Thyroid Tumors in Dogs

Thyroid tumors arise from the thyroid tissue located in the neck.  The majority (80 to 90 %) of thyroid tumors are malignant (carcinomas).  The majority of dogs with thyroid tumors have normal thyroid function.  Decreased thyroid gland production can occur due to tumor destruction of normal thyroid tissue.  Thyroid carcinomas have a moderate potential for metastases (spreading of the cancer), with approximately 33% of patients having evidence of metastases at the time diagnosis.  The most common organ for this tumor to spread (metastasize) to is the lungs. 

Diagnosis

Most dogs will present for a mass or swelling in the neck. Difficulty swallowing, eating or a dry cough are also common.  Tumors may be discrete and freely moveable or may cause a large diffuse swelling of the neck.  Diagnosis may be made with either a fine needle aspirate or incisional biopsy.  Because these tumors have a large blood supply, blood contamination may prevent identification of cancer cells in samples with limited tissue or fine needle aspiration.  For small, moveable tumors, removal with biopsy will yield a definitive diagnosis.  Ultrasound evaluation is often helpful with large masses to determine the degree of invasion and possibility of surgical removal. Once a thyroid tumor has been diagnosed, chest x-rays are recommended to evaluate for possible metastases (spread) to the lungs.   Routine blood work, including a thyroid level is also recommended to evaluate your pet’s overall health, including thyroid function.

Treatment

Surgery:

Treatment recommendations for thyroid tumors are dictated by the size of the mass, degree of invasion, and whether the tumor is functional.  For small, moveable masses, surgical removal is recommended.  If the tumor is contained within the capsule of the gland, is completely removed, and low grade, no further therapy may be needed.  For tumors where surgery is unable to remove all of the tissue or there is evidence of invasion into blood and lymphatic vessels, additional therapy is warranted. A board-certified veterinary surgeon can determine the optimal surgical treatment plan for your pet.  

Radiation Therapy:

Definitive (curative intent)- Definitive course radiation therapy is recommended for patients whose tumors have been “debulked” with surgery, but surgery fails to remove all microscopic tumor tissue.  Radiation therapy is administered in order to kill any remaining tumor cells at the surgical site.  Chemotherapy is often recommended in combination with radiation to try to prevent or delay metastatic disease. 

Chemotherapy:

Chemotherapy is recommended for patients whose tumors exhibit characteristics of aggressive behavior such as invasion into blood or lymphatic vessels.  Chemotherapy is also used in combination with radiation therapy for patients whose tumors have been removed or for patients undergoing palliative radiation for large unresectable tumors.  Chemotherapy without surgery or radiation is useful for controlling thyroid carcinoma, even in cases of metastatic disease.  Most patients can be managed well for months to up to two years.  Carboplatin and doxorubicin chemotherapies appear to have some efficacy in thyroid carcinomas.  Chemotherapy is administered intravenously every 3 weeks for 4 to 5 treatments.  Low-dose oral chemotherapy (metronomic) is another option which is cost effective, provides excellent quality of life and delays regrowth and metastasis by interfering with the tumors ability to form new blood vessels. 

Prognosis

The prognosis for benign thyroid tumors (adenomas) is good, as most benign tumors can be cured with surgery.  The prognosis for thyroid carcinomas is dependent on size of the tumor, grade (differentiation), degree of local invasion, and presence of lymphatic and/or vascular invasion.  For small tumors, surgery alone may yield survival times of 2 to 3 years or longer. 

For tumors that cannot be completely removed with surgery or tumors that have evidence of lymphatic and/or vascular invasion, additional therapy (radiation and/or chemotherapy) is recommended. Ultimately, most patients with thyroid carcinomas will develop metastatic disease; however, with combination therapy, many patients will enjoy cancer-free, good quality of life for 1 to 2 years. 

For large, invasive tumors that cannot be removed with surgery, combination chemotherapy and radiation therapy will often result in decrease of the size of the tumor and a significant improvement in your pet’s quality of life. 

 

 

 

 

 

 

 

 

 

 

Soft Tissue Sarcomas

Soft Tissue Sarcomas (STS) in Cats and Dogs

Soft tissue sarcomas

Soft tissue sarcoma is a general term that refers to a group of tumors that form in tissues of mesenchymal origin such as the connective tissue (e.g. fat, smooth-muscle, blood vessels, lymph vessels, skeletal muscle, etc.) They tend to have similar histologic appearance and biological behavior, and can be either benign (noncancerous) or malignant (cancerous). Soft tissue sarcomas can arise in any part of the body although skin and subcutaneous (the layer of tissue directly underlying the skin) tumors are the most commonly observed.

Soft tissue sarcomas (STS) behave in a locally invasive manner. The incidence of metastasis (spread to different sites) varies from about 8% to 20%. This rate is generally lower than other types of tumors in animals; therefore, aggressive local control of the disease is the key goal.

Diagnosis

The individual STS tumor types can be challenging to distinguish between. Fine-needle aspirates or tissue biopsies are required to confirm a diagnosis. Not infrequently, additional pathology tests are required to more precisely determine the tissue of origin. Also, additional tests are performed in order to evaluate how advanced the disease is. The tests will depend on the type of soft tissue sarcoma but generally involve blood and serum biochemical tests, chest X-rays and imaging.

Disease Staging

Imaging studies of the local tumor may be recommended prior to planning the surgical removal of the tumor and/or radiation therapy, especially in animals with suspected intra-abdominal soft-tissue sarcomas. Advanced imaging techniques such as CT (computed tomography) and MRI (magnetic resonance imaging) are especially useful due to their high level of resolution and detail.

Diagnostic tests that evaluate whether the tumors have spread to other organs include chest X-rays (to check for metastasis to the lungs), abdominal ultrasound (to check for metastasis in the spleen, liver, etc.) and fine-needle aspirates/biopsy of regional lymph nodes (to check for lymph node metastasis). At the very minimum, chest X-rays should be performed prior to initiating treatment since soft tissue sarcomas commonly spread to the lungs. Lymph node metastasis is not common for typical soft tissue sarcoma but their biopsy/cytology should be assessed in animals whose lymph nodes appear abnormal and/or whose specific tumor type is suspected to have a high metastatic potential.

Treatment Options

Surgery

Invasive STS can be challenging to treat as they expend into surrounding structures and require extensive surgery to achieve complete removal. The first surgery is the key opportunity to achieve complete excision. A general principle for removing such tumors is that the tumor should be removed with a significant margin of normal tissue around it (in all directions) to ensure complete removal of all malignant cells. An experienced, board-certified veterinary surgeon is recommended for STS resections.

Some STS appear in locations in which complete resection is difficult without disturbing normal tissue. Depending upon the tumor location, such surgeries as limb amputation, rib resection, and nasal/jaw reconstructions may be required. It is important to note that veterinary patients recover quickly and cosmetically even from these more extensive surgeries.

Radiation Therapy

Radiation therapy can be combined with surgery in either a pre or post-surgical manner. If given prior to surgery, the tumor may decrease in size and be subsequently easier to remove. If radiation therapy is given after surgery, it is intended to eradicate tumor cells which may have left behind during an incomplete excision.





Veterinary patients are quite tolerant of this form of cancer treatment and it can increase the changes for successful long term disease management. This is a highly specialized form of cancer treatment and is provided by veterinary radiation oncologists at:

  • New England Veterinary Oncology Group (NEVOG), Waltham, MA. 781-684-8688

  • Angell Memorial Animal Hospital, Boston, MA. 781-522-7282

  • Tufts University School of Veterinary Medicine, N. Grafton, MA. 508-839-5395

Chemotherapy

The benefit of chemotherapy in the treatment of soft tissue sarcomas has not been quantified. However, recent research has shown that chemotherapy can delay regrowth or spread of aggressive soft tissue sarcomas. Chemotherapeutic agents used include doxorubicin, carboplatin, and certain alkylating agents. Low-dose daily metronomic chemotherapy is also showing promise as treatment for STS. In general, chemotherapy is recommended in patients deemed to have an aggressive tumor (high grade), metastatic disease, and/or intra-abdominal tumors.

Prognosis

The prognosis for soft tissue sarcoma is variable, though long term control or cure is possible. Local control of the tumor is very challenging and local tumor recurrence rates after surgery (with or without radiation) range from 7% to 32%. Poor prognostic factors for local tumor recurrence include large tumor size, incomplete surgical removal and high histologic tumor grade (high grade corresponds with aggressive tumor behavior). Management of recurrent soft tissue sarcomas is usually more difficult than the original tumor, emphasizing the need for aggressive treatment of the initial tumor. Because the median time for tumor recurrence is 368 days, the pets should undergo long term follow-up and frequent check-ups. The metastatic rate for soft tissue sarcomas varies from 8% to 17% with a median time to metastasis of 1 year, depending on the tumor’s properties. The median survival time for dogs with soft tissue sarcomas is 1416 days with surgical treatment and 2270 days with surgical and radiation treatment. Overall, up to 33% of dogs eventually die of tumor related causes.

Types of Soft Tissue Sarcomas

Tissue of origin

Benign tumor

Malignant tumor

Primary sties

Risk of malignant tumor metastasis

Organ of metastasis

Adipose (fat) tissue

Lipoma

Liposarcoma

Limbs, abdominal or chest cavity

Low to moderate

Lungs, liver, spleen, bone

Fibrous tissue

Fibroma

Fibrosarcoma

Limbs, oral cavity

Low to moderate

Lungs

Histiocytic cells

Histiocytoma

Histiocytic sarcoma

Limbs

Moderate to high

Lymph nodes, lungs, spleen, liver, kidneys

Lymph vessels

Lymphangioma

Lymphangiosarcoma

Limbs

Moderate

Lymph nodes

Blood vessels

Hemangioma

Hemangiosarcoma

Spleen, heart, liver, muscle, bone, kidneys

High

Lungs, liver, lymph nodes, distant dermal sites

Nervous tissue

-

Peripheral nerve sheath tumor

Limbs

Low to moderate

Lugns

Skeletal muscle

Rhabdomyoma

Rhabdomyosarcoma

Tongue, larynx, heart, bladder

Low to moderate

Lungs, liver, spleen, kidneys

Synovial tissue

Synovioma

Synovial cell sarcoma

Joints

Moderate to high

Lymph nodes, lungs

Myxoma tissue

Myxoma

Myxosarcoma

Limbs, joints

Low to moderate

Lungs

Source: Withrow Stephen J, and David M. Vail. Small Animal Clinical Oncology, St. Louis: Saunders Elsevier, 2007.

Palladia Treatment

Palladia (toceranib phosphate) tablets

Client Information Sheet

This summary contains important information about Palladia. You should read this information before you start giving your dog Palladia and review it each time the prescription is refilled as there may be new information. This sheet is provided only as a summary and does not take the place of instructions from your veterinarian. Talk with your veterinarian if you do not understand any of this information or if you want to know more about Palladia.

What is Palladia?
Palladia, a tyrosine kinase inhibitor, is a drug used to treat mast cell tumors, a common
form of cancer that affects dogs.

Palladia works in two ways:
    • By killing tumor cells.
    • By cutting off the blood supply to the tumor.

Your veterinarian has decided to include Palladia as a part of your dog’s treatment plan
for mast cell tumor. Other types of treatment, such as surgery, drug treatment and/or
radiation may be included in the plan. Be sure to speak with your veterinarian about all
parts of your dog’s treatment plan.

What do I need to tell my veterinarian about my dog before administering Palladia?
Tell your veterinarian about all other medications your pet is taking, including: prescription drugs; over the counter drugs; heartworm, flea & tick medications; vitamins and supplements, including herbal medications.

Tell your veterinarian if your dog is pregnant, nursing puppies, or is intended for breeding purposes.

How do I give Palladia to my dog?
Palladia should be given to your dog by mouth (orally).

Palladia may be hidden inside a treat; be certain your dog swallows the entire tablet(s).

Follow your veterinarian’s instructions for how much and how often to give Palladia.
See the Handling Instructions section below in order to administer Palladia safely to
your dog.

How will Palladia affect my dog?
Palladia may help shrink your dog’s tumor. Like other cancer treatments, it can be
difficult to predict whether your dog’s tumor will respond to Palladia, and if it does
respond, how long it will remain responsive to Palladia. Regular check ups by your
veterinarian are necessary to determine whether your dog is responding as expected,
and to decide whether your dog should continue to receive Palladia.


What are some possible side effects of Palladia?
Like all drugs, Palladia may cause side effects, even at the prescribed dose. Serious
side effects can occur, with or without warning, and may in some situations result in death.
    • The most common side effects which may occur with Palladia include diarrhea,
    decreased or loss of appetite, lameness, weight loss and blood in the stool.

Stop Palladia immediately and contact your veterinarian if you notice any of the following changes in your dog:
   • Refusal to eat
   • Vomiting or watery stools (diarrhea), especially if more frequent than two times in 24 hours
   • Black tarry stools
   • Bright red blood in vomit or stools
   • Unexplained bruising or bleeding
   • Or if your dog experiences other changes that concern you

There are other side effects which may occur. For a more complete list, ask your veterinarian.

HANDLING INSTRUCTIONS

What do I need to know to handle Palladia safely?
Because Palladia is an anti-cancer drug, extra care must be taken when handling the
tablets, giving the drug to your dog and cleaning up after your dog.

Palladia is not for use in humans.

You should keep Palladia in a secure storage area out of the reach of children. Children should not come in contact with Palladia. Keep children away from feces, urine, or vomit of treated dogs.

If you are pregnant, a nursing mother, or planning to become pregnant and you choose to administer Palladia to your dog, you should be particularly careful and follow the handling procedures described below.

Palladia prevents the formation of new blood vessels in tumors. In a similar manner Palladia may affect blood vessel formation in the developing fetus and may harm an unborn baby (cause birth defects). For pregnant women, accidental ingestion of Palladia ay have adverse effects on pregnancy.

If Palladia is accidentally ingested by you or a family member, seek medical advice immediately. It is important to show the treating physician a copy of the package insert or label. In cases of accidental human ingestion of Palladia, you may experience gastrointestinal discomfort, including vomiting or diarrhea.

The following handling procedures will help to minimize exposure to the active ingredient in Palladia for you and other members of your household:

Anyone who administers Palladia to your dog should wash their hands after handling
tablets.

When you or others are handling the tablets:
• Do not split or break the tablets to avoid disrupting the protective film coating.
• Palladia tablets should be administered to your dog immediately after they are removed from the bottle.
• Protective gloves should be worn if handling broken or moistened tablets. If your dog spits out the Palladia tablet, the tablet will be moistened and should be handled with protective gloves.
• If the Palladia tablet is “hidden” in food, make sure that your dog has eaten the entire dose. This will minimize the potential for exposure to children or other household members.

Cleaning up after your dog:
• Because Palladia is present in the stool, urine and vomit of dogs under treatment, you must wear protective gloves to clean up after your treated dog.
• While your dog receives Palladia, place the stool, feces or vomit, and any disposable towels used to clean up in a plastic bag which should be sealed for general household disposal. This will minimize the potential for exposure to people in contact with the trash.
• You should not wash any items soiled with stool, urine or vomit from your dog with other laundry.

This client information sheet gives the most important information about Palladia. For more information about Palladia, talk with your veterinarian.

To report a suspected adverse reaction call Pfizer Animal Health at 1-800-366-5288.

Made in Italy
Distributed by Pharmacia & Upjohn Company
Division of Pfizer Inc, New York, NY 10017
Issued March 31, 2009

Nasal Cavity Cancer

Cancer of the Nasal Cavity

  • Common symptoms include nasal discharge, nose bleeds, “snorting”, or facial deformity.

  • Radiation therapy is the current standard of care for nasal tumors.

  • Median survival time after full course of radiation treatment ranges from 8 to 19.7 months.

  • Median survival time with surgery alone ranges from 3 to 6 months.

Nasal cavity tumors:

The nasal cavity is a large air-filled space above and behind the nose. Paranasal sinuses are air-filled spaces that communicate with the nasal cavity. The most common type of cancers affecting this region are carcinomas and sarcomas, both of which are locally destructive. Carcinomas form in the lining of the nose and include adenocarcinomas, squamous cell carcinoma and undifferentiated carcinoma subtypes. Sarcomas form in the cartilage, bone or connective tissue within the nose. Although less frequent, other tumor types have been reported in the nasal cavity including melanoma or mast cell tumors. The metastatic rate (spread to other organs) is considered low at the time of diagnosis but can be as high as 50% at the time of death. The most common organs to which the tumors spread are the lymph nodes and the lungs, but can also include other sites like bone, kidneys, liver, skin, or the brain.

Symptoms of nasal cavity tumors in dogs:

The average duration of symptoms before diagnosis is 3 months and include bleeding from the nose, nasal discharge, facial deformity from bone erosion and tumor growth, sneezing, difficulty breathing, or eye discharge due to tumor obstruction of the ducts. Nasal bleeding or discharge will often occur in one nostril but may affect both sides over time. Some of these symptoms overlap with other medical conditions such as fungal infection, foreign body, or inflammation but as the tumor grows, signs such as facial deformity, swelling or eye protrusion may be observed. In cases where the nasal tumor is close to the brain, the dog may suffer from seizures or behavior changes.

Diagnosis of nasal cavity tumors:

To confirm a diagnosis of nasal tumors, the veterinarian will typically perform a physical exam, imaging and biopsy. Advanced imaging techniques such as CT scan and MRI are superior tools for evaluating the extent of tumors in the nasal cavity as well as for planning radiation therapy treatment. In order to definitively confirm the presence of a nasal tumor, a tissue biopsy should be obtained. This can usually be completed with a small fiberoptic instrument in a procedure called a rhinoscopy. Once diagnosis is confirmed as cancer, it is usually recommended to stage the disease (determining how extensive it is) so that an appropriate treatment plan can be developed by the veterinary oncologist. Staging of nasal tumors usually includes lymph node aspiration (to determine whether the tumor spread to the nearby lymph nodes), chest radiographs (to determine whether the tumor spread to the lungs) and blood tests/urinalysis (to determine the overall health of the pet and if the pet is well enough to undergo treatment).

Does cancer cause pain in dogs?

Pain is common in pets with cancer, with some tumors causing more pain than others. In addition to pain caused by the actual tumors, pets will also experience pain associated with cancer treatments such as surgery, radiation therapy or chemotherapy. Untreated pain decreases the pet’s quality of life, and prolongs recovery from the illness, treatment or injury. It is, therefore, essential that veterinary teams taking care of pets with cancer should also play a vital role in educating pet owners about recognizing and managing pain in their pets. The best way to manage cancer pain in pets is to prevent it, a term referred to as preemptive pain management. This strategy anticipates pain ahead of time and administers pain medication before the pet actually experiences pain, thus ensuring the pet’s maximum comfort.

Treatment options for nasal cavity tumors:

Because nasal cancer begins to invade the bone early, surgery (called rhinotomy) alone is not sufficient to control the cancer and is not usually recommended. Radiation therapy directly to the affected area is currently the treatment of choice for nasal tumors and has been shown to improve survival times. The advantage of radiation therapy is that it treats the entire nasal cavity together with the affected bone and has shown the greatest improvement in survival. At this time, it is uncertain whether surgical removal of the tumor prior to radiation therapy provides even better benefit to the patient. The radiation therapy is typically delivered in 10 to 18 treatment sessions over the course of 2 to 4 weeks, thus requiring commitment from the pet owners to complete the course of radiation treatment. More recent protocols involving one treatment per week for 3 weeks has demonstrated efficacy as well. It has been shown that megavoltage radiation therapy results in better survival compared to cobalt radiation therapy. The use of CT imaging prior to initiating radiation therapy can be of tremendous help for effectively directing radiation only toward the affected area while sparing normal healthy tissue. It should be emphasized that radiation therapy is remarkably well-tolerated in animals and usually can reduce or resolve disease symptoms in a short period of time.

For pets unable to undergo radiation therapy, chemotherapy is an option, but one with limited efficacy that does not improve overall survival times. If the tumor is small and did not invade surrounding tissues, surgical removal may be an option; however, very few dogs meet this criteria at the time of diagnosis. As mentioned above, surgical removal of large and/or invasive tumors does not provide any substantial benefit.

 

What are the side effects of radiation therapy?

Unfortunately, radiation therapy will affect some normal tissues that cannot be excluded from the radiation field (the area scheduled for irradiation). The amount of damage will depend on the daily dose of radiation, total radiation and how much of the tissue is being treated. Immediate side effects of radiation therapy usually include inflammation of the oral cavity (mouth), inflammation of the nasal cavity, shedding of the skin, and eye dryness. It is very important to prevent any additional damage to the area caused by the pet’s pawing or licking so Elizabethan collars should be used as needed. The majority of animals tolerate this therapy surprisingly well.

Prognosis for dogs with nasal cavity tumors:

One study of 139 dogs showed that without treatment, the average survival time is 95 days. Another study showed that dogs that underwent surgery alone had a median survival of 3 to 6 months, which is comparable to that reported for no treatment. Prognosis of dogs who show symptoms of nasal bleeding appears to be worse (medial survival of 88 days) compared to those without it (medial survival of 224 days). The median survival time after a full course of radiation treatment alone ranges from 8 to 19.7 months and 43 to 60% of dogs are alive 1 year after radiation and 11 to 44% are alive 2 years after radiation. The use of CT imaging to plan radiation treatment can increase the survival range to 11 to 19.7 months. Although radiation therapy alone is able to provide local control of nasal tumors for approximately 10 months, and thus prolong the patients’ overall survival, most dogs will eventually die or are humanely euthanized as a result of local disease progression.

 

Several characteristics are associated with poorer outcomes (shorter survival) in dogs with nasal tumors such as the patient being over 10 years old, having a tumor-induced facial deformity, presence of lymph node or other organ metastasis, or lack of resolution of clinical signs after radiation therapy.

 

Mast Cell Tumors in Dogs

Dr. Gail Mason, DVM, MA, DACVIM
Kathi L. Smith, RVT
 

Mast cell tumors (MCTs) are fairly common tumors in dogs. They are most frequently found in the superficial layers of the skin, on any part of the body. Frequently, there will be ulceration over the area of the tumor, and the dog may scratch or bite at the affected area. The appearance of the tumor does not reveal its potential for spread or recurrence with any certainty. The tumors are usually singular, but dogs may present with multiple nodules, or recurrent ones. Some nodules occasionally enlarge and then regress in size on their own, due to swelling within the tumor itself. This should always raise the suspicion of the presence of an MCT.

Diagnosis of Mast Cell Tumors

Mast cell tumors do not have a specific appearance. However, they are fairly easily detected by a "needle aspirate and cytology." Insertion of a small needle into the tumor (virtually painless) area is followed by examination of the cells under a microscope. Mast cells are large, round cells that usually have dark granules in them. The granules contain substances which, when released, cause swelling, itching, and redness. Infrequently, when a large number of granules spontaneously discharge their chemical contents into the bloodstream, vomiting, stomach ulcers, shock and even death may result.

Mast Cell Tumor Staging

Mast cell tumors can be somewhat unpredictable in their behavior, relative to other types of tumors in dogs. Because of this, care is taken to "grade" the tumors that are discovered. The grade reflects the degree to which the malignant mast cells differ from normal, non-malignant mast cells. The stage can generally be correlated with tumor behavior, tumor recurrence, and survival of the patient. Mast cell tumors affecting the limbs, head, or neck tend to correlate with a more favorable prognosis than those found on the trunk or groin. Multiple mast cell tumors or those exhibiting rapid growth tend to have a more guarded prognosis. A pathologist determines the tissue grade of the tumor after the tumor is biopsied or removed.

*Grade I: well-differentiated-25% recurrence rate post-surgery

*Grade II: moderately differentiated-44% recurrence rate post-surgery

*Grade III: poorly differentiated-76% recurrence rate post-surgery

 

Treatment for Mast Cell Tumors

Treatment for mast cell tumors may involve surgery (the mainstay), chemotherapy, and/or radiation therapy. Recommendations for treatment are based on the type and grade of the tumor, surgical feasibility, and the presence or absence of spread (dissemination) of malignant mast cells throughout the body. Your veterinarian will usually submit blood tests and request abdominal ultrasound or radiographs (x-rays) to determine the likelihood of malignant mast cells elsewhere in the dog's body. Bone marrow biopsies are no longer routinely done, as they have not shown to have high predictive value for tumor staging.

 

Surgery
For single mast cell tumors, a surgical procedure known as a "wide resection" by an experienced surgeon is performed. This means aggressively excavating the tumor and surrounding tissues so that at least 2-3 cm of normal tissue in all directions is removed. This must include a "deep margin" which involves removing tissue below the tumor. The margins of the removed tissue are marked and examined by a pathologist to determine the presence of any lingering malignant cells. If negative, we refer to it as "clean margins". If the pathologist suspects the presence of mast cells in the remaining tissues of the surgery site, we refer to it as "dirty margins". If the remaining, malignant cells are less than 2 cm from the edge of the biopsy specimen, it is referred to as "close margins".

An aggressive surgery early in the course of mast cell tumor disease is associated with the best overall prognosis. A grade I or II tumor that has been completely removed usually requires no other immediate therapy. A grade III tumor, multiple tumors, recurrent tumors, or tumors with dirty margins (those which for anatomical reasons could not be subjected to further surgery) often require follow-up or "adjunct" therapy.

Radiation Therapy
Radiation therapy is an option for dogs whose mast cells tumors are localized, but too large for a clean resection or in an area difficult to resect such as tissues of the facial region, or as follow-up therapy for tumors with dirty margins. Dogs tolerate radiation therapy well, and it can offer long-term control for these tumors. Radiation therapy would not be appropriate for dogs with multiple tumors or those with evidence of disease throughout the body since the radiation beam treats only a single focus of disease. Radiation treatment can be accessed at New England Veterinary Oncology Group (NEVOG) in Waltham MA., Angell Memorial Animal Hospital in Boston, MA. and Tufts University School of Veterinary Medicine in Grafton, MA. This is a highly specialized form of therapy and we are pleased to refer your pet to these centers if need arises.

Chemotherapy
Chemotherapy denotes the administration of certain anti-cancer drugs in order to delay/prevent tumor growth or spread. It may be used before or after surgery, or alone.

Prednisone (a cortisone) is the most commonly used drug for therapy of mast cell tumors. It is well tolerated by dogs and is usually employed for a minimum of six months. If no new tumors appear within that time, your doctor may wean your dog off the prednisone completely. The side effects of prednisone include weight gain, increased appetite and thirst, bladder or skin infections, and panting. Occasionally, stomach irritation or ulcers can occur, or inflammation of the pancreas. Most of the time, the drug dose can be titrated to the patient to minimize any overt symptoms. If the tumor type is determined to be aggressive, additional drugs such as stomach protectants may be prescribed to guard against untoward tumor effects. By itself, prednisone is considered to have only mild anti-cancer effects on MCTS.

Chlorambucil Protocol
If your pet is deemed to have an increased risk of tumor recurrence, we may recommend combination oral therapy with prednisone and chlorambucil (Leukeran¨). Chlorambucil is a chemotherapy drug that is extremely well tolerated in most patients and yet offers more tumor protection than prednisone alone. This drug is usually administered twice weekly and requires that your pet be monitored at least every 6-8 weeks. The minimum treatment period is 6 months.

Vinblastine Protocol
For recurrent or multiple tumors, and for those tumors that cannot be surgically removed, combination chemotherapy can be effective in controlling tumor growth and spread for weeks to months or more. A cure per se is generally not realistic, but many dogs tolerate therapy extremely well. The six-month protocol involves:

Prednisone: high dose at first, then taper over 4 months
Vinblastine: an outpatient injection, given once every 21 days
Cyclophosphamide (Cytoxan¨): an oral chemotherapy drug, given by the owners on days 8,9,10, and 11 of a 21-day cycle.

This protocol has produced a 1 and 2 year survival rate for grade 2 tumors of 91%. For patients with grade 3 tumors, the 1-year survival rate is 66%.

Side Effects
The side effects of prednisone are discussed above. Vinblastine and Cytoxan have the ability to cause nausea and or vomiting, though this is not usual. The most important possible side effects are lowering the body's defenses so that infections occurs, or (rarely) causing many mast cells to release their contents at once. Both situations can be life threatening. However, these are NOT common, and the risk of these is significantly lower than the risk of untreated mast cell disease. You will be given instructions on what to do if any side effects occur, so do not hesitate to contact us.

Lomustine (CeeNu¨) 
CeeNu is a potent oral chemotherapy drug that can be used once every three weeks in patients who MCTs have become resistant to other treatments. It is very well tolerated in general. However, because it can increase the risk of infection (especially seven days after it is given), any noted fever, depression, weakness, or refusal to eat should be reported to us or your veterinarian, or an emergency hospital immediately. Infection is almost always completely reversible. This drug is more potent than Cytoxan¨ and maybe substituted for it if indicated. Occasionally, this drug may decrease patient blood cell counts, which requires a dose reduction or discontinuance.

Prognosis
The factors that are known to influence patient outcome are grade of tumor (I is best, III is most dangerous), completeness of surgical removal (clean margins), and tumor location. Dogs with high-grade tumors, multiple or recurrent tumors, or evidence of spread to the bloodstream or other organs have a much more guarded prognosis for a lengthy survival.

Patient Monitoring
Close patient monitoring is essential in dogs with a history of mast cell tumors. As with many tumors, early detection and treatment increases the chances of successful treatment. You may be asked to have your dog examined and monitored every 6-8 weeks following surgery, or every 21 days during chemotherapy. Blood tests and/or needle aspirates are often requested to assess tumor control. Any time you suspect a new or recurrent tumor, or that your dog is physically ill, contact us immediately. We welcome the opportunity to help you and your dog in any manner we can.

 

Reference: Mast cell tumors in dogs; In: Managing The Veterinary Cancer Patient; Ogilvie, OK and Moore, As. © 1995 Veterinary Learning Systems. Trenton, NJ. *Based on protocol published by Elmslie, Robin; published in the Veterinary Cancer Newsletter.

 

Mammary Gland Tumors

       Carcinomas are the most common type of mammary gland cancer in both dogs and cats, and approximately 50% of all canine mammary tumors are malignant. Most tumors appear in dogs between 8-10 years of age (similar to cats). The exact etiology of mammary cancer is unknown. It is known that spaying a cat or dog before her first estrus (heat) cycle dramatically decreases the risk of mammary tumors (0-5% risk vs. 26%).

        It is general consensus among veterinary oncologists that no mammary lump should ever be left in place and "observed." Needle biopsies are frequently inconclusive and misleading in this case. Biopsy with wide excision is the primary recommendation. These results help determine the best treatment plan for the patient.

        Mammary tumors can develop either as a single mass or as multiple masses within the mammary gland.  Dogs and cats have multiple mammary glands, all of which can develop one or more benign or malignant tumors.  Benign tumors are typically well defined and firm upon examination whereas the clinical symptoms of malignant tumors include rapid growth, ill-defined boundaries, ulceration and/or inflammation.  Inflammatory carcinomas are typically rapidly growing, affect multiple mammary glands and are characterized by firmness, warmth, observable swelling, redness/rash on the skin, thickening and signs of pain.  Extensive swelling (lympedema) of a limb next to the affected gland(s) can also be observed.  
        Tumor size in both dogs and cats has been found to be prognostic. Dogs with tumors less than 5 cm in diameter (cats less than 2 cm) have significantly longer survival times than animals with larger tumors.


Disease Staging
As with other cancers, it is important to assess the extent of cancer in a particular patient. Complete staging usually requires: 
1. Complete blood count
2. Serum chemistry panel
3. Urinalysis
4. Chest radiographs (x-rays) 
5. Abdominal radiographs
6. +/- Ultrasonography
7. Cytology of regional lymph nodes
8. Review and assessment of biopsy results. This includes complete vs. incomplete resection borders as well as cell types and degree of tumor invasiveness.


Treatment
The traditional method of treatment for mammary tumors in dogs and cats is surgery. Treatment by local excision with wide and deep (at least 2 cm) margins is advised. This means that the surgeon needs to take some healthy tissue from around the tumor to ensure the best chance for complete removal. Remember, even though the incision may be quite large, it heals in the same amount of time as a "short one." There appears to be no advantage of a bilateral chain masectomy (over local excision) unless multiple mammary glands are involved. Local and wide excision for tumors that are less than 5 cm (2 cm for cats) may be curative.

As in human medicine, chemotherapy can be considered for patients that have a high risk for recurrent or metastatic disease. These patients would include: 
1. those in which complete tumor resection is not possible
2. those having sarcomas vs. carcinomas
3. those having large and/or multiple tumors
4. those whose biopsy results indicate aggressive disease
5. those with local or distant metstasis

        Chemotherapeutic agents that have been used as adjunct therapy include doxorubicin, cyclophosphamide, mitoxantrone and carboplatin. Most dogs can be treated without serious side effects and owner acceptance of costs and potential for complications is generally good. Overall, anti-estrogen drugs (e.g. Tamoxifen) have failed to show clinical benefit in veterinary patients. Radiation therapy has not yet been evaluated as a treatment modality in animals but may hold promise as it does in humans.

        Survival times for patients with invasive carcinomas are difficult to predict. Published medical reports generally state ranges of 6.5-30 months for patients on adjuvant chemotherapy.


Good Prognostic Factors

Poor Prognostic Factors

Indifferent Prognostic Factors

Tumor is less than 3 cm in diameter

Tumor is greater than 3 cm in diameter

Age

Well defined tumor boundaries

Poorly defined tumor boundaries, ulceration

Breed

Negative lymph nodes

Positive lymph nodes

Weight

Carcinoma-well differentiated, complex, tubular/papillary

Carcinoma-poorly differentiated, simple, solid, anaplastic, inflammatory carcinom, sarcoma

Type of surgery (simple or radical)

Tumor grade I

Tumor grade III

Number of tumors

Positive estrogen and progesterone receptors

Negative estrogen receptors

Glands involved

Index of proliferation

Low AgNOR

Low Ki-67

Low PCNA

Index of proliferation

High AgNOR

High Ki-67

High PCNA

P53 gene mutation

 

Anal Sac Tumors in Cats and Dogs

Anal Sac (Apocrine Gland) Tumors in Dogs and Cats


KEY TAKEAWAYS
*    Anal sac (apocrine gland) tumors can be found by rectal examination.
*    Common symptoms include difficult or painful bowel movements, scooting, swelling around the anus, ribbon-like stool and bleeding as a result of local irritation.
*    Anal sac tumors can result in high calcium levels, which will cause increased thirst increased urination, decreased appetite, weight loss, vomiting, muscle weakness, and low heart rate.                                        
*    Surgical removal of anal sac tumors is the treatment of choice whenever possible.
*    It is estimated that the cancer has spread in 50-80% of cases at the time of diagnosis.
*    Dogs whose cancer spread to other organs have a median survival of 6 months after surgery compared to 15.5 months for dogs without metastases (spread of the cancer).
*    The tumors typicall occur in older dogs and some studies suggest that females may be at higher risk of anal sac cancer.  


Anal sac tumors
     Anal sacs are paired structures, one sac on each side of the anus, which are lined by many glands. These glands produce liquid that is expelled with each bowel movement as a form of territorial marking. Anal sac tumors arise from the glands of the anal sac, and may be either benign (known as anal sac adenomas) or malignant (known as anal sac adenocarcinomas). Anal sac adenocarcinoma is very rare in cats, but has been reported. The tumor itself usually affects only one of the two anal sacs; however, some pets may have tumors in both. The tumor can be very small or quite large, sometimes producing a hormone which causes blood calcium levels to rise above normal levels. The high level of calcium is called hypercalcemia, and can cause problems by damaging the kidneys. Unfortunately, by the time the diagnosis of anal sac adenocarcinoma is made, the tumor may have already metastasized (spread) to other sites such regional lymph nodes, lumbar spine or the liver, spleen, or lungs.


Diagnosis
     Anal sac adenocarcinomas are usually identified during physical examination of the anus, although some tumors are not always easily felt. Some tumors are found during routine rectal examination for impacted anal glands or when taking the animal's rectal temperature. If a mass is detected veterinarians will typically perform several follow-up tests. Complete blood count (CBC), serum chemistry profile, and urinalysis will identify possible hypercalcemia, evaluate the pet’s overall health, and help identify any other abnormalities. To confirm whether the mass is benign or malignant, a fine needle aspirate or tissue biopsy is performed. Incisional biopsy (when a small piece of the tumor is taken) is usually performed on large tumors under sedation and local anesthesia whereas excisional biopsy (when the entire tumor is removed) is usually performed on small tumors under general anesthesia. Additionally, cells can also be isolated from the sublumbar lymph nodes (lymph nodes that are close to the anal sac and the first site to which the tumor will spread) to determine if the tumor has already spread to this region. To test whether the cancer has spread to other organs, abdominal X-rays, chest X-rays and abdominal ultrasound are performed. Advanced imaging techniques such as CT scans can be used to get a more precise and more complete assessment. 


Treatment options
Surgery 
    The initial treatment for anal sac tumors is complete surgical excision. Whenever possible, the surgery will remove the anal sac tumor as well as a wide margin of normal tissue around and under it in order to maximize the likelihood that no tumor cells are left behind. Depending on the tumor’s size, its surgical removal may very infrequently result in fecal incontinence and you should discuss this with your veterinary surgeon to get a clearer idea of its severity given your pet’s condition. If recovering well without complications, most pets are discharged 1-2 days after surgery. Pets may need to take stool softeners until tissue swelling is resolved, and pain medications should be prescribed to make the pet more comfortable given the invasive nature of surgery.

     Metastasis (spread of the cancer) to the nearby sublumbar lymph nodes occurs in more than 50% of cases, therefore, their surgical removal may be required if the lymph nodes are enlarged. If the pets showed increased levels of calcium (hypercalcemia), it will usually resolve on its own 24-96 hours after the surgery, however, it is recommended to periodically measure the pet’s calcium levels to monitor possible cancer recurrence or metastasis. Pets with persistently high calcium levels may be given medication in order to prevent damage to the kidneys. 

Chemotherapy
     In addition to surgery, chemotherapy may be used to kill any remaining cancer cells left behind after the surgery. Even if there is no evidence of metastasis at the time of diagnosis, it is possible that some tumor cells are already circulating throughout the pet’s body, getting ready to establish new tumors in distant organs. Chemotherapy can also be used in pets if the tumor could not be removed with surgery, has already metastasized at the time of diagnosis, or if the surgery was not able to remove all of the tumor. While unlikely to cure the cancer, it can offer the pet more quality time.  Many patients experience successful management of their disease for months to up to two years.  

Radiation therapy
     Radiation therapy is typically used to treat anal sac tumors that could not be removed by surgery or if the surgery was not able to remove the entire tumor.


Treatment associated risks
     Any surgical procedure has the rare risk of anesthetic death but use of modern anesthetic protocols and careful monitoring have largely minimized the risk. Because the surgery is performed near the anus, there is an increased likelihood of developing an infection but the administration of antibiotics after the procedure should control this potential complication. If the sublumbar lymph nodes are also being removed, there is a risk of bleeding during the surgery because the tumor-invaded lymph nodes are often closely associated with blood vessels. These lymph nodes are also very close to nerves, especially those connecting with the bladder, and their removal may cause nerve damage leading to temporary or in some cases permanent post-operative urinary incontinence (inability to control urination). Fecal incontinence (inability to control bowel movement) can occur in a small percentage of animals after the surgery. For pets having difficulty defecating, high-fiber diet and/or stool softeners are usually prescribed to alleviate this problem. Pets undergoing radiation treatment may experience radiation complications such as mild to severe moist desquamation (shedding of skin cells that were exposed to radiation), colitis, difficulty to empty the bowel, and discomfort.


Prognosis
     The prognosis will largely depend on the extent of the disease at the time of diagnosis. Pets with local disease (has not spread to other organs) whose tumor was completely removed by surgery have a much better prognosis than pets whose cancer has already spread, or whose tumor could not be completely removed. 

     There is only limited number of published studies regarding outcomes of anal sac tumors in pets. One study of 32 dogs showed that female dogs had a worse prognosis compared to male dogs, and had a 50% chance of cancer recurrence (cancer coming back) after surgery. It is estimated that by the time diagnosis of anal sac tumors is made, the cancer has spread in 50-80% cases. Dogs whose cancer metastasized had a median survival after surgery of 6 months (range from 1.5 to 39 months) whereas dogs without metastasis had median survival after surgery of 15.5 months (range from 3to 35 months).

     The largest published study involved 113 dogs with varying stages of anal sac cancer treated with different therapies. Of these 113 dogs, 104 underwent treatment consisting of surgery, radiation therapy, chemotherapy or combination. The results showed that median survival for the treated dogs was 544 days (meaning that at 544 days, 50% of the dogs were alive). The study also showed that dogs treated with chemotherapy alone had shorter survival (median of 212 days) compared to those who received other treatments (median of 584 days). Dogs who did NOT receive surgery experienced shorter survival (median of 402 days) compared to those who did undergo surgery (median of 548 days). For dogs with large tumors (>10cm2), the median survival was 292 days compared to 584 days for those with smaller tumors (<10cm2). Dogs whose blood tests show increased calcium levels faced shorter survival (median of 256 days) compared to those with normal calcium levels (median of 584 days). Dogs with metastases to the lungs had significantly shorter median survival (219 days) compared to those without metastases (548 days) (Williams, J Am Vet Med Assoc, 2003)