Diagnosis

A large proportion of patients with chronic lymphocytic leukaemia (CLL) are diagnosed incidentally following a routine full blood count. The diagnosis of CLL is currently established by the following criteria (Eichhorst et al., 2015; Hallek, 2017; Oscier et al., 2012):

  • Presence of ≥ 5 x 109/L monoclonal B cells in peripheral blood persisting for at least 3 months.
  • Lymphocyte morphology: in a blood smear, leukaemic cell characteristics include small, mature lymphocytes with a narrow cytoplasmic border, dense nucleus with no discernible nucleoli and partially aggregated chromatin.

Differential Diagnosis

Chronic lymphocytic leukaemia (CLL) B cells co-express the cell surface antigens CD5, CD19, CD20 and CD23 as well as having characteristically low levels of cell surface immunoglobulins CD20 and CD79b. Each clone of leukaemia cells is limited to expression of either kappa or lambda light chains. Differential diagnosis from other CD5+ lymphoproliferative disorders such as mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), hairy cell leukaemia (HCL), follicular lymphoma, immunocytoma, small lymphocytic leukaemia (SLL) and monoclonal B-lymphocytosis (MBL) is required. Therefore, additional investigations, including cytogenetic analysis, immunophenotyping and histology, may be required. Differences between CLL, SLL and MBL are outlined in Table 1 (Eichhorst et al., 2015; Hallek et al., 2008; Hallek, 2017; Oscier et al., 2012):

Table 1: Distinguishing between CLL, MBL and SLL (Oscier et.al., 2012).
Criteria CLL MBL SLL

Clonal B lymphocytes >5 x 109/L

Y

N

N

Disease-related cytopenias

Y/N

N

Y/N

B symptoms

Y/N

N

Y/N

Lymphadenopathy and/or splenomegaly

Y/N

N

Y

CLL, chronic lymphocytic leukaemia; MBL, monoclonal B cell lymphocytosis; SLL, small lymphocytic leukaemia; Y, yes; N, no.

Furthermore, patients with bulky or progressive asymmetric lymphadenopathy, high serum lactate dehydrogenase (LDH), extranodal lesions and/or unexplained B symptoms may have lymphomatous transformation (Richter’s transformation), which develops in 5-15% of patients with CLL (Oscier et al., 2012).