Presentation is loading. Please wait.

Presentation is loading. Please wait.

Week 10: Leukemia AML AML ALL ALL FAB classification FAB classification WHO classification WHO classification Cytochemistries Cytochemistries MPO MPO SBB.

Similar presentations


Presentation on theme: "Week 10: Leukemia AML AML ALL ALL FAB classification FAB classification WHO classification WHO classification Cytochemistries Cytochemistries MPO MPO SBB."— Presentation transcript:

1 Week 10: Leukemia AML AML ALL ALL FAB classification FAB classification WHO classification WHO classification Cytochemistries Cytochemistries MPO MPO SBB SBB PAS PAS ORO CD markers Flowcytometry CML CLL Karyotype Ph chromosome LAP

2 Signs and Symptoms of AML Insidious nonspecific onset Insidious nonspecific onset Pallor due to anemia Pallor due to anemia Febrile due to ineffective WBC Febrile due to ineffective WBC Petechiae due to thrombocytopenia Petechiae due to thrombocytopenia Mucus membrane and gum bleed in M4 and M5 Mucus membrane and gum bleed in M4 and M5 Bone pain Bone pain

3 Typical Labs of AML Leukocytosis Leukocytosis Blastemia Blastemia Leukemic hiatus Leukemic hiatus Auer rods in M2, M3, M4 Auer rods in M2, M3, M4 Thrombocytopenia Thrombocytopenia Anemia Anemia >20% blasts in BM >20% blasts in BM

4 Other Findings CD 13 and CD 33 in flowcytometry CD 13 and CD 33 in flowcytometry Cytochemistries Cytochemistries  Myeloperoxidase  Sudan black B  Choloroacetate esterase (specific)  Nonspecific esterase

5 FAB (1976) Classification M0 -- Undifferentiated AML M0 -- Undifferentiated AML M1 -- AML without maturation M1 -- AML without maturation M2 -- AML with maturation M2 -- AML with maturation M3 -- Acute Promyelocytic Leukemia M3 -- Acute Promyelocytic Leukemia M4 -- Acute Meylomonocytic Leukemia M4 -- Acute Meylomonocytic Leukemia M5 -- Acute Monocytic Leukemia M5 -- Acute Monocytic Leukemia M6 -- Erythroleukemia (DiGuglielmo’s) M6 -- Erythroleukemia (DiGuglielmo’s) M7 -- Megakaryoblastic Leukemia M7 -- Megakaryoblastic Leukemia

6

7 M1 and M2

8

9

10 Myeloperoxidase (MPO) p-Phenylene diamine + Catecol + H 2 O 2 MPO > Brown black deposits

11 M3 M5 M4

12 Chloracetate (Specific) Esterase Myeloid Cell Line Naphthol-ASD-chloracetate CAE > Free naphthol compounds + Stable diazonium salt (eg, Fast Corinth) > Red deposit

13 Non-Specific Esterase Monocytic Line  Naphthyl acetate ANAE > Free naphthyl compounds +Stable diazonium salt (eg, Fast blue RR) > Brown deposits

14 Double Esterase in M4 NSE with Fl inhibition Histiocyte

15 FAB vs WHO Classifications of Hematologic Neoplasm FAB criteria FAB criteria  Morphology  Cytochemistry WHO criteria  Morphology  Immunophenotyping  Genetic features  Karyotyping  Molecular testing  Clinical features

16 WHO Classification of AML AML with recurrent cytogenic translocations AML with recurrent cytogenic translocations AML with multi-lineage dysplasia AML with multi-lineage dysplasia AML and myelodysplasia, therapy related AML and myelodysplasia, therapy related AML, not otherwise categorized AML, not otherwise categorized

17 AML with Recurrent Cytogenetic Translocations (WHO 1995) t(8;21) -- some maturation of neutrophilic line; rare in older patients; AML1/ETO fusion protein; >90% FAB M2 t(8;21) -- some maturation of neutrophilic line; rare in older patients; AML1/ETO fusion protein; >90% FAB M2 t(15;17) -- APL (granular and microgranular variants); retinoic acid receptor (RAR) leukemias; middle aged adults; DIC t(15;17) -- APL (granular and microgranular variants); retinoic acid receptor (RAR) leukemias; middle aged adults; DIC inv(16) or t(16;16) -- monocytic and granulocytic; abnormal eosinophilic component inv(16) or t(16;16) -- monocytic and granulocytic; abnormal eosinophilic component 11q23 -- monocytic; children; most common is t(9;11) 11q23 -- monocytic; children; most common is t(9;11)

18

19

20

21 FAB Classification of ALL L1: Small homogeneous blasts; mostly in children L1: Small homogeneous blasts; mostly in children L2: Large heterogeneous blasts; mostly in adults L2: Large heterogeneous blasts; mostly in adults L3: “Burkitt” large basophilic B-cell blasts with vacuoles L3: “Burkitt” large basophilic B-cell blasts with vacuoles

22 L3L2

23 Periodic Acid Schiff Periodic acid + Glycogen oxidation > Aldehyde + Schiff reagent (para-rosaniline, Na metabisulfite) > Red deposit

24 ALL Cytochemistries Oil Red O: stains L3 vacuoles Oil Red O: stains L3 vacuoles Terminal deoxynucleotidyl transferase (Tdt): DNA polymerase in early lymphoblasts Terminal deoxynucleotidyl transferase (Tdt): DNA polymerase in early lymphoblasts Cell surface markers (CD’s) Cell surface markers (CD’s) Cytoplasmic and surface immunoglobulins: B-cell line Cytoplasmic and surface immunoglobulins: B-cell line T-cell receptor (TCR) T-cell receptor (TCR)

25 WHO Classification of Lymphoproliferative Syndromes Precursor B Lymphoblastic Leukemia/Lymphoma (ALL/LBL) -- ALL in children (80-85% of childhood ALL); LBL in young adults and rare; FAB L1 or L2 blast morphology Precursor B Lymphoblastic Leukemia/Lymphoma (ALL/LBL) -- ALL in children (80-85% of childhood ALL); LBL in young adults and rare; FAB L1 or L2 blast morphology Precursor T ALL/LBL -- 15% of childhood ALL and 25% of adult ALL Precursor T ALL/LBL -- 15% of childhood ALL and 25% of adult ALL Burkitt Leukemia/Lymphoma (FAB L3) Burkitt Leukemia/Lymphoma (FAB L3)

26 AntigensB-LineageT-Lineage HLA Dr Tdt CD to CD19 C 22 CD10 CD20 Cyt-  SIg + cALL and older Pre-B and older B-ALL Pre-T 0 CD7 CD3 CD5 CD2 CD1 0 + T-ALL

27 IndicatorsFavorablePoor WBC < 50,000/  L  50,000/  L Age < 1 or  10 GenderFemaleMale BlastB-cell T-cell and mixed KaryotypeHyperploidy Trisomy 4, 10, 17 t(12;21) (TEL/AML1) Hypoploidy Trisomy 5 t(1;19 (E2A/PBX1) Mixed lineage leukemia T(9;22) (Ph) BM blast count during induction Mkd reduction at day 7 Mild reduction at day 7 Prognosis

28 Typical Labs in CML Leukocytosis with blastemia Leukocytosis with blastemia Thrombocytosis Thrombocytosis Basophilia Basophilia Micro-megakaryocytes Micro-megakaryocytes Low LAP score (intermediate if infected) Low LAP score (intermediate if infected) About 10% blasts in BM About 10% blasts in BM Philadelphia chromosome Philadelphia chromosome

29 CML

30 Bone marrow aspirate and biopsy

31 Pseudo-Gaucher’s cells in BM

32 Leukocyte Alkaline Phosphatase (LAP) Naphthol AS-MX phosphate LAP at pH8.6 > Naphthol AS-MX + Diazonium salt (eg, Fast blue RR) > Insoluble pigment

33 LAP Score Count 100 consecutive segs and bands Count 100 consecutive segs and bands Score: Score: 0 = no granules 1+ = occasional diffuse granules 2+ = moderate number of granules 3+ = many strongly positive granules 4+ = confluent strongly positive granules

34

35 LAP Score Example: 0x35 cells= 0 1+x30 cells= 30 2+x20 cells= 40 3+x10 cells= 30 4+x5 cells= LAP Score

36 Philadelphia Chromosome 9 and 22 translocation almost specific to CML 9 and 22 translocation almost specific to CML Karyotype to visualize Ph chromosome Karyotype to visualize Ph chromosome Produces BCR/c-abl fusion oncogene Produces BCR/c-abl fusion oncogene Gene product p190 is a hyperactive tyrosine kinase Gene product p190 is a hyperactive tyrosine kinase Ph chromosome seen in ALL produces p210 and chronic neutrophilic leukemia produces p230 Ph chromosome seen in ALL produces p210 and chronic neutrophilic leukemia produces p230

37 Karyotype 46,XX,t(9;22)(q34;q11.2) -- Ph chromosome

38

39 FISH showing the BCR (green), ABL (orange), and BCR-ABL fusion signals (arrow): A=positive (contains a residual ABL signal), B=normal

40 FAB (1982) Classification of Myeloproliferative Disease (MPD) Chronic Myelocytic Leukemia (CML) Chronic Myelocytic Leukemia (CML) Polycythemia Vera (PV) Polycythemia Vera (PV) Essential Thrombocythemia (ET) Essential Thrombocythemia (ET) Agnogenic Myeloid Metaplasia with or without Myelofibrosis (AMM) Agnogenic Myeloid Metaplasia with or without Myelofibrosis (AMM) Benign Leukemoid Reaction Benign Leukemoid Reaction

41 WHO Classification of MPS (1997) CML becomes CML becomes  CML, Ph + t(9;22) BCR/ABL  Chronic Neutrophilic Leukemia (CNL)  Chronic Eosinophilic Leukemia and Hyper- eosinophilic Syndrome (CEL/HES) PV remains PV PV remains PV ET remains ET ET remains ET AMM becomes AMM becomes  Chronic Idiopathic Myelofibrosis

42 Myelofibrosis

43

44

45 Chronic Lymphocytic Leukemia Exclusive in elderly Exclusive in elderly Lyphocytosis unrelated to viral infection Lyphocytosis unrelated to viral infection Hyper-mature lymphocytes with highly condensed nuclei Hyper-mature lymphocytes with highly condensed nuclei Smudge cells: preventable with a drop of bovine albumin Smudge cells: preventable with a drop of bovine albumin

46 CLL PB and BM

47

48

49 Bone Marrow

50

51 WHO Lymphoid Neoplasms B cell neoplasms B cell neoplasms T/NK cell neoplasms T/NK cell neoplasms Hodgkin lymphoma (disease) Hodgkin lymphoma (disease)

52 Mature B Cell Neoplasms B cell CLL/SLL B cell CLL/SLL B prolymphocytic leukemia B prolymphocytic leukemia Burkitt’s lymphoma / leukemia Burkitt’s lymphoma / leukemia Splenic marginal zone B lymphoma Splenic marginal zone B lymphoma Extranodal marginal B lymphoma Extranodal marginal B lymphoma Hairy cell leukemia Lymphoplasmocytic leukemia Mantle cell lymphoma Plasma cell myeloma / plasmacytoma Follicular lymphoma Diffuse large B lymphoma

53 T/NK Cell Neoplasms T prolymphocytic leukemia T prolymphocytic leukemia T granular lymphocytic leukemia T granular lymphocytic leukemia Aggressive NK cell leukemia Aggressive NK cell leukemia Adult T lymphoma / leukemia Adult T lymphoma / leukemia Mycosis fungoides (Sezary syndrome) Anaplastic large cell lymphoma Hepatosplenic T lymphoma Peripheral T lymphoma Immunoblastic T lymphoma


Download ppt "Week 10: Leukemia AML AML ALL ALL FAB classification FAB classification WHO classification WHO classification Cytochemistries Cytochemistries MPO MPO SBB."

Similar presentations


Ads by Google