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British Journal of Haematology May 2024Systemic mastocytosis (SM) is a rare haematological neoplasm associated with the gain of function mutation KIT D816V in 90% of adult patients. Classically, cytogenetic...
Systemic mastocytosis (SM) is a rare haematological neoplasm associated with the gain of function mutation KIT D816V in 90% of adult patients. Classically, cytogenetic aberrations are not common except in cases of SM associated with another haematological neoplasm. We highlight here an unusual clinical presentation of SM and demonstrate the utility of advanced cytogenetic analysis (optical genome mapping, OGM) in detecting a novel cytogenetic abnormality resulting in an unusual mechanism of DNMT3A and TET2 loss of function.
PubMed: 38702998
DOI: 10.1111/bjh.19501 -
Blood May 2024
Topics: Humans; Male; Middle Aged; Mastocytosis, Systemic; Myelolipoma
PubMed: 38696191
DOI: 10.1182/blood.2024023917 -
Clinics and Research in Hepatology and... Jun 2024
Topics: Humans; Abdominal Pain; Recurrence; Male; Female; Middle Aged
PubMed: 38692352
DOI: 10.1016/j.clinre.2024.102360 -
Cureus Mar 2024The authors would like to report a rare case of telangiectasia macularis eruptiva perstans (TMEP), a form of cutaneous mastocytosis, in a 55-year-old female patient with...
The authors would like to report a rare case of telangiectasia macularis eruptiva perstans (TMEP), a form of cutaneous mastocytosis, in a 55-year-old female patient with a recent diagnosis of type 2 diabetes mellitus on empagliflozin. The patient presented with a two-month history of rash and itching on her lower extremities, unresponsive to topical treatment. A dermoscopic evaluation and a skin biopsy confirmed the diagnosis of TMEP. The patient demonstrated significant improvement with antihistamine and topical steroid treatment.
PubMed: 38690480
DOI: 10.7759/cureus.57333 -
American Journal of Clinical Pathology Apr 2024Systemic mastocytosis (SM) is a neoplasm of mast cells (MCs) characterized by their proliferation in extracutaneous organs. Systemic mastocytosis includes several...
OBJECTIVES
Systemic mastocytosis (SM) is a neoplasm of mast cells (MCs) characterized by their proliferation in extracutaneous organs. Systemic mastocytosis includes several entities with different clinical courses and prognoses. The rarity of this disease and the diversity of clinical and morphologic presentation make the diagnosis of SM very challenging. The aim of this review is to share our approach to the diagnosis of SM.
METHODS
We present 4 cases that highlight the spectrum of clinical and laboratory features of SM and outline the diagnostic process with an emphasis on morphology.
RESULTS
Pathology and laboratory medicine play a key role in investigation of SM, as correct diagnosis requires integration of morphologic, molecular, and serologic findings. In addition to awareness of microscopic findings in SM, a pathologist must keep abreast with an expanding menu of ancillary studies, particularly molecular testing.
CONCLUSIONS
Systemic mastocytosis is a challenging diagnosis that requires not only a demonstration of a clonal proliferation of MCs but also a correct subclassification based on the recently updated criteria.
PubMed: 38683762
DOI: 10.1093/ajcp/aqae047 -
Hematological Oncology May 2024
Comparative Study
Topics: Humans; Mastocytosis, Systemic; Retrospective Studies; Male; Female; Middle Aged; Aged; World Health Organization; Adult
PubMed: 38682493
DOI: 10.1002/hon.3277 -
Cytometry. Part B, Clinical Cytometry Apr 2024Flow cytometry has been widely used to study immunophenotypic patterns of maturation of most hematopoietic lineages in normal human bone marrow aspirates, thus allowing...
BACKGROUND
Flow cytometry has been widely used to study immunophenotypic patterns of maturation of most hematopoietic lineages in normal human bone marrow aspirates, thus allowing identification of changes in patterns in many myeloid malignancies. Eosinophils play an important role in a wide variety of disorders, including some myeloid neoplasms. However, changes in flow cytometric immunophenotypic patterns during normal and abnormal bone marrow eosinophilopoiesis have not been well studied.
METHODS
Fresh bone marrow aspirates from 15 healthy donors, 19 patients with hypereosinophilic syndromes (HES), and 11 patients with systemic mastocytosis (SM) were analyzed for candidate markers that included EMR-1, Siglec-8, CCR3, CD9, CD11a, CD11b, CD11c, CD13, CD16, CD29, CD34, CD38, CD45, CD44, CD49d, CD49f, CD54, CD62L, CD69, CD117, CD125 (IL-5Rα), HLA-DR, using 10 parameter flow cytometry. Putative CD34-negative immature and mature normal eosinophil populations were first identified based on changes in expression of the above markers in healthy donors, then confirmed using fluorescence-based cell sorting and morphological evaluation of cytospin preparations. The normal immunophenotypic patterns were then compared to immunophenotypic patterns of eosinophilopoiesis in patients with HES and SM.
RESULTS
The eosinophilic lineage was first verified using the human eosinophil-specific antibody EMR-1 in combination with anti-IL-5Rα antibody. Then, a combination of Siglec-8, CD9, CD11b, CCR3, CD49d, and CD49f antibodies was used to delineate normal eosinophilic maturational patterns. Early stages (eosinophilic promyelocytes/myelocytes) were identified as Siglec-8 dim/CD11b dim to moderate/CD9 dim/CCR3 dim/CD49d bright/CD49f dim, intermediate stages (eosinophilic myelocytes/metamyelocytes) as Siglec-8 moderate/CD11b moderate to bright/CD9 moderate/CCR3 moderate/CD49d moderate/CD49f moderate and mature bands/segmented eosinophils as Siglec-8 bright/CD11b bright/CD9 bright/CCR3 bright/CD49d dim/CD49f bright. Overall maturational patterns were also similar in patients with HES and SM; however, the expression levels of several surface markers were altered compared to normal eosinophils.
CONCLUSION
A novel flow cytometric antibody panel was devised to detect alterations in immunophenotypic patterns of bone marrow eosinophil maturation and evaluated in normal, HES and SM samples. This approach will allow us to elucidate changes in immunophenotypic patterns of bone marrow eosinophilopoiesis in other hematological diseases.
PubMed: 38666394
DOI: 10.1002/cyto.b.22174 -
Allergy Apr 2024Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on...
BACKGROUND
Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry.
METHODS
Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow-up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18-91 years).
RESULTS
Nine hundred and forty eight patients (38.1%) reported one or more HR`. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti-inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy-sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug-induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow-up.
CONCLUSIONS
HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years.
PubMed: 38651829
DOI: 10.1111/all.16132 -
Polish Archives of Internal Medicine Jun 2024
Topics: Humans; Imatinib Mesylate; Mastocytosis, Systemic; Pyrimidines; Female; Piperazines; Antineoplastic Agents; Benzamides; Male; Middle Aged; Syndrome
PubMed: 38640058
DOI: 10.20452/pamw.16730 -
Blood Apr 2024Timely diagnosis of systemic mastocytosis (SM) remains challenging due to care heterogeneity. We implemented a standardized approach for SM screening and diagnosis...
Timely diagnosis of systemic mastocytosis (SM) remains challenging due to care heterogeneity. We implemented a standardized approach for SM screening and diagnosis utilizing a novel healthcare system-wide international screening registry. A retrospective analysis assessed rates of SM, cutaneous mastocytosis (CM), and molecular diagnoses before and two years after care standardization. Accuracy of individual and combined SM screening tests - basal serum tryptase (BST) ≥11.5 and ≥20.0 ng/mL, REMA ≥2, monomorphic maculopapular CM, and elevated BST based upon tryptase genotype - was analyzed. Tryptase genotyping and high-sensitivity KIT p.D816V testing increased substantially two years following care standardization. SM diagnoses doubled from 47 to 94 and KIT p.D816V molecular diagnoses increased from 24 to 79. Mean BST and KIT p.D816V variant allele frequency (VAF) values were significantly lower in patients diagnosed after standardization. Hereditary-alpha tryptasemia prevalence was increased in SM prior to care standardization at 4/30 (13.3%) but reflected the general population prevalence two years later at 5/76 (6.6%). Elevated BST based upon genotype and BST ≥11.5 ng/mL had the highest sensitivities at 84.2% and 88.3%, respectively. Presence of monomorphic MPCM, elevated BST based upon tryptase genotype, and the combination of REMA ≥2 with elevated BST based upon tryptase genotype had specificities >90%. BST >20.0 ng/mL had low sensitivity and specificity and was not required to establish any indolent SM diagnosis. Care standardization increased SM diagnosis rates, particularly in patients with low BSTs. Stratifying BST based upon genotype had the best overall sensitivity and specificity of any indolent SM screening test and improved the REMA score specificity.
PubMed: 38635793
DOI: 10.1182/blood.2023023347