1. NEOPLASTIC DISORDERS OF THE BONE MARROW
Those that are not leukemias

2. NEOPLASTIC BONE MARROW DISORDERS
Neoplastic disorders of the bone marrow are grouped into 3 categories:
Acute leukemias (to be discussed later) which represent clearly malignant neoplasms with a proliferation of blasts
Myelodysplastic disorders which are characterized by peripheral pancytopenia
Myeloproliferative disorders which are characterized by an increase in WBCs, and/or RBCs, and/or platlets
Myelodysplastic and myeloproliferative disorders may be acute or chronic and may terminate in acute leukemias

3. MUTATIONS RESULTING IN NEOPLASTIC DISORDERS OF THE BONE MARROW

4. NEOPLASTIC BONE MARROW DISORDERS
Myeloproliferative disorders are characterized by
Panhypercellularity of the bone marrow
Erythrocytosis, granulocytosis, and thrombocytosis in the peripheral blood
One cell line is usually more prominent than the others.
Hematologic classification is based on the most prominent cell line:

5. NEOPLASTIC BONE MARROW DISORDERS
Prominent cell Disorder
Myeloid series Chronic myelocytic leukemia
(will be discussed later)
Erythroid Polycythemia vera
Megakaryocytic Essential thrombocythemia
Fibroblast Myelofibrosis with myeloid
metaplasia

6. NEOPLASTIC BONE MARROW DISORDERS
Features common to all myeloproliferative disorders are:
Occur gradually
Occur in the middle aged or elderly
Clinically the patients present with anemia or polycythemia, leukocytosis and thrombocytosis with bizarre, abnormally functional platlets
Hepatosplenomegaly
Hypercellular bone marrow that may become fibrotic
May terminate in an acute leukemia

7. NEOPLASTIC BONE MARROW DISORDERS
Polycythemia – polycythemia is a general term used to describe an erythrocytosis with increased RBCs and hemoglobin.
Need to distinguish between relative (due to decreased plasma volume) and absolute
Is classified into 3 groups
Relative – caused by dehydration, hemoconcentration
Primary polycythemia (polycythemia vera)
Secondary polycythemia
Both the primary and secondary forms result in an absolute increase in the number of RBCs

8. HEMACRIT IN POLYCYTHEMIA

9. POLYCYTHEMIA VERA
Polycythemia vera is a primary, unregulated increase in RBCs with no identifiable initiating cause.
All cells are usually increased with RBCs increased the most.
The RBCs mature and function normally with a normal life span.
The increase in RBCs is independent of erythropoietin stimulation

10. POLYCYTHEMIA VERA Clinically: Lab findings
The increased RBCs result in a sluggish circulation and when the hematocrit exceeds 60% this leads to hypertension
After 2-10 years the bone marrow may fail
5-10% terminate in an acute leukemia – this is exacerbated by treatment with myelosuppressive drugs
Splenomegaly is common
Lab findings
Increased RBC count and hematocrit
Normochromic, normocytic cells
Normal to slightly increased reticulocyte count

11. POLYCYTHEMIA VERA Treatment
2/3 show a leukocytosis with a slight shift to the left
Increased platlets that are giant and functionally abnormal
The arterial oxygen saturation is normal
Treatment
Phlebotomy
Myelosuppressive drugs

12. POLYCYTHEMIA VERA

13. SECONDARY POLYCYTHEMIA
There are three groups of causes of secondary polycythemia:
Secondary to tissue hypoxia
Arterial oxygen saturation is low
The increase in RBCs is due to a normal physiologic increase in erythropoietin
Causes include
Living at high altitudes
Chronic pulmonary disease

14. SECONDARY POLYCYTHEMIA
Familial and associated with a high affinity oxygen or a 2,3 DPG deficiency
Arterial oxygen saturation is normal
Partial pressure at which hemoglobin is 50% saturated is decreased
The increase in RBCs is due to a normal physiologic increase in erythropoietin
Secondary to tumors
Partial pressure at which hemoglobin is 50% saturated is normal
The increase in RBCs is due to an inappropriate increase in erythropoietin

15. LAB DIFFERENTIATION OF POLYCYTHEMIA

16. ESSENTIAL THROMBOCYTHEMIA
In essential thrombocythemia the megakaryocytic cell line is most prominently affected
Clinical and lab findings include:
Occurs most often in those that are or years-old.
Most common feature is bleeding and thrombosis
Platlet count is x 109/L and the platlets are giant, bizarre and functionally abnormal. They tend to aggregate leading to clogged capillaries and the production of tear drop RBCs
Anemia may occur due to bleeding, but 1/3 have a slight erythrocytosis
Leukocytosis with a shift to the left occasionally occurs

17. ESSENTIAL THROMBOCYTHEMIA
Prognosis/therapy
Platlet pheresis (remove the platlets)
Anticoagulants to prevent thrombosis
Radiation or chemotherapy

18. ESSENTIAL THROMBOCYTHEMIA

19. MYELOFIBROSIS WITH MYELOID METAPLASIA
Myelofibrosis with myeloid metaplasia (extramedullary hematopoiesis) – there are three features associated with this disease:
Unchecked proliferation of hematopoietic elements
Progressive bone marrow fibrosis
Extramedullary hematopoiesis
Clinical findings:
This is a chronic, gradual disease occurring in individuals over 50 years of age
Most symptoms come from anemia or pressure from the enlarged spleen
Hematopoiesis may occur in the kidneys, adrenal glands, and lymph nodes as well as in the spleen and and liver
Osteosclerosis ( increased bone density) is common

20. MYELOFIBROSIS WITH MYELOID METAPLASIA
Lab findings:
A moderate leukoerythroblastic anemia with striking anisocytosis and poikilocytosis. Many tear drop cells, which are formed as the RBCs try to squeeze into the circulation, are found.
Leukocytosis with a shift to the left
Giant, bizarre platlets
The bone marrow may be difficult to aspirate
A bone marrow biopsy reveals a hypercellular bone marrow with diffuse fibrosis and increased megakaryocytes

21. MYELOFIBROSIS WITH MYELOID METAPLASIA

22. MYELOFIBROSIS WITH MYELOID METAPLASIA

23. MYELOFIBROSIS WITH MYELOID METAPLASIA

24. DIFFERENTIATION OF MYELOPROLIFERATIVE DISORDERS

25. MYELODYSPLASTIC DISORDERS
Myelodysplastic disorders are primary pluripotential stem cell disorders characterized by:
One or more peripheral blood cytopenias resulting from ineffective hematopoiesis
Prominent maturation abnormalities in the bone marrow (dyspoiesis or dysplasia)
Usually occurs in the elderly
Commonly progress to an acute leukemia
Are refractory to treatment

26. MYELODYSPLASTIC DISORDERS
Clinically:
Patients usually present with weakness due to anemia that is refractory to treatment
Patients may have chronic infections due to neutropenia
Patients may have hemorrhaging due to thrombocytopenia
Laboratory findings:
Cytopenias and dysplasia are seen on the peripheral smear
Abnormal maturation of RBCs leads to oval macrocytes
Abnormal maturation of WBCs leads to hyposegmented, hypogranulated neutrophils
Abnormal maturation of platlets leads to giant platlets with abnormal granulation

27. MYELODYSPLASTIC SYNDROME
Note oval macrocytes:

28. MYELODYSPLASTIC SYNDROME
Note hyposegmented, hypogranulated neutrophil:

29. MYELODYSPLASTIC SYNDROME
Note large platlets

30. MYELODYSPLASTIC SYNDROME
Note micromegakaryocyte:

31. MYELODYSPLASTIC SYNDROME
Note large, agranular platlet:

32. MYELODYSPLASTIC SYNDROME
Myelodysplastic syndromes are classically classified into five subgroups:
Refractory anemia (RA)
Refractory anemia with ringed sideroblasts (RARS)
Refractory anemia with excess blasts (RAEB)
Chronic myelomonocytic leukemia (CMML)
Refractory anemia with excess blasts in transformation (RAEBt)
A new classification system has been developed, but will not be discussed here.

33. DIFFERENTIATION OF MDS

34. SURVIVAL AND LEUKEMIC PROGRESSION OF MDS SUBGROUPS

35. OVERLAP OF MDS WITH OTHER HEMATOLOGIC DISORDERS