Beyond Mast Cell Tumor Grade: Other Prognostic Factors - Dog Cancer Blog

Featuring Demian Dressler, DVM and Susan Ettinger, DVM, Dip. ACVIM (Oncology), authors of The Dog Cancer Survival Guide.

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Beyond Mast Cell Tumor Grade: Other Prognostic Factors

In my last blog on mast cell tumor (MCT) grade, I discussed that grade is one of the most important prognostic factors, or predictors, for dogs with MCT. And I also discussed the challenges of using the grade as a predictor: a good percentage of grade 2 MCT behave more aggressively than the rest of grade 2 MCT, and the recent news that the grade from a pathologist might not be reliable. What is a dog Guardian to do?

Well the good news is that there are additional tests besides grade that can help us predict your dog’ outcome.

Mitotic Index

One very important test is the tumor’s mitotic index, which measures how many MCT cells are dividing when the pathologist examines the biopsy under a microscope. Thankfully, this test is now routinely included on the pathology report.

Here’s what the numbers associated with mitotic index mean. In a recent study, it turned out that the higher the mitotic index, the poorer the prognosis.

For example, if the score was over 5 on the mitotic index, the median survival time was only two months, regardless of grade.

If the score was under 5, however, the median survival time was seventy months (over five years), regardless of grade.

So, you see, it is very important to know your dog’s mitotic index for their mast cell tumor. This knowledge can really help your oncologist to plan treatments, and you to understand your dog’s prognosis.

It should be noted that reported cutoffs for these prognoses can vary — from 5 all the way to 10. In the newer 2-tiered system described in this post, the cutoff was 7, not five. I expect that the cutoff will continue to be refined as more studies evaluate mitotic index as it relates to the different grading systems.

MCT Prognostic Panel

There is other prognostic information that can be drawn from a biopsy sample that may be helpful. This is often referred to as the MCT prognostic panel or proliferation panel, and it involves evaluating certain markers related the MCT’s proliferation (how much it multiplies) and how much cell division is happening.

The panel typically measures AgNOR, PCNA, Ki-67, c-Kit, and tests for c-Kit mutation status. This a panel helps me to predict whether the MCT will metastasize in the future, whether chemotherapy is recommended, and what chemotherapy to include in the protocol (based on the c-kit mutation result).

One of the most important numbers in the panel is c-Kit and it’s mutation status. One-third of dogs with MCT have a genetic mutation in the c-Kit gene. When there is a mutation, an enzyme called tyrosine kinase is stuck in the “on” position, leading to uncontrolled growth and survival of these mast cells. Studies have shown the presence of the mutation is a negative predictor, but now there are 2 relatively new chemotherapy drugs that target this mutation. I will discuss the c-kit inhibitors Palladia and Kinavet in a future blog.

Only a handful of laboratories have the special stains and expertise needed to analyze the MCT prognostic markers, so I recommend consulting with your oncologist to see if this information is necessary before adding these expensive tests to the biopsy. I find this panel especially informative for Grade II and grade III tumors.

There are several other prognostic factors for MCT included in the Guide, including rapid growth, size, recurrence and location.

Remember what I said in the 1st blog on MCT: MCT are not one size fits all tumors. Not one test – grade, mitotic index, c-kit mutation, or other prognostic factor – can definitively predict your dog’s outcome. But we can use these to help make good recommendations, so your dog can not only live longer with MCT, but live well.

About the Author: Susan Ettinger, DVM, Dip. ACVIM (Oncology)


Susan Ettinger, DVM. Dip. ACVIM (Oncology) is a veterinarian oncologist at VCA Animal Specialty & Emergency Center in New York, and the co-author of The Dog Cancer Survival Guide: Full Spectrum Treatments to Optimize Your Dog's Life Quality and Longevity.

  • Mary Emmons

    This sounds like more positive news for my American Bulldog Dozer. Thanks Dr. Ettinger for the update. Your information is not only informative, but gives us guardians a little bit of peace of mind. Thank you from the bottom of my heart!

    • Dr. Susan Ettinger

      Thanks Mary. Glad you are finding the posts helpful. Belly rubs to Dozer!
      All my best, Dr Sue

  • what holistic treatments would you recommend for a 6 year old Labrador with a grade 2 MCT that has a mitotic index of 0 — 1

    • Dr. Susan Ettinger

      Lots of options. Have you checked out the Guide? There is a ton of great info there. I would add Apocaps. I use it most of my MCT patients as long as they are not on steroids, like prednisone.
      Good luck! All my best, Dr Sue

  • blair

    My 14 year old kerry blue terrier was just diagnosed with stage 3mast cell cancer. She had it removed and the margins were clean. That is basically all the info I got. She has so many lumps and bumps on her it was never recommened to biopsy or remove them unless they bothered her. This one however, was huge, horrific looking and she would chew on it.
    She’s a happy dog and otherwise in good shape. She has a good appetite and still gets excited about going to the park. Is it worth doing chemo on such an old dog with many lumps? should I do another treatment and if so which? Should I do nothing? My vet has not been very helpful as far as directing me.
    thanks for any response.

    • Dr. Susan Ettinger

      Blair,
      It’s hard to give specifics for your dog’s MCT, but I do recommend chemo for grade 3 MCT (did you mean grade or stage). And you should consider aspirates of the other masses, but it’s really hard thru the blog to make good specific recommendations. If your vet is not helpful, I would consider a 2nd opinion. Her age alone should not prevent you from treating. There is more to consider – other health issues, how advanced the cancer is, etc.
      All my best, Dr Sue

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  • Korina

    I have a 9 1/2 year old german shorthair pointer who has had 4 surgeries to remove MCT stage II. It is now in his inguinal lymph nodes and we have him on a palliative care regimen. Just in the last few days he’s not as interested in his meals that I make from the Dog Cancer Book. He still will eat chicken and turkey but definitely no veggies, cottage cheese, or carbs of any sort. Do you have a recommendation? He still has a zest for life !

    Thanks

    • Dr. Susan Ettinger

      Korina,
      It’s hard to know for sure why his appetite has recently changed. It could be tumor related or related to his palliative meds. Dogs with metastatic MCT are also at risk for stomach ulcers due to increased histamine levels. He should be on an antacid and an anti-histamine. Check with your vet. Also if the appetite change is new, I recommend blood work to look for a systemic issue. Good luck!
      All my best, Dr Sue

  • Kevin d

    My 9.5 yr yellow lab Julius was diagnosed w grade 3 MCT 4 mths ago. After reviewing the report and noting a MI of 2-5 hpf, is there some room for optimism? I have read study after study ( including your blog ) suggesting an MI of 5 or below has a good prognosis, regardless of grade. There has been no spread or lymphatic vascular invasion.
    Thanks so much.

    • Dr. Demian Dressler

      Dear Kevin- I am sorry, but a grade 3 is bad news. Not a grade 2?? The MI issue is for grade 2 (intermediate grade tumors, to clarify those…)
      If it is really grade 3 and not grade 2, I would be hitting this cancer hard.
      http://www.dogcancerblog.com/an-overview-of-what-else-can-i-do/

      I hope his helps
      Dr D

  • Dotty McDowell

    I have a pit bull he is 8yrs. Old, he was diagnosed last month with carcinoma cancer possibly. Caine had a large lump come up on his back virtually overnight, and the Vet when he saw it said it was cancer. When he drew the fluid out to ck under microscope, the fluid he said looked like fatty tissue, even under the microscope, he could not see that it was cancer, but because the lump was so big, he sent it off to have it checked, the next day, he called and said they felt it was Carcanomia, but that to be sure they needed the lump, which is so large it can’t be taken off. He put Caine on Neoplasene and a pill for neasua, started him at 2cc 2x’s a day after 5days up it to 3cc and then up eventually to 5cc. We haven’t gotten past the 2cc yet. Caine goes back to the Vet today. To me it looks like a mass cell tumor, if it’s cancer, but the Vet says it’s Carconoma. I’m really worried about this, as Caine had a small mass on his side for over a yr now, but the Vet said it was nothing so it was not to this day checked. When we see him today, I don’t know how to approach him about this, and also why he doesn’t want Caine on human food not even the cancer diet for dogs, yet Caine has always eaten human food, if we ate a steak, he had a steak to he has never eaten table scraps or regular dog food except for the dog treats or beggin strips. He won’t eat dog ood at all, so he’d never get his Medcine, the liquid unless we put it in ice cream, which I don’t like to give him so I just keep feeding Caine the human food diet. I’m not sure why the Vet wants him to only eat the can dog fod they sell even when we tell him Caine want eat it, the Vet just says he’ll eat it before he’ll starve, but to give him the Medcine in ice cream? Can you help me with this? The large lump is on the top of his back about 5-6 inches before his tail, all his blood work came back normal, and all his x-rays and tests showed no organs are affected by the cancer and no other tumors are inside of him or on vital organs!

    • Dr. Demian Dressler

      Dear Dotty,
      Sorry to hear about your dog. As you may have found out, a carcinoma is a kind of cancer, I’m afraid. Have you read The Dog Cancer Survival Guide? I think it might be a good idea. I would not use Neoplasene orally without also mirtazapine or something similar to help with appetite and vomiting..ask your vet about that. Personally, my opinion is that a balanced, complete home made diet with a vitamin supplement is fine for dogs, better than bagged or canned food often. You need a good recipe though (and it sounds like you know what recipe I’d suggest…). I hope this helps
      and here’s another post for you:
      http://www.dogcancerblog.com/an-overview-of-what-else-can-i-do/
      Dr D

  • Kevin D

    Thanks.

    According to Romansik (07) and follow up by London (09), dogs with MI of 5 or below lived for median of 70 m. Regardless of grade. Yes the sampling for G3 positive prognosis was small but that’s because most grade 3’s have a higher than 5 MI. I’ve seen similar studies and analysis by intl groups, particularly one in Australia where it’s rare for MCT to spread if MI 5 and below. I also see a recent study for prognosis whereby MI is just one marker. (Mich). and even if MI 5 or below other markers come into play. As a financial guy, I must admit the sampling in all of these studies are statistically weak and each dog should be treated differently. Most studies use 30-100 dogs and based on those specific dogs. I don’t buy any of these studies good or bad. At least viewed w skepticism. As a vet at Smith Ridge told me, I’ve seen grade 3’s never come back and I’ve seen grade 1’s come back w veracity. They like you treat the body to fight, not just cut, chemo and radiate.

    Btw: in addition to the Smith Ridge protocol, I am using Apocaps. So far so good.

    Thanks for your amazing work.

    • Dr. Demian Dressler

      Great work, Kevin D.
      Its not often that we have such astute analysis by a guardian even among those with medical degrees.
      Best
      Dr D

  • Melissa Z

    My ~ 10 year old greyhound/lab mix has been plagued with benign lipomas for several years now..that is until recently. In February she developed a very fast growing lump on her trunk. The fine needle aspirate was inconclusive and the lump (between her mammary glands) was surgically removed. A good deal of tissue was also excised to ensure clean margins. Chest x-rays were also clear. She recovered from the surgery in no time at all and continues to do well clinically.

    Pathology confirmed a grade II MCT with MI of 3. Given how much tissue was removed the surgeon was concerned with how narrow the lateral margins were. He referred us to a specialty oncology group that has only has one location in the state (and I am extremely thankful that it happens to be in the town where I live).

    They have been amazing about going through all the options and possible scenarios. Although they don’t recommend it for every case, the oncologist thought it would be helpful to have the additional testing done at Michigan State, specifically because there seemed to be some disconnect between the pathology and clinical picture. At that point we were discussing additional surgery and perhaps radiation.

    The results finally came back last week. There is a c-kit mutation (exon 8), and my understanding is that this is the one they know less about. This result meant radiation and surgery were off the table.. We were now talking chemo, but first she had to go through staging this past Tuesday. The ultrasound showed an enlarged lymph node, which because of its location (near spine in the region of aorta and vena cava) cannot be biopsied or surgically removed. All the other tests and blood work were normal. She does also have another small surface MCT on her chest (independent of the one removed previously).

    Apologies for the long winded story, but I have just received your book, and reading/digesting as fast as I can. She was started on Palladia yesterday, and we are going to hold off removing the smaller tumor in the hopes that it might also respond to the chemo. I was just about to order the apocaps, when i read their primary side effect appear to be GI related. Since this is also true for the Palladia I am wondering if the two can be used together, or is there an alternative nutraceutical that I should be giving her instead? The palladia is being given every other day, with daily Pepcid AC (20mg).

    I just want to make sure there is no known reason the two can’t be given together?

    If anyone ever doubts that cancer is an epidemic they need only visit the waiting room of a specialty veterinary oncology practice. The waiting room is always, always full.

    Thank you for providing us with such a comprehensive and well thought out resource.

  • Susan Kazara Harper

    Melissa, I’m so sorry to hear that you lost your girl to what was a very aggressive mix of problems. As you noted, all the information necessarily focuses on one subject, one type of cancer at a time. Yet the body is complex and each system relies on the other. You did the greatest job being her guardian and protector and doing everything possible to not only support her system but to also work closely with the vet professionals as they treated her. Although you felt a bit blindsided by the problems she faced, you can stand strong and know that you did everything possible for her, and she undoubtedly knew it. I hope you use her story and your experience to help educate others about good nutrition and signs to watch out for, so your girl’s legacy will be great memories and long life for others. All the best.

  • Katherine

    My boxer has a recurring MCT. She is 8 years old. The tumor is located below her rear hock. It is a grade II with a mitotic index of 0-1. The tumor was removed 9 months ago and due to the location, full clean margins were not possible. The tumor has returned (9months later) but it is very small and the lymph nodes are not involved. Ellie is very happy and seems perfectly sound and healthy. What Treatment should I pursue at this point. I am not inclined to pursue radiation or Chemo. I have read about palladium. I am wondering if surgery alone is an option or if I should watch it for now. Again, with the mitotic index 0-1 the tumor has proved to be very slow growing. I am afraid of the chemo as the efficacy seems to be hit or miss.

    • DrSueCancerVet

      Hi Katherine,
      Sorry the tumor has recurred. I would strongly recommend you see a boarde oncologist so he or she can make specific recommendations for Ellie. With recurrence, she should have staging test including an ultrasound to make sure the MCT has not spread. If it has not and the tumor is still small enough for surgery, I would do that, and consider a surgeon who is more likely to get margins around the tumor. If surgery is not an option, chemo can be considered. Palladia is more effective for dogs with the c-kit mutation, so discussed testing for this with the oncologist. There are lots of options for Ellie- good luck!
      All my best, Dr Sue