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The International Workshop on CLL (IwCLL) recommends that a diagnosis of CLL is confirmed by haematopathology (blood count and blood smear) and a combination of immunophenotyping and flow cytometric studies to establish the clonality of B lymphocytes.¹

 

The minimum requirement for a diagnosis of CLL is the presence of ≥5 x 10⁹/l B lymphocytes (5,000/µl) in the peripheral blood, sustained for at least 3 months.¹

B cells are characteristically small, round and mature cells with a narrow or no cytoplasmic border and a dense nucleus containing clumped chromatin (nucleoli are indistinct or absent). Other cell types that may be found among the B cells are smudge cells (Gumprecht’s Shadows), larger/atypical or cleaved cells, and prolymphocytic (PL) cells. Increasing numbers of PL cells are generally associated with a more aggressive disease course.

 

Cell surface markers such as CD5, CD23, CD20 and FMC7 may be abnormally expressed in CLL, and can be used to verify a diagnosis and differentiate between CLL and other lymphoproliferative disorders.

A number of additional diagnostic tests are available. These can help to predict patient outcomes and assess tumour burden (but not to determine treatment).

 

Cytogenetics

A number of chromosomal aberrations are now used as prognostic indicators of CLL outcome, and some translocations can be used in the differential diagnosis of CLL from other lymphoproliferative disorders, e.g. t(11:14) which is usually found in mantle cell lymphoma.¹

 

IgV_H mutational status

Around 50% of CLL patients’ leukaemic cells contain somatic mutations in the variable regions of the immunoglobulin heavy chain (IgV_H). Patients lacking a somatic mutation in this region tend to have a more progressive and advanced form of CLL than patients with mutated IgV_H.²

 

ZAP-70 and CD38 expression

Expression of ZAP-70 and CD38 on CLL B cells indicates a poor prognosis. Evaluation of CD38 expression can be performed using immunophenotyping and flow cytometry, whereas ZAP-70 expression can be detected using a variety of techniques including flow cytometry.

 

Serum markers

A number of serum markers (e.g. soluble CD23) can provide prognostic information about disease progression and survival. The IWCLL recommends that assays for serum markers should be standardised and tested in prospective clinical trials to assess their value in the treatment of CLL.¹

 

Bone marrow biopsy

The extent and pattern (diffuse versus non-diffuse) of the marrow infiltration by CLL can be assessed, and this provides information on tumour burden as well as an evaluation of factors that may contribute to cytopenias.¹

 

References

1. Hallek M, Cheson BD, Catovsky D, et al. Blood 2008;111;5446–5456.
2. Hamblin TJ, Davis Z, Gardiner A, et al. Blood 1999;94:1848–1854.