RESUMO
OBJECTIVE: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. METHODS: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. RESULTS: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). CONCLUSION: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.
Assuntos
Neoplasias Hematológicas , Leucemia Linfocítica Crônica de Células B , Linfoma de Zona Marginal Tipo Células B , Linfoma Folicular , Linfoma Difuso de Grandes Células B , Humanos , Feminino , Pessoa de Meia-Idade , Leucemia Linfocítica Crônica de Células B/epidemiologia , Estudos Retrospectivos , Linfoma Folicular/patologia , Organização Mundial da SaúdeRESUMO
BACKGROUND: Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a chronic Epstein-Barr virus (EBV)-positive lymphoproliferative disease which may either present as an indolent condition or progress to a systemic T-cell lymphoma. METHODS: All HVLPD diagnosed over a 10-year period were retrieved, and clinical data regarding sex, age, oral and systemic manifestations, and clinical follow-up were obtained. Immunohistochemistry was done in order to characterize the lymphoid cells, and in situ hybridization was used to demonstrate the presence of EBV. RESULTS: Eleven cases were included, with a male predominance and a mean age of 25.1 years. Buccal mucosa and the lips were the most affected oral sites, appearing as painful ulcers. All patients exhibited facial oedema, usually affecting the lips, nose and periorbital region. The clinical course was gradual but progressive, with four patients having fever and 3 showing lymphadenopathies. All cases showed a moderate to severe lymphocytic infiltrate with angiotropism, angiocentricity and epidermotropism. Two cases affecting the lip skin exhibited a periappendageal lymphocytic infiltrate. Few large pleomorphic cells were found, surrounded by smaller and medium-sized lymphoid cells, as well as reactive plasma cells, macrophages, neutrophils and eosinophils. All lesions exhibited a cytotoxic T-cell (CD8+) phenotype with a variable proliferative index. All cases were associated with EBV, and all patients died due to complications of the disease. CONCLUSIONS: HVLPD is a rare disease that may show oral involvement with a cytotoxic T-cell phenotype, and is strongly associated with EBV. As shown in this series, HVLPD may show aggressive clinical behaviour.
Assuntos
Infecções por Vírus Epstein-Barr , Hidroa Vaciniforme , Transtornos Linfoproliferativos , Adulto , Infecções por Vírus Epstein-Barr/complicações , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , PeruRESUMO
Lymphoma is a neoplasm of hematopoietic origin that affects canines. The proper establishment of prognosis and rapid institution of treatment are essential for a better quality of life, and immunophenotyping is one of the tools used for this purpose. The objective of this study was to perform a clonality test for immunophenotypic characterization of canine lymphomas using the polymerase chain reaction (PCR) for antigen receptor rearrangements (PARR) technique in real-time from samples fixed in formalin and embedded in paraffin. The 23 analyzed samples were fixed in formalin and embedded in paraffin canine lymphoma from the collection Laboratory of Histopathology of the Animal Pathology Area of the Departament of Veterinary Medicine - Federal Rural University of Pernambuco (UFRPE). Samples were processed, their DNA was extracted, quantified, diluted, and standardized at a concentration of 50 ng/µL. After extraction, all samples were subjected to conventional PCR for endogenous control (detection of the IgM target region), in which the extracted DNA was amplified in a final volume of 25 µL. The 128 bp amplified product was detected by 1.5% agarose gel electrophoresis. Of the 23 samples analyzed for the detection of the conserved region referring to the endogenous gene, 91.30% (21/23) amplified the conserved region Cµ by conventional PCR, and two samples 8.70% (2/23) were negative. Endogenous control positive samples were subjected to real-time PCR-PARR for detection of IgH Major and IgH Minor for B lymphocytes (LB), and TCRy for lymphocytes T (LT) target regions. All reactions were performed in duplicate to reduce the risk of false-positive or false-negative results due to technical errors. Samples previously confirmed by immunohistochemistry were used as positive controls for T cell and B cell lymphoma, and MilliQ water was used as a negative reaction control. After amplification, the melting curve gradually increased the temperature by 1o C/5 s to 95o C during continuous fluorescence monitoring. Of the 21 samples analyzed, 100.00% (21/21) demonstrated clonal amplification. Of these, 57.15% (12/21) were positive for phenotype B, and 42.85% (9/21) were positive for phenotype T. Due to the importance of researching and confirming samples from files fixed and embedded in paraffin samples in laboratories, PCR-PARR is a good tool for this purpose. In the present study, real-time PCR analysis demonstrated greater sensitivity in the characterization of the immunophenotype of lymphomas from old samples fixed in formalin and embedded in paraffin. The temperature of melting curve analysis may vary depending on the amount of DNA and its quality. In the present study, it was found that the average melting temperature in the samples varied between ± 3o C when compared to that in the control sample for LB and LT, 83.5o C and 80o C, respectively: in the literature, there is a relative difference in this temperature, which may vary up to 4o C. Real-time PCR-PARR was satisfactory in the characterization of the immunophenotype of canine lymphomas from formalin-fixed and paraffin-embedded samples; therefore, its use is recommended for both retrospective studies. The use of PCR-PARR associated with histopathological and/or cytopathological examination in cases of canine lymphomas strongly helps pathologists, provide a safe establishment of the immunophenotype, minimize errors, and optimize the diagnosis, thus directly contributing to the establishment of the prognosis.(AU)
Assuntos
Animais , Imunofenotipagem/veterinária , Doenças do Cão/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Tecido Linfoide , Linfoma/veterinária , CãesRESUMO
Vanishing bile duct syndrome is a rare acquired condition, characterized by progressive loss of intrahepatic bile ducts leading to ductopenia and cholestasis. It can be associated with infections, ischemia, drug adverse reactions, neoplasms, autoimmune disease, and allograft rejection. Prognosis is variable and depends on the etiology of bile duct injury. We report the case of a 25-year-old female with cholestatic hepatitis and concomitant intakes of hepatotoxic substances, such as garcinia, field horsetail, and ketoprofen. On suspicion of a drug-induced liver injury, the drugs were promptly withdrawn and ursodeoxycholic acid was started with initial clinical and laboratory improvement, and the patient was discharged from the hospital. One month later, she had a new increase in bilirubin levels and canalicular enzymes, requiring a liver biopsy that showed significant loss of intrahepatic bile ducts, which was compatible with vanishing bile duct syndrome. This was confirmed by using cytokeratin 19 on immunohistochemistry. There was subsequent lymph node enlargement in several chains, and relevant weight loss. Histological analysis of a cervical lymph node revealed nodular sclerosis-subtype classic Hodgkin lymphoma. In this setting, vanishing bile duct syndrome was related to Hodgkin lymphoma and a drug-induced liver injury overlap, leading to progressive cholestasis with a worse prognosis. The patient's response to chemotherapy was poor, requiring biological therapy with brentuximab vedotin. It is crucial for physicians to create a broad differential diagnosis in suspected vanishing bile duct syndrome patients, especially to rule out malignancies.
Assuntos
Ductos Biliares Intra-Hepáticos/patologia , Doença Hepática Induzida por Substâncias e Drogas/complicações , Colestase Intra-Hepática/etiologia , Doença de Hodgkin/complicações , Fígado/patologia , Linfonodos/patologia , Adulto , Alanina Transaminase/sangue , Anti-Inflamatórios não Esteroides/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biópsia , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colagogos e Coleréticos/uso terapêutico , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/tratamento farmacológico , Colestase Intra-Hepática/patologia , Equisetum/efeitos adversos , Feminino , Garcinia/efeitos adversos , Gastrite/etiologia , Hematemese/etiologia , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Cetoprofeno/efeitos adversos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
Fifty years after the first reports of Epstein-Barr virus (EBV)-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease). This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis.
A cincuenta años de los primeros reportes de asociación del linfoma de Burkitt con el virus de Epstein-Barr (VEB), el VEB ha emergido como el tercer virus de tipo oncogénico con mayor prevalencia a escala mundial. La infección por VEB se asocia con diversas neoplasias, incluyendo el linfoma de Hodgkin y el no Hodgkin, linfoma de células T/NK y carcinoma nasofaríngeo. A pesar del control inmunológico altamente específico en el huésped inmunocompetente, el VEB puede ocasionar complicaciones severas en el huésped inmunocomprometido (es decir, la enfermedad linfoproliferativa post-trasplante). Esto es un problema particularmente en pacientes en quienes se retrasa la reconstitución de la inmunidad después de un trasplante de células madre hematopoyéticas o un trasplante de órganos sólidos. A pesar de los avances en las técnicas de diagnóstico y los algoritmos de tratamiento que permiten la identificación temprana y el tratamiento de pacientes de alto riesgo, las tasas mortalidad siguen siendo muy altas (del 90%) si no se recibe tratamiento temprano. La piedra angular del tratamiento incluye la disminución de la inmunosupresión y la depleción de células B in vivo con un anticuerpo monoclonal anti-CD20. Sin embargo, estas modalidades de tratamiento no son siempre posibles debido al rechazo del injerto, la enfermedad de injerto contra huésped y la toxicidad. Nuevas modalidades de tratamiento incluyen el uso de la terapia adoptiva de células T, que ha mostrado resultados promisorios en diversas neoplasias relacionadas con el VEB. En este artículo se revisan los avances más recientes en cuanto a los factores de riesgo, diagnóstico y tratamiento de las neoplasias asociadas con VEB, particularmente la enfermedad linfoproliferativa post-trasplante. También se discuten los tratamientos más recientes e innovadores, que incluyen la terapia adoptiva de células T así como el manejo de situaciones especiales, como la infección crónica activa de VEB y la linfohistiocitosis hemafagocítica asociada con VEB.
RESUMO
Fifty years after the first reports of Epstein-Barr virus (EBV)-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease). This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis.
RESUMO
Introducción: Se conoce que la incidencia de malignidad es significativamente mayor en los pacientes trasplantados que en la población general. La incidencia de enfermedad linfoproliferativa post trasplante (PTLD) es aproximadamente de 1% a 2% en los receptores de trasplante renal. El objetivo principal de este estudio fue evaluar la incidencia de PTLD en el seguimiento de pacientes trasplantados de riñón entre el 2005 y el 2010. Material y Métodos: Se tomaron de forma retrospectiva los datos de pacientes trasplantados de riñón entre los años 2005 a 2010 para determinar el número de casos de PTLD según el esquema inductor usado. Resultados: Se trasplantaron 425 pacientes en el periodo 2005 - 2010. Recibieron alemtuzumab 76.2%, daclizumab 10.7%, basiliximab 3.6% y timoglobulina 2.4%. No recibieron inducción con anticuerpos el 7 %. Durante este tiempo se presentaron 2 casos de PTLD: 1 con mieloma múltiple y otro con linfoma. Uno de ellos recibió alemtuzumab y otro timoglobulina. Conclusiones: En esta cohorte de pacientes donde se usó predominantemente alemtuzumab, la incidencia de PTLD fue más baja que lo reportado en estudios previos.
Introduction: It is well known that the incidence of malignancy is significantly higher in transplanted patients than in general population. The incidence of lymphoproliferative disease post-transplantation (PTLD) is approximately of 1% to 2% in kidney transplantation recipients. The main objective of this study was to evaluate the PTLD incidence when monitoring kidney transplanted patients between the years 2005 and 2010. Material and Methods: Kidney transplanted patients' data was retrospectively taken between the years 2005 to 2010 in order to determine the number of PTLD cases according to the inductor scheme used. Results: 425 patients were transplanted between 2005 and 2010. They received alemtuzumab 76.2%,daclizumab 10.7%, basiliximab 3.6% and thymoglobulin 2.4%. The 7% did not receive antibody induction. During this period 2 cases of PTLD ocurred: One with multiple myeloma and the other with lymphoma. One of them had been treated with alemtuzumab and the other with thymoglobulin. Conclusions: The PTLD incidence in our group, where alemtuzumab was used predominantly as inductor, was very low; this might suggest that alemtuzumab is a medication that does not increase the risk of this kind of neoplasia.
Assuntos
Humanos , Masculino , Feminino , Anticorpos Monoclonais , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/terapiaAssuntos
Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Diagnóstico Diferencial , Humanos , Síndromes de Imunodeficiência/diagnóstico , Inflamação , Ativação Linfocitária , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Linfócitos T Citotóxicos/citologiaRESUMO
Post transplant lymphoproliferative disease (PTLD) associated with EBV infection is one of the most life-threatening complications in SOT and HSCT. Risk factors for infection or reactivation of EBV in SOT are the use of greater immunosuppression, seronegative receptor and CMV infection. In HSCT, the risk factors are related to type of transplant, HLA disparity, the greater immunosuppression, T-cell depletion and severe GVHD. There is no scientific evidence to support the use of specific therapy for prophylaxis of EBV infection. Prophylaxis recommendations focus on avoid exposure of transplant recipients to sources of virus, through hygiene practices such as hand washing (A3), avoid sharing utensils (B3) and avoid contact with potentially infected secretions (respiratory or saliva) (A2). For PTLD prevention, the recommendation is regular EBV viral load monitoring by rtPCR. In SOT with logarithmic rising of EBV loads, it is recommended to reduce immunosuppression and periodically perform exams to diagnose PTLD. In HSCT, it is recommended to reduce immunosuppression whenever possible, and use rituximab according to speciic protocol. Acyclovir or gancyclovir have not proven to be of any eficacy in PTLD prophylaxis in SOT (C3) or HSCT (D2), so their administration as preemptive therapy is no recommended.
El síndrome linfoproliferativo (SLP) asociado a VEB constituye una grave complicación en TOS y en TPH. Los factores de riesgo de infección o reactivación de VEB en TOS son el uso de mayor inmunosupresión, la seronegatividad del receptor previa al trasplante y la infección por CMV. En TPH se consideran factores de riesgo el tipo de trasplante, disparidad HLA, mayor inmunosupresión, depleción linfocitaria y enfermedad injerto contra hospedero (EICH) grave. No hay evidencia cientíica que apoye el uso de medidas especíicas de proilaxis en prevención de infección por VEB. Se recomienda evitar la exposición a fuentes del virus de los candidatos a trasplantes a través de prácticas de higiene tales como lavado de manos (A3), evitar el compartir utensilios (B3) y evitar el contacto con potenciales secreciones infectadas (respiratorias o saliva) (A2). Para la prevención de SLP, se recomienda un esquema de monitoreo periódico de carga viral de VEB por RPC-TR. En el caso de TOS con cargas de VEB en ascenso logarítmico, se recomienda disminuir inmuno-supresión y buscar activa y periódicamente la aparición de SLP. En TPH, se recomienda, en lo posible, disminuir la inmunosupresión y se reserva el uso de rituximab para casos especíicos según protocolo. El uso de aciclovir o ganciclovir no han demostrado constituir medidas profilácticas efectivas en TOS (C3) ni en TPH (D2), no siendo recomendada su administración en esquemas de terapia anticipada.
Assuntos
Adulto , Criança , Humanos , Antivirais/uso terapêutico , Infecções por Vírus Epstein-Barr/prevenção & controle , Transtornos Linfoproliferativos/prevenção & controle , Transplante de Órgãos , Complicações Pós-Operatórias/prevenção & controle , Transplante de Células-Tronco , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/imunologia , Incidência , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/virologia , Guias de Prática Clínica como Assunto , Complicações Pós-Operatórias/imunologia , Fatores de RiscoRESUMO
JUSTIFICATIVA E OBJETIVOS: Leucemia de células pilosas é uma doença linfoproliferativa rara caracterizada pelo achado de esplenomegalia, pancitopenia, associado à linfocitose relativa e monocitopenia. Pode mimetizar ou coexistir com outras doenças hematológicas clonais e tem sido associado a desordens auto-imunes e, por isso, deve ser considerado como alternativa no diagnóstico diferencial de alguns processos patológicos. O objetivo desse estudo foi relatar o caso de um paciente portador de leucemia de células pilosas com marcador para linfócitos B positivos, que iniciou quadro clínico com pneumonia, revendo aspectos relacionados à essa doença. RELATO DO CASO: Paciente do sexo masculino, 73 anos, com esplenomegalia sem linfadenopatia, com ascite e pneumonia. Sua leucometria na admissão era normal e não havia relato de linfócitos atípicos no hemograma. Evoluiu, após um mês de internação, com pancitopenia progressiva grave. Realizada biópsia de medula óssea e análise de sangue periférico com microscopia de linfócitos grandes com citoplasma proeminente simulando pêlos. A análise imuno-histoquímica mostrou positividade para CD20 e DBA44, definindo o diagnóstico de leucemia de células pilosas. CONCLUSÃO: Embora a leucemia de células pilosas seja um diagnóstico raro deve ser pensado no diagnóstico diferencial de outras alterações linfoproliferativas. O atraso em seu diagnóstico pode levar a sérias complicações infecciosas e culminar com a morte do paciente, antes mesmo de sua definição. O fármaco de primeira linha é a cladribina, com poucos casos resistentes, devendo ser avaliada, individualmente, a persistência de doença após o tratamento.
BACKGROUND AND OBJECTIVES: Hairy cell leukemia is a rare linfoproliferative disorder characterized by the aspects of splenomegaly and pancytopenia associated with a relatively linfocitosis and monocytopenia. It can mimic or coexist with other clonal hematologic disorders and has been associated with autoimmune diseases and for that has to be considered in the differential diagnosis of some pathologic process. The objectives of this study are to report the case of a hairy cell leukemia patient with B positive lymphocyte marker that initiated his condition with pneumonia and to review the aspects related to this disease. CASE REPORT: Male patient, 73 year-old with splenomegaly and ascitis without linfadenopathy cursing with pneumonia. His white blood count was normal at admission and there was no sign of abnormality with his lymphocytes. He developed in a period of one month a severe progressive pancytopenia. After bone marrow biopsy and peripheric blood analysis it could be found microscopic lymphocytes bigger with a hairy-simulating cytoplasm. The imunohistoquimic analysis showed positively for CD20 and DBA44 ensuring the diagnosis of hairy cell leukemia. CONCLUSION: Although hairy cell leukemia is a rare disease it should be thought along other llinfoproliferatives disorders for the differential diagnosis in some cases. The delay in its diagnosis can lead to serious infectious complications and may terminate in patient death before even its discrimination. Claribin is the first line drug with a few resistance cases. The persistence of the disease must be evaluated individually after treatment.