Lymphoma And Lymphosarcoma
In Your Ferret


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Ron Hines DVM PhD ...............An important message from Dr. Hines

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What Is Lymphoma?

All mammals have, as part of their immune system, white blood cells called lymphocytes. These cells move through the body through the blood and lymphatic systems. They reside in depositories called lymph nodes and are also found in the spleen, bone marrow and thymus gland.

These cells sometime become cancerous. When they do, the tumors they form tend to be spread throughout the body. There are several types and stages of lymphocyte. When tumors arise, they are assigned names based on the type of lymphocyte that gave rise to them. That is why some of these tumors are called lymphoma, lymphoblastic lymphoma, lymphosarcoma, immunoblastic-polymorphous lymphoma, malignant lymphoma, etc. These classifications are not absolute and may overlap. They and are based on the judgment call of the pathologist that examine tissues taken from your pet.

These lymphoid tumors are one of the most common cancers that occur in ferrets. Lymphoma, along with adrenal gland tumors and insulinomas account for most of the cancers that veterinarians see in ferrets.

Lymphomas in ferrets are usually divided into two basic categories, adult form and juvenile form.

Adult Onset Lymphoma

The adult form of lymphoma usually occurs in ferrets over three years of age. The majority are 5-7 years old when their decline in health is noticed. This form of lymphoma usually progresses slowly. So the signs one sees usually depend on how long the problem has been present in your pet.

Early in the disease, the signs can be easily overlooked. Some pets are brought to veterinarians because of vague signs - like poor appetite, weight loss, and mopiness. Others are brought in because the owner has noticed firm swellings under the ferret’s chin or at the points of the shoulder and thigh.

Animals that have had the condition for longer periods may come in with signs related to multiple or single organ failure. In these ferrets, the tumorous (cancerous) cells have moved and invaded organs like the liver, kidneys and lungs. The spleen of these ferrets is usually also invaded by cancerous lymphocytes and can be many times it normal size.

Juvenile Form

Lymphoma occurs less frequently in ferrets younger than two. When it does, it is called the juvenile form. When it occurs in these young pets, it produces a different set of symptoms that progress much faster. It is also referred to as the lymphoblastic form. This alludes to the fact that the cancerous lymphocytes seen in this type of lymphoma are less well developed and larger in size.

In these younger ferrets, the thymus gland is often the initial focus of their problem. The thymus gland is the normal repository of a type of lymphocyte called a T-cell. This cell is critical in important cellular immunity.

This form of lymphoma progresses rapidly and the cancerous lymphocytes soon leave the thymus to invade other organs in the pet’s body.

The massively enlarged thymus gland that usually occurs in this form of lymphoma presses on the pet’s heart and lungs causing chest fluid accumulation, coughing and difficulty breathing. ( I created a fanciful image of this situation in the ferret on the top of this webpage.) However, some die from sudden bleeding of the spleen or liver before these signs can occur. In other young ferrets, the walls of the digestive system are invaded, causing vomiting and diarrhea.
In juvenile cases, the superficial lymph nodes are usually not enlarged.

Veterinarians do not know if the adult form and the juvenile form of lymphoma have the same cause. The disease progress very differently. It could be that the causes are different. But the difference in symptoms could also be due to the immaturity of the lymphatic system in younger pets. The way the disease proceeds seems to follow the involution timeline of the thymus gland.

Atypical Form

Occasionally, a ferret may develop lymphomas that have some characteristics of both forms.

What Signs Will I See In My Pet?

The signs you might see are quite variable. They depend on the age of your ferret and how long the problem has been present in your pet.

If your pet is an adult ferret, the initial signs are usually quite subtle and vague. Your pet may be less active than usual. It may be loosing weight and have become a picky eater.

As the disease progresses, so do the signs. The first very distinctive symptom in mature ferrets that owners see is the enlargement of lymph nodes that are present under the pet’s skin. (the larger fanciful ferret on top of the page) These lymph nodes are usually inapparent and difficult to locate. But in ferrets with lymphoma, they become large, bean-shaped and firm. They are not painful to your pet when you squeeze them.

Some of these ferrets develop hind leg weakness. For unknown reasons, hind leg weakness occurs in many conditions that ferrets suffer that have nothing to do with lymphoma. Late in adult onset lymphoma the cancerous lymphocytes invade and destroy many organs of the body. By then, signs can be present that reflect loss of function of the liver, kidneys, bone marrow, and nervous system. Some of these older pets have other concurrent diseases such as adrenal or pancreatic cancers.

When lymphoma occurs in younger ferrets, the pets go down hill much faster. Many of these younger ferrets have problems related to the greatly increased size of their thymus gland. The gland sits in the chest just ahead of the heart and lungs. When it grows in size, it’s presence prevents the heart and lungs from moving normally. So these ferrets have difficulty with breathing and heart function.

Some young ferrets develop other signs that are very variable. Some of these symptoms are related to enlargement of the spleen and the increased space in the abdomen that it occupies. Other pets run fevers.

How Would My Veterinarian Diagnose These Tumors?

Enlarged superficial lymph nodes, similar to the ones in the ferret image to the top right, make the diagnosis of lymphoma likely. However, many ferrets are brought to their veterinarian before lymph node enlargement becomes this striking. In those cases, your veterinarian may want to send a biopsy sample from one of your pet’s lymph nodes off for examination by a pathologist. That will confirm the diagnosis and eliminate the much rarer conditions that might also account for enlarged nodes.

Lymphoma diagnosis is also more challenging when it is just your pet’s spleen that is enlarged. There are a number of causes for enlarged spleens that do not involve lymphoma.

In cases where only vague signs are present, your veterinarian may send off a blood sample. In most early cases, these tests will not be diagnostic. But occasionally there will be a hint of problems in the lymphatic system causing unusually shaped or abnormally low lymphocyte numbers circulating in your pet’s blood. However, the diagnosis of lymphoma can not be made on the basis of a blood count alone.

Your veterinarian may also suggest an x-ray or ultrasound examination. These examinations can confirm an enlarged spleen or enlargement of other organs due to the presence of cancerous lymphocytes in them.

In ferrets with the juvenile form of lymphoma, the diagnosis can also be difficult. The pet’s thymus gland is not in an area where it can be palpated. But when it is enlarged, it can often be seen on x-rays of the pet’s chest. Excess fluid in the pet’s chest, seen on x-ray, can also suggest juvenile lymphoma – particularly when the enlarged thymus has crowded and moved the normal placement of the heart and lungs.

Some young ferrets with the acute form will have elevated circulating lymphocyte numbers in their blood. Some also show evidence of low blood glucose, liver dysfunction, and high blood calcium – but these results do not confirm the diagnosis. They have many potential causes.

Are There Conditions That Might Be Confused With Lymphoma?

Yes. When the disease is seen early or when superficial lymph node enlargement is not very apparent, it is possible to confuse lymphoma with many other health issues that ferrets face. When the ferret is overly plump, it can be hard to distinguish superficial fat from enlarged lymph nodes.

Many case do not present all the signs we associate with this disease. Some are brought to veterinarians with complaints of constipation, difficult urination or diarrhea. In others, populations of cancerous lymphoma cells are the underlying cause of destructive changes occurring in the pet’s liver or kidneys, persistent anemia or digestive tract disturbances. In those cases, only a biopsy will reveal lymphoma as the true underlying problem.

In the juvenile form of lymphoma, the respiratory problems can be mistaken for heart disease, chronic lung problems or pneumonia. Since blood enzyme levels are often abnormal in these young animals, the problem can be mistakenly attributed to sudden hepatitis or kidney failure.

What Is The Outlook (Prognosis) For My Ferret?

Lymphoma in mature ferrets is usually a slowly progressive disease. Treatment can slow this progress – but it is unlikely to entirely go away. The rate at which the disease progresses is quite variable. Some survive with the condition for months or even years with no treatment. Treatment often prolongs the period that the pet can live with the disease.

In young ferrets, the juvenile onset form progresses much more rapidly and aggressively. These younger ferrets rarely if ever respond to treatment. They are quite ill. Those that have difficulty breathing are not enjoying life and owners need to decide if prolonging the pet’s life is a kind thing to do.

What Treatments Are Available For My Ferret?

Ferrets with the juvenile onset form of lymphoma decline rapidly despite treatment. No treatment plan is consistent in extending their lives. But ferrets with adult onset lymphoma have several treatment options:

Minimal Treatment

Chronic lymphocytic leukemia in humans is not a painful condition. It is generally not treated for many years after it is diagnosed . Lymphoma, in ferrets does not appear to be a painful condition either. Some ferrets live happily for many years with the condition and eventually die from other unrelated conditions. As in people, when these cancerous cells eventually affect other organs, the result is primarily tiredness, and loss of body weight. So you may decide that no treatment is the right option for your pet – particularly if your ferret is an oldster in ferret years.

Corticosteroids

Most adult onset lymphomas respond quite favorably to oral corticosteroid administration. The primary corticosteroid used for lymphoma in ferrets is prednisone. There is usually a significant improvement in the ferret’s general health once it begins receiving this medication. This improvement, however, does not usually last many months. Some veterinarians feel that lymphomas in ferrets that have been previously treated with corticosteroids are more difficult to keep in check with chemotherapy once they have returned. This has not yet been confirmed scientifically.

Chemotherapy

Chemotherapy, with drugs developed for humans, is another option. They may prolong your ferret’s life, but they will not cure it. The treatment plans used in ferrets are ones that have been used successfully in dogs and cats with similar conditions. These are powerful drugs with multiple side effects. Original treatment plans required that they be given intravenously which is a difficult procedure in ferrets.

At least one chemotherapy plan, developed at Tufts, allows some of the medications to be given under the skin (subcutaneously) and the rest orally. In this treatment plan, a combination of prednisone, cytarabine (Cytosar) , cyclophosphamide, methotrexate, L-asparaginase, chlorambucil and procarbazine are used.

More traditional treatments use cyclophosphamide, vincristine, asparaginase, doxorubicin and prednisone.

Ferrets receiving any of these powerful medications need to be closely monitored for bad side effects. This can require frequent blood work and bone marrow examinations. Some ferrets tolerate the medications quite well. But some experience weakness, vomiting, lack of appetite and loss of their whiskers.

Consider yourself blessed if you gain another 2-10 months time with your pet through these treatments. Please do not feel guilty if you elect not to try them.

Radiation Therapy

Radiation is occasionally used to treat lymphoma in ferrets. As with many lymphoma treatments, its benefits are difficult to judge. Some ferrets seem to improve after radiation treatment or when radiation is combined with medications. Because the progress of lymphoma is so variable, it is difficult to judge treatment effectiveness.

Splenectomy

Many ferrets with lymphoma develop tremendously enlarged spleens. They only need removal if they are so large as to displace other organs in the abdomen to the extent that the pet’s general health suffers or when there is evidence that the enlarged spleen has ruptured and bled or may do so.

Scientifically Unproven Alternative Care

There are innumerable unproven treatments for cancer in humans and pets. They take advantage of our desperation to save the animals we love. Many ferret owners and some veterinarians who have exhausted scientifically proven treatments turn to alternative medicine. Before you go that route, ask yourself if you have exhausted everything that traditional veterinary medicine has to offer your ferret. Hope is an essential part of the human condition - there is no harm in trying unproven therapy when you have no other options.

Can My Ferret Be Cured?

A permanent cure for lymphoma is not possible. Perhaps in the future there may be such cures. The best you can hope for is more time with your pet.

What Causes Lymphoma?

Veterinarians have long suspected that lymphoma in ferrets might be caused by a virus. This is because certain lymphomas and leukemias in other animal species and humans are thought to be caused by virus. (ref 1, ref 2)

In 1995, veterinarians and researches at MIT succeeded in transmitting lymphoma from one ferret to another with cell-free extracts from an infected ferret. (ref) The presence of the enzyme, reverse transcriptase - a calling card of the retrovirus group - made them suspect that virus were replicating and playing a part in Ferret Lymphoma.

Their studies also indicated that lymphoma may be only one end-stage of a complex infectious viral disease.

When I served at the National Institutes of Health, I was involved in developing rodent and avian animal models that were free of certain tumor and leukemia producing retrovirus. Some of these viruses are handed down from parent to offspring through the parent’s DNA and could not be eliminated. (ref) But others, such as the mouse leukemia virus (MuLV) - another retrovirus that produces leukemia with many similarities to ferret lymphoma - could be eliminated by taking the pups from the mother at term by cesarean section and either bottle feeding them or fostering them on virus-free mothers.

I do not know if this has been considered by the ferret community. If the retrovirus theory of ferret lymphoma proves to be true and if the virus should be passed primarily through milk, it might be possible to remove it this way from ferrets as well. That is a big if – but it should be considered and attempted if it has not already been tried.