Mast Cell Tumor Prognostic Panels

KIT staining patterns for MCTs. Upper left: grade I; upper right, grade II; lower left, grade III; lower right, negative control. Courtesy of Dr. Matti Kuipel, MSU.

Cutaneous mast cell tumors (MCT) are one of the most common tumors in dogs. Currently, prognostic and therapeutic determinations for MCTs are primarily based on the histologic grade of the tumor, but a vast majority of the tumors are of an intermediate grade, and the prognostic relevance is highly questioned, especially when pathologists assign the "grade II/high" category. Kiupel M, Webster JD et al; The use of KIT and tryptase expression patterns as a prognostic tool for canine cutaneous mast cell tumors. Vet Pathol 41[4]:371-7, 2004 July.

Dr. Matti Kiupel and his colleagues at MSU currently recommend a battery of tests on any mast cell tumor removed or biopsied. These tests include the following: PCR for c-kit mutation (tumors caused by c-kit mutations are highly aggressive but respond well to tyrosine kinase inhibiting therapies), KIT immunohistochemistry (see pictures above), immunohistochemistry for Ki67, AgNOR count, and PCNA (determines cell-cycle phase of proliferating cells). While there is some association between each independent test, prognoses developed from the interpretation of all the above listed tests offer us the highest level of certainty.

At ACIC, we also recommend that prognostic panels be performed on all mast cell tumors. It is especially helpful when pet owners are on the fence about whether or not to pursue additional surgery or treatment. For example, we are less likely to take a "monitoring approach" with a patient that had a mast cell tumor removed that was reported to be a grade II with clean, but narrow margins, if the prognostic panel indicates the potential for more aggressive biologic behavior. This particular patient should go back to surgery to obtain wider margins. Although the panels add additional cost for the client, they are extremely valuable in making treatment decisions that are best for the patient.

Don't be afraid to explore (for Cash's mom!)

Hello everyone! I have just completed 4 evening lectures over the past several weeks so it's been hectic for me and the reason for no recent posts!

I wanted to share with you a recent case that presented to our hospital for a second opinion. It brings an excellent point home about the value of exploratory surgery. The patient had an ultrasound prior to referral to our hospital and thought to have a large liver tumor. The client was informed at the previous hospital that the tumor was probably inoperable and the risk of exploratory was extremely high because the patient would likely have massive bleeding.

On presentation to Dr. Walshaw for a second opinion, the patient was in relatively good health other than the suspected mass. Our ultrasound revealed that the mass appeared to be associated with the spleen. It can sometimes be difficult to determine the origin of a mass when it becomes very large - it can appear to be involving one organ when in fact it's only closely adjacent to it. In addition, as discussed in my previous post, even massive liver tumors can be removed. So, for this reason it is better to pursue exploratory surgery than just assume a tumor can't be removed or assume that nothing more should be done beyond the ultrasound. In this patient's case, not only was the tumor associated with the spleen and easily removed, the histopathology (biopsy) report revealed that it was benign - therefore surgery cured the dog. Without surgery, the patient's benign tumor could have ruptured and caused a deadly bleed.

Primary liver tumors in dogs

Surprisingly, hepatocellular carcinoma can carry a favorable prognosis, despite the sometimes huge size of some of these tumors. In dogs, malignant liver tumors outnumber benign tumors in which hepatocellular and biliary carcinomas are the most common primary liver tumors. They tend to occur in older animals (10-11 years old) and males are more commonly affected than females. The cause of liver tumors is unknown in dogs: the liver functions to detoxify mutagenic (potentially cancer causing) compounds and this may render the hepatobiliary system more susceptible to their effects. Liver tumors present in three different forms: solitary (massive), nodular and diffuse. Hepatocellular carcinomas most commonly present in the solitary (massive) form.

The treatment of choice for solitary masses is surgery. Seventy-five percent of the liver can be surgically removed and the liver will regenerate to complete functional levels in 6-8 weeks. Chemotherapy is reserved for high grade solitary tumors or the diffuse/nodular forms, but is often not effective. For dogs with massive (solitary) hepatocellular carcinomas metastatsis is less common and tumor regrowth is slow. One recent study of 48 cases of hepatocellular carcinomas reported a metastatic rate of only 4.8%. Reported survival times for massive hepatocellular carcinomas are > 1,460 days in which the ability to perform surgery was the main prognostic factor. In this study, no further treatment beyond surgery was pursued or recommended. JAVMA Liptak et al. Oct. 15, 2004.

Dr. Walshaw has removed quite a few extremely large liver tumors at our practice with excellent outcomes for the patients! If you do an ultrasound and find a massive tumor, it doesn't mean we can't help that patient!

Vaccine Associated Sarcomas

Hello everyone! Finally back from 2 quick vacations spread over the past several weeks!



I have been speaking to veterinary groups for the last 2 years on the topic of vaccine associated sarcomas in cats, and have 4 lectures planned for this month alone. It always amazes me that so many veterinarians do not believe that this disease exists anymore. Sadly, I can assure you it does. Just today, we saw a 3 year old patient that was diagnosed with a vaccine associated sarcoma in the hip area. This patient has already undergone surgery at her referring veterinarian's hospital and will now undergo radiation therapy.



This disease is preventable. As veterinarians, we need to inform our clients of the risks of vaccination and offer vaccines known to reduce or eliminate the risk of future tumor formation. ALWAYS INFORM!!!



As pet owners, we need to be aware and informed of the care our pets receive. Just as you would for your children, ask as many questions as possible before vaccinating your cats. BE INFORMED!!!!



For more detailed information, go to our website http://www.veterinarycancer.com/ and click on "cancer types" and go to vaccine associated sarcomas. It contains a PDF file of an article Dr. Walshaw and I wrote regarding VAS in cats.

Chemotherapy Safety at Home

Of course, anyone using or dispensing chemotherapy in their clinic needs to follow basic safety precautions to protect their patients and their staff. However, practicing chemotherapy safety doesn't end at the clinic door. Clients need to be informed of the potential risks of handling oral chemotherapy and/or the risks of handling the wastes of a patient who has had chemotherapy after they leave the clinic. You should have a very rigid protocol in place for in house and at home chemotherapy handling before ever considering using and handling chemotherapy. We make the following recommendations to clients:

Handling Waste

Most chemotherapeutic agents are eliminated in the feces or urine. In most cases, the drugs are eliminated in a changed form that poses little risk. However, pets should be walked and allowed to urinate or defecate outside your children’s play area for 48 hours after your pet’s last treatment.
Disposable latex gloves should be used to clean up any urine, stool or vomit for 48 hours after your pet’s last treatment. Place soiled paper towels and gloves in a sealed plastic container to dispose of.
For cats, clean litter box frequently. Remove feces and flush down the toilet. Dispose of litter in a sealed plastic container.
Contaminated bedding should be washed separately from other laundry.
Clients who are pregnant, breastfeeding, trying to conceive, immune suppressed or taking immunosuppressive drugs should avoid their pet’s waste for 48 hours following treatment.

Handling Chemotherapy Drugs

Wear latex gloves when handling oral chemotherapy medications at home. Wash hands immediately and thoroughly after handling medication. Gloves may be resealed and returned to the clinic for disposal.
Never break or crush chemotherapy tablets.
Do not store chemotherapy medication near food, cosmetics, or other medications. Keep out of the reach of children and pets
If you come in contact with chemotherapy medication, wash the area immediately with soap and water. If exposed skin becomes irritated and does not quickly resolve, contact your physician.
Wash any surfaces, such as counter tops or floors that may have come in contact with the chemotherapy medication with a rubbing alcohol wipe followed by soap and water, then wipe dry with a paper towel.

For more information, please contact us at 734-459-6040.

Happy Monday!

Instead of posting pictures of the little Chihuahua ("Stevie") on the blog, it's better to go to our website www.veterinarycancer.com and view the video! Little Stevie is doing great post-operatively and was adopted by my mother and dad!! He's enjoying the love and attention and every day becomes more lovable.

Exploring better options: Chemotherapy protocols for diseases such as lymphoma and osteosarcoma have not changed significantly in over 20 years, nor have the median survival times despite the addition of new drugs. In an attempt to investigate new ways of giving chemotherapy, we are now routinely using metronomic (low dose) chemotherapy for a variety of tumors at ACIC, including hemangiosarcoma and osteosarcoma.

What exactly is metronomic chemotherapy?

“The definition of metronomic chemotherapy varies, but generally it refers to repetitive, low doses of chemotherapy drugs designed to minimize toxicity and target the endothelium or tumor stroma as opposed to targeting the tumor.” ...Dr. Harold Burstein of the Dana-Farber Cancer Institute.

An excellent basic description of metronomic chemotherapy comes from Dr. Robert S. Kerbel, one of the leaders in this field of metastasis and anti-angiogenesis who is highly regarded for discoveries that are helping to improve cancer therapies and the quality of life of cancer patients:

“For almost half a century, systemic therapy of cancer has been dominated by the use of cytotoxic chemotherapeutics. Most of these drugs are DNA-damaging agents that are designed to inhibit or kill rapidly dividing cells. They are often administered in single doses or short courses of therapy at the highest possible dosage without causing life-threatening levels of toxicity. This is referred to as the “Maximum Tolerated Dose” (MTD). MTD therapy requires prolonged breaks (generally 2-3 weeks in duration) between successive cycles of therapy. Progress had been modest in terms of curing or significantly prolonging the lives of patients with cancer using MTD—particularly those with advanced-stage or metastatic disease. The higher the dosage of chemotherapy, the more likely we are to kill the cancer, but the limiting factor is always the adverse side effects that occur with increasing dosages. More recently, a lot of research has been directed towards a reappraisal of the best ways of administering chemotherapy. Instead of using short bursts of toxic MTD chemotherapy interspersed with long breaks to allow recovery from the harmful side effects, there is now a shift in thinking towards the view that more compressed or accelerated schedules of drug administration using much smaller dosages than MTD might be more effective—not only in terms of reducing certain toxicities but perhaps even improving antitumor effects as well.” (Kerbel RS and Kamen BA, The Anti-Angiogenic Basis of Metronomic Chemotherapy, Nature Reviews Cancer 2004.)

In dogs and cats, we utilize chemotherapy agents such as cyclophosphamide at dosages approximately one-tenth of standard MTD dosages. These drugs are given daily to every other day. We have been using metronomic therapy for over 2 years and have experienced negligible side effects. Metronomic chemotherapy appears to be as effective as MTD (Adriamycin in this case) in dogs treated for hemangiosarcoma. Studies have also shown that metronomic chemotherapy may be effective in delaying recurrence of incompletely excised soft tissue sarcomas (STS). Of course, more aggressive surgery or radiation therapy is most effective in the setting of incompletely excised STS, but metronomic chemotherapy could provide a reasonable alternative for pet owners who cannot afford surgery or radiation.

Hoping to make a difference!

Yesterday, Dr. Walshaw performed a premaxillectomy on one of the sweet Chihuahua's rescued from that horrible scene in Dearborn where over a hundred live dogs were found in a home along with over a hundred that had died. This little 7-10 year old male Chihuahua, named Stevie, was found to have a tumor on the rostral (front) part of the maxilla which was protruding under the lip. Today, he looks great! He's still having to be encouraged to eat but is expected to make a full recovery. Although biopsy and margin reports are still pending, our suspicion is either benign epulis or low grade malignancy. Treatment, hopefully, will be curative. Without this surgery, the mass would have continued to grow and destroy the architecture of his maxilla, become ulcerated and bleed, and cause great difficulty in eating. Without surgery, adoption would have been difficult. This type of surgery typically costs between $2500-3500, but in order to join the overwhelming effort to help these poor dogs, our hospital donated these services so that Stevie will be able to find a "forever" home disease-free and pain-free. Steve's foster mom said that he just recently barked for the first time and didn't know what grass was when she put him down on her lawn. I'll keep you updated on the biopsy results and Stevie's progress and will add pictures soon!

Monday's hint for the day!

The information/results that your pathologist gives you is only as good as the sample and information you provide. Don't just cut a "representative" sample, be sure to send the sample in it's entirety if possible (obviously some limitations exist such as those 10 pound splenic tumors!). Mark your margins with India Ink or suture material to help orient the pathologist, as tumors shrink and distort in formalin on their way to the lab. If you do have a larger size tumor, you can "bread loaf" cut it, leaving the base in tact so that the formalin will fix the tissue, but it stays in it's original configuration. Give a good, complete clinical history.

Most importantly, develop a close relationship with your pathologist! If the diagnosis doesn't fit the clinical picture, call and find out why. The basic information need with each histologic cancer diagnosis should be 1.) what is it 2.) did I get it all (margins) 3.) how wide the microscopic margins are 3.) indication of biologic behavior (poorly differentiated, etc.). Don't forget to ask regarding immunohistochemistry stains if the diagnosis is not clear with routine H and E staining.

Most clinicians identify a pathologist that is more experienced in certain areas (e.g. a pathologist that is more experienced in dermatology or one more experienced in cancer) when submitting a sample. Never be afraid to call your pathologist and ask for a re-read if all the information listed above is not provided for you. Some labs charge more for a more detailed report, but you really need a more detailed report to decide if post-operative cancer treatment is necessary.

Good morning!

We currently have 3 clinical trials up and running successfully! Significant financial assistance for diagnosis and treatment is provided for clients whose pets enter the clinical trial. Eligible patients include those with transitional cell carcinoma, metastatic osteosarcoma, and lymphoma. Please contact our office for more information. Phone consultations are available but are limited to referring veterinarians only. If your pet is diagnosed or suspected to have one of these cancers, contact your primary care veterinarian and have him/her call us for more details about our clinical trials.

Hint for the day: Therapy for transitional cell carcinoma (TCC) of the bladder is usually limited to non-surgical therapies. TCC is rarely amenable to complete surgical excision due to the location within the bladder and also it's infiltrative nature along the bladder wall. Therefore, if clinical symptoms are suggestive of bladder cancer, an ultrasound should be done prior to any surgical intervention. If a lesion consistent with cancer is evident, a diagnosis should be attempted through non-surgical means. I have seen many cases over the years that have come to me after a surgical diagnosis of TCC with disease transplanted to the surgical incision line. This occurs because instruments used to operate on the bladder were also used to close the abdominal wall incision. Surgery should be reserved for patients whose tumors are in locations of the bladder that would suggest a non-TCC tumor. Routine cystocentesis should also be avoided if patients are known to have TCC.

Welcome to the Animal Cancer and Imaging Center's new blog!

This blog is designed to provide a resource on animal cancer for veterinarians and pet owners. There are thousands and thousands of publications, articles, book chapters, etc. on veterinary oncology topics available to the knowledgeable reader. But new information is constantly evolving and by the time publications get to print, they are already on the road to being outdated. Some of the most valuable and up to date information is gained from all of those countless patients whose cases are never published. In short, experience is an important resource and reference that shouldn't be overlooked.

I want to share our experience with you in hopes of helping your patients or your own pets whose circumstances may be similar to patients we have already treated. My intense oncology experience began in 1988 at the beginning of my medical oncology residency at Colorado State University. I became board certified in 1992. It has now been 21 years since I have practiced oncology exclusively. We also have the valuable resource of Dr. Richard Walshaw, board certified surgeon, member of the prestigious Veterinary Society of Surgical Oncology, and professor emeritus, MSU College of Veterinary Medicine whose experience and dedication to the practice of medical and surgical oncology spans over 3 decades. There are very few types of cancer cases that we have not yet seen or treated. However, there are always new and challenging patients presented to us every day. I will periodically share more interesting cases, share with you ongoing updates on our clinical trials, and discuss novel therapies and ideas regarding the treatment of various cancers.

"Make no judgements where you have no compassion" .....Anne McCaffrey