Accurate diagnosis of WM is difficult in some cases, due to the ill-defined overlap of clinical features between WM and two related conditions i.e. IgM monoclonal gammopathy of undetermined significance (IgM MGUS), and asymptomatic WM . New evidence suggests that FLC and HLC analysis may allow improved discrimination between these conditions.
Leleu et al.  compared involved sFLC concentrations in WM (n=98) and IgM MGUS (n=68). An abnormal κ/λ sFLC ratio was present in 76.5% and 23.5% of WM and IgM MGUS patients, respectively (p<0.001). Involved FLC concentrations were significantly higher in WM (median = 36 mg/L; range 16 - 140 mg/L) than in IgM MGUS (median 20 mg/L; range 16 - 33 mg/L): p<0.0003. Leleu and colleagues concluded that a sFLC cut-off of 60 mg/L separated WM from IgM MGUS with >95% specificity. Similar findings were also reported by Murillo-Florez et al. .
In a separate report, Andrade-Campos et al.  compared IgM HLC results from 19 WM patients and 32 asymptomatic WM with those of 39 IgM MGUS patients. The median involved/uninvolved HLC ratio was significantly higher in WM (117.5), than asymptomatic WM (62.1) or IgM MGUS (16.1; p=0.0002) patients. Furthermore, the proportion of patients with HLC pair suppression was significantly higher in WM (83.3%) and asymptomatic WM (64.3%) than IgM MGUS (46.2%, both p=0.0002). Further work is now required to study the combined use of FLC and HLC analysis to better discriminate WM and IgM MGUS.