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Veterinary Clinical Pathology Mar 2024Cutaneous mast cell tumors are rarely reported in cattle. Although mutations in the c-KIT gene have been shown to play a central role in the oncogenesis of canine mast...
Cutaneous mast cell tumors are rarely reported in cattle. Although mutations in the c-KIT gene have been shown to play a central role in the oncogenesis of canine mast cell tumors, few data are available in cattle. This report describes the clinical, histologic, immunohistochemical, and genetic features of a multicentric cutaneous mast cell tumor in an adult cow. An 11-year-old Prim'Holstein cow was presented for a 5-month history of multiple skin nodules. Cytologic and histologic analyses of the nodules led to a diagnosis of mast cell tumors. Immunohistochemical analysis for KIT expression showed a moderate to strong signal in neoplastic mast cells with a cytoplasmic and membranous pattern. Sequencing of the c-KIT gene coding sequence revealed no mutation. Despite partial response after corticosteroid treatment, euthanasia was elected. No metastases to the lymph nodes, spleen, and liver were identified at post-mortem and histologic examinations.
Topics: Female; Cattle; Animals; Dogs; Mast Cells; Dog Diseases; Skin Neoplasms; Mastocytoma, Skin; Mutation; Proto-Oncogene Proteins c-kit; Cattle Diseases
PubMed: 38418393
DOI: 10.1111/vcp.13336 -
Clinical Case Reports Feb 2024Low dose Avapritinib is a new medication that is a potential treatment option not just for advanced systemic mastocytosis, but also for the indolent form.
Low dose Avapritinib is a new medication that is a potential treatment option not just for advanced systemic mastocytosis, but also for the indolent form.
PubMed: 38405360
DOI: 10.1002/ccr3.8500 -
Vaccines Feb 2024In the past three years, COVID-19 has had a significant impact on the healthcare systems and people's safety worldwide. Mass vaccinations dramatically improved the...
In the past three years, COVID-19 has had a significant impact on the healthcare systems and people's safety worldwide. Mass vaccinations dramatically improved the health and economic damage caused by SARS-CoV-2. However, the safety of COVID-19 vaccines in patients at high risk of allergic reactions still has many unmet needs that should be clarified. A retrospective, single-centre study was performed by collecting demographic and clinical data of patients with Mast Cell Disorders (MCDs) to evaluate the safety and tolerability of COVID-19 vaccinations. Moreover, any changes in the natural history of the underlying disease following the vaccine have been evaluated. This study included 66 patients affected with MCDs. Out of them, 52 (78.8%) received a COVID-19 vaccination and 41 (78.8%) completed the vaccination course. Premedication came first in 86.6% of our patients. A total of seven (4.5%) patients complained about an immediate reaction and two (1.3%) had a late reaction. Worsening of MCD history was observed in a single patient. Despite the overall high risk of allergic reactions, our study did not reveal any increased risk for SARS-CoV-2 allergic reactions in MCD patients, thus supporting the recommendation in favour of the SARS-CoV-2 vaccination. However, due to the potentially increased rate of anaphylactic reactions, MCD patients should receive vaccine premedication and should be treated in a hospital setting after an allergological specialistic evaluation.
PubMed: 38400185
DOI: 10.3390/vaccines12020202 -
The Journal of Allergy and Clinical... May 2024Eosinophilic esophagitis (EoE) is diagnosed and monitored using esophageal eosinophil levels; however, EoE also exhibits a marked, understudied esophageal mastocytosis.
BACKGROUND
Eosinophilic esophagitis (EoE) is diagnosed and monitored using esophageal eosinophil levels; however, EoE also exhibits a marked, understudied esophageal mastocytosis.
OBJECTIVES
Using machine learning, we localized and characterized esophageal mast cells (MCs) to decipher their potential role in disease pathology.
METHODS
Esophageal biopsy samples (EoE, control) were stained for MCs by anti-tryptase and imaged using immunofluorescence; high-resolution whole tissue images were digitally assembled. Machine learning software was trained to identify, enumerate, and characterize MCs, designated Mast Cell-Artificial Intelligence (MC-AI).
RESULTS
MC-AI enumerated cell counts with high accuracy. During active EoE, epithelial MCs increased and lamina propria (LP) MCs decreased. In controls and EoE remission patients, papillae had the highest MC density and negatively correlated with epithelial MC density. MC density in the epithelium and papillae correlated with the degree of epithelial eosinophilic inflammation, basal zone hyperplasia, and LP fibrosis. MC-AI detected greater MC degranulation in the epithelium, papillae, and LP in patients with EoE compared with control individuals. MCs were localized further from the basement membrane in active EoE than EoE remission and control individuals but were closer than eosinophils to the basement membrane in active EoE.
CONCLUSIONS
Using MC-AI, we identified a distinct population of homeostatic esophageal papillae MCs; during active EoE, this population decreases, undergoes degranulation, negatively correlates with epithelial MC levels, and significantly correlates with distinct histologic features. Overall, MC-AI provides a means to understand the potential involvement of MCs in EoE and other disorders.
Topics: Eosinophilic Esophagitis; Humans; Mast Cells; Machine Learning; Male; Female; Esophagus; Adult; Adolescent; Middle Aged; Eosinophils
PubMed: 38395083
DOI: 10.1016/j.jaci.2024.01.026 -
Acta Oncologica (Stockholm, Sweden) Feb 2024Mastocytosis is a disease characterized by accumulation of aberrant mast cells and mediator-related symptoms and is divided into systemic mastocytosis (SM) and cutaneous...
BACKGROUND
Mastocytosis is a disease characterized by accumulation of aberrant mast cells and mediator-related symptoms and is divided into systemic mastocytosis (SM) and cutaneous mastocytosis (CM). The epidemiology of mastocytosis remains incompletely understood.
OBJECTIVE
To estimate the incidence, prevalence, overall survival (OS) and burden of comorbidities in adult mastocytosis patients identified in Swedish population-based registries.
METHODS
Individuals (≥ 20 years of age) with a mastocytosis diagnosis in the National Patient Register (NPR) and/or the Swedish Cancer Register (SCR) between 2001 and 2018, were identified. In a matched cohort design, for each case five randomly selected mastocytosis-free comparators matched on age, sex, and county of residence were chosen from the Population Register. The Kaplan-Meier method was used to compare OS between individuals with mastocytosis and comparators. Information on concomitant disease at baseline was assessed by use of the Charlson Comorbidity Index (CCI).
RESULTS
We identified 2,040 adults with a mastocytosis diagnosis yielding an annual incidence of 1.56 per 100,000 (95% CI 1.29-1.87) and a prevalence of 23.9 per 100,000 (95% CI 22.8-25.0). The comorbidity burden was higher, and the OS lower, in patients with mastocytosis compared to comparators.
INTERPRETATION
We found a higher incidence and prevalence of mastocytosis compared to assessments in other settings and confirmed that the prognosis generally is favorable. Of special note was evidence of a higher comorbidity burden in mastocytosis patients compared to the background population.
LIMITATIONS
Underreporting and inconsistencies in the use of diagnostic codes.
Topics: Adult; Humans; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Prognosis; Sweden; Young Adult; Male; Female
PubMed: 38380845
DOI: 10.2340/1651-226X.2024.31406 -
American Journal of Clinical Pathology Jun 2024Flow cytometric immunophenotyping (FCI) is a fast and sensitive method for characterizing hematolymphoid neoplasms. It is not widely used in the workup of systemic...
OBJECTIVES
Flow cytometric immunophenotyping (FCI) is a fast and sensitive method for characterizing hematolymphoid neoplasms. It is not widely used in the workup of systemic mastocytosis (SM), in part because of the technical challenges and in part because the utility of FCI in assessing mast cells is not well understood. The objectives of this study were to assess the diagnostic utility of FCI in establishing a diagnosis of SM and distinguishing SM from nonneoplastic mast cells and to examine the immunophenotypic findings among SM subtypes.
METHODS
We performed FCI on bone marrow samples suspicious for SM using a panel consisting of CD2, CD25, CD30, CD45, CD117, and HLA-DR.
RESULTS
The cohort included 88 SM cases: 67 without an associated hematologic neoplasm (AHN) (PureSM) and 21 with an AHN (SM-AHN). We also assessed 40 normal/reactive controls. Overall, FCI was adequate for interpretation in 87 of 88 (99%) cases and detected at least 1 immunophenotypic aberrancy in 100% of SM cases. CD2, CD25, and CD30 were positive in 78%, 98%, and 90% of SM cases vs 0%, 13%, and 13% of cases with normal/reactive mast cells (P < .0001 for all). Two or 3 abnormalities were observed in 92% of SM cases but not in normal/reactive mast cells. Among SM cases, SM-AHN showed statistically significant less CD2 (38% vs 91%, P < .0001) and less co-expression of all 3 aberrant markers (CD2, CD25, and CD30 positive in 38% vs 86% of cases; P < .0001) than PureSM. Immunohistochemical analysis showed consistently weaker or focal expression of CD2, CD25, and CD30 than FCI, with CD2 and CD30 being falsely negative in 40% and 50% cases, respectively. A KIT D816V mutation was detected in 67% of PureSM cases and 76% of SM-AHN cases.
CONCLUSIONS
Flow cytometric immunophenotyping is a quick, sensitive, high-yield tool for evaluating the immunophenotype of mast cells. An abnormal FCI finding should prompt careful histologic evaluation and sensitive KIT D816V mutation testing to address the possibility of SM. CD2, CD25, and CD30 are important markers for the detection of immunophenotypic aberrancy of mast cells, and their frequencies of aberrancy differ across SM subtypes.
Topics: Humans; Immunophenotyping; Mastocytosis, Systemic; Flow Cytometry; Mast Cells; Middle Aged; Female; Male; Adult; Aged; Sensitivity and Specificity; Aged, 80 and over; Young Adult; Adolescent
PubMed: 38372648
DOI: 10.1093/ajcp/aqad187 -
Current Gastroenterology Reports Apr 2024Mast cell activation syndrome (MCAS) is a clinical disorder that may explain irritable bowel syndrome (IBS) type symptoms as well as other allergic symptoms experienced... (Review)
Review
PURPOSE OF REVIEW
Mast cell activation syndrome (MCAS) is a clinical disorder that may explain irritable bowel syndrome (IBS) type symptoms as well as other allergic symptoms experienced by an individual. The diagnosis and treatment of MCAS with specific focus on gastrointestinal (GI) manifestations is reviewed.
RECENT FINDINGS
Although biomarkers for MCAS remain elusive, testing for baseline serum tryptase will distinguish the type of mast cell disorder and urine tests for mast cell mediator metabolites may support the diagnosis. Endoscopy and Colonoscopy with biopsies is not used to diagnose MCAS but is important to rule out other conditions that may cause symptoms. There is increased awareness of the association between MCAS and autonomic dysfunction, small fiber neuropathy, and connective tissue disorders which all impact GI symptoms. MCAS is a disorder often of unknown etiology (idiopathic) and characterized by intermittent allergy type symptoms that affect multiple organ systems after exposure to a trigger. GI symptoms including abdominal cramping and loose stool are prominent and mimic those of IBS. Diagnostic testing is performed to assess for elevations in mast cell mediators during symptoms and to rule out other conditions. A comprehensive treatment plan includes medications that target mast cells, treatments for associated conditions including autonomic dysfunction, and management of comorbid psychiatric illness and nutritional deficits.
Topics: Humans; Mastocytosis; Mast Cell Activation Syndrome; Irritable Bowel Syndrome; Mast Cells; Gastrointestinal Diseases
PubMed: 38353900
DOI: 10.1007/s11894-024-00924-w -
Cancers Jan 2024Within our nationwide registry, we identified a D816V mutation ( D816V in 280/299 (94%) patients with advanced systemic mastocytosis (AdvSM). Age, cytopenias and the...
Within our nationwide registry, we identified a D816V mutation ( D816V in 280/299 (94%) patients with advanced systemic mastocytosis (AdvSM). Age, cytopenias and the presence of additional somatic mutations confer inferior overall survival (OS). However, little is known about the characteristics of D816V-negative (D816V) AdvSM. In 19 D816V patients, a combination of clinical, morphological and genetic features revealed three subgroups: (a) D816H- or Y-positive SM ( D816H/Y, = 7), predominantly presenting as mast cell leukemia (MCL; 6/7 patients), (b) MCL with negative sequencing ( MCL, = 7) and (c) SM with associated hematologic neoplasm ( SM-AHN, = 5). Although >70% of patients in the two MCL cohorts ( D816H/Y and ) were classified as low/intermediate risk according to prognostic scoring systems (PSS), treatment response was poor and median OS was shorter than in a D816V MCL control cohort ( = 29; 1.7 vs. 0.9 vs. 2.6 years; < 0.04). The SM-AHN phenotype was dominated by the heterogeneous AHN (low mast cell burden, presence of additional mutations) with a better median OS of 4.5 years. We conclude that (i) in MCL, negativity for D816V is a relevant prognostic factor and (ii) PSS fail to correctly classify D816V patients.
PubMed: 38339343
DOI: 10.3390/cancers16030593 -
International Journal of Molecular... Jan 2024Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM)... (Review)
Review
Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM) is a rare and most severe form of cutaneous mastocytosis, which typically occurs in childhood. There have been reports of a familial DCM with specific gene mutations, indicating both sporadic and hereditary factors involved in its pathogenesis. DCM is associated with severe MC mediator-related symptoms and an increased risk of anaphylaxis. The diagnosis is based on the appearance of skin lesions, which typically show generalized thickening, erythroderma, blistering dermographism, and a positive Darier's sign. Recognition, particularly in infants, is challenging due to DCMs resemblance to other bullous skin disorders. Therefore, in unclear cases, a skin biopsy is crucial. Treatment focuses on symptom management, mainly including antihistamines and mast cell stabilizers. In extremely severe cases, systemic steroids, tyrosine kinase inhibitors, phototherapy, or omalizumab may be considered. Patients should be equipped with an adrenaline autoinjector. Herein, we conducted a comprehensive review of literature data on DCM since 1962, which could help to better understand both the management and prognosis of DCM, which depends on the severity of skin lesions, intensity of mediator-related symptoms, presence of anaphylaxis, and treatment response.
Topics: Infant; Humans; Anaphylaxis; Rare Diseases; Mastocytosis, Cutaneous; Mastocytosis; Skin; Lupus Erythematosus, Cutaneous; Mast Cells
PubMed: 38338679
DOI: 10.3390/ijms25031401 -
Frontiers in Allergy 2023Hereditary alpha-tryptasemia (HαT) is associated with elevated basal serum tryptase (bST) and is associated with a higher risk of severe anaphylactic reactions in...
CONTEXT
Hereditary alpha-tryptasemia (HαT) is associated with elevated basal serum tryptase (bST) and is associated with a higher risk of severe anaphylactic reactions in patients with clonal mast cell disorders or IgE-mediated Hymenoptera venom-induced anaphylaxis. The consequence of this genetic trait remains to be determined in other allergic diseases and food allergy in particular.
OBJECTIVES
Here, we describe three cases of peanut allergy among siblings from a single family of four: two of them were associated with HαT, and the third one was associated with the tryptase wild-type genotype.
METHODS
genotypes were determined by digital PCR. After the case description, we provided a review of the literature regarding bST levels and tryptase genotypes in anaphylaxis, with a particular focus on food allergy.
RESULTS
Compared to the sibling with the conventional tryptase genotype, the two siblings with HαT presented a lower peanut threshold at the initial oral food challenge, higher peanut skin prick test reactivity, higher levels of specific IgE to peanut, Ara h 2, and Ara h 6, and a lower IgG4/IgE ratio after 10 years of oral immunotherapy.
CONCLUSION
The tryptase genotype and HαT status might modify the clinical presentation and biological features of food allergy.
PubMed: 38327735
DOI: 10.3389/falgy.2023.1322117