Near-Infrared Spectroscopy for Distinguishing Malignancy in Thyroid Nodules.

Thyroid nodules are common clinical entities, with a significant proportion being malignant. Early, accurate, and non-invasive tools to differentiate benign and malignant nodules can optimize patient management and reduce unnecessary surgery. This study aimed to evaluate the efficacy and accuracy of near-infrared spectroscopy (NIRS) in distinguishing benign from malignant thyroid nodules. A diffuse reflectance spectrum for a total of 20 thyroid nodule samples (10 samples as colloid goiter and 10 samples as thyroid cancer), were acquired in the wavelength range from 1000 to 2500 nm. Spectral data from NIRS were analyzed by means of principal component analysis (PCA), quadratic discriminant analysis (QDA), and linear discriminant analysis (LDA) to classify and differentiate thyroid nodule samples. The present study found that NIRS effectively distinguished colloid goiter and thyroid cancer using the first two principal components (PCs), explaining 90% and 10% of the variance, respectively. QDA discrimination plot displayed a clear separation between colloid goiter and thyroid cancer with minimal overlap, aligning with reported 95% accuracy. Additionally, applying LDA to seven PCs from PCA achieved a 100% accuracy rate in classifying colloid goiter and thyroid cancer from near-infrared spectral data. In conclusion, NIRS offers a promising, non-invasive complementing diagnostic tool for differentiating benign from malignant thyroid nodules with high accuracy. Future work should integrate these results into predictive model development, emphasizing external validation, alternative performance metrics, and protecting against potential overfitting translation of a machine learning model to a clinical setting.

Parathyroid hormone in situ measurement in patients with hyperparathyroidism: single-centre experience of 179 patients.

Context: The measurement of parathyroid hormone(PTH) in situ (PTHis) by fine-needle aspiration (FNA) has been proposed as a tool to preoperatively help localize parathyroid glands detected on ultrasound. However, the accuracy of PTHis is highly variable according to the few available studies. Aim: We aimed to develop and validate the PTHis procedure and assessed the performance of PTHis in a large series of patients with hyperparathyroidism and/or undetermined cervical lesions. Patients and methods: The technique set-up consisted of PTHis measurement in thyroid samples from patients with thyroid nodules and patients with high circulating PTH levels (tertiary hyperparathyroidism). Consecutive patients were recruited at one tertiary referral centre from 2017 to 2020 and submitted to ultrasound-guided FNA-PTHis determination. Results: During the method set-up, we obtained undetectable PTHis levels in all non-parathyroid tissues after sample dilutions. PTHis was higher in patients with hyperparathyroidism (n = 145; 1817 ± 3739 ng/L; range: <4.6-31 140) than in those with thyroid or undetermined cervical lesions (n= 34; <4.6 ng/mL; P < 0.0001). When evaluating PTHis performance in histologically proven samples (158 lesions from 121 patients), PTHis was detectable in 85/97 parathyroid lesions (87%; range: 22-31;140 ng/L) and undetectable in all non-parathyroid lesions (n = 61; P < 0.0001). The specificity and positive predictive value were 100%, and the sensitivity was 87.6%. False-negative lesions (n= 12) were smaller (9.4 ± 5.9 mm) and more often consisted of hyperplasias (75%) than true-positive lesions (16.1 ± 8.4 mm and 33%, P = 0.009 and P = 0.0089, respectively). The method was safe and well tolerated. Four educational cases are also provided. Conclusions: PTHis determination is a safe and well-tolerated procedure that enhances the specificity of ultrasound-detected lesions. If accurately set-up, it confirms the parathyroid origin of uncharacterized cervical lesions.

Clinical challenges with calcitonin-negative medullary thyroid carcinoma: three case reports and a review of the literature.

Medullary thyroid carcinoma (MTC) is relatively rare, and has the main feature of calcitonin (Ct) secretion. However, a few cases of MTC with negative serum calcitonin have been reported in the literature, so the diagnosis and follow up of Ct-negative MTCs are still a challenge. Here we present three cases of Ct-negative MTCs, illustrating the rarity of the disease and challenges in managing it, together with a review of the literature of 39 MTCs with negative serum Ct.

Challenge in the Pathological Diagnosis of the Follicular- Patterned Thyroid Lesions.

BACKGROUND: The follicular-patterned thyroid lesions (FPTLs) include hyperplastic nodules (HN), follicular adenoma (FA), non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP), follicular carcinoma (FC), and the follicular variant of papillary carcinoma (FVPTC). Sometimes the pathologists cannot accurately separate these lesions from each others on a histological basis. AIMS: To evaluate the utility of immunohistochemistry in the diagnosis of FPTLs. MATERIALS AND METHODS: Immunohistochemical analysis, incorporating 83 cases of histologically confirmed FPTLs out of which 20 carcinomas, 51 benign FPTLs (38 HN and 13 FA), and 12NIFTP were separated from each others using four immunostains (HBME-1, CK19, Galectin-3, and CD56). RESULTS: We found statistically significantly more frequent expression of HBME-1, CK19, Galectin-3 proteins in carcinomas as compared to benign FPTLs (p = <0.01). HBME-1 and Galectin-3 were the most sensitive markers for the diagnosis of malignant FPTLs (75%). Galectin-3 was the most specific marker for the diagnosis of carcinoma (90.3%). CONCLUSIONS: The histomorphological features remain the cornerstone of the diagnosis of FPTN. Although HBME-1, Galectin-3, and CK19 immunostains have some diagnostic value in the separation of malignant from benign FPTLs, they are variably expressed in the benign and malignant FPTLs. No single immunostain has sufficient sensitivity and specificity and therefore their diagnostic use is controversial. Future studies are mandated to find more reliable markers that can separate between benign and malignant FPTLs.

Periostin expression and its supposed roles in benign and malignant thyroid nodules: an immunohistochemical study of 105 cases.

BACKGROUND: Thyroid tumors are often difficult to histopathologically diagnose, particularly follicular adenoma (FA) and follicular carcinoma (FC). Papillary carcinoma (PAC) has several histological subtypes. Periostin (PON), which is a non-collagenous extracellular matrix molecule, has been implicated in tumor invasiveness. We herein aimed to elucidate the expression status and localization of PON in thyroid tumors. METHOD: We collected 105 cases of thyroid nodules, which included cases of adenomatous goiter, FA, microcarcinoma (MIC), PAC, FC, poorly differentiated carcinoma (PDCa), and undifferentiated carcinoma (UCa), and immunohistochemically examined the PON expression patterns of these lesions. RESULTS: Stromal PON deposition was detected in PAC and MIC, particularly in the solid/sclerosing subtype, whereas FA and FC showed weak deposition on the fibrous capsule. However, the invasive and/or extracapsular regions of microinvasive FC showed quite strong PON expression. Except for it, we could not find any significant histopathological differences between FA and FC. There were no other significant histopathological differences between FA and FC. Although PDCa showed a similar PON expression pattern to PAC, UCa exhibited stromal PON deposition in its invasive portions and cytoplasmic expression in its carcinoma cells. Although there was only one case of UCa, it showed strong PON immunopositivity. PAC and MIC showed similar patterns of stromal PON deposition, particularly at the invasive front. CONCLUSIONS: PON may play a role in the invasion of thyroid carcinomas, particularly PAC and UCa, whereas it may act as a barrier to the growth of tumor cells in FA and minimally invasive FC.

Application of biomarkers in the diagnosis of uncertain samples of core needle biopsy of thyroid nodules.

Core needle biopsy (CNB) is now more frequently used for the preoperative diagnosis of thyroid nodules. Based on morphology alone, 5-20% of CNB samples cannot be determined as malignant or benign. Compared to fine-needle biopsy (FNB), samples collected by CNB are more accessible for various tests. Therefore, studying biomarkers' application in distinguishing uncertain CNB samples of thyroid nodules is a practical need. Patients of thyroid nodules with both CNB and matched resected specimens were reviewed. Cases classified as indeterminate lesions, follicular neoplasms, and suspicious for malignancy were retrieved. All CNB samples were stained by immunohistochemistry (IHC) using antibodies against CK19, galectin-3, HBME-1, and CD56 and detected by next-generation sequencing (NGS) using an OncoAim® thyroid cancer multigene assay kit (Singlera Genomics) that detected 26 genes. Taking the resected specimens' classification as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy of a single biomarker, and various combinations for discriminating malignancy from benignity were calculated. The sensitivity, specificity, PPV, NPV, and accuracy for preoperative malignancy evaluation were as follows. In the cohort of non-follicular-neoplasm-lesions (non-FN-lesion), they were 95.16%, 53.85%, 90.77%, 70.00%, and 88.00% for CK19; 95.16%, 38.46%, 88.06%, 62.50%, and 85.33% for galectin-3; 77.42%, 76.92%, 94.12%, 41.67%, and 58.00% for HBME-1; 66.13%, 100.00%, 100.00%, 38.24%, and 72.00% for CD56; 90.32%, 92.31%, 98.25%, 66.67%, and 90.67% for NGS; and 88.71%, 92.30%, 98.21%, 63.16%, and 89.33% for integrated IHC. In the cohort of follicular neoplasms (FN), they were 30.43%, 77.77%, 77.77%, 30.43%, and 43.75% for CK19; 73.91%, 66.67%, 85.00%, 50.00%, and 71.88% for galectin-3; 26.09%, 88.89%, 85.71%, 32.00%, and 43.75% for HBME-1; 26.09%, 100.00%, 100.00%, 34.62%, and 46.88% for CD56; 52.17%, 88.89%, 92.31%, 42.11%, and 62.50% for NGS; 82.61%, 66.67%, 86.36%, 60.00%, and 78.13% for integrated IHC; and 100%, 66.67%, 88.46%, 100%, and 90.63% for integrated IHC-NGS. The application of biomarkers in distinguishing uncertain CNB samples of thyroid nodules is available and capable. CD56 negative or NGS positive suggests malignancy strongly for both FN and non-FN-lesion, which may be used as a "rule in" tool. The negative predictive value of the integrated IHC and the integrated IHC-NGS implies a high possibility to be benign for non-FN-lesion and FN separately, which can work as a "rule out" tool. Considering the balance of specificity and sensitivity, NGS is the best for non-FN-lesion and the integrated IHC-NGS is the best for FN.

Diagnostic pitfall of thyroid fine-needle aspiration induced fibrosis: follicular adenoma mimicking medullary thyroid carcinoma in frozen section.

BACKGROUND: Fine-needle aspiration (FNA) is a frequently utilized method for the diagnosis of thyroid nodules. Although the technique has clear advantages, the injury caused by the aspiration needle can induce various histological alterations. Herein, we report a case of follicular adenoma showing histological alterations possibly caused by FNA biopsy. Furthermore, the histological appearance of the lesion mimicked those of medullary thyroid carcinoma, particularly in the frozen section. CASE PRESENTATION: Ultrasonography of a thyroid nodule in a 39-year-old man revealed a mass (2.2 cm in diameter) in the right thyroid lobe. FNA was performed three times on the mass, and the results of the cytology were atypia of undetermined significance. Thereafter, the patient underwent right hemithyroidectomy. The histological findings of the operative frozen section analysis indicated medullary thyroid carcinoma. However, after evaluation and immunohistochemical staining of the permanent section, the mass was diagnosed as follicular adenoma with extensive fibrosis. CONCLUSION: The histological alterations observed in the follicular adenoma are believed to have been caused by injury during the repeated FNA procedures.

Objective analysis of collagen organization in thyroid nodule capsules using second harmonic generation microscopy images and the Hough transform.

Papillary carcinoma is the most prevalent type of thyroid cancer. Its diagnosis requires accurate and subjective analyses from expert pathologists. Here we propose a method based on the Hough transform (HT) to detect and objectively quantify local structural differences in collagen thyroid nodule capsules. Second harmonic generation (SHG) microscopy images were acquired on non-stained histological sections of capsule fragments surrounding the healthy thyroid gland and benign and tumoral/malignant nodules. The HT was applied to each SHG image to extract numerical information on the organization of the collagen architecture in the tissues under analysis. Results show that control thyroid capsule samples present a non-organized structure composed of wavy collagen distribution with local orientations. On the opposite, in capsules surrounding malignant nodules, a remodeling of the collagen network takes place and local undulations disappear, resulting in an aligned pattern with a global preferential orientation. The HT procedure was able to quantitatively differentiate thyroid capsules from capsules surrounding papillary thyroid carcinoma (PTC) nodules. Moreover, the algorithm also reveals that the collagen arrangement of the capsules surrounding benign nodules significantly differs from both the thyroid control and PTC nodule capsules. Combining SHG imaging with the HT results thus in an automatic and objective tool to discriminate between the pathological modifications that affect the capsules of thyroid nodules across the progressions of PTC, with potential to be used in clinical settings to complement current state-of-the-art diagnostic methods.

Diagnostic value of the candidate microRNAs in thyroid fine-needle aspiration biopsy (FNAB) samples.

Background Thyroid cancer (TC) is known to be the most common endocrine malignancy with an incidence rate which has increased by 2.3-fold over the past 30 years. Approximately, 30% of the thyroid fine-needle aspiration biopsy (FNAB) outcomes are indecisive. Moreover, researchers recognized multiple differentially expressed microRNAs (miRNAs) as candidate diagnostic markers for thyroid nodules. The purpose of this study was to identify thyroid tumor-associated miRNAs in FNAB with the capacity to be developed as unique biomarkers. Materials and methods According to the study design, a quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) was applied to evaluate the expression levels of nine miRNAs (Let7, miR-34a, miR-146b, miR-221, miR-151, miR-155, miR-181b, miR-222 and miR-375) among 224 FNA samples as the training set. Results The findings of this study revealed that miR-181b and miR-146b are the best predictors to diagnose benign thyroid FNA samples from malignant samples. However, the remaining miRNAs were co-expressed and had no significant effect on the predictor model. On the other hand, sensitivity and specificity of miR-181b and miR-146b were reported at 83.0%-83.0% and 83.0%-66.0%, respectively. Conclusions According to the results of this study, miR-146b and miR-181b might be considered as adjunct markers contributing to thyroid FNAB in tumor types. In addition, miR-146b and miR-181b were recognized as biomarkers for discriminating benign thyroid nodules from malignant ones. It is suggested that further prospective clinical trials be conducted to evaluate the accuracy of such findings in a larger cohort and determine the clinical uses.

Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies.

Thyroid neoplasia is common and requires appropriate clinical workup with imaging and fine-needle aspiration (FNA) biopsy to evaluate for cancer. Yet, up to 20% of thyroid nodule FNA biopsies will be indeterminate in diagnosis based on cytological evaluation. Genomic approaches to characterize the malignant potential of nodules showed initial promise but have provided only modest improvement in diagnosis. Here, we describe a method using metabolic analysis by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for direct analysis and diagnosis of follicular cell-derived neoplasia tissues and FNA biopsies. DESI-MS was used to analyze 178 tissue samples to determine the molecular signatures of normal, benign follicular adenoma (FTA), and malignant follicular carcinoma (FTC) and papillary carcinoma (PTC) thyroid tissues. Statistical classifiers, including benign thyroid versus PTC and benign thyroid versus FTC, were built and validated with 114,125 mass spectra, with accuracy assessed in correlation with clinical pathology. Clinical FNA smears were prospectively collected and analyzed using DESI-MS imaging, and the performance of the statistical classifiers was tested with 69 prospectively collected clinical FNA smears. High performance was achieved for both models when predicting on the FNA test set, which included 24 nodules with indeterminate preoperative cytology, with accuracies of 93% and 89%. Our results strongly suggest that DESI-MS imaging is a valuable technology for identification of malignant potential of thyroid nodules.

Cytomorphologic, Imaging, Molecular Findings, and Outcome in Thyroid Follicular Lesion of Undetermined Significance/Atypical Cell of Undetermined Significance (AUS/FLUS): A Mini-Review.

OBJECTIVES: Since the introduction of the entity of "Atypical cell of undetermined significance /follicular lesion of undetermined significance" (AUS/FLUS) by The Bethesda System for Reporting Thyroid Cytology (TBSRTC) in 2007, there have been many published studies about the cytomorphologic criteria, subclassification, outcome, and management of patients with the diagnosis of AUS/FLUS. There have been many studies in different aspects of this indeterminate category, i.e., cytologic and molecular findings, ultrasonographic findings, and in some instances even core-needle biopsy to address a better and safer way of the management of patients with this fine-needle aspiration cytology diagnosis. The second edition of TBSRTC and the 2015 American Thyroid Association guidelines provide an update on the follow-up and management of AUS/FLUS. A multidisciplinary team consisting of pathologists, endocrinologists, surgeons, and radiologists should be involved in the diagnosis and management of AUS/FLUS, and all of them should be aware of the heterogeneity of this lesion for the prediction of the treatment and outcome. STUDY DESIGN: In this review, we consider different research platforms (2008-2017) to find the best and key reports for the above-mentioned challenging aspects of AUS/FLUS. CONCLUSION: AUS/FLUS is now a well-defined group of thyroid lesions, which can be most accurately diagnosed and managed with cytomorphology, molecular, and ancillary studies.

Primary thyroid biphasic synovial sarcoma and synchronous papillary carcinoma: report of a remarkable case.

Synovial Sarcoma (SS) is the fourth most common soft tissue sarcoma, characterized by translocation t(X;18) (p11.2;q11.2). Although its histological features have been extensively described, this entity is characterized by a wide morphological spectrum so that the recognition can be very challenging at atypical anatomical localization, like the thyroid. We describe a case of a 42-ys-old female patient complaining a cervical swelling due to left intrathyroid nodule, measuring 35 mm in its greatest dimension. A Fine Needle Aspiration Cytology (FNAC) was performed and diagnosis of indeterminate neoplastic lesion, indefinite whether primary or metastatic, was formulated. After complete thyroidectomy, the histological picture of the nodule was characterized by a dual cellular population: several glandular structures composed by columnar cells with clear cytoplasm were embedded in a highly cellular stroma composed of spindle-shaped elements. Immunohistochemistry and molecular biology confirmed the morphological suspicion of SS identifying the fusion transcript SYT-SSX1 and thus ruling out several differential diagnoses which include more common thyroid malignancies. Moreover a synchronous papillary microcarcinoma was detected in the controlateral lobe.This case is noteworthy since it describes the synchronous presence in the thyroid of two completely different malignancies, the first one belonging to the soft tissue neoplasm category and the other one originating from the thyroid follicular epithelium.

Incidental thyroid carcinoma in patients with TIR1, TIR2 and TIR3 FNA.

AIM: The aim of our study was to evaluate the presence of incidental differentiated thyroid carcinomas, at final histological examination, in patients undergoing thyroidectomy or lobectomy for presumed benign pathology or in those with cytological diagnosis of indeterminate nodules (TIR3). MATERIAL OF STUDY: 457 patients who underwent surgery for benign disease and 179 patients with indeterminate FNA were included in our study. RESULTS: 77 out of 457 patients had the diagnosis of differentiated thyroid carcinoma. 29 out of 179 patients had the same diagnosis as previous ones, but not on the undetermined FNA nodule. In the most of the cases, the istotype was follicular variant of papillary carcinoma. DISCUSSION: The incidence of incidental carcinomas, approximately the same in the two groups of patients, respectively 16.8% and 16.2%, shows that there is still a group of patients with benign thyroid disease escaping a careful ultrasound evaluation and therefore a targeted FNA. Even in patients with indeterminate cytology, the presence of an incidental carcinoma suggests that on the one hand there has been an overestimation and on the other a non-recognition of the really suspect nodule. Although in most cases it is a microcarcinoma, we must not overlook the presence of many tumors at stage T3. CONCLUSIONS: Surely the analysis of the set of risk factors with a wider application of molecular biology surveys will in the future lead to better selection of patients to undergo surgery sooner than those that can be followed in follow up even for a longer period of time. KEY WORDS: Differentiated thyroid carcinoma, Fine needle aspiration, Incidental carcinoma.

Application of Immunocytochemistry on Cell Block Sections for the Investigation of Thyroid Lesions.

OBJECTIVE: To investigate the potential of Classification and Regression Trees (CARTs) for the diagnosis of thyroid lesions based on cell block immunocytochemistry and cytological outcome. STUDY DESIGN: A total of 956 histologically confirmed cases (673 benign and 283 malignant) from patients with thyroid nodules were prepared via liquid-based cytology and evaluated; 4 additional slides were stained for cytokeratin 19 (CK-19), galectin 3 (Gal-3), Hector Battifora mesothelial cell 1 (HBME-1), and thyroglobulin. On the basis of immunocytochemistry and the cytological diagnosis, a CART algorithm was constructed and used for evaluation. RESULTS: The major important factors contributing to the diagnostic CART model were: cytological outcome, CK-19, Gal-3, and HBME-1. The sensitivity and specificity of the cytological diagnosis were 96.27% and 88.26%, respectively (cut-off: category 3 of The Bethesda System [TBS-3]). The introduction of immunocytochemistry and the CART model increased the sensitivity and specificity to 98.88% and 99.11%, respectively. CK-19 presented the best performance for discriminating papillary thyroid carcinomas, followed by HBME-1 and Gal-3. In the TBS-2 cases, CK-19 and, subsequently, Gal-3 were important immunocytochemistry markers. Ultimately, CK-19 and HBME-1 on TBS-5 or TBS-6 cases demonstrated the best results. CONCLUSIONS: The hierarchical structure of the CART model provides a diagnostic algorithm linked with the risk of malignancy at every step of the procedure. It also provides guidance on the use of ancillary examinations as it goes by simple, human understandable rules.

Clinical performance of a next-generation sequencing assay (ThyroSeq v2) in the evaluation of indeterminate thyroid nodules.

BACKGROUND: Molecular testing with the Thyroseq v2 next generation sequencing panel ("Thyroseq") is used to estimate the risk of cancer in indeterminate thyroid nodules. METHODS: We analyzed 156 indeterminate thyroid nodules evaluated with Thyroseq, across 3 institutions. Thyroseq data and surgical pathology were matched via pathologic re-review. A result was considered Thyroseq positive if molecular alterations were annotated on the report with malignancy probability >30%. Performance characteristics were estimated using Bayes theorem. RESULTS: The Thyroseq-negative call rate was 65% (102/156). On surgical pathology, 16% (10/63) of nodules were malignant. The positive predictive value of a Thyroseq-positive result was 22% (8/37; if 2 noninvasive follicular thyroid neoplasm with papillary-like nuclear features are counted as malignant, 27%, 10/37). There was 1 false-negative result (negative predictive value 96%, 22/23). The most common mutation was NRAS (19/37) with a positive predictive value of 7% (1/15). The positive predictive value of all RAS mutations (HRAS, KRAS, NRAS) was 9% (2/22). The second most common mutation, BRAF V600E, had positive predictive value of 100% (3/3). CONCLUSION: We report an external analysis of Thyroseq performance in the evaluation of indeterminate thyroid nodules. These data indicate that Thyroseq is likely to offer high negative predictive value but low positive predictive value. Many genetic alterations appear to be nonspecific for malignancy, and positive results should be interpreted with caution. These findings have implications for the management of indeterminate thyroid nodules profiled with Thyroseq.

Proof-of-concept Raman spectroscopy study aimed to differentiate thyroid follicular patterned lesions.

Inter-observer variability and cancer over-diagnosis are emerging clinical problems, especially for follicular patterned thyroid lesions. This challenge strongly calls for a new clinical tool to reliably identify neoplastic lesions and to improve the efficiency of differentiation between benign and malignant neoplasms, especially considering the increased diagnosis of small carcinomas and the growing number of thyroid nodules. In this study, we employed a Raman spectroscopy (RS) microscope to investigate frozen thyroid tissues from fourteen patients with thyroid nodules. To generate tissue classification models, a supervised statistical analysis of the Raman spectra was performed. The results obtained demonstrate an accuracy of 78% for RS based diagnosis to discriminate between normal parenchyma and follicular patterned thyroid nodules, and 89% accuracy - for very challenging follicular lesions (carcinoma versus adenoma). RS translation into intraoperative diagnosis of frozen sections and in preoperative analysis of biopsies can be very helpful to reduce unnecessary surgery in patients with indeterminate cytological reports.

RAS-positive thyroid nodules.

PURPOSE OF REVIEW: The current review focuses on the uncertainty regarding the management of rat sarcoma viral oncogene homolog RAS-positive thyroid nodules. The application of oncogene testing has been heralded for improving risk assessment for indeterminate cytology thyroid nodules and has grown in clinical use. RAS mutations are historically considered oncogenic. However, RAS mutation detection in thyroid nodules has proven problematic, as these mutations are found in benign and malignant lesions. RECENT FINDINGS: RAS-positive thyroid nodules frequently have indeterminate cytology and a finding of a positive RAS mutation identifies a significant number of benign lesions as well as thyroid cancers. Long-term follow-up of RAS-positive nodules with benign cytology shows an indolent course not consistent with eventual malignant transformation. Many RAS-positive nodules previously diagnosed as follicular variant of papillary thyroid carcinoma now will be reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features, indicating a more indolent nature of these RAS-positive lesions. SUMMARY: Recent findings have underscored that diagnosis of a RAS-positive thyroid nodule is not synonymous with thyroid malignancy. The ideal clinical and surgical management of these nodules remains challenging.

Identification of benign and malignant thyroid nodules by in vivo iodine concentration measurement using single-source dual energy CT: A retrospective diagnostic accuracy study.

This study proposed to determine whether in vivo iodine concentration measurement by single-source dual energy (SSDE) CT can improve differentiation between benign and malignant thyroid nodules. In total, 53 patients presenting with thyroid nodules underwent SSDE CT scanning. Iodine concentrations were measured for each nodule and normal thyroid tissue using the GSI-viewer image analysis software. A total of 26 thyroid nodules were malignant in 26 patients and confirmed by surgery; 33 nodules from 27 patients were benign, with 10 confirmed by surgery and others after follow-up. Iodine concentrations with plain CT were significantly lower in malignant than benign nodules (0.47 ±â€Š0.20 vs 1.17 ±â€Š0.38 mg/mL, P = 0.00). Receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.93; with a cutoff of 0.67, iodine concentration showed 92.3% sensitivity and 88.5% specificity in diagnosing malignancy. Iodine concentration obtained by enhanced and plain CT were significantly higher in malignant than benign nodules (9.05 ±â€Š3.35 vs 3.46 ±â€Š2.24 mg/mL, P = 0.00). ROC curve analysis showed an AUC of 0.93; with a cutoff value of 3.37, iodine concentration displayed 78% sensitivity, 95% specificity in diagnosing malignancy. Combining unenhanced with enhanced iodine concentrations, the diagnostic equation was: Y = -8.641 × unenhanced iodine concentration + 0.663 × iodine concentration. ROC curve showed an AUC of 0.98 (95% CI, 0.94, 1.00). With Y ≥ -2 considered malignancy, diagnostic sensitivity and specificity were 96%, 96.3%, respectively. This study concluded that SSDE CT can detect the differences in iodine uptake and blood supply between benign and malignant thyroid lesions.