Myeloid neoplasi

erytrocytter

granulocytter

trombocytter

Hæmatopoietisk

stamcelle Blod

Myeloid neoplasi

Myeloproliferativ neoplasi

(hyperproliferation)

Myelodysplastisk syndrom(ineffektiv hæmatopoiese)

Akut myeloid leukæmi(modnings- og differentieringsstop)

Myeloproliferativ neoplasi

erytrocytter

granulocytter

trombocytter

Hæmatopoietisk

stamcelle Blod

Myelodysplasi

erytrocytter

granulocytter

trombocytterHæmatopoietisk

stamcelle

Blod

Akut Myeloid Leukæmi

erytrocytter

granulocytter

trombocytterHæmatopoietisk

stamcelle

Blod

Modnings og differentieringsstop

WHO classification of tumours of haematopoietic and lymphoid tissues

• MPN, myeloproliferativ neoplasi anno 2008

– Kronisk myeloid leukæmi m. BCR-ABL1 (CML)

– Kronisk neutrofil leukæmi (CNL)

– Polycytæmia vera (PV)

– Primær myelofibrose (PMF, tidl. CIMF)

– Essentiel trombocytose (ET)

– Kronisk eosinofil leukæmi, NOS (CEL NOS)

– Mastocytose

– Myeloproliferativ neoplasi, uklassificerbar (MPN,U)

MPN, myeloproliferativ neoplasi

Generelle træk

• Initielt hypercellulær KM• Trombo-, leuko- og erythrocytose varierende• Bevaret opmodning af poieserne• Hepato- og splenomegali varierende• Progression til myelofibrose varierende• Transformation – accelereret fase 10-19% blaster

blastfase >20% blaster

Case 13a

� 53-årig tidligere rask mand indl. grundet svær leukocytose. Igennem ca. 6 mdr. åndenød og tyngdefornemmelse under ve. kurvatur. Vekslende nattesved. Vægttab på få kg. Ingen feber.På mistanke om iskæmisk hjertesygdom henvises e.l. til arbejdstest, og i forbindelse hermed tages i dag forblodprøver, der viser svær leukocytose 370. Differentialtælling viser neutrofile 218, metamyelocytter 28,7, myelocytter 24,6, promyelocytter 20,5, blastceller 16,4. Desuden svær basofili, eosinofili og monocytose. Hb 6,2, trombocytter 200, nyre-, væsketal upåfaldende.

ObjektivtFremtræder upåvirket. Klar, relevant og orienteret. Ikke forpint. Varm og tør. Ej dyspnøisk. Ingen cyanose eller icterus. Lidt blege conjunctivae. RES: ingen palp. glandler på hals, periklavikulært, aksillært eller ingv. Abd.: blødt og indolent. Splenomegali ca. 1 håndsbredde under kurvaturen. Der er diskret ømhed ved palp. Ingen hepatomegali. Hud: intet at bemærke.

IHC MPO IHC CD61

IHC CD117

Sea blue histiocytes

Diagnose Differentialdiagnose Undersøgelser

CML i blastfase

Kronisk myeloid leukæmi

CML

CML Anden myeloproliferativ

sygdom

Translokationsundersøgelse

(BCR-ABL1)

CML (kronisk myeloid leukæmi)

Kronisk myeloid leukæmi (CML),

formentligt kronisk fase.

Flowcytometri. FISH mhp

translokation 9;22.

Kronisk myeloid leukæmi (CML),

kronisk fase

Kronisk myeloid leukæmi 9/22-translokationen

Kronisk myeloid leukæmi m. BCR-ABL1 (CML)

• Kronisk fase: <10% blaster i PB/KMbasofili, evt. eosinofili, fortykket myeloid cuff, mange små megakar., fibrose, sea-blue histiocytes

• Accelereret fase: 10-19% blaster i PB/KMsvær at definere efter RTKI beh. (>20% basofile)

• Blast fase: >20% blaster i PB/KM (70% myeloide 30% lymfoide NB!)

Philadelphia kromosom

�Translokation mellem komosom 9 og 22

�Fusionsgen abl;bcr

Philadelphia kromosom

�Translokation mellem komosom 9 og 22

�Fusionsgen abl;bcr

Druker, B. J. et al. N Engl J Med 2001;344:1031-1037

Hematologic Responses in Six Patients Receiving 500 mg of STI571 per day

Bone marrow changes:Reduced granulocytic cellularityNormalized megakaryocytesRegression of fibrosisIncreased apoptosisReactive lymphocytic infiltrates

Myeloproliferativ neoplasi - MPD

� Essentiel trombocytose

� Polycytæmia vera

� Primær myelofibrose

� Kronisk myeloid leukæmi

Philadelphia negative

PCV 90 %

ET 50 %

PMF 50 %

Diagnostisk i JAK2 wt ET og PMF

Reasons to perform a bone marrow biopsy in MPN

1. Confirmation of diagnosis in the absence or failing data concerning mutation status

2. Identification and quantification of blast population (accelerated

phase)

3. Discrimination between PV and secondary polycythemia as well as

ET

4. Recognition of early myelofibrosis (baseline - stage of disease)

Checkliste til diagnosticering af MPN (WHO)

� KM biopsi fra ubehandlet pt.Cellularitet ift. alder

�

� Erythropoiese Kvantitet, venstreforskydning

� Granulopoiese Kvantitet, venstreforskydning

� Megakaryopoiese Antal, størrelse, lejring: peritrabekulært, klyngerKerne lobulering , atypi, nøgne kerner

� Fibre Mængde (score 0,1,2,3)reticulin/collagen

Incidence of BM

features (%)PV SP

Megakaryocytes

• pleomorphous aspect(differences in size)

97 0

• increased nuclear lobulation 87 11

• loose clusters 63 2

• naked nuclei 15 0

Stroma

• perivascular plasmocytosis 4 91

• iron-laden macrophages 12 87

• cellular debris 0 94

Discrimination between PV and SP

SP

Discrimination between initial PV and ET

Incidence of BM

features (%) PV ET

Increase in

• cellularity 100 20

• erythropoiesis 98 9

• granulopoiesis 78 21

Megakaryocytes

• giant forms 25 98

• pleomorphous aspect(differences in size)

97 5

PV

PCVPolycytæmia vera

PCVPolycytæmia veraPCV - CD61Polycytæmia vera

Impact of BM morphology on the differential diagnosis

of true ET and early stages of PMF

PMF-0ET

Staghorn

Cloudlike

Megakaryocytmorfologi

Tight

Loose

Megakaryocytklynger

Staghorn vs.hypercellulær

Staghorn + cloudlike

Staghorn vs. tight cluster

Staghorn

Cloudlike

Megakaryocytmorfologi

Tight

Loose

Megakaryocytklynger

Staghorn vs.hypercellulær

Staghorn + cloudlike

Staghorn vs. tight cluster

Semiquantitative grading of myelofibrosis

ny pt. CML med trombocytose44 år kvinde trombocytose, Mb Bechterew, MTX beh. 3683

Quiz Quiz CD61

Quiz Find tre fejl!

Quiz Find tre fejl! Quiz CD138

PMFny pt.PMF - CD61

PMF PMF - CD61 paratrabekulært

PMF - AVGMyeloproliferative neoplasm, unclassifiable

Cases that

- have definite clinical, laboratory and morphologic features of MPD, but fail to meet the criteria for any of the specific MPD entities.

- present with features that overlap two or more of the categories.

MPN differential diagnostics –

SP

secondary polycythemia - reactive

neupog

MPN differential diagnostics –

secondary polycythemia iatrogen

MPD differential diagnostics – neupogenMPN differential diagnostics –

secondary polycythemia iatrogen

MPN differential diagnostics – iatrogen – CD61

MPN differential diagnostics – iatrogen - MPO MPN differential diagnostics – reticulin

c.mam.

MPN differential diagnostics – AVG MPN differential diagnostics -

MPN differential diagnostics – carcinoma – CK7 MPN differential diagnostics – carcinoma - ER