Follicular adenoma with a papillary architecture originating from an ectopic thyroid gland: a case report.

BACKGROUND: Follicular adenomas with papillary architecture are rare tumors of thyroid origin and are composed of completely encapsulated follicular cells with a papillary architecture lacking the nuclear characteristics of papillary carcinoma. Herein, we present a case of follicular adenoma with papillary architecture originating from an ectopic thyroid gland, diagnosed from a mass in the submandibular region. CASE PRESENTATION: A 70-year-old woman was referred to our hospital with the chief complaint of a painless left submandibular mass that had been present for one year. The patient underwent left submandibular dissection for therapy and diagnosis. Microscopically, papillary lesions with fibrovascular cores were observed in the interior, and the epithelial cells were cylindrical in shape with eosinophilic cytoplasm, round or oval nuclei, with no pathological features, leading to a diagnosis of papillary carcinoma or follicular carcinoma. The mass was diagnosed as a follicular thyroid adenoma with papillary architecture. This is the first report of a follicular adenoma with a papillary architecture originating from an ectopic thyroid gland. CONCLUSION: This experience suggests that follicular adenoma should be included in the differential diagnosis of ectopic thyroid tumors.

NIFTPs may be reclassified not only from FVPTCs but also from follicular adenomas.

Few studies have focused on reclassifying follicular adenomas (FAs) as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), but none have been conducted in America or Europe. The aims of this study were to analyze the prevalence of NIFTP reclassified from follicular variant of papillary thyroid carcinomas (FVPTCs) and FAs before NIFTP was defined in the literature, the rate of NIFTP among PTC (papillary thyroid carcinomas) established in real time between 2017 and 2022, and demographic, ultrasonographic, and cytologic characteristics of NIFTPs compared with FVPTCs and FAs. This was a retrospective cohort study of tumors diagnosed as PTCs (n = 247) and FAs (n = 144) at a Brazilian hospital. Overall, 13.4% of PTCs and 7% of FAs were reclassified as NIFTPs. The rate of real-time diagnosed NIFTPs among PTC was 12.3%. The median tumor size was larger among NIFTPs (3.0 cm) than FVPTCs (1.1 cm; P < 0.01). A high-risk ultrasonographic pattern was rare in NIFTPs (5.6%). The cytologic classifications differed between FVPTCs and NIFTPs (P < 0.01), and the most frequent category among NIFTPs was 'follicular neoplasm' (52.6%). The category 'suspicious for malignancy' was frequent in FVPTCs and rare (5.3%) in NIFTPs. In conclusion, FVPTCs and FAs may be reclassified as NIFTPs. The prevalence of NIFTPs reclassified from FAs was lower in our cohort than in Asian studies. The rate of NIFTPs reclassified from PTC was similar to that of NIFTPs diagnosed in real time and was aligned with rates reported in studies from America and Europe. Preoperative features could not differentiate NIFTPs from FVPTCs or FAs.

Utility of the Growth Differentiation Factor-15 in the Differential Diagnosis of Follicular-Patterned Lesions of the Thyroid on Cytopathologic and Histopathologic Samples.

Background Follicular-patterned lesions are a major gray zone in thyroid cytopathology. The recently introduced 2022 World Health Organization (WHO) classification emphasizes the importance of genetic alterations in thyroid neoplasms with the introduction of certain newer terminologies that are expected to cause remarkable changes in cytopathologic and histopathologic reporting. Although molecular assays such as the Afirma gene expression classifier and the ThyroSeq are already in use, there has been an ongoing search for further reliable molecular markers. The growth differentiation factor-15 (GDF-15) is one among them. This study aimed to determine the diagnostic utility of GDF-15 mRNA expression in frozen tissue and fine-needle aspiration (FNA) samples from follicular-patterned thyroid lesions and neoplasms. Methodology The real-time quantitative polymerase chain reaction was performed on 75 frozen tissue and FNA samples each from 19 cases of follicular thyroid hyperplasia (FTH), 10 nodular goiters (NGs), 17 follicular thyroid adenomas (FTAs), eight follicular thyroid carcinomas (FTCs), 12 follicular variant of papillary thyroid carcinomas (FVPTCs), and nine classic papillary thyroid carcinomas (CPTCs) that were diagnosed according to the 2017 WHO classification of thyroid neoplasms. The GDF-15 mRNA expression in all these cases was assessed and compared with the control thyroid tissue samples. One-way analysis of variance and the Kruskal-Wallis test were performed using GraphPad Prism 8 software to determine the significance of differences in the GDF-15 mRNA levels among various thyroid lesions. Results A higher GDF-15 mRNA expression was noted in the malignant thyroid neoplasms including FTC, FVPTC, and CPTC in comparison to FTA, with a fold change between the malignant and benign groups being more than 244.18 times. A difference in the fold change was noted between FTH and FTA with an increase in GDF-15 mRNA level in the latter, which was statistically not significant. Conclusions The fact that GDF-15 mRNA was studied both on fine-needle aspiration cytologic and the frozen tissue material and that the majority of the lesions studied were follicular-patterned establishes the GDF-15 as a potential marker not only for diagnosing malignant thyroid neoplasms of the follicular epithelium but also in distinguishing benign and malignant follicular-patterned neoplasms of the thyroid.

Deep Learning-Based Differential Diagnosis of Follicular Thyroid Tumors Using Histopathological Images.

Deep learning systems (DLSs) have been developed for the histopathological assessment of various types of tumors, but none are suitable for differential diagnosis between follicular thyroid carcinoma (FTC) and follicular adenoma (FA). Furthermore, whether DLSs can identify the malignant characteristics of thyroid tumors based only on random views of tumor tissue histology has not been evaluated. In this study, we developed DLSs able to differentiate between FTC and FA based on 3 types of convolutional neural network architecture: EfficientNet, VGG16, and ResNet50. The performance of all 3 DLSs was excellent (area under the receiver operating characteristic curve = 0.91 ± 0.04; F1 score = 0.82 ± 0.06). Visual explanations using gradient-weighted class activation mapping suggested that the diagnosis of both FTC and FA was largely dependent on nuclear features. The DLSs were then trained with FTC images and linked information (presence or absence of recurrence within 10 years, vascular invasion, and wide capsular invasion). The ability of the DLSs to diagnose these characteristics was then determined. The results showed that, based on the random views of histology, the DLSs could predict the risk of FTC recurrence, vascular invasion, and wide capsular invasion with a certain level of accuracy (area under the receiver operating characteristic curve = 0.67 ± 0.13, 0.62 ± 0.11, and 0.65 ± 0.09, respectively). Further improvement of our DLSs could lead to the establishment of automated differential diagnosis systems requiring only biopsy specimens.

Identification of Diagnostic Metabolic Signatures in Thyroid Tumors Using Mass Spectrometry Imaging.

"Gray zone" thyroid follicular tumors are difficult to diagnose, especially when distinguishing between benign follicular thyroid adenoma (FTA) and malignant carcinoma (FTC). Thus, proper classification of thyroid follicular diseases may improve clinical prognosis. In this study, the diagnostic performance of metabolite enzymes was evaluated using imaging mass spectrometry to distinguish FTA from FTC and determine the association between metabolite enzyme expression with thyroid follicular borderline tumor diagnosis. Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFAIDESI-MSI) was used to build a classification model for thyroid follicular tumor characteristics among 24 samples. We analyzed metabolic enzyme marker expression in an independent validation set of 133 cases and further evaluated the potential biological behavior of 19 thyroid borderline lesions. Phospholipids and fatty acids (FAs) were more abundant in FTA than FTC (p < 0.001). The metabolic enzyme panel, which included FA synthase and Ca2+-independent PLA2, was further validated in follicular thyroid tumors. The marker combination showed optimal performance in the validation group (area under the ROC, sensitivity, and specificity: 73.6%, 82.1%, and 60.6%, respectively). The findings indicate that AFAIDESI-MSI, in combination with low metabolic enzyme expression, could play a role in the diagnosis of thyroid follicular borderline tumors for strict follow-up.

Clinical, cytological, and pathological characteristics of metastatic renal cell carcinoma to the thyroid: A study of 14 cases at a Japanese single institution.

A preoperative diagnosis of metastatic renal cell carcinoma to the thyroid (MRCCT) is important for determining clinical management but is challenging even in cases with a clinical history of renal cell carcinoma (RCC). This study aimed to elucidate the clinical, cytological, and pathological characteristics of MRCCT. Fourteen MRCCT cases extracted from 18 320 malignant thyroid tumors were included in this study. Twelve MRCCT (85.7%) occurred as solitary lesions and the most frequently suspected lesions on ultrasonography were follicular tumors. On cytology, 46.2% of cases were reported as RCC or suspected RCC; a medical history of RCC and immunocytochemistry were helpful in interpretation. RCC metastasized to a follicular adenoma in 50.0% of the solitary lesions. MRCCTs with a long interval from the initial presentation, solitary lesion, and Ki-67 labeling index <10% showed significantly longer disease-free survival. MRCCT is characterized by a long interval from the initial presentation of RCC, appearance as a solitary nodule, ultrasonographic similarity to follicular tumors, sharing cytological findings with primary thyroid tumors, and high frequency of metastasis within follicular adenoma. A long interval from the initial presentation, occurrence as a solitary lesion, and low Ki-67 labeling index may be favorable prognostic factors.

Expression of micro-ribonucleic acids in thyroid nodules and serum to discriminate between follicular adenoma and cancer in patients with a fine needle aspiration biopsy classified as suspicious for follicular neoplasm: A preliminary study.

BACKGROUND: Approximately 10% of thyroid nodules undergoing fine needle aspiration biopsy (FNAB) receive a suspicious for follicular neoplasm (SFN) classification. Currently, there is no diagnostic tool to preoperatively discriminate between follicular adenoma (FA) and thyroid cancer (TC), and most patients require surgery to exclude malignancy. OBJECTIVES: To characterize the micro-ribonucleic acid (miRNA) signature of tumors assessed as SFN and define circulating miRNA patterns to distinguish FA from follicular cancer in patients with thyroid nodules biopsied using FNAB. MATERIAL AND METHODS: The study included excised tumor and thyroid tissue samples from 80 consecutive patients collected by a pathologist in the operating theater. The miRNA was isolated from specimens at the Center for Medical Genomics OMICRON, and next-generation sequencing (NGS) was used to obtain target miRNAs. In addition, miRNA expression was detected in serum using polymerase chain reaction (PCR). RESULTS: Well-differentiated thyroid cancer (WDTC) samples had significantly higher expression levels of hsa-miR-146b-5p (p = 0.030) and hsa-miR-146b-3p (p = 0.032), while the expression levels of hsa-miR-195-3p were significantly lower (p = 0.032) in WDTC samples compared to FA specimens. The serum of TC patients showed markedly higher expression of the unique miRNA hsa-miR-195-3p (p = 0.039). CONCLUSIONS: The overexpression of hsa-miR-146b-5p and hsa-miR-146b-3p, and the downregulation of hsa-miR-195-3p expression could be used as biomarkers to distinguish FA from WDTC in patients with FNAB results classified as Bethesda tier IV. In addition, hsa-miR-195-3p could act as a serum biomarker for differentiating patients with FA from those with WDTC, and preoperative measurement of its expression would help avoid unnecessary surgeries. However, this concept needs further verification in a more substantial prospective study.

Beware the recurrent 'benign' multinodular goitre.

BACKGROUND: The diagnosis of follicular carcinoma is often difficult to make on pathological analysis, as the histological distinction from follicular adenoma rests solely on the presence of capsular or vascular invasion. Even on retrospective review of the histopathology after the disease biology has declared itself as malignant, the pathological diagnosis of malignancy may not be possible to make. METHODS: We report three cases in which patients were initially diagnosed with benign follicular lesions, but re-presented with locally recurrent disease and a subsequent malignant disease course. RESULTS: We describe a rare entity of follicular thyroid carcinoma that demonstrates a locally recurrent and eventually metastatic disease phenotype, despite persistently benign pathological findings. CONCLUSION: We highlight that if local recurrence occurs in discrete anatomical tissue planes, or in the thyroid bed following open total thyroidectomy for 'benign multinodular goitre', the possibility of this rare presentation of follicular thyroid carcinoma should be considered.

An attempt to reduce unnecessary surgical procedures... Can ultrasound characteristics help in differentiating adenoma vs carcinoma in follicular thyroid neoplasms?

INTRODUCTION AND OBJECTIVES: Thyroid nodules frequently require ultrasound and Fine Needle Aspiration Cytology (FNAC) evaluation. However, FNA cytology does not allow differentiation between follicular adenoma and carcinoma on Bethesda type IV lesions. This situation leads to many unnecessary surgical procedures because it is not possible to assure the benignity of the lesions, even when most of the specimens correspond to adenomas or even other benign lesions. The objective is this study is to establish if there are any US characteristics that would help us to predict the risk of malignancy of nodules with a pathological diagnosis of follicular neoplasm in order to achieve a more conservative management for non-suspicious nodules. MATERIAL AND METHODS: We studied 61 nodules in 61 patients (51 women and 10 men) that underwent thyroid surgery and had histopathological results of either follicular adenoma or carcinoma. Different US characteristics of the nodules were analysed (composition, echogenicity, margin, calcification status, the presence of halo and overall observer suspicion of malignancy) and were correlated with the histopathological analysis. RESULTS: We have found a statistically significant association between the presence of calcifications, ill-defined borders and overall observer suspicion or impression (defined by well-known suspicious for malignancy ultrasonographic features, such as calcification, poorly defined margin, and a markedly hypoechoic solid nodule; and benign ultrasonographic features, such as predominantly cystic echogenic composition and the presence of a perinodular hypoechogenic halo) with follicular carcinoma. However all those features have shown low sensitivities in the present study (30%, 30% and 50%, respectively). On the other hand, the absence of halo sign has shown a sensitivity of 100% and a negative predictive value (NPV) of 100% in our study. CONCLUSIONS: The presence of calcifications, ill-defined borders and the overall impression or suspicion of malignancy associate with a higher risk for follicular carcinoma in Bethesda type IV thyroid nodules but their absence do not allow to predict benignity in these nodules. Inversely, when a halo sign lesion is observed, benign follicular neoplasm should be considered.

Un intento de reducir intervenciones quirúrgicas innecesarias... ¿Pueden ayudar las características ecográficas a diferenciar el adenoma del carcinoma en las neoplasias tiroideas foliculares? / An attempt to reduce unnecessary surgical procedures... Can ultrasound characteristics help in differentiating adenoma vs carcinoma in follicular thyroid neoplasms?

Introducción y objetivosLos nódulos tiroideos requieren con frecuencia evaluación mediante ecografía y biopsia por aspiración con aguja fina (BAAF). No obstante, la BAAF no permite la diferenciación entre adenoma y carcinoma folicular en lesiones de tipo IV según la clasificación de Bethesda. Esto provoca numerosas intervenciones quirúrgicas innecesarias porque no es posible garantizar el carácter benigno de las lesiones, ni siquiera cuando la mayoría de las muestras corresponden a adenomas o incluso a otras lesiones benignas. El objetivo de este estudio es establecer si hay características ecográficas que nos ayudarían a pronosticar el riesgo de malignidad de los nódulos con un diagnóstico anatomopatológico de neoplasia folicular para conseguir un abordaje más conservador de los nódulos sin sospecha de malignidad.Material y métodosEstudiamos 61 nódulos en 61 pacientes (51 mujeres y 10 varones) que se habían sometido a intervención quirúrgica de la glándula tiroides y tenían resultados histopatológicos de adenoma o carcinoma folicular. Se analizaron diversas características ecográficas de los nódulos (composición, ecogenicidad, borde, estado de calcificación, presencia de halo y sospecha general de malignidad según el observador) y se estableció su correlación con el análisis histopatológico.ResultadosObservamos una relación estadísticamente significativa entre el carcinoma folicular y la presencia de calcificaciones, bordes mal definidos y la sospecha o impresión general del observador (definida por sospecha clara de signos ecográficos de malignidad, como calcificación, borde mal definido y un nódulo sólido marcadamente hipoecoico; y signos ecográficos de benignidad, como composición ecogénica predominantemente quística y presencia de halo hipoecogénico perinodular). Sin embargo, todas estas características han mostrado una sensibilidad baja en el estudio que nos ocupa (30%, 30% y 50%, respectivamente)...(AU)

Introduction and objectivesThyroid nodules frequently require ultrasound and Fine Needle Aspiration Cytology (FNAC) evaluation. However, FNA cytology does not allow differentiation between follicular adenoma and carcinoma on Bethesda type IV lesions. This situation leads to many unnecessary surgical procedures because it is not possible to assure the benignity of the lesions, even when most of the specimens correspond to adenomas or even other benign lesions.The objective is this study is to establish if there are any US characteristics that would help us to predict the risk of malignancy of nodules with a pathological diagnosis of follicular neoplasm in order to achieve a more conservative management for non-suspicious nodules.Material and methodsWe studied 61 nodules in 61 patients (51 women and 10 men) that underwent thyroid surgery and had histopathological results of either follicular adenoma or carcinoma.Different US characteristics of the nodules were analysed (composition, echogenicity, margin, calcification status, the presence of halo and overall observer suspicion of malignancy) and were correlated with the histopathological analysis.ResultsWe have found a statistically significant association between the presence of calcifications, ill-defined borders and overall observer suspicion or impression (defined by well-known suspicious for malignancy ultrasonographic features, such as calcification, poorly defined margin, and a markedly hypoechoic solid nodule; and benign ultrasonographic features, such as predominantly cystic echogenic composition and the presence of a perinodular hypoechogenic halo) with follicular carcinoma. However all those features have shown low sensitivities in the present study (30%, 30% and 50%, respectively). On the other hand, the absence of halo sign has shown a sensitivity of 100% and a negative predictive value (NPV) of 100% in our study... (AU)

The Role of Claudin-1 Expression in Follicular and Papillary Thyroid Neoplasm.

OBJECTIVE: This study evaluated differences in Claudin-1 expression between follicular adenoma (FA), follicular thyroid carcinoma (FTC), follicular variant papillary thyroid carcinoma (FV-PTC), and papillary thyroid carcinoma (PTC). MATERIAL AND METHODS: This study used a cross-sectional approach. Immunostaining using the polyclonal antibody Claudin-1 was performed on 75 samples divided into 20 samples for follicular adenoma, follicular thyroid carcinoma, papillary carcinoma, and 15 samples of follicular variant thyroid carcinoma, respectively. RESULTS: Claudin-1 expression is detected on the cytoplasmic membrane of tumor cells and appears to be varied among thyroid neoplasms. The claudin-1 expression score revealed a statistically significant difference between FA against FV-PTC, FA versus (vs) PTC, and FTC vs PTC, with median values of 4 vs 6 (p = 0.016), 4 vs 8 (p = 0.001), and 5 vs 8 (p = 0.002), respectively. However, there was no statistically significant difference in scores between the FA and the FTC (4 vs 5), or between the FTC and the FV-PTC groups (5 vs 6 (p=1,000). CONCLUSION: These results suggest that Claudin-1 may be capable of discriminating follicular adenoma from classic and follicular variant of papillary thyroid carcinoma. It can also differentiate follicular thyroid carcinoma and papillary thyroid carcinoma, especially for cases challenging to assess by hematoxylin and eosin staining. It still holds promise in providing targeted cancer therapy.

Diagnostic performance of six ultrasound-based risk stratification systems in thyroid follicular neoplasm: A retrospective multi-center study.

This study aimed to compare the diagnostic performances of six commonly used ultrasound-based risk stratification systems for distinguishing follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC), including the American Thyroid Association Sonographic Pattern System (ATASPS), ultrasound classification systems proposed by American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinology (AACE/ACE/AME), Korean thyroid imaging reporting and data system (K-TIRADS), European Thyroid Association for the imaging reporting and data system (EU-TIRADS), American College of Radiology for the imaging reporting and data system (ACR-TIRADS), and 2020 Chinese Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules (C-TIRADS). A total of 225 FTA or FTC patients were retrospectively analyzed, involving 251 thyroid nodules diagnosed by postoperative pathological examinations in three centers from January 2013 to October 2021. The diagnostic performances of six ultrasound-based risk stratification systems for distinguishing FTA from FTC were assessed by plotting the receiver operating characteristic (ROC) curves and compared at different cut-off values. A total of 205 (81.67%) cases of FTA and 46 (18.33%) cases of FTC were involved in the present study. Compared with those of FTA, FTC presented more typical ultrasound features of solid component, hypoechoic, irregular margin and sonographic halo (all P<0.001). There were no significant differences in ultrasound features of calcification, shape and comet-tail artifacts between cases of FTA and FTC. There was a significant difference in the category of thyroid nodules assessed by the six ultrasound-based risk stratification systems (P<0.001). The areas under the curve (AUCs) of ATASPS, AACE/ACE/AME, K-TIRADS, EU-TIRADS, ACR-TIRADS and C-TIRADS in distinguishing FTA from FTC were 0.645, 0.729, 0.766, 0.635, 0.783 and 0.798, respectively. Our study demonstrated that all the six ultrasound-based risk stratification systems present potential in the differential diagnosis of FTA and FTC. Specifically, C-TIRADS exerts the best diagnostic performance among the Chinese patients. ATASPS possesses a high sensitivity, while K-TIRADS possesses a high specificity in distinguishing FTA from FTC.

Case report: Intraoperative frozen section analysis of Thyroid paraganglioma.

Paraganglioma (PGL) is a neuroendocrine tumor that arises from the sympathetic or parasympathetic paraganglia. Primary thyroid PGL is extremely rare. PGL may be difficult to diagnose on frozen sections because its histopathological features, such as polygonal tumor cells with eosinophilic cytoplasm arranged irregularly, overlap with those of thyroid follicular adenoma. We present a case of thyroid PGL in a female patient and provide a detailed description of the patient's clinicopathologic characteristics. Cervical computed tomography showed a left thyroid mass with uneven density. Intraoperative frozen section analysis showed an uneven fibrous septa and rich networks of delicate vessels surrounding tumor cell nests. The tumor cells were polygonal or epithelioid with eosinophilic cytoplasm, arranged in a nest, trabecular, or organoid pattern were and diagnosed as thyroid follicular adenoma. However, in postoperative immunohistochemistry, these were diagnosed as thyroid PGL. The postoperative recovery was uneventful. The patient showed no signs of tumor recurrence or metastasis until 16 months of follow-up. Herein, we summarize the characteristic features of thyroid PGL based on frozen section analysis. In the appropriate clinical context, its proper use as diagnostic and differential diagnostic management strategies is recommended.

DICER1 Mutations Occur in More Than One-Third of Follicular-Patterned Pediatric Papillary Thyroid Carcinomas and Correlate with a Low-Risk Disease and Female Gender Predilection.

Some pediatric papillary thyroid carcinoma (PPTC) cohorts have suggested a preliminary correlation with respect to DICER1 mutation status and histomorphology in both benign and malignant follicular cell-derived nodules; however, the data regarding correlates of DICER1-related sporadic PPTCs subtyped based on the 2022 WHO classification criteria are largely unavailable. The current study investigated the status of hotspot DICER1 mutations with clinical, histological and outcome features in a series of 56 patients with PPTCs with no clinical or family history of DICER1-related syndromic manifestation. Fifteen (27%) PPTCs harbored BRAF p.V600E. Eight (14%) cases of PPTCs harbored DICER1 mutations with no associated BRAF p.V600E. DICER1 mutations were identified in exons 26 and 27. A novel D1810del (c.5428_5430delGAT) mutation was also detected. We also confirmed the absence of hotspot DICER1 mutations in the matched non-tumor tissue DNA in all 8 DICER1-related PPTCs. The mean age of DICER1-harboring PPTCs was 15.1 (range: 9-18) years whereas the rest of this cohort had a mean age of 14.8 (range 6-18) years. With the exception of one PPTC, all DICER1-related PPTCs were seen in females (female-to-male ratio: 7). The female to male ratio was 3.8 in 48 DICER1-wild type PPTCs. In terms of histological correlates, 5 of 8 (63%) DICER1-mutant PPTCs were invasive encapsulated follicular variant papillary thyroid carcinomas (FVPTCs) including 4 minimally invasive FVPTCs and 1 encapsulated angioinvasive FVPTC, whereas the remaining 3 PPTCs were infiltrative classic papillary thyroid carcinomas (p < 0.05). The incidence of DICER1 mutations was 19.5% in BRAF p.V600E-wild type PPTCs. Sixty-three percent of DICER1 hotspot mutations occurred in invasive encapsulated FVPTCs, and this figure represents 38% of invasive encapsulated FVPTCs. Only one (12%) patient with DICER1-related disease showed a single lymph node with micro-metastasis. Unlike DICER1-wild type patients, no distant metastasis is identified in patients with DICER1-related PPTCs. The current series expands on the surgical epidemiology of somatic DICER1-related PPTCs by correlating the mutation status with the clinicopathological variables. Our findings underscore that female gender predilection and enrichment in low-risk follicular-patterned PTCs are characteristics of DICER1-related PPTCs.

ACR TI-RADS classification combined with number of nodules, halo features optimizes diagnosis and prediction of follicular thyroid cancer.

OBJECTIVES: To investigate the application value of The American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) category combined with other ultrasound features of nodules in distinguishing follicular thyroid carcinoma (FTC) from thyroid follicular adenoma (FTA). METHODS: We collected and retrospectively analyzed clinical and ultrasound data for 118 and 459 patients with FTCs and FTAs, respectively, at our hospital. Next, we used ACR TI-RADS classification combined with other ultrasound features of nodules to distinguish FTC from FTA. Multivariate Logistic regression was used to screen independent risk factors for FTC, which were subsequently used to construct a nomogram for predicting FTC. RESULTS: ACR TI-RADS categories 4 and 5, unilateral multiple nodules, and halo thickness≥2 mm were independent risk factors for FTC. ACR TI-RADS category combined with number of nodules, halo features of the nodule was a significantly better prediction model for FTC diagnosis (AUC = 0.869) than that of ACR TI-RADS classification alone (AUC = 0.756). CONCLUTIONS: Clinicians need to pay attention to the halo of nodules when distinguishing FTA from FTC. Notably, ACR TI-RADS combined with other nodule ultrasound features has superior predictive performance in diagnosis of FTC compared to ACR TI-RADS classification alone, thus can provide an important reference value for preoperative diagnosis of FTC.

Search for New Target Genes of MicroRNA for Differential Diagnosis of Benign and Malignant Neoplasms of the Thyroid Gland by In Silico Methods.

Differential diagnosis of thyroid gland neoplasms is an urgent problem in modern oncothyroidology. This is especially true for the diagnosis of follicular thyroid cancer and follicular thyroid adenoma at the preoperative stage. In this study, in silico methods were used to search for potential markers that are microRNA target genes. A list of 19 microRNAs was compiled, the expression of which varies depending on the type of thyroid neoplasms. For these microRNAs, the target genes were selected considering tissue specificity and association with thyroid diseases. We selected 9 target genes (MCM2, RASSF2, SPAG9, SSTR2, TP53BP1, INPP4B, CCDC80, GNAS, and PLK1), which can be considered as promising markers according to published data. Also, 6 new potential markers (CDK4, FGFR1, ERBB3, EGR1, MYLK, and SRC) were found, which make it possible to distinguish between follicular thyroid cancer and follicular thyroid adenoma. The proposed algorithm using various bioinformatics tools allows us to identify potential markers for the differential diagnosis of thyroid neoplasms.

Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule Practice.

Histopathological diagnosis of papillary thyroid carcinomas (PTCs) is prone to significant observer variation due to different thresholds of RAS-like nuclear changes among pathologists. This gap recently widened due to a defensive attitude by Western pathologists where malpractice litigation is significant. Cases with delicate RAS-like nuclear changes are follicular adenomas when they are noninvasive, follicular carcinomas when invasive, and follicular variant PTCs when they have fully developed PTC-type nuclear features in Asian practice. The different diagnostic threshold of PTC nuclear features resulted in a high (50-90%) incidence of BRAFV600E mutation of PTCs in most Asian countries, whereas it was low (35-50%) in most Western patient cohorts. The contamination of indolent RAS-like tumors in the malignant PTC category in Western patient cohorts explains why the BRAFV600E gene test identifies aggressive PTCs. However, the BRAFV600E test has no prognostic value for Asian PTC patients because most biologically benign or low-risk RAS-like tumors are excluded from PTC. All prognostic analyses of thyroid carcinomas before 2017 must be re-evaluated because most clinical guidelines were established based on data obtained from Western patient cohorts where a significant number of indolent RAS-like tumors were misclassified in the malignant category.

The Combined Utility of HBME-1 and Galectin-3 Immunohistochemistry and BRAF V600E Mutations in the Diagnosis of Papillary Thyroid Carcinoma.

Newer diagnostic modalities have revolutionized the pathologist's approach to diagnosing thyroid malignancies. Molecular characterization of these malignancies has helped circumvent common morphologic diagnostic difficulties by integrating their genotypic, phenotypic, and immunohistochemical features. BRAF V600E mutation has been characterized as highly specific for thyroid carcinoma, especially papillary thyroid carcinoma (PTC); human bone marrow endothelial marker-1 (HBME-1) and galectin-3 are also such markers that are highly specific for PTC. We propose to study HBME-1 and galectin-3 expression and BRAF V600E mutation in thyroid neoplasms and do a comparative analysis to determine whether there is a correlation between BRAF V600E expression and that of HBME-1 and galectin-3. We further propose to analyze the individual and combined diagnosed utility of the above-mentioned ancillary diagnostic techniques.

Logistic regression analysis of contrast-enhanced ultrasound and conventional ultrasound of follicular thyroid carcinoma and follicular adenoma.

BACKGROUND: Follicular thyroid carcinoma (FTC) is prone to recurrence and hematogenous metastasis, preoperative accurate diagnosis is still needed to help clinicians select the best surgical methods to improve the prognosis of patients. The aim of this study was to find specific conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) characteristics of FTC and to explore their diagnostic value in the differential diagnosis between FTC and follicular adenoma (FA). METHODS: This retrospective study included 258 thyroid follicular neoplasms (172 FAs and 86 FTCs) in 244 consecutive patients who underwent preoperative conventional US, and 72 of them underwent both conventional US and CEUS. Sonograms were reviewed in consensus by two experienced radiologists for various conventional US and CEUS features. Multivariate logistic regression analysis was performed to determine independent risk factors for FTC. RESULTS: Independent risk factors of conventional US for FTC were heterogenicity (OR =7.477, 95% CI: 2.848-19.629), unevenly thick halo (OR =5.643, 95% CI: 3.234-9.848) and calcifications (OR =1.748, 95% CI: 1.098-2.783). While independent risk factors determined with the combination of CEUS and conventional US were unevenly thick halo (OR =5.770, 95% CI: 1.310-25.409) and absent or irregular rim enhancement (OR =27.000, 95% CI: 2.445-298.178). The area under the receiver operating characteristic curve of the final two logistic regression models was 0.835 and 0.838. CONCLUSIONS: Conventional US is an efficient diagnostic tool in the differential diagnosis of FTC and FA to help clinicians in making appropriate decisions while CEUS failed to provide additional diagnostic value in the study, thus the value of CEUS remains to be verified by further studies with larger sample sizes.

Development and Validation of an Ultrasonic Diagnostic Model for Differentiating Follicular Thyroid Carcinoma from Follicular Adenoma.

BACKGROUND: High-resolution ultrasound is the first choice for the diagnosis of thyroid nodules, but it is still difficult to distinguish between follicular thyroid carcinoma (FTC) and follicular adenoma (FA). Our research aimed to develop and validate an ultrasonic diagnostic model for differentiating FTC from FA. METHODS: This study retrospectively analyzed 196 patients who were diagnosed as FTC (n=83) and FA (n=113). LASSO regression analysis was used to screen clinical and ultrasonic features. Multivariate logistic regression analysis was used to establish the ultrasonic diagnostic model of FTC. Nomogram was used for the visualization of diagnostic models. C-index, ROC, and calibration curves analysis were used to evaluate the accuracy of the diagnostic model. Decision curve analysis (DCA) was used to evaluate the net benefits of the ultrasonic diagnostic model for FTC diagnosis under different threshold probabilities. The bootstrap method was used to verify the ultrasonic diagnostic model. RESULTS: After Lasso regression analysis, 10 clinical and ultrasonic features were used to construct the ultrasonic diagnostic model of FTC. The C-index and AUC of the model were 0.868 and 0.860, respectively. DCA showed that the ultrasonic model had good clinical application value. The C-index in the validation group was 0.818, which was close to the C-index in the model. CONCLUSION: Ultrasonic diagnostic model constructed with 10 clinical and ultrasonic features can better distinguish FTC from FA.