Aggressive systemic mastocytosis (SM) can present with nonspecific symptoms like fever that complicate diagnosis, particularly in older adults, as illustrated by a recently published case report in Cureus.
SM is classified by the World Health Organization into various subtypes, ranging from indolent to aggressive forms. Aggressive SM involves extensive organ infiltration and dysfunction and represents only 2%-6% of SM cases. Its nonspecific manifestations — such as weight loss, fever and bone abnormalities — especially in older adults, often delay diagnosis, as these symptoms mimic more common diseases like metastatic cancer or infections.
The case involved an 83-year-old man whose recurrent fever, low blood cell counts (cytopenias) and hardened (sclerotic) bone lesions led to significant diagnostic challenges.
The patient initially presented with mild anemia and later experienced recurrent hospital admissions for fever, shortness of breath and weight loss. Imaging studies revealed sclerotic rib lesions and an enlarged liver and spleen (hepatosplenomegaly). These findings raised concerns for cancer. However, extensive microbiological, autoimmune and malignancy workups were inconclusive.
Read more about SM testing and diagnosis
A bone marrow biopsy, which showed dense mast cell infiltration expressing CD117, CD25 and CD2, was the turning point that led to SM being considered as a possible diagnosis. Genetic testing confirmed the KIT D816V mutation, and serum tryptase levels were markedly elevated at 810 µg/L. These findings fulfilled WHO criteria for an ASM diagnosis.
Following diagnosis, the patient began treatment with midostaurin, a multikinase inhibitor approved for advanced systemic mastocytosis. Despite initial gastrointestinal side effects, the patient showed rapid clinical improvement, including resolution of fever and improved quality of life. Laboratory markers — such as tryptase, liver enzymes and hemoglobin levels — steadily improved over 12 months of therapy.
The case underscores the importance of considering rare entities like ASM in complex clinical scenarios and highlights the critical role of multidisciplinary collaboration in arriving at a timely diagnosis.
“Despite significant progress in understanding its immunological mechanisms and pathophysiology, SM remains a complex disorder that’s challenging to diagnose, especially in those without skin involvement or familiar symptoms of MC activation,” the authors noted.
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