Serum Free Light Chain Analysis in Plasma Cell Disorders
Serum Free Light Chain Analysis in Plasma Cell Disorders
The study population consisted of 2,799 patients with a median age of 66 years (interquartile range, 26 years), 1,683 (60.1%) of whom were female. Of the 124 patients (4.4% of study population) with plasma cell disorders, 17 had malignant disease (0.6% of study population). Acceptable paired urine samples were received for 579 (20.7%) of the patients in the study cohort.
Of the individual index tests, SPE had the least number (n = 7) of false-negative results Table 1, the highest clinical sensitivity (94.4%), and good specificity (97.9%) for detecting plasma cell disorders Table 2. UPE had the highest specificity (99.2%), with only four false-positive results, but the lowest sensitivity (37.7%). The sFLC assays had poor sensitivity (46.8%) for detecting plasma cell disorders but good specificity (98.9%).
When considering different first-line diagnostic testing strategies involving two index tests, the combination of SPE and sFLC testing had the highest sensitivity (100.0%) and excellent specificity (96.9%). Used together, SPE and UPE had good sensitivity (96.1%) and specificity (95.2%) but lower than the corresponding values for the combination of SPE and sFLC. UPE used together with sFLC testing had the best specificity (97.8%) but poor sensitivity (59.7%). A first-line testing strategy incorporating all three index tests did not improve the sensitivity compared with using just SPE and sFLC testing, while the specificity of using all three index tests was lower (94.0%) than for any two tests in combination (Table 2).
All cases of plasma cell disorders in the study population were detected by a diagnostic testing strategy of SPE and sFLC analysis Figure 1, but seven cases were missed by the combination of SPE and UPE, one of which was malignant disease (light chain deposition disease) Table 3. The other six cases detected only by sFLC testing were patients with MGUS Table 4. However, in three of these six patients, there was discordance between the clonality recognized by serum free light chain testing and serum immunofixation. In each of these cases, the light chain concentration was very close to the detection limit of immunofixation, and intact immunoglobulin MGUS was identified, which was missed by SPE.
(Enlarge Image)
Figure 1.
Study flow diagram showing alternative diagnostic testing strategies for detection of plasma cell disorders in the clinical laboratory. The case of plasmacytoma is in italics for the SPE/UPE testing strategy because although SPE gave a weak positive result, it did not reflect the patient's malignant disease. LCDD, light chain deposition disease; MGUS, monoclonal gammopathy of undetermined significance; sFLC, serum free light chains; SPE, serum protein electrophoresis; UPE, urine protein electrophoresis.
Of the 17 patients diagnosed with plasma cell dyscrasias (Table 3), all had an abnormal sFLC result, 16 had an abnormal SPE result, but BJP was detected in urine samples from only 11 of these patients. Of particular relevance was a patient diagnosed with multiple plasmacytomas; only a small paraprotein was detected by SPE (<2 g/L), but the patient's sFLC result was grossly abnormal (κ = 14.27, λ = 1,652, and κ/λ = 0.01) and reflected the malignant disease present. No urine sample was received for the patient despite requests on reports issued by the clinical laboratory.
Results
Study Population
The study population consisted of 2,799 patients with a median age of 66 years (interquartile range, 26 years), 1,683 (60.1%) of whom were female. Of the 124 patients (4.4% of study population) with plasma cell disorders, 17 had malignant disease (0.6% of study population). Acceptable paired urine samples were received for 579 (20.7%) of the patients in the study cohort.
Diagnostic Accuracy of the Index Tests
Of the individual index tests, SPE had the least number (n = 7) of false-negative results Table 1, the highest clinical sensitivity (94.4%), and good specificity (97.9%) for detecting plasma cell disorders Table 2. UPE had the highest specificity (99.2%), with only four false-positive results, but the lowest sensitivity (37.7%). The sFLC assays had poor sensitivity (46.8%) for detecting plasma cell disorders but good specificity (98.9%).
Diagnostic Accuracy of Different First-line Testing Strategies
When considering different first-line diagnostic testing strategies involving two index tests, the combination of SPE and sFLC testing had the highest sensitivity (100.0%) and excellent specificity (96.9%). Used together, SPE and UPE had good sensitivity (96.1%) and specificity (95.2%) but lower than the corresponding values for the combination of SPE and sFLC. UPE used together with sFLC testing had the best specificity (97.8%) but poor sensitivity (59.7%). A first-line testing strategy incorporating all three index tests did not improve the sensitivity compared with using just SPE and sFLC testing, while the specificity of using all three index tests was lower (94.0%) than for any two tests in combination (Table 2).
Clinical Utility of Different First-line Diagnostic Testing Strategies
All cases of plasma cell disorders in the study population were detected by a diagnostic testing strategy of SPE and sFLC analysis Figure 1, but seven cases were missed by the combination of SPE and UPE, one of which was malignant disease (light chain deposition disease) Table 3. The other six cases detected only by sFLC testing were patients with MGUS Table 4. However, in three of these six patients, there was discordance between the clonality recognized by serum free light chain testing and serum immunofixation. In each of these cases, the light chain concentration was very close to the detection limit of immunofixation, and intact immunoglobulin MGUS was identified, which was missed by SPE.
(Enlarge Image)
Figure 1.
Study flow diagram showing alternative diagnostic testing strategies for detection of plasma cell disorders in the clinical laboratory. The case of plasmacytoma is in italics for the SPE/UPE testing strategy because although SPE gave a weak positive result, it did not reflect the patient's malignant disease. LCDD, light chain deposition disease; MGUS, monoclonal gammopathy of undetermined significance; sFLC, serum free light chains; SPE, serum protein electrophoresis; UPE, urine protein electrophoresis.
Of the 17 patients diagnosed with plasma cell dyscrasias (Table 3), all had an abnormal sFLC result, 16 had an abnormal SPE result, but BJP was detected in urine samples from only 11 of these patients. Of particular relevance was a patient diagnosed with multiple plasmacytomas; only a small paraprotein was detected by SPE (<2 g/L), but the patient's sFLC result was grossly abnormal (κ = 14.27, λ = 1,652, and κ/λ = 0.01) and reflected the malignant disease present. No urine sample was received for the patient despite requests on reports issued by the clinical laboratory.
