Malignant Nodules Research Articles

8414 Utilization of Cell Free DNA Integrity Index to Differentiate Benign from Malignant Thyroid Nodules

Abstract Disclosure: S. Tarafdar: None. S. Dutta: None. P. Mukhopadhyay: None. N.P. Bhattacharya: None. S. Ghosh: None. Introduction: Recent advances in molecular genetics have evaluated a potential role for plasma cell-free DNA (cfDNA) integrity index as a non-invasive cancer marker. Data on cfDNA integrity in differentiated thyroid cancer is sparse and needs to be investigated further. Aim of the study: The purpose of this study is to investigate the hypothesis that longer DNA strands in plasma may serve as a marker for thyroid cancer. Methods: Patients presenting with thyroid nodules underwent ultrasonography with Thyroid Image Reporting and Data Systems (TIRADS) scoring and FNAC (Bethesda classification).Patients with Bethesda 3, 4, 5, and 6 had surgery and confirmation by histopathology. Patients with Bethesda 2 presenting with compressive symptoms and cosmetic concerns underwent surgery; the remaining patients were considered benign based on clinical follow-up, USG, and FNAC characteristics. Blood sample collected prior to FNAC was used to extract and quantify cfDNA. To assess the integrity index 180/67, 306/67, and 476/67 for the APP gene, we used a quantitative real-time PCR (qPCR) method based on the quantification of four amplicons of varying lengths (67, 180, 306, and 476 bp, respectively). Because culture cells had extremely intact genomic DNA, the genomic DNA obtained from the MDA-T32 papillary thyroid cancer cell line was utilised as a reference to estimate the relative DNA strand integrity in plasma DNA. To determine the (ΔCt) value for 67,180, 306, and 476 bp, the Ct value of the sample was subtracted from that of the MDA-T32 control. Results: A total of 161 subjects were recruited, of these 92 were benign and 69 had differentiated thyroid cancer(confirmed by histopathology). Using the 180/67 bp integrity index benign thyroid nodule patients had significant lower value (median 0.39, 95% CI: 0.33-0.46) compared to patients with differentiated thyroid cancer (median 0.62, 95% CI: 0.56-0.68). A cfDNA integrity index of 180/67 bp could significantly differentiate between benign and malignant thyroid nodules (P<0.001). However, there was no significant difference between malignant and benign thyroid nodules based on the cell free DNA integrity indexes of 306/67 and 476/67. Conclusions: The cfDNA integrity score of 180/67 exhibits potential as a circulating marker for the detection of thyroid nodules and as a means of monitoring cfDNA fragmentation in patients with thyroid cancer. However, further confirmation through prospective trials is necessary. Presentation: 6/3/2024

8791 A Case of Hyperfunctioning Thyroid Nodules Evaluated for Thyroid Metastasis in the Setting of Oropharyngeal Squamous Cell Carcinoma

Abstract Disclosure: M. Alashoor: None. J. Gogineni: None. A. Bakar: None. Introduction: Identifying and evaluating hyperfunctioning thyroid nodules in the setting of metastatic head and neck cancers represents a diagnostic challenge that may result in inaccurate identification of perithyroidal lymph node metastasis as malignant or metastatic thyroid nodules with standard workup. Case presentation: A 72-year-old male with a history of stage IV metastatic oropharyngeal squamous cell carcinoma, metastasized to the lymph nodes, lungs, mediastinum, and bilateral iliac bones. He was diagnosed two years ago and received chemotherapy, maintenance immunotherapy with pembrolizumab, and targeted palliative radiation therapy, with good clinical response. Restaging PET-CT two years later revealed local progression. During his workup, he was noted to have persistently abnormal thyroid function test with low TSH (0.03​​µIU/mL, n 0.3-5.33), normal free T4 (0.97ng/dL, n 0.60 - 1.40), mildly elevated free T3 (3.91pg/mL, n 2.5-3.9), negative thyrotropin receptor antibodies levels, negative TSI, negative TPO antibody, noted evidence of subclinical hyperthyroidism consistent over the past year. Radioactive iodine uptake demonstrated multinodular gland, mildly elevated 24-hour uptake of 28% consistent with hyperthyroidism, with decreased activity in the left lobe. Thyroid ultrasound revealed multiple probable malignant thyroid nodules, a 1.8 cm TI-RADS 5 lesion of the deep margin of the lower pole of the right lobe, and a 1.6 cm TI-RADS 5 lesion of the upper pole on the right lobe. He was treated with methimazole 5 mg. Further workup with fine needle aspiration demonstrated the right upper lobe nodule sample was positive for squamous cell carcinoma, findings suspicious for metastasis. He subsequently proceeded with radical tonsillectomy, right neck dissection, and right hemithyroidectomy. Surgical pathology results noted, right neck metastatic HPV-associated squamous cell carcinoma involving the lymph nodes with extranodal extension, right oropharyngeal HPV-mediated squamous cell carcinoma. The thyroid gland biopsy was significant for incidental papillary microcarcinoma 2mm, thyroid follicular nodular disease, without evidence of squamous cell carcinoma or metastatic infiltration. Post-hemithyroidectomy, his thyroid function normalized, and methimazole was discontinued. Conclusion: Thyroid metastasis from head and neck cancers represent a rare entity. In patients with a history of malignancy, evaluation of new thyroid masses remains crucial. While FNA is a sensitive method for detecting thyroid metastases, inaccuracies may occur, impacting the identification of thyroid nodules in the presence of local metastatic lymphadenopathy. Identifying squamous cell carcinoma in the thyroid can significantly influence the treatment plan of patients with metastatic carcinomas, therefore careful consideration must be undertaken on evaluation. Presentation: 6/1/2024

8414 Utilization Of Cell Free DNA Integrity Index To Differentiate Benign From Malignant Thyroid Nodules

Abstract Disclosure: S. Tarafdar: None. S. Dutta: None. P. Mukhopadhyay: None. N.P. Bhattacharya: None. S. Ghosh: None. Introduction: Recent advances in molecular genetics have evaluated a potential role for plasma cell-free DNA (cfDNA) integrity index as a non-invasive cancer marker. Data on cfDNA integrity in differentiated thyroid cancer is sparse and needs to be investigated further. Aim of the study: The purpose of this study is to investigate the hypothesis that longer DNA strands in plasma may serve as a marker for thyroid cancer. Methods: Patients presenting with thyroid nodules underwent ultrasonography with Thyroid Image Reporting and Data Systems (TIRADS) scoring and FNAC (Bethesda classification).Patients with Bethesda 3, 4, 5, and 6 had surgery and confirmation by histopathology. Patients with Bethesda 2 presenting with compressive symptoms and cosmetic concerns underwent surgery; the remaining patients were considered benign based on clinical follow-up, USG, and FNAC characteristics. Blood sample collected prior to FNAC was used to extract and quantify cfDNA. To assess the integrity index 180/67, 306/67, and 476/67 for the APP gene, we used a quantitative real-time PCR (qPCR) method based on the quantification of four amplicons of varying lengths (67, 180, 306, and 476 bp, respectively). Because culture cells had extremely intact genomic DNA, the genomic DNA obtained from the MDA-T32 papillary thyroid cancer cell line was utilised as a reference to estimate the relative DNA strand integrity in plasma DNA. To determine the (ΔCt) value for 67,180, 306, and 476 bp, the Ct value of the sample was subtracted from that of the MDA-T32 control. Results: A total of 161 subjects were recruited, of these 92 were benign and 69 had differentiated thyroid cancer(confirmed by histopathology). Using the 180/67 bp integrity index benign thyroid nodule patients had significant lower value (median 0.39, 95% CI: 0.33-0.46) compared to patients with differentiated thyroid cancer (median 0.62, 95% CI: 0.56-0.68). A cfDNA integrity index of 180/67 bp could significantly differentiate between benign and malignant thyroid nodules (P<0.001). However, there was no significant difference between malignant and benign thyroid nodules based on the cell free DNA integrity indexes of 306/67 and 476/67. Conclusions: The cfDNA integrity score of 180/67 exhibits potential as a circulating marker for the detection of thyroid nodules and as a means of monitoring cfDNA fragmentation in patients with thyroid cancer. However, further confirmation through prospective trials is necessary. Presentation: 6/3/2024

8229 Prevalence of Thyroid Cancer in Patients with Hashimotos Thyroiditis Presenting Concomitant Thyroid Nodular Disease

Abstract Disclosure: M.A. Alvarez Castillo: None. L. Sanchez Arriaga: None. A. Segovia Palomo: None. Introduction: Hashimoto's thyroiditis (HT) is the most frequent autoimmune thyroid disease and the main cause of goiter and hypothyroidism; it induces a process of aseptic autoimmune inflammation. Fibroinflammatory changes lead to the development of thyroid nodules (TN), additionally chronic inflammation is an important player in the development of cancer, although this association is controversial. The prevalence of thyroid cancer (TC) in patients with HT ranges from 0.61-58.4% (25.01%), being higher than in patients with TN without concomitant HT. Objective: To know the prevalence of malignancy in patients with HT who present thyroid nodular disease. Methodology: An observational, descriptive, retrospective, and longitudinal study was carried out. Patients with HT diagnosis were selected by measuring Ab TPO and/or Ab TG who presented an ultrasound diagnosis of TN and FNAB of the thyroid lesion had been performed. Descriptive statistics and linear regression were used. Results: 87 patients: 6 (6.9%) men and 81 (93.1%) women aged 47.9 (12.7) years. 4 (4.5%) required FNAB in 2 TN, for a total of 91 TN studied. 64% had a diagnosis of hypothyroidism and were taking LT4, TSH 4.40 (4.44) mUI/mL, FT4 1.00 (0.27) ng/dL. Mean Ab TPO was 794.7 ± 1354.6. Diagnosis time 19.5 (29.1) months. 39.6% the detection was made by the patient and 35.2% by the doctor. Major axis was 18.8 (12.1) mm. Ultrasound pattern of single TN 58.2% and multinodular 41.8%. Median TIRADS was 4, with a mode of 5. 81.3% reported Bethesda II and 18.7% malignant or suspected, were sent for surgery, malignancy was confirmed in 16/ 17 lesions. 14 (15.3%) were TPC and 2 lymphomas, the main subtypes were classic papillary and NHL, respectively. Mode of ATA risk was intermediate. Multivariate analysis only TIRADS represented risk factor (OR 2.08) Conclusions: The frequency of TC in our population was 15.3%, which reflects a higher prevalence of malignancy in thyroid nodules in patients with chronic thyroiditis, in accordance with what has been reported in other series. Presentation: 6/3/2024

12351 Real World Performance of the Afirma Xpression Atlas in Bethesda V and Vi Thyroid Nodules: A Private Practice Experience

Abstract Disclosure: M.S. Tkach: None. E. Coughlin: None. A. Pinero-Pilona: None. Fine Needle Aspiration (FNA) is a cornerstone of the diagnosis of thyroid cancer. The Bethesda System for Reporting Thyroid Cytopathology (BS-TCP), developed in 2010, and genomic sequencing classifiers (GSC) now allow clinicians to objectively identify the risk of malignancy of thyroid nodules (“TN”) prior to surgical interventions. For further characterization, the Afirma Xpression Atlas (XA) was created and launched in May 2018, utilizing RNA sequencing to evaluate fusions and variants. As of 2023, the Afirma XA panel includes 905 genomic variants and 235 fusions from 593 genes. Post-validation studies for the Afirma XA have focused on large academic centers, but applicability or extrapolation to smaller endocrinology practices is less clear, potentially due to different patient population and thyroid cancer prevalence. This study was designed to analyze and measure the performance of the Afirma XA in BS-TCP V and VI TN classified as GSC suspicious for malignancy in a small endocrinology practice. We conducted a retrospective cohort analysis comparing all BS-TCP V and VI TN with their respective final surgical pathology results between June 2018 and December 2023. 76 TN meeting the criteria for BS-TCP V or VI classification were identified. We excluded any TN (12 total) for which pathology data was unavailable; reasons ranged from lack of patient follow-up to patient's death with no autopsy available. Forty-seven thyroid TN were therefore included, and the BS-TCP VI category was the predominant cytopathology discovered, representing 78.7% of the TN in this group. Afirma XA was able to identify genomic alterations in 78.7% of all included TN (thus 78.7% is its sensitivity). Sensitivity of XA was found to be 70% in BS-TCP V (n=10) and 81.1% in BS-TCP VI (n=37). 83% of the analyzed TN were from female patients and 17% were from male patients; there was no statistically significant difference between XA frequency in TN from male vs. female patients. 100% of all BS-TCP V and VI TN (n=47) as determined by the cytopathologist were associated with cancer on pathology; thus, the sensitivity of the cytopathology itself is 100%, and positive predictive value of XA in both groups was 100%. Age and nodule size were not significantly associated with XA presence or absence overall. XA was overwhelmingly comprised of BRAF :p:V600E c.1799T>A mutations: 70.2% of of XA findings showed this mutation (50% in V and 75.6% in VI). Our percentage of XA on BS-TCP V and VI nodules reflects similarity to prior large studies in academic centers. Based on this data, we conclude that XA is a valuable tool for high-risk TN classification and treatment guidance; it can both aid in surgical planning and determine options for potential pharmacotherapy. We conclude that in our study, the relation between XA and cytopathology in BS-TCP V and VI nodules correlates well with data from large academic center studies, even in a small private practice. Presentation: 6/3/2024

6689 A Multicentric Study for Validation of the Diagnostic Accuracy of ACR-TIRADS in a Mexican population

Abstract Disclosure: M. Romero Ibarguengoitia: None. I.A. Villarreal-Ondarza: None. J. Mercado Basurto: None. A. González Cantu: None. The diagnostic performance of ultrasonographic ACR-TIRADS classification to evaluate thyroid nodules is poorly studied in a Mexican population. The aim was to assess the diagnostic accuracy of ACR-TIRADS classification for identifying malignant thyroid nodules in adults aged >18 years. This retrospective research study was conducted in 4 medical centers in Northern Mexico from 2022 to 23 to obtain ACR-TIRADS classification of nodules from thyroid ultrasound. Information about Bethesda classification after fine needle aspiration and cytology from thyroidectomy was analyzed for diagnostic performance tests. A total of 160 patients were included. Thyroid nodules were classified as TIRADS 3 in 12%, TIRADS 4 in 44%, and TIRADS 5 in 41%. Twenty-six (16%) were classified as Bethesda 1, 39 (24%) were classified as Bethesda 5, and 30 (19%) were classified as Bethesda 6. The sensitivity (S) of TIRADS 4 was 41%, specificity (E) was 50%, positive predictive value (PPV) was 59%, negative predictive value (NPV) was 32%, and accuracy was 44%. The S of TIRADS 5 was 51%, E 77%, PPV 80%, NPV 47%, and accuracy of 61%. When comparing with other populations, the performance was the same as the Turkish (their accuracy was 59.93%) population but lower than a population from China (their accuracy was 86%) and Germany (PPV 100% for TIRADS 5). The proportion of malignancy in our sample compared with a reference sample from Germany was lower, 36 vs. 85% for TIRADS 3, 59 vs. 85% for TIRADS 4, and 80% vs. 100%, p< 0.001. Concerning Bethesda's classification, the proportion of malignancy was the same according to the reference sample from the American Thyroid Association. In conclusion, there was a moderate accuracy of the ACR-TIRADS classification system in our population, the same in comparison with the Turkish population; slightly lower than what is reported in a population from Germany and China. Presentation: 6/1/2024

8385 Coexistence of Parathyroid Adenoma & Papillary Thyroid Cancer: A Rare Case Report

Abstract Disclosure: K. Dash: None. S. Verma: None. U. Ayyagari: None. M. Roy: None. S. Rathore: None. Prevalence of primary hyperparathyroidism (pHPT) ranges from 0.1- 0.4% in general population. Nodular thyroid disease is an increasingly common incidental diagnosis due to widespread use of ultrasound. Papillary thyroid cancer (PTC) is the most common cancer of thyroid gland. Here we report a 53 year old post-menopausal woman presented with weight loss, generalised body aches, arthralgia, myalgia, and proximal muscle weakness. She was hypertensive and clinically euthyroid. Physical examination revealed generalized tenderness all over the body but no thyroid or parathyroid nodules on palpation. Biochemical evaluation showed hypercalcemia 12.1mg/dl (8.4-10.2mg/dl), PTH>2000pg/ml (14-72pg/ml), ALP-1855 U/L (40–125 U/L), decreased phosphorous of 2.4mg/dl (25-4.6 mg/dl), and vitamin-D of 46 nmol/L ( 75-250 nmol/L). USG neck revealed a heterogeneous lesion at the lower pole of right lobe of thyroid gland & two small hypoechoic nodules seen in the right lobe of thyroid gland. FNAC from nodules was inconclusive. USG abdomen revealed nephrocalcinosis. DEXA scan showed severe osteoporosis. Tc99mSestamibi SPECT-CT showed uptake at lower pole of right lobe of thyroid. On exploration, two nodules were palpated in the right lobe of the thyroid and simultaneous right hemi-thyroidectomy was performed. Histopathologic report confirmed parathyroid adenoma (figure 1) as well as presence of carcinoma in the two nodules: one was a papillary thyroid cancer (Classic variant) and the other a follicular variant of papillary thyroid carcinoma (figure 2). Margins were negative for malignancy. She was treated with levothyroxine to maintain TSH <0.1U/L and followed up with annual ultrasound screening. At 2 year follow up, patient was symptom free with improved T score on DEXA scan and no nodule over residual thyroid gland. Discussion: Co-existence of pHPT and PTC ranges from 2.3-4.3%. The use of ultrasound neck as a routine imaging modality for localisation of parathyroid adenoma allows detection of thyroid nodules. Benign and/or malignant thyroid nodules are commonly seen in patients with pHPT and this can range from 2-15%. Women have higher risk for co-existence. The relationship between the two diseases is thought to be incidental. Some authors have suggested possible role of shared genes, embryological factors, transcription factors, vitamin-D deficiency and hyperparathyroidism that could lead to activation of angiogenic factors and carcinogenesis. Fig. 1. Parathyroid adenoma. (a)Tc99m sestamibi scan showing right inferior parathyroid adenoma (b) Parathyroid adenoma (400x high power) comprising predominantly of Chief cells with mild pleomorphism. Fig. 2. Histopathology of PTC. (a)Papillary Carcinoma thyroid. 10xPhotomicrograph showing areas of calcification. (b) Papillary Carcinoma thyroid. Photomicrograph showing thyroid with papillary pattern with areas of infiltration. Presentation: 6/1/2024

12465 Unraveling The Enigma: A Multifaceted Presentation Of Hormonal Dysregulation In A 37-year-old Woman

Abstract Disclosure: S.Y. Rizvi: None. N. Ahmad: None. Title: Unraveling the Enigma: A Multifaceted Presentation of Hormonal Dysregulation in a 37-Year-Old Woman Background: Leydig cell tumors (LCTs) are rare gonadal tumors, arising from the interstitial cells of the testis or, less commonly, the ovary, 0.1%. These tumors are known for their potential to produce androgens, leading to virilization symptoms such as hirsutism. While LCTs are typically benign, they can occasionally exhibit malignant features. Accurate diagnosis and appropriate management are crucial to prevent complications and ensure favorable outcomes. Clinical Case: A 37-year-old, G3P3A0 woman, presented to our endocrinology clinic for a follow-up visit following the removal of a malignant thyroid nodule. During the visit, her endocrinologist noted elevated testosterone levels and worsening hirsutism. She reported mild abdominal pressure but denied other symptoms. She also complained of pain in the lower abdomen, although physical examination findings were limited due to type II obesity. Diagnostic investigations revealed a history of imaging studies, including CT scans and pelvic ultrasounds, demonstrating various findings such as a fibroid uterus, ovarian abnormalities, and a heterogeneous mass in the left adnexa. Laboratory evaluations over time showed fluctuations in androgen levels, with notable values including DHEA-sulfate (137.5 ug/dL), total testosterone (309.6 NG/dL), and free testosterone (12.85 NG/dL). Tumor markers, including CA 19-9= 16 U/mL, CA 125= 23.3 U/mL, CEA = 1.7 NG/mL, and HCG, were unremarkable. Gynae/Oncology was consulted, and she underwent surgical exploration with laparoscopic left oophorectomy. It revealed a Leydig cell tumor without overt malignant features, as confirmed by histopathological examination and immunohistochemical analysis. Her testosterone improved since oophorectomy. Patient undergoes frequent post-op follow up of her testosterone, free+total lc/MS to monitor for hyperandrogenism. Conclusion: This case highlights the importance of considering Leydig cell tumors in the differential diagnosis of hirsutism, particularly in the presence of elevated androgen levels. Multidisciplinary collaboration involving endocrinologists, gynecologists, oncologists, radiologists, and pathologists is essential for accurate diagnosis and optimal management. Surgical resection remains the cornerstone of treatment for Leydig cell tumors, with careful histopathological evaluation necessary to assess for potential malignancy. Long-term follow-up is warranted to monitor for recurrence or metastasis, although the prognosis for benign Leydig cell tumors is generally favorable. Patients with large body habitus may present challenges in physical examination, necessitating reliance on imaging and laboratory studies for diagnostic evaluation. Keywords: hirsutism, testosterone, ovary Presentation: 6/2/2024

6913 Clinical Prognosis in Patients with Thyroid Nodules Expressing PPAR-Gamma Gene Fusion on Thyroid FNA Cytology

Abstract Disclosure: R. Hammoudeh: None. E. Morariu: None. A. Wald: Other; Self; Technical consultant to Sonic Healthcare USA.. W.R. Doerfler: None. Y. Linwah: None. M. Nikiforova: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Y.E. Nikiforov: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Background: PPARG rearrangements, typically PAX8-PPARG, are common genetic alterations in follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma (FVPTC). Most tumors appear to be indolent, however distant metastasis has been reported. The aim of this study was to determine the prevalence and type of malignancy in a series of thyroid nodules positive for PAX8 rearrangement in thyroid fine-needle aspiration (FNA) samples. We also aimed to evaluate the impact on patient management, prognosis and outcomes. Methods: Thyroid nodules positive for PAX8 fusion on ThyroSeq v2 and v3 genomic classifier testing of FNA samples from May 2008 to February 2022 were identified. Clinical data was obtained by retrospective chart review. Results: Overall, 44 nodules positive for PAX8/PPARG fusion were identified. None of these nodules expressed additional genetic mutations on molecular testing. Surgical pathology was available for 40 patients, which identified 35 (87.5%) malignant, 3 NIFTP (7.5%), and 2 benign (5%) lesions. In the malignant group, FNA cytology revealed 1 (2.8%) benign, 13 (37.1%) AUS/FLUS, 12 (34.2%) suspicious for SFN/FN, 5 (14.3%) suspicious for PTC and 4 were not classified. In the non-malignant group, FNA cytology revealed 2 (40%) benign, 2 (40%) AUS/FLUS, 1 (20%) SFN/FN. With regards to surgical intervention, 30 (75%) patients had total thyroidectomy and 10 (25%) underwent lobectomy, of which 8 were followed by completion thyroidectomy. Among the malignant and non-malignant groups, there was no difference in sex (82.8% vs 100% female, p=1), age (43.6 vs 50.2 years, p=0.2), or tumor size on surgical pathology (3.26 vs 4 cm, p=0.23). In the malignant group, histology showed 30 (85.7%) FVPTC, 2 (5.7%) conventional PTC, 2 (5.7%) follicular carcinoma and 1 (2.9%) solid variant PTC. Of the FVPTC group, 9 had oncocytic cell features, 3 focal solid patterns, and 1 showed focal solid growth and progression to poorly differentiated thyroid carcinoma. Only 1 showed lymphatic invasion, 10 showed angioinvasion. Following the ATA thyroid cancer risk stratification, 23 (65.7%%) had low risk, 9 (25.7%) intermediate risk and 3 (8.6%) high risk. 18 patients in the malignant group underwent RAI ablation. Average follow up for the malignant nodules was 49.7 months (0-170). 1 had suspected recurrence on thyroid ultrasound after a year. No evidence of distant metastasis was documented. Conclusions: The majority of thyroid nodules with PAX8/PPARG rearrangement found on FNA were cancers, predominantly follicular variant PTC, and some were benign or NIFTP. The majority were low risk, but intermediate and high-risk cancers with more aggressive histology, angioinvasion, and poorly differentiated cancer were also identified. While only one recurrence was identified on short follow-up, longer follow-up duration is required for better understanding the behavior of these tumors. Presentation: 6/3/2024

Low false-positive lymph nodes for 18F-fibroblast activation protein inhibitors PET/computed tomography in preoperative staging of patients with nonsmall cell lung cancer.

This study aimed to evaluate the diagnostic accuracy of 18F-fibroblast activation protein inhibitor (FAPI) PET/computed tomography (CT) in identifying primary tumors and mediastinal lymph node metastases in nonsmall cell lung cancer (NSCLC), with histopathological findings serving as the reference standard. Nineteen patients underwent preoperative 18F-FAPI PET/CT and subsequent surgery; of these, 13 also underwent 18F-fluorodeoxyglucose (FDG) PET/CT within 1 week. The diagnostic accuracy of primary tumors and lymph node metastases was evaluated for both modalities. Semiquantitative parameters, including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBRs), for both primary tumors and lymph node metastases were assessed for both modalities. For primary tumors, 18 of 19 (94.7%) showed positive results on 18F-FAPI PET/CT scans. In 13 patients who also underwent 18F-FDG PET/CT, 18F-FAPI PET/CT demonstrated a higher detection rate compared with 18F-FDG PET/CT (100% vs. 69.1%). The overall accuracy of lymph node assessment with 18F-FAPI PET/CT (95.9-97.1%) was significantly higher compared to 18F-FDG PET/CT (51.0%). Malignant lymph nodes exhibited significantly higher SUVmax and TBR on 18F-FAPI scans (SUVmax: 7.0 vs. 0.9, P < 0.001; TBRmuscle: 5.0 vs. 0.8, P < 0.001) than on 18F-FDG scans (SUVmax: 3.9 vs. 1.8, P = 0.01), except for the liver TBR on 18F-FDG scans (TBRliver: 1.8 vs. 1.0, P = 0.055). 18F-FAPI could be utilized in the preoperative staging of NSCLC to mitigate the incidence of false positives associated with 18F-FDG, due to its higher accuracy in identifying mediastinal lymph node metastasis.

A clinically applicable model more suitable for predicting malignancy or benignity of pulmonary ground glass nodules in women patients

BackgroundIn recent years, clinicians often encounter patients with multiple pulmonary nodules in their clinical practices. As most of these ground glass nodules (GGNs) are small in volume and show no spicule sign, it is difficult to use Mayo Clinic Model to make early diagnosis of lung cancer accurately, especially in large numbers of nonsmoking women who have no tumor history. Other clinical models are disadvantaged by a relatively high false-positive or false-negative rate. Therefore, there is an urgent need to establish a new model of predicting malignancy or benignity of pulmonary GGNs for the sake of making accurate and early diagnosis of lung cancer.MethodsIncluded in this study were GGNs surgically resected from patients who were admitted to Yiwu Central Hospital from January 2018 to March 2024, including both male and female patients, there is no gender specific issue. The nature of all these GGN tissues was confirmed pathologically. The case data were statistically analyzed to establish a mathematical prediction model, the prediction performance of which was verified by the pathological results.ResultsAltogether 261 GGN patients met the inclusion criteria. Using the results of logistic regression analysis, a mathematical prediction equation was established as follows: Malignant probability (mP) = ex/ (1 + ex); when mP was > 0.5, the GGN was considered as malignant, and when mP was ≤ 0.5, it was considered as benign. x= -2.46 + 1.032*gender + 1.85*mGGN + 1.40*VCS-0.0027*mean CT value of the nodule + 0.078*maximum diameter of the nodule, where e represents the natural logarithm; if the patient was a female, gender = 1 (otherwise = 0); if the pulmonary nodule was a mixed GGN, mGGN = 1 (otherwise = 0); if the pulmonary nodule had vascular convergence sign, VCS = 1 (otherwise = 0). The prediction performance of the mathematical prediction model was verified as follows: the negative prediction value was 0.97156 and the positive prediction value was 0.3800 in the model group versus 1 and 0.25 in the verification group.ConclusionIn this study, we identified female gender, mGGN, VCS, mean CT value and maximum nodule diameter as five key factors for predicting malignancy or benignity of pulmonary nodules, based on which we established a mathematical prediction model. This novel innovation may provide a useful auxiliary tool for predicting malignancy and benignity of pulmonary nodules, especially in women patients.

Deep learning-based CT image for pulmonary nodule classification with intrathoracic fat: A multicenter study

Correctly distinguishing between benign and malignant pulmonary nodules can avoid unnecessary invasive procedures. However, existing models exhibit a deficiency in the study of fat regions. We aim to create a multimodal deep learning nomogram (DLN) using pulmonary nodule and intrathoracic fat (ITF) features to distinguish between benign and malignant nodules and further demonstrate that intrathoracic fat can enhance the performance of lung cancer prediction models. A segmentation methodology was devised for precisely delineating intranodular and perinodular region (IPN). The Swin Transformer was used for feature extraction. The least absolute shrinkage and selection operator (LASSO) regression was employed for feature selection. The nomogram integrating IPN and ITF signatures revealed better diagnostic accuracy than IPN signature alone (net reclassification improvement = 0.134, P<0.05, and integrated discrimination improvement = 0.078, P<0.05). In the internal test cohort, DLN obtained an area under the curve (AUC) of 0.913 (95 % CI: 0.870, 0.952). In the external test cohort, the AUC was 0.906 (95 % CI: 0.867, 0.938). There was no significant difference between the calibrated curve and perfectly calibrated curve in all cohorts (P>0.05). Decision curve analysis showed that the DLN was clinically useful. The DLN demonstrated substantial diagnostic value for distinguishing between benign and malignant pulmonary nodules. The incorporation of the ITF signature has enhanced the performance of DLN.

The evaluation of fine needle aspiration biopsy results in differentiating between benign and malignant thyroid nodules

Introduction: Thyroid fine-needle aspiration biopsy (FNAB) has begun playing an important role in the evaluation of thyroid nodules, in addition to physical examination and imaging techniques. The purpose of this study was to evaluate the results of patients who underwent thyroid FNAB together with their demographic data, imaging findings, and follow-up compliance. Methods: Patients who underwent thyroid FNAB procedures in our hospital’s interventional radiology unit between January 2022 and May 2024 were evaluated retrospectively. Data were retrieved from patient records. Cytological results were classified as malignant, atypia of undetermined significance, benign, and non-diagnostic material. Results: Two hundred twelve solid nodules were detected in the patients who underwent biopsy, and 59 mixed nodules with a cystic component. Non-diagnostic material was reported in 51 cases at cytological examination, benign cytology in 150, atypia of undetermined significance in 53, and malignant material in 17. The incidence of non-diagnostic results was significantly higher in hypoechoic nodules and low-volume nodules. Conclusions: Thyroid FNAB is a valuable diagnostic tool due to its ease of application and provision of useful information in benign-malignant differentiation. Once it becomes capable of application by primary physicians and local state hospitals in Türkiye it will reduce delayed diagnoses, unnecessary surgical procedures, and economic burdens on social security institutions.

B-242 Improved Patient Satisfaction With Novel Capillary Blood Collection Devices as an Alternative to Venipuncture for Applications in Clinical Proteomic Assays

Abstract Background Two new clinical diagnostic tests are available that aid in the identification of lung nodules as likely malignant or likely benign. One test is an ELISA that measures the levels of seven autoantibodies to tumor-associated antigens that aids in the identification of patients with likely malignant lung nodules who may benefit from timely intervention. The other is an LC-MS/MS-based (MRM) test that measures the ratio of two proteins (LG3BP and C163A) combined with several clinical and radiological factors to aid in the identification of patients with likely benign lung nodules who may benefit from additional CT surveillance. Since commercialization, we have found that test access may be improved by providing alternatives to traditional venipuncture. Therefore, we conducted evaluation studies with two novel non-fingerstick capillary blood collection devices. These devices puncture the skin by utilizing either microneedles (Device A) or a lancet (Device B) for capillary blood collection. Methods Blood specimens were collected from consented donors using one of the two capillary blood collection devices and by venipuncture into K2EDTA blood collection tubes. Feedback was also solicited from the healthcare professionals and donors via a standard questionnaire. The whole blood specimens were shipped to the testing laboratory where the samples were processed according to the respective clinical assay workflows. Feasibility testing for the ELISA-based assay was conducted with both devices using normal healthy donor specimens (105 donors for Device A and 43 for Device B). Clinical evaluation was executed utilizing only Device B (77 donors with lung cancer and 13 with an indeterminate lung nodule). Feasibility testing for the LC-MS/MS-based assay was conducted with both devices using healthy donor specimens (103 donors for Device A and 41 for Device B), while clinical evaluation utilized only Device B (80 donors with lung cancer and 30 with an indeterminate lung nodule). Results Both capillary blood collection devices revealed good correlations to venous blood draws for the ELISA-based test during feasibility. The two devices also showed good correlations for the LC-MS/MS-based test, with the results from Device A requiring a correction factor. Due to technical and operational challenges throughout feasibility, Device B became the preferred device to be evaluated for the clinical study. Good correlations for both diagnostic tests were observed from the clinical study. During clinical evaluation, healthcare professionals and donors were asked to rate the ease-of-use, pain, and speed of collection when using Device B. Most healthcare professionals (108/126) rated the device as easy to use. Ninety-five percent of the donors reported minimal pain while the remainder reported moderate pain. Ninety-one percent of the donors felt that the time required to collect blood using Device B was acceptable. Sixty percent of the donors preferred the capillary collection device (Device B), 17% preferred venipuncture, while 23% reported no preference for blood collection. Conclusions The novel capillary blood collection devices demonstrated high correlations for two clinical diagnostic tests. Feedback collected from healthcare professionals and donors revealed that the majority preferred the capillary blood collection device as compared to traditional venipuncture for blood collection.

Sonographic characteristics of thyroid nodules with a Halo

ObjectiveTo investigate the sonographic characteristics of thyroid nodules with a halo, explore the value of contrast-enhanced ultrasound (CEUS) combined with fine needle aspiration (FNA) in identifying nodules with a halo, and predict the risk of metastasis by analyzing the pathological features of the halo.MethodsA retrospective analysis was conducted on 185 postoperative cases of thyroid nodules accompanied by halos between January 2019 and December 2022. After describing the ultrasound characteristics of the thyroid nodules and their halos, all patients were divided into three groups, the first group (group I = CEUS only) of patients underwent CEUS, the second group (group II = CEUS + FNA) underwent FNA based on the first group, and the third group (group III = FNA only) underwent FNA directly. The CEUS and FNA results were graded using the Chinese Thyroid Imaging Report and Data System (C-TIRADS) and Bethesda Reporting System for Thyroid Cytopathology, respectively. Those graded below C-TIRADS 4b or Bethesda IV were defined as benign, and the results of FNA were referenced when the two methods were combined. The surgical pathology results were used as the gold standard. We plotted working curves to compare the diagnostic efficacy of CEUS and FNA alone and in combination in the diagnosis of thyroid nodules with halos. The pathological features of the halo were analyzed and the number of patients with cervical lymph node metastases was recorded.ResultsOne hundred and sixty patients met the requirements. Benign nodules were mainly characterized by a thin (0.75 ± 0.31 mm) and uniform halo with good integrity, while malignant nodules had a thicker (1.48 ± 0.51 mm) halo with uneven and irregular margins (P < 0.05). The sensitivity and specificity were highest when the cutoff value was 1.09 mm, with 76.08% and 84.29%, respectively. The halos of benign nodules were mostly hyper- or iso-enhanced, whereas the halos of malignant nodules were predominantly hypo-enhanced (P < 0.05). The areas under the curve (AUCs) for CEUS, FNA, and CEUS + FNA were 0.751(95% CI = 0.642–0.841), 0.863(95% CI = 0.767–0.929), and 0.918(95% CI = 0.834–0.967), respectively. Cervical lymph node metastasis occurred in only 13 (11.5%) malignant nodes with halos. The primary pathological components of the halo around malignant nodules were almost reactive hyperplastic fibrous tissue.ConclusionThe halo surrounding malignant thyroid nodules is thicker, with uneven and irregular margins, and shows hypo-enhancement on CEUS. Combining CEUS with FNA improves the diagnostic efficacy of thyroid nodules with halos. The reactive hyperplastic fibrous halo may be one of the reasons why malignant nodules are less likely to metastasize.

Value of spectral parameters in the differential diagnosis of benign and malignant breast nodules in non-enhanced chest CT.

Dual-layer spectral computed tomography (DSCT) is capable of acquiring both conventional and spectral images during one routine scan, and is widely used for the quantitative and qualitative analyses of substances, differential diagnosis, and disease staging. However, limited research has been conducted on its performance in the differential diagnosis of benign and malignant breast nodules using non-enhanced scans. This study aimed to assess the diagnostic performance of multiple quantitative parameters derived from non-enhanced DSCT in differentiating benign from malignant breast nodules. This retrospective cross-sectional study examined a total of 121 breast nodules from 114 patients (malignant group: n=68; benign group: n=53) identified during chest physical examination or routine admission for the treatment of breast diseases at The First Affiliated Hospital of Soochow University from March 2023 to December 2023. All the patients underwent DSCT scanning and pathological diagnosis. The DSCT quantitative parameters, including the effective atomic number (Zeff), computed tomography (CT) attenuation values at 40-70 keV, and the slope of the spectral Hounsfield unit curve (λHU), in non-enhanced images were measured. The λHU was calculated as follows: λHU = CT70 keV - CT40 keV/30 HU. Additionally, typical radiological features were analyzed. A DSCT parameter diagnostic model and a conventional CT diagnostic model were assessed using receiver operating characteristic (ROC) curves. The Delong test was used to assess and compare the diagnostic performance of each model. The DSCT parameters, including the Zeff (P<0.001), λHU (P<0.001), and CT attenuation values at 40 keV (P<0.001) and 50 keV (P=0.001), as well as the presence of the lobular sign (P<0.001) and spicule sign (P<0.001), exhibited statistically significant differences between the benign and malignant groups. The logistic regression analysis revealed that the Zeff [odds ratio (OR): 9.22; 95% confidence interval (CI): 2.11-40.35; P=0.003], λHU (OR: 0.64; 95% CI: 0.52-0.79; P<0.001), 40 keV CT attenuation value (OR: 8.69; 95% CI: 3.28-23.06; P<0.001), 50 keV CT attenuation value (OR: 0.01; 95% CI: 0.001-0.07; P<0.001), and lobular sign (OR: 3.95; 95% CI: 1.52-10.31; P=0.005) were independent predictors of malignancy. Compared to the benign group, the malignant group had a higher likelihood of presenting with the lobular sign and higher Zeff values but lower λHU values. The ROC curve indicated that the Zeff had the highest diagnostic efficacy [area under the curve (AUC) of the ROC =0.792, 95% CI: 0.71-0.87]. Further, the DSCT parameter diagnostic model had improved diagnostic efficacy with an AUC of 0.899 (95% CI: 0.84-0.96), which was higher than the AUC of the conventional CT diagnostic model (AUC =0.796, 95% CI: 0.72-0.87). The Delong test revealed a statistically significant difference between these two models (P=0.04). DSCT parameters derived from non-enhanced DSCT images, such as the Zeff value and λHU, can be used to differentiate benign and malignant breast nodules, and the differential diagnosis efficacy of the DSCT parameters is higher than that of conventional CT parameters.

Diagnosis of Benign and Malignant Breast Nodules by Conventional Ultrasound in Combination with S-Detect Technology and Elastic Imaging.

To determine the diagnostic value of conventional ultrasound combined with S-Detect and elastic imaging technology in differentiating between benign and malignant breast nodules. Observational study. Place and Duration of the Study: Department of Ultrasound Imaging, Yichang Central People's Hospital, Yichang, China, from October 2019 to October 2022. The study included all breast nodules diagnosed using ultrasound, with patients undergoing conventional ultrasound for BI-RADS classification, elasticity score, and S-Detect examination. Benign and malignant breast nodules were classified according to the three tests and their combinations. The diagnostic sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under curve (AUV) of those alone and combinations were calculated and compared. Of the three methods, BI-RADS, elasticity score, and S-Detect, BI-RADS had the highest accuracy (89.29%), elasticity score had the highest specificity (96.20%), and S-Detect had the highest sensitivity (93.92%). The accuracy of combined groups were higher than that of the single group. When combined with elasticity score, the AUC of the new BI-RADS increased from 0.882 to 0.917 (p <0.001); and combined with S-Detect, the AUC of the new BI-RADS increased from 0.882 to 0.927 (p <0.001). The combination of conventional ultrasound BI-RADS classification with elasticity score or S-Detect technology has a higher diagnostic efficacy for breast nodules, which can improve breast cancer detection and provide valuable diagnostic evidence for clinical practice. S-Detect technology, Ultrasound elastic imaging, Elasticity scoring, Elasticity strain ratio value, Breast tumour.

Diagnostic performance of European and ACR-TIRADS classification systems in thyroid nodules over 20 mm in diameter

BackgroundThe challenge of selecting thyroid nodules for fine-needle aspiration (FNA) cytology has led to the development of the Thyroid Imaging Reporting and Data System (TIRADS), primarily in two formats: EU-TIRADS and ACR-TIRADS. Clinical observations suggest imperfect risk assessment for TIRADS 3 nodules ≥20 mm. This study aimed to evaluate the efficacy of TIRADS systems in distinguishing benign from malignant nodules in this subgroup. Materials and MethodsFrom May 2023 to March 2024, 1,094 patients with thyroid nodules were referred for ultrasound (US) at a University Hospital. Data on clinical, ultrasound, cytological, and histopathological parameters were collected. Nodules ≥20 mm were categorized by EU-TIRADS and ACR-TIRADS, and their predictive performance for malignancy was assessed through post-thyroidectomy histopathology or FNA cytology (Bethesda classification). Results267 patients (mean age 60.3 ± 14.3 years; 46 men, 221 women) with 308 nodules were analyzed. Twenty-two malignancies and 286 benign nodules were recorded. Recalculating EU-TIRADS 3 performance using 25 mm and 30 mm thresholds (ACR-modified EU-TIRADS) avoided 24% and 41% of FNAs, respectively, while ACR-TIRADS would prevent 26.6% (p>0.05). Two malignancies were missed. ConclusionEU-TIRADS and ACR-TIRADS show similar efficacy when using a 25 mm FNA threshold. Raising the cut-off for FNA in EU-TIRADS 3 nodules could reduce unnecessary procedures but may increase the risk of missed malignancies, impacting patient outcomes.

Utility of Sonoelastography and Magnetic Resonance Imaging in Characterization of Thyroid Nodules.

To evaluate thyroid nodules with sonoelastography and magnetic resonance imaging (MRI). The study included 28 patients with 40 thyroid nodules. Clearance was obtained from the institute's ethical clearance committee. Patients with pure cystic nodules or nodules with eggshell calcification, diffuse thyroid pathology (such as Graves' disease, Hashimoto's thyroiditis, De Quervain thyroiditis, and Riedel's thyroiditis), inaccessible nodules via fine needle aspiration cytology (FNAC), or patients with a history of thyroid gland surgery were excluded from the study. Strain elastography was performed on a Phillips iU22 machine, producing qualitative color-coded strain maps (graded using the Rago 5-point system) and semiquantitative strain ratios. MRI was performed on a Phillips ACHIEVA 1.5T magnet with a head and neck coil. Rago scores statistically correlated (χ2 = 18.052, p < 0.001) with malignant nodules, and using the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUROC) for the mean strain ratio predicting malignant outcomes was 0.88 [95% confidence interval (CI): 0.767-0.992], which was also statistically significant (p < 0.001). A cutoff of mean strain ratio ≥2.48 predicted malignant outcomes with 100% specificity. T2 signal intensity ratio (SIR) and apparent diffusion coefficient (ADC) values were not statistically significant in predicting malignant outcomes. Kinetic curves were statistically significant for Rago scores (χ2 = 11.356, p = 0.045); however, no significant difference was found in predicting malignant outcomes. We concluded that sonoelastography, along with grayscale ultrasound, is a useful noninvasive technique for predicting histological outcomes. However, MRI should largely be reserved as a problem-solving tool rather than a standalone imaging modality. The kinetic curves show some degree of overlap between histologically distinct diseases, and thus large-scale multicenter trials are needed for further standardization.

Risk Stratification of Thyroid Nodules Diagnosed as Bethesda Category III by Ultrasound, Size, and Cytology.

This study aimed to evaluate the performance of an integrated risk stratification system (RSS) based on ultrasound (US) RSSs, nodule size, and cytology subcategory for diagnosing malignancy in thyroid nodules initially identified as Bethesda category III on fine-needle aspiration. This retrospective study was conducted at two institutions and included consecutive patients with Bethesda category III nodules, and final diagnoses confirmed by repeat biopsy or surgery. A total of 320 Bethesda category III nodules (≥1 cm) from 309 patients (223 female and 86 male; mean age, 50.9 ± 12.0 years) were included. The malignancy risk of Bethesda category III nodules and predictors of malignancy were assessed according to US RSSs, nodule size, and cytology subcategory. The diagnostic performances of US-size cytology (USC) RSS and US RSS alone for malignancy were compared. The intermediate or high suspicion US category independently increased the malignancy risk in all US RSSs (P ≤ 0.001). Large nodule size (≥3 cm) independently increased the malignancy risk of low- or intermediate suspicion US category nodules. Additionally, the atypia of undetermined significance cytology subcategory independently increased the malignancy risk of low suspicion US category nodules in most US RSSs. The area under the receiver operating characteristic curve of the USC RSSs was greater than that of the US RSSs alone (P < 0.048). Malignancy was not found in the very low risk category of USC RSS. The diagnostic performance of USC RSS for malignancy was superior to that of US RSS alone in Bethesda category III nodules. Malignancy can be ruled out in the very low-risk category of USC RSS.