Vaccine-associated sarcoma
Encyclopedia
A vaccine-associated sarcoma (VAS) is a type of malignant tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 found in cats (and rarely, dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...

s and ferret
Ferret
The ferret is a domesticated mammal of the type Mustela putorius furo. Ferrets are sexually dimorphic predators with males being substantially larger than females. They typically have brown, black, white, or mixed fur...

s) that has been linked to certain vaccines. VAS has become a concern for veterinarians and cat owners alike and has resulted in changes in recommended vaccine protocols. These tumors have been most commonly associated with rabies
Rabies
Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...

 and feline leukemia virus
Feline leukemia virus
Feline leukemia virus is a retrovirus that infects cats. FeLV can be transmitted between infected cats when the transfer of saliva or nasal secretions is involved. If not defeated by the animal’s immune system, the virus can be lethal...

vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

s, but other vaccines and injected medications have also been implicated.

History

VAS was first recognized at the University of Pennsylvania
University of Pennsylvania
The University of Pennsylvania is a private, Ivy League university located in Philadelphia, Pennsylvania, United States. Penn is the fourth-oldest institution of higher education in the United States,Penn is the fourth-oldest using the founding dates claimed by each institution...

 School of Veterinary Medicine in 1991. An association between highly aggressive fibrosarcoma
Fibrosarcoma
Fibrosarcoma is a malignant tumor derived from fibrous connective tissue and characterized by immature proliferating fibroblasts or undifferentiated anaplastic spindle cells.Usually in males ages 30 to 40. Originates in fibrous tissues of the bone. Invades long or flat bones such as femur, tibia,...

s and typical vaccine location (between the shoulder blades) was made. Two possible factors for the increase of VAS at this time were the introduction in 1985 of vaccines for rabies and feline leukemia virus (FeLV) that contained aluminum adjuvant
Adjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...

, and a law in 1987 requiring rabies vaccination in cats in Pennsylvania
Pennsylvania
The Commonwealth of Pennsylvania is a U.S. state that is located in the Northeastern and Mid-Atlantic regions of the United States. The state borders Delaware and Maryland to the south, West Virginia to the southwest, Ohio to the west, New York and Ontario, Canada, to the north, and New Jersey to...

. In 1993, a causal
Causality
Causality is the relationship between an event and a second event , where the second event is understood as a consequence of the first....

 relationship between VAS and administration of aluminum adjuvanted rabies and FeLV vaccines was established through epidemiologic
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...

 methods, and in 1996 the Vaccine-Associated Feline Sarcoma Task Force was formed to address the problem.

In 2003, a study of ferret fibrosarcomas indicated that this species also may develop VAS. Several of the tumors were located in common injection sites and had similar histologic features to VAS in cats. Also in 2003, a study in Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...

 compared fibrosarcomas in dogs from injection sites and non-injection sites to VAS in cats, and found distinct similarities between the injection site tumors in dogs and VAS in cats. This suggests that VAS may occur in dogs.

Pathology

Inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 in the subcutis following vaccination is considered to be a risk factor in the development of VAS, and vaccines containing aluminum were found to produce more inflammation. Furthermore, particles of aluminum adjuvant have been discovered in tumor macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s. The incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

 of VAS is between 1 in 1000 to 1 in 10000 vaccinated cats and has been found to be dose-dependent. The time from vaccination to tumor formation varies from three months to eleven years. Fibrosarcoma
Fibrosarcoma
Fibrosarcoma is a malignant tumor derived from fibrous connective tissue and characterized by immature proliferating fibroblasts or undifferentiated anaplastic spindle cells.Usually in males ages 30 to 40. Originates in fibrous tissues of the bone. Invades long or flat bones such as femur, tibia,...

 is the most common VAS; other types include rhabdomyosarcoma
Rhabdomyosarcoma
A rhabdomyosarcoma is a type of cancer, specifically a sarcoma , in which the cancer cells are thought to arise from skeletal muscle progenitors. It can also be found attached to muscle tissue, wrapped around intestines, or in any anatomic location...

, myxosarcoma, chondrosarcoma
Chondrosarcoma
Chondrosarcoma is a cancer composed of cells derived from transformed cells that produce cartilage. Chondrosarcoma is a member of a category of "soft tissue" malignancies known as sarcomas. About 30% of skeletal system cancers are chondrosarcomas...

, malignant fibrous histiocytoma
Malignant fibrous histiocytoma
Pleomorphic undifferentiated sarcoma , also undifferentiated pleomorphic sarcoma and previously malignant fibrous histiocytoma , is a type of soft tissue sarcoma....

, and undifferentiated sarcoma.

Similar examples of sarcomas developing secondary to inflammation include tumors associated with metallic implants and foreign body material in humans, and sarcomas of the esophagus
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...

 associated with Spirocerca lupi
Spirocerca lupi
Spirocerca lupi is a species of nematode. In dogs, infestation can cause osteosarcoma of the esophagus. Doramectin has been used against it....

infection in dogs and ocular sarcomas in cats following trauma. Cats may be the predominant species to develop VAS because they have an increased susceptibility to oxidative injury, as evidenced also by an increased risk of Heinz body anemia and acetaminophen toxicity.

Diagnosis

VAS appears as a rapidly growing firm mass in and under the skin. The mass is often quite large when first detected and can become ulcerated or infected. It often contains fluid-filled cavities, probably due to its rapid growth. Diagnosis of VAS is through a biopsy. The biopsy will show the presence of a sarcoma, but information like location and the presence of inflammation or necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

 will increase the suspicion of VAS. It is possible for cats to have a granuloma
Granuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...

 form after vaccination, so it is important to differentiate between the two before radical surgery is performed. One guideline for biopsy is if a growth is present three months after surgery, if a growth is greater than two centimeters, or if a growth is becoming larger one month after vaccination.

X-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...

s are taken prior to surgery because about one in five cases of VAS will develop metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

, usually to the lungs but possibly to the lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

s or skin.

Treatment and prognosis

Treatment of VAS is through aggressive surgery. As soon as the tumor is recognized, it should be removed with very wide margins to ensure complete removal. Treatment may also include chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 or radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

. The most significant prognostic factor is initial surgical treatment. One study showed that cats with radical (extensive) initial surgery had a median time to recurrence of 325 days versus 79 days for cats with marginal initial excision. The expression of a mutated form of p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

, a tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...

, is found commonly in VAS and indicates a poorer prognosis.

Precautionary measures

New vaccine protocols have been put forth by the American Association of Feline Practitioners that limit type and frequency of vaccinations given to cats. Specifically, the vaccine for feline leukemia virus should only be given to kittens and high risk cats. Feline Rhinotracheitis/Panleukopenia/Calicivirus vaccines should be given every 3 years. Non-adjuvanted Rabies vaccine (given yearly) is preferred to administration of adjuvanted 3 year Rabies vaccine products. Also, vaccines should be given in areas making removal of VAS easier. There have been no specific associations between development of VAS and vaccine brand or manufacturer, concurrent infections, history of trauma, or environment.

External links

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