Journal of Clinical Pathology最新文献

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: 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.

Aim: To analyse the expression of early, intermediate and late neuronal immunomarkers in multinodular and vacuolating neuronal tumour (MVNT) and understand the histogenesis of this rare tumour.

Materials and methods: This is a retrospective study over a period of 5 years and included seven cases. Demographic, radiological and histopathological features were assessed. Immunohistochemistry was done for early (OLIG2, MAP2, Doublecortin), intermediate (alpha-internexin, neurofilament) and late neuronal immunomarkers (NeuN, synaptophysin).

Results: All tumours were located in the cerebral hemisphere, mostly confined to temporal lobes with long-standing seizure as the most common symptom. On Magnetic resonance imaging (MRI), these tumours appeared mostly solid and were hypointense on T1 weighted image, hypointense to hyperintense on T2 weighted image. Six out of the seven cases showed nodular as well as diffuse growth pattern, located within deep cortical and superficial subcortical white matter. The nodules were composed of intermediate to large neuronal cells with prominent nucleoli and cytoplasmic vacuolation. The vacuolated neuronal cells showed immunolabelling for early neuronal immunomarkers and an autophagic immunomarker p62. The expression of late and intermediate neuronal immunomarkers was variable to absent. CD34 positive ramified neural elements were observed in the adjoining cortex of six cases. Follow-up data for four cases showed indolent behaviour.

Conclusion: MVNT tumour cells consistently express early neuronal immunomarkers with variable expression of intermediate and late, suggesting maturation arrest early in the development. A combination of neuronal immunomarkers may be useful to diagnose these tumours when the classical histopathological pattern is not present.

Aims: Seminal vesicle invasion (SVI) in prostatic adenocarcinoma (PCa) is a high-risk feature associated with lymph node (LN) metastasis and adverse outcomes. However, the impact of SVI laterality on LN metastasis patterns, nodal burden, metastatic focus size and extranodal extension (ENE) remains underexplored.

Methods: We retrospectively analysed 225 PCa patients with SVI who underwent radical prostatectomy with LN dissection. Associations between SVI laterality, tumour grade, volume and nodal parameters were assessed using univariable and multivariable models.

Results: LN metastases were identified in 97 of 225 (43.1%) patients. Bilateral SVI was significantly associated with higher odds of LN metastasis (OR=2.01; p=0.040), nodal burden (IRR=1.89; p=0.004) and ENE (OR=3.76; p=0.013), independent of tumour volume, grade, age and race. Tumour volume and grade independently predicted LN metastasis (p=0.004 and p=0.048, respectively) and were associated with metastatic focus size (p=0.003 and p<0.001, respectively) and nodal burden (p=0.061 and p=0.045, respectively). LN spread mirrored SVI extent: unilateral SVI primarily led to ipsilateral involvement (22/36; 61.1%; p<0.001), while bilateral SVI increased the risk of bilateral spread (OR=3.81; p=0.003). White patients had significantly higher LN metastasis rates than black patients (p=0.010).

Conclusions: Bilateral SVI is a strong, independent predictor of LN metastasis, nodal burden and ENE. SVI laterality also correlates with LN spread patterns and could inform future risk stratification, though further validation is needed.

Aims: Schistosomiasis remains endemic in various parts of the world, and insights into pathogen immunobiology are mainly based on experimental models, while studies on human tissues are limited.

Methods: We explored the role of immune checkpoint pathway by evaluating the immunohistochemical expression of programmed death-ligand 1 (PD-L1) in a retrospective cohort of patients with bilharzial cystitis. Inflammation severity by conventional histology and staining intensity by immunohistochemistry were assigned three-tier scores (0/1+/2+), and a cut-off for staining percentage was set at 5%.

Results: 38 biopsies from 31 patients were considered adequate for evaluation, and positive staining was detected in 80.6% of patients (34 biopsies). High expressors (22.6%) showed strong positive membranous staining (score 2+) with high staining density (more than 5% of inflammatory cells). Low expressors (58.1%) showed mild/moderate staining (score 1+) predominantly in less than 5% of the cells (91.6%) or expressed restricted cytoplasmic staining (6/31). All high expressors showed severe inflammation (score 2+) (p<0.001), and viable ova were only observed in these cases. Calcified ova were associated with mild/moderate inflammation or absent/minimal inflammation, correlating with low expressors or non-expressors (19.4%), respectively.

Conclusion: Schistosomal granuloma exhibits upregulated PD-L1 expression proportional to inflammation severity and pathogen viability, highlighting a critical immune checkpoint engagement in disease pathology.

Aims: Adequate lymph node examination is key to accurate cancer staging. This study investigates the effectiveness of shortwave infrared imaging in increasing the overall and positive lymph node numbers.

Methods: Specimens from various anatomic sites, including colorectal, pancreatic, breast, gastric, skin and small bowel resections, were evaluated. 104 specimens were first grossed with manual palpation and then grossed with the assistance of shortwave infrared imaging. The overall and positive lymph node numbers were documented.

Results: In 90 of the 104 cases (86.5%), shortwave infrared imaging helped identify additional lymph nodes. On average, 4.81 additional lymph nodes were found. In 11 of the 104 cases (10.6%), additional positive lymph nodes were found. In 4 of the 104 cases (3.8%), cancer stages were changed.

Conclusions: Shortwave infrared imaging may increase the number of lymph nodes identified and has the potential to improve cancer staging accuracy. Further validation in larger, randomised or prospective studies is warranted.