Page 1117 - Clinical Immunology_ Principles and Practice ( PDFDrive )

ChaPter 80 Monoclonal Gammopathies 1081

may also result in anemia. Myeloma patients often present with serum (SPEP) and/or of urine (UPEP) from a 24-hour collection
6
pain and hypercalcemia caused by osteolytic lesions and/or combined with SIF and urine (UIF). SPEP will demonstrate
pathological fractures. Overproduction of M-protein over time a localized band or peak in 82% of patients with myeloma
can contribute to renal failure, hyperviscosity syndrome, and/ (Figs. 80.1 and 80.2).
or recurrent bacterial infections. Addition of serum protein immunofixation electrophoresis
increases the sensitivity to 93%. Adding either the sFLC assay or
Epidemiology urine monoclonal protein studies (UPEP and UIF) increases the
MM accounts for approximately 1% of all cancers and slightly diagnostic sensitivity to 97% or more. The very rare patient who
more than 10% of hematological malignancies in the United lacks detectable M-protein by any of these tests is considered to
States. The annual incidence in the United States is approximately have “nonsecretory myeloma.” Among the 20% with no localized
4 to 5 per 100 000. The incidence of MM in people of African band on SPEP, hypogammaglobulinemia is seen in approximately
background is two to three times that in Caucasians, whereas one-half, with no apparent abnormality in the remainder. 6
the risk is lower in Japanese and in Mexicans. MM is also slightly SIF confirms the presence of an M-protein and determines
more frequent in men than in women with an incidence ratio its type. The malignant plasma cells can produce a complete
of approximately 1.4 : 1. The median age at diagnosis is 66 years; clonal immunoglobulin molecule consisting of heavy and light
only 10% and 2% of patients are diagnosed before 50 and 40 chains, light chains alone, or neither, with the following frequen-
years, respectively. The risk of developing MM is approximately cies on serum immunofixation electrophoresis: IgG 52%, IgA
3.7-fold higher for persons with a first-degree relative diagnosed 21%, IgD 2%, IgM 0.5%, biclonal 2%, kappa or lambda light
with MM. 6 chain only 16%, and negative 17%. 7
Kappa is the predominant light chain compared with lambda
Clinical Presentation by a ratio of 2 to 1, with the exception that lambda light chains
Most patients with MM present with signs and symptoms related are more common in IgD myeloma and myeloma associated
to the infiltration of plasma cells into the bone or other organs with amyloidosis. The level of one of the major uninvolved
as well as kidney damage from excess light chains. Patients often immunoglobulins (i.e., IgM or IgA in the case of IgG myeloma)
complain of fatigue and display pallor upon physical examination. 6 is reduced in 91% of patients overall, and both isotypes are
Bone pain, particularly in the back or chest, and less often reduced in 73%. Up to 20% of myeloma patients have only
in the extremities, is present at the time of diagnosis in approxi- monoclonal light chains in the serum or urine. Approximately
mately 60% of patients. The pain is usually induced by movement 3% of patients with MM have no M-protein in the serum or
and does not occur at night except with change of position. The urine on immunofixation at the time of diagnosis. In approxi-
patient’s height may be reduced by several inches as a result of mately 60% of patients with myeloma who have a normal serum
vertebral collapse. Plasmacytomas of the ribs occur and can and urine immunofixation, monoclonal sFLC can be detected
6
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present either as expanding costal lesions or soft-tissue masses. in the serum using FLC assays. M-proteins can increase the
Radiculopathy, usually in the thoracic or lumbosacral area, is serum viscosity and erythrocyte sedimentation rate (ESR). The
the most common neurological complication of MM and is due ESR is >20 mm/h in 84% and >100 mm/h in one-third of patients
to compression of the nerve by a paravertebral plasmacytoma with MM.
or, in rare instances, by the bone collapse itself. 6 The sFLC assay measures kappa and lambda light chains that
Extramedullary plasmacytomas (EP) are seen in approximately are unbound to heavy chains in the serum. These assays typically
7% of patients with MM at the time of diagnosis. An additional report out three values: quantitation of free kappa chains,
6% of patients will develop EP later during the course of disease, quantitation of free lambda chains, and the kappa/lambda ratio.
and these can present as large, purplish subcutaneous masses. The kappa/lambda ratio is obtained by dividing the free kappa
Spinal cord compression from an extramedullary plasmacytoma value by the free lambda quantitation (For example, the kappa/
or a bone fragment due to fracture of a vertebral body occurs lambda ratio of a patient with a kappa value of 6.32 mg/dL and
in approximately 5% of patients. Intracranial plasmacytomas a lambda value of 0.51 mg/dL would have a kappa/lambda ratio
are rare and almost always represent extensions of myelomatous of 12.4). The kappa/lambda ratio currently plays a key role in
lesions of the skull or plasmacytomas involving the clivus or the diagnosis and management of patients with monoclonal
6
base of the skull. Patients with MM are at increased risk for gammopathies. The normal kappa/lambda FLC ratio is 0.26 to
infection with Streptococcus pneumoniae and gram-negative 1.65. Abnormal FLC ratios outside this range are usually seen
organisms representing the most frequent pathogens. 6 in clonal plasma cell disorders when there is excess production
of one type of light chain (kappa or lambda). Abnormal FLC
Laboratory Findings ratios are seen in approximately 90% of patients with MM.
Biochemical Tests Patients with otherwise asymptomatic myeloma who have an
The serum creatinine concentration is increased in almost one-half involved/uninvolved FLC ratio of 100 or greater have a risk of
of patients at diagnosis. Hypercalcemia was found in 28% of progression to end-organ damage in the next 2 years of approxi-
one series of patients with MM at the time of diagnosis. Serum mately 80%. For this reason, an involved/uninvolved FLC ratio
calcium greater than 11 mg/dL has been found in 13% of patients of 100 or more is now considered diagnostic of MM. 6
and can require emergent treatment. Elevation of the serum
calcium may be due to binding of the monoclonal protein to Hematology
calcium. A low anion gap may be present due to severe hyper- A normocytic, normochromic anemia (hemoglobin ≤12 g/dL)
calcemia and the presence of a cationic IgG molecule. 6 is present in 73% at diagnosis and in 97% at some time during
The vast majority (97%) of patients with MM will have an the course of MM. Macrocytosis (mean corpuscular volume
M-protein produced and secreted by the malignant plasma cells. >100 fL) has been shown to be present in 9% of patients. The most
M-proteins can be detected by protein electrophoresis of the frequent findings on peripheral smear are rouleaux formation,