Mast cell tumors are a rare group of conditions characterized by the uncontrolled growth and accumulation of mast cells. These specialized immune cells originate in the bone marrow and are distributed throughout the body’s connective tissues. Normally, they release potent chemical mediators like histamine in response to injury or allergens. When mast cells multiply abnormally, they form localized growths or infiltrate various organs, leading to a complex array of symptoms. This spectrum of diseases caused by abnormal mast cell proliferation is often referred to as mastocytosis.
What Mast Cell Tumors Are
Mast cell tumors are broadly classified based on where the abnormal cells accumulate: cutaneous mastocytosis (CM) or systemic mastocytosis (SM).
Cutaneous Mastocytosis (CM)
CM is the most common form, especially in children, where mast cells are largely confined to the skin. This typically presents as localized lesions or nodules. Even when localized, these cells are still capable of releasing their inflammatory contents.
Systemic Mastocytosis (SM)
SM is generally seen in adults and involves the accumulation of mast cells in internal organs, such as the bone marrow, spleen, liver, and gastrointestinal tract. The bone marrow is nearly always affected in systemic disease. SM is further subdivided into categories ranging from indolent (slow-growing) to aggressive forms, with the prognosis varying widely.
The underlying cause is frequently a genetic change, most commonly a mutation in the KIT gene. This gene provides instructions for a protein receptor found on the mast cell surface. A mutation often causes this receptor to be constantly “turned on,” stimulating continuous cell growth. In over 80% of adult systemic mastocytosis cases, the specific change is the D816V point mutation, which drives the proliferation of the neoplastic mast cells.
Recognizing Symptoms and Diagnosis
The symptoms stem from both the physical accumulation of cells and the inappropriate release of chemical mediators. Cutaneous lesions often appear as pigmented, reddish-brown spots or nodules on the skin. A characteristic sign, Darier’s sign, occurs when rubbing a skin lesion causes it to become red, swollen, and itchy due to the sudden local release of histamine.
The systemic release of mediators affects multiple body systems, leading to symptoms like flushing, itching, rapid heartbeat, and episodes of low blood pressure or fainting. Gastrointestinal issues, such as diarrhea, abdominal pain, and peptic ulcers, can also occur because histamine stimulates stomach acid production.
For diagnosis, a skin biopsy of a suspected lesion is performed to confirm the presence and accumulation of mast cells.
Diagnosing Systemic Disease
Confirming systemic disease requires a bone marrow aspiration and biopsy, as the bone marrow is the primary site of involvement. Blood tests measure the level of serum tryptase, an enzyme specifically released by mast cells. Significantly elevated baseline tryptase levels strongly suggest systemic involvement. Genetic testing is also used to detect the common KIT D816V mutation in bone marrow cells.
Treatment Approaches
Treatment strategies depend on the classification and severity of the disease, aiming to reduce abnormal cells and manage symptoms caused by mediator release. Localized cutaneous mastocytomas may only require simple surgical excision to completely remove the tumor.
For patients with indolent systemic mastocytosis, the primary focus is supportive care to block the effects of released mediators. This typically involves a combination of antihistamines to manage itching and flushing, and proton pump inhibitors to control excessive stomach acid production and prevent ulcers.
Patients with advanced systemic forms, such as aggressive systemic mastocytosis or mast cell leukemia, require therapies that actively reduce the mast cell burden. Targeted therapies focus on inhibiting the constant signaling from the mutated KIT receptor.
Drugs like midostaurin or avapritinib are targeted kinase inhibitors approved for advanced systemic mastocytosis, as they block the activity of the D816V mutation. For patients who do not have the D816V mutation, other tyrosine kinase inhibitors like imatinib may be effective. In extremely aggressive cases, conventional chemotherapy or allogeneic stem cell transplantation may be considered to replace the diseased bone marrow.
Long-Term Monitoring and Prognosis
The long-term outlook varies significantly depending on the specific diagnosis. Most children with cutaneous mastocytosis have a favorable prognosis, and the lesions often diminish or disappear entirely by puberty. Adults with indolent systemic mastocytosis typically maintain a normal life expectancy, as the condition is manageable with supportive care.
The prognosis for advanced systemic mastocytosis, including aggressive forms and mast cell leukemia, is less favorable. These patients require continuous, intensive management. Long-term monitoring is necessary for all patients to watch for signs of progression or recurrence. Regular blood tests tracking serum tryptase levels are a standard part of follow-up care, serving as a reliable indicator of the overall mast cell burden in the body.