Plasma cell disorders

plasma cell disorders, multiple myeloma, waldenstorms macroglobulinemia, lymphoplasmacytic lymphoma,

1. PLASMA CELL DISORDERS Dr Vijay Shankar S

2. Learning objectives Introduction Multiple myeloma Waldenstorms macroglobulinemia Lymphoplasmacytic lymphoma

3. PLASMA CELL

4. B lymphocyte Reactive B lymphocyte Plasmablast Proplasmacyte Plasmacyte/ plasma cell

5. Proliferation of a B – cell clone that synthesizes and secretes a single homogeneous immunoglobulin or its fragments . Accounts for 15 % of deaths from white cell neoplasms Free light chains ( Bence Jones Proteins ) Free heavy chains PLASMA CELL DISORDERS

6. Monoclonal immunoglogulin – M component Freely excreted in the urine in the absence of glomerular damage. Disorders associated with abnormal immunoglobulins – Gammopathy/ Monoclonal gammopathy/ Dysproteinemia/ Paraproteinemia.

7. Clinicopathologic entities associated with monoclonal gammopathies Multiple myeloma( Plasma cell myeloma) Waldenstrom macroglobulinemia Heavy – chain disease. Primary or immunocyte associated Amyloidosis Monoclonal gammopathy of undetermined significance (MGUS)

8. MULTIPLE MYELOMA Plasma cell neoplasm characterized by involvement of skeleton at multiple sites. Multifocal , monoclonal proliferation of plasma cells 1% of all cancer deaths. more frequent in elderly modest male predominance Osseous and extraosseus manifestations

9. Proliferation of a plasma cell clone that synthesizes and secretes a single homogeneous immunoglobulin or its fragments . Free light chains ( Bence Jones Proteins ) Free heavy chains

10. MORPHOLOGY Presents most commonly as multifocal destructive bone tumors. Bones in axial skeleton affected most. Most common in vertebral column.

11. DISTRIBUTION Vertebral column- 66% Ribs - 44% Skull - 41% Pelvis – 28% Femur – 24% Clavicle - 10% Scapula –10%

12. Round lesions filled with a soft reddish material are indicative of foci of myeloma in this section of vertebral bone .

13. The skull demonstrates the characteristic rounded "punched out" lesions of multiple myeloma.

14. The rounded "punched out" lesions of multiple myeloma appear as lucent areas with this skull radiograph.

15. Lytic lesion in Tibia Lesions in the lower end of femur Lesion in the upper end of femur

16. Bone marrow aspirate

17. ↑↑ no of Plasma cells, usually more than 30% of marrow cellularity

18. BONE MARROW At low power, the abnormal plasma cells of multiple myeloma fill the marrow.

19. BONE MARROW At medium power, the plasma cells of multiple myeloma here are very similar to normal plasma cells, but they may also be poorly differentiated.

20. Flame cells

21. Crystalline inclusions Mott cell

22. Russel bodies Dutcher bodies

23. Pathologic rouleaux formation, Multiple myeloma

24. William Russell Scottish pathologist and physician (1852 – 1940)

25. CLINICAL FEATURES Manifestations are due to Infiltration of organs by neoplastic plasma cells Production of excessive immunoglobulins with abnormal physiochemical properties. Suppression of normal Humoral immunity

26. CLINICAL FEATURES Bone pain, pathological fractures, hypercalcemia Recurrent Bacterial infections Renal failure Anemia Hyperviscosity syndrome Extensive skeletal destruction by neoplastic plasma cells Depressed normal immunoglobulin production due to displacement by neoplastic clone. Tubular damage due to light chain proteinuria. Marrow replacement & renal damage with resultant loss of erythropoietin. Excessive production and aggregation of M proteins

27. LABORATORY STUDIES Increased levels of immunoglobulins in the blood and /or light chains ( Bence Jones proteins) in urine in 99% of cases

28. Most common serum monoclonal immunoglobulin ( M protein) – IgG (55%) IgA (25%) IgM, IgD, or IgE - Rare Both Bence Jones Proteins & serum M protein : 60 – 70% Only Bence Jones proteins : 20% Nonsecretory : 1%

29. DIAGNOSIS & PROGNOSIS Radiographic & laboratory findings Definitive diagnosis – Bone marrow study PROGNOSIS - Variable , but generally poor

30. "The gem cannot be polished without friction, nor man perfected without trials or problems or exams …!." --Chinese proverb

31. 1944 Two patients with oronasal bleeding, lymphadenopathy, anemia and thrombocytopenia, an elevated ESR, a high serum viscosity level, normal bone radiographs and a bone marrow demonstrating predominately lymphoid cells.

32. Waldenstrom’s Macroglobulinemia Dr. Jan Gosta Waldenstrom( Swedish internist) (1906-1996), in 1944

33. 2003 2nd International Workshop on WM, which was held in Athens, Greece clinicopathological entity that was represented by the underlying pathological diagnosis of lymphoplasmacytic lymphoma , as defined by the WHO and REAL classification systems which secretes IgM

34. LYMPHOPLASMACYTIC LYMPHOMA (SLL/CLL with plasmacytic differentiation., Immunocytoma) B - cell neoplasm of older adults. 6 th or 7 th decades of life Resemble CLL/SLL .. But.. Good no of tumor cells undergo terminal differentiation into plasma cells. Secrete monoclonal IgM Hyperviscosity syndrome(W M) Heavy & light chain synthesis is usually balanced

35. MORPHOLOGY Bone marrow :heavy infiltrates of lymphocytes, plasma cells and plasmacytoid lymphocytes. Russel bodies and Dutcher bodies may be present. Often involves lymph nodes, liver & spleen. Infiltration of nerve roots, meninges & brain may be seen.

36. IMMUNOPHENOTYPE & MOLECULAR GENETICS B – cell marker – CD20 Plasma cell - expresses monoclonal immunoglobulin. MC cytogenetic abnormality – del 6q

37. CLINICAL FEATURES Non- specific : weakness, fatigue, weight loss. Hyperviscosity syndrome: Visual impairment Neurologic problems : headache , dizziness, deafness etc Bleeding tendencies Anemia

38. Rests on Laboratory data & bone marrow study. ↑↑ Serum proteins ↑↑ Serum monoclonal M component( due to IgM) ↑↑ ESR Normocytic hypochromic anemia Characteristic marrow infiltration DIAGNOSIS

39. PROGNOSIS Incurable progressive disease. Plasmapherisis might help Median survival - 4 yrs.

40. “Ninety-nine percent of failures come from people who have a habit of making excuses.” –George Washington Carver