High-risk and silent clonal hematopoietic genotypes in patients with nonhematologic cancer.

ABSTRACT: Clonal hematopoiesis (CH) identified by somatic gene variants with variant allele fraction (VAF) ≥ 2% is associated with an increased risk of hematologic malignancy. However, CH defined by a broader set of genotypes and lower VAFs is ubiquitous in older individuals. To improve our understanding of the relationship between CH genotype and risk of hematologic malignancy, we analyzed data from 42 714 patients who underwent blood sequencing as a normal comparator for nonhematologic tumor testing using a large cancer-related gene panel. We cataloged hematologic malignancies in this cohort using natural language processing and manual curation of medical records. We found that some CH genotypes including JAK2, RUNX1, and XPO1 variants were associated with high hematologic malignancy risk. Chronic disease was predicted better than acute disease suggesting the influence of length bias. To better understand the implications of hematopoietic clonality independent of mutational function, we evaluated a set of silent synonymous and noncoding mutations. We found that silent CH, particularly when multiple variants were present or VAF was high, was associated with increased risk of hematologic malignancy. We tracked expansion of CH mutations in 26 hematologic malignancies sequenced with the same platform. JAK2 and TP53 VAF consistently expanded at disease onset, whereas DNMT3A and silent CH VAFs mostly decreased. These data inform the clinical and biological interpretation of CH in the context of nonhematologic cancer.

Liquid biopsy and tumor derived exosomes in clinical practice / Biopsia líquida y exosomas derivados del tumor en la práctica clínica

Tumors are complex tissues that interact in many different ways. Tissue biopsies provide a great amount of information and remain the gold standard for tumor diagnosis. However, they cannot always be performed due to the invasive nature of the procedure and in such circumstances, a liquid biopsy could provide a solution. Liquid biopsy is defined as the search of biomarkers in peripheral blood. To date, there are three main research fields: (1) circulating tumor cells (CTCs); (2) circulating free tumor nucleic acids (cfNA) and (3) exosomes, small vesicles containing various types of signaling molecules capable of modulating a tumor-immune response. In recent years, exosomes have arisen as a powerful tool both to further our understanding of cancer biology and to improve clinical management. We review how the isolation and study of exosomes from liquid biopsies may affect clinical practice (AU)

Las biopsias tisulares, aunque otorgan gran cantidad de información y son el gold standard para el diagnóstico tumoral, no pueden ser realizadas continuamente para monitorizar la evolución tumoral dada su inherente naturaleza invasiva. Por otro lado, la biopsia líquida surge como una herramienta capaz de compensar estas limitaciones. En este momento se han identificado 3 tipos principales de biomarcadores en la biopsia líquida: (1) células tumorales circulantes (CTC); (2) ácidos nucleicos tumorales circulantes libres (cfNA), y (3) exosomas. En los últimos años los exosomas (pequeñas vesículas que contienen moléculas capaces de modular la respuesta inmune-tumoral) han surgido como una potente herramienta para comprender mejor la biología del cáncer así como una manera para intentar mejorar el manejo de los pacientes oncológicos. El objetivo de este artículo es presentar una revisión sobre cómo la caracterización de los exosomas a través de la biopsia líquida podría influir sobre la práctica clínica (AU)

Classical Hodgkin's lymphoma of the thyroid / Linfoma de Hodgkin clásico del tiroides

Hodgkin's lymphoma is characterized by the presence of Reed–Sternberg cells. The majority of cases originate at nodal sites and only rarely does it occur in extranodal locations. Here we report a case of a woman with a classical Hodgkin's lymphoma of the thyroid developed from a Hashimoto thyroiditis. She presented with a mass in her thyroid which was surgically removed. Biopsy showed a nodular sclerosis classical Hodgkin's lymphoma. Our results were similar to previously reported cases. It would appear that the lesions grew over a MALT tissue created by the lymphoid proliferation of the thyroiditis. Differential diagnosis was made between the different types of lymphomas considering those most commonly occurring in extranodal lymphoid tissues. A final diagnosis was reached after consideration of the histopathology, immunophenotyping and molecular biology (AU)

El linfoma de Hodgkin se caracteriza por la presencia de células de Reed–Sternberg. La mayor parte de los casos se originan en ganglios linfáticos y raramente en localizaciones extranodales. Comunicamos un caso de una paciente con un linfoma de Hodgkin clásico desarrollado sobre una tiroiditis de Hashimoto. Se presentó como una masa tiroidea que fue extirpada. Histológicamente mostró un linfoma de Hodgkin clásico de tipo esclerosis nodular. Nuestros resultados concuerdan con casos publicados anteriormente. La lesión posiblemente se originó sobre un tejido MALT creado por la proliferación linfoide relacionada con la tiroiditis. Realizamos diagnósticos diferenciales entre diferentes tipos de linfoma que tienen lugar en tejido linfoide extranodal. El diagnóstico final fue realizado tras considerar su histopatología, inmunofenotipo y genética molecular (AU)