feline-vaccination-site sarcomas in cats

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Vol.18, No. 8 August 1996

Vaccination-SiteSarcomas in Cats

Mississippi State University Auburn University

Claire M. Weigand, DVM William G. Brewer, Jr, DVM

V accination-site fibrosarcomas in cats were first brought to the attentionof the veterinary profession by Hendrick and Goldschmidt at theSchool of Veterinary Medicine of the University of Pennsylvania.1 After

enactment of a Pennsylvania state law requiring rabies vaccination of cats, thenumber of fibrosarcomas among feline histopathologic samples submitted tothe University of Pennsylvania increased. The most common sites of the fi-brosarcomas corresponded to sites commonly used for vaccination—the inter-scapular area, hindlimb, and lumbar area. Numerous studies and case reportsaddressing the cause and incidence of vaccination-site sarcomas followed(Figures 1 and 2).

EPIZOOTIOLOGYTo investigate the epidemiologic evidence for vaccination-site fibrosarcomas,

Kass and coworkers examined three sets of records: (1) 345 feline fibrosarco-mas submitted to a private laboratory serving northern and central Californiaand Hawaii between January 1, 1991 and May 15, 1992; (2) 37 feline cases of fibrosarcomas diagnosed at the University of California Veterinary MedicalTeaching Hospital between 1984 and 1992; and (3) 17 Hawaiian cats that

were found to have fibrosarcomas between February 1990 and October 1992. 2

The Hawaiian cats represented a cohort that was unexposed to rabies vaccine.Because rabies has not been reported in Hawaii and because of the state’s strictquarantine regulations, cats in Hawaii are rarely vaccinated against rabies.

The 1993 Kass and coworkers report found no sex predisposition for vacci-nation-site fibrosarcomas in cats. Cats with fibrosarcomas at vaccination sites

were younger than cats with fibrosarcomas at other sites.2,3 The age distribution

among cats with vaccination-site fibrosarcomas was bimodal, with peaks at 6 to7 years and 10 to 11 years.2 The number of fibrosarcomas increased each year, with a 25% increase from 1987 to 1991. At the University of California, fewerthan half of the feline fibrosarcomas before 1988 were at vaccination sites. Be-ginning in 1988, more than half of feline fibrosarcomas were at vaccinationsites.

Kass and coworkers considered four vaccines: feline viral rhinotracheitis-cali-civirus-panleukopenia (FVRCP), FeLV, rabies, and pneumonitis-chlamydiavaccines. The FeLV vaccine was most commonly associated with an increased

Continuing Education Article

FOCAL POINT

KEY FACTSI Rabies and FeLV vaccines are

most commonly implicated in

vaccination-site sarcomas in

cats.

I Simultaneous administration

of multiple vaccinations at one

site may increase the risk of

vaccination-site sarcomas.

I Vaccination-site sarcomas have

been attributed to adjuvantcomposition or high

concentrations of antigen.

I Current recommendations are

to inject rabies vaccine on the

caudal half of the right side and

FeLV vaccine on the caudal half

of the left side of the cat’s body.

I Diagnosis of vaccination-site

sarcomas is based on

documentation of injection sites

and histopathologic diagnosis of

a sarcoma.

#Vaccination of cats may increase

the risk of sarcomas at the

vaccination site.



risk for the development of fibrosarcomas at the injec-tion site (risk ratio was2.82). The most commonsite for FeLV vaccination

was the interscapular area.

Rabies vaccination (with arisk ratio of 1.99) came insecond. The odds that fi-brosarcomas would developat the interscapular region

were increased by 50% afterone vaccination, 127% aftertwo vaccinations, and 175%after three vaccinations atthat site.

The data from the privatelaboratory in Californiafound that Hawaiian cats

had significantly fewer fi-brosarcomas at vaccinationsites (17.6% [3 of 17] versus53.6% [185 of 345]). Noneof the Hawaiian cats withvaccination-site fibrosarco-mas had received a rabiesvaccine within the 5 yearsbefore diagnosis, but all of the Hawaiian cats had re-ceived FeLV vaccines within2 years of diagnosis.

The findings of this study suggest that vaccination,particularly repeated vacci-nation at the same site, hasled to a few cases of fibro-sarcomas in cats. No partic-ular brand of vaccine wasimplicated. FeLV and rabiesvaccines, both of which areinactivated vaccines withadjuvants, had the highest risk ratios. It was speculatedthat tumorigenesis may result from an inflammatory re-sponse to localized, highly concentrated antigen deposi-

tion or from residual adjuvant.2

A study of 239 histopathologic samples of fibrosarco-ma submitted to the University of Pennsylvania andTufts University further characterized vaccination-sitefibrosarcoma in cats.3 A questionnaire was sent to eachveterinarian who submitted a histopathologic sample.The questionnaire asked about the patient’s signalmentand vaccination history (the date and site of injections,the manufacturer of the vaccines, and postvaccination

reactions). Some of the vac-cines that had been admin-istered contained aluminumadjuvant. In many cases, in-formation about adjuvantcomposition was considered

proprietary and was un-available.The questionnaire also

asked for a description of the tumor (site, size, shape,and color). The cats wereclassified according to whe-ther the fibrosarcoma aroseat a vaccination site.

The age distribution andthe lack of a sex predisposi-tion were consistent withthe findings of Kass and

coworkers. In both studies,FeLV and rabies vaccines

were implicated most com-monly.

Hendrick and coworkersalso studied the size of thetumors, rate of recurrence,incidence of postvaccinationinflammatory reactions, andincidence of metastasis.3 Thefibrosarcomas at vaccinationsites were significantly larg-er (48% had a diameter >4cm) than those at sites notused for vaccination (25%had a diameter >4 cm). Thevaccination-site fibrosarco-mas also had a higher rate of recurrence (86% within 6months; 22% had betweentwo and four recurrences).In contrast, the feline fi-

brosarcomas at sites not used for vaccination had a14% recurrence rate in the first 3 to 8 months after ex-cision. A documented or suspected inflammatory reac-

tion following vaccination was seen in only two cats. Inone cat, an inflammatory reaction at the vaccinationsite was confirmed by biopsy 1 to 2 months after rabiesvaccination; a fibrosarcoma developed at that site 1 yearlater. In a second cat, a presumably inflammatory reac-tion followed administration of an FVRCP vaccine; afibrosarcoma developed at the site 5.9 years later.

In general, vaccination-site fibrosarcomas were con-sidered to be more aggressive. Metastasis was not con-

Small Animal The Compendium August 1996

I M P L I C A T E D V A C C I N E S I S T U D Y R E S U L T S I S I T E S O F S A R C O M A S

Figure 2—Same cat as in Figure 1 after hair was clipped fromarea of the tumor. Note that the mass is multinodular. It isalso ulcerated as can occur when fibrosarcomas become large.(Courtesy of Dr. William Brawner, Department of Radiolo-gy, Auburn University)

Figure 1—Cat with probable vaccination-site fibrosarcoma.Note that the tumor started in the interscapular region, acommon site for the administration of subcutaneous vac-cines. (Courtesy of Dr. William Brawner, Department of Ra-diology, Auburn University)



As for public health, the low incidence of rabies inhumans is the result of effective animal vaccinationprograms.4 However, cats are still recognized as poten-tial sources for human exposure. In California in 1991,the number of reported cases of rabies in cats equaledthat in all other domestic species combined.9 Anotherpublic health issue is the cost of human postexposuretreatment for rabies. In two New Jersey counties in1990, the estimated average cost of such treatment was$1138 per exposed person.10 The emotional traumaand physical discomfort of postexposure treatmentmust also be considered.

The benefits of vaccination clearly outweigh the risk of vaccination-site sarcomas, but what can be done tominimize the risk? A 3-year rabies vaccine for cats (in-

stead of yearly vaccination) is an option permitted by some states.Public health concerns supersede clients’ wishes

about rabies vaccination. In contrast, clients have op-tions related to FeLV vaccination for their cats. Conse-quently, accurate history taking and client educationare imperative. Identification of high-risk animals andclient counseling on risks versus benefits will allow theowner to make an informed decision.

PRECAUTIONSSimple changes in the routine vaccination procedure

have been suggested (see the box).8 Unnecessary vacci-nation should be avoided. For example, cats that re-ceive a 3-year rabies vaccination should not have yearly rabies boosters—unless they are required by state law.

Clients should be told to watch for masses forming atthe site of vaccination and should return the cat for abiopsy of the mass, if needed. The current recommen-dation is that reactions that persist for more than 3months should be excised and submitted for histo-pathologic examination.11

Administration of killed vaccines in the interscapularspace should be avoided because it is difficult to excisea tumor from that location. Administration on limbs ispreferable. Survival time is longer after amputation of atumor-bearing limb than after regional excision of a tu-mor in the interscapular area.

Vaccination sites should be standardized. It is sug-

gested that the FeLV vaccine be given on the caudalhalf of the left side of the body and the rabies vaccineon the caudal half of the right side. Sites where theanimal has previously received vaccinations should beavoided.

The site of injection, route of injection (subcuta-neous or intramuscular), vaccine manufacturer, vaccinetype, and vaccine serial number should be recorded inthe medical record. In addition, owners should be ad-vised to watch for postvaccination reactions, whichshould also be recorded in the medical record.

There is currently no clear evidence that excisionof inflammatory reactions will prevent the develop-ment of sarcomas at the vaccination site. To differen-tiate inflammatory reactions from sarcomas, biopsy samples should be taken from all masses that developat sites where vaccinations have been administered.

Because inactivated vaccines and adjuvants have beenimplicated in vaccination-site sarcomas, modified-liveFVRCP vaccines should be used whenever possible (ex-cept, of course, in pregnant queens).

Caution should be exercised when making a diag-nosis of vaccination-site sarcoma. Vaccination-sitesarcomas are reportedly infiltrated with inflammatory lymphocytes and macrophages. Macrophages fre-

quently contain bluish-gray material that has beenhypothesized to represent aluminum or other adju-vant.5 Histopathologic confirmation of the diagnosisof sarcoma and accurate documentation of the vac-cine or multiple vaccines given at the site of the sar-coma are necessary. Detailed records of injection sitesand standardization of vaccination sites are also re-quired to detail the prevalence and character of thesesarcomas.


B E N E F I T S O F V A C C I N A T I O N I S C H E D U L I N G & S I T E S O F V A C C I N A T I O N I R E C O R D K E E P I N G

Minimizing the Risk of

Vaccination-Site Sarcomas

I Avoid unnecessary vaccinations.

I

Do not administer killed vaccines into theinterscapular space.

I Standardize vaccine sites—caudal half of the left

side of the body for FeLV vaccines and caudal half

of the right side of the body for rabies vaccines;

limbs may be preferable.

I Avoid previous vaccination sites.

I Maintain detailed records about vaccinations—

site of injection, route of injection (subcutaneous

or intramuscular), vaccine manufacturer, vaccine

type, vaccine serial number.

I Instruct owners to watch for postvaccination

reactions and document such reactions.

I Use modified-live virus FVRCP vaccine whenever

possible; do not use modified-live virus FVRCP

vaccine in pregnant queens.




TREATMENTTreatment of sarcomas at a vaccination site does not

differ significantly from that of sarcomas at other sites.Clinicians should keep in mind, however, that vaccina-tion-site sarcomas tend to be aggressive and have a highrate of recurrence. Biopsy is necessary to distinguish a

postvaccination reaction from a vaccination-site sarco-ma. Wide surgical excision may be inadequate.8 Radia-tion therapy should be considered before or after surgi-cal excision. Radiation therapy may be administered by teletherapy (cobalt-60 therapy) or brachytherapy (iridi-um implants). Chemotherapy can be used as a pallia-tive. Doxorubicin (alone or in combination with cy-clophosphamide) can be administered intravenously every 3 weeks to patients with metastatic disease or if surgery or radiation therapy provides inadequate re-sults.8

About the AuthorsDr. Weigand is currently affiliated with The Animal Health

Center, College of Veterinary Medicine, Mississippi State

University, Starkville, Mississippi. When this article was

written, Dr. Weigand was with Dr. Brewer at the Depart-

ment of Small Animal Medicine and Surgery, College of

Veterinary Medicine, Auburn University, Auburn, Alaba-

ma. Dr. Brewer is a Diplomate of the American College of

Veterinary Internal Medicine (Oncology and Internal

Medicine).

REFERENCES1. Hendrick MJ, Goldschmidt MH: Do injection site reactions

induce fibrosarcomas in cats? JAVMA 199:968, 1991.2. Kass PH, Barnes WC Jr, Spangler WL, et al: Epidemiologic evi-

dence for a causal relationship between vaccination and fi-brosarcoma tumorigenesis in cats. JAVMA 203:396–405, 1993.

3. Hendrick MJ, Shofer FS, Goldschmidt MH, et al: Compari-son of fibrosarcomas that developed at vaccination sites andat nonvaccination sites in cats: 239 cases (1991–1992). JAV- MA 205:1425–1429, 1994.

4. Esplin DC, McGill L, Meininger AC, et al: Postvaccinationsarcomas in cats. JAVMA 202:1245–1247, 1993.

5. Hendrick MJ, Goldschmidt MH, Shofer F, et al: Post-vacci-nal sarcomas in the cat: Epidemiology and electron probe

microanalytical identification of aluminum. Cancer Res 52:5391–5394, 1992.

6. Hendrick MJ, Dunagan CA: Focal necrotizing granuloma-tous panniculitis associated with subcutaneous injection of rabies vaccine in dogs and cats: 10 cases (1988–1989). JAVMA 198:304–305, 1991.

7. Fawcett HA, Smith NP: Injection-site granuloma due to alu-minum. Arch Dermatol 120:1318–1322, 1984.

8. Macy DW: Vaccine-induced sarcomas in cats. Proc Thir- teenth Annu Vet Med Forum :842–843, 1995.

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9. Krebs JW, Holman RC, Hines U, et al: Rabies surveillancein the United States during 1991. JAVMA 201:1838–1848,1992.

10. Uhaa IJ, Dato VM, Sorhage FE, et al: Benefits and costs us-ing an orally absorbed vaccine to control rabies in raccoons.

JAVMA 201:1873–1848, 1992.11. Ogilvie GK, Moore AS: Vaccine associated sarcomas in cats,

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