RESUMO
Despite advancements in diagnostic modalities, delineating the etiology of fever of unknown origin (FUO) remains a significant challenge for clinicians. Notably, cases with hematological malignancies often have a poor prognosis due to delayed diagnosis. This study investigated the potential of readily obtainable laboratory markers to differentiate hematological causes from other etiologies during the early stages of FUO. A retrospective analysis was conducted on the medical records of 100 patients who fulfilled the modified FUO criteria between January 2010 and April 2023. Hematological etiologies were identified in 26 of the 100 patients. Peripheral blood neutrophil, lymphocyte, platelet counts, and the systemic immune inflammation (SII) index, were significantly lower in the hematological group compared to the non-hematological group. Conversely, serum ferritin levels were demonstrably higher in the hematological group. ROC analysis identified a neutrophil-to-ferritin ratio (NFR) cutoff value of < 8.53 as optimal for predicting hematological etiology. Subsequent multivariate analysis demonstrated that the NFR was the sole independent predictor of hematological etiology (p = 0.013).This study proposes a novel approach for early diagnosis of a potentially life-threatening subset of FUO patients. The NFR presents as an inexpensive and readily available marker for predicting hematological etiology in FUO cases.
Assuntos
Biomarcadores , Ferritinas , Febre de Causa Desconhecida , Neutrófilos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Ferritinas/sangue , Febre de Causa Desconhecida/sangue , Febre de Causa Desconhecida/etiologia , Febre de Causa Desconhecida/diagnóstico , Estudos Retrospectivos , Idoso , Adulto , Biomarcadores/sangue , Curva ROC , Doenças Hematológicas/sangue , Doenças Hematológicas/complicações , Doenças Hematológicas/diagnóstico , Idoso de 80 Anos ou maisRESUMO
To our knowledge, this is the first report of a patient with both genetically confirmed Kabuki and Marfan syndrome demonstrating a perifoveal macular degeneration in one eye. Progressive loss of the outer retinal layers was captured and demonstrated with spectral-domain optical coherence tomography imaging. Fundus autofluorescence imaging revealed perifoveal hypoautofluorescence. The patient had initially presented with a spontaneously resolved serous-exudative retinal detachment associated with tortuous retinal vasculature and preretinal proliferative vitreoretinopathy in the other eye. Prior to presentation, the patient had an ocular history of bilateral ectopia lentis treated with crystalline lens removal and placement of iris-claw intraocular lenses. [Ophthalmic Surg Lasers Imaging Retina 2024;55:541-544.].
Assuntos
Degeneração Macular , Síndrome de Marfan , Descolamento Retiniano , Tomografia de Coerência Óptica , Humanos , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Degeneração Macular/diagnóstico , Degeneração Macular/etiologia , Degeneração Macular/complicações , Tomografia de Coerência Óptica/métodos , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/complicações , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/etiologia , Angiofluoresceinografia/métodos , Anormalidades Múltiplas/diagnóstico , Face/anormalidades , Acuidade Visual , Feminino , Masculino , Fundo de Olho , Progressão da DoençaRESUMO
Macrophage activation syndrome (MAS), is a severe and fatal complication of various pediatric inflammatory disorders. Kabuki syndrome (KS), mainly caused by lysine methyltransferase 2D (KMT2D; OMIM 602113) variants, is a rare congenital disorder with multi-organ deficiencies. To date, there have been no reported cases of MAS in patients with KS. This report describes a case of a 22-year-old male with Kabuki syndrome (KS) who developed MAS. This unique case not only deepens the understanding of the involvement of KMT2D in immune regulation and disease, but expands the phenotype of the adult patient to better understand the natural history, disease burden, and management of patients with KS complicated with autoimmune disorders.
Assuntos
Anormalidades Múltiplas , Face , Doenças Hematológicas , Síndrome de Ativação Macrofágica , Doenças Vestibulares , Humanos , Masculino , Doenças Vestibulares/etiologia , Doenças Vestibulares/genética , Doenças Vestibulares/diagnóstico , Doenças Hematológicas/etiologia , Doenças Hematológicas/diagnóstico , Face/anormalidades , Anormalidades Múltiplas/genética , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/etiologia , Adulto Jovem , Proteínas de Neoplasias/genética , Fenótipo , Histona-Lisina N-Metiltransferase/genética , Proteínas de Ligação a DNA/genéticaRESUMO
BACKGROUND: Pulmonary mucormycosis is most common in patients with hematologic malignancies and transplant recipients. This article describes a case of mucormycosis in the lungs secondary to a hematologic disorder with suspected lung cancer. METHODS: Rhizopus (Rhizopus microspores) was detected by blood NGS and bronchoalveolar lavage fluid NGS, and pulmonary mucormycosis was confirmed. RESULTS: Secondary to hematologic disease, pulmonary pneumonia, mycosis, and symptoms improved after comprehensive treatment. CONCLUSIONS: Clinical data and radiologic knowledge are combined to diagnose invasive pulmonary mycoses; early empirical medicine is very important.
Assuntos
Pneumopatias Fúngicas , Mucormicose , Rhizopus , Humanos , Mucormicose/diagnóstico , Mucormicose/complicações , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/complicações , Rhizopus/isolamento & purificação , Masculino , Líquido da Lavagem Broncoalveolar/microbiologia , Antifúngicos/uso terapêutico , Pessoa de Meia-Idade , Doenças Hematológicas/complicações , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/microbiologia , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/complicaçõesRESUMO
There are 2 techniques for detecting red blood cell survival (RBCS) detection techniques: red blood cell labeling test and carbon monoxide (CO) breath test. The former has disadvantages such as long measurement times and complicated procedures, while the latter is simple, convenient, moderately priced, and capable of dynamically monitoring changes in RBCS before and after treatment. Currently, the CO breath test is gradually being implemented in clinical practice. RBCS is not only applied to hematologic diseases such as multiple myeloma, myelodysplastic syndromes, lymphoma, and thalassemia, but also to non-hematologic diseases like type 2 diabetes and chronic kidney disease. It can assist in diagnosis, guide treatment, evaluate drug treatment efficacy, and predict disease progression.
Assuntos
Eritrócitos , Humanos , Eritrócitos/citologia , Monóxido de Carbono/sangue , Testes Respiratórios/métodos , Sobrevivência Celular , Diabetes Mellitus Tipo 2/sangue , Doenças Hematológicas/sangue , Doenças Hematológicas/diagnósticoRESUMO
Kabuki syndrome (KS) is a rare congenital disorder with distinctive characteristics. Herein, we describe a KS patient carrying a novel mutation in the KMT2D gene, c.11785C > T (p.Gln3929*). The patient presented with typical eyelid deformities, including eversion of the lateral lower eyelids, long palpebral fissures, hypertelorism, and medial epicanthus. Orbital computed tomography revealed orbital bone malformation with temporally and inferiorly displaced zygomatic bone. The bilateral orbits were shallow with an enlarged angle between the lateral walls. Zygomatic and maxillary bone dysplasia were also observed. Orbital bone anomalies are thought to be one of the characteristics of KS.
Assuntos
Anormalidades Múltiplas , Face , Doenças Hematológicas , Órbita , Tomografia Computadorizada por Raios X , Doenças Vestibulares , Humanos , Doenças Vestibulares/genética , Doenças Vestibulares/diagnóstico , Doenças Hematológicas/genética , Doenças Hematológicas/diagnóstico , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Face/anormalidades , Órbita/diagnóstico por imagem , Órbita/anormalidades , Proteínas de Neoplasias/genética , Proteínas de Ligação a DNA/genética , Mutação , Feminino , Masculino , Análise Mutacional de DNARESUMO
Distinguishing key morphologic features and understanding the pathophysiology of common cutaneous manifestations of hematologic disorders is essential to ensure prompt and appropriate treatment. In fact, classic cutaneous signs may provide the first clue to the diagnosis of an underlying hematologic disease. Disorders of coagulation, vascular abnormalities, or cutaneous infiltration and deposition are responsible for the underlying pathophysiology of cutaneous manifestations in the majority of cases. Hematologists often feel ill-equipped in identifying morphologic changes in the skin. Thus, the purpose of this review is to provide a comprehensive overview of classic cutaneous manifestations and diagnostic considerations of the associated hematologic conditions. Though there is a specific focus on non-malignant disorders, those straddling the spectrum of malignancy are also discussed. In many disease states, the skin may serve as an important marker of an emerging hematologic disorder, so close collaboration and multidisciplinary input remain essential to provide optimal and timely care for these patients.
Assuntos
Doenças Hematológicas , Dermatopatias , Humanos , Doenças Hematológicas/etiologia , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/complicações , Dermatopatias/etiologia , Dermatopatias/diagnóstico , Pele/patologiaRESUMO
BACKGROUND: Having a haematological condition can adversely affect the quality of life (QoL) of family members/partners of patients. It is important to measure this often ignored burden in order to implement appropriate supportive interventions. OBJECTIVE: To measure current impact of haematological conditions on the QoL of family members/partners of patients, using the Family Reported Outcome Measure-16 (FROM-16). METHODS: A cross-sectional study, recruited online through patient support groups, involved UK family members/partners of people with haematological conditions completing the FROM-16. RESULTS: 183 family members/partners (mean age = 60.5 years, SD = 13.2; females = 62.8%) of patients (mean age = 64.1, SD = 12.8; females = 46.4%) with 12 haematological conditions completed the FROM-16. The FROM-16 mean total score was 14.0 (SD = 7.2), meaning 'a moderate effect on QoL'. The mean FROM-16 scores of family members of people with multiple myeloma (mean = 15.8, SD = 6.3, n = 99) and other haematological malignancies (mean = 13.9, SD = 7.8, n = 29) were higher than of people with pernicious anaemia (mean = 10.7, SD = 7.5, n = 47) and other non-malignant conditions (mean = 11, SD = 7.4, n = 56, p < .01). Over one third (36.1%, n = 183) of family members experienced a 'very large effect' (FROM-16 score>16) on their quality of life. CONCLUSIONS: Haematological conditions, in particular those of malignant type, impact the QoL of family members/partners of patients. Healthcare professionals can now, using FROM-16, identify those most affected and should consider how to provide appropriate holistic support within routine practice.
Assuntos
Anemia Perniciosa , Família , Mieloma Múltiplo , Qualidade de Vida , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/psicologia , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Família/psicologia , Idoso , Anemia Perniciosa/diagnóstico , Anemia Perniciosa/epidemiologia , Anemia Perniciosa/etiologia , Efeitos Psicossociais da Doença , Inquéritos e Questionários , Adulto , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/etiologia , Doenças Hematológicas/psicologiaRESUMO
Autosomal dominant Kabuki syndrome (KS) is a rare multiple congenital anomalies/neurodevelopmental disorder caused by heterozygous inactivating variants or structural rearrangements of the lysine-specific methyltransferase 2D (KMT2D) gene. While it is often recognizable due to a distinctive gestalt, the disorder is clinically variable, and a phenotypic scoring system has been introduced to help clinicians to reach a clinical diagnosis. The phenotype, however, can be less pronounced in some patients, including those carrying postzygotic mutations. The full spectrum of pathogenic variation in KMT2D has not fully been characterized, which may hamper the clinical classification of a portion of these variants. DNA methylation (DNAm) profiling has successfully been used as a tool to classify variants in genes associated with several neurodevelopmental disorders, including KS. In this work, we applied a KS-specific DNAm signature in a cohort of 13 individuals with KMT2D VUS and clinical features suggestive or overlapping with KS. We succeeded in correctly classifying all the tested individuals, confirming diagnosis for three subjects and rejecting the pathogenic role of 10 VUS in the context of KS. In the latter group, exome sequencing allowed to identify the genetic cause underlying the disorder in three subjects. By testing five individuals with postzygotic pathogenic KMT2D variants, we also provide evidence that DNAm profiling has power to recognize pathogenic variants at different levels of mosaicism, identifying 15% as the minimum threshold for which DNAm profiling can be applied as an informative diagnostic tool in KS mosaics.
Assuntos
Anormalidades Múltiplas , Metilação de DNA , Proteínas de Ligação a DNA , Face , Doenças Hematológicas , Mosaicismo , Proteínas de Neoplasias , Doenças Vestibulares , Humanos , Doenças Vestibulares/genética , Doenças Vestibulares/diagnóstico , Face/anormalidades , Doenças Hematológicas/genética , Doenças Hematológicas/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico , Proteínas de Ligação a DNA/genética , Masculino , Feminino , Proteínas de Neoplasias/genética , Criança , Pré-Escolar , Adolescente , Mutação em Linhagem Germinativa , Lactente , Fenótipo , AdultoRESUMO
Analysis of bone marrow aspirates (BMAs) is an essential step in the diagnosis of hematological disorders. This analysis is usually performed based on a visual examination of samples under a conventional optical microscope, which involves a labor-intensive process, limited by clinical experience and subject to high observer variability. In this work, we present a comprehensive digital microscopy system that enables BMA analysis for cell type counting and differentiation in an efficient and objective manner. This system not only provides an accessible and simple method to digitize, store, and analyze BMA samples remotely but is also supported by an Artificial Intelligence (AI) pipeline that accelerates the differential cell counting process and reduces interobserver variability. It has been designed to integrate AI algorithms with the daily clinical routine and can be used in any regular hospital workflow.
Assuntos
Inteligência Artificial , Doenças Hematológicas , Humanos , Medula Óssea , Microscopia , Doenças Hematológicas/diagnóstico , AlgoritmosRESUMO
BACKGROUND: Kabuki Syndrome is a rare and genetically heterogenous condition with both ophthalmic and systemic complications and typical facial features. We detail the macular phenotype in two unrelated patients with Kabuki syndrome due to de novo nonsense variants in KMT2D, one novel. A follow-up of 10 years is reported. Pathogenicity of both de novo nonsense variants is analyzed. METHODS: Four eyes of two young patients were studied by full clinical examination, kinetic perimetry, short wavelength autofluorescence, full field (ff) ERGs, and spectral-domain optical coherence tomography (SD-OCT). One patient had adaptive optic (AO) imaging. Whole exome sequencing was performed in both patients. RESULTS: Both patients had de novo nonsense variants in KMTD2. One patient had c.14843C>G; p. (Ser4948ter) novel variant and the second c.11119C>T; p. (Arg3707ter). Both had a stable Snellen visual acuity of 0.2-0.3. The retinal multimodal imaging demonstrated abnormalities at the fovea in both eyes: hyperreflectivity to blue light and a well-delimited gap-disruption of ellipsoid and interdigitation layer on OCT. The dark area on AO imaging is presumed to be absent for, or with structural change to photoreceptors. The ff ERGs and kinetic visual fields were normal. The foveal findings remained stable over several years. CONCLUSION: Kabuki syndrome-related maculopathy is a distinct loss of photoreceptors at the fovea as shown by multimodal imaging including, for the first time, AO imaging. This report adds to the literature of only one case with maculopathy with two additional macular dystrophies in patients with Kabuki syndrome. Although underestimated, these cases further raise awareness of the potential impact of retinal manifestations of Kabuki syndrome not only among ophthalmologists but also other healthcare professionals involved in the care of patients with this multisystem disorder.
Assuntos
Anormalidades Múltiplas , Eletrorretinografia , Face , Angiofluoresceinografia , Doenças Hematológicas , Imagem Multimodal , Proteínas de Neoplasias , Fenótipo , Tomografia de Coerência Óptica , Doenças Vestibulares , Acuidade Visual , Humanos , Doenças Vestibulares/genética , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/fisiopatologia , Face/anormalidades , Doenças Hematológicas/genética , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/fisiopatologia , Tomografia de Coerência Óptica/métodos , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico , Seguimentos , Masculino , Feminino , Proteínas de Neoplasias/genética , Angiofluoresceinografia/métodos , Proteínas de Ligação a DNA/genética , Degeneração Macular/genética , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Pescoço , Fundo de Olho , DNA/genética , Sequenciamento do Exoma , Análise Mutacional de DNA , Macula Lutea/patologia , Fatores de Tempo , Adulto , AdolescenteRESUMO
Kabuki syndrome (KS) is characterized by growth impairment, psychomotor delay, congenital heart disease, and distinctive facial features. KMT2D and KDM6A have been identified as the causative genes of KS. Craniosynostosis (CS) has been reported in individuals with KS; however, its prevalence and clinical implications remain unclear. In this retrospective study, we investigated the occurrence of CS in individuals with genetically diagnosed KS and examined its clinical significance. Among 42 individuals with genetically diagnosed KS, 21 (50%) exhibited CS, with 10 individuals requiring cranioplasty. No significant differences were observed based on sex, causative gene, and molecular consequence among individuals with KS who exhibited CS. Both individuals who underwent evaluation with three-dimensional computed tomography (3DCT) and those who required surgery tended to exhibit cranial dysmorphology. Notably, in several individuals, CS was diagnosed before KS, suggesting that CS could be one of the clinical features by which clinicians can diagnose KS. This study highlights that CS is one of the noteworthy complications in KS, emphasizing the importance of monitoring cranial deformities in the health management of individuals with KS. The findings suggest that in individuals where CS is a concern, conducting 3DCT evaluations for CS and digital impressions are crucial.
Assuntos
Anormalidades Múltiplas , Craniossinostoses , Face/anormalidades , Doenças Hematológicas , Doenças Vestibulares , Humanos , Estudos Retrospectivos , Prevalência , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/epidemiologia , Anormalidades Múltiplas/genética , Doenças Hematológicas/complicações , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/epidemiologia , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/epidemiologia , Doenças Vestibulares/genética , Craniossinostoses/complicações , Craniossinostoses/diagnóstico , Craniossinostoses/epidemiologia , Histona Desmetilases/genética , MutaçãoRESUMO
Although considered "benign," mild blood count abnormalities, genetic factors imparting inconsequential thrombotic risk, and low-risk premalignant blood disorders can have significant psychological and financial impact on our patients. Several studies have demonstrated that patients with noncancerous conditions have increased levels of anxiety with distress similar to those with malignancy. Additionally, referral to a classical hematologist can be a daunting process for many patients due to uncertainties surrounding the reason for referral or misconstrued beliefs in a cancer diagnosis ascribed to the pairing of oncology and hematology in medical practice. If not properly triaged, incidental laboratory abnormalities can trigger extensive and costly evaluation. These challenges are compounded by a lack of consensus guidance and generalizability of modern reference ranges that do not adequately account for common influencing factors. Although often benign, incidental hematologic findings can lead to emotional suffering and careful consideration of the potential psychological and financial duress imparted to an individual must be considered. In this article, we will review the current literature describing the psychological effect of some commonly known hematologic conditions, identify benign causes for variations in hematologic laboratory values, and provide recommendations to reduce psychological toxicity as it pertains to hematologic testing.
Assuntos
Doenças Hematológicas , Hematologia , Neoplasias , Humanos , Doenças Hematológicas/diagnóstico , Testes Hematológicos , AnsiedadeRESUMO
Kabuki syndrome is a recognizable Mendelian disorder characterized by the clinical constellation of childhood hypotonia, developmental delay or intellectual impairment, and characteristic dysmorphism resulting from monoallelic pathogenic variants in KMT2D or KDM6A. In the medical literature, most reported patients are children, and data is lacking on the natural history of the condition across the lifespan, with little known about adult-specific presentations and symptoms. Here, we report the results of a retrospective chart review of eight adult patients with Kabuki syndrome, seven of whom are molecularly confirmed. We use their trajectories to highlight the diagnostic challenges unique to an adult population, expand on neurodevelopmental/psychiatric phenotypes across the lifespan, and describe adult-onset medical complications, including a potential cancer risk and unusual and striking premature/accelerated aging phenotype.
Assuntos
Anormalidades Múltiplas , Doenças Hematológicas , Humanos , Estudos Retrospectivos , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Face/patologia , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/genética , Doenças Hematológicas/complicações , Fenótipo , MutaçãoRESUMO
The concomitant presence of Castleman disease (CD) with other hematological pathology is an event described in the literature with increasing frequency, able to modify the diagnostic and curative approach in such patients. Very few studies in the literature describe the association of CD with concomitant neoplastic diseases; the most frequent are Kaposi's sarcomas (especially in HIV and human herpes virus-8-positive patients) and lymphoproliferative disorders, such as lymphomas. Instead, since the association with plasma cell diseases such as multiple myeloma and plasmacytoma is infrequent, there is a lack of literature. This manuscript aimed to revise the literature by describing a rare case of CD and plasmacytoma and attempting to explain the underlying triggering mechanisms.
Assuntos
Hiperplasia do Linfonodo Gigante , Doenças Hematológicas , Plasmocitoma , Humanos , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/patologia , Plasmocitoma/complicações , Plasmocitoma/diagnóstico , Doenças Hematológicas/complicações , Doenças Hematológicas/diagnósticoRESUMO
Multiparametric flow cytometry is an extensively used technique to assess the presence of different cellular populations in immunology and hematology. During routine immunophenotyping analysis, it is not uncommon to face cells of non-hemopoietic origin, negative for CD45 and other myeloid, megakaryocytic, B and T lineage antigens and positive for at least one antibody among CD56, CD117 and CD138. If cytology cannot identify cell origin, especially in cases of unclear interpretation, the contribution of multiparametric flow cytometry analysis can be crucial. We report 6 patients with a clinical suspicion of hematological disease in which multiparametric flow cytometry was extremely useful to quickly exclude blood disorders in order to initiate patients to the most appropriate diagnostic process.
Assuntos
Medula Óssea , Doenças Hematológicas , Humanos , Citometria de Fluxo , Doenças Hematológicas/diagnóstico , Células da Medula Óssea , Megacariócitos , ImunofenotipagemRESUMO
Kabuki syndrome is a rare hereditary disease characterized by distinctive facial features, skeletal abnormalities, mental retardation, developmental delay, and anomalies in multiple organ systems development.Congenital hyperinsulinism is a rare manifestation of his Kabuki syndrome. However, early diagnosis is crucial to prevent neurological complications of hypoglycemia.There are 2 types of Kabuki Syndrome depending on severity of symptoms. Kabuki syndrome Type 1 is associated with heterozygous mutations in gene KMT2D. Kabuki syndrome Type 2 is inherited in an X-linked manner. It's associated with heterozygous mutations in gene KDM6A and characterized by more severe course of the disease.This paper presents 2 cases of children with congenital hyperinsulinism as the feature of Kabuki syndrome Type 1 and Type 2.
Assuntos
Anormalidades Múltiplas , Hiperinsulinismo Congênito , Doenças Hematológicas , Doenças Vestibulares , Criança , Humanos , Doenças Vestibulares/complicações , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/genética , Doenças Hematológicas/complicações , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/genética , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico , Hiperinsulinismo Congênito/complicações , Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/genéticaRESUMO
OBJECTIVES: Kabuki syndrome (KS) is a rare congenital malformation syndrome associated with germline KMT2D mutations. Recurrent somatic mutations in KMT2D have frequently been observed in B-cell lymphoma, but limited studies are available that evaluate the genetic landscape of B-cell lymphomas in the setting of KS. METHODS: We describe a unique case of B-cell lymphoma that illustrates histologic features of pediatric-type follicular lymphoma (FL) in a young patient with KS and autoimmune disease who showed a systemic presentation of widespread lymphadenopathy and clonal lymphocytosis. RESULTS: We present the first reported case of a young patient with KS harboring a germline KMT2D variant and presenting with a systemic CD10-positive, BCL2-negative B-cell lymphoma of follicle center origin illustrating histologic features of pediatric-type FL. Targeted next-generation sequencing of the B-cell lymphoma showed somatic TET2 and subclonal CXCR4 variants. These findings suggest that abnormal epigenetic regulation caused by alterations in KMT2D and TET2 may have played critical roles in promoting lymphomagenesis in this patient. CONCLUSIONS: This unique case presentation highlights the importance of close clinical monitoring and the value of clinical context in the diagnosis of pediatric FL-like lesions in patients with KS.
Assuntos
Dioxigenases , Doenças Hematológicas , Linfoma de Células B , Doenças Vestibulares , Criança , Humanos , Epigênese Genética , Doenças Vestibulares/genética , Doenças Vestibulares/complicações , Doenças Vestibulares/diagnóstico , Doenças Hematológicas/complicações , Doenças Hematológicas/genética , Doenças Hematológicas/diagnóstico , Linfoma de Células B/complicações , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Células Germinativas/patologia , Mutação , Proteínas de Ligação a DNA/genética , Dioxigenases/genéticaRESUMO
Introduction: Hematological disorders are the third cause of hypereosinophilia, after allergic and parasitic disease. The objective of our study is to show the epidemiological, clinical, biological and therapeutic characteristics of hematological hypereosinophilia. Patients and methods: This is a retrospective study over a 4-year period (March 2017-March 2021) concerning 14 patients with hematological hypereosinophilia. Results: Fourteen patients were included (9 women and 5 men). The median age at diagnosis was 55 years. Hematological hypereosinophilia was mainly of clonal etiology. Clinical manifestations were either specific to hypereosinophilia, such as organ damage, or related to the etiology of hypereosinophilia, such as hepato-splenomegaly and lymphadenopathy. Moderate and severe forms were the most commonly reported. Several other quantitative and qualitative abnormalities of the blood picture were reported. Identification of the FIP1L1-PDGFRA fusion gene by molecular biology (RT-PCR) was positive in two patients. Imatinib was the main treatment for clonal forms. Conclusion: Hematological hypereosinophilia is a rare and complex pathology. Our study has confirmed this epidemiological, clinical, biological and therapeutic heterogeneity and has enabled us to realize the contribution of molecular biology in the diagnosis and the treatment of hypereosinophilia.
Introduction: Les affections hématologiques représentent la troisième cause des hyper éosinophilies. L'objectif de notre travail est d'étudier les caractéristiques épidémiologiques, étiologiques, cliniques, biologiques et thérapeutiques des hyperéosinophilies hématologiques. Patients et méthodes: Il s'agit d'une étude rétrospective menée sur une période de 4 années (mars 2017-mars 2021). Cette étude a colligé 14 patients atteints d'hyperéosinophilie hématologique. Résultats: Quatorze patients ont été inclus (9 femmes et 5 hommes). L'âge médian au moment du diagnostic était de 55 ans. L'hyperéosinophilie hématologique était principalement d'étiologie clonale. Les manifestations cliniques étaient soit spécifiques à l'hyperéosinophilie telles que les atteintes d'organes, soit liées à l'étiologie de l'hyperéosinophilie telles que l'hépato-splénomégalie et les adénopathies. Les formes modérées et sévères étaient les plus fréquemment rapportées. Plusieurs autres anomalies quantitatives et qualitatives de l'hémogramme ont été rapportées. L'identification du gène de fusion FIP1L1-PDGFRA par biologie moléculaire (RT-PCR) était positive chez deux patients. L'imatinib était le traitement de choix des formes clonales. Conclusion: L'hyperéosinophilie hématologique est une pathologie rare et complexe. Notre étude a permis de confirmer cette hétérogénéité épidémiologique, étiologique, clinique, biologique et thérapeutique et de montrer l'apport de la biologie moléculaire dans le diagnostic et le traitement de cette pathologie.
Assuntos
Doenças Hematológicas , Síndrome Hipereosinofílica , Feminino , Doenças Hematológicas/complicações , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/epidemiologia , Humanos , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/epidemiologia , Síndrome Hipereosinofílica/etiologia , Mesilato de Imatinib/uso terapêutico , Masculino , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Estudos RetrospectivosRESUMO
OBJECTIVE: This study is the first to analyse the prevalence of oral candidiasis in onco-haematological patients by physical and oral cytopathological examinations. METHODS: This is a cross-sectional and observational study with a retrospective sample composed of participants hospitalised in the haematology clinic, who were diagnosed with haematological diseases. All participants received an oral mucosal examination and scraping from oral mucosa. RESULTS: Of the 62 participants, 56.5% were male and 82.3% were white, with mean age of 57 years. Lymphoma was the most common haematological disease (24.2%). In total, 48.4% of the sample was diagnosed with oral candidiasis. Of the participants with oral candidiasis, 13 (21.0%) had a clinical diagnosis. Cytopathological analysis revealed 17 more (27.4%) cases without oral lesions indicative of candidiasis. Erythematous candidiasis (P = 0.02), pseudomembranous candidiasis (P < 0.001), clinical candidiasis (P < 0.001), fibrous hyperplasia (P = 0.032), and coated tongue (P = 0.012) showed a correlation with a candidiasis cytopathological diagnosis. CONCLUSIONS: Oral candidiasis is common among patients with haematological disease, and the cytopathological examination proved to be a useful tool, confirming clinical diagnosis of candidiasis and identifying subclinical cases. These data are of great relevance considering the possible complications that these patients may develop, such as longer hospitalisations, worsening of the general condition or even death due to candidemia.