Journal of Clinical Pathology最新文献

Aim: We assessed the feasibility of storing sera in primary gel separator tube over medium-term for retrospective serological tests to facilitate investigation of intra-uterine infection.

Method: 120 residual serum samples, consisting of 30 positive samples each for rubella, cytomegalovirus, parvovirus B19 and varicella zoster IgG were aliquoted into secondary propylene tubes and stored together with the original primary tubes at -20°C for 1 year. The serum was subsequently retested to compare results from both storage methods.

Results: Haemolysis was observed in 49.2% of serum stored in the primary tubes. However, there was no difference in both the qualitative and quantitative results after storage of serum samples in either receptacle.

Conclusion: Sera can be stored in primary blood tube for up to 1 year without affecting serological results. For laboratories with adequate freezer space to store samples in primary blood tubes, this would streamline workflow saving manpower and time, avoid mislabelling of aliquots, reduce consumable costs and prevent unnecessary biohazard exposures.

Aims: Secretory carcinoma of breast (SCB) typically harbours ETV6-NTRK3 gene fusion. Pan-Trk immunohistochemistry analysis (IHC) has been shown to be sensitive for SCB diagnosis. However, weak focal pan-Trk nuclear staining was previously found in 10% of non-secretory breast carcinomas. To further examine pan-Trk IHC specificity, we evaluated pan-Trk staining in various breast carcinoma subtypes.

Methods: The study cohort consisted of 346 invasive breast carcinomas (IBCs), including 8 SCBs and 48 triple-negative histological mimickers (36 metaplastic carcinomas, including 12 matrix-producing carcinomas; 5 adenoid cystic carcinomas; 5 apocrine carcinomas; 2 acinic cell carcinomas), 101 triple-negative IBCs of no special type, 101 estrogen receptor (ER)-positive/HER2-negative IBCs and 88 HER2-positive IBCs. Six salivary gland secretory carcinomas were also included. Pan-Trk IHC was performed on tumours using a rabbit monoclonal pan-Trk antibody. Any nuclear staining in the invasive carcinoma cells was considered positive.

Results: All 14 secretory carcinomas from breast and salivary gland exhibited moderate to strong pan-Trk nuclear staining. In contrast, no pan-Trk nuclear staining was identified in any of the 338 non-secretory IBCs. Focal cytoplasmic pan-Trk staining was observed in nine non-secretory IBCs (2.7%), and was considered nonspecific and negative.

Conclusions: Our results indicate that pan-Trk nuclear staining is highly specific for SCB. In low-grade to intermediate-grade IBCs that share histological features with SCB, adding pan-Trk to a routing panel of estrogen receptor/progesterone receptor/HER2 is highly diagnostic. Our results also support using pan-Trk IHC to differentiate SCB from its triple-negative histological mimickers, such as adenoid cystic carcinoma, matrix-producing carcinoma, apocrine carcinoma and acinic cell carcinoma.

Aims: The international system for reporting serous fluid cytopathology (ISRSFC) set forth a five-tiered reporting system with comprehensive validation on pleural and peritoneal fluid cytology. An algorithmic approach for cytomorphological assessment and immunocytochemistry was also described in ISRSFC. Limited data on pericardial fluid are supportive but would benefit from further investigation.

Methods: Consecutive pericardial fluid cytology over a 4-year period was reviewed by multiple board-certified pathologists according to the ISRSFC. Cytomorphology and immunocytochemistry were assessed sequentially, with respective diagnostic performances computed and compared. Literature review was performed.

Results: In total 358 specimens, including 53 with immunocytochemistry available, were reviewed. There were 137 benign and 221 malignant (MAL) cases. The risks of malignancy were 23.5% non-diagnostic (ND), 29.2% negative for malignancy (NFM), 56.0% atypia of undetermined significance (AUS), 82.6% suspicious for malignancy (SFM) and 99.2% (MAL) for cytomorphological assessment, improving to 23.5% (ND), 29.1% (NFM), 56.8% (AUS), 78.9% (SFM) and 99.3% (MAL) incorporating immunocytochemistry. Ten cases (2.8%) received a change in diagnosis after review of immunocytochemistry. All revisions of diagnostic category were appropriate upgrades/downgrades referenced against clinical information. Cytomorphological typing was accurate for adenocarcinoma (n=81/83, 97.6%), while other carcinomas and lymphomas required immunocytochemistry. Certain subcategories within AUS and SFM pertaining to bland indeterminate epithelial cells or mucinous material were not seen for pericardial fluid.

Conclusions: The ISRSFC shows robust diagnostic performance for pericardial fluid cytology. For pericardial effusion, disease composition and applicable cytological subcategories differ from its peritoneal and pleural counterparts. Incorporating immunocytochemistry by an algorithmic approach improves diagnostic accuracy. Cytomorphology is accurate for identifying adenocarcinomas, but further typing necessitates immunocytochemistry is necessary.

Aims: To study programmed death ligand 1 (PD-L1) expression and tumour infiltrating lymphocytes (TILs) in patients with early-stage non-small cell lung carcinoma (NSCLC) with artificial intelligence (AI) algorithms.

Methods: The study included samples from 50 early-stage NSCLCs. PD-L1 immunohistochemistry (IHC) stained slides (clone SP263) were scored manually and with two different AI tools (PathAI and Navify Digital Pathology) by three pathologists. TILs were digitally assessed on H&E and CD8 IHC stained sections with two different algorithms (PathAI and Navify Digital Pathology, respectively). The agreement between observers and methods for each biomarker was analysed. For PD-L1, the turn-around time (TAT) for manual versus AI-assisted scoring was recorded.

Results: Agreement was higher in tumours with low PD-L1 expression regardless of the approach. Both AI-powered tools identified a significantly higher number of cases equal or above 1% PD-L1 tumour proportion score as compared with manual scoring (p=0.00015), a finding with potential therapeutic implications. Regarding TAT, there were significant differences between manual scoring and AI use (p value <0.0001 for all comparisons). The total TILs density with the PathAI algorithm and the total density of CD8+ cells with the Navify Digital Pathology software were significantly correlated (τ=0.49 (95% CI 0.37, 0.61), p value<0.0001).

Conclusions: This preliminary study supports the use of AI algorithms for the scoring of PD-L1 and TILs in patients with NSCLC.

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: The field of molecular pathology has undergone significant advancements in the clinical impact of sarcoma diagnosis, resulting in challenges to nosology of bone and soft tissue tumours. The surge in molecular data has led to the identification of novel fusions and description of new 'entities'. To illustrate this, we have selected five emerging entities with novel fusions: clear cell stromal tumour of the lung with YAP1::TFE3 fusion, GAB1::ABL1 fusion spindle cell neoplasm, NUTM1-rearranged sarcomas, NR1D1-rearranged sarcomas and calcified chondroid mesenchymal neoplasms.

Methods: Literature for the relevant case reports and case series of these five entities were reviewed and clinicopathological data was collected. Additionally, this review includes a table format of recently described fusion-associated mesenchymal neoplasms.

Results: The morphological and immunohistochemical features, along with diagnostic challenges, are discussed for each entity.

Conclusions: Here, we have provided a review of selected emerging mesenchymal neoplasms, which of these neoplasms will meet the threshold to be 'new entities' remains to be determined.

Aims: Structured reporting in pathology is not universally adopted and extracting elements essential to research often requires expensive and time-intensive manual curation. The accuracy and feasibility of using large language models (LLMs) to extract essential pathology elements, for cancer research is examined here.

Methods: Retrospective study of patients who underwent pathology sampling for suspected hepatocellular carcinoma and underwent Ytrrium-90 embolisation. Five pathology report elements of interest were included for evaluation. LLMs (Generative Pre-trained Transformer (GPT) 3.5 turbo and GPT-4) were used to extract elements of interest. For comparison, a rules-based, regular expressions (REGEX) approach was devised for extraction. Accuracy for each approach was calculated.

Results: 88 pathology reports were identified. LLMs and REGEX were both able to extract research elements with high accuracy (average 84.1%-94.8%).

Conclusions: LLMs have significant potential to simplify the extraction of research elements from pathology reporting, and therefore, accelerate the pace of cancer research.

Aims: Patients with haemochromatosis (HFE) are known to have an increased risk of developing hepatocellular carcinoma (HCC). Available data are conflicting on whether such patients have poorer prognosis, and there is lack of data regarding the biology of HFE-HCC. We compared the course of HFE-HCC with a matched non-HFE-HCC control group and examined tumour characteristics using immunohistochemistry.

Methods: In this tertiary care-based retrospective analysis, 12 patients with HFE and 34 patients with alcohol/non-alcoholic steatohepatitis who underwent initially successful curative HCC therapy with ablation or resection were identified from our registry. Time to tumour progression was compared. Resected liver tissue from a separate cohort of 11 matched patients with HFE-HCC and without HFE-HCC was assessed for the expression of progenitor and epithelial-mesenchymal transition markers using immunohistochemistry.

Results: The median follow-up was 24.39 and 24.28 months for patients with HFE-HCC and those without HFE-HCC, respectively (p>0.05). The mean time to progression was shorter in the HFE group compared with the non-HFE group (12.87 months vs 17.78 months; HR 3.322, p<0.05). Patients with HFE-HCC also progressed to more advanced disease by the end of follow-up (p<0.05). Immunohistochemical analysis of matched HFE-HCC and non-HFE-HCC explants demonstrated increased expression of the cancer stem cell markers EpCAM (epithelial cell adhesion molecule) and EpCAM/SALL4 (spalt-like transcription factor 4) coexpression in HFE-HCC specimens (p<0.05). There was a high frequency of combined tumour subtypes within the HFE cohort.

Conclusions: This study demonstrates that the clinical course of patients with HFE-HCC is more aggressive and provides the first data indicating that their tumours have increased expression of progenitor markers. These findings suggest patients with HFE-HCC may need to be considered for transplant at an earlier stage.

Aims: The reference method for low-density lipoprotein-cholesterol (LDL-C) is ultracentrifugation. However, this is unsuitable for routine use and therefore direct LDL-C assays and predictive equations are used. In this study, we compared the Friedewald, extended Martin/Hopkins, Sampson/NIH and four other equations to a direct assay.

Methods: We analysed 44 194 lipid profiles from a mixed South African population. The LDL-C predictive equations were compared with direct LDL-C assay and analysed using non-parametric statistics and error grid analysis.

Results: Both the extended Martin/Hopkins and Sampson/NIH equations displayed the best correlation with direct LDL-C in terms of desirable bias and total allowable error. The direct LDL-C assay classified 13.9% of patients in the low LDL-C (1.0-1.8 mmol/L) category, in comparison to the extended Martin/Hopkins equation (13.4%), the Sampson equation (14.6%) and the Friedewald equation (16.0%). The Sampson/NIH was least biased in the low LDL-C category (<1.8 mmol/L) and produced the least overall clinically relevant errors compared with the extended Martin/Hopkins and Friedewald equations in the low-LDL-C category.

Conclusions: Our findings suggest only a marginal difference between the extended Martin/Hopkins equation and the Sampson/NIH equation with the use of the Beckman Coulter DxC800 analyser in this population. The results favour the implementation of the Sampson/NIH equation when the Beckman Coulter DxC analyser is used, but the extended Martin/Hopkins may also be safely implemented. Both of these equations performed significantly better than the Friedewald equation. We recommend that patients be monitored using one of these methods and that each laboratory perform its own validation of either equation to ensure continuation and accuracy, and to prevent between-method variation.

Aims: Liposarcoma is a malignant soft tissue tumour with adipocytic differentiation. Dedifferentiated liposarcoma (DDLS) and myxoid liposarcoma (MLS) are classified as high-grade liposarcomas. Lipid droplet-associated protein (also known as perilipin 1 (PLIN1)) is the predominant perilipin and has utility as a specific marker of adipogenic differentiation. Adipose differentiation-related protein (also known as adipophilin (ADRP)) is ubiquitously expressed in a range of tissues. High ADRP expression is reportedly a poor prognostic factor in several cancer types. However, no previous studies have examined the association between PLIN1 or ADRP expression and prognosis in sarcoma. This study therefore aimed to evaluate the association between PLIN1 or ADRP expression and prognosis in liposarcoma.

Methods: In total, 97 primary resection specimens (53 MLS and 44 DDLS) were examined in this study. PLIN1 and ADRP expression was evaluated by immunohistochemistry. Survival analyses were performed for MLS and DDLS.

Results: Of the 53 MLS specimens, 15 (28.3%) exhibited high PLIN1 expression. PLIN1 expression was not observed in DDLS specimens. High PLIN1 expression was significantly associated with increased disease-free survival (DFS) among patients with MLS (p=0.045). Distinct ADRP expression was observed in 13 of 53 (24.5%) MLS specimens and 5 of 44 (11.4%) DDLS specimens. High ADRP expression was associated with shorter overall survival (OS) in MLS (p=0.042) and DFS and shorter OS in DDLS (p=0.024 and p<0.001, respectively).

Conclusions: PLIN1 and ADRP expression is associated with poor prognosis in high-grade liposarcoma.