Search

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity. Lately, several algorithms achieving therapeutically and prognostically relevant DLBCL subclassification have been published., Methods: A cohort of 74 routine DLBCL cases was broadly characterized by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) of the BCL2, BCL6, and MYC loci, and comprehensive high-throughput sequencing (HTS). Based on the genetic alterations found, cases were reclassified using two probabilistic tools - LymphGen and Two-step classifier, allowing for comparison of the two models., Results: Hans and Tally's overall IHC-based subclassification success rate was 96% and 82%, respectively. HTS and FISH data allowed the LymphGen algorithm to successfully classify 11/55 cases (1 - BN2, 7 - EZB, 1 - MCD, and 2 - genetically composite EZB/N1). The total subclassification rate was 20%. On the other hand, the Two-step classifier categorized 36/55 cases, with 65.5% success (9 - BN2, 12 - EZB, 9 - MCD, 2 - N1, and 4 - ST2). Clinical correlations highlighted MCD as an aggressive subtype associated with higher relapse and mortality., Conclusions: The Two-step algorithm has a better success rate at subclassifying DLBCL cases based on genetic differences. Further improvement of the classifiers is required to increase the number of classifiable cases and thus prove their applicability in routine diagnostics., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Since the outbreak of coronavirus disease 2019 (COVID-19), there has been a debate whether pregnant women are at a specific risk for COVID-19 and whether it might be vertically transmittable through the placenta. We present a series of five placentas of SARS coronavirus 2 (SARS-CoV-2)-positive women who had been diagnosed with mild symptoms of COVID-19 or had been asymptomatic before birth. We provide a detailed histopathologic description of morphological changes accompanied by an analysis of presence of SARS-CoV-2 in the placental tissue. All placentas were term deliveries (40th and 41st gestational weeks). One SARS-CoV-2-positive patient presented with cough and dyspnoea. This placenta showed prominent lymphohistiocytic villitis and intervillositis and signs of maternal and foetal malperfusion. Viral RNA was present in both placenta tissue and the umbilical cord and could be visualized by in situ hybridization in the decidua. SARS-CoV-2 tests were negative at the time of delivery of 3/5 women, and their placentas did not show increased inflammatory infiltrates. Signs of maternal and/or foetal malperfusion were present in 100% and 40% of cases, respectively. There was no transplacental transmission to the infants. In our cohort, we can document different time points regarding SARS-CoV-2 infection. In acute COVID-19, prominent lymphohistiocytic villitis may occur and might potentially be attributable to SARS-CoV-2 infection of the placenta. Furthermore, there are histopathological signs of maternal and foetal malperfusion, which might have a relationship to an altered coagulative or microangiopathic state induced by SARS-CoV-2, yet this cannot be proven considering a plethora of confounding factors., (© 2020 S. Karger AG, Basel.)

It has become evident that the microenvironment - lymphocytes, macrophages, fibroblasts as well as the extracellular matrix, cytokines, chemokines, and a plethora of other cells, structures and substances residing in the vicinity of tumor cells - plays an important part in the maintenance of cancer growth and survival. This is also relevant in lymphomas. In this review, we give an outline on the importance of the microenvironment for tumors in general and lymphomas in particular, by highlighting certain basic principles of tumor-microenvironment interaction. The relationship of lymphomas and their microenvironment is multifaceted: lymphoma cells need growth factors and cytokines derived from microenvironmental cells for their sustenance and growth. On the contrary, many lymphomas silence or at least deregulate the immune system to escape recognition and subsequent elimination by immune cells, while giving advantage to suppressive microenvironmental compounds such as M2 polarized macrophages, regulatory T-cells, mast cells, and immunosuppressive fibroblasts. We also give a detailed insight across different lymphoma types to show the variety of tumor-microenvironment interactions. Due to its tremendous importance, the microenvironment has also become a new target for oncologic therapy. The most important finding concerning lymphomas with a focus on immunomodulatory substances is also, therefore, highlighted., (© 2019 S. Karger AG, Basel.)

Amyloidosis is the result of various, differently approachable diseases. It is vital to subtype the amyloid deposits in order to establish and finally treat the underlying disease properly. Besides the classical staining with Congo red, further procedures like immunohistochemical staining are needed for classification. Here, we present a more accurate approach using Congo red/immunohistochemical double staining easily applicable in routine diagnostics. Modifications of the Congo red staining technique and the immunohistochemical procedures were needed in order to combine both staining procedures on one slide. The evaluation was done using conventional light and fluorescence microscopy. By shortening the staining time for Congo red to 10 s and by modification regarding endogenous peroxidase blockage, accurate results could be obtained for evaluating the Congo red/immunohistochemistry double staining using a fluorescence microscope. Sections of 2 μm instead of 4 μm thickness were superior for evaluation, since they increased staining specificity. The combination of Congo red and immunohistochemistry as in situ double staining on one slide is a feasible approach in the diagnosis of amyloidosis. It allows focusing on the fluorescent Congo red-positive areas when evaluating immunohistochemistry, thus avoiding signing out false-positive results. Additionally, it increases the signal-to-noise ratio of the immunohistochemically stained sections on conventional microscopy., (© 2016 S. Karger AG, Basel.)

There is an increased susceptibility and mortality in the elderly due to pneumonia caused by Streptococcus pneumoniae. We aimed to assess the inflammatory cell composition with respect to age in pneumococcal pneumonia patients. Neutrophilic granulocytes and various lymphocyte and macrophage subpopulations were immunohistochemically quantified on lung tissue specimens of young (n = 5; mean age 8.4 years), middle-aged (n = 8; mean age 55.9 years) and elderly (n = 9; mean age 86.6 years) pneumonia patients with microbiologically proven S. pneumoniae pneumonia. We discovered a higher percentage of neutrophilic granulocytes in elderly as opposed to young patients (95 vs. 75%, p = 0.012). Conversely, young patients versus elderly patients had more alveolar macrophages (CD11c+: 20 vs. 9%, p = 0.029) and M1 macrophages (CD14+: 30 vs. 10%, p = 0.012 and HLA-DR+: 52 vs. 11%, p = 0.019). There was no significant difference concerning M2 macrophages and lymphocytes. Comparison of young patients with middle-aged patients showed similar significant results for alveolar macrophages (p = 0.019) and subsignificant results for M1 macrophages and neutrophilic granulocytes (p < 0.08). This is the first study characterizing the inflammatory infiltrate of pneumococcal pneumonia in situ. Our observations improve the understanding of the innate immune mechanisms of pneumococcal lung infection and point at the potential of therapies for restoring macrophage function and decreasing neutrophilic influx in order to help prevent or cure pneumonia., (© 2014 S. Karger AG, Basel.)