Suspicious Results Research Articles

A-016 Can You Believe Your Troponin? Using Laboratory Automation and Programmed Rules to Reduce Non-Repeatable False Positive Troponin Results

Abstract Background Cardiac troponin is currently the standard biomarker for evaluating patients with suspected acute coronary syndrome. Like all immunoassays, troponin testing is susceptible to non-repeatable positive results. Because this can cause a clinical challenge, we assessed our false positive rate by manipulating the timing and conditions of repeat troponin testing. Methods A prospective observational study established the repeatability failure (RF) rate in three scenarios, where a suspicious initial result prompts a repeat test. Protocol 1: We programed our middleware (Remisol, Beckman Coulter) to route the specimen to online storage after initial testing. After a 120-minute delay, the specimen was automatically retrieved from storage and tested again. Protocol 2: We programmed DxI 800 systems (Beckman Coulter) to aspirate a specimen reserve volume sufficient for two test replicates simultaneously. Protocol 3: We restricted repeat testing to 18-50 ng/L where the majority of RF occurred. To analyze RF in 4 and 18 ng/L interval (limit of reporting and URL, respectively), an absolute 3.5 ng/L bias was considered an RF. For specimens >18 ng/L, a difference of ±4.0 SD difference between replicates with a CV of 7% was a RF, equating to a relative difference of 28% (Method 1). Method 2 used a relative difference of 35% for RF. Method 3 defined RF as a critical difference of z×√2×SDanalytical where z=3.5 and SD=1.8 for results <19 ng/L and SD for results ≥19 ng/L were calculated from a fixed 7% CV for each result. A z-value of 3.5 represents a probability of 0.0005 (5 in 10,000). Results Using Protocol 1, RF rate was significantly higher in delayed repeat testing (1.6%, CI 1.5-1.8, n=23,525) compared to immediate repeat testing (0.4%, CI 0.4-0.5, n=14,880, p<0.0001) in two-tailed analysis. Because the first result was more commonly larger than the second (77.7% v. 52.2%, respectively), one-tailed analysis was used and found RF in delayed repeat testing was 0.9% (CI 0.8-1.0) v. immediate repeat testing (0.4%, CI 0.3-0.4, p<0.0001). A similar percentage of results were found in the 18-50 ng/L range in delayed testing (88.6%) v. immediate repeat (86.8%). Protocol 2 (with one-tailed analysis) yielded similar RF rates: 0.8%, CI 0.8-1.0 v. 0.3%, CI 0.3-0.4, delayed and immediate repeat testing, respectively. Protocol 3 yielded RF rate of 0.6%, CI 0.5-0.7 v. 0.2%, CI 0.2-0.3, delayed and immediate repeat testing, respectively, with all p-values <0.0001. Conclusions By programming auto-repeating hsTnI testing only in the 18-50 ng/L range, we found >80% of specimens with potential RF results could be retested using either the delayed- or immediate-repeat protocols. This suggests automated protocols could repeat testing with potential RFs without staff intervention or increasing container movement on the automation line. Reagent usage because of repeat testing could be conserved by limiting repeat testing to specimens most likely to create provider confusion. Rules to automate selected retesting of hsTnI in testing systems and/or middleware can enhance quality of results without human intervention and subsequent burden on staff, reduce reagent waste and enhance provider decision making in a critical population.

The skinny on skin: The role of skin-aware professionals in skin cancer surveillance.

Licensed nonmedical, skin-aware professionals (e.g., hairdressers, massage therapists, etc.) have the potential to identify skin cancer, but baseline knowledge may not be sufficient to accomplish this goal. Following educational intervention, self-efficacy is one of the best surrogate metrics for behavior change. Curricula that increase knowledge and confidence levels can improve screening behaviors, but few have been tested for efficacy in this population AIMS: We assessed whether an online curriculum could reliably improve skin screening knowledge, attitudes, and behaviors of nonmedical professionals PATIENTS/METHODS: Skin-aware professionals were recruited through the Oregon Health Authority and IMPACT Melanoma TM. Participants completed a pre-survey, online training module, post-survey, and one-year follow-up survey. We evaluated participants' indicated levels of concern for suspicious and nonsuspicious lesions relative to "gold standard" physician ratings. We also assessed confidence and self-reported behavior change regarding talking to clients about skin cancer and recommending they see a provider to evaluate suspicious lesions RESULTS: The pre-survey was completed by 9872 skin-aware professionals; 5434 completed the post-survey, and 162 completed the one-year follow-up survey. Participants showed a significant improvement in ability to indicate the correct level of concern for all lesion types in concordance with "gold standard" physician ratings (p < 0.001). Participants reported increased comfort levels in discussing health-related topics with their clients posttraining CONCLUSIONS: Our training module effectively increased skin-aware professionals' knowledge, confidence, and concern for malignant lesions. Skin-aware professionals may serve as a valuable extension of the skin self-exam, but additional studies are needed to evaluate the impact of these curricula long-term, including potential downstream consequences.

Bayesian Modeling of Travel Times on the Example of Food Delivery: Part 1—Spatial Data Analysis and Processing

Online food delivery services are rapidly growing in popularity, making customer satisfaction critical for company success in a competitive market. Accurate delivery time predictions are key to ensuring high customer satisfaction. While various methods for travel time estimation exist, effective data analysis and processing are often overlooked. This paper addresses this gap by leveraging spatial data analysis and preprocessing techniques to enhance the data quality used in Bayesian models for predicting food delivery times. We utilized the OSRM API to generate routes that accurately reflect real-world conditions. Next, we visualized these routes using various techniques to identify and examine suspicious results. Our analysis of route distribution identified two groups of outliers, leading us to establish an appropriate boundary for maximum route distance to be used in future Bayesian modeling. A total 3% of the data were classified as outliers, and 15% of the samples contained invalid data. The spatial analysis revealed that these outliers were primarily deliveries to the outskirts or beyond the city limits. Spatial analysis shows that the Indian OFD market has similar trends to the Chinese and English markets and is concentrated in densely populated areas. By refining the data quality through these methods, we aim to improve the accuracy of delivery time predictions, ultimately enhancing customer satisfaction.

Monitoring of Astroviruses, Brno-Hantaviruses, Coronaviruses, Influenza Viruses, Bornaviruses, Morbilliviruses, Lyssaviruses and Pestiviruses in Austrian Bats.

Here, we report the results of a monitoring study of bat viruses in Austria to strengthen the knowledge of circulating viruses in Austrian bat populations. In this study, we analyzed 618 oropharyngeal and rectal swab samples from 309 bats and 155 pooled tissue samples from dead bats. Samples were collected from 18 different bat species from multiple locations in Austria, from November 2015 to April 2018, and examined for astroviruses, bornaviruses, coronaviruses, hantaviruses, morbilliviruses, orthomyxoviruses (influenza A/C/D viruses), pestiviruses and rhabdoviruses (lyssaviruses) using molecular techniques and sequencing. Using RT-qPCR, 36 samples revealed positive or suspicious results for astroviruses, Brno-hantaviruses, and coronaviruses in nine different bat species. Further sequencing revealed correspondent sequences in five samples. In contrast, none of the tested samples was positive for influenza viruses A/C/D, bornaviruses, morbilliviruses, lyssaviruses, or pestiviruses.

Practical steps to develop a transcriptomic test for blood doping

Abstract Blood doping remains a significant problem that threatens the integrity of sport. The current indirect method for detecting blood doping involves the longitudinal measurement of an athlete’s haematological variables and identification of suspicious results that are indicative of doping (i.e., the athlete biological passport). While this has played a significant role in the protection of clean sport, improvements are needed. The development of a transcriptomic test, that can be used to detect the use of blood doping has been discussed and researched for decades and yet, an anti-doping test that can be adopted by the World Anti-Doping Agency (WADA) is yet to be established. With recent advancements in our understanding, as well as in methods of sample collection, the possibility of a transcriptomic test that can be used by WADA, is imminent. There are, however, several practical considerations that must first be made, that will be highlighted in this perspective article.

Comparison between BIRAD Scores and Histological features in Diagnosis of Breast Neoplasia at Warith International Cancer Institution.

Introduction: Accurate evaluation and classification of breast lesions using the Breast Imaging-Reporting and Data System (BIRADS) are crucial for appropriate management and treatment planning of breast cancer. This study explores the relationship between BIRADS scores and histological features in the diagnosis of breast neoplasia at the Warith International Cancer Institution in Karbala, Iraq. Methods: This descriptive study included 520 patients diagnosed with breast neoplasia with a pre-diagnostic malignancy probability (BI-RADS 3, 4, or 5) between June 2023 and June 2024. Based on the diagnostic imaging method, patients were classified into mammography and ultrasonography groups. Clinicopathological factors, including age, BI-RADS categories, and histological findings, were analyzed. Results: Mammogram findings revealed that 63.65% of patients had benign results, while 20.77% had findings indicative of malignancy. Ultrasound findings showed that 71.35% of patients had benign results, and 11.35% had findings suggestive of malignancy. Histological analysis indicated that 23.85% of patients had malignant results, 68.07% had benign findings, and 2.31% showed suspicious results. Patients aged 50 years and above had a significantly higher likelihood of detecting malignant breast lesions through mammography compared to younger patients. At the same time, no significant association was found between age groups and ultrasound findings. Conclusion: Mammography demonstrated high sensitivity and specificity in detecting breast neoplasia, although there were false positives and negatives. Ultrasound screening also effectively detected breast abnormalities, particularly in identifying lesions that required further evaluation. The study highlights the importance of age in influencing breast cancer detection through mammography, with older patients having a higher detection rate than younger patients.

Admission Cardiotocography and Neonatal Outcomes at a Tertiary Health Facility in Southwestern Nigeria

Background: Admission cardiotocography (CTG), a noninvasive procedure, is used to indicate the state of oxygenation of the fetus on admission into the labor ward. Objective: This study assessed the association of admission CTG findings with neonatal outcome at a tertiary health facility. Materials and Methods: A prospective, observational study of 206 pregnant women who were admitted into the labor ward with singleton live pregnancies. Information on the demographic characteristics, obstetrics and medical history, admission CTG tracing, and neonatal outcome was obtained using a structured data collection form. Data were analyzed using the SPSS software version 20.0 with the level of significance set at P &lt; 0.05. Results: The admission CTG findings were normal in 73.3%, suspicious in 13.6%, and pathological in 13.1% of the women. The occurrence of low birth weight, special care baby unit (SCBU) admission, asphyxiated neonates, neonatal death, and prolonged hospital admission was significantly more frequent among those with pathological admission CTG results compared with normal and suspicious results (P &lt; 0.05). The incidence of vaginal delivery was more common when the CTG findings were normal, whereas all women with pathological CTG result had a cesarean delivery. Conclusion: Admission CTG was effective in identifying fetuses with a higher incidence of perinatal asphyxia. Neonatal outcome such as low birth weight, APGAR score, SCBU admission, and prolonged hospital admission was significantly associated with pathological CTG findings. In the absence of facilities for further investigations, prompt intervention for delivery should be ensured if admission CTG is pathological.

Sex differences in normal fetal regional brain apparent diffusion coefficient changes assessed by in utero DWI.

There are differences in the vulnerability of male and female fetal brains to adverse intrauterine exposure, preterm birth, and associated perinatal brain injury. The main objective of this study was to identify any statistically significant difference in the change of apparent diffusion coefficient (ADC) in the intracranial regions of male and female fetuses in the second and third trimesters. Diffusion-weighted imaging (DWI) was performed in 200 fetuses between 20 and 37 gestational ages (GA) with normal results or suspicious results on sonography followed by structural MRI. Pairwise ADC values of the regions of interest (ROIs) were manually delineated on either side of the cerebral white matter: frontal white matter (FWM), parietal white matter (PWM), occipital white matter (OWM), temporal white matter (TWM), basal ganglia (BG), thalamus (THA), cerebellar hemisphere (CBM), and a single measurement in the pons. The changes in these values were studied over the gestational range, along with potential sex differences and asymmetries of the cerebral hemispheres. During the third trimester, ADC values in OWM, TWM, and CBM were significantly higher in male fetuses than those in female fetuses (p < 0.05). After the correction of false-discovery rates (FDR), the difference in CBM was the only statistically significant (p = 0.0032). However, the decreased rate of ADC values in male fetuses in CWM (except for FWM), BG, THA, CBM, and pons was higher than that in female fetuses during the second and third trimesters. We have shown some differences in the intracranial regional ADC changes between male and female fetuses using in utero DWI during the second and third trimesters.

Enhancing monitoring of suspicious activities with AI-based and big data fusion.

This study provides an AI-based detection tool for the surveillance of suspicious activities using data fusion. The system leverages time, location, and specific data pertaining to individuals, objects, and vehicles associated with the agency. The study's training data was obtained from Thailand's military institution. The study focuses on comparing the efficiency between MySQL and Apache Hive for big data processing. According to the findings, MySQL is better suited for quick data retrieval and low storage capacity, while Hive demonstrates higher scalabilities for larger datasets. Furthermore, the study explores the practical utilization of web applications interfaces, enabling real-time display, analysis, and identification suspicious activity results. The web application, built with NuxtJS and MySQL, includes statistics charts and maps that show the status of suspicious items, cars, and people, as well as data filtering options. The system utilizes machine-learning algorithms to train the suspicious identification model, with the best-performing algorithms being the decision tree, reaching 98.867% classification accuracy.

The Prevalence of Central Auditory Processing Disorder in Elementary School Students of Kerman, Iran.

This study aimed to determine the prevalence of central auditory processing disorder (CAPD) in elementary school students in Kerman, Iran, during 2018-2019. This cross-sectional study was conducted on 1369 elementary school students in Kerman. These students were selected by cluster sampling from different areas of Kerman and then screened using the Buffalo Model Questionnaire (BMQ). Based on the data obtained from the questionnaire, normal children were excluded from the study. Then, children with suspected central auditory processing disorder (CAPD) underwent ear exams and were excluded from the study in case of abnormal results in the tympanic membrane examination (rapture-effusion). The remaining subjects underwent peripheral audiometry evaluation, and children with abnormal audiometry were excluded from the study. Finally, the remaining children with suspicious screening results, a normal examination, and normal audiometry underwent a specific test to detect Central auditory processing disorder. Data analysis was carried out using SPSS software. One thousand three hundred sixty-nine primary school students with a mean age of 9.15 ±2.63 years enrolled in this study. 52%% of students were male. 8.03% of them had CAPD. A statistically significant relationship was found between the prevalence of CAPD and gender (P<0.001), place of residence (P<0.001), history of middle ear inflammation (P<0.001) and history of head injury. The quality of life of these students with CAPD can be improved via timely recognition of CAPD and the provision of appropriate preventive and therapeutic facilities.

Fine Needle Aspirate Flow Cytometry's Ancillary Utility in Diagnosing Non-Hodgkin Lymphoma in the Head and Neck.

While ultrasound-guided fine-needle aspiration cell block (FNACB) is a cost-effective, expeditious, and reliable procedure used routinely in the initial evaluation of head and neck masses, it has limited efficacy in diagnosing lymphoproliferative disorders such as non-Hodgkin lymphoma (NHL). Flow cytometry performed on an fine-needle aspiration (FNA) sample [ultrasound-guided fine-needle aspirate flow cytometry or flow cytometry performed on an FNA sample (FNAFC)], has been shown to be a valuable adjunct to FNACB in the diagnosis of lymphoproliferative disorders of the spleen, kidney, and thyroid. The objective of this study was to appraise FNAFC's utility as an ancillary tool to detect NHL arising in the head and neck region in adult patients. This is a retrospective study involving 52 adult patients with head and neck lymphadenopathies and masses suspicious for lymphoproliferative disorders, who underwent ultrasound-guided FNACB and ultrasound-guided FNAFC between January 2017 and November 2022. Patient demographics, FNACB histopathological and immunophenotypic results, postoperative histopathology results (when available), and follow-up information until May 2023 were reviewed. Of the 52 FNACB samples, 23 samples (44.2%) yielded a diagnosis negative for carcinoma, 20 samples (38.5%) were nondiagnostic on account of scant cellularity, 8 samples (15.4%) were suspicious for malignancy, and a single sample (1.9%) was compatible with malignancy. Regarding FNAFC samples, 37 samples (71.2%) were diagnosed as showing no evidence for a lymphoproliferative disorder, 4 samples (7.7%) as nondiagnostic because of insufficient cell count, 4 samples (7.7%) as suspicious for a lymphoproliferative neoplasm, and 7 samples (13.5%) as compatible with a lymphoproliferative neoplasm, most frequently a B-cell lymphoma. 7 of the 11 patients (63.6%) with a suspicious/positive FNAFC result underwent excisional biopsy for additional work up. Postoperative histopathology reports corroborated FNAFC's findings in 6 patients (85.7%), while the remaining patient's (14.3%) suspicious FNAFC result was discordant with postoperative histopathology results. The other 4 patients (36.4%) did not require excisional biopsy as the hemato-oncologist deemed the information provided by the FNAFC as sufficient for the diagnosis and treatment of an NHL in the specific clinical contexts of those patients. All patients with nondiagnostic (due to insufficient cell count), inconclusive, or negative FNAFC (ie, nondiagnostic of a lymphoproliferative disorder) were followed up for a mean follow-up period of 11.9 months (range: 61.2 months; SD: 10.2 months), during which no new lymphadenopathies/masses nor progression was observed. FNAFC is a useful and practical supplementary tool in the diagnosis of lymphoproliferative disorders in the head and neck region, principally B-cell lymphoma. While conventional FNACB offers a valuable insight into the initial work up of head and neck masses, FNAFC can routinely detect small abnormal cell populations. Furthermore, in specific clinical contexts, it can reliably diagnose NHL, thereby averting the need for an excisional biopsy in a subset of patients.

Anterior Thigh Myxofibrosarcoma with Management of Wide Excision and Modified Anterior Thigh Compartment Resection : A Case Report

Introduction: Myxofibrosarcoma (MFS) is a type of malignancy from the group of malignant fibrous histiocytoma. Myfxofibrosarcoma is a type of soft tissue neoplasm that is aggressive. The clinical symptoms are not pathognomonic and the histological picture is very heterogeneous, often receiving delayed treatment and causing misdiagnosis. Complementary histochemical and immunohistochemical staining is mandatory to confirm the diagnosis of MFS. Extensive surgical treatment and followed by radiotherapy is the first choice of myxofibrosarcoma treatment.&#x0D; Case Presentation: A 54-years old woman complained of a lump on her left thigh that had been getting bigger for the past 2 years. The lump initially looked the size of a marble, then grew to the size of a tennis ball in the last 7 months. On physical examination, a mass was found in the left thigh area, a hard, fixed mass, the size of a tennis ball. Fine needle aspiration examination showed suspicious results for myxofibrosarcoma. The patient underwent a Magnetic Resonance Imaging examination in the left lower extremity area and underwent wide excision and anterior thigh compartment resection surgery.&#x0D; Discussion: Wide resection is the standard treatment for MFS [4]. The choice of procedure for each patient is different and should be based on tumor size, location, stage, surrounding neurovascular and bony elements, as well as functional and cosmetic considerations [4]. The minimum resection margin in MFS is at least 1 cm which aims to minimize the risk of local recurrence [4]. The recommended resection margin is at least 2 cm for MFS resection [4]. We had plan a 2 cm margin of the entire preoperative MRI enhancement area. It should be noted that the local recurrence rate for MFS in margin-negative resections is relatively high compared with other STS subtypes.&#x0D; Conclusion: We recommend Wide Excison and Modified Anterior Thigh compartment Resection is recommended procedure for anterior thigh myxofibrosarcoma. This procedure involves preserving uncontaminated thigh neurovascular, and only resecting one of the sarcoma-infiltrated muscle heads and preserving the other quadriceps muscle head of the thigh to maintain knee extension function. This paper is the first report on the successful treatment of anterior thigh myxofibrosarcoma without weakness of knee extension complication.

Evaluation of Neurodevelopmental Screening Test Scores in Children with Vitamin B12 Deficiency.

Vitamin B12 deficiency can lead to hematological findings, neurological symptoms, and neurodevelopmental delay. The aim of this study was to investigate the impact of vitamin B12 deficiency on the neurodevelopment of children. This study included 89 children aged between 6 and 24 months without any complaints; 44 of these were evaluated in the study group (serum vitamin B12 <300 pg/mL) and 45 in the control group (serum vitamin B12 ≥300 pg/mL). Denver Developmental Screening Test II (DDST-II) and the Social Communication Area Screening Test (SCAST) were evaluated in each participant. The mean vitamin B12 level in the study group was 206.11 ± 9.1 pg/mL, and in the control group, it was 540.65 ± 24.1 pg/mL. When DDST-II results were analyzed, the rate of getting suspicious and abnormal results in the study group was significantly higher compared with the control group (p = 0.001). The rate of the "risky" SCAST results of the cases was found to be statistically significantly higher in the study group than in the control group (p = 0.003). Vitamin B12 values of patients with suspicious or abnormal DDST-II results and with risky SCAST results were found to be statistically significantly lower than those with normal neurodevelopmental screening tests results (p = 0.001 and p = 0.001, respectively). Vitamin B12 deficiency can lead to neurodevelopmental delay in children, even in the absence of neurological and hematological symptoms or complaints, which highlights the importance of early detection and intervention of vitamin B12 deficiency.

Diagnostic performance of molecular testing in indeterminate (Bethesda III and IV) thyroid nodules with Hürthle cell cytology

BackgroundIndeterminate thyroid nodules with Hürthle cell cytology remain a diagnostic challenge. The low benign call rate and positive predictive value of first-generation molecular tests precluded their use to rule out malignancy. We examined the diagnostic performance of current tests. MethodThis subset analysis of our prospective randomized trial compared the benign call rate and positive predictive value of Afirma Gene Sequencing Classifier and Thyroseq v3 in Bethesda III and IV nodules with Hürthle cell cytology. Molecular test samples were obtained at initial fine-needle aspiration (8/2017–7/2022) and reflexively sent for processing. ResultsMolecular testing was performed on 140 Hürthle cell nodules. Of 79 nodules tested with the Afirma Gene Sequencing Classifier, the benign call rate was 84% (66/79). Nine of 66 nodules with benign results were resected, with no malignancies. Twelve of 13 nodules with suspicious results were resected, revealing 3 malignancies—2 papillary thyroid carcinomas and one Hürthle cell carcinoma (positive predictive value 25%). Of 61 nodules tested with Thyroseq v3, the benign call rate was 56% (34/61; (P < .01 versus Afirma Gene Sequencing Classifier). Five of 34 nodules with negative results were resected, with no malignancies. Nineteen of 27 nodules with positive results were resected, revealing 3 malignancies—2 papillary thyroid carcinomas and 1 Hürthle cell carcinoma (positive predictive value 16%). ConclusionThe high benign call rate of current molecular tests in Hürthle cell nodules strengthens their value in enabling patients to avoid surgery.

Revisitation of thyroid lesions in natives from hilly region: A four years perspective

Clinically palpable thyroid nodules pose a challenge in diagnosis and management for surgeons and pathologists as thyroid malignancies may show overlapping characteristics with their benign counterparts in terms of physical characteristics, hormonal levels and imaging details. This study was aimed to revisit the spectrum of thyroid lesions in surgically resected specimens, their clinicopathological characteristics and to compare the cytological and imaging findings in discrepant cases.The present retrospective study retrieved a total of 69 cases of thyroid resection specimens with available relevant demographic, clinicoradiological and cytological findings. The histopathological diagnosis was considered gold standard.Colloid goitre (37.7%) and papillary carcinoma (17.4%) were found to be the commonest non-neoplastc and neoplastic lesions respectively. Peak incidence in 20-40 years of age group and M:F ratio of 1:3.6 in overall thyroid disorders was noted. 08 discrepent cases were observed while comparing histological diagnosis with radiological and /or cytological findings.Histopathological diagnoses were in agreement with imaging findings and /or FNAC results in most of the cases, however, patients with indeterminate or suspicious FNAC results, need to be followed-up for early surgical intervention if required.

Binary subclassification scheme (AUS-Nuclear versus AUS-Other) adequately risk-stratifies thyroid fine needle aspiration specimens classified as Atypia of Undetermined Significance

The Bethesda System for Reporting Thyroid Cytopathology previously described 4subclassesof atypia within the Atypia of Undetermined Significance (AUS) category: nuclear (AUS-Nuc), architectural (AUS-A), oncocytic (AUS-Onc), and atypia not otherwise specified (AUS-NOS). Accumulating evidence supports a binary AUS subclassification scheme based primarily on the presence of nuclear atypia only. The purpose of this study is to compare the risk stratification of binary versus 4-tier AUS subclassification systems among AUS nodules with molecular and/or histologic follow-up. Thyroid aspirates classified as AUS and tested using Afirma (Veracyte, Inc.) between 6/2013 and 7/2021 were included. For resected nodules, histological classification was considered as the final outcome. For unresected nodules, benign Afirma results were considered low-risk outcomes, similar to histologically benign nodules. Suspicious or nondiagnostic Afirma results were considered indeterminate outcomes. The prevalence of outcomes warranting surgery (noninvasive follicular thyroid neoplasm with papillary-like nuclear features [NIFTP] or cancer) was calculated for each AUS subclass. A total of 559 AUS nodules with Afirma testing were identified. Excluding nodules with indeterminate molecular outcomes, NIFTP/cancer prevalence for AUS-Nuc was 21% (57/266), which was higher than that for AUS-A (6%, 11/188), AUS-Onc (8%, 4/53), and AUS-NOS (0%, 0/9). A binary AUS subclassification scheme based on nuclear atypia showed a significant difference in NIFTP/cancer prevalence (21% versus 6%, P < 0.0001). Binary reporting of AUS subclasses based on nuclear atypia distinguishes cases with a higher risk of NIFTP/cancer. There is a low but non-negligible prevalence of NIFTP/cancer in cases without nuclear atypia.

THU678 Real-world Performance Of Afirma Genomic Sequencing Classifier (GSC) In A Community Healthcare Setting

Abstract Disclosure: V. Master: None. J. Syeda: None. S. Charatz: None. D. Reidy: None. K. Clary: None. Introduction: Indeterminate thyroid nodules pose a significant clinical challenge due to their potential risk of malignancy. The Afirma GSC has emerged as a valuable tool for the non-invasive management of these nodules. However, its real-world performance in community healthcare settings remains poorly understood. Aim: Comparison of GSC performance in a community healthcare setting to the validation study (VS) metrics. Method: A retrospective study was conducted in a community endocrine practice, where 91 Afirma GSC samples were obtained from patients who had either suspicious cytology or atypia of undermined significance (AUS) between 1/1/2021 and 12/31/2022. Ten samples were excluded due to insufficient material. Surgical pathology was used as the gold standard for diagnosis. Molecular benign results without surgical pathology were considered true negatives, and 2 unoperated patients with suspicious results were excluded from analysis. We calculated observed positive predictive value (oPPV) and observed specificity (oSP) to account for these exclusions. Non-invasive follicular neoplasm with papillary-like features is considered malignant. The prevalence of thyroid cancer in the study population was 19%. Results are compared to previously published VS of 191 samples. Result: Our study showed a higher accuracy of 89% of the Afirma GSC in our community healthcare setting, with a sensitivity (SN) of 93%, oSP of 88%, oPPV of 63%, and negative predictive value (NPV) of 98%. In comparison, the VS had a SN of 91%, SP of 68%, PPV of 47%, NPV of 96%, and accuracy of 74%. Additionally, our study showed a higher benign call rate (BCR) of 70% compared to 54% in the VS. Conclusion: Our study provides evidence of the real-world performance of the Afirma GSC and supports its use as a non-invasive tool for the management of indeterminate thyroid nodules. Better oSP and oPPV are suggestive of higher yield of cancers for resected nodules based on suspicious GSC.

THU680 Cytologic And Molecular Assessment Of Isthmus Thyroid Nodules

Abstract Disclosure: S. Jasim: None. Y. Chen: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. R. Jiang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. Y. Hao: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J. Huang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J.P. Klopper: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. R.T. Kloos: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. T.C. Brown: None. Thyroid nodules arising in the isthmus are more likely to be malignant and demonstrate more aggressive behavior relative to thyroid nodules from either thyroid lobe. Preliminary studies of papillary thyroid cancers (PTC) studied in The Cancer Genome Atlas (TCGA) indicate molecular profiles that may explain the more aggressive phenotype of isthmic PTC, including an increased ERK signaling molecular profile. The goal of this study was to interrogate the Veracyte Afirma thyroid nodule database and assess cytologic and molecular differences of thyroid aspirates sent for Afirma Genomic Sequencing (GSC) testing from isthmus nodules relative to lobar nodules. Samples from isthmus nodules represented 4.8% of all samples. Most Afirma nodules had indeterminate cytology (ITN, Bethesda III or IV) and there were more ITN samples from the thyroid lobes (95.7%) compared to the isthmus (91.8%). For Bethesda V or VI nodules, the proportion from the isthmus was almost double that from the lobes (8.2% vs 4.3%). There were no significant differences observed in the Afirma benign or suspicious result of ITN samples comparing isthmus versus lobar location. Analysis of molecular alterations in Afirma suspicious nodules from ITN and Bethesda V-VI nodules showed that isthmus nodules had twice the frequency of BRAFV600E mutations compared to lobar nodules (21% vs 10%), an increased frequency of ALK/NTRK/RET fusions (4.6% vs 2.5%), and a lower frequency of NRAS (7.7% vs 13%) and HRAS (4.5% vs 8.2%) variants (all comparisons significant (p &amp;lt; 0.001)). Additionally, isthmus nodules had significantly higher BRAF-like signature, ERK signaling, and follicular-mesenchymal transition scores compared to lobar nodules (p &amp;lt; 0.01). In summary, thyroid nodules sent for Afirma molecular testing arising from the isthmus are more likely to have Bethesda V and VI cytology and, amongst Afirma suspicious ITN and Bethesda V and VI lesions, have higher levels of molecular markers of aggressiveness relative to lobar nodules. This study expands upon the data seen in PTCs from the TCGA as most thyroid tumors referred for molecular testing have Bethesda III and IV cytology and thus are enriched for follicular lesions including follicular variants of PTC and follicular carcinomas. Future studies should investigate the final histopathology of these molecularly tested isthmus nodules as well as oncologic outcomes. Presentation: Thursday, June 15, 2023

Maternal Malignancy After Atypical Findings on Single-Nucleotide Polymorphism-Based Prenatal Cell-Free DNA Screening

ABSTRACT Technological advances in prenatal testing are allowing for earlier screening to detect fetal aneuploidies, infection, or abnormalities. Noninvasive tests in particular have enabled clinicians to screen early in pregnancy for conditions that severely affect fetal and neonatal outcomes (trisomies 21, 18, and 13, among others). Some of these methods rely on cell-free DNA (cfDNA) circulating in the maternal blood stream; although cfDNA can be released by the placenta, malignancy can be another cause for the release of cfDNA. The detection of such malignancies on noninvasive prenatal tests is rare but occurs. This study was designed to assess the incidence of cfDNA results indicating maternal malignancy and compare these findings to the existing literature. This was a retrospective cohort study, including data obtained from a commercial laboratory that performed single-nucleotide polymorphism (SNP)–based noninvasive prenatal screening between January 2015 and October 2021. Screenings were considered suggestive of malignancy if retrospective bioinformatics and SNP plots suggested multiple maternal copy number variants for at least 2 chromosomes; the laboratory returned these tests as fetal uninterpretable results. Of 2,004,428 samples included in the analysis, 38 (0.002%, or 1 in 52,748) were considered suggestive of malignancy. For 30 patients where follow-up was completed, health outcomes were analyzed for mother and child with maternal malignancy observed in 20 of them (66.7%). Six individuals had a preexisting diagnosis of cancer, 2 of which had a personal history of cancer but were thought to be in remission. Malignancies included lymphoma (10 patients), breast cancer (5 patients), and colon cancer (3 patients). Fetal outcomes for 15 of these patients were normal, with a few abnormal outcomes in the others; negative outcomes included fetal abnormality, multiple soft markers on prenatal ultrasound, and fetal growth restriction. Of the 10 patients without reported malignancy, 2 had identified fetal triploidy, 1 had maternal glomerulonephritis, and 1 had uterine leiomyomas. Of the original 30 patients with results suggestive of malignancy, 6 had no issues reported on follow-up. The findings reported in this study are similar to previous findings of maternal malignancy detected by noninvasive prenatal screenings. The prevalence of maternal malignancy identified in this study was lower than in previous studies, which estimated the prevalence to range from 1/2000 to 1/21,000. The percentage of patients with a confirmed malignancy after suspicious results in this study was 67% and has ranged from 8% to 73% in other studies. Some patients who had an identified malignancy were diagnosed as long as 11 months after the noninvasive prenatal screening; this indicates that longitudinal follow-up may result in higher rates of identified malignancy among those who have screening results suggestive of malignancy. Clinically, these findings highlight the need for information given to expectant mothers about incidental findings pertaining to noninvasive prenatal screenings, as well as the importance of reporting suspicious results of these screenings. Further research should focus on determining rates of underreporting for maternal malignancy, as well as obtaining more complete follow-up data and potentially developing a standardized procedure or diagnostic workup to determine the true incidence.

Evaluation of elastosonography and fine-needle aspiration biopsy results in the diagnosis of thyroid nodules

Objective The aim of our study is to investigate the importance of strain sonoelastography (SSE) in the diagnosis of thyroid nodules and in the selection of indications for fine-needle aspiration biopsy (FNAB). Materials and methods We included 481 patients who visited our clinic between 2019–2022 with thyroid nodules in the study and used a stepwise diagnostic approach to choose patients to perform surgery on and follow-up. All patients were ranked into 2 groups: Group 1 included 135 (28,1%) patients were assessed as SSE along with traditional examinations. The 2nd group included 346 (71.9%) patients who underwent ultrasound examination using SE, only the hard nodule or hard regions of the nodule detected by SSE were obtained with FNAB. We followed up on nodules with benign FNAB results, and nodules with suspicious or malignant results underwent thyroidectomy. Histopathology results of surgically removed nodules were compared with SSE and FNAB results. AUROC was the primary, while sensitivity, specificity, PPV and NPV were the secondary outcome. Results Out of 481 patients, 420 (87.3%) were female, 61 (12.7%) were male, and the age range was 17–83 (CI=45.57±25.9). The mean nodule size was 23.33±16.7 mm. After evaluating elastography results, FNAB was performed on 346 (71.9%) nodules. Surgical treatment was performed in 114 (group 1) (84.4%) of 135 patients, benign tumors were diagnosed in 107 (93.8%), and malignant tumors in 7 (6.2%). Surgical treatment in group 2 was performed in 146 (42.2%) of 346 patients, benign tumors were detected in 105 (71.9%) patients, and malignant in 41 (28.9%). The combined use of the sonoelastography and fine-needle aspiration biopsy contributed to a significant increase in the frequency of detection of thyroid nodules of malignant structure, which amounted to 28.9% in patients of the main group (versus 6.2% in patients of the control group) and a decrease in the frequency of surgical interventions by more than 2 times in patients of the second group. The area of the ROC curve for SSE was S=0.851±0.029; 95% CI (0.794 to 0.908); P=0.000. It is a statistically significant marker in the diagnosis of thyroid nodules. The most important marker in the diagnosis of thyroid nodules was the FNAB test: S=0.874±0.034; 95% CI (0.807 to 0.940); P =0.000. Sensitivity, specificity, PPV, and NPV of elastosonography of the I group were 42.9±18.7%, 96.3±1.8%, 42.9%, 96.3; of II group 68.3±7.3%, 87.6±3.2%, 68.3%, 87.6%; FNAB 90.2±4.6%, 90.5±2.9%, 76.2%, 91.3%, respectively. Conclusion Combined use of SE and Bethesda system was able to detect malignancy in the early stages and to reduce the number of operations.