1. Chicago Medical School

2. MYELOPROLIFERATIVE SYNDROMES AND PLASMA CELL DISORDERS
Arthur S. Schneider, M.D.
2012
Department of Pathology
Chicago Medical School at
Rosalind Franklin University of Medicine and Science

3. DISORDERS OF WHITE BLOOD CELLS
myeloproliferative syndromes
chronic myelogenous leukemia
polycythemia (rubra) vera (PRV)
agnogenic myeloid metaplasia
essential thrombocythemia

5. JAK2V617F mutations
Most, if not all, patients with polycytheia rubra vera and a significant number of patients with agnogenic myeloid metaplasia and essential thrombocythemia are JAK2V617F positive

6. POLYCYTHEMIA RUBRA VERA
RBC 8-10 million
rubor due to increased absolute red cell mass
pruritus (itching)

7. POLYCYTHEMIA RUBRA VERA
splenomegaly
WBC and platelets moderately increased
hyperviscosity causes thrombotic phenomena and hemorrhage
erythropoietin decreased

8. POLYCYTHEMIA RUBRA VERA
treat with phlebotomy
late phase clinically resembles CML
blastic transformation into acute leukemia most often associated with chemotherapy or P32 therapy

9. SECONDARY POLYCYTHEMIA
chronic hypoxia
pulmonary pathology
congenital heart disease
high altitude
inappropriate production of erythropoietin
renal cell carcinoma and adult polycystic disease
hepatocellular carcinoma
cerebellar hemangioma

10. SECONDARY POLYCYTHEMIA
endocrine abnormalities
pheochromocytoma
hypercorticism (Cushing syndrome)
exogenous androgens

11. Fibrotic marrow in fully
developed agnogenic myeloid
metaplasia

12. Hypercellular marrow with positive reticulin stain in early agnogenic myeloid metaplasia

13. Agnogenic myeloid metaplasia (teardrop cells)

14. AGNOGENIC MYELOID METAPLASIA
extensive extramedullary hematopoiesis in spleen, liver, and lymph nodes
massive splenomegaly
non-neoplastic myelofibrosis
megakaryocytosis and thrombocytosis
may be primary abnormality
PDGF and TGF-ß from platelets and megakaryocytes may be cause of fibroblastic proliferation

15. AGNOGENIC MYELOID METAPLASIA
anemia, teardrop-shaped erythrocytes
scattered late granulocytic precursors
occasional blasts
scattered nucleated red cells
can mimic CML

16. Agnogenic myeloid metaplasia (teardrop cell, nucleated RBC, and a myelocyte in peripheral blood

17. Agnogenic myeloid metaplasia (teardrop cells)

18. Agnogenic myeloid metaplasia (teardrop cell and a basophil)

19. Agnogenic myeloid metaplasia (nucleated RBC)

20. PLASMA CELL DISORDERS
multiple myeloma
Waldenström macroglobulinemia

21. Plasma cells

22. PLASMA CELL DISORDERS
neoplastic clonal proliferations of well- differentiated immunoglobulin-producing cells
multiple myeloma
solitary plasmacytoma
Waldenström macroglobulinemia
benign monoclonal gammopathy (monoclonal gammopathy of undetermined significance)
heavy chain (Franklin) disease
primary amyloidosis

23. Multiple myeloma

24. MULTIPLE MYELOMA malignant multifocal plasma cell tumor
characteristically involves bone
protein abnormalities in serum and urine
lytic lesions in bone, especially in skull and axial skeleton
"punched-out" lesions
osteoclast activating factor secreted by neoplastic plasma cells

25. Multiple myeloma (punched out lesions)

26. Multiple myeloma (punched out lesions)

27. Multiple myeloma (punched out lesions)

28. Multiple myeloma (punched out lesions

29. PROTEIN ABNORMALITIES
proliferation of large quantities of monoclonal identical immunoglobulin molecules
results in serum M spike
M protein most often IgG of either kappa or lambda specificity
IgA myeloma also common
IgM and IgE very rare

30. PROTEIN ABNORMALITIES
Bence Jones protein in urine (isolated free light chains, either kappa or lambda)
heat test: precipitation of B.J. protein at 60 C, with redissolution 97 C

31. “M” protein

32. “M” protein

34. IgA kappa

35. IgG kappa

36. Multiple myeloma

37. CLINICAL FEATURES OF MULTIPLE MYELOMA
bone lesions often associated with severe bone pain and spontaneous fractures
anemia
rouleaux formation of RBC on blood smear
susceptibility to infection due to deficiency of normal immunoglobulins
hypercalcemia secondary to bone destruction

38. CLINICAL FEATURES OF MULTIPLE MYELOMA
amyloidosis of primary amyloidosis type
renal insufficiency due to myeloma kidney (myeloma nephrosis)
interstitial infiltrates of myeloma cells
tubular casts of Bence Jones protein
multinucleated macrophage-derived giant cells
metastatic calcification

39. WALDENSTRÖM MACROGLOBULINEMIA
generalized lymphadenopathy and mild anemia
lymphoplasmacytic lymphoma
infiltration of blood, bone marrow, lymph nodes, and spleen with mature-appearing plasmacytoid lymphocytes

40. WALDENSTRÖM MACROGLOBULINEMIA
plasmacytoid lymphocytes are intermediate stage between B lymphocytes and immunoglobulin- producing plasma cells
Dutcher bodies are round PAS-positive inclusions of immunoglobulin

41. Waldenström macroglobulinemia

42. Waldenström macroglobulinemia

43. Dutcher bodies in Waldenström
macroglobulinemia

45. CLINICAL FEATURES
serum protein IgM spike of either kappa or lambda specificity
Bence Jones protein in 10% of cases
no bone lesions
slowly progressive course
most frequent in males over age 50
bleeding related to platelet dysfunction secondary to abnormal protein

46. CLINICAL FEATURES hyperviscosity syndrome
retinal vascular dilatation, sometimes with hemorrhage, confusion, and other CNS changes
emergency plasmapheresis to prevent blindness

47. CASE FOURTEEN
A 67-year-old woman is referred because of bone pain, spontaneous fractures, and anemia. Significant laboratory abnormalities include a normochromic normocytic anemia with a hemoglobin of 8.5 gm, a "spike" protein on serum protein electrophoresis, Bence Jones proteinuria, and increased serum calcium.

48. CASE FOURTEEN
1. What single further diagnostic procedure is necessary to confirm the diagnosis? Describe the anticipated findings.
2. What procedures are used to further define the nature of the "spike" protein?

49. CASE FOURTEEN
3. What would you expect to find on roentgenographic examination of the bones? Why does the patient have hypercalcemia?
4. What are some of the problems you might anticipate in the management of this patient?

50. Thank you for your attention.