Pathologe最新文献

A prerequisite for all HER2 directed therapies is the demonstration of HER2 receptor protein overexpression and/or gene amplification by in situ hybridization (ISH). ASCO and CAP have published several HER2 test guidelines over the past 15 years for both breast and gastric cancer. The latest version for breast cancer (2018) focuses on special issues of ISH related to the definitions of special diagnostic groups (1-5). The guidelines for gastroesophageal adenocarcinoma (2017), essentially based on ToGA trial data, are now also being used for other tumors such as pancreas, gallbladder, and non-small-cell lung cancer. For colorectal cancer, a modified testing procedure has been proposed. Recently, besides overexpression and amplification, a third type of HER gene alteration, namely mutation, has gained much interest. Next-generation sequencing (NGS) allows detection of both amplification and mutation of the HER2 gene providing new options of therapy especially in the case of activating mutations.

During the Second World War, the German Wehrmacht and the SS tested various chemical warfare agents on prisoners of concentration camps. The SS needed a pathologist to do this. Therefore, Reichsarzt SS Ernst-Robert Grawitz recruited the 32-year-old Hans Wolfgang Sachs. Despite his position as senior pathologist at the office of the Reichsarzt SS, Sachs was spared interrogation and prosecution after 1945, although the prosecution presented a document about chemical warfare and human experiments during the Nuremberg medical trial. In this, Sachs was named as a participant in so-called "N-Stoff" (chlorine trifluoride) experiments. Little is known about Sachs to this day. This article is intended to close this gap. Of particular interest are the motives and reasons why Sachs joined the party and the SS, as well as his career after 1945.

Background: Herbert Siegmund (1892-1954) was undoubtedly one of the most influential German pathologists of the 20th century. He received numerous high honors both during the Third Reich and after 1945. He was, among other things, rector of the University of Münster (1943-1945), holder of the Goethe Medal awarded by Hitler (1944), honorary doctor of the University of Cologne (1949), recipient of the Paracelsus Medal (1953), and president of the German Society for Pathology (DGP, 1954). The almost seamless post-war career was possible above all because Siegmund was counted among the politically uninvolved university physicians after 1945. It was not until after the turn of the millennium that this picture cracked.

Material and methods: The article is based on primary sources from the State Archives of Schleswig-Holstein and North Rhine-Westphalia, the University Archives of Münster, the Federal Archives of Berlin, the University Archives of Cologne, and the City Archives of Stuttgart, some of which were evaluated for the first time. Two questions are at the center of this article: (1) To what extent can it be proven that Siegmund benefited from the Nazi state in terms of his career after 1933? (2) Are there indications that he served the Nazi regime and its networks? In addition, we will discuss how Siegmund himself described his role in the Third Reich and whether his statements stand up to critical scrutiny.

Results: The paper concludes that Siegmund contributed to valorizing the Nazi system. After 1945, he did not position himself at a critical distance from his activities in the Third Reich; rather, he drew of himself - largely unopposed - the image of a politically blameless scholar.

Background: Autopsy is an important tool for understanding the pathogenesis of diseases, including COVID-19.

Material and methods: On 15 April 2020, together with the German Society of Pathology and the Federal Association of German Pathologists, the German Registry of COVID-19 Autopsies (DeRegCOVID) was launched ( www.DeRegCOVID.ukaachen.de ). Building on this, the German Network for Autopsies in Pandemics (DEFEAT PANDEMIcs) was established on 1 September 2020.

Results: The main goal of DeRegCOVID is to collect and distribute de facto anonymized data on potentially all autopsies of people who have died from COVID-19 in Germany in order to meet the need for centralized, coordinated, and structured data collection and reporting during the pandemic. The success of the registry strongly depends on the willingness of the respective centers to report the data, which has developed very positively so far and requires special thanks to all participating centers. The rights to own data and biomaterials (stored decentrally) remain with each respective center. The DEFEAT PANDEMIcs network expands on this and aims to strengthen harmonization and standardization as well as nationwide implementation and cooperation in the field of pandemic autopsies.

Conclusions: The extraordinary cooperation in the field of autopsies in Germany during the COVID-19 pandemic is impressively demonstrated by the establishment of DeRegCOVID, the merger of the registry of neuropathology (CNS-COVID19) with DeRegCOVID and the establishment of the autopsy network DEFEAT PANDEMIcs. It gives a strong signal for the necessity, readiness, and expertise to jointly help manage current and future pandemics by autopsy-derived knowledge.

Based on new trial data regarding immune checkpoint inhibitors (ICIs), the detection of high-grade microsatellite instability (MSI-H) or underlying deficient mismatch repair protein (dMMR) is now becoming increasingly important for predicting treatment response. For the first time, a PD‑1 ICI (pembrolizumab) has been approved by the European Medicines Agency (EMA) for first-line treatment of advanced (stage IV) dMMR/MSI‑H colorectal cancer (CRC). Further indications, such as dMMR/MSI‑H endometrial carcinoma (EC), have already succeeded (Dostarlimab, 2nd line treatment) and others are expected to follow before the end of 2021. The question of optimal testing in routine diagnostics should therefore be re-evaluated. Based on a consideration of the strengths and weaknesses of the widely available methods (immunohistochemistry and PCR), a test algorithm is proposed that allows quality assured, reliable, and cost-effective dMMR/MSI‑H testing. For CRC and EC, testing is therefore already possible at the primary diagnosis stage, in line with international recommendations (NICE, NCCN). The clinician is therefore enabled from the outset to consider not only the predictive but also the prognostic and predispositional implications of such a test when counseling patients and formulating treatment recommendations. As a basis for quality assurance, participation in interlaboratory comparisons and continuous documentation of results (e.g., QuIP Monitor) are strongly recommended.