Division of Hematology, Department of Translation Medicine, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, Via Solaroli 17, 28100 Novara, Italy
Andrea Patriarca
Division of Hematology, Department of Translation Medicine, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, Via Solaroli 17, 28100 Novara, Italy
Annalisa Andorno
Division of Pathology, Department of Health Sciences, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy
Abdurraouf Mokhtar Mahmoud
Division of Hematology, Department of Translation Medicine, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, Via Solaroli 17, 28100 Novara, Italy
Alessandra Gennari
Division of Oncology, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy
Renzo Boldorini
Division of Pathology, Department of Health Sciences, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy
Gianluca Gaidano
Division of Hematology, Department of Translation Medicine, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, Via Solaroli 17, 28100 Novara, Italy
Elena Crisà
Division of Hematology, Department of Translation Medicine, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, Via Solaroli 17, 28100 Novara, Italy
Mastocytosis is a rare hematological neoplasm characterized by the proliferation of abnormal clonal mast cells (MCs) in different cutaneous and extracutaneous organs. Its diagnosis is based on well-defined major and minor criteria, including the pathognomonic dense infiltrate of MCs detected in bone marrow (BM), elevated serum tryptase level, abnormal MCs CD25 expression, and the identification of KIT D816V mutation. The World Health Organization (WHO) classification subdivides mastocytosis into a cutaneous form (CM) and five systemic variants (SM), namely indolent/smoldering (ISM/SSM) and advanced SM (AdvSM) including aggressive SM (ASM), SM associated to hematological neoplasms (SM-AHN), and mast cell leukemia (MCL). More than 80% of patients with SM carry a somatic point mutation of KIT at codon 816, which may be targeted by kinase inhibitors. The presence of additional somatic mutations detected by next generation sequencing analysis may impact prognosis and drive treatment strategy, which ranges from symptomatic drugs in indolent forms to kinase-inhibitors active on KIT. Allogeneic stem cell transplant (SCT) may be considered in selected SM cases. Here, we review the clinical, diagnostic, and therapeutic issues of SM, with special emphasis on the translational implications of SM genetics for a precision medicine approach in clinical practice.