Definition of NHL and CLL

Part of the problem here is one of continuing knowledge. It was first believed that CLL and SLL were two different diseases, albeit with some overlapping signs and symptoms. Essentially it was thought that in CLL, the disease began in the bone marrow and eventually spread to the nodes while the reverse was true for SLL. In addition, it was thought that the cells, while morphologically similar, were different.
But - in the past 20 years with the use of flow cytometry and genetic analysis, it turned out that CLL and SLL were quite close, perhaps even the same disease that simply showed up in different places. This observation was part of a huge rearrangement of ideas concerning lymphoproliferative disease in general.
So now we think of lymphoproliferative diseases as a straight line. At one end are the acute leukemias; at the other CLL and SLL. Somewhere in between are the more aggressive forms of disease such as prolymphocytic leukemia or hairy cell leukemia.
And this doesn't mean that CLL and SLL are are the very end of the straight line. there exists a fairly wide variety of presentations within these 2 diseases so that some people only show the "leukemic" phase and other will start with only nodular involvement.
Even the cells themselves will vary so that a person with CLL/SLL may not have the same cells or the same issues as the next person with CLL/SLL.
 

Jo Ann, an answer to your question about the difference between CLL and non-Hodgkin's lymphoma is one that might deserve a Nobel prize. the short answer to why no one responded is that no one truly knows.
We must first start out by saying that there are many presentations of Non-Hodgkin's lymphoma which have little to nothing to do with the classic small resting lymphocyte. They include histiocytes and immunoblasts, etc. So for the rest of these discussion I will be referring to only that 1 presentation of NHL that is characterized by the presence of small, resting, mature appearing lymphocytes and is referred to as small cell lymphoma (SLL).
In the beginning of scientific investigation into diseases, it was fairly easy to divide the two by saying that SLL arises in the lymph nodes and CLL arises in the marrow. But, as our understanding of the immune system revealed in the mid to late 60s, the bone marrow is a lymph node so the highlighted difference became not where the malignancy arose but that in NHL there dominant presentation is in the nodes and in CLL the presentation is in the peripheral blood. And that seemed okay until it was clearly recognized that lymphoma cells are found in the peripheral blood and CLL cells can be seen in nodes. So then the highlighted difference was that these were significantly different cells except, of course, we now know that in many instances, they are the same cells as demonstrated by immune phenotyping. So for now at least, the thought is that Small cell non-Hodgkin's lymphoma and CLL are the two ends of a straight line and no one is comfortable pointing to a place in the middle where one presentation begins and the other stops.
Indeed the new World Health Organization's nomenclature further blurs that difference by suggesting the use of the term CLL/SLL as a disease entity.
 

19 April 2005

CLL and the classification of lymphomas.

There have been so many classifications of lymphomas that Humphrey Kay, the British hematologist, proposed an annual meeting on the Island of Bermuda to produce a new one every year. He was also upset by the habit of defining things by what they are not (non-Hodgkin's lymphoma; acute non-lymphoblastic leukemia) that he wrote a funny poem (published in The Lancet, look it up on PubMed) called Hey-Nonny-No.

Every classification starts with the separation of Hodgkin's disease from the rest which are called non-Hodgkin's lymphoma or NHL. I doubt nowadays whether this is a valid separation, and one of the forms of Hodgkin's disease, lymphocyte predominant, has been reclassified as NHL.

So NHL contains the great bulk of lymphomas and needs to be split up further. The most obvious way is to separate them according to the cell of origin, B cells, T cells and (rarely) NK cells. 85% of NHL are B cell lymphomas. For a long time, especially in America, there were divided into high grade, intermediate grade and low grade. This was known as the working formulation, but because it did not reflect the nature of the disease, just the clinical manifestations, it was not popular among pathologists nor in Europe. In Germany The Kiel Classification developed by Karl Lennert held sway for a long time, but it was too detailed and driven by histopathology minutiae. The REAL (Revised European American Lymphoma) classification was a real advance, and this was revised to become the WHO classification which also incorporated myeloid malignancies, and which currently holds sway.

As far as CLL is concerned, the WHO classification does not go quite far enough. In WHO it is classified as small lymphocytic lymphoma (SLL), though it is an improvement on previous classifications.

In a separate classification the French-American-British (FAB) group of hematologists has classified CLL into typical and atypical types and the atypical type into CLL/PLL and mixed cell type.

SLL and CLL are interchangeable, it simply reflects the different terminology used by histopathologists and hematopathologists. A small caveat is that a very small proportion of patients present with disease only in a lymph node and not in blood or marrow, and these can legitimately be called SLL. In order to mollify both hematologists and histologists the term CLL/SLL is used in America for the whole disease category, though never in the UK.

In my opinion the FAB terminology of typical/atypical CLL is outmoded. What really matters in classifying CLL is VH gene mutations, ZAP-70 and FISH.