In 2009, Walker and colleagues published a paper called “Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia.” The term “mastocytosis” as used here is not equivalent the term “mastocytosis” as in cutaneous mastocytosis or systemic mastocytosis. It is one of several papers to do so and has generated a lot of confusion as a result.
The suffix –osis is commonly used in medical terminology. It means increase or production of something, but it also connotes that this increase results from a disease process. Here, the author means not that these patients meet the criteria for systemic mastocytosis, which we know to be a neoplastic disease originating in the bone marrow, but that there are more mast cells than expected in these biopsies.
Excessive production of mast cells in an organ that is not the skin is the defining feature of systemic mastocytosis. SM patients show some combination of the following characteristics: infiltration of tissue with mast cells clustered together; expression of receptors CD25 and/or CD2 on the mast cells; spindle shaped mast cells; presence of the CKIT D816V mutation; and baseline tryptase over 20 ng/ml. When a patient shows too many mast cells without having any of these markers, it is not called mastocytosis. It is called mast cell hyperplasia.
Consider the following two scenarios:
Let’s imagine that you are a house builder. For many years, you only build houses when people call your boss and say they need a house. After your boss gets the call, she calls you to tell you to build a house for these people in the location they have requested. Sometimes more people need houses than others, so at times you make more, and other times, you make less. You never build houses unless your boss tells you to and you are able to build them correctly due to having the correct time and resources. You may think that your boss is telling you to build too many houses sometimes but it is always because she is getting lots of requests from customers to build houses.
In this scenario, mast cells are house builders. They only make new mast cells when they receive appropriate signals from the body. Sometimes your body makes more mast cells, like to fight an infection or when you have an allergic response. But the mast cells ALWAYS wait for the correct signal from the body to make more cells. They do not decide to make too many cells on their own.
Now let’s imagine that after years of being a house builder, you wake up one day with a compulsion to see how fast you can build a house. Your boss calls you and says she needs one house, so you build that house and then you build four more at the same time. Instead of building carefully one at a time, you are building five houses at the same time. This means the houses are not built correctly. You call your boss to say you are done with the five houses and your boss gets mad. Where are we going to put these extra four houses? She decides to move those four houses to another town that doesn’t have too many houses yet. She tells you not to make too many houses again.
But you just cannot stop making houses. Making houses is the best! Who cares if there are little mistakes? People can still live in them safely. You wake up every day with a fervent need to build houses. Your friends and family are concerned about you and stage an intervention. You will not be moved. You are building tons of houses at once now. Your boss is calling you screaming at you to stop making houses because they are defective and she doesn’t have anywhere to put them. She has been sending them to places that already have too many houses so it is getting really crowded and people are complaining. You stop answering your boss’s calls. These people don’t understand the importance of building houses. No matter what anyone says to you, you will not stop making houses and they cannot make you stop.
In this scenario, the problem isn’t that the boss is telling the builder to make too many houses. The problem here is that the builder is ignoring all the signals to stop. This scenario represents systemic mastocytosis. The mast cells here are making too many mast cells for the wrong reasons and they don’t work right.
I want to be very clear about something – the fact that a person has a lot of mast cells per hpf but doesn’t have markers for SM does NOT mean that these people are not suffering. Regardless of how the mast cells ended up there in excessive populations, they will cause large scale inflammation and GI symptoms. Nor am I saying that phenomena like mastocytosis enterocolitis or allergic mastocytic enterocolitis are definitely not mast cell diseases – it is possible that the mast cells in those cases demonstrate markers we have not yet found or that there is an error in the cells that become mast cells. I am just describing the way these two categories are distinguished from one another at this time. It is not my intention to disenfranchise anyone. We are all united in the suckage that is GI symptoms as a result of mast cells.
How do you tell the difference between systemic mastocytosis and mast cell hyperplasia? That is the purpose of the SM diagnostic criteria. As I said before, you need to meet one major and one minor criterion, or three minor criteria, from the WHO Systemic mastocytosis criteria. If you meet some of the criteria, but not enough for SM, that is still evidence of a clonal, proliferative mast cell disease. This means that it is still evident that too many mast cells are being made despite signals to stop. The state of meeting some criteria for SM but not enough for an SM diagnosis is called monoclonal mast cell activation syndrome (MMAS). This topic will be covered in detail in a later post in this series.
Many diseases involve mast cells, including various cancers and autoimmune diseases, among others. So why aren’t they considered mast cell diseases like systemic mastocytosis and mast cell activation syndrome? These are not mast cell diseases because in these situations, mast cells are getting signals to make too many mast cells and to cause inflammation. They are the house builder when the boss is telling them to make more houses than usual, but the boss is doing that because customers need those houses. Mast cell diseases are the house builder that has a compulsion to build houses even when they aren’t needed and everyone is telling them to stop.
Remember this distinction when you are reviewing papers and pathology reports. The word mastocytosis is often used when they really mean mast cell hyperplasia. Mastocytosis in proper usage means too many mast cells because the mast cells are defective. Mast cell hyperplasia means too many mast cells because the mast cells are receiving inflammatory signals from elsewhere.