Chronic lymphocytic leukaemia


Morphology can vary, but there are typical features that can strongly suggest a diagnosis of CLL in many cases. However, a significant proportion of CLL cases have atypical morphology and in those cases careful consideration must be used.



  • CLL morphology is in fact quite variable and several different appearances may each be considered typical
  • Cells are of medium size, cytoplasm is typically pale blue and agranular and may partly flow around adjacent red cells
  • Nuclei appear mature with either clumped or "washed out" chromatin patterns and nucleoli indistinct or absent, they may have an angular appearance
  • Smear cells that represent fragile cells damaged during film preparation are frequently present but are not entirely specific for the diagnosis
  • Look also at red cells - are there any spherocytes, autoimmune haemolysis is frequent in CLL


  • When the circulating B-lymphocyte count is lower than 5x109/ml a diagnosis of monoclonal B lymphocytosis should be considered
  • Where prolymphocytes form more than 10% of cells but fewer than 55% then the mixed condition CLL/PLL may be diagnosed

CLLa large.jpg

Chronic Lymphocytic leukaemia

This film shows many typical features. Not all these lymphocytes are CLL cells. In any film some cells will be normal T cells or B cells (especially when overall counts are not greatly elevated). In this case the cell on the left of the field is different to the others, being smaller with more dense chromatin and deeper blue cytoplasm. This is likely to be a normal lymphocyte.

CLL lymphocytes are fragile and may form smear cells as the film is spread (4 on this image) Remember though that smear cells may be seen in other disorders, although often at lower frequency. The appearance of the CLL cells themselves can vary, but most commonly they are a little bigger than normal lymphocytes with a slightly angular (squared-off) nucleus. Chromatin may have very dense areas alternating with pale regions (described a "mosaic" appearance or "blueberry muffin" viewed from the top) or chromatin can be indistinct ("rag-rolled" appearance). Nucleoli are rarely prominent. The blue/grey cytoplasm is more extensive than in normal lymphocytes, and often touches adjacent erythrocytes (this is a subtle process that differs from the more extensive interaction by activated lymphocytes).

AUDIO COMMENTARY: The morphology of follicular lymphoma cells



CLL is often confidently identified by the typical immunophenotype of the abnormal cells. However, in some instances markers may be atypical and require careful evaluation (particularly in the distinction between CLL and MCL).

Click for a description of the CLL immunophenotype