Journal of Clinical Pathology最新文献

Aims: Multifocal hepatocellular carcinoma (HCC) is traditionally classified as multicentric occurrence (MO) or intrahepatic metastasis, a distinction that is difficult to apply in routine practice and not reflected in current staging systems. We aimed to assess the prognostic significance of different multifocal HCC patterns using simple, clinically applicable criteria.

Methods: We retrospectively analysed 153 patients with synchronous multifocal HCC who underwent surgical resection, including cases with two discrete nodules, more than two nodules and satellite nodules. 76 patients with solitary HCC served as controls. Histological classification based on Liver Cancer Study Group of Japan criteria was supplemented with TERT promoter mutation analysis in selected cases. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using Kaplan-Meier and Cox regression analyses.

Results: Histologic criteria alone failed to classify a substantial proportion of two-nodule HCCs. Although TERT promoter analysis allowed partial reclassification, patients with undetermined two-nodule HCC had survival outcomes comparable to those classified as MO. In contrast, HCCs with satellite nodules showed significantly poorer OS and RFS. Multivariate analysis identified microvascular invasion and the presence of satellite nodules-but not two-nodule multifocality-as independent adverse prognostic factors. Notably, patients with two discrete nodules without satellite lesions did not show a statistically significant difference in OS or RFS compared with those with solitary HCC.

Conclusions: Synchronous two-nodule HCC without satellite nodules represents a prognostically favourable subgroup distinct from satellite-nodule HCC. A simplified morphology-based stratification may better reflect clinical outcomes in multifocal HCC.

Aims: To assess the impact of adding clinical comments to reports of thyroid function testing in patients treated for hypothyroidism.

Methods: We compared thyroid function test results in primary care patients being treated for hypothyroidism from January 2016 to August 2023 at two NHS Trusts with similar demographics and using the same instruments, but with different interpretative comment policies. One laboratory, Buckinghamshire Health Trust (Bucks), adds interpretative comments, whereas the other, Oxford University Hospitals (Oxford), does not. We used two outcome measures: the percentage of patients with thyroid-stimulating hormone (TSH) within the reference interval on repeat testing and the timing of repeat TSH testing samples, according to the National Institute for Health and Care Excellence guidance (NG145).

Results: We identified 18 242 and 31 655 hypothyroid patients (9.0% and 7.7% of the population tested) in Bucks and Oxford, with a total of 121 961 and 247 639 tests over the evaluation period, respectively. The proportion of TSH results within the reference interval (83.4% in Bucks, 83.9% in Oxford) was similar in both Trusts, as was TSH concentration (median TSH concentration 1.60 (IQR 0.78-2.82) mU/L in Bucks, 1.68 (IQR 0.97-2.76) in Oxford). The interval between tests was shorter in Oxford, but differed significantly from NG145 in both Trusts. Differences were statistically significant for both outcome measures, but of questionable clinical significance.

Conclusions: Adding interpretative comments to results of thyroid function tests does not appear to affect the distribution of TSH concentrations in primary care patients on thyroxine replacement or the intervals between tests in a clinically meaningful way.

Primary lung tumours are rare in paediatric patients. Mucoepidermoid carcinoma (MEC), typically low-grade and diagnostically straightforward, is the second most common tumour of the bronchus after carcinoid tumours. However, rare MEC may show divergent differentiation, be misdiagnosed as low-grade adenocarcinoma, not otherwise classified, and pose clinical challenges, especially when mastermind-like protein 2 (MAML2) gene arrangement is negative by fluorescence in situ hybridisation (FISH). Here, we report an MAML2 FISH-negative low-grade bronchial tumour in a juvenile patient that demonstrates both mucoepidermoid and acinar differentiation based on morphology and immunophenotype. Next-generation sequencing identified a CREB regulated transcription coactivator 3 (CRTC3::MAML2) fusion gene, located upstream of traditional translocation points and potentially undetectable by currently available FISH probes. This tumour appears to be a novel presentation of a bronchial tumour with dual mucoepidermoid and acinar differentiation, first described as mucoacinar carcinoma-a newly proposed subtype of MEC, originally described in the major salivary gland.

Aims: Despite continually improving guidelines, human epidermal growth factor receptor 2 (HER2) testing for breast and gastro-oesophageal carcinoma continues to be a technical challenge in clinical laboratories. Manual HER2 fluorescence in situ hybridisation (FISH) testing is labour-intensive and prone to inter-run and interoperator variability. We aimed to adopt and validate a Leica BOND-III automated staining platform for HER2 FISH testing.

Methods: We recently validated the Leica BOND-III automated staining platform for HER2 FISH testing and compared it to our previous manual FISH (Agilent HER2 IQFISH pharmDx) methodology using 77 breast cancer cases and 8 gastric cancer cases.

Results: Using the automated Leica BOND-III automated staining platform, we achieved 0.95 sensitivity and 0.97 specificity in HER2 FISH testing for breast cancer cases and 1.0 sensitivity and specificity for gastric carcinoma cases. There was a 98% concordance rate between results of automated testing versus our previous manual method. The automated staining platform decreased technical hands-on time significantly while also reducing overall supply costs for the laboratory.

Conclusions: We were able to implement and validate the automated Leica BOND-III staining platform seamlessly into a complex laboratory for HER2 FISH testing that has overall significantly decreased hands-on time by technologists and supply costs. Automated Leica BOND-III HER2 FISH staining results were highly concordant with our previous manual FISH method in both breast cancer and gastric cancer cases.

Aims: HER2/neu gene is amplified in 15%-20% of invasive breast cancers (IBCs), serving as critical prognostic and predictive marker. HER2-targeted therapies have improved outcomes for HER2-positive patients, highlighting the importance of accurate assessment. Immunohistochemistry is commonly used for screening HER2 overexpression, with equivocal cases reflex tested using in situ hybridisation (ISH) methods like fluorescence (FISH) or dual-colour dual ISH (D-DISH). While FISH displays quantitative accuracy, it is expensive, time-consuming and technically demanding. D-DISH offers a faster, automated alternative using bright-field microscopy for easier interpretation and better archiving. Advances in digital pathology, such as whole slide imaging and automated image analysis (IA), promise to improve HER2 evaluation. The CE-IVD marked uPath HER2 Dual ISH IA algorithm by Ventana Medical Systems (Tucson, Arizona, USA) is designed to assist in this process, providing computer-assisted evaluation of HER2/neu. Thus, we undertook this study to standardise and validate uPath Dual ISH IA algorithm and assess interobserver reproducibility in interpreting D-DISH assay.

Methods: This study retrospectively analysed 106 IBC cases, evaluating the concordance between manual and algorithm-assisted D-DISH evaluations.

Results: A consensus concordance rate of 91.5% and a Cohen's kappa value of 0.83 was observed between the manual and on-site IA evaluations, indicating near-perfect agreement. Remote IA evaluations also demonstrated substantial concordance, with a concordance rate of 88.89% and kappa value of 0.70.

Conclusions: We successfully validated the uPath IA algorithm as a time-efficient, screening modality as well as viable alternative to manual interpretation for both on-site and remote interpretation of HER2 D-DISH in a high-volume centre.