CML blood smear

Q. 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.