32.5. Use of sFLC and HLC analysis to differentiate IgM MGUS, asymptomatic WM and WM

Chapter 32

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 [668]. New evidence suggests that FLC and HLC analysis may allow improved discrimination between these conditions.

Leleu et al. [668] 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. [724].

In a separate report, Andrade-Campos et al. [950] 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.


  1. Why are sFLCs useful for monitoring WM patients with cryoglobulinaemia?
  2. Is sFLC and HLC analysis included in international WM guidelines?


  1. Because sFLCs do not cryoprecipitate (Section 32.3).
  2. Yes, guidelines state that whilst they are not essential for the routine management of WM patients, further prospective evaluation is encouraged (Sections 32.3.2,32.4.1 and 32.4.2)[703].