Title: Vaccine-associated sarcoma

{{Short description|Type of malignant tumor found in animals}}
A '''vaccine-associated sarcoma''' ('''VAS''') or '''feline injection-site sarcoma''' ('''FISS''') is a type of [[malignancy|malignant]] [[tumor]] found in [[cat]]s (and, often, [[dog]]s and [[ferret]]s) which 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 [[sarcoma]]s have been most commonly associated with [[rabies]] and [[feline leukemia virus]] vaccines, but other vaccines and injected medications have also been implicated.&lt;ref name=roundtable&gt;{{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|access-date=2006-08-27}}&lt;/ref&gt;

==History==
VAS was first recognized at the [[University of Pennsylvania School of Veterinary Medicine]] in 1991.&lt;ref&gt;{{cite journal |vauthors=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}}&lt;/ref&gt;  An association between highly aggressive [[fibrosarcoma]]s 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]].&lt;ref name=Kitchell&gt;{{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 | year = 2005 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2005&amp;PID=10915&amp;O=Generic | access-date = 2006-08-27 }}&lt;/ref&gt;  In 1993, a [[Causality|causal]] relationship between VAS and administration of aluminium adjuvanted rabies and FeLV vaccines was established through [[epidemiology|epidemiologic]] methods, and in 1996 the Vaccine-Associated Feline Sarcoma Task Force was formed to address the problem and promote research.&lt;ref&gt;{{cite journal |vauthors=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|doi-access=free }}&lt;/ref&gt;

In 2003, a study of ferret fibrosarcoma indicated that this species also may develop VAS.  Several of the tumors were located in common injection sites and had similar [[Histology|histologic]] features to VAS in cats.&lt;ref&gt;{{cite journal |vauthors=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}}&lt;/ref&gt;  Also in 2003, a study in [[Italy]] compared fibrosarcoma 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.&lt;ref&gt;{{cite journal |vauthors=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 |doi=10.1046/j.1439-0442.2003.00544.x|s2cid=3753206 }}&lt;/ref&gt;

==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.&lt;ref name=&quot;O'Rourke&quot;&gt;{{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|access-date=2006-08-27}}&lt;/ref&gt;  Furthermore, particles of aluminum adjuvant have been discovered in tumor [[macrophage]]s.&lt;ref name=Hershey&gt;{{cite journal |vauthors=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|doi-access=free }}&lt;/ref&gt; In addition, individual genetic characteristics can also contribute to these injection-site sarcomas.&lt;ref name=Martano&gt;{{cite journal |vauthors=Martano M, Morello E, Buracco P |title=Feline injection-site sarcoma: past, present and future perspectives. |journal=Veterinary Journal |volume=188 |issue=2 |pages=136–41 |date=May 2011 | pmid=20510635 |doi=10.1016/j.tvjl.2010.04.025|hdl=2318/73932 |hdl-access=free }}&lt;/ref&gt;  The [[incidence (epidemiology)|incidence]] of VAS is between 1 in 1,000 to 1 in 10,000 vaccinated cats and has been found to be dose-dependent.&lt;ref name=roundtable/&gt;  The time from vaccination to tumor formation varies from three months to eleven years.&lt;ref name=Canvet&gt;{{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 |pmc=340241}}&lt;/ref&gt;  [[Fibrosarcoma]] is the most common VAS; other types include [[rhabdomyosarcoma]], [[myxosarcoma]], [[chondrosarcoma]], [[malignant fibrous histiocytoma]], and [[undifferentiated sarcoma]].&lt;ref&gt;{{cite journal |vauthors=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|s2cid=23721821 }}&lt;/ref&gt;

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 [[oxidation|oxidative]] injury, as evidenced also by an increased risk of [[Heinz body anemia]] and [[acetaminophen]] toxicity.&lt;ref name=Canvet/&gt;

==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 because of its rapid growth.&lt;ref&gt;{{cite journal |vauthors=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|s2cid=24469628 }}&lt;/ref&gt;  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.&lt;ref name=roundtable/&gt;

[[X-ray]]s 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 node]]s or skin.&lt;ref name=Hershey/&gt;

==Treatment==
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.&lt;ref name=Kitchell/&gt;  The expression of a mutated form of [[p53]], a [[tumor suppressor gene]], is found commonly in VAS and indicates a poorer prognosis.&lt;ref&gt;{{cite journal |vauthors=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|s2cid=29956787 }}&lt;/ref&gt;

==Precautionary measures==
New vaccine protocols have been put forth by the American Association of Feline Practitioners that limit the type and frequency of vaccinations given to cats.&lt;ref name=davis&gt;{{cite web | title = Canine and Feline Vaccination Guidelines | work = UC Davis School of Veterinary Medicine | url = http://www.vetmed.ucdavis.edu/vmth/small_animal/internal_medicine/newsletters/vaccination_protocols.cfm | access-date = 2012-06-23 }}&lt;/ref&gt;  Specifically, the vaccine for feline leukemia virus should only be given to kittens and high risk cats. Feline [[Feline viral rhinotracheitis|rhinotracheitis]]/[[Feline panleukopenia|panleukopenia]]/[[Feline calicivirus|calicivirus]] vaccines should be given as kittens, a year later and then every three years.  Also, vaccines should be given in areas making removal of VAS easier,&lt;ref name=protocol&gt;{{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 | access-date = 2006-08-27 | archive-date = 2002-07-17 | archive-url = https://web.archive.org/web/20020717143828/http://www.winnfelinehealth.org/health/vaccination-guidelines.html#recommendations | url-status = dead }}&lt;/ref&gt; namely: as close as possible to the tip of the right rear paw for rabies, the tip of the left rear paw for feline leukemia (unless combined with rabies), and on the right shoulder—being careful to avoid the midline or interscapular space—for other vaccines (such as FVRCP).&lt;ref name=locations&gt;{{cite web | title = VAFSTF Vaccine Site Recommendations | work = Vaccine-Associated Feline Sarcoma Task Force of the American Association of Feline Practitioners (AAFP), American Animal Hospital Association (AAHA), American Veterinary Medical Association (AVMA), and Veterinary Cancer Society (VCS) | url = https://www.avma.org/About/AlliedOrganizations/Pages/sitercmnd.aspx | access-date = 2012-12-04 }}&lt;/ref&gt;  There have been no specific associations between the development of VAS and vaccine brand or manufacturer, concurrent infections, history of trauma, or environment.&lt;ref&gt;{{cite journal |vauthors=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|doi-access=free }}&lt;/ref&gt;

==See also==
* [[Vaccine injury]]

==References==
{{reflist|2}}

==External links==
* [http://www.avma.org/vafstf/ Vaccine-Associated Feline Sarcoma Task Force (VAFSTF)]
* [https://www.vet.cornell.edu/fhc/brochures/vaccsarc.html Vaccines and Sarcomas Informational Brochure] from the [https://www.vet.cornell.edu/fhc Cornell Feline Health Center]
* [http://www.petcancercenter.org/Cancer_Types_soft_tissue_fibrosarcoma_vaccine.html &quot;Vaccine-Associated Fibrosarcoma in Cats&quot; from Pet Cancer Center]
* [http://www.catvets.com/uploads/PDF/2006_Vaccination_Guidelines_JAVMA.pdf 2006 Feline Vaccination Guidelines]{{Dead link|date=July 2025 |bot=InternetArchiveBot |fix-attempted=yes }} [https://archive.today/20130118221304/http://www.catvets.com/uploads/HTML/VaccineSummary.html (Summary)]
* [http://catvaccines.misterlinks.net Cat Vaccines Can Lead to Cancer]
{{Vaccine safety}}
[[Category:Cat diseases]]
[[Category:Sarcoma]]
[[Category:Vaccination|Vaccine-associated sarcoma in animals]]