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* Context.--Diagnostic testing for SARS-CoV-2 in symptomatic and asymptomatic children remains integral to care, particularly for supporting return to and attendance in schools. The concordance of SARS-CoV-2 detection in children, using various specimen types, has not been widely studied. Objective.--To compare 3 sample types for SARS-CoV-2 polymerase chain reaction (PCR) testing in children, collected and tested at a single facility. Design.--We prospectively recruited 142 symptomatic and asymptomatic children/young adults into a sample comparison study performed in a single health care system. Each child provided self-collected saliva, and a trained health care provider collected a mid-turbinate nasal swab and nasopharyngeal (NP) swab. Specimens were assayed within 24 hours of collection by using reverse transcription-polymerase chain reaction (RT-PCR) to detect SARS-CoV-2 on a single testing platform. Results.--Concurrently collected saliva and mid-turbinate swabs had greater than 95% positive agreement with NP swabs when obtained within 10 days of symptom onset. Positive agreement of saliva and mid-turbinate samples collected from children with symptom onset >10 days prior, or without symptoms, was 82% compared to NP swab samples. Cycle threshold (Ct) values for mid-turbinate nasal samples more closely correlated with Ct values from NP samples than from saliva samples. Conclusions.--These findings suggest that all 3 sample types from children are useful for SARS-CoV-2 diagnostic testing by RT-PCR, and that concordance is greatest when the child has had symptoms of COVID-19 within the past 10 days. This study provides scientific justification for using sample types other than the NP swab for SARS-CoV-2 testing in pediatric populations. (Arch Pathol Lab Med. 2022;146:1056-1061; doi: 10.5858/arpa.2021-0625-SA), A pandemic provides a unique setting upon which the basic tenets of laboratory medicine are challenged. Specimen collection for SARS-CoV-2 is one such example, for which validation studies, which are [...]

Accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical for patient management and infection control (1). Molecular diagnostics are highly sensitive in the acute phase of [...]

Background: DICER1 mutations, though infrequent, are encountered on preoperative molecular testing of indeterminate adult and pediatric thyroid fine‐needle aspiration (FNA) specimens. Yet, published cytomorphologic features of DICER1‐altered thyroid lesions are limited. Cytomorphological features of DICER1‐altered thyroid lesions were examined in a multipractice FNA cohort with clinical, radiological, and histologic data. Methods: The cohort comprised 18 DICER1‐altered thyroid FNAs, with 14 having slides available and eight having corresponding surgical resections. Smears, ThinPrep, and formalin‐fixed cell block slides were reviewed and correlated with histology, when available. Clinical and radiologic data were obtained from the medical record. Results: Most DICER1‐altered FNAs were classified as atypia of undetermined significance (94.4%). DICER1 mutations occurred in codons 1709 (50%), 1810 (27.8%), and 1813 (22.2%). One patient had an additional DICER1 p.D1822N variant in both of their FNAs. Lesions were often hypoechoic (35.3%) and solid (47.1%) on ultrasound. Notable cytomorphologic features include mixed but prominent microfollicular or crowded component, variable colloid, and insignificant nuclear atypia. On resection (n = 10), histologic diagnoses ranged from benign follicular adenoma and low‐risk follicular thyroid carcinoma to high‐grade follicular–derived nonanaplastic thyroid carcinoma. Subcapsular infarct‐type change was the most common histologic change. There was no evidence of recurrence or metastasis in eight patients on limited follow‐up. Conclusion: DICER1‐altered thyroid lesions occurred frequently in young females and FNAs show RAS‐like cytomorphology including crowded, mixed macro‐/microfollicular pattern, and bland nuclear features. On resection, DICER1‐altered thyroid lesions include benign (50%), low‐risk lesions (30%), or high‐risk malignancies (20%). A comprehensive multipractice cytologic‐histologic‐molecular correlation of a DICER1‐altered thyroid lesion cohort, comprising one of the largest to date. [ABSTRACT FROM AUTHOR]

Diffuse midline gliomas are among the deadliest human cancers and have had little progress in treatment in the last 50 years. Cell cultures of these tumors have been developed recently, but the degree to which such cultures retain the characteristics of the source tumors is unknown. DNA methylation profiling offers a powerful tool to look at genome-wide epigenetic changes that are biologically meaningful and can help assess the similarity of cultured tumor cells to their in vivo progenitors. Paraffinized diagnostic tissue from three diffuse intrinsic pontine gliomas with H3 K27M mutations was compared with subsequent passages of neurosphere cell cultures from those tumors. Each cell line was passaged 3–4 times and analyzed with DNA methylation arrays and standard algorithms that provided a comparison of diagnostic classification and cluster analysis. All samples tested maintained high classifier scores and clustered within the reference group of H3 K27M-mutant diffuse midline gliomas. There was a gain of 1q in all cell lines, with two cell lines initially manifesting the gain of 1q only during culture. In vitro cell cultures of H3 K27M-mutant gliomas maintain high degrees of similarity in DNA methylation profiles to their source tumor, confirming their fidelity even with some chromosomal changes. [ABSTRACT FROM AUTHOR]

* Context.--Disruption of outpatient laboratory services by routing the samples to commercial reference laboratories may seem like a cost-saving measure by the payers, but results in hidden costs in quality and resources to support this paradigm.Objective.--To identify differences when outpatient tests are performed at the Children's Healthcare of Atlanta (Children's) Hospital lab compared to a commercial reference lab, and the financial costs to support the reference laboratory testing.Design.--Outpatient testing was sent to 3 different laboratories specified by the payer. Orders were placed in the Children's electronic health record, blood samples were drawn by the Children's phlebotomists, samples were sent to the testing laboratory, and results appeared in the electronic health record. Data comparing the time to result, cancelled samples, and cost to sustain the system of ordering and reporting were drawn from multiple sources, both electronic and manual.Results.--The median time from phlebotomy to result was 0.7 hours for testing at the Children's lab and 20.72 hours for the commercial lab. The median time from result posting to caregiver acknowledgment was 5.4 hours for the Children's lab and 18 hours for the commercial lab. The commercial lab cancelled 2.7% of the tests; the Children's lab cancelled 0.8%. The financial cost to support online ordering and reporting for testing performed at commercial labs was approximately $640,000 per year.Conclusions.--Tangible monetary costs, plus intangible costs related to delayed results, occur when the laboratory testing system is disrupted.doi: 10.5858/arpa.2017-0529-OA), 'Care delivery has become increasingly fragmented, leading to coordination and communication challenges for patients and clinicians,' according to the Institute of Medicine. (1) The publication recognizes the increasing complexity of [...]

To the Editor.--In their recent paper, Rogers et al (1) highlighted the increased costs that occur when a local laboratory testing system is disrupted and outpatient tests are sent to [...]

Context.--Evolution of polymerase chain reaction testing for infectious pathogens has occurred concurrent with a focus on value-based medicine. Objective.--To determine if implementation of the FilmArray rapid respiratory panel (BioFire Diagnostics, Salt Lake City, Utah) (hereafter RRP), with a shorter time to the test result and expanded panel, results in different outcomes for children admitted to the hospital with an acute respiratory tract illness. Design.--Patient outcomes were compared before implementation of the RRP (November 1, 2011, to January 31, 2012) versus after implementation of the RRP (November 1, 2012, to January 31, 2013). The study included inpatients 3 months or older with an acute respiratory tract illness, most admitted through the emergency department. Testing before RRP implementation used batched polymerase chain reaction analysis for respiratory syncytial virus and influenza A and B, with additional testing for parainfluenza 1 through 3 in approximately 11% of patients and for human metapneumovirus in less than 1% of patients. The RRP tested for respiratory syncytial virus, influenza A and B, parainfluenza 1 through 4, human metapneumovirus, adenovirus, rhinovirus/enterovirus, and coronavirus NL62. Results.--The pre-RRP group had 365 patients, and the post-RRP group had 771 patients. After RRP implementation, the mean time to the test result was shorter (383 minutes versus 1119 minutes, P < .001), and the percentage of patients with a result in the emergency department was greater (51.6% versus 13.4%, P < .001). There was no difference in whether antibiotics were prescribed, but the duration of antibiotic use was shorter after RRP implementation (P = .003) and was dependent on receiving test results within 4 hours. If the test result was positive, the inpatient length of stay (P = .03) and the time in isolation (P = .03) were decreased after RRP implementation compared with before RRP implementation. Conclusions.--The RRP decreases the duration of antibiotic use, the length of inpatient stay, and the time in isolation. (Arch Pathol Lab Med. 2015; 139:636-641; doi: 10.5858/arpa.2014-0257-0A), The Institute of Medicine1 has identified the need to develop a systems approach to health care delivery, to be a 'continuously learning healthcare system.' Having real-time access to knowledge provides [...]

The OncoKids panel is an amplification-based next-generation sequencing assay designed to detect diagnostic, prognostic, and therapeutic markers across the spectrum of pediatric malignancies, including leukemias, sarcomas, brain tumors, and embryonal tumors. This panel uses low input amounts of DNA (20 ng) and RNA (20 ng) and is compatible with formalin-fixed, paraffin-embedded and frozen tissue, bone marrow, and peripheral blood. The DNA content of this panel covers the full coding regions of 44 cancer predisposition loci, tumor suppressor genes, and oncogenes; hotspots for mutations in 82 genes; and amplification events in 24 genes. The RNA content includes 1421 targeted gene fusions. We describe the validation of this panel by using a large cohort of 192 unique clinical samples that included a wide range of tumor types and alterations. Robust performance was observed for analytical sensitivity, reproducibility, and limit of detection studies. The results from this study support the use of OncoKids for routine clinical testing of a wide variety of pediatric malignancies., (Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)