1. MULTIPLE MYELOMA AND PLASMACYTOMA
DR KARANU JK

2. INTRODUCTION Most common primary malignancy of bone
It is a plasma cell disorder-
monoclonal neoplasms related to each other by virtue of their development from common progenitors in the B lymphocyte lineage

3. Plasmacytoma
Thoughts that plamacytoma is simply an early, isolated form of multiple myeloma
There are two important variants of myeloma,
solitary bone plasmacytoma
extramedullary plasmacytoma

4. Plasmacytoma
Solitary bone plasmacytoma is a single lytic bone lesion without marrow plasmacytosis
Extramedullary plasmacytomas usually involve the submuscosal lymphoid tissue of the nasopharynx or paranasal sinuses without marrow plasmacytosis.

5. Etiology The cause of myeloma is not known
Incresed frequency in those exposed to radiation
Seen more frequently among farmers, wood workers, leather workers and those exposed to petroleum products

6. Etiology Chromosomal alterations identified: 13q14 deletions
17p13 deletions
11q abnormalities
Common translocations
t(11;14)(q13;q32) and t(4;14)(p16;q32)

7. Etiology
Overexpression of myc or ras genes has been noted in some cases
Mutations in p53 and Rb1 have also been described

8. No common molecular pathogenesis has yet emerged
Etiology
No common molecular pathogenesis has yet emerged

9. Incidence Represents more than 40% of primary bone cancers
Peak incidence is in 5th to 7th decades
2:1 male predominance
Blacks have nearly twice the incidence of whites.
Yearly incidence is around 4 per

10. Incidence
Knh multiple myeloma 337 cases in 5 years, average of 67 per year
Plasmacytoma 16 cases in 5 years, average of 3 per year

11. Pathogenesis and clinical manifestation
Multiple myeloma cells bind via cell surface adhesion molecules to bone marrow stromal cells and extracellular matrix.
This triggers multiple myeloma cell growth, survival, drug resistance and migration in the bone marrow milieu

12. Pathogenesis
The cell effect is due to direct multiple myeloma and bone marrow stromal cell interaction , as well as induction of cytokines
Cytokines involved include
IL6,
insulin like growth factor 1,
vascular endothelial growth factor
stromal cell derived growth factor

13. Pathogenesis
Growth, drug resistance and migration are mediated via Ras/Raf/mitogen- activated protein kinase, PI3-K/Akt and protein kinase c signaling cascades

14. Symptoms
The clinical manifestation of all the plasma cell disorders relate to
expansion of the neoplastic cells
secretion of cell products- immunoglobulins, lymphokines
Host’s response to the tumour

15. Symptoms Bone pain most common complaint- precipitated my movement
Weakness
Weight loss
Anaemia and thrombocytopenia
Peripheral neuropathy
Hypercalcaemia
Renal failure

16. Symptoms Pathological fractures
Symptoms are usually of short duration because of the aggressive nature of the disease
The spine is the most common location followed by the ribs and pelvis.

17. Symptoms
Hypercalcaemia, osteoporosis, pathological fracture, lytic bone lesions, bone pain
Tumor expansion, osteoclast activating factor, osteoblast inhibitory factors
Renal failure-
Hypercalcaemia, light chain deposition, urate nephropathy, drugs

18. Symptoms Easy fatigue- anaemia
Bone marrow infiltration, haemolysis, decreased erythropoietin levels
Recurrent infections
Hypogammaglobulinaemia, low cd4 count, decreased neutrophil migration

19. Symptoms Neurologic symptoms
Hyper viscosity, croglobulinemia, Hypercalcaemia, nerve compression, POEMS syndrome
Nausea and vomiting
Renal failure, Hypercalcaemia

20. Diagnosing and staging
The classic triad of myeloma is
Marrow plasmacytosis (>10%)- CD138+, monoclonal
Lytic bone lesions
Serum and/ or urine M component

21. MGUS Monoclonal gammopathies of uncertain significance
1% go on to develop myeloma
M protein in serum<30g/l
Bone marrow clonal plasma cells<10%
No evidence of other B cell proliferative disorder

22. Diagnosis
Clinical evaluation of patients with myeloma includes a careful physical examination searching for tender bones and masses.
Chest and bone radiographs may reveal lytic lesions or diffuse osteopenia

23. Radiography
Multiple ‘punched out’ sharply demarcated, purely lytic lesions without any surrounding reactive sclerosis

26. Bone scan
The lack of reactive bone formation is shown by the fact that most lesions are negative on bone scan

27. MRI
MRI offers a sensitive means to document extent of bone marrow infiltration and cord or root compression in patients with pain syndromes

28. Microscopy
Histologically multiple myeloma appears as sheets of plasma cells
These are
small round blue cells
clock face nuclei
abundant cytoplasm
perinuclear clearing or halo
Amyloid production can be abundant and may be pathognomonic for the disease

31. Laboratory Serum immunoelectrophoresis shows monoclonal gammopathy
A 24 hr urine specimen
quantitate protein excretion
concentrated aliquot is used for electrophoresis and immunologic typing of any M component

32. Laboratory
The serum M component will be IgG in 53%, IgA in 25%, and IgD in 1%.
20% of patients will have only light chains in serum and urine.

33. Laboratory
Fewer than 1% of patients will have no identifiable M component
The heat test for detecting Bence Jones proteins is falsely negative in 50% of patients with light chain myeloma

34. Laboratory Complete blood count with differential may reveal anaemia
ESR is elavated
Serum chemistries calcium, urea, nitrogen, creatinine and uric acid levels may be elevated.

35. Differential diagnosis
Solitary plasmacytoma pathological differentials may include chronic osteomyelitis with abundant plasma cells
Plasmcytoma has monoclonal light chains whereas in COM they are polyclonal
Myeloma cells stain positive for natural killer antigen CD56, whereas reactive cells do not

36. Differentials
In poorly differentiated cases lymphoma could be a differential
Lymphoma cells usually stain positive for CD45 (leukocyte common antigen)
and CD20 ( a B cell marker),

37. Myeloma staging system- Durie-Salmon staging system
Stage 1
Hb>10g/dl,
serum calcium <3 mmol/l,
normal bone xray or solitary lesion,
low M component production

38. Myeloma staging system- Durie-Salmon staging system
Stage 2- neither fitting stage 1 or 2
Stage 3- one or more of the following:
Hb <8.5g/dl
Serum calcium >3 mmol/l
Advanced lytic bone lesion
High M component production

39. Treatment
10% of patients will have an indolent course- slow progression
These patients only require antitumor therapy when the disease becomes symptomatic
anaemia, hypercalcaemia, progressive lytic bone lesions, progressive rise in serum myeloma protein levels or recurrent infections.

40. Treatment Primary treatment of multiple myeloma is chemotherapy
Symptomatic bone lesions usually respond rapidly to radiation treatment 40 Gy
Treatment of impending or actual pathological fractures of the spine, acetabulum, proximal femur or proximal humerus

41. Treatment
Patients with symptomatic and/ or progressive myeloma require therapeutic intervention
2 sorts of such therapy
Systemic therapy to control the progression of myeloma
Symptomatic supportive care to prevent serious morbidity from the complications of the disease

42. Treatment
Standard treatment for newly diagnosed cases depends on whether the patient is a candidate for high dose chemotherapy with autologous stem cell transplant
Transplant candidates avoid alkylating agents such as melphalan
Glucorticoids, vincristine, doxorubicin, thalidomide

43. Treatment Supportive care directed at the anticipated complications
Hypercalcaemia-bisphosphonates, glucocorticoids,hydration, natriuresis
Prophylactic IV gamma globulin in recurrent serious infections
Anaemia- erythropoietin, along with haematinics

44. Treatment
Short life expectancy in these patients operations aimed to earliest resumption of full activity
Tumor debulking
Internal fixation augmented with methacrylate
Cemented total joint arthroplasty or hemiarthroplasty

46. Preop embolization

47. Treatment
In most patients local radiation treatment should be instituted approximately 3 weeks after surgery or when the wound appears to be healed.

48. HIV and multiple myeloma
No conclusive evidence on the corelation
Aggressive course and worse prognosis in HIV
Multiple myeloma can accelerate progression of HIV infection
HIV plays a major role in the evolution of malignant plasma cell tumors

49. Prognosis
Patients with solitary plasmacytoma without evidence of systemic involvement have a better prognosis
More than half of patients who present with a solitary plasmacytoma eventually go on to develop multiple myeloma.

50. prognosis
Patients in stage 1A have a median survival of more than 5 years and those in 3B about 15 months
The median overall survival is 5-6 years with subsets of patients surviving over 10 years.

51. Prognosis
The major causes of death are progressive myeloma,renal failure, sepsis or therapy related acute leukaemia or myelodysplasia.
Nearly a quarter die of myocardial infarction, chronic lung disease, diabetes or stroke.

52. Knh -multiple myeloma ALIVE DEAD TOTAL CASES 2008 43 15 58 2009 41 2061
2010 50 22 72
2011 31 74
2012 48 24

53. KNH-PLASMACYTOMA
ALIVE
DEAD
TOTAL CASES
2008 2 1 3
2009
2010
2011 4 5
2012