RESUMEN
Systemic mastocytosis (SM) with RUNX1-RUNX1T1 positive acute myeloid leukemia (AML) is a rare myeloid tumor with no standard treatment. Two cases of SM patients with RUNX1-RUNX1T1 positive AML treated with sequential avapritinib after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were reported in Henan Cancer Hospital. Mast cell in bone marrow disappeared, C-KIT mutation and RUNX1-RUNX1T1 fusion gene remained negative. Allo-HSCT sequential avapritinib is an effective treatment for SM patients with RUNX1-RUNX1T1 positive AML.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Mastocitosis Sistémica , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/genética , Mastocitosis Sistémica/genética , Mastocitosis Sistémica/terapia , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Masculino , Femenino , Adulto , Proteína 1 Compañera de Translocación de RUNX1/genética , Proteínas de Fusión Oncogénica/genética , Persona de Mediana Edad , Trasplante Homólogo , Pirazinas/administración & dosificación , Pirazoles , Pirroles , TriazinasRESUMEN
Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.
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Mastocitosis Sistémica , Humanos , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/terapia , Manejo de la Enfermedad , Oncología Médica/normas , Oncología Médica/métodosRESUMEN
Systemic Mastocytosis (SM) is a multifaceted clinically heterogeneous disease. Advanced SM (AdvSM) comprises three entities: aggressive SM (ASM), mast cell leukaemia (MCL) and SM with an associated hematologic neoplasm (SM-AHN), the latter accounting for 60-70% of all AdvSM cases. Detection of a disease-triggering mutation in the KIT gene (esp. KIT D816V) in >90% of the patients with ASM or SM-AHN has led to a significant improvement in therapeutic options by the implementation of two KIT-targeting kinase inhibitors: midostaurin and avapritinib. Although complete remissions have been reported, neither of these targeted agents is 'curative' in all patients and the duration of responses varies. The median overall survival, depending on the WHO subtype and scoring result, is approximately 1 to 4 years. Although the European Competence Network on Mastocytosis (ECNM) and American Initiative in Mast Cell Diseases (AIM) consensus groups recommend allogeneic haematopoietic cell transplantation (allo-HCT) in drug-resistant and other high-risk patients, there is a relative lack of information to guide clinicians on which patients with AdvSM should be considered for transplant, and how KIT inhibitors may fit into the transplant algorithm, including their use pre- and post-transplant to optimise outcomes. Following the generation of an expert panel with a specialist interest in allo-HCT and mastocytosis, these best practice recommendations were generated according to the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonisation and guidelines and ECNM methodology. We aim to provide a practical, clinically relevant and up-to-date framework to guide allo-HCT in AdvsM in 2024 and beyond.
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Antineoplásicos , Trasplante de Células Madre Hematopoyéticas , Leucemia de Mastocitos , Mastocitosis Sistémica , Mastocitosis , Humanos , Mastocitosis Sistémica/terapia , Mastocitosis Sistémica/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Mastocitosis/terapia , Leucemia de Mastocitos/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-kit/genética , MastocitosRESUMEN
Mastocytosis is a rare, clinically heterogenous clonal hematological neoplasm. Over 95% of patients harbor the driver KIT D816V mutation resulting in mast cell (MC) accumulation and proliferation in various organs, leading to variable symptom manifestations that result from MC mediator release in patients with systemic mastocytosis (SM) and end-organ damage in those with advanced SM. The accurate diagnostic and clinical classification of patients with SM is vital to underpin appropriate treatment options and personalize therapy. This review evaluates the current diagnostic criteria, clinical classification, risk stratification, and therapeutic options available for adult patients with nonadvanced and advanced SM.
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Mastocitosis Sistémica , Mastocitosis , Adulto , Humanos , Mastocitosis/diagnóstico , Mastocitosis/terapia , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/genética , Mastocitosis Sistémica/terapia , Mastocitos , Proteínas Proto-Oncogénicas c-kit/genética , MutaciónRESUMEN
Advanced systemic mastocytosis (SM) is a heterogeneous group of myeloid neoplasms characterized by an uncontrolled expansion of mast cells (MC) in one or more internal organs, SM-induced tissue damage, and poor prognosis. Advanced SM can be categorized into aggressive SM (ASM), MC leukemia (MCL), and SM with an associated hematologic neoplasm (SM-AHN). In a vast majority of all patients, neoplastic cells display a KIT mutation, mostly D816V and rarely other KIT variants. Additional mutations in other target genes, such as SRSF2, ASXL1, or RUNX1, may also be identified, especially when an AHN is present. During the past 10 years, improved treatment approaches have led to a better quality of life and survival in patients with advanced SM. However, despite the availability of novel potent inhibitors of KIT D816V, not all patients enter remission and others relapse, often with a multi-mutated and sometimes KIT D816V-negative disease exhibiting multi-drug resistance. For these patients, (poly)chemotherapy, antibody-based therapies, and allogeneic hematopoietic stem cell transplantation may be viable treatment alternatives. In this article, we discuss treatment options for patients with drug-resistant advanced SM, including novel KIT-targeting drugs, antibody-based drugs, and stem cell-eradicating therapies.
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Mastocitosis Sistémica , Mastocitosis , Humanos , Calidad de Vida , Mastocitosis/genética , Mastocitosis/terapia , Mastocitosis Sistémica/terapia , Mastocitosis Sistémica/tratamiento farmacológico , Mastocitos , Mutación , Proteínas Proto-Oncogénicas c-kit/genéticaRESUMEN
Mastocytosis is a heterogeneous group of neoplasms defined by a numerical increase and accumulation of clonal mast cells (MCs) in various organ systems. The disease may present as cutaneous mastocytosis or systemic mastocytosis (SM). On the basis of histopathological and molecular features, clinical variables, and organ involvement, SM is divided into indolent SM, smoldering SM, SM with an associated hematologic neoplasm, aggressive SM, and MC leukemia. Each variant is defined by unique diagnostic criteria and a unique spectrum of clinical presentations. A key driver of MC expansion and disease evolution is the oncogenic machinery triggered by mutant forms of KIT. The genetic background, additional somatic mutations, and comorbidities also contribute to the course and prognosis. Patients with SM may also suffer from mediator-related symptoms or even an MC activation syndrome. This article provides an update of concepts on the genetics, etiology, and pathology of mastocytosis, with emphasis on diagnostic criteria and new treatment concepts.
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Mastocitosis Sistémica , Mastocitosis , Humanos , Mastocitosis/diagnóstico , Mastocitosis/genética , Mastocitosis/terapia , Mastocitos/patología , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/genética , Mastocitosis Sistémica/terapia , Pronóstico , Proteínas Proto-Oncogénicas c-kit/genéticaRESUMEN
Mast cell disorders include mastocytosis and mast cell activation syndromes. Mastocytosis is a rare clonal disorder of the mast cell, driven by KIT D816V mutation in most cases. Mastocytosis is diagnosed and classified according to World Health Organization criteria. Mast cell activation syndromes encompass a diverse group of disorders and may have clonal or nonclonal etiologies. Hematologists may be consulted to assist in the diagnostic workup and/or management of mast cell disorders. A consult to the hematologist for mast cell disorders may provoke anxiety due to the rare nature of these diseases and the management of nonhematologic mast cell activation symptoms. This article presents recommendations on how to approach the diagnosis and management of patients referred for common clinical scenarios.
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Síndrome de Activación de Mastocitos , Mastocitosis Sistémica , Mastocitosis , Humanos , Mastocitos , Mastocitosis/diagnóstico , Mastocitosis/genética , Mastocitosis/terapia , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/genética , Mastocitosis Sistémica/terapiaRESUMEN
Systemic mastocytosis is a rare disease which is being better recognized and managed. While the vast majority of patients have indolent disease with variable symptom burden, a small proportion evolve or present with aggressive disease. This may be due to increases in mast cell burden (leukemic, associated with tumour masses) or more commonly due to the presence of an additional hematologic neoplasm (SM-AHN). These patients with advanced systemic mastocytosis have poor outcome; however, recent advances in diagnosis, molecular genetics and treatment have changed the prognostic landscape for this group of patients. In this review we address the most topical questions related to diagnostics, classification, new disease entities, treatment and multiparameter prognostic scoring systems.
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Neoplasias Hematológicas , Mastocitosis Sistémica , Enfermedades Mielodisplásicas-Mieloproliferativas , Humanos , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/genética , Mastocitosis Sistémica/terapia , Mastocitos/patología , Neoplasias Hematológicas/patología , PronósticoRESUMEN
ABSTRACT Introduction: Systemic Mastocytosis comprises a group of neoplastic diseases characterized by clonal expansion and infiltration of mast cells into several organs. The diagnosis and treatment of this disease may be challenging for non-specialists. Objective: Make suggestions or recommendations in Systemic Mastocytosis based in a panel of Brazilian specialists. Method and results: An online expert panel with 18 multidisciplinary specialists was convened to propose recommendations on the diagnosis and treatment of Systemic Mastocytosis in Brazil. Recommendations were based on discussions of topics and multiple-choice questions and were graded using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Chart. Conclusion: Twenty-two recommendations or suggestions were proposed based on a literature review and graded according to the findings.
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Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/terapia , Niño , AdultoRESUMEN
Mastocytosis is a rare and heterogeneous disease characterized by various clinical and biological features that affect different prognoses and treatments. The disease is usually divided into 2 principal categories: cutaneous and systemic disease (SM). Clinical features can be related to mast cell (MC) mediator release or pathological MC infiltration. SM is a disease often hard to identify, and the diagnosis is based on clinical, biological, histological, and molecular criteria with different specialists involved in the patient's clinical work-up. Among all manifestations of the disease, gastrointestinal (GI) symptoms are common, being present in 14%-85% of patients, and can significantly impair the quality of life. Here we review the data regarding GI involvement in SM, in terms of clinical presentations, histological and endoscopic features, the pathogenesis of GI symptoms, and their treatment.
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Gastroenterólogos , Enfermedades Gastrointestinales , Mastocitosis Sistémica , Mastocitosis , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/terapia , Humanos , Mastocitos , Mastocitosis/diagnóstico , Mastocitosis/patología , Mastocitosis/terapia , Mastocitosis Sistémica/complicaciones , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/terapia , Calidad de VidaRESUMEN
BACKGROUND: Systemic mastocytosis (SM) is a rare clonal neoplasm driven by the KIT D816V mutation and has a broad range of debilitating symptoms. In this study, the authors evaluated SM disease perceptions and management strategies among US health care providers (HCPs). METHODS: Hematologist/oncologist (H/O) HCPs and allergist/immunologist (A/I) HCPs who were treating four or more patients with SM completed an online, 51-item TouchStone HCP Survey, which queried provider characteristics, perceptions of disease burden, and current management. Descriptive analyses by specialty and SM subtype were performed. RESULTS: Of 304 HCPs contacted, 111 (37%) met eligibility criteria, including 51% A/I specialists and 49% H/O specialists. On average, the HCPs had 14 years of practice experience and cared for 20 patients with SM. A/I HCPs saw more patients with nonadvanced SM (78%) compared with H/O HCPs, who saw similar proportions of patients with nonadvanced SM (54%) and advanced SM (46%). HCPs reported testing 75% of patients for the KIT D816V mutation and found an estimated prevalence of 47%. On average, HCPs estimated 8 months between symptom onset and SM diagnosis. HCPs reported that 62% of patients with indolent SM felt depressed or discouraged because of symptoms. In terms of treatment goals for SM, both types of specialists prioritized symptom improvement for nonadvanced SM and improved survival for advanced SM while also prioritizing improving patient quality of life. CONCLUSIONS: Both A/I and H/O specialists highlighted unmet needs for patients with SM. The HCPs surveyed reported a lower rate of KIT D816V mutations and a perceived shorter time between symptom onset and SM diagnosis compared with published estimates. LAY SUMMARY: Specialists treating systemic mastocytosis (SM) completed a 51-item questionnaire about their clinical practices and perceptions of disease impact. The study included 111 hematology, oncology, allergy, and immunology physicians. Physicians reported that most patients had nonadvanced disease, yet SM symptoms significantly disrupted their patients' lives. Physicians estimated that SM is diagnosed within months of symptom onset, in contrast with published reports of years' long delays reported by patients with SM. This study identified unmet needs that can inform educational and patient management priorities in this rare disease.
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Mastocitosis Sistémica , Costo de Enfermedad , Personal de Salud , Humanos , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/genética , Mastocitosis Sistémica/terapia , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Calidad de Vida , Encuestas y CuestionariosRESUMEN
BACKGROUND: Systemic mastocytosis (SM) is a rare clonal neoplasm driven by KIT D816V and other mutations. Data were collected from the patient perspective on disease burden and included an SM-specific symptom assessment tool. METHODS: US adults aged 18 years and older with a self-reported SM diagnosis completed an online TouchStone SM Patient Survey of 100 items, including the 12-item Short-Form Health Survey, the Indolent Systemic Mastocytosis Symptom Assessment Form, and the Work Productivity and Activity Impairment Questionnaire, as well as questions about SM diagnosis, the impact of SM on daily activities, work impairment, and health care use. The results were analyzed using descriptive statistics. RESULTS: Fifty-six individuals completed the survey (89% women; median age, 48 years; mean time since diagnosis, 6.7 years), reporting indolent SM (66%), aggressive SM (9%), smoldering SM (5%), and unknown SM subtype (18%). Over a 1-year recall, respondents reported seeking emergency care for anaphylaxis (30%) and taking three or more prescription medications (52%) for SM. Over one half of patients (54%) reduced their work hours because of SM, and 64% avoided leaving home because of symptoms. A majority of respondents (93%) had experienced ≥10 SM-related symptoms, noting that the most bothersome were anaphylactic episodes (18%), abdominal/stomach pain (16%), diarrhea/loose stools (13%), and fatigue (11%). Whereas an Indolent Systemic Mastocytosis Symptom Assessment Form-derived total symptom score of 28 is used to indicate moderate-to-severe symptoms, the mean total symptom score was 52.7. Mental and physical component summary scores from the 12-item Short-Form Health Survey were below population norms. CONCLUSIONS: Patients who were surveyed reported substantial symptom burden and unmet needs because of SM, as evidenced by seeking emergency care and reporting bothersome symptoms, poor quality of life, and reduced work hours and productivity. LAY SUMMARY: The objective of this research was to understand the burden and unmet needs in the rare disease of systemic mastocytosis (SM) to guide future care. Fifty-six patients completed an online survey containing questions about their diagnosis, medications, health care use, quality of life, and SM symptoms. The results demonstrated that SM is associated with severe and burdensome symptoms, anaphylactic events, emergency department visits, use of multiple medications, reduced ability to work, and poor physical and psychological quality of life. These findings suggest the need for future advances to address unmet needs in patients affected by SM.
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Anafilaxia , Mastocitosis Sistémica , Adulto , Anafilaxia/diagnóstico , Diarrea , Femenino , Humanos , Masculino , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/epidemiología , Mastocitosis Sistémica/terapia , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Proteínas Proto-Oncogénicas c-kit/genética , Calidad de Vida , Encuestas y CuestionariosRESUMEN
Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma. In most patients with SM, somatic mutations in KIT are detected. Patients with indolent SM have a normal to near-normal life expectancy, whereas patients with advanced SM, including aggressive SM and MC leukemia, have a poor prognosis. In those with advanced SM, multiple somatic mutations and an associated hematologic neoplasm may be detected. Mediator-related symptoms can occur in any type of mastocytosis. Symptoms may be mild, severe, or even life-threatening. In patients with severe acute symptoms, an MC activation syndrome may be diagnosed. In these patients, relevant comorbidities include IgE-dependent and IgE-independent allergies. Management of patients with SM is an emerging challenge in daily practice and requires in-depth knowledge and a multidisciplinary and personalized approach with selection of appropriate procedures and interventions. In this article, we review the current knowledge on SM and MC activation syndrome, with emphasis on multidisciplinary aspects in diagnosis and patient-specific management. In addition, we provide a user's guide for application of markers, algorithms, prognostic scores, and treatments for use in daily practice.
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Mastocitosis Sistémica , Mastocitosis , Humanos , Inmunoglobulina E/metabolismo , Mastocitos/patología , Mastocitosis/diagnóstico , Mastocitosis/genética , Mastocitosis/terapia , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/genética , Mastocitosis Sistémica/terapia , Proteínas Proto-Oncogénicas c-kit/genética , Triptasas/metabolismoRESUMEN
A 60-year-old woman developed a fifth thoracic spine fracture with progressive paraplegia and underwent posterior spine fusion in June 2018. Based on the histopathological analysis of the surgical specimen, she was diagnosed with KIT D816V-positive systemic mastocytosis (SM). In June 2019, peripheral blood examination revealed remarkable eosinophilia. She was given prednisolone, which resulted in the resolution of eosinophilia. In May 2020, she developed acute myeloid leukemia (AML). Induction therapy was initiated and complete remission achieved. Subsequently, she received one course of consolidation therapy and allogeneic hematopoietic stem cell transplantation (allo-SCT). Although the residual mast cell tumor aggravated during chemotherapy for AML, the tumor regressed after allo-SCT, suggesting a graft-versus-mastocytosis effect. Nine months after the transplantation, the patient is alive and healthy without recurrence of AML and SM.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Mastocitosis Sistémica , Trastornos Mieloproliferativos , Femenino , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Mastocitosis Sistémica/complicaciones , Mastocitosis Sistémica/terapia , Persona de Mediana Edad , Inducción de RemisiónRESUMEN
Mastocytosis is a rare hematologic disorder characterized by abnormal proliferation and accumulation of neoplastic mast cells in various body sites. Isolated skin involvement is termed cutaneous mastocytosis (CM) and the term systemic mastocytosis (SM) refers to multi-organ involvement, most commonly of the bone marrow, skin, liver, and spleen. A subset of patients with SM have an associated clonal hematologic neoplasm which is most commonly myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myelogenous leukemia and this entity is termed SM with associated hematological neoplasm (AHN). Bone marrow involvement is present in all patients regardless of the subtype of SM. The genetic hallmark of SM is a somatic gain-of-function point mutation within the KIT gene. Other molecular aberrations that have been reported include somatic mutations in TET2, SRSF2, ASXL1, CBL, RUNX1, and RAS and these are common in SM-AHN. The clinical presentation of SM can range from indolent to advanced depending on extent of mast cell burden and genetic profile. In the case of indolent SM, the goal of treatment is to control mediator release-related effects as well as to reduce mast cell burden. In the case of SM-AHN, therapy is primarily that of the AHN and allogeneic hematopoietic stem cell transplantation is the preferred therapy in suitable candidates.
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Neoplasias Hematológicas , Mastocitosis Sistémica , Médula Ósea , Humanos , Mastocitos , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/genética , Mastocitosis Sistémica/terapia , Proteínas Proto-Oncogénicas c-kitRESUMEN
Mastocytosis is a heterogeneous group of hematologic neoplasms defined by an accumulation of neoplastic mast cells (MC) in the skin, bone marrow, and other visceral organs [...].
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Diagnóstico Diferencial , Neoplasias Hematológicas/diagnóstico , Mastocitosis Sistémica/diagnóstico , Mastocitosis/diagnóstico , Médula Ósea/patología , Neoplasias Hematológicas/clasificación , Neoplasias Hematológicas/terapia , Humanos , Mastocitos/patología , Mastocitosis/clasificación , Mastocitosis/terapia , Mastocitosis Sistémica/clasificación , Mastocitosis Sistémica/terapia , Piel/patologíaRESUMEN
Systemic mastocytosis (SM) is a hematologic disease with a wide range of clinical courses ranging from an indolent condition with normal life expectancy to exceedingly aggressive disorder with a poor prognosis. The symptoms and signs of SM result from the release of mast cell mediators with heterogeneous functions, and/or organ damage from neoplastic mast cell infiltration, or both. Diagnostic criteria for SM are well-defined by the World Health Organization (WHO). However, the diagnosis of SM can be difficult when especially it is not in the differential diagnosis. Routinely used radiologic techniques (e.g., X-ray, ultrasound, CT scans can show findings such as lytic-, sclerotic- or mixed-bone lesions, splenomegaly, hepatomegaly, retroperitoneal or periportal mesenteric lymphadenopathy, and omental thickening). It is essential to emphasize that the constellation of these radiologic findings should strongly concern of SM, especially in patients who also have a skin rash, allergic reactions, gastrointestinal tract symptoms (lasting, intermittent nausea, diarrhea), paroxysmal tachycardias, unexplained weight loss, persistent bone pain, cytopenias, liver dysfunction, eosinophilia. These findings, even coincidentally noted, will likely lead to a tissue biopsy, which reveals diagnosis (as we discussed and illustrated some tissue biopsies here). Moreover, the role of MRI and new techniques such as [18-fluorodeoxyglucose positron emission computed tomography, fibroscan] in the diagnosis of SM have been discussed. Furthermore, we reviewed the use of radiologic methods to evaluate treatment response and prognostication of SM..
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Biopsia , Mastocitosis Sistémica/diagnóstico , Radiografía , Biopsia/métodos , Biopsia/normas , Toma de Decisiones Clínicas , Terapia Combinada , Manejo de la Enfermedad , Humanos , Mastocitosis Sistémica/etiología , Mastocitosis Sistémica/mortalidad , Mastocitosis Sistémica/terapia , Imagen Multimodal/métodos , Imagen Multimodal/normas , Pronóstico , Radiografía/métodos , Radiografía/normas , Evaluación de Síntomas , Resultado del TratamientoRESUMEN
In recent years, molecular characterization and management of patients with systemic mastocytosis (SM) have greatly benefited from the application of advanced technologies. Highly sensitive and accurate assays for KIT D816V mutation detection and quantification have allowed the switch to non-invasive peripheral blood testing for patient screening; allele burden has prognostic implications and may be used to monitor therapeutic efficacy. Progress in genetic profiling of KIT, together with the use of next-generation sequencing panels for the characterization of associated gene mutations, have allowed the stratification of patients into three subgroups differing in terms of pathogenesis and prognosis: i) patients with mast cell-restricted KIT D816V; ii) patients with multilineage KIT D816V-involvement; iii) patients with "multi-mutated disease". Thanks to these findings, new prognostic scoring systems combining clinical and molecular data have been developed. Finally, non-genetic SETD2 histone methyltransferase loss of function has recently been identified in advanced SM. Assessment of SETD2 protein levels and activity might provide prognostic information and has opened new research avenues exploring alternative targeted therapeutic strategies. This review discusses how progress in recent years has rapidly complemented previous knowledge improving the molecular characterization of SM, and how this has the potential to impact on patient diagnosis and management.