Histopathology最新文献

Background and objectives: Testicular frozen section examination on excisional biopsy (FSEB) is an underused pathological and surgical approach, considering the increasing number of small benign testicular lesions found on radical orchidectomy specimens. This study aims to determine the diagnostic accuracy of FSEB and to provide a pathological summary of the most frequent diagnoses and pitfalls.

Methods: We report the pathological findings and definitive outcome of 135 FSEB for small testicular masses performed between 2005 and 2024 in a single institute.

Results: The median tumour size was 0.9 cm (Interquartile Range [IQR] 0.5-1.3 cm). The most common FSEB diagnoses were Leydig cell hyperplasia/tumour (n = 37; 28%) and seminoma (n = 36; 27%). On FSEB, benign diagnoses represented 58% of cases which allowed us to avoid 81 unnecessary radical orchidectomies. The sensitivity and specificity of FSEB for malignancy were 100% and 96.3%, respectively. Excluding three indeterminate cases on FSEB, the concordance rate was 97.7% (129/132). On definitive assessment, the majority of cases were benign (84/135, 62%) and 51 (38%) cases were malignant. The three indeterminate cases were ultimately confirmed as benign. There were three false-positive diagnoses of (favoured) malignancy and no false negatives.

Conclusions: FSEB is accurate for patient management of small testicular lesions, allowing us to save young men from unnecessary radical orchidectomy. We provide an in-depth overview of the most prevalent pathological diagnoses encountered.

Introduction: The risk stratification of gastric cancer (GC) is graded by assessing well-established precursor lesions, glandular atrophy (GA), and intestinal metaplasia (IM), resulting in both the operative link on gastritis assessment (OLGA), and intestinal metaplasia (OLGIM) systems. Although the OLGIM stage is reproducible among pathologists, the OLGA system is laborious to calculate and has poor reproducibility. In addition, it does not comprehensively address the severity of both GA and IM as recommended by the Sydney consensus. We aimed to propose the Operative Link on Gastric Intestinal Metaplasia and Glandular Atrophy Assessment (OLGIMA) system, which identifies OLGIM III-IV and upstages 0-II with advanced GA.

Methods: A cross-sectional study of consecutive diagnostic gastroscopies in adults was designed. Systematic gastric biopsies were taken. The updated Sydney guidelines were used for histological grading of GA and IM. Higher GC risk was defined as OLGIM III-IV and advanced GA.

Results: The OLGIMA stage was assessed based on the most severe GA and/or IM findings in both antrum and corpus. We included 998 patients (median age 57; 64% women; 35% Helicobacter pylori infection). Thirty-nine (3.9%) patients had higher GC risk: 17 (1.7%) with OLGIM III-IV; 12 (1.2%) with advanced GA, and 10 (1%) meeting both criteria. Among OLGIM 0-II, 12 (1.2%) patients had advanced GA. The OLGIMA system upstaged 39 (3.9%) patients to III-IV, being more sensitive than OLGIM.

Conclusions: The new OLGIMA system identifies patients at higher GC risk (OLGIMA III-IV), encompassing all OLGIM III-IV patients, and upstaging those OLGIM 0-II with advanced GA. This approach addresses the OLGA and OLGIM limitations by integrating GA and IM severity as recommended by the Updated Sydney consensus.

Aims: Pathological evaluation of colorectal carcinoma (CRC) diagnosed at stage pT1 is challenging. Nevertheless, it is crucial for treatment guiding and to determine the patient's prognosis. This study aimed to assess the interobserver variability in the histopathological evaluation of pT1 CRC.

Methods and results: A retrospective multicentre pT1 CRC cohort study was designed (EpiT1 consortium). A task force comprising 20 experienced pathologists conducted the histopathological evaluation using digitalized haematoxylin-eosin (H&E) slides. A pilot study was performed with 10 cases, and afterwards, a consensus meeting was held to assess interobserver variability. Then, a concordance study was performed by assessing 70 new pT1 CRC cases. We used percentage agreement and Gwet's Agreement Coefficient 1 for categorical variables, and intraclass correlation coefficient (ICC) for continuous variables. In the pilot study, histological grade and perineural invasion (PNI) demonstrated 100% agreement, with good concordance for lymphovascular invasion (LVI), tumour budding (TB), poorly differentiated clusters (PDC) and margin assessment. The concordance study showed high agreement (≥90%) on histological grade, PDC, PNI and LVI. Submucosal invasion depth showed excellent reliability in the concordance study (ICC = 0.97). Notably, in both studies, the agreement of PDC was higher than for TB. Lower concordance was observed on stromal lymphocytes and the status of muscularis mucosae.

Conclusions: Our results emphasize the need for standardization in evaluating pT1 CRC to improve the concordance among pathologists, and the precision of digital measurements. Moreover, the addition of PDC assessment in pT1 CRC diagnostic guidelines could help to improve the accuracy of risk stratification and reliably predict prognosis.

Invasive breast carcinomas with papillary features (IBCP) constitute a distinct and morphologically diverse group of breast cancers characterised by varying degrees of papillary architecture and invasive behaviour. IBCP encompass (1) papillary carcinoma in situ associated with invasion, (2) invasive solid papillary carcinoma (ISPC), (3) encapsulated papillary carcinoma (EPC)-like invasive carcinoma, (4) Papillary DCIS-like invasive carcinoma, (5) high-grade carcinomas with EPC-like or SPC-like morphology, and (6) invasive papillary carcinoma not otherwise specified (IPC), including the tubulopapillary pattern. This review summarises the evolving classification, histopathological features, diagnostic criteria, differential diagnoses, clinical prognosis, and treatment implications of various subtypes of IBCP. Particular attention is given to the diagnostic challenges and clinical relevance of recognising these tumour types. Standardised diagnostic criteria and further research into the biological behaviour of these entities are essential to guide appropriate management and improve prognostication.

Aims: Oncotype DX has played a critical role in guiding treatment decisions for hormone receptor (HR)-positive, HER2-negative early-stage breast cancer. Clinically, a subset of patients with low Oncotype recurrent score (RS) will still progress on standard therapy and ultimately develop metastasis. Our goal was to explore potential molecular mechanisms, including specific genetic alterations and pathway activity associated with disease progression.

Methods and results: We retrospectively reviewed a small series of low RS breast cancers with subsequent metastasis and analysed the clinicopathological characteristics and comprehensive genomic profiling (CGP) data from tumour tissue and circulating tumour DNA (ctDNA) by liquid biopsy.

Results: These tumours demonstrated a range of histopathologic features and molecular profiles. Common findings included enrichment of PIK3CA and TP53 mutations and treatment-emergent ESR1 mutations, observed in both tissue and ctDNA. CDKN2A, SPEN, KIT, CTNNB1, MYC, EMSY, KMT2C, MAP3K1 gene alterations were only found in low RS group in low frequency. Copy number amplifications events were less common in low RS group. In cases with both tissue and ctDNA data, tissue CGP proved useful baseline for identifying driver mutations such as PIK3CA and for contextualizing ctDNA findings, and ctDNA analysis was adequate for disease monitoring and tracking molecular evolution over time.

Conclusions: Using real-world CGP of tumour tissue and ctDNA, we identified key molecular features associated with endocrine resistance in patients with low RS who later developed metastases. PIK3CA mutation and other ER group-related mutations contributed to the low RS. Tissue CGP provides baseline for interpreting ctDNA, and ctDNA monitoring PIK3CA, TP53, ESR1 and other pathogenic or driver mutations in the early course of low RS cases may represent an excellent non-invasive option for identifying targets and early intervention to prevent disease progression, though a large validation study is needed.

Aims: PAX8 immunohistochemistry (IHC) is often used to distinguish urothelial carcinomas (UCs) from tumours of renal and Mullerian origin. However, some UCs have been shown to be PAX8-positive. This study investigates the frequency of PAX8-positive conventional UCs of the urinary bladder without subtype morphology and/or divergent differentiation and their molecular profiles.

Methods: One hundred and one consecutive transurethral resections of the urinary bladder from 2019 to 2022 with a diagnosis of conventional urothelial carcinoma (UC) without subtype morphology and/or divergent differentiation were retrospectively reviewed. Representative sections were selected for whole-slide PAX8 IHC (10336-1-AP; polyclonal). Next-generation sequencing (NGS) was performed on all PAX8-positive cases and on a subset of PAX8-negative cases.

Results: PAX8 IHC was positive in 10% (10/101) of cases. Twenty cases underwent NGS, including all 10 PAX8-positive UCs. All PAX8-positive UCs had TERT promoter mutations. TSC1 alterations, NOTCH1 loss and WT1 loss were more frequent in the PAX8-positive cases compared with the PAX8-negative cases. RB1 loss was not seen in the PAX8-positive UCs, while it was present in 40% of the PAX8-negative UCs.

Conclusions: A subset of conventional UCs of the urinary bladder without subtype morphology and/or divergent differentiation are PAX8-positive and have frequent alterations in TERT promoter, TSC1, NOTCH1, and WT1, with an absence of RB1 loss. PAX8 positivity should be interpreted with caution if UC is in the differential, and NGS could be helpful in diagnostic workups as this study shows PAX8-positive UCs may have a distinct molecular profile.

Aim: The aim of this study was to evaluate whether the utility of cytokeratin (AE1/AE3) rapid immunohistochemistry (IHC) in combination with haematoxylin-eosin (H&E) staining improves the intraoperative diagnosis of spread through air spaces (STAS) on frozen sections (FS).

Methods and results: This study included 153 patients. Three pathologists independently evaluated STAS on FS using either HE staining alone or in combination with rapid IHC, with postoperative paraffin sections serving as the gold standard. Sensitivity and specificity were compared, along with interobserver and intraobserver agreement (κ values), diagnostic time, and causes of misdiagnosis. Compared with HE alone, HE combined with rapid IHC staining increased mean diagnostic sensitivity from 73.7% to 87.8% and specificity from 85.5% to 89.9% across pathologists with varying levels of experience. Mean intraobserver agreement improved from κ = 0.644 (83.9%) to κ = 0.907 (95.9%), and mean interobserver agreement improved from κ = 0.485 (65.0%) to κ = 0.671 (77.2%). Average diagnostic time decreased from 2 min 53-23 s. Misdiagnoses were primarily attributable to a limited number of STAS clusters, confusion with macrophages, and artefacts.

Conclusions: Intraoperative H&E combined with rapid IHC enhanced the sensitivity and specificity of STAS detection, improved interobserver/intraobserver agreement and reduced diagnostic time during FS evaluation without significantly extending the overall intraoperative FS processing time. Nevertheless, additional multicenter validation is required.

In the era of immune checkpoint inhibitors for cancers, the need for prognostic biomarkers to identify patients most likely to achieve a durable response has become increasingly more relevant. Tumour-infiltrating lymphocytes (TILs) have gained significant interest, as they can be evaluated using standard haematoxylin and eosin-stained slides, making it a widely accessible and cost-effective biomarker. In addition to their practicality, TILs provide prognostic insights into the interplay between the immune system and tumour cells. While the morphological assessment of TILs has been standardised in breast cancer, comprehensive guidelines for their evaluation in gastro-oesophageal carcinomas (GEC) are still lacking. This narrative review examines the current literature on the composition, clinical implications and therapeutic utility of TILs in GEC. These insights are used to propose a framework with recommendations for standardised evaluation and reporting of TILs in GEC, while also highlighting pitfalls specific to GEC pathology. These recommendations serve as a vital first step towards the widespread use and validation of TILs as a biomarker.

Aims: Many studies have highlighted interobserver variability in histologic distinction between colorectal sessile serrated lesion (SSL) and hyperplastic polyp (HP). In 2019, the WHO updated their criteria for the diagnosis of SSL, requiring 'at least 1 unequivocal architecturally distorted serrated crypt'. Even with this simplified criterion, as well as experience accumulated in recognizing SSL over 25 years, SSL and HP remain difficult to distinguish in some instances. This study aimed to assess observer variability and preferred criteria in diagnosing SSL among gastrointestinal pathologists.

Methods and results: We retrospectively identified 60 serrated colorectal polyps, produced uniform H&E recuts, and created whole-slide images for each case. Cases were selected to cover a spectrum of non-dysplastic serrated lesions, as confirmed via review by four pathologists who individually interpreted each as SSL, HP, or serrated polyp NOS (SP-NOS). The cases were then reviewed by nine additional pathologists. A second round of review followed after a 5-month washout period. A third round of reviews was completed after 5 additional months, at which time reviewers were provided information regarding polyp size and site. Fleiss and Cohen kappa values were calculated to determine overall inter- and intra-observer agreement. The top three criteria pathologists used to favour a diagnosis of SSL over HP included crypt distortion (13/13), polyp location (8/13) and size (4/13). There was moderate agreement among all 13 pathologists when classifying the 60 cases for rounds 1 (κ = 0.50) and 2 (κ = 0.46), and good agreement for round 3 (κ = 0.63), the round using criteria beyond those of the WHO; stratification by location showed agreement was worst for transverse polyps. Twenty-one (35%) cases were called SSL >80% of the time, and 16 (27%) cases were classified as HP >80% of the time. Agreement was moderate (κ = 0.43) for polyps measuring ≥1.0 cm and was good (κ = 0.63) for polyps measuring ≤0.4 cm. In keeping with current WHO criteria, crypt distortion was the only feature all pathologists considered useful to diagnose SSL. Overall interobserver agreement improved from moderate to good when pathologists were aware of the polyp size and site. Pathologists had the worst agreement when classifying lesions in the transverse colon or polyps ≥1.0 cm.

Conclusions: Non-histologic criteria (e.g. polyp site and size) may be necessary to accurately and reproducibly distinguish SSL from HP, if properly validated.