Malignant Leukocyte Disorders - Leukemia

Flashcards about Malignant Leukocyte Disorders - Leukemia

Leukemia

A clinical disorder recognized by Virchow between 1839 and 1845, characterized by the white appearance of blood in patients with fever, weakness, and lymphadenopathy.

Leukemia

Characterized by abnormal, uncontrolled proliferation and accumulation of one or more hematopoietic cells.

Acute Leukemia

Rapid, clonal proliferation in the bone marrow of lymphoid or myeloid progenitor cells known as lymphoblasts and myeloblasts, respectively.

Leukemia

A disease, usually of leukocytes, in the blood and bone marrow, involving overproduction of immature or mature leukocytes in the bone marrow and/or peripheral blood.

Lymphoma

A malignancy that starts in the lymph system, mainly the lymph nodes.

Myeloma

A form of cancer of the plasma cells, where the cells overgrow, forming a mass or tumor located in the bone marrow.

Potential Predisposing Factors for Development of Leukemia and Lymphoma

Benzene, hydrocarbons, hair dyes, ionizing radiation, insecticides, herbicides, fungicides, alkylating agents, chloramphenicol, EBV, HIV, HTLV, Down syndrome, Fanconi anemia, myelodysplastic syndromes.

Chronic Myelogenous Leukemia (CML)

BCR-ABL gene

Benzene

Chemical commonly used in histopath that is associated with leukemia and aplastic anemia

HTLV-1

Associated with adult T cell leukemia

HTLV-2

Associated with hairy cell leukemia

Common Lymphoid Progenitors (CLP)

Origin of ALL

Common Myeloid Progenitors (CMP)

Origin of AML

days to 6 months

Duration of Acute leukemia

2 to 6 months

Duration of Subacute leukemia

1 or 2 years or more

Duration of Chronic leukemia

Aleukemic leukemia

WBC ct. <15,000 cells/ul, no immature or abnormal WBC

Sub leukemic leukemia

WBC ct. <15,000cells/ul, with immature or abnormal form

Leukemic leukemia

WBC ct. >15,000cells/ul, with immature and abnormal form

Acute leukemia (Type of WBC Involved)

predominance of immature (blast) WBC

Chronic Leukemia (Type of WBC Involved)

predominance of mature/old WBC

Acute Leukemia

of short duration & predominantly immature cells

≥20%

Percent of blast to tell that a person has leukemia

FRENCH AMERICAN BRITISH (FAB)

Classifies acute leukemia as presence of ≥ 30% blast in the peripheral blood and bone marrow.

WORLD HEALTH ORGANIZATION

Defines acute leukemia as ≥ 20% peripheral blood and bone marrow blasts.

Cellular morphology and cytochemistry

First tool used to distinguish ALL from AML

Immunophenotyping and genetic analysis

Most reliable indicators of a cell’s origin to differentiate ALL from AML

Cytogenetic (Karyotyping) analysis

Devoted to the laboratory study of visible chromosome abnormalities, such as deletions, translocations, and aneuploidy.

Cytochemistry

Use of specialized stains to detect cellular enzymes and other chemicals in peripheral blood films and bone marrow aspirate smears. Used to differentiate hematologic diseases, especially leukemias.

Immunophenotyping (flow cytometry)

Used to identify cells on the basis of the types of markers or antigens present on the cell’s surface, nucleus, or cytoplasm. This technique helps identify the lineage of cells using antibodies that detect markers or antigens on the cells.

Acute lymphoblastic leukemia (ALL)

Primarily a disease of childhood and adolescence, accounting for 25% of childhood cancers and up to 75% of childhood leukemia

Between 2 and 5 years of age

Peak incidence of ALL in children

ALL (subtype L1)

Most common childhood leukemia

AML

Most common leukemia in adults

CLL

Most common leukemia in adults in western countries

fatigue, fever, and mucocutaneous bleeding

Patients with B cell ALL typically present with

anemia, thrombocytopenia, organomegaly, and bone pain

T-ALL may present with

ALL L1

Lymphoblasts are small and homogenous, varies little in size; most common CHILDHOOD ALL with best prognosis

ALL L2

Lymphoblasts are large and heterogenous, variable in size; Adult type ALL

ALL L3

Lymphoblasts are large, homogenous and vacuolated; Rarest subclass, can be found in both children and adult with Poor prognosis

L1

homogeneous FAB lymphoma

L2

heterogeneous FAB lymphoma

L3

Burkitt lymphoma type

AML

Most common type of leukemia in adults, and the incidence increases with age. AML is less common in children.

Anemia (esp. M6), thrombocytopenia, and neutropenia

ANT

normocytic/normochromic anemia (except AML M6)

What subtype of anemia according to morphology is usually seen in acute leukemia?

M0

Acute myeloid leukemia, minimally differentiated

M1

Acute myeloid leukemia without maturation

M2

Acute myeloid leukemia with maturation

M3

Acute promyelocytic leukemia

M4

Acute myelomonocytic leukemia

M4eo

Acute myelomonocytic leukemia with eosinophilia

M5a

Acute monocytic leukemia, poorly differentiated

M5b

Acute monocytic leukemia, well differentiated

M6

Acute erythroleukemia

M7

Acute megakaryocytic leukemia

M0 ACUTE MYELOID LEUKEMIA, MINIMALLY DIFFERENTIATED

The blasts in AML with minimal differentiation are positive with CD13, CD33, CD34, and CD117. Auer rods typically are absent, and there is no clear evidence of cellular maturation. The cells yield negative results with the cytochemical stains myeloperoxidase and Sudan black B

M1 ACUTE MYELOID LEUKEMIA WITHOUT MATURATION

The blasts in AML without maturation are also CD13, CD33, with CD117 and CD34 being positive in the majority of cases. At least 3% of blasts give positive results with myeloperoxidase or Sudan black B stains. Associated with CHLOROMA.

M2 ACUTE MYELOBLASTIC LEUKEMIA WITH MATURATION

A common variant that presents with greater than 20% blasts, at least 10% maturing cells of neutrophil lineage and fewer than 20% precursors with monocytic lineage; Auer rods are often present

M3 ACUTE PROMYELOCYTIC LEUKEMIA

The most aggressive type AML; Characterized by “butterfly” or “coin-on-coin” nucleus of the promyelocyte, Associated with DIC; Treatment includes all-trans-retinoic acid (ATRA) and arsenic trioxide

M4 ACUTE MYELOMONOCYTIC LEUKEMIA / NAEGILI TYPE

The cells are positive for the myeloid antigens CD13 and CD33 and the monocytic antigens CD14, CD4, CD11b, CD11c, and CD64. Associated with leukostasis together with M5

M5 ACUTE MONOBLASTIC LEUKEMIA /SCHILLING TYPE

Malignant cells are CD14, CD4, CD11, CD11c, and CD64 positive. Only cells in the monocyte series can be seen in this type of leukemia

M6 Di GUGLIELMO’S SYNDROME (ERYTHROLEUKEMIA/ERYTHREMIC MYELOSIS)

Acute leukemia characterized by a proliferation of both erythroid and myeloid precursors in bone marrow, with erythroblasts with bizarre lobulated nuclei and abnormal myeloblasts in peripheral blood

M7 ACUTE MEGAKARYOCYTIC OR MEGAKARYOBLASTIC LEUKEMIA

requires the presence of at least 20% blasts, of which at least 50% must be of megakaryocyte origin

M6 erythroleukemia

abnormal proliferation of both erythroid and granulocytic precursors; may include abnormal megakaryocytic and monocytic proliferations

M3

promyelocytic - which AML classification?

M4

myelomonocytic - which AML classification?

M5

monocytic - which AML classification?

M6

erythroleukemia - which AML classification?

M7

megakaryocytic - which AML classification?

+

MPO in AML

+

SBB in AML

differentiating chronic myelogenous (CML) from a leukemoid reaction

Main use of Leukocyte Alkaline Phosphatase (LAP)

Peroxidase

differentiate acute myelogenous and monocytic leukemia from acute lymphocytic leukemia

Sudan Black B

differentiate acute myelogenous and myelomonocytic leukemias from acute lymphocytic leukemia

Periodic Acid Schiff

help in the diagnosis of DiGugleilmo’s syndrome and may be an aid, when used in conjunction with other stains, to classify some acute leukemias

Using L (+) tartaric acid in Acid Phosphatase

helpful in diagnosing hairy cell leukemia

Myeloperoxidase

Marker for primary granules of auer rods

Sudan Black B

Marker for phospholipids and lipids

Periodic Acid Schiff

Marker for glycogen, glycoproteins, mucoproteins and high molecular weight carbohydrates

Naphthol AS-D Chloroacetate Esterase

Marker for mature and immature neutrophils and mast cells

Leukocyte Alkaline Phosphatase (LAP)

Neutrophils is the only leukocyte that contain this activity

Myeloproliferative Disorders/Neoplasms cause

due to abnormal stem cells within the BM

MPNs

Interrelated clonal hematopoietic stem cell disorders characterized by excessive proliferation of one or more mature myeloid cell lines

Chronic Myelogenous Leukemia

Stem cell disorder affecting the granulocytic, monocytic, erythrocytic, and megakaryocytic cell lines – mature cells are the ones mainly affected

Philadelphia chromosome

In 90% of the cases of CML, one arm of chromosome 22 translocated to chromosome 9

JAK2 V617F mutation

Gene involved in the pathogenesis and is found in 65% of PMF patients

Thrombocythemia

increased platelet count with abnormal function

Polycythemia

increased RBC mass and count in the body

specific JAK2 mutation, JAK2 V617F

Gene abnormality detected in 90% to 97% of patients with PV

ruddy skin coloration

Patients with Polycythemia vera exhibit a

RELATIVE (or TRANSIENT) POLYCYTHEMIA

Normal RBC mass, Increase hematocrit, Normal EPO

ABSULUTE POLYCYTHEMIA

Increased RBC mass, increased hematocrit, decrease EPO

Hemoglobin >18.5 g/dL in males, 16.5 g/dL in females or other evidence of increased red cell volume

MAJOR DIAGNOSTIC CRITERIA FOR POLYCYTHEMIA VERA (M/F Hgb)

Thrombopoiesis

The generation of platelets from MKs (precursors) in the bone marrow

Megakaryopoiesis

The process by which mature megakaryocytes (MKs) develop from hematopoietic stem cells (HSCs)

TPO (MPL Ligand)

A specific hormone responsible for Megakaryopoiesis and Thrombopoiesis

Proliferative

Endomitosis occurs at what phase of platelet maturation series?

Burst forming unit-Meg (BFU-Meg)

The least mature specific progenitor

Light density CFU-Meg (LD-CFU-Meg)

The most mature specific progenitor