Plasma Cell Disorders & Histiocytosis

Question 1

What are the three major plasma cell disorders?

Answer 1

• multiple myeloma: malignant proliferation of plasma cells in the bone marrow (usually IgG or IgA)
• MGUS (monoclonal gammopathy of undetermined significance): essentially an asymptomatic precursor to multiple myeloma
• Waldenstrom macroglobulinemia: a B-cell lymphoma that produces monoclonal IgM antibodies

Question 2

What is the most common primary malignancy of bone? An increase in which factor drives most cases of this disease? What three things do the malignant cells produce/secrete? What results from each?

Answer 2

• multiple myeloma is the most common primary bone malignancy!
• this is a proliferation of plasma cells in the bone marrow (anemia can result due to decreased room)
• most cases are driven by an increase in IL-6
• the malignant cells produce osteoclast stimulating factor (IL-1), immunoglobulins (60% make IgG, 20% IgA), and free light-chain (20% of cases have just the light-chain without the antibodies)
• stimulation of osteoclasts: bone pain, hypercalcemia, lytic lesions on x-ray, pathologic fractures
• Ig production: M-spike (monoclonal antibody) on electrophoresis; monoclonal nature results in an increased risk of infection
• overproduction of free light-chain: amyloidosis and Bence-Jones proteinuria (free light-chains in urine); can lead to renal failure (“myeloma kidney”)

Question 3

What is SPEP? How does it compare in normal patients vs. patients with multiple myeloma?

Answer 3

• SPEP is serum protein electrophoresis
• in normal patients: the gamma band (representing the immunoglobulins) is wide and shallow (not nearly as tall as the albumin band)
• in multiple myeloma: the gamma band is narrow and as tall if not taller than the albumin band (indicates large amount of a monoclonal antibody); this is called an M-spike (M stands for monoclonal, NOT IgM; most cases involve IgG or IgA)

Question 4

What is the Rouleaux formation?

Answer 4

• the Rouleaux formation is a sign of excess plasma protein (as seen in multiple myeloma) on blood smear
• the excess proteins interfere with the charge between RBCs, resulting in an uneven piling up of these cells on blood smear

Question 5

What is MGUS? What percent of cases will develop into multiple myeloma each year?

Answer 5

• monoclonal gammopathy of undetermined significance
• MGUS is characterized by an M-spike on SPEP, but without any symptoms associated with multiple myeloma
• it is essentially an asymptomatic precursor to multiple myeloma; 1-2% of cases evolve into multiple myeloma each year

Question 6

What is Waldenstrom macroglobulinemia? Why is it called a “macro” globulinemia? How do patients present?

Answer 6

• this is a B-cell lymphoma with monoclonal IgM production
• IgM forms a pentamer, hence the name of the disease entailing “macro”globulinemia
• patients present with an M-spike on SPEP, generalized lymphadenopathy, and have bleeding, visual, and neurological defects due to the increased viscosity of the blood (because of the increased IgM pentamers)
• patients do NOT have the bone lesions/involvement that is seen in multiple myeloma

Question 7

How do patients with multiple myeloma classically present? What does BM aspiration reveal?

Answer 7

• C.R.A.B.
• hyperCalcemia, Renal insufficiency, Anemia, Bone lytic lesions
• others: back pain, infection, AL amyloidosis, peripheral neuropathy, hyperviscosity (headaches, bleeding, thrombosis, blurred vision, CHF; hyperviscosity more associated with Waldenstrom macroglobulinemia)
• BM aspiration reveals more than 10% monoclonal plasma cells