eMedicine Specialties > Orthopedic Surgery > Neoplasms

Myeloma

Author: Seema S Rizvi, MD, Associate Medical Director, Lutheran Care Center
Coauthor(s): Howard A Chansky, MD, Associate Professor, Department of Orthopedics and Sports Medicine, University of Washington Medical Center
Contributor Information and Disclosures

Updated: May 29, 2009

Introduction

Background

Multiple myeloma (MM) is characterized by neoplastic proliferation of plasma cells involving more than 10% of the bone marrow. The disease results in the production of monoclonal immunoglobulins, which may be identified with serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP). Plasma-cell proliferation causes extensive skeletal destruction with osteolytic lesions, anemia, and hypercalcemia. Excessive production of M proteins can lead to renal failure, hyperviscosity, and recurrent infections. MM accounts for 10% of all hematologic cancers.1,2

The American Cancer Society estimates that about 20,580 new cases of multiple myeloma (11,680 in men and 8,900 in women) will be diagnosed during 2009. In the United States, the lifetime risk of getting multiple myeloma is 1 in 161 (0.62%).3

About 10,580 Americans (5,640 men and 4,940 women) are expected to have died of multiple myeloma in 2008.3

The 5-year relative survival rate for multiple myeloma is around 35%. Survival is higher in younger people and lower in the elderly.3,4,5  

Pathophysiology

The malignant cells of multiple myeloma (MM), plasma cells, and plasmacytoid lymphocytes are the most mature cells of B-lymphocytes. B-cell maturation is associated with a programmed rearrangement of DNA sequences in the process of encoding the structure of mature immunoglobulins. It is characterized by overproduction of monoclonal immunoglobulin G (IgG), immunoglobulin A (IgA), and/or light chains. The role of cytokines in the pathogenesis of MM is an important area of research. Interleukin (IL)–6 is also an important factor promoting the in vitro growth of myeloma cells. Other cytokines are tumor necrosis factor and IL-1b.

The pathophysiologic basis for the clinical sequelae of MM involves the skeletal, hematologic, renal, and nervous systems and also general processes.

Regarding skeletal factors, isolated plasmacytomas (which affect 2-10% of patients) lead to hypercalcemia due to production of the osteoclast-activating factor. Destruction of bone and its replacement by tumor may lead to pain, spinal cord compression, and pathologic fracture.

Among the hematologic processes, bone marrow infiltration by plasma cells results in neutropenia, anemia, and thrombocytopenia. In terms of bleeding, M components may interact specifically with clotting factors, leading to defective aggregation.

Renal conditions include hypercalcemic nephropathy, hyperuricemia due to renal infiltration of plasma cells resulting in myeloma, light-chain nephropathy, amyloidosis, and glomerulosclerosis.

The nervous system may be involved as a result of radiculopathy and/orcordcompression due to nerve compression and skeletal destruction(amyloid infiltration of nerves).

General pathophysiologic processes include hyperviscosity syndrome. This syndrome is infrequent in MM and occurs with IgG1, IgG3, or IgA. MM may involve sludging in the capillaries, which results in purpura, retinal hemorrhage, papilledema, coronary ischemia, or CNS symptoms (eg, confusion, vertigo, seizure). Cryoglobulinemia causes Raynaud phenomenon, thrombosis, and gangrene in the extremities.

Frequency

United States

The American Cancer Society estimates that in the United States, 20,580 new cases of multiple myeloma will be diagnosed during 2009, with 11,680 cases occurring in men and 8,900 in women. The lifetime risk of getting multiple myeloma is 1 in 161 (0.62%).3

International

The incidence is 4 cases per 100,000 population per year. Multiple myeloma is rare among the Asian population, with an incidence of 2 cases per 100,000.

Mortality/Morbidity

Survival rates of patients with myeloma vary substantially. See also Workup, Histologic Findings; Follow-up, Complications; and Follow-up, Prognosis.

  • About 10,580 Americans (5,640 men and 4,940 women) are expected to die of multiple myeloma in 2008.3
  • The 5-year relative survival rate for multiple myeloma is around 35%. Survival is higher in younger people and lower in the elderly.3
  • Bacterial infection is the leading cause of death in patients with myeloma.3

Race

  • In the United States, African Americans are twice as likely as whites to have myeloma, with a ratio of 2:1.
  • Myeloma is rare among people of Asian descent, with an incidence of only 1-2 cases per 100,000 population.

Sex

The American Cancer Society estimates that in the United States, 20,580 new cases of multiple myeloma will be diagnosed during 2009, with 11,680 cases in men and 8,900 in women.3

Age

  • Myeloma is age dependent, with less than 2% of cases occurring in individuals younger than 40 years.
  • The median patient age at diagnosis is 65 years.
  • Only 18% of patients are younger than 50 years, and 3% of patients are younger than 40 years.

Clinical

History

  • The diagnosis is incidental in 30% of cases. Multiple myeloma (MM) is often discovered when patients are being evaluated for unrelated problems.
  • In one third of patients, MM is diagnosed after a pathologic fracture occurs; such fractures commonly involve the axial skeleton.
  • Two thirds of patients complain of bone pain, commonly with lower back pain. This bone pain is frequently located in the back, long bones, skull, and/or pelvis.
  • Patients may complain of nonspecific constitutional symptoms related to hyperviscosity and hypercalcemia.
  • Symptoms of hyperviscosity include the following:
    • Generalized malaise
    • Infections
    • Fever
    • Bleeding
    • Headaches
    • Bruising
    • Paresthesia
    • Sensory loss
    • Sluggish mentation
  • Symptoms of hypercalcemia include the following:
    • Nausea
    • Fatigue
    • Thirst

Physical

  • On head, ears, eyes, nose, and throat (HEENT) examination, the eyes may show exudative macular detachment, retinal hemorrhage, or cotton-wool spots.
  • Macroglossia may occur secondary to amyloid deposition in the tongue.
  • On evaluation of the abdomen, hepatosplenomegaly may be discovered.
  • Cardiovascular system (CVS) examination may reveal cardiomegaly secondary to immunoglobulin deposition.
  • On central nervous system (CNS) examination, the patient may have neuropathy, myopathy, a Tinel sign, or a Phalen sign due to carpel tunnel compression secondary to amyloid deposition.
  • Bone pain and pathologic fractures may be observed.
    • In general, painful lesions that involve at least 50% of the cortical diameter of a long bone or lesions that involve the femoral neck or calcar femorale are at high (50%) risk for a pathologic fracture.
    • The risk of fracture is lower in lesions of the upper extremity than those of the lower extremity.
    • Even a small cortical defect can decrease torsional strength by as much as 60% (stress riser effect).

Causes

The precise etiology of multiple myeloma (MM) has not yet been established.

  • Radiation may play a role in some patients. An increased risk has been reported in atomic-bomb survivors exposed to more than 50 Gy.
  • An increased risk has been reported in farmers, especially in those who use herbicides and insecticides, and in people exposed to benzene and other organic solvents.
  • MM has been reported in 2 or more first-degree relatives and in identical twins, although no evidence suggests a hereditary basis for the disease.
  • A relationship between MM and preexisting chronic inflammatory diseases has been suggested. However, a case-control study provides no support for the role of chronic antigenic stimulation.
  • Human herpesvirus 8 (HPV8) infection of bone marrow dendritic cells was found in patients with MM and in some patients with monoclonal gammopathy of undetermined significance (MGUS).
  • Some studies have shown that abnormalities of certain oncogenes, such as c-myc, are associated with development early in the course of plasma cell tumors and that abnormalities of oncogenes such as N-ras and K-ra are associated with development after bone marrow relapse. Abnormalities of tumor suppressor genes, such as p53, have been shown to be associated with spread to other organs.3

More on Myeloma

Overview: Myeloma
Differential Diagnoses & Workup: Myeloma
Treatment & Medication: Myeloma
Follow-up: Myeloma
References
Further Reading
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References

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  2. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. Jan 2009;23(1):3-9. [Medline].

  3. Detailed Guide: Multiple Myeloma What Are the Key Statistics About Multiple Myeloma?. American Cancer Society. Available at http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_multiple_myeloma_30.asp. Accessed May 28, 2009.

  4. Rodon P. Management and treatment of multiple myeloma in elderly patients. Ann Long-Term Care. 2002;10:20-7.

  5. Ludwig H, Durie BG, Bolejack V, Turesson I, Kyle RA, Blade J, et al. Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group. Blood. Apr 15 2008;111(8):4039-47. [Medline].

  6. Alexanian R, Dimopoulos M. The treatment of multiple myeloma. N Engl J Med. Feb 17 1994;330(7):484-9. [Medline].

  7. Anderson KC, Hamblin TJ, Traynor A. Management of multiple myeloma today. Semin Hematol. Jan 1999;36(1 suppl 3):3-8. [Medline].

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  9. Desikan KR, Dhodapkar MV, Munshi NC, Barlogie B. Recent advances in the treatment of multiple myeloma. Curr Opin Hematol. Jul 1999;6(4):216-21. [Medline].

  10. Kanis JA, McCloskey EV. Bisphosphonates in multiple myeloma. Cancer. Jun 15 2000;88(12 suppl):3022-32. [Medline].

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  12. Lust JA, Lacy MQ, Zeldenrust SR, Dispenzieri A, Gertz MA, Witzig TE, et al. Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin Proc. Feb 2009;84(2):114-22. [Medline].

  13. Ocio EM, Mateos MV, Maiso P, Pandiella A, San-Miguel JF. New drugs in multiple myeloma: mechanisms of action and phase I/II clinical findings. Lancet Oncol. Dec 2008;9(12):1157-65. [Medline].

  14. Palumbo A, Rajkumar SV. Treatment of newly diagnosed myeloma. Leukemia. Mar 2009;23(3):449-56. [Medline].

  15. Bensinger WI. Role of autologous and allogeneic stem cell transplantation in myeloma. Leukemia. Mar 2009;23(3):442-8. [Medline].

  16. Kumar S, Witzig TE, Rajkumar SV. Thalidomid: current role in the treatment of non-plasma cell malignancies. J Clin Oncol. Jun 15 2004;22(12):2477-88. [Medline].

  17. Ludwig H, Hajek R, Tóthová E, Drach J, Adam Z, Labar B, et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood. Apr 9 2009;113(15):3435-42. [Medline].

  18. van Rhee F, Dhodapkar M, Shaughnessy JD Jr, Anaissie E, Siegel D, Hoering A, et al. First thalidomide clinical trial in multiple myeloma: a decade. Blood. Aug 15 2008;112(4):1035-8. [Medline].

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  20. Rotta M, Storer BE, Sahebi F, Shizuru JA, Bruno B, Lange T, et al. Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting. Blood. Apr 2 2009;113(14):3383-91. [Medline].

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Keywords

myeloma, multiple myeloma, MM, plasma cell dyscrasia, plasma cell proliferation, hematologic cancer, plasmacytoid lymphocytes, M proteins

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Contributor Information and Disclosures

Author

Seema S Rizvi, MD, Associate Medical Director, Lutheran Care Center
Seema S Rizvi, MD is a member of the following medical societies: American Academy of Family Physicians and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Howard A Chansky, MD, Associate Professor, Department of Orthopedics and Sports Medicine, University of Washington Medical Center
Howard A Chansky, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons
Disclosure: Nothing to disclose.

Medical Editor

Miguel A Schmitz, MD, Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic
Miguel A Schmitz, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, and Arthroscopy Association of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Sean P Scully, MD, PhD, Professor, Department of Orthopedics, University of Miami
Sean P Scully, MD, PhD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, International Society on Thrombosis and Haemostasis, and Society of Surgical Oncology
Disclosure: Nothing to disclose.

CME Editor

Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital
Dinesh Patel, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Association of Physicians of Indian Origin, American College of International Physicians, and American College of Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Harris Gellman, MD, Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine
Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society
Disclosure: Nothing to disclose.

 
 
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