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The Curious Case of CLL and SLL: Leukemia, Lymphoma, or Both?

The Curious Case of CLL and SLL: Leukemia, Lymphoma, or Both?
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Published on April 29, 2021

Understanding the Connection Between CLL and SLL

Let’s be absolutely clear — the naming system of the different types of blood cancer sucks. There are lots of three-letter acronyms that don’t even follow the same naming convention for all subtypes. The classification of blood cancers is based on which cell type the cancer cells originated from and, in many cases, what they look like under the microscope.

You can see on the diagram below where the different names come from. Don’t worry — you won’t be tested! A huge number of different types of blood cancer come from the B lymphocytes. This includes almost all Hodgkin and non-Hodgkin lymphomas (with the exception of the rare T-cell and NK lymphomas) and one of the leukemias, CLL (chronic lymphocytic leukemia).

Blood Cancer Family Tree

Illustration is courtesy of Adrian Warnock

For the sake of clarity, let’s call all of these subtypes lymphocyte blood cancers. The lymphocytes are designed to mutate during their maturation phase so that the body can produce many different types of antibodies. They are also designed to grow really rapidly when their antibody is needed. No wonder lymphocytes can be the source of so many very different types of blood cancer. Some of these are acute, aggressive, and fast-growing. Others are chronic, indolent, and slow-growing.

One type of lymphocyte blood cancer that causes confusion has two names: small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL). For more than 20 years, what was once thought to be two different diseases has been considered as one. And to make matters worse, this disease is both a leukemia and a type of non-Hodgkin lymphoma (NHL). No wonder it gets confusing. I discovered one person on a forum whose doctor informed him/her that he/she had four separate types of blood cancer: leukemia, CLL, SLL, and NHL. That must have been worrying! In reality, this is all the same disease.

Unfortunately, many patient information sites don’t make this point as clearly as we would like. Here is a clearer explanation that includes citations from official medical journal articles and refers to the WHO definitions of CLL and SLL.

CLL involves your blood, your bone marrow, and sometimes your lymph nodes. On the other hand, SLL typically involves the lymph nodes and sometimes your bone marrow. That said, if you have CLL (there is blood involvement) and it includes lymph node growth, the CLL diagnosis supersedes and replaces the SLL diagnosis.

It’s amazing to me how even some doctors seem to get confused with all of this or communicate in a way that is confusing to patients. It’s very possible that many people with CLL originally had cancerous lymphocytes that started to grow in their lymph nodes. Under the microscope, these cells look small, and if they are found in a lymph node they will be described as having the appearance of “small lymphocytic lymphoma.” When those cells spill out into the blood and grow there as well, then it is called CLL. It’s really a lymphoma that wants to be a leukemia in most people. So, it’s not possible to have both diagnoses at once. It’s only called SLL if it isn’t in your blood.

Sometimes on biopsy reports, doctors will write “has the appearance of CLL / SLL,” either to indicate the single combined condition (as SLL is considered the same disease as CLL) or to make it clear that, on the basis of looking at the biopsy alone, you can’t tell the difference. Unless the person writing the report knows what your lymphocyte count is in your blood, they can’t specify which diagnosis is correct. The small cells they see under the microscope look exactly the same, whether or not they are also growing in the blood.

For more than 20 years we have only used SLL to describe a variation of CLL that for some reason doesn’t grow in the blood. Any doctor who has left you with the idea that you have two separate cancers is either confused themself or has not explained it very well. CLL is a crazy confusing cancer that cannot decide if it wants to be a leukemia or a lymphoma, so in most people it is both.

On Patient Power, one of the top CLL experts, Dr. Nicole Lamanna, explains it as follows:

“They’re a disorder of the same B cell. Under the microscope, they’re exactly the same . . . But SLL patients are truly patients who have just lymph node involvement… you might actually have some bone marrow involvement.”1

Here are a few other credible quotes that explain this further:

“To diagnose chronic lymphocytic leukemia (CLL), there needs to be ≥5,000 monoclonal (genetically identical) B-lymphocytes (a type of white blood cell) in the blood for the duration of at least three months . . . Small lymphocytic lymphoma (SLL) and CLL are considered to be the same disease (at least since 1994). The diagnosis of SLL requires the finding of enlarged lymph nodes and/or an enlarged spleen with less than 5,000 B-lymphocytes in the blood. SLL cells show the identical immunophenotype (cell surface fingerprint) as CLL cells. The diagnosis of SLL should be confirmed by lymph node biopsy. CLL/SLL is considered both a lymphoma and leukemia.”2

“Chronic lymphocytic leukemia cells have a distinctive immunophenotype, and the disease has a characteristic pattern of histological infiltration in the lymph node and bone marrow… Some patients may present solely with lymphadenopathy, organomegaly, and presence of infiltrating monoclonal B cells with the same immunophenotype as CLL cells but lacking peripheral blood lymphocytosis. This disease is called small lymphocytic lymphoma (SLL) and has been considered for almost two decades to be the tissue equivalent of CLL. Both CLL and SLL are currently considered different manifestations of the same entity by the fourth edition of the World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues”3

I hope this helps lift the shroud of confusion around CLL versus SLL. In either case, it is critically important that you seek out and consult with a leukemia expert as you go on this journey — hopefully toward better health with empowered knowledge!

~Adrian Warnock

Adrian Warnock is a medical doctor who worked in the UK’s National Health Service as a psychiatrist for eight years, then in the pharmaceutical industry for 15 years helping to run clinical trials that bring us new medicines and communicate the results. Adrian was diagnosed with blood cancer in May 2017. He is a published author, the founder of Blood Cancer Uncensored, and has written a Christian blog since 2003 at Patheos. He is passionate about learning how to approach suffering with hope and compassion. Adrian’s articles are not medical advice. Always seek individualized advice from your health care professionals. E-mail Adrian here.



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