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Blood Neoplams
March 2010
id4356578 pdfMachine by Broadgun Software - a great PDF writer! - a great PDF creator! - http://www.pdfmachine.com http://www.broadgun.com
Learning issues
Understand the nature of common blood neoplasms (AML, ALL, CML, CLL): Clinical presentation, Pathology, complications and prognosis
Classification of Blood neoplasms To know the different laboratory
methods in diagnosis of blood neoplasms
White Blood Cells:
Leucopoiesis:
1. Myeloblast2. Promyelocyte3. Myelocyte4. Metamyelocyte5. Band Neutrophil6. Segmented Neutrophil.
Myeloid cells
WBC disorders:
Reactive increase in number philias Neutrophilia Bacterial sepsis Lymphocytosis viral, Immune Eosinophilia Allergy & Parasites.
Decreased number penias Neutropenia, Lymphopenia &
Eosinopenia, Pancytopenia Drugs, viral infections, Radiation,
chemotherapy etc.
WBC Neoplastic disorders
Leukemias Bone marrow, blood, blast cells Acute/Chronic & Myeloid/Lymphoid AML / ALL & CML / CLL
Lymphomas Lymph nodes, tumor Hodgkins Non-Hodgkins
Myeloma Premalignant conditions:
Myeloproliferative syndromes (MPS) Myelodysplastic syndromes (MDS)
Classification
Clinically: Acute, chronic Morphology: Myeloid, Lymphoid Old classification followed was FAB
Using peripheral smear, bone marrow study, cytochemistry
Latest is WHO classification of blood neoplasms Immunophenotyping, cytogenetics, Molecular
biology
Leukemia Classification
Acute Leukemias: Acute Myeloid Leukemia - AML
AML M0, M1, M2, M3, M4, M5, M6 & M7 Acute Lymphoid Leukemia - ALL
ALL - L1, L2 & L3 Chronic Leukemias:
Chronic Myeloid Leukemia- CML Chronic Lymphoid Leukemia - CLL
General Age Distribution:
ALL- Younger age population: 4-10 yrs AML- Young Adults: 15-40 yrs CML- Older adults: 30-60 yrs CLL- Old age group: 50-70 yrs
Acute Leukemias:
Rapid onset & Rapid progression High Mortality Plenty of Blasts >20% (in PS & or BM) Anemia, infection & bleeding ALL-Typically presents as
Lymphadenopathy AML- Associated with
Hepatosplenomegaly
Etiology
Radiation: Ionizing, Non ionizing. Chemicals: Benzene, alkyalating agents. Viruses: Leukemogenic viruses with RT
enzyme, HTLV-1. Genetic factors: Downs, Blooms,
Fanconis, Ataxia talengiectasia.
Ac Leukemia - Clinical Features
Suppression of normal hematopoesis Anemia (low RBC) Fever - Infections (low WBC) Bleeding tendency (low PLT) Tender bones, lymphadenopathy,
spleenomegaly etc. (Leukemic infiltration)
Clinical features of AML
Primarily in adults and in infants less than 1 yr
15 to 20% of all leukemias Less No. of cases after age 50 yrs. Abrupt onset of symptoms.. Within
weeks to months.
Palor, fatigue, weakness, anaemia. Bleeding, bruising, petichial
hemorrhages. Infections, pneumonia, meningitis Spleenomegaly, hepatomegaly,
lymphadenopathy. DIC in AML-M3, skin infiltration soft
tissue masses in AML- M5 etc.
PlateletCoagulation
Petechiae, Purpura Hematoma, Joint bl.
AML-M5 - Gum Hypertrophy:
Organomegaly
Diagnosis of AML
High index of clinical suspicion Family history, past history. Simple PS examination. PS, Bone marrow, Cytochemistry,
Immunophenotyping, Cytogenetics, Other lab tests: Serum uric acid, LDH,
RFT, Sr.Ca, electrolytes
PS EXAMINATION IN AML
RBC are normocytic normochromic WBC count is increased , Rarely it is
decreased or Normal. Majority of cells are Immature cells- Blasts PS shows > 20% Myeloblasts Mature neutrophils are less Morphology of AML M0- M7 type Low platelets
BM examination in AML
Hypercellular Marrow Blasts are > 20% Blasts with intracytoplasmic rods- Auer
Rods Increased M: E ratio Less of Megakaryocytes
AML-M2 - with maturation
AML-M3 Promyelocytic
Special investigations
Difficult to distinguish blasts among other cells Cytochemistry
Blast cells show reaction to cytochemical stains. This property is used to identify & differentiate cells
Myeloblasts are +ve for Sudan black B & Myeloperoxidase (MPO)
Lymphoblasts are +ve for Periodic acid schiff (PAS) AML M4 & M5 blasts are +ve for Non- specific esterase
(NSE) Immunophenotyping
Identifying cells by surface markers using antibodies
NSE positive in AML-M5
Cytogenetics in AML
To detect genetic abnormality in leukemias
Confirms the diagnosis Prognostication of patients t(15;17) in AML M3 t(8;21) in AML M2 inv16 in AML M4
ALL-Acute Lymphoblastic Leukemia
Common in Children. FAB classification L1, L2 & L3 Neoplastic cells are CD10 +ve & most are
Pre B cell type. 2% of child ALL & 20-30% of adult onset
ALL has t(9;22) Growth failure, Fever, Anemia
Lymphadenopathy, bleeding. Mild to Moderate Hepatosplenomegaly
ALL:Cervical Lymphadenopathy
Mediastinal Lymphadenopathy - ALL
ALL-L2
Diagnosis of ALL
High clinical suspicion PS & BM study (aspiration/ biopsy)
Morphological diagnosis Lymphnode aspiration & biopsy Immunophenotyping, cytogenetics Imaging (USG scan, CT)
Chronic leukemias
Also divided as Myeloid and lymphoid (FAB)
Have indolent course. More mature forms are seen in the PS
like lymphocyte and neutrophil Blasts in PS or BM is less than 20% (5-
10%) WBC counts are very high
Chronic Myeloproliferative syndrome
1. Chronic myeloid leukemia (CML)2. Polycythaemia vera3. Essential thrombocytosis4. Myelofibrosis.
Marrow fibrosis Cytopenias
Acute leukemia
Chronic Myeloid Leukemia
Middle age 40-60y, insidious onset Philadelphia chromosome, t(9:22) Anemia, Fever & Bleeding Marked leucocytosis >1,00,000/ cumm Marked splenomegaly, Hepatomegaly,
weight loss Sometimes, discovered accidentally Three phases: Chronic, Accelerated, Blast
crisis
PATHOPHYSIOLOGY
Clonal stem cell disorder. Targeted at PSC.
All hemopoetic cells are involved in the neoplasm.
Acquired chromosomal abnormality Ph (Philadelphia) chromosome is found in all neoplastic blood cells
PHILADELPHIA CHROMOSOME
Reciprocal translocation b/w Chr 9 & 22 t (9;22) Movement of ABL (Abelson) gene on
Chr 9 to BCR (Break point cluster) gene on Chr 22.
The translocation produces abnormal protein called p210.
Additional Chr abnormalities: Tri 8, Loss of Y, additional Ph.
PHILADELPHIA CHROMOSOME
Expressed in all blood cells except in T lymphocytes & few B cells.
2-5% of child ALL, 25% of adult ALL & some AML are also Ph Positive.
The abnormal protein may by p210 or p190.
BLOOD PICTURE in CML
Moderate anemia: 8 to 11 gm/dl Markedly elevated WBC count with full
spectrum. Counts up to 500 X 109 /L Myeloblasts up to 10%. PLT count may be normal, decreased or
increased. Increased in early CML (Chronic) Late CML Thrombocytopenia
BLOOD PICTURE
Segmented neutrophils & myelocytes constitute majority of cells
Monocytes, Basophils, eosinophils are also increased
Basophilia & eosinophilia > 20% Aggressive course
Decreased LAP score (Increased in Leukaemoid reaction) LAP = Leukocyte alkaline phosphatase
COURSE OF CML
Chronic phase may last 30 40 months.
Accelerated phase: Increasing spleen, severe prostration, raising WBC count, worsening of anaemia, Thrombocytopenia, blasts 10-19%, increasing Basophils, eosinophils.
Blast crisis: 1/3rd may develop blast crisis.= AML.
BLAST CRISIS
Now classified as AML. Survival 1-2 months. Blasts in PS & or BM >20%. Need aggressive treatment. Counts may decrease in PS. Few patients go in for
Myelofibrosis.
NOW..CML what Next??
Chronic course Spontaneous remission Accelerated phase Blast crisis
LEUKEMOID REACTION
Leukocytosis exceeding 50,000 WBC/mm3 Increase in band cells, myelocytes,
metamyelocytes, promyelocytes Generally benign and are not dangerous Response to a chronic bacterial disease state Blood picture is similar to CML Blast cells in BM aspirate are < 2% Increase in Leukocyte alkaline phosphatase (LAP
score) No Basophilia No Ph cromosome Counts return to normal following Antibiotics
Leukemoid Reaction:
CMLMalignancyHepatosplenomegalyLarge spleenSlow courseTotal count IncreasedThrombocytosisLAP decreasedPh chromosomeBasophilia
Leukemoid reactionInflammatory lesionHepatomegalyMild spleen if presentShort durationIncreased but not muchPlatelets- NormalLAP increasedNo Ph chromosomeAntibiotics
Differences between CML & Leukemoid Rn
CLL:
Most common in Older age (60-70yr). May be asymptomatic. Present with Lymphadenopathy Indolent course. No need of aggressive therapy.
Morphology in CLL
PS: Total count increased, Majority are Mature lymphocytes, Smudge cells, (Smear cells, Basket cells), Less of neutrophils
Some prolymphocytes + Identical tumor of Lymphnode SLL (small
lymphocytic lymphoma) Autoimmune HA, Autoimmune Thrombocytopenia
is common (10% of cases) May progress to aggressive types
Prolymphocytic leukemia Diffuse large B cell lymphoma (Richter syndrome)
CLL:
Myeloproliferative Syndromes:
Neoplasms, Slow, Chronic, Proliferation Increased, Functionally abnormal cells. Extramedullary hemopoiesis - Organomegaly Progress to Leukemia end stage. Classification:
Polycythemia rubra vera (PV) Chronic Myeloid Leukemia (CML) Essential Thrombocythemia (ET) Myelofibrosis (MF)
MPS: Classification
POLYCYTHEMIA VERA
Increase in cellular blood elements Unregulated proliferation of erythroid
elements in BM. Affects the pluripotent stem cells
granulocytes & platelets are also affected.
CLASSIFICATION OF POLYCYTHEMIA
Polycythemia Vera (Primary) Secondary Polycythemia:
High altitude, COPD, Obesity, Tumors, CRF,
Relative Polycythemia:Giasbocks syndrome, dehydration.
PATHOPHYSIOLOGY OF PV
Clonal stem cell defect EPO independent unregulated
erythrocyte hyperplasia. Hypersensitivity of erythroid stem cells
to EPO, GF & abnormal GF.
CLINICAL FEATURES
Ages of 40-60 yrs. Asymptomatic for several years Increased red cell massheadache,
weakness, pruritis, Wt. loss. Thrombotic episodes. Splenomegaly, hepatomegaly. Hypertension, plethora, congestion of eyes
BLOOD & BM
Hb: >18gm%, PCV > 52% in males. ESR < 4 mm/hr Leukocytosis: 12-20K, shift to left. LAP is > 100. Plt > 4,00,000., giant forms, abnormal
aggregation. Hypercellular marrow, M:E ratio is normal,
increase in Megakaryocytes
COURSE & PROGNOSIS
No known cure. Phlebotomy, Myelosuppression Progression to Myelofibrosis or rarely
acute leukemia.
Summary: Leukemias Starts in marrow spread to blood
Anemia, infections & Bleeding Enlargement of Liver, Spleen lymphnodes Acute/Chronic & Myeloid & Lymphoid.
Lymphomas Tumors of lymphnodes. Fever & lymphadenopathy Types - Hodgkins & non- hodgkins, special types.
Premalignant conditions MDS: Myelodysplastic syn Less & Dysplastic MPS: Myeloproliferative dis -Excess & abnormal
Learning issues
Understand the nature of common blood neoplasms (AML, ALL, CML, CLL): Clinical presentation, Pathology, complications and prognosis
Classification of Blood neoplasms To know the different laboratory
methods in diagnosis of blood neoplasms