What is Vaccine Associated Sarcoma in Pets?

MANAGEMENT OF VACCINE ASSOCIATED SARCOMA IN CATS

Soft tissue sarcomas (STC) account for 7-9% of all malignant skin and subcutaneous tumors in cats.  Although the underlying cause is not fully understood, development of some of these tumors in cats has been associated with previous trauma or vaccine-site injections.  These tumors arise from mesenchymal tissue including fibrous connective tissue, cartilage, blood vessels, muscles, nerves or fat.  They are histologically distinct, but share many common clinical features: particularly the propensity for local invasion.  

Vaccine-associated sarcomas (VAS) can include (but are not limited to) fibrosarcomas, neurofibrosarcomas, nerve sheath tumors, malignant fibrous histiocytoma, leiomyosarcomas, liposarcomas, and myxosarcomas.  These sarcomas are characterized by having a ‘pseudocapsule’, poorly defined margins, and fingerlike projections that infiltrate tissue planes (ie. between muscles and layers f 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 via blood or lymphatics.  Because of these characteristics, STS in cats present a significant clinical challenge.  The way in which the primary care veterinarian manages the initial phases of the diagnosis and treatment can dramatically affect the patient’s outcome.  Multimodality therapy is usually necessary along with careful preplanning so that diagnostics and early treatment do not ultimately interfere with possible future treatment.

Patient Evaluation and Presumptive Diagnosis

Presence of a mass- Any mass that develops in a previous injection site should be considered malignant until proven otherwise.  A lesion should be fully assessed and aggressively treated if it persists for more than 3 months after injection, is larger than 2 cm in diameter, or is increasing in size after 1 month post injection.

HISTORY AND TESTING

If a vaccine-associated sarcoma is suspected based on history, clinical presentation, and location of the mass, the following database should be obtained:Thoracic radiographsBlood analysis to include CBC, serum chemistry panelUrinalysisPreoperative FeLV and FIV testingAbdominal ultrasoundBiopsy and cytology-fine needle aspirates can be performed, but are not always a reliable indicator of neoplasia. Sarcomas typically do not exfoliate well; therefore, a negative aspirate does not rule out cancer.

Histology

A histologic diagnosis obtained in this manner helps the surgeon lan appropriate therapy without jeopardizing a future definitive surgical resection or radiation therapy.

Excisional biopsy

If the mass is too small for incisional biopsy, then an excisional biopsy may need to be performed.  Wide and deep margins, whenever possible, should be attempted in hopes that the excisional biopsy will be both diagnostic and therapeutic. 

Advanced imaging

When feasible, computed tomography (CT scan) is recommended for all patients with a histologic diagnosis of STS.  McEntee, et al, showed that the volume of tumor based on the contrast enhanced CT images was on average twice the size of the tumor based on physical examination and caliper measurements, showing the importance of accurate delineation of disease for surgical and/or radiation treatment planning (more often than not, treatment decisions regarding operability changer one the CT images are reviewed).  Patients with seemingly small tumors that would have been taken to surgery are often noted to have more extensive disease in a CT scan that was anticipated, and warrant undergoing radiation therapy first.

Surgery

Surgery is the mainstay of treatment for STS and offers the best change for a cure, but appropriate preoperative decision making and planning are critical for the best possible outcome.  It has been said that surgical oncologists should be both good technicians, and dedicated tumor biologists.  A thorough understanding of the biologic behavior of this cancer will help in the decision-making process.  Basic principles of oncologic surgery should always be employed, and implementation of these principles starts long before the surgery is performed.  In fact it starts with obtaining the initial presumptive diagnosis.  Any aspiration or biopsy tract that is made needs to be obtained from a site in the tumor where excision of the tract can be done at the time of subsequent definitive surgery. 

Radiation and Chemotherapy

A multimodal approach appears to be superior to any one modality alone, except for radical complete surgical excision with 5 cm margins and 2 fascial planes below the tumor.  Time-to-recurrence and survival times are more favorable when a combination of surgery and radiation therapy is used.

Several chemotherapy agents have been used in cats with vaccine-associated sarcomas including carboplatin, doxorubicin, liposome encapsulated doxorubicin, mitoxantrone, and cyclophosphamide to name a few.  Once study failed to show a survival advantage when comparing cats treated with surgery, radiation and chemotherapy to cats treated with surgery and radiation and no chemotherapy.  Other studies have suggested a benefit for chemotherapy when partial responses were observed in patient with nonresectable disease.  Chemotherapy as a sole modality is not adequate for definitive therapy, but may be valuable for palliation of large, unresectable tumors. 

Reducing the risk on injection-site sarcomas

These tumors may be one of the most serious vaccine-associated adverse events reported in cats, although the precise cause of the injection-site sarcomas is not currently known.  They were first recognized with the transition to killed rabies vaccines and the introduction of feline leukemia virus vaccine, each contained an aluminum adjuvant.  A study published in 1993 provided epidemiological evidence of a casual relationship between vaccinating with rabies and FeLV vaccines containing aluminum and several studies have implicated vaccine-adjuvant-induced inflammation at the injection site as the potential cause.  Chronic inflammation can contribute to oncogenesis in many species.  Cats with a history of ocular trauma and leakage of lens material can develop ocular sarcomas.  It is believed that reducing inflammation may reduce the risk of sarcoma development.  In one study, four different adjuvant-free vaccines containing modified-live virus and a vectored component were compared to saline controls.  None of the tested vaccine combinations produced detectable inflammation.  Microscopically, the sites were similar to saline control injection sites at 21 days later.  The American Association of Feline Practitioners (AAFP) Advisory Panel has suggested that veterinarians use less inflammatory vaccine precuts whenever possible.