scholarly journals The Recurrent Flush: A Case and Review of Systemic Mastocytosis

2018 ◽  
Vol 13 (2) ◽  
Author(s):  
Wasim Mansoor ◽  
Rodrigo Cavalcanti ◽  
Shaan Chugh
Keyword(s):  
Weight Loss ◽  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Myeloproliferative Disorders ◽  
Acute Onset ◽  
Future Directions ◽  
Visceral Organs ◽  
Hematologic Neoplasm ◽  
Specific Symptoms ◽  
Current Practices

Systemic Mastocytosis (SM) is a hematologic neoplasm characterized by an abnormal proliferation of mast cells, which have the potential to infiltrate one or more visceral organs.  Patients can present with a wide constellation of symptoms making it a challenging diagnosis for clinicians.  Non-specific symptoms such as fatigue, headache, and weight loss may predominate; however, some patients may present with acute onset of urticaria, flushing, and diarrhea. Due to its rarity, clinicians often face a challenge in evaluating, diagnosing and effectively treating systemic mastocytosis.  Identification during the indolent phase is important as SM can progress to aggressive leukemias or myeloproliferative disorders. In this article, we present a case of SM, and discuss current practices in diagnosis, evaluation and management.  We conclude with future directions for treatments and diagnosis

scholarly journals Epigenetic Changes in Neoplastic Mast Cells and Potential Impact in Mastocytosis

2021 ◽  
Vol 22 (6) ◽  
pp. 2964
Author(s):  
Edyta Reszka ◽  
Ewa Jabłońska ◽  
Edyta Wieczorek ◽  
Peter Valent ◽  
Michel Arock ◽  
...  
Keyword(s):  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Epigenetic Changes ◽  
Hematologic Neoplasm ◽  
Epigenetic Events ◽  
Organ Systems ◽  
Abnormal Accumulation ◽  
Current Article ◽  
Potential Impact ◽  
Methylation Patterns

Systemic mastocytosis (SM) is a hematologic neoplasm with abnormal accumulation of mast cells in various organ systems such as the bone marrow, other visceral organs and skin. So far, only little is known about epigenetic changes contributing to the pathogenesis of SM. In the current article, we provide an overview of epigenetic changes that may occur and be relevant to mastocytosis, including mutations in genes involved in epigenetic processes, such as TET2, DNMT3A and ASXL1, and global and gene-specific methylation patterns in neoplastic cells. Moreover, we discuss methylation-specific pathways and other epigenetic events that may trigger disease progression in mast cell neoplasms. Finally, we discuss epigenetic targets and the effects of epigenetic drugs, such as demethylating agents and BET-targeting drugs, on growth and viability of neoplastic mast cells. The definitive impact of these targets and the efficacy of epigenetic therapies in advanced SM need to be explored in future preclinical studies and clinical trials.

scholarly journals Response Criteria in Advanced Systemic Mastocytosis: Evolution in the Era of KIT Inhibitors

2021 ◽  
Vol 22 (6) ◽  
pp. 2983
Author(s):  
William Shomali ◽  
Jason Gotlib
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Myeloproliferative Neoplasms ◽  
Organ Damage ◽  
Response Criteria ◽  
Molecular Response ◽  
Tryptase Level ◽  
Hematologic Neoplasm ◽  
Kit D816v

Systemic mastocytosis (SM) is a rare clonal hematologic neoplasm, driven, in almost all cases, by the activating KIT D816V mutation that leads to the growth and accumulation of neoplastic mast cells. While patients with advanced forms of SM have a poor prognosis, the introduction of KIT inhibitors (e.g., midostaurin, and avapritinib) has changed their outlook. Because of the heterogenous nature of advanced SM (advSM), successive iterations of response criteria have tried to capture different dimensions of the disease, including measures of mast cell burden (percentage of bone marrow mast cells and serum tryptase level), and mast cell-related organ damage (referred to as C findings). Historically, response criteria have been anchored to reversion of one or more organ damage finding(s) as a minimal criterion for response. This is a central principle of the Valent criteria, Mayo criteria, and International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria. Irrespective of the response criteria, an ever-present challenge is how to apply response criteria in patients with SM and an associated hematologic neoplasm, where the presence of both diseases complicates assignment of organ damage and adjudication of response. In the context of trials with the selective KIT D816V inhibitor avapritinib, pure pathologic response (PPR) criteria, which rely solely on measures of mast cell burden and exclude consideration of organ damage findings, are being explored as more robust surrogate of overall survival. In addition, the finding that avapritinib can elicit complete molecular responses of KIT D816V allele burden, establishes a new benchmark for advSM and motivates the inclusion of definitions for molecular response in future criteria. Herein, we also outline how the concept of PPR can inform a proposal for new response criteria which use a tiered evaluation of pathologic, molecular, and clinical responses.

scholarly journals Highly Aggressive CD4-Positive Mast Cell Leukaemia (Leukaemic Variant) Associated with Isolated Trisomy 19 and Hemophagocytosis by Neoplastic Mast Cells: A Case Report with Challenging Experience and Review

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Dina Sameh Soliman ◽  
Ahmad Al-Sabbagh ◽  
Feryal Ibrahim ◽  
Amna Gameil ◽  
Mohamed Yassin ◽  
...  
Keyword(s):  
Mast Cell ◽  
Case Report ◽  
T Cell ◽  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Peripheral Blood Smear ◽  
Skin Lesions ◽  
Acute Onset ◽  
Cell Leukaemia ◽  
First Case

Background. Mast cell leukaemia is a unique disease among hematopoietic neoplasms, being one of the rarest leukaemia subtypes. In addition, its prompt diagnosis is usually challenging. This is due to its heterogeneity in clinical presentations and cytomorphological and immunophenotypical features together with potential associations with other hematologic neoplasms which can complicate the condition and delay accurate diagnosis. To the best of our knowledge, this is the first case report of CD4-positive mast cell leukaemia. Case Presentation. A 39-year-old male presented with acute onset of fever, abdominal pain, and generalized body aches of two-week duration. Peripheral blood smear showed circulating blasts (13%) with coarsely basophilic granulation. Bone marrow (BM) aspirate showed extensive infiltration with immature mast cells of blast-like morphology with trilineage dysplasia and evident hemophagocytic activity exhibited by histiocytes and neoplastic mast cells. BM biopsy was diffusely infiltrated with many atypical mast cells positive for CD45, CD117, mast cell tryptase, CD25, and CD4 with partial positivity for CD7 and CD30. Cytogenetics showed an abnormal karyotype: 47, XY, +1947, XY, +19[13]/46, XY[9]. Molecular analysis revealed a KIT D816V mutation consistent with a diagnosis of systemic mastocytosis, mast cell leukaemia. Conclusion. The expression of T-cell associated markers by abnormal mast cells is well documented; however, CD4 and CD7 expression have not previously been described in association with mast cell leukaemia. Coexpression of CD2, CD4, CD7, and CD30 by the mast cells particularly in skin lesions may provoke misinterpretation as a cutaneous T-cell neoplasm. To the best of our knowledge, this is the first report of CD4-positive mast cell leukaemia. Moreover, hemophagocytic mast cell leukaemia is a very rare morphologic variant, and possible correlation between this finding and expression of CD4 by neoplastic mast cells is a topic for further investigation.

Renal Infarction and Pulmonary Embolism in Patient with Myelodysplastic

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Mounia Bendari ◽  
Nouama Bouanani ◽  
Mohamed Amine Khalfaoui ◽  
Maryam Ahnach ◽  
Aziza Laaraj ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Myeloproliferative Neoplasms ◽  
Bone Biopsy ◽  
Bone Marrow Aspiration ◽  
Myeloproliferative Disorders ◽  
Acute Onset ◽  
International Prognostic Scoring System ◽  
Renal Infarction ◽  
The Right ◽  
Enhanced Computed Tomography

The myelodysplastic syndrome-myeloproliferative neoplasms (MDS/MPNs) are defined by a group of heterogeneous hematological malignancies resulting from stem cell−driven clonal growth of pathological hematopoietic progenitors and ineffective hematopoiesis, they are characterized concomitant myelodysplastic and myeloproliferative signs. Myelodysplastic/myeloproliferative disorders have been considered to have a higher risk of thrombus formation.We report a rare case about a 64 years old Moroccan woman, experienced renal infarction (RI) associated with pulmonary embolism as a complication of a myelodysplastic/myeloproliferative disorder.The patient complained of acute-onset severe left flank pain, a contrast-enhanced computed tomography (CT) of the chest and abdomen revealed RI by a large wedge-shaped defect in the right kidney with pulmonary embolism.Biological exam showed deep anemia, the bone marrow aspiration found myelodysplasia.the bone biopsy showed signs of myeloproliferatif disease. The karyotype was normal, BCR-ABL, JAK2, CALR mutations were absents, and MPL mutation was positive. The International Prognostic Scoring System (IPSS-R) was 0, and the patient was included to the low risk group.Anticoagulation therapy was initiated with heparin to treat RI and pulmonary embolism. Three months later, pulmonary embolism had resolved without the appearance of additional peripheral infarction.This case emphasizes the need to consider myelodysplastic/myeloproliferative disorders as a cause of infraction renal and pulmonary embolism.

PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects

Blood ◽  
2006 ◽  
Vol 107 (2) ◽  
pp. 752-759 ◽  
Author(s):  
Karoline V. Gleixner ◽  
Matthias Mayerhofer ◽  
Karl J. Aichberger ◽  
Sophia Derdak ◽  
Karoline Sonneck ◽  
...  
Keyword(s):  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Drug Effects ◽  
Kit Mutation ◽  
Growth Inhibitory ◽  
Ic50 Values ◽  
Tk Inhibitors ◽  
Mast Cell Leukemia ◽  
Kit D816v

AbstractIn most patients with systemic mastocytosis (SM), including aggressive SM and mast cell leukemia (MCL), neoplastic cells express the oncogenic KIT mutation D816V. KIT D816V is associated with constitutive tyrosine kinase (TK) activity and thus represents an attractive drug target. However, imatinib and most other TK inhibitors fail to block the TK activity of KIT D816V. We show that the novel TK-targeting drugs PKC412 and AMN107 counteract TK activity of D816V KIT and inhibit the growth of Ba/F3 cells with doxycycline-inducible expression of KIT D816V as well as the growth of primary neoplastic mast cells and HMC-1 cells harboring this KIT mutation. PKC412 was a superior agent with median inhibitory concentration (IC50) values of 50 to 250 nM without differences seen between HMC-1 cells exhibiting or lacking KIT D816V. By contrast, AMN107 exhibited more potent effects in KIT D816V- HMC-1 cells. Corresponding results were obtained with Ba/F3 cells exhibiting wild-type or D816V-mutated KIT. The growth-inhibitory effects of PKC412 and AMN107 on HMC-1 cells were associated with induction of apoptosis and down-regulation of CD2 and CD63. PKC412 was found to cooperate with AMN107, imatinib, and cladribine (2CdA) in producing growth inhibition in HMC-1, but synergistic drug interactions were observed only in cells lacking KIT D816V. Together, PKC412 and AMN107 represent promising novel agents for targeted therapy of SM. (Blood. 2006;107: 752-759)

scholarly journals Are Gastrointestinal Mucosal Mast Cells Increased in Patients With Systemic Mastocytosis?

2004 ◽  
Vol 122 (4) ◽  
pp. 560-565 ◽  
Author(s):  
Sabine I. Siegert ◽  
Joachim Diebold ◽  
Dagmar Ludolph-Hauser ◽  
Udo Löhrs
Keyword(s):  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Mucosal Mast Cells

Vascular Endothelial Growth Factors and Angiopoietins As New Players in Mastocytosis

2021 ◽  
Author(s):  
Simone Marcella ◽  
Angelica Petraroli ◽  
Mariantonia Braile ◽  
Roberta Parente ◽  
Anne Lise Ferrara ◽  
...  
Keyword(s):  
Growth Factors ◽  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Vascular Endothelial Growth Factors ◽  
Vascular Endothelial ◽  
Serum Concentrations ◽  
Kit Receptor ◽  
Clinical Variants ◽  
Endothelial Growth Factors ◽  
Kit D816v

Abstract Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patients are related to the MC-derived mediators that exert local and distant effects. MCs produce angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (ANGPTs). Serum concentrations of VEGF-A, VEGF-C, VEGF-D, ANGPT1 and ANGPT2 were determined in 64 mastocytosis patients and 64 healthy controls. Intracellular concentrations and spontaneous release of these mediators were evaluated in the mast cell lines ROSAKIT WT and ROSA KIT D816V and in human lung mast cells (HLMCs). VEGF-A, ANGPT1, ANGPT2 and VEGF-C concentrations were higher in mastocytosis patients compared to controls. The VEGF-A, ANGPT2 and VEGF-C concentrations were correlated with the symptom severity. ANGPT1 concentrations were increased in all patients compared to controls. ANGPT2 levels were correlated with severity of clinical variants and with tryptase levels. VEGF-A, ANGPT1 and VEGF-C did not differ between indolent and advanced mastocytosis. ROSAKIT WT, ROSAKIT D816V and HLMCs contained and spontaneously released VEGFs and ANGPTs. Serum concentrations of VEGFs and ANGPTs are altered in mastocytosis patients.

scholarly journals Conservative management of eosinophilic enteritis presenting with acute abdominal syndrome

2013 ◽  
pp. 124-127
Author(s):  
Marco Bassi ◽  
Gelorma Belmonte ◽  
Carmelo Luigiano ◽  
Paola Billi ◽  
Angela Salerno ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Relevant Literature ◽  
Inflammatory Cells ◽  
Therapeutic Strategies ◽  
Acute Onset ◽  
Peripheral Eosinophilia ◽  
Diffuse Infiltration ◽  
Appropriate Therapy ◽  
Specific Symptoms

Eosinophilic enteritis, an increasing recognized condition, is rare and often presents with non-specific symptoms. We report a case of a 46-year old female who presented with acute onset abdominal pain and nausea associated with ascites, small bowel thickening and peripheral eosinophilia. Diagnosis was confirmed by biopsies taken at esophagogastroduodenoscopy demonstrating diffuse infiltration by inflammatory cells, mainly eosinophils. Appropriate therapy was instituted. The patient recovered well and was symptom-free at 1-month follow up. In this report, we discuss the clinical presentation and the diagnostic criteria of the eosinophilic enteritis, and examine the pathophysiological theories and therapeutic strategies. The relevant literature on eosinophilic enteritis is summarized.

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