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 PlasmacytomaThoughts that plamacytoma is simply an early, isolated form of multiple myelomaThere are two important variants of myeloma,solitary bone plasmacytomaextramedullary plasmacytoma
4 PlasmacytomaSolitary bone plasmacytoma is a single lytic bone lesion without marrow plasmacytosisExtramedullary 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 radiationSeen more frequently among farmers, wood workers, leather workers and those exposed to petroleum products
7 EtiologyOverexpression of myc or ras genes has been noted in some casesMutations in p53 and Rb1 have also been described
8 No common molecular pathogenesis has yet emerged EtiologyNo common molecular pathogenesis has yet emerged
9 Incidence Represents more than 40% of primary bone cancers Peak incidence is in 5th to 7th decades2:1 male predominanceBlacks have nearly twice the incidence of whites.Yearly incidence is around 4 per
10 IncidenceKnh multiple myeloma 337 cases in 5 years, average of 67 per yearPlasmacytoma 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 PathogenesisThe cell effect is due to direct multiple myeloma and bone marrow stromal cell interaction , as well as induction of cytokinesCytokines involved includeIL6,insulin like growth factor 1,vascular endothelial growth factorstromal cell derived growth factor
13 PathogenesisGrowth, drug resistance and migration are mediated via Ras/Raf/mitogen- activated protein kinase, PI3-K/Akt and protein kinase c signaling cascades
14 SymptomsThe clinical manifestation of all the plasma cell disorders relate toexpansion of the neoplastic cellssecretion of cell products- immunoglobulins, lymphokinesHost’s response to the tumour
15 Symptoms Bone pain most common complaint- precipitated my movement WeaknessWeight lossAnaemia and thrombocytopeniaPeripheral neuropathyHypercalcaemiaRenal failure
16 Symptoms Pathological fractures Symptoms are usually of short duration because of the aggressive nature of the diseaseThe spine is the most common location followed by the ribs and pelvis.
20 Diagnosing and staging The classic triad of myeloma isMarrow plasmacytosis (>10%)- CD138+, monoclonalLytic bone lesionsSerum and/ or urine M component
21 MGUS Monoclonal gammopathies of uncertain significance 1% go on to develop myelomaM protein in serum<30g/lBone marrow clonal plasma cells<10%No evidence of other B cell proliferative disorder
22 DiagnosisClinical 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 RadiographyMultiple ‘punched out’ sharply demarcated, purely lytic lesions without any surrounding reactive sclerosis
26 Bone scanThe lack of reactive bone formation is shown by the fact that most lesions are negative on bone scan
27 MRIMRI offers a sensitive means to document extent of bone marrow infiltration and cord or root compression in patients with pain syndromes
28 MicroscopyHistologically multiple myeloma appears as sheets of plasma cellsThese aresmall round blue cellsclock face nucleiabundant cytoplasmperinuclear clearing or haloAmyloid production can be abundant and may be pathognomonic for the disease
31 Laboratory Serum immunoelectrophoresis shows monoclonal gammopathy A 24 hr urine specimenquantitate protein excretionconcentrated aliquot is used for electrophoresis and immunologic typing of any M component
32 LaboratoryThe 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 LaboratoryFewer than 1% of patients will have no identifiable M componentThe 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 elavatedSerum 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 cellsPlasmcytoma has monoclonal light chains whereas in COM they are polyclonalMyeloma cells stain positive for natural killer antigen CD56, whereas reactive cells do not
36 DifferentialsIn poorly differentiated cases lymphoma could be a differentialLymphoma cells usually stain positive for CD45 (leukocyte common antigen)and CD20 ( a B cell marker),
37 Myeloma staging system- Durie-Salmon staging system Stage 1Hb>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 2Stage 3- one or more of the following:Hb <8.5g/dlSerum calcium >3 mmol/lAdvanced lytic bone lesionHigh M component production
39 Treatment10% of patients will have an indolent course- slow progressionThese patients only require antitumor therapy when the disease becomes symptomaticanaemia, 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 GyTreatment of impending or actual pathological fractures of the spine, acetabulum, proximal femur or proximal humerus
41 TreatmentPatients with symptomatic and/ or progressive myeloma require therapeutic intervention2 sorts of such therapySystemic therapy to control the progression of myelomaSymptomatic supportive care to prevent serious morbidity from the complications of the disease
42 TreatmentStandard treatment for newly diagnosed cases depends on whether the patient is a candidate for high dose chemotherapy with autologous stem cell transplantTransplant candidates avoid alkylating agents such as melphalanGlucorticoids, vincristine, doxorubicin, thalidomide
43 Treatment Supportive care directed at the anticipated complications Hypercalcaemia-bisphosphonates, glucocorticoids,hydration, natriuresisProphylactic IV gamma globulin in recurrent serious infectionsAnaemia- erythropoietin, along with haematinics
44 TreatmentShort life expectancy in these patients operations aimed to earliest resumption of full activityTumor debulkingInternal fixation augmented with methacrylateCemented total joint arthroplasty or hemiarthroplasty
47 TreatmentIn 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 corelationAggressive course and worse prognosis in HIVMultiple myeloma can accelerate progression of HIV infectionHIV plays a major role in the evolution of malignant plasma cell tumors
49 PrognosisPatients with solitary plasmacytoma without evidence of systemic involvement have a better prognosisMore than half of patients who present with a solitary plasmacytoma eventually go on to develop multiple myeloma.
50 prognosisPatients in stage 1A have a median survival of more than 5 years and those in 3B about 15 monthsThe median overall survival is 5-6 years with subsets of patients surviving over 10 years.
51 PrognosisThe 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 20 6120105022722011317420124824
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