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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The term 'mastocytosis' denotes a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MC) in one or more organ systems. Over the last 20 years, there has been an evolution in accepted classification systems for this disease. In light of such developments and novel useful markers, it seems appropriate now to re-evaluate and update the classification of mastocytosis. Here, we propose criteria to delineate categories of mastocytosis together with an updated consensus classification system. In this proposal, the diagnosis cutaneous mastocytosis (CM) is based on typical clinical and histological skin lesions and absence of definitive signs (criteria) of systemic involvement. Most patients with CM are children and present with maculopapular cutaneous mastocytosis (=urticaria pigmentosa, UP). Other less frequent forms of CM are diffuse cutaneous mastocytosis (DCM) and mastocytoma of skin. Systemic mastocytosis (SM) is commonly seen in adults and defined by multifocal histological lesions in the bone marrow (affected almost invariably) or other extracutaneous organs (major criteria) together with cytological and biochemical signs (minor criteria) of systemic disease (SM-criteria). SM is further divided into the following categories: indolent systemic mastocytosis (ISM), SM with an associated clonal hematologic non-mast cell lineage disease (AHNMD), aggressive systemic mastocytosis (ASM), and mast cell leukemia (MCL). Patients with ISM usually have maculopapular skin lesions and a good prognosis. In the group with associated hematologic disease, the AHNMD should be classified according to FAB/WHO criteria. ASM is characterized by impaired organ-function due to infiltration of the bone marrow, liver, spleen, GI-tract, or skeletal system, by pathologic MC. MCL is a 'high-grade' leukemic disease defined by increased numbers of MC in bone marrow smears (>or=20%) and peripheral blood, absence of skin lesions, multiorgan failure, and a short survival. In typical cases, circulating MC amount to >or=10% of leukocytes (classical form of MCL). Mast cell sarcoma is a unifocal tumor that consists of atypical MC and shows a destructive growth without (primary) systemic involvement. This high-grade malignant MC disease has to be distinguished from a localized benign mastocytoma in either extracutaneous organs (=extracutaneous mastocytoma) or skin. Depending on the clinical course of mastocytosis and development of an AHNMD, patients can shift from one category of MC disease into another. In all categories, mediator-related symptoms may occur and may represent a serious clinical problem. All categories of mastocytosis should be distinctively separated from reactive MC hyperplasia, MC activation syndromes, and a more or less pronounced increase in MC in myelogenous malignancies other than mastocytosis. Criteria proposed in this article should be helpful in this regard.
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PMID:Diagnostic criteria and classification of mastocytosis: a consensus proposal. 1191 23

Clonal cytogenetic abnormalities similar to those observed in other haematological neoplasms are demonstrable in a proportion of patients with systemic mastocytosis and in a smaller proportion of adults with urticaria pigmentosa without apparent systemic disease. These clonal abnormalities are not likely to represent the primary event in mast cell neoplasms. Although no recurrent cytogenetic abnormalities specific for mastocytosis have yet been recognized, the majority of cases display one of several mutations in c-KIT, the gene encoding the receptor for stem cell factor. That most commonly observed is the Asp816Val mutation, which permits proliferation independent of growth factors. c-KIT mutations may play a significant role in the biology of mast cell malignancies, although other mutations may be needed for a malignant phenotype.
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PMID:Cytogenetic and molecular genetic abnormalities in systemic mastocytosis. 1191 94

The most common skin tumor in dogs is the mast cell tumor (MCT), with an incidence of close to 20% in the canine population. MCTs range from relatively benign to extremely aggressive, leading to metastasis and eventual death from systemic disease. Although surgical removal with or without radiation therapy may cure most patients with low-grade MCTs, there are no effective treatments for dogs with aggressive high-grade MCTs. This article reviews the current understanding of MCT biology with regard to diagnosis, staging, identification of prognostic indicators, and appropriate treatment planning.
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PMID:Mast cell tumors in the dog. 1285 32

Systemic mast cell disorders in most instances appear to be clonal disorders of the mast cell and its progenitor. Symptoms result from a pathological release of mast cell mediators and a destructive mast cell infiltration. Cutaneous mastocytosis is most frequently seen in children and may regress. Systemic mastocytosis (SM) is a persistent disease. A somatic c-kit mutation at codon 816 is often detectable in haematopoietic cells. The clinical course of mastocytosis is variable, ranging from indolent to aggressive. Five categories of disease are recognized: Indolent SM, aggressive SM, SM with associated clonal haematological non-mast cell-lineage disease (AHNMD) and mast cell leukaemia (MCL). In SM-AHNMD, additional genetic abnormalities have been reported. Patients with cutaneous or indolent systemic disease are treated symptomatically. Patients with aggressive disease are candidates for cytoreductive therapy. The use of 'Kit-targeting' tyrosine kinase inhibitors are best selected following a mutational analysis of c-kit. For instance, the D816V mutation appears to be associated with relative resistance against imatinib. However, imatinib has been used with success in patients with SM-hypereosinophilic syndrome (HES) and the FIPL1/PDGFRA fusion gene and in a patient with mastocytosis with a mutation outside of codon 816. The value of bone marrow transplantation remains under investigation.
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PMID:Mastocytosis. 1660 39

Mastocytosis refers to a rare collection of disorders, both cutaneous and systemic, that are characterized by increased numbers of mast cells. Depending on the extent of the disease, these disorders may present with symptoms resulting from mast cell degranulation including flushing, diarrhea, vomiting, cramping, syncope, or anaphylaxis. In pediatric patients, cutaneous involvement is most prevalent in the form of urticaria pigmentosa, which is typically asymptomatic or minimally so with resolution by adolescence. In this case report and review of literature, we review a case of a 3-year-old child with uritcaria pigmentosa displaying recurrent syncope and anaphylaxis as the first presentation of systemic mastocytosis. We found data to be limited on this topic, and concluded that pediatric patients with prior diagnoses of cutaneous mastocytosis could benefit from either more aggressive screening for systemic disease or prophylactic treatment with antihistamines and rescue subcutaneous epinephrine.
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PMID:Recurrent syncope and anaphylaxis as presentation of systemic mastocytosis in a pediatric patient: case report and literature review. 1663 42

Urticaria pigmentosa (UP) is a clinicopathologic term used to describe reddish-brown cutaneous macules and papules, characterized histologically by mast cell infiltration of the papillary and upper reticular dermis and reactive basal hyperpigmentation of the overlying epidermis. Although typically a benign, self-limited disorder of childhood, a significant proportion (up to 30%) of adolescent and adult-onset UP represents cutaneous involvement by underlying systemic mastocytosis (SM). Predicting the course of cutaneous mast cell disease has been limited by a lack of diagnostic and prognostic markers. In patients with SM, neoplastic bone marrow mast cells show aberrant surface expression of CD25. However, whether CD25 expression on cutaneous mast cells is associated with underlying SM is unknown. In this study, we performed a clinicopathologic analysis of 30 adult patients presenting with UP between 1987 and 2007. Cutaneous mast cell infiltration pattern, cytomorphology, density, and CD25 immunoreactivity were correlated with underlying or subsequent SM. On the basis of clinical and pathologic follow-up, 10 of 30 (33%) patients were diagnosed with SM and 20 of 30 (67%) with limited cutaneous mastocytosis (CM). Although cutaneous mast cell density was slightly higher in patients with SM compared to those with limited CM (P=0.047), neither mast cell cytomorphology nor infiltration pattern correlated with underlying systemic disease. However, cutaneous mast cells from all 10 patients with SM (100%) were immunoreactive for CD25, compared to only 5 of 20 (25%) with limited CM (P<0.001). Our findings suggest that immunoreactivity for CD25 in cutaneous mast cells may be useful for stratifying adult patients presenting with UP for additional clinical evaluation.
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PMID:CD25 expression on cutaneous mast cells from adult patients presenting with urticaria pigmentosa is predictive of systemic mastocytosis. 1816 81

Mastocytosis is a heterogeneous entity that may present as either a cutaneous or systemic disease. Progression of pediatric cutaneous mastocytosis (CM) is uncommon, but in adults, this condition persists and often progresses to systemic disease. Mast cell proliferation and differentiation from stem cell precursors depend on a number of factors, including a mast cell tyrosine kinase receptor (kit) and its ligand (the stromal cell-derived cytokine stem cell factor). A gain-of-function mutation in codon 816 of c-kit is frequently present in mast cells of patients with systemic mastocytosis (SM). The diagnostic approach for a patient with suspected mast cell disease includes a thorough skin examination, a skin biopsy, a serum tryptase level, and bone marrow aspiration and biopsy. The treatment is directed toward avoidance of triggers of mast cell mediator release and management of symptoms. Aggressive cases are managed with cytoreductive therapies, such as interferon alfa-2b and cladribine. Research has been directed at more specific treatment modalities, including specific kit tyrosine kinase inhibitors.
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PMID:Systemic mastocytosis: classification, pathogenesis, diagnosis, and treatment. 1927 68

Urticaria involves intensely pruritic, raised wheals, with or without edema of the deeper cutis. It is usually a self-limited, benign reaction, but can be chronic. Rarely, it may represent serious systemic disease or a life-threatening allergic reaction. Urticaria has a lifetime prevalence of approximately 20 percent in the general population. It is caused by immunoglobulin E- and nonimmunoglobulin E-mediated mast cell and basophil release of histamine and other inflammatory mediators. Diagnosis is made clinically. Chronic urticaria is usually idiopathic and requires only a simple laboratory workup unless elements of the history or physical examination suggest specific underlying conditions. Treatment includes avoidance of triggers, although these can be identified in only 10 to 20 percent of patients with chronic urticaria. First-line pharmacotherapy for acute and chronic urticaria is nonsedating second-generation antihistamines (histamine H1 blockers), which can be titrated to larger than standard doses. First-generation antihistamines, histamine H2 blockers, leukotriene receptor antagonists, and brief corticosteroid bursts may be used as adjunctive treatment. More than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within one year.
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PMID:Urticaria: evaluation and treatment. 2153 21

Mastocytosis arises from clonal mast cell expansion and the resultant accumulation of mast cells in cutaneous and sometimes extracutaneous tissues. Recent studies have demonstrated that c-kit mutations seem to be more prevalent in pediatric mastocytosis than previously assumed, but what determines disease evolution and severity in the individual patient remains elusive. For the large majority of children, mastocytosis is a self-limited cutaneous disease that spontaneously regresses before they reach adult age. Rarely, children develop systemic disease progression that is the hallmark of adult-onset disease. Therefore, invasive diagnostic testing, including performing a bone marrow biopsy, is not routinely recommended and usually reserved for children that present with signs of systemic involvement and persistently elevated serum tryptase levels. Despite its often-transient nature and limited skin involvement, some children experience challenging disease-associated symptoms due to spontaneous or trigger-induced mast cell degranulation. Anticipation of and preparation for potential complications can in many instances avoid symptomatic exacerbations. Proper symptomatic treatment and supportive care can often improve the child's quality of life. Cytoreductive therapy is usually not indicated given the natural history of spontaneous disease resolution.
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PMID:Primary mast cell disorders in children. 2415 Jul 53

Mastocytosis is a disorder of abnormal mast cell proliferation, with clinical features that include flushing, pruritus, abdominal pain, diarrhea, hypotension, syncope, and musculoskeletal pain. These features are the result of mast cell mediator release and infiltration into target organs. Patients of all ages may be affected, although in children, manifestations primarily involve the skin. Most patients with systemic disease have a somatically acquired activating mutation in the KIT oncogene. This article discusses the causes and pathogenesis of mastocytosis, with an overview of the clinical features and the approach to diagnosis, evaluation, and therapy in adults and pediatric patients.
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PMID:Mastocytosis. 2426 98


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