In most instances, a diagnosis of lymphoma is “straightforward” for dogs and cats. Dogs present with palpably enlarged external lymph nodes. Cats typically have gastrointestinal masses with concurrent abdominal lymph node enlargement.
There are several cancers that identically mimic lymphoma in dogs and cats, including physical exam findings and test results, and even the most astute veterinarian and most experienced clinical pathologist may not have the experience to know these alternative diagnoses exist.
One of the most common scenarios I’m faced with is determining whether a patient truly has lymphoma or if they have something called an acute leukemia. Despite being very different disease processes, with different treatment recommendations and prognoses, distinguishing the difference between the two can be exceptionally challenging.
Lymphoma is a cancer of lymphocytes, which are a type of white blood cell. There are several different forms of lymphomas in dogs and cats, but the most common form involves an excessive proliferation of lymphoblasts (immature lymphocytes) within lymph nodes and organs of the body.
Leukemia is more of a “catch all” phrase, and refers to several different types of cancers arising from the different blood cell elements within bone marrow. Animals can develop leukemia of white blood cells, red blood cells, or platelets.
White blood cells are created in the bone marrow via a complicated hierarchy of cell division. Stem cells are the most primitive forms of the blood cell elements, and are the “highest” up on the chain. These cells divide and give rise to slightly more specialized cells, each of which give rise to progressively further differentiated cells in an exponential fashion, until all of the finalized mature blood elements are created and “ready” to be released into the blood stream.
One of the main “splitting” points during the maturation of blood cells in the bone marrow occurs when cells are slated to mature into what are known as lymphoid cells or myeloid cells.
Those destined to the lymphoid path start out as lymphoblasts and will further develop into B-lymphocytes, T-lymphocyte, or plasma cells. Those destined to the myeloid pathway also start out as blasts and will further develop into one of the other four types of white blood cells (neutrophils, monocytes, eosinophils, or basophils), red blood cells, or platelets.
When we examine bone marrow cells prior to their acquisition of specialization towards a specific lineage (i.e., when they are “higher up” on the hierarchy: the “blast” cells), they are virtually indistinguishable from each other based on appearance alone. There are no accurate ways to simply look at a very primitive blast cell and know whether it is destined to become a lymphocyte, a neutrophil, or a monocyte.
In leukemia, somewhere along the maturation process within the bone marrow, a single cell begins dividing uncontrollably and the progeny are released into the blood stream where they can cause the total white blood cell count to rise and also accumulate within lymph nodes, where they can then cause these organs to enlarge. The tricky part is the same changes (abnormal cells in circulation and enlarged lymph nodes) are seen with pets with lymphoma as well.
These cells are often picked up on routine blood tests or can be tested via an aspirate of an enlarged lymph node. The abnormal results are usually “flagged” so a lab technician or clinical pathologist can be called in to look at a blood smear and evaluate the results.
Inexperienced individuals look at the cells and type them as “lymphoblasts” and the pet will be incorrectly diagnosed with lymphoma. Experienced individuals recognize the abnormal cells and correctly call them “blasts,” but will also know the cells lack the distinguishing features necessary to truly typify them as lymphoblasts and will keep an open mind that they could be non-lymphoid or lymphoid leukemia cells.
Here’s an analogy for you: Imagine the bone marrow as an assembly line of donuts. At the onset, all the donuts are plain and look exactly the same until they split off to get their toppings. The initial plain donuts are the equivalent of blast cells. Donuts destined to be “lymphoblasts” will move towards a different assembly line, and have a thin layer of glaze added to their tops. At a quick glance, it would be easy to mistake a plain donut for a lightly glazed, just as it would be easy to mistake a blast for a lymphoblast on a blood smear. Only a donut connoisseur (or very good clinical pathologist) would note the difference.
I probably see at least one patient per month incorrectly diagnosed with lymphoma when they truly have leukemia. In veterinary school we are taught that it’s not our fault when we incorrectly diagnose patients with diseases we didn't know exist. This lack of culpability doesn’t hold up outside of the teaching hospital though, so my goal is to raise awareness about how sometimes a straightforward diagnosis isn’t so straightforward.
In my upcoming articles I’ll describe some of the advanced testing we recommend to help distinguish lymphoma from leukemia and why it’s important to seek consultation with a veterinary oncologist even when things seem “straightforward.”
Dr. Joanne Intile