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International Journal of Molecular... Mar 2021Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to... (Review)
Review
Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier's sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.
Topics: Administration, Topical; Adult; Anaphylaxis; Child; Humans; Insect Bites and Stings; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Risk Factors; Skin; Tryptases
PubMed: 33799959
DOI: 10.3390/ijms22052684 -
Journal of Clinical Medicine Aug 2022The term mastocytosis refers to a heterogeneous group of disorders characterised by accumulation of clonal mast cells in different organs, most commonly in the skin.... (Review)
Review
The term mastocytosis refers to a heterogeneous group of disorders characterised by accumulation of clonal mast cells in different organs, most commonly in the skin. Little is known about the role of dermoscopy in the diagnostics of mastocytosis. To date, no systematic review on the dermoscopic features of cutaneous mastocytosis has been performed. The aim of this study was to summarise the current knowledge in the field as well as to identify the knowledge gaps to show possible directions for further studies, based on a systematic search of PubMed, Scopus, and Web of Science databases and related references published before 3 January 2022. Dermoscopic features, type of dermoscope, polarisation mode, magnification, and number of cases were analysed. In total, 16 articles were included in this review (3 case series and 13 case reports), analysing 148 patients with different variants of cutaneous mastocytosis; all of the studies analysed had a low level of evidence (V). The main dermoscopic features of urticaria pigmentosa included brown structureless areas, brown lines arranged in a network, and linear vessels distributed in a reticular pattern, with this last finding also being typical of telangiectasia macularis eruptiva perstans. The presence of either circumscribed yellow structureless areas or diffuse yellowish background was a constant pattern of mastocytoma, while nodular, pseudoangiomatous xanthelasmoid, and plaque-type mastocytosis were typified by light-brown structureless areas and/or pigment network, though the first two variants also showed yellow/yellow-orange structureless areas. Finally, pigmented streaks of radial distribution surrounding hair follicles were described to be a pathognomonic dermoscopic feature of pseudoxanthomatous mastocytosis. Although this review shows that the various clinical forms of cutaneous mastocytosis may feature diagnostic dermoscopic clues, it also underlines the need for further investigation as several relevant data are missing, including evaluation of dermoscopic pattern according to anatomical locations or "lesion age", studies on rare mastocytosis variants, evaluation of the prognostic role of dermoscopy in the context of systemic involvement, and comparative analyses with common clinical mimickers.
PubMed: 36012900
DOI: 10.3390/jcm11164649 -
Metabolic Engineering Mar 2022Heparin is an essential anticoagulant used for treating and preventing thrombosis. However, the complexity of heparin has hindered the development of a recombinant...
Heparin is an essential anticoagulant used for treating and preventing thrombosis. However, the complexity of heparin has hindered the development of a recombinant source, making its supply dependent on a vulnerable animal population. In nature, heparin is produced exclusively in mast cells, which are not suitable for commercial production, but mastocytoma cells are readily grown in culture and make heparan sulfate, a closely related glycosaminoglycan that lacks anticoagulant activity. Using gene expression profiling of mast cells as a guide, a multiplex genome engineering strategy was devised to produce heparan sulfate with high anticoagulant potency and to eliminate contaminating chondroitin sulfate from mastocytoma cells. The heparan sulfate purified from engineered cells grown in chemically defined medium has anticoagulant potency that exceeds porcine-derived heparin and confers anticoagulant activity to the blood of healthy mice. This work demonstrates the feasibility of producing recombinant heparin from mammalian cell culture as an alternative to animal sources.
Topics: Animals; Anticoagulants; Gene Editing; Heparin; Heparitin Sulfate; Mice; Swine
PubMed: 35038554
DOI: 10.1016/j.ymben.2022.01.002 -
European Annals of Allergy and Clinical... Mar 2020Tryptase is a serin-protease produced and released by mast cells after IgE-mediated or non-IgE mediated stimuli. We here review the various aspects related to the... (Review)
Review
Tryptase is a serin-protease produced and released by mast cells after IgE-mediated or non-IgE mediated stimuli. We here review the various aspects related to the molecular characteristics of the enzyme and its biological effects, the genetic basis of its production and the release kinetics. Recommendations for the clinical use of tryptase measurement developed by a task force of Società Italiana di Patologia Clinica e Medicina di Laboratorio and Associazione Allergologi Immunologi Italiani Territoriali e Ospedalieri are given on the best procedure for a correct definition of the reference values in relation to the inter-individual variability and to the correct determination of tryptase in blood and other biological liquids, in the diagnosis of anaphylaxis (from drugs, food, insect sting, or idiophatic), death from anaphylaxis (post mortem assessment) and cutaneous or clonal mastcell disorders.
Topics: Animals; Humans; Advisory Committees; Allergy and Immunology; Anaphylaxis; Autopsy; Biomarkers; Immunoglobulin E; Italy; Leukemia, Biphenotypic, Acute; Mastocytoma; Mastocytosis; Practice Guidelines as Topic; Reproducibility of Results; Tryptases
PubMed: 31994369
DOI: 10.23822/EurAnnACI.1764-1489.133 -
Clinical Endoscopy Nov 2022Extracutaneous mastocytoma is a rare benign tumor composed of mature mast cells and is located in tissues other than the skin. We report the case of a 61-year-old male...
Extracutaneous mastocytoma is a rare benign tumor composed of mature mast cells and is located in tissues other than the skin. We report the case of a 61-year-old male who was diagnosed with extracutaneous mastocytoma via colonoscopic polypectomy and biopsy. To our knowledge, this was the first case of a solitary extracutaneous mastocytoma of the colon. We reported this case and reviewed the literature.
PubMed: 34233110
DOI: 10.5946/ce.2021.003 -
Animals : An Open Access Journal From... Apr 2020Spaying and neutering dogs is commonly used to prevent the birth of unwanted animals and eliminate the risk of reproductive diseases. However, removal of the gonads... (Review)
Review
Spaying and neutering dogs is commonly used to prevent the birth of unwanted animals and eliminate the risk of reproductive diseases. However, removal of the gonads prevents the feedback of estrogen and testosterone on the pituitary and hypothalamus. As a result, luteinizing hormone (LH) is continuously elevated at supraphysiologic concentrations. Although the main role of LH is for reproductive function (e.g., ovulation), there are LH receptors present in several normal tissues including the thyroid and adrenal glands, gastrointestinal tract, cranial cruciate ligament and round ligament, and lymphocytes. In addition, there are LH receptors present in several neoplastic tissues (e.g., lymphoma, hemangiosarcoma, mastocytoma, transitional cell carcinoma, and osteosarcoma). The role of LH receptors in non-reproductive normal and neoplastic tissues is not known but may stimulate nitric oxide release and induce cell division. The precise etiology of the increased incidence of several non-reproductive long-term health complications following spaying and neutering is not known but may be related to LH receptor activation in these non-reproductive target tissues. How these effects may be mediated is described in this review.
PubMed: 32244716
DOI: 10.3390/ani10040599 -
Genes Jan 2024Mast cell tumors are a large group of diseases occurring in dogs, cats, mice, as well as in humans. Systemic mastocytosis (SM) is a disease involving the accumulation of... (Review)
Review
Mast cell tumors are a large group of diseases occurring in dogs, cats, mice, as well as in humans. Systemic mastocytosis (SM) is a disease involving the accumulation of mast cells in organs. gene mutations are very often seen in abnormal mast cells. In SM, high KIT/CD117 expression is observed; however, there are usually no gene mutations present. Mastocytoma (MCT)-a form of cutaneous neoplasm-is common in animals but quite rare in humans. KIT/CD117 receptor mutations were studied as the typical changes for human mastocytosis. In 80% of human cases, the gene substitution p.D816H was present. In about 25% of MCTs, metastasis was observed. Changes in the gene expression of certain genes, such as overexpression of the gene, promote metastasis. In contrast, the gene blocks the expression of metastasis genes. The panel of , , and has a good efficiency in discriminating healthy and MCT-affected dogs, as well as MCT-affected dogs with and without nodal metastasis. Further studies on the pathobiology of mast cells can lead to clinical improvements, such as better MCT diagnosis and treatment. Our paper reviews studies on the topic of mast cells, which have been carried out over the past few years.
Topics: Humans; Animals; Dogs; Mice; Mast Cells; Proto-Oncogene Proteins c-kit; Mastocytosis; Prognosis; Myeloproliferative Disorders; MicroRNAs
PubMed: 38275618
DOI: 10.3390/genes15010137 -
Veterinary Pathology Mar 2022Mast cell tumors (MCTs) are one of the most common cutaneous malignancies in dogs. Previous studies have reported expression of mast cell-specific proteases chymase and...
Mast cell tumors (MCTs) are one of the most common cutaneous malignancies in dogs. Previous studies have reported expression of mast cell-specific proteases chymase and tryptase in canine cutaneous MCTs and in connective tissue and mucosal mast cells. In humans and rodents, mast cells express an additional specific protease, carboxypeptidase A3 (CPA3). In this article, we describe CPA3 immunoreactivity in connective tissue, visceral, mucosal, and neoplastic mast cells in dogs. Positive immunolabeling for CPA3 was observed in nonneoplastic mast cells in 20/20 formalin-fixed paraffin-embedded normal tissues (skin, liver, spleen, intestine), and in 63/63 MCTs irrespective of their histological grade. CPA3 protein expression was comparable to that of c-kit in both the nonneoplastic and neoplastic mast cells. Three distinct labeling patterns (membranous, diffuse, and focal cytoplasmic) were observed for CPA3 in MCTs. The focal cytoplasmic labeling pattern was associated with high-grade MCTs staged with the Kiupel 2-tier grading criteria. We propose CPA3 as a novel immunohistochemical marker for canine mast cells in health and disease.
Topics: Animals; Carboxypeptidases; Dog Diseases; Dogs; Mast Cells; Proto-Oncogene Proteins c-kit; Skin Neoplasms; Tryptases
PubMed: 34894899
DOI: 10.1177/03009858211062636 -
Dermatology Practical & Conceptual Jul 2022
PubMed: 36159113
DOI: 10.5826/dpc.1203a83 -
Journal of Veterinary Diagnostic... Mar 2022Quantitative morphologic parameters assessed in cytologic samples of canine cutaneous mast cell tumors (ccMCTs) may assist with surgical planning and prognostication....
Quantitative morphologic parameters assessed in cytologic samples of canine cutaneous mast cell tumors (ccMCTs) may assist with surgical planning and prognostication. Robust cutoffs can be defined, with high reproducibility, for parameters such as the nuclear area (NA). The NA may be determined by morphometry (image analysis, NAI) or by stereology, such as the 2D-nucleator method (NAN); stereologic techniques have not been applied to cytologic specimens of ccMCT, to our knowledge. We retrospectively selected routine cytology smears from 51 ccMCT cases and screened them to determine the percentage of neoplastic mast cells with indistinct nuclear borders; this was repeated after the slides were restained with H&E. The NAI and the NAN were estimated in 100 mast cells per animal in H&E-stained slides. All nuclei were visible in H&E smears, and unbiased quantification was feasible. The NAN was similar to NAI, but less time-consuming. Both the NAN and NAI determined by cytology differed in histologic low- and high-grade ccMCTs, and in histologic grade I plus II versus grade III ccMCTs. Stereologic parameters such as the NAN could be considered as complementary techniques for the cytologic evaluation of ccMCTs.
Topics: Animals; Cytodiagnosis; Dog Diseases; Dogs; Mastocytoma, Skin; Reproducibility of Results; Retrospective Studies
PubMed: 34763591
DOI: 10.1177/10406387211058825