Malignant Leukocyte Disorders

• A disease, usually of leukocytes, involving the blood and bone marrow

• It is characterized by the overproduction of various types of immature or mature leukocytes in the bone marrow and/or peripheral blood

Leukemia

• A general term for malignancies that start in the lymphatic system, mainly the lymph nodes

Lymphoma

Two main types of Lymphoma

• Hodgkin Lymphoma - characterized by presence of Reed-Sternberg cells

• Non-Hodgkin Lymphoma

• A form of cancer of the plasma cells

• Abnormal plasma cells overgrow and form a mass/tumor that is located in the bone marrow

Myeloma

Characterized by abnormal and uncontrolled proliferation and accumulation of one or more hematopoietic cell lines

Leukemia

Leukemia comes from the Greek word _ (white), and _ (blood)

• leukos - white

• haima - blood

Leukemia

• Generalization (4):

• More blasts: shorter, more fatal course of disease

• High WBC count with shift to the left

• M:E ratio of 10:1

• Normocytic, normochromic

Differences between Acute and Chronic Leukemia

FAB Classification of Leukemia

• Based on (2)

• Based on morphology of cells in Romanowsky-stained smear

• Based on cytologic and histochemical characteristics of cells involved

Lymphocytic Leukemia

• General Cytochemical Characteristics (2)

• Myeloperoxidase (MPO): NEGATIVE

• Sudan Black B (SBB): NEGATIVE

Most common form of childhood leukemia

Acute Lymphocytic Leukemia (ALL)

Acute Lymphocytic Leukemia (ALL)

• FAB subtypes include:

• L1

• L2

• L3

• Most common type of leukemia in elderly

• Characterized by persistent lymphocytosis

Chronic Lymphocytic Leukemia (CLL)

Chronic Lymphocytic Leukemia (CLL)

• Common Findings: (2)

• Smudge cells

• Rieder cells

Chronic Lymphocytic Leukemia (CLL)

• Example of clinical variations:

• Hairy-cell leukemia (TRAp+)

• Lymphosarcoma cell leukemia

• Prolymphocytic leukemia

Solid Tumor Counterparts of Leukemia Types

Non-lymphocytic Leukemia / Myelogenous Leukemia

• General Cytochemical Characteristics: (2)

• Myeloperoxidase (MPO): POSITIVE

• Sudan Black B (SBB): POSITIVE

WHO Classification of Acute Myelogenous Leukemia (AML) (7)

• AML with certain genetic abnormalities

• AML with myelodysplasia-related changes

• AML related to previous chemotheraphy or radiation

• AML, NOS (not otherwise specified)

• Myeloid sarcoma

• Myeloid proliferation related to Down syndrome

• Undifferentiated and biphenotypic acute leukemia

AML with certain genetic abnormalities:

• AML with translocation between chromosomes 8 and 21 [t(8;21)]

• AML with PML-RARA fusion gene (t(15;17))

• AML with mutated NPM1 gene

Similar to FAB but with

• Acute Basophilic Leukemia

• Acute Panmyelosis with fibrosis

AML, NOS

Example of Myeloid sarcoma

• Granulocytic sarcoma

• Chloroma

Undifferentiated and biphenotypic acute leukemia

• Not strictly _

• Leukemias that have both _ and _ features

• Aka _

• Not strictly AML

• Leukemias that have both lymphocytic and myeloid features

• Aka Mixed Phenotype Acute Leukemias (MPALs)

Chronic Myelogenous Leukemia (CML)

• Aka _

Chronic Granulocytic Leukemia

Chronic Myelogenous Leukemia (CML)

• Characterized by: (3)

• Presence of Philadelphia chromosome (Ph1) in approximately 90% of patients

• A reciprocal translocation involving the long arms of chromosome 9 and 22

• Formation of BCR-ABL1 fusion gene

Chronic Myelogenous Leukemia (CML)

• 3 Clinical Phases

• Chronic phase

• Accelerated phase

• Blast crisis

Chronic Myelogenous Leukemia (CML)

• Must be differentiated from _

Leukemoid Reaction (LR)

Generally used to distinguish LR from CML

Leukocyte (Neutrophil) Alkaline Phosphatase (LAP/NAP) Test

Leukocyte (Neutrophil) Alkaline Phosphatase (LAP/NAP) Test

• Principle:

• High LAP activity can be observed in neutrophils that have undergone normal growth

Leukocyte (Neutrophil) Alkaline Phosphatase (LAP/NAP) Test

• KAPLOW'S METHOD

→Principle:

• Hydrolysis of sodium alpha naphthyl phosphate by alkaline phosphatase produces a colored precipitate with a diazotized amine

Leukocyte (Neutrophil) Alkaline Phosphatase (LAP/NAP) Test

• KAPLOW'S METHOD

Leukocyte (Neutrophil) Alkaline Phosphatase (LAP/NAP) Test

• KAPLOW'S METHOD

→PROCEDURE

1. Immerse dry blood smear in fixative for 30 seconds

2. Pour onto smear the working substrate (made of buffer, substrate, and initial stain) and allow to stand for at least 10 minutes

3. Rinse with distilled water and dry

4. Counterstain for 10 to 15 minutes

5. Rinse with distilled water and mount in mounting solution like glycerol

6. Examine immediately under microscope and look for the presence of reddish brown to black precipitate of alkaline phosphatase activity in cytoplasm of neutrophils

7. Count 100 segmented neutrophils and bands, and score each cells

Leukocyte (Neutrophil) Alkaline Phosphatase (LAP/NAP) Test

• KAPLOW'S METHOD

→SCORES

Leukocyte (Neutrophil) Alkaline Phosphatase (LAP/NAP) Test

• KAPLOW'S METHOD

→Normal Kaplow's Score

20 to 100

• High LAP score = LR

• Low LAP score = CML

Disorders with INCREASED Kaplow's (LAP) Score

• 3rd Trimester of pregnancy

• Polycythemia vera (PCV)

• Infections

• Intoxications

Disorders with DECREASED Kaplow's (LAP) Score

• Chronic Myelogenous Leukemia (CML)

• Paroxysmal Nocturnal Hemoglobinuria (PNH)

• Sideroblastic anemia

• Myelodysplastic syndrome