Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future

Abstract

Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis and mast cell leukemia. The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis. In addition, new treatment options are available for patients with advanced systemic mastocytosis, including allogeneic hematopoietic stem cell transplantation and multikinase inhibitors directed against KIT D816V and other key signaling molecules. Our current article provides an overview of recent advances in the field of mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic mastocytosis. Cancer Res; 77(6); 1261-70. ©2017 AACR.

Figure 1

Overview of KIT mutations described in patients with mastocytosis Mutations described primarily in pediatric cases with cutaneous mastocytosis (CM) are depicted in green color and those found preferentially in adults with systemic mastocytosis (SM) in blue color. The most frequently detected KIT mutations are marked with dark colors (CM: dark-green; SM: dark-blue). In addition, the frequency of mutations is defined by the following score: ±: found in less than 1% of the pediatric or adult patients; +: found in 1 to 5% of pediatric patients; ++: found in 5 to 20% of pediatric patients; +++ (KIT D816V): mutation found in around 30% of pediatric patients and in > 80% of all adult patients. Abbreviations: ABD: ATP-binding domain; Del: deletion; ECD: Extracellular domain; Ins: Insertion; ITD: Internal tandem duplication; JMD: Juxtamembrane domain; KI: Kinase insert; PTD: Phosphotransferase domain; TMD: Transmembrane domain. The asterisk (*) denotes KIT mutations that have also been described in other neoplasms such as gastro-intestinal stromal tumors (GIST), acute myeloid leukemia (AML), lymphomas, or seminomas. These neoplasms may also present with other KIT mutants not yet described in mastocytosis (not shown in this figure).