CONTEXT.—: Smart glasses are a wearable technology that enable hands-free data acquisition and entry. OBJECTIVE.—: To develop a surgical pathology grossing application on a smart glass platform. DESIGN.—: An existing logistics software for the Google Glass Enterprise smart glass platform was used to create surgical pathology grossing protocols. The 2 grossing protocols were developed to simulate grossing a complex (heart) and a simple (kidney) specimen. For both protocols, users were visually prompted by the smart glass device to perform each task, record measurements, or document the field of view. In addition to measuring the total time of the protocol performance, each substep within the protocol was automatically recorded. Subsequently, a report was generated that contained the dictation, images, voice recordings, and the timing of each step. The application was tested by 3 users using the 2 grossing protocols. The users were tracked across 3 grossing procedures for each protocol. RESULTS.—: For the complex specimen grossing the average time across repeated procedures was not significantly different between users (P > .99). However, when grossing times of the complex specimen were compared for repeated performances of the same user, a significant reduction in grossing times was observed with each repetition (P = .002). For the simple specimen, the average grossing time across multiple attempts was different among users (P = .03); however, no improvement in grossing time was observed with repeated performance (P = .499). CONCLUSIONS.—: Augmented reality based grossing applications can provide automated data collection to track the changes in grossing performance over time.

CONTEXT.—: Autopsy pathologists, including medical examiners, provide valuable public health support for infectious disease deaths through surveillance for deaths of public health concern including emerging infections, identifying causative organisms for unexplained deaths, and providing insights into the pathology and pathogenesis of novel or unusual infections. However, autopsy poses biosafety risks to workers within and outside the laboratory. The highest rates of laboratory-acquired infections occur in autopsy workers. OBJECTIVE.—: To design and construct an appropriately biosafe autopsy laboratory. DESIGN.—: We conducted a biosafety risk assessment for autopsy workers using the process developed by the US Centers for Disease Control and Prevention and National Institutes of Health and applied these findings as the basis of laboratory design and construction. RESULTS.—: Autopsy workers are unpredictably exposed to a variety of infectious organisms, including hepatitis C virus, HIV, and Mycobacterium tuberculosis. Hazardous autopsy procedures include using and encountering sharp objects and the generation of aerosols from dissection, fluid aspiration, rinsing tissues, and dividing bone with an oscillating saw. CONCLUSIONS.—: Exposure to blood-borne and airborne pathogens from procedures that can cause cutaneous inoculation and inhalation of aerosols indicates that human autopsies should be performed at biosafety level 3. We designed a large, entirely biosafety level 3 medical examiner autopsy laboratory using design principles and characteristics that can be scaled to accommodate smaller academic or other hospital-based autopsy spaces. Containment was achieved through a concentric ring design, with access control at interface zones. As new autopsy laboratories are planned, we strongly recommend that they be designed to function uniformly at biosafety level 3.

The rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has propelled the rapid development of serologic tests that can detect anti-SARS-CoV-2 antibodies. These have been used for studying the prevalence and spread of infection in different populations, and helping establish a recent diagnosis of coronavirus disease 2019 (COVID-19), and will likely be used to confirm humoral immunity after infection or vaccination. However, nearly all lab-based high-throughput SARS-CoV-2 serologic assays require a serum sample from venous blood draw, limiting their applications and scalability. Here, we present a method that enables large-scale SARS-CoV-2 serologic studies by combining self or office collection of fingerprick blood with a volumetric absorptive microsampling device (Mitra, Neoteryx LLC) with a high-throughput electrochemiluminescence-based SARS-CoV-2 total antibody assay (Roche Elecsys, Roche Diagnostics Inc) that is emergency use authorization approved for use on serum samples and widely used by clinical laboratories around the world. We found that the Roche Elecsys assay has a high dynamic range that allows for accurate detection of SARS-CoV-2 antibodies in serum samples diluted 1:20 as well as contrived dried blood extracts. Extracts of dried blood from Mitra devices acquired in a community seroprevalence study showed near identical sensitivity and specificity in detection of SARS-CoV-2 antibodies compared with neat sera using predefined thresholds for each specimen type. Overall, this study affirms the use of Mitra dried blood collection device with the Roche Elecsys SARS-CoV-2 total antibody assay for remote or at-home testing as well as large-scale community seroprevalence studies.

Erratum in Arch Pathol Lab Med. 2021 Aug 1;145(8):918.

Comment in Arch Pathol Lab Med. 2021 Apr 1;145(4):391b-391.

CONTEXT.—: The coronavirus disease 2019 pandemic, caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2, has resulted in worldwide disruption to the delivery of patient care. The Seattle, Washington metropolitan area was one of the first in the United States affected by the pandemic. As a result, the anatomic pathology services at the University of Washington experienced significant changes in operational volumes early in the pandemic. OBJECTIVE.—: To assess the impact of coronavirus disease 2019 and both state and institutional policies implemented to mitigate viral transmission (including institutional policies on nonurgent procedures) on anatomic pathology volumes. DESIGN.—: Accessioned specimens from January to June 2020 were evaluated as coronavirus disease 2019 and institutional policies changed. The data were considered in these contexts: subspecialty, billable Current Procedural Terminology codes, and intraoperative consultation. Comparable data were retrieved from 2019 as a historical control. RESULTS.—: There was a significant reduction in overall accessioned volume (up to 79%) from prepandemic levels during bans on nonurgent procedures when compared with 2020 pre-coronavirus disease 2019 volumes and historical controls. The gastrointestinal and dermatopathology services were most impacted, and breast and combined head and neck/pulmonary services were least impacted. Current Procedural Terminology code 88305, for smaller/biopsy specimens, had a 63% reduction during nonurgent procedure bans. After all bans on procedures were lifted, the overall volume plateaued at 89% of prepandemic levels. CONCLUSIONS.—: A significant decrease in specimen volume was most strongly associated with bans on nonurgent procedures. Although all departmental areas had a decrease in volume, the extent of change varied across subspecialty and specimen types. Even with removal of all bans, service volume did not reach prepandemic levels.

CONTEXT.—: Autism spectrum disorder is a neurodevelopmental condition that affects over 1% of the population worldwide. Developing effective preventions and treatments for autism will depend on understanding the neuropathology of the disorder. While evidence from magnetic resonance imaging indicates altered development of the autistic brain, it lacks the resolution needed to identify the cellular and molecular underpinnings of the disorder. Postmortem studies of human brain tissue currently represent the only viable option to pursuing these critical studies. Historically, the availability of autism brain tissue has been extremely limited. OBJECTIVE.—: To overcome this limitation, Autism BrainNet, funded by the Simons Foundation, was formed as a network of brain collection sites that work in a coordinated fashion to develop a library of human postmortem brain tissues for distribution to researchers worldwide. Autism BrainNet has collection sites (or Nodes) in California, Texas, and Massachusetts; affiliated, international Nodes are located in Oxford, England and Montreal, Quebec, Canada. DATA SOURCES.—: Pubmed, Autism BrainNet. CONCLUSIONS.—: Because the death of autistic individuals is often because of an accident, drowning, suicide, or sudden unexpected death in epilepsy, they often are seen in a medical examiner's or coroner's office. Yet, autism is rarely considered when evaluating the cause of death. Advances in our understanding of chronic traumatic encephalopathy have occurred because medical examiners and neuropathologists questioned whether a pathologic change might exist in individuals who played contact sports and later developed severe behavioral problems. This article highlights the potential for equally significant breakthroughs in autism arising from the proactive efforts of medical examiners, pathologists, and coroners in partnership with Autism BrainNet.

CONTEXT.—: Fetal growth restriction is a risk factor for intrauterine fetal death. Currently, definitions of fetal growth restriction in stillborns are heterogeneous. OBJECTIVES.—: To develop a consensus definition for fetal growth restriction retrospectively diagnosed at fetal autopsy in intrauterine fetal death. DESIGN.—: A modified online Delphi survey in an international panel of experts in perinatal pathology, with feedback at group level and exclusion of nonresponders. The survey scoped all possible variables with an open question. Variables suggested by 2 or more experts were scored on a 5-point Likert scale. In subsequent rounds, inclusion of variables and thresholds were determined with a 70% level of agreement. In the final rounds, participants selected the consensus algorithm. RESULTS.—: Fifty-two experts participated in the first round; 88% (46 of 52) completed all rounds. The consensus definition included antenatal clinical diagnosis of fetal growth restriction OR a birth weight lower than third percentile OR at least 5 of 10 contributory variables (risk factors in the clinical antenatal history: birth weight lower than 10th percentile, body weight at time of autopsy lower than 10th percentile, brain weight lower than 10th percentile, foot length lower than 10th percentile, liver weight lower than 10th percentile, placental weight lower than 10th percentile, brain weight to liver weight ratio higher than 4, placental weight to birth weight ratio higher than 90th percentile, histologic or gross features of placental insufficiency/malperfusion). There was no consensus on some aspects, including how to correct for interval between fetal death and delivery. CONCLUSIONS.—: A consensus-based definition of fetal growth restriction in fetal death was determined with utility to improve management and outcomes of subsequent pregnancies.

CONTEXT.—: There is a clear need to educate health professionals in genomic medicine. Pathologists, given their critical role in cancer diagnostics, must understand core concepts in genomic oncology. Although high-quality evaluation is a cornerstone of medical education, to our knowledge a rigorously validated genomic oncology assessment tool has not been published. OBJECTIVE.—: To develop and validate a genomic oncology exam. DESIGN.—: A previously developed exam was updated and validated using 3 approaches: pretesting/posttesting in relation to a live genomic pathology workshop; comparison of scores of individuals at a priori defined knowledge levels; and use of Rasch analysis. This last approach is used in high-stakes testing, such as licensing exams. The exam included both knowledge-based as well as skills-based questions related to the use of online genomics tools. RESULTS.—: There was a significant difference in exam scores preworkshop and postworkshop (37.5% to 75%; P < .001). Individuals at a priori defined beginner, intermediate, and expert levels scored 35%, 58%, and 89%, respectively (P < .001). Rasch analysis demonstrated excellent fit and reliability and led to further exam refinement with the removal of 2 questions deemed unnecessary for assessment. CONCLUSIONS.—: A rigorously validated exam has now been created to assess pathologist genomic oncology knowledge and skills. The exam can be used to assess both individual learners as well as educational interventions. The exam may also be applicable to other specialties involved in genomic-based cancer care.

CONTEXT.—: The identification of paraganglia (PG) in the gallbladder (GB) is infrequent, and easily overlooked as it is not something routinely reported. Occasionally they may be misinterpreted as neoplastic cells, such as low-grade carcinomas, germ cell tumors, or because of their close resemblance to neuroendocrine cells, as low-grade neuroendocrine neoplasms. OBJECTIVE.—: To evaluate the incidence and histological features of PG of the GB in patients that underwent cholecystectomy, and discuss the potential misinterpretation of these benign structures as clusters of neoplastic cells. DESIGN.—: A retrospective study of cholecystectomy specimens performed during a 6-month period were reviewed for identification of PG. Immunohistochemical studies for chromogranin, synaptophysin, S100, and cytokeratin AE1/AE3 were performed in selected cases. RESULTS.—: A total of 365 GBs were reviewed and in 16 cases (4.4%) PG was identified within the subserosal connective tissue of the GB wall or cystic duct adjacent to small capillaries, nerves, and ganglia. They consisted of well-demarcated, lobular structures ranging in size from 0.2 to 0.5 cm, which were predominantly composed of chief cells, with strong expression for chromogranin and synaptophysin and negative CKAE1/AE3, and a minor component of S100-positive sustentacular cells. CONCLUSIONS.—: PG is an uncommon finding with a prevalence of 4.4% in our study. Awareness of their location, histologic features, and immunohistochemical profile may help practicing pathologists to confirm their benign nature, avoid a misdiagnosis of malignancy, and prevent unnecessary diagnostic work-up and treatment.

CONTEXT.—: There is interest in using transbronchial cryobiopsies (CBs) for the diagnosis of fibrotic (chronic) hypersensitivity pneumonitis (FHP), but with little information in the literature about what features are diagnostic in CBs. OBJECTIVE.—: To determine, using in silico investigation, whether features supporting a diagnosis of FHP in video-assisted thoracoscopic (VATS) biopsies can be identified in CBs. DESIGN.—: In silico circular "cryobiopsies," 5.25 mm in diameter (21.6 mm2), were created on the slides of 15 VATS biopsy cases that had been assigned a 60% or greater confident diagnosis of FHP at a specially devised multidisciplinary discussion. Using stratified random sampling, up to 8 "cryobiopsies" per case were analyzed for the presence of giant cells/granulomas or peribronchiolar metaplasia affecting 50% or more of the bronchioles, features that had statistically supported a diagnosis of FHP on the VATS biopsies in the multidisciplinary discussion exercise. RESULTS.—: Giant cells/granulomas were detected with very low sensitivities in the "cryobiopsies." Using peribronchiolar metaplasia in 50% or more of bronchioles alone, the sensitivity/specificity for a diagnosis of FHP of 2 "cryobiopsies" compared to the corresponding VATS biopsy was 0.57/0.63; for 4 "cryobiopsies," 0.86/0.75; and for 8 "cryobiopsies," 0.83/0.71. Adding giant cells/granulomas slightly improved these numbers to 0.63/0.71 for 2 "cryobiopsies"; 1.00/0.86 for 4; and 1.00/0.80 for 8. CONCLUSIONS.—: In the setting of a multidisciplinary discussion where FHP is part of the differential diagnostic choices, 4 actual CBs with an area of roughly 20 mm2 each should have good sensitivity and reasonable specificity for diagnosing FHP using these specific morphologic criteria.

CONTEXT.—: Treatment of chronic viral hepatitis C (HCV) infection with direct-acting antiviral agents (DAAs) results in cure, or sustained viral response (SVR), in more than 90% of patients. However, there are subsets of patients who have persistent liver inflammation and fibrosis and develop hepatocellular carcinoma (HCC) despite achieving SVR. A possible reason for these phenomena may be the presence of virus particles in liver tissue but not blood, otherwise defined as occult infection. OBJECTIVE.—: To describe liver histologic findings following successful DAA therapy, test HCV RNA by (liver) tissue polymerase chain reaction in treated cases, and identify predictive markers for HCC development in treated cases. DESIGN.—: A total of 96 identified patients were divided into 4 groups, each differentiated by the presence or absence of SVR and HCC. Groups were compared for several clinicopathologic variables, including degree of inflammation and fibrosis, and the 'directionality' of fibrosis in cirrhotic livers using the novel progressive-indeterminate-regressive scoring system. RESULTS.—: Overall, we found a significant decrease in inflammation in SVR patients. None of the patients showed regression of their cirrhosis following treatment. No evidence of occult HCV infection was seen in 40 livers tested, including 21 with HCC. The number of patients who developed HCC was similar in the SVR and non-SVR groups, and increased inflammation and fibrosis were associated with HCC development. CONCLUSIONS.—: Following DAA-SVR there appears to be an overall decrease in inflammation, but the fibrosis tends to persist, at least in the short term (median follow-up of 20.2 months).

CONTEXT.—: Controversies and uncertainty persist in prostate cancer grading. OBJECTIVE.—: To update grading recommendations. DATA SOURCES.—: Critical review of the literature along with pathology and clinician surveys. CONCLUSIONS.—: Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern" in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5)," and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)" is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.