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The Journal of Allergy and Clinical... Aug 2022Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology... (Review)
Review
Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma. In most patients with SM, somatic mutations in KIT are detected. Patients with indolent SM have a normal to near-normal life expectancy, whereas patients with advanced SM, including aggressive SM and MC leukemia, have a poor prognosis. In those with advanced SM, multiple somatic mutations and an associated hematologic neoplasm may be detected. Mediator-related symptoms can occur in any type of mastocytosis. Symptoms may be mild, severe, or even life-threatening. In patients with severe acute symptoms, an MC activation syndrome may be diagnosed. In these patients, relevant comorbidities include IgE-dependent and IgE-independent allergies. Management of patients with SM is an emerging challenge in daily practice and requires in-depth knowledge and a multidisciplinary and personalized approach with selection of appropriate procedures and interventions. In this article, we review the current knowledge on SM and MC activation syndrome, with emphasis on multidisciplinary aspects in diagnosis and patient-specific management. In addition, we provide a user's guide for application of markers, algorithms, prognostic scores, and treatments for use in daily practice.
Topics: Humans; Immunoglobulin E; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Proto-Oncogene Proteins c-kit; Tryptases
PubMed: 35342031
DOI: 10.1016/j.jaip.2022.03.007 -
Medicina (Kaunas, Lithuania) Oct 2021Mastocytosis is a rare hematological neoplasm characterized by the proliferation of abnormal clonal mast cells (MCs) in different cutaneous and extracutaneous organs.... (Review)
Review
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 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 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 . 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.
Topics: Humans; Leukemia, Mast-Cell; Mastocytosis, Systemic; Mutation; Precision Medicine; Proto-Oncogene Proteins c-kit; Tryptases
PubMed: 34833353
DOI: 10.3390/medicina57111135 -
Acta Medica Portuguesa Apr 2020Mastocytosis is characterized by the clonal expansion of morphological and immunophenotypically abnormal mast cells in different organs. The skin is the most frequently... (Review)
Review
INTRODUCTION
Mastocytosis is characterized by the clonal expansion of morphological and immunophenotypically abnormal mast cells in different organs. The skin is the most frequently affected tissue. Virtually all children and more than 80% of adult patients with mastocytosis show cutaneous lesions.
MATERIAL AND METHODS
The present article describes the symptoms and signs in cutaneous mastocytosis, based on the review of recently published international consensus guidelines.
DISCUSSION
According to the 2016 World Health Organization classification, mastocytosis can be divided in cutaneous mastocytosis, systemic mastocytosis and mast cell sarcoma. Cutaneous mastocytosis is subclassified in three subtypes: maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis and cutaneous astocytoma. Telangiectasia macularis eruptiva perstans is no longer considered a distinct entity.
CONCLUSION
Based on the age of onset, cutaneous manifestations of mastocytosis can be variable. The classification of cutaneous mastocytosis has recently been updated. Typically, in patients with childhood-onset mastocytosis, the disease occurs as cutaneous mastocytosis and shows spontaneous resolution around puberty. In contrast, adult patients, despite having also cutaneous lesions, often show systemic involvement and the course of the disease is usually chronic.
Topics: Adolescent; Adult; Age of Onset; Child; Humans; Mastocytosis; Mastocytosis, Cutaneous; Symptom Assessment
PubMed: 32238242
DOI: 10.20344/amp.12189 -
The Journal of Allergy and Clinical... Jun 2023In 2002, the European Competence Network on Mastocytosis (ECNM) was launched as a multidisciplinary collaborative initiative to increase the awareness and to improve... (Review)
Review
In 2002, the European Competence Network on Mastocytosis (ECNM) was launched as a multidisciplinary collaborative initiative to increase the awareness and to improve diagnosis and management of patients with mast cell (MC) disorders. The ECNM consists of a net of specialized centers, expert physicians, and scientists who dedicate their work to MC diseases. One essential aim of the ECNM is to timely distribute all available information about the disease to patients, doctors, and scientists. In the past 20 years, the ECNM has expanded substantially and contributed successfully to the development of new diagnostic concepts, and to the classification, prognostication, and treatments of patients with mastocytosis and MC activation disorders. The ECNM also organized annual meetings and several working conferences, thereby supporting the development of the World Health Organization classification between 2002 and 2022. In addition, the ECNM established a robust and rapidly expanding patient registry and supported the development of new prognostic scoring systems and new treatment approaches. In all projects, ECNM representatives collaborated closely with their U.S. colleagues, various patient organizations, and other scientific networks. Finally, ECNM members have started several collaborations with industrial partners, leading to the preclinical development and clinical testing of KIT-targeting drugs in systemic mastocytosis, and some of these drugs received licensing approval in recent years. All these networking activities and collaborations have strengthened the ECNM and supported our efforts to increase awareness of MC disorders and to improve diagnosis, prognostication, and therapy in patients.
Topics: Humans; Mastocytosis; Mastocytosis, Systemic; Forecasting; Mast Cells
PubMed: 36868470
DOI: 10.1016/j.jaip.2023.02.021 -
Clinical Reviews in Allergy & Immunology Jun 2018Mast cells (MCs) are physiologically activated by binding of stem cell factor (SCF) to the extracellular domains of the Kit receptor. This binding increases the... (Review)
Review
Mast cells (MCs) are physiologically activated by binding of stem cell factor (SCF) to the extracellular domains of the Kit receptor. This binding increases the proliferation and prolongs the survival of normal mature MCs, as well as intensifies the release of mediators. In mastocytosis, somatic mutations of the coding Kit gene cause autocrine dysregulation and lead to constitutive KIT activation even in the absence of its ligand SCF. Clinical symptoms are caused by MC-mediator release and/or infiltration of MCs into tissues. Aberrant KIT activation may result in increased production of MCs in the skin and extracutaneous organs. Depending on the affected organ(s), the disease can be divided into cutaneous mastocytosis (CM), systemic mastocytosis (SM), and localized MC tumors. The updated classification of WHO discriminates between several distinct subvariants of CM and SM. While the prognosis in CM and indolent SM (ISM) is excellent with (almost) normal life expectancy, the prognosis in aggressive SM (ASM) and MC leukemia (MCL) is dismal. The symptoms may comprise urticaria, angioedema, flush, pruritus, abdominal pain, diarrhea, hypotension, syncope, and musculoskeletal pain and are the results of MC infiltration and mediator release into target organs, i.e., the skin, gastrointestinal tract, liver, spleen, lymph nodes, and bone marrow. Mastocytosis differs from a lot of other hematological disorders because its pathology is not only based on the lack of normal function of a specific pathway or of a specific cell type but additionally is a proliferative disease. Currently available treatments of mastocytosis include symptomatic, antimediator and cytoreductive targeted therapies.
Topics: Animals; Humans; Mast Cells; Mastocytosis; Mutation; Prognosis; Proto-Oncogene Proteins c-kit; Skin; Stem Cell Factor
PubMed: 28725969
DOI: 10.1007/s12016-017-8619-2 -
Immunology and Allergy Clinics of North... Aug 2018Understanding experiences, perceptions, and perspectives of patients with a mast cell disorder (MCD), including cutaneous mastocytosis, systemic mastocytosis, mast cell... (Review)
Review
Understanding experiences, perceptions, and perspectives of patients with a mast cell disorder (MCD), including cutaneous mastocytosis, systemic mastocytosis, mast cell activation syndromes, and hereditary α-tryptasemia, is an important aspect of successful care, treatment, and informed development of novel therapies. This article reviews existing studies and presents new data on MCD patient perceptions regarding medical care, symptoms, allergies/sensitivities, triggers, future health/disease progression, treatment, impact on daily living, quality of life, support needs, and concerns regarding possible familial disease. Discussion includes aspects affecting the MCD community that require further consideration and development.
Topics: Emotions; Government Regulation; Humans; Mast Cells; Mastocytosis; Patient Preference; Patient Reported Outcome Measures; Perception; Physician-Patient Relations; Quality of Life; United States; United States Food and Drug Administration
PubMed: 30007467
DOI: 10.1016/j.iac.2018.04.006 -
Haematologica Jan 2020
Topics: Humans; Interleukin-6; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Oncogenes
PubMed: 31894094
DOI: 10.3324/haematol.2019.234864 -
Hematology. American Society of... Dec 2022The historically poor prognosis of patients with advanced systemic mastocytosis (AdvSM) and primary eosinophilic neoplasms has shifted to increasingly favorable outcomes... (Review)
Review
The historically poor prognosis of patients with advanced systemic mastocytosis (AdvSM) and primary eosinophilic neoplasms has shifted to increasingly favorable outcomes with the discovery of druggable targets. The multikinase/KIT inhibitor midostaurin and the highly selective KIT D816V inhibitor avapritinib can elicit marked improvements in measures of mast cell (MC) burden as well as reversion of MC-mediated organ damage (C-findings) and disease symptoms. With avapritinib, the achievement of molecular remission of KIT D816V and improved survival compared with historical therapy suggests a potential to affect disease natural history. BLU-263 and bezuclastinib are KIT D816V inhibitors currently being tested in trials of AdvSM. In the new World Health Organization and International Consensus Classifications, the category of "myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions" is inclusive of rearrangements involving PDGFRA, PDGFRB, FGFR1, JAK2, FLT3, and ETV6::ABL1. While the successful outcomes with imatinib in FIP1L1::PDGFRA-positive cases and PDGFRB-rearranged neoplasms have become the "poster children" of these disorders, the responses of the other TK-driven neoplasms to small-molecule inhibitors are more variable. The selective FGFR inhibitor pemigatinib, approved in August 2022, is a promising therapy in aggressive FGFR1-driven diseases and highlights the role of such agents in bridging patients to allogeneic transplantation. This review summarizes the data for these approved and investigational agents and discusses open questions and future priorities regarding the management of these rare diseases.
Topics: Child; Humans; Mastocytosis, Systemic; Protein Kinase Inhibitors; Myeloproliferative Disorders; Imatinib Mesylate; Eosinophilia; Proto-Oncogene Proteins c-kit; Mastocytosis
PubMed: 36485158
DOI: 10.1182/hematology.2022000368 -
British Journal of Haematology Jan 2018Rapid advances in the understanding of the molecular biology, data from translational and clinical trials, and retrospective analyses has influenced the diagnosis and... (Review)
Review
Rapid advances in the understanding of the molecular biology, data from translational and clinical trials, and retrospective analyses has influenced the diagnosis and treatment of systemic mastocytosis (SM). Many options have existed for the symptomatic management of SM patients, but recent evolution in regards to the molecular underpinnings of this disease and our ability to distinguish clonal mastocytosis from mast cell activation syndrome has changed our treatment paradigm and opened new opportunities for understanding genetic risk, transformation to mast cell leukaemia, and treatment choices. Key to this change has been the discovery of the KIT mutation and the use of next generation sequencing to evaluate for co-existing molecular mutations that may define the disease course. Careful diagnosis, judicious symptom management and close surveillance of those who may have yet undiagnosed disease is paramount in providing optimal management. In this article, we review the diagnosis and provide a paradigm for the management of SM patients.
Topics: Adult; Combined Modality Therapy; Diagnosis, Differential; Disease Progression; Genetic Predisposition to Disease; Hematopoietic Stem Cell Transplantation; Humans; Mastocytosis, Systemic; Mutation; Prognosis
PubMed: 29048112
DOI: 10.1111/bjh.14967 -
International Journal of Molecular... Jun 2023Mastocytosis is a heterogeneous group of diseases associated with excessive proliferation and accumulation of mast cells in different organs. Recent studies have... (Review)
Review
Mastocytosis is a heterogeneous group of diseases associated with excessive proliferation and accumulation of mast cells in different organs. Recent studies have demonstrated that patients suffering from mastocytosis face an increased risk of melanoma and non-melanoma skin cancer. The cause of this has not yet been clearly identified. In the literature, the potential influence of several factors has been suggested, including genetic background, the role of cytokines produced by mast cells, iatrogenic and hormonal factors. The article summarizes the current state of knowledge regarding the epidemiology, pathogenesis, diagnosis, and management of skin neoplasia in mastocytosis patients.
Topics: Humans; Mastocytosis; Mast Cells; Skin Neoplasms; Cytokines; Melanoma; Skin
PubMed: 37372988
DOI: 10.3390/ijms24129840