Also called vaccine associated fibrosarcoma and vaxosarcoma.
What is an Injection Site Sarcoma and why do we Think Vaccination Might Cause it?
Photo by Dr. Teri Ann Oursler
Soft tissue sarcomas have been recognized as difficult, deeply rooted tumors of cats for a very long time. Probably the most common of the injection site sarcomas, the fibrosarcoma is a tumor that does not usually spread throughout the body in the way we usually think of cancer; instead, it digs in deeply and widely in a localized area. After surgical removal, it is notorious for recurring even more aggressively than before. Distant spread does occur but much later in the course of the disease.
Fibrosarcomas can result spontaneously in either dogs or cats, as can any cancer, or they can be virally induced in cats via the feline sarcoma virus. While spontaneous and viral fibrosarcomas have been described for decades, the potential for vaccination to lead to the formation of these tumors is a relatively new concern. There are still many unanswered questions about how this is actually happening, the role of vaccination, which vaccinations have been implicated, and how serious the risks actually are. What we do know is:
Despite the extremely low incidence of this problem, the problem is still serious and the veterinary profession has responded with numerous studies on how vaccines might be related to tumor formation, why the incidence is so low given how many vaccines are given to cats annually, and what can be done for prevention.
How Might Vaccination Cause Cancer?
Photo by MarVistaVet
First, it isn't only vaccines; it is believed that other injections can generate the same tumor though this is hard to sort out as vaccine-associated tumors can arise many years after the implicated injection was given, and for many years the scruff of the neck was used to deliver all injections, vaccines or otherwise, so it is hard to know which injection caused the tumor. Still, after years of study, the issue seems to be the creation of a focal spot of on-going inflammation that causes some cats to react with a tumor at that site. Killed virus vaccines seem to fit that bill perfectly.
Killed virus does not stimulate the immune system as well as modified live virus and efforts must be made to generate an effective vaccine when the virus involved has been killed. To facilitate immune stimulation with a killed virus, a substance called an adjuvant is often used. This material holds the virus in the area of the vaccination for a couple of weeks so it can be released slowly, allowing immune stimulation to take place over a longer time period. This kind of stimulation can lead to local inflammation in the area of vaccination and one theory is that this inflammation is what leads to precancerous changes in the local cells. Indeed, some fibrosarcomas have been found to have vaccine adjuvant embedded within them.
Adjuvants are different between manufacturers and no particular brand of vaccine has been singled out as the culprit. Any adjuvant can create the necessary stimulation. The critical aspects of tumor development appear to be a chronic, low grade inflammatory process (as might be caused by an adjuvanted vaccine) and a genetic predisposition to form tumors in response to such inflammation. If a cat's genetics are right for it, the offending injection need not be a vaccination; other injectable products may generate enough inflammation to generate a sarcoma though certainly no injectable medication generates a comparable amount of inflammation to an adjuvanted vaccine.
It can take as short a time as two months and as long as ten years to develop a vaccine site tumor, but most appear within four years of the offending injection. While most (80 percent) of the tumors that develop are fibrosarcomas, other types of tumors that can develop through this phenomenon include:
- the malignant fibrous histiocytoma
- the osteosarcoma
- the rhabdomyosarcoma
- the liposarcoma
- the chondrosarcoma
- the undifferentiated sarcoma.
All are tumors of muscle, bone, cartilage, or fat.
Should I Still Vaccinate my Cat?
The answer is still an unequivocal yes. The incidence of these tumors is exceedingly rare relative to the incidence of the diseases that we vaccinate against. Vaccination remains one of the most important aspects of preventive care for cats but now that the vaccine-associated sarcoma has been recognized, some changes have been made in the way cats are vaccinated. For example, vaccinations are made differently now. Instead of the simple modified live versus killed option, we now have recombinant vaccinations, which allow a live non-adjuvanted approach to vaccination against diseases like rabies and feline leukemia virus. These are preferentially used over the adjuvanted killed vaccines that have been heavily implicated in sarcoma formation. Some vaccines are given in a needle-free manner (such as nasally) to avoid creating a depot of vaccine in the muscle and skin tissues. Vaccines are divided into core vaccines, which all cats should have regardless of their indoor/outdoor lifestyle (rabies and FVRCP distemper vaccines are considered core), while other vaccines are given depending on the cat's realistic risk of exposure.
See the 2013 vaccinations guidelines for cats from the American Association of Feline Practitioners.
Guidelines for Preventing Injection Site Sarcoma
Avoid Unnecessary Vaccination
Be wary of vaccination recommendations that encourage you to vaccinate for every possible disease. Recommendations are highly regional and individualized according to the philosophy of your veterinarian, and they all may have a different philosophy, but the guidelines developed by the American Veterinary Medical Association, American Association of Feline Practitioners are a good place to start (see link above).
Use Live Vaccine when Possible
Live virus vaccines do not employ adjuvant to stimulate the immune system. Because there is live vaccine involved, a more natural approximation of the infection is achieved and this stimulates the immune system much better than any adjuvant. Vaccine that has traditionally involved killed virus (feline leukemia and rabies) can be given in a recombinant form, which means a harmless virus is used to carry the relevant DNA from the target virus through the body. In this way a live virus is used but the actual virus of the infection is not, just pieces of its DNA. This sophisticated method is widely used to vaccinate cats against rabies and feline leukemia virus.
Cat FLV diagram
Vaccines should be given as low on the leg as possible and in the legs depicted above. Graphic by MarVistaVet
Vaccinations Should go in Standardized Areas
This not only helps researchers track which vaccines are associated with which tumors but also moves vaccination away from the area between the shoulder blades where a cat is likely to have had many vaccines administered in the past. Accepted vaccination guidelines recommend giving vaccines in the areas shown, using the lower limbs. Cats generally do not appreciate this and sometimes it is not possible. The lower legs are selected because if a fibrosarcoma erupts on a leg, the leg can be amputated and the tumor permanently removed. This sounds like a radical surgery and it is; however, the fibrosarcoma is a very aggressive and malignant tumor and extreme measures are generally needed to control it.
Detailed records should be kept by the veterinarian indicating the vaccine lot number and type as well as the site of vaccination. This also helps researchers determine what is occurring with regard to tumor development.
Be Aware of Lumps Forming after Vaccination (the 3-2-1 Rule)
Lumps commonly form in the weeks following vaccination due to the immune stimulation and inflammation centered on this area. These lumps are usually normal and do not represent fibrosarcomas (which generally take years to develop, not weeks). If your cat develops one of these lumps under the skin (they are generally noticed by owners 3-4 weeks after vaccination), the lump may be left alone to resolve naturally. If the lump is still there three months from the time of vaccination, it should be removed and biopsied. Any lumps greater than 2 cm in diameter (approximately one inch) should be removed no matter how long a time has past since vaccination. Also, any lump should be removed if it is felt to be getting larger rather than smaller one month after its discovery. (3-2-1 refers to three months post vaccine, two cm in size, and growing bigger after one month.)
Sometimes one such lump will break open. This usually means there is an infection and must be treated rather than that a fibrosarcoma has developed. Your veterinarian should be informed of this occurrence and the pet should return for therapy.
Recently some research has gone into giving vaccinations in the tail. As morbid as it sounds, vaccinations are given low on the legs in case a tumor develops and the limb must be amputated. As you will see in the treatment section, surgery must be extremely aggressive to remove the entire tumor and very large margins (at least 2 inches in all directions) are necessary. Limb amputation is disfiguring at best. If tumor development could be shifted to the tail instead of a limb, then the tail can be removed without much loss of function and without the expense or invasiveness of a radical surgery.
Studies have shown that the immune response to the vaccine is no different when the vaccine is given in the tail. The trick to tail vaccination is the limited space between the skin and bone. There is not a lot of room for vaccine fluid in this space, especially in a small kitten, but in an adult cat - especially a cat of a friendly cooperative nature - this could be an effective alternative to vaccination in the legs.
Treatment for Vaccine Associated Fibrosarcomas
Rocky on a Chair
Photo by Dr. Teri Ann Oursler
Step One: Biopsy only a Small Piece First
Injection site sarcomas can be thought of as being similar to an octopus in structure. There is the body that you see but there are also far-reaching tentacles that cannot be seen extending far from the tumor's visible body. The best treatment results are based on aggressive surgery so it is important to know the exact positioning of the tumor and image the tentacles if possible. The problem is that when one is presented with a lump on a cat's body, especially one that seems readily moveable, the tendency is to perform an excision biopsy, which is an attempt to remove the tumor, a decent margin around it, and send the tissue out for analysis. This will determine if the tumor was completely excised or not and will identify the tumor as an injection-site sarcoma. This sounds well and good but it does not work for this type of tumor. Margins are invariably dirty (meaning tumor extends to the edge of the sample) and with the body of the growth no longer there, it is difficult to plan the margins of the second surgery.
With a conservative tumor removal, there is a 70 percent chance of tumor recurrence and the average time until the tumor recurs is only 3 months.
This means a whole other approach is needed: a small chunk of the growth must be removed so as to identify the tumor. If it is not an injection site sarcoma, then removal can be a second surgery. If it is an injection site sarcoma, the body of the tumor is still there so that a more definitive surgery can be planned properly.
The goal is to surgically excise the body of the growth and 5 cm (about 2 inches) around it on all sides. Think about how far into the cat's body that will extend.
In one study of 91 cats, this type of surgery led to recurrence rate of only 14 percent.
Even if the biopsy margins are clean (meaning the tumor appears to have been removed fully), recurrence rates can be as high as 50 percent (meaning even though the biopsy looked clean it really wasn't). This speaks to the invasive nature of this tumor.
Step Two: Staging
Tumor spread is usually late in the course of this tumor but that does not mean staging should be skipped. It is important to know where this tumor exists in the cat's body if we are to win against it. This means the lymph nodes are carefully checked and the chest is radiographed to check for tumor spread. If possible, advanced imaging, such as CT scanning, is done to image the extent of the tumor.
Your veterinarian may not feel comfortable treating these fibrosarcomas, and you and your vet should discuss whether referral to a specialist is best for your pet.
Step Three: Radiotherapy
Radiotherapy definitely seems to extend the disease-free interval. There is some question as to whether radiotherapy is best done after surgery or before. More and more, radiotherapy is used before surgery as the field of radiation ends up smaller than if radiotherapy is delivered afterwards. Further, there is no scar before surgery to alter penetration of the radiation. The goal in radiotherapy in this setting is to kill the microscopic bits of tumor that may escape surgical removal.
Step Four: Surgery
The incredible invasiveness of this tumor necessitates aggressive surgery. Two inches may not seem like a big margin but consider how deep into the cat that goes. Frequently what looks like a relatively small growth under the skin necessitates removal of part of the abdominal wall or limb amputation. One must be prepared for this type of radical surgery.
When radiation is combined with surgery, the disease-free interval is extended to 32 months for cats with clean margins and 10 months for those with dirty margins.
What Happens if you Don't do Anything?
Early in the course of this tumor's growth, the tumor is a relatively small albeit firm growth on the body, neck or leg of the cat. It will probably not be bothering the cat much at this stage but, as we have discussed, even early in its course this tumor will have far-reaching tentacles whose grasp is deeper and stronger every day. If the tumor is incompletely removed, it is likely to grow back more aggressively. If the tumor is left to progress, it will continue its growth until the skin cannot cover it and it bursts forth. By that time, it will be painful, weepy, stinky, and infected. Surgery will no longer be an option but it is possible that palliative radiotherapy (radiation) might create some control on a temporary basis. How long does it take to go from a firm lump with good life quality to an infected mass with poor life quality? On the average about six months.
Curative treatment is disfiguring and expensive but currently it is the only means of addressing this tumor.
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