[Unusual progression of polycythemia vera].

The case of a male patient with newly diagnosed polycythemia vera showing rare and unusually rapid progression with phenotypic change towards chronic myelomonocytic leukemia is presented. The case report illustrates remarkably rapid disease progression including a structural change in usually indolent polycythemia vera and highlights the prognostic relevance of enhanced molecular genetic testing.

Molecular Cytogenetic Profiling Reveals Similarities and Differences Between Localized Nodal and Systemic Follicular Lymphomas.

Recently, we have developed novel highly promising gene expression (GE) classifiers discriminating localized nodal (LFL) from systemic follicular lymphoma (SFL) with prognostic impact. However, few data are available in LFL especially concerning hotspot genetic alterations that are associated with the pathogenesis and prognosis of SFL. A total of 144 LFL and 527 SFL, enrolled in prospective clinical trials of the German Low Grade Lymphoma Study Group, were analyzed by fluorescence in situ hybridization to detect deletions in chromosomes 1p, 6q, and 17p as well as translocations to determine their impact on clinical outcome of LFL patients.

Tumour cell characteristics and microenvironment composition correspond to clinical presentation in newly diagnosed nodular lymphocyte-predominant Hodgkin lymphoma.

Different studies have characterized the microenvironment and its prognostic impact in classic Hodgkin lymphoma whereas such analyses are pending for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). We thus investigated characteristics of tumour cells and microenvironment in NLPHL and evaluated possible correlations with the clinical presentation. Lymph node samples from 152 NLPHL patients who had first-line treatment within the randomized German Hodgkin Study Group HD16-HD18 trials were available and analysed with regard to IgD status and nuclear size of the tumour cells as well as presence of PD1-positive follicular T helper cells and CD163-positive macrophages in the microenvironment.

Comparative analysis of international prognostic indices in gray-zone lymphoma.

Gray-zone lymphoma (GZL) reflects an aggressive B-cell neoplasm with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). The International Prognostic Index (IPI) and its derivatives (R-IPI, NCCN-IPI, and the Hasenclever IPS) have been established for DLBCL or cHL while the most suitable scoring system for GZL remains undetermined. In an exploratory multi-centric cohort of GZL ( = 61), we performed a comparative analysis of prognostic indices with regard to model fit and mutual concordance.

Integrative genomic and transcriptomic analysis in plasmablastic lymphoma identifies disruption of key regulatory pathways.

Plasmablastic lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive B-cell non-Hodgkin lymphoma. Targeted-sequencing studies and a single-center whole-exome sequencing (WES) study in HIV-positive patients recently revealed several genes associated with PBL pathogenesis; however, the global mutational landscape and transcriptional profile of PBL remain elusive. To inform on disease-associated mutational drivers, mutational patterns, and perturbed pathways in HIV-positive and HIV-negative PBL, we performed WES and transcriptome sequencing (RNA-sequencing) of 33 PBL tumors.

Histopathological growth patterns in patients with advanced nodular lymphocyte-predominant Hodgkin lymphoma treated within the randomized HD18 study: a report from the German Hodgkin Study Group.

We retrospectively investigated histopathological growth patterns in individuals with advanced nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) treated within the randomized HD18 study. In all, 35/60 patients (58%) presented with atypical growth patterns. Patients with atypical growth patterns more often had stage IV disease (P = 0·0354) and splenic involvement (P = 0·0048) than patients with typical growth patterns; a positive positron emission tomography after two cycles of chemotherapy (PET-2) tended to be more common (P = 0·1078).

[Mastoid cavity obliteration with allogenic and autologous material].

Introduction: Surgical obliteration is the treatment of choice for symptomatic mastoid cavities. Various methods and materials are available. Allogeneic material is easily available but can lead to wound infections due to rejection, granulation and inflammatory reactions.

Evolutionary clonal trajectories in nodular lymphocyte-predominant Hodgkin lymphoma with high risk of transformation.

The B-cell architecture of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is complex since it is composed of malignant lymphocyte-predominant cells along with a rich B-cell bystander environment. To gain insight into molecular determinants of disease transformation, we studied B-cell evolutionary trajectories in lymphoma tissue from diagnosis to relapse or transformation to non- Hodgkin lymphoma by next-generation sequencing of immunoglobulin heavy chains. Patients with NLPHL that later transformed were older and showed IgD negativity, absence of the characteristic IGHV3/IGHD3/IGHJ6 lymphocyte-predominant rearrangement and high repertoire clonality.

Performance of international prognostic indices in plasmablastic lymphoma: a comparative evaluation.

Purpose: Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell malignancy with a heterogenous clinical and prognostic spectrum, determined by multiple factors, including age, HIV- and MYC-status. While there exist several validated scoring systems for diffuse large B-cell lymphoma, which incorporate basic clinical features (age, lactate dehydrogenase, sites of (extranodal) involvement, stage and performance), none of these have been systematically assessed in PBL.

Methods: We determined the (age-adjusted; aa)-International Prognostic Index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI) in a comprehensive multi-center cohort (n = 78) of PBL patients.

[Electronic learning for otorhinolaryngology students using the content management system ILIAS].

Background: With increasing access to online teaching materials, traditional teaching methods at universities need to be questioned in the context of digital transformation. The aim of this study was to evaluate whether electronic learning may serve as or replace conventional internship in otorhinolaryngology.

Materials And Methods: A completely digital electronic learning concept was created and made available at the online learning platform ILIAS.

Mapping the ChOLE classification to hearing outcomes and disease-specific health-related quality of life.

Objectives: To investigate the association between the "ChOLE" classification, hearing outcomes and disease-specific health-related quality of life (HRQoL).

Methods: In two tertiary referral centers, patients requiring primary or revision surgery for cholesteatoma were assessed for eligibility. Audiometric assessment was performed pre- and postoperatively.

Localized- and advanced-stage follicular lymphomas differ in their gene expression profiles.

The genetic background of follicular lymphomas (FLs) diagnosed in advanced clinical stages III/IV, and which are frequently characterized by t(14;18), has been substantially unraveled. Molecular features, as exemplified in the clinicogenetic risk model m7FLIPI, are important tools in risk stratification. In contrast, little information is available concerning localized-stage FL (clinical stages I/II), which accounts for ∼20% of newly diagnosed FL in which the detection rate of t(14;18) is only ∼50%.

The time to relapse correlates with the histopathological growth pattern in nodular lymphocyte predominant Hodgkin lymphoma.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) can present with different histopathological growth patterns. The impact of these histopathological growth patterns on relapse characteristics is unknown. We therefore analyzed paired biopsies obtained at initial diagnosis and relapse from 33 NLPHL patients who had received first-line treatment within German Hodgkin Study Group (GHSG) trial protocols, and from a second cohort of 41 relapsed NLPHL patients who had been treated outside GHSG studies.

Three-dimensional force analysis of surgical manipulations at the long process of the incus.

Purpose: Surgical manipulation with application of inappropriate force may damage middle ear structures leading to hearing loss. This work analyzes the forces applied in simulated otosurgical exercises in a laboratory set-up by measuring the spatial components of applied forces with objective assessment criteria. With these criteria, the individual force characteristics applied by the surgeon can be quantified and an objective feedback can be given about their surgical maneuvers.

Clinical Impact of the Cell-of-Origin Classification and the MYC/ BCL2 Dual Expresser Status in Diffuse Large B-Cell Lymphoma Treated Within Prospective Clinical Trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group.

Purpose To explore the prognostic impact and interdependence of the cell-of-origin (COO) classification, dual expression (DE) of MYC and BCL2 proteins, and MYC, BCL2, and BCL6 translocations in two prospectively randomized clinical trials of patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Overall, 452 formalin-fixed paraffin-embedded samples from two prospective, randomized DLBCL trials (RICOVER-60, prospective, randomized study for patients > 60 years, all IPI groups; and R-MegaCHOEP, prospective, randomized study for patients ≤ 60 years with age-adjusted IPI 2,3) of the German High-Grade Non-Hodgkin Lymphoma Study Group were analyzed with the Lymph2Cx assay for COO classification, with immunohistochemistry for MYC and BCL2, and with fluorescent in situ hybridization for MYC, BCL2, and BCL6 rearrangements. Results COO classification was successful in 414 of 452 samples.

Hodgkin's lymphoma as a rare variant of Richter's transformation in chronic lymphocytic leukemia: A case report and review of the literature.

Richter's transformation induces an aggressive clinical course in chronic lymphocytic leukemia (CLL). In the majority of cases, Richter's transformation manifests itself as a high-grade B-cell non-Hodgkin's lymphoma (B-NHL). However, other histological types, such as classical Hodgkin lymphoma (cHL), lymphoblastic lymphoma, hairy cell leukemia and high-grade T-cell NHL have been described previously.

Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network.

Purpose: Mantle-cell lymphoma (MCL) is a rather aggressive B-cell malignancy whose considerable variability of individual outcome is associated with clinical characteristics (Mantle Cell Lymphoma International Prognostic Index [MIPI]). The Ki-67 index is a strong independent prognostic factor; however, the biologic MIPI (MIPI-b) distinguishes only two groups, which does not appropriately depict the clinical heterogeneity. By using the cohort from the European MCL Younger and MCL Elderly trials, we aimed to evaluate the additional prognostic impact of cytology and growth pattern and to improve risk stratification with the Ki-67 index and MIPI.

Similar clinical features in follicular lymphomas with and without breaks in the BCL2 locus.

Approximately 15% of follicular lymphomas (FLs) lack breaks in the BCL2 locus. The aim of this study was to better define molecular and clinical features of BCL2-breakpoint/t(14;18)-negative FLs. We studied the presence of BCL2, BCL6 and MYC breaks by fluorescence in situ hybridization and the expression of BCL2, MUM1, CD10, P53 and Ki67 in large clinical trial cohorts of 540 advanced-stage FL cases and 116 early-stage disease FL patients treated with chemotherapy regimens and radiation, respectively.

Different biological risk factors in young poor-prognosis and elderly patients with diffuse large B-cell lymphoma.

Prognostically relevant risk factors in patients with diffuse large B-cell lymphoma (DLBCL) have predominantly been evaluated in elderly populations. We tested whether previously described risk factors are also valid in younger, poor-prognosis DLBCL patients. Paraffin-embedded samples from 112 patients with de novo DLBCL, enrolled in the R-MegaCHOEP trial of the German High Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) were investigated using immunohistochemistry (MYC, FOXP1, LMO2, GCET1, CD5, CD10, BCL2, BCL6, IRF4/MUM1) and fluorescence in situ hybridization (MYC, BCL2, BCL6).

MicroRNA profiling of low-grade and transformed nodal marginal zone lymphoma reveals a similar signature pattern distinct from diffuse large B cell lymphoma.

Background/aims: As critical post-transcriptional regulators of gene expression, microRNAs are involved in several cellular processes of vital impact including cell growth and apoptosis. Many hematologic malignancies exhibit distinct microRNA signatures. MicroRNA implication in the pathogenesis of nodal marginal zone lymphoma (NMZL), however, remains widely elusive.

Histopathological features and their prognostic impact in nodular lymphocyte-predominant Hodgkin lymphoma--a matched pair analysis from the German Hodgkin Study Group (GHSG).

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity. We performed a matched-pair analysis to evaluate the prognostic impact of several histopathological features in this distinct Hodgkin lymphoma subtype. Lymph node samples of NLPHL patients were tested for CD15, IgD, phosphorylated STAT6, ICOS and Epstein-Barr virus status of the malignant lymphocyte-predominant cells as well as epithelioid cell clusters and activated T cells in the microenvironment.