A recent case report published in Cancer Nexus describes an individual with KIT mutation-negative indolent systemic mastocytosis (ISM) that progressed to smoldering SMSmoldering SM A subtype of nonadvanced SM, with a higher mast cell burden than the indolent subtype. Smoldering SM has a higher likelihood of progressing to an advanced form. (SSM), highlighting that progression can still occur even when the KIT mutation isn’t found.
The individual, a woman in her early 30s, originally presented in 2018 with a persistent rash, along with hot flashes that were disrupting her sleep quality. Topical treatments and antihistaminesAntihistamines Medications that block the effects of histamine, the chemical found in mast cells that is responsible for many of the symptoms of SM, as well as many allergic reactions. did not resolve her symptoms. A skin biopsy showed signs of mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults., which was confirmed with a bone marrow biopsyBone marrow biopsy A procedure to collect a sample of bone marrow using a needle. Often used to examine the characteristics of mast cells and diagnose SM.. Her baseline serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. level was 29.8 ng/mL, meeting one of the minor criteria for SM.
The treatment plan consisted of an epinephrineEpinephrine Also called adrenaline, this hormone is used in emergency situations to reverse symptoms during a severe allergic reaction (anaphylaxis). auto-injector for severe reactions, along with montelukast, ketotifen, cromolyn sodium and ondansetron. Even with treatment, though, she experienced several episodes of anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis.. With time, she began to develop progressive gastrointestinal discomfort, musculoskeletal symptoms and fatigue.
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Blood testing showed an increase in serum tryptase level from 46.2 ng/mL to 88.5 ng/mL. Moreover, repeat bone marrow biopsy demonstrated 40% mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. infiltration, compared with 5% to 10% in the original biopsy.
Computed tomography imaging revealed swelling in the lymph nodes; together with rising tryptase levels and mast cell burden, the woman met the World Health Organization criteria for SSM.
Initially, the patient was prescribed omalizumab to manage symptoms. However, she continued to experience episodes of severe hypersensitivity, leading to discontinuation. Next, she initiated imatinib, a tyrosine kinase inhibitorTyrosine kinase inhibitor Targeted therapies designed to block the KIT D816V mutation that drives most cases of SM. Includes avapritinib, midostaurin and imatinib. which has been successful in patients without the KIT D816V mutation.
Over the next four months, the individual experienced notable improvements in symptoms including hot flashes, diarrhea and cold intolerance, as well as stabilization of skin symptoms. Her tryptase levels also decreased to 75.2 ng/mL.
Although the patient did not meet the formal criteria for complete or partial remission, her improvement in symptoms highlights the potential of imatinib in patients who react poorly to other treatment options and do not harbor the KIT D816V mutation.
“Nonadvanced classification does not equate to minimal clinical impact,” the authors concluded. “Greater awareness of mutation‐negative progression may help refine precision‐based management strategies in systemic mastocytosis.”
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