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1.
Bull Cancer ; 107(4): 428-437, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32204890

RESUMO

INTRODUCTION: An in-patient clinical service has been set up in March 2016 in the Occupational Diseases Center of Brest University Hospital, France, to seek for work-relatedness of diseases in patients hospitalized into the oncology and hematology departments. We present here data after two years of existence. METHODS: All cases of cancers or malignant hematological diseases (ICD-10 codes C00 to C97 and D37 to D48) seen between March 1, 2016, and March 1, 2018, have been identified. We present sociodemographic data, occupational exposures, occupation, business sector, and tobacco consumption. The causation level between the disease and each of the occupational exposures has been rated as strong, intermediate, weak or null by the occupational medicine specialist of the Occupational Diseases Center. RESULTS: Among the 196 patients encountered, there are 127 work-related diseases and 82 of these had one occupational exposure rated as strong or intermediate. The most frequent occupational hazards were asbestos (48 cases) and ionizing radiation (23 cases). The most frequent business sectors were metallurgy, mechanical engineering, and agriculture. Lung cancer was the most frequently reported disease (49 cases). DISCUSSION: . We identified well-known couples with occupational exposures and diseases, such as asbestos and lung cancer. We also identified a link between pesticides and leukemias. This in-patient clinical service is helpful to identify work-related exposures and in helping patients to get compensated.


Assuntos
Neoplasias/etiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Asbestos/toxicidade , Carcinógenos/toxicidade , Feminino , França , Hospitais Universitários , Humanos , Leucemia/induzido quimicamente , Neoplasias Pulmonares/etiologia , Linfoma/etiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/etiologia , Exposição Ocupacional/classificação , Serviços de Saúde do Trabalhador/organização & administração , Ocupações , Praguicidas/toxicidade , Exposição à Radiação/efeitos adversos , Radiação Ionizante , Neoplasias da Bexiga Urinária/etiologia , Adulto Jovem
2.
Arch. argent. pediatr ; 118(1): 11-17, 2020-02-00. tab, graf
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1095278

RESUMO

Introducción. Las causas más frecuentes de la linfadenopatía cervical son las afecciones inflamatorias y reactivas; solo unos pocos casos representan una patología seria. El objetivo fue evaluar la relación entre los hallazgos ecográficos y el diagnóstico histopatológico. Población y métodos. Este estudio retrospectivo abarcó la linfadenopatía cervical en los menores de 20 años seguidos en nuestro centro, entre enero de 2007 y diciembre de 2016. Según los informes anatomopatológicos, se dividió a los pacientes en dos grupos: benigno y maligno. Se compararon los resultados anatomopatológicos y los hallazgos ecográficos. Resultados. Después del análisis de los resultados histopatológicos y los hallazgos ecográficos, se incluyó a 107 pacientes con linfadenopatía cervical persistente (44 casos malignos; 63, benignos). La media de edad de los grupos maligno y benigno fue de 14 ± 6,1 años y de 11,9 ± 4,8 años, respectivamente. La presencia de vascularidad hiliar fue estadísticamente significativa (p < 0,0001) en la linfadenopatía benigna, mientras que el flujo periférico y la vascularidad mixta lo fueron (p < 0,05) en la linfadenopatía maligna. No se observó una diferencia significativa en el diámetro máximo (27,3 ± 11,1 mm y 29,8 ± 12,3 mm, respectivamente), pero sí en el diámetro mínimo entre los grupos benigno y maligno (13,7 ± 7,3 mm y 18,7 ± 8,8 mm, respectivamente). Conclusiones. Este estudio sugiere que existe una relación entre los hallazgos ecográficos y de la biopsia para la diferenciación entre la linfadenopatía benigna y maligna, en especial, en el patrón vascular intraganglionar y el hilio ganglionar.


Introduction. The most common causes of cervical lymphadenopathy (LAP) are inflammatory and reactive conditions; only a small proportion have serious pathology, such as malignancy. The objective of this study was to evaluate the relationship between USG findings and histopathological diagnosis of the cervical LAP. Population and Methods. This retrospective study comprised the cases of cervical LAP in patients aged under 20 years old followed in our center between January 2007 to December 2016. Based on pathology reports, we divided the patients into two groups: benign and malignant. Pathology results and USG findings were compared. Results. After the analyze of the histopathological results and USG findings, 107 patients with persistent cervical LAP (44 malignant; 63 benign) were included in the study. Mean age of malignant and benign group were 14 ± 6.1; 11.9 ± 4.8 years, respectively. Hilar vascularity for benign LAP was highly statistically significant (P < 0.0001) and peripheral flow and mixed vascularity for malignant LAP were also statistically significant (p < 0.05). There was not a significant difference in the maximum diameter (27.3 ± 11.1 mm and 29.8 ± 12.3 mm, respectively), however, there was a significant difference in the minimum diameter between benign and malignant groups (13.7 ± 7.3 mm and 18.7 ± 8.8 mm, respectively).Conclusions. The present study suggests that there is a relationship between US and biopsy findings for the differentiation of benign from malignant LAP, especially in terms of nodal hilus and intranodal vascular pattern.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Ultrassonografia , Linfadenopatia/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Biópsia por Agulha Fina , Linfadenopatia/patologia , Linfonodos/patologia , Doenças Linfáticas/fisiopatologia , Linfoma/diagnóstico , Linfoma/etiologia
3.
Blood ; 134(21): 1787-1795, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31751486

RESUMO

Common variable immune deficiency (CVID) is one of the most common congenital immune defects encountered in clinical practice. The condition occurs equally in males and females, and most commonly in the 20- to 40-year-old age group. The diagnosis is made by documenting reduced serum concentrations of immunoglobulin G (IgG), IgA, and usually IgM, together with loss of protective antibodies. The genetics of this syndrome are complex and are still being unraveled, but the hallmarks for most patients, as with other immune defects, include acute and chronic infections of the sinopulmonary tract. However, other noninfectious autoimmune or inflammatory conditions may also occur in CVID, and indeed these may be the first and only sign that a significant immune defect is present. These manifestations include episodes of immune thrombocytopenia, autoimmune hemolytic anemia, or neutropenia, in addition to splenomegaly, generalized or worrisome lymphadenopathy, and malignancy, especially lymphoma. These issues commonly bring the patient to the attention of hematologists for both evaluation and treatment. This article discusses 3 cases in which patients with CVID had some of these presenting issues and what hematology input was required.


Assuntos
Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/diagnóstico , Anemia Hemolítica Autoimune/etiologia , Humanos , Linfadenopatia/etiologia , Linfoma/etiologia , Masculino , Pessoa de Meia-Idade , Esplenomegalia/etiologia
5.
Immunol Rev ; 291(1): 190-213, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31402495

RESUMO

Signals emanating from the B-cell receptor (BCR) promote proliferation and survival in diverse forms of B-cell lymphoma. Precision medicine strategies targeting the BCR pathway have been generally effective in treating lymphoma, but often fail to produce durable responses in diffuse large B-cell lymphoma (DLBCL), a common and aggressive cancer. New insights into DLBCL biology garnered from genomic analyses and functional proteogenomic studies have identified novel modes of BCR signaling in this disease. Herein, we describe the distinct roles of antigen-dependent and antigen-independent BCR signaling in different subtypes of DLBCL. We highlight mechanisms by which the BCR cooperates with TLR9 and mutant isoforms of MYD88 to drive sustained NF-κB activity in the activated B-cell-like (ABC) subtype of DLBCL. Finally, we discuss progress in detecting and targeting oncogenic BCR signaling to improve the survival of patients with lymphoma.


Assuntos
Leucemia Linfoide/etiologia , Leucemia Linfoide/metabolismo , Linfoma/etiologia , Linfoma/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Transdução de Sinais , Animais , Autoantígenos/imunologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Humanos , Leucemia Linfoide/diagnóstico , Leucemia Linfoide/terapia , Linfoma/diagnóstico , Linfoma/terapia , Receptores de Antígenos de Linfócitos B/genética
6.
Medicina (Kaunas) ; 55(7)2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311098

RESUMO

Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD can also involve other organs and manifest as an extraintestinal disease. Among the extraintestinal features of CD, hematologic ones are rather frequent and consist of anemia, thrombocytosis (thrombocytopenia also, but rare), thrombotic or hemorrhagic events, IgA deficiency, hyposplenism, and lymphoma. These hematologic alterations can be the sole manifestation of the disease and should prompt for CD testing in a suggestive clinical scenario. Recognition of these atypical, extraintestinal presentations, including hematologic ones, could represent a great opportunity to increase the diagnostic rate of CD, which is currently one of the most underdiagnosed chronic digestive disorders worldwide. In this review, we summarize recent evidence regarding the hematological manifestations of CD, with focus on practical recommendations for clinicians.


Assuntos
Doença Celíaca/complicações , Doenças Hematológicas/etiologia , Anemia/etiologia , Anemia/fisiopatologia , Doença Celíaca/fisiopatologia , Doenças Hematológicas/fisiopatologia , Humanos , Deficiência de IgA/etiologia , Deficiência de IgA/fisiopatologia , Linfoma/etiologia , Linfoma/fisiopatologia
7.
Pediatr Blood Cancer ; 66(11): e27938, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31347793

RESUMO

The therapies used to treat Ewing sarcoma are associated with a risk of second malignant neoplasm (SMN). We conducted a systematic review to pool available evidence on the risks, types, and outcomes after SMN. We obtained 52 articles that met inclusion criteria. Cumulative incidence rates of SMN ranged from 0.9 to 8.4% and 10.1 to 20.5% at 5 and 30 years after initial diagnosis. Of the 327 reported SMNs, 63.6% were solid tumors, although acute myeloid leukemia /myelodysplastic syndrome was the single most commonly diagnosed SMN, with generally poor outcomes. Patients treated for Ewing sarcoma are at substantial risk of SMN, with a broad range of reported secondary cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Radioterapia/efeitos adversos , Sarcoma de Ewing , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Carcinoma/epidemiologia , Carcinoma/etiologia , Carcinoma/terapia , Humanos , Incidência , Leucemia Mieloide/epidemiologia , Leucemia Mieloide/etiologia , Leucemia Mieloide/terapia , Linfoma/epidemiologia , Linfoma/etiologia , Linfoma/terapia , Melanoma/epidemiologia , Melanoma/etiologia , Melanoma/terapia , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/terapia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/terapia , Risco , Sarcoma/epidemiologia , Sarcoma/etiologia , Sarcoma/terapia , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/radioterapia , Sarcoma de Ewing/cirurgia , Fatores de Tempo , Resultado do Tratamento
8.
Hematol Oncol ; 37 Suppl 1: 15-18, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187523

RESUMO

Primary central nervous system lymphoma is a rare subtype of non-Hodgkin lymphoma that is confined to the brain, leptomeninges, or the eye and is associated with a relatively poor prognosis compared to other extranodal diffuse large B-cell lymphomas. However, methotrexate-based induction chemotherapy followed by consolidative chemotherapy or high-dose therapy and autologous stem cell transplantation is associated with improved survival and reduced neurotoxicity. Aberrant activation of B-cell receptor signaling and activation of nuclear factor kappa beta is a frequent genetic alteration and offers opportunities for targeted therapies in this lymphoma subtype.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Linfoma/terapia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/etiologia , Terapia Combinada , Gerenciamento Clínico , Humanos , Incidência , Linfoma/diagnóstico , Linfoma/epidemiologia , Linfoma/etiologia , Imagem Multimodal/métodos , Guias de Prática Clínica como Assunto , Prognóstico , Resultado do Tratamento
9.
Pesqui. vet. bras ; 39(6): 393-401, June 2019. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1012761

RESUMO

The pathological, immunohistochemical (IHC), and etiological features of lymphoma involving the nervous system (NS) in cats were analyzed through a retrospective study (2004-2017) in Rio Grande do Sul State, Brazil. The NS involvement was observed in 16 (12.2%) of 125 felines with lymphoma. Young cats were mainly affected, with a median of 24 months old. Most cases were secondary central NS lymphoma, whereas in three cats, the NS involvement was primary. IHC revealed 14 (87.5%) FeLV-positive, six FIV-positive, and one FeLV/FIV-negative cats. Distribution of feline lymphoma in the NS was 8/16 in the spinal cord, 7/16 in the brain, and 1/16 in the paravertebral nerves and ganglia (neurolymphomatosis). The lymphoma pattern in the spinal cord was exclusively extradural, often focal (6/8), and located in the lumbar (3/6), sacral (1/6), thoracic (1/6), and cervical segments (1/6). Brain neuroanatomical patterns were: leptomeningeal lymphomatosis (4/7), lymphomatous choroiditis (2/7), and intradural lymphoma (1/7). The feline with primary neurolymphomatosis presented a marked thickening of paravertebral nerves and ganglia from the sacral region. B-cell lymphoma (75%) was often diagnosed, and diffuse large B-cell lymphoma (DLBCL) (11/16) was the main subtype. T-cell lymphoma (25%) was less commonly observed and was classified as peripheral T-cell lymphoma (PTCL) (3/16) and T-cell lymphoblastic lymphoma (T-LBL) (1/16).(AU)


Os aspectos patológicos, imuno-histoquímicos (IHQ) e etiológicos do linfoma envolvendo o sistema nervoso de felinos foram analisados através de um estudo retrospectivo (período de 2004-2017) no Estado do Rio Grande do Sul, Brasil. O envolvimento do sistema nervoso foi observado em 16 (12,2%) dos 125 felinos com linfoma desse estudo e afetou principalmente, jovens com idade mediana de 24 meses. A grande maioria dos casos o linfoma era secundário no sistema nervoso central e somente em três gatos o linfoma foi primário do sistema nervoso. Na IHQ, 14 (87,5%) casos foram positivos para FeLV, seis (37,5%) para FIV, e um foi negativo para ambos. A distribuição do linfoma no sistema nervoso foi em 8/16 felinos na medula espinhal, 7/16 no encéfalo e em 1/16 em nervos e gânglios paravertebrais (neurolinfomatose). Na medula espinhal, o padrão do linfoma foi exclusivamente extradural e frequentemente focal (6/8), localizadas nos segmentos lombares (3/6), sacrais (1/6), torácicos (1/6) e cervicais (1/6). No encéfalo, os padrões neuroanatômicos observados foram: linfomatose leptomeningeal (4/7), coroidite linfomatosa (2/7), linfoma intradural (1/7). No felino diagnosticado com neurolinfomatose primária, foi observado acentuado espessamento dos nervos e gânglios paravertebrais da região sacral. Os linfomas de células de células B (75%) foram os mais frequentes e o principal tipo foi o linfoma difuso de grandes células B (11/16). Os linfomas de células T (25%), menos observados, foram classificados como linfomas de células T periférico inespecífico (3/16) e linfoma linfoblástico T (1/16).(AU)


Assuntos
Animais , Gatos , Gatos/anormalidades , /patologia , Linfoma/etiologia , Linfoma/patologia
10.
Blood ; 134(4): 363-373, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31101621

RESUMO

Targeting the B-cell receptor and phosphatidylinositol 3-kinase/mTOR signaling pathways has shown meaningful, but incomplete, antitumor activity in lymphoma. Glycogen synthase kinase 3 (GSK3) α and ß are 2 homologous and functionally overlapping serine/threonine kinases that phosphorylate multiple protein substrates in several key signaling pathways. To date, no agent targeting GSK3 has been approved for lymphoma therapy. We show that lymphoma cells abundantly express GSK3α and GSK3ß compared with normal B and T lymphocytes at the messenger RNA and protein levels. Utilizing a new GSK3 inhibitor 9-ING-41 and by genetic deletion of GSK3α and GSK3ß genes using CRISPR/CAS9 knockout, GSK3 was demonstrated to be functionally important to lymphoma cell growth and proliferation. GSK3ß binds to centrosomes and microtubules, and lymphoma cells treated with 9-ING-41 become arrested in mitotic prophase, supporting the notion that GSK3ß is necessary for the progression of mitosis. By analyzing recently published RNA sequencing data on 234 diffuse large B-cell lymphoma patients, we found that higher expression of GSK3α or GSK3ß correlates well with shorter overall survival. These data provide rationale for testing GSK3 inhibitors in lymphoma patient trials.


Assuntos
Quinase 3 da Glicogênio Sintase/genética , Linfoma/etiologia , Terapia de Alvo Molecular , Animais , Biomarcadores Tumorais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Modelos Animais de Doenças , Expressão Gênica , Marcação de Genes/métodos , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Indóis/farmacologia , Linfoma/diagnóstico , Linfoma/mortalidade , Linfoma/terapia , Maleimidas/farmacologia , Camundongos , Camundongos Transgênicos , Mitose/efeitos dos fármacos , Mitose/genética , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Fuso Acromático/efeitos dos fármacos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
11.
World Neurosurg ; 127: 227-231, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30981796

RESUMO

BACKGROUND: Neurologic complications are common in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Although both the central nervous system (CNS) and the peripheral nervous system can be affected, 80% of patients with HIV/AIDS have CNS involvement during the course of their illness. The brain is the primary site of HIV/AIDS-associated CNS complications. Spinal cord involvement is rare, particularly focal intramedullary spinal cord lesions without any associated cerebral lesions. Among various opportunistic infections and malignancies, toxoplasmosis and CNS lymphoma are the most common causes of focal neurologic disease in patients with HIV/AIDS. Distinguishing between toxoplasmosis and CNS lymphoma is challenging, as the diseases have similar clinical presentations. CASE DESCRIPTION: In a woman with newly diagnosed HIV infection, myelopathy manifested as an isolated, single intramedullary spinal cord lesion. CONCLUSIONS: Common methods to distinguish the diagnoses of toxoplasmosis and CNS lymphoma are addressed. There should be a high index of suspicion for toxoplasmosis in patients with HIV/AIDS presenting with a focal intramedullary spinal cord lesion.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Linfoma/diagnóstico , Doenças da Medula Espinal/diagnóstico , Toxoplasmose/diagnóstico , Síndrome de Imunodeficiência Adquirida/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Linfoma/etiologia , Doenças da Medula Espinal/etiologia , Toxoplasmose/etiologia
12.
Cancer Sci ; 110(4): 1442-1452, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30719848

RESUMO

Although a possible role of reproductive factors in lymphomagenesis has been hypothesized, results of epidemiological studies have been inconsistent. Here, we investigated the association between reproductive factors and the risk of lymphoid neoplasm and its subgroups. We used data from a large-scale, population-based prospective study in a Japanese cohort with 42 691 eligible women aged 40-69 years from 1990 to 1994. During a mean follow up of 18.7 years, we identified 176 cases of lymphoid neoplasm and 90 of non-Hodgkin lymphoma (NHL). A multivariable-adjusted Cox proportional hazards regression model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the risk of lymphoid neoplasms and its subgroups according to self-reported reproductive factors. Parous women had an increased risk of lymphoid neoplasm compared with nulliparous women (HR = 2.51, 95% CI, 1.03-6.13). An increased risk of lymphoid neoplasms was found in women with later onset of menarche (≤13 years old; reference: 14-15; HR = 1.75, 95% CI = 1.10-2.79: ≥16; HR = 1.93, 95% CI = 1.17-3.19: P-trend: 0.01) and a shorter menstrual cycle (28-29 days; reference: ≤27; HR = 1.60, 95% CI = 1.05-2.43, P-trend = 0.81). No association was observed between lymphoid neoplasms and other reproductive factors, including age at first birth, breastfeeding, type of menopause, or exogenous hormone use. Our study suggests that ever parity, late age at menarche and a short menstrual cycle length may be associated with the development of lymphoid neoplasms. The inconsistency seen in epidemiological research to date warrants further investigation.


Assuntos
Suscetibilidade a Doenças , Leucemia Linfoide/epidemiologia , Leucemia Linfoide/etiologia , Linfoma/epidemiologia , Linfoma/etiologia , História Reprodutiva , Adulto , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco
13.
Autoimmun Rev ; 18(2): 137-143, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30572133

RESUMO

Sjögren's syndrome (SS) is characterized by B cell hyperactivity documented by the production of plethora of autoantibodies and a strong tendency for NHL of B cell origin. Classical predictors of lymphoma have been already proposed and proved their validity, including clinical, serological and histopathologic biomarkers. The process of lymphomagenesis is multistep and encompasses mechanisms of antigen driven selection of the BCR with RF activity and various genetic contributors implicated in B cell proliferation, cell growth and cell cycle control, enhanced by a complex milieu of cytokines and trophic agents that are abundant within the inflammatory lesion of minor salivary glands of SS patients. Extensive efforts in the basic research field have revealed several novel biomarkers for lymphoma prediction while the major cellular and molecular mechanisms of evolutionary transition of B cells towards malignancy are under investigation. In this review, we present the current data regarding the newly proposed biomarkers for SS associated lymphoma prediction and a hypothetical model of lymphomagenesis based on the emerging data.


Assuntos
Biomarcadores/metabolismo , Linfoma/etiologia , Medicina de Precisão/métodos , Síndrome de Sjogren/complicações , Feminino , Humanos , Linfoma/imunologia , Masculino , Síndrome de Sjogren/imunologia
14.
Front Immunol ; 9: 2400, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30386345

RESUMO

Serine/threonine kinase 4 (STK4) deficiency is an autosomal recessive genetic condition that leads to primary immunodeficiency (PID) typically characterized by lymphopenia, recurrent infections and Epstein Barr Virus (EBV) induced lymphoproliferation and -lymphoma. State-of-the-art treatment regimens consist of prevention or treatment of infections, immunoglobulin substitution (IVIG) and restoration of the immune system by hematopoietic stem cell transplantation. Here, we report on two patients from two consanguineous families of Turkish (patient P1) and Moroccan (patient P2) decent, with PID due to homozygous STK4 mutations. P1 harbored a previously reported frameshift (c.1103 delT, p.M368RfsX2) and P2 a novel splice donor site mutation (P2; c.525+2 T>G). Both patients presented in childhood with recurrent infections, CD4 lymphopenia and dysregulated immunoglobulin levels. Patient P1 developed a highly malignant B cell lymphoma at the age of 10 years and a second, independent Hodgkin lymphoma 5 years later. To our knowledge she is the first STK4 deficient case reported who developed lymphoma in the absence of detectable EBV or other common viruses. Lymphoma development may be due to the lacking tumor suppressive function of STK4 or the perturbed immune surveillance due to the lack of CD4+ T cells. Our data should raise physicians' awareness of [1] lymphoma proneness of STK4 deficient patients even in the absence of EBV infection and [2] possibly underlying STK4 deficiency in pediatric patients with a history of recurrent infections, CD4 lymphopenia and lymphoma and unknown genetic make-up. Patient P2 experienced recurrent otitis in childhood, but when she presented at the age of 14, she showed clinical and immunological characteristics similar to patients suffering from Autoimmune Lymphoproliferative Syndrome (ALPS): elevated DNT cell number, non-malignant lymphadenopathy and hepatosplenomegaly, hematolytic anemia, hypergammaglobulinemia. Also patient P1 presented with ALPS-like features (lymphadenopathy, elevated DNT cell number and increased Vitamin B12 levels) and both were initially clinically diagnosed as ALPS-like. Closer examination of P2, however, revealed active EBV infection and genetic testing identified a novel STK4 mutation. None of the patients harbored typically ALPS-associated mutations of the Fas receptor mediated apoptotic pathway and Fas-mediated apoptosis was not affected. The presented case reports extend the clinical spectrum of STK4 deficiency.


Assuntos
Síndrome Linfoproliferativa Autoimune/etiologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Síndromes de Imunodeficiência/etiologia , Linfoma/etiologia , Fenótipo , Proteínas Serina-Treonina Quinases/deficiência , Síndrome Linfoproliferativa Autoimune/diagnóstico , Estudos de Casos e Controles , Biologia Computacional/métodos , Análise Mutacional de DNA , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Síndromes de Imunodeficiência/diagnóstico , Linfoma/diagnóstico , Masculino , Mutação , Linhagem , Sequenciamento Completo do Exoma
16.
J Vet Intern Med ; 32(6): 2054-2060, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30307659

RESUMO

BACKGROUND: Lymphoma is common in the dog. Studies of population risk factors primarily have been derived from referral institution or insurance data. OBJECTIVE: To identify and quantify the host risk factors for lymphoma in a broad population of Australian dogs. ANIMALS: Data on 6201 client owned dogs were retrieved from a commercial veterinary laboratory, a general practice group and 2 referral hospitals. METHODS: Data collected included breed, sex, and neuter status. A reference population of 640 105 dogs was generated from the referral hospitals and from council registration data. The risk of lymphoma by sex and neuter status was calculated as odds ratios (OR). RESULTS: The study identified 30 breeds at increased risk of lymphoma, 15 that have not been reported previously, and 26 breeds at decreased risk, 18 that have not been reported previously. Males were over represented compared to females with an OR of 1.1 (95% CI, 1.1-1.2; P < .001). Neutered animals were at higher risk compared to intact animals with an OR of 3.2 (95% CI, 2.9-3.5) which was found in both males (OR, 2.8; 95% CI; 2.5-3.2) and females (OR, 4.4; 95% CI, 3.5-5.1). CONCLUSIONS AND CLINICAL IMPORTANCE: Breed, sex, and neuter status alter the risk of lymphoma in dogs. These 3 factors must be considered when evaluating lymphoma risk as potential markers of underlying differences in disease etiology. Comparison of breeds at increased and decreased risk could be advantageous when evaluating specific etiological factors.


Assuntos
Doenças do Cão/etiologia , Linfoma/veterinária , Animais , Austrália , Castração/efeitos adversos , Castração/veterinária , Cães , Feminino , Linfoma/etiologia , Masculino , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Especificidade da Espécie
17.
Rev Med Brux ; 39(4): 307-311, 2018.
Artigo em Francês | MEDLINE | ID: mdl-30320993

RESUMO

Despite recent advances in combined anti- retroviral therapy that have profoundly changed the prognosis of HIV infection, HIV-associated haematological complications remains frequent whatever the stage of the disease. Some types of lymphoma observed a dramatic reduction in their incidences but others such as diffuse B-cell lymphoma and Hodkin lymphoma remain as frequent as before the CART era. Treatments for lymphoma are nowadays not different for people living with HIV than for others. Other non- neoplastic diseases such as immune thrombo- penic purpura, thrombotic microangiopathies and hemophagocytic lymphohistiocytosis are still associated with HIV infection and will be discussed.


Assuntos
Infecções por HIV/complicações , Doenças Hematológicas/etiologia , Humanos , Linfoma/etiologia
18.
Malar J ; 17(1): 349, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30290813

RESUMO

BACKGROUND: Malaria is known to cause acute and deadly complications. However, malaria can cause unforeseen pathologies due to its chronicity. It increases the risk of endemic Burkitt Lymphoma development by inducing DNA damage in germinal centre (GC) B cells, and leading higher frequency of Epstein-Barr virus (EBV)-infected cells in GCs. EBV is well known for its tropism for B cells. However, less is known about EBV's interaction with T cells and its association with T cell lymphoma. CASE PRESENTATION: A 43-year-old Sudanese male admitted to hospital in Istanbul, Turkey, a non-endemic country, with hyperpigmented painful skin rashes on his whole body. A complete blood count and a peripheral blood smear during admission revealed large granular lymphocytes (LGLs) with abnormally higher CD8 T cell numbers. Additional skin biopsy and pathology results were compatible with CD8+ T cell lymphoproliferative disorder with skin involvement. Patient was treated and discharged. However, a pathologist noticed unusual structures in skin tissue samples. Careful evaluation of skin biopsy samples by polarized microscopy revealed birefringent crystalloid structures resembling malarial haemozoin mainly loaded in macrophages and giant histiocytes. After purification of DNA from the skin biopsy samples, nested PCR was performed for the detection of Plasmodium parasites and Plasmodium falciparum DNA was amplified. Because, the co-presence of EBV infection with malaria is a well-known aetiology of lymphoma, EBV-early RNA (EBER) transcripts were investigated in paraffin-embedded tissue samples and found to be positive in macrophage-like histiocytes. CONCLUSIONS: This is a unique case of malaria and EBV infection in a T-LGL lymphoma patient who presented in a non-endemic country. This case emphasizes the clinical importance of EBV monitoring in T-LGL patients with skin involvement. Notably, Plasmodium infection should be examined in patients from malaria endemic regions by pathological and molecular investigations.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Vírus Epstein-Barr/virologia , Linfoma/etiologia , Malária Falciparum/parasitologia , Adulto , Humanos , Masculino , Multimorbidade , Plasmodium falciparum/isolamento & purificação , Sudão/etnologia , Turquia
19.
Mol Med Rep ; 18(5): 4650-4656, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30221663

RESUMO

Post­transplant lymphoproliferative disorder (PTLD), despite its rarity, is an important mortality/morbidity event in transplant patients. The purpose of the present study was to retrospectively examine the clinical and pathologic characteristics, and outcomes of PTLD at the Portuguese Oncology Institute of Porto. A retrospective review of patient information was performed for patients that developed PTLD following allogeneic hematopoietic stem cell transplant (aHSCT) and were diagnosed between 2005 and 2012. The present study included a total of 15 patients, 8 females (53.3%) and 7 males (46.7%), with different clinicopathological characteristics. The most frequent clinical condition inducing aHSCT was acute lymphocytic leukemia (40.0%). Conditioning regimens consisted primarily in busulfan and cyclophosphamide, with anti­thymocyte globulin, and myeloablation was the preferential treatment. Epstein­Barr virus (EBV) was present in all patients with a median time of diagnosis following transplant of 75 days (range, 25­485 days) and a median viral load of 4.75 log10 copies/ml (range, 3.30­6.26 log10 copies/ml). PTLD diagnosis was mainly assessed by clinical findings, and histological confirmation was available for 5 patients: 3 monomorphic, 1 polymorphic and 1 with early lesions of PTLD. To the best of our knowledge, this is the first study to describe PTLD cases in HSCT patients in Portugal. The data reinforces the importance of performing EBV monitoring in high­risk patients, particularly those receiving a transplant from mismatch/unrelated donors, and those with myeloablative conditioning regimen including antithymocyte globulin. The results also suggested that EBV viral load may be significant for the prediction of PTLD development.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Bussulfano , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/patogenicidade , Humanos , Linfoma/tratamento farmacológico , Linfoma/etiologia , Linfoma/patologia , Linfoma/virologia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/virologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Carga Viral/efeitos dos fármacos , Adulto Jovem
20.
J Vet Diagn Invest ; 30(6): 830-836, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30264662

RESUMO

Flow cytometry (FC) is widely applied to characterize and stage nodal lymphomas in dogs because it has a short turnaround time, requires minimally invasive sampling, and allows contemporary evaluation of neoplastic cells in the primary lesion and of blood and marrow involvement. We investigated advantages and limitations of FC in suspected extranodal lymphomas in dogs. The likelihood of obtaining a suitable FC sample was significantly lower for aspirates of extranodal lesions than for lymph node aspirates. However, we noted no differences among different extranodal lesion sites. We also describe FC results for 39 samples compatible with extranodal lymphoma. A dominant population of large cells was easily identified on morphologic FC scattergrams in many cases. Phenotypic aberrancies were frequently present, mainly in T-cell lymphomas. Lymphoma cells were distinguishable from normal residual lymphocytes in >85% of cases, facilitating the quantification of putative blood and marrow involvement by FC. Despite the high percentage of non-diagnostic samples (32 of 73, >40%), we support the inclusion of FC in the diagnostic workup of suspected extranodal lymphomas in dogs, in conjunction with histopathology. Histopathology is the gold standard for diagnosing lymphoma, provides relevant information, including tissue invasion and epitheliotropism, but has a longer turnaround time.


Assuntos
Doenças do Cão/diagnóstico , Citometria de Fluxo/veterinária , Linfoma/veterinária , Animais , Doenças do Cão/etiologia , Cães , Citometria de Fluxo/métodos , Linfoma/diagnóstico , Linfoma/etiologia , Estudos Retrospectivos
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