The diagnosis of CLL is easy, but the criteria for the diagnosis have recently changed. The first thing that is necessary is a raised lymphocyte count. Back in the days when I started in CLL you needed 15,000 lymphocytes per microlitre for the diagnosis. Gradually this was reduced, first to 10,000 and then to 5000. In fact the upper limit of normal for lymphocytes is either 3,500 or 4000, depending on which set of normal values you go by, so we might have suspected CLL even if the lymphocyte count were less than 5000.
The second requirement is the peculiar immunophenotype of CLL. The cells must be positive for CD5, CD19 and CD23, have low levels of surface immunoglobulin and CD79b and be FMC7 negative. There is actually a CLL scoring system that gives 1 point for each of these (except CD19 which is present on all B cells tumors). A score of 4 or 5 is required for the diagnosis of CLL. Very occasionally a true CLL will only score 3, but these really are exceptional cases that require an expert eye over them.
I will say more about this when we talk about the differential diagnosis (that just means answering the question, "If it's not CLL, what else could it be?").
It is also necessary to demonstrate monoclonality. To be accurate, we don't actually demonstrate monoclonality, but instead take advantage of the fact that the immunoglobulin molecules can have one of two possible types of light chains, called kappa or lambda (those are just the Greek letters that stand for 'K' or 'L'). Normal B cell sometimes have kappa light chains and sometimes lambda light chains; usually the ration is 2 kappa for each lambda. Since CLL cells are derived from a single cells, in any individual all the CLL cells have a single light chain, either kappa or lambda.
The thing that has changed has been the threshold count. Instead of 5000 lymphocytes per microlitre, now you must have 5000 B-cells per microlitre. Since many cases of CLL have well in excess of 4000 T-cells per microlitre, this equates to a lymphocyte count of at least 8000 and sometimes as much as 15,000 per microlitre.
This all sounds like a circular route back to 1975. But the reason for the redefinition is clear. I have been saying for some time now that many cases of stage 0 CLL live out a normal life span and never require treatment - to label such patients as having leukemia is unnecessarily frightening. Especially since Andy Rawstron discovered monoclonal B cell lymphocytosis, which I will write about tomorrow.