CML blood smear

Q. ย Can you please simplify for me how to pick if the case is leukemia or lymphoma ?

A. Great question! The big difference between leukemias and lymphomas is that leukemias start in the bone marrow (and blood), whereas lymphomas start in lymph nodes (or lymphoid tissue). From there, each disease can spread to other parts of the body. Leukemias can eventually involve lymph nodes, and lymphomas can eventually involve bone marrow and blood. So the distinction gets a bit murky.

The first thing to do is establish the place where the tumor is. If it is in the blood, take a look at the cells and see if there is an increase in blasts. If so (and if it’s over 20% of the nucleated cells in the blood or bone marrow), then you are dealing with an acute leukemia. From there, you need to look closely at the blasts to see if you see anything specific for the myeloid or lymphoid lineage (Auer rods, for example, would identify the blasts as myeloid). You can also do flow cytometry (immunophenotyping) to look at the markers on the surface of the blasts to identify whether they are myeloid or lymphoid. Beyond that, you’d do cytogenetics to see if there are any cytogenetic changes that would help put the acute leukemia in one category or another.

If the cells in the blood are more mature, then you’re probably dealing with a chronic leukemia. If the cells in question are lymphoid, then it’s a chronic lymphoproliferative disorder (either chronic lymphocytic leukemia, hairy cell leukemia, prolymphocytic leukemia, or large granulated lymphocyte leukemia). If the cells are mostly myeloid, then you’re probably dealing with a chronic myeloproliferative disorder (chronic myeloid leukemia, as shown in the photo above, polycythemia vera, chronic myelofibrosis, or essential thrombocythemia). Those can be a bit difficult to sort out – that’s the subject of another post.

One note: sometimes, cells from lymphomas can get into the blood. So you can see circulating follicular lymphoma cells, Burkitt lymphoma cells, etc. These you would identify by their morphology (follicular lymphoma cells often look like little “butts” when they get into the blood; Burkitt lymphoma cells are large, with deep blue cytoplasm and lots of vacuoles).

If the tumor is in a lymph node, then right there you’ve ruled out a myeloid process (pretty much). Myeloid malignancies rarely go to lymph nodes. So you’re either dealing with a lymphoma or a leukemia of lymphoid origin. Many of these diseases have been simply lumped together. Chronic lymphocytic leukemia (CLL), for example, is considered to be the same disease as small lymphocytic lymphoma (SLL) – same cells, same prognosis – and the disease is simply designated as CLL/SLL.

To figure out what kind of process it is, start by looking at the lymph node architecture and seeing if there is any pattern. If there are follicle-like structures (without mantle zones), that would make you think of follicular lymphoma. Follicles with prominent mantle zones indicate mantle cell lymphoma, and follicles with prominent marginal zones indicate marginal zone lymphoma. If there are sheets of small, mature cells, with cloud-like (at low power) collections of larger cells with more cytoplasm and prominent nucleoli, that would make you think of CLL/SLL. If all you have are sheets of cells, with no architecture whatsoever, then you have to look carefully at the cells on high power (you’d do this for all lymphomas anyway!) to decide what kind it is.

Whether you’re looking at bone marrow, blood or lymph nodes, immunophenotyping and cytogenetic (or molecular) studies are often necessary for making a definitive diagnosis.


12 Responses to A crash course in how to tell apart leukemia and lymphoma

  1. zeeshan khan says:

    Thank you so much this post is very helpful’
    you Are Patho Queen

  2. Vishal Varma says:

    Awesome explanation. You were helping me a lot in my haematology study .most of ur topics are clinically relevant .thanks to u sir

  3. marwa says:

    Many thanks its so useful to me

  4. Sandeep says:

    your posts synthesize 3-4 lectures worth of material into a memorable scheme, thank you!

  5. Maya says:

    I have one question, that I can’t find the answer in the books.. What does it mean, when somebody says “these cells look monocytoid”?
    Thank you so much for path bites, and all your wonderful books, they helped me a lot!

  6. Kristine says:

    Hi Maya –
    That’s a good question. When a lymphocyte is said to look “monocytoid” it basically means that it has a lot of cytoplasm (and therefore kind of looks like a monocyte). The lymphocytes in the marginal zone layer of splenic follicles look monocytoid – they have lymphocyte nuclei, but they also have a lot of cytoplasm (more than normal lymphocytes). That’s why the marginal zone looks pale on low power: the lymphocytes have this abundant cytoplasm that looks pale. Especially in comparison to the lymphocytes in the mantle zone, which have very little cytoplasm (so the mantle zone is mostly just dark lymphocyte nuclei pressed up against each other with very little cytoplasm in between – and therefore at low power it looks dark).

    I hope that helps ๐Ÿ™‚

  7. tooba says:

    Thanks a lot

  8. KANOPO says:

    Thanks for sharing such a useful knowledge, it does help a lot.
    After reading this article, some questions popped out. May I ask if we see lymphoma cell in blood(no matter it is follicular lymphoma cell or Burkitt’s lymphoma), what should we call of this disease. Should we call it still lymphoma with leukemic phase or just call it leukemia(more like CLL)?

    Thanks for your patiently answering. Great thanks.

  9. Kristine says:

    Sure – great question! As you mention, some lymphomas have a corresponding leukemia, and both are lumped together in one name (like chronic lymphocytic leukemia/small lymphocytic lymphoma). In that case, it’s easy: the diagnosis is just CLL/SLL. Some lymphomas don’t have a corresponding leukemia, though (like follicular lymphoma). In those lymphomas, if you see a lymphoma cell in the blood, you’d use the same name for the diagnosis (“follicular lymphoma”) but you’d note that there is a leukemic phase (that you are seeing lymphoma cells in the blood).

  10. Kanopo says:

    Thanks for the detailed reply, it does really help!
    I am a medical student so that I have few chances to checked up blood smear, may I ask further that what is the difference between lymphoma cell in blood from the mature lymphocyte like in CLL?

    Sorry for that bothering question, it quite confusing that I need expertise! And I really want to have clear cut between leukemia and lymphoma, haha.

    Thanks for the patiently answering! All the best!

  11. Kristine says:

    Hi Kanopo – it’s okay! Leukemias and lymphomas can be confusing, for sure. To answer your question: there is no difference between the cells of small lymphocytic lymphoma and chronic lymphocytic leukemia (or any of the other leukemia/lymphoma pairs, like lymphoblastic leukemia/lymphoma). So when a patient has small lymphocytic lymphoma, and some cells get out in to the blood, there is no difference between those cells and the cells of chronic lymphocytic leukemia. I hope that is what you were asking – if not, please feel free to write in again!

  12. Gopal says:

    Very nice simple explanation

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