The diagnostic algorithm proposed in the classic 1993 study by Rougraff et al. excluded patients with SPEP levels suggestive of myeloma2
. The implication is that a positive SPEP indicates a high likelihood of a plasma cell neoplasm and a negative value insinuates absence of this disease. It has been our general impression that this is not the cause. Our goal was to calculate the sensitivity, specificity, positive predictive value, and nega-tive predictive value of serum protein electrophoresis in the population of patients presenting for evaluation of a radiolucent bone lesion of unknown etiology. Determina-tion of the inherent characteristics of this test allows for further discussion regarding the necessity and timing of the SPEP in these patients.
The main limitation of this study is that it is a ret-rospective review. This is problematic because it is dependent upon accurate data entry at the time of patient presentation. Another weakness is the possibil-ity that some selection bias has been incorporated into our patient group. An overall prevalence of a plasma cell neoplasm of 25% is quite high, as previous studies have indicated a prevalence of 17%7,8
. It is possible that patients were selected to have an SPEP lab drawn by the practitioner only if there were radiographic and clinical history characteristics consistent with multiple myeloma. Although this would undoubtedly introduce a selection bias, it should theoretically bias our results towards an improved diagnostic performance of the SPEP (i.e. improved PPV).
Our primary goal was to evaluate the diagnostic per-formance of the SPEP in the setting of a lytic lesion of unknown origin. It has been suggested that the SPEP alone is not a definitive test for myeloma, as a review of 1027 patients from the Mayo Clinic noted a positive SPEP in only 83% of the new diagnoses10
. We found a sensitivity of 73% and a specificity of 81% when analyzing patients presenting with a lytic bone lesion who were eventually diagnosed with a plasma cell neoplasm. That same study from the Mayo Clinic, however, did note an improved diagnostic accuracy when incorporating the urine protein electrophoresis (UPEP), immunofixation electrophoresis (IFE) and free-light chain (FLC) assay10
. Although there are no defined “acceptable” values for a diagnostic test, obviously the goal is to optimize both the sensitivity and specificity to prove that the test is reliable, reproducible, and accurate. For example, a widely used diagnostic tool, computed tomography (CT) scanning, has been shown in some studies to have 100% sensitivity and 98.9% specificity in the diagnosis of acute appendicitis11
. Our results indicate that the SPEP has suboptimal performance as a definitive diagnostic test in isolation.
However, when compared to screening tests (studies performed in an asymptomatic population at risk of a disease), it performed similarly. For example, a prostate specific antigen (PSA) value of greater than 4 ng/mL has a sensitivity of 21% and specificity of 91% in the screening of prostate cancer12,13
. PPV and NPV are reported at 30% and 85%, respectively. Mammography for breast cancer screening has been shown to have a sensitivity of 70% and specificity of 92% with a PPV of 5%9
. For a screening test to be a good one, it should have a high specificity, or very low false positive rate. Although the SPEP is not truly a screening test, as it is being performed because a clinical finding prompted further work-up, it is help-ful to consider its performance in this context. When viewed as such, it performs reasonably well to “rule out” multiple myeloma. A negative predictive value of 94% shows that, when negative, the SPEP reliably indicates a low likelihood of the diagnosis of myeloma in patients presenting with at least one lytic bone lesion.
As a secondary outcome we were interested in the diagnostic performance of the SPEP in patients present-ing with multiple lytic lesions. It would seem logical that this would enhance the diagnostic performance of the SPEP as those with multiple lytic lesions would be more likely to have a diagnosis of myeloma; however, our data indicates that this was not the case. The performance was essentially unchanged, with sensitivity and specific-ity of 71% and 79%, respectively.
Additionally, we found that there was a trend towards larger absolute values of monoclonal spikes in the patients with a “positive” SPEP in the patients with a diagnosis of a plasma cell neoplasm compared to those with a false positive (p=0.07). Although the total num-bers are relatively small, the wide range in values for the SPEP for each group (true and false positives) and the presence of several histologically confirmed cases of a plasma cell neoplasm with no measurable SPEP further supports the notion that this test is lacking substantially in terms of diagnostic performance.
It is interesting to note that our comparison screening tests (PSA and mammography) are quite controversial in their clinical utility. Both have both been publicly criticized as unhelpful in the overall care of patients, even though their inherent characteristics may be acceptably accurate14,15
. One may make a similar argument in this example, as an SPEP value at the initial evaluation of these patients means little by itself. Our data indicate that SPEP lacks the sensitivity, specificity, PPV, and NPV characteristic of a good diagnostic test; however, it may have some utility in ruling out myeloma at initial presentation. Given that plasma cell neoplasms are readily characterized on histopathologic exam without knowledge of the SPEP result, our findings raise the question of whether this test should be used at all prior to a histologically confirmed diagnosis of a plasma cell neoplasm. This test may be best utilized as a baseline, after
a confirmatory biopsy, by which to measure the response to therapy16
. Alternatively, if the SPEP is to be used in the work-up of a patient with a lytic bone lesion, it should be combined with UPEP, IFE and FLC assay so as to avoid the diagnostic errors that our data indicates would ensue from reliance upon SPEP alone.