Primary colorectal diffuse large B-cell lymphoma: A report of eighteen cases in a tertiary care center.

Primary colorectal diffuse large B-cell lymphoma (DLBCL) is very rare colon malignancy. It is important to know the main demographic and clinical characteristics of these patients. We conducted a retrospective analysis of 18 patients diagnosed with primary colorectal DLBCL during a 17-year period at the National Cancer Institute of Brazil (INCA) between 2000 and 2018. Demographic characteristics, tumor localization, HIV status, lactate dehydrogenase (LDH) levels, treatment modality and follow-up status were obtained from medical records. Survival was estimated from the date of diagnosis until death. There were 11 male and seven female patients in our cohort, the median age at diagnosis was 59.5 years and four patients were HIV positive. Tumor was mainly localized in the right colon. Patients were treated with chemotherapy (CT) and/or surgical resection. Eleven patients died during a median follow-up of 59 months and the median survival time was 10 months. Six or more cycles of CT (HR=0.19; CI 95% 0.054-0.660, p = 0.009), LDH levels below 350 U/L (HR=0.229; CI 95% 0.060-0.876, p = 0.031) and surgical resection (HR=0.23; CI 95% 0.065-0.828, p = 0.030) were associated with reduced risk of death in univariate analysis. Patient's age and DLBCL right colon localization should be considered at diagnosis to distinguish between DLBCL and other diseases for differential diagnosis. Six cycles of CT, LDH levels below 350 U/L and surgical resection were associated with better survival. Our results are consistent with previous publications and address the importance of correct colorectal DLBCL diagnosis and treatment.

Molecular Predictors for Advanced Papillary Thyroid Carcinoma Recurrence.

Despite its indolent course, one-third of the papillary thyroid carcinoma (PTC) cases relapses, which directly impact on the quality of patients' lives. The molecular predictors of recurrence of PTC are poorly defined. We aimed at evaluating the long-term (10-20 years) prognostic value of aggressiveness markers in advanced PTC. To this end, immunohistochemistry for BRAFV600E, Estrogen receptor α, Progesterone receptor, Ki-67, and E-cadherin were performed in 53 primary advanced PTC from an up to 20 years follow-up patients from a well-characterized Brazilian cohort. Categorical data were summarized using frequencies and groups were compared using Chi-squared and Fisher's exact tests. The expressions of the aggressiveness markers were associated with clinical-pathological data using the single-covariate logistic regression analysis. The Kaplan-Meier method with the Log-rank and Peto tests was used to estimate the probability of PTC-free survival. Persistence and recurrence (active disease) were associated with age (≥55 years), tumor size (>2 cm), extrathyroidal extension, local aggressiveness, macroscopic lymph node metastasis, and TNM stage at initial treatment. The BRAFV600E mutation status was associated with extrathyroidal extension, local aggressiveness, and inversely associated with distant metastasis at initial treatment. All progesterone receptor-positive patients had active disease and displayed a shorter time of PTC-free survival than the negative ones using the Kaplan-Meir analysis (p = 0.001, Log Rank; p = 0.005, Peto). Loss of E-cadherin expression was associated with an increase in the probability of active disease (OR = 3.75). BRAFV600E could be useful as a biomarker of local aggressiveness, while PR positive and E-cadherin loss of expression could predict the recurrence of advanced PTC.

Nasal-type extranodal T-cell/NK lymphoma in association with hemophagocytic syndrome.

Extranodal NK/T-cell lymphoma nasal type is a rare disease that mainly affects the nasal cavity and paranasal sinuses of males in the fifth decade of life. It has aggressive and locally destructive behaviour, and can be complicated by the hemophagocytic syndrome, conferring high lethality to the disease. This article describes a case of NK/T-cell lymphoma nasal type in a previously healthy patient, exemplifying its rapid and fulminant course.

Nasal-type extranodal T-cell/NK lymphoma in association with hemophagocytic syndrome

Abstract: Extranodal NK/T-cell lymphoma nasal type is a rare disease that mainly affects the nasal cavity and paranasal sinuses of males in the fifth decade of life. It has aggressive and locally destructive behaviour, and can be complicated by the hemophagocytic syndrome, conferring high lethality to the disease. This article describes a case of NK/T-cell lymphoma nasal type in a previously healthy patient, exemplifying its rapid and fulminant course.

MiR-29 silencing modulates the expression of target genes related to proliferation, apoptosis and methylation in Burkitt lymphoma cells.

PURPOSE: Burkitt lymphoma (BL) is a B-cell lymphoma frequently diagnosed in children. It is characterized by MYC translocations, which lead to the constitutive expression of the MYC oncogene. MYC contributes to miR-29 repression through an E-box MYC binding site on the miR-29b-1/miR-29a promoter region. We evaluated the role of miR-29a/b/c and their predicted targets in BL pathogenesis. METHODS: Mature sequences of miR-29a/b/c were transfected to the BL cell lines BL41 and Raji, and evaluated for DNMT3B, MCL1, BIM, CDK6, AKT and TCL1 protein expression as well as for MCL-1 and CDK6 mRNA expression. BL cells were treated with 5-aza-2'-deoxycytidine (decitabine) and evaluated for miR29 expressions and methylation status. DNMT3B inhibition was performed by DNMT3B siRNA. RESULTS: Ectopic expression of miR-29s in BL cells decreased CDK6, DNMT3B, TCL1 and MCL-1 protein levels, but CDK6 and MCL-1 mRNA expression was unaffected by miR-29. Decitabine enhanced miR-29 expression levels and decreased CDK6 protein expression. Additionally, inhibition of DNMT3B by siRNA increased miR-29a/b expression. Notably, the miR-29a/b1 and miR-29b2/c promoter genes showed methylated CpG sequences that were demethylated after decitabine treatments. Furthermore, MYC-negative tumours had higher levels of miR-29 expression compared with MYC-translocated cases, suggesting that MYC regulates miR-29 in BL tumours. CONCLUSIONS: Our results suggest a significant role for miR-29s in BL pathogenesis in altering the expression of targets involved in critical cancer pathways, such as cell cycle control, apoptosis inhibition and DNA methylation. Moreover, methylation-mediated miR-29 epigenetic silencing may occur during BL development.

Simultaneous lymph node involvement by Castleman disease and Kaposi sarcoma

Both multicentric Castleman disease and Kaposi sarcoma are more frequently observed in HIV infected patients. The coexistence of these Human herpesvirus 8 related lesions, in the same tissue, has been observed, but literature reports are scant. On the other hand, the expression of HHV-8-LANA-1 is easily demonstrable by immunohistochemistry. This has been shown to be a powerful tool for the diagnosis of these entities. The aim of this report is to communicate our experience with a case of multicentric Castleman disease occurring in the setting of HIV infection, which demonstrated microscopic Kaposi sarcoma in the same lymph node during the pathological work-up.

Simultaneous lymph node involvement by Castleman disease and Kaposi sarcoma.

Both multicentric Castleman disease and Kaposi sarcoma are more frequently observed in HIV infected patients. The coexistence of these Human herpesvirus 8 related lesions, in the same tissue, has been observed, but literature reports are scant. On the other hand, the expression of HHV-8-LANA-1 is easily demonstrable by immunohistochemistry. This has been shown to be a powerful tool for the diagnosis of these entities. The aim of this report is to communicate our experience with a case of multicentric Castleman disease occurring in the setting of HIV infection, which demonstrated microscopic Kaposi sarcoma in the same lymph node during the pathological work-up.

Glioblastomas: correlation between oligodendroglial components, genetic abnormalities, and prognosis.

It has been demonstrated that a small percentage (approximately 15%) of glioblastomas (GBM) presents an oligodendroglial component with a variable frequency of chromosome 1p and 19q deletions, the genetic alteration related to chemotherapy response and longer survival in oligodendrogliomas. There is a growing interest in investigating 1p and 19q losses in hybrid gliomas and their impact on prognosis. A series of 88 GBMs was investigated regarding 1p and/or 19q losses, 24 with oligodendroglioma-like areas, using quantitative microsatellite analysis and/or fluorescent in situ hybridization. When present, the oligodendroglial and astrocytic components were independently investigated. Clinical data, histology, and 1p/19q status were correlated. Tumors with oligodendroglial components showed three cases each of 1p or 19q loss and one with combined 1p/19q loss. No difference in 1p or 19q status was observed between the oligodendroglial and astrocytic components. Conventional GBM demonstrated isolated 1p loss in four cases and 19q loss in five. No association was seen between 1p/19q status and histology. Deletions at 1p and/or 19q were infrequent in GBMs with oligodendroglial components. Despite the hybrid phenotype, the pattern of genetic changes at 1p and 19q was not different from that usually observed in conventional GBMs, nor did it show any correlation with survival.

Correlação entre componente oligodendroglial, anormalidades cromossômicas e prognóstico nos glioblastomas / Correlation between oligodendroglial component, genetic abnormalities and prognosis in glioblastomas

Glioblastoma é a neoplasia glial mais comum e de maior agressividade nos adultos. Apesar do tratamento multimodal, o prognóstico é pobre e a média de sobrevida de menos de 1 ano. O padrão histológico é bastante variado e uma pequena fração destes tumores pode apresentar um componente oligodendroglial. O significado clínico da distinção entre tais tumores e glioblastomas convencionais ainda permanece desconhecido, mas já foi sugerido que a presença do componente oligodendroglial pode estar associada a uma maior sobrevida. Os estudos moleculares de glioblastomas com componente oligodendroglial têm mostrado alterações genéticas heterogêneas, com freqüências variadas na literatura de perda de heterozigosidade em 1p e 19q, alterações relacionadas com sobrevida prolongada e resposta à quimioterapia em tumores oligodendrogliais e que levaram a um interesse na investigação destas alterações em outros gliomas. A literatura apresenta dados controversos e ainda não foi possível estabelecer uma associação definitiva entre a maior sobrevida observada em alguns pacientes e o perfil genético/molecular. O objetivo deste estudo foi pesquisar as alterações cromossômicas associadas ao fenótipo oligodendroglial em uma série de 88 glioblastomas, 24 deles com componente oligodendroglial, utilizando duas técnicas complementares (FISH e análise quantitativa de microssatélites) para investigação de perdas alélicas, correlacionando os resultados com o prognóstico. Os resultados mostraram que deleções nos cromossomos 1p e 19q são infreqüentes nos glioblastomas com componente oligodendroglial. Apesar do fenótipo híbrido, o padrão de alterações genéticas nos cromossomos 1p/19q foi semelhante aquele observado nos glioblastomas convencionais e não mostrou impacto na sobrevida. O presente estudo também confirmou a relação da idade e do tratamento adjuvante com o prognóstico nos pacientes com glioblastomas.

Glioblastoma is the most frequent and aggressive astrocytic tumor in adults. Despite the multimodal therapy, the prognosis remains poor and the mean survival is of less than a year. The histology of glioblastomas can be quite variable and a small fraction of the tumors may present an oligodendroglial component. The clinical significance of the distinction between these tumors and conventional glioblastomas remains uncertain, but the presence of an oligodendroglial component has been associated with longer survival. Molecular genetic studies of glioblastomas with oligodendroglial component have shown heterogeneous genetic alterations, with a variable frequency of LOH on chromosomes 1p and 19q. The presence of 1p/19q deletions has been related to prolonged survival and response to chemotherapy in oligodendrogliomas and led to a growing interest in search for the same genetic alterations in other gliomas. At present, literature data is not sufficient to establish a definite correlation between the longer survivals observed in some patients and the molecular genetic profile. The aim of this study was to identify chromosomal alterations related to oligodendrogliomas (1p/19q loss) in a series of 88 glioblastomas, 24 of them with an oligodendroglial component, through quantitative microsatellite analysis using real time PCR and fluorescent in situ hybridization, correlating genetic data with prognosis. Deletions on 1p and/or 19q were infrequent in glioblastomas with oligodendroglial component. Despite the hybrid phenotype observed, the pattern of genetic changes on chromosomes 1p and 19q wasn't different from that usually observed in conventional glioblastomas and showed no correlation with survival. Our study also confirmed the already known impact of young age and adjuvant treatment on prognosis (AU)

[Oligodendroglial and neuronal component in glioblastomas: possible relation with prognosis]. / Componente oligodendroglial e neuronal em glioblastomas: possível relação com o prognóstico.

Glioblastomas are high grade astrocytic tumors and current histology criteria does not explain the longer survival in some cases. Presence of oligodendroglial component has been suggested as possible marker for better outcome by the international WHO Working Group of experts and by the proponents of the Sainte-Anne Hospital Classification (2000). The latter also states that a neuronal component is associated with better survival. The aim of this study was to analyze a series of 40 patients with tumors classified as glioblastomas based on the WHO criteria, in order to identify: the presence of an oligodendroglial component, using morphologic criteria; the presence of a neuronal component, using immunohistochemical markers (antibodies anti-neurofilament and synaptofisin). The histological and immunohistochemical findings were correlated with patients' survival and other variables of possible prognostic significance were also studied. Oligodendroglial component was identified in 11 cases and neuronal component in 7. Despite the small number of patients studied, this review detected a longer survival in patients with oligodendroglial component. The significance of expression of neuronal markers in malignant gliomas is still to be confirmed, with the evaluation of larger series.

Componente oligodendroglial e neuronal em glioblastomas: possível relação com o prognóstico / Oligodendroglial and neuronal component in glioblastomas: possible relation with prognosis

Glioblastomas são tumores astrocíticos de alto grau de malignidade e o diagnóstico baseado nos critérios histológicos atuais não tem explicado a maior sobrevida observada em alguns casos. A presença de um componente oligodendroglial foi proposta mais recentemente como um possível indicador de maior sobrevida, tanto pela OMS quanto pela classificação de Sainte Anne 2000. Esta última propõe ainda que um componente neuronal está relacionado com maior sobrevida. O objetivo deste estudo foi rever tumores de 40 pacientes diagnosticados como glioblastomas pelos critérios da OMS, com o propósito de identificar: a presença de um componente oligodendroglial utilizando critérios morfológicos; a presença de um componente neuronal utilizando marcadores imuno-histoquímicos (anticorpos anti-neurofilamento e sinaptofisina). Objetivou-se também correlacionar os achados histológicos e imuno-histoquímicos com a sobrevida dos pacientes, estudando também outras variáveis que podem ter influência na sobrevida. Foram identificados 11 tumores com componente oligodendroglial e 7 com componente neuronal. Apesar do pequeno número de casos estudados, a presença de um componente oligodendroglial associou-se com maior sobrevida. O valor da expressão de marcadores neuronais em gliomas malignos precisa ser confirmado com a avaliação de séries maiores.