Vaccine-associated sarcoma

A vaccine-associated sarcoma (VAS) is a type of malignant tumor found in cats (and rarely, dogs and ferrets) that has been linked to certain vaccines. VAS has become a concern for veterinarians and cat owners alike and has resulted in changes in recommended vaccine protocols. These tumors have been most commonly associated with rabies and "feline leukemia virus" vaccines, but other vaccines and injected medications have also been implicated.cite journal|title=Vaccine-Associated Feline Sarcoma Task Force: Roundtable Discussion|journal=Journal of the American Veterinary Medical Association|year=2005|volume=226|issue=11|url=http://www.avma.org/journals/javma/articles_public/vafstf_050601.asp|accessdate=2006-08-27]

History

VAS was first recognized at the University of Pennsylvania School of Veterinary Medicine in 1991. [cite journal |author=Hendrick M, Goldschmidt M |title=Do injection site reactions induce fibrosarcomas in cats? |journal=J Am Vet Med Assoc |volume=199 |issue=8 |pages=968 |year=1991 |pmid=1748617] An association between highly aggressive fibrosarcomas and typical vaccine location (between the shoulder blades) was made. Two possible factors for the increase of VAS at this time were the introduction in 1985 of vaccines for rabies and "feline leukemia virus" (FeLV) that contained aluminum adjuvant, and a law in 1987 requiring rabies vaccination in cats in Pennsylvania.cite web | last = Kitchell | first = Barbara E. | title = Feline Vaccine-Associated Sarcomas | work = Proceedings of the 30th World Congress of the World Small Animal Veterinary Association | date = 2005 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2005&PID=10915&O=Generic | accessdate = 2006-08-27 ] In 1993, a causal relationship between VAS and administration of aluminum adjuvanted rabies and FeLV vaccines was established through epidemiologic methods, and in 1996 the Vaccine-Associated Feline Sarcoma Task Force was formed to address the problem. [cite journal |author=Richards J, Elston T, Ford R, Gaskell R, Hartmann K, Hurley K, Lappin M, Levy J, Rodan I, Scherk M, Schultz R, Sparkes A |title=The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel report |journal=J Am Vet Med Assoc |volume=229 |issue=9 |pages=1405–41 |year=2006 |pmid=17078805 |doi=10.2460/javma.229.9.1405]

In 2003, a study of ferret fibrosarcomas indicated that this species also may develop VAS. Several of the tumors were located in common injection sites and had similar histologic features to VAS in cats. [cite journal |author=Munday J, Stedman N, Richey L |title=Histology and immunohistochemistry of seven ferret vaccination-site fibrosarcomas |journal=Vet Pathol |volume=40 |issue=3 |pages=288–93 |year=2003 |pmid=12724570 |doi=10.1354/vp.40-3-288] Also in 2003, a study in Italy compared fibrosarcomas in dogs from injection sites and non-injection sites to VAS in cats, and found distinct similarities between the injection site tumors in dogs and VAS in cats. This suggests that VAS may occur in dogs. [cite journal |author=Vascellari M, Melchiotti E, Bozza M, Mutinelli F |title=Fibrosarcomas at presumed sites of injection in dogs: characteristics and comparison with non-vaccination site fibrosarcomas and feline post-vaccinal fibrosarcomas |journal=J Vet Med A Physiol Pathol Clin Med |volume=50 |issue=6 |pages=286–91 |year=2003 |pmid=12887620]

Pathology

Inflammation in the subcutis following vaccination is considered to be a risk factor in the development of VAS, and vaccines containing aluminum were found to produce more inflammation.cite journal|author=O'Rourke, Kate|title=Researchers probe vaccine-associated feline sarcoma|journal=Journal of the American Veterinary Medical Association|year=2004|volume=225|issue=6|url=http://www.avma.org/onlnews/javma/sep04/040915k.asp|accessdate=2006-08-27] Furthermore, particles of aluminum adjuvant have been discovered in tumor macrophages.cite journal |author=Hershey A, Sorenmo K, Hendrick M, Shofer F, Vail D |title=Prognosis for presumed feline vaccine-associated sarcoma after excision: 61 cases (1986-1996) |journal=J Am Vet Med Assoc |volume=216 |issue=1 |pages=58–61 |year=2000 |pmid=10638320 |doi=10.2460/javma.2000.216.58] The incidence of VAS is between 1 in 1000 to 1 in 10000 vaccinated cats and has been found to be dose-dependent. The time from vaccination to tumor formation varies from three months to eleven years.cite journal |author=Martin M |title=Vaccine-associated fibrosarcoma in a cat |journal=Can Vet J |volume=44 |issue=8 |pages=660–3 |year=2003 |pmid=13677599] Fibrosarcoma is the most common VAS; other types include rhabdomyosarcoma, myxosarcoma, chondrosarcoma, malignant fibrous histiocytoma, and undifferentiated sarcoma. [cite journal |author=Chang H, Ho S, Lo H, Tu Y, Jeng C, Liu C, Wang F, Pang V |title=Vaccine-associated rhabdomyosarcoma with spinal epidural invasion and pulmonary metastasis in a cat |journal=Vet Pathol |volume=43 |issue=1 |pages=55–8 |year=2006 |pmid=16407487 |doi=10.1354/vp.43-1-55]

Similar examples of sarcomas developing secondary to inflammation include tumors associated with metallic implants and foreign body material in humans, and sarcomas of the esophagus associated with "Spirocerca lupi" infection in dogs and ocular sarcomas in cats following trauma. Cats may be the predominant species to develop VAS because they have an increased susceptibility to oxidative injury, as evidenced also by an increased risk of Heinz body anemia and acetaminophen toxicity.

Diagnosis

VAS appears as a rapidly growing firm mass in and under the skin. The mass is often quite large when first detected and can become ulcerated or infected. It often contains fluid-filled cavities, probably due to its rapid growth. [cite journal |author=Couto S, Griffey S, Duarte P, Madewell B |title=Feline vaccine-associated fibrosarcoma: morphologic distinctions |journal=Vet Pathol |volume=39 |issue=1 |pages=33–41 |year=2002 |pmid=12102217 |doi=10.1354/vp.39-1-33] Diagnosis of VAS is through a biopsy. The biopsy will show the presence of a sarcoma, but information like location and the presence of inflammation or necrosis will increase the suspicion of VAS. It is possible for cats to have a granuloma form after vaccination, so it is important to differentiate between the two before radical surgery is performed. One guideline for biopsy is if a growth is present three months after surgery, if a growth is greater than two centimeters, or if a growth is becoming larger one month after vaccination.

X-rays are taken prior to surgery because about one in five cases of VAS will develop metastasis, usually to the lungs but possibly to the lymph nodes or skin.

Treatment and prognosis

Treatment of VAS is through aggressive surgery. As soon as the tumor is recognized, it should be removed with very wide margins to ensure complete removal. Treatment may also include chemotherapy or radiation therapy. The most significant prognostic factor is initial surgical treatment. One study showed that cats with radical (extensive) initial surgery had a median time to recurrence of 325 days versus 79 days for cats with marginal initial excision. The expression of a mutated form of p53, a tumor suppressor gene, is found commonly in VAS and indicates a poorer prognosis. [cite journal |author=Hershey A, Dubielzig R, Padilla M, Helfand S |title=Aberrant p53 expression in feline vaccine-associated sarcomas and correlation with prognosis |journal=Vet Pathol |volume=42 |issue=6 |pages=805–11 |year=2005 |pmid=16301577 |doi=10.1354/vp.42-6-805]

Precautionary measures

New vaccine protocols have been put forth by the American Association of Feline Practitioners that limit type and frequency of vaccinations given to cats. Specifically, the vaccine for feline leukemia virus should only be given to kittens and high risk cats, and the core vaccines for rabies, feline panleukopenia, feline viral rhinotracheitis, and feline calicivirus should only be given every three years to adult cats. Also, vaccines should be given in areas making removal of VAS easier.cite web | last = Eigner | first = Diane R. | title = Feline Vaccine Guidelines | work = The Winn Feline Foundation | url = http://www.winnfelinehealth.org/health/vaccination-guidelines.html#recommendations | accessdate = 2006-08-27 ] A new canarypox vector rabies vaccine is on the market that is non-adjuvanted and creates little inflammation at the injection site.cite web | last = Lappin | first = Michael R. | title = Feline vaccines | work = Proceedings of the 29th World Congress of the World Small Animal Veterinary Association | date = 2004 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2004&PID=8684&O=Generic | accessdate = 2006-08-27 ] There have been no specific associations between development of VAS and vaccine brand or manufacturer, concurrent infections, history of trauma, or environment. [cite journal |author=Kass P, Spangler W, Hendrick M, McGill L, Esplin D, Lester S, Slater M, Meyer E, Boucher F, Peters E, Gobar G, Htoo T, Decile K |title=Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats |journal=J Am Vet Med Assoc |volume=223 |issue=9 |pages=1283–92 |year=2003 |pmid=14621215 |doi=10.2460/javma.2003.223.1283]

References

*Z. Deim, N. Pálmai and G. Cserni: Vaccine-associated fibrosarcoma induced by aluminium compound in two cats, Acta Veterinaria Hungarica, volume 56 (2008)

External links

* [http://www.avma.org/vafstf/ Vaccine-Associated Feline Sarcoma Task Force (VAFSTF)]
* [http://www.vet.cornell.edu/fhc/brochures/vaccsarc.html Vaccines and Sarcomas Informational Brochure] from the [http://www.vet.cornell.edu/fhc Cornell Feline Heath Center]
* [http://www.petcancercenter.org/Cancer_Types_soft_tissue_fibrosarcoma_vaccine.html "Vaccine-associated fibrosarcoma in cats" from Pet Cancer Center]