A new case report published in the Annals of Medicine & Surgery describes an 86-year-old man who developed aleukemic mast cell leukemiaMast cell leukemia The most severe subtype of SM, caused by the rapid buildup of immature mast cells in the bone marrow and blood. Mast cell leukemia accounts for less than 5% of SM cases and has a poor prognosis. (MCL), alongside a complex pattern of genetic alterations. Researchers say the case highlights the diagnostic challenges of this rare and aggressive form of systemic mastocytosis (SM).
The report details a patient with a history of paranasal sinus diffuse large B-cell lymphoma, which had been in remission since 2017 following treatment. He also had prostate cancer that was treated in 2019.
The man later presented with low red blood cell, white blood cell and platelet levels (called acute pancytopenia), which initially raised concern that his lymphoma had returned. But further testing pointed to MCL. His 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 greater than 11,999 ng/mL, and a bone marrow aspirate showed that 20% of cells were pleomorphic mast cells. The mast cells were positive for CD117, weakly positive for CD25 and negative for CD2. These findings supported a diagnosis of aleukemic MCL.
Sign up here to get the latest news, perspectives, and information about SM sent directly to your inbox. Registration is free and only takes a minute.
The case was complicated by concerns about a possible associated myeloid neoplasm (blood cancer). The researchers could not formally confirm chronic myelomonocytic leukemia because monocyte differential data were unavailable. SM with an associated hematologic neoplasm remained an alternative classification.
Next-generation sequencing (NGS) — a genetic testing method that quickly analyzes large amounts of DNA — revealed several disease-causing genetic alterations, including changes affecting TP53, RB1, DAXX, ASXL1, TET2 and SRSF2. Testing also identified a rare KIT p.D419del mutation, while the more common KIT D816V mutation was not detected. However, the researchers said a very low-level D816V mutation could still have been present, since NGS doesn’t always catch mutations when they are in very small amounts.
What is a KIT gene mutationKIT gene mutation Most SM cases are caused by the KIT D816V mutation. The KIT gene codes for a type of protein called a receptor tyrosine kinase, which signals mast cells to grow, divide and move.?
SM is usually caused by a sporadic mutation in the KIT gene, which codes for a protein called CD117 transmembrane tyrosine kinase. The protein is involved in the growth, survival and migration of mast cells. The most common KIT mutation associated with SM is the D816V mutation, which results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain.
The researchers considered the MCL potentially therapy-related, although they emphasized that this could not be confirmed.
The man declined inpatient treatment with midostaurin. His condition subsequently deteriorated rapidly, and he died two weeks later.
The researchers noted that the case highlights the importance of thorough genetic testing as part of diagnosis. “The identification of a rare KIT p.D419del extracellular-domain mutation in the absence of detectable D816V highlights the importance of comprehensive NGS profiling and the use of sensitive assays to exclude low-VAF D816V, given its therapeutic implications,” they said.
Learn more about MCL: “Subtypes explained: What is mast cell leukemia?”
