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Cureus Dec 2023KIT gene mutations in Ewing sarcomas are rare; however, they are much more frequent in other neoplasms, namely mastocytosis. We describe a case of an adult male with a...
KIT gene mutations in Ewing sarcomas are rare; however, they are much more frequent in other neoplasms, namely mastocytosis. We describe a case of an adult male with a one-year duration of recurrent episodes of pain, swelling, and redness on the proximal phalanx of the third finger of his right hand. A core biopsy suggested a possible mastocytosis. After four years of recurrent episodes and worsening symptoms, an incisional biopsy revealed an Ewing sarcoma with a KIT gene mutation (M541L, on exon 10). KIT gene mutations with gain-of-function were identified in 2.6% of Ewing sarcomas. In this case, the detection of a KIT mutation in an Ewing sarcoma developed at the site of previous mast cell proliferation raises the hypothesis of a possible sarcomatous evolution of the original lesion. To the best of our knowledge, similar cases are not described in the current literature. This is also the first report describing the KIT M541L mutation (exon 10) in Ewing sarcoma.
PubMed: 38222235
DOI: 10.7759/cureus.50537 -
Case Reports in Hematology 2024Systemic mastocytosis is defined by the clonal proliferation of abnormal mast cells. The clinical course can range from indolent forms with normal life expectancy to...
Systemic mastocytosis is defined by the clonal proliferation of abnormal mast cells. The clinical course can range from indolent forms with normal life expectancy to advanced mast cell leukemia with dismal prognosis. An association with other diseases, including myeloproliferative neoplasia, has been described. We present a case of a 75-year patient with a history of cutaneous mastocytosis who was diagnosed with mast cell leukemia more than 9 years ago and did not receive treatment. The patient presented to our clinic with acute kidney failure because of renal extramedullary hematopoiesis. Bone marrow histopathology revealed extensive fibrosis and 50% infiltration by mast cells with a c D816V mutation. No mutations supporting primary myelofibrosis were identified. Treatment with midostaurin was started, and the patient was discharged after improvement of renal function. Here, we discuss diagnostic challenges between different forms of mast cell leukemia and overlaps with other hematological malignancies.
PubMed: 38213502
DOI: 10.1155/2024/3502887 -
Scientific Reports Jan 2024In 70 patients with KIT D816V positive systemic mastocytosis (SM) including 36 patients with advanced SM (AdvSM), we correlated the extent of reported mucosal mast cell...
In 70 patients with KIT D816V positive systemic mastocytosis (SM) including 36 patients with advanced SM (AdvSM), we correlated the extent of reported mucosal mast cell ([m]MC) infiltration of the upper and/or lower gastrointestinal tract (UGIT, n = 63; LGIT, n = 64; both, n = 57) with symptoms and markers of MC burden/subtype. GI symptoms were reported by all patients (mean 2.1 number of symptoms). A strong mMC infiltration was identified in 24 patients (UGIT, 17/63, 27%; LGIT, 19/64, 30%). Concurrent involvement of UGIT and LGIT (n = 12) correlated with female gender (75%) and a higher symptom burden (mean 2.7) but not with MC burden or subtype. Significant differences between non-AdvSM and AdvSM were reported regarding food intolerance (54% vs. 17%), cramping (54% vs. 22%) and weight loss (0% vs. 64%). KIT D816V was identified in 54/56 (96%) available biopsies. In 46 patients, digital PCR revealed a correlation with low albumin levels (r = - 0.270, P = 0.069) and the KIT D816V VAF in peripheral blood (r = 0.317, P = 0.036) but not with the extent of mMC infiltration or markers of MC burden/subtype. Although MC mediator triggered GI symptoms have a substantial impact on the quality of life, correlation to objective disease parameters is lacking thus making its systematic assessment challenging.
Topics: Humans; Female; Mastocytosis, Systemic; Quality of Life; Gastrointestinal Tract; Biopsy; Food Intolerance
PubMed: 38184670
DOI: 10.1038/s41598-023-49749-z -
Cirugia Pediatrica : Organo Oficial de... Jan 2024Cutis marmorata telangiectatica congenita (CMTC) is a rare capillary malformation characterized by persistent reticular and violaceous erythema. We present two cases of...
INTRODUCTION
Cutis marmorata telangiectatica congenita (CMTC) is a rare capillary malformation characterized by persistent reticular and violaceous erythema. We present two cases of CMTC.
CLINICAL OBSERVATION
The first case involved a 13-month-old male with a reticular violaceous macule on the left gluteal region and a brownish papule with Darier's sign on the inner malleolus of the left foot, which was biopsied, revealing > 15 mast cells per field, leading to a diagnosis of CMTC and solitary cutaneous mastocytoma. The second case involved a newborn with a characteristic CMTC lesion without other malformations at birth, who subsequently developed two cutaneous tumors consistent with infantile hemangiomas during follow-up.
DISCUSSION
CMTC is a benign condition. However, approximately 50% of cases exhibit associated anomalies. When CMTC is suspected, musculoskeletal, ophthalmological, and cutaneous malformations should be ruled out. To the best of our knowledge, this is the first report of CMTC associated with mastocytoma and one of the few cases associated with infantile hemangioma.
Topics: Infant, Newborn; Male; Humans; Infant; Biopsy; Livedo Reticularis; Mastocytoma
PubMed: 38180100
DOI: 10.54847/cp.2024.01.15 -
Blood Advances Feb 2024
Comparative Study
Topics: Humans; Leukemia, Myeloid, Acute; Mastocytosis, Systemic; Mutation; Retrospective Studies
PubMed: 38170739
DOI: 10.1182/bloodadvances.2023012006 -
Diagnostics (Basel, Switzerland) Dec 2023Tryptase has proven to be a very useful and specific marker to demonstrate mast cell activation and degranulation when an acute (i.e., within 4 h after the event) and... (Review)
Review
Tryptase has proven to be a very useful and specific marker to demonstrate mast cell activation and degranulation when an acute (i.e., within 4 h after the event) and baseline value (i.e., at least 24 h after the event) are compared and meet the consensus formula (i.e., an increase of 20% + 2). The upper limit of normal determined by the manufacturer is 11.4 ng/mL; however, this boundary has been the subject of debate. According to ECNM and AIM experts, the normal range of baseline tryptase should be 1 to 15 ng/mL. A genetic trait, hereditary alpha tryptasemia, characterized by an increased alpha coding copy number is associated with a baseline value above 8 ng/mL. Elevated tryptase can also be found in chronic kidney disease, obesity, and hematological neoplasms. A tryptase > 20 ng/mL serves as a minor criterion to diagnose systemic mastocytosis and an increase in tryptase > 20% + 2 during an acute event is a required criterion in the diagnosis of mast cell activation syndrome. The goal of this review is to demonstrate the (in)significance of tryptase using some clinical vignettes and to provide a practical guide on how to manage and interpret an elevated tryptase level.
PubMed: 38132246
DOI: 10.3390/diagnostics13243662 -
Revista de Gastroenterologia de Mexico... 2023
Topics: Humans; Mastocytosis, Systemic; Intestinal Perforation
PubMed: 38129248
DOI: 10.1016/j.rgmxen.2023.08.006 -
Cancers Nov 2023Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical... (Review)
Review
Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. The new ICC classifies SM slightly differently. The diagnosis of SM requires the integration of bone marrow morphologic, immunophenotypic, and molecular findings, as well as clinical signs and symptoms. Moreover, understanding the wide range of clinical presentations for patients with mast cell disorders is necessary for accurate and timely diagnosis. This review provides an updated overview of mast cell disorders, with a special emphasis on SM, including the latest approaches to diagnosis, prognostic stratification, and management of this rare disease.
PubMed: 38067330
DOI: 10.3390/cancers15235626 -
The Journal of Allergy and Clinical... Mar 2024Idiopathic mast cell activation syndrome (iMCAS) is characterized by severe, episodic systemic mast cell (MC) activation and mediator-related symptoms, an event-related...
BACKGROUND
Idiopathic mast cell activation syndrome (iMCAS) is characterized by severe, episodic systemic mast cell (MC) activation and mediator-related symptoms, an event-related increase in serum tryptase levels, and response to MC-targeted therapies in the absence of underlying IgE-mediated allergy or clonal MC disorder. Studies indicating its prevalence using evidence-based diagnostic criteria are lacking.
OBJECTIVE
To assess the prevalence and clinical and laboratory features of patients with iMCAS.
METHODS
We conducted a retrospective evaluation of data from 703 consecutive patients (aged ≥18 years) referred to our center based on suspicion of having MC disorders. Patients underwent a thorough clinical workup including patient history, allergy tests, KIT D816V mutation analysis, and/or bone marrow investigation. Disease activity was prospectively assessed during follow-up visits.
RESULTS
We identified 31 patients with confirmed iMCAS. Furthermore, hereditary α-tryptasemia was detected in three patients with baseline tryptase levels greater than 8 ng/mL. The most common clinical presentation during MCAS episodes was mucocutaneous symptoms in patients with iMCAS, especially urticaria or angioedema. However, these symptoms were less prevalent in patients with clonal MCAS (P = .015). The duration of diagnostic delay was significantly longer in patients with iMCAS compared to those with clonal MCAS (P = .02).
CONCLUSIONS
The overall prevalence of iMCAS was 4.4% in the entire cohort, which indicates that iMCAS is an uncommon condition. To accurately diagnose iMCAS, it is crucial to evaluate suspected patients using the three diagnostic MCAS criteria. This involves performing a comprehensive allergy work-up including laboratory tests and ultrasensitive mutation analysis of KIT D816V. Subsequently, recommended diagnostic algorithms should be applied.
Topics: Humans; Adolescent; Adult; Mast Cells; Mast Cell Activation Syndrome; Tryptases; Retrospective Studies; Prevalence; Delayed Diagnosis; Mastocytosis; Hypersensitivity; Anaphylaxis
PubMed: 38056692
DOI: 10.1016/j.jaip.2023.11.041 -
Oxford Medical Case Reports Nov 2023Systemic mastocytosis is a rare malignancy whose main diagnostic finding is the abnormal proliferation of clonal mast cells. In this report, a 63-year-old woman is...
Systemic mastocytosis is a rare malignancy whose main diagnostic finding is the abnormal proliferation of clonal mast cells. In this report, a 63-year-old woman is presented who was referred to the emergency department with lower back pain. Due to the hypereosinophilia in blood tests, a bone marrow biopsy was performed, and except for the presence of a large number of mastocytes, no other pathologic findings were seen. Furthermore, the immunohistochemistry test showed positive CD117 and CD25 markers, and the patient's platelet-derived growth factor receptor alpha test was positive. Hence, the patient was diagnosed with aggressive systemic mastocytosis. Treatment was initiated with the Cladribine regimen, but unfortunately, in the third course, the patient experienced bradycardia and loss of consciousness and expired. Systemic mastocytosis can manifest itself with non-cutaneous symptoms. Non-cutaneous symptoms do not rule out systemic mastocytosis as a differential diagnosis in patients with hypereosinophilia.
PubMed: 38033410
DOI: 10.1093/omcr/omad095