myeloproliferative disorders

1. Myeloproliferative disorder
Dr.T.Arivazhagan
Department of Pathology

2. Definition
Clonal neoplastic cell disorder of pluripotent
hematopoietic stem cell characterized by excessive
proliferation of one or more of the myeloid cell
lineage.

3. Types
1. CML
2. Polycythemia
3. Essential thrombocythemia
4. Primary Myelofibrosis
5. Systemic Mastocytosis
6. Chronic eosinophilic leukemia
7. Stem cell leukemia

4. Characterized
1. Presence of mutation
2. Constitutively activated tyrosine kinase
3. Growth factor independence
4. It does not impair the differentiation
5. Only the production increases

5. Common features
1. Increased proliferation drive
2. Extra medullary hematopoiesis
3. Marrow fibrosis
4. Peripheral blood cytopenias
5. Transformation into acute leukemia's

6. POLYCYTHEMIA

7. Definition
• It is a type of myeloproliferative disorder in which
the body produce many red blood cells as a result of
problem with the bone marrow or increased
production of erythropoietin hormone.

10. Pathogenesis
JAK2 V617F Mutation
Constitutive activation
Activation of STAT/AKT/MAPK pathway
Transcription activation
Growth factor independent cell survival & proliferation

11. Morphology
• Hypercellular bone marrow
• Increased red cell count
• Increased granulocytic & megakaryocytic precursor cells
• Peripheral smear
• Increased red cell count
• Increased basophils
• Abnormally large platelets

12. Later stage
• Progress to spent phase
• Characterized by extensive marrow fibrosis
• Increased extra medullary hematopoiesis
• Transformation into AML in 1% cases

13. Clinical features
• Appears insidiously
• Adults
• Symptoms are related to increased red cell count
• Plethoric
• Cyanotic
• Headache
• Dizziness
• Hypertension
• GI symptoms
• Intense pruritis
• Peptic ulceration Histamine released from basophils
• Hyperuricemia

15. Complication
1. Bleeding manifestations
2. Thrombotic episodes

16. Investigation
1. Hematocrit = >60%
2. HB = 18 to 28 gm/dl
3. Peripheral smear
4. Bone marrow examination

17. Peripheral smear
1. Increased red cell count
2. Increased white cell & platelets
3. Giant forms of platelets

18. Treatment
1. Phlebotomy
2. Radioactive phosphorous
3. Low dose aspirin
4. Anti histamine
5. H2 blockers
6. Ruxolitinib

19. ESSENTIAL
THROMBOCYTOSIS

20. Introduction
1. Adults
2. 1 to 3 /100000/year

21. DEFINITION
• It is a type of myeloproliferative disorder in which
mutation of JAK2 pathway leads to increased
production of platelets in the bone marrow.

22. Pathogenesis
1. Mutation in JAK2 in 50% cases
2. Mutation in MPL in 5 to 10% 0f cases
3. Mutation in calreticulin
4. Increases the JAK2 / STAT signaling pathway
5. Constitute activation leads to Thrombopoietin
independent proliferation

23. Characterized
1. Increased platelet count
2. Absence of polycythemia
3. Absence of marrow fibrosis

24. Morphology
• Hypercellular bone marrow
• Increased megakaryocyte
• Abnormally large forms
• Mild extra medullary hematopoiesis
• Mild organomegaly

27. Complications
Platelet dysfunction
• Thrombosis
• Hemorrhage

28. Investigations
1. Peripheral smear
2. Bone marrow

29. Treatment
1. Chemotherapeutic agents

31. DEFINITION
• It is a type of myeloproliferative disorder in which
development of obliterative marrow fibrosis that
leads to replacement of normal marrow by fibrous
tissue which gives the reduced bone marrow
hematopoiesis

32. Pathogenesis
• Mutation of JAK2 in 50 to 60 % cases
• Activation of MPL in 1 to 5 % cases
• Excessive deposition of collagen in the bone marrow
• Due to inappropriate release of fibrogenic factors from
neoplastic megakaryocytes

33. Morphology
• Marrow
• Early – Hyper cellular
• Later – Hypocellular
• Erythroid & granulocytic precursors are appear normal
• Megakaryocyte appears large, dysplastic
• Cloud like – clusters of atypical megakaryocyte with unusual nuclear shapes
• Osteosclerosis
• Extra medullary hematopoiesis
• Cytopenias

34. Clinical features
• Less common
• Adults
• Usually 60 years
• Anemia
• Splenomegaly- fullness in the left upper quadrant
• Fatigue
• Weight loss
• Night sweats
• Hyperuricemia

35. Complications
1. Intercurrent infections
2. Thrombotic episodes
3. Bleeding tendency
4. Transform into AML in 5 to 20%

36. Investigations
• Peripheral smear
• Leukoerythyroblastosis – Premature release of nucleated Rbc’s & early
granulocytic progenitors.
• Tear drop shaped red cells
• Bone marrow
• Marrow fibrosis

37. Treatment
1. Chemotherapeutic agents
2. Hematopoietic stem cell transplantation