Multiple Myeloma: Pathogenesis and clinical findings
Plasma cell populations in the body normally produce non-clonal (a diverse array of) immunoglobulins
Normal SPEP: no spike in the gamma (γ) region
Notes:
• MGUSismuchmorecommon than MM!
• “Plasmacell”:Blymphocytes that produce antibodies/ immunoglobulins
Stimulation by specific antigens
Genetic changes/mutations accumulate over time in one type of plasma cell
Abbreviations/Definitions: • SPEP – Serum Protein
Electrophoresis
• Ig – Immunoglobulin • Monoclonal – “of one
specific genetic strain or subtype”
One type of plasma cell starts to proliferate abnormally
Monoclonal Gammopathy of Undetermined Significance (MGUS) (Premalignant, mild monoclonal plasma cell proliferation; asymptomatic)
In 1-2% of cases, further cytogenetic changes over time stimulate further proliferation of this plasma cell line
Multiple Myeloma (MM)
(extensive monoclonal B lymphocyte proliferation, causing end organ damage)
Slightly more monoclonal plasma cells will produce slightly more monoclonal Immunoglobulins
Small spike in the gamma (γ) region of the SPEP (less prominent compared to the spike in MM)
More monoclonal plasma cells result in far greater amounts of monoclonal immunoglobulins being secreted
Large spike in gamma (γ) region of the SPEP
Ig light chains accumulate in the tubules of kidney nephrons
Light chain casts obstruct tubules
Renal Insufficiency (↓GFR)
Osteoblasts ↑ expression of RANK-ligand (RANKL, an apoptosis regulator), and ↓ expression of Osteoprotegerin (OPG, a decoy receptor for RANKL)
↑ osteoclast activity vs osteoblast activityàbone loss
Clonal plasma cells overrun normal bone marrow, crowding out production of red blood cells, ↓ red blood cell counts
Anemia
Authors: Tristan Jones, Tyler Anker, Yan Yu Reviewers: Jennifer Au, Crystal Liu, Man- Chiu Poon*, Lynn Savoie* * MD at time of publication
Damaged bones hurt, & become more brittle
Bony pain, pathologic fractures
Osteolytic bone lesions
Osteoclasts release calcium from bone and into blood
Hypercalcemia
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published January 12, 2020 on www.thecalgaryguide.com