Lymphoma In Your Cat
To see how intestinal lymphoma migh affect me, click here.
Ron Hines DVM PhD............................................................................. Perhaps New Treatments On The Horizon ?
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Is Lymphoma - How Does This Disease Develop ?
Is Lymphoma - How Does This Disease Develop
Lymphoma is a tumor of one type of white blood cells that is an important part of your cat’s immune system. The purpose of that cell, the lymphocyte, is to defend your cat’s body from invaders. As a sentinel and soldier of your cat’s defensive system, lymphocytes need a natural capacity to increase their numbers rapidly. But when changes (mutations) occur in their DNA program, their increase in numbers has nothing to do with defending the cat’s body. At that point, the lymphocytes have become a loosely organized tumor, a cancer that has forgotten its original purpose, a lymphoma.
This tumor is one of the most common forms of cancer in cats. And cats suffer from it more than any other animal. (ref)
It can form in any area of your cat’s body that harbor large numbers of lymphocytes and for a number of different reasons. Those reasons, and the locations the tumor resides have shifted over the last twenty years. Currently, your cat’s digestive system (alimentary system) is the most common target of the problem. That is because the digestive system is home to the largest population of lymphocytes in your cat’s body and, perhaps, because those cells are under constant stimulation by the compounds and organisms passing through the cat’s digestive system.
The frequency of lymphoma in cats and the characteristics of the tumor appear to differ somewhat depending on the area of the World where they are measured. It is hard to explain those moderate differences. Perhaps cat populations and care differ somewhat in different continents, perhaps research studies, techniques and interpretation differ in different environments. Whatever the reason, in the United States today, lymphoma is the most common gastro-intestinal tumor of cats and form about 20% of all tumors discovered in cats . Being a Siamese cat, a shorthaired cat, a male cat or a cat from a cigarette-smoking household appear to increase the chance of this disease slightly. Cats over 7 years of age are at considerably more risk of developing the disease. When the cat’s digestive system is affected, about two-thirds of the time, these lymphomas form in the cat’s small intestine. You can read more about some of these statistics here , and here .
Lymphocytes – The Original Source Of The Problem
You can read about some general characteristics
of lymphocytes here.
Over the last 20 years, lymphoma has become a rather common disease - primarily of older cats. The intestines are a common site of the problem and fewer cases can now be attributed to infection with the feline leukemia virus (FLV) or the feline immunodeficiency virus (FIV,= feline AIDS). Good vaccines to prevent FLV and FIV explain much of that shift. Improved awareness, attentive veterinary care and better diagnostic methods might explain some of the rest. But in cats, intestinal lymphoma is often the result of chronic digestive tract inflammation and that has been on the rise as well. (ref) Although lifestyle is important in the development of all cancers, your cat's unique genetic makeup is probably quite important as well. I do not know of studies in cats that examined this, but in dogs, defects in specific genes have been found that favor the development of lymphoma. (ref1,ref2)
And the way they are classified and named can be terribly confusing. The same problem occurs when lymphomas occur in humans. The World Health Organization attempted to bring some order to naming the types of lymphomas. (ref)
Grouped By The Age Of The Cat :
Feline Leukemia and Feline Immunodeficiency Virus
When lymphomas occur in cats under the age of 7, they are most often associated with the feline leukemia virus or the feline immunodeficiency virus. Both these virus greatly increase the tendency for the cat’s lymphocytes to mutate and become cancerous. Since both these virus are generally detected in a cat’s youth, they are a significant cause of lymphoma in younger cats. When the tumor develops due to the influence of these viruses, the lymphomas produced often occur in multiple locations outside of the digestive tract (lymph nodes, chest, etc.).
As feline leukemia becomes less common in cats due to vaccination and in-office testing, the prevalence of lymphoma in young cats has decreased. There was some speculation among veterinarians that lingering feline leukemia virus fragments (= provirus DNA, latent FLV, FeLV-A/B recombinants) in cats that overcame FLV and tested negative on in-office tests might still be at a higher risk of developing lymphoma. Most studies have not found that to be true. You can read some of those studies here , here , here and here
When the virus of FIV is involved in lymphoma, it is usually the cat’s B lymphocytes that become cancerous. You can read more about that situation here.
Grouped By The Shape And Size Of The Malignant Lymphocytes
This has been the traditional way veterinary pathologists classify lymphomas. It is important because how successful treatment in your cat is likely to be is very dependent on the characteristics of the lymphocytes involved. The smaller and closer these cancerous lymphocytes are to normal lymphocytes, the more likely it is that treatment will be successful. The limitations of this method is that, much like a baseball umpire, it can be somewhat subjective depending on the veterinary pathologist making the call and the specimen of tumor with which he/she has been provided.
This is the most treatable form of lymphoma in cats. Pathologists generally compare the diameters of the cancerous lymphocytes to the diameters of the cats red blood cells seen in the same slide. However, it can sometimes be difficult to decide if these cancerous cells would be better called intermediate size lymphocytes - cells a bit less likely to respond well to the medications veterinarians have available. You can read about this form of lymphoma in cats here. It can also be quite difficult for the pathologist to determine if abnormal numbers of lymphocytes represent a true tumor or are normal lymphocytes that are simply there in response to chronic inflammation.
In general, larger lymphocyte size is an indication that the cat’s outlook is poorer. Lymphomas that occur very high in the intestine or stomach and those that occur in the large intestine have a tendency to be this type. They also have a greater tendency to penetrate into the deeper layers of the intestine and the surrounding lymph nodes. You can read a bit about large-cell lymphomas here.
Feline Alimentary Tract Lymphoma
When a major instigator of feline lymphomas was the feline leukemia and the feline aids viruses, the lymphomas tended to spring up in multiple locations outside of the digestive tract (multi-centric). They still do, but not in the quantity that they once did. They now tend to occur in the cat’s digestive (alimentary) tract and the organs that adjoin it (pancreas, liver and gall bladder) - particularly in older cats. Many of the lymphomas that occur in the alimentary tract are quite treatable. You can read more about these tumors and their treatment here , here and here .
Lymphomas In Other Locations
Lymphomas have the potential to form in any tissue
that contains a large number of lymphocytes – either naturally or
due to chronic inflammation. This includes the area surrounding the cats
heart (mediastinum) (ref)
, lungs (ref) ,
Gall bladder (ref) , nervous system (ref)
, and lymph nodes. Some associate infection with a bacteria, helicobacter,
as predisposing cats to lymphoma of the stomach. (ref)
The physical signs that one sees in cats suffering from lymphoma could be the same in many, non-cancerous and cancerous disease that cats develop. Only a pathological examination of tissue samples (biopsies) taken from suspicious areas can determine if the cat suffers from lymphoma. Even that examination is not always clear-cut. That is because common disease of cats that cause chronic inflammation produced clusters of lymphocytes that could be confused with lymphoma. The most common confusion surrounds triad disease of cats which you can read about here. triad.htm Veterinary pathologists have made great efforts to find ways to tell the difference between lymphocytes present because of chronic inflammation and those that are present in a cancerous accumulation. You can read some of the studies that pertain to that problem here , here and here. In late 2015, the Winn Feline Foundation, recognizing how hard lymphoma and IBD are to tell apart, provided a modest grant in the hope of developing a blood test that might help your veterinarian tell the difference. (ref)
Those signs are quite variable. Transformation of lymphocytes into a discrete or diffuse tumor is a gradual process. Early in that process you will notice little to no effect on your cat. Even veterinary exams and test results other than tissue biopsies often offer no clues that the cat is ill.
The other determining factor is what area of your cat’s body harbors the tumor. Whatever the area, the first signs you will usually notice are interruption of normal function, abnormal breathing – should the lymphoma be in the chest, nervous function-should it affect the brain or spine, liver or kidney function – should those organs harbor the tumor and painless swellings when lymph nodes are involved. When lymphoma affects your cat’s digestive system, the first signs seen are usually poor appetite and weight loss, followed later by vomiting or diarrhea. In other cats, an unkempt hair coat and lack of energy and interest may be the only initial signs.
The vagueness of early signs of lymphoma are why most cats are initially treated just for symptoms in the hope that whatever the underlying problem, it will heal with time. It is only when these symptoms persist over months that veterinarians begin to consider more serious problems – like lymphoma.
With time, your veterinarian may detect lumps (swollen lymph nodes) as he/she palpates your cat’s body. With time, the vet may notice intestines thicker and more rigid than they should be when the intestine is the site of the tumor. As lymphoma progresses, many cats become moderately anemic. You can follow Nick, a 10-year old cat, through his diagnostic journey here.
As I mentioned earlier, physical exams in early lymphoma cases are often normal, and physical exams that note weight loss and an unkempt appearance often give no indication of the underlying cause. When an abnormal lump, organ shape, or mass is detected, the vet is well along toward a diagnosis but palpation of the abdomens of cats even in advanced stages of lymphoma can appear completely normal.
No blood test that veterinarians currently have can definitively diagnose lymphoma tumors unless the tumor is of lymphocytes circulating within the blood itself (leukemia). You can see how those results arrive back at the vet's office here.
However, complete blood cell counts (CBC/WBCs) sometimes show a mild to moderate anemia (nonregenerative anemia). Even more common is low blood albumin levels (hypoalbuminema). Low blood albumin protein in lymphomas occurs when cats do not eat sufficiently, when there are changes in their intestinal lining that limit their ability to absorb protein (malassimilation) and when changes caused by intestinal lymphomas cause their intestines to leak protein from their circulation. Some of these cats have elevated serum globulin antibodies as well.
Blood cobalamine (vitamin B-12) and folate levels are often reduced in these cats due to decreased intestinal absorption of these nutrients.
Occasional cats have higher than normal numbers of lymphocytes circulating in their blood (lymphocytosis). (ref)
FLV And FIV Test
Because veterinarians know that cats that are positive for feline leukemia or feline AIDs are at a higher risk for lymphoma, your veterinarian will want to determine their status. You can read about that test as it is commonly performed here.
Lymphoma cannot be diagnosed through conventional x-rays. However, your veterinarian may wish to rule out other possible causes for your pet’s poor health, and x-rays assist in doing that. Occasionally signs of enlarged mesenteric lymph nodes (ref), thickend or dilated loops of intestine and a blurring of abdominal image detail will bring lymphoma to mind – as will increased mass present between your cat’s lungs when its chest is the site of the problem (mediastinal masses).
An ultrasound examination, performed by a veterinary radiologist, will tell your vet more. Evidence that the walls of your cat’s intestines or stomach have thickened, enlarged lymph nodes, and a loss of normal intestinal layers and a narrowed intestinal internal diameter are all compatible with lymphoma or a chronic inflammatory condition such as IBD. You can read how attempts are made to tell them apart here.
Ultrasound availability is also invaluable in guiding a needle through the cat’s abdominal wall and into suspected lesions to withdraw cell samples for analysis (fine needle aspiration, cytology and sample histopathology).
When performed periodically, ultrasound is also quite helpful in determining if the medications being administered are shrinking the cat’s lymphoma.
Endoscopes are optical apparatus that allow your veterinarian to peer into your cats digestive tract. Veterinary endoscopes are similar, but narrower in diameter to those used in human coloscopy. Your veterinarian will be looking for abnormally thickened areas in the stomach and intestinal wall, abnormal coloration and, perhaps, ulceration of the intestinal lining. These scopes are designed with a retrieval channel (tube) that allows small snippets of tissue (biopsies) to be harvested and withdrawn whenever the veterinarian encounters a suspicious area. To fully examine the intestinal tract, common endoscopes must be inserted both down the mouth and up the cat’s anus.
Although it is uncommon to use Magnetic resonance imaging in typical lymphoma diagnosis; MRI’s can provide important information when lymphomas occur in unusual locations. You can read about one situation like that here.
As with MRIs, CAT scans are seldom necessary in diagnosing lymphoma. But they can be helpful in judging treatment progress. You can read about a case in which CT scans was helpful here.
Microscopic Examination Of Tissue Samples (= Histopathologic evaluation of biopsy specimens)
Having a veterinary pathologist examine tissue
from a site suspected of harboring a lymphoma is the key method veterinarians
rely upon to diagnose lymphoma. There are many ways that pathologists
decide when cells are cancerous. Cancerous cells tend to be in the process
of division more frequently than they should, they tend to be larger than
the normal cells from which they originated, they tend to loose the distinctive
Because it can be impossible for pathologists to decide with certainty if a group (nest) of lymphocytes constitute a cancerous lymphoma tumor (a neoplastic population of lymphocytes) or are simply there to respond to chronic inflammation (a reactive population of lymphocytes), veterinarians have found techniques that analyze the composition of the lymphocytes to give them additional clues. This is particularly helpful when lymphoma is suspected in the cat’s digestive tract. These techniques also allow veterinarians to determine if the lymphoma originated from the cat’s T-lymphocytes or B-lymphocytes – something that can be helpful in devising the best treatment plan.
We know that cancerous lymphocytes tend to arise
from a single defective cell. One, that, like the broom in Disney’s
Sorcerer’s Apprentice, has become oblivious to its environment.
Is How Those Tissue Samples (biopsies) Are Collected Important ?
Yes, it is very important.
When tissue samples are collected using the aid of an endoscopic tube inserted through the cat’s digestive tract the cat needs no surgery and no more than light anesthesia to perform the procedure. That is a great plus. The drawback is that samples obtained that way sample only the most inner layers of the cat’s intestinal wall. That makes differentiation between chronic inflammatory changes like IBR and Triad Disease and true lymphoma more difficult. That is because one gauge of malignancy (cancerous nature) is the extent to which cells have invaded deeper or surrounding tissues. These same drawbacks occur when specimens are obtained through a long ultrasound-guided needle.
When actual surgery is performed to harvest samples,
tinny full-thickness specimens can be harvested. Those specimens can often
tell the pathologist things that endoscopically-harvested samples cannot.
Such surgery also offers your veterinarian the best view of what is actually
happening within your cat, what other organs are affected, potential blockages,
etc. The drawback is the stress and risk of general surgery in a cat that
may already be weakened.
That is very dependent on a process called staging. Staging refers to a detailed consideration of the problem and the extent of the area affected by lymphoma, the lymphoma cell-type involved, the general health of the cat and its ability to withstand the possible side effects of the drugs used to treat it.
All the tests I discussed earlier will be used in making that decision. And that decision must have input from both the pet owner and the attending veterinarian – just because something can be done does not mean that it should be done or that it is in the cat’s best interest to do it. Colorado State University understood that when they added a philosophy course on bioethics to their vet-student curriculum. You can read one of the professor’s articles here.
A study, conducted in 1996 in Texas and Ohio found
certain factors that were quite important in a cat-owners long-term satisfaction
with the decisions they made upon learning that their cat had life-threatening
cancer. Chief among them were the knowledge that their veterinarian explained
all treatment options to them compassionately and in detail, and gave
them a realistic picture of the number of return visits, setbacks, adverse
reactions and the emotional toll the long-term care of a sick animal can
take on family members. When owners elected not to treat their cat with
advanced methods, concerns over the future quality of the cat’s
life, perceived pain and suffering of the cat, cost, time commitment and
previous experience with pet cancer were their chief considerations. You
can read that study here.
Your cat is truly fortunate if pathologists inform
your veterinarian that the diagnosis is small-cell lymphoma. That form
of lymphoma is the most treatable of all.
Therapy For More Aggressive Large-cell ("high-grade")Lymphomas
I included links to studies on the used of chemotherapy drugs for cats with lymphoma. They all report impressively positive results. Please remember that
There are a number of accepted treatment plans for these more-malignant lymphomas. However, all those plans include the use of a combination of drugs that have the potential to cause severe side effects and the additional time your cat might realistically gain on this Earth will be quite shorter (60-200 days) than when battling the small-cell forms.
COP And CHOP Treatment Protocols
Veterinary oncologists commonly use a combination
of cyclophosphamide, vincristine and prednisolone (COP) or a combination
of cyclophosphamide, doxorubicin , vincristine and prednisolone (CHOP)
to treat cats with the more aggressive large-cell lymphomas.
The University of Wisconsin - Madison Treatment Protocol
Other veterinary oncologists prefer what is known as the Madison protocol. This treatment plan combines intermittent (pulsed) use of vincristine, L-Asparaginase, prednisone, cyclophosphamide and Doxorubicin. The median survival time for cats undergoing this procedure is about 210 days although a few isolated cats survive much longer. You can read how this protocol is performed here.
A modified method switches prednisolone for prednisone and throws in methotrexate. (ref)
When radiation is used to treat lymphoma in cats, it is usually as a “rescue” protocol when other techniques no longer keep the lymphoma under control. It does have its place in treating lymphomas that occur in isolated areas of the body susceptible to a focused radiation beam. You can read some articles that explain its use in lymphoma treatment in cats here lymphomacat-Parshley2011 and here lymphomacat-Williams2010.pdf I never recommend it as an option for my clients but I do mention it and some do go that rout.
Rescue therapies and last-ditch efforts to keep the cat alive that are not based on radiation also exist. You can read about one here ;but I am philosophically opposed to extending these cat’s suffering.
Surgery is an option for very isolated, well-demarcated (circumscribed) lymphomas – primarily those present in a single isolated lymph node or a single well-defined tumor that is blocking the cat’s intestine. But surgery is usually ineffective in treating the diffuse lymphomas as they usually occur in the cat’s digestive system. When used, surgery in those other cases tended to actually shorten the cat’s remaining life.
It can be difficult to convince a cat to do what you think is in its best interest. Cats are independent creatures that do not willingly make changes in their basic lifestyles.
When a cat is feeling poorly, its relationship with other cats and other pets in the household will change. Most ill cats seem to do better when you define special spaces for them. Keep them in visual or sound contact with the family members – but give them defined areas they have to themselves.
Cancer affect the appetite of cats more than it
does dogs. I do not know why that is, but cats with lymphoma often have
a poor appetite. The best sign that your cat is dealing well with its
problem is its ability to maintain its body weight. Purchase an accurate
table-top digital scale to monitor that. With time, you will probably
have to tempt your cat with savory foods that have the odors and mouth-feel
that your cat most prefers. Commercial prescription diet producers do
a miserable job in providing foods that do that and veterinarians are
drilled by those companies every day not to suggest you make your cat’s
meals at home.
Here are some hints:
There may come a point when you will need to rely on assisted feeding, feeding tubes and appetite stimulants to get your cat the nutrients it requires. Squeeze mustard bottles or turkey basters work well to deliver food into your cat’s mouth. Never elevate the cats head too high when attempting to feed it.
The most frustrating problem owners of cats with lymphoma face are the cat’s reluctance to eat. I hope I have given you some ideas that will help you in dealing with that.
The second most frustrating problem for owners of cats with intestinal tract lymphoma is soiling the house and a reluctance to use the litter box. Add several more, easy-entry boxed in scattered locations. Experiment with different brands of litter.
Dehydration, due to vomiting, diarrhea and a refusal to drink will need your immediate attention when they occur. Talk with your vet on how best to manage those problems. Take on as much of those duties yourself to avoid stressful trips to the veterinary hospital. Vets differ in their willingness to instruct you in home nursing care. Make it clear to the veterinarian that you are willing and committed to assume those responsibilities.
When lymphoma affects the intestine, blockages sometimes occur. Those need to be deal with promptly by your veterinarian. Their occurrence can sometimes be minimized by altering your cats diet as well as the amount of fiber and water-drawing ingredients (lactulose, polyethylene glycol, etc. ) it contains.
When lymphoma affects organs and areas outside of the digestive tract, it will eventually interfere with the proper function of those organs. Those problems are too numerous for me to list, but your veterinarian will devise strategies to maintain organ function as long as possible.
Your cat’s ability to maintain or gain weight
is the most accurate way of judging your cats progress in fighting lymphoma.
A second key point is that your cat’s long-term prognosis (outlook)
is very dependent on its improvements during the first few weeks of chemotherapy.
The cats that make the most noticeable and dramatic improvements in general
health are also the ones that tend to benefit long term.
Veterinarians have few object ways of telling you that. We do know that cats on the young end of the age scale when the tumor is first discovered tend to live longer. It also appears that cats that develop T-cell lymphoma types also seem to have a more favorable outlook – although all do not agree on that point.
The size of the individual lymphoma cells (small-cell type vs. large-cell or high-grade type) greatly affects survivability. Whereas about 69% of cats with the small-cell types survive an additional 17 month after initiating treatment, only 18% of the more malignant large-cell types live an additional 2.7 months after beginning treatment.
The degree with which the lymphoma has penetrated adjoining tissue layers and organs (infiltrative) is also a major factor in survival, as is metastasis of the tumor to other body sites.
Vets have also noticed that the severity of weight loss and general condition when therapy is first begun greatly affects its future longevity. The more the cat weight has decreased from its traditional body weight, the less likely therapy is to gain the cat extensive additional time.
Nothing is set in stone. There will always be cats and people who defy the odds when struggling with lymphoma. You might take heart in reading about one woman’s remarkable experiences here.
Lymphomas are not, in themselves, painful. But they can affect structures adjacent to them in painful ways. There are many medications to help deal with that. My preference are for fentanyl patches. (these patches can cause constipation which is a manageable problem in some cats and a welcome one in others ref )
When lymphoma affects the digestive tract, it can cause blockages that are painful (colic). That will need to be addressed by your veterinarian. You can read about that problem here.
Most cats tell their owners that themselves. You know your cat. Do not let anyone else tell you it is time, or it is not time to let go. Do not let anyone lay guilt at your feet for doing or not doing what they suggest. If you have read this far, you know that veterinarians cannot really predict the outcomes of any therapies they suggest. Specialists tend to paint a rosier picture than veterinarians in general practice. When questionares were given to the owners of cats with lymphoma six month after deciding to treat or euthanize their pets, those that were most comfortable with their decision were the ones that had the most caring, empathetic vets who gave them realistic an complete information on their cats outlook that included cost, number of return visits, adverse treatment reactions and realistic possible lifespan. You can read that study here (I linked to it earlier) and another here. You can read some of my thoughts on dealing with the grief that will bring, here.