Plasma Cell Dyscrasias

Plasma Cell Dyscrasias

 

The spectrum of plasma cell dyscrasias is broad and includes:

Monoclonal Gammopathy of Uncertain Significance (MGUS)

  • Prevalence
    • Most common plasma cell dyscrasia
      • MGUS is found in 3% of individuals aged 50 years, 5% among persons 70 years or older and 7.5% among those 85 year or older
      • 1% lifelong risk per year of progression to multiple myeloma or other related disorders
  • Clinical Presentation
    • Asymptomatic premalignant disorder  
    • Serum monoclonal (M) protein levels <3g/dL, bone marrow plasma cells <10%
    • Absence of end-organ damage – lytic bone lesions, anemia, hypercalcemia or renal failure
  • Treatment
    • None required
    • Follow patient to detect appearance of malignancy

Multiple Myeloma (MM)

  • Epidemiology
    • Incidence – the annual age-adjusted incidence in the U.S. is 4.3 per 100,000 people, resulting in more than 15,000 new cases every year
    • Age – the median age at onset is 66 years
    • Sex – M:F;  1.4:1
    • Ethnicity – higher incidence in African Americans
  • Categories
    • Light-chain MM
      • Up to 20% of patients with MM lack heavy-chain expression in the M protein
    • Nonsecretory MM
      • 3% have no detectable M protein in serum or urine
  • Clinical Presentation
    • Malignant proliferation of plasma cells
    • Serum and or urinary M protein levels >3g/dL
    • Bone marrow plasma cells >10%
    • End-organ damage – lytic bone lesions, anemia, hypercalcemia or renal failure
    • Most common presenting symptoms of MM – fatigue, bone pain, recurrent infections, anemia, elevated serum creatinine and hypercalcemia
    • Similar to normal heavy chain distribution in serum, approximately 50-75% of monoclonal gammopathies are IgG, 20% are IgA and <1 % are IgD
    • IgE gammopathies are rare
  • Treatment
    • Oral chemotherapy and bone marrow transplantation

Waldenström Macroglobulinemia (WM)

  • Clinical Presentation
    • Malignant proliferation of lymphoid and plasma cells
    • Serum IgM M protein (regardless of the size of the M protein)
    • Bone marrow lymphoplasmatic infiltration >10%
    • Evidence of end-organ damage – anemia, constitutional symptoms (weakness, fatigue, night sweats, weight loss), hyperviscosity, lymphadenopathy, hepatosplenomegaly
    • Most common presenting symptoms – hyperviscosity, anemia and constitutional symptoms 
  • Treatment
    • Oral chemotherapy and plasmapheresis for hyperviscosity

Monoclonal Light-Chain (AL) Amyloidosis

  • Clinical Presentation
    • Malignant disorder of plasma cells
    • Deposit of a fibrillar proteinaceous material (detected by Congo red staining) in various tissues such as liver, kidney, heart, peripheral nerves, tongue and subcutaneous tissue
    • Evidence of a monoclonal plasma cell proliferative disorder by serum or urine M protein, or clonal plasma cells in the bone marrow
    • The clinical presentation of SA varies
      • Depends on the dominant organ involved
      • Nephrotic syndrome, restrictive cardiomyopathy and peripheral neuropathy are common presenting syndromes
  • Treatment
    • Oral chemotherapy and bone marrow transplantation

Solitary Plasmacytoma (SP)

  • Clinical Presentation
    • Malignant disorder
    • Biopsy-proven solitary lesions of bone
      • Evidence of local clonal plasma cells, normal bone marrow, normal skeletal survey of spine and pelvis
      • Absence of end-organ damage that can be attributed to a plasma cell proliferative disorder
    • Patients with SP are at risk of progression to MM
    • Most common in medullary sites
    • SP can occur in extramedullary sites
      • Most frequently localized in the upper respiratory tract (nasal cavity, sinuses and nasopharynx)
  • Treatment
    • Therapy for SP includes radiation of the involved site

Rare Plasma Cell Dyscrasias 

  • POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Multiple Myeloma and Skin changes) syndrome
  • Immunoglobulin heavy chain disease

Diagnosis

  • Major differential diagnosis is between MGUS, multiple myeloma and light-chain amyloidosis. Use of the following tests aids the clinician in determining disease. (Also refer to Indications for Ordering list of tests)
  • Serum protein electrophoresis (SPEP)
    • Abnormal patterns of protein fraction values are observed in various conditions
      • Inflammatory and infectious disorders (polyclonal gamma increase)
      • Rheumatic disease (polyclonal gamma increase)
      • Protein-losing disorders
      • Chronic liver disease (polyclonal gamma increase)
      • Chronic renal disease (polyclonal gamma decrease)
      • Genetic and metabolic disorders
    • SPEP provides quantification of the M protein
      • Initial testing for multiple myeloma
      • SPEP can be normal in patients with oligo-secretory (~10-15%) on non-secretory myeloma (~1%)
  • Immunofixation electrophoresis (IFE)
    • Serum IFE is a more sensitive method for detection and characterization of M protein
    • Particularly useful in early identification of minor M proteins or monoclonal free light chain components initially identified by abnormal banding patterns seen on SPEP
  • Bence-Jones Proteinuria
    • In plasma cell dyscrasia, a proteinuria pattern may show a discrete band in the alpha-2, beta, or gamma region, produced by monoclonal free light chains, or Bence-Jones protein (BJP)
  • Free light chain (FLC) assay
    • Patients with plasma cell dyscrasias, have an abnormal kappa to lambda FLC ratio due to the clonal secretion of a single FLC by malignant plasma cells
      • The FLC ratio may is indicated for the diagnosis and monitoring of patients with oligo-secretory or non-secretory multiple myeloma and light-chain amyloidosis

See Also