Systemic mastocytosis (SM) is a rare clonal mast cell disease characterized by heterogeneous clinical presentations and molecular features that vary across different regions; however, data from Central-Eastern Europe remain limited. This study aimed to describe the demographic, clinical, laboratory, and molecular characteristics of Romanian adults diagnosed with SM and followed at the national reference center for mast cell disorders in Bucharest, while also exploring real-world management patterns and outcomes. We conducted a retrospective observational study including 162 adult patients evaluated between January 2006 and March 2025 who met the 2022 World Health Organization criteria for SM. Data extracted from electronic medical records included WHO subtype, KIT mutation status, serum tryptase levels, organ involvement, treatment history, and survival outcomes. A descriptive statistical approach was used, with continuous variables expressed as medians and interquartile ranges, and categorical variables as counts and percentages. A subset of eight patients underwent bone marrow flow cytometry immunophenotyping to assess the diagnostic contribution of CD2 and CD25. Among the entire cohort, indolent SM was the most frequent form (53.1%), followed by cutaneous mastocytosis (17.3%), smoldering SM (5.6%), aggressive SM (3.7%), and SM with associated hematologic neoplasm (8%). The KIT D816V mutation was detected in 43% of tested individuals, and the median baseline serum tryptase was 20.55 μg/L. Common organ-related findings included osteoporosis (17.9%), osteopenia (21.7%), cutaneous lesions (29%), and hepatomegaly (4%). First-line symptomatic therapy (H1/H2 antihistamines ± montelukast) was administered to 77% of patients, while four patients with advanced disease received midostaurin treatment. Immunophenotyping confirmed aberrant expression of CD2 and CD25 in all eight analyzed cases. This first national series from Romania underscores the predominance of indolent SM and the clinical burden of organ involvement, reinforcing the need for early diagnosis and personalized, risk-adapted therapeutic approaches.

Systemic mastocytosis is a rare disease which is being better recognized and managed. While the vast majority of patients have indolent disease with variable symptom burden, a small proportion evolve or present with aggressive disease. This may be due to increases in mast cell burden (leukemic, associated with tumour masses) or more commonly due to the presence of an additional hematologic neoplasm (SM-AHN). These patients with advanced systemic mastocytosis have poor outcome; however, recent advances in diagnosis, molecular genetics and treatment have changed the prognostic landscape for this group of patients. In this review we address the most topical questions related to diagnostics, classification, new disease entities, treatment and multiparameter prognostic scoring systems.