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VACCINE-ASSOCIATED SARCOMA

Wallace B. Morrison, DVM, MS
Diplomate, American College of Veterinary Internal Medicine (Internal Medicine)

Sites of vaccinations in cats have previously been associated with localized inflammation and granuloma formation. Considerable and convincing epidemiological evidence has accumulated since 1991 that the incidence of sarcomas in the skin of cats at vaccination sites is increasing and that these sarcomas are frequently associated with inflammation similar to what is seen with vaccine reactions. Vaccine-associated sarcomas in cats are typically surrounded by, and infiltrated with, lymphocytes and macrophages. The phenomenon of sarcoma formation in cats at vaccination sites is apparently unique to cats, and they typically develop 3 months to 3 years after vaccination. This suggests that the inflammatory reaction in cats to vaccines sometimes results in malignant transformation of mesenchymal cells. Apparent transition from chronic inflammation to tumor development has been observed in surgical biopsies from these sarcomas. The cells of origin for these sarcomas appear to be the fibroblasts and myoblasts that normally are involved with the fibrous tissue repair response to chronic inflammation. These cells probably participate in the production of the fibrous capsule present in the majority of postvaccinal sarcomas. When these cells are stimulated by a highly immunogenic and persistent adjuvant or other vaccine component, they may undergo some event, which by itself or in association with unidentified carcinogens or oncogenes, leads to the tumor development. Fibrosarcoma is the most common tumor type developing at vaccination sites in cats, but other sarcomas including malignant fibrous histiocytoma, osteosarcoma, myofibroblastic fibrosarcoma, rhabdomyosarcoma, neurofibrosarcoma,and undifferentiated sarcoma have also been reported.

The increased incidence of feline fibrosarcoma was first recognized in 1991 after a 1987 Pennsylvania state law was passed requiring rabies vaccination for cats. This event coincided with the approval and availability of a subcutaneous killed rabies vaccine for use in cats. Sarcoma development has since been linked to vaccination for feline leukemia virus (FeLV). As with rabies vaccines, most currently available vaccines for FeLV are killed vaccines.

Adjuvants are routinely added to killed (inactivated) vaccines to enhance the immune response. Veterinary vaccines may contain a variety of substances that act as adjuvants (bacterial fractions, surface-active agents, complex carbohydrates, and aluminum salts). Aluminum has been identified in up to 42% of the macrophages that partially infiltrate these sarcomas. The presence of adjuvants, with and without aluminum, has been the target of much speculation regarding the postvaccination inflammatory reaction in cats and, in some cases, the subsequent sarcoma development. At this time, it is unknown which of the adjuvant fractions or other vaccine components is responsible for the sarcoma development.

Fibrosarcoma associated with a vaccination is different in many ways from fibrosarcoma owing to other causes (See Table). The incidence of these tumors is "estimated" to occur after one in 10,000 vaccinations. However, some studies report that the incidence of sarcoma development increases with the numbers of vaccines that are given (50% increase after one vaccination, 127% increase after two vaccinations, and 175% increase after three or four vaccinations) simultaneously at the same location.

COMPARISON OF VACCINE-ASSOCIATED AND NONVACCINE-ASSOCIATED   FIIBROSARCOMA IN CATS

Vaccine-associated sarcomas are usually well demarcated by a fibrous capsule, but they are highly invasive and complete surgical removal from a location other than the thigh (by high amputation) is very difficult. Metastasis is common.

There is no best way to treat these tumors. Usually, aggressive surgery offers the best hope of control or cure. Recurrence following surgery is possible.

Vaccination site recommendations have been established by the AAFP and the Vaccine-Associated Feline Sarcoma Task Force. These recommendations are designed to facilitate treatment and to further understanding about the potential causal link between vaccination and tumor development. They are not designed, in and of themselves, to decrease the risk of tumor development. At our present level of understanding this very complex problem, it is clear that for most cats, the benefits of vaccination far outweigh the risk of tumor development.

Vaccination site recommendations

Numerous articles have suggested a causal relationship between vaccinations (and other injections) and development of tumors (fibrosarcoma, rhabdomyosarcoma, malignant histiocytoma, osteosarcoma, liposarcoma, and others) in cats. To further identify the causal link and to facilitate treatment, the American Association of Feline Practitioners and Academy of Feline Medicine have established general guidelines for vaccine administration.

• Veterinarians should use standardized injection protocols within their practices and should document in the permanent medical record the location of all injections.
• Vaccines containing antigens from feline parvavirus, feline herpes-virus-1, feline calicivirus, or Chlamydia spp should be administered over the right shoulder as distally as practical, according to manufacturer's recommendations.
• Vaccines containing feline leukemia virus antigen (with or without other antigens, except rabies virus antigen) should be administered in the left hind leg as distally as practical, according to manufacturer's recommendations.
• Vaccines containing rabies virus antigen (and any other antigens) should be administered in the right hind leg as distally as practical, according to manufacturer's recommendations.
• For other intramuscular injections, the right hind leg should be avoided. Other subcutaneous injections should be administered on a side of the body or over the left shoulder as distally as practical.
• Interscapular and spinous process regions should be avoided for all injections

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