VII. TEACHING POINTS

1. A monoclonal (M-) protein increase consists of an excess of one type of heavy chain and one type of light chain. A polyclonal gammopathy usually consists of more than one type of heavy chain and both κ (kappa) and λ (lambda) light chains.
2. The differentiation of a monoclonal and polyclonal increase in immunoglobulins is essential. Patients with a monoclonal increase of immunoglobulins have either a neoplastic process or a potentially malignant disease, whereas patients with a polyclonal increase in immunoglobulins have a reactive or inflammatory process.
3. Typically, a monoclonal protein is characterized by a tall, narrow-based spike on the densitometer pattern, or a localized band on the agarose gel when serum is electrophoresed. However, a small monoclonal protein in the serum may be obscured by normal components. Immunofixation is needed to determine whether a monoclonal protein is present and to determine its type.
4. A 24-hour urine specimen must be collected and measured for total protein, electrophoresis, and immunofixation. Again, small amounts of monoclonal light chain may not produce a spike. Consequently, immunofixation of an adequately concentrated urine specimen is needed.
5. Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM), and Multiple Myeloma each have specific criteria for diagnosis, and it is important for the physician to characterize these diseases accurately and to plan treatment (observation versus drug-therapy).
6. Multiple myeloma is characterized by end-organ damage. (A mnemonic for end-organ damage is: CRAB = hypercalcemia, renal insufficiency, anemia and lytic bone lesions.) Physicians should try to diagnose patients prior to the development of these.
7. Patients who are candidates for autologous peripheral stem cell transplant will have their initial treatment individualized in order to avoid certain agents that would cause difficulty in harvesting stem cells later on.
8. The amount of monoclonal protein in the urine is a direct reflection of the number of monoclonal plasma cells in the bone marrow and is thus a measure of tumor mass.
9. The presence of a monoclonal light chain in the urine of a patient with nephrotic syndrome is almost always associated with primary amyloidosis (AL) or light chain deposition disease.
10. The presence of a monoclonal protein in the serum or in the urine of a patient with an unexplained nephrotic syndrome, congestive heart failure, sensorimotor peripheral neuropathy, carpal tunnel syndrome, or orthostatic hypotension is strongly suggestive of primary amyloidosis (AL).
11. Tissue must be obtained to make a diagnosis of primary amyloidosis. A subcutaneous fat aspirate and/or a positive bone marrow stain for amyloid is found in 90% of patients. If the clinician still suspects primary amyloidosis in a patient with a negative subcutaneous fat aspirate and bone marrow biopsy, he/she should obtain tissue from a clinically involved organ.

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