Diagnosing thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology with the deep convolutional neural network.
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ABSTRACT:
SUBMITTER: Youn I
PROVIDER: S-EPMC8501016 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe management of thyroid nodules classified as atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) has been a subject of ongoing debate. Therefore, the aim of this study was to investigate a cost-effective approach for managing these nodules by combining BRAFV600E mutation analysis with the guidelines provided by the American Thyroid Association (ATA) or the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TIRADS).MethodsThis study included 762 AUS/FLUS nodules in 551 patients with a postoperative pathology. A preoperative BRAFV600E gene test and an evaluation using the ATA guidelines and ACR-TIRADS were performed. Two combined diagnostic approaches were employed: In method 1, all nodules underwent BRAFV600E gene testing, and nodules testing positive for BRAFV600E or for risk stratification systems (RSSs) were diagnosed as malignant, while those with negative results in both tests were considered benign. In method 2 (modified combination method), nodules were reclassified into low-risk (category 2 and 3 in the ATA guidelines and ACR-TIRADS), medium-risk (category 4), and high-risk (category 5) groups based on the malignancy rate of the RSSs. BRAFV600E gene testing was applied only with the medium-risk group. Nodules with positive BRAFV600E mutation were upgraded to the high-risk group, while negative cases remained in the medium-risk group.ResultsBoth malignancy rates and positive BRAFV600E mutation rates increased with the increase in RSS category (P<0.001). The combination of ACR with BRAFV600E gene testing significantly improved the area under the curve (AUC) compared to the use of ACR or BRAFV600E alone (the AUCs for ACR combined with BRAFV600E, modified ACR combined with BRAFV600E, ACR alone, and BRAFV600E alone were 0.875, 0.878, 0.832, and 0.839, respectively; P<0.05 for both combinations vs. ACR or BRAFV600E alone). Similarly, ATA combined with BRAFV600E showed significant improvements in AUC compared to ATA alone (the AUCs for ATA combined with BRAFV600E, modified ATA combined with BRAFV600E, and ATA alone were 0.851, 0.846, 0.809, respectively; P<0.001 for both combination methods vs. ATA alone), but there was no significant difference observed compared to using BRAFV600E alone (P=0.450 and P=0.680 for both combination methods vs. BRAFV600E). Notably, the AUC of ACR combined with BRAFV600E was greater than that of ATA combined with BRAFV600E (P=0.047 and P=0.007 for both combination methods, respectively). There were no significant differences in diagnostic performance between the two combination approaches (P=0.428 for ACR combined with BRAFV600E and P=0.314 for ATA combined with BRAFV600E). Performing BRAFV600E gene testing only on the medium-risk groups (modified combination method) significantly reduced the rate of BRAFV600E gene testing (P<0.001) without increasing the false-negative rate (P=0.818 and P=0.394 for ACR and ATA, respectively).ConclusionsIncorporating the BRAFV600E gene test exclusively for nodules in the medium-risk group significantly improved diagnostic efficacy, reduced the utilization of gene tests, and maintained a consistent false-negative rate.
| S-EPMC10784030 | biostudies-literature
Project description:Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in thyroid fine needle aspiration (FNA) is a challenging category. The malignancy risk is different by multiple factors and subsequent management strategy is inconclusive. Therefore, we analyzed the malignancy risk of AUS/FLUS according to radiological and clinical features. A total of 687 nodules that had been initially diagnosed as AUS/FLUS were retrospectively reviewed from 6365 thyroid FNAs between 2011 and 2014. The ultrasonographic (US) features were categorized using the Korean Thyroid Imaging Reporting and Data System. Radiological and clinical features were compared according to the second FNA results or histologically confirmed results from surgery. Repeat FNA was performed on 248 (36%) nodules, and 49 (7%) nodules underwent immediate surgery. Among the 248 nodules subjected to repeated FNA, 49 (20%) nodules were diagnosed again as AUS/FLUS, 123 (50%) were found to be benign, and 47 (19%) were diagnosed as follicular neoplasm, suspicious for malignancy or malignant. Among histologically confirmed nodules, the US features were more unfavorable in malignant nodules, and hypo- or anechogenicity was associated with a higher risk of malignancy after adjusting for age, size, and other US features (P < 0.01). In conclusion, we observed that malignant nodules tended to show unfavorable US features, especially hypo- or anechogenicity. Age, sex, and thyroid function were not significantly associated with malignancy risk. We also found out that malignancy risk was not different between the group which underwent immediate operation following the AUS/FLUS diagnosis and the group which underwent repeated FNA after the initial diagnosis.
| S-EPMC6091291 | biostudies-literature
Project description:We modified the nondiagnostic/unsatisfactory category of the Bethesda system for reporting thyroid cytopathology to inform cytopathologic adequacy to better stratify the malignancy risk. Malignancy rates from 1,450 cytopathologic specimens not satisfying adequacy criteria from April 2011 to March 2016 were calculated based on sub-classification of the nondiagnostic/unsatisfactory category and sonographic patterns using matched surgical pathology. Rates were compared with those of 1,446 corresponding adequate specimens from July to December 2013. Upon resection, 63.2% of nondiagnostic, 36.7% of unsatisfactory?+?benign, 72.5% of unsatisfactory?+?atypia (follicular lesion) of undetermined significance, 98.1% of unsatisfactory?+?suspicious for malignancy, and 100.0% of unsatisfactory?+?malignant cases were confirmed to be malignant on surgical pathology. In nodules with inadequate specimens, those with high suspicion sonographic patterns had a malignancy rate (93.2%) higher than the others (45.5%) (p?<?0.001). Nodules with unsatisfactory?+?benign specimens had a higher malignancy rate (36.7%) than satisfactory benign specimens (14.3%) (p?=?0.020). For atypia (follicular lesion) of undetermined significance, the malignancy rate of inadequate specimens (72.5%) was higher than that of adequate specimens (51.3%) (p?=?0.027). Sparse cellular samples with a few groups of benign follicular cells should not represent a benign lesion. There might be value in qualifying atypia (follicular lesion) of undetermined significance cases less than optimal.
| S-EPMC6131141 | biostudies-literature
Project description:BackgroundMicroRNA (miR) expression signatures are proposed to be able to differentiate thyroid cancer from benign thyroid lesions. We selected eight miRs (miR-146b, -221, -187, -197, -346, -30d, -138, and -302c) to examine the potential use of miRs to supplement diagnostic cytology in cases designated as "atypia of undetermined significance."MethodsmiR expression was measured in thyroid fine needle aspiration (FNA) specimens by quantitative polymerase chain reaction. Gene expression analyses and linear discriminant analysis (LDA) were performed in a training sample set (n=60) to obtain a classification rule to predict FNA cases as benign or malignant. The predictions were cross-validated by comparing with the corresponding histological diagnoses. A validation sample set (n=68) was further tested with the established four-miR LDA classification rule.ResultsA set of four miRs (miR-146b, -221, -187, and -30d) was identified that could differentiate malignant from benign lesions. A four-miR LDA classification rule was obtained and used to predict FNA cases as benign or malignant. For the training sample set, we obtained a diagnostic accuracy of 93.3%, sensitivity of 93.2%, specificity of 93.8%, positive predictive value (PPV) of 0.98, and negative predictive value (NPV) of 0.83. For the validation sample set, we obtained a diagnostic accuracy of 85.3%, sensitivity of 88.9%, specificity of 78.3%, PPV of 0.89, and NPV of 0.78. For the 30 atypia cases in the validation sample set, we obtained a diagnostic accuracy of 73.3%, sensitivity of 63.6%, specificity of 78.9%, PPV of 0.64, and NPV of 0.79. Based on the miR predictions, we classified the atypia cases predicted as "malignant" into "high risk" and those predicted as "benign" into "low risk" categories. While thyroid carcinomas, particularly papillary thyroid carcinomas (PTCs), were relatively enriched in the high-risk category, this particular miR panel is subject to inaccurate results in follicular neoplasias in atypia cases.ConclusionsWe demonstrate that miR amplification from FNA samples is feasible and that the particular four miR profile in this study can identify PTCs. However, further refinement is required for application to FNA cytology of "atypia of undetermined significance" cases due to low accuracy in classifying follicular neoplasias.
| S-EPMC3247703 | biostudies-literature
Project description:BackgroundThe follicular variant of papillary thyroid cancer (FVPTC), especially the encapsulated non-invasive subtype, is a controversial entity. Recent study suggested using 'non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)' for these indolent carcinomas. We evaluated the impact of reclassification from non-invasive encapsulated FVPTCs (EFVPTCs) to NIFTPs in the diagnosis of thyroid nodules with architectural atypia.MethodsWe reviewed 1301 thyroid nodules with architectural atypia in core needle biopsy (CNB) specimens obtained from March 2012 to February 2013. Nodules were classified into atypia of undetermined significance with architectural atypia (AUS-A, 984, 76%) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN, 317, 24%). Among them, diagnostic surgery was performed in 384 nodules (30%).ResultsIn total, 160 nodules (42%) presented final malignant diagnoses including 39 non-invasive encapsulated FVPTCs (10%). The malignancy rate was estimated to be 7-35% in AUS-A nodules and 28-49% in FN/SFN nodules. After reclassification, the malignancy rate was much decreased and estimated to be 5-24% in AUS-A nodules, and 23-39% in FN/SFN nodules. Thyroid nodules with final malignant diagnoses were significantly more likely to have a FN/SFN CNB diagnosis, malignant US features and concomitant nuclear atypia in CNB specimens. However, these factors could not differentiate NIFTPs from other malignancies.ConclusionsAfter reclassification of non-invasive EFVPTCs to NIFTPs, the malignancy rate of thyroid nodules with architectural atypia in CNB specimens was decreased. However, there were no preoperative factors differentiating other malignancies from NIFTPs. The presence of malignant US features or concomitant nuclear atypia might help clinicians deciding diagnostic surgery but, these features also might indicate NIFTPs.
| S-EPMC5147963 | biostudies-literature
Project description:BACKGROUND: Following fine needle aspiration, 15-30% of thyroid nodules are not clearly benign or malignant. These cytologically indeterminate nodules are often referred for diagnostic surgery, though most prove benign. A novel diagnostic test measuring the expression of 167 genes has shown promise in improving pre-operative risk assessment. We evaluated this test in a prospective, multicenter study. METHODS: Over 19 months, we performed a prospective study at 49 clinical sites enrolling 3,789 patients and collecting 4,812 samples from thyroid nodules >1cm requiring evaluation. We obtained 577 cytologically indeterminate aspirates with corresponding histopathology of excised lesions on 413. Central blinded histopathologic review served as the reference (“gold”) standard. After applying inclusion criteria, gene expression classifier results were obtained for 265 indeterminate nodules used in this analysis, and performance was calculated. RESULTS: 85 of 265 indeterminate nodules were malignant. The gene expression classifier correctly identified 78 of 85 as ‘suspicious’ (92% sensitivity, [84%-97%] 95% CI). Specificity was 52%, [44%-59%]. The negative predictive value was 95%, 94%, and 85%, respectively, for aspirates with AUS/FLUS, FN/SFN, or ‘suspicious’ cytology. Analysis of 7 false negative cases revealed 6 with a paucity of thyroid follicular cells, suggesting that insufficient sampling of the nodule had occurred. CONCLUSIONS: Though individualized clinical care is recommended, these data support consideration of a conservative approach for most patients with indeterminate FNA cytology and benign gene expression classifier results.
2012-06-25 | GSE34289 | GEO
Project description:BackgroundThe classification of nodules by Thyroid Imaging Reporting and Data Systems (TIRADS) is important in guiding management. Whether sensitivity in identifying thyroid cancers varies with thyroid cancer phenotype remains unclarified.MethodsThe ultrasound (US) characteristics of nodules of 26,908 nodular goiter patients were recorded. Fine-needle aspiration cytology (FNA) was performed in all nodules >1 cm irrespective of US findings (n = 25,025) and in nodules between 5 mm and 10 mm with suspicious US characteristics (n = 1,883). Of the 3281 operated cases, 221, 30, and 23 were papillary (PTC), follicular (FTC), and medullary (MTC) cancers, respectively. The US-based indication of FNA, as defined by EU-TIRADS scores, combined with lesion size, was calculated. This study design is unique in avoiding the common selection bias when TIRADS' sensitivity is tested in a cohort selected for FNA and surgery based on the same US characteristics on which TIRADS is based.ResultsThe EU-TIRADS score influences decision of FNA in the 10-20 mm range. In such nodules (n = 118), the number of suspicious features (marked hypoechogenicity, microcalcifications, irregular shape, and irregular border) per lesion was lower in FTC (0.7 ± 0.6) than in PTC (1.7 ± 1.0) or MTC (1.8 ± 0.7; p < 0.02), resulting in EU-TIRADS scores of 4.1 ± 0.6, 4.8 ± 0.3, and 4.9 ± 0.2, respectively (p < 0.01). The EU-TIRADS-based FNA indication rate was lower in FTC (55.5%) compared to PTC (85.0%) and MTC (88.9%) (p=0.02).ConclusionsEU-TIRADS-defined suspicious US features are less common in FTC than in PTC and MTC. Therefore, a substantial number of FTCs in the 10-20 mm range escape surgery.
| S-EPMC8490077 | biostudies-literature
Project description:Fluorescence lifetime imaging microscopy of a fluorescence probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide (o-BMVC), provides an objective method for preoperative diagnosis of fine-needle aspiration (FNA) of thyroid nodules. The key of this o-BMVC test of FNA smears is the measurement of the digital number of o-BMVC foci in the nucleus. Thus, there are three categories classified in the o-BMVC test, which are nondiagnostic for unsatisfactory samples, benign for less numbers of o-BMVC foci, and malignant for more numbers of o-BMVC foci. The discrimination of indeterminate (including atypia, follicular neoplasm, suspicious) cytology into benign or malignant cases can reduce diagnostic uncertainty and benefit clinical decision making. This pilot study strongly suggests that the o-BMVC test is an invaluable method for diagnosing FNA samples. Particularly, the combination of FNA cytology and the o-BMVC test holds great promise to improve the efficacy of diagnosis and reduce the healthcare costs.
| S-EPMC8648827 | biostudies-literature
Project description:BACKGROUND: Following fine needle aspiration, 15-30% of thyroid nodules are not clearly benign or malignant. These cytologically indeterminate nodules are often referred for diagnostic surgery, though most prove benign. A novel diagnostic test measuring the expression of 167 genes has shown promise in improving pre-operative risk assessment. We evaluated this test in a prospective, multicenter study. METHODS: Over 19 months, we performed a prospective study at 49 clinical sites enrolling 3,789 patients and collecting 4,812 samples from thyroid nodules >1cm requiring evaluation. We obtained 577 cytologically indeterminate aspirates with corresponding histopathology of excised lesions on 413. Central blinded histopathologic review served as the reference (“gold”) standard. After applying inclusion criteria, gene expression classifier results were obtained for 265 indeterminate nodules used in this analysis, and performance was calculated. RESULTS: 85 of 265 indeterminate nodules were malignant. The gene expression classifier correctly identified 78 of 85 as ‘suspicious’ (92% sensitivity, [84%-97%] 95% CI). Specificity was 52%, [44%-59%]. The negative predictive value was 95%, 94%, and 85%, respectively, for aspirates with AUS/FLUS, FN/SFN, or ‘suspicious’ cytology. Analysis of 7 false negative cases revealed 6 with a paucity of thyroid follicular cells, suggesting that insufficient sampling of the nodule had occurred. CONCLUSIONS: Though individualized clinical care is recommended, these data support consideration of a conservative approach for most patients with indeterminate FNA cytology and benign gene expression classifier results. 265 cytologically indetermine samples, 47 cytologically benign and 55 cytologically malignant samples
2012-06-24 | E-GEOD-34289 | biostudies-arrayexpress
Project description:BACKGROUND:Fine-needle aspiration (FNA) cytology is a common approach to evaluating thyroid nodules, although 20% to 30% of FNAs have indeterminate cytology, which hampers the appropriate management of these patients. Follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN) is a common indeterminate diagnosis with a cancer risk of approximately 15% to 30%. In this study, the authors tested whether the most complete next-generation sequencing (NGS) panel of genetic markers could significantly improve cancer diagnosis in these nodules. METHODS:The evaluation of 143 consecutive FNA samples with a cytologic diagnosis of FN/SFN from patients with known surgical outcomes included 91 retrospective samples and 52 prospective samples. Analyses were performed on a proprietary sequencer using the targeted ThyroSeq v2 NGS panel, which simultaneously tests for point mutations in 13 genes and for 42 types of gene fusions that occur in thyroid cancer. The expression of 8 genes was used to assess the cellular composition of FNA samples. RESULTS:In the entire cohort, histologic analysis revealed 104 benign nodules and 39 malignant nodules. The most common point mutations involved the neuroblastoma RAS viral oncogene homolog (NRAS), followed by the Kirsten rat sarcoma viral oncogene homolog (KRAS), the telomerase reverse transcriptase (TERT) gene, and the thyroid-stimulating hormone receptor (TSHR) gene. The identified fusions involved the thyroid adenoma associated (THADA) gene; the peroxisome proliferator-activated receptor ? (PPARG) gene; and the neurotrophic tyrosine kinase, receptor, type 3 (NTRK3) gene. Performance characteristics were similar in the retrospective and prospective groups. Among all FN/SFN nodules, preoperative ThyroSeq v2 performed with 90% sensitivity (95% confidence interval [CI], 80%-99%), 93% specificity (95% CI, 88%-98%), a positive predictive value of 83% (95% CI, 72%-95%), a negative predictive value of 96% (95% CI, 92%-100%), and 92% accuracy (95% CI, 88%-97%). CONCLUSIONS:The current results indicate that comprehensive genotyping of thyroid nodules using a broad NGS panel provides a highly accurate diagnosis for nodules with FN/SFN cytology and should facilitate the optimal management of these patients.
| S-EPMC7737376 | biostudies-literature