Myelodysplastic syndromes (WHO 2008)
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Refractory cytopenia with uniliniage dysplasia
Refractory anaemia with ringed sideroblasts
Refractory cytopenia with multiliniage dysplasia
Refractory anaemia with excess blasts
Myelodysplastic syndrome with isolated del(5q)
Myelodysplastic syndrome, unclassifiable
Childhood myelodysplastic syndrome
Myelodysplastic syndromes (WHO 2008)
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CYTOLOGI:
Anæmi, normokrom, makrocytose +/- , umodne -/+
Neutropeni: hypogranulære, bilobære pseudo-Pelger
Leukoblastose +/Trombopeni +/- , makrotrombocytter +/HISTOLOGI:
Marv: ofte hypercellulær
Dysplastiske megakaryocytter, mikro-megakaryocytter, klynger
ALIP, paratrabekulær erythropoiese og megakaryocytter
Fibrose +/-
Morfologi ved MDS
Dysgranulopoiese:
– anisocytose: små eller megaloblastære
– abnorm kerne: bilobær, ”pelger”,
hypersegmenteret
– hypogranuleret cytoplasma
– auerstave
Myelodysplastic/myeloproliferative
neoplasms (WHO 2008)
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Chronic myelomonocytic leukemia (CMML)
Atypical chronic myeloid leukemia, BCR/ABL1 neg.
Juvenile myelomononcytic leukemia
Myelodysplastic/myeloproliferative neoplasm,
unclassifiable
Morfologi ved MDS
Dyserytropoiese:
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megaloblastære
intercellularbroer
flere kerner
multilobære kerner
nuclear budding
ringsideroblaster
cytoplasmatiske vakuoler
Morfologi ved MDS
Dystrombopoiese:
– mikromegakaryocytter
– abnorm kerne uden lobulering
– multinukleære
Myelodysplastic syndromes (WHO 2008)
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Skelne tMDS fra reversible toxiske forandringer, som ka'
persistere flere mdr. efter beh.
CAVE G-CSF beh.
Toxiske forandringer kan sagtens være mere udtalte end MDS.
Alkohol: makrocytær erythropoiese m. ringsideroblaster
MDS med megaloblastære forandr. vs. megaloblastær anæmi:
check metamyelocytter og hypersegmenterede neutrofile
Case 5a
77 årig mand med dissemineret c. prostata beh. med
Zoladex. Knoglemarvsus. pga. faldende Hb: 6,9,
ferritin: 3215, let forhøjet ALAT.
Myelodysplastic syndrome with isolated del(5q)
Therapy related myeloid neoplasms (WHO 2008)
tAML / tMDS / tMDS/MPN
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Kemo for hæmat. eller solide tumorer
To kategorier
5-10 år alkylerende ell. stråling
1-5 år TOP hæmmere
Multiliniedysplasi, RSB+, fibrose +/AML ofte ”M4 / M5”
AML ofte ukarakteristisk immunfænotype
Myelodysplastic syndrome with isolated del(5q)
Myelodysplastic syndrome with isolated del(5q)
Myelodysplastic syndrome with isolated del(5q)
Ringsideroblast
RCMD med ringsideroblaster i snitpræparatet
Acute myeloid leukaemia (WHO 2008)
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Case 12
26-årig kvinde indlægges med anæmi og
trombocytopeni. Igennem den sidste måned
tiltagende træt, svimmel og dyspnøisk. Har tabt 7 kg
har været svedende både nat og dag. Hb: 5,6.
Trombocytter 20. Blå mærker, et på armen og i et på
maveskindet.
Objektivt
BT 122/72. Puls 98. Iltsaturation 98%. Temp. 37,7.
Alment fremstår pt. moderat akut medtaget, bleg og
træt.
AML with recurrent genetic abnormalities
NB! blasttal uden betydning
AML with myelodysplasia-related changes
Therapy related myeloid neoplasms
AML NOS (FAB M0-M7)
Myeloid sarcoma
Myeloid proliferations related to Downs syndrome
Blastic plasmacytoid dendritic cell neoplasm
CD34
CD117
MPO
PAX-5
AML with t(8;21) RUNX1-RUNX1T1
AML NOS (FAB M0-M7) (WHO 2008)
FAB
FAB
FAB
FAB
FAB
FAB
FAB
FAB
M0
M1
M2
M4
M5a
M5b
M6
M7
AML with minimal differentiation
AML without maturation
AML with maturation
Acute myelomonocytic leukaemia
Acute monoblastic leukaemia
Acute monocytic leukaemia
Acute erythroid leukaemia
Acute megakaryoblastic leukaemia
Laboratorieteknikker
Yngre ptt.
Kan debutere med myeloidt sarkom + <20% blaster i KM.
Blaster : store m. basofilt cp m. perinukleær opklaring +
granulae evt. auerstave
Andre fra granulopoiesen ofte m. dysplasi og
modningsasynkroni (CD34+CD15 co-ekspression)
CD34+, MPO+, CD13+
svag CD33+ evt. svag TdT
Evt. eosinofili, men uden atypisk granulering som v. inv. (16)
God prognose
Acute leukaemias of ambigous linieage
(WHO 2008)
Acute
Mixed
undifferentiated leukaemia (AUL)
phenotype acute leukaemia (MPAL)
Myeloid lineage: myeloperoxidase (MPO) or monocytic differentiation
(CD11, CD14,CD64, lysozyme)
T lineage: CD3 (monoclonal)
B lineage: CD19 + CD79 or CD10 or CD22
Laboratorieteknikker – IHC
Antistoffer:
Immunhistokemi
Flowcytometri
Cytogenetik
FISH
PCR
Blastmarkører:
Granulo/monocyt:
Megakaryocyt:
Erythroid:
Mast cell:
Lymfoide;
CD34, CD117, TdT, PAX5
MPO, CD13, CD33, CD11, CD14, CD64,
lysozyme, CD68 PG-M1
CD61
Glycophorin-A
Mast cell tryptase, CD117
CD10, CD19, CD79, CD138, CD3, CD4
81 år kvinde trombopeni, tidl. C.Mam. – adjuv.beh.
4491
Akut leukæmi – IHC WHO 2001
81 år kvinde trombopeni, tidl. C.Mam. – adjuv.beh.
4491
Blaster:
+ MPO, CD13, lysozym, CD117, CD34, TdT, PAX-5, CD79, CD15
-CD3, CD4, CD68, CD10, CD61, Glycophorin
Diff.-diagnoser:
AML with t(8;21) RUNX1-RUNX1T1
Terapi-relateret myeloid neoplasi obs. pro.
AML med myelodysplasi relaterede forandringer obs.pro.
AML M0
AML M0
AML M0
AML M0
CD34
AML M0
AML M0
TdT
CD13
AML with t(15;17): APL promyelocytleukæmi
AML with t(15;17): APL promyelocytleukæmi
Hæmatopoietisk stamcelle
Myeloblast
Promyelocyt
Myelocyt Metamyelocyt Granolocyt
Modnings, differentieringsstop
DIC + hæmoragisk diatese
AML with t(15;17): APL promyelocytleukæmi
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15;17
11;17
t 11;17
t 5;17
t
RARα – gen
RARα:
retinoic acid receptor alpha
retinolsyrereceptor
regulerer myeloid uddifferentiering
defekt i PML
PML; RAR
PLZF; RAR
NUMA; RAR
NPM; RAR
AML NOS (FAB M0-M7) (WHO 2008)
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FAB M0
AML with minimal differentiation. Diff. ALL
<3% blaster MPO+, - lymf. markører,
TdT+, CD34+, CD117+
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FAB M1
AML without maturation
Blaster >90% af NEC, >3% blaster MPO+,
ingen modning
AML NOS (FAB M0-M7) (WHO 2008)
FAB M4
Acute myelomonocytic leukaemia
granuloc. >20%, monoc. >20%, (PB monoc. >5%)
FAB M5
Acute monoblastic / monocytic leukaemia
Monoblaster + promonoc. + monocyt. >80%
FAB M5a monoblaster >80%
FAB M5b monoblaster <80%
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FAB M2
AML with maturation
Blaster <90% af NEC. Granulocytær modning.
Monocyt. <20% NEC
AML NOS (FAB M0-M7) (WHO 2008)
FAB M6
Acute erythroid leukaemia
Erythroide forstadier > 50% af leukocytter
Diff. diagn.: Fulminant megaloblastær anæmi NB!
NB! Hele monocytlinien er blastækvivalenter
AML with myelodysplasia-related changes
3 mulige ”scenarier”
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FAB M7
Acute megakaryoblastic leukaemia
>50% af blasterne har megakaryocytdiff.
Diff. diagn.: transformeret MPN / akut panmyelose
med myelofibrose
behandling:
– rettet imod denne defekt (ATRA – All trans
retinoic acid) og genskaber differentiering, men
eliminerer ikke den maligne klon.
RAR, kromosom 17
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AML efter tidligere MDS eller MDS/MPN
AML med MDS relateret cytogenetik
AML med multiliniedysplasi
Ny pt.
Ny pt.
Ny pt.
Ny pt.
Ny pt.
PMF med transformation til AML
Ny pt.
6 mdr. senere
Vigtige diff. diagnoser
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Akut promyelocytleukmæmi vs. AML NOS
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Peni: AML vs. MDS vs. aplastisk anæmi vs. HCL
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Leukæmoid reaktion vs. AML
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AML vs. fulminant megaloblastær anæmi
Glædelig jul
Ny pt.
Megaloblastær anæmi