Multiple myeloma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Multiple myeloma is a disorder affecting post germinal center B lymphocytes. A chromosomal translocation between the immunoglobulin heavy chain gene and one of many oncogenes leads to dysregulated multiplication of plasma cells. This leads to a localized damage, resulting in punched out bony lesions as well as various organ damage among other symptoms.

Pathophysiology

• Multiple myeloma develops in post-germinal center B lymphocytes.
• Proliferation of a plasma cell clone and genomic instability leads to further mutations and translocations.
• Production of cytokines (especially IL-6) by the plasma cells causes much of their localised damage, such as osteoporosis, and creates a microenvironment in which the malignant cells thrive. Angiogenesis (the attraction of new blood vessels) is increased.
• Increased risk of infection is due to immune deficiency resulting from diffuse hypogammaglobulinemia, which is due to decreased production and increased destruction of normal antibodies.
• The produced antibodies are deposited in various organs leading polyneuropathy and various other multiple myeloma associated symptoms.
• Renal failure due to glomerular deposition of amyloid or tubular damage from excretion of light chains called Bence Jones proteins, which can manifest as the Fanconi syndrome (type II renal tubular acidosis).

Genetics

• A genetic mutation results in dysregulation of the oncogene which is thought to be an important initiating event in the pathogenesis of multiple myeloma.
• A chromosomal translocation between the immunoglobulin heavy chain gene (on the fourteenth chromosome, locus 14q32) and an oncogene (often 11q13, 4p16.3, 6p21, 16q23 and 20q11) is frequently observed in patients with multiple myeloma.
• The chromosome 14 abnormality is observed in about 50% of all cases of myeloma. Deletion of (parts of) the thirteenth chromosome is also observed in about 50% of cases.

Gross Pathology

• 
  Vertebras in multiple myeloma
  (Image courtesy of Melih Aktan M.D.)
• 
  Calvarium in multiple myeloma.
  (Image courtesy of Melih Aktan M.D.)

Microscopic Pathology

• 
  Multiple Myeloma slide showing plasma cells with large nucleus and scant cytoplasm
• 
  Bone marrow aspiration in multiple myeloma.
  (Image courtesy of Melih Aktan M.D.)
• 
  Bone marrow biopsy in multiple myeloma.
  (Image courtesy of Melih Aktan M.D.)
• 
  Bone marrow in multiple myeloma.
  (Image courtesy of Melih Aktan M.D.)
• 
  Bone marrow in multiple myeloma.
  (Image courtesy of Melih Aktan M.D.)

References

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