Pathologe最新文献

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.

Prostate cancer is the most prevalent noncutaneous cancer in men. The Gleason grading is considered to be the strongest prognostic parameter regarding progression-free survival and overall survival. The original grading system has been modified during the last decade resulting in a more precise prognostic tool. The pretreatment Gleason score guides clinical management and is a key component in S3 guidelines for prostate cancer. In addition to Gleason score several other histologic findings in prostate needle biopsy influence patient management. In this second part of our CME series about prostate cancer, we will discuss the diagnosis of prostate cancer and current guidelines for reporting prostate cancer. In addition, we will highlight prostate lesions of urothelial origin and neuroendocrine prostate cancer as well as prognostic biomarkers.

In the past 25 years, treatment of metastatic colorectal cancer (mCRC) has undergone profound changes. The approval of newer chemotherapeutics such as irinotecan and oxaliplatin was followed in 2005 by the first targeted therapies, for example, monoclonal antibodies directed against the epidermal growth factor receptor (EGFR), as cetuximab and panitumumab, or the angiogenesis inhibitors bevacizumab, ramucirumab, and aflibercept. With the rapidly progressing molecular characterization of mCRC in the last 10 years and the classification of the disease in four consensus subtypes, further changes are emerging, which will promote, among other things, the introduction of protein-kinase inhibitors developed for specific molecular aberrations as well as immune checkpoint inhibitors into the treatment algorithm.Thorough molecular pathologic testing is indispensable today for guideline-compliant treatment of mCRC patients. In addition to RAS testing as a precondition for the therapy decision with regard to cetuximab and panitumumab, BRAF testing is of considerable relevance to allow decision making with regard to the newly approved chemotherapy-free combination of the BRAF inhibitor encorafenib and cetuximab in cases where a BRAF-V600E mutation is detected. Additional diagnostic tests should also include genome instability (microsatellite instability). Overall, more and more molecular alterations need to be investigated simultaneously, so that the use of focused next-generation sequencing is increasingly recommended.This overview describes the prognostic relevance of BRAF testing in the context of molecular pathologic diagnostics of mCRC, presents new treatment options for BRAF-mutated mCRC patients, and explains which modern DNA analytical and immunohistochemical methods are available to detect BRAF mutations in mCRC patients.

Background: Recent developments in differential diagnosis have led to new knowledge about oncocytic renal neoplasms.

Objectives: Overview of differential diagnosis of oncocytic tumours.

Materials and methods: We performed a literature search on oncocytic renal tumours and mapped known tumour types. Possible differential diagnoses are discussed.

Results: Besides the tumour types already acknowledged by the 2016 WHO classification, there is new evidence regarding the group of hard-to-classify oncocytic neoplasms. Findings point to immunohistochemical and molecular characteristics that may lead to the establishment of new entities in the future. In addition, important differential diagnosis can now be identified, facilitating specific therapies for oncocytic renal tumours.

Conclusion: A correct diagnosis of oncocytic renal tumours not only improves prognostic assessment (and, if necessary, specific therapies) but is also clinically relevant regarding a possible association with hereditary tumour syndromes.

Background: A dysregulated immune response is considered one of the major factors leading to severe COVID-19. Previously described mechanisms include the development of a cytokine storm, missing immunoglobulin class switch, antibody-mediated enhancement, and aberrant antigen presentation.

Objectives: To understand the heterogeneity of immune response in COVID-19, a thorough investigation of histomorphological patterns in regional lymph nodes was performed.

Materials and methods: Lymph nodes from the cervical, mediastinal, and hilar regions were extracted from autopsies of patients with lethal COVID-19 (n = 20). Histomorphological characteristics, SARS-CoV‑2 qRT-PCR, and gene expression profiling on common genes involved in immunologic response were analyzed.

Results: Lymph nodes displayed moderate to severe capillary stasis and edema, an increased presence of extrafollicular plasmablasts, mild to moderate plasmacytosis, a dominant population of CD8⁺ T‑cells, and CD11c/CD68⁺ histiocytosis with hemophagocytic activity. Out of 20 cases, 18 presented with hypoplastic or missing germinal centers with a decrease of follicular dendritic cells and follicular T‑helper cells. A positive viral load was detected by qRT-PCR in 14 of 20 cases, yet immunohistochemistry for SARS-CoV-2 N-antigen revealed positivity in sinus histiocytes of only one case. Gene expression analysis revealed an increased expression of STAT1, CD163, granzyme B, CD8A, MZB1, and PAK1, as well as CXCL9.

Conclusions: Taken together, our findings imply a dysregulated immune response in lethal COVID-19. The absence/hypoplasia of germinal centers and increased presence of plasmablasts implies a transient B‑cell response, implying an impaired development of long-term immunity against SARS-CoV‑2 in such occasions.

Despite its descriptive name, eosinophilic, solid, and cystic renal cell carcinoma (ESC-RCC) represents a distinctive epithelial renal tumor entity defined by characteristic clinicopathological and molecular features. ESC-RCC occurs predominantly in women and is characterized in the majority of cases by sporadic (somatic) TSC mutations. A small subset of cases, however, affects patients with TSC germline mutations (tuberous sclerosis syndrome). TSC mutations have therefore been shown to be pathogenetic in this type of tumor. Most tumors present as small (pT1) well circumscribed but not encapsulated lesions with variable macrocystic spaces on their cut surface. Immunohistochemically, their CD117-/CK7-/CK20+ profile is characteristic. Although the tumor cell nuclei of the ESC-RCC occasionally correspond to ISUP/WHO grade 2-3, these tumors are essentially indolent with aggressive cases being only rarely observed. Single case reports have documented effective treatment of aggressive cases with mTOR inhibitors. ESC-RCC needs to be distinguished from a variety of eosinophilic RCC types with secondary cystic changes including cystic SDH-deficient RCC, the recently proposed eosinophilic vacuolated tumor (EVT; also mTOR-related), oncocytoma, and low-grade oncocytic tumor (LOT). The generally indolent behavior and frequent TSC/mTOR alterations in ESC-RCC, EVT, and some LOTs raise the question of whether these lesions represent independent tumor entities or are merely morphological variants on the spectrum of eosinophilic low-grade TSC/mTOR-related neoplasms.

The present study focuses on the group of pathologists who (1) were appointed honorary members or bearers of the Rudolf Virchow Medal by the German Society for Pathology (DGP) and (2) experienced the Third Reich as a citizen of the Third Reich. In particular, it examines the relationship between those distinguished persons and National Socialism, and, at the same time, the criteria of the professional society when awarding such honors. Specifically, it is important to clarify what role the DGP officials ascribed to the political stance or experience of the candidates in the Nazi dictatorship during the selection process: were there victims of the Nazis among the honorees whose repressive experiences and personal fates were intended to be acknowledged in this way? Of equal interest is the counter-question: were pathologists honored who had made (party) political commitments to National Socialism during the Third Reich?A total of nine Virchow medallists and three honorary members met the inclusion criteria. None of those affected belonged to the group of pathologists who suffered injustice during the Third Reich or who could be described as victims of the Nazis. On the other hand, four of the nine German Virchow medal winners and one of the three honorary members had joined the National Socialist Party and to some extent other Nazi organisations. Obviously, previous closeness to National Socialism was not a decisive factor in the selection of honorary members and Virchow medallists and, in particular, was not an exclusion criterion.The aforementioned results correspond to the findings of a parallel study, in which the political past of the German DGP chairmen appointed up to 1986 was examined. This showed that two thirds of them had joined the National Socialist Party during the Third Reich.