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Tumors

by Debbie “The Rat Lady” Ducommun

updated 7/28/14

Along with respiratory infections, tumors are one of the most common health problems and causes of death in rats, especially in females.  There are two main types of tumors, benign and malignant.  Benign tumors are almost always encapsulated in a membrane and separate from nearby tissues.  Although they can grow as fast as malignant tumors, they don’t usually cause as much damage and they don’t metastasize (spread to other parts of the body).  Benign tumors can cause death by pressing on vital organs, bleeding internally, or by growing so large that the rat has difficulty moving around and can’t eat enough to support both the tumor and normal body functions.  Benign tumors can often be removed depending on their location.

 

In contrast, malignant tumors, also called cancer, usually invade and damage nearby tissues.  They sometimes also metastasize (rarely in rats).  Death can be caused by failure of damaged organs or mechanical interference with normal functions, such as eating.  The symptoms of cancer can include a skin ulcer, infected lump, or abscess that won’t heal, an ulcerated or bleeding tumor, a distended abdomen, weight loss, and lethargy.

 

In some cases, cancer involves the internal organs, so symptoms often aren’t seen until the disease is well advanced and euthanasia is the only alternative.  This is why it’s important to give your rats a weekly exam.  Many benign tumors can be removed, depending on the location, and surgery for some types of cancer can give a rat many more months of quality life.  Some tumors can be temporarily shrunk with prednisone.

 

Mammary Tumors

The most common tumor in female rats is the benign mammary tumor, most being a fibroadenoma (fibro—from connective tissue, aden—from a gland, oma—a benign tumor).  These tumors are often stimulated by estrogen and usually occur after a rat stops ovulating at around 18 months of age.  About half of all female rats will get mammary tumors, and it’s common for them to get several during their life either at the same time or one after the other. The most common locations for mammary tumors are in the armpits, in the belly or groin area, on the chest, and next to the vulva and anus. Feel your rat all over frequently so you can identify tumors early.

 

Mammary tumors often start out squishy and flat, and then become more firm, but they can also be quite hard from the start.  Because the tumors grow so quickly, a portion will sometimes outgrow its blood supply, die and become necrotic and filled with pus. Mammary tumors also commonly contain pockets of milk, which can grow very quickly. 

 

Benign mammary tumors are usually distinct lumps just under the skin that are only loosely attached.  When you feel the lump, you can usually move it separately from the skin and underlying muscle. If your rat gets one of these tumors, you can be 99.9% sure it’s benign.  If a tumor feels tightly attached to the underlying tissue, this can be a sign that it is malignant, but I have found that some benign tumors also feel attached because they are underneath connective tissue and turn out to be easily removed by surgery.  Benign mammary tumors can grow huge (up to 4" across). They tend to have a basically round shape that tends to protrude. A malignant mammary tumor will rarely get more than 2" across and tends to stay more flat.

 

Here is a Pumkin with a large benign mammary tumor.  By her back leg, you can see a staple from a previous tumor removal surgery.

 

This rat has a medium-sized benign mammary tumor in her groin.

 

This rat has a medium-sized mammary tumor under her left arm.

 

For pictures of surgically removed mammary tumors, click here.

 

In my experience, malignant mammary tumors most commonly appear in the vulva/anus area, but not all tumors in this area are malignant. The location alone is not enough for diagnosis.  Malignant mammary tumors can also appear under the arm. A mammary tumor that appears dark is almost sure to be malignant.  Malignant mammary tumors also commonly develop ulcers, abscesses and open sores that weep bloody fluid and tissue. A benign mammary tumor won’t develop an ulcer until it is huge. A needle biopsy is not usually helpful in the diagnosis of the type of tumor.

 

The blue color of this mass indicates it is a malignant mammary tumor.

 

Surgery is not recommended for malignant mammary tumors, as they quickly grow back, but they can be successfully treated with tamoxifen. See Tamoxifen to Prevent and Treat Tumors.

 

Tamoxifen does not seem to be an effective treatment for benign mammary tumors.  They must be surgically removed.  If you decide not to have a benign mammary tumor removed, you can expect it to keep growing, until it is as big as the rat herself.  Within a few months you must be prepared to have your rat euthanized when she is no longer enjoying life.  In the meantime, you can help your rat maintain her quality of life by making sure she eats a very nutritious diet, high in protein, fat, and vitamins, because the tumor will be drawing resources and energy from her body.

 

A more rare cause of a lump near a nipple is a blocked milk duct or inflamed mammary gland.  Treatment with warm compresses 2-3 times a day and an antibiotic should resolve this within a week.

 

Male rats can also get mammary tumors, but they are uncommon and almost always benign.

 

Lumps on the Throat

A lump on the throat can be an abscess, an inflamed salivary gland, a swollen lymph node, or a tumor.

 

Salivary glands can enlarge as an inflammatory response to the SDA virus or a bacterial infection. A lymph node can enlarge in response to a bacterial infection or cancer. These structures are paired on either side of the throat.

 

A gland or lymph node can swell up overnight, and an abscess can also appear quickly. Tumors tend to grow more slowly.  For a sudden lump, try an anti-inflammatory first as this will usually cause a swollen gland or lymph node to shrink within 12-24 hours. You can also wait to see if it is an abscess (See Abscesses and Cysts, next article). See Abscesses. 

 

Pituitary Tumors

The second most common type of tumor in female rats is an adenoma (benign tumor) of the pituitary gland, which lies beneath the brain.  In fact, this is probably the third most common cause of death in female rats.  The incidence in my unspayed female rats has been 20% and in my male rats 7%.  Scientific studies show that having rats spayed reduces the chance of a pituitary tumor down to 4%. For photos of rat pituitary tumors (warning, very graphic) click here.

 

A pituitary tumor is not as obvious as a mammary tumor as it grows inside the skull. As the tumor grows it presses on the brain and eventually causes neurological impairment.  Symptoms may appear slowly, over a period of a few days or a few weeks, or quickly.  These tumors are highly vascular and in some cases they can hemorrhage, which can cause acute severe symptoms, such as paralysis, seizures and death.  It also seems that a slight hemorrhage from the tumor can cause symptoms that later clear up.

For a typical pituitary tumor causing a slow onset of symptoms over a week or two, the usual first symptom is a loss of coordination, followed by some loss of function of the arms and legs and mouth.  Sometimes the rat is hyperactive, and she may walk in circles and run into objects. She may also have other strange behaviours. Eventually, as the symptoms progress and the neurological impairment progresses, some become very infant-like and cuddly. At some point, all victims of a pituitary tumor will need to be hand-fed, and eventually they will lose the ability to swallow and must be euthanized.

One symptom that is common with a pituitary tumor is a quite distinctive posture: first the front, then the hind legs are held out stiffly forward and cannot be flexed by the rat.  When you pick the rat up, the arms and legs will often be held forward, although sometimes the hands are curled.  Another behavior that is common is when a rat butts her head up against your hand when you pet her. 

Neurological symptoms, including seizures, a head tilt, circling, and lethargy, can also have other causes, such as a stroke, toxins, encephalitis, or an inner ear infection (head tilt).  Fortunately, the recommended treatment for neurological impairment from any cause is with antibiotics and prednisone at 1 mg/lb twice a day.  These can reduce the size of a pituitary tumor and temporarily relieve the symptoms, but the treatment doesn’t always help.  In one case, prednisone did not help but dexamethasone did help.

The antibiotic that seems to help the most with pituitary tumors is amoxicillin. In fact, when my first rat with a pituitary tumor developed symptoms, my vet thought she might have meningitis, and we treated her with amoxicillin. Her symptoms improved drastically for almost a week! Then her symptoms returned, and it wasn’t until she died and I performed an autopsy that I found the pituitary tumor.

If the treatment is going to help, you should see improvement in the symptoms within a week.  The treatment then needs to be continued for the rest of the rat’s life.  I know of a few cases where this treatment was able to give a good quality life to the rat for 3 to 10 months.  If despite treatment the rat is no longer able to eat, she should be euthanized.

In 2011, I reported on a new treatment for pituitary tumors in the Rat-a-tat Chat, the quarterly newsletter of the non-profit Rat Assistance & Teaching Society (www.petrats.org), and here is that report:

An Exciting New Treatment for Pituitary Tumors

            Earlier this year, I heard from a couple of rat owners that their veterinarians had prescribed a drug called cabergoline for rats suspected of having a pituitary tumor. In April, a veterinarian had even emailed me to see if I had heard of cabergoline being used in rats, but it was all new to me. I did some research online and learned that it is a drug used to treat the most common type of pituitary tumor in humans, called a prolactinoma, which is a benign tumor (adenoma) of the pituitary gland that overproduces a hormone called prolactin. The overproduction of prolactin can result in abnormal milk production. At first I thought the cabergoline only reduced the production of prolactin, but apparently it can actually reduce the size of a pituitary tumor, which is very exciting.

            A case study published in the September 1, 2011 issue of the Journal of the American Veterinary Medical Association reported that a male rat with a large pituitary tumor was given about 8 more good months of life through treatment with cabergoline. The 2-year-old unneutered male rat was taken to the Tufts Cummings School of Veterinary Medicine in North Grafton, MA, with a 3-week history of apparent blindness, aggressive behavior and a reduction in water intake. The veterinary exam also found the rat’s hind legs were partial paralyzed. An MRI scan, which was done with the rat anesthetized, showed a large pituitary tumor measuring 11.4 X 8.6 X 8.3 mm (about 7/16 X 5/16 X 5/16 inch—about the size of an unshelled peanut) which was half the length of the rat’s brain. The rat was put on cabergoline at 0.27 mg/lb once every 3 days and there was improvement in his behavior within three days of starting the treatment. Eight weeks later the rat’s behavior had returned to normal and another MRI showed that the tumor was reduced to 41% of its original size, and was now only 8.4 X 6.7 X 5.9 mm (which is still pretty big—about the size of a large raisin).

            The rat apparently did well until eight and half months after the onset of treatment, when he was taken back to the vet with hind leg paralysis, weight loss, and respiratory distress. A third MRI found the tumor had regrown to 9.1 X 8.0 X 7.3 mm, and the rat was euthanized. A biopsy confirmed the diagnosis of a prolactinoma.

            The most common side effects of cabergoline in humans are digestive-related, such as nausea and constipation, or behavioral, such as dizziness, insomnia, or depression. The only medication that interacts with cabergoline that rats might also be given is metoclopramide, a treatment for mega-esophagus, which is a very rare problem.

            The only problem with using cabergoline to treat pituitary tumors in rats at this time is the cost. Currently, my vet found that it would cost about $190 a month for the treatment. If that cost would not be a problem for you, then you might want to ask your vet about cabergoline treatment for any rat who shows symptoms of a possible pituitary tumor.

A treatment alternative to cabergoline is bromocriptin, a similar-type drug. Bromocriptine is less expensive, but perhaps less effective. One rat with severe symptoms had rapid improvement and did well for 2 months. It seems to work best in combination with prednisone. It can cause stomach upset and bleeding, so you need to start with a small dose, and gradually increase it. Always give it with food. Start with a dose of 0.15 mg and slowly increase to 0.63 mg twice a day.

Other Types of Tumors

Another fairly common tumor in rats is a fibroma.  Because these tumors derive from fibrous tissue they are usually quite hard, but they are benign and easily removed.  They are most common on the side or back.

One of the most common types of cancer in rats is squamous cell carcinoma.  I’ve seen 6 of them, 2 on the face, one from the eyelid, and 3 under the jaw, and I’ve heard of several more.  This type of tumor is most common on the face and should be suspected with any swelling or abscess in this area. 

Another very common place for cancers to appear is directly below the ear. These cancers usually seem to be an abscess, and you should suspect any abscess in or around the ear of being cancer. These cancers can arise from the Zymbal’s gland, but in one of my rats, pathology found that such a tumor was a skin tumor. You’ll know that it is cancer if the abscess contains tiny lumps of white tissue or a soft mass of fibrous tissue instead of pus. These cancers also often bleed severely.

I know of several cases of fibrosarcoma. These commonly occur on the leg, but can also occur on the side.

I know of several cases of benign tumors growing in the vagina. At first appearance these are often mistaken for a prolapsed vagina. It appears that for such a tumor to be successfully removed, that portion of the vagina itself must be removed. This is possible in the rat, unlike dogs or cats, as the vagina is completely separate from the urethra.

To see photos of examples of these tumors, click here.

Less Common Tumors

I’ve known of two cases of histiocytic sarcoma. This is a cancer of the immune system, and in my rat there was no tumor in evidence, only abscesses resulting from the depressed immune system. I’ve known of 5 cases of lymphosarcoma in the chest, 2 in the abdomen, and one in the skin. I know of 3 cases of leukemia.

I know of one case of malignant melanoma on the scrotum, one case of a liposarcoma in the vagina, which was unfortunately also attached to the bladder, and one case of bladder cancer.

I had a semi-hairless rat who grew numerous sebaceous epitheliomas during his life, and died at the age 2 years from a basal cell carcinoma with sebaceous and epithelial differentiation.

Tumor Surgery

Since 1985 I have done more than 1000 surgeries to remove tumors from rats, and only a few turned out to be malignant.  I have removed tumors from only a few males; the vast majority were females, almost all of them with benign mammary tumors.  I have good success removing this type of tumor.

Benign mammary tumors can be removed by minor surgery.  The smaller the tumor, the more easily it can be removed (although I do not recommend doing anything for a lump the size of a pea as it could be just a cyst).  But even huge tumors can be removed as long as your rat is otherwise in good health and steps are taken to prevent shock.  I successfully removed a mammary tumor that weighed 340g from a rat that only weighed 244g! 

I’ve removed many tumors from rats well over two years old, so age should not be the only factor when considering surgery.  Because mammary tumors and fibromas are just under the skin, the surgery to remove them is minor, as opposed to major surgery which enters a body cavity, and rats usually recover quite quickly.  In fact, even rats with congestive heart failure appear to tolerate surgery well if their symptoms are controlled with medications.

If a rat younger than 24 months has a mammary tumor removed, consider having her spayed at the same time to help prevent future mammary and pituitary tumors.

The cost for rat surgery has gone up alarmingly in recent years.  In Chico (a town of 100,000) the charge is $200-300 depending on the size of the tumor.  The fee is usually higher in larger cities. The cost for a spay usually ranges between $100-150.  It’s usually cheaper and easier on your rat in the long run to have her spayed when she is young. (See Preventing Tumors below.)

Surgery can be beneficial for a fibrosarcoma. I know of 4 cases where having the tumor debulked gave the rat up to 8 more months of comfortable life. However, surgery on most cancers just results in a nasty wound that won’t heal and causes the cancer to grow back more quickly.

Tamoxifen Treatment

Tamoxifen, which blocks estrogen receptor sites in tissue, is a highly effective treatment for cancerous mammary tumors in rats.  It is not a cure, but can retard the tumor for many months.  I know of 7 cases where it was highly effective and gave the rat up to a year of quality life.  However, tamoxifen does not seem to be an effective treatment for benign mammary tumors.

A safety study showed that tamoxifen is a safe treatment in adult female rats.  It only caused problems when given to the rat for its whole life starting at 8-12 weeks of age.  This study, Results of Three Life-Span Experimental Carcinogenicity and Anticarcinogenicity Studies on Tamoxifen in Rats, C. Maltoni et al, 1997, Ann. NY Acad Sci, 837, 469-512). To see the published conclusions and summary of this study, click here.  To see the abstracts of 4 studies that show the positive effect of tamoxifen on mammary cancer, click here.

Tamoxifen is readily available from human pharmacies in the U.S. and veterinarians can call in a prescription. The dose is 3 mg/lb once a day for treatment of mamary cancer, and 1.5 mg/lb once a day for prevention.  Ideally it should be given for the rest of the rat’s life.  However, while most rats don’t object to the taste of tamoxifen at first, I know several cases where rats given tamoxifen have developed a strong reluctance to take the oral medication after a few weeks.  This can make it difficult to carry out long-term treatment.  I successfully treated one of my rats for almost a year, one month on and one month off.  Even short-term treatment can help retard the growth of cancerous mammary tumors.

You may not see any shrinkage of the tumor for 2-3 weeks, so don’t give up too soon; measure and record the size of the tumor at the start of treatment so you can keep track.  Laboratory studies show that using it along with melatonin (try 0.2 mg/day) seems to boost its effect.  Feeding soy products also seems to boost its effect.

In a few cases, owners have reported side effects from tamoxifen.  The most common visible side effect seems to be hair loss.  In some rats is has also seemed to cause fatigue.

A less obvious side effect of tamoxifen is that it reduces the number of platelets in the blood.  This interferes with the blood’s ability to clot.  If a rat on tamoxifen needs surgery, you should stop tamoxifen treatment for 1-2 weeks before the surgery to prevent excessive and perhaps fatal bleeding.

In one study leuprolide, which blocks the release of estrogen, was slightly more effective than tamoxifen against induced tumors, but it is very expensive.  Having the rats spayed is less expensive and more effective.

Other Non-Surgical Treatments

A compound that has been shown to both treat and prevent cancerous mammary tumors induced (not natural tumors) in the lab is conjugated linoleic acid (CLA).  This compound has even been shown to help rats lose weight!  When given 75 mg a day, the body fat of rats was reduced by 23%.  Another study found that DHEA given at a dose of 6-12 mg/day protected against induced cancerous mammary tumors.  Other studies show that giving curcumin, an ingredient in turmeric, reduced tumors induced in the lab.  They gave about 150 mg per day. 

Shark cartilage can help to prevent the formation of new blood vessels, which tumors need to grow.  You must start it as soon as you notice the tumor.  I know 3 cases where it has helped but I do not recommend using it for a tumor larger than a marble, because it can cause the tumor to die.  You can buy 200 g for $36 at www.myvitanet.com.  Try 360 mg/lb per day mixed in food.  It may work better when combined with co-enzyme Q-10 (try 0.2 mg/day), and tamoxifen.

Treatment with prednisone for some cancers other than mammary cancer can slow their growth.

There is some evidence that a high fat/high protein diet is best for cancer patients.  It seems that a diet high in carbohydrates may be more easily used by tumors.  You might try giving soy baby formula plus additional protein and B vitamins.

Preventing Tumors

There are 4 ways to try to prevent tumors in your rats.  The most effective way to prevent mammary tumors in females is to have them spayed.  Three studies have shown that spaying drastically reduces the incidence of these tumors, from 40-70% to only 4%!  Spaying also decreases the incidence of pituitary tumors.  In the laboratory, spayed rats also tend to live longer than unspayed rats.  For more on these studies, click here.

Spaying is most effective at 3-6 months, but has benefits at any age.  Lab studies showed that spaying will often cause mammary tumors to shrink.  The cost of having a rat spayed is usually much less than having a tumor removed, and since many female rats get multiple mammary tumors, requiring multiple surgeries, having them spayed may actually save money in the long run, as well as extending your rat’s life. 

 

An alternative to spaying is to give your female rats tamoxifen, starting at age 18 months.  Laboratory studies have shown that it does reduce the incidence of both benign and malignant mammary tumors and pituitary tumors when given preventatively.  However, as I said earlier, many rats object to taking oral tamoxifen over a long period of time.

An alternative to giving tamoxifen orally is to use a pellet implanted under the skin.  This method has been used in the lab, however, the pellets are expensive.  A pellet lasting 90 days costs $22-32 each depending on how many are purchased (25-200 tablets which have a 3-year shelf-life).  You can buy them from Innovative Research of America at 800-421-8171.  It may be more practical to have the rat spayed, which will accomplish the same thing more effectively.

The third way to prevent tumors is to choose male rats over female rats.  While males can get other tumors, the benign mammary tumors and pituitary tumors that are so common in females occur in only about 2-7% of males.

Finally, diet can help prevent cancer.  You should feed your rat a nutritious low-fat diet that includes fresh fruits and vegetables that have been shown to have cancer preventing components, such as cooked dry beans (especially soybeans), broccoli, and tomatoes.

Several studies have shown that feeding female rats miso, a soybean product, as 10% of their diet, had a protective effect against induced mammary tumors.  When combined with tamoxifen, the soy diet was almost 100% effective in preventing the tumors.  For more on these studies, click here.

Another study found that flaxseeds given at 375-1500 mg per day also had a protective effect against mammary tumors.

Some of the non-surgical treatments discussed earlier, especially CLA, have preventative effects as well.  A study showed that giving pre-pubescent female rats about 150 mg of conjugated linoleic acid (CLA) per day provided significant life-long protection against induced breast cancer.

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