Discordant Diagnoses Research Articles

Radiographically confirmed pneumonia in Malawian children and associated pneumococcal carriage after introduction of the 13-valent pneumococcal conjugate vaccine

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced in Malawi in 2011 with an expected impact of reducing pneumococcal pneumonia in children. We aimed to describe clinical characteristics and nasopharyngeal (NP) carriage of pneumococcus by serotype in children hospitalized with primary end-point pneumonia (PEP) between 2013 and 19 after the introduction of PCV-13.MethodsWe conducted a secondary analysis of children aged under-5-years hospitalized with acute respiratory illness (ARI) in Malawi. Chest radiographs conducted at admission were read by two independent clinicians according to WHO criteria for PEP, and a third reviewer resolved discordant diagnoses. NP swab specimens were processed and Streptococcus pneumoniae growth was serotyped. Multivariable regression analysis was conducted to assess the association between clinical characteristics, NP serotypes, and PEP.ResultsWe had complete radiographic and NP serotype data for 500 children, of which 54 isolates were vaccine-type (VT) (10.8%), 165 were non-VT (NVT; 33.0%), and 281 had no pneumococcal growth (56.2%). Among these, 176 (35.2%) had PEP on chest x-ray. Among those with PEP, pneumococcal carriage was documented in 43.8% of cases, and VT serotypes accounted for 10.8%. For children with PEP, we found no association between clinical characteristics and carrying either VT, NVT, or no pneumococcus.ConclusionCarriage of S. pneumoniae remains high among children hospitalized with ARI in Malawi, but children with VT carriage were no more likely to have PEP than children carrying no pneumococcus or those with NVT carriage. There were no differences in clinical characteristics between those carrying VT, NVT, or no pneumococcus.

Influence of Different Diagnostic Criteria on Alzheimer Disease Clinical Research.

Updates in Alzheimer disease (AD) diagnostic guidelines by the National Institute on Aging-Alzheimer's Association (NIA-AA) and the International Working Group (IWG) over the past 11 years may affect clinical diagnoses. We assessed how these guidelines affect clinical AD diagnosis in a cohort of cognitively unimpaired (CU) and cognitively impaired (CI) individuals. We applied clinical and biomarker data in algorithms to classify individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort according to the following diagnostic guidelines for AD: 2011 NIA-AA, 2016 IWG-2, 2018 NIA-AA, and 2021 IWG-3, assigning the following generic diagnostic labels: (1) not AD (nAD), (2) increased risk of developing AD (irAD), and (3) AD. Diagnostic labels were compared according to their frequency, convergence across guidelines, biomarker profiles, and prognostic value. We also evaluated the diagnostic discordance among the criteria. A total of 1,195 individuals (mean age 73.2 ± 7.2 years, mean education 16.1 ± 2.7, 44.0% female) presented different repartitions of diagnostic labels according to the 2011 NIA-AA (nAD = 37.8%, irAD = 23.0%, AD = 39.2%), 2016 IWG-2 (nAD = 37.7%, irAD = 28.7%, AD = 33.6%), 2018 NIA-AA (nAD = 40.7%, irAD = 9.3%, AD = 50.0%), and 2021 IWG-3 (nAD = 51.2%, irAD = 8.4%, AD = 48.3%) frameworks. Discordant diagnoses across all guidelines were found in 512 participants (42.8%) (138 [91.4%] occurring in only β-amyloid [CU 65.4%, CI 34.6%] and 191 [78.6%] in only tau-positive [CU 71.7%, CI 28.3%] individuals). Differences in predicting cognitive impairment between nAD and irAD groups were observed with the 2011 NIA-AA (hazard ratio [HR] 2.21, 95% CI 1.34-3.65, p = 0.002), 2016 IWG-2 (HR 2.81, 95% CI 1.59-4.96, p < 0.000), and 2021 IWG-3 (HR 3.61, 95% CI 2.09-6.23, p < 0.000), but not with 2018 NIA-AA (HR 1.69, 95% CI 0.87-3.28, p = 0.115). Over 42% of the studied population presented discordant diagnoses when using the different examined AD criteria, mostly in individuals with a single positive biomarker. Except for 2018 NIA-AA, all guidelines identified asymptomatic individuals at risk of cognitive impairment. Our findings highlight important differences between the guidelines, emphasizing the necessity for updated criteria with enhanced staging metrics, considering clinical, research, therapeutic, and trial design aspects.

Cost Analysis of Routine Histopathologic Evaluation of Specimens Following Total Ankle Arthroplasty.

Routine histopathologic examination of orthopaedic surgical specimens is a standard practice at many institutions. Previous studies have demonstrated that this practice seldom altered patient management for several orthopaedic procedures. As a result, the value of such practices has come into question. The purpose of this study is to determine the cost-effectiveness of routine histopathologic analysis of specimens obtained during total ankle arthroplasty (TAA). A retrospective analysis was performed of patients who underwent uncomplicated primary TAA at a large, academic, health system between January 2015 and December 2021. The postoperative histopathologic diagnoses were compared with the respective patient's preoperative clinical and intraoperative diagnoses. The prevalence of concordant, discrepant, and discordant diagnoses was determined. Cost-effectiveness analysis was conducted to assess the financial implications of obtaining routine specimens for histopathologic examination for TAA. A total of 85 TAAs were identified in 85 individual patients and were included in the present study. A total of 172 specimens were sent for routine histopathologic review. On histopathologic analysis, a final diagnosis was confirmed in 82 (96.5%) of the total specimens reviewed. A discrepant diagnosis was discovered in 3 (3.5%; 2 cases of gout/pseudogout and 1 case of osteonecrosis) cases and 0 (0%) discordant diagnoses were discovered, corresponding to positive and negative predictive values of 97% and 100%, respectively The total estimate of costs incurred for the routine analysis of all specimens included in the study was between $12 299.20 and 17 846.00. The estimated cost to establish each discrepant diagnosis ranged between $4099.73 and $5948.67, and the cost for a discordant diagnosis was unable to be established. Routine histopathologic analysis of specimens obtained during TAA rarely revealed a discordant diagnosis and resulted in no alterations to patients' plan of care. Furthermore, the additional costs of routine histopathologic examination are significant. As such, it is recommended that such interventions in TAA should be performed on a per-case basis at the operating surgeon's discretion.

Diagnostic Discordance, Uncertainty, and Treatment Ambiguity in Community-Acquired Pneumonia : A National Cohort Study of 115 U.S. Veterans Affairs Hospitals.

Evidence-based practice in community-acquired pneumonia often assumes an accurate initial diagnosis. To examine the evolution of pneumonia diagnoses among patients hospitalized from the emergency department (ED). Retrospective nationwide cohort. 118 U.S. Veterans Affairs medical centers. Aged 18 years or older and hospitalized from the ED between 1 January 2015 and 31 January 2022. Discordances between initial pneumonia diagnosis, discharge diagnosis, and radiographic diagnosis identified by natural language processing of clinician text, diagnostic coding, and antimicrobial treatment. Expressions of uncertainty in clinical notes, patient illness severity, treatments, and outcomes were compared. Among 2 383 899 hospitalizations, 13.3% received an initial or discharge diagnosis and treatment of pneumonia: 9.1% received an initial diagnosis and 10.0% received a discharge diagnosis. Discordances between initial and discharge occurred in 57%. Among patients discharged with a pneumonia diagnosis and positive initial chest image, 33% lacked an initial diagnosis. Among patients diagnosed initially, 36% lacked a discharge diagnosis and 21% lacked positive initial chest imaging. Uncertainty was frequently expressed in clinical notes (58% in ED; 48% at discharge); 27% received diuretics, 36% received corticosteroids, and 10% received antibiotics, corticosteroids, and diuretics within 24 hours. Patients with discordant diagnoses had greater uncertainty and received more additional treatments, but only patients lacking an initial pneumonia diagnosis had higher 30-day mortality than concordant patients (14.4% [95% CI, 14.1% to 14.7%] vs. 10.6% [CI, 10.4% to 10.7%]). Patients with diagnostic discordance were more likely to present to high-complexity facilities with high ED patient load and inpatient census. Retrospective analysis; did not examine causal relationships. More than half of all patients hospitalized and treated for pneumonia had discordant diagnoses from initial presentation to discharge. Treatments for other diagnoses and expressions of uncertainty were common. These findings highlight the need to recognize diagnostic uncertainty and treatment ambiguity in research and practice of pneumonia-related care. The Gordon and Betty Moore Foundation.

Reproducibility of the Paris System in Urine Cytology by Third-Year Pathology Residents.

Standardized basic morphology and the algorithmic approach make the Paris System (TPS) for Reporting Urinary Cytology understandable and applicable. This study examined how well the TPS categories are understood by pathology residents and how well these criteria are enabling them reaching accurate diagnosis. A hundred consecutive cases representing all categories were selected. Authors reevaluated slides using TPS regardless of their original diagnosis. In the next step, the TPS was explained to four residents and trained them by five optimal urine cytology samples from each category. Then they were asked to diagnose the selected slides according to the TPS. The diagnoses were compared to authors. The agreement was assessed using kappa. Discordant diagnoses were classified as high and low impact based on potential on clinical practice. The sensitivity of authors was 62.8%, and residents' were 24-31.8%. The specificity of authors was 98.8%, and residents' were 82.3-92.8%. Reproducibility of TPS was 40-46%. Kappa values were below 0.40 except for one resident. The highest rate of concordance was for negative for high-grade urothelial carcinoma (NHGUC): authors assigned 38 NHGUC (35 biopsy-proven benign cases). Twenty to twenty-six of them were assigned as NHGUC by residents. While authors assigned 42 cases as suspicious for high-grade urothelial carcinoma (SHGUC) or high-grade urothelial carcinoma (HGUC) (35 biopsy-proven malignant cases), residents assigned 22-29 of them. Discordant diagnosis with high clinical implication was 56-63%. Diagnostic accuracy rates of junior pathology residents using the TPS were unsatisfactory. The best agreement was observed in NHGUC and HGUC categories. Combining HGUC and SHGUC doubled the sensitivity of residents.

Digital Pathology is a Fast and Effective Platform for Providing Head and Neck Pathology Consultations.

Surgical pathology of the head and neck is one of the more challenging areas in all of diagnostic pathology. Its unparalleled diversity and complexity renders it highly vulnerable to diagnostic error compelling unconstrained access to specialized diagnostic expertise. Digital pathology (DP) is a state-of-the-art tool that could facilitate access to specialized expertise, but it is relatively untested in the context of pathology consultations. In a collaboration between Labcorp Dianon and a large academic hospital with subspecialized surgical pathology, DP was implemented to provide the pathology community access to head and neck pathology expertise. From this collaborative experience, glass slides from consecutive consult cases that had been previously diagnosed using DP were reviewed by an expert consultant in a blinded manner following an extended wash-out period. The intraobserver discrepancy rate was recorded. Major discrepancies were defined as those resulting in significant impact on clinical management and/or prognosis, whereas minor discrepancies were those with no impact on care or prognosis. Slides from 57 cases were available for review. The average wash-out period was 19 months. Five discrepancies were recorded (intraobserver concordance rate of 91%). All discrepancies were minor (major discrepancy rate, 0%; minor discrepancy rate, 9%). On appraisal of the discrepant cases, discordant diagnoses were attributed to subjective differences in interpretation rather than objective differences related to the inferiority of DP. DP decreased the median turnaround time by 97% (from 70h 26min to 2h 25min). DP provides efficient and fast access to expert consultants. The speed of case delivery does not compromise diagnostic precision. Discrepancies are uncommon, minor, and reflect subjective interpretative differences inherent to difficult and ambiguous head and neck cases, and not the inferiority of DP as a diagnostic platform. High concordance can be achieved even for those difficult and complex cases that are concentrated in the consultation practice. This observation carries profound implications regarding universal health care access to specialized diagnostic expertise.

Second opinion for pulmonary and pleural cytology is valuable for patient care

IntroductionThoracic cytology can be challenging due to limited procured material or overlapping morphology between benign and malignant entities. In such cases, expert consultation might be sought. This study aimed to characterize all pulmonary and pleural cytology consult cases submitted to our practice and provide recommendations on approaching difficult cases. Materials and MethodsAll thoracic (pulmonary and pleural) cytology cases submitted for expert consultation to the University of Michigan (MLabs) from 2013 to mid-2022 were reviewed. Cases where cytology was only part of a hematopathology or surgical pathology consult were excluded. Patient demographics, specimen location, procedure performed, referring diagnosis, and our diagnoses were recorded for each case. Diagnoses were categorized according to the Papanicolaou Society of Cytopathology recommendations for pulmonary and effusion cytology. Discordant diagnoses were stratified as major or minor. Data was analyzed using Chi-Square analysis and logistic models. ResultsWe received 784 thoracic cytology consult cases, including 530 exfoliative samples and 307 fine needle aspirations (FNAs). The most common anatomic locations sampled were the bronchial wall (n=194, 23%), lung nodule (n=322, 38%), and pleura (n=296, 35%). 413 cases had a diagnostic discrepancy (48.3%), with 274 (66%) minor and 139 (34%) major discrepancies. By location, pleural effusion specimens had the highest probability of a discrepant diagnosis (p=0.003). By specimen type, FNA samples were significantly more likely to have a discrepant diagnosis (p=0.06). ConclusionNearly half of the thoracic cytology cases submitted for expert second opinion had diagnostic discrepancies. Consequently, consulting a tertiary medical care center with cytopathology expertise for challenging thoracic cytology diagnoses is beneficial.

The Limited Utility of Routine Pathologic Examination of Ganglion Cyst Excision From the Hand and Digits.

It is routine practice at many institutions to send surgically excised ganglion cysts for pathologic analysis. This adds significant cost to the procedure with questionable benefit. The purpose of this study was to determine the necessity of routine pathologic examination of ganglion cysts excised from the hand. We conducted a retrospective review of 443 patients who underwent ganglion excision from the hand with routine pathologic examination between 2012 and 2022. The final pathologic diagnosis was compared with the treating surgeon's clinical diagnosis, and the rates of concordant, discrepant, and discordant diagnoses were identified. Discrepant diagnoses were defined as differing clinical and pathologic diagnoses that did not change clinical management. Discordant diagnoses were defined as differing clinical and pathologic diagnoses that altered the treatment plan. The prevalence of a concordant diagnosis was 96.2% (426 of 443; 95% confidence interval, 94.4%-98.0%). The prevalence of a discrepant diagnosis was 3.8% (17 of 443; 95% confidence interval, 2.1%-5.6%), and the prevalence of a discordant diagnosis was 0. The odds ratio was 0.04 for a discrepant diagnosis and 0 for a discordant diagnosis. Our study suggests abandoning routine pathologic analysis in patients undergoing ganglion cyst excision from the hand will not compromise quality of care when the surgeon is able to make a confident diagnosis. Discrepant diagnoses were rare and discordant diagnoses that did not occur. We recommend pathologic evaluation only when there is uncertainty in the clinical diagnosis.

Comparison of two parathyroid hormone (pth) assay methods in the monitoring of black african hemodialysis patients in the ivory coast (Maglumi® vs Vidas Biomerieux® Kits)

Parathyroid hormone (PTH) testing is recommended once or twice a year to prevent bone complications resulting from chronic kidney disease. However, its interpretation is subject to many factors, including the generation of the PTH test used. For this reason, it is recommended that each laboratory establish its own PTH Upper Limit of Normality (ULN). In order to guarantee optimal management of hemodialysis patients in the public sector in Côte d'Ivoire (West Africa), it proved important to compare the diagnosis of hyperparathyroidism made using two platforms used in the laboratory in charge of monitoring these patients: PTH VIDAS® (3rd Generation) and PTH MAGLUMI® (2nd Generation). This was a cross-sectional study of 65 haemodialysis patients in Abidjan. PTH determinations were performed simultaneously on VIDAS® and MAGLUMI® platforms. The results obtained were interpreted on the basis of PTH threshold values pre-established in the laboratory. 86.15% of patients had concordant diagnoses on both platforms, compared with 13.85% with discordant diagnoses. Statistical analysis of these results showed a non-statistically significant difference.: The limitation posed by differences in PTH concentration given by different platforms can be circumvented by using PTH ULN stablished for each platform for a given population. Conclusion: The diagnoses made by the two platforms are thus superimposable using their respective PTH ULN.

Concordance Between Biopsy and Resection Diagnoses of Uterine Cervical Adenocarcinoma According to the Updated World Health Organization 2020 Classification: A Multi-Institutional Study Elucidating Real-World Practice in Japan.

Endocervical adenocarcinoma is divided into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) in the 5h edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphological criteria used for biopsy specimens in real-world practice remains undetermined. To validate the utility of the 5th edition of the WHO classification for biopsy samples, focusing on its diagnostic criteria with the aid of ancillary studies. We retrieved 217 cases of endocervical adenocarcinoma from 6 institutions, in which glass slides of both biopsy and resection specimens were available for review. Concordance between the biopsy and resection specimen diagnoses was evaluated. For discordant diagnoses, an algorithmic approach with ancillary studies proposed by the international group was applied to confirm their utility to improve the accuracy of biopsy diagnosis. The biopsy diagnosis matched the resection specimen diagnosis in 197 cases (concordance rate, 91%; κ = 0.75). The concordance rate was significantly higher for HPVA than HPVI (95% versus 81%, P = .001). There were no significant differences in the proportions of HPVA and HPVI or the accuracy of biopsy diagnosis between the participating institutions. All 19 discordant cases with unstained glass slides available were accurately recategorized as HPVA or HPVI using HPV in situ hybridization; p16 immunohistochemistry was positive in 3 of 9 cases of gastric-type HPVI that were negative by in situ hybridization. The 5th edition of the WHO criteria for biopsy diagnosis of endocervical adenocarcinoma distinguishes HPVA from HPVI well when ancillary studies are adequately applied.

Impact of the transition from radioimmunoassay (RIA) to chemiluminescent enzyme immunoassay (CLEIA) for the measurement of plasma aldosterone concentration (PAC) on the diagnosis of primary aldosteronism (PA) via retrospective analyses in Okinawa, Japan.

In Japan, the traditional method for measuring plasma aldosterone concentration (PAC) was radioimmunoassay (RIA), which had several challenges, including poor traceability of certified reference materials and reduced detection sensitivity at low concentrations. To overcome these issues, a chemiluminescent enzyme immunoassay (CLEIA) for PAC measurement was introduced in April 2021 and the Japan Endocrine Society published new guidelines for primary aldosteronism (PA). This study aimed to evaluate the impact of the transition from RIA to CLEIA for PAC measurement on PA diagnosis. Data from 190 patients admitted to the Second Department of Internal Medicine, University of the Ryukyus Hospital, between April 2012 and March 2021 were analyzed. Patients who were diagnosed with PA underwent adrenal venous sampling. The PAC measured by RIA (PAC(RIA)) was converted to the estimated PAC measured by CLEIA (ePAC(CLEIA)) using a conversion formula. The present study evaluated the discordance rates in diagnoses based on screening (SC), captopril challenge test (CCT), saline infusion test (SIT), and diagnosis of PA between results judged by PAC(RIA) according to the previous guidelines and those judged by ePAC(CLEIA) according to the new guidelines. The results revealed discordant diagnosis rates of 6.4% for SC and 10.1% for CCT, with no discordance for SIT. The discordant diagnosis rate for PA was 3.7%. Our study reveals the challenges in establishing appropriate diagnostic criteria for PA using PAC(CLEIA) and highlights the demand for further research on provisionally positive categories.

Accuracy of the Diagnosis of Subsegmental Pulmonary Embolism Among General Radiologists

Background: Diagnosis and treatment of subsegmental pulmonary embolism (SSPE) are challenging. Contrary to segmental PE, little is known about the accuracy of the diagnosis of SSPE Methods A retrospective matched cohort study was conducted at a university-affiliated community hospital. Computed tomographic angiography (CTAs) were reviewed from August 2018 to December 2021. Patients who were 18-year-old or older with the diagnosis of SSPE were included. Patients with a concurrent segmental PE or deep venous thrombosis (DVT) were excluded. Another radiologist reviewed each CTA. Results Total of 43 patients with SSPE without segmental PE were identified. The mean age of subjects was 67 years. 24 (56%) patients were males, and 41 (95%) were white. 42 (97%) of CTAs were performed for suspected PE. One case was found incidentally. Forty patients (93%) received therapeutic anticoagulation. Three patients (7%) were discharged from the Emergency Department (ED) without therapeutic anticoagulation. The average duration of anticoagulation therapy was four-months. Another radiologist's review of the CTA on admission revealed a discordant diagnosis: 13 out of 43 (30%) cases were reported negative for SSPE. One case was reported for segmental PE Conclusion The accuracy of the diagnosis of SSPE is low as the discordance rate by different radiologists is high.More studies are needed to establish the diagnosis and guide treatment of SSPE.

Splenectomy outcomes in immune cytopenias: Treatment outcomes and determinants of response.

Splenectomy is commonly used to treat refractory immune-mediated cytopenia, but there are no established factors that are associated with response to the procedure. A cohort study was conducted to evaluate the hematologic and surgical outcomes of splenectomy in adult patients with immune cytopenias and identify preoperative factors associated with response. Data from the Cleveland Clinic Foundation for 1824 patients aged over 18 who underwent splenectomy from 2002 to 2020 were analyzed. The study found that the most common indications for splenectomy were immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia, with a median age of 55 years and median time from diagnosis to splenectomy of 11 months. Hematologic response rates were 74% overall, with relapse in 12% of cases. Postsplenectomy discordant diagnoses were present in 13% of patients, associated with higher relapse rates. Surgery-related complications occurred in 12% of cases, whereas only 3% of patients died from disease complications. On univariate analysis, preoperative factors associated with splenectomy treatment failure were ≥3 lines of pharmacologic treatment, whereas isolated thrombocytopenia, primary ITP, and age ≤40 years had a strong association with response. The multivariable regression confirmed that treatment failure with multiple lines of medical therapy was associated with the failure to respond to splenectomy. Overall, the study demonstrates that splenectomy is an effective treatment option for immune-mediated cytopenias with a low complication rate.

DISP-09. HISTOPATHOLOGIC AND MOLECULAR PROFILE OF GLIOMAS: A 9-YEAR RETROSPECTIVE STUDY OF CASES DIAGNOSED IN LAGOS NIGERIA

Abstract BACKGROUND The diagnosis and management of patients with brain tumors currently uses WHO defined morphologic and molecular features. However, neuro-oncology practice in low resource settings relies on histomorphology. This study aims to reclassify glioma cases diagnosed in the Department of Anatomic and Molecular Pathology Lagos University Teaching Hospital using the 2021 WHO classification. METHODS Fifty-six cases of glioma diagnosed between 2013 to 2021 were evaluated. Morphologic diagnosis was reassessed. Five-micron sections were obtained for immunohistochemistry (IHC), and genetic testing (DNA and RNA); after manual macrodissection for tumor enrichment using 10μm sections. IHC for IDH1-R132H, ATRX, BRAFV600E, P53,Ki67, and H3K27M and OncoScan chromosomal microarray analysis were performed. NGS mutation/fusion analysis and EPIC methylation array profiling are in progress. RESULTS Of 56 cases evaluated, median age was 22 years (range=1-60 years); 71% were males. The initial morphologic diagnosis include 21 pilocytic astrocytoma, 11 glioblastoma, 9 ependymoma, 7 diffuse astrocytoma, 3 anaplastic astrocytoma, 2 high-grade gliomas, 1 oligodendroglioma, 1 diffuse midline glioma, and 1 pleomorphic xanthoastrocytoma (PXA). Histomorphologic re-evaluation revealed discordant diagnosis in 29% (16/56) of cases. Of the 56 cases, 73% (41/56) had usable DNA yield and 38% (21/56) had DNA yield of ≥ 750ng. Chromosomal microarray analysis was completed for 50% (28/56) cases. The revised 2021 WHO diagnosis were: 5 glioblastoma, IDH-wildtype, 5 pilocytic astrocytoma, 4 glioma NEC, 3 posterior fossa ependymoma, group B, 3 PXAs, 3 astrocytoma, IDH-mutant, 2 pediatric low-grade glioma, 2 supratentorial ependymoma, ZFTA fusion-positive, 1 posterior fossa ependymoma, group A. In 71% (20/28) of cases, diagnosis was revised using the 2021 WHO criteria. CONCLUSION Most cases had usable DNA yield. Overall, hsitologic re-evaluation and molecular testing based on the 2021 WHO classification guidelines refined the diagnosis in 48% (27/56) of cases.

GLIOMA-02 HISTOPATHOLOGIC AND MOLECULAR PROFILE OF GLIOMAS: A 9-YEAR RETROSPECTIVE STUDY OF CASES DIAGNOSED IN LAGOS NIGERIA

Abstract BACKGROUND The diagnosis and management of patients with brain tumors currently uses WHO defined morphologic and molecular features. However, neuro-oncology practice in low resource settings relies solely on histomorphology. This study aims to reclassify glioma cases diagnosed in the Department of Anatomic and Molecular Pathology Lagos University Teaching Hospital using the WHO 2021 classification. METHODS Fifty-six cases of glioma diagnosed between 2013 to 2021 were evaluated. Morphologic diagnosis was reassessed. Five-micron sections were obtained for immunohistochemistry (IHC), and genetic testing (DNA and RNA) after manual macrodissection for tumor enrichment used 10-µm sections. IHC for IDH1-R132H, ATRX, BRAF-V600E, p53, Ki67 and H3-K27M and Oncoscan chromosomal microarray analysis were performed. NGS mutation/fusion analysis and EPIC methylation array profiling are in progress. RESULTS Of the 56 cases evaluated, median age was 22 years (range, 1-60); 71% were male. The initial morphologic diagnoses included 21 pilocytic astrocytoma, 11 glioblastoma, 9 ependymoma, 7 diffuse astrocytoma, 3 anaplastic astrocytoma, 2 high-grade gliomas, 1 oligodendroglioma, 1 diffuse midline glioma, and 1 pleomorphic xanthoastrocytoma (PXA). Histomorphologic re-evaluation revealed discordant diagnosis in 29% (16/56) of cases. Of the 56 cases, 73% (41/56) had usable DNA yield and 38% (21/56) had DNA yield of ≥750ng. Chromosomal microarray analysis was completed for 50% (28/56) cases. The revised WHO 2021 diagnosis was: 5 glioblastoma IDH-wildtype, 5 pilocytic astrocytoma, 4 glioma NEC, 3 posterior fossa ependymoma, group B, 3 PXA, 3 astrocytoma IDH-mutant, 2 pediatric low-grade gliomas, 2 supratentorial ependymoma, ZFTA fusion-positive, 1 posterior fossa ependymoma, group A. In 71% (20/28) of cases with molecular testing, diagnosis was revised using WHO 2021 criteria. CONCLUSION Most cases had usable DNA. Overall, histologic re-evaluation and molecular based on the WHO 2021 criteria refined the diagnosis in 48% (27/56) of cases.

Routine Histopathologic Examination of Bone Obtained During Elective Primary Total Knee Arthroplasty May Not Be Necessary.

Many institutions require the routine collection of pathology samples from every primary total knee arthroplasty (TKA) performed. These policies are controversial, and their cost-effectiveness is difficult to define. We sought to judge the cost-effectiveness of one such policy according to World Health Organization recommendations. We analyzed 3200 consecutive primary TKAs, comparing our presumed preoperative diagnoses against the diagnoses made by the pathologist. Diagnoses were categorized as concordant (matching), discrepant (not matching but without impact to patient management), or discordant (not matching and resulting in a direct change to patient management). An incremental cost-utility ratio analysis was performed to determine the cost-effectiveness of our institution's policy to routinely collect pathology samples from every primary TKA performed. Cost-effectiveness was defined by World Health Organization guidelines as a cost of less than $228,090 per quality-adjusted life year gained. Twelve pathology samples were lost before reaching a pathologist. From the remaining 3188 samples, we identified 3158 concordant cases, 29 discrepant diagnoses, and 1 discordant diagnosis. It cost an estimated $10,522.60 to identify each discrepant diagnosis and an estimated $305,155.36 to diagnose one discordant case in our cohort. Our incremental cost-utility ratio analysis revealed that we spent $305,155.36 to gain 0 quality-adjusted life years for our patients. Routine histopathologic analysis of TKA samples was cost-ineffective in our patient cohort and may not be necessary during routine TKA.

Discordant pathologic diagnoses of myelodysplastic neoplasms and their implications for registries and therapies

AbstractMyelodysplastic neoplasms (MDS) are a collection of hematopoietic disorders with widely variable prognoses and treatment options. Accurate pathologic diagnoses present challenges because of interobserver variability in interpreting morphology and quantifying dysplasia. We compared local clinical site diagnoses with central, adjudicated review from 918 participants enrolled in the ongoing National Heart, Lung, and Blood Institute National MDS Natural History Study, a prospective observational cohort study of participants with suspected MDS or MDS/myeloproliferative neoplasms (MPNs). Locally, 264 (29%) were diagnosed as having MDS, 15 (2%) MDS/MPN overlap, 62 (7%) idiopathic cytopenia of undetermined significance (ICUS), 0 (0%) acute myeloid leukemia (AML) with <30% blasts, and 577 (63%) as other. Approximately one-third of cases were reclassified after central review, with 266 (29%) diagnosed as MDS, 45 (5%) MDS/MPN overlap, 49 (5%) ICUS, 15 (2%) AML with <30%, and 543 (59%) as other. Site miscoding errors accounted for more than half (53%) of the local misdiagnoses, leaving a true misdiagnosis rate of 15% overall, 21% for MDS. Therapies were reported in 37% of patients, including 43% of patients with MDS, 49% of patients with MDS/MPN, and 86% of patients with AML with <30% blasts. Treatment rates were lower (25%) in cases with true discordance in diagnosis compared with those for whom local and central diagnoses agreed (40%), and receipt of inappropriate therapy occurred in 7% of misdiagnosed cases. Discordant diagnoses were frequent, which has implications for the accuracy of study-related and national registries and can lead to inappropriate therapy. This trial was registered at www.clinicaltrials.gov as #NCT05074550.

Peripheral arterial tonometry versus polysomnography in suspected obstructive sleep apnoea

BackgroundPolysomnography (PSG) is the gold standard for the diagnosis of obstructive sleep apnoea (OSA). Home sleep apnoea testing with peripheral arterial tonometry (PAT) is a recommended diagnostic alternative for patients with an increased risk for OSA.In a large clinical cohort, we investigated concordance and predictors for discordance in diagnosing OSA using PAT and PSG, and three-year cardiovascular risk in patients with discordant OSA diagnosis.MethodsRetrospective monocentric cohort study. Patients with a PAT AHI ≥ 5/h followed by an in-hospital PSG within three months were included. All patients with a PAT AHI ≥ 5/h but a PSG AHI < 5/h were classified as discordant. Patients with PAT and PSG AHI ≥ 5/h were classified as concordant. To ascertain cardiovascular risk, major adverse cardiovascular events (MACE) were analyzed in discordant patients and sex, age, body mass index (BMI) and cardiovascular disease-matched concordant patients over a follow-up time of 3.1 ± 0.06 years.ResultsA total of 940 patients, 66% male with an average age of 55 ± 0.4 years and BMI of 31 ± 0.2 kg/m2 were included. Agreement in OSA diagnosis was observed in 80% of patients (55% in mild and 86% in moderate and severe OSA). Factors significantly associated with a discordant diagnosis were female sex, younger age and lower BMI, but not comorbidities. There was no significant difference in MACE (p = 0.920) between discordant patients (n = 155) and matched concordant patients (n = 274) with or without therapy.ConclusionsConcordance between PAT and PSG diagnosis of sleep apnoea is good, particularly in moderate and severe OSA. Predictors for discordant results between PAT and PSG were age, sex and BMI. MACE risk is similar in those with OSA diagnosed by PAT or PSG.

Consensus classification of pediatric hepatocellular tumors: A report from the Children's Hepatic tumors International Collaboration (CHIC).

Liver tumors are rare in children with histologic heterogeneity that makes diagnosis challenging. Systematic histopathological review, performed as part of collaborative therapeutic protocols, identified relevant histologic subtypes that are important to distinguish. The Children's Hepatic tumors International Collaboration (CHIC) was established to study pediatric liver tumors on a global scale and led to establishment of a provisional consensus classification for use in international clinical trials. The current study is the validation of this initial classification and first large-scale application by international expert reviewers. The CHIC initiative includes data from 1605 children treated on eight multicenter hepatoblastoma (HB) trials. Review of 605 available tumors was performed by seven expert pathologists from three consortia (US, EU, Japan). Cases with discordant diagnoses were collectively reviewed to reach a final consensus diagnosis. Of 599 cases with sufficient material for review, 570 (95.2%) were classified as HB by all consortia, and 29 (4.8%) as non-HB, which included "hepatocellular neoplasm, NOS" and malignant rhabdoid tumors. 453 of 570 HBs were classified as epithelial by final consensus. Some patterns (i.e., small cell undifferentiated, macrotrabecular, cholangioblastic) were selectively identified by reviewers from different consortia. All consortia identified a similar number of mixed epithelial-mesenchymal HB. This study represents the first large-scale application and validation of the pediatric malignant hepatocellular tumors consensus classification. It is a valuable resource to train future generations of investigators on accurate diagnosis of these rare tumors and provides a framework for further international collaborative studies and refinement of the current classification of pediatric liver tumors.

Use of nongynecologic cytologic-histologic correlation to identify patterns of error: An institutional experience.

Quality management practices empower cytology laboratories to deliver consistent, high-quality patient care. Monitoring of key performance indicators is one way by which laboratories can identify patterns of error and focus their improvement activities. Cytologic-histologic correlation (CHC) identifies error by retrospectively reviewing cytology cases when discordant surgical pathology diagnoses are reported. Analysis of CHC data can elucidate patterns of error and direct quality improvement initiatives. CHC data of nongynecologic cytology specimens were reviewed over a 3-year period (2018-2021). Errors were separated by anatomic site and classified as either sampling or interpretive errors. A total of 364 discordant cases were identified out of 4422 cytologic-histologic pairs (a discordant rate of 8%). The majority (272; 75%) were sampling errors, with fewer interpretive errors (92; 25%). Sampling errors were found to occur most commonly in lower urinary tract and lung. Interpretive errors were most commonly found in lower urinary tract and thyroid. Nongynecologic CHC data can be a valuable resource for cytology laboratories. By studying the types of errors, quality improvement activities can be targeted toward problem areas.