Fine-needle Aspiration Biopsy Research Articles

Thyroid Papillary Carcinoma Invasion of the Ipsilateral Internal Jugular Vein: A Case Report

Thyroid cancer is the common malignancy of the endocrine system. Thyroid neoplasms are usually asymptomatic and slow growing. Uncommonly, aggressive thyroid neoplasms may invade adjacent blood vessels. Internal jugular vein invasion is a rare complication of an aggressive thyroid malignancy. Careful sonographic examination of a thrombus-like structure inside a blood vessel adjacent to the affected thyroid could reveal that the “thrombus” is part of the thyroid mass. The continuity of a thyroid neoplasm into the vascular lumen and inner-“thrombus” vascularity confirms the cancerous invasion. Ultrasound-guided fine-needle aspiration biopsy is standard for differentiating benign versus malignant thyroid nodules. Genetic testing of thyroid nodules provides valuable clinical information in addition to the routine cytological analysis.

Intraparotid plexiform neurofibroma: A rare diagnostic challenge.

Isolated intraparotid neurofibromas are exceptionally rare and often associated with neurofibromatosis type 1 (NF1). Diagnosing these tumors proves challenging because of the clinical resemblance to primary salivary gland masses. This case report details an 18-year-old with a painful, enlarging parotid mass, diagnosed through fine needle aspiration biopsy (FNAB) revealing myxoid stroma and spindle cells. Magnetic resonance imaging confirmed a plexiform neurofibroma involving the parotid gland and facial nerve. Histopathology validated the diagnosis, emphasizing the importance of cytological and radiological correlation. Notably, the absent NF1 association makes this case unique. Surgical excision with facial nerve reconstruction was performed, highlighting the complexity of managing such rare intraparotid neurofibromas. Awareness of this entity is crucial for accurate diagnosis and appropriate management.

A case series of thyroid fine needle aspiration biopsies diagnosed as follicular neoplasm with oncocytic features.

Oncocytic lesions of the thyroid are a heterogeneous group encompassing nonneoplastic and neoplastic entities ranging from benign to malignant and have traditionally been classified as separate entities in thyroid pathology. To illustrate the diversity of these thyroid lesions, we describe three cases of fine needle aspiration biopsies (FNAB) diagnosed as Bethesda Category IV: Follicular neoplasm, oncocytic type, under the 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), with ThyroSeq v3 molecular testing and subsequent surgical excision.

Abstract LB276: qPCR in the diagnosis of papillary thyroid cancer: Assessment of BRAF V600E mutation in FNA biopsies of thyroid nodules

Abstract Papillary thyroid carcinoma (PTC) accounts for up to 90% of thyroid cancer cases, and its differentiation from benign conditions presents a challenge in clinical practice. Fine needle aspiration biopsy (FNAB) has become a recommended practice for evaluating thyroid nodules (TN) with imaging features suspicious of malignancy. Although FNAB demonstrates high accuracy in discriminating TN, a significant number are classified as malignant indeterminate (MTI), which can only be fully diagnosed by post-surgical histologic evaluation. Up to 30% of FNAB findings are expected to be MTI, leading to a high rate of unnecessary hemithyroidectomies in about 75% of patients. In PTC, the most common mutation is c.T1799A in the BRAF gene (rs113488022), resulting in V600E in the B-raf protein, leading to an increase expression by altering the MAPK pathway. The aim of this study was to evaluate the efficacy of discriminating patients with malignant and benign TNs by detecting BRAF V600E in tissue from FNAB for molecular diagnosis of PTC. The qPCR technique with allele-specific probes was used to detect the BRAF c.1799T>A mutation in somatic DNA samples extracted by FNAB from TN (n=99) with suspected malignancy by ultrasonography. Cytologic diagnosis of biopsies was performed using the Bethesda System (TBSRTC). Diagnostic accuracy measures for evaluation of BRAF c.1799T>A as a diagnostic tool were performed with MedCalc software. Of the 99 patients, it was determined by cytology that 50 patients (50.51%) had PTC and 49 benign neoplasms (49.49%). The mutation was detected in 28 of the PTC samples (56%) (AA homozygotes [n=12, 24%] and AT heterozygotes [n=16, 32%). No mutation carriers were found among patients with benign neoplasms. Regarding accuracy measures were 56% for sensitivity of 56% and 100% specificity. The positive predictive value was 100% and the negative predictive value was 69.01%, with an accuracy of 77.78%. Finally, the negative likelihood ratio (LR-) value was 0.44 (95% CI: 0.32 to 0.60), while the positive likelihood ratio (LR+) value could not be calculated as there were no patients with the mutation in the group of patients with benign TN. In conclusion, our results suggest that the presence of BRAF c.1799T>A mutation could be indicative of PTC, confirming its usefulness in the differentiation between malignant and benign tumors. BRAF V600E detection may be valuable as an adjunct to conventional cytology, improving diagnostic accuracy and reducing the need for unnecessary surgical procedures. While highlighting the potential utility of this technique as a diagnostic tool, further analysis and consideration of other metrics is recommended for a full evaluation of its clinical relevance. Citation Format: Anette R. Gastelum-Quiroz, Andrea Ross-Orozco, Marco A. Álvarez-Arrazola, Eliakym Arambula-Meraz, Karla L. Morales-Hernández, Hanna M. Tolosa-Lerma, Fred Luque-Ortega, Paola Y. Sánchez-Aboytes, Noemí García-Magallanes. qPCR in the diagnosis of papillary thyroid cancer: Assessment of BRAF V600E mutation in FNA biopsies of thyroid nodules [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB276.

A vocal cord palsy caused by the uterine cancer metastatic tumor in the mediastinum revealed in a patient with a thyroid lesion: a case report and review of the literature

BackgroundThe main cause of vocal cord palsy (VCP) is idiopathic impairment of the recurrent laryngeal nerve (RLN). However, solid tumors along the pathway of the RLN can also impact the nerve’s function. We presented a patient with a thyroid lesion and VCP due to a bulky metastatic mass (uterine cancer) on the aortic arch field in the mediastinum. The report aims to show the significance of comorbid tumors in thyroid pathology and the importance of additional diagnostic methods in avoiding unnecessary surgeries. A patient’s lifetime and the outcome of the disease were also presented.Case presentationA 58-year-old Ukrainian woman with a hoarse voice, intermittent dry cough, and weakness was presented to an endocrine surgeon. Thyroid pathology included signs of hypothyroidism treated with Thyroxine 112.5 µg and a nodule in the left lobe. The lesion is located on the posterior aspect of the lobe, which could probably be a cause of RLN involvement. Fine needle aspiration biopsy (FNAB) was performed twice with Bethesda category 2 result. Fibrolaryngoscopy (FLS) revealed the median position of the left vocal cord. Idiopathic, laryngeal, and thyroid causes of the VCP were excluded. Additionally, the patient displayed her anamnesis of the endometrial clear cell carcinoma following hysterectomy, external beam radiation therapy, and chemotherapy. The mediastinal metastasis was revealed sixteen years later. A chest computed tomography (CT) with intravenous contrast was done. A bulky tumor was found right under the aortic arch. Subsequently, the voice complaints reduced significantly after 4 chemotherapy courses. Cancer progression had led to the appearance of lymph node metastases on the supraclavicular region. Following six months the 60-year-old patient had passed away.ConclusionA history of the disease should always be kept in mind when assessing a patient’s complaints. VCP in case of thyroid pathology and previous secondary malignancy may be caused by metastatic tumor anywhere along the RLN pathway. Such a rare case shows the importance of additional methods of examination which may avoid unnecessary thyroid surgeries.

Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study

BackgroundThyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy.MethodsThis study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes.ResultsThe DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies.ConclusionsThis is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.

Using the DNA Integrity Number (DIN) to analyze DNA quality in specimens collected from liquid-based cytology after fine needle aspiration of breast tumors and lesions.

Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded (FFPE) sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage. We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA Integrity Number (DIN) score analysis. Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens. Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis.

Abstract 3675: Design of high-performance tumor-informed minimal residual disease (MRD) panels from low FFPE tumor input

Abstract Background: Minimal residual disease (MRD) testing can detect cancer recurrence months to years earlier than the current standard of care, enabling earlier treatment of recurrence and improved patient outcomes. Tumor-informed MRD assays typically utilize formalin-fixed paraffin-embedded (FFPE) tumor tissue, which is available in limited quantities for some patients, for example, following core needle biopsy (CNB), after neoadjuvant treatment or when patients need multiple tests from the same tumor sample. To determine the lower limit of tissue input, we evaluated our MRD assay performance across a range of extracted tumor volumes. Methods: Resected tumors and CNBs were sectioned, H&E stained, and macro-dissected. Tumor gDNA was extracted, quantified, prepared into libraries and sequenced. Sequenced libraries were aligned and evaluated for depth of coverage, variation of coverage, and duplication rate. Somatic calling was performed on matched tumor and normal samples. Up to 1000 target sites were selected for high-depth targeted sequencing of the tumor and normal gDNA for confirmation of somatic variant calls. The positive predictive value (PPV) was computed as the percent of putative somatic variant sites that were present in the tumor capture library and absent in the normal capture library. Results: Extracted tumor volumes varied by almost two orders of magnitude, from 0.06mm3 (equivalent to needle core or fine needle aspirate biopsies) to 5mm3 (achievable with resected tumor). gDNA amount varied linearly (3.6ng to 1549ng) with tumor tissue input, indicating the low tissue to paraffin ratio did not have an adverse effect on yield. Tumor gDNA inputs into library prep ranged from 2.5ng to 100ng. DNA amounts above 100ng into library prep had no discernable benefit. Below 10 ng, depth of coverage and the coefficient of variation in coverage indicated poor-quality libraries. Samples with ~10 ng of gDNA input into library prep showed depth of coverage comparable to higher inputs and saturated the achievable library complexity. Additionally, PPV of somatic calling was consistent across the range of gDNA inputs from 10-100 ng, demonstrating equivalent assay performance. Conclusion: Tumor-informed MRD assays have immense potential for increasingly sensitive treatment response and recurrence monitoring that can inform better treatment decisions. FFPE tumor tissue is a critical input into MRD assays but is a limited resource. This study supports a minimum DNA input of 10 nanograms for a single attempt at extraction, corresponding to a tissue volume of 0.2mm3 or a single 10µm slide with a 20mm2 area, representing one of the lowest tissue input requirements for an MRD assay. Low FFPE tissue requirements expand the patient population that benefit from MRD testing by utilizing samples that have low tumor content, are post-neoadjuvant therapy or do not meet the tumor volume requirements of competing MRD offerings. Citation Format: Matt LaBella, Ashley Acevedo, Ravi Patel, Kiefer Haug, Sangita Ganesh, Elise Buser, Nafei Xu, Shalee Carlson, Kyle Trettin, Sarah Ratzel, Kieko Hara, Pavlos Msaouel, Kanishka Sircar, Chad Tang, Dale Muzzey, Genevieve Gould. Design of high-performance tumor-informed minimal residual disease (MRD) panels from low FFPE tumor input [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3675.

Abstract 4168: Pre-clinical demonstration of Raman spectroscopy-assisted photothermal therapy for prostate cancer

Abstract Prostate cancer (PCa) ranks among the most prevalent malignancies in men. The combination of ultrasound and fine-needle aspiration biopsy has greatly facilitated early diagnosis and expanded the range of treatment options. Traditional treatments primarily involve anti-androgens and androgen deprivation therapy; however, a recurrence occurs in approximately 30% of cases following these interventions. Our current focus is on the exploration of photothermal therapies using nanoparticles for precise tumor ablation. Among these nanoparticles, multiwalled carbon nanotubes (MWCNTs) exhibit unique structural, optical, and thermal properties that make them exceptionally appealing for biomedical applications, especially as a foundation for photothermal therapy. Our platform employs the copper (I)-catalyzed azide alkyne cycloaddition of prostate-specific membrane antigen (PSMA)-targeting peptidomimetic (Glu-urea-Lys) ligand to the MWCNTs. We used confocal microscopy to observe a significantly enhanced binding of the targeted Glu-urea-Lys-MWCNTs to the surfaces of PSMA-expressing LNCaP cells compared to IgG-MWCNTs and to PSMA-null PC3 cells. Raman microscopy further confirmed the increased presence of Glu-urea-Lys-MWCNTs on LNCaP spheroids compared to non-targeting MWCNTs. We also confirmed enhanced photothermal cell ablation in vitro using the targeted MWCNTs. Based on in vitro evidence, we established LNCaP and PC3 xenografts in nu/nu mice and evaluated the therapeutic efficacy. Using fluorescence-based imaging, we observed the enhanced localization of Glu-urea-Lys-MWCNTs within the tumors. Furthermore, we collected the tumors and conducted ex vivo analysis using Raman microscopy for a label-free detection of the targeted MWCNTs, which complemented the fluorescence imaging and laying the foundation for real-time Raman imaging in vivo. Subsequently, we applied photothermal ablation of the tumor xenografts based on a pre-optimized treatment protocol established from COMSOL simulations and prior experiments. This treatment led to complete tumor ablation with minimal recurrence and minimal non-specific damage. In conclusion, we have assessed the effectiveness of our targeted nano-photothermal platform in a pre-clinical model of PCa. Further studies will aid in the transition of photothermal therapy to clinical trials. Moreover, we aim to investigate the role of photothermal therapy in the PCa tumor microenvironment and whether such an approach can trigger post-therapeutic activation of immune responses against the tumor. Ultimately, we anticipate that our nanotherapeutic platform will contribute to a focused therapeutic approach where targeted MWCNT-laser treatment exploits overexpressed tumor markers in conjunction with various irradiation strategies to enhance ablation while minimizing damage to surrounding tissue. Citation Format: Seung Soo Lee, Gabriel Beaudoin, Jun Hui Yeoh, Frederic Leblond, Mark Trifiro, Miltiadis Paliouras. Pre-clinical demonstration of Raman spectroscopy-assisted photothermal therapy for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4168.

Abstract 5054: Optimization and evaluation of an FFPE dual extraction protocol for next-generation sequencing applications

Abstract Formalin-fixed paraffin-embedded (FFPE) biopsies are highly valuable and widely used tissue specimens for clinical diagnostics. However, obtaining sufficient and high-quality nucleic acid material from limited FFPE samples presents a challenge for downstream molecular analysis, such as next-generation sequencing (NGS). We present an optimized sequential extraction method that generates high-quality DNA and RNA from a single set of input tissues that is automatable and operation-friendly. This workflow performs well with reduced FFPE tissue input and efficiently supports various high-throughput clinical NGS applications. The DNA/RNA yield, quality, purity, and impacts on NGS assay performances were on par or better than an existing validated comparator extraction method. With comparable FFPE input, the new method demonstrated a superior extraction performance with significantly higher yield, quality, and purity. For DNA, NGS libraries were made with two different library preparation methods: a TA-ligation-based method and a single-strand-based method, followed by hybrid capturing and sequencing. The DNA from the new extraction method demonstrated a superior library conversion rate and improved target enrichment uniformity with both chemistries. This provides the potential of reduced input requirements, allowing very limited tissue, such as fine needle aspirate or core needle biopsy, for clinical NGS testing. The sequencing results were highly concordant between the existing and new extraction methods when the extracted DNA was subjected to a validated comprehensive genomic profiling (CGP) clinical test, demonstrating the quality and robustness of the extraction. For RNA, NGS libraries were made following the validated CGP clinical test with hybrid capturing, and the results were comparable between the two extraction methods. In conclusion, an FFPE extraction method was optimized to allow more clinical biopsy samples to be tested with different NGS workflows, providing a better diagnostic value for patient care. Citation Format: Rebecca Hong, Jieying Chu, Steven Hsiao, Daniel Whang, Steven P. Rivera, Heng Xie, Jiannan Guo. Optimization and evaluation of an FFPE dual extraction protocol for next-generation sequencing applications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5054.

Abstract 2310: Integrating real-world histopathological and clinicogenomic data from 1799 lung cancer patients by applying unsupervised deep learning

Abstract Hematoxylin and eosin (H&E) stained histologic sections contain invaluable information that remains largely untapped because of its complexity. To this end, AI applications employing deep learning (DL) can facilitate the translation of image data to enable human interpretation and yield novel oncological insights that would have otherwise remained imperceptible. DL-based methodologies are multimodal, capable of integrating imaging with clinicogenomic data to furnish a more holistic perspective and affording more accurate predictions in oncology. Here, we developed an unsupervised DL workflow to analyze 1,799 H&E images of lung cancer (NSCLC n = 951; SCLC n = 50; others n = 798) incorporating comprehensive patient-level clinical data (electronic health records [ConcertAI]) integrated with genomics (WES and RNA-seq [Caris Labs]). There are three steps in our approach: (1) image preprocessing and filtering, yielding > 30 million image patches; (2) utilizing pretrained SimCLR models from 57 public oncology histopathology datasets with ResNet-18 as a backbone structure to extract 512-dimensional-feature vectors for each patch; (3) using three unsupervised clustering methods (kmeans, DBSCAN, Leiden clustering) to cluster patches and selected Leiden clustering. We identified 635 primary imaging clusters using an elbow method and generated an image feature matrix by calculating correlations between each patch and cluster centroids; these were aggregated and mapped back to source slides. In this proof-of-concept, distinct image feature patterns characterized SCLC and NSCLC samples. For SCLC, one of the salient features was the presence of hemorrhage, which may be associated with higher rates of fine-needle aspiration biopsy procedure for SCLC compared with NSCLC which was confirmed in the EHR data (p = 0.032). Derived morphological clusters were correlated with tumor-immune genomic features (Tumor Mutational Burden [TMB], Immunologic Constant of Rejection [ICR], and Miracle scores1) serving as predictors of response to immune-checkpoint inhibitor therapy. By applying linear models, we detected 11, 96 and 249 significantly associated imaging clusters, respectively, highly enriched with immune cells e.g., plasma cells, macrophages, lymphocytes, and supporting an infiltrated and inflamed tumor-immune microenvironment. In summary, a multimodal, unsupervised deep learning workflow combining H&E imaging with clinicogenomic data was developed to identify histologic feature clusters associated with well-established tumor-immune genomic signatures of NSCLC immune infiltration and molecular phenotypes. These studies demonstrate enormous potential to yield histopathological and translational insights in NSCLC and SCLC that can empower clinicians to make better therapeutic response predictions. Citation Format: Si Wu, Yujie Zhao, Hugo Luo, Kevin Kolahi, Thanh Bui, Xu Shi, Aditee Shrotre, Alexander Liede, Xi Zhao, Josue Samayoa, Weilong Zhao. Integrating real-world histopathological and clinicogenomic data from 1799 lung cancer patients by applying unsupervised deep learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2310.

Comparison of ultrasound risk stratification systems for pediatric thyroid nodules.

There is currently insufficient data to validate adult-based US risk stratification systems (RSSs) for the identification of malignant thyroid nodules in a pediatric population. From October 2016 and May 2023, 173 thyroid nodules of pediatric patients (age ≤ 18 years) with definitive pathology results and ultrasound (US) examination within 1 month before surgery or fine-needle aspiration (FNA) biopsy in our institution were enrolled in this study. The clinical and US characteristics of these nodules were retrospectively reviewed and categorized according to the ACR-TIRADS, C-TIRADS, and ATA guidelines. The diagnostic performance of US-based FNA criteria (original and simulating) of the three guidelines in thyroid cancer detection was estimated. The three RSSs had similar AUC according to the categories(0.849-0.852, all P > 0.05). When combined with the original FNA criteria of the three RSSs to manage the nodules, the FNA rate of ACR-TIRADS and C-TIRADS were significantly less than ATA guidelines (53.18% vs. 64.63%, P < 0.05, and 52.60% vs. 64.63%, P < 0.05). The missed malignancy rate (MMR) and unnecessary FNA rate (UFR) of ATA guidelines (50.00%, 35.85%) was highest among the three RSSs, followed by the C-TIRADS (37.80%, 19.57%) and the ACR-TIRADS (37.04%, 19.57%). When nodules < 1cm with the highest category in each RSS biopsied, that is when using the simulating FNA thresholds, the MMR was reduced overall (all P < 0.001), without a change in the UFR (all P > 0.05). All the three RSSs showed a substantial improvement in accuracy and malignant detection rate (all P < 0.05). The ACR-TIRADS, C-TIRADS, and ATA guidelines showed high missed malignancy rates when using their original recommended FNA criteria. When nodules < 1cm with the highest category in each RSS biopsied, the missed malignancy rate of each RSS was decreased. Decreasing the FNA thresholds for highly suspicious malignant nodules may therefore be an effective means of managing malignant thyroid nodules in pediatric patients.

The accuracy of fine needle aspiration biopsy (FNAB) in diagnosing musculoskeletal lesion

Fine needle aspiration biopsy (FNAB) is a relatively non-invasive diagnosis of musculoskeletal lesions that is very challenging in some musculoskeletal cases. This study aimed to evaluate the diagnostic utility of FNAB in musculoskeletal lesions. This was a retrospective cross-sectional study involving 180 musculoskeletal patients who underwent FNAB procedure, with or without ultrasound-guided in the Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta between 2018 and 2021. The obtained data were then statistically analyzed for sensitivity, specificity, and accuracy. Of 180 cases, 90 (50%) were confirmed with histopathology examination. Further analysis revealed that 33 cases were confirmed positive, 45 patients were true negative, 2 cases were false positive, and 10 were cases false negative. The overall diagnostic sensitivity, specificity, and accuracy of FNAB in musculoskeletal lesions were 76.8, 95.7, and 83%, respectively. FNAB can lead to misinterpretation in cases that show similar morphologic features. Therefore, clinical information and imaging results are necessary to be correlated. In conclusion, FNAB is an efficient and effective technique for early diagnosis in musculoskeletal cases. FNAB can be used to establish the diagnosis of an inoperable tumor because of its high accuracy.

Přínos tenkojehlové aspirační bio psie a klasifi kace Bethesda v diagnostice tumorů štítné žlázy – retrospektivní studie

Introduction: Thyroid nodule is a pathology with a prevalence of 19–68% of the population, with a thyroid gland carcinoma proven in 7–15% of these cases. Bethesda classifi cation is a standardized system for cytology fi ndings evaluation. Aim of work: The aim of our work was to compare a predicted preoperative dia gnosis including Bethesda classifi cation and the fi nal histology results, to defi ne malignancy risk for Bethesda categories and to compare our fi ndigs with foreign papers. Material and methods: A retrospective, observational study. In a group of 330 patients with performed operation on the thyroid gland (total thyroidectomy or hemithyroidectomy) at the ENT department of the University hospital in Pilsen between 2016 and 2017 there was a group of 180 patients (147 female and 33 male patients) with preoperatively known Bethesda category. We have compared an expected dia gnosis and postoperatively known histology dia gnosis, determined a risk of malignancy rate for each category of Bethesda classifi cation and compared our results with a foreign literature. Results: In the group of our patients, we have determined a risk of malignancy rate for Bethesda I. category as 14.29%, same as for Bethesda II. For Bethesda III. as 15.79%, Bethesda IV. as 10.64%, Bethesda V. as 52.17% and Bethesda VI. category as 100%. Conclusion: Fine- -needle aspiration bio psy of thyroid gland nodules is a basic dia gnostic method, which facilitates categorization and stratifi cation of a risk of malignancy in cytological fi ndings. In our group of patients, a risk of malignancy rate diff ers in Bethesda I. and II. category, our risk of malignancy rate is higher compared to foreign literature, which, we believe, is a statistical error due to a rather small set of patients. Key words thyroid nodule – fine-needle aspiration bio psy – Bethesda classifi cation – risk of malignancy rate

PACULIARITIES OF CLINICAL PRESENTATION, DIAGNOSIS, AND TREATMENT FOR INJURIES OF THE LARGE SALIVARY GLANDS

Background. Salivary gland lesions of various genesis are quite widespread among patients, tumorous processes involving these organs make up 2.2-3.7% of the total number of head and neck tumors, 78-82% of salivary gland tumor cases, and sialoadenitis, which makes 3.8-6.7% of the total number of inflammatory diseases of maxillofacial organs. The initial diagnostic imaging for parotid gland tumors typically involves an ultrasound examination; however, it does not definitively indicate the need for surgical intervention. While computed tomography or magnetic resonance imaging are not obligatory elements of patient assessment, they may be recommended in specific instances to facilitate accurate treatment planning.&#x0D; Fine-needle aspiration biopsy can serve as an obligatory diagnostic test, irrespective of whether an ultrasound examination has been conducted, particularly when there are suspicions of atypical presentations of polymorphic adenoma. Incisional biopsy is contraindicated, as it frequently leads to neoplastic implantation, thereby increasing the risk of recurrence of polymorphic adenomas and malignant neoplasms.&#x0D; The purpose of the study is to conduct a comparative analysis of the data of clinical examinations, laboratory tests, surgical treatment, complications and postoperative results, taking into account the prevalence of tumor and inflammatory processes of the parotid salivary glands.&#x0D; Material and methods. We have conducted a retrospective study of the medical histories of 174 patients operated on at the Department of Maxillofacial Surgery of the “Poltava Regional Clinical Hospital named after M.V. Sklifosovsky”.&#x0D; Results. According to our data, pleomorphic adenoma was the most common benign tumor, and mucoepidermoid carcinoma was the most frequently detected malignant tumor. Regarding initial presentations, the primary observation was a tumor mass in 96.1% of all cases. Additional findings included incidental lesions detected during imaging studies and localized pain or inflammation. Isolated occurrences of inadvertent lesions during imaging of neoplasms have also been documented. Palpation was recognized as an excellent clinical parameter for topographic localization and classification of lesions for malignancy, with proven value in the specimen due to its high sensitivity for demonstrating nodules in the superficial lobe (97.1%) and high specificity for nodules in the deep lobe. We established that the average evolution time of benign tumors was approximately three times longer than that of malignant tumors. These data are consistent with literature data that malignant tumors are more aggressive and have a rapid evolution, while benign, in turn, have an insidious onset and slow growth. During intraoperative examination, high specificity is desirable because it can reliably exclude malignancy, preventing unnecessary radical interventions. Another intervention that we have analyzed in the treatment of benign tumors is dermal parotidectomy, which showed a recurrence rate similar to superficial parotidectomy, although with a lower rate of serious complications (12.4% less on average). It has been found that the choice of this intervention is mainly related to the incidence of recurrence, and in 51-56% of cases in patients with a previous fine-needle aspiration biopsy.&#x0D; Conclusion. According to this study, taking into account the experience of our clinic, the presence and visualization of a single nodule in the parotid area is the main clinical manifestation of parotid gland cancer. Pleomorphic adenoma is the most common histological type, and facial nerve-sparing subtotal parotidectomy is the best treatment for these patients.

Uveal melanoma: the value of molecular genetic testing for early detection of metastatic disease. Clinical case

To date, the issue of not only timely diagnosis and treatment of patients with uveal melanoma (UM), but also the prediction of this pathology remains relevant. The technology of fine needle aspiration biopsy (FNAB) makes it possible to assess the risk of developing metastatic disease using tumor specimen in patients undergoing organ-preserving treatment by cytological and molecular genetic testing in the primary intraocular lesion. Here we present a case of newly identified locally advanced (T3a) UM, outline the possibilities of organ-preserving treatment using Gamma Knife stereotactic radiosurgery, and also demonstrate the feasibility of conducting a comprehensive prognostic testing on FNAB material, including cytological and molecular genetic and morphological prognostic factors. The results of this testing have made it possible to recommend a more frequent surveillance monitoring regime for metastatic disease, which ultimately led to the early detection of UM liver metastases, followed by their successful treatment.

DIAGNOSTIC ACCURACY OF TIRADS CLASSIFICATION IN DIFFERENTIATING BENIGN AND MALIGNANT THYROID NODULES KEEPING FINE NEEDLE ASPIRATION CYTOLOGY (FNAC) AS GOLD STANDARD

Thyroid nodules represent a joint clinical presentation of various benign and malignant thyroid diseases. Diagnostic ultrasound, particularly utilizing the Thyroid Imaging Reporting and Data System (TI-RADS), has emerged as a pivotal tool for stratifying the risk of malignancy in thyroid nodules and guiding decisions regarding fine-needle aspiration biopsy (FNAC). However, comprehensive validation studies are warranted to assess the diagnostic accuracy of ultrasound-based TI-RADS classification compared to FNAC as the gold standard. This cross-sectional validation study, conducted at the Department of Radiology, CPE Institute of Cardiology Multan from August 2, 2021, to February 1, 2022, enrolled 243 patients presenting with thyroid nodules, including multiple and solitary nodules. Baseline demographic variables, including age, gender, and nodule duration, were recorded for each participant. Ultrasonography was performed in all patients, and TI-RADS scores were calculated. Subsequently, fine-needle aspiration biopsies, guided by ultrasound, were obtained in the radiology department and sent to the histopathology department for confirmation of malignancy. The mean age of the cohort was 42.05 ± 12.27 years, with a mean nodule duration of 6.87 ± 3.56 months. The mean TI-RADS score was 3.46 ± 2.00. Of the participants, 176 (72.43%) were male and 67 (27.57%) were female. Malignancy was detected in 84 (34.57%) patients based on TI-RADS score, whereas FNAC confirmed malignancy in 50 (20.58%) patients. Evaluating diagnostic accuracy with FNAC as the gold standard, the TI-RADS score demonstrated a sensitivity of 84.0%, specificity of 78.2%, positive predictive value (PPV) of 50.0%, and negative predictive value (NPV) of 95.0%. Our findings indicate that the TI-RADS scoring system is reliable in predicting malignancy in patients with thyroid nodules. With a sensitivity of 84.0% and specificity of 78.2%, TI-RADS represents a valuable adjunctive tool in the diagnostic algorithm for thyroid nodules, offering considerable potential for improved clinical decision-making and patient management strategies.

Comparative evaluation of shear wave elastography elasticity values in thyroid nodules with cytology results and TI-RADS scoring in differentiation of benign-malignant nodules.

The aim of this prospective study was to investigate the diagnostic performance of shear wave elastography (SWE) in differentiating benign and malignant thyroid nodules and their correlation with the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). This prospective study included 370 thyroid nodules in 308 patients aged 18-70years. All the patients underwent B-mode ultrasound (US), Doppler examination, and SWE and were given an ACR TI-RADS risk score before fine needle aspiration biopsy (FNAB) and/or surgery. The correlation between SWE parameters and ACR TI-RADS categories was investigated statistically and compared with histopathologic results. Additionally, the diagnostic performance of SWE was evaluated to distinguish malignant and benign thyroid nodules. One hundred and thirty-five of the 370 thyroid nodules were malignant, and 235 nodules were benign. The mean shear wave velocity (SWV) value of the malignant nodules (3.70 ± 0.98m/s) was statistically higher than that of the benign nodules (2.70 ± 0.37m/s). The best cutoff value of the mean SWV for differentiating benign and malignant nodules was found to be 2.94m/s (sensitivity 90.4%, specificity 89.9%, positive predictive value 81.3%, negative predictive value 94.1%, p < 0.001). The average score of the nodules according to the ACR TI-RADS was 3.57 ± 1.83 in benign nodules and 7.38 ± 2.69 in malignant nodules (p ≤ 0.001). This study showed that combining SWE and TI-RADS improves the specificity of TI-RADS alone in differentiating benign and malignant nodules.

Uses and limitations of small-volume biopsies for the diagnosis of lymphoma.

Although surgical biopsy remains the gold standard for the diagnosis of lymphoma, small-volume biopsies including fine-needle aspiration and core needle biopsy are increasingly being used as a first line diagnostic tool. Small-volume biopsies are safe, rapid and cost effective; however, diagnostic utility varies by lymphoma subtype. It is important for pathologists and clinicians to recognize both the strengths and limitations of such biopsies.

[Stratified application of gene expression in diagnosis of thyroid nodules].

Objective: To investigate the value of BRAF V600E and multigene detection and stratified application for the diagnosis of thyroid nodules. Methods: A total of 1 117 patients with thyroid nodules resection at Nanjing Gulou Hospital from December 2020 to July 2022 were enrolled in the study. Fine needle aspiration (FNA) and core biopsy samplings were performed for cytopathologic examination and genetic testings; the findings were combined with BSRTC classification. The diagnostic performance of BRAF V600E and multigene detection were compared. Results: Among the 1, 117 patients who underwent thyroid nodules resection, 285 were male and 832 were female, with a median age of 46 years (range: 24-76 years). Postoperative histopathologic examination confirmed 1 040 cases of thyroid cancer and 77 cases of benign nodules. The sensitivity (87.0% vs. 80.8%, P<0.01) and diagnostic accuracy (87.9% vs. 82.1%, P<0.01) of multigene detection were significantly higher than those of BRAF V600E detection. The result of multigene detection showed that BRAF V600E mutation was the most common finding, followed by CCDC6-RET (E1-E12) fusion, ETV6-NTRK3 fusion, and KRAS mutation. Multigene detection had a higher sensitivity (81.9% vs. 72.8%, P<0.01) and lower cancer risk in wild-type (47.6% vs. 57.7%, P=0.069) than BRAF V600E detection in BSRTCⅠ-Ⅴ lesions. Compared with BRAF V600E detection, multigene had no significant difference of sensitivity in BSRTC Ⅰ lesions, but significantly higher sensitivity (86.3% vs 74.0%, P<0.01) in BSRTC Ⅲ lesions. Conclusions: Genetic detection can be used as an effective tool for the diagnosis of thyroid nodules. A stratified application of molecular markers in the diagnosis of thyroid nodules is proposed. Combined with FNA, single gene or multigene detection both can effectively assist in the diagnosis of thyroid nodules. Moreover, multigene detection is superior to single gene detection. For BSRTC Ⅲ lesion with wild-type BRAF, multigene detection can be considered with a repeated FNA.