Our data underscore the pathogenetic potential of ANCA by demonstrating a more aggressive disease state and a poorer outcome in patients with PR3-ANCA.

No abstract

Objective. The histopathologic lesions in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been studied extensively, but the exact composition of the cellular infiltrate is unclear. We undertook this study to analyze renal leukocyte infiltration and the cellular distribution within glomeruli and interstitium in 65 renal biopsy samples obtained from patients newly diagnosed as having AAV.Methods. Renal cellular tissue infiltration was assessed with an immunoperoxidase method. Furthermore, the infiltrating cell types were correlated with clinical and histopathologic data.Results. The predominant interstitial infiltrating cells were T lymphocytes, while monocytes and, to a lesser extent, granulocytes constituted the dominant infiltrating cell types in glomeruli. Interestingly, lymphocyte infiltration was predominantly periglomerular, especially around glomeruli with sclerosis or heavy crescent formation, while interstitial monocyte and neutrophil infiltration was diffusely distributed over the interstitial tissue. A significant correlation was found for the glomerular infiltration of CD68-positive macrophages with the presence of glomerular necrosis as well as with the number of glomeruli with crescents (P < 0.0001 and P ‫؍‬ 0.005, respectively). No correlation was found for interstitial fibrosis with the infiltration of any leukocyte subset. Furthermore, a significant correlation was found for the interstitial as well as for the glomerular infiltration of CD68-positive macrophages with serum creatinine concentration at the time of biopsy (P ‫؍‬ 0.001 and P ‫؍‬ 0.006, respectively).Conclusion. These data underscore a major role of monocytes in addition to neutrophils in the tissue damage of AAV.

No abstract

In the following, we describe the very rare case of Langerhans cell sarcoma (LCS) in the lung. Throughout the medical literature, only a few cases have been published, and, to the best of our knowledge, this is the first case to be reported in Germany. The patient was an 81-year-old man who showed symptoms such as chronic cough and weight loss. Clinical examination including needle biopsy indicated a high possibility of carcinoma in the right lung and in the mediastinum; however, the final histopathological diagnosis after immunohistochemistry gave evidence of LCS. LCS is a neoplastic proliferation of Langerhans cells with malignant cytological features exhibiting a very aggressive behaviour. LCS can be distinguished from other carcinomas, lymphomas and sarcomas by the typical morphological features of Langerhans cells and the immunophenotype with a consistent expression of S-100 protein and CD1a. In contrast to Langerhans cell histiocytosis, the LCS consists of Langerhans cells with high atypia and a very high mitotic rate.

We conclude that the transcription factor Egr-1 plays a critical role for mesangial cell proliferation in vivo. Interfering with the induction of Egr-1 or with its target genes could give rise to novel therapeutic principles in mesangioproliferative glomerulonephritis.

No abstract

The simultaneous detection of multiple somatic mutations in the context of molecular diagnostics of cancer is frequently performed by means of amplicon-based targeted next-generation sequencing (NGS). However, only few studies are available comparing multicenter testing of different NGS platforms and gene panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK) performed a multicenter interlaboratory trial for targeted NGS using the same formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre-characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed information regarding pre-characterized mutations was not disclosed to the partners. Commercially available and custom-designed cancer gene panels were used for library preparation and subsequent sequencing on several devices of two NGS different platforms. For every case, centrally extracted DNA and FFPE tissue sections for local processing were delivered to each partner site to be sequenced with the commercial gene panel and local bioinformatics. For cancer-specific panel-based sequencing, only centrally extracted DNA was analyzed at seven sequencing sites. Subsequently, local data were compiled and bioinformatics was performed centrally. We were able to demonstrate that all pre-characterized mutations were re-identified correctly, irrespective of NGS platform or gene panel used. However, locally processed FFPE tissue sections disclosed that the DNA extraction method can affect the detection of mutations with a trend in favor of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a very robust method for simultaneous detection of various mutations in FFPE tissue specimens if certain pre-analytical conditions are carefully considered.