Systemic Mastocytosis: Advances in Diagnosis and Current Management

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Mastocytosis is a rare hematologic disorder characterized by neoplastic mast cell proliferation.
• Cutaneous mastocytosis (CM) involves isolated skin lesions, while systemic mastocytosis (SM) affects multiple organs, including bone marrow, skin, liver, and spleen.
• SM can be associated with other hematologic neoplasms (SM-AHN), such as myelodysplastic syndrome or leukemia.

Purpose of the Study:

• To describe the characteristics of mastocytosis, including its subtypes and genetic underpinnings.
• To outline the clinical presentation and treatment goals for different forms of SM.
• To highlight the role of genetic mutations in SM pathogenesis and patient management.

Main Methods:

• Review of mastocytosis classification, including cutaneous and systemic forms.
• Analysis of the genetic landscape of SM, focusing on KIT mutations and other molecular aberrations.
• Description of clinical presentations and treatment strategies for indolent SM and SM-associated hematologic neoplasms.

Main Results:

• Bone marrow involvement is a defining feature of all SM subtypes.
• The KIT gene mutation is the primary genetic hallmark of SM.
• Mutations in TET2, SRSF2, ASXL1, CBL, RUNX1, and RAS are frequently observed in SM-AHN.
• Clinical presentation varies from indolent to advanced, influenced by mast cell burden and genetic profile.

Conclusions:

• Mastocytosis management requires understanding its diverse subtypes and genetic basis.
• Treatment for indolent SM focuses on symptom control and mast cell reduction.
• For SM-AHN, treatment prioritizes the associated hematologic neoplasm, with stem cell transplantation as a key option for eligible patients.