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The Veterinary Clinics of North... Sep 2019Canine cutaneous mast cell tumors (MCTs) are among the most common canine cutaneous tumors, with highly variable biological behavior. This review describes in detail... (Review)
Review
Canine cutaneous mast cell tumors (MCTs) are among the most common canine cutaneous tumors, with highly variable biological behavior. This review describes in detail current approaches for cytologic and histologic diagnosis and prognosis, including advantages and limitations of cytologic and histologic grading and utilization of molecular markers, for example, Ki67, AgNORs, KIT expression, and c-Kit mutations, for a more accurate detection of aggressive MCTs. Furthermore, the current approach to evaluate surgical margins and spread to local lymph nodes is discussed.
Topics: Animals; Biomarkers, Tumor; Biopsy; Dog Diseases; Dogs; Mastocytosis, Cutaneous; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis
PubMed: 31178200
DOI: 10.1016/j.cvsm.2019.04.002 -
Journal of Investigational Allergology... Dec 2021The diagnosis of mast cell activation syndrome (MCAS) is defined by 3 criteria: (1) typical clinical signs and symptoms of acute, recurrent (episodic), and systemic mast... (Review)
Review
The diagnosis of mast cell activation syndrome (MCAS) is defined by 3 criteria: (1) typical clinical signs and symptoms of acute, recurrent (episodic), and systemic mast cell activation (MCA); (2) increase in tryptase level to >20% + 2 ng/mL within 1-4 hours after onset of the acute crisis; and (3) response of MCA symptoms to antimediator therapy. Classification of MCAS requires highly sensitive and specific methodological approaches for the assessment of clonal bone marrow mast cells at low frequencies. The Spanish Network on Mastocytosis score has been used successfully as a predictive model for selecting MCAS candidates for bone marrow studies based on a high probability of an underlying clonal mast cell disorder. In this article, we propose a diagnostic algorithm and focus on the practical evaluation and management of patients with suspected MCAS.
Topics: Anaphylaxis; Humans; Mast Cell Activation Syndrome; Mast Cells; Mastocytosis; Neoplasm Recurrence, Local; Tryptases
PubMed: 33541851
DOI: 10.18176/jiaci.0675 -
Virology Journal Oct 2022Most COVID-19 patients recovered with low mortality; however, some patients experienced long-term symptoms described as "long-COVID" or "Post-COVID syndrome" (PCS).... (Review)
Review
Most COVID-19 patients recovered with low mortality; however, some patients experienced long-term symptoms described as "long-COVID" or "Post-COVID syndrome" (PCS). Patients may have persisting symptoms for weeks after acute SARS-CoV-2 infection, including dyspnea, fatigue, myalgia, insomnia, cognitive and olfactory disorders. These symptoms may last for months in some patients. PCS may progress in association with the development of mast cell activation syndrome (MCAS), which is a distinct kind of mast cell activation disorder, characterized by hyper-activation of mast cells with inappropriate and excessive release of chemical mediators. COVID-19 survivors, mainly women, and patients with persistent severe fatigue for 10 weeks after recovery with a history of neuropsychiatric disorders are more prone to develop PCS. High D-dimer levels and blood urea nitrogen were observed to be risk factors associated with pulmonary dysfunction in COVID-19 survivors 3 months post-hospital discharge with the development of PCS. PCS has systemic manifestations that resolve with time with no further complications. However, the final outcomes of PCS are chiefly unknown. Persistence of inflammatory reactions, autoimmune mimicry, and reactivation of pathogens together with host microbiome alterations may contribute to the development of PCS. The deregulated release of inflammatory mediators in MCAS produces extraordinary symptoms in patients with PCS. The development of MCAS during the course of SARS-CoV-2 infection is correlated to COVID-19 severity and the development of PCS. Therefore, MCAS is treated by antihistamines, inhibition of synthesis of mediators, inhibition of mediator release, and inhibition of degranulation of mast cells.
Topics: COVID-19; Fatigue; Female; Histamine Antagonists; Humans; Inflammation Mediators; Mastocytosis; SARS-CoV-2
PubMed: 36210445
DOI: 10.1186/s12985-022-01891-2 -
Annual Review of Pathology Jan 2023Mastocytosis is a heterogeneous group of neoplasms defined by a numerical increase and accumulation of clonal mast cells (MCs) in various organ systems. The disease may... (Review)
Review
Mastocytosis is a heterogeneous group of neoplasms defined by a numerical increase and accumulation of clonal mast cells (MCs) in various organ systems. The disease may present as cutaneous mastocytosis or systemic mastocytosis (SM). On the basis of histopathological and molecular features, clinical variables, and organ involvement, SM is divided into indolent SM, smoldering SM, SM with an associated hematologic neoplasm, aggressive SM, and MC leukemia. Each variant is defined by unique diagnostic criteria and a unique spectrum of clinical presentations. A key driver of MC expansion and disease evolution is the oncogenic machinery triggered by mutant forms of . The genetic background, additional somatic mutations, and comorbidities also contribute to the course and prognosis. Patients with SM may also suffer from mediator-related symptoms or even an MC activation syndrome. This article provides an update of concepts on the genetics, etiology, and pathology of mastocytosis, with emphasis on diagnostic criteria and new treatment concepts.
Topics: Humans; Mastocytosis; Mast Cells; Mastocytosis, Systemic; Prognosis; Proto-Oncogene Proteins c-kit
PubMed: 36270293
DOI: 10.1146/annurev-pathmechdis-031521-042618 -
International Archives of Allergy and... 2022Mast cell activation syndromes (MCASs) are defined by systemic severe and recurrent mast cell activation, usually in form of anaphylaxis, a substantial, event-related... (Review)
Review
Mast cell activation syndromes (MCASs) are defined by systemic severe and recurrent mast cell activation, usually in form of anaphylaxis, a substantial, event-related increase of the serum tryptase level beyond the individual's baseline and a response of the symptomatology to drugs directed against mast cells, mast cell-derived mediators, or mediator effects. A number of predisposing genetic conditions, underlying allergic and other hypersensitivity states, and related comorbidities can contribute to the clinical manifestation of MCASs. These conditions include hereditary alpha tryptasemia, mastocytosis with an expansion of clonal KIT-mutated mast cells, atopic diathesis, and overt IgE-dependent and IgE-independent allergies. Several of these conditions have overlapping definitions and diagnostic criteria and may also develop concomitantly in the same patient. However, although criteria and clinical features overlap, each of these conditions is characterized by a unique constellation of variables and diagnostic criteria. Since two, three, or more conditions can coexist in the same patient, with obvious clinical implications, it is of crucial importance to diagnose the variant of MCAS precisely and to take all accompanying, underlying and potentially complicating conditions, and comorbidities into account when establishing the management plan. Indeed, most of these patients require multidisciplinary investigations and only a personalized treatment approach can lead to an optimal management plan providing an optimal quality of life and low risk of anaphylaxis.
Topics: Anaphylaxis; Humans; Immunoglobulin E; Mast Cell Activation Syndrome; Mast Cells; Mastocytosis; Quality of Life; Tryptases
PubMed: 35605594
DOI: 10.1159/000524532 -
Hematology. American Society of... Dec 2023Mastocytosis is a rare, clinically heterogenous clonal hematological neoplasm. Over 95% of patients harbor the driver KIT D816V mutation resulting in mast cell (MC)... (Review)
Review
Mastocytosis is a rare, clinically heterogenous clonal hematological neoplasm. Over 95% of patients harbor the driver KIT D816V mutation resulting in mast cell (MC) accumulation and proliferation in various organs, leading to variable symptom manifestations that result from MC mediator release in patients with systemic mastocytosis (SM) and end-organ damage in those with advanced SM. The accurate diagnostic and clinical classification of patients with SM is vital to underpin appropriate treatment options and personalize therapy. This review evaluates the current diagnostic criteria, clinical classification, risk stratification, and therapeutic options available for adult patients with nonadvanced and advanced SM.
Topics: Adult; Humans; Mastocytosis; Mastocytosis, Systemic; Mast Cells; Proto-Oncogene Proteins c-kit; Mutation
PubMed: 38066855
DOI: 10.1182/hematology.2023000505 -
American Journal of Hematology Jul 2023Systemic mastocytosis (SM) results from clonal proliferation of mast cells (MC) in extracutaneous organs.
OVERVIEW
Systemic mastocytosis (SM) results from clonal proliferation of mast cells (MC) in extracutaneous organs.
DIAGNOSIS
The major criterion is presence of multifocal MC clusters in the bone marrow and/or extracutaneous organs. Minor diagnostic criteria include elevated serum tryptase level, MC CD25/CD2/CD30 expression, and presence of activating KIT mutations.
RISK STRATIFICATION
Establishing SM subtype as per the International Consensus Classification/World Health Organization classification systems is an important first step. Patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, including aggressive SM (ASM), SM with associated myeloid neoplasm (SM-AMN), and mast cell leukemia. Identification of poor-risk mutations (i.e., ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Several risk models are available to help assign prognosis in SM patients.
MANAGEMENT
Treatment goals for ISM patients are primarily directed toward anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to reverse disease-related organ dysfunction. Tyrosine kinase inhibitors (TKI) (midostaurin, avapritinib) have changed the treatment landscape in SM. While deep biochemical, histological and molecular responses have been documented with avapritinib treatment, its efficacy as monotherapy against a multimutated AMN disease component in SM-AMN patients remains unclear. Cladribine continues to have a role for MC debulking, whereas interferon-α has a diminishing role in the TKI era. Treatment of SM-AMN primarily targets the AMN component, particularly if an aggressive disease such as acute leukemia is present. Allogeneic stem cell transplant has a role in such patients. Imatinib has a therapeutic role only in the rare patient with an imatinib-sensitive KIT mutation.
Topics: Humans; Adult; Mastocytosis, Systemic; Imatinib Mesylate; Mast Cells; Leukemia, Mast-Cell; Risk Assessment
PubMed: 37309222
DOI: 10.1002/ajh.26962 -
The Journal of Allergy and Clinical... Feb 2020The current consensus diagnostic criteria for mast cell activation syndrome(s) (MCAS[s]) were first established in 2012 and updated in 2019. This diagnosis has been... (Review)
Review
The current consensus diagnostic criteria for mast cell activation syndrome(s) (MCAS[s]) were first established in 2012 and updated in 2019. This diagnosis has been attached to multiple medical conditions not intended as part of the diagnosis. In this article, the diagnostic criteria are reviewed and other diseases in the differential diagnosis outlined. The goal of this review is to provide a tool for evaluation of patients with conditions that can mimic MCAS. Furthermore, the potential role for hereditary alpha-tryptasemia in this group of disorders is discussed.
Topics: Diagnosis, Differential; Humans; Mast Cells; Mastocytosis; Motivation
PubMed: 31470118
DOI: 10.1016/j.jaip.2019.08.022 -
Topics in Companion Animal Medicine Nov 2020Mast cell tumor (MCT) or mastocytoma is one of the most frequent malignant cutaneous tumors in the dog, and the second most frequent in the cat. Several mast cell tumor...
Mast cell tumor (MCT) or mastocytoma is one of the most frequent malignant cutaneous tumors in the dog, and the second most frequent in the cat. Several mast cell tumor therapeutic approaches have been proposed in the past years for dogs and cats, resulting in very distinct outcomes. The current comprehensive literature review presents a critical approach to the scientific information published about the MCTs treatments and the subsequent prognosis and survival times, in dogs and in cats diagnosed with MCTs. A systematic review of the literature following the Cochrane principles and methodology was performed. The authors resorted to MEDLINE, Scopus, Google Scholar and Web of Science databases to select the 133 publications with evidence-based treatments for MCTs in companion animals. Results of the review suggest that the recommended treatment, prognosis and survival times for dogs and cats with MCTs depends at all times on the clinical staging, histological grade and location of the tumor.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Mastocytoma; Skin Neoplasms; Treatment Outcome
PubMed: 32891740
DOI: 10.1016/j.tcam.2020.100472 -
Current Opinion in Pediatrics Aug 2020The current article highlights recent developments in the field of pediatric cutaneous mastocytosis. Mastocytosis is a spectrum of conditions that range from fleetingly... (Review)
Review
PURPOSE OF REVIEW
The current article highlights recent developments in the field of pediatric cutaneous mastocytosis. Mastocytosis is a spectrum of conditions that range from fleetingly benign to aggressively malignant. Through recognizing the natural progression of disease, the role of biomarkers and mutational analysis, treatment and risk of triggers, physicians can confidently stage, counsel and manage patients with pediatric cutaneous mastocytosis.
RECENT FINDINGS
Many lesions of cutaneous mastocytosis are chronic with some resolving around the mid-teenage years. KIT mutations are found in the majority of pediatric cutaneous mastocytosis but are not correlated with prognosis. Serum tryptase levels may be elevated in pediatric cutaneous mastocytosis patients without systemic mastocytosis. Pimecrolimus, omalizumab and tyrosine kinase inhibitors are effective treatment options. The low risk of NSAIDs and vaccinations has been characterized and epinephrine autoinjectors are rarely utilized in the pediatric cutaneous mastocytosis patient.
SUMMARY
Pediatric cutaneous mastocytosis is a heterogeneous disease with good outcome overall. Organomegaly, elevated tryptase levels and the presence of KIT mutation in peripheral blood may aid in the decision to pursue bone marrow biopsy. The armamentarium of treatments has expanded and better understanding of the significance of triggers and vaccination safety allows the clinician to thoughtfully counsel and allay anxiety around pediatric cutaneous mastocytosis.
Topics: Adolescent; Biomarkers; Biopsy; Bone Marrow; Child; DNA Mutational Analysis; Enzyme Inhibitors; Humans; Mastocytosis; Omalizumab; Tacrolimus; Tryptases
PubMed: 32692050
DOI: 10.1097/MOP.0000000000000922