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PARAPROTEINEMIAS                     ha               h eik           S
Professor             Anwar Sheikha MD, FRCP, FRCPath., FCAP, FRCPA, FRCPI, FACPSenior Consultant Clinical & Lab. Hematolo...
PARAPROTEINEMIAS                           kha                   S   hei
khaS   hei
MULTIPLE MYELOMA    WALDENSTROM’S   MACROGLOBULINEMIA               PARA                               PROTEINEMIAS     PR...
ANEMIA                  BONE PAIN                                #                      VERTEBRAL COLLAPSE  BLEEDING      ...
1% of All Cancers          2% of All Cancer Deaths                    MULTIPLE                     MYELOMA Average Age ~ 6...
MULTIPLEMYELOMA           BONE MARROW           INFILTRATION OSTEOLYTIC               PARAPROTEINBONE LESIONS             ...
↓ PLATELET↓ WBC      PANCYTOPENIA   ANEMIA           BONE MARROW           INFILTRATIONMULTIPLEMYELOMA                    ...
ha                                          h eik                                      S INFECTION                        ...
   Chemotherapy myelosuppression INFECTION                 Steroid immunosuppression                                    ...
MULTIPLEMYELOMA                                    ANEMIA             BONE              PAIN BONE                 OSTEOLYT...
MULTIPLEMYELOMA                                 ANEMIA                                  HEMO-                             ...
MULTIPLEMYELOMA            INTERFERENCE            WITH CLOTTING                            BLEEDING               FACTORS...
MULTIPLEMYELOMA            LIGHT            CHAINS           PARAPROTEIN            PRODUCTION                          RE...
?RENALINFECTION            PYELONEPHRITIS             FAILURE            LIGHT            CHAINS            ↑ Ca++        ...
PARAPROTEIN       ?BLEEDINGINTERFERENCEWITH CLOTTING   FACTORS    BONE MARROW   INFILTRATION        BLEEDING              ...
MULTIPLEMYELOMA                                     ?ANEMIA                      BLEEDING           BONE MARROW           ...
a                 BONE MARROW                          heikh                                                  S           ...
The cytoplasm of Myeloma Cells contains abundantEndoplasmic Reticulum (ER) , which may contain retained,condensed or cryst...
ha                IgG                 S   h eik               >50%             MULTIPLE             LightIgA             M...
Immunofixationperformed on serum    IgG kfrom a patient with    monoclonalimmunoglobulin Gk      (IgGk)        &a patient ...
OAF                    (IL-1/ TNF)                                    OSTEOCLASTS  PLASMA CELLSIL- 6                  PDGF...
Interleukin-6-mediated myeloma cell growth        BMSC: bone marrow stromal cell           IL: interleukin        NF: nucl...
IL-1 β                  Osteoclast     OSTEO-                  ActivationOAF   TGF- β                      LYTIC          ...
STAGING OF MYELOMA                                       ikh                                                              ...
Durie-Salmon Myeloma Staging System            Stage I                    Stage II     All of the following:              ...
Durie-Salmon Myeloma Staging System            Stage I                   Stage II     All of the following:               ...
Criteria for Diagnosis of Multiple MyelomaMajor criteria1. Plasmacytomas on tissue biopsy2. Bone marrow plasmacytosis (>30...
Normal Ig Values         g/L                    mg/dLIgM   0.5 – 1.5              50 - 150IgA   1.5 – 5.0              150...
PresentingFeatures      Feature                                    Incidence, %of Multiple              Age >40 yr        ...
Frequency of Different Types of Monoclonal Proteins                    Produced By Plasma Cell TumorsMonoclonal Protein   ...
A. M-GUSMonoclonal Gammopathy of Unclear Significance1. Monoclonal component level:   IgG <35 g/L       IgA <20 g/L   Benc...
IMMUNOPHENOTYPING OF MYELOMA CELLS       Myeloma cells typically express monotypic Cytoplasmic Ig & lack SmIg             ...
Prognostic Parameters in Multiple Myeloma                                        Chromosome        Β2-   Microglobulin    ...
MANAGEMENT    OF  MULTPLE  MYELOMA                       ha                 h eik             S
VAD                       M2MP                                         PROTOCOL                 Quicker Response          ...
VAD                        M2    MP                                          PROTOCOL                     Vincristine     ...
Thalidomide                 Begin at                 200 mg                 p.o. daily                                    ...
ThalidomideBegin at 200 mg p.o. dailyIncrease by 200 mg every2 weeks for a goal of800 mg p.o. daily                       ...
Thalidomide
DexamethasoneDescribed as the single most effective agent in MyelomaEffective efficacy comparable to VAD in Primary Refrac...
2006 ASH UPDATE     MP                VAD                           DEXA   THALID-                                   OMIDE...
French randomized trial ofconventional versus high-dose therapy
BONE               MARROW                 or   PERIPHERAL    STEM CELLTRANSPLANTATION  HIGH DOSE CHEMOTHERAPY            A...
Stem Cell Transplantation                     as Up-Front versus Rescue TreatmentMeasure                                  ...
ADJUVANT TREATMENTS IN MULTIPLE MYELOMA         BIS­    PHOSPHONATES                                                      ...
Novel treatment approaches to Myeloma              from the bench to the bedsideDC: dendritic cell IL: interleukin IMIDS: ...
Angio-                  genesis                   Thalidomide:potential mechanisms of antimyeloma activity.          • Dir...
AMYLOIDOSIS                        ha                  h eik              S
PRIMARYAMYLOIDOSIS                        ha                  h eik              S
Primary Amyloidosis    PC neoplasm that secretes an abnormal Ig,  Which deposits in various tissues & forms aβ-pleated she...
Primary Amyloidosis  Deposition in organs                   BLEEDING                                     Increased vessel...
SOP                ha          h eik      S
SOP   Solitary   OsseousPlasmacytoma                         ha                   h eik               S
SOP                                   a                                                                      heikh        ...
EXTRA-OSSEOUS PLASMACYTOMA                          ha                    h eik                S
EOP    Extra   OsseousPlasmacytoma                         ha                   h eik               S
Role                                                                  of                                                  ...
EOP                                              ha                                                                       ...
WALDENSTOROM’SMACROGLOBULINEMIA                              ha                        h eik                    S
MONOCLONAL GAMMOPATHYOF UNDETERMINATE SIGNIFICANCE     M-GUSBENIGN MONOCLONAL GAMMOPATHY                                  ...
ha    h eikS
HCD HEAVY CHAINDISEASES                     ha               h eik           S
αμ         γ    HCD                        ha                  h eik              S
HCD  γ            α             μGamma        Alpha          mu HCD         HCD            HCD   A variant                ...
α            Heavy Chain Disease                IPSIDImmunoproliferative Small Intestinal Disaese             Mediterranea...
OSTEOSCLEROTICPOLYNEUROPATHY           MYELOMA         ORGANOMEGALY  (Sensorimotor                              (Hepato-  ...
Cellular origin of myeloma:genetic and cellular events in disease pathogenesis
Interleukin-6-mediated myeloma cell growth. BMSC, bone marrow stromal cell; IL, interleukin;NF, nuclear factor; TGF, trans...
Apoptosis signaling cascades in myeloma cells.IL, interleukin; JNK, c-jun N-terminal kinase;PYK, proline-rich tyrosine kin...
Interleukin-6 growth and antiapoptotic cascades in myeloma cells. MAP, mitogen-activated protein; RAFTK,related adhesion f...
Role                                                                  of                                                  ...
None   6
medicine.myeloma.(dr.anwar shexa)
medicine.myeloma.(dr.anwar shexa)
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  • I never had a problem in MM Dx but sometimes it can become an issue
  • Transcript of "medicine.myeloma.(dr.anwar shexa)"

    1. 1. PARAPROTEINEMIAS ha h eik S
    2. 2. Professor Anwar Sheikha MD, FRCP, FRCPath., FCAP, FRCPA, FRCPI, FACPSenior Consultant Clinical & Lab. Hematologist Clinical Professor of HematologyUniversity of Mississippi Medical Center, Jackson, Mississippi Professor of Hematology, University of Salahaddin, Erbil, Kurdistan, IRAQ
    3. 3. PARAPROTEINEMIAS kha S hei
    4. 4. khaS hei
    5. 5. MULTIPLE MYELOMA WALDENSTROM’S MACROGLOBULINEMIA PARA PROTEINEMIAS PRIMARY AMYLOIDOSIS HEAVY CHAIN DISEASES M-GUS a h h eik S
    6. 6. ANEMIA BONE PAIN # VERTEBRAL COLLAPSE BLEEDING LYTIC BONE LESIONS INFECTION ORTHOPEDIC SURGEONNEURO- NEPHRO-LOGIST HEMATOLOGIST LOGISTS RENAL HYPERVISCOSITY FAILURE kha S hei
    7. 7. 1% of All Cancers 2% of All Cancer Deaths MULTIPLE MYELOMA Average Age ~ 65 Black: White = 2:1
    8. 8. MULTIPLEMYELOMA BONE MARROW INFILTRATION OSTEOLYTIC PARAPROTEINBONE LESIONS PRODUCTION ha h eik S
    9. 9. ↓ PLATELET↓ WBC PANCYTOPENIA ANEMIA BONE MARROW INFILTRATIONMULTIPLEMYELOMA ha h eik S
    10. 10. ha h eik S INFECTION BLEEDING ↓ PLATELET ↓ WBC PANCYTOPENIA ANEMIA IMMUNE BONE MARROW MULTIPLSUPPRESSION INFILTRATION E MYELOM A
    11. 11.  Chemotherapy myelosuppression INFECTION  Steroid immunosuppression MULTIPLE MYELOMA ↓ WBC PANCYTOPENIA IMMUNE BONE MARROWSUPPRESSION INFILTRATION ha h eik S
    12. 12. MULTIPLEMYELOMA ANEMIA BONE PAIN BONE OSTEOLYTIC # BONE LESIONS VERTEBRAL COLLAPSE ↑ Ca++ RENAL a FAILURE heikhS
    13. 13. MULTIPLEMYELOMA ANEMIA HEMO- DILUTION PARAPROTEIN PRODUCTION HYPER VISCOSITY CNS SYMPTOMS ha h eik S
    14. 14. MULTIPLEMYELOMA INTERFERENCE WITH CLOTTING BLEEDING FACTORS ANEMIA PARAPROTEIN COATING OF PRODUCTION PLATELETS ha h eik S
    15. 15. MULTIPLEMYELOMA LIGHT CHAINS PARAPROTEIN PRODUCTION RENAL FAILURE AMYLOID a h h eik S
    16. 16. ?RENALINFECTION PYELONEPHRITIS FAILURE LIGHT CHAINS ↑ Ca++ RENAL FAILURE MULTIPLE AMYLOID a h MYELOMA h eik S
    17. 17. PARAPROTEIN ?BLEEDINGINTERFERENCEWITH CLOTTING FACTORS BONE MARROW INFILTRATION BLEEDING MULTIPLE MYELOMA PARAPROTEIN COATING OF ha PLATELETS h eik S
    18. 18. MULTIPLEMYELOMA ?ANEMIA BLEEDING BONE MARROW INFILTRATION HEMO- DILUTION RENAL kha FAILURES hei
    19. 19. a BONE MARROW heikh S INFILTRATION OSTEOLYTIC PARAPROTEIN BONE LESIONS PRODUCTION INFECTION RENAL BLEEDING FAILURE MULTIPLE BONE PAIN, MYELOMA HYPER- # & VERT.↑ Ca++ ANEMIA VISCOSITY COLLAPSE
    20. 20. The cytoplasm of Myeloma Cells contains abundantEndoplasmic Reticulum (ER) , which may contain retained,condensed or crystallised cytoplasmic Ig producinga variety of morphologically distinctive findings, including:Multiple pale bluish-white, grape-like accumulation  Mott or Morula CellsCherry-red refractive round bodies  Russell BodiesVermilion staining glycogen-rich IgA  Flame CellsOverstuffed fibrils  Gaucher-like cells; thesaurocytes&Crystalline RodsTHESE CHANGES ARE NOT PATHOGNOMONIC FOR MMSINCE THEY MAY BE FOUND IN REACTIVE PLASMA CELLS
    21. 21. ha IgG S h eik >50% MULTIPLE LightIgA MYELOMA Chain25% 20% Bi-clonal IgD rare Non- Secretory ? IgM
    22. 22. Immunofixationperformed on serum IgG kfrom a patient with monoclonalimmunoglobulin Gk (IgGk) &a patient without amonoclonal protein normal
    23. 23. OAF (IL-1/ TNF) OSTEOCLASTS PLASMA CELLSIL- 6 PDGF/ IL-6 BMSC ha h eik S “Bone Marrow Stromal Cells”
    24. 24. Interleukin-6-mediated myeloma cell growth BMSC: bone marrow stromal cell IL: interleukin NF: nuclear factor TGF: transforming growth factor MM rely  on contact with BM Stromal Cells “BMSC”Adhesive interaction between MM cells & BMSC induce cells to secrete IL­6which then acts a paracrine growth factor promoting survival of MM cells & inhibiting apoptosis 
    25. 25. IL-1 β Osteoclast  OSTEO- ActivationOAF TGF- β LYTIC BONE Osteoblast  LESIONS Other Suppression Cytokines
    26. 26. STAGING OF MYELOMA ikh a S he 1 trillion PC (1012) = 1 Kg I II III < 1 > 1 to 2 Kg 2 Kg PC Kg PC PC HIGH LOW CELL CELL MASS MASS<0.6 x 1012/m2 >1.2 X 1012/m2
    27. 27. Durie-Salmon Myeloma Staging System Stage I Stage II All of the following: Stage III Overall one or more of the following:Hemoglobin value >10 g/dL data minimally Hemoglobin value <8.5 g/LSerum calcium value normal(<12 mg/dL) abnormal Serum Ca value >12 mg/dL as shown Advanced lytic bone lesionsOn roentgenogram, for (scale 3) normal bone structure(scale) or solitary bone stage I High monoclonal component plasmacytoma only and no production rates SingleLow monoclonal component IgG value >70 g/L value production rates abnormal IgA value >50 g/LIgG value <50 g/L as defined Urine light chain monoclonalIgA value <30 g/L For component on electrophoresisUrine light chain monoclonal stage III >12 g/24 hcomponent onelectrophoresis <4 g/24 h Sh Subclassification: eik h a: Relatively normal renal function (serum creatinine value <2.0 mg/dL) a b: Abnormal renal function (serum creatinine >2.0 mg/dL)
    28. 28. Durie-Salmon Myeloma Staging System Stage I Stage II All of the following: Stage III Overall one or more of the following:Hemoglobin value >10 g/dL data minimally Hemoglobin value <8.5 g/LSerum calcium value normal(<12 mg/dL) abnormal Serum Ca value >12 mg/dL 1 <On roentgenogram, as shown > Advanced lytic bone lesions normal bone structure to for (scale 3) 1(scale) or solitary bone stage I 2 plasmacytoma only 2 and no High monoclonal component Kg Single Kg production ratesLow monoclonal component Kg IgG value >7 g/dL PC production rates value PCIgG value <5 g/dL PC abnormal as defined IgA value >5 g/dL Urine light chain monoclonalIgA value <3 g/dL For component on electrophoresisUrine light chain monoclonal stage III >12 g/24 hcomponent onelectrophoresis <4 g/24 h Sh Subclassification: ei a: Relatively normal renal function (serum creatinine value <2.0 mg/dL) kh a b: Abnormal renal function (serum creatinine >2.0 mg/dL)
    29. 29. Criteria for Diagnosis of Multiple MyelomaMajor criteria1. Plasmacytomas on tissue biopsy2. Bone marrow plasmacytosis (>30% plasma cells)3. Monoclonal immunoglobulin spike on serum electrophoresis: IgG >35 g/L or IgA >20g/L; κ or λ light-chain excretion >1.0 g/d on 24-h urine protein electrophoresisMinor criteriaa. Bone marrow plasmacytosis (10-30% plasma cells)b. Monoclonal immunoglobulin spike present but of lesser magnitude than in 3c. Lytic bone lesionsd. Normal IgM <0.50 g/L, IgA <1.00 g/L, or IgG <6.00 g/LAny of the following sets of criteria will confirm the diagnosis:Any two major criteriaMajor criterion 1 plus minor criterion b, c, or dMajor criterion 3 plus minor criterion a or cMinor criteria a, b, and c or a, b, and d ha h eik S
    30. 30. Normal Ig Values g/L mg/dLIgM 0.5 – 1.5 50 - 150IgA 1.5 – 5.0 150 - 500IgG 5.0 – 15.0 500-1500
    31. 31. PresentingFeatures Feature Incidence, %of Multiple Age >40 yr 98Myeloma Male 61 Bone pain 68 Anemia 62 Renal insufficiency 55 Hypercalcemia 30 Hepatomegaly 21 Splenomegaly 5 Proteinuria 88 Bence Jones proteinuria 49 Skeletal roentgenographic abnormalities 79 IEP: Spike on SEP 76 Immuno- Hypogammaglobulinemia on SEP 9 electro- phoresis; Minor or no abnormalities on SEP 15 Spike on urinary protein electrophoresis 75 SEP: Monoclonal heavy chain on serum IEP 83 Serum Monoclonal light chain on IEP 8 protein Nonsecretory 0.3 electro- Amyloidosis 7 phoresis
    32. 32. Frequency of Different Types of Monoclonal Proteins Produced By Plasma Cell TumorsMonoclonal Protein Frequency, %IgG 52IgA 21IgD 2IgE <0.01IgM (Waldenströms) 12Light chain only 11Heavy chain only <12 or more 0.5None detected 1
    33. 33. A. M-GUSMonoclonal Gammopathy of Unclear Significance1. Monoclonal component level: IgG <35 g/L IgA <20 g/L Bence Jones protein <1.0 g/24 h Classification2. Bone marrow plasma cells <10% of3. No bone lesions Monoclonal4. No symptoms GammopathiesB. Indolent myeloma (as in A except:)1. No bone lesions or only limited bone lesions (<3 lytic lesions); no compression fractures2. Monoclonal component levels a. IgG <70 g/L b. IgA <50 g/L C. Smoldering3. No symptoms or associated disease features myelomaa. Performance status >70% (as in B except:)b. Hemoglobin >10 g/dL 1. No bone lesionsc. Serum calcium normal 2. Bone marrowd. Serum creatinine <2.0 mg/dL plasma cells <30%e. No infections
    34. 34. IMMUNOPHENOTYPING OF MYELOMA CELLS Myeloma cells typically express monotypic Cytoplasmic Ig & lack SmIg CD19+ CD56/58 - CD Most NORMAL PCMyeloma  38 Cells CD45 - Lack  Pan­B CD79a CD56/58 + CD19  CD19 - &  MYELOMA CELL CD20Markers CD 138 h eik ha S
    35. 35. Prognostic Parameters in Multiple Myeloma Chromosome Β2- Microglobulin LDH 13 abnormalities Β2- Microglobulin Albumin MEDIAN SUVIVAL ug/mL g/L Months<6 Plus  > 30 55>6 Plus  > 30 19>6 Plus  < 30 4 ha h eik S
    36. 36. MANAGEMENT OF MULTPLE MYELOMA ha h eik S
    37. 37. VAD M2MP PROTOCOL Quicker Response Better control of symptoms Less Myelotoxic & Aggressive more convenient beforeSTANDARD Alkylating autologous Transplant REGIMEN Combination Good after MP relapse NO OTHER Better reserved REGIMEN for relapse after 4 day infusion isPRODUCED  autotransplant cumbersome & needBETTER OS failure & other central Line Special casesOS  > 3YRS Sh eik ha
    38. 38. VAD M2 MP PROTOCOL Vincristine 0.4 mg/m2/dayMelphalan i.v. infusion over 4 days1 mg/kg Vincristine÷ 5 days Adriamycin 9 mg/m2/day CarmustineEach 5 weeks i.v. infusion over 4 daysTailor dose ~  CyclophosphamideANC nadir Dexamethasone 20 mg/m2 MelphalanPrednisolone p.o. on days60 mg/day 1-4, 9-12, & 17-20 PrednisoloneFor 5 days REPEAT COURSE ShEach 5 weeks eik EACH 28 DAYS ha
    39. 39. Thalidomide Begin at 200 mg p.o. daily Thalidomide Increase by is  200 mg every NOT 2 weeks Myelotoxic for a goal of 800 mg p.o. daily Sh eikConstipation Neuropathy Somnolence ha
    40. 40. ThalidomideBegin at 200 mg p.o. dailyIncrease by 200 mg every2 weeks for a goal of800 mg p.o. daily Angio­ genesisThalidomidepotential mechanisms of antimyeloma activity:(a) Direct effects (b) antiadhesive action(a)(c) GF inhibition (d) antiangiogenesis (a)(e) immunomodulationbFGF: basic fibroblast growth factor TNF: tumor necrosis factorICAM: intracellular adhesion molecule IFN: interferonIL: interleukin VEGF: vascular endothelial growth factor
    41. 41. Thalidomide
    42. 42. DexamethasoneDescribed as the single most effective agent in MyelomaEffective efficacy comparable to VAD in Primary Refractory MyelomaNot Myelosuppressive and suits patients with severe marrow compromiseIn Frail & Elderly patients start with a lower dose Dexamethasone 20 mg/m2 p.o. on days 1-4, 9-12, & 17-20 a heikh REPEAT COURSES EACH 28 to 42 DAYS
    43. 43. 2006 ASH UPDATE MP VAD DEXA THALID- OMIDE MDT * MPTThalidomideLenalidomide “Revlimid” Thal RMPBortezomib “Velcade”Pegylated Ribosomal Doxorubicin DD VMP Revlimid Pegylated “Lena- Ribosomal Velcade lidomide” Doxorubicin + “Bortezomib” Dexa
    44. 44. French randomized trial ofconventional versus high-dose therapy
    45. 45. BONE MARROW or PERIPHERAL STEM CELLTRANSPLANTATION HIGH DOSE CHEMOTHERAPY ALLOGENEIC “VAD” TRANSPLANTAutologous Ideal for Young Patients withTransplant Histocompatible Donor Sibling ha eik Sh
    46. 46. Stem Cell Transplantation as Up-Front versus Rescue TreatmentMeasure PBSCT Early PBSCT LateEstimated median overall survival 64.6 mo 64.0 moMedian event-free survival 39.0 mo 13.0 moQuality-adjusted time without symptoms or toxicity 27.8 mo 22.3 mo PBSCT, peripheral blood stem cell transplantation
    47. 47. ADJUVANT TREATMENTS IN MULTIPLE MYELOMA BIS­ PHOSPHONATES INTERFERON PAMIDRONATE ZOLEDRONATE HEMO­ EPO DIALYSIS RADIATIONInhibit Bone ResorptionReduces Bone #Suppresses Hypercalcemia PneumovaxConvenient 1 injection/month ha h eik S
    48. 48. Novel treatment approaches to Myeloma from the bench to the bedsideDC: dendritic cell IL: interleukin IMIDS: immunomodulatory drugs MM: multiple myeloma VEGF: vascular endothelial growth factor
    49. 49. Angio- genesis Thalidomide:potential mechanisms of antimyeloma activity. • Direct effects; (b) antiadhesive action; • (c) growth factor inhibition; (d) antiangiogenesis; • (e) immunomodulation. bFGF, basic fibroblast growth factor; • ICAM, intracellular adhesion molecule; IFN, • interferon; IL, interleukin; TNF, tumor necrosis factor; • VEGF, vascular endothelial growth factor
    50. 50. AMYLOIDOSIS ha h eik S
    51. 51. PRIMARYAMYLOIDOSIS ha h eik S
    52. 52. Primary Amyloidosis PC neoplasm that secretes an abnormal Ig, Which deposits in various tissues & forms aβ-pleated sheet structure that binds Congo Red dye with characteristic birefringence 80% of 15% of Diagnostic Rare Patients have Myeloma Biopsy Sites Monoclonal Ig have or Adult develop Abd. s.c. fat-pad Disease 20% have 10 Bone Marrow Myeloma Amyloidosis Rectum GUT NERVES HMG SensorimotorCHF N.S. Mal- neuropathy Absorp- Loss of Sphincter CRF tion control Macroglossia Sheikha
    53. 53. Primary Amyloidosis Deposition in organs  BLEEDING Increased vessel fragility ORGANOMEGALY Coagulation factors bindingAmyloid is a fibrillary protein that causes organ failure AL AA β2 Primary or Secondary AF Micro-Ig- light chain globulin Amyloidosis ~ Familial inflammation ~ Dialysis(~ Myeloma) Sheikha
    54. 54. SOP ha h eik S
    55. 55. SOP Solitary OsseousPlasmacytoma ha h eik S
    56. 56. SOP a heikh S 5% of PC neoplams No other Lytic lesions should be detected Marrow away from the lesion should not have plasmacytosis Site depends on marrow activity In order of frequency sites are: Vertebrae  Ribs  Skull  Pelvis  Femur  Clavicle  Scapula Treatment RT 35% CUREDIf Paraprotein +veit should disappear after treatment 10% 55% >10 Local Recurrennce MM years or Another SOP
    57. 57. EXTRA-OSSEOUS PLASMACYTOMA ha h eik S
    58. 58. EOP Extra OsseousPlasmacytoma ha h eik S
    59. 59. Role of adhesion molecules in disease pathogenesisBMSC, bone marrow stromal cell ECM, extracellular matrix ICAM, intracellular adhesion molecule IL, interleukin LFA, lymphocyte function-associated antigen MM, multiple myeloma VCAM, vascular cell adhesion molecule VLA, very late antigen
    60. 60. EOP ha h eik S EXTRA EXTRA OSSEOUS MEDULLARY 5% of PC neoplasms No Lytic lesions or marrow plasmacytoma 80% Median Age: 55 years UPPER RESPIRATORY M/F ratio: 2:1 TRACT L. N. PAROTID SKIN Oropharynx TESTIS Nasopharynx Sinuses Larynx GIT BLADDER CNS BREAST THYROID15% 25%MM Treatment RT Recurrence 15 – 20% may have PARAPROTEINEMIA
    61. 61. WALDENSTOROM’SMACROGLOBULINEMIA ha h eik S
    62. 62. MONOCLONAL GAMMOPATHYOF UNDETERMINATE SIGNIFICANCE M-GUSBENIGN MONOCLONAL GAMMOPATHY ha h eik S
    63. 63. ha h eikS
    64. 64. HCD HEAVY CHAINDISEASES ha h eik S
    65. 65. αμ γ HCD ha h eik S
    66. 66. HCD γ α μGamma Alpha mu HCD HCD HCD A variant A A of variant variant of LPC of Extranodal CLLLymphoma Margianl Zone MALT ha Lymphoma h eik S
    67. 67. α Heavy Chain Disease IPSIDImmunoproliferative Small Intestinal Disaese Mediterranean Lymphoma ~ H. pylori kha S hei
    68. 68. OSTEOSCLEROTICPOLYNEUROPATHY MYELOMA ORGANOMEGALY (Sensorimotor (Hepato- Demyelination) Splenomegaly) POEMS SYNDROME ENDOCRINOPATHY SKIN CHANGES (Diabetes;(Hyperpigmentation; Gynecomastia; Hypertrichosis) MONOCLONAL Testicular Atrophy; GAMMOPATHY Impotence)Marrow infiltrated by PC & bone trabeculae thickenedRare: 1 to 2% of PC dyscrasias Median Age: 50 years
    69. 69. Cellular origin of myeloma:genetic and cellular events in disease pathogenesis
    70. 70. Interleukin-6-mediated myeloma cell growth. BMSC, bone marrow stromal cell; IL, interleukin;NF, nuclear factor; TGF, transforming growth factor
    71. 71. Apoptosis signaling cascades in myeloma cells.IL, interleukin; JNK, c-jun N-terminal kinase;PYK, proline-rich tyrosine kinase; RAFTK, related adhesion focal tyrosine kinase;SAPK, stress-activated protein kinase
    72. 72. Interleukin-6 growth and antiapoptotic cascades in myeloma cells. MAP, mitogen-activated protein; RAFTK,related adhesion focal tyrosine kinase;SHP, Src homology protein tyrosine phosphatase
    73. 73. Role of adhesion molecules in disease pathogenesisBMSC, bone marrow stromal cell ECM, extracellular matrix ICAM, intracellular adhesion molecule IL, interleukin LFA, lymphocyte function-associated antigen MM, multiple myeloma VCAM, vascular cell adhesion molecule VLA, very late antigen
    74. 74. None 6
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