monika Myeloproliferative neoplasm1.pptx

Haematological malignancy for pathology presentation

1. MYELOPROLIFERATIVE NEOPLASMS-1 Presented by -Dr. Monika Lukkad C o Coordinated by-Dr. Neelam Jain

2. Topics to be covered 1. Definition of MPN 2.WHO 2016 classification 3. WHO 2022 classification 4.Chronic myeloid leukemia 5. Juvenile myelomonocytic leukemia 5. .Chronic neutrophillic leukemia 6.Chronic eosinophillic leukemia

3. MYELOPROLIFERATIVE NEOPLASMS (M PN) are a group of stem cell disorders characterised by overproduction of mature white cells, red cells or platelets suggesting that, the maturation of the neoplastic cell line is relatively normal. MPN are clonal neoplastic disorders.

4. Classification of MPN WHO 2022

5. CHRONIC MYELOID LEUKEMIA CML is clonal myeloproliferative neoplasm associated with BCR-ABL1 fusion gene located on Philadelphia chromosome.

6. Molecular biology of Philadephia chromosome

7. FAB classification of CML 3 subtypes:- Chronic granulocytic leukemia Atypical CML Chronic myelomonocytic leukemia(CMML)

8. 1. Chronic granulocytic leukemia (CGL) : This is the classical CML with Ph+ chromosome or Ph-ve chromosome but bcr/abl 1 positive. 2. Atypical CML (aCML): This is the Ph -ve disease with monocytosis intermediate between classical CML and CMML.TLC is between 20 x l0*9/l and 50 * 10*9/l. 3. Chronic myelomonocytic leukemia (CMML) : This is the Ph -ve leukemia with prominence of monocytes in the peripheral blood. Now. this entity has been placed in the MDS/MPN category (WHO, 2016)

9. Phases of CML Chronic phase of massive leucocytosis Blastic phase with blasts>20% in bone marrow. NOTE: - Accelerated phase is omitted from current classification.

10. Chronic phase c Clin Clinical features

11. Peripheral blood findings 1. WBC - Leucocytosis:-30-500x10*9/l.blasts<3%. Myelocyte bulge ,basophillia and mild eosinophillia is also observed 2. RBC :-normocytic normochromic anemia. n RBCs are also observed. 3. Platelets -Thrombocytosis 300-1000x10*9/l 4. NAP score :- Diminished 0-20.

12. Bone marrow findings 1. Myelopoeisis -hypercellular 90-100% cellularity. M:E ratio elevated. Proliferation of neutrophilic precursor ,eosinophilic precursors,basophils and their precursors is observed.

13. Megakaryopoeisis - Hyperplasia with focal clustering. Dwarf megakaryocytes with hypolobation seen. 3. Erythropoiesis :- Decreased. Pseudo-Gaucher cells and sea blue histiocytes also seen

14. Bone marrow histology Classified CML into two morphological classification:- Granulocytic proliferation Granulocytic- megakaryocytic proliferation

15. Differential diagnosis Leukemoid reaction 2. Chronic neutrophillic leukemia 3. Atypical CML 4.Chronic myelomonocytic leukemia 5.Essential thrombocythymia 6.Cellular phase of primary myelofibrosis 7.Fibrotic phase of PMF

16. Transformations of CML Accelerated phase

17. Blastic phase WHO criteria for diagnosis of blastic phase:- 1. Blasts > 20% of peripheral blood white cells or bone marrow cells 2. Extramedullary blast proliferation which may occur in skin, lymph nodes, spleen, bone or central nervous system • 3. Large foci of blasts in the bone marrow biopsy or entire intertrabecular region even if the remainder biopsy shows chronic phase

18. CML blast crisis(Blastic phase)

19. PRINCIPLES OF MANAGEMENT OF CML To control high TLC b) to reduce the symptoms of massive splenomegaly c) to treat metabolic complications, if any. d) to carry out the disease monitoring by hematologic, cytogenetic and BCR-ABL transcript levels e) to target the BCR-ABL positive stem cells and achieve a complete molecular response.

20. JUVENILE MYELOMONOCYTIC LEUKEMIA Juvenile myelomonocytic leukaemia (JMML) is a haematopoietic stem cell-derived myeloproliferative neoplasm of early childhood.

21. The pathogenetic mechanism in at least 90% of cases involves unchecked activation of the RAS pathway. JMML was previously categorised under MDS/MPN but now categorised under MPN.

22. Updates in diagnostic criteria WHO 5th edition 1) exclusion of KMT2A rearrangements; (2) elimination of monosomy 7 as a cytogenetic criterion; and, (3) emphasizing the significance of diagnostic molecular studies, particularly those aimed at demonstrating RAS pathway activation

23. CHRONIC NEUTROPHILLIC LEUKEMIA CNL is a BCR::ABL1-negative MPN. characterized by sustained peripheral blood neutrophilia (white blood cell count (WBC) ≥ 25 × 10*9 / L, with ≥80% segmented neutrophils and bands). Bone marrow hypercellularity due to neutrophilic granulocyte proliferation, Hepatosplenomegaly.

24. Updates to diagnostic criteria according to WHO 5th edition (1)peripheral blood neutrophilia (white blood cell count (WBC) ≥ 25 × 109 / L, with ≥80% segmented neutrophils and bands), (2) bone marrow hypercellularity due to neutrophilic granulocyte proliferation, and hepatosplenomegaly. (3) CSF3R mutations are common in this disease and detected in >60% of cases

25. CHRONIC EOSINOPHILLIC LEUKEMIA Chronic eosinophilic leukaemia (CEL) is a multi-system disorder characterized by a sustained clonal proliferation of morphologically abnormal eosinophils and eosinophil precursors resulting in persistent hypereosinophilia in blood and bone marrow .

26. CEL NOS (not otherwise specified) is no longer needed and is now omitted so its called CEL only. There are some updates in diagnostic criteria.

27. Updates to diagnostic criteria WHO 5th edition (1) the time interval required to define sustained hypereosinophilia is reduced from 6 months to 4 weeks; (2) addition of requirement for both clonality and abnormal bone marrow morphology (e.g., megakaryocytic or erythroid dysplasia); and, (3) elimination of increased blasts (≥2% in peripheral blood or 5-19% in bone marrow) as an alternative to clonality

28. Take home message CML phases consolidated into chronic and blast phases. Emphasis on risk features in chronic phase of CML Diagnostic criteria of CEL are updated, and qualifier NOS is omitted. JMML is categorized under myeloproliferative neoplasms .