Specialty Spotlight: Feline Injection Site Sarcomas

Feline Injection Site Sarcomas
Ariana Verrilli, DVM, DACVIM (Oncology)

Feline injection site sarcomas (FISS) are malignant mesenchymal tumors of the skin that are associated with vaccination in 1-16 of every 10,000 vaccinated cats.  FISS have been associated not only with vaccinations but also with a variety of other substances, including injectable steroids and antibiotics, microchips, and suture material.  It is suspected that the post-injection inflammation results in malignant transformation of the local mesenchymal cells and tumor development.  Tumor development can take anywhere from several weeks to 10 years.

FISS are often rapidly growing tumors arising from the subcutaneous space and in locations consistent with vaccine or injection administration.  If a FISS is suspected, advanced imaging, such as contrast CT, is strongly recommended to allow for proper surgical planning.  The extent of the tumor on a CT scan is often larger than what is suspected based on physical examination alone.  Additionally, these tumors are highly invasive, arise in locations where the surgical approach can be complicated, and have a very high rate of local recurrence if not completely excised.  Excisional biopsy or marginal excision is not recommended for suspected FISS, as this increases the risk of local recurrence and significantly decreases the disease-free interval and overall survival time.

Aggressive surgical excision is the treatment of choice for FISS, aiming for 5cm lateral margins and 2 fascial layers for the deep margin.  When FISS are excised with 2-3 cm margins, less than 50% of tumors will be completely excised.  If 4-5 cm margins are obtained, 95% of tumors will be completely excised.  Complete excision is the most important positive predictive factor for cats with FISS, with clean margins resulting in a disease-free interval of 700 days vs. 170 days for cats with incomplete excision.  Cats who undergo aggressive surgical excision as the primary treatment also have a longer disease-free interval, compared to cats who have marginal excision as their first line treatment.  Each attempt at surgical excision increases the tumor margins and makes future aggressive surgical excision more difficult and less likely to be successful.

Adjuvant radiation therapy (RT) may be indicated in cases where clean surgical excision is not able to be obtained.  Post-operative RT has been shown to decrease recurrence rates and improve the disease-free interval.  RT should be started 10-14 days post-operatively, as the disease-free interval and survival times decrease with increasing time between surgery and starting RT.  Even with combination surgery and RT, 30-45% of these tumors will recur locally.  Palliative radiation therapy can also be considered for cats with FISS that are not amenable to surgery; however, the progression-free intervals are relatively short (4 months).

The role of adjuvant chemotherapy for FISS remains unclear.  The metastatic rate of FISS ranges from 0-25%.  There appears to be little benefit of adjuvant chemotherapy for FISS that are treated with curative-intent surgery and RT.  There is some evidence to support the use of adjuvant chemotherapy for cats with residual gross disease after surgery, as it may prolong survival times compared to treatment with surgery and RT alone.  Treatment with toceranib, a tyrosine kinase inhibitor, has not been shown to have a significant clinical response in cats with FISS.

Despite the high risk for local recurrence, the overall prognosis for cats with FISS is good.  When treated with wide surgical excision (4-5cm), the median survival is 800 days or more.  When treated with less aggressive surgical margins (2-3cm), the median survival is around 400 days.  Prognostic factors include tumor size, treatment type, mitotic count, local recurrence, and the presence of metastatic disease.

Some measures can be taken to minimize the risk of FISS development or to improve surgical excision if a FISS develops.  Vaccinations should no longer be administered in the interscapular region.  It is recommended that the rabies vaccine be administered in the distal right hindlimb, and the FeLV vaccine be administered in the distal left hindlimb.  All other vaccination should be administered in the distal right forelimb.  It is strongly recommended that all vaccinations be given on the distal limb, below the stifle or elbow, as 5cm margins could be obtained with amputation alone if a FISS were to develop.  Alternatively, consideration can be given to administering vaccinations in the distal third of the tail if the cat is amenable to this approach.  Any subcutaneous masses that develop in a cat should be sampled, with fine needle aspirate or incisional biopsy, prior to excision biopsy.  If a FISS is suspected, the initial surgical approach should plan for wide surgical margins.

– Ariana Verrilli, DVM, DACVIM (Oncology)