Last week I discussed the difficulties distinguishing between lymphoma and acute leukemia in pets. To recap: lymphoma is a cancer of a specific white blood cell called a lymphocyte, which starts in the periphery of the body. Leukemia is a broader term describing cancers of blood cell precursor cells and starts within the bone marrow.
Lymphoma is typically classified as either being of a B-lymphocyte or T-lymphocyte origin. Acute leukemias are first classified into one of 2 categories: acute lymphoid leukemias (ALL), which arise from immature lymphocytes (and can be of either a B-cell or T-cell origin), and acute non-lymphoid leukemias (also referred to as acute myeloid leukemias or AML), which arise from all other immature blood cell precursors in the bone marrow.
Pets with lymphoma and leukemia have very similar clinical signs and laboratory test results, and even the most astute pathologist can easily confuse the two diagnoses. The prognosis and treatment options vary greatly, therefore it’s extremely important that we are completely certain of what disease our patient has.
I recommend several diagnostic tests to help distinguish the difference between lymphoma and leukemia, including:
Bone marrow cytology: This test is considered part of routine staging for pets with any hematological (blood-borne) cancer. Many owners fear this test because they worry it is painful and very invasive, but this is a very routine and safe procedure, and since it’s performed under a light sedation, animals do not feel any discomfort.
Bone marrow analysis provides information as to what percent of this tissue is comprised of cancerous blast cells, which is useful in distinguishing lymphoma from acute leukemia. Most dogs with lymphoma have a low-level of cancer cells in their bone marrow, however if the percent of blast cells exceeds >20-30 percent of the entire sample, it is more typical for a case of leukemia.
Bone marrow cytology, though accurate in giving the percent of cancer cells within this tissue, can be inaccurate in determining the exact cell of origin of the abnormal cells in question. Fortunately, additional testing can be performed on bone marrow samples to help determine the difference between lymphoid precursor cells and non-lymphoid (aka myeloid) precursor cells (see below).
Flow cytometry: This test is designed to look for specific markers located on the surface of cancer cells to aid in determining their origin (e.g., whether lymphoid or non-lymphoid [aka myeloid] in origin). This test can be performed on blood, bone marrow, and also fine needle aspirates of tissues (e.g., lymph nodes). Samples must contain cells that are viable (alive) in order for it to be accurate, so we can’t hold them for days before deciding to submit them. One of the main markers this test can examine for is called CD34. In general, cells of bone marrow origin will express CD34, whereas those located in the periphery of the body will not. If detected, the presence of CD34 strongly supports the diagnosis of an acute leukemia.
PCR for antigen receptor rearrangement (PARR): This is a DNA based test that can determine if a population of abnormal lymphocytes is monoclonal (meaning they are all genetically identical to one another as seen with cancerous conditions) or polyclonal (meaning they are genetically different from one another as seen with infections or inflammatory conditions). This test can be run on blood samples, bone marrow samples, and even aspirates or biopsies of tissues, and samples do not need to be fresh to be diagnostic.
PARR is only valuable for testing lymphocytes, so when we choose this test, we must be at least reasonably certain the cells in question in our samples are lymphocytes. Additionally, PARR cannot distinguish lymphoma from acute leukemia of lymphocyte origin. Essentially, what PARR tells us is 1) If the sample is from a cancerous condition of lymphocytes, and 2) if it is of a B-lymphocyte or a T-lymphocyte origin.
Cytochemistry staining: Similar to flow cytometry, this type of test looks for markers on the surface of, or within, white blood cells. Unlike flow cytometry, this form of staining does not require live cells and is performed on samples affixed to slides (the equivalent of this test on a biopsy sample would be called immunohistochemistry).
Ideally, I have results from most (or even all) of these tests when diagnosing pets, but in many cases restrictions are placed due to finances, owners' unsupported concerns about invasiveness of the testing, or even the calendar (e.g., being unable to sample to submit samples for flow cytometry on a Friday because the lab won't receive them until Monday, and by then the cells will all be non-viable).
In many cases I am forced to select the one test I think will provide an accurate diagnosis. I’m asked to rely on my experience or my gut feelings about what will provide the most information with the least amount of expense and impact to the patient. Obviously this is less than ideal, given the complex nature of such cases.
It’s frustrating not to automatically have access to every piece of information I need. It’s equally frustrating when I feel unsuccessful in my ability to translate the importance of each of the tests to owners, especially when they become fixated on “cost to benefit” ratios. The limitations can sometimes impede patient care, and I often wonder if my human doctor counterparts ever face the same constraints.
Next week I’ll describe a case illustrating the typical difficulties I face when presented with such challenging patients, as well as tie together the concepts I’ve discussed in this article and last week’s article.
Hopefully I’ll continue to drive the message home that sometimes the straightforward isn’t so straightforward.
Dr. Joanne Intile