The Role of Inflammation in Injection Site Sarcomas

Dr. Marlene Siegel, DVM

Vaccine safety has been a long standing concern in veterinary medicine. The association of feline soft tissue sarcomas with Rabies vaccines and Feline Leukemia Virus (FeLV) vaccinations was made over twenty years ago and named Feline Injection-Site Sarcomas (FISS). Subsequent epidemiological studies have estimated an incidence of 0.3 to 1.0 Injection-Site Sarcomas per 10,000 vaccinations in the US and Europe while other studies estimate the risk of developing a Feline Injection-Site Sarcoma (FISS) is as high as 10/100,000 to 100/100,000.

Injection-site sarcomas in dogs, (Vaccine-Associated Sarcoma or VAS), have been rarely reported, but in those that get them, they appear to have the characteristics of FISS. In more than 50% of the cases in dogs, aluminum was detected in the tumor.

In the mid “80’s, research studies showed that Injection Site Sarcomas outnumbered sarcomas at non injection sites, showing an eightfold increase in the number of sarcomas diagnosed from 1988 to 1994 which correlated with an eightfold increase in Injection Site Associated Sarcomas. This spike coincided with widespread use of a killed rabies vaccine that contained an aluminum adjuvant and a large increase in the number of cats receiving a Feline Leukemia (FeLV) vaccine (which also contained an aluminum adjuvant) in the United States. Other vaccines, antibiotic injections, administration of subcutaneous fluids, Program® 6 month injectable (flea prevention) or trauma could induce tumor formation as well.

Vaccine related sarcomas arise from mesenchymal tissues, including connective tissue, cartilage, blood vessels, muscles, nerves or fat. The sarcomas are all locally invasive, characterized by having a ‘pseudocapsule’, poorly defined margins, and fingerlike projections that infiltrate tissue planes (project between muscles and layers of connective tissues). As a result, they tend to be difficult to completely excise, making local recurrence common. In addition to local invasion, they can also metastasize (spread) via blood or lymphatics.

Vaccine-associated sarcomas can include (but are not limited to) fibrosarcomas, neurofibrosarcomas, nerve sheath tumors, malignant fibrous histiocytoma, leiomyosarcomas, liposarcomas, and myxosarcomas.

The reason for these tumors to develop is not fully understood, but chronic inflammation at the injection site along with a potential genetic predisposition (suppression of the tumor suppressor genes like p53) seems to play a role in the transformation to malignancy. The inflammatory infiltrate, primarily macrophages, are frequently reported to contain bluish "foreign material” and may include giant cells. Aluminum has been associated with this inflammation and may play a role in cancer formation.

Trials with adjuvanted killed vaccines in 36 cats showed that 80% to 100% of cats had a local inflammatory reaction following vaccination and that rabies vaccination created a larger inflammatory response than did vaccination for FeLV.

Inflammatory reactions were most common with aluminum adjuvant vaccines, less common with non-aluminum adjuvant vaccines, and not seen with non-adjuvant vaccines. This evidence leads me to recommend using non-adjuvant vaccines, especially for cats.

Soft tissue sarcomas (STC) account for 7-9% of all malignant skin and subcutaneous tumors in cats. Tumors can present months or years after vaccination or trauma.

Injections site sarcomas are more common in younger cats than sarcomas at non-injection sites, with a peak at 6 to 7 years of age.

Most FISS are found subcutaneously and makes sense, because most injections are administered SQ. Evidence shows that the same inflammatory response occurs when the injection is administered intramuscularly but the tumor development may be less frequent.

According to an article published in the World Small Animal Veterinary Association World Congress Proceedings, 2004 by Gregory K. Ogilvie, DVM, DACVIM (Internal Medicine, Oncology) CVS Angel Care Cancer Center San Marcos, CA, USA, adjuvants used with killed vaccines appear responsible for much of the inflammation, though some sarcomas have been associated with modified-live virus vaccination too.

The risk of sarcoma development increases with the number of vaccines given at a site. In one study, cats receiving three to four vaccinations in the inter-scapular region were nearly twice as likely to develop a sarcoma than if they received one vaccine at that site.

Up-to-date information regarding research can be obtained from the Vaccine Associated Fibrosarcoma Task Force on the American Veterinary Medical Association website

Importance of a thorough workup for a suspected Soft Tissue Sarcoma

If a vaccine-associated sarcoma is suspected based on history, clinical presentation, and location of the mass, the following database should be obtained:

1. Thoracic radiographs 3 views

2. Abdominal radiographs 3 views

3. Blood analysis to include CBC, Serum Chemistry Panel, Thyroid, FeLV and FIV testing

4. Urinalysis (preferable obtained by cystocentesis)

5. Thymidine Kinase Type 1 (TK1-DNA Proliferation marker to detect cancer)

6. Feline Haptoglobin (inflammation marker for cats) and

cCRP (canine specific c-reactive protein, inflammation marker for dogs).

7. B12

8. Folate

9. Vit D

10. Magnesium

11. Heavy metals testing (Quick Silver Scientific offers a veterinary test that checks for 8 heavy metals and 8 micro nutrients).

12. Bioenergetic scanning

13. Abdominal ultrasound

14. Biopsy and cytology-fine needle aspirates (can be performed, but are not always a reliable indicator of neoplasia. Sarcomas typically do not exfoliate well, so a negative aspirate does not rule out cancer).

15. Pretreatment staging should include a computed tomography (CT) scan or magnetic resonance imaging (MRI) to more clearly define the tumor margins and areas of infiltration.

Treatment For Soft Tissue Sarcomas

Traditionally surgical excision +/- radiation has been the principal treatment modality for soft tissue sarcomas. Radiation comes with varying degrees of toxicity to other organs. Due to the extensive infiltration and invasion of surrounding normal tissue, it is imperative to resect a wide and deep (more than 2 cm) margin of normal tissue in all surgical planes around the palpable tumor (or as indicated on CT). While this is sometimes possible in larger species such as dogs and humans, it is rarely possible in cats.

There is very little information regarding chemotherapy in the treatment of soft tissue sarcomas in cats.

As soft tissue sarcomas grow, they compress a cuff of tumor cells to form a pseudocapsule, thereby giving the false impression that the sarcoma is encapsulated, but evidence confirms there is extensive infiltration and invasion into surrounding normal tissue.

In a study of 84 cats surgically treated for soft tissue sarcoma, 60 cats (70%) had tumor recurrence an average of 3.5 months later with a median survival of 8 months. Tumors recurred as soon as 2.5 weeks and as long as 1.5 years after surgery.

Alternative Strategies

There are many alternative therapies, from herbs, homotoxicology, Ozone, Hyperbaric Oxygen, Full spectrum Infrared, High dose Vit C, Crystal Light Fusion and Low Level Light Therapy (also known as Photo Dynamic Therapy- PDT) to name a few. Each of these modalities are a topic in and of themselves and worthy of further investigation.

Cancers in general (and especially FISS) are aggressive and require a multimodality approach to see good results.

The goal is to provide safe and effective therapies while extending quality of life. The approach is based on each patient’s needs, and may include surgery along with diet improvement (feeding an organic balanced species appropriate diet), removing toxins in the environment (including EMF), repairing gut health and the microbiome, providing essential nutrient supplementation, removal of toxins, detoxification of the organs of elimination, immune and mitochondrial support and manipulation of the bodies innate pathways to support and facilitate the removal of abnormal tissue. This is not a fast and cheap approach and it requires behavioral changes on the part of the pet parent. In my practice I have experienced successful outcomes using this approach.

We can not continue to create the conditions for dis-ease to flourish and expect the therapies (allopathic, alternative or an integrative approach) to stop the dis-ease!

Prevention Is Key

The more we understand the risk factors that lead to dis-ease, the more we can intervene with better lifestyle choices.

Inflammation is at the root of all dis-ease. The more we reduce the factors leading to inflammation, the lower the risk of developing cancer and other degenerative dis-ease’s.

Implementation Strategies

1. Choose vaccination wisely based on risk factors. If vaccination is indicated or required (like Rabies) choose Non-adjuvanted vaccines.

2. Good injection technique to minimize trauma.

3. Give injections (especially in cats) in the rear legs/ lower thigh.

4. Give only one injection at a given site.

5. Give homeopathic remedies for the injections/vaccinations.

For more information on my 5 step approach to holistic health download my free ebook at or visit for an on line in depth course that covers diagnostic testing, diet/digestion/gut health, detoxification and mitochondrial support.


1. Doddy FD, Glickman LT, Glickman NW, Janovitz EB: Feline fibrosarcomas at vaccination sites and non-vaccination sites. J Comp Pathol 114:165-174, 1996.

2. Kass PH, Barnes Jr WG, Spangler WL, et al: Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats. JAVMA 203:396-405, 1993.

3. Hendrick MJ, Shofer FS, Goldschmidt MH, et al: Comparison of fibrosarcomas that developed at vaccination sites and at non-vaccination sites in cats: 239 cases (1991-1992). JAVMA 205: 1425-1429, 1994.

4. Hendrick MJ, Brooks JJ: Postvaccinal sarcomas in the cat: Histology and immunohistochemistry. Vet Pathol 31:126-129, 1994.

5. Esplin DG, McGill LD, Meininger AC, Wilson SR: Postvaccination sarcomas in cats. JAVMA 202:1245-1247, 1993.

6. Lester S, Clemett T, Burt A: Vaccine site-associated sarcomas in cats: Clinical experience and a laboratory review (1982-1993). JAAHA 32:91-95, 1996.

7. Burton G, Mason KV: Do postvaccinal sarcomas occur in Australian cats? Aust Vet J 75:102-106, 1997.

8. Macy DW: Current understanding of vaccination site-associated sarcomas in the cat. J Feline Med Surg 1:15-21, 1999.

9. Gagnon A-C: Drug injection-associated fibrosarcoma in a cat. Feline Pract 28:18-21, 2000.

10. Esplin DG, Bigelow M, McGill LD, Wilson SR: Fibrosarcoma at the site of a lufenuron injection in a cat. Vet Cancer Soc Newsl 23:8-9, 1999.

11. Coyne MJ, Postorino Reeves NC, Rosen DK: Estimated prevalence of injection-site sarcomas in cats during 1992. JAVMA 210:249-251, 1997.

12. Macy DW, Hendrick MJ: The potential role of inflammation in the development of postvaccinal sarcomas in cats. Vet Clin North Am Small Anim Pract 26:103-109, 1996.

13. Hendrick M, Goldschmidt MH, Shofer F, et al: Postvaccinal sarcomas in the cat: epidemiology and electron probe microanalytical identification of aluminum. Cancer Res 52:5391-5394, 1992.

14. Dubielzieg RR, Hawkins KL, Miller PE: Myofibroblastic sarcoma originating at the site of rabies vaccination in a cat. J Vet Diagn Invest 5:637-638, 1993.

15. Peiffer RL, Monticello T, Bouldin TW: Primary ocular sarcomas in the cat. J Small Anim Pract 29:105-116, 1988.

16. Dubielzig RR, Everitt J, Shadduck JA, Albert DM: Clinical and morphologic features of post-traumatic ocular sarcomas in cats. Vet Pathol 27:62-65, 1990.

17. Hardy Jr WD: The feline sarcoma viruses. JAAHA 17:981-997, 1981.

18. Ellis JA, Jackson ML, Bartsch RC, et al: Use of immunohistochemistry and polymerase chain reaction for detection of oncornaviruses in formalin-fixed, paraffin-embedded fibrosarcomas from cats. JAVMA 209:767-771, 1996.

19. Goad MEP, Lopez MK, Goad DL: Expression of tumor suppressor genes and oncogenes in feline injection-site associated sarcomas [abstract 129]. J Vet Intern Med 13:258, 1999.

20. Devauchelle P: Interest and limits of brachytherapy (interstitial radiotherapy) as adjuvant treatment of feline soft tissue sarcomas. Proc ESVIM #7:44, 1997.

21. Straw RC, Withrow SJ, Powers BE: Partial or total hemipelvectomy in the management of sarcomas in nine dogs and two cats. Vet Surg 21:183-188, 1992.

22. Bowmann KLT, Birchard SJ, Bright RM: Complications associated with the implantation of polypropylene mesh in dogs and cats: A retrospective study of 21 cases (1984-1996). JAAHA 34:225-233, 1998.

23. Davidson EB, Gregory CR, Kass PH: Surgical excision of soft tissue fibrosarcomas in cats. Vet Surg 26:265-269, 1997.

24. Cronin K, Page RL, Spodnick G, et al: Radiation therapy and surgery for fibrosarcoma in 33 cats. Vet Radiol Ultrasound 39:51-56, 1998.

25. Brown NO, Hayes AA, Mooney S,: Combined modality therapy in the treatment of solid tumors in cats. JAAHA 16:719-722, 1980.

26. Hilmas DE, Gillette EL: Radiotherapy of spontaneous fibrous connective-tissue sarcomas in animals. J Natl Cancer Inst 56:365-368, 1976.

27. Bongiovanni S, Bengtson AE, Gliatto JM, et al: Prognostic indicators associated with adjuvant radiotherapy for cats with soft tissue sarcoma. Proc 19th Annu Conf Vet Cancer Soc:44, 1999.

28. Bregazzi VS, LaRue SM, McNiel E, et al: Treatment with a combination of doxorubicin, surgery, and radiation versus surgery and radiation alone for cats with vaccine-associated sarcomas: 25 cases (1995-2000). JAVMA 218:547-550, 2001

29. Hershey AE, Sorenmo KU, Hendrick MJ, et al: Prognosis for presumed feline vaccine-associated sarcoma after excision: 61 cases (1986-1996). JAVMA 216:58-61, 2000.

30. Kleiter M, Leschnik M: Postoperative chemotherapie zur behandlung eines zweifach rezidivierten vakzine-assoziierten fibrosarkoms. Kleintierpraxis 43:295-302, 1998.

31. Mir LM, Devauchelle P, Quintin-Colonna F, et al: First clinical trial of cat soft-tissue sarcomas treatment by electrochemotherapy. B J Cancer 76:1617-1622, 1997.

32. King GK, Yates KM, Greenlee PG, et al: The effect of acemannan immunostimulant in combination with surgery and radiation therapy on spontaneous canine and feline fibrosarcomas. JAAHA 31:439-447, 1995.

33. Quintin-Colonna F, Devauchelle P, Fradelizi D, et al: Gene therapy of spontaneous canine melanoma and feline fibrosarcoma by intratumoral administration of histoincompatible cells expressing human interleukin-2. Gene Therap 3:1104-1112, 1996.

Dr. Marlene Siegel