Systemic Mastocytosis: Epidemiology and Diagnostic Criteria

Dan DeAngelo, MD, PhD: Hello, and welcome to this OncLive® Peer Exchange® discussion on systemic mastocytosis. My name is Dan DeAngelo from the Dana-Farber Cancer Center in Boston, Massachusetts. My clinical practice is focused on the treatment of patients with acute and chronic leukemias, as well as myeloproliferative disorders. Joining me in this discussion are my colleagues Dr Sa Wang, a hematopathologist from The University of Texas MD Anderson Cancer Center in Houston, Texas; Dr Prithviraj Bose, an expert in leukemia and myeloproliferative disorders, also from MD Anderson Cancer Center; and Dr Patricia Lugar, an expert in allergy and immunology from Duke Health in Durham, North Carolina. Today we’re going to discuss systemic mastocytosis. This is a challenging condition with multiple classifications and presentations. Also, as part of our discussion, our expert multidisciplinary panel will review 6 clinical cases to try to illustrate this important point, as well as aspects of optimal diagnosis and treatment for these patients. Let’s begin. First, I’d like to open it up, to try and tease out some of the epidemiology and some of the referring patterns that each of us has. This is a rare disease. Let me start with you, Dr Bose, in terms of how patients come to your clinical practice, who refers you, and what types of patients are these?

Prithviraj Bose, MD: What I’ve seen mostly is that they come to me from another hematologist. Usually, they have been picked up by a dermatologist who has biopsied the rash and sent them to a community hematologist, who then refers the patient to us. That’s what I’ve seen more than other patterns of reference.

Dan DeAngelo, MD, PhD: Dr Lugar, it’s supposed to be a different pattern for an allergist and immunologist. What about your practice?

Patricia Lugar, MD, MS: We certainly see patients with recurrent anaphylaxis. As part of the work-up, if the story fits with potentially some other symptoms that have been ongoing, we will usually screen for mast cell disorders. We do that quite a bit. The most common symptom besides recurrent anaphylaxis would be reactions to venom stings, like flying insects. When we see individuals who’ve had either profound allergic symptoms during the sting—anaphylaxis or cardiovascular symptoms, syncope, hard to resuscitate, multiple doses of epinephrine—or who’ve had maybe an episode of anaphylaxis that they can identify, such as a sting, or a similar episode that they can’t put their fingers on, those individuals will be screened. We pick up a number of patients based on that.

Dan DeAngelo, MD, PhD: By screen, do you mean checking the tryptase? Also, when would you check a bone marrow exam or refer to a hematologist to do that?

Patricia Lugar, MD, MS: Excellent question. The screening is the physical exam. We’re all trained to look for the telltale clinical symptoms, such as the urticaria pigmentosa or telangiectasia macularis eruptiva perstans, or TMEP. We do a skin exam, we take clinical history, and then we screen for serum tryptase. We don’t usually do urine histamine or prostaglandins at that point in time. We usually do screening tryptase. Even if the tryptase is not excessively over 12 or 11 or whatever the reference range—or over 20—if the patient has symptoms that have been persistent, such as flushing, or if we see signs of possible lesions consistent with cutaneous mastocytosis, then we might at that point do a c-KIT, looking for mutations D816V and c-KIT by peripheral blood. At that point, if we see signs and symptoms that the person has a mast cell disorder, based on the level of tryptase, we’d recommend a bone marrow biopsy. We do a lot of management locally before we refer. Certainly, that may change as we expand our therapeutics.

Dan DeAngelo, MD, PhD: Thank you. I work in a general hospital, so my referral pattern is a little different. I get referrals from allergy and immunology. Patients with recurrent anaphylaxis—mostly flying insects—will get referred if they meet those criteria that you nicely outline. But I get referrals from dermatology patients, who are seen in the dermatology clinic, and dermatology will say, “This is a rash. This is urticaria pigmentosa or the telangiectasia macularis eruptiva perstans.” They would also make a biopsy and refer a patient to allergy immunology: patients with irritable bowel syndrome who finally come to an urgent evaluation with a gastroenterologist refer in that way. Then just like Dr. Bose, I’ll see patients who are a tertiary referral from an outside hematologist. I’m seeing patients in all ways. But turning the baton over to you, Dr Wang, as a hematopathologist, what is important to you in terms of really defining a diagnosis of systemic mastocytosis?

Sa Wang, MD: I do mostly systematic…everything…in a myeloproliferative neoplasm. Also, SM [system mastocytosis] is 1 of the…in the bone now. For us, it’s easy; you guys only screen. You already have suspicion of SM, system mastocytosis. We know what we do. When we get a specimen, we’re going to automatically run the immunoassay, like a c-KIT and the tryptase and on the bone marrow biopsy. We also have psychometry assays, which look at mast cell proliferation. That’s 1 thing. It’s like a referral… Automatically, we’re going to all these tests. Usually, there’s no suspicion. The patient comes with myeloneoplasms, and then we identify no SM, in association with underlying MPS [myeloproliferative syndrome]/CMML [chronic myelomonocytic leukemia]. That’s something we initiate in the work-up.

Dan DeAngelo, MD, PhD: Thank you. One of the questions or pet peeves I’ve had is when patients get referred in, not with suspected systemic mastocytosis but a sample. For example, with liver dysfunction and a liver biopsy, where the pathologist may not be thinking about systemic mastocytosis or a colon or rectal or other GI [gastrointestinal] biopsy, maybe the referring physician, the gastroenterologist, in that circumstance did not specify to the pathologist. Also, under H&E [hematoxylin and eosin staining], sometimes these mast cells can be hard to elucidate. Is there something in these tissues, not bone marrow, that will help you try to move down the road to systemic mastocytosis to do this special stain you described?

Sa Wang, MD: You’re absolutely right. Mast cells can be very subtle, especially in the GI tract, where they can mimic a lot of things because the submucosa always has a lot of cells, such as stromal cells, like plasma cells. When plasma cells lose the cytoplasm, they can look like mast cells too. We just cannot afford to do mast cell work up for every GI biopsy. We have to have some suspicions. The GI pathologists have to know the typical presentation for mast cells. They have to consider the differential diagnosis to initiate the work-up. Another scenario is in the bone marrow; it’s the same thing. With bone marrow, sometimes you can have patchy fibrosis just not as sensitive. If you don’t do the markers, you may miss it.

Dan DeAngelo, MD, PhD: That’s an important point.

Transcript Edited for Clarity