multiple%20myeloma
MULTIPLE MYELOMA

Multiple myeloma is a bone marrow disease characterized by the presence of malignant plasma cells, & abnormal serum &/or urine immunoglobulin secondary to clonal plasma cell expansion.

It accounts for 1-2% of all cancers worldwide & mostly affects patients at ages 65-74 years old.

Patient usually presents with bone pain & nonspecific symptoms, or due to abnormalities in laboratory exams.

 

Definition

  • A bone marrow disease characterized by the presence of malignant plasma cells, & abnormal serum &/or urine immunoglobulin secondary to clonal plasma cell expansion

Signs and Symptoms

  • Patients usually present w/ bone pain & fatigue due to anemia
  • Nonspecific symptoms eg nausea, vomiting, malaise, weight loss, generalized body weakness, fatigue

Etiology

  • There are 2 processes being considered to be the root cause of multiple myeloma

Premalignant Stage: Appearance of MGUS

  • Brought about by the cytogenic abnormalities &/or abnormal cellular response to an antigenic stimulus
  • Malignant transformation of plasma cells leads to production of monoclonal paraprotein (M-protein) composed of single heavy & light chain immunoglobulins
    • Abnormal immunoglobulins include IgG, IgM, IgA, & rarely IgE & IgD
    • Light chain protein κ & λ are also seen
    • These immunoglobulins cause hyperviscosity & end-organ damage
  • Chromosomal aberrations identified w/ multiple myeloma include del17p13, IgH gene rearrangement at 14q32, 14q32 translocations [t(11;14)(q13;q32), t(4;14)(p16;q32), t(14;16)(q32;q23), t(14;20)(q32;q12)], & chromosome 1 abnormalities
    • These aberrations lead to the development of plasma cell clones 
  • An antigenic stimulus when interpreted by cells [eg toll-like receptors (TLRs) on myeloma cells, interleukin-6 (IL-6)] abnormally causes an increase in plasma cells, thereby causing chromosomal changes leading to plasma cell clones & abnormally produced immunoglobulins

Disease Progression from MGUS to Multiple Myeloma

  • Triggering factors that contribute to the development of MGUS into multiple myeloma include secondary cytogenic aberrations (secondary IgH translocation, Ras mutations, activation of the NF κ B pathway), abnormalities in the cell cycle pathway, interrupted apoptosis, & various factors affecting the bone marrow

Risk Factors

  • Age (increases risk)
  • Immunosuppression
  • Environmental exposures
  • Gender (more common in men)
  • Occupational exposure to toxic substances such as radiation, solvents, herbicides, insecticides

Epidemiology

  • Accounts for 1-2% of all cancers worldwide
    • 2nd most frequent hematologic malignancy in the US, w/ rapidly increasing incidence rate in Asia
  • Median age of onset is 66 years old

Pathophysiology

  • Always preceded by a premalignant stage, monoclonal gammopathy of undetermined significance (MGUS)
    • Only 10% of patients w/ newly diagnosed multiple myeloma have a history of pre-existing MGUS since patients w/ MGUS are asymptomatic
    • Rate of progression of MGUS to multiple myeloma is 1% per year
    • Non-IgM immunoglobulin MGUS (non-IgM MGUS) makes up 80% of premalignant multiple myeloma
    • Light-chain immunoglobulin MGUS makes up 20% of premalignant multiple myeloma
    • IgM immunoglobulin MGUS usually develops into Waldenström macroglobulinemia but may rarely evolve into multiple myeloma (IgM myeloma)
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