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Context.--In 2018 the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee designed and implemented a new plasma cell neoplasia flow cytometry proficiency testing program--PCNEO--to allow clinical flow cytometry laboratories to monitor and assess their performance compared with a peer group. Objective.--To report the results from the first 4 years of the PCNEO program. Design.--Program participants were sent 2 sets of challenges per year, each including 1 wet challenge and 2 dry challenges, with associated clinical and laboratory findings. The wet challenges were composed of myeloma cell line specimens (with or without dilution in preserved whole blood) for flow cytometric analysis. The dry (paper) challenges were composed of clinical case summaries and images of flow cytometric test results from various flow cytometry laboratories of committee members. Results.--A total of 116 to 145 laboratories from 17 countries enrolled in the proficiency testing program. For the wet challenges, almost all participants (97%--100%; cumulative, 98.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of undiluted myeloma cell lines. Slightly fewer participants (89.0%--97.4%; cumulative, 95.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of diluted myeloma cell lines (10% or 50% dilutions into peripheral blood) intended to better represent a typical clinical sample. There was generally agreement among 80% or more of participants for positive or negative staining for CD38, CD138, CD19, CD20, and surface and cytoplasmic K and λ light chains. Similarly, 84% to 100% of participants were able to correctly identify the presence of neoplastic plasma cell populations in paper challenges, including the presence of small, neoplastic plasma cell populations (0.01%--5.0% clonal plasma cells) and the presence of nonneoplastic plasma cell populations (correctly identified by 91%--96% of participants). Conclusions.--Participant performance in the new proficiency testing program was excellent overall, with the vast majority of participants able to perform flow cytometric analysis and identify neoplastic plasma cell populations and to identify small plasma cell clones or expanded populations of reactive plasma cells in dry challenge flow cytometry results. This program will allow laboratories to verify the accuracy of their testing program and test interpretations for the assessment of patients suspected of having a plasma cell neoplasm. [ABSTRACT FROM AUTHOR]

The article comments on a paper by B. Magnani and C. R. Taylor on the regulation of immunohistochemistry (IHC) as an assay. Topics mentioned include the challenges for achieving accuracy and precision with IHC, the impact of signal detection on how IHC and immunoassay should be regulated by government agencies in the U.S., the need to incorporate clinical immunoassay concepts into the IHC laboratory, and some developments in the staining/technical aspects of IHC.

* Context.--Coronavirus disease 2019 (COVID-19) rapid antigen tests generate intrinsically fast, inherently spatial, and immediately actionable results. They quickly confirm COVID-19, but weakly rule out infection. Test performance depends on prevalence and testing protocol. Both affect predictive values. Objectives.--To use original mathematics and visual logistics for interpreting COVID-19 rapid antigen test performance patterns, gauge the influence of prevalence, and evaluate repeated testing. Design.--Mathematica and open access software helped graph relationships, perform recursive computations, and compare performance patterns. PubMed retrieved articles addressing endemic COVID-19 were reviewed. Results.--Tiered sensitivity/specificity comprise the following: T1 (90%/95%), T2 (95%/97.5%), and T3 (100%/ >99%). Performance of self-tests and home antigen tests with US Food and Drug Administration Emergency Use Authorization peaks in low prevalence. Fall-off in performance appears with increasing prevalence because sub-optimal sensitivity creates false negatives. The rate of false omissions limits clinical use because of prevalence boundaries based on tolerance for risk. Mathematical analysis supports testing twice to improve predictive values and extend prevalence boundaries nearly to levels of herd immunity. Conclusions.--COVID-19 is quickly becoming endemic. Suboptimal sensitivity of rapid antigen tests limits performance in high prevalence. Risk of contagion in packed spaces (eg, airplanes) might be avoided with dual testing 36 hours apart, allowing time for viral load to increase. Awareness of community prevalence and proof of improved performance with repeated testing will help manage COVID-19 risk, while meeting rapid decision-making needs for highly contagious and new variants (eg, Delta). New COVID-19 variants call for high-quality, low cost, readily accessible, fast, user friendly, and ubiquitous point-of-care testing., GOALS The goals of this research are to apply mathematical relationships and visual logistics to reveal patterns of coronavirus disease 19 (COVID-19) rapid antigen test (RAgT) performance and to facilitate [...]

Context.--Although most primary cancers of the lung carry a heavy mutational load and will potentially present many 'nonself' antigens to the immune system, there are a wide range of possible mechanisms for tumors to avoid so-called immune surveillance. One such mechanism is the adoption of immune checkpoints to inhibit the host immune response. Immune checkpoint inhibitors show great promise in the treatment of advanced non-small cell lung cancer. Objective.--To discuss the possibility of biomarker selection of patients for these therapies. This is becoming a much debated issue, and the immunohistochemical detection of Programmed Death Ligand 1 (PD-L1), the ligand for the inhibitory Programmed Death receptor 1 (PD-1) checkpoint, is one possible biomarker. Data so far available show some conflicting results, but PD-L1 immunohistochemistry looks likely to be introduced into clinical use for selecting patients for treatment with anti-PD-1 or anti-PD-Ll therapies. Given that there are 4 such drugs rapidly approaching regulatory approval, each with its own independent PD-L1 immunohistochemistry biomarker test, both oncologists and pathologists face some significant challenges. Data Sources.--Peer-reviewed literature and meeting proceedings, especially during the last 12 months, were used. Conclusions.--The biology of PD-1/PD-L1 is complex, the clinical data for these drugs show considerable variation, the selection performance of the PD-L1 biomarker test is not perfect, and the existence of 4 drug/test combinations adds significantly to the problems faced. This article addresses some of the background to this therapeutic problem and discusses some of the issues ahead. (Arch Pathol Lab Med. 2016; 140:249-254; doi: 10.5858/arpa.2015-0303-SA), Traditionally the treatment of advanced non-small cell lung cancer (NSCLC) was limited to radiotherapy, chemotherapy, or a combination of both, depending on tumor stage and patient fitness. (1,2) In recent [...]