The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 81

94. How are mast cells involved in cancer?

  • Mast cells are very involved in cancer biology. They are frequently found in tumors. Tumors can trick mast cells into doing things they need to stay alive, like make blood vessels to supply the tumor with blood, and tissue remodeling, to push aside the healthy tissue and make room for the tumor.
  • Cancer is mast cell activating. All cancers. This is because cancers often trick the body into doing things that help the cancer and not the body, like I just described above. Having cancer frequently causes allergy symptoms because of mast cell activation.
  • Cancer can also cause the body to make more mast cells than normal, a condition called mast cell hyperplasia. This can happen because the body is trying to fight off the cancer with more immune cells or because it has been tricked by the cancer to make more mast cells to help the cancer.
  • Please note that mast cell hyperplasia is NOT the same as mastocytosis. Mast cell hyperplasia is too many healthy mast cells that function normally. Mastocytosis is too many aberrant mast cells that do not function normally. Cancer does not cause mastocytosis.
  • Long term inflammation increases future risk of cancer at the site of inflammation. This applies almost universally. Mast cells participate significantly in inflammation so they can contribute to the risk of cancer. For example, patients with long term colon inflammation, which may be caused by mast cells, are at increased risk of colon cancer.
  • Patients with mastocytosis have increased risk of developing cancer, especially those with systemic mastocytosis. As many as 40% of patients with systemic mastocytosis develop another blood disorder with too many broken cells. Frequently, the other blood disorder is a blood cancer like chronic myelogenous leukemia.
  • It is not yet known if mast cell activation carries an increased risk of developing cancer.
  • Two forms of systemic mastocytosis are cancerous, mast cell leukemia and mast cell sarcoma. These are both extremely rare and it is extremely rare for a person with a history of mast cell disease to develop either of these conditions.

For further reading, please visit the following post:

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 48

Mast cells in the GI tract: How many is too many? (Part Three)

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 48

59. Is systemic mastocytosis a form of cancer? Why do some papers say the life expectancy for systemic mastocytosis patients is much shorter?

Systemic mastocytosis is a term that different people use in different ways, often without defining them for the audience. This can lead to some confusion.

In its broadest sense, systemic mastocytosis is actually a disease category rather than one specific diagnosis. The subtypes of systemic mastocytosis are indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), systemic mastocytosis with associated hematologic disease (SM-AHD), aggressive systemic mastocytosis (ASM), and mast cell leukemia (MCL).

When patients talk about systemic mastocytosis without specifying which diagnosis, they almost always mean indolent systemic mastocytosis (ISM), the most common form of SM. ISM is benign and has a normal life expectancy. But when providers and researchers talk about systemic mastocytosis, they usually mean the disease category that includes all of these diagnoses.

I just recently explained in another post what a neoplasm is. It is essentially when the body grows something that doesn’t belong there, like extra cells or a tumor. Cancers are neoplasms but not all neoplasms are cancerous. Indolent systemic mastocytosis is not cancerous. Even without taking drugs to kill off lots of mast cells, the prognosis is excellent with a normal life span. However, aggressive systemic mastocytosis and mast cell leukemia are considered cancerous. Without taking drugs to kill off mast cells, the body would be unable to cope with the huge number of mast cells and the damage they cause. Smoldering systemic mastocytosis is sort of a bridge between ISM, which is benign, and ASM, which is not.

If you are not aware that research papers usually use the term systemic mastocytosis to mean all forms of systemic mastocytosis and not just indolent systemic mastocytosis (ISM), it is easy to get confused and misunderstand what is being said. There was a paper published in 2009 that discussed expected survival for the various forms of systemic mastocytosis. It provides a very jarring statistic for patients who may not understand the context. This study found that many patients with systemic mastocytosis died 3-5 years after diagnosis.

Let’s pull this apart. We know there are five forms of SM: indolent SM, the most common form, which usually has a normal life span; smoldering SM, which usually has a shortened life span; aggressive SM, which can have a very shortened life span; mast cell leukemia, which has a very shortened life span; and SM with an associated hematologic disorder, which may have a shortened life span. When you average the life expectancies for a mixed group of patients with these various diagnoses, it shows that overall, SM patients are more likely to die 3-5 years after diagnosis when compared to healthy people of the same age.

Additionally, a lot of the patients in this study group were older and died of causes unrelated to systemic mastocytosis. However, because they were part of the study, their deaths of unrelated causes were still included in this data.

Let’s recap: in a research paper, the term systemic mastocytosis includes forms of SM that are malignant and can really shorten your life expectancy as well as forms that are benign and do not shorten your life expectancy. When you average the life expectancies of all of these forms together, it looks like patients are more likely to die 3-5 years after diagnosis. A bunch of other papers then used the data from this study in 2009 without explaining the details behind it. However, most patients with SM have normal life spans.

For more detailed information, please visit these posts:

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Natural history of SM-AHD, MCL and MCS

The question I get asked the most

Whether or not SM is cancer is, by far, the question I get asked the most.  Because I get asked so often, I have done a lot of digging on this topic in the last few months.  Here’s what I found.

On the surface, from a biological point of view, SM looks like cancer.  It is characterized by excessive, improper cell growth.  It can cause organ infiltration and damage.  Over 90% of patients have a mutation in the CKIT gene, which is a proto-oncogene.  A proto-oncogene is a gene that becomes an oncogene when mutated.  An oncogene is a gene that contributes to cancer.  CKIT mutations can lead to gastrointestinal stromal tumors (GIST), melanoma, acute myeloid leukemia and, of course, mast cell disease.  So if SM has unregulated cell growth and a mutation in a proto-oncogene, that makes it cancer, right?
The World Health Organization (WHO), an organization I generally consider to know what they are doing, says it doesn’t.  To find out exactly why, I talked to a pathologist familiar with mast cell disease.  This is what she said:
“All cancers are neoplasms, but not all neoplastic cells are cancerous.  It is cancerous when the cells grow out of control.  In mastocytosis, even if you do nothing (meaning take no medications designed to kill off the mast cells), most of the time, the prognosis is very good because the cells are not growing that much.  Not like a cancer.  The other thing is when the cells invade other organs and the bloodstream and damage the organs.  When it is widespread and damaging, it is malignant.”
The majority of people with systemic mastocytosis have indolent disease, for which the life expectancy is normal, usually without any kind of therapy to kill off mast cells.  So if we follow the guidelines laid out above, SM is not cancer.   It is a myeloproliferative neoplasm (MPN.)
I know some people with ASM identify as having cancer.  ASM has a lot more features we typically associate with cancer, so I think that’s fine.  And MCL, obviously, is leukemia.
There is some terminology that gets thrown around incorrectly and I think it scares people who don’t understand that the wrong terms are being used.  One of them is chemo.  People with more aggressive types of mast cell disease may need chemo drugs.  People sometimes use the term incorrectly to reference more common treatments.  If you’re a rookie, I can see how you might get scared thinking that lots of people with indolent disease are on chemo.
Another term is compassionate use.  Compassionate use is the use of an experimental drug outside of a clinical trial.  It is generally allowed only when the person has no other treatment options and is gravely ill.  I have seen some people use it when discussing patient assistance programs, in which a pharmaceutical company will distribute a drug to a patient at a significant discount or at no cost.  They are not the same thing.
In the last few months, I have noticed that some people with SM will tell people that they have a “rare kind of leukemia.”  This is not accurate.  With the obvious exception of MCL, mast cell disease is not leukemia.  SM is a blood disorder. 
I think that part of why some people with mast cell disease say they have leukemia is because they want the sort of empathy given to cancer patients.  I understand that.  I wrote a whole post about how I hate when people say, “At least it’s not cancer.”  But it’s important to remember that cancer has two entities: the medical, biological aspect of the disease, and the social construct.  When you have ISM and you tell someone you have leukemia, their first thought is that you could die from it.  Mast cell disease is scary enough with scaring everyone around you extra with misinformation. 
I know that it’s frustrating that people know what cancer is and they probably don’t know what mast cell disease is.  And to be clear, I’m not talking about an offhand comment you make to some stranger asking you why you have a port at the grocery store to get them to go away.  I’m talking about the people who are actually in your life.  (I’m also obviously not referring to the SM-AHNMD people, who may very well have leukemia in addition to SM.)  If our mission is to educate people, stuff like this matters.  The words we use  matter.  A lot.  
I’m aware that this post is probably going to make some people angry, and that’s fine.  You can feel however you want to feel.  But I’m getting enough questions about this from people who are really worried, so I feel it’s important to set the record straight.