Presentation is loading. Please wait.

Presentation is loading. Please wait.

DR KARANU JK.  Most common primary malignancy of bone  It is a plasma cell disorder-  monoclonal neoplasms related to each other by virtue of their.

Similar presentations


Presentation on theme: "DR KARANU JK.  Most common primary malignancy of bone  It is a plasma cell disorder-  monoclonal neoplasms related to each other by virtue of their."— Presentation transcript:

1 DR KARANU JK

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

7  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

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

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

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

16  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  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  Easy fatigue- anaemia  Bone marrow infiltration, haemolysis, decreased erythropoietin levels  Recurrent infections  Hypogammaglobulinaemia, low cd4 count, decreased neutrophil migration

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

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

21 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  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 Multiple ‘punched out’ sharply demarcated, purely lytic lesions without any surrounding reactive sclerosis

24

25

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

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

28  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

29

30

31  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  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  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  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 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 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  Stage 1  Hb>10g/dl,  serum calcium <3 mmol/l,  normal bone xray or solitary lesion,  low M component production

38  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  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  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  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  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  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  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

45

46

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

48  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  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  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  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 ALIVEDEADTOTAL CASES

53 ALIVEDEADTOTAL CASES


Download ppt "DR KARANU JK.  Most common primary malignancy of bone  It is a plasma cell disorder-  monoclonal neoplasms related to each other by virtue of their."

Similar presentations


Ads by Google