The largest study that compared the relative diagnostic contributions of serum and urine assays in the detection of plasma cell proliferative disorders was reported by Katzmann and colleagues . Samples from 1,877 untreated patients diagnosed with various plasma proliferative diseases underwent a full panel of five screening tests (SPE, UPE, sIFE, uIFE and sFLCs; Table 23.1). This allowed different screening protocols to be compared, and addressed the question of whether sFLC analyses could replace urine studies.
|Diagnosis||n||Diagnostic performance (% sensitivity)|
|All 5 tests||SPE, sIFE & uIFE||SPE, sIFE & sFLC||SPE & sFLC||sIFE||SPE||sFLC|
|Primary AL amyloidosis||581||98.1||94.2||97.1||96.2||73.8||65.9||88.3|
Table 23.1. Sensitivity of monoclonal gammopathy screening panels . MM: multiple myeloma; WM: Waldenström’s macroglobulinaemia; SMM: smouldering multiple myeloma; MGUS: monoclonal gammopathy of undetermined significance; LCDD: light chain deposition disease.
The combined results from all five tests identified 1,851 (98.6%) samples as abnormal. Of those not detected, 11 were AL amyloidosis (1.9% of total), 8 extramedullary plasmacytoma (80%), 3 plasmacytoma (10.3%), 3 light chain deposition disease (LCDD, 16.7%) and 1 POEMS syndrome (3%).
The same data are used to produce a simpler comparison of different potential screening panels in Table 23.2. The table quantifies the nature and number of additional diagnoses that would have been missed if alternative screening panels had been used (compared with the use of all five tests). The major differences were that omission of sFLC analysis from the panel resulted in six additional MM and 23 additional primary amyloidosis patients being undetected whereas the inclusion of sFLCs but omission of urine analysis resulted in 15 additional MGUS and six amyloidosis patients being undetected.
Palladini et al.  also found that uIFE, sIFE and sFLCs are necessary for the optimal detection of amyloidosis. Katzmann and colleagues commented that MGUS patients with negative SPE results and normal sFLC ratios (i.e. the 15 detected only by urinalysis) would all be defined as having a low risk of progression, and the consequences of failing to identify them were unlikely to be severe . Furthermore, the authors concluded that because urine studies and sIFE gave only a small incremental increase in sensitivity, SPE plus sFLCs provide an efficient initial diagnostic screen for monoclonal gammopathies with a high tumour burden such as MM, smouldering multiple myeloma (SMM) and Waldenström’s macroglobulinaemia (with sIFE used only as a reflex test).
|Diagnosis||n||Alternative test panels with associated missed diagnoses|
|SPE, sIFE, UPE, uIFE, sFLC||SPE, sIFE, UPE, uIFE||SPE, sIFE & sFLC||SPE (with reflex sIFE) & sFLC|
|Primary AL amyloidosis||581||0||23||6||11|
Table 23.2. Diagnoses that would have been missed using alternative test panels compared with the use of all five diagnostic tests . MM: multiple myeloma; WM: Waldenström’s macroglobulinaemia; SMM: smouldering multiple myeloma; MGUS: monoclonal gammopathy of undetermined significance; LCDD: light chain deposition disease.
An earlier, smaller study was designed specifically to address whether sFLC analysis could eliminate the need for urine testing when screening for monoclonal gammopathies . In this investigation, records from 428 patients with a monoclonal gammopathy and positive uIFE (at presentation) were examined to determine whether sIFE and sFLC analysis had also been positive. Only two (0.5%) patients were negative by both sIFE and sFLC, and further investigation indicated that the urine of one had almost certainly been contaminated with monoclonal immunoglobulin in the laboratory, while the other patient had a light chain MGUS and did not require medical intervention. This suggested that the addition of sFLC analysis to SPE and sIFE made the inclusion of urine tests unnecessary in a screening algorithm for monoclonal gammopathies.
The overall findings of both studies provide significant support for the IMWG recommendations, which state that initial screening should use a combination of serum electrophoresis and sFLC tests, with uIFE required only to maximise sensitivity when AL amyloidosis is suspected (Chapter 25) .