The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 .1

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Background: The pathophysiology of lethal head trauma in infants and young children involves repetitive rotational forces of sufficient magnitude to produce subdural hemorrhage and brain swelling, which leads to considerable morbidity and mortality. The precise mechanism for brain swelling is unclear. Materials and Methods: We examined cerebral tissue from ten pediatric deaths due to blunt force trauma, along with seven control infants who asphyxiated in unsafe sleep environments. To assess the competence of the blood–brain barrier, we performed immunohistochemical stains for albumin and immunoglobulin G (IgG). Results: IgG and albumin were increased in subpial and superficial perivascular tissue in those cases due to blunt force trauma, and in particular, the blunt force trauma associated with subdural hematoma. This included two deaths at the scene without hospital survival time. Conclusions: Our findings suggest disruption of the blood–brain barrier with vasogenic edema as an early event in head trauma involving young children upstream of global ischemic brain injury. We hypothesize that mechanical injury to the cortical vasculature results in vasogenic edema by oncotic (increased plasma proteins in the cortical interstitium) and hydrostatic (increased capillary pressure) mechanisms, with subsequent cortical ischemia. This may explain why ischemic sequelae appear to occur in head trauma involving young children, regardless of whether anoxia, hypotension, or cardiac arrest complicate the disease course and may in part underlie the high morbidity and mortality of head trauma in early childhood.

Background Therapeutic monoclonal antibodies can be a source of assay interference in clinical serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE), producing monoclonal bands that can be misinterpreted as a monoclonal gammopathy related to a B-cell or plasma cell neoplasm. The extent to which new anti-COVID-19 monoclonal antibodies produce this interference is unknown. Methods Casirivimab plus imdevimab, sotrovimab, and bamlanivimab plus etesevimab were spiked into patient serum samples to evaluate for SPEP/IFE interference, to characterize the position of therapy-derived bands relative to a reference band (either combined beta band or beta 1 band, depending on instrument platform), and to confirm heavy and light chain utilization of each medication. Serum samples from patients who had recently received casirivimab plus imdevimab or sotrovimab were also evaluated for comparison. Results When spiked into serum samples, all tested anti-COVID-19 monoclonal antibodies generated interference in SPEP/IFE. Importantly, the patterns of interference differed between spiked serum samples and serum from patients who had recently received casirivimab plus imdevimab or sotrovimab. Conclusions Imdevimab can be added to the growing list of therapeutic monoclonal antibodies that produce sustained interference in SPEP/IFE. Although casirivimab and sotrovimab also produce assay interference in vitro, these antibodies are not reliably detected in serum from recently infused patients. The value of relative band position in recognizing bands that may represent therapeutic monoclonal antibodies is also emphasized. Clinicians and laboratorians should consider therapeutic monoclonal antibody interference in diagnostic SPEP/IFE and review a patient’s medication list when new or transient monoclonal bands are identified.