Journal of Clinical Pathology最新文献

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.

Aims and methods: Idiopathic multicentric Castleman disease (iMCD) is currently considered to be classified into three clinical subtypes, including idiopathic plasmacytic lymphadenopathy (IPL), thrombocytopaenia, anasarca, fever, reticulin fibrosis/renal dysfunction, organomegaly (TAFRO) and not otherwise specified (NOS). Among the three, iMCD-IPL closely mimics IgG4-related disease (IgG4-RD). In diagnosing IgG4-RD, it is sometimes challenging to distinguish iMCD-IPL patients that also meet the histological diagnostic criteria for IgG4-RD. In this study, we focused on the number of IgG4-positive cells in the lymph nodes and analysed the relationship with laboratory findings to distinguish iMCD-IPL from IgG4-RD. Thirty-nine patients with iMCD-IPL and 22 patients with IgG4-RD were included.

Results: Among the cases considered to be iMCD-IPL, 33.3% (13/39) cases also met the histological diagnostic criteria for IgG4-RD and serum IgG4 levels were not different between the two groups. However, the serum IgG4/IgG ratio was significantly higher in IgG4-RD, with a cut-off value of 19.0%. Additionally, a significant positive correlation between serum IgG levels and the number of IgG4-positive cells was observed in iMCD-IPL (p=0.001). The serum IgG cut-off value for distinguishing iMCD-IPL meeting histological criteria for IgG4-RD from other iMCD-IPL was 5381 mg/dL.

Conclusions: iMCD-IPL cases with high serum IgG levels (>5000 mg/dL) were likely to meet the diagnostic criteria for IgG4-RD because of the numerous IgG4-positive cells observed. A combination of clinical presentations, laboratory values including the serum IgG4/IgG ratios and histological analysis is crucial for diagnosis of IgG4-RD and iMCD-IPL.

Aims: Breast cancer (BC) during pregnancy (PrBC) and the postpartum period (PPBC) often exhibits more aggressive tumour characteristics and is associated with a poorer prognosis compared with age-matched nonpregnant patients with BC. The underlying mechanisms for this increased aggressiveness remain unresolved. Intratumoral hypoxia, a known adverse prognostic marker in nonpregnant BC, has not yet been studied in PrBC/PPBC. This is particularly intriguing due to the potential exposure to angiogenesis-stimulating factors during pregnancy, which may influence tumour behaviour.

Methods: Tumour tissues from 148 patients with PrBC and 45 patients with PPBC were used to create a tissue microarray (TMA), and clinical and outcome data were obtained. The TMAs were stained for hypoxia-associated protein markers: glucose transporter-1, carbonic anhydrase IX and hypoxia-inducible factor-1α.

Results: Of all 193 tumours, 152 (79%) expressed at least one of these proteins indicative of intratumoral hypoxia. The presence of intratumoral hypoxia was associated with a higher histological grade (83% grade III vs 63%) and frequent hormone receptor negativity (68% vs 39%). In a multivariable analysis, the presence of intratumoral hypoxia indicated a significantly worse prognosis (HR 2.532, 95% CI 1.1 to 5.7) for patients with PrBC and PPBC.

Conclusion: This unique study, the first in patients with PrBC and PPBC, showed that, despite their likely exposure to angiogenesis-stimulating factors, intratumoral hypoxia is frequent and affects 79% of patients. Importantly, patients with tumours overexpressing hypoxia markers have significantly worse survival. This suggests that hypoxia may be an important mechanism in carcinogenesis and clinical behaviour of PrBC and PPBC.

Aims: Research reporting checklists are itemised writing standards to improve transparency and facilitate reproducibility. Previous assessments of their recommendation or requirement have demonstrated improved checklist adherence across medical specialties and study designs. Here, we investigated the endorsement of reporting checklists within pathology, laboratory medicine and forensic science journals.

Methods: We queried Google Scholar Metrics and the Scopus CiteScore tool to identify top pathology and forensic medicine journals. Two authors independently assessed for the mention, recommendation or requirement or checklists-derived from the Enhancing the Quality and Transparency Of Health Research (EQUATOR) network-as well as study preregistration within each journal's aims and instructions for authors. Journal editors were contacted by one author every 3 weeks to confirm whether or not certain study designs would be considered for publication.

Results: Of the 88 journals evaluated, most did not mention or endorse the EQUATOR Network (73.9%) or International Committee of Medical Journal Editors reporting standards (51.1%). The most commonly reported checklists included Animal Research: Reporting of In Vivo Experiments (38.6%), Consolidated Standards of Reporting Trials (28.4%) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (25.0%). The CARE reporting checklist for case reports was required most often by five journals (5.7%). The final email response from journal editors and contacts was 9.1%.

Conclusions: Reporting checklists were suboptimally mentioned and rarely required. Even with many basic and diagnostic science reporting checklists and initiatives, endorsement remains low. We recommend that authors, reviewers and editors become familiar with relevant reporting checklists for their fields and publishing spaces to improve checklist visibility and adherence for scientific transparency, reproducibility and rigour.

Aims: To study the clinicopathological, immunohistochemical and molecular features of carcinoma arising in microglandular adenosis (MGACA) of the breast.

Methods: Clinicopathological features of 13 cases of MGACA were analysed. All tumours were molecular subtype by immunohistochemistry (IHC) of AR, CD8, FOXC1 and DCLK1 expression. Next-generation sequencing including 511 genes was analysed.

Results: All tumours showed a histological spectrum ranging from microglandular adenosis (MGA) to atypical MGA (AMGA), ductal carcinoma in situ (DCIS) and MGACA. Invasive components in 10 of 13 tumours were invasive carcinoma of no special type (NST), 3 were metaplastic carcinoma with mesenchymal differentiation (including two cases of matrix-producing carcinoma) mixed with NST. All lesion-associated epithelial cells were triple negative (TNBC) and positive for S-100. Reticulin staining showed the presence of basement membrane in MGA, AMGA and DCIS, and its absence in invasive carcinoma. According to IHC-based TNBC molecular subtyping, 10 tumours were basal-like immune-suppressed (BLIS), 2 were luminal androgen receptor and 1 was immunomodulatory. 10 patients had gene mutations. Pathogenic germline mutations of the BRCA1 and BRCA2 genes were detected in four tumours (30.7%) and one tumour (7.7%). Somatic mutation rate of the TP53 gene was 69.2%. Amplification rates of MYC, FGFR2, JAK2 and MCL1 genes in our cohort were 46.2%, 15.4%, 15.4% and 7.7%, respectively.

Conclusion: MGACA is a rare breast carcinoma, with distinct morphological, immunohistochemical and molecular features. Most MGACA were BLIS molecular subtype of TNBC. TP53 and BRCA1 gene mutation and MYC gene amplification were the most common genetic changes in MGACA.

Aims: Whole-genome sequencing (WGS) is beginning to be applied to cancer samples in the clinical setting. This ideally requires high-quality, minimally degraded DNA of high tumour cell content, while retaining sufficient tissue with excellent morphology for histopathological diagnosis and immunohistochemistry. The aim of this study was to investigate alternative ways of handling cancer samples to fulfil both diagnostic and molecular requirements.

Methods: Ex vivo biopsies were taken to investigate the feasibility of using cancer cells 'shaken' from the surface of a biopsy for WGS, while maintaining the tissue biopsy for histological diagnosis. WGS from the shaken cells was compared with the gold standard of a fresh-frozen (FF) biopsy. The procedure was piloted in the real-world setting for breast cancer samples.

Results: Cells shaken from ex vivo biopsies can yield DNA of sufficient quantity and quality for WGS, while having no discernible impact on quality of tissue morphology. WGS data showed good coverage, comparable variant calls and generally higher tumour content in shaken cell samples compared with the control FF samples. For real-world biopsies, DNA yields were lower, but WGS data were of excellent quality for the cases analysed.

Conclusions: Shaken biopsy sampling allows genomic sequencing from patients with cancer who may otherwise not receive a genome sequence due to limited sample availability. It represents a way of overcoming the logistics of obtaining and storing FF tissue making it a suitable technique for wider scale implementation in the clinical setting.