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Actas Dermo-sifiliograficas 2016Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in different organs. The organ most often... (Review)
Review
Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in different organs. The organ most often affected is the skin. The World Health Organization classifies cutaneous mastocytosis into mastocytoma, maculopapular cutaneous mastocytosis, and diffuse mastocytosis. The systemic variants in this classification are as follows: indolent systemic mastocytosis (SM), aggressive SM, SM with an associated clonal hematological non-mast cell lineage disease, mast cell leukemia, mast cell sarcoma, and extracutaneous mastocytoma. The two latest systemic variants are rare. Although the course of disease is unpredictable in children, lesions generally resolve by early adulthood. In adults, however, the disease tends to persist. The goal of treatment should be to control clinical manifestations caused by the release of mast cell mediators and, in more aggressive forms of the disease, to reduce mast cell burden.
Topics: Humans; Leukemia, Mast-Cell; Mast Cells; Mast-Cell Sarcoma; Mastocytosis; Mastocytosis, Cutaneous; Mastocytosis, Systemic; Prognosis
PubMed: 26525106
DOI: 10.1016/j.ad.2015.09.009 -
World Journal of Gastroenterology Aug 2022Mastocytosis is a rare and heterogeneous disease characterized by various clinical and biological features that affect different prognoses and treatments. The disease is... (Review)
Review
Mastocytosis is a rare and heterogeneous disease characterized by various clinical and biological features that affect different prognoses and treatments. The disease is usually divided into 2 principal categories: cutaneous and systemic disease (SM). Clinical features can be related to mast cell (MC) mediator release or pathological MC infiltration. SM is a disease often hard to identify, and the diagnosis is based on clinical, biological, histological, and molecular criteria with different specialists involved in the patient's clinical work-up. Among all manifestations of the disease, gastrointestinal (GI) symptoms are common, being present in 14%-85% of patients, and can significantly impair the quality of life. Here we review the data regarding GI involvement in SM, in terms of clinical presentations, histological and endoscopic features, the pathogenesis of GI symptoms, and their treatment.
Topics: Gastroenterologists; Gastrointestinal Diseases; Humans; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Quality of Life
PubMed: 36157547
DOI: 10.3748/wjg.v28.i29.3767 -
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 -
International Journal of Molecular... Mar 2021Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline... (Review)
Review
Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline mutations in the proto-oncogene are detected in most patients. Cutaneous mastocytosis is the most common form of the disease in children. In the majority of cases, skin lesions regress spontaneously around puberty. However, in few patients, mastocytosis is not a self-limiting disease, but persists into adulthood and can show signs of systemic involvement, especially when skin lesions are small-sized and monomorphic. Children with mastocytosis often suffer from mast cell mediator-related symptoms. Severe hypersensitivity reactions can also occur, mostly in patients with extensive skin lesions and blistering. In a substantial number of these cases, the triggering factor of anaphylaxis remains unidentified. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers, treatment with H1 and H2 histamine receptor blockers, and equipment of patients and their families with epinephrine auto-injectors for use in severe anaphylactic reactions. Advanced systemic mastocytosis occurs occasionally. All children with mastocytosis require follow-up examinations. A bone marrow investigation is performed when advanced systemic mastocytosis is suspected and has an impact on therapy or when cutaneous disease persists into adulthood.
Topics: Child; Epinephrine; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Mast Cells; Mastocytosis, Cutaneous; Mastocytosis, Systemic; Proto-Oncogene Mas; Skin
PubMed: 33806685
DOI: 10.3390/ijms22052586 -
American Journal of Hematology Mar 2019Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MCs) in extra-cutaneous organs. (Review)
Review
OVERVIEW
Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MCs) in extra-cutaneous organs.
DIAGNOSIS
The major criterion is presence of multifocal clusters of abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation.
RISK STRATIFICATION
Establishing SM subtype as per the World Health Organization classification system is an important first step. Broadly, patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, the latter includes aggressive SM (ASM), SM with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). Identification of poor-risk mutations (ie, ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Recently, clinical and hybrid clinical-molecular risk models have been developed to more accurately assign prognosis in SM patients.
MANAGEMENT
ISM patients have a normal life expectancy and treatment is generally limited to anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to ameliorate disease-related organ dysfunction. High response rates have been seen with small-molecule inhibitors that target mutant-KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational). Other options for MC cytoreduction include cladribine or interferon-α, although head-to-head comparisons are lacking. Treatment of SM-AHN primarily targets the AHN component, if an aggressive disease such as acute myeloid leukemia is present. Allogeneic stem cell transplant can be considered in such patients, or in those with relapsed/refractory advanced SM. Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib-sensitive KIT mutations.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Bone Marrow; Cladribine; Disease Management; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Interferon-alpha; Interleukin-2 Receptor alpha Subunit; Mast Cells; Mastocytosis, Systemic; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit; Risk Assessment; Staurosporine; Survival Analysis; Transplantation, Homologous; Tryptases
PubMed: 30536695
DOI: 10.1002/ajh.25371 -
Acta Dermato-venereologica Mar 2016Mastocytosis comprises a heterogeneous group of disorders characterized by clonal, neoplastic proliferation of mast cells accumulating in one or multiple organs. In the... (Review)
Review
Mastocytosis comprises a heterogeneous group of disorders characterized by clonal, neoplastic proliferation of mast cells accumulating in one or multiple organs. In the majority of cases skin involvement is the first clinical manifestation of the disease. Clinical work-up consists of a combination of morphological, immunohistochemical, flow cytometric immunophenotyping and molecular examination. Cutaneous mastocytosis predominates in children, whereas systemic mastocytosis is the most common form of the disease in adults. Therefore, different diagnostic algorithms have to be applied in adult patients and children with suspected mastocytosis. This comprehensive review presents currently defined variants of the disease and recommendations to facilitate diagnostic work-up in children and adults with suspected mastocytosis in daily clinical practice.
Topics: Adult; Age of Onset; Child; Diagnosis, Differential; Humans; Mastocytosis, Cutaneous; Mastocytosis, Systemic; Predictive Value of Tests; Prognosis
PubMed: 26270728
DOI: 10.2340/00015555-2210 -
Immunology and Allergy Clinics of North... Nov 2023A KIT activating mutation (usually KIT D816V) is detected in neoplastic cells in greater than 90% of indolent patients with systemic mastocytosis (SM). In more advanced... (Review)
Review
A KIT activating mutation (usually KIT D816V) is detected in neoplastic cells in greater than 90% of indolent patients with systemic mastocytosis (SM). In more advanced variants of SM, additional genetic defects can be found in several myeloid malignancy-related genes, which can be detected by applying next-generation sequencing. Currently, the techniques recommended to detect the KIT D816V mutation and quantify the mutational burden in peripheral blood, bone marrow, or other organs/tissues are allele specific-quantitative PCR or droplet digital PCR. These techniques are useful for diagnosis, prognostication, follow-up and monitoring of therapeutic efficacy of cytoreductive agents in patients with SM.
Topics: Humans; Proto-Oncogene Proteins c-kit; Mastocytosis; Mutation; Mastocytosis, Systemic; Bone Marrow; Mast Cells
PubMed: 37758404
DOI: 10.1016/j.iac.2023.04.008 -
Annals of Hematology Feb 2021Systemic mastocytosis (SM) is a rare disease calling for integrated approaches involving onco-hematologic competences for appropriate clinical management and treatment.... (Review)
Review
Systemic mastocytosis (SM) is a rare disease calling for integrated approaches involving onco-hematologic competences for appropriate clinical management and treatment. The wide variability of manifestations and disease course claims for an accurate risk stratification, currently relying on the appraisal of the benefit/risk ratio of treatment modalities within indolent and advanced variants according to WHO classification. More objective parameters are progressively incorporated and integrated into comprehensive models, on which to support the adoption of therapeutic strategies, since the mere clinical distinction between mediator-related signs/symptoms and "true" organ damage can sometimes be complicated. The development of novel targeted drugs is progressively extending the therapeutic alternatives available, which ranges from conventional agents such as interferon and cladribine, to the more modern approach based on KIT inhibition. Ultimately, the choice of the most appropriate therapy should be rationalized on the basis of the clinical picture and molecular data. The focus of the present review is on the areas still open in the current evaluation of SM patients, particularly when considering the need of a treatment.
Topics: Cladribine; Humans; Interferons; Mast Cells; Mastocytosis, Systemic; Proto-Oncogene Proteins c-kit
PubMed: 33156374
DOI: 10.1007/s00277-020-04323-9 -
International Journal of Molecular... Mar 2021Systemic mastocytosis (SM) is a rare clonal hematologic neoplasm, driven, in almost all cases, by the activating D816V mutation that leads to the growth and... (Review)
Review
Systemic mastocytosis (SM) is a rare clonal hematologic neoplasm, driven, in almost all cases, by the activating D816V mutation that leads to the growth and accumulation of neoplastic mast cells. While patients with advanced forms of SM have a poor prognosis, the introduction of KIT inhibitors (e.g., midostaurin, and avapritinib) has changed their outlook. Because of the heterogenous nature of advanced SM (advSM), successive iterations of response criteria have tried to capture different dimensions of the disease, including measures of mast cell burden (percentage of bone marrow mast cells and serum tryptase level), and mast cell-related organ damage (referred to as C findings). Historically, response criteria have been anchored to reversion of one or more organ damage finding(s) as a minimal criterion for response. This is a central principle of the Valent criteria, Mayo criteria, and International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria. Irrespective of the response criteria, an ever-present challenge is how to apply response criteria in patients with SM and an associated hematologic neoplasm, where the presence of both diseases complicates assignment of organ damage and adjudication of response. In the context of trials with the selective D816V inhibitor avapritinib, pure pathologic response (PPR) criteria, which rely solely on measures of mast cell burden and exclude consideration of organ damage findings, are being explored as more robust surrogate of overall survival. In addition, the finding that avapritinib can elicit complete molecular responses of D816V allele burden, establishes a new benchmark for advSM and motivates the inclusion of definitions for molecular response in future criteria. Herein, we also outline how the concept of PPR can inform a proposal for new response criteria which use a tiered evaluation of pathologic, molecular, and clinical responses.
Topics: Cell Proliferation; Enzyme Inhibitors; Female; Humans; Mast Cells; Mastocytosis, Systemic; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit; Pyrazoles; Pyrroles; Staurosporine; Triazines
PubMed: 33804174
DOI: 10.3390/ijms22062983 -
Medicine May 2023Mastocytosis is a group of rare neoplastic diseases characterized by monoclonal proliferation of mast cells in the skin or other tissues and organs, including cutaneous...
RATIONALE
Mastocytosis is a group of rare neoplastic diseases characterized by monoclonal proliferation of mast cells in the skin or other tissues and organs, including cutaneous mastocytosis and systemic mastocytosis (SM). Mastocytosis can also occur in the gastrointestinal tract, mostly manifested as increased mast cells dispersed in various layers of the intestinal wall; a few may present as polypoid nodules, but rarely as soft tissue mass formation. Pulmonary fungal infections mostly occur in patients with low immune function and have not been reported in the literature as the initial manifestation in patients with mastocytosis. In this case report, we present the enhanced computed tomography (CT), fluorodeoxyglucose (FDG) positron emission tomography/CT, and colonoscopy findings of a pathologically confirmed patient with aggressive SM of the colon and lymph nodes and extensive fungal infection of both lungs.
PATIENT CONCERNS
A 55-year-old female patient visited our hospital because of repeated cough for more than half a month. Laboratory tests revealed a significantly high CA125 serum level. Chest CT showed multiple plaques and patchy high-density shadows in both lungs, and a small amount of ascites was observed in the lower-level image. Abdominal CT revealed a soft tissue mass with an ill-defined boundary in the lower ascending colon. Whole-body positron emission tomography/CT images showed multiple nodular and patchy density-increasing lesions with significantly increased FDG uptake in both lungs. The wall of the ascending colon in the lower segment was significantly thickened with soft tissue mass formation, and retroperitoneal lymph node enlargement was accompanied by increased uptake of FDG. Colonoscopy revealed a soft tissue mass at the base of the cecum.
DIAGNOSIS
Colonoscopic biopsy was performed and the specimen was diagnosed with mastocytosis. At the same time, a puncture biopsy was also performed on the patient's lung lesions, and pulmonary cryptococcosis was considered a pathological diagnosis.
INTERVENTIONS
The patient was in remission after repeated treatment with imatinib and prednisone for 8 months.
OUTCOMES
In the ninth month, the patient suddenly died of a cerebral hemorrhage.
LESSONS
Gastrointestinal involvement due to aggressive SM presents with nonspecific symptoms and different endoscopic and radiologic findings. This is the first report of a single patient with colon SM, retroperitoneal lymph node SM, and extensive fungal infection in both lungs.
Topics: Female; Humans; Middle Aged; Mastocytosis, Systemic; Fluorodeoxyglucose F18; Mastocytosis; Colon; Lymph Nodes; Colonoscopy
PubMed: 37233424
DOI: 10.1097/MD.0000000000033813