Virchows Archiv最新文献

The WHO Classification of Tumours (WCT) guides cancer diagnosis, treatment, and research. However, research evidence in pathology continuously changes, and new evidence emerges. Correct assessment of evidence in the WCT 5th edition (WCT-5) and identification of high level of evidence (LOE) studies based on study design are needed to improve future editions. We aimed at producing exploratory evidence maps for WCT-5 Thoracic Tumours, specifically lung and thymus tumors. We extracted citations from WCT-5, and imported and coded them in EPPI-Reviewer. The maps were plotted using EPPI-Mapper. Maps displayed tumor types (columns), descriptors (rows), and LOE (bubbles using a four-color code). We included 1434 studies addressing 51 lung, and 677 studies addressing 25 thymus tumor types from WCT-5 thoracic tumours volume. Overall, 87.7% (n = 1257) and 80.8% (n = 547) references were low, and 4.1% (n = 59) and 2.2% (n = 15) high LOE for lung and thymus tumors, respectively. Invasive non-mucinous adenocarcinoma of the lung (n = 215; 15.0%) and squamous cell carcinoma of the thymus (n = 93; 13.7%) presented the highest number of references. High LOE was observed for colloid adenocarcinoma of the lung (n = 11; 18.2%) and type AB thymoma (n = 4; 1.4%). Tumor descriptors with the highest number of citations were prognosis and prediction (n = 273; 19.0%) for lung, and epidemiology (n = 186; 28.0%) for thymus tumors. LOE was generally low for lung and thymus tumors. This study represents an initial step in the WCT Evidence Gap Map (WCT-EVI-MAP) project for mapping references in WCT-5 for all tumor types to inform future WCT editions.

Traditionally, psammoma bodies (PB) have been considered as tale-tell evidence of papillary thyroid carcinoma (PTC) and are frequently encountered in classic and other subtypes of PTCs. However, the presence of PBs in the thyroid gland does not always indicate malignancy. The leading hypothesis on their origin suggests that PB are remnants of papillary structures that have undergone thrombosis, necrosis, and subsequent calcification. From January 2010 to May 2024, 26 patients with psammoma bodies associated with benign thyroid lesions, mainly thyroid follicular nodular disease (TFND), Hashimoto thyroiditis (HT), Graves' disease, and follicular adenomas, were found. The case cohort included 16 females and 10 males with a median age of 49.3 years. The series included 12 TFND, two HT, and 12 follicular adenomas (11 out of 12 were oncocytic adenomas). Twenty-four out of 26 underwent total thyroidectomy. In 24 out of 26 cases, the entire lobes and parenchyma were included and serial cuts at multiple levels were performed in cases with PB but without any evidence of malignancy. Even though the detection of PB is associated with a malignant thyroid lesion, especially PTC and its subtypes, our multi-institutional series showed that in a minority PB can be found in a variety of benign thyroid lesions. Evaluation of the entire thyroid parenchyma at multiple levels is mandatory to exclude sub-centimeter papillary thyroid carcinoma.

Uterine mesenchymal tumours harboring KAT6B/A::KANSL1 gene fusions typically exhibit histological and immunophenotypic overlap with endometrial stromal and smooth muscle tumours. To date it remains uncertain whether such neoplasms should be regarded as variants of smooth muscle or endometrial stromal neoplasm, or if they constitute a distinct tumour type. In this study we investigated DNA methylation patterns and copy number variations (CNVs) in a series of uterine tumours harboring KAT6B/A::KANSL1 gene fusions in comparison to other mesenchymal neoplasms of the gynecological tract. Unsupervised hierarchical clustering and t-SNE analysis of DNA methylation data (Illumina EPIC array) identified a distinct cluster for 8/13 KAT6B/A::KANSL1 tumours (herein referred to as core cluster). The other 5 tumours (herein referred to as outliers) did not assign to the core cluster but clustered near various other tumour types. CNV analysis did not identify significant alterations in the core cluster. In contrast, various alterations, including deletions at the CDKN2A/B and NF1 loci were identified in the outlier group. Analysis of the DNA methylation clusters in relation to histological features revealed that while tumours in the core KAT6B/A::KANSL1 cluster were histologically bland, outlier tumours frequently exhibited "high-grade" histologic features in the form of significant nuclear atypia, increased mitotic activity and necrosis. Three of the five patients with outlier tumours died from their disease while clinical follow-up in the remaining two patients was limited (less than 12 months). In comparison, none of the 7 out of 8 patients with tumors in the core KAT6B/A::KANSL1 sarcoma cluster, where follow-up was available, died from disease. Furthermore, only 1 out of 7 patients recurred (mean follow-up of 30 months). In conclusion, KAT6B/A::KANSL1 uterine sarcoma is a molecularly unique type of uterine tumour that should be recognized as a distinct entity. These tumors typically exhibit low-grade histologic features but are occasionally morphologically high-grade; the latter have a DNA methylation profile different from the typical low-grade neoplasms and may be associated with aggressive behaviour.

Theragnostic biomarkers are still needed to select patients with digestive neuroendocrine neoplasms (NENs) for an optimal management. The PD-1/PD-L1 pathway plays a pivotal role in T cells activation and host immune response to cancer and PD-L1 expression in tumor and/or immune cells is used to identify patients who would benefit of treatment with immune checkpoint inhibitors. However, its role as a biomarker is still unclear in digestive NENs. We investigated PD-L1 expression in 68 well-characterized digestive NENs (32 NETs, 32 NECs and 4 MiNENs) and TPS and CPS scores were calculated. In addition, tumor infiltrating T-lymphocytes and mismatch repair protein expression (MMR) were evaluated. All results were correlated with clinicopathological features. PD-L1 expression was higher in NECs than in NETs: TPS > 1% and/or CPS > 1 were observed in 16% of NETs, 68.8% of NECs and 50% of MiNENs (p: 0.05). The mean TPS score in positive cases was 6.3% in NETs, 16.2% in NECs and 5% in MiNENs. The CPS score was 4.8 in NETs, 8.1 in NECs and 6 in MiNENs. MMR-deficient neoplasms were more frequently observed in NECs than in NETs (p: < 0.05) as well as intra-tumor immune infiltration (p: 0.00001). No correlation between PD-L1 expression and survival or other clinicopathological parameters was observed. Our results suggest that treatment with immune checkpoint inhibitors may have a potential role only in selected cases, mainly in NECs and MiNENs.

Correctly diagnosing neuroendocrine neoplasm (NEN) has become increasingly challenging, given that more histomorphologic and immunophenotypic NEN mimics have been identified in recent years. A systemic review was conducted on the 4795 consult cases submitted with initial diagnoses of NEN to a national reference center in China from 2013 to 2021. Among them, 443 cases were misdiagnosed as epithelial NENs after reevaluation with the help of immunohistochemical and/or molecular tests, ranging from 7.1 to 13.2%, with yearly increases. The misdiagnoses varied among age groups and tumor sites. Exocrine carcinoma was the most common (63.2%), followed by mesenchymal tumors. Other common tumors that were misdiagnosed included hepatocellular carcinoma, salivary gland tumor, and gastrointestinal stromal tumor. Aberrant expression of neuroendocrine markers was frequent (218/408, 53.4%), with diffuse positivity ranging from 8.2 to 51.7% for synaptophysin, chromogranin A, and INSM1 stains in all non-NEN cases. Selecting appropriate immunohistochemical stains based on H&E morphology is the key to avoiding diagnostic pitfalls. Medical history and molecular genomic information greatly assist in correctly diagnosing NENs and their mimics.

Checkpoint inhibitors (CPIs) have been widely applied in the treatment of patients with bladder cancer (BLCA). However, there is still unmet need to dissect response predict biomarkers. To uncover CPI response-related marker genes in cancer cells, we utilized SCISSOR, integrating single-cell RNA and bulk RNA sequencing data. Transcriptomic and clinical data from IMvigor210, UNC-108, and BCAN/HCRN datasets were collected to evaluate and validate the identified biomarkers and signatures. Additionally, we analyzed TCGA-BLCA and local-BLCA RNA-seq data to investigate alternative splicing events (ASEs). Cell viability was assessed in T24 and UMUC3 cells with RBM17 upregulation or downregulation. Through SCISSOR analysis, we discovered that the expression levels of RBM17, TAP1, and PSMB8 were significantly associated with CPI response. Since PSMB8 displayed a highly positive correlation with TAP1, we developed a CPI response score (CRS) signature based on the expression profiles of RBM17 and TAP1. The CRS demonstrated robust predictive capacity in IMvigor210, UNC-108, and BCAN/HCRN datasets and was associated with higher tumor mutational burden (TMB), PD-L1 expression, and unique genomic features. Notably, RBM17 was not linked to the clinical outcomes of BLCA patients but positively correlated with BLCA cell proliferation in vitro. In the meantime, RBM17 was correlated with higher activity in core biological pathways, including antigen processing machinery, CD8 + T effector cells, cell cycle, DNA damage repair, epithelial-mesenchymal transition, histone regulation, and immune checkpoints. Moreover, the high-RBM17 group showed enrichment of LumU/Ba/sq subtypes but fewer FGFR3 alterations. Lastly, RBM17 significantly upregulated ASEs in BLCA samples, leading to higher neoantigen levels, a more inflamed tumor microenvironment, and improved CPI response. RBM17 is associated with higher ASEs and neoantigen levels, thereby potentiating the efficacy of CPI in BLCA. The established predictive signature, utilizing only two genes, has the potential to streamline clinical applications, providing a cost-effective alternative to expensive genomic, transcriptomic, and biological feature tests.