Plasma cell disorders are a group of hematological malignancies that primarily occur in the elderly, and are characterized by unregulated proliferation of plasma cells in the bone marrow.
They include multiple myeloma, monoclonal gammopathy of unknown significance or MGUS, and Waldenström’s macroglobulinemia.
Each of them produces a monoclonal or M-protein, which is a unique protein of a single type, like a protein “clone”.
In multiple myeloma the most common M-protein that’s produced is IgG, followed by IgA - and these M-proteins have both a heavy and light chain.
More rarely, the myeloma cells only make the kappa or lambda light chain of the immunoglobulin, and in that situation, the resulting protein is called the Bence-Jones protein.
The clinical presentation of multiple myeloma can be summarized by the mnemonic CRAB, where “C” is for hypercalcemia resulting from increased osteoclast activity due to the release of osteoclast activating factor from the plasma cells.
“R” is for renal disease, which is generally due to the light chains depositing and obstructing the renal tubules - this is called light chain cast nephropathy or myeloma kidney.
Renal disease can also be due to type two renal tubular acidosis, secondary amyloidosis, or even hypercalcemia.
“A” is for anemia, which causes fatigue and shortness of breath, and is often due to infiltration of the bone marrow by the plasma cells.
And finally, “B” is for bone pain, which is due to increased osteoclast activity causing lytic bone lesions.
Other manifestations include spinal cord compression if the tumor infiltrates from the vertebrae, and infections, because the immunoglobulins produced by the malignant plasma cells are not useful in fighting infections.
A workup for multiple myeloma includes a CBC, which often shows normocytic normochromic anemia, and a peripheral smear, which can show a rouleaux formation due to IgG proteins attaching to red blood cell membranes, and then connecting with other red blood cell membranes, making the red blood cells stick to one other, causing them to look like a stack of coins.
Additionally, serum calcium levels, blood urea nitrogen, and creatinine concentrations may be elevated.
Also uric acid levels may be elevated due to increase cell turnover.
Serum and urine protein electrophoresis, or SPEP and UPEP, respectively, are important to see which M protein is predominantly being produced, and is seen as an M-spike.
SPEP detects most multiple myeloma patients that predominantly make IgG, followed by IgA, while UPEP is used to detect the minority of multiple myeloma patients, who only make the Bence-Jones protein.
UPEP is needed because these light chains are rapidly filtered from the blood, so they may not be seen on SPEP.
A urine dipstick is not sufficient, as it only detects albumin.
Also beta-2 microglobulin, a component of the major histocompatibility class 1 antigens found on all nucleated cells, can be shed in the serum.
Serum levels of beta-2 microglobulin are checked in multiple myeloma, because the higher they are, the higher the severity of the disease.
Then, a skeletal radiographic survey should be done to look for “punched out” lytic lesions.
A bone scan should not be obtained, as it only detects osteoblastic lesions, not osteolytic lesions.
Finally, a bone marrow aspiration and biopsy must be obtained, to look for more than 10% plasma cells which infiltrate into the bone marrow.
Now, three criteria must be met to diagnose multiple myeloma.
First, at least one of the CRAB symptoms.
Second, M-protein in either the urine or serum.
And third, more than 10% plasma cells in the bone marrow.
