Journal of Clinical Pathology最新文献

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.

Background: Frozen section (FS) and touch imprint (TI) are common intraoperative evaluation (IOE) techniques for sentinel lymph nodes (SLNs) in breast cancer surgery. Their accuracy in patients receiving neoadjuvant systemic therapy (NST) remains variable.

Objective: To summarise evidence on the diagnostic accuracy of FS and TI in the NST context.

Methods: A systematic search of PubMed, Embase, Scopus and Web of Science was conducted through April 2024 for studies evaluating FS and/or TI in SLNs of breast cancer patients treated with NST. Meta-analysis was performed using the logit function, and Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 and Grading of Recommendation, Assessment, Development and Evaluation were employed to assess risk of bias and evidence certainty.

Results: 20 studies were included. At the lymph node level, TI demonstrated pooled sensitivity and specificity of 0.54 and 1.00, respectively, while FS achieved 0.85 and 0.99. At the patient level, TI showed sensitivity and specificity of 0.72 and 1.00, while FS reached 0.82 and 0.98. Combined, FS and TI presented pooled sensitivity and specificity of 0.59 and 1.00 at the patient level. Risk of bias was frequently unclear, and the certainty of evidence for both techniques ranged from low to very low.

Conclusion: FS exhibits higher sensitivity and specificity than TI at both lymph node and patient levels, but evidence certainty remains limited. Further prospective, blinded studies are needed to validate these findings and optimise IOE methods for NST-treated patients.

Prospero registration number: CRD42023483079.

Aims: Mutations affecting exon 3 of the β-catenin (CTNNB1) gene result in constitutive activation of WNT signalling and are a diagnostic hallmark of several tumour entities including desmoid-type fibromatosis. They also define clinically relevant tumour subtypes within certain entities, such as endometrioid carcinoma. In diagnostics, β-catenin immunohistochemistry is widely used as a surrogate for CTNNB1 mutations. Yet, it is often difficult to assess in practice, given that the characteristic nuclear translocation may be focal or hard to distinguish from the spillover of the normal membranous staining.

Methods: We therefore examined lymphoid enhancer-binding factor 1 (LEF1) immunostaining, a nuclear marker of WNT activation that serves as a potential surrogate for CTNNB1 mutations.

Results: In a cohort of endometrial carcinomas with known mutation status (n=130) LEF1 was 85% accurate in predicting CTNNB1 mutation status (64% sensitivity, 90% specificity) while β-catenin was 76% accurate (72% sensitivity; 77% specificity). Across a variety of entities characterised by CTNNB1 mutations as putative drivers, we found diffuse and strong expression of LEF1 in 77% of cases. LEF1 immunostaining proved easier to interpret than β-catenin immunostaining in 54% of cases, more difficult in 1% of cases and comparable in the remaining cases.

Conclusion: We conclude that LEF1 immunostaining is a useful surrogate marker for CTNNB1 mutations. It favourably complements β-catenin immunohistochemistry and outperforms the latter as a single marker.

Aims: Progesterone receptor (PR) is a crucial prognostic marker in breast cancer. However, achieving consistent results in PR immunohistochemistry (IHC) remains challenging due to the lack of well-defined low-positive controls. This study aimed to identify benign tissues with consistent low-level PR expression to serve as ideal controls for IHC.

Methods: We evaluated PR expression in the squamous epithelium of the uterine cervix, nipple smooth muscle and pancreatic islets. QuPath digital image analysis was employed to compare the intensity and quantity of PR staining in target cells within a 2×2 mm area.

Results: The squamous epithelium of the secretory phase cervix, nipple smooth muscle and pancreatic islets displayed appreciable weak PR expression, with mean values of 73, 55 and 60 cells, respectively. Notably, 62% (8/13) of the 2×2 mm areas in the atrophic cervix were completely negative for PR expression. The coefficients of variation for weak PR-expressing cells in pancreatic islets (57.4%) and nipple smooth muscle (65.0%) were lower than those observed in the cervix (96.2%-222.0%). The squamous epithelium of the cervix, especially during the secretory phase, exhibited weak positivity confined to the basal layers, providing another viable control option. However, variations in PR expression may be influenced by physiological factors, such as hormonal fluctuations.

Conclusions: Pancreatic islets and nipple smooth muscle, with their consistent low-level PR expression, offer a promising solution to the challenges associated with PR IHC. This approach may help minimise variations resulting from differing staining methods across laboratories.