Multidisciplinary Challenges in Mastocytosis and How to Address with Personalized Medicine Approaches

Abstract

Mastocytosis is a hematopoietic neoplasm defined by abnormal expansion and focal accumulation of clonal tissue mast cells in various organ-systems. The disease exhibits a complex pathology and an equally complex clinical behavior. The classification of the World Health Organization (WHO) divides mastocytosis into cutaneous forms, systemic variants, and localized mast cell tumors. In >80% of patients with systemic mastocytosis (SM), a somatic point mutation in KIT at codon 816 is found. Whereas patients with indolent forms of the disease have a normal or near-normal life expectancy, patients with advanced mast cell neoplasms, including aggressive SM and mast cell leukemia, have a poor prognosis with short survival times. In a majority of these patients, multiple somatic mutations and/or an associated hematologic neoplasm, such as a myeloid leukemia, may be detected. Independent of the category of mastocytosis and the serum tryptase level, patients may suffer from mediator-related symptoms and/or osteopathy. Depending on the presence of co-morbidities, the symptomatology in such patients may be mild, severe or even life-threatening. Most relevant co-morbidities in such patients are IgE-dependent allergies, psychiatric, psychological or mental problems, and vitamin D deficiency. The diagnosis and management of mastocytosis is an emerging challenge in clinical practice and requires vast knowledge, a multidisciplinary approach, and personalized medicine procedures. In this article, the current knowledge about mastocytosis is reviewed with special emphasis on the multidisciplinary aspects of the disease and related challenges in daily practice.

Mast Cells: Fascinating but Still Elusive after 140 Years from Their Discovery

“…Mast cells and their mediators can be involved in several aspects of tumor initiation and growth [21,39,[69][70][71], presumably through the production of several angiogenic and lymphangiogenic factors [19,20,75]. Systemic mastocytosis is a clonal disease associated with a somatic gain-of-function KIT mutation [56,57,123]. Mast cells, strategically located in different sections of the human heart [51,52] and atherosclerotic plaque [32,33], are involved in different phases of atherosclerosis and myocardial infarction.…”

“…The authors also illustrate the different symptoms and associated co-morbidities of various forms of mastocytosis. Finally, they emphasize the multidisciplinary aspects of the disease and discuss related challenges in daily practice [57]. Another group of mastocytosis experts demonstrate the expression of programmed death ligand 1 (PD-L1) on mast cells from patients with mastocytosis [58].…”

KIT D816V and the cytokine storm in mastocytosis: production and role of interleukin-6

“…ast cell disorders (mastocytosis) are a hematologic neoplasm defined by abnormal expansion and dense accumulation of clonally altered mast cells in various organ systems. [1][2][3][4][5] The disease exhibits a complex pathology and an equally complex pattern of clinical presentations. [1][2][3][4][5] The classification of the World Health Organization (WHO) splits mast cell disorders into cutaneous entities, systemic variants, and localized mast cell tumors.…”

“…[1][2][3][4][5] The disease exhibits a complex pathology and an equally complex pattern of clinical presentations. [1][2][3][4][5] The classification of the World Health Organization (WHO) splits mast cell disorders into cutaneous entities, systemic variants, and localized mast cell tumors. [2][3][4][5] In more than 80% of all cases with systemic mastocytosis (SM), a somatic point mutation in KIT at codon 816 is detected.…”

“…[1][2][3][4][5] The classification of the World Health Organization (WHO) splits mast cell disorders into cutaneous entities, systemic variants, and localized mast cell tumors. [2][3][4][5] In more than 80% of all cases with systemic mastocytosis (SM), a somatic point mutation in KIT at codon 816 is detected. [3][4][5][6] Whereas patients with indolent forms of the disease have a normal or close-to-normal life expectancy, patients with advanced mast cell neoplasms, including aggressive SM (ASM) and mast cell leukemia (MCL), have an unfavorable prognosis with clearly reduced survival times.…”