SOCS1 deficiency-crossroads of autoimmunity and autoinflammation-two case reports.

Suppressors of cytokine signaling (SOCS) proteins play a critical role in regulating immune signaling pathways. Deficiency of SOCS1 leads to various autoimmune pathologies. We present two unrelated patients with distinct clinical manifestations.

High interobserver variability of PTEN immunohistochemistry defining PTEN status in low- to intermediate-risk prostate cancer: results of the first German ring trial.

The prognostication of individual disease trajectory and selection of optimal therapy in patients with localized, low-grade prostate cancer often presents significant difficulty. The phosphatase and tensin homolog on chromosome 10 (PTEN) has emerged as a potential novel biomarker in this clinical context, based on its demonstrated prognostic significance in multiple retrospective studies. Incorporation into standard clinical practice necessitates exceptional diagnostic accuracy, and PTEN's binary readout-retention or loss-suggests its suitability as a biomarker.

Practical hints for the diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasms of the digestive system.

In this editorial, a comment on the article by Díaz-López published in the recent issue of the 2024 is provided. We focus on the practical implications critical for providing a correct and complete diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) in the gastrointestinal system. The diagnosis of MiNEN begins with the recognition of neuroendocrine features in one component of a biphasic tumor.

MSIreg: an R package for unsupervised coregistration of mass spectrometry and H&E images.

Summary: Joint analysis of mass spectrometry images (MS images) and microscopy images of hematoxylin and eosin (H&E) stained tissues assists pathologists in characterizing the morphological structure of the tissues, and in performing diagnosis. Unfortunately, the analysis is undermined by substantial differences between these modalities in terms of aspect ratios, spatial resolution, number of channels in each image, as well as by large global or small local elastic spatial deformations of one image with respect to the other. Therefore, accurate coregistration of the images is a critical pre-requisite for their joint interpretation.

Chemotherapy increases CDA expression and sensitizes malignant pleural mesothelioma cells to capecitabine treatment.

The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge. Cytidine deaminase (CDA) is a key enzyme in the nucleotide salvage pathway and is involved in the adaptive stress response to chemotherapy. The cytidine analog capecitabine and its metabolite 5'-deoxy-5-fluorocytidine (5'-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism.

Multicenter Study on Tumor Budding in Lung Squamous Cell Carcinoma: Comparison Between Biopsy and Resection With Interobserver Variability Assessment.

Grading lung squamous cell carcinoma (LUSC) is controversial and not universally accepted. The histomorphologic feature of tumor budding (TB) is an established independent prognostic factor in colorectal cancer, and its importance is growing in other solid cancers, making it a candidate for inclusion in tumor grading schemes. We aimed to compare TB between preoperative biopsies and resection specimens in pulmonary squamous cell carcinoma and assess interobserver variability.

Artificial Intelligence-based Segmentation of Residual Pancreatic Cancer in Resection Specimens Following Neoadjuvant Treatment (ISGPP-2): International Improvement and Validation Study.

Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking.

Histopathological tumour response scoring in resected pancreatic cancer following neoadjuvant therapy: international interobserver study (ISGPP-1).

Background: Most tumour response scoring systems for resected pancreatic cancer after neoadjuvant therapy score tumour regression. However, whether treatment-induced changes, including tumour regression, can be identified reliably on haematoxylin and eosin-stained slides remains unclear. Moreover, no large study of the interobserver agreement of current tumour response scoring systems for pancreatic cancer exists.

Deciphering imprints of impaired memory B-cell maturation in germinal centers of three patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID), characterized by recurrent infections, low serum class-switched immunoglobulin isotypes, and poor antigen-specific antibody responses, comprises a heterogeneous patient population in terms of clinical presentation and underlying etiology. The diagnosis is regularly associated with a severe decrease of germinal center (GC)-derived B-cell populations in peripheral blood. However, data from B-cell differentiation within GC is limited.

Communicator-Driven Data Preprocessing Improves Deep Transfer Learning of Histopathological Prediction of Pancreatic Ductal Adenocarcinoma.

Pancreatic cancer is a fatal malignancy with poor prognosis and limited treatment options. Early detection in primary and secondary locations is critical, but fraught with challenges. While digital pathology can assist with the classification of histopathological images, the training of such networks always relies on a ground truth, which is frequently compromised as tissue sections contain several types of tissue entities.

Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM).

Background: Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors.

Multiple Immunostainings with Different Epitope Retrievals-The FOLGAS Protocol.

We describe a sequential multistaining protocol for immunohistochemistry, immunofluorescence and CyTOF imaging for formalin-fixed, paraffin-embedded specimens (FFPE) in the formalin gas-phase (FOLGAS), enabling sequential multistaining, independent from the primary and secondary antibodies and retrieval. Histomorphologic details are preserved, and crossreactivity and loss of signal intensity are not detectable. Combined with a DAB-based hydrophobic masking of metal-labeled primary antibodies, FOLGAS allows the extended use of CyTOF imaging in FFPE sections.

Monocyte progenitors give rise to multinucleated giant cells.

The immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear.

Stroma composition and proliferative activity are related to therapy response in neoadjuvant treated pancreatic ductal adenocarcinoma.

Background: Tumor regression grading (TRG) based on histopathology is the main tool to assess therapy effects after neoadjuvant therapy (NAT) of pancreatic ductal adenocarcinoma (PDAC). However, reliable markers to distinguish therapy effects from pre-existing tumor features are lacking. The aim of this study was the characterization of PDAC after NAT, focusing on the stroma.

Molecular analysis of cyst fluids improves the diagnostic accuracy of pre-operative assessment of pancreatic cystic lesions.

Pancreatic cystic lesions (PCL) are increasingly diagnosed. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) cytology is often used for diagnostic confirmation but can be inconclusive. In this study, the role of molecular analyses in the pre-operative diagnostics of PCL is evaluated.

Nonmucinous Cystic Lesions of the Pancreas.

Context.—: Pancreatic cystic lesions are increasingly diagnosed. Among other criteria, they are often distinguished in mucinous versus nonmucinous cysts.

Dusseldorf autopsies 1914-1918.

This article presents an evaluation of 4255 autopsy cases recorded at the Dusseldorf Pathology Institute in the years 1914 to 1918. Diagnoses were coded according to the International Classification of Diseases, 10th edition (ICD-10), and the contemporaneous history of the Pathology Institute was reviewed. We found a proportion of 54.

Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer.

Currently available serum biomarkers for pancreatobiliary cancers lack sensitivity and specificity and ultimate diagnosis still requires invasive procedures for histological confirmation. The detection of tumor-specific genetic aberrations with utilization of cell free DNA (cfDNA) is a less invasive approach than traditional tissue biopsies; however, it has not been implemented into clinical routine. In this study, we investigated bile as a liquid biopsy source in pancreatobiliary cancers and compared its potential as cell-free DNA source to plasma.

Improved detection of sentinel lymph node metastases allows reliable intraoperative identification of patients with extended axillary lymph node involvement in early breast cancer.

An improved procedure that allows accurate detection of negative sentinel lymph node (SLN) and of SLN macrometastases during surgery would be highly desirable in order to protect patients from further surgery and to avoid unnecessary costs. We evaluated the accuracy of an intraoperative procedure that combines touch imprint cytology (TIC) and subsequent frozen section (FS) analysis. 2276 SLNs from 1072 patients with clinical node-negative early breast cancer were evaluated during surgery using TIC.

Amsterdam International Consensus Meeting: tumor response scoring in the pathology assessment of resected pancreatic cancer after neoadjuvant therapy.

Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands.

High Numbers and Densities of PD1 T-Follicular Helper Cells in Triple-Negative Breast Cancer Draining Lymph Nodes Are Associated with Lower Survival.

Breast cancer tumor draining lymph nodes (TDLNs) display distinct morphologic changes depending on the breast cancer subtype. For triple-negative breast cancers (TNBC), draining LNs display a higher amount of secondary lymphoid follicles, which can be regarded as a surrogate marker for an activated humoral immune response. In the present study, we focus on PD1 T-follicular helper cells (Tfh) in TDLNs of TNBC, since PD1 Tfh are drivers of the germinal center (GC) reaction.

Pathology of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy and estimated to become the second leading cause of cancer-related deaths by 2030. Although overall 5-year survival rates have constantly remained below 10% for the last decades, several key points important for accurate patient stratification have emerged during recent years. These key points include a highly standardized gross examination of PDAC resection specimens, using an axial slicing technique and inking of the circumferential resection margin (CRM), as well as a meticulous microscopic examination, taking into account the prognostic relevance of factors such as the exact resection status (R0 R1 1-mm R1 resection), histopathological tumor grading and the so-called lymph node ratio (LNR).