| 1. |
- Clarke, Emily L., et al.
(author)
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Development and Evaluation of a Novel Point-of-Use Quality Assurance Tool for Digital Pathology
- 2019
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In: Archives of Pathology & Laboratory Medicine. - : COLL AMER PATHOLOGISTS. - 0003-9985 .- 1543-2165. ; 143:10, s. 1246-1255
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Journal article (peer-reviewed)abstract
- Context.-Flexible working at diverse or remote sites is a major advantage when reporting using digital pathology, but currently there is no method to validate the clinical diagnostic setting within digital microscopy. Objective.-To develop a preliminary Point-of-Use Quality Assurance (POUQA) tool designed specifically to validate the diagnostic setting for digital microscopy. Design.-We based the POUQA tool on the red, green, and blue (RGB) values of hematoxylin-eosin. The tool used 144 hematoxylin-eosin-colored, 5x5-cm patches with a superimposed random letter with subtly lighter RGB values from the background color, with differing levels of difficulty. We performed an initial evaluation across 3 phases within 2 pathology departments: 1 in the United Kingdom and 1 in Sweden. Results.-In total, 53 experiments were conducted across all phases resulting in 7632 test images viewed in all. Results indicated that the display, the users visual system, and the environment each independently impacted performance. Performance was improved with reduction in natural light and through use of medical-grade displays. Conclusions.-The use of a POUQA tool for digital microscopy is essential to afford flexible working while ensuring patient safety. The color-contrast test provides a standardized method of comparing diagnostic settings for digital microscopy. With further planned development, the color-contrast test may be used to create a "Verified Login" for diagnostic setting validation.
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| 2. |
- Elfving, Hedvig, et al.
(author)
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Tumor Heterogeneity Confounds Lymphocyte Metrics in Diagnostic Lung Cancer Biopsies
- 2024
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In: Archives of Pathology & Laboratory Medicine. - : Archives of Pathology and Laboratory Medicine. - 0003-9985 .- 1543-2165. ; 148:1, s. e18-e24
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Journal article (peer-reviewed)abstract
- Context.—The immune microenvironment is involved in fundamental aspects of tumorigenesis, and immune scores are now being developed for clinical diagnostics. Objective.—To evaluate how well small diagnostic biopsies and tissue microarrays (TMAs) reflect immune cell infiltration compared to the whole tumor slide, in tissue from patients with non–small cell lung cancer. Design.—A TMA was constructed comprising tissue from surgical resection specimens of 58 patients with non–small cell lung cancer, with available preoperative biopsy material. Whole sections, biopsies, and TMA were stained for the pan-T lymphocyte marker CD3 to determine densities of tumor-infiltrating lymphocytes. Immune cell infiltration was assessed semiquantitatively as well as objectively with a microscopic grid count. For 19 of the cases, RNA sequencing data were available. Results.—The semiquantitative comparison of immune cell infiltration between the whole section and the biopsy displayed fair agreement (intraclass correlation coefficient [ICC], 0.29; P ¼ .01; CI, 0.03–0.51). In contrast, the TMA showed substantial agreement compared with the whole slide (ICC, 0.64; P , .001; CI, 0.39–0.79). The grid-based method did not enhance the agreement between the different tissue materials. The comparison of CD3 RNA sequencing data with CD3 cell annotations confirmed the poor representativity of biopsies as well as the stronger correlation for the TMA cores. Conclusions.—Although overall lymphocyte infiltration is relatively well represented on TMAs, the representativity in diagnostic lung cancer biopsies is poor. This finding challenges the concept of using biopsies to establish immune scores as prognostic or predictive biomarkers for diagnostic applications.
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| 3. |
- Schwartz, David A., et al.
(author)
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Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury
- 2022
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In: Archives of Pathology & Laboratory Medicine. - : COLL AMER PATHOLOGISTS. - 0003-9985 .- 1543-2165. ; 146:6, s. 660-676
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Journal article (peer-reviewed)abstract
- Context.-Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. Objective.-To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design.-Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Results.-Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. Conclusions.-The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.
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| 4. |
- Schwartz, David A., et al.
(author)
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Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury : A Study of 68 Cases With SARS-CoV-2 Placentitis From 12 Countries
- 2022
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In: Archives of Pathology & Laboratory Medicine. - : Archives of Pathology and Laboratory Medicine. - 0003-9985 .- 1543-2165. ; 146:6, s. 660-676
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Journal article (peer-reviewed)abstract
- Context: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear.Objective: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Design: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19.Results: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs.Conclusions: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.
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| 6. |
- Staaf, Johan, et al.
(author)
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Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers : A Comprehensive Study and Review of the Literature
- 2020
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In: Archives of Pathology & Laboratory Medicine. - 0003-9985 .- 1543-2165. ; 144:9, s. 1075-1085
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Research review (peer-reviewed)abstract
- Context.—The diagnostic distinction of pulmonary neuroendocrine (NE) tumors from non–small cell lung carcinomas (NSCLCs) is clinically relevant for prognostication and treatment. Diagnosis is based on morphology and immunohistochemical staining.Objective.—To determine the diagnostic value of insulinoma-associated protein 1 (INSM1), in comparison with established NE markers, in pulmonary tumors.Design.—Fifty-four pulmonary NE tumors and 632 NSCLCs were stained for INSM1, CD56, chromogranin A, and synaptophysin. In a subset, gene expression data were available for analysis. Also, 419 metastases to the lungs were stained for INSM1. A literature search identified 39 additional studies with data on NE markers in lung cancers from the last 15 years. Seven of these included data on INSM1.Results.—A positive INSM1 staining was seen in 39 of 54 NE tumors (72%) and 6 of 623 NSCLCs (1%). The corresponding numbers were 47 of 54 (87%) and 14 of 626 (2%) for CD56, 30 of 54 (56%) and 6 of 629 (1%) for chromogranin A, and 46 of 54 (85%) and 49 of 630 (8%) for synaptophysin, respectively. Analysis of literature data revealed that CD56 and INSM1 were the best markers for identification of high-grade NE pulmonary tumors when considering both sensitivity and specificity, while synaptophysin also showed good sensitivity. INSM1 gene expression was clearly associated with NE histology.Conclusions.—The solid data of both our and previous studies confirm the diagnostic value of INSM1 as a NE marker in pulmonary pathology. The combination of CD56 with INSM1 and/or synaptophysin should be the first-hand choice to confirm pulmonary high-grade NE tumors. INSM1 gene expression could be used to predict NE tumor histology.
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| 7. |
- Williams, Bethany J., et al.
(author)
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A Systematic Analysis of Discordant Diagnoses in Digital Pathology Compared With Light Microscopy
- 2017
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In: Archives of Pathology & Laboratory Medicine. - : COLL AMER PATHOLOGISTS. - 0003-9985 .- 1543-2165. ; 141:12, s. 1712-1718
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Journal article (peer-reviewed)abstract
- Context.-Relatively little is known about the significance and potential impact of glass-digital discordances, and this is likely to be of importance when considering digital pathology adoption. Objective.-To apply evidence-based medicine to collect and analyze reported instances of glass-digital discordance from the whole slide imaging validation literature. Design.-We used our prior systematic review protocol to identify studies assessing the concordance of light microscopy and whole slide imaging between 1999 and 2015. Data were extracted and analyzed by a team of histopathologists to classify the type, significance, and potential root cause of discordances. Results.-Twenty-three studies were included, yielding 8069 instances of a glass diagnosis being compared with a digital diagnosis. From these 8069 comparisons, 335 instances of discordance (4%) were reported, in which glass was the preferred diagnostic medium in 286 (85%), and digital in 44 (13%), with no consensus in 5 (2%). Twenty-eight discordances had the potential to cause moderate/severe patient harm. Of these, glass was the preferred diagnostic medium for 26 (93%). Of the 335 discordances, 109 (32%) involved the diagnosis or grading of dysplasia. For these cases, glass was the preferred diagnostic medium in 101 cases (93%), suggesting that diagnosis and grading of dysplasia may be a potential pitfall of digital diagnosis. In 32 of 335 cases (10%), discordance on digital was attributed to the inability to find a small diagnostic/prognostic object. Conclusions.-Systematic analysis of concordance studies reveals specific areas that may be problematic on whole slide imaging. It is important that pathologists are aware of these areas to ensure patient safety.
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