diagnostic logy
TRANSCRIPT
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 22
Objectives:
By the end of this lesson, the students will be
able to:•Differentiate between different types of anaemia.
• Choose the proper laboratory tests to diagnose
different types of anaemia.
• Interpret laboratory test results of a case of
anaemia.
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 33
How to approach a case of anaemia?
A case of anaemia is diagnosed first bycomplete blood count with special stress on the
indices
RBC morphologyReticulocyte count
Leukemia must be excluded.
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 44
Hypochromic microcytic anaemiaHypochromic microcytic anaemia
MCV < 75 fl, MCH < 26 pgMCV < 75 fl, MCH < 26 pg
1.1. IIron deficiency anaemia2. Anaemia of chronic diseasehronic disease
3.3. Sideroblastic anaemiaSideroblastic anaemia
4.4. Thalassaemia (Thalassaemia (αα,, ββ))
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 55
Lab d agnos s o hypochrom c
microcytic anaemia
Iron def. Chronic dis. Thalassemia Sideroblastic
Serum iron Reduced Normal/ Reduced Normal/Increased Increased
TIBC Increased Reduced Normal Normal
Serum Ferritin Reduced Increased Increased Increased
BM Iron stores Absent Increased Increased Increased
BM ringedsideroblasts
Absent Absent Absent Ringed sideroblasts
Hb electroph. Normal Normal Raised Hb A2, Hb Fin β thalassaemia
Normal
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 66
Iron deficiency anaemia Thalassemia
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 77
Sideroblastic Anaemia
Ringed Sideroblasts PB in a case of
Sideroblastic anaemia
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 88
Macrocytic AnaemiaMacrocytic Anaemia
A-Macrocytic Anaemia with reticulocytosis
1-Acute bleeding
2-Haemolytic anaemias
B-Macrocytic Anaemia without reticulocytosis
1. Megaloblastic anaemia (B12 or folate def.)
2. Myelodysplasia
3. Aplastic anaemia
4. Liver disease
5. Thyroid disease
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 99
Megaloblastic AnaemiaMegaloblastic Anaemia
A group of anaemias in which the
erythroblasts in the bone marrow show
asynchronous maturation of nucleus &
cytoplasm i.e. the nucleus maturation is
delayed due to DNA synthesis . It is due to
vit. B12 or folate deficiency (commonest
folate )
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 1010
Lab tests for B12 & folate deficiency
1. Complete blood picture:
Macrocytic anaemia MCV>100 flMacrocytic anaemia MCV>100 flLeucopenia, neutrophil hypersegmentationLeucopenia, neutrophil hypersegmentation
ThrombocytopeniaThrombocytopenia
2. B.M. examination:
Hypercellular, with megaloblasts, giant metamyelocytes.Hypercellular, with megaloblasts, giant metamyelocytes.3. Other tests:
Serum B12Serum B12
Serum folate, Red cell folateSerum folate, Red cell folate
Anti-parietal Ab & anti-intrinsic factor Ab.Anti-parietal Ab & anti-intrinsic factor Ab.
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 1111
Megaloblastic features in the BM:
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Lab Approach to HaemolyticLab Approach to Haemolytic
AnaemiaAnaemiaScreening testsScreening tests
1.1. Increased reticulocyte countIncreased reticulocyte count
2.2. Increased urine urobilinogenIncreased urine urobilinogen
3.3. Increased indirect bilirubinIncreased indirect bilirubin
CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 1212
L b A h H l i
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Lab Approach to HaemolyticLab Approach to Haemolytic
AnaemiaAnaemia
Specific tests:Specific tests:1.1. Hemoglobin Electrophoresis to detect abnormalHemoglobin Electrophoresis to detect abnormal
hemoglobins.hemoglobins.
2.2. Osmotic fragility test for heriditary spherocytosisOsmotic fragility test for heriditary spherocytosis
3.3. Coombs’ test for immune hemolytic anaemiasCoombs’ test for immune hemolytic anaemias
4.4. G-6-PD assay for favismG-6-PD assay for favism
5.5. Red cell morphologyRed cell morphology
6.6. B.M. examination.B.M. examination.
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Two Types of HaemolysisTwo Types of Haemolysis
1-Extravascular (in RES e.g spleen)1-Extravascular (in RES e.g spleen)
2-Intravascular (inside vessels)2-Intravascular (inside vessels)
Main cause : ??????Main cause : ??????Specific tests include :Specific tests include :
HemoglobinaemiaHemoglobinaemia
MethemoglobiaemiaMethemoglobiaemia
HemoglobinuriaHemoglobinuria
Decreased haptoglobinDecreased haptoglobin
CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 1414
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 1515
Normochromic Normocytic anaemia
Normal MCV , MCH & MCHC
Haemolytic anaemias other than thalassemia
Ex :sickle cell , hereditary spherocytosis, G6PD deficiency.
Acute bleeding
Acute systemic disease
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 1616
Normochromic, normocytic anaemia in a
case of anaemia of chronic disease
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 1717
Hereditary Elliptocytosis
G6PD deficiencySickle cell Anaemia
Sickle cell Anaemia
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 1818
Hereditary Spherocytosis
Red cell membrane defect
Diagnostic criteria:
1-Normochromic Normocytic anaemia with increased
MCHC
2-Blood film show micro-spherocytes
3-Reticulocytosis
4-Increased Saline Osmotic Fragility
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 2020
Immune haemolytic anaemia
Autoimmune Alloimmune
Coombs’ test positiveCoombs’ test positive Coombs’ test positiveCoombs’ test positive
No history of blood transfusionNo history of blood transfusion -Positive history of blood transfusion-Positive history of blood transfusion-Haemolytic disease of the newborn.-Haemolytic disease of the newborn.
Warm type : at 37º CWarm type : at 37º C
Cold type : at 4º CCold type : at 4º C
-Primary-Primary
-Secondary to lymphoma, SLE,-Secondary to lymphoma, SLE,
drugs…etcdrugs…etc
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 2121
RBCs fragments in haemolyticanaemiaCold Agglutinins
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 2222
Aplastic anaemia & BM failureAplastic anaemia & BM failure
DefinitionDefinition::
Pancytopenia resulting from aplasia of the bone marrow.
ClassificationClassification::
Primary:
Congenital (Fanconi, non Fanconi types) and acquired
(idiopathic)Secondary:
Ionizing radiation, drugs, chemicals & infections.
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 2323
Laboratory findings of aplastic anemiaLaboratory findings of aplastic anemia::
1. Normochromic normocytic anaemia withlow reticulocyte count.
2. Leucopenia
3. Thrombocytopenia
4. No abnormal cells are seen in blood films.
5. Hypocellular bone marrow withreplacement of haemopoietic tissue by fatspaces.
Aplastic anaemia
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 2424
Haemostasis
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2525 CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT
Bleeding disordersBleeding disorders
Bleeding disorders may be due toBleeding disorders may be due to
abnormalities of the vascular system,abnormalities of the vascular system,
platelets, coagulation system or fibrinolyticplatelets, coagulation system or fibrinolyticsystem.system.
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Lab tests for bleeding disordersLab tests for bleeding disorders
SCREENING TESTS:SCREENING TESTS:
1.1. BTBT
2.2. CTCT3.3. PT /INR to standardize PT resultsPT /INR to standardize PT results
among different labsamong different labs
4.4. PTTPTT5.5. TTTT
2626 CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT
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2727 CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT
Lab diagnosis of vascular Lab diagnosis of vascular
causescauses1.1. BT: prolongedBT: prolonged
2.2. CT : normalCT : normal
3.3. Hess test: > 5 purpuric spotsHess test: > 5 purpuric spots
4.4. Platelet count : normalPlatelet count : normal
5.5. Platelet function: normalPlatelet function: normal
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PROLONGED BLEEDINGPROLONGED BLEEDING
TIMETIME
1.1. CBC to diagnose thrombocytopeniaCBC to diagnose thrombocytopenia
2.2. PT normal & PTT prolonged…..?PT normal & PTT prolonged…..?
VWD??VWD??
3.3. BM for thrombocytopeniaBM for thrombocytopenia
4.4. Platelet function tests (aggregometer) toPlatelet function tests (aggregometer) to
diagnose qualitative plateletdiagnose qualitative plateletdisorders.eg. Glanzman diseasedisorders.eg. Glanzman disease
2828 CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT
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2929 CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT
Clotting cascade
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PROLONGED PTPROLONGED PT
1.1. With normal PTTWith normal PTT
1.1. Hereditary:DEFECT IN extrinsic pathway:Hereditary:DEFECT IN extrinsic pathway:
factor VII deficiencyfactor VII deficiency
2.2. Acquired:Acquired:
1.1. Hemorrhagic disease of the newborn due to vit KHemorrhagic disease of the newborn due to vit K
deficiencydeficiency
2.2. Liver disease (synthetic function of the liver)Liver disease (synthetic function of the liver)
3131
CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT
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Prolonged thrombin timeProlonged thrombin time
In cases of fibrinogen defects :In cases of fibrinogen defects :
dysfibrinogenemia, afibrinogenemia, DICdysfibrinogenemia, afibrinogenemia, DIC
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT
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LAB INVESTIGATIONS OF DICLAB INVESTIGATIONS OF DIC
1.1. All screening tests are prolonged: BT,CTAll screening tests are prolonged: BT,CT
PT PTTPT PTT
2.2. THROMBOCYTOPENIATHROMBOCYTOPENIA
3.3. D-DIMER /FDP’S positiveD-DIMER /FDP’S positive
4.4. Factor assay : decreased activityFactor assay : decreased activity
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 3636
ACUTE& CHRONICACUTE& CHRONIC
LEUKAEMIASLEUKAEMIAS
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 3737
HAEMATOLOGIC MALIGNANCYHAEMATOLOGIC MALIGNANCY
ACUTE LEUKAEMIASACUTE LEUKAEMIAS
CHRONIC MYELOPROLIFERATIVECHRONIC MYELOPROLIFERATIVEDISORDERSDISORDERS
CHRONIC LYMPHOPROLIFERATIVECHRONIC LYMPHOPROLIFERATIVE
DISORDERSDISORDERS
MULTIPLE MYELOMA and PLASMA CELLMULTIPLE MYELOMA and PLASMA CELL
DYSCRASIASDYSCRASIAS
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 3838
What are LeukemiasWhat are Leukemias??
Leukemias are malignant counterparts of normalLeukemias are malignant counterparts of normalhematopoietic cells at different stages of maturation.hematopoietic cells at different stages of maturation.
Leukemias are primary disorders of bone marrow.Leukemias are primary disorders of bone marrow.
Malignant cells replace bone marrow, may infiltrateMalignant cells replace bone marrow, may infiltratespleen, liver, lymph nodes and circulate in blood streamspleen, liver, lymph nodes and circulate in blood stream
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 3939
Classification of leukemiasClassification of leukemias
According to the courseAccording to the courseof leukemiaof leukemia
ACUTE LEUKAEMIA:ACUTE LEUKAEMIA:
-Proliferation of immature-Proliferation of immature
cellscells-If untreated is rapidly-If untreated is rapidlyfatal.fatal.
CHRONICCHRONIC LEUKAEMIA:LEUKAEMIA:-Proliferation of mature-Proliferation of mature
cellscells-chronic course.-chronic course.
According to the cellAccording to the cellof originof origin
LYMPHOIDLYMPHOID
((T, B or NK) ALL andT, B or NK) ALL andCLPDCLPD
MYELOIDMYELOID
AML and CMPDAML and CMPD
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 4040
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 4141
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 4242
ACUTE LEUKAEMIASACUTE LEUKAEMIAS
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 4343
ACUTE LEUKAEMIAACUTE LEUKAEMIA
EPIDEMIOLOGYEPIDEMIOLOGY
AML is predominantly a disease of adults.AML is predominantly a disease of adults.
ALL is predominantly a disease of childhoodALL is predominantly a disease of childhood
Acute leukaemia comprises 1/3 cases of childhood cancerAcute leukaemia comprises 1/3 cases of childhood cancer..
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 4444
French-American-British (FAB)French-American-British (FAB) ClassificationClassification
Based on morphology assisted by cytochemistry andBased on morphology assisted by cytochemistry and
immunophenotypingimmunophenotyping
WHO Classification (most recent)WHO Classification (most recent)
Based on morphology, cytogenetics, molecularBased on morphology, cytogenetics, moleculargenetics , immunophenotyping & clinical features.genetics , immunophenotyping & clinical features.
Classification of Acute leukemiaClassification of Acute leukemia
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 4545
FAB Classification of Acute Leukaemia
AMLM0 Minimally differentiated
M1 Myeloblastic
M2 Myeloblastic with differentiation.
M3 Promyelocytic
M4 Myelomonocytic
M5 Monoblastic
M6 Erythroleukemia
M7 Megakaryocytic
ALLL1
L2
L3Sta
ge
of
Diffe
re
ntiati
on
Lineag
eo
f
Blasts
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 4747
M0 Minimally
differentiated
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 4848
M1 Myeloblastic
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 4949
M2 Myeloblastic with differentiation.
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 5050
M3 Promyelocytic: Hypergranular
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 5151
M3 Promyelocytic: Microgranular
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 5252
M4 Myelomonocytic
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 5353
M5a Monoblastic without maturation
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 5454
M5 b Monoblastic with maturation
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 5555
M6 Erythroleukemia
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 5656
M7 Megakaryocytic
ACUTE LYMPHOBLASTICACUTE LYMPHOBLASTIC
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 5757
ACUTE LYMPHOBLASTICACUTE LYMPHOBLASTIC
LEUKAEMIALEUKAEMIA
FAB ClassificationFAB Classification ALL-L1ALL-L1
ALL-L2ALL-L2 ALL-L3ALL-L3
Immunologic ClassificationImmunologic Classification
T or B lymphoblastic leukemiaT or B lymphoblastic leukemia
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 5858
ALL L1
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 5959
ALL L2
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 6060
ALL L3
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 6161
Burkitt’s Lymphoma
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 6363
LABORATORY DIAGNOSISLABORATORY DIAGNOSIS
4-4- ImmunophenotypingImmunophenotyping
A panel of monoclonal antibodies (CDs) are used toA panel of monoclonal antibodies (CDs) are used to
detect : myeloid markers and lymphoid markers (for B &detect : myeloid markers and lymphoid markers (for B &
T cells).T cells).
CD: cluster of differentiationCD: cluster of differentiation
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 6464
LABORATORY DIAGNOSISLABORATORY DIAGNOSIS
5- Genetic Analysis (karyotyping, FISH and PCR)5- Genetic Analysis (karyotyping, FISH and PCR)
Karyotyping Karyotyping
Chromosomal analysis is important for the diagnosis , classificationChromosomal analysis is important for the diagnosis , classification
and follow up of haematologic malignancies.and follow up of haematologic malignancies.
Chromosomes are visible only in metaphase ( mitosis).Chromosomes are visible only in metaphase ( mitosis).
FISH (fluorescence in situ hybridization)FISH (fluorescence in situ hybridization)
Using a labelled probe that hybridizes to DNAUsing a labelled probe that hybridizes to DNA Hybridization is visualizedHybridization is visualized
using fluorescent microscope.using fluorescent microscope.
PCR PCR ( polymerase chain reaction)( polymerase chain reaction)
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 6565
CMLCML
CML arises from a neoplastic proliferation of CML arises from a neoplastic proliferation of
a pluripotential stem cell that can differentiatea pluripotential stem cell that can differentiate
into granulocyte, monocyte, erythroid,into granulocyte, monocyte, erythroid,megakaryocyte and lymphoid lineages .megakaryocyte and lymphoid lineages .
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Lab diagnosis ofLab diagnosis of
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CLINICAL PATHOLOGYCLINICAL PATHOLOGYDEPARTMENTDEPARTMENT 6767
Lab diagnosis of Lab diagnosis of
CML -CHRONIC PHASECML -CHRONIC PHASE
1-Blood picture1-Blood picture
a-Normochromic normocytic anaemiaa-Normochromic normocytic anaemia
b-Leucocytosisb-Leucocytosis
-- Neutrophil leucocytosis with 2 peaksNeutrophil leucocytosis with 2 peaks (myelocytes & neutrophils)(myelocytes & neutrophils)
-- BasophiliaBasophilia
-- Eosinophilia.Eosinophilia.
-- Blasts < 2 %Blasts < 2 %
c-Thrombocytosis .c-Thrombocytosis .
2- Bone marrow examination2- Bone marrow examination
-Hypercellular Bone marrow-Hypercellular Bone marrow-3% of blasts-3% of blasts
Lab diagnosis of Lab diagnosis of
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 6868
ggCML -CHRONIC PHASECML -CHRONIC PHASE
3-Genetic Analysis (karyotyping, FISH and PCR)3-Genetic Analysis (karyotyping, FISH and PCR)
All Cases of CML are Philadelphia chromosome positive :All Cases of CML are Philadelphia chromosome positive :
(translocation between chromosomes # 9, & #22 :t (9;22))(translocation between chromosomes # 9, & #22 :t (9;22))
This translocation fuses the BCR gene on #22 with regions of This translocation fuses the BCR gene on #22 with regions of
the ABL gene from # 9 & results in the formation of athe ABL gene from # 9 & results in the formation of a
hybrid gene : BCR/ABL fusion gene.hybrid gene : BCR/ABL fusion gene.
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 6969
t (9 ; 22) (q34 ; q11)
BCR-ABL
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 7070
BCR-ABL by FISH
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 7171
Peripheral Blood
CML Chronic Phase
Bone Marrow
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 7272
CML: Blast crisis
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 7373
CHRONIC LYMPHOCYTICCHRONIC LYMPHOCYTIC
LEUKAEMIALEUKAEMIA
Chronic lymphocytic leukemiaChronic lymphocytic leukemia
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CLINICAL PATHOLOGYCLINICAL PATHOLOGY
DEPARTMENTDEPARTMENT 7474
y p yy p y
(CLL(CLL))
Old age >40yOld age >40y
Accidental discovery by routine CBC showing lymphocytosis.Accidental discovery by routine CBC showing lymphocytosis.
Lab diagnosisLab diagnosis
1-CBC : Lymphocytosis with characteristic CLL morphology1-CBC : Lymphocytosis with characteristic CLL morphology
2-BM xamination : Hypercellular with lymphocytosis2-BM xamination : Hypercellular with lymphocytosis3-Immunophenotyping3-Immunophenotyping
4-( trisomy 12)4-( trisomy 12)
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B-CLL