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 calll 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. Itis 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
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 accumulat
coughing and difficulty breathing, ( | 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 FormOccasionally, a ferret may develop lymphomas that have some characteri:
both forms,
What Signs Will 1 See In My Pet?
The signs you might see are quite variable. They depend on the age of your ferret
and how tong 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 aro 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 inthe abdomen that it occupies. Other pets run fevers.
How Would My Veterinarian \qnose 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 circulatinglymphocyte 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
iarrhea. 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 itis 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 arequite 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 pian 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 itis 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
protong your ferret’s life, but they will not cure it. The treatment plans used inferrets are ones that have been used successfully in dogs and cats with sir
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.
ilar
Atleast 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 tra
doxorubi
ional treatments use cyclophosphamide, vincristine, asparaginase,
in 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 effecti
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 theenlarged 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?
Apermanent 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. (cof, ref2)
In 1995, veterinarians and researches at MIT succeeded in transmitting lymphoma
from one ferret to another with cell-free extracts from an infected ferret. (rof) 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 | served at the National Institutes of Health, | 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 tooffspring through the parent’s DNA and could not be eliminated. (ref) But others,
‘such as the mouse leukemia virus (mutv) - 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.
| 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 i
not already been tried.
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