Pathology
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly increased demand on laboratory throughput and reagents for nucleic acid extraction and polymerase chain reaction (PCR). Reagent shortages may limit the expansion of testing required to scale back containment measures. The aims of this study were to investigate the viability of sample pooling as a strategy for increasing test throughput and conserving PCR reagents; and to report our early experience with pooling of clinical samples. ⋯ Increased workflow complexity imparts a higher risk of errors, and requires risk mitigation strategies. Turnaround time for individual samples increased, hence urgent samples should not be pooled. Pooling is a viable strategy for high-throughput testing of SARS-CoV-2 in low-prevalence settings.
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Intratumoural heterogeneity of pulmonary adenocarcinoma challenges the accurate interpretation of programmed death ligand 1 (PD-L1) immunohistochemistry, which is the only validated predictive marker for successful anti-PD-1/PD-L1 immunotherapy. The aim of this study was to determine whether PD-L1 expression is related to adenocarcinoma histological differentiation in a retrospective analysis of tumour biopsies with intratumoural histological heterogeneity. Adenocarcinomas with high intratumoural heterogeneity were categorised as 'mixed adenocarcinomas'. ⋯ In conclusion, PD-L1 expression is associated with poorly differentiated morphology in adenocarcinomas with intratumoural histological heterogeneity. Consequently, a TPS approach may not account for the contribution of more aggressive tumour components with higher levels of PD-L1 expression in within the tumour. Performing spectral analyses of PD-L1 expression across tumours is likely to be more accurate.
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Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, representing approximately one-third of all cases worldwide. In the World Health Organization (WHO) classification of lymphomas, most cases of DLBCL are designated as not otherwise specified (NOS). About 20% of cases, however, are designated as specific variants of DLBCL. ⋯ Two additional variants recognised in the WHO classification, EBV-positive diffuse large B-cell lymphoma and EBV-positive mucocutaneous ulcer are discussed elsewhere in another review within this issue of Pathology. Although not recognised as a specific variant in the current WHO classification, primary testicular diffuse large B-cell lymphoma also has unique biological features and requires some modification of the standard treatment approach for patients with DLBCL. Therefore, we suggest that primary testicular diffuse large B-cell lymphoma also should be recognised as a specific variant of DLBCL in a future version of the WHO classification.
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We and others have previously highlighted the potential problems with testing of lupus anticoagulants (LA) in patients on anticoagulant therapy, including most recently as related to the direct oral anticoagulants (DOACs). Thus, current DOACs in use (e.g., dabigatran, a direct thrombin inhibitor, and apixaban and rivaroxaban, both direct Xa inhibitors), affect a wide variety of coagulation assays, including those used in LA investigation. The Russell viper venom time (RVVT) assay in particular, key to the investigation of LA, is highly sensitive to DOACs. ⋯ LA testing in the presence of DOACs also led to lower intra-patient consistency in LA test results. We conclude that ex-vivo data appears to confirm the potential for false positive (with rivaroxaban) and potential for false negative (with apixaban) identification of LA in patients on DOAC treatment. We also make some recommendations in regards to such testing.