Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mastocytosis is a neoplastic disease involving mast cells (MC) and their CD34+ progenitors. Symptoms in mastocytosis are caused by biological mediators released from MC and/or the infiltration of neoplastic MC in various organs, the skin and the bone marrow being predominantly involved. A WHO consensus classification for mastocytosis exists, which is widely accepted and includes three major categories: (1) Cutaneous mastocytosis (CM), a benign disease in which MC infiltration is confined to the skin, is preferentially seen in young children and exhibits a marked tendency to regress spontaneously. (2) Systemic mastocytosis (SM) which is commonly diagnosed in adults and includes four major subtypes: (i) indolent SM (ISM, the most common form involving mainly skin and bone marrow); (ii) a unique subcategory termed SM with an associated non-mast cell clonal hematological disease (SM-AHNMD); (iii) aggressive SM usually presenting without skin lesions, and (iv) MC leukemia, probably representing the rarest variant of human leukemias. (3) The extremely rare localized extracutaneous MC neoplasms, either presenting as malignancy (MC sarcoma) or as benign tumor termed extracutaneous mastocytoma. Diagnostic criteria for mastocytosis are available and are widely accepted. SM criteria include one major criterion (multifocal compact tissue infiltration by MC) and four minor criteria: (1) prominent spindling of MC; (2) atypical immunophenotype of MC with coexpression of CD2 and/or CD25 (antigens which have not been found to be expressed on normal/reactive MC); (3) activating (somatic) point mutations of the c-kit proto-oncogene usually involving exon 17, with the imatinib-resistant type D816V being most frequent, and (4) persistently elevated serum tryptase level (>20 ng/ml). To establish the diagnosis of SM, at least one major and one minor criterion, or at least three minor criteria, have to be fulfilled. The natural clinical course of mastocytosis is variable. Most patients, in particular those with CM and ISM, remain in an indolent stage over many years or even decades, while others, in particular those with aggressive SM, SM-AHNMD, or mast cell leukemia, show a progressive course, usually with a fatal outcome.
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PMID:Mastocytosis: state of the art. 1758 83

The WHO has published an updated classification of mastocytosis and the criteria for the diagnosis of systemic mastocytosis (SM). These include one major criterion, compact mast cell (MC) infiltrates in extracutaneous tissues, and four minor criteria, i.e. cytomorphologic atypia with spindling of MC (>25 %), detection of the activating somatic c-kit mutation D816 V in MC, aberrant expression of CD2 and/or CD25 on MC, and an elevated serum tryptase level (>20 ng/ml). Systemic mastocytosis is diagnosed when the major plus one minor, or three minor criteria are fulfilled. In the present study, we have established methods for the detection of CD25 and the c-kit mutation D816V in paraffin-embedded bone marrow trephine biopsy specimen of 57 patients with various subtypes of mastocytoses and 239 controls. While MCs in almost all patients with SM (55/57) expressed CD25, only 2/239 of the control samples contained CD25-positive MCs. With newly designed molecular pathological methods, c-kit codon 816 mutations were detected by "peptide nucleic acid" (PNA)-mediated PCR-clamping and/or analysis of microdissected MC in 52/57 cases with SM. All cases with detectable c-kit mutations also contained CD25-positive MC. The c-kit mutation D816 V was also detected in microdissected cells of associated hematologic neoplasias in 6/15 cases. With the methods established for the investigation of paraffine-embedded tissues, the pathologist plays a central role in the diagnosis of SM.
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PMID:[Immunohistochemical and molecular characterization of systemic mastocytoses]. 1803 98

Systemic mastocytosis (SM) is characterized by the accumulation of neoplastic mast cells in bone marrow and other organs. Gastrointestinal (GI) symptoms are common in both SM and cutaneous mastocytosis [urticaria pigmentosa (UP)], and are usually caused by the release of histamine and other inflammatory mediators. Occasionally, neoplastic mast cells may also directly infiltrate the GI tract. Previous studies have suggested that enumeration of the mast cells in GI biopsies may help establish the diagnosis of SM. However, mast cells have been reported to be increased in various inflammatory diseases, and mast cell density has not been systematically evaluated in other GI disorders. Recently, expression of CD25 by mast cells in bone marrow has been shown to be specific for SM. The purpose of this study was (1) to quantitate and compare mast cells in mucosal biopsies from patients with SM involving the GI tract, UP with GI symptoms, and a control group of diverse inflammatory disorders, and (2) to determine whether immunostaining for CD25 can be used to distinguish neoplastic from reactive mast cells in GI biopsies. Seventeen GI biopsies from 6 patients with SM; 17 GI biopsies from 5 patients with UP; and 157 control cases including 10 each normal stomach, duodenum, terminal ileum, and colon, Helicobacter pylori gastritis, bile reflux gastropathy, peptic duodenitis, celiac disease, Crohn disease, ulcerative colitis, lymphocytic colitis, and collagenous colitis, 20 biopsies from 16 patients with irritable bowel syndrome, 8 biopsies from 5 patients with parasitic infections, and 9 biopsies from 7 patients with eosinophilic gastroenteritis were immunostained for mast cell tryptase, c-kit (CD117), and CD25. Mucosal mast cells were quantitated, and the presence or absence of CD25 expression on mast cells was determined. In SM patients, mast cells in the small intestine and colon numbered >100/high-power field (HPF) in nearly all cases (mean 196/HPF; range 74 to 339). This was significantly higher than in GI biopsies from UP patients (mean 17/HPF; range 8 to 32, P<0.0001) and all inflammatory diseases (P<0.01). Mast cell density in other disorders ranged from a mean of 12/HPF in H. pylori gastritis to 47/HPF in parasitic infections. Interestingly, all SM biopsies (and none of the other cases) contained aggregates or confluent sheets of mast cells. In addition, mast cells in all SM cases were positive for CD25, whereas GI mucosal mast cells in UP and all other control cases were negative. In conclusion, quantitation of mast cells can be helpful to diagnose SM in GI mucosal biopsies, although mast cells are also markedly increased in parasitic infections. Aggregates or sheets of mast cells are only seen in SM. Immunoreactivity for CD25 in GI mucosal mast cells is specific for SM and can be used to confirm the diagnosis.
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PMID:Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis. 1805 23

Systemic mastocytosis (SM) comprises a heterogeneous group of disorders characterized by infiltration of bone marrow and other tissues by neoplastic mast cells. A subset of patients with SM has associated hematologic malignancy usually of myeloid origin and comprises an entity termed systemic mastocytosis with associated clonal hematological non-mast cell lineage disease (SM-AHNMD) by the current WHO classification. Reports of clonal lymphoid malignancies associated with SM are rare. We describe a patient who was simultaneously diagnosed with indolent SM and a plasma cell dyscrasia fitting the definition of monoclonal gammopathy of undetermined significance (MGUS). We also discuss the pathologic interaction between the neoplastic mast cells of SM and the lymphoid/plasma cell malignancy when these two entities coexist.
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PMID:Systemic mastocytosis with plasma cell dyscrasia: report of a case. 1806 67

Systemic mastocytosis is an uncommon condition characterized by abnormal proliferation of mast cells in one or more organ. The specific D816V KIT mutation is present in most cases. Gastrointestinal symptoms occur commonly but histologic characterization of gastrointestinal involvement is incomplete. The purpose of this study was (1) to describe the clinicopathologic features in five patients with systemic mastocytosis involving the gastrointestinal tract and (2) to determine whether gastrointestinal involvement is associated with the usual D816V mutation or a different mutation. Clinical details were obtained from the hospital of origin or referring pathologist. Histologic features were documented in slides stained with hematoxylin and eosin, mast cell tryptase and CD117. Molecular analysis for the D816V KIT mutation was performed on formalin-fixed paraffin-embedded sections. Symptoms included diarrhea/loose stools (n=5), abdominal pain (n=4), vomiting (n=3) and weight loss (n=3). Other findings included cutaneous lesions of mastocytosis (n=4), malabsorption (n=2), hypoalbuminemia (n=2) and constitutional growth delay (n=1). Sites of gastrointestinal involvement included the colon (n=5), duodenum (n=3) and terminal ileum (n=3). Endoscopic/gross findings included mucosal nodularity (n=4), erosions (n=2) and loss of mucosal folds (n=2). In three patients the endoscopic appearance was considered consistent with inflammatory bowel disease. All cases showed increased mast cell infiltration of the lamina propria, confirmed by immunohistochemistry for mast cell tryptase and CD117. In two cases, mast cells had abundant clear cytoplasmic resembling histiocytes. Marked eosinophil infiltrates were present in four patients, in one patient leading to confusion with eosinophilic colitis. Architectural distortion was noted in three cases. The D816V KIT mutation was present in all four cases tested. In conclusion, gastrointestinal involvement by systemic mastocytosis is characterized by a spectrum of morphologic features that can be mistaken for inflammatory bowel disease, eosinophilic colitis or histiocytic infiltrates. Systemic mastocytosis involving the gastrointestinal tract is associated with the usual D816V KIT mutation.
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PMID:Systemic mastocytosis involving the gastrointestinal tract: clinicopathologic and molecular study of five cases. 1893 52

Systemic mastocytosis is an extremely rare disease characterised by abnormal mast cell production and accumulation of mast cells in the bone marrow or organs, and to some extent also in the skin (urticaria pigmentosa). To date there have been no descriptions of death caused by systemic mastocytosis. The present first description of such a fatality is based upon a case of anaphylactic histamine shock, probably caused by the consumption of peanuts. The affected person suffered from urticaria pigmentosa and developed a fairly typical pruritus prior to death. In the serum sample taken post-mortem the tryptase concentration was markedly elevated. The diagnosis of systemic mastocytosis was established on the basis of two primary and three secondary criteria according to the WHO classification, which underlines the importance of histological investigations in cases where the cause of death is unclear.
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PMID:[Sudden death in the presence of systemic mastocytosis and urticaria pigmentosa]. 1921 69

Mastocytosis is a clonal disorder of the mast cell and its precursor cells, and is characterised by proliferation and accumulation of mast cells within various organs, most commonly the skin. Systemic mastocytosis is a rare but well-recognised cause of secondary osteoporosis, accounting for about 1.25% of cases. The pathophysiological mechanism is probably multifactorial, including increased osteoclastic activity, and a direct effect of mast cell mediators like histamine, heparin, tryptase and cytokines. Here, we report the case of a middle-aged male patient with osteoporotic vertebral fractures as a rare presenting manifestation of systemic mastocytosis. In summary, systemic mastocytosis, although rare, should be considered as a cause in patients with idiopathic osteoporosis.
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PMID:Systemic mastocytosis presenting as osteoporosis--a case report. 1930 45

Systemic mastocytosis is a stem cell disorder characterized histologically by the presence of multifocal compact aggregates of mast cells in at least one extracutaneous organ with or without evidence of skin lesions. The mast cell aggregates are accompanied by fibrosis, which is often significant. However, in spite of its frequent occurrence and severity, little is known about its characteristics. In this study, we evaluated the composition of the fibrotic mast cell aggregates by studying eight bone marrow biopsies and two spleens involved by systemic mastocytosis, and compared the findings with those observed in other fibrotic bone marrow disorders such as primary myelofibrosis and metastatic malignancy. Histochemistry and immunohistochemistry were used to evaluate: (a) extracellular matrix (reticulin, trichrome, collagen IV, laminin); (b) stromal reticulum cells (low-affinity nerve growth factor receptor); (c) presence of myofibroblastic differentiation (smooth muscle actin) and (d) microvessel density (CD34). We found that all cases showed marked reticulin and collagen fibrosis. However, unlike primary myelofibrosis and metastatic malignancy, which are usually associated with increased low-affinity nerve growth factor receptor positivity, its expression was low in all cases of systemic mastocytosis. Myofibroblastic differentiation was only focally detected in two of eight bone marrow biopsies. In all cases, the systemic mastocytosis lesions were largely devoid of type IV collagen and laminin. The latter findings were in contrast with those seen in cases of primary myelofibrosis and metastatic malignancy where smooth muscle actin, collagen IV and laminin were expressed in most cases. Also in contrast with the other two conditions, only minimal vascularity was detectable within the fibrotic mast cell lesions. These findings indicate that systemic mastocytosis exhibits a distinct pattern of stromal change, and suggest that the fibrogenetic mechanism in systemic mastocytosis is most likely different from that of other bone marrow neoplasms which are also associated with fibrosis.
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PMID:The stromal composition of mast cell aggregates in systemic mastocytosis. 1939 55

Mastocytosis denotes a wide range of disorders characterized by having abnormal growth and accumulation of mast cells. Mast cells contain histamine and other inflammatory mediators, which have diverse actions within the body, and play crucial roles in acquired and innate immunity. The diverse actions of these inflammatory mediators can lead to puzzling symptoms in individuals with mastocytosis. These symptoms can include flushing, pruritus, nausea, vomiting, abdominal pain, diarrhea, vascular instability, and headache. These clinical features generally divide into cutaneous and systemic manifestations, giving rise to the two divisions of mastocytosis: cutaneous mastocytosis (CM) and systemic mastocytosis. CM has a highly favorable clinical prognosis. Systemic mastocytosis has a range of severity, with the milder forms often remaining chronic conditions, while the severe forms have rapid complex courses with poor prognoses. Generally, treatment is aimed at avoiding mast cell degranulation, inhibiting the actions of the constitutive mediators released by mast cells and, in severe cases, cytoreductive and polychemotherapeutic agents. Behavioral intervention includes avoidance of triggers, such as heat, cold, pressure, exercise, sunlight, and strong emotions. Treatment for released histamine and other inflammatory mediators includes H1 antihistamines, H2 antihistamines, proton pump inhibitors, anti-leukotriene agents, and injectible epinephrine (for possible anaphylaxis). For severe cases, treatment includes cytoreductive agents (interferon alpha, glucocorticoids, and cladribine) and polychemotherapeutic agents (daunomycin, etoposide, and 6-mercaptopurine). For very specific and severe cases, tyrosine kinase inhibitors, imatinib and midostaurine, have shown promise.
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PMID:Contemporary challenges in mastocytosis. 1963 28

Systemic mastocytosis comprises disorders characterized by an accumulation of genetically altered mast cells in all organs and tissues due to an increased proliferation rate and reduced apoptosis of those pathologic mast cells. Release of their mediators can effectively influence organ function and can lead to systemic effects without inducing traces in routinely used laboratory parameters or imaging methods. In most cases, little invasive investigations allow diagnosing the disease and, hence, an appropriate therapy consisting of a basic medication with antihistamine and mast cell membrane-stabilizing compounds that should be supplemented, if required, by a medication adapted to individual symptoms, can be initiated. Because of the probably high prevalence of the disorder, systemic mastocytosis should be considered as a differential diagnosis in particular in the case of chronic gastrointestinal complaints such as abdominal pain/discomfort possibly associated with diarrhea, at an early stage.
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PMID:[Systemic mastocytosis--definition of an internal disease]. 2082 12


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