Injection-Site Sarcoma (Vaccine-Site Sarcoma)

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An injection-site sarcoma, also known as vaccine site sarcoma, vaccine-associated fibrosarcoma, and vaccine associated sarcoma, is a tumor thought to be induced by an injection – most often a vaccination. Post-vaccinal sarcomas are very rare but may occur in cats as a consequence of an overzealous inflammatory or immune system reaction to the vaccine.

A sarcoma is a malignant tumor composed of cells derived from connective tissue. These tumors often develop quickly and can spread (metastasize) to distant locations in the body. These tumors often are not responsive to treatment and result in serious illness and ultimately death of the animal. Recurrence of such tumors is common after surgical removal.

Injection-site sarcomas were first recognized in the late 1980's when some changes occurred in the vaccine manufacturing process. At that time, manufacturers changed from production of modified live virus vaccines to killed virus products as directed by the United States Department of Agriculture (USDA). This change in manufacturing process resulted in the inclusion of aluminum into vaccines. It is this aluminum component of the vaccines that is suspected to be associated with development of post-vaccinal sarcomas. The feline leukemia virus and rabies vaccines are most frequently suspected in pets that develop post-vaccinal sarcomas.

The actual incidence of injection-site sarcomas is not known with certainty. Some investigators estimate that post-vaccinal sarcomas occur in as many as 1 of every 1,000 to as few as 1 in every 10,000 cats vaccinated. Injection-site sarcomas are recognized primarily in cats. The average age for onset of vaccine-site sarcomas is 7 to 9 years. There is no known breed predisposition. It is believed that tumors develop week to years after injection.

Despite the localized appearance of these tumors, microscopic branches of the tumor extend like fingers into the surrounding healthy tissue. During surgery to remove the tumor, these microscopic branches can remain and contribute to re-growth of the tumor. According to one study, as many as 62 percent of post-vaccinal sarcomas recur within 6 months after surgical removal.

There are several types of injection-site sarcomas:

  • Fibrosarcoma – a malignant tumor arising from cells called fibroblasts in connective tissue. This is the most common type.
  • Histiocytoma – a malignant tumor arising from tissue cells called histiocytes
  • Osteosarcoma – a malignant tumor arising from bone
  • Chondrosarcoma – a malignant tumor arising from cartilage
  • Rhabdomyosarcoma – a malignant tumor arising from muscle
  • Myxosarcoma – a malignant tumor arising from loose connective tissue
  • Liposarcoma – a malignant tumor arising from fat
  • Neurofibrosarcoma - a malignant tumor arising from cells called fibroblasts in connective tissue and nerve tissue.
  • Hemangiopericytoma – a malignant tumor that arises from the pericytes, cells that are located around vessels.
  • Schwanoma –are tumors of the nerve sheath
  • Leiomyosarcoma – a tumor arising from smooth muscle.
  • Nerve sheath tumor – a tumor arising from the deep soft tissue, usually in close proximity of a nerve trunk
  • Myofibroblastic sarcoma – a malignant soft tissue tumor in which myofibroblasts are quantitatively the predominant cell type.
  • What To Watch For

    You should watch for a firm, painless swelling in a subcutaneous (under the skin) location in the region of the body in which the cat was vaccinated or received an injection. It is wise to run your hand over your cat's shoulders, back and rear legs periodically to monitor for development of abnormal lumps or tumors. The mass maybe hairless or ulcerated in some cats.

    • Regular visits to your veterinarian are critical to monitor your cat and treat this problem if it arises. Your veterinarian will examine the mass, measure and record its size and location, and discuss biopsy procedures with you.

     

    Diagnosis

    A swelling, nodule or mass under your cat's skin in a region of the body that was previously used for injection or vaccination should be taken very seriously. If this occurs, you should schedule an appointment with your veterinarian to have your cat examined and the mass evaluated. This approach is recommended especially if the mass has persisted for 3 or more months, is larger than 2 cm (just under one inch) in diameter, or if you notice that the mass has been increasing in size during the one month after injection or vaccination. Have your veterinarian examine your cat as soon as possible in this situation.

    Diagnostic tests are needed to recognize injection-site sarcomas and exclude other diseases.

  • A complete medical history and thorough physical examination. An injection-site sarcoma is suspected based on a history of vaccination (or other injection) in the location on the cat's body in which the tumor has been identified.

  • Fine needle aspirate. A fine needle aspirate inovles placing a needle into the mass and sucking back tumor cells. The cells are injected onto a microscope slice and examined. This can help identify the tumor type to help determine the stage of the tumor and the treatment recommendations. Fine needle aspiration not considered reliable for the diagnosis because often this type of tumor does not readily shed cells during routine needle aspiration. A biopsy is often preferred as a first step for diagnosis of the mass.

  • Biopsy. A swelling that develops at the site of a previous vaccination or other injection should be considered malignant until proven otherwise. Such a swelling should be subjected to surgical biopsy and microscopic examination if the mass has been present for 3 or more months, if the mass is larger than 2 cm (just under one inch) in diameter or if the mass is increasing in size one month after injection.
    Biopsy is a procedure in which a small portion of the mass is removed, preserved in a fixative solution, and sent to a laboratory for microscopic examination by a veterinary pathologist. Biopsy specimens can be obtained by an instrument called a Tru-Cut® needle (which collects a very small core of tissue) or by surgical incision of the mass to obtain a small wedge of tissue.

  • Radiographs. X-rays of the chest or nearby area of bone is often recommended to determine if any metastasis has occurred.
  • Treatment

    Because of the aggressive nature of the injection-site sarcoma, no single treatment has proved effective. However, treatment may include one or more of the following:

  • Surgical excision
  • Radiation therapy
  • Chemotherapy

    Home Care

    The most important thing you can do at home is to observe the area of concern carefully. Record when you first noticed the mass and seek advice from your veterinarian.

    Regular visits to your veterinarian are critical to monitor your cat and treat this problem if it arises. Your veterinarian will examine the mass, measure and record its size and location, and discuss biopsy procedures with you.

    After a veterinary pathologist has examined the biopsy specimen and given a diagnosis, appropriate treatment can be discussed and implemented by your veterinarian.
  • Preventative Care

    The only prevention is to eliminate vaccinations. However, since the incidence of injection-site sarcomas is low, it is wise to continue your immunization schedule. Consider vaccination every 3 years (rather than yearly) for rabies and panleukopenia. Limit vaccination for FeLV (feline leukemia virus) and FIP (feline infectious peritonitis) to at-risk cats as needed.

    After immunizations, monitor your cat for swellings that may develop in body regions of previous injection or vaccination and see your veterinarian as soon as possible for early diagnosis and treatment.

    Other conditions both benign and malignant can occur and are often confused with injection-site sarcoma. Following is a partial list of such swellings:

  • Subcutaneous abscess – a localized collection of pus in a cavity formed by the disintegration of tissue that is common in cats that roam and fight with other cats.

  • Infectious granuloma – an inflammatory mass associated with unusual bacteria or fungal infectious agents

  • Sterile granuloma – cat an inflammatory mass associated with administration of certain medications under the skin.

  • Panniculitis – cat the inflammation of the subcutaneous tissue

  • Steatitis – cat inflammation of subcutaneous fat

  • Epidermal inclusion cyst – cat a cyst in the outermost layer of skin derived from a hair follicle that has accumulated debris or fluid

  • Pilomatrixoma – benign tumor of the hair follicle

  • Sebaceous gland adenoma – cat a benign tumor of the glands that empty into the hair follicle

  • Other benign tumors

  • Chondrosarcoma – cat a malignant tumor derived from cartilage cells

  • Malignant fibrous histiocytoma – malignant tumor derived from tissue cells called histiocytes.

  • Mast cell tumor – malignant tumor derived from inflammatory tissue cells called mast cells

  • Lymphosarcoma – malignant tumor derived from immune cells called lymphocytes

  • Osteosarcoma – malignant tumor derived from bone cells

  • Rhabdomyosarcoma – malignant tumor derived from muscle

  • Sebaceous gland adenocarcinoma – malignant tumor derived from glands that empty into hair follicles

  • Apocrine gland adenocarcinoma – malignant tumor derived from sweat glands

  • Other malignant tumors
  •  

    Diagnosis In-depth

    Diagnostic tests must be performed to confirm the diagnosis of injection-site sarcoma and exclude other types of masses. Tests may include:

  • A complete medical history and physical examination

  • Tests may be required to determine the nature of a swelling and the risk of distant spread (metastasis). For example, X-rays of the chest may be taken to evaluate for spread of a tumor to the lungs. Routine blood and urine tests may be completed to determine your pet's general health and ability to safely tolerate sedation or anesthesia for biopsy or removal of the mass.

  • Injection-site sarcomas can be diagnosed by history of vaccination and occurrence of a mass in a region of the body where vaccination has been performed. Biopsy of any mass that has developed in an area of previous injection or vaccination is recommended. The location, shape and size of the mass should be determined and recorded.

  • Radiographs. X-rays of the chest or nearby area of bone is often recommended to determine if any metastasis has occurred.

  • Advanced imaging. CT or MRI scans may be recommended to help determine the full extent of the tumor. Many tumors have root-like projections that extend further than the palpable mass. The best treatment success requires a full understanding of the extent of the tumor.

  •  

    Treatment In-depth

    The current recommendations for management of injection-site sarcomas are as follows:

    Consider any mass that develops in the area of a previous injection or vaccination to be malignant until proven otherwise. A mass should be treated aggressively if it meets the following criteria:

  • Persists for 3 months or more
  • Is larger than 2 cm (just under 1 inch) in diameter
  • Is increasing in size one month after injection or vaccination

    If the lesion meets one or more of these criteria, a biopsy is recommended before surgical excision. A biopsy is a procedure in which a small portion of the mass is removed and sent to a laboratory for microscopic examination by a veterinary pathologist. Biopsy samples can be collected by a special biopsy needle (called a Tru-Cut® needle) or by surgical incision of the mass to obtain a small wedge of tissue for microscopic examination. Fine needle aspiration and cytological examination using a conventional syringe and needle is not recommended because tumors of the sarcoma type generally do not readily shed cells during this procedure. Sedation or anesthesia may be required to obtain the biopsy sample.

    Tumors typically are firm, well-demarcated, and gray to white in appearance. Many tumors are 4.0 cm (about 1 1/2 inches) in size when first noticed.

    If the diagnosis of neoplasia (cancer) is determined by microscopic examination of the biopsy specimen:

  • The cat should be evaluated for distant spread of the tumor (metastasis). The initial evaluation can be completed by your veterinarian but more specialized procedures like computed tomography will require referral to a veterinary specialty clinic or university veterinary teaching hospital.

    Diagnostic procedures to evaluate for metastasis include:

  • Chest X-rays to evaluate for any masses that may have spread to the lungs

  • Computed tomography (CT) or magnetic resonance imaging (MRI) are imaging techniques that provide images of computer-generated "slices" through a patient's body. If necessary, these tests require referral to a veterinary specialty clinic or university veterinary teaching hospital. Some sarcomas spread along the tissue planes that cannot be adequately evaluated by palpation or routine X-rays. These sophisticated imaging tests can be very useful to determine the extent of the mass and to evaluate the area that may require radiation treatment.

  • Routine blood tests and urinalysis may be recommended to identify co-existing medical conditions that may alter recommendations for anesthesia and treatment.

    Treatment of injection-site sarcomas must be individualized based on the extent of the mass, distant spread of the tumor (metastasis) and other factors that must be analyzed by your veterinarian. Treatment options include some combination of surgery, radiation treatment and chemotherapy. Currently, no cure for injection-site sarcomas exists, and research is ongoing regarding the best recommendations for prevention and treatment.

    Treatment recommendations may include:

  • Consultation with a veterinary oncologist before initiating therapy. Such consultation will help determine the best approach for your pet and will identify any need for specialty referral, such as for extensive surgery, radiation therapy, or chemotherapy.

  • Surgical removal of the tumor. You may be referred to a specialist in veterinary surgery if an extensive or complicated procedure is deemed necessary. The removed mass should be submitted for microscopic examination by a veterinary pathologist to determine if the entire mass was removed. Routine surgical recommendations include handling the tumor carefully to avoid any potential spread and performing a very wide excision (removal) of the tumor to try and remove all of the small finger-like projections that may extend into surrounding tissues. Recurrence is common, and it is recommended to remove at least 2 cm of healthy tissue around all sides of the tumor. This may involve very aggressive surgical techniques, including reconstruction of the body wall and removal of bone. The best treatment success involves very aggressive surgery at time of initial diagnosis by a surgeon.

  • Amputation of an involved limb. It is recommended that the surgeon mark the location of the mass in the event that the pathologist reports tumor cells "in the margins" of the submitted sample and a second surgery is required. Complete surgical excision of low-grade tumors may result in survival times of 16 to 24 months.

  • Radiation treatment is recommended before surgery in some cases to try and minimize tumor size and after surgery in some cases if the surgical removal is thought to have been incomplete.

  • Chemotherapy may be recommended for non-resectable tumors but is likely to be of limited benefit.

  • A complete blood count (CBC) and platelet count will be recommended prior to each chemotherapy treatment to evaluate for drug toxicity.

  • Chemotherapy protocols for injection-site sarcomas vary based on the experience of the veterinary oncologist.

    Recommendations may include the following drugs:

  • Carboplatin
  • Doxorubicin (Adriamycin®) and Cyclophosphamide (Cytoxan®)
  • Vincristine (Oncovin®) and Cyclophosphamide (Cytoxan®)
  • Ifosfamide
  • Acemannan use has been tried for tumors less than 2 cm in diameter
  • Prognosis

    The prognosis for this type of cancer depends on the location and stage of the tumor. For example, tumors on the tail, on the distal legs or that are small and localized have a very good prognosis. Tumors that are large and treated aggressively with radiation, surgery and chemotherapy still have a fairly good prognosis; however some cats can have either reoccurrence or metastasis. Cats that are treated with aggressive surgery at the first diagnosis have the best chance of survival. Ask your surgeon about the specifics about your cat's tumor.

    Optimal treatment for your pet requires a combination of home and professional veterinary care. Follow-up can be critical. Administer as directed all medications and contact your veterinarian if you are experiencing problems treating your pet.

    Have your pet rechecked by your veterinarian on a regular basis. Examinations are recommended monthly for the first three months, and then every three months for one year.

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    About The Author

    debra-primovic Dr. Debra Primovic

    Debra A. Primovic, BSN, DVM, Editor-in-Chief, is a graduate of the Ohio State University School of Nursing and the OSU College of Veterinary Medicine. Following her veterinary medical training, Dr. Primovic practiced in general small animal practices as well as veterinary emergency practices. She was staff veterinarian at the Animal Emergency Clinic of St. Louis, Missouri, one of the busiest emergency/critical care practices in the United States as well as MedVet Columbus, winner of the AAHA Hospital of the year in 2014. She also spends time in general practice at the Granville Veterinary Clinic. Dr. Primovic divides her time among veterinary emergency and general practice, editing, writing, and updating articles for PetPlace.com, and editing and indexing for veterinary publications. She loves both dogs and cats but has had extraordinary cats in her life, all of which have died over the past couple years. Special cats in her life were Kali, Sammy, Pepper and Beanie.