Organ Systems, Bone Marrow, Multiple Myeloma, WHO Classification, Hematopathology

MGUS – Non-IgM

Monoclonal Gammopathy of Uncertain Significance (MGUS)
  • < 3 gm/dL serum M protein (and)
  • <10% clonal bone marrow plasma cells (and)
  • Asymptomatic patients, no end organ damage (CRAB: hypercalcemia, renal insufficiency, anemia, bone lesions)
  • No evidence of other B-cell lymphoproliferative disorder

MGUS is not considered “neoplastic” since most patients do not develop overt malignancy.   A monoclonal M-protein is found in approximately 1 in 20 individuals after the age of 70.  Similar to multiple myeloma, approximately 20% of patients will only have detectable free light chains.
 
The plasma cells are still clonal and patients have the following features
  • 1% chance per year of progressing to multiple myeloma (0.3% for light chain MGUS).
  • Non-IgM M-protein.
    • 65% IgG
    • 15% IgA
    • 1% IgD
    • 1% IgE
    • 3% Biclonal
  • Average bone marrow involvement of 3% plasma cells. 
  • Plasma cells have a mature appearance (cytoplasmic inclusions and nucleoli – occasionally).
  • By flow cytometry these two populations can often be separated: (1) normal plasma cells CD19+/CD56- and (2) abnormal plasma cells CD19-/CD56+ or CD19-/CD56- (other aberrant antigen expression may also be present).
  •  From a molecular prospective, there are no definite differentiating factors between MGUS and multiple myeloma (although this may change).
  • Free Light Chain MGUS
    • Urine light chain excretion <0.5 g/24 hours
    • <10% plasma cells in bone marrow
    • No end-organ damage
IgM MGUS is considered as a precursor to lymphplasmacytic lymphoma (LPL) and/or Waldenstrom and is separate from Non-IgM MGUS (IgG, IgA), which is a precursor to multiple myeloma.  
References
Robbins and Cotran Pathologic Basis of Disease.  V Kumar, et al. 9th Edition. Elsevier Saunders. 2015. pp. 599-601.
 
WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues.  SH Swerdlow, et al. International Agency for Research on Cancer. Lyon, 2008.  pp. 200-213
 
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127: 2375–2390. doi:10.1182/blood-2016-01-643569