Frequency of EBV associated classical Hodgkin lymphoma decreases over a 54-year period in a Brazilian population.

The epidemiology of classical Hodgkin lymphoma varies significantly in populations with different socioeconomic conditions. Among other changes, improvement in such conditions leads to a reduction in the association with EBV infection and predominance of the nodular sclerosis subtype. This study provides an overview of the epidemiology of 817 cases of classical Hodgkin lymphoma diagnosed in five reference hospitals of the State of Sao Paulo, Brazil, over 54 years (1954-2008). The cases were distributed in 3 periods (1954-1979; 1980-1999; and 2000-2008). EBV-positive cases decreased from 87% to 46%. In children and adolescents (<15 years) and in young adults (15-45 years), EBV-positive cases decreased respectively from 96% to 64%, and from 85% to 32%. The percentage of male patients declined from 80% to 58%. In older patients (>45 years), the decrease in EBV infection was not significant. Nodular Sclerosis was the most common subtype in all periods. These results support the hypothesis that, in the Brazilian State of Sao Paulo, classical Hodgkin lymphoma has changed and now shows characteristics consistent with Pattern III observed in populations that experienced a similar socioeconomic transition.

Pitfalls and major issues in the histologic diagnosis of peripheral T-cell lymphomas: results of the central review of 573 cases from the T-Cell Project, an international, cooperative study.

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of neoplasms that are derived from post-thymic lymphoid cells at different stages of differentiation with different morphological patterns, phenotypes and clinical presentations. PTCLs are highly diverse, reflecting the diverse cells from which they can originate and are currently sub-classified using World Health Organization (WHO) 2008 criteria. In 2006 the International T-Cell Lymphoma Project launched the T-Cell Project, building on the retrospective study previously carried on by the network, with the aim to prospectively collect accurate data to improve knowledge on this group of lymphomas. Based on previously published reports from International Study Groups it emerged that rendering a correct classification of PTCLs is quite difficult because the relatively low prevalence of these diseases results in a lack of confidence by most pathologists. This is the reason why the T-Cell Project requested the availability of diagnostic material from the initial biopsy of each patient registered in the study in order to have the initial diagnosis centrally reviewed by expert hematopathologists. In the present report the results of the review process performed on 573 cases are presented. Overall, an incorrect diagnosis was centrally recorded in 13.1% cases, including 8.5% cases centrally reclassified with a subtype eligible for the project and 4.6% cases misclassified and found to be disorders other than T-cell lymphomas; 2.1% cases were centrally classified as T-Cell disorders not included in the study population. Thus, the T-Cell Project confirmed the difficulties in providing an accurate classification when a diagnosis of PTCLs is suspected, singled out the major pitfalls that can bias a correct histologic categorization and confirmed that a centralized expert review with the application of adequate diagnostic algorithms is mandatory when dealing with these tumours. Copyright © 2016 John Wiley & Sons, Ltd.

A microRNA signature profile in EBV+ diffuse large B-cell lymphoma of the elderly.

Currently, there is no characteristic microRNA (miRNA) expression pattern in Epstein-Barr virus+ diffuse large B-cell lymphoma of the elderly (EBV+DLBCLe). This study aims to characterize a signature profile and identify miRNAs that can be used as biomarkers and alternative therapeutic targets for EBV+DLBCLe. Seventy-one DLBCL patients aged 50 years and older were included and four EBV+ and four EBV- samples were analyzed in two miRNA array platforms (pilot study). A larger multicenter cohort (29 EBV+DLBCLe and 65 EBV-DLBCL patients) was used to validate the results by real-time polymerase chain reaction. In the pilot study, 9% of DLBCL were EBV+DLBCLe by in situ hybridization. In multicenter study, EBV+DLBCLe group showed a predominance of non-germinal center B-cell origin. Overall survival duration of EBV+DLBCLe was significantly inferior to that of EBV-DLBCL patients. We found 10 deregulated miRNAs in the two groups, but only seven were statistically different. We confirmed overexpression of hsa-miR-126, hsa-miR-146a, hsa-miR-146b, hsa-miR-150, and hsa-miR-222 and underexpression of hsa-miR-151 in EBV+DLBCLe cases compared to EBV-DLBCL cases. Hsa-miR-146b and hsa-miR-222 showed high specificity for identifying EBV+DLBCLe. The present study proposed a miRNA signature for EBV+DLBCLe and our findings suggest that hsa-miR-146b and hsa-miR-222 could be biomarkers and therapeutic targets.

Secondary infiltration of the central nervous system in patients with diffuse large B-cell lymphoma.

OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7%) patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5%) patients of this cohort received rituximab as first-line treatment and nine (7.1%) received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7%) had parenchymal central nervous system involvement; seven (77.7%) had stage III or IV disease; one (11.1%) had bone marrow involvement; two (22.2%) had received intrathecal chemoprophylaxis; and 3 (33.3%) had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. CONCLUSION: Central nervous system infiltration in this cohort is similar to that of previous reports in the literature. As this was a small cohort with a rare event, only three risk factors were important for this infiltration.

Secondary infiltration of the central nervous system in patients with diffuse large B-cell lymphoma

OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7%) patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5%) patients of this cohort received rituximab as first-line treatment and nine (7.1%) received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7%) had parenchymal central nervous system involvement; seven (77.7%) had stage III or IV disease; one (11.1%) had bone marrow involvement; two (22.2%) had received intrathecal chemoprophylaxis; and 3 (33.3%) had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. ...

Classificação dos tumores hematopoéticos e linfoides de acordo com a OMS: padronização da nomenclatura em língua portuguesa, 4ª edição / Classification of haematopoietic and lymphoid tumors: WHO, standardization of nomenclature in Portuguese, 4th edition

INTRODUÇÃO: A classificação da Organização Mundial da Saúde (OMS) para os tumores do tecido hematopoético e linfoide (4ª edição, 2008) representa uma revisão atualização da 3ª edição publicada em 2001. A tradução da nomenclatura utilizada para identificar as entidades descritas deve ser clara, precisa e uniforme no sentido de reproduzir de forma correta as diversas entidades clinicopatológicas para clínicos, patologistas e pesquisadores envolvidos na área da onco-hematopatologia. OBJETIVO: Os autores apresentam uma proposta de atualização e padronização terminológica em língua portuguesa, com base na OMS/2008.

INTRODUCTION: The World Health Organization (WHO) classification of hematopoietic and lymphoid tissue (4th edition, 2008) tumors constitutes an updated review of the 3rd edition published in 2001. The translation of the nomenclature used to describe the entities should be clear, precise and uniform so that clinicians, pathologists and researchers involved in the onco-hematopathological area may identify them accurately. OBJECTIVE: With this purpose, the authors present an updated proposal and a terminological standardization in Portuguese based on WHO/2008.

Classificação da Organização Mundial da Saúde para os tumores dos tecidos hematopoético e linfoide, 4ª edição, 2008: principais modificações introduzidas em relação à 3ª edição, 2001 / World Health Organization classification of tumors of hematopoietic and lymphoid tissues, 4th edition, 2008: major changes from the 3rd edition, 2001

A Classificação da Organização Mundial da Saúde (OMS) para os tumores do tecido hematopoético e linfoide (4ª edição, 2008)¹ representa uma atualização da 3ª edição, 2001². Apresentamos a seguir um resumo dessas alterações nos grupos das doenças mieloproliferativas, mileodisplásicas, leucemias mieloides agudas, neoplasias de células precursoras B e T, e neoplasias de células B, T e NK maduras. O entendimento das alterações genético-moleculares e os resultados alcançados com propostas terapêuticas inovadoras nesses grupos de doenças demandam constante reavaliação de sua classificação, justificando as alterações importantes aqui discutidas1,3-5.

The World Health Organization (WHO) Classification of tumors of hematopoietic and lymphoid tissues (4th edition, 2008)¹ presents an updated version of the 3rd edition published in 2001². A summary of these changes relates to the groups of chronic myeloproliferative disorders, myelodisplasia, acute myeloid leukemias, neoplasms of precursor B and T cells and neoplasms derived of mature B, T and NK cells. A better understanding of molecular genetic changes and results achieved with innovative therapeutic approaches in these groups of diseases requires constant reassessment of the classifications, supporting the major changes discussed here, including interesting comments from literature1, 3-5.

Tratamento conservador do câncer de mama T2 (≥ 4 cm) e T3 por quimioterapia neoadjuvante, quadrantectomia, braquiterapia com alta taxa de dose como reforço de dose, teleterapia complementar e quimioterapia adjuvante: análise de controle local e sobrevida global / Breast conserving treatment of breast carcinoma T2 (≥ 4 cm) and T3 by neoadjuvant chemotherapy, quadrantectomy, high dose rate brachytherapy as a boost, external beam radiotherapy and adjuvant chemotherapy: local control and overall survival analysis

OBJETIVO: Avaliar o tratamento de carcinomas de mama T2 (≥ 4 cm) e T3, por quimioterapia neoadjuvante, quadrantectomia e braquiterapia com alta taxa de dose como reforço de dose (boost), radioterapia complementar e quimioterapia adjuvante, quanto ao controle local e sobrevida global.MATERIAL E MÉTODO: Trata-se de estudo clínico prospectivo descritivo que avaliou 88 pacientes com idade entre 30 e 70 anos, portadoras de carcinoma ductal infiltrante, nos estádio clínico IIb e IIIa, responsivas à quimioterapia neoadjuvante, tratadas entre junho de 1995 e dezembro de 2006. A resposta do tumor foi avaliada por método clínico antes e após três ou quatro ciclos de quimioterapia contendo antracíclicos. O seguimento mediano foi de 58 meses. Sobrevida global e controle local foram analisados segundo o método de Kaplan-Meier. RESULTADOS: O controle local e a sobrevida global em cinco anos foram de 90% e 73,5%, respectivamente. CONCLUSÃO: O controle local e a sobrevida global são comparáveis aos observados em outras formas terapêuticas.

OBJECTIVE: To assess the treatment of breast cancer T2 (≥ 4 cm) and T3 through neoadjuvant chemotherapy, quadrantectomy and high dose rate brachyterapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering local control and overall survival. MATERIAL AND METHOD: This clinical prospectivedescriptive study was based on the evaluation of 88 patients rangingfrom 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIb and IIIa, responsive to the neoadjuvant chemotherapy, treated from June/1995 to December/2006. Median follow-up was 58 months. Using clinical methods the tumor was evaluated before and after three or four cycles of chemotherapy based on antraciclins. Overall survival and local control were assessed according to Kaplan-Meier methodology. RESULTS: Local control and overall survival in five years were 90% and 73.5%, respectively. CONCLUSION: Local control and overall survival were comparable to other forms of treatment.

Histological classification of 1,025 cases of Hodgkin's lymphoma from the State of São Paulo, Brazil.

CONTEXT AND OBJECTIVE: It is currently asserted that, in industrialized countries, nodular sclerosis is the most frequent type of Hodgkin's lymphoma, in contrast to developing countries, where mixed cellularity and lymphocyte depletion are more frequently seen. The objective was to review histological data from cases of Hodgkin's lymphoma from São Paulo and Campinas cities. DESIGN AND SETTING: Cross-sectional histopathological analysis, in four university hospitals and one cancer care center. METHODS: 1,025 cases diagnosed as Hodgkin's lymphoma between 1990 and 2000 were collected from five institutions; 631 of them (61.5%) had been immunophenotyped using antibodies to CD20, CD3, CD15 and CD30. The relative frequencies of histological types (as informed by the contributing authors, who are hematopathologists in their institutions) were determined according to age and gender. RESULTS: The Hodgkin's lymphoma types were distributed as follows: lymphocyte predominance 4.8%, nodular sclerosis 69.2%, mixed cellularity 21.1% and lymphocyte depletion 4.6%. CONCLUSIONS: The controversy regarding the frequencies of Hodgkin's lymphoma types within the Brazilian setting seems to be due to the small number of cases in previous studies. The present data show a picture close to the situation in the industrialized countries.

Histological classification of 1,025 cases of Hodgkin's lymphoma from the state of São Paulo, Brazil

CONTEXTO E OBJETIVO: Tem-se afirmado correntemente que, em países industrializados, a esclerose nodular é o tipo mais freqüente de linfoma de Hodgkin, ao contrário de países em desenvolvimento, onde a celularidade mista e a depleção linfocitária são mais freqüentes. O objetivo do estudo é rever os dados histológicos de linfoma de Hodgkin das cidades de São Paulo e Campinas. TIPO DE ESTUDO E LOCAL: Transversal, por análise histopatológica, em quatro hospitais universitários e um centro oncológico de referência. MÉTODOS: 1.025 casos com o diagnóstico de linfoma de Hodgkin entre 1990 e 2000 foram coletados de cinco instituições. Em 631 (61,5%) casos fora feito estudo imunoistoquímico para os marcadores CD20, CD3, CD15 e CD30. As freqüências relativas dos tipos histológicos (informadas pelos autores que são hematopatologistas de suas respectivas instituições) foram determinadas nos diversos grupos etários e por gênero. RESULTADOS: Os tipos de linfoma de Hodgkin foram assim distribuídos: predominância linfocitária 4,8%, esclerose nodular 69,2%, celularidade mista 21,1% e depleção linfocitária 4,6%. CONCLUSÕES: Dados controversos sobre a freqüência dos tipos de linfoma de Hodgkin em nosso meio parecem ser devidos ao pequeno número de casos dos trabalhos anteriores. Nossos dados são comparáveis aos dos países industrializados.

Freqüência de neoplasia intra-epitelial cervical em portadoras do vírus da imunodeficiência humana / Frequency of cervical intraepithelial neoplasia in human immunodeficiency virus-infected women

Objetivo: verificar a freqüência de neoplasia intra-epitelial cervical (NIC) em mulheres infectadas pelo vírus da imunodeficiência humana (HIV). Métodos: foram estudadas 99 mulheres HIV -soropositivas; o diagnóstico da infecção pelo HIV foi realizado por meio de dois testes ELISA, complementados por teste Western blot ou de imunofluorescência indireta. Como grupo controle foram analisadas 104 mulheres que não apresentavam positividade no teste ELISA. Em ambos os grupos o rastreamento de NIC foi realizado por meio da associação de colpocitologia oncológica e colposcopia. Nos casos em que a colposcopia revelou existência de zonas de transformação anormal, o diagnóstico de NIC foi realizado mediante biopsia dirigida, complementada ou não por conização. Resultados: em 15 das 99 pacientes do grupo de estudo (15,2 por cento) foi encontrada neoplasia intra-epitelial cervical, sendo dez casos de NIC I, um de NIC II e quatro de NIC III. Entre as 104 mulheres do grupo controle, quatro (3,8 por cento) eram portadoras de neoplasia intra-epitelial cervical, encontrando-se um caso de NIC I e três de NIC III. Conclusão: a análise comparativa dos resultados evidenciou que freqüência de neoplasia intra-epitelial cervical foi significantemente mais elevada entre as pacientes infectadas pelo HIV

Efeitos da inoculação de endotoxina produzida por Escherichia coli, na morfologia tímica e no desenvolvimento ponderal de camundongos jovens / Effects of inoculation of endotoxin produced by Escherichia coli on thymic morphology and weight development in young mice

Este estudo descreve o efeito da injeção única, intraperitoneal de dose subletal de endotoxina, produzida por Escherichia coli na morfologia tímica e no desenvolvimento ponderal de camundongos jovens. Os animais foram separados em grupos de doze, sacrificados a cada 24 horas durante cinco dias e ao final de cada experimen.to, um grupo controle recebeu injeção intraperitoneal de solução salina. Observou-se, neste experimento, nítida redução de peso corpóreo nas primeiras 48 horas, com recuperação após esta fase e redução no peso dos timos, assim como alterações histológicas importantes. Um outro grupo, formado por oito camundongos, teve seu desenvolvimento ponderal acompanhado durante dois meses. Neste experimento foram constatados sinais de recuperação após as primeiras horas, mas cujo desenvolvimento não chegou a alcançar níveis normais como os controles (AU).

Reavaliaçäo dos resultados obtidos com a técnica de imunofluorescência direta em lesöes de lúpus eritematoso discoíde / Re-evaluation of the results obtained with the direct immunofluorescence technic in lesions of discord lupus erythematosus

A técnica de imunofluorescência direta aplicada a doentes com lúpus eritematoso está sendo intensamente reavialada nestes últimos anos. No presente trabalho, trazemos nossa colaboraçäo a essa discussäo, apresentando os resultados correspondentes a 60 pacientes com lúpus eritematoso discóide. Nossos resultados permitem avaliar o comportamento de imunofluorescência direta no que se refere aos seguintes dados: padräo de fluorescência da zona da membrana basal, natureza do material imunológico detectado, influência da idade e da localizaçäo das lesöes examinadas sobre o resultado. Em apenas 35 doentes (58,33%), a imunofluorescência foi positiva. Houve nítida influência da localizaçäo da lesäo e da idade da mesma sobre os resultados. No estado atual de nossos conhecimentos, temos de levar em conta os dados clínicos e histopatológicos disponíveis, para interpretar corretamente os resultados de imunofluorescência direta em lúpus eritematoso discóide