Lecture 7 Acute Myelogenous Leukemias Chapter 31

Question 1

What are the key differentiating morphological features of AML-M0, Acute Myeloid Leukemia, minimally differentiated?

Answer 1

1. > 30% Type I Blasts without granules and no auer rods.
2. Large N/C ratio, nucleus usually round or slightly irregular
3. Nucleoli may be present
4. <3% positive for Sudan Black B (SBB) and Myeloperoxidase (MPO)

Question 2

What are the key differentiating morphological features of AML-M1, Acute Myeloid Leukemia without maturation?

Answer 2

1. > 30% Myeloblasts of nucleated cells.
   Type I and Type II Blasts (few granules<20) make up >90% of non-erythroid cells in the bone marrow.
2. Auer rods present in 50% of cases and blasts may have numerous auer rods.
3. <10% of non-erythroid cells are maturing granulocytes (beyond the promyelocyte stage) and monocytes
4. > 3% Myeloblasts are positive for SBB and MPO

Question 3

What are the key differentiating morphological features of AML-M2, Acute Myeloid Leukemia with maturation?

Answer 3

1. > 30% Myeloid blasts Type I, II, III Auer rods are often present.
2. > or = 3% blasts positive for SBB & MPO
3. > 10% granulocytes at or beyond promyelocyte stage.
4. <20% are monocytic cells. (Note: differentiates it from M4)

Question 4

What are the key differentiating morphological features of AML-M3, Acute Promyelocytic Leukemia?

Answer 4

1. Abnormal promyelocytes with heavy granulation filling cytoplasm-sometimes obscuring nucleus.
2. Bundles of Auer rods (called faggot cells) may be seen in the promyelocytes.
3. Nuclear shape variable: often kidney or bilobed shape.

Question 5

What are the key differentiating morphological features of AML-M3m, Acute Promyelocytic Leukemia?

Answer 5

1. Nucleus is usually deeply notched or folded which can be mistaken for monocytes. Morphology described as butterfly, bi-lobed, reniform (kidney shaped)
2. Few cells display prominent azurophilic granules, appears devoid of granules
   Auer rods occasionally present (not very evident though)
3. Requires cytochemical differentiation. Combination stain of chloroacetate/non-specific esterase will separate M3m from Monoctyic Leukemia.

Question 6

What are the key differentiating morphological features of AML-M4, Acute Myelomonocytic Leukemia?

Answer 6

1. > 30% blasts
2. 30 to 80% of non-erythroid cells are myeloid blasts, promyelocytes and later granulocytes.
3. > 20% of non-erythroid cells are of monocytic lineage at various stages of maturation.

Question 7

What are the key differentiating morphological features of AML-M4e?

Answer 7

Acute Myelomonocytic Leukemia with eosinophilia
1. Eosinophils >5% of non-erythroid cells in marrow.
2. Eosinophils are abnormal: immature, single lobed, unsegmented and may have large basophilic granules. Generally, these cells only seen in marrow.

Question 8

What are the key differentiating morphological features of AML-M5a?

Answer 8

Acute Monocytic Leukemia, poorly differentiated (Schilling Leukemia)
1. Blood and Bone Marrow display large blast cells with delicate lacy chromatin usually with prominent nucleoli (1-3).
2. Generally large amounts of cytoplasm with increased basophilia with or without pseudopods.
3. >80% of non-erythroid cells are monoblasts with possible auer rods.
4. Auer rods may be present. Less common than M1, M2,M3

Question 9

What are the key differentiating morphological features of AML-M5b?

Answer 9

Acute Monocytic Leukemia, well differentiated (Schilling Leukemia)
1. <80% of non-erythroid cells are monoblasts
2. >80% of non-erythroid are monoblasts, promonocytes and monocytes.
3. < than 10% of non-erythroid cells are of granulocyte series.

Question 10

What are the key differentiating morphological features of AML-M6?

Answer 10

Acute Erythroleukemia
1. Hypercellular erythrocytic component (all stages) which exceeds 50% of nucleated cells (erythroid hyperplasia).
2. Bizarre morphology includes multiple lobulation of nucleus, multiple nuclei, nuclear fragments, cytoplasmic vacuolation and budding, megaloblastoid (fine chromatin) pattern.
3. > 30% of non-erythroid cells are Type I and Type II Myeloblasts which may contain auer rods.

Question 11

What are the key differentiating morphological features of AML-M7?

Answer 11

1. Peripheral Blood:
   a) Megakaryocytic fragments and abnormal giant platelets.
   b) Platelet counts normal or increased
   c) Micromegakaryocytes some with naked nuclei and groups of platelets surrounding them may be seen.
2. Bone Marrow:
   a) Frequent diffuse fibrosis
   b) Aggregates of Megakaryocytes
   c) Sheets of Megakaryoblasts

Question 12

What are the laboratory findings of AML-M0?

Answer 12

1. Pancytopenic with circulating blasts (although may be absent)
2. Dysplastic maturing granulocytes may be present (i.e., Pseuo-Pelger Huet, Hypogranulation)

Question 13

What are the laboratory findings of AML-M1?

Answer 13

1. Variable WBC count, circulating blasts variable (typically proportional to WBC but may be absent)
2. Usually low RBC count (anemic)
3. Platelet count is usually low
4. Dysplastic maturing granulocytes may be present (i.e., Pseuo-Pelger Huet, Hypogranulation)
5. Bone marrow is hypercellular with abnormal WBC, RBC, and platelet precursors.

Question 14

What are the clinical findings of AML-M0?

Answer 14

1. Bruising, bleeding, and infection are common symptoms
2. Patients generally are either infants or older adults

Question 15

What are the clinical findings of AML-M1?

Answer 15

1. Onset is sudden or takes months or years.
2. Fever, malaise, petechiae (pin point bleeding on skin)
3. Usually little or no organ involvement; but can affect liver, spleen, or lymph nodes

Question 16

What are the laboratory findings of AML-M2?

Answer 16

1. Reduced numbers of normal cells due to infiltration of leukemic blasts in the bone marrow.
2. Hypercellular marrow with abnormal features, such as: Dysplastic maturing granulocytes may be present (i.e., Pseuo-Pelger Huet, Hypogranulation)
3. Some cases have marked increase of eosinophils or basophils or both.
4. Shows maturation at or beyond the promyelocyte stage.
5. MPO and SBB positive with large percentage of blasts and more mature granulocytes causing increased reactivity.

Question 17

What are the clinical findings of AML-M2?

Answer 17

1. Similar to M1
2. Anemia, infection, bleeding (bruising, epistaxis, gingival bleeding, petechiae)

Question 18

What are the laboratory findings of AML-M3?

Answer 18

Abnormal promyelocytes with heavy granulation filling cytoplasm-sometimes obscuring nucleus.
Bundles of auer rods (faggot cells) may be seen.
Nuclear shape is variable (kidney or bilobed can be common).
Cytochemically SBB and MPO are intensely positive.

Question 19

What are the clinical findings of AML-M3?

Answer 19

Found in all age groups, slightly higher frequency in males.
Frequently associated with DIC.

Question 20

What are the laboratory findings of AML-M3m?

Answer 20

Nucleus of blasts usually deeply notched or folded (can be confused with monocytes)
Nucleus is butterfly, bilobed or kidney shaped.
Appears devoid of granules under light microscope, only a few cells display prominent azurophilic granules
Auer rods may be present (not very evident)
SSB, MPO, chloroacetate positive

Question 21

What are the clinical findings of AML-M3m?

Answer 21

High incidence of DIC

Question 22

What are the laboratory findings for AML-M4?

Answer 22

1. Significantly elevated WBC count
2. Low number of neutrophils
3. Majority of peripheral blood cells are blasts or abnormal cells. Monoblasts are large with abundant cytoplasm containing small granules and pseudopodia. Nucleus is large, immatue and may contain numerous nucleoli.
4. Both granulocytic and monocytic differentiation observed in peripheral blood and bone marrow.
5. Positive reaction for SBB, MPO and both specific and non-specific esterases confirms M4.
6. 50% of patients secrete large amounts of lysozyme in urine (found in neutrophils and monocytes)

Question 23

What are the clinical findings for AML-M4?

Answer 23

1. Symptoms related to cytopenia (fatigue, bleeding, infection and organomegaly)
2. Soft tissue infiltrates due to monocytic component resulting in gum hypertrophy and infiltration, rectal ulcers, and skin involvement.
3. Meningeal symptoms: Headache, nausea, vomiting, blurring of vision and occasional intracranial hemorrhage.
4. 50% of patients secrete large amounts of lysozyme in urine (helps recognize monocytic component).

Question 24

What are the specific laboratory findings for AML-M4e?

Answer 24

1. Increased eosinophils in the marrow.
2. Eosinophils are chloracetate esterase and PAS positive whereas normal eosinophils are negative.

Question 25

What is the main laboratory finding for AML-M5a?

Answer 25

Leukocytosis common.

Question 26

What is the laboratory findings for AML-M5b?

Answer 26

1. Well differentiated meaning all stages of monocytes (monoblasts, promonocytes, monocytes) are present.
2. Predominant cell in marrow usually promonocyte
3. Predominant cell in blood: monocyte
4. Auer rods may be present. Less common than in M1, M2,M3
5. Strongly positive for non-specific esterase. Weak reactions of non-specific esterase can be verified by addition of sodium fluoride which inhibits monocytic enzymes.
6. Serum and urine lysozyme are high because of monocytes.

Question 27

What are the clinical findings for AML-M5a and M5b?

Answer 27

Skin and gum involvement.
Extramedullary tissue masses and central nervous involvement.
Spleen and liver sometimes greatly enlarged.
Frequent lymphadenopathy.
Bleeding disorders are common.
For M5b occurrence of DIC second only to M3

Question 28

What are the laboratory findings for AML-M6?

Answer 28

1. Displays prominent percentage of Myeloblasts and Erythroblasts
2. Peripheral blood shows variable leukocyte count, cytopenia and numerous nucleated RBCs.
3. RBC morphology (peripheral blood) displays large variety: anisocytosis, poikilocytosis, macrocytosis with oval forms, schistocytes, dimorphic population.
4. Abnormal erythroid precursors often are PAS positive.

Question 29

What are the clinical findings for AML-M6?

Answer 29

1. M6 frequently progresses to M1, M2 or M4.
2. M6 can be confused with B12, folate deficiencies and Myelodysplastic syndromes when diagnosing.
3. Increased risk of infection

Question 30

What are the laboratory findings for AML-M7?

Answer 30

1. Patients usually have cytopenias, and some may have thrombocytosis
2. Blasts display wide range of morphology
3. Blasts can be small cell with scant cytoplasm, fine chromatin OR blasts can also be large cell, moderate cytoplasm fine chromatin.
4. Cytoplasmic projections (blebs) and or vacuolation sometimes present
5. Presence of fine granules variable

Question 31

What are the clinical findings for AML-M7?

Answer 31

1. Symptoms similar to other AML subgroups
2. Increased risk of infection.

Question 32

What cellular abnormality is common to all AML types?

Answer 32

Functional abnormalities of granulocytes in phagocytosis, microbial killing, and chemotaxis resulting in increased risk of infection.