THE LEUKEMIAS

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

LEUKEMIA
Uncontrolled malignant proliferation of WBC present in the BM and in peripheral blood Definitive cause is unknown Risk factors : Signs and Symptoms : Pallor Anorexia Palpitation
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

PATHOPHYSIOLOGY of LEUKEMIA : BONE MARROW FAILURE

MANIFESTATION INFECTION REASON Leukemic cells outgrow normal WBC in BM Signs and Symptoms Immunocompromised, fever, sepsis, severe infection Pallor, tachycardia, weakness Easy bruisability, bleeding gums, hemorrhage

ANEMIA BLEEDING

Leukemic cells outgrow normal RBC in BM Leukemic cells outgrow megakaryocytes in the BM

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

THE LEUKEMIAS
CLASSIFICATION (FAB) According to course of disease: Acute Sub-acute Chronic According to cell type Myelocytic, Monocytic, Erythrocytic Lymphocytic, Plasmacytic According to blood picture Leukemic Subleukemic Aleukemic
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE VS CHRONIC LEUKEMIA

ACUTE LEUKEMIA MYELOID Myeloblast, Promyelocyte, Monoblast, Normoblast, Megakaryoblast LYMPHOID T or B lymphoblast CHRONIC LEUKEMIA MYELOID Myelocyte, Metamyelocyte, Stab, Neutrophils, Eosinophils, Basophils, RBC, Platelets, Monocytes LYMPHOID T or B lymphocytes, plasma cells

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

THE LEUKEMIAS
ACUTE LEUKEMIAS
AML ALL CRITERION FOR DIFFERENTIATION Auer Rods

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIA

Most common leukemia in the first months of life AML by FAB Classification : >30% of all nucleated cells in the BM are MYELOBLASTS

AML by WHO Classification : >20% of all nucleated cells in the BM are MYELOBLASTS
AUER RODS are seen; mostly in myeloblasts and promyelocytes
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

AML : CYTOCHEMICAL STAINING

CYTOCHEMICAL STAINS CELLS STAINED

PEROXIDASES, SUDAN BLACK B

MYELOID (Myeloblast, Promyelocyte, Neutrophil)

MYELOID (Myeloblast, Promyelocyte, Neutrophil) MONOCYTIC (Monoblast, Promonocyte, Monocyte) Erythroblast, Megakaryocytes

NAPHTHOL ASD CHLOROACETATE

A-NAPHTHYL ACETATE ESTERASE A-NAPHTHYL BUTYRATE ESTERASE PAS, ACID PHOSPHATASE

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

BLOOD PICTURE : AML

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

BLOOD PICTURE : AML

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIAS

M0 : MYELOBLASTIC LEUKEMIA with MINIMAL DIFFERENTIATION
Criteria for diagnosis : Non granular blasts; <3% are MPO (+) by enzyme cytochemistry; blasts express myeloid but not classic lymphocyte antigens; blasts may abnormally express some lymphocyte antigens
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIAS

M1 : MYELOBLASTIC LEUKEMIA WITHOUT MATURATION
Criteria for diagnosis :
At least 90% of nonerythroid cells are myeloblasts; At least 3% of blasts must be (+) for MPO or SBB PBS : Very immature cells, usually round with few granules or Auer rods; little maturation beyond myeloblast stage
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

M1 LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIAS

M2 : MYELOBLASTIC LEUKEMIA WITH MATURATION
Criteria for diagnosis : 20 89% of nonerythroid cells are myeloblasts PBS : full range of myeloid maturation through granulocytes; Auer rods usually present, maturing neutrophils, erythroid and megakaryocyte precursors may have dysplastic change; 70% of patients have Auer rods Enzyme cytochemistry : (+)MPO or SBB
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

M2 LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

M2 LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIAS

M3 : HYPERGRANULAR PROMYELOCYTIC LEUKEMIA DIC

Criteria for Diagnosis Most cells (>50%) are abnormal promyelocytes with heavy cytoplasmic granulation, often with reniform nucleus; cells with multiple Auer bodies usually present Microscopic : most cells are hypergranular promyelocytes with heavy red / purple cytoplasmic granulation
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIAS

M3v : MICROGRANULAR PROMYELOCYTIC LEUKEMIA
Distinct Auer Rods Microgranular promyelocytes

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

M3 LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIAS

M4 : MYELOMONOCYTIC LEUKEMIA (Naegelis Leukemia)
Often with markedly elevated WBC, organomegaly, lymphadenopathy and other tissue infiltration (monocytes infiltrate) Criteria for diagnosis Myeloblasts and monoblasts are 20% or more of nonerythroid cells; 60% of patients have Auer rods in myeloblasts >20% of ANC SBB/POD (+) >20% of ANC aNAE/aNBE (+)
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIAS

M4E : MYELOMONOCYTIC LEUKEMIA with EOSINOPHILIA Diagnostic features are similar with M4 but with the presence of eosinophila

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

M4 LEUKEMIA
M4 M4E

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIAS

M5 : MONOCYTIC LEUKEMIA
(Schillings Leukemia) Older patients, high incidence of organomegaly, lymphadenopathy, tissue infiltration Criteria for diagnosis 80% or more nonerythroid BM cells belong to the monocytic lineage Types : M5A : M5B : Enzyme Cytochemistry : >80% ANC are (+) for aNAE/aNBE
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

M5A LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

M5 LEUKEMIA
M5A M5B

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIAS

M6 : ERYTHROLEUKEMIA (DiGuglielmos Leukemia)
Criteria for Diagnosis: 50% or more of ANC are erythroblasts; 20 % or more of nonerythroid cells are myeloblasts Dyserythropoiesis is prominent Enzyme Cytochemistry : PAS (+)
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

M6 LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ACUTE MYELOGENOUS LEUKEMIAS

M7 : MEGAKARYOBLASTIC LEUKEMIA
Associated with marrow fibrosis due to megakaryoblast secretion of fibrogenic cytokines PB often contains micromegakaryocytes and atypical platelets Criteria for diagnosis 20% or more blasts are present in BM MGB are medium/large cells with dense chromatin, blue vacuolated cytoplasm, fine granules, cytoplasmic projections resembling platelets
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

M7 LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

THE LYMPHOCYTIC LEUKEMIAS

Acute Lymphoblastic Leukemias
Most common of all leukemia Signs and Symptoms : Organ involvement: Manifestations : Anemia, thrombocytopenia, WBC >100x109/L
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

FAB CLASSIFICATION
L1
Size Small

L2
Large varied cells

L3
Large varied cells with vacuoles (bubble-like features) Finely stippled Round to oval 1 to 3

Chromatin Shape Nucleoli

Homogenous Regular Rare

Variable Irregular Present

Cytoplasm
Basophilia

Scanty
Moderate

Moderate
Variable

Moderate
Intense

In children
In adults

80%
35%

10-20%
60%

35%
<5%

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

Acute Lymphoblastic Leukemias

WHO CLASSIFICATION
ALL (includes former L1/L2) Burkitts Lymphoma (former L3) Pre B ALL Pre-T ALL Biphenotypic Acute Leukemia
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

ALL

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

THE CHRONIC LEUKEMIAS

CHRONIC GRANULOCYTIC LEUKEMIA

Chronic Myelogenous Leukemia Chronic Eosinophilic Leukemia Chronic Myelomonocytic Leukemia

CHRONIC LYMPHOCYTIC LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

CHRONIC MYELOGENOUS LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

CHRONIC LYMPHOCYTIC LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

OTHER WBC DYSCRASIAS

HAIRY CELL LEUKEMIA
Also known as LEUKEMIC RETICULOENDOTHELIOSIS Hairy Cells : 12 20 microns, round to oval nucleus, cytoplasm has fine filamentous projections arising from the membrane

Leukemic cells stain (+) to TRAP

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

HAIRY CELL LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

PLASMA CELL DYSCRASIA

Multiple Myeloma Plasma Cell Leukemia

Waldenstroms macroglobulinemia
Heavy Chain Disease
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

PLASMA CELL DYSCRASIA

PARAMETER PBS MULTIPLE MYELOMA Rouleaux, rare plasma cells PLASMA CELL LEUKEMIA Rouleaux, >2.0 x 109/L abnormal plasma cells Small type, abnormal plasma cells Monoclonal Peak WALDENSTROM MACROGLOBULINEMIA Rouleaux, rare plasma cells

Bone Marrow

10% to 15% myeloma cells Monoclonal peak, Urine L chain Bone Fractures, Bone Lesions

Plasmacytoid plasma cell Monoclonal IgM Increased plasma viscosity

Serum Proteins Others

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

PLASMA CELL DYSCRASIAS

MULTIPLE MYELOMA PLASMA CELL LEUKEMIA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

LYMPHOMA
Malignant tumors of lymphoid tissues TYPES HODGKINS Lymphoma Lymphogranulomatosis Reed Sternberg Cells NON-HODGKINS Lymphoma Other Lymphomas Sezary Syndrome Burkitts Lymphoma
MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

BURKITTS LYMPHOMA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

REED-STERNBERG CELLS

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

LYMPHOPLASMACYTIC LYMPHOMA

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology

LYMPHOMAS

MarjiSimMeingJamias-Raganit,RMT Clinical Hematology