Diagnosis

A definitive diagnosis of CLL is achieved through a combination of a lymphocytosis and characteristic lymphocyte morphology and immuno-phenotype (1,2,3).

Although a lymphocyte count of >5 x 10^9/l is classically considered to be the arbitrary threshold for the diagnosis of CLL, the diagnosis relies on the presence of a chronic, absolute increase in blood lymphocytes together with morphologic and immunophenotypic characteristics

The International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) proposed the following criteria for the diagnosis of CLL (based on modified criteria proposed originally by the National Cancer Institute):

• peripheral blood lymphocytes (x 109/l) -
  • not specified (a lower value than 5 × 10^9/L, is acceptable provided there is chronic, absolute increase in blood lymphocytes with the characteristic morphology and immuno-phenotype)
    
    
• morphology -
  • small mature lymphocytes without visible nucleoli
  • smudge cells
    
    
• immuno-phenotype of lymphocytes
  • >=1 B cell marker (CD19, CD 20 or CD 23) and CD 5 positivity in the absence of other pan-T-cell marker
  • monoclonal expression of either kappa or lambda immunoglobulin light chains
  • low density surface Ig
    
    
• atypical cells (e.g. - prolymphocytes)
  • <55% and/or <15 x 109/l
    
    
• duration of lymphocytosis
  • not specified but needs to be chronic
    
    
• bone marrow lymphocytes (%)
  • bone marrow evaluation not required (bone marrow evaluation is no longer required for the diagnosis but useful to determine extent and pattern of involvement and clarification of aetiology of cytopenias)

References:

1. Eichhorst B, Robak T, Montserrat E, et al; ESMO Guidelines Committee. Chronic lymphocytic leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021 Jan;32(1):23-33.
2. Hallek M, Al-Sawaf O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. Am J Hematol. 2021 Dec 1;96(12):1679-705.
3. Walewska R, Parry-Jones N, Eyre TA, et al. Guideline for the treatment of chronic lymphocytic leukaemia. Br J Haematol. 2022 Jun;197(5):544-57.