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The Australasian Journal of Dermatology Feb 2021Mastocytosis is a rare disease characterised by expansion and collection of clonal mast cells in various organs including the skin, bone marrow, spleen, lymph nodes and... (Review)
Review
Mastocytosis is a rare disease characterised by expansion and collection of clonal mast cells in various organs including the skin, bone marrow, spleen, lymph nodes and gastrointestinal tract. The prevalence of mastocytosis has been estimated to be one in 10 000, while the estimated incidence is one per 100 000 people per year. Cutaneous mastocytosis is classified into (i) maculopapular cutaneous mastocytosis, also known as urticaria pigmentosa; (ii) diffuse cutaneous mastocytosis; and (iii) mastocytoma of the skin. In adults, cutaneous lesions are usually associated with indolent systemic mastocytosis and have a chronic evolution. Paediatric patients, on the contrary, have often cutaneous manifestations without systemic involvement and usually experience a spontaneous regression. Diagnosis of cutaneous mastocytosis may be challenging due to the rarity of the disease and the overlap of cutaneous manifestations. This short review describes pathogenesis and clinical aspects of cutaneous mastocytosis with a focus on diagnosis and currently available therapies.
Topics: Genetic Predisposition to Disease; Humans; Mastocytosis, Cutaneous; Phospholipases; Physician's Role; Prognosis; Skin; Tryptases; Urticaria Pigmentosa
PubMed: 33040350
DOI: 10.1111/ajd.13443 -
Diagnosis (Berlin, Germany) May 2021The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis,... (Review)
Review
The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of "mast cell activation syndrome" (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a "consensus" (re-termed here as "consensus-1"). Another sizable contingent of investigators and practitioners favor a different approach (originally published in 2011, newly termed here as "consensus-2"), resembling "consensus-1" in some respects but differing in others, leading to substantial differences between these proposals in the numbers of patients qualifying for diagnosis (and thus treatment). Overdiagnosis by "consensus-2" criteria has potential to be problematic, but underdiagnosis by "consensus-1" criteria seems the far larger problem given (1) increasing appreciation that MCAS is prevalent (up to 17% of the general population), and (2) most MCAS patients, regardless of illness duration prior to diagnosis, can eventually identify treatment yielding sustained improvement. We analyze these proposals (and others) and suggest that, until careful research provides more definitive answers, diagnosis by either proposal is valid, reasonable, and helpful.
Topics: Consensus; Humans; Mast Cells; Mastocytosis
PubMed: 32324159
DOI: 10.1515/dx-2020-0005 -
Current Opinion in Allergy and Clinical... Oct 2022To discuss our evolving knowledge about the genetic variations in human tryptase and recent advances in associated clinical phenotypes. (Review)
Review
PURPOSE OF REVIEW
To discuss our evolving knowledge about the genetic variations in human tryptase and recent advances in associated clinical phenotypes.
RECENT FINDINGS
Hereditary alpha-tryptasemia (HAT) is an autosomal dominant genetic trait and a common cause of elevated basal serum tryptase (BST) in Western populations. It is a risk factor for severe anaphylaxis and an established modifier of mast cell mediator-associated symptoms among patients with systemic mastocytosis (SM).
SUMMARY
The unique properties of naturally occurring alpha/beta-tryptase heterotetramers may explain certain elements of phenotypes associated with HAT. Understanding the physiology of tryptases and how this may relate to the clinical features associated with HAT is the first step in identifying optimal medical management and targets for novel therapeutics.
Topics: Anaphylaxis; Humans; Mast Cell Activation Syndrome; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Tryptases
PubMed: 35942852
DOI: 10.1097/ACI.0000000000000849 -
Digestive Diseases and Sciences Apr 2021Mast cell activation syndrome is thought to be a common, yet under-recognized, chronic multi-system disorder caused by inappropriate mast cell activation.... (Review)
Review
Mast cell activation syndrome is thought to be a common, yet under-recognized, chronic multi-system disorder caused by inappropriate mast cell activation. Gastrointestinal symptoms are frequently reported by these patients and are often mistaken by physicians as functional gastrointestinal disorders. This syndrome can be diagnosed by the medical history and measurable biomarkers. Gastroenterologists manage diseases associated with active inflammatory cells including neutrophils, lymphocytes, macrophages, and eosinophils. The mast cell has only recently been recognized as a major player in our specialty. Gastrointestinal disorders from mast cell mediators often present with apparent irritable bowel syndrome, dyspepsia, chronic or cyclical nausea, and heartburn. Individuals with mast cell activation syndrome experience significant delays in diagnosis. The gastrointestinal symptoms are often refractory to symptom-targeted prescription medications. Beyond avoiding triggers, the best therapy is directed at modulating mast cell activation and the effects of the mediators. Many of these therapies are simple over-the-counter medications. In this article, we review mast cell function and dysfunction and the gastrointestinal symptoms, comorbid conditions, diagnosis, and management of mast cell activation syndrome. Gastroenterologists who become aware of this syndrome can dramatically improve the quality of life for their patients who previously have been labeled with a functional gastrointestinal disorder.
Topics: Diagnosis, Differential; Disease Management; Gastrointestinal Diseases; Humans; Mastocytosis; Quality of Life
PubMed: 32328892
DOI: 10.1007/s10620-020-06264-9 -
American Journal of Hematology Apr 2021Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in extra-cutaneous organs. (Review)
Review
OVERVIEW
Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in extra-cutaneous organs.
DIAGNOSIS
The major criterion is presence of multifocal clusters of spindled 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
Treatment goals for ISM patients are primarily directed towards 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, particularly 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: Adult; Algorithms; Animals; Bone Marrow; Disease Management; Disease Models, Animal; Drugs, Investigational; Gain of Function Mutation; Hematologic Neoplasms; Humans; Hydroxyurea; Interleukin-2 Receptor alpha Subunit; Kaplan-Meier Estimate; Leukemia, Mast-Cell; Mast Cells; Mastocytosis, Systemic; Mice; Mice, Transgenic; Mutation, Missense; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit; Risk Assessment; Tryptases
PubMed: 33524167
DOI: 10.1002/ajh.26118 -
Virchows Archiv : An International... Jan 2023Mastocytosis is a neoplasm characterized by a clonal proliferation of mast cells, which accumulate in one or multiple organs, associated with an extremely heterogeneous... (Review)
Review
Mastocytosis is a neoplasm characterized by a clonal proliferation of mast cells, which accumulate in one or multiple organs, associated with an extremely heterogeneous clinical presentation. The disease can be limited to the skin (cutaneous mastocytosis) that is mostly seen in childhood and usually behaves in a benign fashion. Adult patients most often present with systemic disease with or without skin lesions. This includes indolent forms such as indolent systemic mastocytosis and its subvariant bone marrow mastocytosis, and smoldering systemic mastocytosis as well as aggressive forms including aggressive systemic mastocytosis, systemic mastocytosis with an associated myeloid neoplasm (previously called systemic mastocytosis with an associated hematologic neoplasm), and mast cell leukemia. In addition, mast cell sarcoma is a rare aggressive form of mastocytosis that can present in the skin as well as at extracutaneous sites. This review article focuses on the updates in mastocytosis of the 2022 international consensus classification (ICC).
Topics: Adult; Humans; Mastocytosis, Systemic; Consensus; Mastocytosis; Mast Cells; Leukemia, Mast-Cell
PubMed: 36214901
DOI: 10.1007/s00428-022-03423-3 -
American Journal of Hematology Aug 2023Based on new data and increased understanding of disease molecular genetics, the international consensus classification (ICC) has made several changes in the diagnosis... (Review)
Review
Based on new data and increased understanding of disease molecular genetics, the international consensus classification (ICC) has made several changes in the diagnosis and classification of eosinophilic disorders and systemic mastocytosis. Myeloid/lymphoid neoplasms with eosinophilia (M/LN-eo) and gene rearrangements have been renamed as M/LN-eo with tyrosine kinase gene fusions (M/LN-eo-TK). The category has been expanded to include ETV6::ABL1 and FLT3 fusions, and to accept PCM1::JAK2 and its genetic variants as formal members. The overlaps and differences between M/LN-eo-TK and BCR::ABL1-like B-lymphoblastic leukemia (ALL)/de novo T-ALL sharing the same genetic lesions are addressed. Besides genetics, ICC for the first time has introduced bone marrow morphologic criteria in distinguishing idiopathic hypereosinophilia/hypereosinophilic syndrome from chronic eosinophilic leukemia, not otherwise specified. The major diagnostic criteria for systemic mastocytosis (SM) in the ICC remain largely based on morphology, but several minor modifications/refinements have been made in criteria related to diagnosis, subclassification, and assessment of disease burden (B- and C-findings). This review is to focus on the ICC updates related to these disease entities, illustrated through changes related to morphology, molecular genetics, clinical features, prognosis, and treatment. Two practical algorithms are provided in navigating through the diagnosis and classification systems of hypereosinophilia and SM.
Topics: Humans; Mastocytosis, Systemic; Consensus; Leukemia; Myeloproliferative Disorders; Hypereosinophilic Syndrome
PubMed: 37283522
DOI: 10.1002/ajh.26966 -
International Journal of Molecular... Oct 2021Mast cells are derived from hematopoietic stem cell precursors and are essential to the genesis and manifestations of the allergic response. Activation of these cells by... (Review)
Review
Mast cells are derived from hematopoietic stem cell precursors and are essential to the genesis and manifestations of the allergic response. Activation of these cells by allergens leads to degranulation and elaboration of inflammatory mediators, responsible for regulating the acute dramatic inflammatory response seen. Mast cells have also been incriminated in such diverse disorders as malignancy, arthritis, coronary artery disease, and osteoporosis. There has been a recent explosion in our understanding of the mast cell and the associated clinical conditions that affect this cell type. Some mast cell disorders are associated with specific genetic mutations (such as the D816V gain-of-function mutation) with resultant clonal disease. Such disorders include cutaneous mastocytosis, systemic mastocytosis (SM), its variants (indolent/ISM, smoldering/SSM, aggressive systemic mastocytosis/ASM) and clonal (or monoclonal) mast cell activation disorders or syndromes (CMCAS/MMAS). Besides clonal mast cell activations disorders/CMCAS (also referred to as monoclonal mast cell activation syndromes/MMAS), mast cell activation can also occur secondary to allergic, inflammatory, or paraneoplastic disease. Some disorders are idiopathic as their molecular pathogenesis and evolution are unclear. A genetic disorder, referred to as hereditary alpha-tryptasemia (HαT) has also been described recently. This condition has been shown to be associated with increased severity of allergic and anaphylactic reactions and may interact variably with primary and secondary mast cell disease, resulting in complex combined disorders. The role of this review is to clarify the classification of mast cell disorders, point to molecular aspects of mast cell signaling, elucidate underlying genetic defects, and provide approaches to targeted therapies that may benefit such patients.
Topics: Animals; Humans; Mast Cell Activation Disorders; Mast Cells; Mastocytosis
PubMed: 34681933
DOI: 10.3390/ijms222011270 -
American Journal of Clinical Pathology Feb 2021The 2019 Workshop of the Society for Hematopathology/European Association for Haematopathology received and reviewed cases covering the spectrum of mastocytosis and...
OBJECTIVES
The 2019 Workshop of the Society for Hematopathology/European Association for Haematopathology received and reviewed cases covering the spectrum of mastocytosis and related diseases, including morphologic mimics, focusing on recent updates and relevant findings for pathologists.
METHODS
The workshop panel reviewed 99 cases of cutaneous and systemic mastocytosis (SM) and SM and associated hematologic neoplasms (SM-AHN).
RESULTS
Despite a common theme of KIT mutation (particularly D816V), mastocytosis is a heterogeneous neoplasm with a wide variety of presentations. This spectrum, including rare subtypes and extramedullary organ involvement, is discussed and illustrated by representative cases.
CONCLUSIONS
In the age of targeted treatment aimed at KIT, the accurate diagnosis and classification of mastocytosis has major implications for therapy and further interventions. Understanding the clinical, pathologic, and genetic findings of mastocytosis is crucial for selecting the proper tests to perform and subsequent arrival at a correct diagnosis in this rare disease.
Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Child; Diagnosis, Differential; Female; Genetic Testing; Humans; Immunohistochemistry; Infant; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Male; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Middle Aged; Mutation; Oncogenes; Prognosis; Proto-Oncogene Proteins c-kit; Tryptases; Young Adult
PubMed: 33313644
DOI: 10.1093/ajcp/aqaa183 -
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