Commentary on the 2008 WHO classification of mature T- and NK-cell neoplasms

In 2008, the World Health Organization (WHO) published a revised and updated edition of the classification of tumors of the hematopoietic and lymphoid tissues. The aims of the fourth edition of the WHO classification was to incorporate new scientific and clinical information in order to refine diagnostic criteria for previously described neoplasms and to introduce newly recognized disease entities. The recognition that T-cell lymphomas are related to the innate and adaptive immune system, as well as enhanced understanding of other T-cell subsets, such as the regulatory T-cell and follicular helper T-cells, has contributed to our understanding of the morphologic, histologic, and immunophenotypic features of T- and NK-cell neoplasms. The purpose of this review is to highlight major changes in the classification of T- and NK-cell neoplasms and to explain the rationale for these changes

The Grey Zones of Classic Hodgkin Lymphoma

Simple Summary Classic Hodgkin lymphoma (CHL) is a well-defined lymphoid neoplasm with a minority of characteristic neoplastic cells of B cell origin, namely Hodgkin and Reed-Sternberg cells immersed in a rich reactive inflammatory infiltrate in the background. Although CHL has always been set apart from non-Hodgkin lymphomas, cases with morphological and phenotypic features intermediate between CHL and other lymphomas have been described. Whereas some of these lymphomas only represent morphological mimics, others exhibit mutational and gene expression profiles which overlap with CHL, indicating that these cases, frequently termed grey zone lymphomas, reside on the biological boundary between CHL and large B-cell lymphomas. In the present review, we aim to describe the current knowledge of these rare lymphomas, address diagnostic issues and summarize today's concepts on the classification of grey zone lymphomas and related tumors. Classic Hodgkin lymphoma (CHL) is a well-defined neoplasm characterized by the presence of a minority of pathognomonic Hodgkin and Reed-Sternberg (HRS) cells in a reactive inflammatory background. Although genotypically of B cell origin, HRS cells exhibit a downregulated B cell program and therefore are set apart from other B cell lymphomas in the current WHO classification. However, cases with morphological and phenotypic features overlapping with CHL have been recognized, and the category of B cell lymphoma-unclassifiable-with features intermediate between diffuse large B cell lymphoma (DLBCL) and CHL, also termed grey zone lymphoma, was first introduced into the WHO classification in 2008 as provisional entity. These cases, as well as others raising a differential diagnosis of CHL can present diagnostic problems, as well as therapeutic challenges. Whereas some of these lymphomas only represent biologically unrelated morphological mimics, others, especially mediastinal grey zone lymphoma, exhibit genetic and gene expression profiles which overlap with CHL, indicating a true biological relationship. In this review, we address areas of diagnostic difficulties between CHL and other lymphoma subtypes, discuss the biological basis of true grey zone lymphoma based on recent molecular studies and delineate current concepts for the classification of these rare tumors

Planifcación Estratégica : Importancia de la formulación de la visión y la misión para el logro de los objetivos organizacionales

El presente trabajo de investigación documental consiste en exponer, sobre la planificación estratégica, específicamente la temática de la importancia de la formulación de la visión y la misión para el logro de los objetivos organizacionales. El propósito de la investigación es analizar la importancia de la formulación de la visión y la misión, a través de la compresión de los elementos de la administración estratégica y los componentes esenciales para la elaboración de las mismas. Se mencionarán los conceptos claves de la administración estratégica para una mejor comprensión del tema a desarrollar, así como temas primordiales las ventajas competitivas, estrategas, declaración de la visión y la misión. Se establecerán los elementos que debe llevar la visión estratégica de una organización, aplicando herramientas metodológicas para desarrollar una amplia declaración de la misma que debe responder a la pregunta básica ¿Qué queremos llegar a ser?, se definirán los componentes para elaborar una clara declaración de la Misión de una organización, es decir que es el pegamento que facilita a la organización en describir el propósito actual de la empresa; quienes somos, que hacemos, y porque estamos aquí. Se procedió a la búsqueda de material bibliográfico, consultando a diferentes autores como David Fred, Charles Hill, Gareth Jones y Arthur Thompson, Margaret Peteraf, John Gamble, A. Strickland Asimismo, aplicamos los criterios de las normas APA que se utilizaron son las orientadas por el Centro de Escritura Javeriano, Normas APA, Sexta Edición (2016)

In vivo imaging enables high resolution preclinical trials on patients' leukemia cells growing in mice.

Xenograft mouse models represent helpful tools for preclinical studies on human tumors. For modeling the complexity of the human disease, primary tumor cells are by far superior to established cell lines. As qualified exemplary model, patients' acute lymphoblastic leukemia cells reliably engraft in mice inducing orthotopic disseminated leukemia closely resembling the disease in men. Unfortunately, disease monitoring of acute lymphoblastic leukemia in mice is hampered by lack of a suitable readout parameter

Diffuse large B-cell lymphomas, not otherwise specified, and emerging entities

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogenous group of diseases and the most common subtype of non-Hodgkin lymphoma. In the past decade, there has been an explosion in molecular profiling that has helped to identify subgroups and shared oncogenic driving mechanisms. Since the 2017 World Health Organization (WHO) classification, additional studies investigating these genomic abnormalities and phenotypic findings have been reported. Here we review these findings in DLBCL and address the proposed changes by the 2022 International Consensus Classification

Mercado de abastos-edificio híbrido en la ciudad de Tumbes

La presente investigación busca resolver y analizar las muchas deficiencias que presentan actualmente los mercados de abastos, esto debería ser una preocupación para las autoridades. Por lo que, como arquitectos forma parte de nuestro trabajo solucionar problemas como el mal dimensionamiento de una infraestructura, la escasa iluminación y uso inadecuado del agua. Además, es necesario desarrollar espacios para otras actividades para incrementar el turismo. La propuesta de tesis es el “MERCADO DE ABASTOS-EDIFICIO HÍBRIDO” en la ciudad de Tumbes, el que se contempló como un medio, a través del cual se podría dar una solución a este problema. Esta, es una alternativa innovadora y adaptable al nuevo entorno sociocultural. Se estableció como objetivo diseñar un mercado de abastos - edificio híbrido con nuevos espacios y servicios en la ciudad de Tumbes. Se analizaron factores como: datos estadísticos, terreno, ciudad, viabilidad y entorno. Por último, el diseño final del proyecto se compone por una propuesta orientada a fortalecer el arraigo de los pobladores y con importantes espacios de desarrollo cultural

CCR8 leads to eosinophil migration and regulates neutrophil migration in murine allergic enteritis

Allergic enteritis (AE) is a gastrointestinal form of food allergy. This study aimed to elucidate cellular and molecular mechanisms of AE using a murine model. To induce AE, BALB/c wild type (WT) mice received intraperitoneal sensitization with ovalbumin (an egg white allergen) plus ALUM and feeding an egg white (EW) diet. Microarray analysis showed enhanced gene expression of CC chemokine receptor (CCR) 8 and its ligand, chemokine CC motif ligand (CCL) 1 in the inflamed jejunum. Histological and FACS analysis showed that CCR8 knock out (KO) mice exhibited slightly less inflammatory features, reduced eosinophil accumulation but accelerated neutrophil accumulation in the jejunums, when compared to WT mice. The concentrations of an eosinophil chemoattractant CCL11 (eotaxin-1), but not of IL-5, were reduced in intestinal homogenates of CCR8KO mice, suggesting an indirect involvement of CCR8 in eosinophil accumulation in AE sites by inducing CCL11 expression. The potential of CCR8 antagonists to treat allergic asthma has been discussed. However, our results suggest that CCR8 blockade may promote neutrophil accumulation in the inflamed intestinal tissues, and not be a suitable therapeutic target for AE, despite the potential to reduce eosinophil accumulation. This study advances our knowledge to establish effective anti-inflammatory strategies in AE treatment.Fil: Blanco-Pérez, Frank. Paul-ehrlich-institut;Fil: Kato, Yoichiro. Tokyo Women's Medical University;Fil: Gonzalez-Menendez, Irene. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Laiño, Jonathan Emiliano. Paul-ehrlich-institut;Fil: Ohbayashi, Masaharu. Toyohashi Sozo University;Fil: Burggraf, Manja. Paul-ehrlich-institut;Fil: Krause, Maren. Paul-ehrlich-institut;Fil: Kirberg, Jörg. Paul-ehrlich-institut;Fil: Iwakura, Yoichiro. Tokyo University Of Science;Fil: Martella, Manuela. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Quintanilla-Martinez, Leticia. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Shibata, Noriyuki. Tokyo Women's Medical University;Fil: Vieths, Stefan. Paul-ehrlich-institut;Fil: Scheurer, Stephan. Paul-ehrlich-institut;Fil: Toda, Masako. Paul-ehrlich-institut; . Tohoku University

A Case of B-cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-cell Lymphoma and Burkitt Lymphoma in a Korean Child

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) (intermediate DLBCL/BL), is a heterogeneous group with some features resembling DLBCL and others resembling BL. Here, we report a case of intermediate DLBCL/BL in a Korean child. A 2-yr-old male was admitted for evaluation and management of left hip pain. Immunohistochemistry of a biopsy of the femur neck revealed tumor cells positive for CD20, CD10, BCL2, BCL6, and Ki67. A bone marrow (BM) aspirate smear revealed that 49.3% of all nucleated cells were abnormal lymphoid cells, composed of large- and medium-sized cells. Immunophenotyping of the neoplastic cells revealed positivity for CD19, CD10, CD20, and sIg lambda and negativity for CD34, Tdt, and myeloperoxidase (MPO). Cytogenetic and FISH analyses showed a complex karyotype, including t(8;14)(q24.1;q32) and IGH-MYC fusion. Intensive chemotherapy was initiated, including prednisone, vincristine, L-asparaginase, daunorubicin, and central nervous system prophylaxis with intrathecal methotrexate (MTX) and cytarabine. One month after the initial diagnosis, BM examination revealed the persistent of abnormal lymphoid cells; cerebrospinal fluid cytology, including cytospin, showed atypical lymphoid cells. The patient was treated again with cyclophosphamide, vincristine, prednisone, adriamycin, MTX, and intrathecal MTX and cytarabine. The patient died of sepsis 5 months after the second round of chemotherapy

Tumor Heterogeneity in Lymphomas: A Different Breed.

The facts that cancer represents tissues consisting of heterogeneous neoplastic, as well as reactive, cell populations and that cancers of the same histotype may show profound differences in clinical behavior have long been recognized. With the advent of new technologies and the demands of precision medicine, the investigation of tumor heterogeneity has gained much interest. An understanding of intertumoral heterogeneity in patients with the same disease entity is necessary to optimally guide personalized treatment. In addition, increasing evidence indicates that different tumor areas or primary tumors and metastases in an individual patient can show significant intratumoral heterogeneity on different levels. This phenomenon can be driven by genomic instability, epigenetic events, the tumor microenvironment, and stochastic variations in cellular function and antitumoral therapies. These mechanisms may lead to branched subclonal evolution from a common progenitor clone, resulting in spatial variation between different tumor sites, disease progression, and treatment resistance. This review addresses tumor heterogeneity in lymphomas from a pathologist's viewpoint. The relationship between morphologic, immunophenotypic, and genetic heterogeneity is exemplified in different lymphoma entities and reviewed in the context of high-grade transformation and transdifferentiation. In addition, factors driving heterogeneity, as well as clinical and therapeutic implications of lymphoma heterogeneity, will be discussed

Impairment of alternative splice sites defining a novel gammaretroviral exon within gag modifies the oncogenic properties of Akv murine leukemia virus

<p>Abstract</p> <p>Background</p> <p>Mutations of an alternative splice donor site located within the <it>gag </it>region has previously been shown to broaden the pathogenic potential of the T-lymphomagenic gammaretrovirus Moloney murine leukemia virus, while the equivalent mutations in the erythroleukemia inducing Friend murine leukemia virus seem to have no influence on the disease-inducing potential of this virus. In the present study we investigate the splice pattern as well as the possible effects of mutating the alternative splice sites on the oncogenic properties of the B-lymphomagenic Akv murine leukemia virus.</p> <p>Results</p> <p>By exon-trapping procedures we have identified a novel gammaretroviral exon, resulting from usage of alternative splice acceptor (SA') and splice donor (SD') sites located in the capsid region of <it>gag </it>of the B-cell lymphomagenic Akv murine leukemia virus. To analyze possible effects <it>in vivo </it>of this novel exon, three different alternative splice site mutant viruses, mutated in either the SA', in the SD', or in both sites, respectively, were constructed and injected into newborn inbred NMRI mice. Most of the infected mice (about 90%) developed hematopoietic neoplasms within 250 days, and histological examination of the tumors showed that the introduced synonymous <it>gag </it>mutations have a significant influence on the phenotype of the induced tumors, changing the distribution of the different types as well as generating tumors of additional specificities such as <it>de novo </it>diffuse large B cell lymphoma (DLBCL) and histiocytic sarcoma. Interestingly, a broader spectrum of diagnoses was made from the two single splice-site mutants than from as well the wild-type as the double splice-site mutant. Both single- and double-spliced transcripts are produced <it>in vivo </it>using the SA' and/or the SD' sites, but the mechanisms underlying the observed effects on oncogenesis remain to be clarified. Likewise, analyses of provirus integration sites in tumor tissues, which identified 111 novel RISs (retroviral integration sites) and 35 novel CISs (common integration sites), did not clearly point to specific target genes or pathways to be associated with specific tumor diagnoses or individual viral mutants.</p> <p>Conclusion</p> <p>We present here the first example of a doubly spliced transcript within the group of gammaretroviruses, and we show that mutation of the alternative splice sites that define this novel RNA product change the oncogenic potential of Akv murine leukemia virus.</p