Lymphoma, An Oncologic Emergency

There are many different types of lymphoma that affect dogs and people. What they have in common is their origin from lymphoid cells that become cancerous. Lymphomas typically start in lymph nodes, spleen or bone marrow, but can develop in almost any tissue in the body.

Lymphoma accounts for roughly 7% to 24% of all canine cancer. It typically affects middle-aged to older dogs. 

Breeds that have been associated with an increased incidence include Boxers, bullmastiffs, basset hounds, St. Bernards, Scottish terriers, Airedales, and bulldogs. Dachshunds and Pomeranians have a lower risk.

Lymphoma is typically considered a fairly chemo-responsive disease. This means that for our "standard" lymphomas (a dog that presents with very large lymph nodes), remission is expected, and can often be achieved after one or two doses of chemotherapy.

Partial remission means that the lymphoma burden (size of lymph nodes) has decreased by half. Complete remission means that there is no evidence of lymphoma on exam, x-rays or ultrasound (lymph nodes are normal).

Types of Lymphoma

The vast majority of dogs (84%) will develop the multicentric form, which is characterized by very large lymph nodes throughout the body. These lymph nodes are easily felt on physical exam or when you're petting your dog. 

See the image below for all of the lymph nodes you can feel on physical exam.
See if you can make out the enlarged mandibular lymph node in the image below. It's located just where the neck and lower jaw meet, feels firm and is probably about the size of a baseball. A normal lymph node should be smaller than a dime (in a golden retriever).

Much less common (5% to 7%) is the intestinal form. Patients with the intestinal form usually experience decreased appetite, nausea, vomiting, weight loss, and diarrhea. These signs prompt a workup that includes an abdominal ultrasound, which typically finds evidence of an intestinal mass and large lymph nodes surrounding the intestines.

The mediastinal form of lymphoma is also less common (5%). This form is characterized by a very large mass in front of the heart, which can be seen on chest x-rays. The mass is a very enlarged lymph node, which must be sampled to make the diagnosis. 

Cutaneous (skin) lymphoma is also possible. In these cases, the patient can either have ulcerations on the gums or tongue (which are lymphoma) or even skin masses (which are lymphoma). This type of lymphoma may or may not be associated with large lymph nodes. It can look very different in different patients, so a biopsy is usually needed to make a diagnosis. 

The images below show examples of lymphoma affecting the gums and the skin.

              

For the remainder of the article, I will describe large cell lymphoma. There are other (less aggressive) forms of lymphoma called indolent lymphoma, which (in most cases) actually don't require treatment. Because the treatments and prognoses are vastly different, having an accurate diagnosis upfront is crucial. 

Signs of Lymphoma

The signs of lymphoma will vary depending on the location.

As mentioned above, patients with intestinal (or "GI") lymphoma will typically have nausea and/or diarrhea

In general, some types of lymphoma are derived from B lymphocytes (B cells) and others are derived from T lymphocytes (T cells). Some dogs with T cell lymphoma have elevated calcium levels

Elevated calcium levels typically cause significantly increased thirst and urination. If the calcium levels are high enough, they also cause nausea, which usually looks like decreased appetite and maybe lethargy. 

If lymphoma is treated and the patient goes into remission, the calcium levels will normalize. 

The most common types of lymphoma to be associated with elevated calcium are the mediastinal, cutaneous and intestinal forms. 

Sometimes dogs with the mediastinal form also have fluid accumulation around the lungs (pleural effusion). In these cases, the dog might have an increased breathing rate, decreased appetite, and may tire easily.

Dogs with the multicentric (common) form of lymphoma may feel perfectly normal, or they may feel lethargic and have a poor appetite. 

How to Diagnose Lymphoma

Lymphoma is usually easy to diagnose. Typically making a diagnosis involves taking a needle aspirate of an enlarged lymph node or intestinal mass, spreading the sample on glass slides and sending the slides to the pathology lab (this is cytology).

Since lymphoma is often considered an emergency (especially if the dog is already not feeling well), these samples should be rushed - the vet should ask the lab to STAT them for an extra charge. 

As mentioned above, in some cases (such as the cutaneous/skin form), a biopsy is recommended. 

In other cases, we have trouble making a diagnosis or want more information other than simply a diagnosis of lymphoma. Often it is very helpful to know exactly which type of lymphoma a patient has.

Knowing if a patient has a T cell lymphoma vs B cell lymphoma (and what type of B cell) will affect how long they live with different treatment protocols. In order to obtain this information, I typically send a lymph node sample to Colorado State for flow cytometry

Prognostic Factors for Multicentric lymphoma

A prognostic factor is something that helps us determine how long a patient might live on average with a certain disease. When we make a diagnosis of lymphoma, we typically try to identify whether the patient has any "negative prognostic factors" - these would suggest that the patient may not live as long as the average patient with lymphoma. This is often helpful for the family and can factor into their decision-making process regarding treatment.

STAGE: When a dog is diagnosed with the multicentric form, we typically give their lymphoma a stage (based on where it is in the body). 

Dogs with one lymph node affected are stage I, dogs with more than one lymph node affected but with lymphoma confined to one half of the body (either the front or the back half) are a stage II. We rarely see a stage I or stage II but these patients have a better prognosis than the other stages.

Most dogs are a stage III (all lymph nodes affected) or stage IV (all lymph nodes + liver or spleen or both). There is no difference in prognosis between a stage III or IV, so abdominal ultrasound is not needed unless the patient is not feeling well or we're worried that a different abdominal organ might be affected.

A stage V patient does have a worse prognosis than the other stages. These patients might even live half as long as a stage III patient. Stage V means that the disease is in the bone marrow or somewhere strange (uncommon), like the kidney, spinal cord, etc.

IMMUNOPHENOTYPE: Whether a dog is a B cell or T cell describes its immunophenotype. B cell patients typically respond much better to treatment and live longer than T cell patients (although there are exceptions).

SUBSTAGE: When a dog feels normal at diagnosis they are considered to be substage a. If they have a decreased appetite,  diarrhea or are otherwise feeling sick, they are substage b. We know that dogs that are substage b typically do not live as long as the average patient.

AGE: Many people think that if a dog is diagnosed with lymphoma at a young age they are stronger and have a better prognosis. It's actually the opposite. If a dog develops lymphoma when young (two years old, etc.) the prognosis is usually very poor. Young dogs typically develop very aggressive forms of the disease that do not respond well (or at all) to treatment.

TREATMENT: We know that dogs treated with a multi-drug protocol (such as CHOP protocols, which include cyclophosphamide, vincristine, doxorubicin, and prednisone) live much longer than those that are not treated, are only treated with prednisone, or that are only treated with one chemotherapy agent.

RESPONSE TO TREATMENT: If we begin treatment and a dog goes into complete remission within the first few weeks, his prognosis is typically more favorable than if his lymph nodes (or intestinal mass) do not shrink with treatment.

Prognosis and Treatment for Lymphoma

We say that lymphoma is an oncologic emergency and typically treat it as such because we know how quickly things can change. 

The population of lymphoma cells doubles both exponentially and rapidly. When clients come in and tell us that the lymph nodes were normal yesterday but are now the size of baseballs, we believe them. 

This isn't a disease where you have the luxury of taking two weeks to decide if you want to pursue treatment. This is because the prognosis without treatment is only 1-2 weeks on average. This means that in most cases, without any treatment, a patient with lymphoma (the standard large cell type) will not be alive after two weeks. 

The body can only support a certain number of lymphoma cells. When that number is reached the patient dies from their disease. More commonly, a family realizes that their dog is not well and is no longer loving life, and elects humane euthanasia before they begin to suffer. 

Thankfully, we do have quite a few treatment options for dogs with lymphoma and most dogs will go into remission.

At diagnosis, however, it is definitely overwhelming and there are many decisions that need to be made in a short amount of time. 

To give the family time to process the information and decide (1) if they want to treat and (2) how they want to treat, we commonly offer a treatment called Lspar (l-asparaginase). 

Lspar is a nice option because (unlike traditional chemotherapy) it strictly kills lymphoma cells and will usually help the patient achieve either a partial or complete remission while the family is trying to decide how to proceed. The oncologist will also typically start prednisone at the same time. Prednisone also kills lymphoma cells. 

If the family decides to pursue traditional chemotherapy, it should be started within the next week (to capitalize on the progress Lspar has made).

Dogs will live the longest if they receive a multi-drug protocol such as a CHOP protocol. A common CHOP protocol is the Wisconsin protocol. This involves giving 16 chemotherapy treatments over 25 weeks. In general, the average survival for a B cell patient receiving this type of protocol is 10-12 months (this is calculated from the time of diagnosis). The average survival for a T cell patient is 6 months, which is about half as long. A small percentage of B cell patients will still be alive at two years. 

Chemotherapy is typically well-tolerated in canine patients - you can read more about chemotherapy in dogs here.

If the patient makes it to the end of a CHOP protocol in remission, chemotherapy is stopped. Recheck visits are then every month to ensure they are still in remission. The patient is expected to come out of remission at some point in the future. When they come out of remission, additional chemotherapy can be pursued (often with different chemotherapy agents than were given the first time). 

Since cancer becomes more resistant over time, the second remission is approximately half the length of the first, the third is half the length of the second, etc.

At some point, the lymphoma will no longer respond to any treatment. At that point stopping and ultimately euthanasia (when the time is right) is recommended. 

For families that do not choose a CHOP protocol based on financial restrictions, logistical considerations, etc.,  other options include:

(1) Injectable doxorubicin + prednisone, every three weeks for six treatments (average survival 6-8 months for B cell patients, less for T cell patients) 
(2) Oral chlorambucil and prednisone daily at home, for as long as it is effective (average survival of 2-4 months)
(3) Oral prednisone daily at home, for as long as it is effective (average survival of 1-2 months)

Don't Give Steroids Alone

If you think you might want to give injectable chemotherapy but you're not sure, keep in mind that giving prednisone alone for roughly a week or more will make your dog's lymphoma resistant to chemotherapy

This means that if you're having trouble deciding whether to treat with chemo, but want to start steroids to "get things moving in the right direction", try to make the decision within a few days from starting prednisone. 

If steroids are given as the sole treatment for over a week, your dog will likely have a poor response to some of our best chemotherapy agents and will likely have a shorter survival because of it.

Bone Marrow Transplant

For clients that are highly motivated and are potentially willing to fly for treatment, bone marrow transplant might be an option. 

This is an intense treatment that involves weeks to months of preparation and weeks of treatment and hospitalization.

Whereas the goal of chemotherapy treatment in dogs is to help extend their life but not compromise their quality of life - that is not the case for bone marrow transplant. You would have to go into this expecting that your dog would feel terrible, that this procedure would be potentially life-threatening, but that it could result in a cure. 

While a cure with bone marrow transplant is possible, it is not a guarantee and is less than 50%. A cure is more likely if you can locate a sibling of your dog and use that dog as the bone marrow donor.

There is typically a waitlist as only a few clinics offer this in the US. Your dog must be in complete remission in order to receive a transplant. 

The rough estimate of cost for this procedure is $20,000 to $45,000, depending on (1) where the transplant is taking place and (2) whether you are using a sibling or not (it's cheaper if you're not using a sibling, but also less effective). 

An excellent comprehensive pet insurance plan might cover a portion of this treatment.

The Prognosis for Mediastinal, Cutaneous & Intestinal forms

These forms of lymphoma are more aggressive than the multicentric (standard) form of lymphoma.

We typically expect an average survival of six months when treating with a CHOP protocol.  Although every patient and every patient's lymphoma is different (yes, some patients do better than six months), this is the typical expectation. 

 If your dog is diagnosed with lymphoma, consider a consult with an oncologist if at all possible. They will be able to ensure that you have the most accurate information about prognosis and available treatment options. 

They can also answer all of your questions about possible side effects as well as give you tips and tricks to decrease the chance of experiencing side effects such as nausea. 

 

Have questions about this article? Reach out!

Dr. Lori Cesario
Board Certified Veterinary Oncologist
lori@caninecanceracademy.com 


A few other articles you might enjoy...

(1) Is Humane Euthanasia Humane?
(2) The MDR1 Mutation - What it is and why you need to know!
(3) Cannabinoids and Your Canine

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