RESUMEN
Epstein-Barr virus (EBV)-positive extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas) were initially described in solid organ transplant recipients, and, more recently, in other immunodeficiency settings. The overall prevalence of EBV-positive MALT lymphomas has not been established, and little is known with respect to their genomic characteristics. Eight EBV-positive MALT lymphomas were identified, including 1 case found after screening a series of 88 consecutive MALT lymphomas with EBER in situ hybridization (1%). The genomic landscape was assessed in 7 of the 8 cases with a targeted high throughput sequencing panel and array comparative genomic hybridization. Results were compared to published data for MALT lymphomas. Of the 8 cases, 6 occurred post-transplant, 1 in the setting of primary immunodeficiency, and 1 case was age-related. Single pathogenic/likely pathogenic mutations were identified in 4 of 7 cases, including mutations in IRF8, BRAF, TNFAIP3, and SMARCA4. Other than TNFAIP3, these genes are mutated in <3% of EBV-negative MALT lymphomas. Copy number abnormalities were identified in 6 of 7 cases with a median of 6 gains and 2 losses per case, including 4 cases with gains in regions encompassing several IRF family or interacting genes (IRF2BP2, IRF2, and IRF4). There was no evidence of trisomies of chromosomes 3 or 18. In summary, EBV-positive MALT lymphomas are rare and, like other MALT lymphomas, are usually genetically non-complex. Conversely, while EBV-negative MALT lymphomas typically show mutational abnormalities in the NF-κB pathway, other than the 1 TNFAIP3-mutated case, no other NF-κB pathway mutations were identified in the EBV-positive cases. EBV-positive MALT lymphomas often have either mutations or copy number abnormalities in IRF family or interacting genes, suggesting that this pathway may play a role in these lymphomas.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma de Células B de la Zona Marginal , Hibridación Genómica Comparativa , ADN Helicasas/metabolismo , Infecciones por Virus de Epstein-Barr/patología , Genómica , Herpesvirus Humano 4/genética , Humanos , Tejido Linfoide/patología , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B de la Zona Marginal/patología , Membrana Mucosa/patología , FN-kappa B/genética , Proteínas Nucleares/genética , Factores de Transcripción/genéticaAsunto(s)
Adenocarcinoma/terapia , Neoplasias Esofágicas/terapia , Leucemia Mieloide Aguda/inducido químicamente , Neoplasias Primarias Secundarias/inducido químicamente , Sarcoma Mieloide/inducido químicamente , Adenocarcinoma/patología , Anciano , Antineoplásicos/efectos adversos , Neoplasias Esofágicas/patología , Esofagectomía , Humanos , Leucemia Mieloide Aguda/diagnóstico , MasculinoRESUMEN
BACKGROUND: Disease-specific skin lesions are rare in patients with multiple myeloma (MM). OBJECTIVE: We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM. METHODS: We identified 13 patients with cutaneous lesions of MM. RESULTS: Cutaneous lesions consisted of pink, red, and violaceous papules, nodules, and/or plaques that varied in size. Histopathology revealed atypical plasma cells with occasional plasmablastic features. MM had aggressive biologic features and was at an advanced stage in the majority of patients. Despite aggressive management, including chemotherapy and stem-cell transplantation, most patients died of progressive disease within a few months after the development of cutaneous lesions. LIMITATIONS: The study group was relatively small. CONCLUSIONS: Cutaneous involvement with MM is associated with aggressive biologic behavior and short survival.
Asunto(s)
Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Células Plasmáticas/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/secundario , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Biopsia con Aguja , Causas de Muerte , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Medición de Riesgo , Neoplasias Cutáneas/fisiopatología , Análisis de SupervivenciaRESUMEN
The calcium-permeable ion channel TRPM2 is highly expressed in a number of cancers. In neuroblastoma, full-length TRPM2 (TRPM2-L) protected cells from moderate oxidative stress through increased levels of forkhead box transcription factor 3a (FOXO3a) and superoxide dismutase 2. Cells expressing the dominant negative short isoform (TRPM2-S) had reduced FOXO3a and superoxide dismutase 2 levels, reduced calcium influx in response to oxidative stress, and enhanced reactive oxygen species, leading to decreased cell viability. Here, in xenografts generated with SH-SY5Y neuroblastoma cells stably expressing TRPM2 isoforms, growth of tumors expressing TRPM2-S was significantly reduced compared with tumors expressing TRPM2-L. Expression of hypoxia-inducible factor (HIF)-1/2α was significantly reduced in TRPM2-S-expressing tumor cells as was expression of target proteins regulated by HIF-1/2α including those involved in glycolysis (lactate dehydrogenase A and enolase 2), oxidant stress (FOXO3a), angiogenesis (VEGF), mitophagy and mitochondrial function (BNIP3 and NDUFA4L2), and mitochondrial electron transport chain activity (cytochrome oxidase 4.1/4.2 in complex IV). The reduction in HIF-1/2α was mediated through both significantly reduced HIF-1/2α mRNA levels and increased levels of von Hippel-Lindau E3 ligase in TRPM2-S-expressing cells. Inhibition of TRPM2-L by pretreatment with clotrimazole or expression of TRPM2-S significantly increased sensitivity of cells to doxorubicin. Reduced survival of TRPM2-S-expressing cells after doxorubicin treatment was rescued by gain of HIF-1 or -2α function. These data suggest that TRPM2 activity is important for tumor growth and for cell viability and survival following doxorubicin treatment and that interference with TRPM2-L function may be a novel approach to reduce tumor growth through modulation of HIF-1/2α, mitochondrial function, and mitophagy.
Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neuroblastoma/metabolismo , Canales Catiónicos TRPM/fisiología , Glándulas Suprarrenales/metabolismo , Animales , Antibióticos Antineoplásicos/farmacología , Autofagia , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo , Doxorrubicina/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Potencial de la Membrana Mitocondrial , Potenciales de la Membrana , Ratones Desnudos , Trasplante de Neoplasias , Neuroblastoma/patología , Isoformas de Proteínas/fisiología , Transporte de Proteínas , Carga TumoralRESUMEN
The precise classification and characterization of primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) has been hindered by clinical and morphologic features that overlap with other lymphomas, especially subcutaneous panniculitis-like T cell lymphoma (SPTCL). The recent World Health Organization/European Organization for Research and Treatment of Cancer (WHO/EORTC) classification distinguishes the more aggressive PCGD-TCL from the usually indolent SPTCL, however. We report a 30-year-old woman with an indurated violaceous plaque on the left cheek that had been present for several years. Biopsies showed a dense lymphocytic infiltrate involving the subcutis and dermis that consisted mostly of small and medium-sized lymphocytes, some with irregular nuclear contours and dense chromatin. These cells were positive for TIA-1, TCR-gamma and CD8, but negative for beta-F1 and granzyme-B. Staging with positron emission tomography-computed tomography (PET/CT), CBC and bone marrow with flow cytometry identified lymphadenopathy as well as blood and marrow involvement by an abnormal TCRgd-positive T-cell proliferation (Ann Arbor Stage IV). The patient's history of a long-standing lesion in this case is unusual, in that gamma-delta T-cell lymphomas are typically rapidly progressive neoplasms. As such, it raises the possibility of 'transformation' of a long-standing inflammatory process into an overt lymphoma.
RESUMEN
Hematologic malignancies, in particular T-cell lymphomas/leukemias, are prevalent in patients with ataxia telangiectasia (AT), with most reported cases being clinically aggressive and high grade. Epstein-Barr virus (EBV) is often associated with lymphoid proliferations/neoplasms arising in immunodeficient patients. Reports of low-grade B-cell neoplasms in the ataxia telangiectasia population are extremely rare. Here, we describe a case of EBV-associated extranodal marginal zone lymphoma (mucosa-associated lymphoid tissue lymphoma) of the parotid gland in a 16-year-old boy with AT. In addition, we review the literature of hematologic malignancies in the AT population as well as the occurrence of EBV in mucosa-associated lymphoid tissue lymphoma.
Asunto(s)
Ataxia Telangiectasia/complicaciones , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/patogenicidad , Linfoma de Células B de la Zona Marginal/diagnóstico , Glándula Parótida/patología , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ataxia Telangiectasia/patología , Ataxia Telangiectasia/virología , Infecciones por Virus de Epstein-Barr/virología , Humanos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/etiología , Masculino , Glándula Parótida/virología , PronósticoAsunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Femenino , Humanos , Quinasas Janus/farmacología , Masculino , Persona de Mediana Edad , Nitrilos , Proyectos Piloto , Pirazoles/farmacología , PirimidinasRESUMEN
Fever of unknown origin in patients with common variable immune deficiency (CVID) can be caused by variety of infectious, autoimmune, or malignancy-related etiologies. We present a 52-year-old man with history of CVID, who presented with 3 weeks of persistent high-grade fevers. During admission, he developed severe pancytopenia with shock and multiorgan failure. An extensive workup was performed for typical and atypical infections, autoimmune pathologies, and malignancy. His peripheral blood smear showed marked anisocytosis and poikilocytosis with elevated atypical lymphocytes. Flow cytometry showed markedly elevated CD8 counts, with abnormal CD4/CD8 ratio. Monospot test was negative but real-time polymerase chain reaction showed high Epstein-Barr virus load. Initial clinical suspicion was high for bacterial infections including pneumonia and acute sinusitis complicated by bacteremia and sepsis. Hematologic malignancy was also high on the differentials because of presence of rapidly progressive pancytopenia. The final diagnosis in this case illustrates a rare but potentially fatal disease that can present in CVID patients with persistent fevers and pancytopenia and can be refractory to standard treatment regimen. Because allergy and immunology physicians commonly treat CVID patients, they should be aware of this disease condition including pathophysiology, clinical presentation, laboratory workup, and treatment options.
Asunto(s)
Inmunodeficiencia Variable Común/complicaciones , Fiebre/etiología , Pancitopenia/complicaciones , Médula Ósea/patología , Diagnóstico Diferencial , Fiebre/tratamiento farmacológico , Histiocitos/patología , Humanos , Linfocitos/patología , Linfohistiocitosis Hemofagocítica/diagnóstico , Masculino , Persona de Mediana Edad , Pancitopenia/diagnósticoRESUMEN
The transient receptor potential (TRP) channel TRPM2 is an ion channel that modulates cell survival. We report here that full-length (TRPM2-L) and short (TRPM2-S) isoform expression was significantly increased in human neuroblastoma compared with adrenal gland. To differentiate the roles of TRPM2-L and TRPM2-S in cell proliferation and survival, we established neuroblastoma SH-SY5Y cell lines stably expressing either TRPM2 isoform or empty vector. Cells expressing TRPM2-S showed significantly enhanced proliferation, downregulation of phosphatase and tensin homolog (PTEN), and increased protein kinase B (Akt) phosphorylation and cell surface glucose transporter 1 (Glut1) compared with cells expressing TRPM2-L or empty vector. ERK phosphorylation was increased, and forkhead box O 3a (FOXO3a) levels were decreased. Inhibitor studies demonstrated that enhanced proliferation was dependent on phosphatidylinositol 3-kinase/Akt, ERK, and NADPH oxidase activation. On the other hand, TRPM2-S-expressing cells were significantly more susceptible to cell death induced by low H2O2 concentrations (50-100 µM), whereas TRPM2-L-expressing cells were protected. This was associated with a significant increase in FOXO3a, MnSOD (SOD2), and membrane Glut1 in TRPM2-L-expressing cells compared with TRPM2-S expressing cells. We conclude that TRPM2 channels occupy a key role in cell proliferation and survival following oxidative stress in neuroblastoma. Our results suggest that overexpression of TRPM2-S results in increased proliferation through phosphatidylinositol 3-kinase/Akt and ERK pathways, while overexpression of TRPM2-L confers protection against oxidative stress-induced cell death through FOXO3a and SOD. TRPM2 channels may represent a novel future therapeutic target in diseases involving oxidative stress.
Asunto(s)
Glándulas Suprarrenales/metabolismo , Proliferación Celular , Neuroblastoma/metabolismo , Estrés Oxidativo , Canales Catiónicos TRPM/metabolismo , Muerte Celular , Línea Celular Tumoral , Supervivencia Celular , Regulación hacia Abajo , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteína Forkhead Box O3 , Factores de Transcripción Forkhead/biosíntesis , Transportador de Glucosa de Tipo 1/biosíntesis , Humanos , Peróxido de Hidrógeno/farmacología , NADPH Oxidasas/metabolismo , Fosfohidrolasa PTEN/biosíntesis , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación , Isoformas de Proteínas/biosíntesis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Superóxido Dismutasa/biosíntesisAsunto(s)
Antígenos CD13/metabolismo , Hipoxia/metabolismo , Leucemia Mieloide Aguda/metabolismo , Infiltración Leucémica/metabolismo , Pulmón/patología , Insuficiencia Respiratoria/metabolismo , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Citometría de Flujo , Humanos , Hipoxia/etiología , Leucemia Mieloide Aguda/complicaciones , Infiltración Leucémica/complicaciones , Masculino , Persona de Mediana Edad , Insuficiencia Respiratoria/etiología , Adulto JovenRESUMEN
Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) with concurrent BCL2 and IRF4 rearrangements are rare. It is unclear whether such cases should be classified as large B- cell lymphoma with IRF4 rearrangement or FL/DLBCL-not otherwise specified. We identified 5 adult patients (FL, N = 3 and FL/DLBCL, N = 2) with concurrent BCL2 and IRF4 rearrangements. The median age at presentation was 77 years, and three patients presented with advanced stage disease. Both nodal and extranodal sites were involved and involvement was not limited to head and neck region. With a median follow-up of 18 months, 1 patient died and 4 patients were alive, including 3 who received chemotherapy and 1 who was observed. The neoplasms were histologically heterogeneous, including grade 2 and 3 FL and DLBCL. Four cases coexpressed CD10, BCL6, BCL2 and MUM1/IRF4. The Ki67 labelling index ranged from 20% to 95%. In 4 patients, the percentage of cells with BCL2 rearrangement was equal to or slightly greater than the cells harboring IRF4 rearrangement. Two cases underwent next generation sequencing tailored for lymphoid neoplasms. Both lacked mutations involving IRF4 and NF-kB pathway genes that are frequently detected in large B-cell lymphoma with IRF4 rearrangement, and one case showed DLBCL-EZH2 type mutations, including KMT2D and BCL2 mutations, similar to 2 previously reported DLBCL with BCL2 and IRF4 rearrangements. Adults with FL and FL/DLBCL with BCL2 and IRF4 rearrangements display clinicopathologic and mutational features more akin to FL and DLBCL and should not be characterized as large B-cell lymphoma with IRF4 rearrangement.
Asunto(s)
Linfoma Folicular , Linfoma de Células B Grandes Difuso , Humanos , Reordenamiento Génico , Hibridación Fluorescente in Situ , Linfoma Folicular/genética , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , AncianoRESUMEN
The TP53 (p53) pathway can be inhibited by TP53 mutation or deletion or by MDM2 overexpression. Both occur in Burkitt lymphoma (BL), but many cases lack either abnormality. Expression patterns of the TP53 inhibitor MDM4 have not been reported in BL, and increased MDM4 could deregulate the TP53 pathway in cases without TP53 or MDM2 abnormalities. We investigated TP53 pathway disruption in paediatric BL patient samples (n = 30) by studying MDM4, MDM2, and CDKN1A (p21) protein and mRNA expression; TP53 mutations; TP53 protein expression; and gene copy number abnormalities. MDM4 protein was expressed in 30/30 tumours, and MDM2 protein was weakly expressed in 7/30 (23%). All cases were negative for CDKN1A protein, and CDKN1A mRNA levels were decreased. TP53 mutations were detected in 5/28 (18%) cases and confirmed by sequencing. TP53 protein was expressed in 15/30 (50%) cases, including 7/8 with TP53 genetic alterations. MDM2 protein and mRNA expression levels did not correlate with lack of TP53 genetic changes or TP53 protein expression; however, there was an inverse relationship between detectable TP53 protein expression and MDM4 copy number gains and mRNA expression. The TP53 pathway is deregulated in paediatric BL cases, and increased MDM4 expression may be the primary mechanism in some cases.
Asunto(s)
Linfoma de Burkitt/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/fisiología , Proteína p53 Supresora de Tumor/fisiología , Linfoma de Burkitt/genética , Linfoma de Burkitt/patología , Proteínas de Ciclo Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , ADN de Neoplasias/genética , Genes p53 , Humanos , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Proteínas Nucleares , Proteínas Proto-Oncogénicas , Proteínas Proto-Oncogénicas c-mdm2/biosíntesis , Proteínas Proto-Oncogénicas c-mdm2/genética , ARN Mensajero/genética , ARN Neoplásico/genética , Transducción de Señal , Proteína p53 Supresora de Tumor/biosíntesisRESUMEN
Mast cell leukemia (MCL) is a leukemic variant of systemic mastocytosis defined by mast cells ≥ 20% of marrow nucleated cells. Its incidence is < 1% of all systemic mastocytosis cases [1]. Clinical characteristics and treatment of the disease are not well established and overall prognosis is very poor. We report a case of de novo mast cell leukemia with novel BRAF variant, concomitant KIT exon 9 missense mutation and complex cytogenetic abnormalities. After careful review of the literature we have not found any prior reports of concomitant BRAF and KIT variants, and complex cytogenetic abnormalities in MCL. This case provides evidence that MCL can have wide spectrum of genetic abnormalities as well as accumulation of mutations in various genes including BRAF. This finding may have significant implications for the understanding of pathogenesis, diagnosis, as well as targeted therapy of MCL.
Asunto(s)
Leucemia de Mastocitos , Mastocitosis Sistémica , Aberraciones Cromosómicas , Humanos , Leucemia de Mastocitos/diagnóstico , Leucemia de Mastocitos/genética , Leucemia de Mastocitos/patología , Mastocitos/patología , Mastocitosis Sistémica/patología , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-kit/genéticaRESUMEN
The prognosis for acute myeloid leukemia (AML) relapse post allogeneic hematopoietic stem cell transplantation (alloSCT) is dismal. Novel effective treatment is urgently needed. Clinical benefit of alloSCT greatly relies on the graft-versus-leukemia (GVL) effect. The mechanisms that mediate immune escape of leukemia (thus causing GVL failure) remain poorly understood. Studies of human GVL have been hindered by the lack of optimal clinically relevant models. Here, using our large, longitudinal clinical tissue bank that include AML cells and G-CSF mobilized donor hematopoietic stem cells (HSCs), we successfully established a novel GVL model in humanized mice. Donor HSCs were injected into immune-deficient NOD-Cg-Prkdcscid IL2rgtm1Wjl /SzJ (NSG) mice to build humanized mice. Immune reconstitution in these mice recapitulated some clinical scenario in the patient who received the corresponding HSCs. Allogeneic but HLA partially matched patient-derived AML cells were successfully engrafted in these humanized mice. Importantly, we observed a significantly reduced (yet incomplete elimination of) leukemia growth in humanized mice compared with that in control NSG mice, demonstrating a functional (but defective) GVL effect. Thus, for the first time, we established a novel humanized mouse model that can be used for studying human GVL responses against human AML cells in vivo. This novel clinically relevant model provides a valuable platform for investigating the mechanisms of human GVL and development of effective leukemia treatments.
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Modelos Animales de Enfermedad , Efecto Injerto vs Leucemia/inmunología , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/citología , Leucemia Mieloide Aguda/terapia , Animales , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Leucemia Mieloide Aguda/inmunología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Trasplante HomólogoRESUMEN
The majority of paediatric Burkitt lymphoma (pBL) patients that relapse will die of disease, but markers for this high-risk subset are unknown. MYC translocations characterize pBL, but additional genetic changes may relate to prognosis and serve as potential biomarkers. We utilized a molecular inversion probe single nucleotide polymorphism assay to perform high resolution, genome-wide copy number analysis on archival formalin-fixed, paraffin-embedded pBL and germline tissues. We identified copy number abnormalities (CNAs) in 18/28 patients (64%) with a total of 62 CNAs that included 32 gains and 30 copy number losses. We identified seven recurrent CNAs including 1q gain (7/28, 25%), 13q gain (3/28, 11%), and 17p loss (4/28, 14%). The minimum common amplified region on 13q was at 13q31 and included the MIR17HG (MIR17-92) locus. Samples with this gain had higher levels of MIR17 RNA and showed a tendency for early relapse. Tumour-specific uniparental disomy was identified in 32% of cases and usually was recurrent. These results demonstrate that high-resolution copy number analysis can be performed on archival lymphoma tissue specimens, which has significance for the study of rare diseases.
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Linfoma de Burkitt/genética , Cromosomas Humanos Par 13 , MicroARNs/biosíntesis , Adolescente , Linfoma de Burkitt/patología , Niño , Preescolar , Variaciones en el Número de Copia de ADN , Femenino , Formaldehído , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , MicroARNs/genética , Adhesión en Parafina , Fijación del TejidoRESUMEN
Myeloid/lymphoid neoplasm with t(8;22)(p11.2;q11.2)/BCR-FGFR1 is an extremely rare diagnosis, with few reported cases to date. In contrast to other FGFR1-partner rearrangements that are associated with chronic eosinophilic leukemia, acute myeloid leukemia, and/or lymphoblastic lymphoma, patients with BCR-FGFR1 have a myeloproliferative disorder that closely resembles chronic myeloid leukemia (CML). The current report describes a rare case of a 61 year old man with an atypical CML phenotype associated with t(8;22)(p11.2;q11.2)/BCR-FGFR1. A literature review is presented to enhance the awareness of this rare diagnostic entity.
Asunto(s)
Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 8/genética , Reordenamiento Génico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/patología , Proteínas Proto-Oncogénicas c-bcr/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Translocación Genética , Humanos , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/genética , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
We describe a 66-year-old man initially diagnosed with primary cutaneous marginal zone B-cell lymphoma who developed four additional monoclonal/monotypic B-cell lymphoid proliferations and a systemic angioimmunoblastic T-cell lymphoma over the course of 19 months. Through retrospective analysis, we identified the evolution of a T-cell clone within the background of clinically and pathologically dominant cutaneous B-cell tumors. In terms of clinical practice, this case supports that patients diagnosed with multiple clonal B-cell proliferation need thorough investigation and close clinical follow up to identify a coexistent or evolving systemic lymphoma, in particular, peripheral T-cell lymphomas of follicular T-helper cell type, such as angioimmunoblastic T-cell lymphoma. Biologically, this case offers unique insight into the interactions between B-cell and T-cell lineages in lymphoid neoplasia.
Asunto(s)
Linfoma de Células B de la Zona Marginal/patología , Linfoma Cutáneo de Células T/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Cutáneas/patología , Anciano , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunohistoquímica , Linfoma de Células B de la Zona Marginal/genética , Linfoma Cutáneo de Células T/genética , Masculino , Neoplasias Primarias Múltiples/genética , Reacción en Cadena de la Polimerasa , Receptores de Antígenos de Linfocitos T/genética , Neoplasias Cutáneas/genéticaRESUMEN
AIMS: Medical literature provides only scarce data about the degree of pain experienced by patients undergoing a bone marrow aspiration and biopsy (BMAB), and little is known about the factors that can modify the perception of pain. In this study, we evaluated the effectiveness of a combination of analgesia and anxiolysis in reducing the pain score of patients undergoing BMAB. MATERIALS AND METHODS: Eighty-four consecutive adult patients underwent BMAB after local anesthesia with 5 mL of lidocaine hydrochloride 1% aqueous solution in the left posterior superior iliac crest. Analgesia was obtained with acetaminophen 650 mg and oxycodone 10 mg, and anxiolysis was obtained with lorazepam 2 mg, all drugs given once orally 30 min before the procedure. We assessed the pain level with the Wong-Baker Faces Pain Rating Scale, which distinguishes six levels of pain, from 0 to 5. RESULTS: The 34 patients who received an oral administration of analgesia and anxiolysis reported pain at lower levels, i.e., in the range of 0-2, more frequently than the 50 patients who underwent BMAB without analgesia/anxiolysis (78% vs 64%, respectively). Among several predictors analyzed using a multivariate regression model, three were found to be associated with decreased pain level: the use of analgesia/anxiolysis, male sex, and increase in age (all with p values <0.05). Length of the extracted bone specimen, body mass index, and need of a spinal needle for anesthesia in obese patients did not predict for pain level. CONCLUSIONS: An oral administration of prophylactic regimen of analgesia and anxiolysis, at the above-mentioned doses, produced a statistically significant reduction of the perception of pain in patients undergoing BMAB, but its effect did not seem to provide a major and clinically significant reduction of pain level.
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Analgésicos/administración & dosificación , Ansiolíticos/administración & dosificación , Biopsia con Aguja/efectos adversos , Médula Ósea/patología , Dolor/prevención & control , Acetaminofén/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Anestesia Local , Femenino , Humanos , Lorazepam/administración & dosificación , Masculino , Persona de Mediana Edad , Oxicodona/administración & dosificación , Dolor/etiología , Dimensión del DolorRESUMEN
We report a unique case of a human immunodeficiency virus (HIV)-infected man with Epstein-Barré virus (EBV) negative diffuse large B-cell lymphoma (DLBCL) that responded solely to highly active antiretroviral therapy (HAART). Our patient presented with a retroperitoneal mass, high viral load, CD4 288 and began therapy with HAART with marked improvement of symptoms. The patient declined chemotherapy since he felt better after HAART, and rescanning at that time demonstrated marked improvement of the lymphoma on HAART alone. Viral load became undetectable, CD4 450 by 8 weeks. By 6 months, the patient had a complete remission verified by positron emission tomography/computed tomography (PET/CT) and has remained in remission to date on HAART alone. We postulate that HIV infection directly precipitated the lymphoma.
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Terapia Antirretroviral Altamente Activa , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Herpesvirus Humano 4 , Humanos , Linfoma de Células B Grandes Difuso/virología , Masculino , Persona de Mediana Edad , Inducción de RemisiónRESUMEN
The aberrant expression of T-cell antigens on B-cell-derived non-Hodgkin lymphomas has been described. However, the expression of the lineage-specific T-cell antigen, CD3, in hematologic malignancies is exceedingly rare and to the best of our knowledge has not been reported in pediatric patients. Here we describe the first case of a CD3+ diffuse large B-cell lymphoma in a 9-year-old male patient that is well documented by immunohistochemistry. In addition, results of a tissue microarray study composed of B-cell-derived non-Hodgkin lymphomas (n=77) and reactive lymphoid hyperplasia (n=13) dual stained for PAX5/CD3 are also reported.