II. Epidemiology

  1. Elderly (mean age 68 years)
  2. Prevalence: 50,000 persons in United States
  3. Incidence: 16,000 new cases per year in United States
  4. Twice as common in black persons
  5. More common in men
  6. Family History confers 2-4 fold increased risk (Autosomal Dominant trait)
  7. Associated conditions
    1. Obesity
    2. Rheumatoid Arthritis
    3. Monoclonal Gammopathy of Undetermined Significance (MGUS)
  8. Associated with certain occupational exposures
    1. Farming Pesticides
    2. Petroleum workers
    3. Woodworkers
    4. Leather workers
    5. Ionizing radiation

III. Pathophysiology

  1. Malignant proliferation of Plasma Cells
    1. Overproduce M Protein
  2. Plasmacytoma may also form solitary plasma cell tumor
  3. Origin
    1. Spontaneous (de novo) onset in 80% of cases
    2. Monoclonal Gammopathy of Undetermined Significance (MGUS) in 20% of cases

IV. Symptoms (Asymptomatic in 34% of cases)

  1. Back pain or bone pain (58%)
  2. Fatigue (32%)
  3. Pathologic Fracture (up to 34% of cases)
  4. Anorexia (24%)
  5. Paresthesias (5%)
    1. Wrist Pain (Carpal Tunnel related Neuropathy)

V. Signs: Bone Findings

  1. Osteolytic lesions
  2. Pathologic Fractures
  3. Palpable swellings on accessible bones
  4. Location
    1. Sternum
    2. Skull
    3. Ribs
    4. Vertebrae (May result in spinal cord compression)

VI. Differential Diagnosis

  1. Common
    1. Monoclonal Gammopathy of Undetermined Significance (MGUS)
  2. Uncommon
    1. Waldenstrom Macroglobulinemia
    2. Amyloidosis
    3. B-Cell non-Hodgkin Lymphoma
  3. Rare
    1. Plasmacytoma
    2. Plasma Cell Leukemia

VII. Labs: Findings

  1. Serum Protein Electrophoresis and Urine Protein electrophoresis for Monoclonal Peak
    1. M Protein in either serum or urine: 97% of patients
    2. Serum M Protein by electophoresis (82%) or immunofixation (93%)
    3. Urine M Protein by electrophoresis: 75%
  2. Immunofixation of serum and urine
  3. Chemistry panel with Serum Calcium
    1. Hypercalcemia
      1. Serum Calcium >11 mg/dl (present in 13% of patients)
    2. Renal Insufficiency
      1. Serum Creatinine >2 mg/dl (present in 23% of patients)
  4. Complete Blood Count with platelets
    1. Normochromic Normocytic Anemia
      1. Hemoglobin <12 grams/dl (present in 65% of patients)
  5. Bone Marrow Biopsy (preferred over aspiration)
    1. HemeoncMultipleMyelomaMarrow.jpg
  6. Peripheral Smear
    1. Myeloma Cells
    2. Rouleaux of Red Blood Cells
  7. Erythrocyte Sedimentation Rate (ESR)
    1. Increased >50 mm/hour in most cases (except bence-jones Myeloma)
  8. Serum Viscosity
  9. Urinalysis
    1. Bence-Jones Protein

VIII. Imaging

  1. Skeletal Survey (including Skull XRay)
    1. Classic "punched out" lytic lesions (66% of patients)
    2. Pathologic Fractures (26% of patients)
  2. Osteoporosis (23% of patients)

IX. Differential Diagnosis

X. Diagnosis

  1. Criteria
    1. Marrow Plasmacytosis >10%
    2. Serum M Protein 3 grams/dl
    3. Symptomatic or end organ findings?
      1. Asymptomatic Multiple Myeloma (smoldering)
      2. Symptomatic Multiple Myeloma
  2. Variants with low M Protein (represent 20% of cases)
    1. Minimally elevated M Protein (<1 g/dl)
    2. Normal M Protein
      1. Bence Jones Myeloma (Increased urine excretion of light chains)
    3. Undetectable M Protein
      1. Non-secretory Multiple Myeloma (abnormal serum-free light chain ratio)

XI. Staging

  1. Stage I
    1. Serum B2 Microglobulin <3.5 mg/L
    2. Serum Albumin >= 3.5 g/dl
  2. Stage 2
    1. Serum B2 Microglobulin 3.5 to 5.5 mg/L
  3. Stage 3
    1. Serum B2 Microglobulin >=5.5 mg/L

XII. Management: Combination Therapy

  1. Indication
    1. Symptomatic Multiple Myeloma
  2. Protocol 1: Age under 65 years (or older patients who are otherwise physically healthy)
    1. Autologous Stem Cell Transplant and
    2. High dose Chemotherapy
      1. Vincristine
      2. Doxorubicin
      3. Dexamethasone
      4. Thalidomide (in some cases)
  3. Protocol 2: Age over 65 years
    1. Melphalan
    2. Prednisolone
    3. Thalidomide (in some cases)
  4. Efficacy
    1. Palliative (Not curative)
    2. Relapse is common

XIII. Complications

  1. Immune Suppression
    1. Infection presenting complaint in 25% of patients
    2. Start empiric antibiotics for febrile illness
    3. See prevention below for Immunizations
  2. Hypercalcemia
    1. Initial Management: Normal Saline Infusion with Corticosteroids
    2. Additional management in Refractory Cases: Furosemide, Bisphosphonates
  3. Renal Failure
    1. Dialysis as indicated
  4. Neuropathy (Nerve infiltration by amyloid)
  5. Anemia
    1. Consider differential diagnosis for Anemia
    2. Often improves with Multiple Myeloma treatment
    3. Consider Erythropoietin or transfusion
  6. Vertebral Fractures
    1. See Vertebral Fracture
    2. Intravenous Bisphosphonates (Pamidronate, Zoledronic acid)
      1. Continue indefinately
      2. Reduces fracture Incidence and pain
    3. Surgical Intervention: Percutaneous Vertebroplasty or Kyphoplasty
      1. Indicated in refractory cases
    4. Radiation Therapy
      1. Indicated for spinal cord compression
  7. Hyperviscosity Syndrome
    1. Findings: Fatigue, Headache, Visual disturbance, Retinopathy
    2. Treat with plasmaphoresis

XV. Monitoring

  1. Symptomatic improvement
  2. Decrease in M Component

XVI. Prognosis

  1. Invariably fatal but relates to staging
    1. Stage I: 62 Month median survival
    2. Stage 3: 29 Month median survival
  2. Treated patients live asymptomatically for years
  3. Mortality from cause unrelated to Myeloma: 25%

XVII. Resources

  1. Multiple Myeloma Research Web Server
    1. http://myeloma.med.cornell.edu
  2. Cleveland Clinic Multiple Myeloma and Amyloidosis
    1. http://www.clevelandclinic.org/myeloma

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Ontology: Multiple Myeloma (C0026764)

Definition (MEDLINEPLUS)

Multiple myeloma is a cancer that begins in plasma cells, a type of white blood cell. These cells are part of your immune system, which helps protect the body from germs and other harmful substances. In time, myeloma cells collect in the bone marrow and in the solid parts of bones.

No one knows the exact causes of multiple myeloma, but it is more common in older people and African Americans. It can run in families. Common symptoms may include

  • Bone pain, often in the back or ribs
  • Broken bones
  • Weakness or fatigue
  • Weight loss
  • Repeated infections
  • Frequent infections and fevers
  • Feeling very thirsty
  • Frequent urination

Doctors diagnose multiple myeloma using lab tests, imaging tests, and a bone marrow biopsy. Your treatment depends on how advanced the disease is and whether you have symptoms. If you have no symptoms, you may not need treatment right away. If you have symptoms, you may have chemotherapy, stem cell transplantation, radiation, or targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells.

NIH: National Cancer Institute

Definition (NCI_NCI-GLOSS) A type of cancer that begins in plasma cells (white blood cells that produce antibodies).
Definition (NCI) A bone marrow-based plasma cell neoplasm characterized by a serum monoclonal protein and skeletal destruction with osteolytic lesions, pathological fractures, bone pain, hypercalcemia, and anemia. Clinical variants include non-secretory myeloma, smoldering myeloma, indolent myeloma, and plasma cell leukemia. (WHO, 2001)
Definition (NCI_CDISC) A malignant neoplasm of the bone marrow composed of plasma cells.
Definition (CSP) malignant neoplasm of plasma cells usually arising in the bone marrow and manifested by skeletal destruction, bone pain, and the presence of anomalous immunoglobulins.
Definition (MSH) A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.
Concepts Neoplastic Process (T191)
MSH D009101
ICD9 203.0
ICD10 C90.0 , M9732/3, C90.00
SnomedCT 55921005, 94705007, 154585004, 109989006
English Multiple Myeloma, Multiple Myelomas, Myeloma, Plasma Cell, Myelomas, Multiple, MYELOMATOSIS MULTIPLE, Myeloma, Plasma-Cell, Myelomas, Plasma-Cell, PLASMA CELL MYELOMA, Plasma-Cell Myeloma, Plasma-Cell Myelomas, Multiple myeloma / Plasma cell neoplasm, MYELOMA, MULTIPLE, [M]Plasma cell myeloma, multiple myeloma (diagnosis), multiple myeloma, Multiple myeloma, no ICD-O subtype, Peripheral plasma cell myeloma, Plasma Cell Myeloma, Cell Myeloma, Plasma, Cell Myelomas, Plasma, Plasma Cell Myelomas, Myelomas, Plasma Cell, Multiple myeloma NOS, Multiple Myeloma [Disease/Finding], Myeloma-Multiple, Kahler Disease, Myelomatoses, Disease, Kahler, Myelomatosis, Myeloma-Multiples, Myeloma Multiple, myelomas, kahler disease, Myeloma;multiple, multiple myeloma (MM), multiple myelomatosis, kahler's disease, multiple myelomas, Myeloma, Multiple, Plasma-cell myeloma, Plasma-cell Myeloma, Multiple myeloma myelomatosis, Myelomatosis multiple, Myeloma (disorder), Multiple myeloma, no International Classification of Diseases for Oncology subtype (morphologic abnormality), Multiple myeloma, no ICD-O subtype (morphologic abnormality), Multiple myeloma, no International Classification of Diseases for Oncology subtype, Plasma cell myelomas, MYELOMA, myeloma, MULTIPLE MYELOMA, MYELOMA, PLASMA CELL, MALIGNANT, Myeloma, NOS, myelomatosis, Kahler disease, Plasma cell myeloma, Plasmacytic myeloma, Myeloma, Multiple myeloma, Kahler's disease, Multiple myeloma (disorder), plasma cell neoplasm, neoplasm, plasma cell, myeloma, plasma cell, plasma cell myeloma, myeloma, multiple, multiple myeloma and other plasma cell neoplasms, plasma cell neoplasms, Kahler, myelomata; multiple, Multiple myeloma (clinical), Multiple myeloma, morphology (morphologic abnormality)
French MYELOME MULTIPLE, Myélome périphérique à cellules plasmatiques, MYELOMATOSE MULTIPLE, Myélomatose multiple, Myélomatose avec myélomes multiples, Myélome des cellules plasmatiques, Myélomatose, Myélome, Myélomes plasmocytaires, Myélome multiple, Maladie de Kahler
Portuguese MIELOMA MULTIPLO, Mieloma plasmocítico periférico, MIELOMATOSE MULTIPLA, Mieloma de Plasmócitos, Mielomatose múltipla, Mieloma múltiplo, Mieloma, Mielomatose, Mieloma de plasmócitos, Mielomatose de mieloma múltiplo, Mieloma Plasmocitário, Mielomas de plasmócitos, Mieloma Múltiplo
Spanish MIELOMA MULTIPLE, Mieloma de células plasmáticas periféricas, mieloma múltiple, morfología (anomalía morfológica), mieloma múltiple (clínico) (trastorno), MIELOMATOSIS MULTIPLE, mieloma múltiple, subtipo sin ICD-O (anomalía morfológica), mieloma múltiple, subtipo sin ICD-O, (M)mieloma de células plasmáticas, mieloma múltiple, no clasificado como subtipo en CIE-O, Mieloma, Mielomatosis, Mieloma de células plasmáticas, Mielomatosis múltiple, Mieloma múltiple, mieloma múltiple, enfermedad (concepto no activo), enfermedad de Khaler, mieloma múltiple, no clasificado como subtipo en la Clasificación Internacional de Enfermedades para Oncología (anomalía morfológica), mieloma múltiple, no clasificado como subtipo en CIE-O (anomalía morfológica), mieloma múltiple, no clasificado como subtipo en la Clasificación Internacional de Enfermedades para Oncología, Mielomas de células plasmáticas, mieloma de células plasmáticas, mieloma múltiple, mielomatosis, mieloma, mieloma múltiple (clínico), enfermedad de Kahler, mieloma múltiple (trastorno), Mieloma de Células Plasmáticas, Mieloma Múltiple
German MULTIPLES MYELOM, peripheres Plasmazellenmyelom, MYELOMATOSE MULTIPLE, Plasmozytom [Multiples Myelom], Plasmazellenmyelom, multiples Myelom, multiples Myelom, Myelomatose, Myelom, Myelomatose multiple, Myelomatose, Plasmazellenmyelome, Multiples Myelom, Myelom, Plasmazell-
Dutch perifeer plasmacelmyeloom, plasmacel myeloom, myelomatosis, multipel myeloom, myeloom, multipel myeloom myelomatosis, myelomatosis multipel, plasmacelmyelomen, myelomata; multipel, Multipel myeloom, Myeloom, multipel, Plasmacelmyeloom
Italian Plasmocitoma maligno periferico, MM, Mieloma plasmacellulare, Malattia di Kahler-Bozzolo, Mieloma, Mielomatosi multipla, Mielomatosi, Mielomatosi da mieloma multiplo, Mielomi delle plasmacellule, Mieloma multiplo
Japanese 末梢形質細胞性骨髄腫, マッショウケイシツサイボウセイコツズイシュ, 骨髄腫-多発性, Kahler病, 骨髄腫症, ミエローマ, ケイシツサイボウセイコツズイシュ, タハツセイコツズイシュ, ミエローマ, コツズイシュショウ, 多発性骨髄腫症, タハツセイコツズイシュショウ, カーレル病, プラスマ細胞性骨髄腫, 多発性骨髄腫, 多発骨髄腫, 形質細胞性骨髄腫, 形質細胞骨髄腫, 骨髄腫-形質細胞, カーラー病
Swedish Multipelt myelom
Finnish Multippeli myelooma
Russian MIELOMNAIA BOLEZN', MIELOMA MNOZHESTVENNAIA, MIELOMATOZ, BOLEZN' RUSTITSKOGO-KALERA, MIELOMA, RETIKULOPLAZMOTSITOZ, MNOZHESTVENNAIA MIELOMA, БОЛЕЗНЬ РУСТИЦКОГО-КАЛЕРА, МИЕЛОМА, МИЕЛОМА МНОЖЕСТВЕННАЯ, МИЕЛОМАТОЗ, МИЕЛОМНАЯ БОЛЕЗНЬ, МНОЖЕСТВЕННАЯ МИЕЛОМА, РЕТИКУЛОПЛАЗМОЦИТОЗ
Czech Myelom z periferních plazmatických buněk, mnohočetný myelom, myelom mnohočetný, nemoc Kahlerova, Kahlerova nemoc, Myelom, Myelomatóza mnohočetná, Myelomatóza, Myelomatóza s mnohočetným myelomem, Mnohočetný myelom, Plazmocytický myelom, mnohotný myelom, myelomatóza, plazmocytární myelom, Myelomy z plazmatických buněk
Korean 다발성 골수종
Croatian MULTIPLI MIJELOM
Polish Siatkowiak plazmocytowy, Choroba Kahlera, Plasmocytoma, Szpiczak mnogi, Szpiczak plazmocytowy
Hungarian Peripheriás plazmasejtes myeloma, Myelomatosis multiplex, Plazmasejtes myeloma, Myeloma multiplex, Multiplex myeloma myelomatosis, Myelomatosis, Myeloma, Plazmasejtes myelomák
Norwegian Medullært plasmocytom, Kahlers sykdom, Multiple myelomer, Plasmacellemyelom, Myelomatose

Ontology: Plasmacytoma (C0032131)

Definition (NCI_NCI-GLOSS) A type of cancer that begins in plasma cells (white blood cells that produce antibodies). A plasmacytoma may turn into multiple myeloma.
Definition (NCI) A single focus of clonal (malignant) plasma cells either in the bone or in another anatomic site without peripheral blood involvement. --2003
Definition (NCI) A malignant (clonal) proliferation of plasma cells that are cytologically and immunophenotypically identical to those of plasma cell myeloma, but manifest a localized osseous or extraosseous growth pattern. (WHO, 2001)
Definition (MSH) Any discrete, presumably solitary, mass of neoplastic PLASMA CELLS either in BONE MARROW or various extramedullary sites.
Concepts Neoplastic Process (T191)
MSH D010954
ICD10 M9731/3 , C90.3, C90.30
SnomedCT 274907000, 269652000, 189507001, 190017008, 302852008, 190019006, 308122007, 190016004, 188719003, 188720009, 154644004, 309571000009106, 10639003, 109987008, 415112005
English Monostotic myeloma, Plasma Cell Tumors, Plasmacytoma, Plasmacytomas, Plasmocytoma, Plasmocytomas, Plasma Cell Tumor, Plasma cell tumor NOS, Plasma cell tumour NOS, Tumor, Plasma Cell, Tumors, Plasma Cell, [M]Plasma cell tumor NOS, [M]Plasma cell tumour NOS, [M]Plasma cell tumors, [M]Plasma cell tumours, Plasma cell tumors, Plasma cell tumours, [M]Plasmacytoma NOS, Plasmacytoma NOS, malignant plasmacytoma (diagnosis), malignant plasmacytoma, plasmacytoma, Solitary plasmacytoma NOS, Plasmacytoma [Disease/Finding], plasmacytomas, plasmocytomas, plasma cell tumors, bone plasmacytoma, plasma cell tumor, plasma cell neoplasms, plasmacytomas solitary, plasmocytoma, Plasma cell tumor (morphologic abnormality), Myeloma, solitary, [M]Plasmacytoma NOS (disorder), [M]Plasma cell tumor NOS (morphologic abnormality), Plasmacytoma NOS (disorder), [M]Plasma cell tumors (morphologic abnormality), Myeloma - solitary, Plasma cell tumour (clinical), Plasma cell tumor (clinical), Solitary myeloma (clinical), Plasmacytoma of animal, Plasmacytoma of animal (disorder), Plasma cell tumor, Solitary myeloma, Solitary plasmacytoma, Plasma cell tumour, Plasmacytoma of bone, solitary plasmacytoma, monostotic; myeloma, plasma cell, monostotic; myeloma, myeloma; monostotic, plasma cell, myeloma; monostotic, myeloma; solitary, plasma cell; tumor, solitary; myeloma, tumor; plasma cell, Plasmacytoma, NOS, Solitary Plasmacytoma, Plasmacytoma (disorder), Plasmacytoma - disorder, Solitary plasmacytoma of bone (morphologic abnormality), Plasmacytoma (morphologic abnormality)
Italian Plasmocitoma, Tumore plasmacellulare, Tumore delle plasmacellule, Plasmacitoma
Dutch plasmaceltumor, monostotisch; myeloom, plasmacel, monostotisch; myeloom, myeloom; monostotisch, plasmacel, myeloom; monostotisch, myeloom; solitair, plasmacel; tumor, solitair; myeloom, tumor; plasmacel, plasmacytoom, Plasmaceltumor, Plasmacytoom
French Tumeur à cellules plasmatiques, Plasmocytome solitaire, Plasmocytome
German Plasmazellentumor, Plasmazelltumor, Plasmozytom
Portuguese Tumor de plasmócitos, Tumor de Células Plasmáticas, Neoplasia de Plasmócitos, Plasmacitoma, Plasmocitoma, Tumor de Plasmócitos
Spanish Tumor de células plasmáticas, plasmocitoma (anomalía morfológica), Plasmacytoma NOS, tumor de células plasmáticas (anomalía morfológica), mieloma solitario (clínico), plasmocitoma, SAI, [M]plasmocitomas, SAI (anomalía morfológica), tumor de células plasmáticas (clínico), [M]plasmocitomas, SAI, plasmocitoma, SAI (trastorno), [M]plasmocitomas (anomalía morfológica), mieloma monostótico, tumor de células plasmáticas, SAI, [M]plasmocitomas, Plasmocitoma, mieloma solitario, plasmocitoma solitario, tumor de células plasmáticas, plasmocitoma (trastorno), plasmocitoma, plasmocitoma solitario óseo (anomalía morfológica), plasmocitoma solitario óseo, Plasmacitoma, Tumor de Células Plasmáticas
Swedish Plasmacytom
Japanese ケイシツサイボウシュ, 骨髄腫, 形質細胞腫, ケイシツサイボウシュヨウ, 形質細胞腫瘍, プラスマ細胞腫, プラスモサイトーマ, ミエローマ
Czech plazmocytom, Plazmocytom, Nádor z plazmatických buněk, plasmocytom, plazmocelulární myelom
Finnish Plasmosytooma
Russian PLAZMOTSITOMA, ПЛАЗМОЦИТОМА
Croatian PLAZMOCITOM
Polish Guz plazmatycznokomórkowy, Plazmocytoma
Hungarian Plazmasejtes tumor, Plasmocytoma
Norwegian Plasmocytom, Plasmacytom