How to Use the Mitotic Index to Make Decisions About Mast Cell Tumors
Dr. Demian Dressler is internationally recognized as “the dog cancer vet” because of his innovations in the field of dog cancer management, and the popularity of his blog here at Dog Cancer Blog. The owner of South Shore Veterinary Care, a full-service veterinary hospital in Maui, Hawaii, Dr. Dressler studied Animal Physiology and received a Bachelor of Science degree from the University of California at Davis before earning his Doctorate in Veterinary Medicine from Cornell University. After practicing at Killewald Animal Hospital in Amherst, New York, he returned to his home state, Hawaii, to practice at the East Honolulu Pet Hospital before heading home to Maui to open his own hospital. Dr. Dressler consults both dog lovers and veterinary professionals, and is sought after as a speaker on topics ranging from the links between lifestyle choices and disease, nutrition and cancer, and animal ethics. His television appearances include “Ask the Vet” segments on local news programs. He is the author of The Dog Cancer Survival Guide: Full Spectrum Treatments to Optimize Your Dog’s Life Quality and Longevity. He is a member of the American Veterinary Medical Association, the Hawaii Veterinary Medical Association, the American Association of Avian Veterinarians, the National Animal Supplement Council and CORE (Comparative Orthopedic Research Evaluation). He is also an advisory board member for Pacific Primate Sanctuary.
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:
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
Dr. Demian Dressler is internationally recognized as “the dog cancer vet” because of his innovations in the field of dog cancer management, and the popularity of his blog here at Dog Cancer Blog. The owner of South Shore Veterinary Care, a full-service veterinary hospital in Maui, Hawaii, Dr. Dressler studied Animal Physiology and received a Bachelor of Science degree from the University of California at Davis before earning his Doctorate in Veterinary Medicine from Cornell University. After practicing at Killewald Animal Hospital in Amherst, New York, he returned to his home state, Hawaii, to practice at the East Honolulu Pet Hospital before heading home to Maui to open his own hospital. Dr. Dressler consults both dog lovers and veterinary professionals, and is sought after as a speaker on topics ranging from the links between lifestyle choices and disease, nutrition and cancer, and animal ethics. His television appearances include “Ask the Vet” segments on local news programs. He is the author of The Dog Cancer Survival Guide: Full Spectrum Treatments to Optimize Your Dog’s Life Quality and Longevity. He is a member of the American Veterinary Medical Association, the Hawaii Veterinary Medical Association, the American Association of Avian Veterinarians, the National Animal Supplement Council and CORE (Comparative Orthopedic Research Evaluation). He is also an advisory board member for Pacific Primate Sanctuary.
Dear Dr. Dressler,
My 10 year old hound/terrier mix was first diagnosed with a fibrosarcoma in her rear area two years ago. She had surgery and underwent a complete round of radiation (21 sessions). The surgery could not get all of the tumor because it is very close to the anal area. She seemed fine for a year. This past summer the tumor came back. The vet did not want to operate again and the oncologist told us that chemo would only give her a 25% chance at extending her life an additional 6 months to a year. We were told she had a “couple of months left.” We did not want to stress her out any further so we decided just to try to keep her as healthy in every other way as possible. We have been using your diet mixing in stasis breaker and wei qi booster. She is completely fine in every way on an appetite and energy level. The problem is the tumor is getting huge. We just tried an experimental round of injections of Kyosenex but it did nothing. The tumor is quite large on her buttocks and we are worried it will soon interfere with her being able to have comfortable bowel movements. We don’t know what to do because she is so fine in every other way. She does not seem like a dog who is anywhere near dying. I just cannot imagine euthanizing a dog that is alert, happy and energetic. Please give us some advice. And thank you so much for the Cancer Diet – I am convinced we would not have had her these additional months without it.
Sincerely,
Amy
[…] However, if you receive a diagnosis of MCT ask your vet some questions. What is the grade? Is it a I, II, or III. A grade I means they caught it early. If it is II or III ask your vet what the lab results say about it. Both of those MAY require additional treatment. Also, ask what is the Mitotic Index. You want it to be below 5 out of 10. That is another measure of aggressiveness and can be correlated to life expectancy. The higher the index the shorter the life expectancy. See Dr. Dressler’s article about grades of MCT and Mitotic Index: https://www.dogcancerblog.com/blog/dog-cancer-decisions-in-the-gray-zone/ […]
My nine year old Jack Russel started vomiting on Thursday, I kept giving her water and chicken broth, she continue on Friday and on Saturday when she began to have diarea. She began to have seizures. On Sunday my Vet met me and began her on IV fluids, he wants to deep her and give her two days of rest for her liver to regenerate bllod cells, she is not any better, what are her chances.
Dear Tricia,
I am so sorry to hear this sad and traumatic experience. Two points for you:
1. The cancer took your dog. That’s the bottom line. When one looks at it from the big picture, even if there were some side effects from the Kinavet (which is possible, in particular the vomiting and dehydration and maybe the liver stuff). The reason is that a dog does not quickly pass away like this (in what sounds like multisystem failure) typically from Kinavet. We know the cancer was disseminated and this was the critical issue causing the tipping point.
2. Please also read this post:
https://www.dogcancerblog.com/blog/signs-of-dog-cancer-and-decompensation/
There are more answers that you should read about in the Guide as to cancer progression and causes that would help you, and some steps for you as well that might help.
Best,
Dr D
Dear Vicki,
this is a good question and a tricky one. You should read the sections on treatment plan analysis in the Guide. I will be writing a blog post as well that will help answer questions like these so stay tuned- should be up today.
Best,
Dr D
My dog Bodie was just diagnosed with osteosarcoma in his front left leg. The vet recommended amputation for pain management which I understand and would not object to, my question concerns his age. He is a 12.5 year old lab mix. Do you think this surgery is too “big” for such an old dog? He is otherwise healthy, the cancer is has not spread and he is happy. They said w/ surgery and chemo he only has 10-12 months on average. I want his final months to be pain free but I dont want him to have to endure a major surgery if it’s not needed. What are your thoughts? Thank you. Vicki
My 11 1/2 years old golden retriever, Honey, passed away Monday August 23. Her path report noted liver cancer – primary hepatic/biliary carcinoma but could also be metastastic – so no definitive report. Her last ultrasound, taken on the 18th, showed that 2 lymph nodes were greatly enlarged along with her liver. She had had surgery 2 years ago to remove a thyroid tumor in her neck. It had not metastisized and she got along great after surgery. I was told that, if the carcinoma in her liver was thyroid, Kinavet could help. I decided to try the drug. At this point, there was no telltale signs of the cancer. I gave her 200 mg on Wed night; I gave her another 200 mg Thursday night. She was feeling bad and had diarrhea – a small amount; also, her nose started running- water would drip freely from her nose; Friday I came home from work to check on her and found that she had vomited bile; She wouldn’t eat Friday but drank water. I decided to stop the Kinavet and called the vet, who agreed and prescribed a nausea tablet. Sat am she had diarrhea; by midday she had drank some water, ginger ale and ate a can of chicken noodle soup by 10pm; however she was totally weak. Sun she wouldn’t eat or drink – water was dripping from her nose and her eyes were running, like she was crying. Sun afternoon she vomited very mucousy bile 3 times – I took her to the emergency room and was told she was dehydrated. Mon am the vet called to tell me she had walked around a bit however, her heart chambers were not pumping in sync – the chambers were pumping randomly although there was oxygen in the blood. She was going to monitor Honey another day and do another blood panel. Less than 20 min after the 1st call, she called to tell me her heart had stopped. Could the dehydration with the Kinavet in her system caused her heart to shut down? How long would the Kinavet remain in her system – (she weighed 61 lbs)? I was supposed to give her 200 mg every 24 hours and I gave her the drug on Wed and Thurs. I had breast cancer – mastectomy and chemotherapy. I had a heart check to determine the strength and health of my heart before chemo was started. I realize that my drug was different and of course I’m a human. Could the 400 mg of Kinavet strained/harmed her heart? The vet also told me Mon that she showed signs of jaundice in the whites of her eyes. The cancer was found in her liver -could the Kinavet have stressed her liver enough to cause it to shut down? I got Honey when she was 7 weeks and she has been my child, best friend and companion. I am trying to deal with the reality that she’s gone (it’s like a bad bad dream ). I made the decision to try the Kinavet as I wanted to keep her with me as long as possible. Please help me find some answers. The vet said that she thought Honey had issues we weren’t aware of. It happened so fast. Wed day she ate well, ate several milk bones and went for a walk with me Wed night albeit she walked slow and wasn’t her usual perky self. Mon she was gone. If her cancer was advanced, would she have gone so fast in the course of 4 days? Please help me.
Dr. Dressler, my almost 6 year old American Bulldog just had a mast cell tumor removed, it was a grade II with mitotic index of 9. She is overall healthy happy and now that the stitches are removed seems to be back to normal. Met with oncologist who recommended Vinblastine and Pred for 8 weeks. My question, the tumor removed had clean margins, they got it all according to pathologist, is chemo worth the side effects given this bad tumor was removed cleanly? This dog gets really nervous at the vet, stresses her out badly, very badly. I hate to take her to the oncologist for 8 weeks unless I knew it was worthwhile for her life. Any comments or recomendations for me on a cleanly excised grade II tumor with mitotic index of 9? Is it possible that it is cured now???
Dear Matt,
Although it is possible you have a cure, the mitotic index suggests that it may be a more aggressive (and potentially life threatening) cancer. The issue of margins does not really apply to cancers that tend to spread to distant sites:
https://www.dogcancerblog.com/blog/dog-cancer-what-is-micrometastasis-and-why-do-we-care/
I hope this helps,
Best,
Dr D
Your book and blog don’t mention hemangiopericytoma or fibrosarcoma. Any input on those?
I’m also wondering if your vitamin D information is up to date.
Vitamin D levels can definitely be improved in humans, and the current recommendations for the majority of people is 10,000 IU for 6 months, then test levels. This is considered the #1 bang for your buck regarding cancer.
So it would be surprising to me that dogs really can’t benefit from supplements, and I wonder if they truly get toxicity at low levels, or if that is that old information. A year ago a lot of doctors were saying that people could get toxicity from 1000 or 2000mg of D. And that has been proven as false.
Hi Dr. Dressler,
I just came across this post and was wondering if you could help me with a question? My dog had a grade II MCT on her skin that was removed in August 2008 and we found in August 2009 that it has spread to a lymph node on her chest. That was removed with clean margins and she underwent chemo (vinblastine and pred) and is doing well.
I came across this post and went and checked her records (which I got from the clinic thanks to your ebook) and saw that it said “one or two” cells were in mitosis per 400x field (on the pathology report from the lymph node.) So, what would be the mitotic index for that? Is it one or two? Or higher?
My dog’s oncologist did not mention M.I. to me, and I did not think to ask about it at the time.
Thank you!
Allie
Dear Allie
The mitotic index refers to the biopsy of the cancer itself, not a lymph node. Which are you referring to here?
Dr D