Journal of Clinical Pathology最新文献

Aim: Pancreatic cyst fluid carcinoembryonic antigen (CEA) is a pivotal test in the diagnosis and management of neoplastic mucinous cysts (NMC) of the pancreas. Cyst fluid CEA levels of 192 ng/mL have been widely used to identify NMC. However, CEA values are unique to and significantly differ between individual assays with various optimal cutoffs reported in the literature for NMC. Here, we investigate the optimal CEA cut-off value of pancreatic cysts from two different assays to identify differences in thresholds.

Methods: Pancreatic cyst fluid CEA levels, CEA assay platform (Beckman Dxl (BD) or Siemens Centaur XP (SC)), and clinical/pathological information were retrospectively collected. Cases were categorised into either NMC or non-NMC. Optimal CEA cut-off values were calculated via a receiver operator characteristic curve. Cut-off values were then identified separately by assay platform.

Results: In total, 149 pancreatic cystic lesions with concurrent CEA values (SC: n=47; BD: n=102) were included. Histological correlation was available for 26 (17%) samples. The optimal CEA cut-off value for all samples at the study institution was 45.9 ng/mL (area under the curve (AUC)=86, Sn=85.7%, Sp=73.8%). When analysed separately by CEA assay, the cut-off values were 45.9 ng/mL (AUC=84.27, Sn=89.7%, Sp=71.4%) for BD and 24.4 ng/mL (AUC=77, Sn=81.8%, Sp=75%) for SC (p=0.48).

Conclusions: This study showed an optimal pancreas cyst CEA cut-off threshold of 45.9 ng/mL, which is lower than commonly cited literature with different cutoffs on the two separate platforms (BD: 45.9 ng/mL, SC: 24.4 ng/mL).

Aims: Metastatic HER2-low breast cancer (HLBC) can be treated by trastuzumab deruxtecan. Assessment of low levels of HER2 protein expression suffers from poor interobserver reproducibility. The aim of the study was to evaluate the interobserver agreement among subspecialised breast pathologists and develop a practical algorithm for assessing HLBC.

Methods: Six breast pathologists (4 juniors, 2 seniors) evaluated 106 HER2 immunostained slides with 0/1+expression. Two rounds (R1, R2) of ring study were performed before and after training with a modified Ki-67 algorithm, and concordance was assessed.

Results: Agreement with 5% increments increased from substantial to almost perfect (R1: 0.796, R2: 0.804), and remained substantial for three categories (<1% vs 1%-10% vs >10%) (R1: 0.768, R2: 0.764). Seniors and juniors had almost perfect agreement with 5% increments (R1: 0.859 and 0.821, R2: 0.872 and 0.813). For the three categories, agreement remained almost perfect among seniors (R1: 0.837, R2: 0.860) and substantial among juniors (R1: 0.792, R2: 0.768). Binary analysis showed suboptimal agreement, decreasing for both juniors and seniors from substantial (R1: 0.650 and 0.620) to moderate (R2: 0.560 and 0.554) using the 1% cut-off, and increasing from moderate to substantial (R1: 0.478, R2: 0.712) among seniors but remaining moderate (R1: 0.576, R2: 0.465) among juniors using the 10% cut-off. The average scoring time per case was higher (72 vs 92 s).

Conclusions: Subspecialised breast pathologists have suboptimal agreement for immunohistochemical evaluation of HLBC using the modified Ki-67 methodology. An urgent need remains for a new assay/algorithm to reliably evaluate HLBC.

Assessing a locally excised colorectal adenoma for malignancy is a common but often challenging scenario. This article outlines a simple, stepwise approach to this diagnostic assessment. The first steps are to assess for high-grade dysplasia and, if present, to determine whether any neoplastic glands lie within the submucosa. If so, a distinction must then be made between epithelial misplacement and adenocarcinoma; this process is aided by certain clinical and endoscopic data together with assessment of six key histological features. If adenocarcinoma is diagnosed, a final step is to report the presence/absence of high-risk features of polyp cancers because this will then determine if further surgical resection is required for that malignancy. Caveats, uncertainties and newly introduced concepts exist at several steps of the assessment pathway presented and are therefore discussed in detail throughout the article.

Aims: Current understanding of oral squamous cell carcinoma (OSCC) is incomplete with regard to prognostic factors that lead to the considerable heterogeneity in treatment response and patient outcomes. We aimed to evaluate the impact of individual tumour-infiltrating lymphocyte (TIL) subsets on prognosis as a possible rationale for this, in a retrospective observational study.

Methods: Immunohistochemistry was performed to quantitatively assess cell densities of CD3+, CD20+, CD4+, CD8+ and FOXP3+TIL subsets in 50 surgically treated OSCC cases. Results were correlated with disease-free survival (DFS) and overall survival (OS). Receiver operating characteristic curve analysis and Youden index were applied to determine prognostically significant cut-off values.

Results: Mean counts for CD3+, CD4+, CD8+, CD20+ and FOXP3+TILs were 243, 52, 132, 53 and 116 cells per high power field, respectively. High CD8+ and low FOXP3+TIL counts, and high ratio of CD8:FOXP3 were significantly associated with longer DFS and OS, as well as with improved tumour-host interface parameters.

Conclusions: Host immune response and its interaction with cancer cells have a significant impact on OSCC outcomes, with some TIL subsets being more clinically relevant than others. High cytotoxic T-cell (CD8) and low Treg (FOXP3) counts, and high cytotoxic T-cell to Treg (CD8:FOXP3) ratio are significantly associated with favourable prognosis. These results may serve as a leading point in identifying novel therapeutic agents that can redesign the tumour immune microenvironment by reducing infiltrating FOXP3-lymphocytes, and modifying their signalling pathways.

Rosai-Dorfman disease (RDD) is a non-Langerhans cell histiocytosis which usually presents as painless lymphadenopathy. Extranodal involvement is known to occur in various organs, and less than ten cases with primary pancreatic involvement have been reported previously. This case report details the clinical course of an elderly female, presenting with upper abdominal discomfort and imaging suggestive of malignancy. Multiple non-diagnostic fine-needle aspirations were followed by surgical intervention. Histopathological evaluation revealed a pancreatic mass with characteristic features of RDD. The large hallmark RDD histiocytes showed pale, watery-clear cytoplasm, central round nucleus, and prominent nucleolus, with and without lymphocyte emperipolesis. The RDD histiocytes showed positive immunostaining for CD68, CD163, S100 (nuclear and cytoplasmic), OCT-2, Cyclin D1 and are negative for CD1a, Factor XIIIa, fascin and langerin. This case underscores the importance of considering RDD in the differential diagnosis of pancreatic masses alongwith comprehensive evaluation, multidisciplinary approach and pancreatic core needle biopsy evaluation.

Aims: Interobserver variability in the assessment of gastric neoplasia biopsies between most Western and Eastern (predominantly represented by Japanese in the literature) pathologists has been documented. It is unknown if such variability exists between the US and Korean pathologists in the current era.

Methods: Ten gastrointestinal (GI) pathologists from the USA (n=5) and South Korea (n=5) evaluated 100 scanned images of gastric (n=50) and colorectal (n=50) neoplasia biopsies and answered multiple questionnaires. Consensus was defined as the answer chosen by the majority. Cohen's (κc) and Fleiss' kappa (κf) values were calculated between the consensus of the two groups and among the raters, respectively.

Results: Both groups reached a consensus in the majority of cases (74%-100%) with slight to perfect intergroup (κc=0.049-1.000) and no to substantial intragroup (κf=-0.083 to 0.660) agreements. For gastric neoplasia, Korean pathologists relied heavily on cytoarchitectural atypia, whereas the US pathologists focused on stromal invasion when diagnosing adenocarcinoma. For colorectal neoplasia, the Korean pathologists identified concurrent intramucosal carcinoma when diagnosing invasive adenocarcinoma, while the presence of desmoplasia was a prerequisite for the diagnosis of invasive adenocarcinoma for the US pathologists.

Conclusions: For GI neoplasia biopsy interpretation, the diagnostic approach of Korean pathologists is similar to that of Eastern/Japanese pathologists. Consensus outperformed kappa statistics in capturing the magnitude of inter-rater and intergroup reliability, highlighting the potential benefit of consensus meetings to decrease the gap between Western and Eastern diagnostic approaches.

Aims: This study aims to summarise published cases of reactive plasmacytosis to provide a resource to aid haematopathologists and clinicians in the diagnostic workup of reactive plasmacytosis.

Methods: We searched published articles on reactive plasmacytosis on PubMed, Scopus and Google Scholar. Data were screened following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Cases were classified into six categories, namely: (1) infection, (2) angioimmunoblastic T-cell lymphoma (AITL), (3) other malignancies, (4) drug associated, (5) autoimmune diseases and (6) others. Plasma cell percentage in peripheral blood and/or bone marrow was tabulated. Descriptive statistics were reported as median with IQR, using JASP Team.

Results: 87 articles which reported on 146 patients were included. Infectious diseases represented most cases associated with reactive plasmacytosis (n=46, 31% of all cases), with viral infections being the most frequent (n=31, 21% of all cases). AITL was the second most frequent aetiology (n=34, 23% of all cases), followed by medications (n=28, 19% of all cases), other malignancies (n=18, 12% of all cases), miscellaneous aetiologies (n=11, 7% of all cases) and autoimmune diseases (n=9, 6% of all cases). The absolute and relative levels of plasma cells in each diagnostic category showed marked variation and ranges largely overlapped between categories.

Conclusions: In patients with an increase in the number and/or proportion of plasma cells in peripheral blood and/or bone marrow, clinical context and a broad differential diagnosis are necessary to direct further evaluation and arrive at a correct diagnosis. Our literature review suggests that evaluation for infectious causes and AITL may be of the greatest yield in many cases.

Aims: Epidermal growth factor receptor (EGFR) belongs to the receptor tyrosine kinases family and overexpression of EGFR has been linked to poor prognosis and cancer progression. Somatostatin receptor 2 (SSTR2) is a G-protein-coupled receptor (GPCR) with diverse biological functions in humans, and it is upregulated through the NF-KB signalling pathway in nasopharyngeal carcinomas (NPC). However, no studies have examined the EGFR and SSTR2 in NPC. This study aimed to investigate whether SSTR2 is associated with EGFR and clinicopathological features in NPC.

Methods: Bioinformatics analysis was performed to assess the correlation between EGFR and SSTR2 based on the GEO database. The expression of SSTR2 and EGFR was evaluated by immunohistochemistry (IHC) in 491 cases of NPC and 50 cases of non-cancerous nasopharyngeal epithelium.

Results: The bioinformatics analysis and IHC showed a positive correlation between SSTR2 and EGFR in NPC. High expression of SSTR2 and EGFR was significantly increased in NPC patients compared with non-cancerous nasopharyngeal epithelium. High expression of SSTR2 and/or EGFR was associated with a worse outcome and a higher risk of progression. The study found that patients receiving chemoradiotherapy (CR) with high expression of SSTR2, high expression of EGFR, and high coexpression of SSTR2 and EGFR had a poorer prognosis in both progression-free survival (PFS) and overall survival (OS). Interestingly, NPC patients with high expression of SSTR2, high expression of EGFR, high coexpression of EGFR and SSTR2, and EGFR/SSTR2 anyone high expression had a better prognosis with CR combined with targeted therapy. Cox multivariate analysis identified SSTR2 and EGFR as independent poor predictors of PFS.

Conclusion: Our study is the first to shed light on the intricate relationship between SSTR2 and EGFR in NPC and provides new insights into the potential benefits of EGFR targeted therapy for patients with high SSTR2 expression. Additionally, SSTR2 has potential as a new biomarker for poor prognosis in NPC patients.