Mar Vista Animal Medical Center

3850 Grand View Blvd.
Los Angeles, CA 90066

(310)391-6741

www.marvistavet.com

INJECTION SITE SARCOMA
also called Vaccine Associated Fibrosarcoma and Vaxsosarcoma

Back in the 1990's, researchers began to take note of locally aggressive tumors developing in the feline scruff of the neck, where vaccinations and therapeutic injections are typically given. The idea that vaccination (and potentially other types of injections) might occasionally cause cancer began to circulate in the feline medical community. By 1997, a task force had assembled to study the situation and make recommendations. We have come a long way since this time and will present to you what you should know about the Feline Injection Site Sarcoma (FISS) situation.

 

WHAT IS AN INJECTION SITE SARCOMA AND WHY DO WE THINK VACCINATION MIGHT CAUSE IT?

Soft tissue sarcomas have been recognized as difficult, deeply rooted tumors of the cat for a very long time, long before injections were ever involved. There are many types of soft tissue sarcomas with the fibrosarcoma being one of the most common. The fibrosarcoma is a tumor that does not usually spread throughout the body in the way we usually think of cancer; instead, it digs in deeply and widely in a localized area. After surgical removal, it is notorious for recurring even more aggressively than before. Distant spread does occur but much later in the course of the disease.


The schematic above shows how a fairly small lump can invade deeply into the body.
(original graphic by marvistavet.com)

Fibrosarcomas can result spontaneously in either dogs or cats, as can any cancer, or they can be virally induced in cats via the feline sarcoma virus. While spontaneous and viral fibrosarcomas have been described for decades, the potential for vaccination to lead to the formation of these tumors is a relatively new concern. The idea that cats could develop a sarcoma associated with vaccination began to receive attention when some of the following facts emerged:

  • When local laws change to require rabies vaccination for cats, the incidence of fibrosarcomas increases in that area.
  • Hawaiian cats have a reduced incidence of fibrosarcoma (rabies vaccination is not generally performed in Hawaii as the islands have successfully eradicated rabies).
  • The most common sites for these new especially deep fibrosarcomas are the area between the shoulder, the lower back & hind limb (areas commonly used for vaccination).
  • Some of these tumors contained vaccine adjuvant (material needed to boost the effectiveness of killed virus vaccines).Dogs are so rarely affected by this phenomenon that is considered of no realistic significance. Vaccine-induced fibrosarcomas seem to be a feline problem only.

Reports of sarcomas stemming from other injections followed and it is now accepted that chronic inflammation concentrated in a small area is the root of the feline injection site sarcoma. Killed virus vaccine especially creates the exact scenario that can create a sarcoma in an individual with the right predisposition for it.

Despite the extremely low incidence of this problem, the problem is still very serious and the veterinary profession has responded with numerous studies on how vaccines might be related to tumor formation, why is the incidence so low given how many vaccines are given to cats annually, what can be done for prevention.

 


(original graphic by marvistavet.com)

The vaccination process uses a modified version of the virus to stimulate the immune system against the natural infectious virus. The modified virus can be alive but weakened or it can killed. (Recombinant vaccines are a story for another time). Modified live virus will circulate through the body in a natural way typical of the infectious virus. As it moves through the body it stimulates the immune response but doesn't generate illness.

A killed virus vaccine presents the virus to the immune system but the virus is dead and doesn't replicate, bind anywhere or do anything that a live virus might do to stimulate immunity. In fact, the body will tend to clear out the dead virus as it clears out other microscopic debris and if this happens too quickly, a quality immune stimulation will not result. To see that this does not happen, adjuvants are added to hold the dead virus in place and attract the attention of the immune system. This kind of localized stimulation can lead to localized inflammation in the area of vaccination and one theory is that this inflammation is what leads to precancerous changes in the local cells. Indeed, some fibrosarcomas have been found to have vaccine adjuvant embedded within them.

Every manufacturer of killed virus vaccines (which in cats are typically rabies vaccine and feline leukemia vaccine) makes its own adjuvant and no single adjuvant has been implicated in the sarcoma phenomenon. In fact, current thinking is that the cat's genetic make up is just as important in determining if this kind of inflammation can lead to a pre-cancerous change in the tissue. Most cats do not generate cancer from localized inflammation: it takes the "right" cat and the "right" vaccine.

  

SO HOW OFTEN DOES THIS ACTUALLY HAPPEN?

Happily, not very often. Sarcoma incidence is extremely rare with different studies reporting an incidence between one in 1000 to one in 10,000 vaccines administered. To put this in perspective, using the traditional vaccination guidelines a cat would receive three vaccines annually during his or her fifteen year lifespan for a total of 45 vaccines, not including the initial kitten series. In other words, a typical cat would receive 45 vaccines in its lifetime and a sarcoma erupts in 1000-10,000 vaccines. And now that we have some prevention strategies, the incidence is likely to be even less.

It can take as short a time as two months and as long as ten years to develop a vaccine site tumor but most appear within 4 years of the offending injection. While most (80%) of the tumors that develop are fibrosarcomas, other types of tumors that can develop through this phenomenon include:

  • the malignant fibrous histiocytoma
  • the osteosarcoma
  • the rhabdomyosarcoma
  • the liposarcoma
  • the chondrosarcoma
  • the undifferentiated sarcoma

(All are tumors of either muscle, bone, cartilage or fat)

 

SHOULD I STILL VACCINATE MY CAT? WHAT HAS BEEN DONE ABOUT THIS PROBLEM?

Vaccination remains one of the most important aspects of preventive care for cats and the risk of tumor development was already low before new policies were developed to make it even lower. So, yes, you should still vaccinate your cat.

To minimize the risk of tumor development even further, there have been several developments in vaccination. For example, vaccinations are made differently now. Instead of the simple modified live versus killed option, we now have recombinant vaccinations which allow a live non-adjuvanted approach to vaccination against diseases like rabies and feline leukemia virus. These are preferentially used over the adjuvanted killed vaccines that have been heavily implicated in sarcoma formation.

Some vaccines are administered in a needle-free manner (such as nasally) to avoid creating a depot of vaccine in the muscle and skin tissues.

Vaccines are divided into "core vaccines" which all cats should have regardless of their indoor/outdoor lifestyle (rabies and FVRCP distemper vaccines are considered "core") while other vaccines are given depending on the cat's realistic risk of exposure.

Vaccines are now given in specific locations so as to control how much inflammation occurs in a given spot.


Two recombinant vaccines
made by Merial®.

(original graphic by marvistavet.com)

For a summary of the 2020 vaccinations guidelines for cats from the American Association of Feline Practitioners visit:

https://journals.sagepub.com/doi/pdf/10.1177/1098612X20941784


GUIDELINES FOR VACCINE-ASSOCIATED SARCOMA PREVENTION

Avoid unnecessary vaccination

Be wary of vaccination recommendations that encourage you to vaccinate for every possible disease. Recommendations are highly regional and individualized according to the philosophy of the animal hospital you are visiting and every veterinarian may have a different philosophy but the guidelines developed by the American Veterinary Medical Association, American Association of Feline Practitioners, American Animal Hospital Association, and Vaccine Associated Sarcoma Task Force are a good place to start (see link above).

 

Vaccinations should go in standardized areas

Each type of injection and each type of vaccine has been assigned an area on the cat's body for administration. This not only helps researchers track which vaccines are associated with which tumors but also separates administration zones so that inflammation from multiple injections does not add together in one spot. Accepted vaccination guidelines recommend giving vaccines in the areas shown, using the lower limbs or even the tail. These areas have been selected so that, in case a tumor develops, the central body is not involved and amputation of the affected body part is possible. This sounds like a very radical surgery and it is; however, the fibrosarcoma is a very aggressive and malignant tumor and extreme measures are generally needed to control it. Should a tumor develop a very wide excision is needed and simply removing the visible "bump" is not going to be helpful in the long term.


Injections should be given below the
elbow/knee or in the tail as depicted above.

(original graphic by marvistavet.com)

 

The 3-2-1 Rule
Be aware of lumps forming after vaccination (the 3-2-1 Rule).

Lumps commonly form in the weeks following vaccination due to the immune stimulation and inflammation centered on this area. These lumps are usually normal and do not represent fibrosarcomas (which generally take years to develop, not weeks). If your cat develops one of these lumps under the skin (they are usually noticed by owners 3-4 weeks after vaccination), the lump may be left alone to resolve naturally. If the lump is still present 3 months from the time of vaccination, it should be removed and biopsied. Any lumps greater than 2 cm in diameter (approximately one inch) should be removed no matter how long a time has past since vaccination. Also, any lump should be biopsied if it is felt to be getting larger rather than smaller one month after its discovery. ("3-2-1" refers to 3 months post vaccine, 2 cm in size, growing bigger after 1 month.)

Sometimes one such lump will break open. This usually means an infection is present rather than that a fibrosarcoma has developed. Your veterinarian should be informed of this occurrence and the pet should return for therapy.

 
(original graphic by marvistavet.com)

TREATMENT FOR VACCINE ASSOCIATED FIBROSARCOMAS

Injection site sarcomas can be thought of as being similar to an octopus in structure. There is the "body" that you see but there are also far-reaching "tentacles" that cannot be seen extending far from the visible body of the tumor. For surgery to be successful, a very broad excision is needed and it is necessary to first determine how far the tumor has spread. Chest radiographs are vital for staging and CT scanning, if available, is very helpful in detecting the extent of the invisible tentacles. If CT scanning is not available, 5 cm (approximately 2 inches) should be removed around the visible portion of the tumor in all directions including any bones. Basic blood work including a feline leukemia virus test is needed to fully assess the cat for treatment.

If it is possible to remove 2 inches in all directions around the visible tumor (and consider for a moment how large a volume of tissue this is), the median survival time is two and a half years. The problem is that, unless the sarcoma is on a limb that can be amputated, it will not be possible to remove that much of the cat's body. If the complete tumor is not removed, it is almost certainly going to grow back. This is where radiation therapy can help a great deal. Whether this should be done before the surgery or after remains controversial and depends on the tumor grade and location. Radiation before surgery can shrink the tumor so as to make surgery more effective. Radiation after surgery can "clean up" bits of tumor not removed in surgery but must be delayed until the surgery site has healed and delay can be a problem. Radiation can also be used for "palliation" which means the goal is slowing the tumor growth rather than curing it. Fewer radiation side effects and less expense is associated with palliative treatment.

Chemotherapy is sometimes used in conjunction with radiation and surgery depending on the grade of the tumor and its location. Expect a referral to an oncologist to be needed to get the best and most up to date treatment plan.

Our goal in creating this web site is to create awareness of an emerging problem in veterinary medicine, not to elicit panic. We believe that intelligent decisions about pet ownership require information and education.

To review our hospital's current vaccination recommendations click here.

Page last updated: 7/27/2021