Myeloproliferative and dysplastic disorders - Pathkids.com

MPN & MDS 

Dr Alastair Whiteway 

Haematology 

Pathology Sciences

Incidence of malignancies in the 

UK 

Cancer Research UK / NICE IOG manual

Why Classify? 

• “Language of medicine: diseases must be 

described, defined and named before they can 

be diagnosed, treated and studied” 

• Disease should be clinically disIncIve and 

non-‐overlapping 

• Outcome 

• Therapy 

• Advance knowledge

Basis of WHO 2008 ClassificaIon 

Clinical and 

laboratory 

features 

DIAGNOSIS 

Morphology & 

immunophenotype 

Cytogenetics & 

molecular genetic findings

Pre-‐requisites: peripheral blood 

• RBC indices from automated analyzer 

• Good quality May-‐Grunwald-‐Giemsa or Wright-‐ 

Giemsa stain is necessary 

• RBC indices from automated analyzer 

• Manual 200 cell differenIal recommended in 

myeloid neoplasms

Pre-‐requisites: 

bone marrow aspirate 

• Good quality aspirate with adequate parIcles 

• Well spread -‐ too thick or thin smear is inadequate 

• High quality staining is essenIal 

• Do not over diagnose on aspirate 

• Cellularity difficult to assess 

• 500 nucleated cell differenIal count in area close 

to parIcles

LeukaemiaNet WP9.6

MyeloproliferaIve Neoplasms 

• CML, BCR-‐ABL1 posiIve* 

• Polycythemia vera* 

• EssenIal thrombocythaemia* 

• Primary myelofibrosis* 

• Chronic neutrophilic leukaemia 

• Chronic eosinophilic leukaemia NOS 

• Mastocytosis 

• MyeloproliferaIve neoplasm, unclassifiable

BCR-‐ABL signalling in chronic 

myeloid leukaemia

Jak2 in signal transducIon 

• Protein tyrosine kinase 

of the non-‐receptor 

type 

• Associates with the 

intracellular domains of 

cytokine receptors 

• JAK2 is the 

predominant JAK kinase 

acIvated in response to 

several growth factors

Molecular basis of Ph’-‐negaIve 

MPN 

• Polycythemia vera: 

– ~95% JAK2(V617F); ~2-‐3% JAK2 exon 12 

• Essen=al thrombocythemia: 

– 50-‐60% JAK2(V617F); ~5% MPL exon 10 

• Primary myelofibrosis: 

– 50-‐60% JAK2(V617F); 5-‐10% MPL exon 10

DiagnosIc algorithm for CML, PV, ET & PMF 

Tefferi, A. et al. (2009) 

Nat. Rev. Clin. Oncol.

Eosinophilia, monocytosis, 

mastocytosis 

Tefferi, A. et al. (2009) 

Nat. Rev. Clin. Oncol.

MDS vs MPN 

• MDS 

• Cytopenias 

• IneffecIve 

haematopoiesis 

• Dysplasia 

• No splenomegaly 

• Risk of transformaIon 

to AML 

• cMPN 

• Normal or elevated 

blood counts 

• EffecIve 

haematopoiesis 

• No dysplasia 

• Splenomegaly 

• Risk of transformaIon 

to AML

MDS/MPN 

• CMML (CMML with eosinophilia) 

• Atypical CML, BCR-‐ABL1 NEGATIVE 

• JMML 

• MDS/MPN, unclassifiable 

• Refractory anemia with ring sideroblasts and 

thrombocytosis (RARS-‐T) -‐ provisional enIty

Atypical CML 

• ↑WBC with mature and maturing 

granulocytes 

• Low percent of monocytes 

• Includes rare cases of BCR-‐ABL negaIve 

leukaemia comprised of mature and maturing 

granulocytes 

• High leukocyte count MDS or chronic 

myeloproliferaIve syndrome with 

myelodysplasIc features

CHRONIC MYELOMONOCYTIC 

LEUKEMIA 

• Monocytosis >1.0 X 10 9 /L 

• No Ph’ chromosome or BCR/ABL 

• 3 months old & 

other causes excluded 

• Splenomegaly in 30 to 50% of cases

MDS/MPD, UNCLASSIFIABLE 

• Features of MDS but with thrombocytosis 

(>600 X 10 9 /L) or leukocytosis (>13.0 X 10 9 /L) 

• (and) No prior history of MDS or MPD 

• (and) No cytogeneIc abnormality associated 

with a specific myeloid disorder 

• (or) Mixed MDS and MPD features and cannot 

be assigned to any other category

MyelodysplasIc Syndromes 

• Blood cytopenias 

• IneffecIve hematopoiesis 

• Dyserythropoiesis 

• Dysgranulopoiesis 

• Dysmegakaryopoiesis 

• Increased myeloblasts 

• Progressive marrow failure 

• Risk of AML

MDS: pre-‐requisites 

• Well stained PB and BM essenIal 

• Dysplasia in >10% of cells in lineage 

• Blast % important 

• GeneIcs also very important in diagnosis and 

• prognosis 

• Always look for ring sideroblasts under oil 

• Detailed history is mandatory and drug/toxin 

exposure and B12/folate deficiency must be 

excluded. Consider copper...

BM trephine in MDS 

• Assessment of cellularity 

• Assess disrupIon of architecture and focal 

collecIon of blasts 

• Assess haematopoieIc dysplasia – parIcularly 

megakaryocytes 

– EssenIal in fibroIc BM 

• Immunohistochemical stains, i.e., CD34

DifferenIal diagnosis 

• Non-‐neoplasIc causes of myelodysplasia 

– MegaloblasIc changes 

– Toxic agents, i.e., heavy metals, acute alcohol 

– Drug effects -‐ primarily anI-‐neoplasIc 

– Congenital dyserythropoieIc anaemia 

• Chronic infecIous disease 

– HIV 

• NeoplasIc Diseases 

– Chronic myeloproliferaIve disease 

– Acute myeloid leukaemia

Summary of WHO categories 

Type 

PB blasts 

(%) 

BM blasts 

(%) 

RS 

(%) 

Monos 

Dysplasia 

RA 0

MDS: RA

MDS: RARS

MDS: RCMLD

Blasts, promyelocytes, abnormal 

promyelocytes 

Mufti, G. J. et al. Haematologica 

2008;93:1712-1717

InternaIonal PrognosIc Scoring 

System 

Score value 

PrognosIc value 0 0.5 1.0 1.5 2.0 

Bone marrow blasts, % < 5 5 -‐ 10 – 11 -‐ 20 21 -‐ 30 

Karyotype Good Intermediate Poor – – 

Del 5q Sole 1 other MulIple – – 

Cytopenias, n 0 -‐ 1 2 -‐ 3 – – – 

IPSS total score 0 0.5 -‐ 1.0 1.5 -‐ 2.0 ≥ 2.5 

IPSS Risk category Low Intermediate-‐1 Intermediate-‐2 High 

25% progression to AML 

if no therapy, yr 

9.4 3.3 1.1 0.2 

Survival, yr 5.7 3.5 1.1 0.4 

Good:normal,-Y,del(5q),del(20q). Poor:complex (>3 abnormalities) 

or chromosome 7 anomalies. Intermediate:other abnormalities 

Greenberg P, et al. Blood. 1997;89:2079-2088 

Erratum 1998

MDS with isolated del(5q) 

• Refractory macrocyIc 

anaemia 

• Thrombocytosis 

• Hypolobulated 

megakaryocytes 

• Stable clinical course 

• Resposive to 

lenalidomide

Myeloproliferative and dysplastic disorders - Pathkids.com

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