Changed concepts and definitions of myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the updated 2008 WHO classification

The purpose of this overview is to discuss the changes in the 2008 WHO classification of myeloid neoplasms, with exclusion of acute myeloid leukaemia. Specific mutations or rearrangements leading to constitutive activation of growth factor receptors or cytoplasmic tyrosine kinases are now recognised as recurrent genetic events characterising the group of myeloproliferative neoplasms (MPN). A newly introduced subgroup consists of patients with persistent eosinophilia and myeloid or lymphoid proliferations harbouring specific genetic changes involving platelet-derived growth factor receptors alpha and beta (PDGFRA and PDGFRB) or fibroblast growth factor receptor 1 (FGFR1). The clinical relevance of recognising myeloid neoplasms with aberrant tyrosine kinase activity is based in novel treatment options with tyrosine kinase inhibitors. The myelodysplastic syndromes (MDS) without increased blasts are further divided into subtypes of refractory cytopaenias with unilineage dysplasia. A new provisional entity is refractory cytopaenia of childhood. Down syndrome- and therapy-related myeloid neoplasms, including MDS, were moved to the section of acute myeloid leukaemia and related precursor neoplasms

Primäres zerebelläres T-Zell-Lymphom

Zusammenfassung: Primäre T-Zell-Lymphome des zentralen Nervensystems (ZNS) sind selten. Sie müssen differenzialdiagnostisch von reaktiven Läsionen unterschieden werden. Die Diagnosestellung sollte integrativ unter Verwendung von immunhistochemischen, molekulargenetischen und/oder zytogenetischen Methoden erfolgen. Wir beschreiben den Fall eines 50-jährigen Mannes, bei welchem ein primäres zerebelläres T-Zell-Lymphom diagnostiziert und eine klonale T-Zell-Rezeptorgen-Umlagerung nachgewiesen wurde. Nach 2Zyklen Chemotherapie entwickelte der Patient eine Pneumozystis-carinii-Pneumonie und verstarb 10Wochen nach Diagnosestellung. Die Autopsie ergab keinen Residualtumor im ZN

Memento for interprofessional learning

The vast increase of technical, diagnostic, and treatment possibilities and deepened understanding of molecular biology has revolutionized diagnosis and treatment of cancer and thus has great impact on pathology. Different professionals are responsible for proper evaluation of the results and their translating into an accurate diagnosis and appropriate treatment. Next to expertise, a close interaction between clinical molecular biologists, pathologists, and oncologists is required; it is crucial that these professionals speak “the same language.” Key to this is communication skills and creating possibilities for collaboration in a meaningful context. Here, we present an interprofessional, educational workshop model and we describe the parameters that contribute to effective learning by specialists

Cryobiopsy increases the EGFR detection rate in non-small cell lung cancer

Objectives: Detection of activating epidermal growth factor receptor (EGFR) mutation is crucial for individualized treatment of advanced non-small-cell lung cancer (NSCLC). However little is known about how biopsy technique affects the detection rate of EGFR mutations. This retrospective, single center study evaluated the detection rate of EGFR mutations in tissue obtained by bronchoscopic cryobiopsy and compared this to other standard tissue sampling techniques. Materials and methods: We retrospectively analyzed 414 patients with histologically confirmed NSCLC and known EGFR mutation status between 3/2008-7/2014. Tumor specimens obtained by tissue preserving bronchoscopic cryobiopsy were compared to those obtained by other techniques. Results and conclusion: Analysis of bronchoscopic cryobiopsy tissue detected 29 activating EGFR mutations in 27 (21.6 ) out of 125 patients, while analysis of tissue obtained by non-cryobiopsy techniques (bronchoscopic forceps biopsies, fine needle aspiration, imaging guided transthoracical and surgical procedures) detected 42 EGFR mutations in 40 (13.8 ) out of 298 patients (p < 0.05). Cryobiopsy increased detection rate of EGFR mutations in central tumors compared with forceps biopsy (19.6 versus 6.5 , p < 0.05), while an insignificant trend was detected also for peripheral tumors (33.3 versus 26.9 ). Bronchosopic cryobiopsy increases the detection rate of activating EGFR mutations in NSCLC in comparison to other tissue sampling techniques. This will help to optimize individualized treatment of patients with advanced tumors. Because of the retrospective nature of this analysis, a prospective trial is mandatory for final assessment. © 2020 The Author(s

Optimal decision-making in mammals : insights from a robot study of rodent texture discrimination

Texture perception is studied here in a physical model of the rat whisker system consisting of a robot equipped with a biomimetic vibrissal sensor. Investigations of whisker motion in rodents have led to several explanations for texture discrimination, such as resonance or stick-slips. Meanwhile, electrophysiological studies of decision-making in monkeys have suggested a neural mechanism of evidence accumulation to threshold for competing percepts, described by a probabilistic model of Bayesian sequential analysis. For our robot whisker data, we find that variable reaction-time decision-making with sequential analysis performs better than the fixed response-time maximum-likelihood estimation. These probabilistic classifiers also use whatever available features of the whisker signals aid the discrimination, giving improved performance over a single-feature strategy, such as matching the peak power spectra of whisker vibrations. These results cast new light on how the various proposals for texture discrimination in rodents depend on the whisker contact mechanics and suggest the possibility of a common account of decision-making across mammalian species

Influence of Biopsy Technique on Molecular Genetic Tumor Characterization in Non-Small Cell Lung Cancer—The Prospective, Randomized, Single-Blinded, Multicenter PROFILER Study Protocol

The detection of molecular alterations is crucial for the individualized treatment of advanced non-small cell lung cancer (NSCLC). Missing targetable alterations may have a major impact on patient’s progression free and overall survival. Although laboratory testing for molecular alterations has continued to improve; little is known about how biopsy technique affects the detection rate of different mutations. In the retrospective study detection rate of epidermal growth factor (EGFR) mutations in tissue extracted by bronchoscopic cryobiopsy (CB was significantly higher compared to other standard biopsy techniques. This prospective, randomized, multicenter, single blinded study evaluates the accuracy of molecular genetic characterization of NSCLC for different cell sampling techniques. Key inclusion criteria are suspected lung cancer or the suspected relapse of known NSCLC that is bronchoscopically visible. Patients will be randomized, either to have a CB or a bronchoscopic forceps biopsy (FB). If indicated, a transbronchial needle aspiration (TBNA) of suspect lymph nodes will be performed. Blood liquid biopsy will be taken before tissue biopsy. The primary endpoint is the detection rate of molecular genetic alterations in NSCLC, using CB and FB. Secondary endpoints are differences in the combined detection of molecular genetic alterations between FB and CB, TBNA and liquid biopsy. This trial plans to recruit 540 patients, with 178 evaluable patients per study cohort. A histopathological and molecular genetic evaluation will be performed by the affiliated pathology departments of the national network for genomic medicine in lung cancer (nNGM), Germany. We will compare the diagnostic value of solid tumor tissue, lymph node cells and liquid biopsy for the molecular genetic characterization of NSCLC. This reflects a real world clinical setting, with potential direct impact on both treatment and survival