADAMTS-13.
227
Thrombotic thrombocytopenic purpura: Cause of familial form.
Inherited deficiency of ADAMTS-13.
228
Thrombotic thrombocytopenic purpura: Treatment.
Daily plasmapheresis with FFP.
229
Thrombocytopenia: Workup.
Peripheral smear: Platelet clumps, schistocytes, leukemic cells, variably (ITP) or abnormally sized platelets.
Laboratory studies: Coagulation, renal function.
History: Radiation, chemotherapy, drugs.
Physical examination: Spleen, signs of inherited syndromes.
Cause unknown, even after examination of bone marrow: Peripheral destruction, collagen-vascular diseases, ITP.
230
Thrombocytosis: Causes in children (4).
Iron deficiency.
Infections.
Kawasaki's syndrome.
ALL.
231
Thrombocytosis: Causes in adults (6).
Systemic infection.
Iron deficiency.
Splenectomy.
Malignancy.
CML.
ET.
232
Thrombocytosis: Likelihood of myeloproliferative neoplasm at different platelet counts.
600,000: 70%.
1,000,000: 80%.
2,000,000: 95%.
233
Lymphomas of B cells that are ___ likely to involve the bone marrow.
A. most (3)
B. least (3)
C. moderately
A. Mantle-cell lymphoma, follicular lymphoma, DLBCL.
B. Marginal-zone lymphoma, Burkitt's lymphoma.
C. Lymphoplasmacytic lymphoma.
234
Typical pattern of infiltration of marrow by ___.
A. follicular lymphoma
B. diffuse large B-cell lymphoma
C. CLL/SLL
A. Paratrabecular.
B. Diffuse.
C. Non-paratrabecular in any pattern.
235
Typical pattern of infiltration of marrow by ___.
A. mantle-cell lymphoma
B. lymphoplasmacytic lymphoma
A. Nodular.
B. Interstitial.
236
Typical pattern of infiltration of marrow by ___.
A. marginal-zone lymphoma
B. Burkitt's lymphoma
A. Nodular.
B. Diffuse.
237
Lymphomas of B cells that are ___ likely to involve the peripheral blood.
A. most (2)
B. least
C. moderately (2)
A. Mantle-cell lymphoma, Burkitt's lymphoma.
B. Lymphoplasmacytic lymphoma.
C. Follicular lymphoma, DLBCL.
238
Lymphomas of B cells: Relation of grade to patient's age.
High-grade lymphomas in younger patients.
Low-grade lymphomas in older patients.
239
Lymphomas of B cells that are more common in females (3).
Primary mediastinal lymphoma.
Follicular lymphoma.
Extranodal marginal-zone lymphoma.
240
Lymphomas of B cells that is most to run in families.
CLL/SLL.
241
Relation of CLL/SLL to ___.
A. autoimmunity.
B. immunodeficiency
A. 30% of patients have a positive DAT.
B. 30-50% of patients have hypogammaglobulinemia.
242
Prolymphocyte counts in leukemias of B cells.
11-55%: PLL/CLL.
Less: CLL.
More: Prolymphocytic leukemia.
243
CLL: Significance of ___.
A. smudge cells
B. lymphocyte count
A. Seen in EDTA but not in heparin.
B. Less than 5000/μL: Monoclonal B-cell lymphocytosis.
244
CLL/SLL: The dim markers (3).
CD20.
sIg.
CD11c (weak and variable).
245
CLL/SLL and FISH:
A. Percentage of cases with normal result.
B. Most common abnormality.
C. Other abnormalities.
A. 20%.
B. del(13q14): More than 50%.
C. +12, -11q, -14q, -17p.
246
CLL/SLL: Transformations (3).
Most common: CLL/PLL or PLL.
Others: DLBCL, classic Hodgkin's lymphoma.
247
CLL/SLL:
A. Favorable karyotypes (2).
B. Unfavorable karyotypes (2).
A. Normal karyotype or isolated -13q.
B. -11q or -17p.
248
CLL/SLL:
A. Unfavorable status of immunoglobulin gene.
B. Normal lymphocyte corresponding to this status.
C. How to test for this status.
A. Unmutated IgVH.
B. The pregerminal-center B cell.
C. Expression of ZAP70 or of CD38 by more than 30% of cells.
249
CLL/SLL: Other prognostic factors (5).
"B" symptoms.
High stage.
Initial lymphocyte count exceeds 30,000.
Doubling of lymphocyte count within 1 year.
Diffuse infiltration of bone marrow.
250
CLL/SLL: Original Rai stages.
0: Lymphocytosis greater than 5000.
I: Lymphadenopathy.
II: Hepatosplenomegaly.
III: Hemoglobin less than 11 g/dL.
IV: Platelets fewer than 100,000.
251
SLL/CLL: Modified Rai stages, including survival.
Low risk (0): More than 13 years.
Intermediate risk (I and II): 8 years.
High risk (III and IV): 2 years.
252
SLL/CLL: Lymphoid areas of Binet stages.
Each side counts as one group:
− Cervical lymph nodes.
− Axillary lymph nodes.
− Inguinal lymph nodes.
Liver.
Spleen.
253
SLL/CLL: Binet stages, including survival.
A (fewer than 3 lymphoid areas): 15 years.
B (more than 3 lymphoid areas): 5 years.
C (Hb less than 11 g/dL or PLT less than 100,000): 3 years.
254
Mantle-cell lymphoma:
A. Frequent extranodal sites (2).
B. Pattern of infiltration.
A. Gastrointestinal tract, Waldeyer's ring.
B. Vaguely nodular or diffuse.
255
Mantle-cell lymphoma: Variants (4).
Pleomorphic, blastoid: More aggressive.
Small-cell: Resembles SLL.
Marginal-zone-like: Resembles marginal-zone lymphoma.
256
Mantle-cell lymphoma: The bright markers.
CD20.
sIg.
257
Mantle-cell lymphoma: Translocation.
t(11;14)(q13;q32) :: CCND1−IGH.
258
Mantle-cell lymphoma: Histologic predictors of poor prognosis.
More than 40% of nuclei express Ki67.
More than 10 mitotic figures per hpf.
259
Expression of ___ by mantle-cell lymphoma.
A. CD23.
B. CD11c.
A. Dim or absent.
| B. Absent.
260
Follicular lymphoma: Traditional grading.
6-15 centroblasts per hpf: Grade 2.
Fewer: Grade 1.
More: Grade 3.
− 3a: Some centrocytes.
− 3b: No centrocytes.
261
Follicular lymphoma: Modified grading.
Grades 1 and 2 are considered low-grade follicular lymphoma.
262
Follicular lymphoma with diffuse growth:
A. Definition.
B. How diagnosed.
A. No residual germinal centers; CD23 and CD21 reveal no follicular dendritic cells.
B. As focal diffuse growth if in the setting of low-grade follicular lymphoma; otherwise, as DLBCL.
263
Follicular lymphoma, intrafollicular variant:
A. Synonym.
B. Definition.
C. Significance.
A. Follicular lymphoma in situ.
B. Confined to follicles; open sinuses.
C. Unclear.
264
Follicular lymphoma, isolated cutaneous variant:
A. Prognosis.
B. Immunophenotype.
C. Cytogenetics.
A. Excellent.
B. Lacks CD10, bcl-2; expresses bcl-6.
C. No rearrangement of BCL2.
265
Follicular lymphoma, isolated gastrointestinal:
A. Prognosis.
B. Typical site.
A. Excellent.
B. Duodenum.
266
Typical grade of follicular lymphoma in ___.
A. children
B. the marrow
A. Grade 3.
B. Discordant.
267
Relevance of grade of follicular lymphoma to expression of ___.
A. CD10.
B. Ki67.
A. Lost in some follicular lymphomas of higher grade.
B. Low grade: less than 20% of nuclei express it; high grade: more than 20%.
268
Follicular lymphoma: Translocation.
t(14;18)(q32;q21) :: IGH−BCL2.
269
Significance of t(14;18) in other lymphomas.
No overexpression of bcl-2.
270
Follicular lymphoma: Adverse prognostic factors (7).
"B" symptoms.
Infiltration of bone marrow.
High stage.
High LDH.
Advanced age.
Low performance status.
Anemia.
271
Follicular lymphoma: Expression of ___.
A. CD23.
B. CD19.
C. CD38.
A,B. Usually absent.
C. Present.
272
Marginal-zone lymphoma: Translocations.
t(11;18)(q21;q21) :: API2−MALT1: Stomach, lungs.
t(14;18)(q32;q21) :: IGH−MALT1: Eyes, parotid, skin.
t(3;14)(p14;q32) :: FOXP1−IGH: Eyes, thyroid, skin.
t(1;14)(p22;q32) :: BCL10−IGH: Lung, small intestine.
273
Marginal-zone lymphoma: Expression of CD43.
Occurs in about 30% of cases.
274
Disease associated with ___ MALT lymphoma.
A. salivary
B. thyroidal
A. Sjögren's syndrome.
B. Hashimoto's thyroiditis.
275
Organism associated with ___ MALT lymphoma.
```
A. gastric
B. ocular
C. small-intestinal (IPSID)
D. cutaneous
E. splenic
```
A. Helicobacter pylori.
B. Chlamydophila psittaci.
C. Campylobacter jejuni.
D. Borrelia burgdorferi.
E. HCV.
276
Splenic marginal-zone lymphoma:
A. Location in the spleen.
B. Other possible sites.
A. White pulp.
B. Splenic hilar lymph nodes; liver.
277
Splenic lymphoma with villous lymphocytes:
A. Origin.
B. Differences from hairy-cell leukemia (3).
A. Peripheral expression of splenic marginal-zone lymphoma.
B. Polar villi, visible nucleolus, no expression of annexin A1.
278
Hairy-cell leukemia: Presentation.
Splenomegaly.
New monocytopenia, neutropenia, or aplastic anemia.
279
Hairy-cell leukemia: Location of infiltrate in the ___.
A. spleen
B. liver
A. Red pulp.
B. Sinusoids.
280
Hairy-cell leukemia:
A. Ultrastructure.
B. Staining for TRAP.
C. Staining for cyclin D1.
A. Ribosomal lamellar complexes.
B. Positive; weak staining is nonspecific.
C. Nuclear; does not imply rearrangement of CCND1 (bcl-1).
281
Hairy-cell leukemia: Relatively specific markers (5).
Bright: CD25, CD11c.
Others: CD103, annexin A1, DBA.44.
282
Hairy-cell leukemia: CD10.
Expressed in about 10% of cases.
283
Lymphomas of mature small B cells: FMC-7.
Expressed in MCL, MZL, FL, PLL, HCL.
Not expressed in CLL/SLL.
284
Lymphomas of mature small B cells that can be plasmacytoid (4).
CLL/SLL, MCL, MZL.
Lymphoplasmacytic lymphoma is diagnosed when the others have been excluded.
285
Waldenström's macroglobulinemia: Definition.
Lymphoplasmacytic lymphoma with
− Monoclonal IgM.
− Infiltration of the bone marrow.
286
Lymphoplasmacytic lymphoma: Special stain.
There may be PAS-positive matter in the nodal sinuses.
287
Heavy-chain disease: Types.
α: Most common; associated with IPSID.
γ: Franklin's disease; found in some cases of LPL.
μ: Found in some cases of CLL/SLL.
288
Diffuse large B-cell lymphoma: Presentation (2).
Rapid enlargement of node or other lymphoid tissue.
Bone marrow is involved initially in about 10% of cases.
289
Diffuse large B-cell lymphoma: CD5.
Such cases must be distinguished from blastoid mantle-cell lymphoma.
290
Diffuse large B-cell lymphoma: Ki67.
Expressed in 60-99% of nuclei.
291
Diffuse large B-cell lymphoma: Translocations.
t(14;18)(q32;q21) :: IGH−BCL2: Germinal-center-B-cell-like.
t(3;14)(q27;q32) :: BCL6−IGH: Activated-B-cell-like.
292
Prognostic types of diffuse large B-cell lymphoma:
A. How best to distinguish them.
B. Significance.
A. Gene-expression profiling.
B. GBC responds better than ABC to treatment.
293
Prognostic types of diffuse large B-cell lymphoma: Immunohistochemistry.
CD10
− Expressed by more than 30% of cells: GBC type.
− Expressed by fewer than 30% of cells: bcl-6.
bcl-6
+: MUM1.
−: ABC type.
MUM1
+: ABC type.
−: GBC type.
294
Primary diffuse large B-cell lymphoma of the CNS:
A. Median age.
B. Radiography.
C. Alternate presentation.
A. 60 years.
B. Can mimic glioblastoma multiforme.
C. Intraocular lymphoma.
295
Primary diffuse large B-cell lymphoma of the CNS:
A. Histology.
B. Mutation.
A. Infiltrates perivascular spaces.
B. Rearrangement of BCL6; overexpression of bcl-6.
296
T-cell/histiocyte-rich diffuse large B-cell lymphoma:
A. Median age.
B. Immunophenotype of small lymphocytes.
A. 40 years.
B. Expression of CD4 or CD8; no CD57 or B-cell markers.
297
T-cell/histiocyte-rich diffuse large B-cell lymphoma: Immunophenotype of tumor cells (2,1,3).
Positive: B-cell markers, bcl-6.
Variable: EMA.
Negative: CD15, CD30, EBV.
298
T-cell/histiocyte-rich diffuse large B-cell lymphoma: Pattern of infiltration of marrow.
Paratrabecular.
299
Primary mediastinal large B-cell lymphoma: Immunophenotype (2,3).
Positive: B-cell markers, CD30.
Negative: CD5, CD10, sIg.
300
Primary mediastinal large B-cell lymphoma: Mutations (3).
Mutation of MAL gene.
+9p (JAK2).
No rearrangement of BCL2 or of BCL6.
301
B-cell neoplasms with plasmablastic morphology (5).
Plasmablastic lymphoma.
Primary effusion lymphoma.
Post-transplant lymphoproliferative disorder.
ALK-positive DLBCL.
Anaplastic plasmacytoma.
302
Plasmablastic lymphoma:
A. Site.
B. Associated viruses.
A. Extranodal, often in the oral cavity.
B. EBV, HIV; HHV8 if arising from multicentric Castleman's disease.
303
Plasmablastic lymphoma: Immunophenotype (4,3).
Positive: CD38, CD138, IRF4/MUM1, cIg.
Negative: CD45, CD20, CD56.
304
Primary-effusion lymphoma:
A. Presentation.
B. Cytology.
A. Pleural, pericardial, or peritoneal effusion.
B. Large lymphocytes with plasmablastic, immunoblastic, or anaplastic appearance; cytoplasmic vacuoles.
305
Primary-effusion lymphoma: Associated viruses.
HIV, HHV8, EBV.
306
Primary-effusion lymphoma: Immunophenotype (5,3).
Positive: CD38, CD138, CD30, CD45, EMA.
Negative: B-cell markers, T-cell markers, NK-cell markers.
307
Primary cutaneous diffuse large B-cell lymphoma, leg type: Typical patient.
Elderly woman.
308
Intravascular large B-cell lymphoma: Presentation.
Signs and symptoms related to occlusion of vessels by the lymphoma.
Nodal disease is rare.
309
EBV-positive neoplasms of large B cells (6).
Plasmablastic lymphoma.
Primary effusion lymphoma.
Lymphomatoid granulomatosis.
DLBCL associated with chronic inflammation.
EBV-positive DLBCL of the elderly.
EBV-positive DLBCL, NOS.
310
Lymphomatoid granulomatosis: Sites (5).
Lungs.
Liver.
Kidneys.
Brain.
Upper aerodigestive tract.
311
Lymphomatoid granulomatosis: Associations.
EBV.
Immunodeficiency.
312
Lymphomatoid granulomatosis: Histology.
Lymphocytes infiltrate vessel walls in a vasculitis-like pattern.
Plasma cells, histiocytes, reactive T cells.
Granulomas are uncommon.
313
Diffuse large B-cell lymphoma associated with chronic inflammation: Association.
Longstanding pyothorax.
314
EBV-positive DLBCL ___: Association.
A. of the elderly
B. NOS.
A. Age greater than 50 years; typically Asian.
B. Immunodeficiency (usually) or age less than 50 years.
315
ALK-positive large B-cell lymphoma: Associated viruses.
None.
316
Most common primary immunodeficiencies associated with lymphoproliferative disorders (5).
Wiskott-Aldrich syndrome.
Ataxia-telangiectasia.
X-linked lymphoproliferative disorder.
Combined variable immunodeficiency.
Nijmegen syndrome.
317
Most common lymphoproliferative disorders in primary immunodeficiency (3).
DLBCL.
Lymphomatoid granulomatosis.
T-cell neoplasms.
318
Most common lymphomas in HIV infection (5).
DLBCL.
Plasmablastic lymphoma.
Primary effusion lymphoma.
Hodgkin's lymphoma.
Burkitt's lymphoma.
319
Post-transplant lymphoproliferative disorder:
A. When it occurs.
B. Warning sign.
C. Variant.
A. Within a year after transplant.
B. Rise in EBV-DNA.
C. Late-onset: More than 5 years after transplant, no EBV, more aggressive.
320
Post-transplant lymphoproliferative disorder, risk factors:
A. Relative to age.
B. Relative to type of transplant.
C. Relative to EBV status before the transplant.
A. More common in children.
B. More common in heart-lung and liver-bowel transplants than in transplants of kidney or bone marrow.
C. More common EBV-negative patients.
321
Post-transplant lymphoproliferative disorder:
A. Origin of neoplastic cells.
B. Site.
A. The recipient.
B. The allograft.
322
Burkitt's lymphoma: Types.
Endemic (African): Child with jaw mass; associated with EBV.
Sporadic (Western): Child or young adult with intraabdominal disease; not associated with EBV.
Immunodeficiency-associated: Immunodeficient person with nodal disease.
323
Burkitt's lymphoma: Phenotype (5,5).
Positive: CD20, CD10, bcl-6, c-myc, sIg.
Negative: CD5, CD23, bcl-2, CD34, TdT.
324
Burkitt's lymphoma: Genetics.
t(8;14).
t(2;8).
t(8;22).
325
Most common lineage of ___.
A. Acute lymphoblastic leukemia.
B. Lymphoblastic lymphoma.
A. B-cell (about 80%).
B. T-cell (about 80%).
326
B-ALL/LBL, NOS: Immunophenotype (7,2).
Positive: CD10, CD19, PAX5, TdT (nuclear), CD34, HLA-DR, CD99.
Negative: CD20, sIg.
327
B-ALL/LBL, NOS:
A. Loss of CD10.
B. Expression of myeloid markers.
A. May indicate mutation of MLL.
B. CD13 and/or CD33 is expressed in 30-50% of cases.
328
B-ALL/LBL, NOS: Favorable prognostic factors (5).
Female sex.
Low initial lymphocyte count.
Age 2-10 years.
Complete remission at 14 days after induction chemotherapy.
Hyperdiploidy
329
B-ALL/LBL, NOS: Unfavorable prognostic factor.
Hypodiploidy.
330
B-ALL/LBL, NOS vs. hematogones (2).
Flow cytometry: On plots of CD10, CD20, CD34, TdT, sIg, B-ALL is homogeneous and hematogones show a continuum of expression.
CD34-stained sections of bone marrow: Similar distinction.
331
B-ALL/LBL, NOS: Genetics.
By definition: No recurrent abnormalities.
Sometimes: Abnormalities of 6q, 9p, 12p.
332
B-ALL/LBL with recurrent cytogenetic abnormalities:
A. Most common abnormality.
B. Most common breakpoint.
C. Resulting protein.
A. t(9;22)(q34;q11.2) :: ABL−BCR.
B. m-bcr (minor).
C. Ph, 190 kD.
333
B-ALL/LBL with t(9;22)(q34;q11.2):
A. Epidemiology.
B. Prognosis.
A. More common in adults than in children.
B. Poor.
334
B-ALL/LBL with t(9;22)(q34;q11.2): Immunophenotype (5+2).
Positive: CD10, CD19, CD34, TdT, CD25.
Weak: CD13, CD33.
335
B-ALL/LBL with t(v;11q23):
A. Typical "v" chromosome.
B. Affected gene.
A. 4.
B. MLL on 11q23.
336
B-ALL/LBL with t(v;11q23):
A. Epidemiology.
B. Prognosis.
A. Affects infants.
B. Poor.
337
B-ALL/LBL with t(v;11q23): Immunophenotype (3,1).
Positive: CD19, CD15, FLT3.
Negative: CD10.
338
B-ALL/LBL with t(12;21)(p13;q22):
A. Involved genes.
B. Epidemiology.
C. Prognosis.
A. ETV6−RUNX1 (TEL−AML1).
B. Occurs in children.
C. Good.
339
B-ALL/LBL with t(12;21)(p13;q22): Immunophenotype (2+2,1).
Positive: CD10, CD19.
Weak: CD13, CD33.
Negative: CD9.
340
B-ALL/LBL with hyperdiploidy:
A. Definition.
B. Epidemiology.
C. Prognosis.
A. More than 50 chromosomes, esp. with extra copies of 4, 14, 21, X.
B. Occurs in children.
C. Good.
341
B-ALL/LBL with hyperdiploidy: Immunophenotype (4).
Positive: CD10, CD19, CD34, TdT.
342
B-ALL/LBL with hypodiploidy:
A. Epidemiology.
B. Prognosis.
A. Rare in children and in adults.
B. Poor.
343
B-ALL/LBL with t(1;19)(q23;p13.3):
A. Involved genes.
B. Epidemiology.
C. Prognosis.
A. TCF3−PBX1 (E2A−PBX1).
B. Uncommon in children.
C. Responds to intensive chemotherapy.
344
B-ALL/LBL with t(1;19)(q23;p13.3): Immunophenotype (2,1).
Positive: CD10, CD19.
Negative: CD34.
345
B-ALL/LBL with t(5;14)(q31;q32):
A. Involved genes.
B. Morphology.
A. IL3−IGH.
B. Eosinophilia.
346
B-ALL/LBL with t(5;14)(q31;q32):
A. Epidemiology.
B. Prognosis.
A. Rare in children and in adults.
B. Intermediate.
347
B-ALL/LBL with t(5;14)(q31;q32): Immunophenotype (4).
Positive: CD10, CD19, CD34, TdT.
348
T-ALL/LBL: Immunophenotype (6,1,1).
Positive: CD2, CD3 (cytoplasmic), CD5, CD7, TdT, CD99.
Variable: CD34.
Negative: HLA-DR.
349
T-ALL/LBL:
A. CD4 and CD8.
B. Myeloid antigens.
A. May be double-positive or double-negative.
B. Some cases express CD13, CD33.
350
T-ALL/LBL: Mutations.
Rearrangement of TCR in nearly all cases.
Rearrangement of IgH in 10-20% of cases.
351
T-ALL/LBL vs. thymoma (3).
Thymoma expresses EMA.
On plots of CD4 vs. CD8, or CD45 vs. CD3
− Thymoma shows dispersal.
− T-ALL/LBL shows clusters.
352
Multiple myeloma: Familial trend.
First-degree relatives have a three- to fourfold risk of multiple myeloma.
353
Multiple myeloma: Renal complications (4).
Myeloma cast nephropathy.
Amyloidosis (mainly λ chains).
Light-chain-deposition disease (mainly κ).
Tubular injury (hypercalcemia, hyperuricemia).
354
Multiple myeloma: Frequency of isotypes.
IgG: 55%.
IgA: 22%.
Light-chain only: 18%.
IgD, biclonal, IgE.
355
Multiple myeloma:
A. Most common idiotype.
B. Frequency of nonsecretory type.
A. κ.
B. About 5%.
356
Multiple myeloma, symptomatic: Criteria.
Monoclonal protein.
Clonal plasma cells in the bone marrow.
Organ impairment ("CRAB").
357
Multiple myeloma, smoldering: Criteria.
Monoclonal protein >3.0 mg/dL.
- or -
Clonal plasma cells >10%.
358
Multiple myeloma: Immunophenotype (5,6).
Positive: CD38, CD138, CD56, κ or λ, PCA1.
Negative: CD45, CD19, CD20, CD21, CD22, sIg.
359
Multiple myeloma: Variable markers (9).
Cyclin D1: Associated with t(11;14).
Myeloid markers: CD13, CD15, CD33, CD11b, CD117.
Others: CD30, CD10, EMA.
360
Multiple myeloma:
A. Locus of most common mutation.
B. Most common translocation.
A. 14q32.
B. t(11;14)(q13;q32) :: CCND1−IGH.
361
Multiple myeloma: How prognosis depends on karyotype.
Best: Normal karyotype or isolated t(11;14).
Intermediate: Isolated del(13q14).
Worst: t(4;14), t(14;16), or del(17p13.1).
362
Multiple myeloma: Other adverse prognostic factors (3).
High stage.
High β₂-microglobulin.
High plasma-cell-labeling index.
363
Plasma-cell leukemia:
A. Definition.
B. Presentation (3).
A. Circulating plasma cells are more than 2.0 × 10⁹/L or more than 20%.
B. Half of cases occur de novo; abrupt onset, aggressive course.
364
Plasma-cell leukemia:
A. Mutation.
B. Immunophenotypic abnormality.
A. −13.
B. Loss of CD56.
365
Solitary osseous plasmacytoma:
A. Sites.
B. Frequency of detectable M protein.
C. Frequency of progression to multiple myeloma.
A. Vertebrae, ribs, pelvis.
B. About 50%.
C. About 75% in 10 years.
366
Solitary extraosseous plasmacytoma:
A. Sites.
B. Frequency of detectable M protein.
C. Frequency of progression to multiple myeloma.
A. Nasal cavity, oropharynx, larynx.
B. Less than 50%.
C. Less than 50%.
367
Monoclonal gammopathy of unknown significance: Risk of progression (2).
Each year: 0.5% to 1%.
After 20 years: 1 in 3.
368
Monoclonal gammopathy of unknown significance: Criteria (4).
Monoclonal protein less than 3.0 g/dL.
Clonal plasma cells less than 10%.
No organ impairment.
No B-cell lymphoma.
369
T-cell neoplasms: Four most common.
Peripheral T-cell lymphoma, NOS.
Angioimmunoblastic T-cell lymphoma.
Anaplastic large-cell lymphoma.
Adult T-cell leukemia/lymphoma.
370
Peripheral T-cell lymphoma, NOS:
A. Pattern in lymph node.
B. Cytology of tumor cells.
C. Background cells.
A. Diffuse; conspicuous high-endothelial venules.
B. Small and large lymphocytes; multilobate nuclei.
C. Plasma cells, histiocytes, eosinophils.
371
Peripheral T-cell lymphoma, NOS: Immunophenotype.
Positive: CD4.
Negative: CD8, CD25.
Many pan-T-cell markers may be lost.
372
Angioimmunoblastic T-cell lymphoma:
A. Age group.
B. Associated virus.
A. Older adults.
B. EBV.
373
Angioimmunoblastic T-cell lymphoma: Presentation (4).
```
Abrupt onset of
− "B" symptoms.
− Generalized lymphadenopathy.
− Pruritic rash.
− Pleural effusion.
```
374
Angioimmunoblastic T-cell lymphoma: Possible immunological abnormalities (5).
Polyclonal hypergammaglobulinemia.
Anti-smooth-muscle antibody.
Rheumatoid factor.
Cold agglutinins.
Hemolytic anemia with positive DAT.
375
Angioimmunoblastic T-cell lymphoma: Pattern in lymph node.
Diffuse, with obscuring of follicles.
Conspicuous high-endothelial venules.
Tumor cells form clusters.
376
Angioimmunoblastic T-cell lymphoma:
A. Cytology of tumor cells.
B. Background cells.
A. Small to medium-sized; pale or clear cytoplasm; minimal atypia.
B. Plasma cells, histiocytes, eosinophils, immunoblasts.
377
Angioimmunoblastic T-cell lymphoma: Immunophenotype (5,1).
Positive: CD4; EBV; CXCL13, bcl-6, CD10 (markers of follicular T helper cells).
Negative: CD8.
One or more pan-T-cell markers may be lost.
378
Anaplastic large-cell lymphoma: Location of anaplastic cells.
In clusters near blood vessels.
379
Anaplastic large-cell lymphoma: Prognosis.
Better if it expresses Alk.
Alk-negative lymphomas have a better prognosis than peripheral T-cell lymphoma, NOS.
380
Anaplastic large-cell lymphoma: Immunophenotype (4,3,2).
Positive: CD30 (membranous and Golgi pattern), CD45, clusterin, EMA.
Variable: CD4, CD13, CD33.
Negative: CD15, EBV.
381
Anaplastic large-cell lymphoma: Translocations and staining patterns.
t(2;5)(p23;p25) :: ALK−NPM: Cytoplasmic and nuclear.
t(1;2)(q25;p23) :: TPM3−ALK: Cytoplasmic and membranous.
382
Anaplastic large-cell lymphoma: Additional mutation.
Rearrangement of TCR.
383
Adult T-cell leukemia/lymphoma: Lifetime risk.
About 5% in those infected before 20 years of age.
384
Adult T-cell leukemia/lymphoma: Presentation (8).
Lymphadenopathy.
Hepatosplenomegaly.
Jaundice.
Weight loss.
Involvement of CNS or of viscera.
Hypercalcemia.
Lytic bone lesions.
Rash.
385
Adult T-cell leukemia/lymphoma: Immunophenotype (5,2).
Positive: CD2, CD3, CD4, CD5, CD25.
Negative: CD7 (usually), CD8.
386
Large-granular-lymphocytic leukemia: Criterion.
Large granular lymphocytes are more than 2.0 × 10⁹ for more than 6 months, with no other explanation.
387
Large-granular-lymphocytic leukemia: Frequent concurrent hematologic abnormalities (3).
Neutropenia.
Splenomegaly.
Polyclonal hypergammaglobulinemia.
388
Large-granular-lymphocytic leukemia of cytotoxic T cells:
A. Epidemiology.
B. Clinical course.
A. More common in males; median age is 60 years.
B. Indolent unless CD56 positive with blastoid cells.
389
Large-granular-lymphocytic leukemia of cytotoxic T cells: Immunophenotype (7,3).
Positive: CD2, CD3, CD8, CD16, CD57, granzyme B, granzyme M.
Negative: CD4; CD5 and CD7 may be dim or absent.
390
Large-granular-lymphocytic leukemia of cytotoxic T cells: Mutation.
Rearrangement of TCR.
391
Large-granular-lymphocytic leukemia of NK cells: Presentation.
Neutropenia.
Anemia.
Jaundice.
Hepatosplenomegaly.
Fever.
392
Large-granular-lymphocytic leukemia of NK cells: Immunophenotype (4,3,2).
Positive: CD2, CD3ε, CD16, CD56.
Variable: CD7, CD8, CD57.
Negative: CD4, surface CD3.
393
Large-granular-lymphocytic leukemia of NK cells:
A. Associated virus.
B. Mutation.
A. None.
B. No rearrangement of TCR.
394
Aggressive NK-cell leukemia:
A. Epidemiology.
B. Associated virus.
A. Occurs in Asians; mean age is 40 years.
B. EBV.
395
Nasal-type NK/T-cell lymphomas:
A. Epidemiology.
B. Pattern in lymph node.
A. Occurs in Asians and in natives of Central and South America.
B. Angioinvasive.
396
Nasal-type NK/T-cell lymphoma: Associated virus.
EBV.
397
Enteropathy-associated T-cell lymphoma:
A. Antecedent disease.
B. Associated HLA types.
A. Ulcerative jejunoileitis (refractory celiac disease) in many cases.
B. DQA1*0501, DQB*0201.
398
Enteropathy-associated T-cell lymphoma: Immunophenotype.
Positive: CD30, CD3.
Negative (usually): CD4, CD8.
399
Hepatosplenic T-cell lymphoma, γδ type:
A. Epidemiology.
B. Immunophenotype.
C. Mutation.
A. Affects young males.
B. Expresses CD8.
C. i(7q).
400
Hepatosplenic T-cell lymphoma, αβ type: Epidemiology.
Affects females; ages vary.
401
Cutaneous T-cell lymphoma:
A. Immunophenotype.
B. When it gets called mycosis fungoides.
A. Expresses CD4.
B. When it involves lymph nodes.
402
Nodular lymphocyte-predominant Hodgkin's lymphoma vs. TCRBCL (3).
NLP-HL:
− T cells that express CD3 and CD57 surround the tumor cells.
− Cells in the background are B cells.
− CD21 stain demonstrates network of follicular dendritic cells.
403
Nodular lymphocyte-predominant Hodgkin's lymphoma: Immunophenotype of tumor cells (6,3).
Positive: CD45, CD20, sIg, bcl-6, Oct2, BOB.1.
Negative: CD15, CD30, EBV.
404
Classical Hodgkin's lymphoma: Immunophenotype of tumor cells (4,3,4).
Positive: CD30, fascin, IRF4/MUM1, PAX5.
Variable: CD20, EBV, Oct2.
Negative: CD45, CD79a, BOB.1, EMA.
405
Classical Hodgkin's lymphoma: Spread.
Contiguous (to adjacent lymphoid regions), except in the lymphocyte-depleted subtype.
406
Classical Hodgkin's lymphoma: Most common sites of presentation.
Cervical lymph nodes.
Mediastinum.
407
Classical Hodgkin's lymphoma in the bone marrow:
A. Overall frequency.
B. Most common subtypes.
C. Definition.
A. 10%.
B. Lymphocyte-depleted, HIV-associated.
C. Presence of atypical, mononuclear, CD30-positive tumor cells in the appropriate background.
408
Subtype of classical Hodgkin's lymphoma most strongly associated with ___.
A. Syncytial histology.
B. EBV.
C. Lacunar cells.
D. Intraabdominal disease.
A,C. Nodular sclerosis.
B,D. Mixed cellularity.
409
Blast equivalents counted in acute leukemias (3).
Promonocytes:
− Acute monocytic/monoblastic leukemia.
− Acute myelomonocytic leukemia.
Promyelocytes: Acute promyelocytic leukemia.
Erythroblasts: "Pure" acute erythroblastic leukemia.
410
Mutations associated with ___.
A. Polycythemia vera (2).
B. Primary myelofibrosis (3).
C. Essential thrombocythemia (3).
A. JAK2: V617F or mutation in exon 12.
B,C. JAK2: V617F; MPL: W151L or W151K.
411
Mutations associated with ___.
A. Some eosinophilic myeloproliferative neoplasms (3).
B. Mastocytosis.
A. PDGFRA, PDGRFB, FGFR1.
B. KIT: D816V.
412
Secondary MDS:
A. Epidemiology.
B. Causes.
C. Mutations.
A. Can occur in younger patients.
B. Benzene, alkylating agents, radiation, Fanconi's anemia.
C. Anomaly of 5q or of 7q is associated with alkylating agents.
413
Refractory cytopenia with unilineage dysplasia: Allowance of blasts.
Blood: Less than 1%.
Marrow: Less than 5%.
No Auer rods.
414
Refractory cytopenia with unilineage dysplasia: Allowance of ringed sideroblasts.
No more than 15%.
415
Refractory anemia with ringed sideroblasts: Allowance of blasts.
Blood: Less than 1%.
Marrow: Less than 5%.
No Auer rods.
416
Refractory anemia with ringed sideroblasts: Peripheral smear.
May show
− Dimorphic population of red cells.
− Pappenheimer bodies.
417
Refractory cytopenias with multilineage dysplasia: Allowance of blasts.
Blood: Less than 1%.
Marrow: Less than 5%.
No Auer rods.
418
Refractory cytopenias with multilineage dysplasia: Allowance of dysplasia.
More than 10% in more than 1 cell line.
419
Refractory anemia with excess blasts: Allowances of blasts.
RAEB-1
− Blood: Less than 5%.
− Marrow: 5-9%.
− No Auer rods.
RAEB-2
− Blood: 5-19%.
− Marrow: 10-19%.
* or Auer rods *
420
Myelodysplastic syndrome with del(5q): Allowance of blasts.
Blood: Less than 1%.
Marrow: Less than 5%.
No Auer rods.
421
Myelodysplastic syndrome with del(5q): Bone marrow.
Megakaryocytes with nuclear hypolobation.
422
Ringed sideroblast: Definition.
Contains at least 5 siderosomes that follow at least one third of the circumference of the nucleus.
423
Functional indicators of dyserythropoiesis (5).
Complement, increased susceptibility to.
Hemoglobin F, elevated.
Enzymatic defects.
Antigens, abnormal expression of.
Thalassemia, acquired.
424
Myelodysplasia: Secondary causes (7).
HIV.
Drugs.
```
Copper deficiency / zinc toxicity.
Arsenic toxicity.
B₁₂ or folate deficiency.
Lead toxicity.
Ethanol.
```
425
Myelodysplasia: Most common karyotypic abnormalities.
Complex karyotype (#1).
−7, −7q.
−5q.
426
Myelodysplasia: Relevance of karyotype to prognosis.
Best: Normal karyotype or isolated −5q, −20q, −Y.
Worst: Complex karyotype (at least 3 abnormalities) or anomaly of chromosome 7.
Intermediate: Anything else.
427
Chronic myelomonocytic leukemia: Criteria (4).
Persistent monocytosis of more than 1 × 10⁹ per L.
Myelodysplasia (usually granulocytic).
Blasts are less than 20% of nucleated cells in the marrow.
No Ph.
428
Chronic myelomonocytic leukemia: Other frequent findings (3).
Hepatosplenomegaly.
Anemia, thrombocytopenia.
Atypical monocytes.
429
Chronic myelomonocytic leukemia: Types.
CMML-1: Blasts + promonocytes are less than 5% in the blood and less than 10% in the marrow; no Auer rods.
CMML-2: Blasts + promonocytes are 5-19% in the blood or 10-19% in the marrow.
430
Chronic myelomonocytic leukemia: Mutation.
JAK2 is mutated in a few cases.
Eosinophilic CMML: Mutation of PDGFRA or of PDGFRB is not allowed.
431
Atypical CML vs. conventional CML.
Atypical CML
− Dysplasia.
− Usually no significant basophilia.
− No rearrangement involving BCR and ABL.
432
Atypical CML: Mutations.
+8, −20q in many cases.
JAK2 is mutated in a few cases.
433
JMML:
A. Most common karyotypic abnormality.
B. Frequent comorbidity.
A. −7.
B. Neurofibromatosis, type 1.
434
JMML: Confirmatory test.
Spontaneous formation in vitro of granulocyte-macrophage colonies that show increased sensitivity to GM-CSF.
435
CML: Translocation.
t(9;22)(q34;q11.2) :: ABL−BCR.
436
CML: Breakpoints of the translocation.
M-bcr (major breakpoint): p210; usual mutation of CML.
m-bcr (minor breakpoint): p190
− Marked monocytosis.
− Also seen in Ph+ ALL.
μ-bcr: p230; marked thrombocytosis, mature neutrophils.
437
CML: Bone marrow (3).
"Dwarf" megakaryocytes.
Mild reticulin fibrosis.
Thickened paratrabecular generative cuffs.
438
CML: Chemical findings (2).
Decreased LAP score.
Markedly increased serum B₁₂.
439
CML, accelerated phase: Criteria.
Progressive basophilia (more than 20%).
Progressive thrombocytosis (more than 1000) or thrombocytopenia (less than 100).
Increasing blasts (between 10% and 20%).
Clonal cytogenetic progression (+8, +19, +Ph, i(17q)).
440
CML, blast phase: Criteria.
Blasts in the marrow (more than 20% or in a large aggregate).
Blasts in the blood (more than 20%).
Myeloid sarcoma.
441
CML, blast phase: Outcomes.
AML: 70%.
ALL: 30%.
442
CML: Most powerful predictor of prognosis.
Response to tyrosine-kinase inhibitors as determined by quantitative RT-PCR.
443
Resistance to imatinib in CML:
A. Frequency.
B. Mechanisms.
A. About 5% initially; increases with time.
B. Mutation in the tyrosine-kinase domain or in the P loop.
444
Polycythemia vera: Major criteria.
Hb exceeds 18.5 g/dL in men or 16.5 g/dL in women, or increased red-cell mass.
Mutation in JAK2: V617F or functionally similar.
445
Polycythemia vera: Minor criteria.
Panmyelosis.
Endogenous formation of erythroid colonies in vitro.
Normal serum erythropoietin.
446
Polycythemia vera, chronic phase: Peripheral blood.
Erythrocytosis.
There may also be neutrophilia, basophilia, and/or thrombocytosis.
447
Polycythemia vera, chronic phase: Bone marrow (3).
Hypercellularity.
Marked hyperplasia of megakaryocytes.
Low or absent stainable iron.
448
Polycythemia vera, spent phase (3).
Marrow: Reticulin fibrosis.
Blood: Myelophthisis.
Tissues: Extramedullary hematopoiesis.
449
Polycythemia vera: Required number of criteria.
Both major criteria and one minor criterion
- or -
One major criterion and two minor criteria.
450
Polycythemia vera: Main causes of death.
Thrombosis.
Acute leukemia.
451
JAK2:
A. Frequency of mutation in myeloproliferative neoplasms.
B. Purpose of protein.
A. More than 90% in PV; more than 50% in ET and in PMF.
B. Stimulates the STAT pathway.
452
JAK2: Most common mutations.
V617F (G to T at position 1849).
Activating mutation in exon 12.
453
Hereditary spherocytosis:
A. Inheritance.
B. Molecular defect.
A. Autosomal dominant.
B. Ankyrin (ANK1 gene).
454
Essential thrombocythemia: Criteria.
Sustained thrombocytosis (more than 450).
Megakaryocytic hyperplasia without panmyelosis.
Does not meet criteria of PV, PML, CML, or MDS.
Presence of V617F in JAK2, or exclusion or reactive causes of thrombocytosis.
455
Essential thrombocythemia: Epidemiology.
Peaks around 30 years and 60 years.
456
Essential thrombocythemia: Peripheral blood.
Isolated thrombocytosis.
457
Essential thrombocythemia: Marrow (4).
Megakaryocytes
− Large, hyperlobate nuclei.
− Paratrabecular.
− May exhibit emperipolesis.
Stainable iron is present, unlike in iron-deficiency anemia.
458
Primary myelofibrosis, cellular phase: Peripheral blood (3).
Anemia.
Mild leukocytosis.
Thrombocytosis.
459
Primary myelofibrosis, cellular phase: Marrow (3).
Hypercellularity.
Megakaryocytes
− Dark, clumped chromatin.
− Next to trabeculae and sinuses.
460
Primary myelofibrosis, fibrotic phase: Peripheral blood.
Leukoerythroblastic pattern.
461
Primary myelofibrosis, fibrotic phase: Marrow (3).
Reticulin fibrosis.
Hematopoiesis in the sinuses.
Atypical, clumped megakaryocytes.
462
Chronic eosinophilic leukemia: Epidemiology.
Nine times more common in males.
Ages 25-45.
463
Chronic eosinophilic leukemia: Number and morphology of eosinophils.
More than 1.5 × 10⁹ per L.
Cyanine-resistant MPO stain highlights hypogranular eosinophils.
464
Chronic eosinophilic leukemia: Sites of infiltration of tissues.
Heart.
Lungs.
Gastrointestinal tract.
CNS.
465
Chronic eosinophilic leukemia vs. the hypereosinophilic syndrome.
Both are diagnoses of exclusion.
Increased blasts and clonal cytogenetic abnormalities occur only in CEL.
466
Genes associated with eosinophilia in hematolymphoid neoplasms.
PDGFRA.
PDGFRB.
FGFR1.
467
Rearrangement of PDGFRA:
A. Usual neoplasm.
B. Other neoplasms.
A. CEL-like disease.
B. AML with eosinophils, T-ALL with eosinophils.
468
Rearrangement of PDGFRA:
A. Epidemiology.
B. Karyotype.
A. 17 times more common in males; median age is 40 years.
B. Normal; rearrangement with NFIP1L1 leads to cryptic deletion of 4q12.
469
Rearrangement of PDGFRB:
A. Usual neoplasm.
B. Other neoplasms.
A. CMML-like disease.
B. AML with eosinophils.
470
Rearrangement of PDGFRB:
A. Epidemiology.
B. Karyotype.
A. Twice as common in males; median age is 40 years.
B. t(5;12) :: PDFGRB−ETV6.
471
Rearrangement of FGFR1:
A. Usual neoplasm.
B. Other neoplasms.
A. T-ALL with eosinophils.
B. CEL-like disease.
472
Rearrangement of FGFR1:
A. Epidemiology.
B. Karyotype.
A. 15 times more common in males; median age is 30 years.
B. t(8;13) :: FGFR1−ZNF198.
473
AML: Median age at presentation.
65 years.
474
Usual blast count in AML:
A. Percentage.
B. Exceptions (3).
A. 20%.
B. Pure erythroleukemia, myeloid sarcoma, recurrent genetic abnormality.
475
AML: Usual phenotype.
Positive: CD13, CD33, CD34, HLA-DR.
Weak: CD45.
476
AML: Exceptions to the usual phenotype (2).
Promyelocytic leukemia: No expression of CD34 or of HLA-DR.
Expression of CD7 or of CD19 by some leukemias.
477
AML: Major categories (4).
AML with recurrent genetic abnormalities.
AML secondary to therapy.
AML with myelodysplasia-related changes.
AML, NOS.
478
AML with t(8;21):
A. Genes.
B. Role of one of the genes.
A. t(8;21)(q22;q22) :: RUNX1T1−RUNX1.
B. RUNX1 encodes the α chain of core-binding factor.
479
AML with t(8;21): Morphology.
Much gray-blue cytoplasm.
Large azurophilic granules.
Auer rods.
480
AML with t(8;21): Immunophenotype.
Usual AML phenotype, but also expresses CD56 and sometimes CD19.
481
AML with t(8;21):
A. Age group.
B. Prognosis.
A. Young adults.
B. Favorable.
482
AML with t(8;21): Mutation in many relapsed cases.
Activating mutation of KIT.
483
AML with inv(16) or t(16;16): Genes.
inv(16)(p13;q22) or t(16;16)(p13;q22) :: MYH11−CBFβ.
484
AML with inv(16) or t(16;16): Properties of eosinophils.
Large granules, including basophilic ones.
Take up α-naphthylacetate esterase.
Usually not abundant in the peripheral blood.
485
AML with inv(16) or t(16;16): Immunophenotype.
Usual AML phenotype plus expression of CD14, CD64, CD2, CD11b, lysozyme.
486
AML with inv(16) or t(16;16):
A. Age group.
B. Prognosis.
A. Young adults.
B. Favorable.
487
AML with t(15;17): Genes.
t(15;17)(q22;q12) :: PML−RARA.
488
AML with t(15;17): Morphology.
Promyelocytes with bilobate or reniform nuclei.
Intensely granular or apparently agranular (microgranular).
489
AML with t(15;17): Properties of the microgranular variant.
Reacts with MPO stain.
Auer rods.
490
AML with t(15;17): Immunophenotype.
Positive: CD13, CD33.
Dim: CD15.
Negative: CD34, HLA-DR.
491
AML with t(15;17): Medical emergency.
DIC on presentation.
492
Promyelocytic leukemia: Translocations of ATRA-resistant disease.
t(11;17) sometimes.
PML with t(5;17) appears to respond to ATRA.
493
Promyelocytic leukemia: Complication of therapy with ATRA.
Differentiation (retinoic acid) syndrome.
494
AML with t(15;17):
A. Age group.
B. Prognosis.
A. Middle-aged adults.
B. Favorable.
495
AML with t(9;11): Genes.
t(9;11)(p22;q23) :: MLLT3−MLL.
496
AML with t(9;11): Morphology.
Monocytic.
497
AML with t(9;11): Immunophenotype (5+3).
Positive: CD33, CD4, CD64, CD11b, HLA-DR.
Weak: CD13, CD14, CD34.
498
AML with t(9;11):
A. Age group.
B. Prognosis.
A. Children.
B. Intermediate.
499
AML with t(6;9): Genes.
t(6;9)(p23;q34) :: DEK−NUP214.
500
AML with t(6;9): Morphology (3).
May resemble FAB M2 or M4.
Often exhibits basophilia.
Often exhibits multilineage dysplasia.
501
AML with t(6;9): Immunophenotype.
Usual immunophenotype of AML.
About half of cases also express TdT.
502
AML with t(6;9):
A. Age group.
B. Prognosis.
A. Children and adults.
B. Poor.
503
AML with t(1;22): Genes.
t(1;22)(p13;q13) :: RBM15−MKL1.
504
AML with t(1;22): Morphology.
Megakaryocytic.
505
AML with t(1;22): Immunophenotype (4,2).
Positive: CD13, CD33, CD41, CD61.
Negative: CD34, HLA-DR.
506
AML with t(1;22):
A. Age group.
B. Prognosis.
A. Infants.
B. Intermediate.
507
AML with inv(3) or t(3;3): Genes.
inv(3)(q21q26) :: RPN1−EVI1.
t(3;3)(q21;q26) :: RPN1−EVI1.
508
AML with inv(3) or t(3;3): Morphology.
May resemble FAB M1, M4, or M7.
Thrombocytosis; giant agranular platelets.
509
AML with inv(3) or t(3;3):
A. Age group.
B. Prognosis.
A. Adults.
B. Poor.
510
AML related to therapy: Genes.
Inhibitors of topoisomerase II may affect
− RUNX1 on 21q22.
− MLL on 11q23.
511
AML related to therapy: Morphology (4).
Multilineage dysplasia.
Erythroid hyperplasia.
Ringed sideroblasts.
Basophilia.
512
AML related to therapy: Causes.
Inhibitors of topoisomerase II.
Alkylating agents.
Ionizing radiation.
513
AML related to therapy: Immunophenotype.
Usual immunophenotype of AML.
May also expresses CD56 and/or CD7.
514
AML related to therapy:
A. Time of onset.
B. Prognosis.
A. About 5 years after therapy.
B. Poor.
515
AML with myelodysplasia-related changes: Criteria.
Blasts are more than 20% in the marrow.
One of the following:
− History of MDS.
− Cytogenetic abnormality related to MDS.
− Multilineage dysplasia (more than 50% of cells in more than 1 cell line).
No history of cytotoxic chemotherapy.
No recurrent cytogenetic abnormality associated with AML.
516
AML with myelodysplasia-related changes:
A. Age group.
B. Prognosis.
A. Elderly patients.
B. Progresses slowly; does not respond to therapy.
517
AML, NOS, with minimal differentiation: Morphology.
Undifferentiated blasts without Auer rods and without granules.
Less than 3% of blasts are positive for MPO or Sudan black B.
518
AML, NOS, with minimal differentiation: Immunophenotype.
Usual immunophenotype of AML, plus CD117.
About half of cases express TdT.
519
AML, NOS, without maturation: Morphology.
Rare Auer rods and granules.
3-10% of blasts are positive for MPO or SBB.
520
AML, NOS, without maturation: Immunophenotype.
Usual immunophenotype of AML, plus CD117.
521
AML, NOS, with maturation: Criteria (3).
Morphologically similar to AML with t(8;21).
Maturation in more than 10% of blasts.
Less than 20% of nonerythroid cells show monocytic differentiation.
522
AML, NOS, with maturation: Immunophenotype.
Positive: Usual immunophenotype of AML, sometimes also with CD15.
523
AML, NOS, myelomonocytic: Criteria (2).
At least 20% of nucleated cells show monocytic differentiation.
At least 20% of nucleated cells show granulocytic differentiation.
524
AML, NOS, myelomonocytic: Immunophenotype (2).
Expresses myeloid markers and monocytic markers.
525
AML, NOS, monocytic/monoblastic: Criteria (3).
At least 80% of nucleated cells show monocytic differentiation.
Acute monoblastic leukemia: Most of the monocytic cells are monoblasts.
Acute monocytic leukemia: Most of the monocytic cells are promonocytes.
526
AML, NOS, monocytic/monoblastic: Immunophenotype (2,1).
Positive: Monocytic markers, HLA-DR.
Variable: Myeloid markers.
527
AML, NOS, monocytic/monoblastic:
A. Age group.
B. Tissues subject to infiltration.
A. Younger patients.
B. Gingiva, CNS.
528
Erythroleukemia: Criteria (2).
At least 50% of nucleated cells are erythroblasts.
At least 20% of non-erythroid cells are myeloblasts.
529
Pure erythroid leukemia: Criteria (2).
At least 80% of nucleated cells are erythroblasts.
No excess of myeloblasts.
530
Acute erythroid leukemia: Peripheral smear.
Anemia.
Many nucleated red blood cells.
531
Acute erythroid leukemia: Aspirate smear (4).
Dysplasia.
Megaloblastoid change.
Sometimes: Vacuoles, globular staining with PAS.
532
Immunophenotype of ___ in acute erythroid leukemia:
A. myeloblasts
B. erythroblasts (4)
A. Usual immunophenotype of AML, plus CD117.
B. CD34, HLA-DR, CD235 (glycophorin), CD71 (may be weak).
533
Acute megakaryoblastic leukemia: Morphology.
At least 50% of blasts are megakaryoblasts.
Megakaryoblasts exhibit nuclear blebs.
534
Acute megakaryoblastic leukemia:
A. How to demonstrate megakaryocytic lineage.
B. Associations.
A. Platelet-peroxidase technique; flow cytometry for CD41, CD61.
B. Mediastinal germ-cell tumors, i(12p).
535
Acute megakaryoblastic leukemia: Immunophenotype (2,2).
Positive: CD41, CD61.
Negative: CD34, HLA-DR.
536
AML, NOS: Prognosis.
Variable: AML with maturation, acute myelomonocytic leukemia.
Poor: All other types.
537
Acute leukemia in Down's syndrome: Types.
ALL: Similar to typical ALL.
AML.
538
AML in Down's syndrome:
A. Morphology.
B. Immunophenotype.
A. Megakaryoblastic.
B. Expresses CD13 and CD11b but not CD34.
539
AML in Down's syndrome:
A. Age.
B. Prognosis.
C. Treatment.
A. One to five years of age.
B. Relatively favorable.
C. Responds well to methotrexate.
540
Transient myeloproliferative disorder / transient abnormal myelopoiesis:
A. Frequency in Down's syndrome.
B. Age at onset.
C. Karyotype.
A. About 10%.
B. One week or less.
C. +21: May be limited to the neoplastic clone.
541
Transient myeloproliferative disorder / transient abnormal myelopoiesis:
A. Clinical presentation.
B. Course (2).
A. Marked leukocytosis, hepatosplenomegaly.
B. Usually resolves without treatment; neonates are at high risk for AML.
542
Transient myeloproliferative disorder / transient abnormal myelopoiesis:
A. Immunophenotype.
B. Mutation.
A. Expresses CD34 but not CD13 or CD11b (inverse of AML).
B. Somatic mutation of GATA1 (also occurs in AML).
543
Congenital acute leukemia:
A. Age at presentation.
B. Differential diagnosis and how to resolve it.
A. Four weeks or less (by definition).
B. TMD / TAM, leukemoid reaction; flow cytometry, cytogenetics.
544
Congenital acute leukemia: Most common type.
About 65% of cases are AML, especially monocytic/monoblastic.
545
Congenital acute leukemia:
A. Presentation.
B. Mutation.
A. There may be blue spots on the skin (leukemia cutis).
B. MLL (11q23) in 10% of cases.
546
Mast-cell neoplasms: Chemical findings.
Increase in
− Serum tryptase.
− Urinary N-methylhistamine.
− Urinary prostaglandin D2.
547
Mast-cell neoplasms: Immunophenotype (7+1).
Positive: CD25, CD2; CD45, CD11b, CD33, CD43, FcεRI.
Weak: CD117.
548
Mast-cell neoplasms: Most common mutation.
D816V in KIT: Corresponds with aberrant expression of CD25.
549
Hematopoietic disorders associated with elevated histamine.
Mast-cell neoplasms.
The hypereosinophilic syndrome.
550
Hemocytometer: Dimensions of one large square.
0.1 cm × 0.1 cm × 0.01 cm deep = 0.1 μL.
551
Manual CBC: Measured indices.
RBC (using the hemocytometer).
Hematocrit (using the centrifuge).
552
Manual CBC: Calculated indices.
MCV = Hematocrit / RBC × 10.
MCHC = Hemoglobin / hematocrit × 100.
553
Automated CBC: Limitations (3).
Relatively low precision in counting of platelets and basophils.
Inability to count band neutrophils.
554
Automated CBC: How hemoglobin is measured.
Red blood cells are lysed.
Potassium ferrocyanide and KCN are added to form HiCN.
Absorbance at 540 nm is measured.
555
Automated CBC: Limitations of the hemiglobin cyanide method (3).
Cannot detect sulfhemoglobin.
Paraproteins and lipemia cause overestimation of hemoglobin.
556
Automated CBC: How red blood cells, leukocytes, and platelets are counted.
Red blood cell: Any particle in the range of 36 fL to 360 fL.
After lysis of red blood cells
− Leukocyte: Any particle greater than 36 fL.
− Platelet: Any particle smaller than 36 fL.
557
Automated CBC: Determination of MCV and RDW.
In a Gaussian distribution of sizes of red blood cells,
− MCV is the mean.
− RDW is the coefficient of variation.
558
Automated CBC: Calculated indices.
Hematocrit = MCV × RBC / 10.
MCHC = Hemoglobin / hematocrit × 100.
559
MCHC: Causes of increase (3).
Spherocytosis.
Cold agglutinins.
Lipemia.
560
Reticulocyte count: Methods.
Manual: Light microscopy.
Automated: Optical light scatter, flow cytometry.
561
Reticulocyte count: Dyes.
Light microscopy and optical light scatter: Supravital stain (new methylene blue or azure B).
Flow cytometry: RNA-specific fluorochrome.
562
Reticulocyte count: Formulas.
Absolute reticulocyte count = % Reticulocytes × RBC.
Corrected reticulocyte count = % Reticulocytes × Hct / 45.
Reticulocyte-production index = Corrected reticulocyte count / maturation index.
563
Reticulocyte count: Maturation index.
Hematocrit
= 36-45%: 1.0.
= 26-35%: 1.5.
= 16-25%: 2.0.
15 or less: 2.5.
564
Automated CBC: Plot of leukocytes.
Mo Ne
Eo
Ly
-- forward scatter -->
565
Hemoglobin-solubility test:
A. Synonym.
B. Principle.
C. Causes of true positive (5).
D. Cause of false negative.
A. Dithionate test.
B. Insoluble hemoglobins cause marked turbidity of the lysate.
C. SS, SA, SC, SD, C-Harlem, others.
D. Low concentration of insoluble hemoglobin, e.g. in a neonate.
566
Sickling test:
A. Synonym.
B. Principle.
C. Causes of true positive (5).
D. Cause of false negative.
A. Metabisulfite test.
B. Reagent causes sickling, which can be demonstrated microscopically.
C. SS, SA, SC, SD, C-Harlem, others.
D. [Hb S] is less than 10%.
567
Acid-elution technique: Interpretation.
Heterocellular pattern: Fetal-maternal hemorrhage or thalassemia.
Pancellular pattern: Hereditary persistence of fetal hemoglobin.
568
Alkali-denaturation technique.
Hb F resists denaturation by 1.25 M NaOH.
The optical density of the supernatant reflects the amount of Hb F.
569
Highly accurate method of quantifying Hb F.
HPLC.
570
Fast hemoglobins:
A. Definition.
B. Examples.
C. Artifact.
A. Those that move faster (i.e. closer to the '+' end) than Hb A on alkaline gel.
B. Hb H, Hb Barts.
C. Bilirubin.
571
Hemoglobin electrophoresis and the thalassemias.
α-Thalassemia: Normal Hb A₂.
β-Thalassemia: Elevated Hb A₂ (unless there is also iron deficiency).
572
HPLC for hemoglobin studies: Limitations (3).
The following get eluted together:
− Hb A₂ and Hb E.
− Hb C and Hb O-Arab.
− Hb Barts and bilirubin.
573
Pulse oximetry: Principle.
LEDs emit light at 2 wavelengths
... 660 nm (red) for deoxyhemoglobin.
... 940 nm (infrared) for oxyhemoglobin.
574
Pulse oximetry: Limitations.
Cannot detect sulfhemoglobin, carboxyhemoglobin, or methemoglobin.
Oxygen saturation is overestimated in the presence of these substances.
575
Analyzers of arterial blood gases:
A. Technique.
B. Limitations (3).
A. Calculate oxygen saturation based on direct measurement of pH, pO₂, pCO₂.
B. Assume normal curve of oxygen saturation, normal level of 2,3-DPG, normal hemoglobins.
576
Co-oximeter: Technique.
Emits many wavelengths to measure oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, methemoglobin.
577
Cytochemical stains: Undifferentiated blasts.
Negative: MPO, SBB, CAE, NSE, PAS.
578
Cytochemical stains: Myeloblasts.
Positive: MPO, SBB, CAE.
579
Cytochemical stains: Promyelocytes.
Positive: MPO, SBB, CAE.
580
Cytochemical stains: Monoblasts.
Positive: NSE.
NaF inhibits staining for NSE.
581
Cytochemical stains: Erythroblasts.
Positive: PAS (diffusely granular).
Variable: MPO, SBB, NSE.
NaF does not affect staining for NSE.
582
Cytochemical stains: Megakaryoblasts.
Positive: PAS (diffusely granular).
Variable: NSE.
NaF does not affect staining for NSE.
583
Cytochemical stains: Lymphoblasts.
Positive: PAS (blocky, "rosary bead" pattern).
Variable: SBB (faintly gray).
584
Myeloperoxidase stain:
A. Target.
B. Limitation.
A. Azurophilic granules.
B. Rapid degradation.
585
Sudan black B stain: Target.
Lipids.
586
Chloroacetate esterase stain:
A. Synonym.
B. Cells that take it up.
A. Leder's stain.
B. Granulocytes, mast cells.
587
Nonspecific esterases: Types.
α-Naphthylacetate esterase.
α-Naphthylbutyrate esterase.
588
Oil red O stain: Use in neoplastic hematopathology.
Stains the cytoplasmic vacuoles of Burkitt's lymphoma.
589
LAP score:
A. Principle.
B. Computation.
A. Leukocyte alkaline phosphate hydrolyzes granules within neutrophils to yield a colored product.
B. The intensity of the reaction is graded 0 to 4+ in each one of 100 neutrophils and bands.
590
LAP score: Normal value.
40-120.
591
LAP score: Causes of decrease (5).
PNH.
CML.
MDS (some cases).
Congenital hypophosphatasia.
Neonatal sepsis.
592
LAP score: Causes of increase (5).
Reactive neutrophilia.
Glucocorticoids.
Polycythemia vera.
Primary myelofibrosis.
Pregnancy (3rd trimester).
593
Cyclin-D1: Positive staining (4).
Mantle-cell lymphoma.
Hairy-cell leukemia.
Plasma-cell myeloma.
Many epithelia.
594
bcl-2: Normal positive staining (3).
In a reactive lymph node:
− Mantle-zone B cells in the mantle zone.
− Mantle-zone B cells in the follicular centers.
− T cells.
595
bcl-6: Normal expression.
B cell of the germinal center.
596
CD1a: Normal expression.
Cortical thymocytes.
Langerhans' cells.
597
CD3:
A. Chains that compose the molecule.
B. Association with the T-cell receptor.
A. γ, δ, ε.
B. Tight but not covalent.
598
CD4: Normal expression.
Helper T cells.
Monocytes.
Dendritic cells.
599
CD7: Normal expression.
T cells.
NK cells.
600
CD10: Normal expression.
Cells of the follicular center, whether benign or neoplastic.
601
CD11b and CD11c: Normal expression.
Monocytes.
Granulocytes.
602
CD15: Significance in AML.
Indicates maturation.
603
CD14 and CD16: Normal expression.
CD14: Monocytes.
CD16: NK cells, granulocytes.
604
CD19: Normal expression.
B cells.
Normal plasma cells.
605
CD20: Normal expression.
B cells.
NOT plasma cells.
606
FMC-7:
A. Definition.
B. Expression in B-cell lymphomas.
A. An antibody to an epitope of CD20.
B. Expressed by most B-cell lymphomas, but not by CLL/SLL, which has dim expression of CD20.
607
CD23: Synonym.
Low-affinity IgE receptor.
608
CD45: Intensity of expression by normal hematopoietic cells.
Weakest: Plasma cells, blasts, erythrocytes.
Intermediate: Granulocytes.
Strongest: Mature lymphocytes, monocytes.
609
CD45RO: Normal expression.
T cells.
610
CD71:
A. Synonym.
B. Significance in neoplastic hematopathology.
A. Transferrin receptor.
B. Expression correlates with grade of tumor.
611
Clusterin:
A. Normal expression.
B. Abnormal expression.
A. Megakaryocytes: Cytoplasmic.
B. Anaplastic large-cell lymphoma: Golgi pattern.
612
HLA-DR: Normal expression.
Monocytes.
B cells.
Activated T cells.
613
PAX5: Abnormal expression.
Nuclear staining in
− Neoplasms of B cells.
− Classic Hodgkin's lymphoma.
614
ZAP-70: Normal expression.
T cells.
NK cells.
615
How many ___ show clonal rearrangement of TCR?
A. non-Hodgkin's lymphomas of mature B cells
B. B-ALLs
A. 5% to 7%.
B. 20% to 40%.
616
How many ___ show clonal rearrangement of IgH?
A. lymphomas of mature T cells
B. T-ALLs
A. 4% to 6%.
B. 10% to 15%.
617
Immunophenotypic evolution of B cells.
Lymphoid stem cells: CD34, TdT, HLA-DR; germline IgH, TCR.
Pro-B cell: Gain of CD19, CD10; rearrangement of IgH.
Pre-B-cell: Loss of CD34, TdT; gain of CD20, cμ chains; rearrangement of Ig light chain.
Mature B cell: Gain of CD21, CD22, sIg.
Plasma cell: Loss of most B-cell markers, sIg; retention of cIg.
618
Immunophenotypic evolution of T cells.
Lymphoid stem cells: CD34, TdT, HLA-DR; germline IgH, TCR.
Prothymocyte: Loss of HLA-DR; gain of CD2, CD7.
Immature thymocyte: Loss of CD34; gain of CD1a, cCD3, CD4, CD5, CD8; rearrangement of TCR.
Mature thymocyte: Loss of TdT, CD1a; loss of either CD4 or CD8.
Mature T cell: Gain of surface CD3.
