blood malignancies

8/15/2019 blood malignancies

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Blood Malignancies-IBlood Malignancies-I

Prof. Herman Hariman S PK KH . Ph.D. U.KProf. Herman Hariman S PK KH . Ph.D. U.K

Prof. Dr. Adikoesoema Aman, SpPK (KH)Prof. Dr. Adikoesoema Aman, SpPK (KH)

De t. Clin ath FKDe t. Clin ath FK--USUUSU


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Hb, WBCS, PlateletsHb, WBCS, Platelets

orp o ogy uc as asts, a norma mononuc ears,orp o ogy uc as asts, a norma mononuc ears,

ordinary cells which shows abnormal appearancesordinary cells which shows abnormal appearances

Unex lained dro of latelet numbersUnex lained dro of latelet numbers

Unexplained drop of HbUnexplained drop of Hb

Unexplained drop or increase of WBCsUnexplained drop or increase of WBCs

Cell Counter


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ndnd

If possible both the aspiration andIf possible both the aspiration and

opsyopsy

BiopsyBiopsy

CytogeneticsCytogenetics

Immuno henot inImmuno henot in Tissue typing (HLA)Tissue typing (HLA)


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DASAR DIAGNOSA LEUKEMIA

MORFOLOGI CELL

RUTIN STAINING

SPESIAL STAINING


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ISLAM biopsy needle set


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CytostainingCytostaining

Sudan Black (SBB), MyeloperoxidaseSudan Black (SBB), Myeloperoxidase

MPO neutro hil alkaline hos hatseMPO neutro hil alkaline hos hatse

They areThey are oudatedoudated by immunophenotyping by immunophenotyping

--

PCR) especially in the implementation ofPCR) especially in the implementation of


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MPO stain, myeloblast but negative for neutrophil


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Sudan Black B


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Flowcytometer together with PCR can be used for cytogenetics


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KLASIFIKASI LEUKEMIAKLASIFIKASI LEUKEMIA

WHO ( 1997 )WHO ( 1997 )

The Euro ean Association of Patholo istThe Euro ean Association of Patholo ist

And the Society for HematopathologyAnd the Society for HematopathologyFAB ( MIC )

-Lymphoid Neoplasma-Morfologi

-

-Histiocytic Neoplasma

- mmunop eno yp ng

-Cytogenetic

-Mast Cell Neoplasma


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( IMMUNOLOGI MARKERS ) SEL :( IMMUNOLOGI MARKERS ) SEL :

DEFINISI :DEFINISI :

permukaan sel baik sel normal maupun selpermukaan sel baik sel normal maupun sel

LeukemiaLeukemia


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Immunophenotyping

( Cluster Differentiation )1s Internat ona Wor s op an Humen Leucocyte

Differentiation Antigen ( 1982 ) di Paris

Nomenclature CD 151 CD

5th Boston Workshop ( 1993 ) Update CD

6th Workshop on HLDA( Tadamatsu Kishimoto dari Osaka University Medical School )

1000 CD


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malignancies

malignancies

FABFAB

ChronicChronic

mye opro era vemye opro era vediseasesdiseases

MyelodysplasticMyelodysplasticsyndromessyndromes

Acute myeloid Acute myeloid


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. .

Myeloid Malignancies

. .

Myeloid Malignancies

Myelodysplastic/myeloproliferativeMyelodysplastic/myeloproliferative

Myelodysplastic syndromesMyelodysplastic syndromes

Acute myeloid leukaemias Acute myeloid leukaemias


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malignancies

malignancies

FABFAB

ChronicChronic

WHOWHO

ChronicChronic



M elod s lastic/m eloM elod s lastic/m elo

MyelodysplasticMyelodysplastic

roliferative diseasesroliferative diseases

MyelodysplasticMyelodysplastic

syndromessyndromes


syn romessyn romes



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Disorders

Disorders FABFAB

Chronic myelogenousChronic myelogenousleukemia (CML)leukemia (CML)

WHOWHO

CML Ph+: t(9;22)(qq34;q11),CML Ph+: t(9;22)(qq34;q11),BCR/ABLBCR/ABL

Agnogenic myeloid Agnogenic myeloidmetaplasia withmetaplasia with

Chronic neutrophilicChronic neutrophilicleukemialeukemia

Chronic eosinophilicChronic eosinophilicmye o ros smye o ros s(Idiopathic myelofibrosis)(Idiopathic myelofibrosis)

eu em a ypereos nop ceu em a ypereos nop csyndromesyndrome

Chronic idiopathicChronic idiopathic

Polycythemia vera (EV)Polycythemia vera (EV)

Essential thrombocytemiaEssential thrombocytemia

Polycythemia veraPolycythemia vera

Essential thrombocytemiaEssential thrombocytemia


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(French American British) F.A.B(French American British) F.A.B

Based on MORPHOLOGYBased on MORPHOLOGY

==

< 5% = normal or Chronic Leukaemia< 5% = normal or Chronic Leukaemia

-- ==

SYNDROME with the exception ofSYNDROME with the exception of

ryt ro eu aem a can eryt ro eu aem a can e -- asts utasts ut

the blast/NEC ratio > 30%the blast/NEC ratio > 30%


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CHRONICCHRONIC

MYELOPROLIFERATIVEMYELOPROLIFERATIVE

CML Ph+: t(9;22)(qq34;q11), BCR/ABLCML Ph+: t(9;22)(qq34;q11), BCR/ABL

Chronic neutrophilic leukemiaChronic neutrophilic leukemia

Chronic eosino hilicChronic eosino hilic

leukemia/hypereosinophilic syndromeleukemia/hypereosinophilic syndrome

Chronic idiopathic myelofibrosisChronic idiopathic myelofibrosis Polycythemia veraPolycythemia vera

Essential thromboc temiaEssential thromboc temia


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Laboratory testsLaboratory tests

FBCs: leucocytosis (>100 x 109/l) withFBCs: leucocytosis (>100 x 109/l) with

immature neutro hil m eloc tesimmature neutro hil m eloc tes

+metamyelocytes)+metamyelocytes)

Neutrophil Alk Phosphatase: reducedNeutrophil Alk Phosphatase: reduced

:: an oncogene + oan oncogene + oHLA typingHLA typing


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BCR/Abl oncogene

BCR/Abl oncogene

PROLIFERATIVE EFFECTPROLIFERATIVE EFFECT

ARREST OF DIFFERENTIATIONARREST OF DIFFERENTIATION

ARREST OF APOPTOSISARREST OF APOPTOSIS


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CMLCML The most important change is, thatThe most important change is, that only theonly the

Ph+ cases are called CMLPh+ cases are called CML b the WHO. b the WHO.TheThe PhPh-- casescases (which show myelodysplastic signs,(which show myelodysplastic signs,and are known to have significantly worseand are known to have significantly worse prognos s are ca e prognos s are ca e aa a yp ca , ana yp ca , an belong to the newly created belong to the newly created myelodysplastic /myelodysplastic /

m elo roliferative roum elo roliferative rou . The aCML term is. The aCML term issomewhat misleading, becausesomewhat misleading, because it is not CMLit is not CML atatall, but it was kept, having no better alternative.all, but it was kept, having no better alternative.


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Chronic phase CML Low power view of this bone marrow aspirate reveals

an increased ME ratio. Eosinophils and larger immature myeloid elements

are also evident.


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CML accelerated phase, leukocytosis with abnormal lobulation nuclei blasts less 20%


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CML BLASTIC CRISIS


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Hypereosinophilic syndrome/CEL


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Idiopathic Myelofibrosis


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Disorders

Disorders

Atypical myelogenous leukemia (aCML) Atypical myelogenous leukemia (aCML) samesamemorphology, Ph (morphology, Ph (--)ve, BCR/Abl (+)ve)ve, BCR/Abl (+)ve

same morphology with > 20% monocytessame morphology with > 20% monocytes

Juvenile myelomonocytic leukemia (JMML)Juvenile myelomonocytic leukemia (JMML)same morp o ogy ut n c ren < ys osame morp o ogy ut n c ren < ys o

..half of the cases show proliferative, the other dysplastic signs,half of the cases show proliferative, the other dysplastic signs,but it looks like these are just different forms of the samebut it looks like these are just different forms of the samedisease.disease.


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SYNDROME

SYNDROME

Refractory anemia (RA)Refractory anemia (RA)

e rac or anem a w r nge s ero as se rac or anem a w r nge s ero as s(RARS)(RARS)

Refractor c to enia with multilinea eRefractor c to enia with multilinea edysplasiadysplasia (new)(new)

Refractory anemia with excess blasts (FAB:Refractory anemia with excess blasts (FAB:

5q5q-- syndromesyndrome (new)(new)

unclassifiableunclassifiable newnew


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No granules

PSEUDO-PELGER (no granules) as sign of dysmyelopoiesis


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DYSERYTHROPOIESIS


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Rin Sideroblast


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RCMD


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Refractory Cytopenia with Multilineage Dysplasia (RCMD)


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Refractory Cytopenia with Multilineage Dysplasia (RCMD)


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RAEB-2


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BELGIAN ANAEMIA 5q- syndrome


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ACUTE MYELOID LEUKAEMIA ACUTE MYELOID LEUKAEMIA AML with recurrent cytogenetic translocationsAML with recurrent cytogenetic translocations

AML with t(8;21)(q22;q22) AML1/CBFalpha/ETO AML with t(8;21)(q22;q22) AML1/CBFalpha/ETO

t(15;17)(q22;q12) and variants PML/RARalphat(15;17)(q22;q12) and variants PML/RARalpha

AML with abnormal bone marrow eosinophils AML with abnormal bone marrow eosinophilsinv(16)(p13;q22) vagy t(16;16)(p13;q22)inv(16)(p13;q22) vagy t(16;16)(p13;q22)CBFbeta/MYH1CBFbeta/MYH1

AML with 11 23 MLL abnormalities AML with 11 23 MLL abnormalities


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(continued)

(continued) AML with multilineage dysplasiaAML with multilineage dysplasia

With prior MDSWith prior MDS

Without prior MDSWithout prior MDS

AML with myelodysplastic syndrome, therapy relatedAML with myelodysplastic syndrome, therapy related

Alkylating agent related Alkylating agent relatedEpipodophyllotoxin relatedEpipodophyllotoxin related

AML not otherwise categorizedAML not otherwise categorized

AML minimally differentiated AML minimally differentiated

AML without maturation AML without maturation

AML with maturation AML with maturation

Acute myelomonocytic leukemia Acute myelomonocytic leukemia

Acute monocytic leukemia Acute monocytic leukemia

Acute erythroid leukemia Acute erythroid leukemia

Acute megakaryocytic leukemia Acute megakaryocytic leukemia

Acute basophilic leukemia Acute basophilic leukemia

Acute panmyelosis with myelofibrosis Acute panmyelosis with myelofibrosis


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A.M.L-M1


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A.M.L-M2; 25% of M2 may contain t-8:21


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AML-M3 hypergranular can be found in t-15:17


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M3 folding nuclei


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AML-M6


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AML-M7


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AML de Novo or secondary

Investigation of risk factors

Good Risk Standard/ Poor Risk

t(8;21), t(15;17) IntermediateRisk Rela sedInv(6) w/wo other No favourable nor unfavourable >15% blasts after C1

Cytogenetic cytogenetic abnormalities -5, -7, abn(3q), complex

abnormalities 5-15% blasts after C1 genetic abnormalities

Induction-C1 Induction-C1

Induction-C2 Induction-C2

2 Courses

Consolidation Consolidation ADE FLAG-CSF G-CSF

Course-4 BMT Course-4 ATRA ATRA

Course-5 BMT Course-5 Off BMT Consolidation


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Cytogenetic, the most significant factors

Good Risk Standard/ Poor Risk

t(8;21), t(15;17) IntermediateRisk Rela sedInv(6) w/wo other No favourable nor unfavourable >15% blasts after C1

Cytogenetic cytogenetic abnormalities -5, -7, abn(3q), complex

abnormalities 5-15% blasts after C1 genetic abnormalities

CN-AML (Cytogenetically Normal)

50% patients are assigned

In the intermediate group


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