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.

O papel da expressão de Bcl-2 em material obtido por PAAF no diagnóstico de doenças linfoproliferativas B / The role of Bcl-2 expression in fine needle aspiration specimens for the diagnostic accuracy in lymphoproliferative diseases

INTRODUÇÃO: O diagnóstico das doenças linfoproliferativas (DLP) tradicionalmente baseia-se no estudo histológico dos linfonodos (LN) acrescido de imuno-histoquímica. A imunofenotipagem (IFT) pela citometria de fluxo (CF) é uma ferramenta sensível e rápida, que pode ser aplicada nas DLP, em material obtido por punção aspirativa por agulha fina (PAAF) de LN. O Bcl-2 é um proto-oncogene que se expressa em várias DLP, porém em níveis especialmente elevados no linfoma folicular (LF). OBJETIVOS: Diagnosticar DLP, através de morfologia e imunofenotipagem por CF, em amostras obtidas por PAAF de LN. MATERIAL e MÉTODO: Amostras de 25 pacientes com adenopatias e de duas tonsilas reacionais foram analisadas pela morfologia e IFT, utilizando um painel inicial de AcMo (CD3, CD4, CD8, CD19, anti-kappa; e anti-lambda;), ampliado conforme a necessidade (CD5, CD10, CD11c, CD23, CD79b, sIgM, FMC-7 e Bcl-2). Os resultados foram comparados com a histologia. RESULTADOS:Dos 25 casos, quatro foram classificados como reacionais e 21 como DLP-B, havendo concordância com resultados histológicos em todos os casos. A intensidade média de fluorescência (IMF) da Bcl-2 no LF (19,92) foi maior que em outras DLP-B (11,93) e que nos controles (3,49) (p = 0,032). CONCLUSÃO:A PAAF de LN combinada com a citomorfologia e a IFT por CF permite uma rápida diferenciação entre os processos reacionais e linfoproliferativos B. A elevada expressão da Bcl-2 nos LFs pela citometria mostra sua utilidade no diagnóstico do tipo mais freqüente das DLP-B. A obtenção de células por PAAF requer treinamento e recomendamos mais de uma punção.

BACKGROUND: The diagnosis of lymphoproliferative disorders (LPD) is routinely made through histological and immunohistochemical analysis of lymph nodes. Immunophenotyping by flow cytometry (FC) is a sensitive and fast tool, which may be applied in samples obtained through fine needle aspiration for the diagnosis of LPD. Bcl-2 is a proto-oncogene that appears in several LPD and it has a significantly high expression in follicular lymphomas. OBJECTIVES: to diagnose LPD in FNA samples through morphology and flow cytometry immunophenotyping. MATERIAL AND METHODS: Samples from 25 patients with lymphadenopathies and 2 reactive tonsils were studied through morphology and immunophenotyping. The antigens expressions were evaluated by using a screening panel of monoclonal antibodies (CD3, CD4, CD8, CD19, light chains kappa; and lambda), followed by CD5, CD10, CD11c, CD23, CD79b, sIgM, FMC-7 and Bcl-2 when required. The results were compared with histology. RESULTS:Four out of 25 samples were reactive processes and 21were B-LPD. In all cases there was consistency with histological results. The mean fluorescence intensity of Bcl-2 in Follicular Lymphoma (19.92) was higher compared with other lymphoproliferative diseases (11.93) and controls (3.49) (p = 0.032). CONCLUSION: Fine needle aspiration of lymph nodes associated with cytomorphology and flow cytometry immunophenotyping allows a fast differentiation between reactive processes and B lymphoproliferative cases. The high expression of Bcl-2 by cytometry shows its usefulness in the diagnosis of the most frequent type of B-LPD. Fine needle aspiration sampling requires training and more than one aspiration is recommended.

Is the follicular lymphoma international prognostic index better than the international prognostic index to identify high-risk follicular lymphoma patients?

The aims of this study are to validate follicular lymphoma international prognostic index (FLIPI) prognostic score and to compare it with the international prognostic index (IPI) in a cohort of 57 Brazilian patients. According to IPI, 24 patients (42%) were in the low-risk, 28 (49%) in the intermediate-risk, and 4 (7%) in the high-risk group. The distribution according to FLIPI was: 20 (35%) in the low-risk, 8 (14%) in the intermediate-risk, and 29 (51%) in the high-risk group. According to IPI score, median OS was not reached for the low-risk, it was 45 months for the intermediate-risk and 25 months for the high-risk group (p < 0.001). When FLIPI score was applied, median OS was not reached for the low and intermediate-risk, and was 42 months for the high-risk group (p = 0.0064). These findings suggest that: (1) FLIPI score could be validated in a Brazilian population; (2) FLIPI is more accurate than IPI to identify FL patients having worse prognosis (51%); (3) IPI seems to be a better tool for clinical decisions because it selected a smaller high-risk group (7%) having worse prognosis. In our opinion, IPI high-risk patients are the real candidates for more aggressive therapies, avoiding unnecessary over-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.

Possible influence of clinical stage and type of treatment in the persistence of residual circulating t(14;18)-positive cells in follicular lymphoma patients.

Many patients with follicular lymphoma (FL) achieve response after treatment but complete remission (CR) rates are very low. Thus the majority of them will relapse, mainly those in advanced stage disease, due to the persistence of residual disease. Therefore, this study had the following aims: to determine the presence of bcl-2/IgH rearrangement in peripheral blood of early and advanced stage FL patients after treatment and to correlate it with their clinical situation at the same moment. We obtained 100 consecutive peripheral blood samples from 30 FL cases and conducted molecular studies using two separate semi-nested PCRs for MBR and mcr rearrangements. These semi-nested PCRs for bcl-2/IgH rearrangement were able to detect one positive cell among 10,000 normal cells. Clinical and molecular evolution of patients diagnosed as early stage disease suggested that molecular response could be obtained even with conventional chemotherapy or radiotherapy. In this group of patients, 64% achieved molecular response in some point during follow-up. However, only 23% of patients diagnosed as advanced stage disease reached molecular response when treated with chemotherapy (with or without radiotherapy). Due to the low number of subjects assessed in this study, we only found a tendency to significance when clinical stage at the diagnosis was associated to molecular response (P = 0.095). We observed 100% of concordance between clinical remission and molecular response in patients after bone marrow transplantation or in those cases treated with monoclonal antibody anti-CD20. This retrospective study, performed in a restricted number of patients, suggests that molecular response can be obtained in FL patients diagnosed at early stage disease, even with conventional chemotherapy and radiotherapy. In advanced stage disease, concordance between clinical remission and molecular response was observed in the majority of patients after bone marrow transplantation or in those cases treated with monoclonal antibody anti-CD20. The prognostic significance of this data should be confirmed with extended follow-up and in a larger number of patients.

Correlation between histological subtype and type of bcl-2/IgH rearrangement in follicular lymphomas.

The aims of this study were: 1) to identify the type of bcl-2 rearrangement in a Brazilian group of FL patients and 2) to correlate it to clinical features, International Prognostic Index (IPI), histological subtype, response to treatment and clinical outcome. We reviewed the diagnosis of 48 patients with FL and investigated the type of bcl-2 gene rearrangement using DNA from paraffin-embedded tumor samples obtained at the time of diagnosis. In 30 cases, we also obtained consecutive peripheral blood samples to search for the presence of bcl-2/IgH rearrangement. Molecular analysis identified 41 (86%) patients with MBR and 5 (10%) patients with mcr rearrangement. In this study, the type of rearrangement was not associated with clinical characteristics or IPI. In addition, the type of rearrangement did not have an impact on response to initial treatment or on clinical outcome. However, we found an association between the type of rearrangement and the histological subtype of FL, i.e., none of mcr-positive patients presented histological grade I (p = 0.043). In this study, we could not demonstrate a relationship between the type of bcl-2 rearrangement and the response to treatment or outcome. However, we found a relationship between the type of rearrangement and FL histological subtype, information not previously reported.

2-Chloro-deoxyadenosine induces durable complete remission in Castleman's disease but may accelerate its transformation to non-Hodgkin's lymphoma.

There is currently no consensus on the best treatment for unresectable hyaline-vascular variant or for multicentric Castleman's disease (MCD), because none of the reported regimens have consistently produced complete response or durable remission in the majority of patients In the present study, we report on the use of 2-CdA (2-chloro-deoxyadenosine) in three patients, two of them with MCD and one with unresectable hyaline-vascular type disease. Relapse-free survival of the responding patients was 24 and 20 months. Later, both patients evolved to non-Hodgkin's lymphoma (NHL) (diffuse large B-cell lymphoma and peripheral T-cell NHL, respectively). 2-CdA typically causes a long-lasting state of immunodeficiency and the profound influence of this drug on the immune system has raised questions concerning the emergence of secondary neoplasms after its use. Therefore, it is reasonable to conclude that: 1) 2-CdA can induce durable complete remission in MCD patients but unfortunately it cannot cure the disease; 2) the possibility that 2-CdA may accelerate the transformation of MCD to NHL cannot be ruled out.

Relação entre angiogênese e estádio no carcinoma do endométrio / The relationship between endometrial adenocarcinoma staging and angiogenesis

OBJETIVO: avaliar se o número de vasos neoformados é fator importante para o prognóstico do adenocarcinoma endometrial, comparando-o com o grau de diferenciaçäo histológica e o estadiamento do tumor. MÉTODOS: foram estudadas 56 amostras de tecido endometrial, sendo 11 com o diagnóstico histológico de endométrio atrófico, 10 endométrios proliferativos (ambos caracterizados como grupos controle), 10 amostras de adenocarcinomas GI, 13 adenocarcinomas GII e 12 adenocarcinomas GIII, caracterizados como grupos de estudo. Dois cortes histológicos foram obtidos de cada caso: um foi corado pela hematoxilina-eosina e o outro, para estudo imuno-histoquímico, foi tratado com anti-CD34, com a finalidade de corar vasos. A contagem vascular foi realizada na interface do crescimento tumoral com o estroma adjacente, em dez campos de 100 vezes de aumento, mediante estudo morfométrico pelo sistema computadorizado Kontron S300. No grupo controle, foi selecionada a interface entre glândulas endometriais e estroma adjacente. RESULTADOS: a média de vasos contados em 10 campos foi de 11,6 para o endométrio atrófico; 13,2 para o proliferativo; 15,3 para o adenocarcinoma GI; 19 para o adenocarcinoma GII e 22,7 para o adenocarcinoma GIII. A média de quantificaçäo vascular para os tumores das pacientes incluídas no estadiamento clínico I foi 18,6, semelhante estatisticamente àquelas dos estadiamentos II, III e IV (20,9) computados em conjunto. CONCLUSÄO: concluímos que o adenocarcinoma pouco diferenciado apresenta maior número de vasos por campo que o endométrio normal e que o carcinoma bem diferenciado. A quantificaçäo vascular näo foi influenciada pelo estadiamento como fator isolado

Clinical management of six cases of low-risk primary tonsillar non-Hodgkin's lymphoma

CONTEXT: There have been many reports that favor aggressive systemic treatment with chemotherapy and radiotherapy, even for well-localized lymphomas, avoiding the need for tonsillectomy of the normal tonsil. CASE REPORT: We report six cases of primary tonsillar lymphoma with a median patient age of 42 years. There were two lymphoma cases with diffuse large cells, two cases with mixed small and large cells, one with small cells and one indeterminate. They were treated with six cycles of chemotherapy and cervical radiotherapy. All patients achieved durable complete remission. Our data agree with previous reports that suggested that primary tonsillar high-grade B-cell NHL has a good prognosis if aggressively treated.

Linfoma de sistema nervoso central com comprometimento intra e extracraniano em paciente näo imunodeprimido: relato de caso e revisäo da literatura / Central nervous system Hodgkin's limphoma with intra and extra cranial envolvent in a non immunocompromised patient. Case report and literature review

Relatamos um caso de linfoma näo Hodgkin de grandes células B em gânglios da regiäo cervical e retroperitôneo e com sítios de comprometimento extra nodal: encéfalo, calota craniana, couro cabeludo e infiltraçäo de vértebra T4. O perfil sorológico se mostrou negativo para anticorpos anti-HIV e a paciente foi tratada com seis ciclos de quimioterapia sistêmica de terceira geraçäo para linfomas agressivos (ProMACE-CytaBOM) em doses convencionais e radioterapia em encéfalo (dose total 4.000 cGY).Encontra-se em remissäo clínica e radiológica completa dez meses após o diagnóstico de linfoma. Discutimos o tratamento do linfoma primário de sistema central em pacientes näo imunodeprimidos.

Chordoma: retrospective analysis of 24 cases

INTRODUCTION: Chordoma is a rare and slow-growing tumor, with local aggressiveness and preferential localization in the vertebral column. OBJECTIVE: The main objective of this study is to evaluate natural history and results of treatment of chordomas. METHODOLOGY: This is a retrospective study from 1953 to 1993. MATERIAL AND METHODS: The age ranged from 2 to 86 years (mean = 34.5). Twelve patients were male and 12 female. The localization of the tumor was: 20 in the sacral region, 3 in head and neck and one out of the spine. RESULTS: The treatment, alone or combined, was surgery, radiation therapy and chemotherapy. The survival rate for patients with lesions in the sacrum ranged from 4 to 119 months, since the date of the symptoms. The 5-year overall survival was 4.2. CONCLUSION: Chordoma is a rare and slow growing tumor, with a very difficult approach by surgery due to its preferential location in the sacrum and poor therapeutic results with radiation therapy or chemotherapy, mainly in patients with advanced disease.

Metástase linfonodal de sarcomade partes moles em adulto. Relato de caso / Lymph node metastasis from soft tissue sarcoma in adult. Case report

Os autores descrevem o caso de um paciente de 33 anos, branco, masculino, com rabdomiossarcoma de alto grau de malignidade da face anterior da coxa direita e metástase linfonodal na regiao ilíaca. Foi tratado com radioterapia pré-operatória, ressecçao ampla em monobloco com linfadenectomia iliinguinal e quimioterapia pós-operatória. Está vivo e assintomático sete anos e três meses após o tratamento. Teve como complicaçoes cirúrgicas imediatas alto débito de secreçao pelo dreno de sucçao e pequena área de deiscência com infecçao da ferida operatória. Como complicaçao tardia, apresentou fratura do colo do fêmur, que foi resolvida com cirurgia de Girdestone.

Peritumorous lymph-vascular invasion, grade of histologic differentiation, and myometrial infiltration as prognostic factors of endometrial carcinoma

The authors evaluated 50 patients with endometrial carcinoma studying the prognostic parameters: histologic grade, myometrial invasion and lymph-vascular space invasion. The patients were divided into two groups: A - a good prognosis group (33 cases) - with no recurrence and/or metastasis occuring for five years; and B - a bad prognosis group (17 cases) - with recurrence and/or metastasis or death within five years. We concluded that lymph-vascular space invasion was more frequent in group B, and was a reliable parameter for vad prognosis. The lymph-vascular space invasion was always accompained by myometrial invasion and patients whose myometrium had not been involved did not have lymph-vascular space invasion. In both groups, in well-differentiated tumors, there was no lymph-vascular space involvement. The well-differentiated tumors were statistically more frequent in the good prognosis group. Myometrial invasion was not statistically significant as a prognostic parameter

Histological study of the endometrium in menopausal women with breast carcinoma

The first reference concerning the multiple primary malignant neoplasms was made by Bilroth, 1880 and since then a large number of studies have been published. Furthermore, an increasing incidence of simultaneous cancers are currently observed (16,18). At the same time, several retrospective populational studies evidenced the association between breast and endometrium carcinoma. It is well known that both uterus and breast are hormone-dependent organs and are likely to be influenced by the same oncogenic stimulus, either of endocrine nature or dietary origin (2, 3, 14). The risk of developing endometrial carcinoma is higher in patients already affected by breast neoplasm and is much more evident in older women within the first five years following the diagnosis of breast tumor. Conversely, patients with endometrial carcinoma may present a second mammary neoplasm and the relative risk is around 2.0 (1, 17). Although the existence of a correlation between these two primary malignant neoplasms is clearly observed, the absence of systematic studies directed to the screening of endometrial cancer in women with breast carcinoma is surprising. This study deals with histological analysis of the endometrium of postmenopausal patients with breast cancer and aims to determine the possible changes that might have occurred in the onset of the disease

Teratoma de hipofaringe: relato de caso e revisäo de literatura / Hipopharynx teratoma: report of a case and review of the literature

Teratomas säo neoplasias que se originam de células pluripotenciais e säo compostos de uma larga diversidade de tecidos estranhos ao órgäo ou sítio anatômico no qual eles aparecem. Ocorrem mais freqüentemente em crianças com menos de um ano de idade, principalmente neona, sendo normalmente notados ao nascimento. Os teratomas localizados na cabeça e pescoço säo raramente observados quando presentes, säo observados na nasofaringe e na regiäo cervical. Relatamos o caso de um recém-nascido portador de desconforto respiratório devido a tumor em regiäo de hipofaringe, que ocasionava uma obstruçäo das vias aéreas superiores. O paciente foi submetido à exérese do tumor por via transoral, tendo o resultado do estudo anatomopatológico demonstrado tratar-se de um teratoma maduro