33.2. Monoclonal and polyclonal sFLCs in CLL

Chapter 33

CLL is thought to originate from the expansion of an antigen-activated B-cell clone. Persistent immune stimulation and polyclonal B-cell activation/dysfunction may play an important role in its pathogenesis [730]. This is supported by research demonstrating that increased concentrations of both monoclonal and polyclonal free light chains (FLCs) exist up to 10 years prior to CLL diagnosis [731].

FLCs are the most commonly detected serum monoclonal proteins in CLL, with an abnormal sFLC ratio being reported in 30 - 40% of patients [675][671][732][673]. By comparison, Maurer et al. [673] reported 16% of patients with a monoclonal protein detected by serum protein electrophoresis. In several published plasma cell disease screening studies, addition of sFLC analysis to the testing panel has identified additional CLL patients (Chapter 23) [501][188][129]. Therefore, identification of abnormal sFLC ratios in screening samples should prompt the consideration of other lymphoproliferative disorders, particularly CLL, in addition to plasma cell dyscrasias.

Maurer et al. [673] characterised both monoclonal and polyclonal FLC abnormalities in 339 newly diagnosed, untreated CLL patients. They defined three different types of FLC abnormality: monoclonal FLC elevation, polyclonal FLC elevation and ratio-only abnormality (Table 33.1).

Abnormality κ and λ concentration κ/λ sFLC ratio Number of patients
Monoclonal sFLC elevation
Elevated κ and/or λ
57 (17%)
Polyclonal sFLC elevation
Elevated κ and/or λ
52 (15%)
Ratio-only abnormality
Normal κ and λ
54 (16%)
Any abnormality
163 (48%)

Table 33.1. sFLC abnormalities in newly diagnosed CLL patients [673].

In patients with an abnormal sFLC ratio (ratio-only abnormality or a monoclonal FLC elevation), the involved sFLC type matched the CLL B-cell light chain restriction in 92% and 96% of cases, respectively [673]. Such findings suggest that an abnormal sFLC ratio is disease-related in the majority of cases. Morabito et al. [675] studied the distribution of monoclonal and polyclonal FLC synthesis in the CLL tumour microenvironment by immunohistochemistry. Lymph node infiltrates comprised a prominent population of plasmacytoid lymphocytes expressing the involved FLC, along with a smaller number of lymphocytes expressing the corresponding uninvolved FLC. These lymphocytes populated the same infiltrates in the lymph node and bone marrow, and were associated with scattered FLC-producing plasma cells (Figure 33.1).

Polyclonal B-cell activation found in CLL also underlies the pathogenesis of some inflammatory/autoimmune conditions (Chapter 35). Interestingly, both CLL and inflammatory/autoimmune conditions may be associated with lymphomatous transformation. This occurs in approximately 5 - 15% of CLL patients, and histologically resembles diffuse large B-cell lymphoma or Hodgkin lymphoma (Chapter 31) [726].