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

How to Use the Mitotic Index to Make Decisions About Mast Cell Tumors

Updated: April 13th, 2021

Summary

Is using the mitotic index mast cell tumor diagnosis useful? In some cases, not as much as others. But when it’s useful, it’s REALLY useful!

There is a lot of uncertainty in canine cancer, and mast cell tumors are the tumor type that proves it. Mast cell tumors are tricksters, with seemingly benign tumors sometimes turning out to be very aggressive … and often enough to be confusing, vice versa. When we’re talking mast cell tumors, we are definitely in what I call “the gray zone.” Determining just how aggressive the tumor is up front is important when it comes to making treatment decisions, which is why Dr. Ettinger, my oncologist co-author, suggests looking at the mitotic index for mast cell tumor assessment.

The most common instance of confusion in mast cell tumor diagnosis is for the grade 2 mast cell tumor.  As you may already know, the “grade” is a measure of how aggressive a cancer is.  When we say a cancer is a “high grade malignancy” we mean it is hard to cure.  A “low grade” growth is easier to cure as a generality (but not always), usually by surgical removal.

Grading Mast Cell Tumors

In mast cell tumors, the grade is usually broken down into three levels, with grade 1 being the lowest and grade 3 being the highest and most aggressive. (There is also a newer, 2-tiered system of grading mast cell tumors that may be available to your oncologist and may be useful in real “gray zone” cases.)

So, if your dog has a grade 3 mast cell tumor, it’s considered aggressive cancer. Aggressive cancers do things like regrow in the same spot even after surgery (recur) or spread to surrounding areas (local invasion). Aggressive cancers can also spread to distant sites … places like the spleen, liver, bone marrow, or other remote areas, which is called metastasis.

If your dog has a grade 1 mast cell tumor, thankfully, it’s considered less aggressive. This means that it is likely going to be cured with a surgery with wide margins that gets the whole tumor out. This doesn’t mean that grade 1 is ALWAYS cured with a surgery — just that it is more likely to. And make sure you ask for wide margins!

Grade 2 mast cell tumors are intermediate, by definition, and highly unpredictable. These are the tumors that earn mast cell tumors their nickname “the trickster.” Grade 2 mast cell tumors can behave aggressively (like grade 3’s) or more like benign growths (grade 1’s).

It’s grade 2 mast cell tumors that can most benefit from a mitotic index measurement. The number will be on your biopsy report.

Get the Biopsy!

You will not know the grade of your dog’s mast cell tumor until after the biopsy is performed, of course, so you can’t use the mitotic index for mast cell tumor assessment until AFTER you get that tumor surgically removed (with wide margins, please!).

If you are looking at a grade 1, the likelihood that your dog will need more treatment is low. For a grade 3 tumor, which is seriously aggressive, you are almost certainly going to get more treatment recommendations. But what about that gray zone, the grade 2 mast cell tumor?

There are a couple of ways to treat a grade 2 mast cell tumor. You could do a second excision (surgery) with wider margins. You could add chemotherapy and/or Palladia to your treatment plan. But which action plan to take is in the gray zone until another bit of information:

The mitotic index!

Mitosis

Mitosis is a part of cell division, the way that cells replicate themselves. You can actually see mitosis happening in cells under a microscope. It looks something like this.

Public Commons Image https://commons.wikimedia.org/wiki/File:Major_events_in_mitosis.svg

To get the mitotic index, the pathologist looks at a slide with a very thin slice of your dog’s tumor tissue on it. The tissue has been stained so it is colored and they can easily see which cells are dividing (in mitosis). They simply count the numbers of these cells to get the mitotic index. The higher the number, the higher the mitotic index and the more aggressive the tumor.

If you think about it, this will make sense. The more cancer cells divide, the faster they replicate themselves, the bigger the tumor, and the bigger the problem for your dog. More cell division, faster growth, higher mitotic index.

Mitotic Index Mast Cell Tumor

So what does the mitotic index actually mean for mast cell tumors?

Well, generally, a lower mitotic index is better. Fewer dividing cells = a less aggressive cancer.

For grade 2 mast cell tumors, the magical number to hope for is a mitotic index of 5 or less.  These dogs, with conventional care alone, have a median survival time of 70 months, or nearly six years. That’s a nice long median survival time.

Unfortunately, dogs with grade 2 mast cell tumors with a mitotic index of greater than 5 have a dramatically shorter median life expectancy of only 5 months. This is quite a dramatic difference.

Here is the abstract to show you where I am getting this information.

Bottom Line: How to Use the Mitotic Index for Mast Cell Tumor

Again, you might not really need to consider the mitotic index if you get a grade 1 or 3 tumor. In those cases, your direction will be more clear-cut.

But in cases where we have a grade 2 mast cell tumor, the mitotic index (MI) can help you make decisions about what to do next.

If you have a grade 2 mast cell tumor with a mitotic index of <5, your minimum treatment surgery with a wide excision of 2 to 3 centimeters. If you have that already, you might not need any more treatments, but your oncologist might want to use other steps, including chemo and/or radiation. With a median survival time of 70 months, taking those extra steps might not feel necessary in every case. (Remember, I don’t make direct advice over the internet, because every case is different. I’m not saying that you should not get extra treatment if your dog’s MI is under 5. I’m just saying in general, they may not be as necessary.)

But in cases where we are looking at grade 2 mast cell tumors with a mitotic index of >5, these cancers should be considered very, very dangerous and aggressive.  If your dog is young, and you would expect her to live a long time if she weren’t sick, you might be more aggressive with the treatments than you would if the MI were <5. I would certainly consider chemo and radiation with your oncologist.  If your dog is close to or beyond his average life expectancy, I would suggest it is time for ethical considerations and maybe a focus on life quality enhancement.

Regardless of the grade of tumor or the mitotic index, your dog will benefit from the dog cancer diet, supplements, life quality enrichment, and the other complementary aspects of care Dr. Ettinger and I cover in detail in our book The Dog Cancer Survival Guide.

Best,

Dr D

Leave a Comment





  1. Nicole on January 10, 2014 at 11:32 am

    Dr. Dressler,

    My 8.5 year old ridgeback has had several mast cells removed all with clean (3cm) margins. Recently an old growth that had been there for >4 years was removed and the pathology came back as a Grade III with a mitotic index of 0-1. Her other newer mast cell removals were all low grade II’s with MI 28wks before removal the prognosis is more favorable. Additionally Roamansik EM et al reports mitotic index predictive of survival in grade II however the sampling of Grade III with MI <5 was too small. The data seems to suggest that MI is a good predictor of the nature of the cancer. My question is this-how can a tumor be graded a III i.e. aggressive yet with a MI approaching 0? My dog is perfectly healthy, has been fully characterized with ultrasound, spleen biopsy, and has not sign of spread. Is chemo is this case the right approach?

  2. Roy Goble on October 23, 2013 at 4:20 pm

    Great article, thanks for the help. One follow-up question: what precisely is meant by “conventional care alone” in this instance? Our 8-year old Golden Retriever has had several mast cells removed, and thankfully the index is zero. Prognosis is good. But is “conventional care” something beyond good diet, regular exercise, and routine checkups?

  3. Wendy on August 20, 2013 at 5:43 am

    My 7 year old labradoodle was just diagnosed with a mast cell tumor, grade 2 with no dividing cells. The tumor, on her toe,was mostly removed except for the part that wrapped around her nerves. Should we watch and wait or go see an oncologist? What do you think they will recommend? And should we do it? In the mean time, is there anything else I can do for her to keep her healthy? Thanks. Wendy

  4. Tony on September 26, 2012 at 4:45 pm

    I have a 7 year old German Shorthair pointer who had a grade 3 mast cell tumor removed that was on his scrotum, he had his whole scrotum removed as a result. All his blood work came back great, I had an ultrasound done on him to see if there was any spreading to his organs, and that all came back clear, and all organs look good and there was no signs that it had spread. They didnt aspirate any lymph nodes, and said it really wasnt nesecary because there was no signs of mast cells on the organs?? Does that sound correct? I guess my major questions are what is the next steps? Should I go see a specialist? He is feeling fine, eating and drinking just like normal, there seems to be nothing out of the ordinary. I just really dont know what to do, and just want to help my buddy.
    Thank you,
    Tony

    • Dr. Demian Dressler on September 28, 2012 at 12:49 pm

      Dear Tony
      don’t play with a grade 3 mast cell tumor and assume it is now gone. Your dog’s body is in a state that is different from that of a healthy dog and stopping at this stage makes no sense, to put it bluntly. You need diet, apoptogens, immune support, other nutraceuticals (read the Guide), and should be considering chemotherapy and other items at least. Get more info ASAP, and discuss with the vet/onc these next steps.
      see:
      https://www.dogcancerblog.com/blog/dog-cancer-what-is-micrometastasis-and-why-do-we-care/
      https://www.dogcancerblog.com/blog/an-overview-of-what-else-can-i-do/
      Best,
      Dr D

    • Dr. Susan Ettinger on September 30, 2012 at 5:02 pm

      Hi Tony,
      Grade 3 mast cell tumors (MCT) are quite aggressive, but still treatable. The rate of metastasis is about 50 to 90%, and a bone marrow is typically recommended in addition to the ultrasound. I would definitely recommend seeing a specialist as I generally recommend chemo for grade 3 MCT, especially considering the location. An oncologist can go through the details and make specific recommendation for your boy.

      I have 4 or 5 posts on MCT so far (mor to come) and I would suggest you check them out. In addition, there is a complete chapter on MCT in the Guide.

      Start here: https://www.dogcancerblog.com/blog/the-oncologists-thoughts-on-mast-cell-tumors/

      Good luck!
      All my best, Dr Sue

  5. ted boganowski on September 2, 2012 at 6:42 am

    i have read that trypsin enzymes have a digestive effect on malignin enzymes in cancer there is evidence that this may be possible even with fast -growing cancer ,. college of natural medicine.some one have information on it thank you

  6. Sue - 19.8.2012 on August 18, 2012 at 10:01 pm

    Hi, Our Jenny (jack russell – 12yrs) has a mast cell tumor on her chest just by her right front leg, she cannot have surgery and has had chemo (Lumestine- not sure of spelling) two sessions but to no avail. It is growing all the time and has now spread to her lymph node in her neck. Like many of the people on this blog, I would like to know what to expect if anything as times goes on. She is still eating well and their is no sign of diaorhea, but she does pant a lot and drink a lot. please could you help We love her dearly she is our baby. Thank you

    • Dr. Susan Ettinger on August 27, 2012 at 3:54 pm

      Hi Sue,
      There are other chemotherapy options for Jenny if you choose. Progression on one drug does not mean others won’t work. Have you discussed other options with an oncologist, like vinblastine, Palladia, Kinavet?
      It’s hard to predict how things will progress. Good questions for your vet who is most familiar with Jenny’s case. Is she on pred? That can cause increased drinking and panting and is often used for MCT. Also check out the MCT chapter in the Guide and more blogs to follow shortly.
      Good luck, Dr Sue

  7. Eileen Tredway on August 14, 2012 at 5:31 am

    Hi,
    I have a 9 year old mixed chow-chow breed. He recently was diagnosed with a mast cell carcinoma (that was quite large) on his side. It was removed. The cells were well differentiated cytologically and his mitotic index was 2. He healed well from the operation and exhibits no other symptoms. BUT, there is another mast cell carcinoma towards his chest area. (An in office aspiration confirmed) We don’t know if it was missed earlier or if it is new. Vet is recommending Carafate 1G to protect his stomach and 4 weeks of Palladia. Thoughts?

  8. Lisa on February 20, 2012 at 6:01 pm

    My 13 year old cocker mix had a tumor removed from his right rear leg in july of 2011. We did not have it analyzed but the vet said it looked like cancer but thought he got good margins. 4 days ago we took him to the groomer and because his hair had grown so long, we did not notice a recurrence of several tumors to the same leg and a large mass in the right lower abdomen. Our vet says it is a recurrence of cancer that has spread to the lymph nodes in the abdomen and nothing can be done. We understand the advancement and are coming to accept his days are numbered but can you give me any idea what to expect in the coming days? He is still acting normal, eating, playing, and frankly seems well. How long can we expect him to be well. What will be the first signs of a decline and how quickly will it go from there? I have never had a pet to go through this sort of illness and we want care for him as best we can but not prolong any suffering. Thank you.

  9. Nunz on February 11, 2011 at 2:54 am

    Hi Dr Dressler

    Thnx for a fantastic site. I’m enjoying reading it and finding out that I’m not on my own!

    Here is our story.

    We have a 6.5 year old dogue de bordeux cross with T cell lymphoma. We caught it early (stage I b) and removed the lump from her tummy and have had 6 months of chemo… Apart from a few chemo side effects, she is enjoying a good remission, almost a second puppyhood!

    We have since discovered another lump on her neck/shoulder, which a Fna showed some mast cells, which led to a biopsy to determine what it was. The first labs report was inconclusive, however a second lab believes it is Subcutaneous (hypodermal) Hemangiosarcoma!

    What is interesting and why I am writing is that the mitotic index is 1-3. And the majority of the biopsy was non cancer cells.

    So, in line with your advice to get as informed as possible, I’d love your opinion as to a course of action.

    Obviously she will have a limited life expectancy due to the lymphoma, so i am wondering whether the removal of the slowly developing sarcoma, will just give her less quality of life (due to the surgery etc) or would removing the sarcoma give her the best chance of seeing out the remission?

    I guess, in a nutshell, which cancer do you think will get her first?

    The reading i have done so far indicates that the sarcoma can be quite quick, however i can find no information about the mitotic index and what kind of growth timescale that may represent..

    FWIW, the original lumps (as measured by the vet) have been steadily reducing in size.

    Anyway, i thought I’d put this out there and see if you could shed some light!

    Once again thanks for listening.

    Kind regards

    Nunz

  10. Amy on February 2, 2011 at 11:01 am

    Hi Dr. Dressler -it’s me again
    I left out above that when my dog’s cancer recurred – another small surgery was done, but the vet knew he did not get it all because of the location. Bella, (my dog), had a hard time healing from the surgery – because of the location her staples an stitches kept coming undone and she had to go back numerous times as well as be treated for an infection. When my vet was on vacation, however, another vet at his practice was able to do the stitches quite well and they stayed. This episode, however, may be attributing to his reluctance to perform surgery yet again. She is now almost 11 and has been through quite a lot – it was something that we had all agreed on regarding not adding stress to her life – but now that we are here and she is just fine in every other way – we don’t know what to do.
    Thanks again
    Amy

    • DemianDressler on March 8, 2011 at 9:41 pm

      Dear Amy,
      have you guys tried Apocaps? This would be an idea. Also, if it regrows, you might consider a salvage procedure: Neoplasene.
      Finally, it might be time to go back to the oncologist..
      I hope this helps,
      Dr D

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