Patterns of change in treatment, response, and outcome in patients with follicular lymphoma over the last four decades: a single-center experience.

Although the introduction of immunotherapy has improved outcomes for follicular lymphoma (FL) patients, histological transformation (HT) and early relapse still confer a poor prognosis. We sought to describe the patterns of change in treatment, response, and outcome of FL patients at our institution over the last four decades. Seven hundred and twenty-seven patients (389 F/338 M; median age, 57 years) consecutively diagnosed with grade 1-3a FL between 1980 and 2017, categorized into four decades according to the time of diagnosis, constituted the study population. Clinical characteristics, treatment, response, absolute and relative survival, HT, second malignancies (SM), and causes of death were assessed. Median OS for the entire cohort was 17.6 years. From decade 1 to 4, there was an increase in the complete response rate (48 to 70%), progression-free survival (40 to 56% at 5 years), OS (77 to 86% at 5 years), and relative survival ratio (0.83 to 0.94 at 5 years), with no significant differences in the risk of HT or SM. Lymphoma remained the most common cause of death in all four decades. These findings illustrate the overall improvement in outcome for FL patients, but support the need for further research into risk stratification and management

Burkitt-like lymphoma with 11q aberration: A germinal center derived lymphoma genetically unrelated to Burkitt lymphoma

Burkitt-like lymphoma with 11q aberration is characterized by pathological features and gene expression profile resembling Burkitt lymphoma but lack MYC rearrangement and carries an 11q-arm aberration with proximal gains and telomeric losses. Whether these lymphomas are a distinct category or a particular variant of other recognized entities is controversial. To improve the understanding of Burkitt-like lymphoma with 11q aberration we have performed an analysis of copy number alterations and targeted sequencing of a large panel of B-cell lymphoma related genes in 11 cases. Most patients had localized nodal disease and a favourable outcome after therapy. Histologically, they were high grade B-cell lymphoma, not otherwise specified (8 cases), diffuse large B-cell lymphoma (2 cases) and only one was considered as atypical Burkitt lymphoma. All cases had a germinal center B-cell signature and phenotype with frequent LMO2 expression. Burkitt-like lymphoma with 11q aberration had frequent gains of 12q12-q21.1 and losses of 6q12.1-q21, and lacked common Burkitt lymphoma or diffuse large B-cell lymphoma alterations. Potential driver mutations were found in 27 genes, particularly involving BTG2, DDX3X, ETS1, EP300, and GNA13. However, ID3, TCF3, or CCND3 mutations were absent in all cases. These results suggest that Burkitt-like lymphoma with 11q aberration is a germinal center derived lymphoma closer to high grade B-cell lymphoma or diffuse large B-cell lymphoma rather than Burkitt lymphoma.Copyright © 2019, Ferrata Storti Foundation

A unifying hypothesis for PNMZL and PTFL: morphological variants with a common molecular profile

Pediatric nodal marginal zone lymphoma (PNMZL) is an uncommon B-cell neoplasm affecting mainly male children and young adults. This indolent lymphoma has distinct characteristics that differ from those of conventional nodal marginal zone lymphoma (NMZL). Clinically, it exhibits overlapping features with pediatric-type follicular lymphoma (PTFL). To explore the differences between PNMZL and adult NMZL and its relationship to PTFL, a series of 45 PNMZL cases were characterized morphologically and genetically by using an integrated approach; this approach included whole-exome sequencing in a subset of cases, targeted next-generation sequencing, and copy number and DNA methylation arrays. Fourteen cases (31%) were diagnosed as PNMZL, and 31 cases (69%) showed overlapping histologic features between PNMZL and PTFL, including a minor component of residual serpiginous germinal centers reminiscent of PTFL and a dominant interfollicular B-cell component characteristic of PNMZL. All cases displayed low genomic complexity (1.2 alterations per case) with recurrent 1p36/TNFRSF14 copy number-neutral loss of heterozygosity alterations and copy number loss (11%). Similar to PTFL, the most frequently mutated genes in PNMZL were MAP2K1 (42%), TNFRSF14 (36%), and IRF8 (34%). DNA methylation analysis revealed no major differences between PTFL and PNMZL. Genetic alterations typically seen in conventional NMZL were absent in PNMZL. In summary, overlapping clinical, morphologic, and molecular findings (including low genetic complexity; recurrent alterations in MAP2K1, TNFRSF14, and IRF8; and similar methylation profiles) indicate that PNMZL and PTFL are likely part of a single disease with variation in the histologic spectrum. The term "pediatric-type follicular lymphoma with and without marginal zone differentiation" is suggested.Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved

Microscopía virtual en la enseñanza de la Anatomía Patológica en Medicina

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524Introducción y objetivos: La microscopía virtual (MV) se ha introducido en la educación post-graduada en las Facultades de Medicina. No obstante, la experiencia acumulada con esta tecnología es aún limitada y existen muy escasas evidencias sobre su impacto sobre los estudiantes. Los objetivos del estudio fueron: 1) determinar si el posible impacto sobre las notas en los exámenes prácticos de la asignatura del paso de las preparaciones de cristal y el microscopio convencional (MC) a las preparaciones virtuales y el MV, y 2) evaluar la impresión subjetiva de los estudiantes en relación con el impacto de la MV en su aprendizaje. Métodos: Se evaluaron dos grupos que realizaron la asignatura de Anatomía Patológica en el curso 2013-2014, uno usando MC y el otro MV. Las mismas preparaciones utilizadas en el grupo de MC fueron digitalizadas en un escáner Ventana iScan HT a 20x y presentadas a los estudiantes con el visor Virtuoso (Roche diagnostics). Se evaluó el nivel de conocimientos alcanzado por los estudiantes mediante un examen online. Se realizó una encuesta a los estudiantes del grupo MV para evaluar sus impresiones sobre el recurso docente. Resultados: No existieron diferencias entre los dos grupos en cuanto a las notas obtenidas en el examen online: 9,87 ± 0,34 para el grupo de MC, vs 9,86 ± 0,53 para el grupo de MV; p=0,880). La característica más valorada de la MV fue la posibilidad de acceder a las imágenes en cualquier lugar y a cualquier hora (93.3%). El 86.6% de los estudiantes encontraron que el software era fáci

Akt-mediated phosphorylation of Bmi1 modulates its oncogenic potential, E3 ligase activity, and DNA damage repair activity in mouse prostate cancer

Prostate cancer (PCa) is a major lethal malignancy in men, but the molecular events and their interplay underlying prostate carcinogenesis remain poorly understood. Epigenetic events and the upregulation of polycomb group silencing proteins including Bmi1 have been described to occur during PCa progression. Here, we found that conditional overexpression of Bmi1 in mice induced prostatic intraepithelial neoplasia, and elicited invasive adenocarcinoma when combined with PTEN haploinsufficiency. In addition, Bmi1 and the PI3K/Akt pathway were coactivated in a substantial fraction of human high-grade tumors. We found that Akt mediated Bmi1 phosphorylation, enhancing its oncogenic potential in an Ink4a/Arf-independent manner. This process also modulated the DNA damage response and affected genomic stability. Together, our findings demonstrate the etiological role of Bmi1 in PCa, unravel an oncogenic collaboration between Bmi1 and the PI3K/Akt pathway, and provide mechanistic insights into the modulation of Bmi1 function by phosphorylation during prostate carcinogenesis

Microscopía virtual en la enseñanza de la Anatomía Patológica en Medicina

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524Introducción y objetivos: La microscopía virtual (MV) se ha introducido en la educación post-graduada en las Facultades de Medicina. No obstante, la experiencia acumulada con esta tecnología es aún limitada y existen muy escasas evidencias sobre su impacto sobre los estudiantes. Los objetivos del estudio fueron: 1) determinar si el posible impacto sobre las notas en los exámenes prácticos de la asignatura del paso de las preparaciones de cristal y el microscopio convencional (MC) a las preparaciones virtuales y el MV, y 2) evaluar la impresión subjetiva de los estudiantes en relación con el impacto de la MV en su aprendizaje. Métodos: Se evaluaron dos grupos que realizaron la asignatura de Anatomía Patológica en el curso 2013-2014, uno usando MC y el otro MV. Las mismas preparaciones utilizadas en el grupo de MC fueron digitalizadas en un escáner Ventana iScan HT a 20x y presentadas a los estudiantes con el visor Virtuoso (Roche diagnostics). Se evaluó el nivel de conocimientos alcanzado por los estudiantes mediante un examen online. Se realizó una encuesta a los estudiantes del grupo MV para evaluar sus impresiones sobre el recurso docente. Resultados: No existieron diferencias entre los dos grupos en cuanto a las notas obtenidas en el examen online: 9,87 ± 0,34 para el grupo de MC, vs 9,86 ± 0,53 para el grupo de MV; p=0,880). La característica más valorada de la MV fue la posibilidad de acceder a las imágenes en cualquier lugar y a cualquier hora (93.3%). El 86.6% de los estudiantes encontraron que el software era fáci

Burkitt-like lymphoma with 11q aberration: A germinal center derived lymphoma genetically unrelated to Burkitt lymphoma

Burkitt-like lymphoma with 11q aberration is characterized by pathological features and gene expression profile resembling Burkitt lymphoma but lack MYC rearrangement and carries an 11q-arm aberration with proximal gains and telomeric losses. Whether these lymphomas are a distinct category or a particular variant of other recognized entities is controversial. To improve the understanding of Burkitt-like lymphoma with 11q aberration we have performed an analysis of copy number alterations and targeted sequencing of a large panel of B-cell lymphoma related genes in 11 cases. Most patients had localized nodal disease and a favourable outcome after therapy. Histologically, they were high grade B-cell lymphoma, not otherwise specified (8 cases), diffuse large B-cell lymphoma (2 cases) and only one was considered as atypical Burkitt lymphoma. All cases had a germinal center B-cell signature and phenotype with frequent LMO2 expression. Burkitt-like lymphoma with 11q aberration had frequent gains of 12q12-q21.1 and losses of 6q12.1-q21, and lacked common Burkitt lymphoma or diffuse large B-cell lymphoma alterations. Potential driver mutations were found in 27 genes, particularly involving BTG2, DDX3X, ETS1, EP300, and GNA13. However, ID3, TCF3, or CCND3 mutations were absent in all cases. These results suggest that Burkitt-like lymphoma with 11q aberration is a germinal center derived lymphoma closer to high grade B-cell lymphoma or diffuse large B-cell lymphoma rather than Burkitt lymphoma.Copyright © 2019, Ferrata Storti Foundation