Vaccination-Related Sarcomas in Cats

By:  Dawn Skupin

The threat of a rare but often fatal condition in cats, vaccine associated feline sarcomas, is prompting veterinary experts to advise cat owners and their veterinarians to think twice about whether all vaccinations are necessary for all cats.  Sarcomas are not new forms of cancer in cats.  In 1991 veterinarians began to notice a higher than normal number of invasive spindle cell sarcomas developing on cats bodies in places where vaccinations are routinely injected, e.g. between the shoulder blades or back legs etc.  In 1993 a relationship between vaccine associated sarcomas and administration of aluminium adjuvanted rabies and FeLV vaccines was established through epidemiologic methods.

Injection site soft tissue sarcomas were first recognized in the late 1980’s when some changes occurred in the vaccine manufacturing process.  At that time manufacturers changed from production of modified live vaccines to killed virus vaccines.  This was directed by the United States Department of Agriculture, (USDA). The USDA encouraged the use of killed vaccines because of concerns about vaccine-induced disease with the use of modified–live rabies virus vaccines.  This change in the manufacturing process resulted in the introduction aluminum into vaccines.  It is this aluminum component of the in-activated, (killed), feline vaccines that is suspected to be associated with the development of post-vaccinal sarcomas.  The syndrome was first documented in 1991, but cases have been seen in the northeastern United States since about 1987.  The first Canadian cases were seen in 1994.  In the United States the appearance of post-vaccinal sarcomas was linked to three historical events.

·         Legislation making rabies vaccination of cats mandatory

·         Introduction of high-potency killed rabies vaccine replacing the modified live products

·         Introduction of killed feline leukemia vaccines

The vaccinations that have been associated with the tumor development are not a specific brand or from any particular manufacturer.  Furthermore, epidemiological evidence supports a relationship between sarcoma development and killed adjuvanted vaccines. (An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents (e.g., drugs, vaccines) while having few if any direct effects when given by itself.  They are often included in vaccines to enhance the recipient's immune response to a supplied antigen while keeping the injected foreign material at a minimum.) There have been no reports statistically linking sarcomas to modified-live vaccines.

In November 1996 the Vaccine-Associated Feline Sarcoma Task Force, (VATSTF), was established to investigate the increased incidence of soft tissue sarcomas occurring at vaccination sites in cats.  The goals of the Task Force were to investigate the epidemiology, etiopathogenesis, treatment and hopefully prevention of the malignancies.  The object was to present the findings of the Task Force to veterinarians and the cat owning public.  The VATSTF recommendations include specific injection site of all vaccines and other injections must be recorded and should be administered as far down a limb as possible.  Injections should be administered as follows:

·         Rabies – right hind limb

·         FVRCP – right front limb

·         FELV – left hind limb

The estimate of feline vaccination sarcomas range from approximately from 1 in 1,000 cats to 1-2 in 10,000 cats. However the true incidence of vaccine-associated sarcomas in cats is unknown.  The interval between vaccination and development of a tumor can be as short as six weeks or as long as 13 years.  It is important to realize that the tumor is not necessarily the result of the cats’ most recent vaccination.  This makes it difficult to pinpoint the true culprit!  There is no known breed predisdposition.

These tumors have been most commonly associated with rabies and feline leukemia virus vaccinations but other vaccines, including inactivated feline viral rhinotracheitis,/calicivirus/panleukopaenia, (FVRCP) and injected medications have also been implicated.  It appears that any killed vaccine containing adjuvant is capable of producing this reaction.   Both subcutaneous and intramuscular injection sites have been affected.  Analysis is complicated by the fact that the vaccine at fault may have been given to the animal as long as 5 to 10 years earlier.  There are reports of other long-acting products like lufenuron, long acting penicillin, methylprednisolone, or even microchips triggering the development of similar sarcomas.  The report of the other long acting products has been particularly difficult to document because one cannot rule out the possibility of previous killed vaccinations at that particular site in the animal.

Post-vaccination sarcomas are very rare but may occur in cats as a consequence of an overzealous inflammatory or immune system reaction to the vaccine.  The most frequently post-vaccinal tumor reported is the fibrosarcoma.  Vaccination site sarcomas are extremely herterogeneous and can also be named as malignant fibrous histiocytomas, (giant cell tumors), liposarcomas, osteosarcomas or chondrosarcomas.

Inflammation in the subcutis, a layer of connective tissue beneath the skin, following vaccination is considered to be a risk factor in the development of vaccine-associated sacaromas.  It is common for a small, firm swelling to form under the skin of a cat after vaccination.  This is usually painless for the animal.  The lump, a granuloma, almost always goes away or disappears on its own.  Rarely, the swelling may develop into a sarcoma.  A malignant tumor, a sarcoma, is composed of cells derived from connective tissue.  These tumors develop slowly at the sites of previous vaccination sites.  Despite the localized appearance of these tumors, microscopic branches of the tumor extend like fingers or tentacles into the surrounding healthy tissue, so the extent of the tumor is extremely difficult to determine.  What is very clear about this type of sarcoma is that the neoplastic transformation occurs even in subcutaneous tissue well beyond the limit of the palpable or visible nodule.  During surgery to remove the tumor, these microscopic branches can remain and contribute to the re-growth of the tumor.  It is important to correctly identify the tumor and completely remove the sarcoma during the first surgical attempt.  Because vaccine-associated sarcomas often mimic benign postvaccinal injection site granulomas, differentiating these lesions is critical.  The resulting sarcomas that redevelop from residual left behind have a greater potential for metastasis and often the time between recurrence shortens with each subsequent attempt at removal.  Following the removal of the tumor the recurrence expectancy is in excess of 90%, almost all within the first six months following tumor removal.

Due to the aggressive nature of these tumors, a single treatment regime that has proven to eliminate or control the feline post-vaccinal sarcomas has not been established.  Combining aggressive surgery in addition to radiation therapy is thought to prolong the life of the animal by increasing tumor control.  Radiation therapy has been shown to be beneficial if given either before or after the definitive surgery.  It is felt that although chemotherapy may improve the cats’ life expectancy for a short period of time; it is seldom a permanent cure.  The unfortunate truth is that there are no good treatment options for cats with these types of tumors, further emphasizing the importance of tumor prevention.

Recently, due to the incidence of vaccination related sarcomas  the veterinarian profession has begun to question some of the old standby’s regarding vaccination protocol and the duration of immunity provided by these vaccines.  In studies of a single commercially available killed adjuvanted feline panleukopaenia, herpesvirus, and calicivirus combination vaccine found evidence that the vaccinated cats were completely protected from challenge exposure to virulent panleukopaenia virus and partially protected from exposure to herpesvirus and calicivirus for substantially longer than one year.  The authors of this study concluded that the duration of immunity following vaccination was in excess of seven years and that the antibody titers against all three viruses for more than three years supports recommendations that cats may need vaccinations against these viruses at three year intervals, not one year as previously thought.

New vaccine technology holds great promise.  New, non-adjuvanted DNA-based vaccines that are safe, effective and cause no tissue injury at the vaccination site that should not cause sarcomas are available now. Vaccine manufacturers are developing recombinant vaccines that do not use adjuvant and that cause less inflammation.  Many modified-live virus vaccines are available for other viral diseases and some of them do not contain adjuvant.  New vaccination guidelines minimize the number of injections given over a cat’s lifetime and also recommend specific sites on the cats body for these injections.

Feline post-vaccinal sarcomas are the only proven example of cancer arising at a site of previous drug administration in any species.  On the whole, vaccinations are much more beneficial than harmful.  They protect our animals from serious infection and disease.  Veterinarians agree that the best chance to reduce the chance of tumor development is to not vaccinate unnecessarily.  Carefully consider the lifestyle of the cat.  Does it go outdoors?  Does it come into contact with other cats?  Cats that never go outdoors usually do not need feline leukemia or FIP vaccinations.  Test every cat in the household for Felv and FIV so that you do not have to worry about these diseases and do not have to vaccinate against them  Test new cats before bringing them into the household and work with your veterinarian on a safe vaccine regime.

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