Systemic mastocytosis (SM) can present in many different ways, with varying symptoms, prognoses and treatment plans. To capture all of these differences, the World Health Organization (WHO) developed a classification system describing each of the six SM subtypes. Understanding these different classifications can be a lot to wrap your head around, but breaking down the basics of each subtype can help make these guidelines feel less intimidating.
Why do we need the WHO classification system?
You may be wondering: What is the purpose of having all of these different SM classifications and subclassifications?
Read more about SM testing and diagnosis
The WHO guidelines provide a standardized framework that allows doctors around the world to use the same or similar approaches to diagnose and treat patients. Knowing which subtype of SM you have allows you to be more informed about what the diagnosis might mean for you.
That being said, no set of guidelines is perfect. Even within each of these six subtypes, there can be a lot of variability in symptom burden and prognosis. Each case should be managed on an individualized basis, using the guidelines as just that — a guide for making treatment decisions that will help you manage your symptoms.
What separates each subtype?
The WHO classification system includes a list of criteria that act as benchmarks for diagnosing the specific subtype of SM. These include a list of “B findings” (different signs that reflect disease burden) and “C findings” (signs that indicate organ damage, and more advanced disease).
As part of your diagnosis, your care team compares your results from various tests to these benchmarks to determine which SM subtype you have. For example, an enlarged liver with signs of abnormal function is one of the findings that indicates an advanced SM subtype; meeting this criteria rules out the nonadvanced SM subtypes.
What does the WHO list as the systemic mastocytosis subtypes?
According to the WHO guidelines, SM can be categorized as advanced or nonadvanced, and then further broken down into six distinct subtypes.
Nonadvanced systemic mastocytosis subtypes
Nonadvanced SM usually involves a better prognosis than advanced SM. The three subtypes of nonadvanced SM are:
- Bone marrow mastocytosis (BMM)
- Indolent systemic mastocytosis (ISM)
- Smoldering systemic mastocytosis (SSM)
As its name suggests, patients with BMM have high levels of mast cells in the bone marrow. They usually do not experience any skin symptoms, which differentiates BMM from other forms of SM. Patients can still experience severe symptoms, though. Another classification system, the International Consensus Classification, considers BMM a variant of ISM.
Individuals with ISM don’t usually have organ failure or impairment, although there may be evidence of disease in several organs.
In general, patients with SSM have more severe symptoms and a poorer prognosis than those with ISM, making it the most severe subtype of nonadvanced SM.
Advanced systemic mastocytosis subtypes
The WHO guidelines include three subtypes of advanced SM:
- Aggressive systemic mastocytosis (ASM)
- Systemic mastocytosis with an associated hematological neoplasm (SM-AHN)
- Mast cell leukemia (MCL)
Patients with ASM usually have some combination of skeletal, gastrointestinal, liver or kidney involvement. Some individuals may only experience symptoms in one of these areas, while others have symptoms in multiple.
Individuals with SM-AHN have both SM and a blood cancer. Most patients have a myeloid neoplasm, which affects the bone marrow, and fewer people have lymphoma, myeloma or chronic lymphocytic leukemia.
MCL is the most severe type of SM with the worst prognosis. These patients have very high levels of mast cells in the bone marrow or blood. Patients with chronic MCL usually don’t have organ damage, giving them a slightly better prognosis than those with acute MCL.
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