Follicular Adenoma Research Articles

Adrenal Incidentalomas and Other Endocrine-Related Adenomas: How Much Does Cortisol Secretion Matter?

Background: Adrenal incidentalomas (AI) are frequent findings in clinical practice. About 40% of AIs are associated with hypercortisolism of variable severity. Although mild autonomous cortisol secretion (MACS) has been associated with the impaired clinical outcome of several diseases, its effect on the development of benign neoplasms is unknown. Aim: To compare the prevalence of adenomas (thyroid, parathyroid, pituitary and other locations) in patients with nonfunctioning AIs (NFAIs) and MACS. Methods: A multicenter, retrospective study of patients with AIs evaluated in four tertiary hospitals was performed. Results: A total of 923 patients were included. Most patients were male (53.6%), with a mean age at diagnosis of 62.4 ± 11.13 years; 21.7% presented with bilateral AIs. MACS was observed in 29.9% (n = 276) of patients, while 69.9% (n = 647) were NFAIs. Adenomas in locations other than the adrenal gland were observed in 36% of the studied population, with a similar distribution in patients with MACS and NFAIs (33% vs. 32%; p > 0.05). There were no statistically significant differences in the prevalence of pituitary, thyroid, parathyroid or other endocrine-related adenomas between both groups, but the prevalence of metabolic comorbidities and mortality was increased in patients with MACS, specifically in patients with thyroid and other endocrine-related adenomas (p < 0.05). Conclusions: Adenomas in locations other than the adrenal glands occur in one third of patients with AIs. Mild autonomous hypercortisolism does not affect the prevalence of other endocrine-related adenomas but is associated with increased metabolic comorbidities and mortality, especially in patients with thyroid adenomas and adenomas in other locations.

ThyroidPrint®: clinical utility for indeterminate thyroid cytology.

Molecular testing contributes to improving the diagnosis of indeterminate thyroid nodules (ITN). ThyroidPrint® is a 10-gene classifier aimed to rule-out malignancy in ITN. Post-validation studies are necessary to determine the real-world clinical benefit of ThyroidPrint® in patients with ITN. A single center, prospective, non-interventional clinical utility study was performed, analyzing the impact of ThyroidPrint® in the physicians' clinical decisions for ITN. Demographics, nodule characteristics, benign call rates (BCR) and surgical outcomes were measured. Histopathological data was collected from surgical biopsies of resected nodules. Of 1272 fine needle aspirations (FNA), 109 (8.6%) were Bethesda III and 135 (10.6%) Bethesda IV. Molecular testing was performed in 155 of 244 ITN (63.5%), of which 104 were classified as benign (BCR of 67.1%). After a median follow-up of 15 months, 103 of 104 (99.0%) patients with a benign ThyroidPrint® remained under surveillance and one patient underwent surgery which was a follicular adenoma. Surgery was performed in all 51 patients with a suspicious ThyroidPrint® result and in 56 patients that did not undergo testing, with a rate of malignancy of 70.6% and 32.1%, respectively. A higher BCR was observed in FLUS (87%) compared to AUS (58%) (p-value <0.05). False-positive cases included four benign follicular nodules, six follicular and four oncotytic adenomas. Our results show that, physicians chose active surveillance instead diagnostic surgery in all patients with a benign ThyroidPrint® result, reducing the need for diagnostic surgery in 67% in patients with preoperative diagnosis of ITN.

Ultrasound characteristics of follicular and parafollicular thyroid neoplasms: diagnostic performance of artificial neural network

BackgroundUltrasound is the first-line imaging modality for detection and classification of thyroid nodules. Certain features observable by ultrasound have recently been equated with potential malignancy. This retrospective cohort study was conducted to test the hypothesis that radiomics of the four categorical divisions (medullary [MTC], papillary [PTC], or follicular [FTC] carcinoma and follicular thyroid adenoma [FTA]) demonstrate distinctive sonographic characteristics. Using an artificial neural network model for proof of concept, these sonographic features served as input.MethodsA total of 148 patients were enrolled for study, all with confirmed thyroid pathology in one of the four named categories. Preoperative ultrasound profiles were obtained via standardized protocols. The neural network consisted of seven input neurons; three hidden layers with 50, 250, and 100 neurons, respectively; and one output layer.ResultsRadiomics of contour, structure, and calcifications differed significantly according to nodule type (p = 0.025, p = 0.032, and p = 0.0002, respectively). Levels of accuracy shown by artificial neural network analysis in discriminating among categories ranged from 0.59 to 0.98 (95% confidence interval [CI]: 0.57–0.99), with positive and negative predictive ranges of 0.41–0.99 and 0.78–0.97, respectively.ConclusionsOur data indicate that some MTCs, PTCs, FTCs, and FTAs have distinctive sonographic characteristics. However, a significant overlap of these characteristics may impede an explicit classification. Further prospective investigations involving larger patient and nodule numbers and multicenter access should be pursued to determine if neural networks of this sort are beneficial, helping to classify neoplasms of the thyroid gland.

Biomarker Discovery for Early Diagnosis of Papillary Thyroid Carcinoma Using High-Throughput Enhanced Quantitative Plasma Proteomics.

The incidence of thyroid cancer (TC) has been increasing over the last 50 years worldwide. A higher rate of overdiagnosis in indolent thyroid lesions has resulted in unnecessary treatment. An accurate detection of TC at an early stage is highly demanded. We aim to develop an enhanced isobaric labeling-based high-throughput plasma quantitative proteomics to identify biomarkers in a discovery cohort. Selected candidates were tested by enzyme-linked immunosorbent assay (ELISA) in the training cohort and validation cohort. In total, 1063 proteins were quantified, and 129 proteins were differentially expressed between patients and healthy subjects. Serum levels of ISG15 and PLXNB2 were significantly elevated in patients with papillary thyroid cancer (PTC) or thyroid adenoma, compared to healthy subjects (p < 0.001) and patients with nodular goiter (p < 0.001). Receiver operating characteristic (ROC) analysis of combined markers (ISG15 and PLXNB2) significantly distinguished PTC from healthy control (HC) subjects. Similar differentiations were also found between thyroid adenoma and HC subjects. Notably, this combined marker could distinguish stage-I PTC from HC subjects (area under the curve (AUC) = 0.872). Our results revealed that ISG15 and PLXNB2 are independent diagnostic biomarkers for PTC and thyroid adenoma, showing a promising value for the early detection of PTC.

Prospects of using the microRNA expression level and parameters of nucleolar organizer regions in the choice of surgical tactics for follicular thyroid tumor of uncertain malignant potential

BACKGROUND: According to modern concepts [1], microRNAs modulate the expression of eukaryotic genes with different oncogenetic directions of action. according to the data from the scientifi literature [2–4], microRNA-146b, -199b can be used for typing thyroid neoplasms, -221, -223, -31, -375, -451a, -551b, etc. Nucleolar organizers (NOR) are sections of chromosomes that form a nucleolus inside the cell nucleus [5–7]. The condition of the regions of nucleolar ribosome organizers (AgNORs) is a marker of the rate of cell proliferation, since they are involved in the regulation of the mitotic cycle [8], and in thyroid pathology [9].AIM: To evaluate the diagnostic significance of the level of expression of some microRNAs and the number of regions of nucleolar organizers in thyroid tissue in the case of follicular thyroid tumor of uncertain malignant potential (FT-UMP) to objectify approaches to the validity of the chosen surgical tactics.MATERIALS AND METHODS: In our study of 3960 patients with surgery due to various thyroidopathies in 2018–2021 on the basis of the thyroid center of Chelyabinsk. 2063 patients were operated on for tumor pathology. In this group, in 98 cases (the study group), FT-UMP was diagnosed based on morphological criteria of neoplasm [10]. This accounted for 4.75% of all surgical tumor pathology during this time. The study group studied the profile, the level of microRNA expression by real-time PCR and the regions of nucleolar organizers in 98 cases of FT-UMP, which amounted to 4.75% of all those operated for thyroid tumors over four years.RESULTS: In 29 (29.6%) cases, a microRNA spectrum characteristic of malignant neoplasms was registered in the tumor tissue. In the remaining 69 (70.4%) cases out of 98 observations, the spectrum and level of microRNA expression corresponded to follicular adenoma. Statistically significant differences in the average number of AgNORs and the ratio between the cell area and the number of AgNORs granules were revealed within the formed subgroups. The study found that an increase in the average number of AgNORs and the ratio of the core area to the number of silver nitrate granules in the 2nd subgroup relative to the 1st, as well as the presence of type II cells indicates the appearance of proliferating tumor cells in the neoplasm and can be considered as prognostic criteria for tumor malignancy. These results are consistent with the obtained indicators of molecular genetic research CONCLUSION: The data can serve as additional criteria for assessing the proliferative activity of the follicular epithelium in thyroid neoplasia. Including clarifying the potential of malignancy. The conditionally malignant variant diagnosed before the operation will justify the need and scope of surgical intervention, and when identifying a set of criteria for conditionally benign HPV, it can be recommended to adhere to wait-and-see tactics.

The value of deep neural networks in the pathological classification of thyroid tumors

BackgroundTo explore the distinguishing diagnostic value and clinical application potential of deep neural networks (DNN) for pathological images of thyroid tumors.MethodsA total of 799 pathological thyroid images of 559 patients with thyroid tumors were retrospectively analyzed. The pathological types included papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), follicular thyroid carcinoma (FTC), adenomatous goiter, adenoma, and normal thyroid gland. The dataset was divided into a training set and a test set. Resnet50, Resnext50, EfficientNet, and Densenet121 were trained using the training set data and tested with the test set data to determine the diagnostic efficiency of different pathology types and to further analyze the causes of misdiagnosis.ResultsThe recall, precision, negative predictive value (NPV), accuracy, specificity, and F1 scores of the four models ranged from 33.33% to 100.00%. The area under curve (AUC) ranged from 0.822 to 0.994, and the Kappa coefficient ranged from 0.7508 to 0.7713. However, the performance of diagnosing FTC, adenoma, and adenomatous goiter was slightly inferior to other types of pathological tissues.ConclusionThe DNN model achieved satisfactory results in the task of classifying thyroid tumors by learning thyroid pathology images. These results indicate the potential of the DNN model for the efficient diagnosis of thyroid tumor histopathology.

The histologic outcomes of indeterminate thyroid nodules with rat sarcoma mutations: A case series.

Molecular testing is an adjunct test for thyroid fine needle aspirations with indeterminate diagnoses, with certain mutations showing a greater risk of malignancy (ROM). Rat sarcoma (RAS) point mutations are the most common alterations in indeterminate thyroid nodules. While they can have a high ROM, they are also found in benign disease. This study describes the histologic outcomes of indeterminate nodules with RAS mutations. Bethesda III and IV thyroid nodules with ThyroSeq results showing RAS mutations (NRAS, KRAS, and HRAS) were identified between November 1, 2018 and February 28, 2023. Baseline patient characteristics, ThyroSeq results, and surgical diagnoses were collected. We identified 18 nodules with RAS mutations from 17 patients. Fourteen were NRAS (isolated NRAS in 6; NRAS with other abnormalities [NRAS+] in 8); one was isolated KRAS; and three were HRAS with other abnormalities (HRAS+). NRAS Q16R was the most common amino acid change. Twelve cases had follow-up. Two were malignant, a minimally invasive follicular carcinoma (NRAS+) and a papillary thyroid carcinoma, follicular variant (HRAS+). Three were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), 2 HRAS+ and 1 NRAS+. Four were follicular adenomas, one being atypical (3 NRAS+ and one isolated NRAS). One was an oncocytic adenoma (isolated NRAS). Two were nodular hyperplasias (isolated NRAS and NRAS+, respectively). Twenty-eight percent of our RAS-mutated nodules were malignant or NIFTP. All three HRAS-mutated nodules were malignant or NIFTP. The three isolated RAS mutations with follow up were benign (adenomas or nodular hyperplasia). These findings were in line with the literature.

DICER1 Mutations Do Not Always Indicate Dismal Prognosis in Pediatric Poorly Differentiated Thyroid Carcinomas.

Progress in the field of pediatric thyroid pathology has linked DICER1 mutations to benign follicular cell-derived thyroid tumors (e.g., follicular adenoma with papillary architecture, follicular nodular disease), low-risk follicular cell-derived differentiated thyroid carcinomas and PDTCs enriched in fatal or recurrent/progressive disease. The dismal outcome of DICER1-harboring pediatric PDTCs stems from a limited number of reported patients' data given the rarity of pediatric PDTCs. In light of the former observations, the current study assessed clinicopathological variables of a series of 5 pediatric (≤ 18 years old) PDTCs using the Turin criteria (WHO 2022) and also examined the status of DICER1 and TERT promoter mutations. Five PDTCs (3 males, 2 females) were included in the study. The mean age at the time of diagnosis was 15.4 years. No patients had a history of DICER1 syndrome-related tumors or other clinicopathological diagnostic features of DICER1 syndrome. The mean tumor size was 3.9 cm. All tumors were completely submitted for microscopic examination. There was increased mitotic activity ranging from 3 to 10 mitoses per 2 mm2. Tumor necrosis was present in two cases. No PDTC harbored TERT promoter mutation. DICER1 hot spot mutation was identified in one (20%) tumor. The DICER1-mutant tumor had neither associated differentiated thyroid carcinoma component nor other pathological findings in the adjacent thyroid parenchyma. The DICER1-mutant PDTC showed widely invasive growth confined to the thyroid parenchyma. Despite the widely invasive growth, the tumor lacked vascular invasion. Two DICER1 wild-type PDTCs had lymphocytic thyroiditis and another one had underlying follicular nodular disease and/or follicular adenomas. Three DICER1 wild-type PDTCs also had an associated differentiated thyroid carcinoma component with no high-grade features. No abnormal p53 expression (overexpression or global loss) was recorded in all tested tumors. Four patients had follow-up data with a mean follow-up time of 60.25 months (range: 18-86 months). One patient with no evidence of disease recurrence died of anunrelated cause after 18 months of the initial surgery, all remaining patients were alive with no distant metastasis at their last visit. Of the 4 patients with lymph node (LN) dissection, one DICER1 wild-type PDTC had recurrent nodal disease. During the follow-up period (72 months), no local recurrence or distant metastases was detected in the DICER1-mutant PDTC. Taken together all reported findings from earlier series, DICER1 mutations alone may not necessarily indicate dismal outcome in a subset of pediatric PDTCs. The occurrence of additional genomic alterations as discussed in some earlier reports may be contributing to tumor progression or aggressivity of pediatric PDTCs. The lack of vascular invasion in the current DICER1-mutant pediatric PDTC may also explain an indolent biologic outcome. The risk escalation of DICER1 mutations should integrate the status of additional genetic events and well-established pathologic variables in order to ensure predictive dynamic risk stratification in DICER1-mutant pediatric PDTCs. Additional studiesare needed to corroborate the findings of this study and advance our knowledge in pediatric thyroid neoplasia.

Cytological Diagnosis of Follicular Patterned Lesion of Thyroid Nodule and its Follow-up Histopathology

The follicular patterned lesion of thyroid nodules is an exciting topic because it is not clear whether the lesion is benign or malignant. It comprises hyperplastic/adenomatoid nodules, follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma. The cytological diagnosis of atypia of undetermined significance/Follicular lesion of undetermined significance, follicular neoplasm/suspicious for follicular neoplasm and suspicious for malignancy remains controversial in terms of management. The study aimed to examine the extent of invasion of malignant lesions in follow-up histopathology diagnosed as undetermined lesions cytologically. A total of 256 cases were included in this study; among these, 199 cases were benign lesions, 15 cases were non-diagnostic and 42 cases were diagnosed either of uncertainty for malignancy with cellular atypia or malignancy. Subsequent follow-up resection and histopathology were done with 48 cases (18.75%), which comprises 1 non-diagnostic, 10 benign lesions, 21 atypia of undetermined significance/Follicular lesion of undetermined significance, 7 Follicular neoplasm/Suspicious for a follicular neoplasm, 5 suspicious for malignancy and 4 malignancies. Also, 6 Follicular variant of papillary thyroid carcinoma, 6 classic papillary carcinoma, 5 follicular carcinoma and 1 anaplastic carcinoma were diagnosed in follow-up resection histopathology of 48 cases. Thirty eight cases were of undetermined significance of malignancy with cytological features of the follicular lesion. Four Follicular variant of papillary thyroid carcinoma, 2 follicular carcinoma and 1 papillary carcinoma were diagnosed in 21 resected cases cytologically reported as Atypia of undetermined significance/Follicular lesion of undetermined significance with malignancy risk of 33.33%. Three malignancies in follicular neoplasm/suspicious for a follicular neoplasm with a risk of 42.85% and 4 malignancies in suspicious malignancy group with a risk of 80% were found. The average risk of malignancy of these three undetermined categories was reduced to 24.24% from 42.42% upon reclassification of the Follicular variant of papillary thyroid carcinoma. All the Follicular variants of papillary thyroid carcinoma diagnosed by histopathology were non-invasive regarding lymph node involvement and microvascular or capsular invasion. Mediscope 2023;10(2): 68-77

Classification of Thyroid Tumors Based on DNA Methylation Patterns.

Background: Alterations in DNA methylation are stable epigenetic events that can serve as clinical biomarkers. The aim of this study was to analyze methylation patterns among various follicular cell-derived thyroid neoplasms to identify disease subtypes and help understand and classify thyroid tumors. Methods: We employed an unsupervised machine learning method for class discovery to search for distinct methylation patterns among various thyroid neoplasms. Our algorithm was not provided with any clinical or pathological information, relying exclusively on DNA methylation data to classify samples. We analyzed 810 thyroid samples (n = 256 for discovery and n = 554 for validation), including benign and malignant tumors, as well as normal thyroid tissue. Results: Our unsupervised algorithm identified that samples could be classified into three subtypes based solely on their methylation profile. These methylation subtypes were strongly associated with histological diagnosis (p < 0.001) and were therefore named normal-like, follicular-like, and papillary thyroid carcinoma (PTC)-like. Follicular adenomas, follicular carcinomas, oncocytic adenomas, and oncocytic carcinomas clustered together forming the follicular-like methylation subtype. Conversely, classic papillary thyroid carcinomas (cPTC) and tall cell PTC clustered together forming the PTC-like subtype. These methylation subtypes were also strongly associated with genomic drivers: 98.7% BRAFV600E-driven cancers were PTC like, whereas 96.0% RAS-driven cancers had a follicular-like methylation pattern. Interestingly, unlike other diagnoses, follicular variant PTC (FVPTC) samples were split into two methylation clusters (follicular like and PTC like), indicating a heterogeneous group likely to be formed by two distinct diseases. FVPTC samples with a follicular-like methylation pattern were enriched for RAS mutations (36.4% vs. 8.0%; p < 0.001), whereas FVPTC- with PTC-like methylation patterns were enriched for BRAFV600E mutations (52.0% vs. 0%, Fisher exact p = 0.004) and RET fusions (16.0% vs. 0%, Fisher exact p = 0.003). Conclusions: Our data provide novel insights into the epigenetic alterations of thyroid tumors. Since our classification method relies on a fully unsupervised machine learning approach for subtype discovery, our results offer a robust background to support the classification of thyroid neoplasms based on methylation patterns.

Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid

Cadherin-16 (CDH16) plays a role in the embryonal development in kidney and thyroid. Downregulation of CDH16 RNA was found in papillary carcinomas of the thyroid. To determine the expression of CDH16 in tumors and to assess the diagnostic utility a tissue microarray containing 15,584 samples from 152 different tumor types as well as 608 samples of 76 different normal tissue types was analyzed. A membranous CDH16 immunostaining was predominantly seen in thyroid, kidney, cauda epididymis, and mesonephric remnants. In the thyroid, CDH16 staining was seen in 100% of normal samples, 86% of follicular adenomas, 60% of follicular carcinomas, but only 7% of papillary carcinomas (p < 0.0001). CDH16 positivity was frequent in nephrogenic adenomas (100%), oncocytomas (98%), chromophobe (97%), clear cell (85%), and papillary (76%) renal cell carcinomas (RCCs), various subtypes of carcinoma of the ovary (16–56%), various subtyped of carcinomas of the uterus (18–40%), as well as in various subtypes of neuroendocrine neoplasms (4–26%). Nineteen further tumor entities showed a weak to moderate CDH16 staining in up to 8% of cases. Our data suggest CDH16 as a potential diagnostic marker—as a part of a panel—for the identification of papillary carcinomas of the thyroid, nephrogenic adenomas, and the distinction of renal cell tumors from other neoplasms.

Ultrasound features and risk stratification system in NIFT-P and other follicular patterned thyroid tumors.

NIFT-P (non-invasive follicular thyroid neoplasm with papillary-like nuclear features) is an encapsulated follicular variant of papillary thyroid carcinoma (PTC) with non-aggressive clinical behavior. However, since its diagnosis is exclusively possible after surgery, it represents a clinical challenge. Neck ultrasound (US) shows good sensitivity and specificity in suggesting malignancy in thyroid nodules. However, few information is available about its ability in identifying NIFT-P. The aim of this study was to evaluate the US features of NIFT-P, comparing them with other follicular patterned thyroid tumors, and to test the ability of the main US risk stratification system (RSS) in identifying NIFT-P. We retrospectively evaluated 403 consecutive patients submitted to thyroid surgery, with positive histology for at least one nodule being NIFT-P, follicular variant of PTC (FV-PTC), follicular thyroid carcinoma (FTC) or follicular adenoma (FA). The US features of NIFT-P (n=116), FV-PTC (n=170), FTC (n=76) and FA (n=90) were reported. FV-PTC and FTC more frequently showed irregular margins, presence of calcifications, "taller than wide" shape, and the absence of halo compared to NIFT-P. Furthermore, FTC but also FA were larger and more frequently hypoechoic than NIFT-P. Most cases (77%) showed an indeterminate cytology. Regardless of the US RSS considered, NIFT-P and FA were less frequently classified in the high-suspicious category compared to FV-PTC and FTC. US features of NIFT-P are frequently superimposable to those of nodules with low-suspicious of malignancy. NIFT-P is almost never classified in the high-suspicious category according to the main US RSS. Therefore, although the pre-operative identification of NIFT-P remains a challenge, neck US can be integrated in the algorithm of management of nodules with indeterminate cytology, suggesting a possible conservative approach in those with low-suspicious features.

The relationship between telomerase reverse transcriptase promoter rs2853669 allele C accompanied by C228T and the grade of thyroid malignancy.

91 Background: Two-point mutations (C228T and C250T) in the promoter region of the telomerase reverse transcriptase (TERT) gene are considered molecular indicators of adverse thyroid tumor biology. The regulatory single nucleotide polymorphism rs2853669 (TrSNP) is located near these TERT promoter mutations and its association with the grade of various cancers has been recently reported. To clarify whether the TrSNP can be a clinically useful molecular marker, we analyzed the relationship of the TrSNP with tumor growth and malignant potential in papillary thyroid cancer and follicular tumors. Methods: DNA was extracted from blood and FFPE specimens of 218 patients with thyroid tumors (133 papillary and 85 follicular), and TrSNP, C228T, and C250T were analyzed. BRAFV600E and NRAS Q61R mutations were also analyzed. The association of these genotypes and mutations with clinicopathological parameters were investigated. Results: The C allele of TrSNP from blood and FFPE specimens were validated with 97.3% concordance, so the C allele of TrSNP from blood samples were used in this study. Univariate analysis of 133 papillary carcinomas for clinicopathologic features showed that the C allele of TrSNP significantly correlated with tumor size as did the C228T mutation (p&lt;0.05, p&lt;0.001). Co-expression of the TrSNP and C228T were significantly corelated with tumor size, extrathyroidal invasion and lymph nodal metastasis (p&lt;0.01, p&lt;0.05). Eighty-five follicular tumors (19 follicular carcinomas and 66 follicular adenomas) were examined. Univariate analysis showed no significant association between the C allele of TrSNP, C228T, or C250T and tumor size. Multivariate analysis demonstrated the C allele TrSNP and C228T were significantly frequent in follicular carcinoma (p&lt;0.05, p&lt;0.001) and therefore were considered a risk factor for malignancy. Conclusions: This study demonstrates that the C-allele of the TrSNP is an indicator of tumor growth of papillary carcinoma and co-expression of the TrSNP and C228T relate tumor progression and malignant grade. These genetic features are expected to be a useful molecular marker for differential diagnosis of benign and malignant tumors and for determining treatment strategies.

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.

Comparative Study of FNAC and Histopathology in Diagnosis of Thyroid Swelling

Background: Neck swelling is a common clinical presentation in ENT practice and it carries significant morbidity and even mortality if not managed properly. Thyroid swelling being the most common type among them. We conducted a study to assess the role of FNAC in diagnosing the nature of thyroid swelling and comparing its result with histopathology finding. The aim and objectives of this study is to observe the correlation between preoperative Fine Needle Aspiration Cytology (FNAC) and post operative histopathology in the diagnosis of thyroid lesions.&#x0D; Materials and methods: A cross sectional study was done in the Department of Otolaryngology-Head &amp; Neck Surgery and Department of Pathology, Chittagong Medical College, Chattogram from January 2018 to December 2020. Eighty (80) patients, both male and female of different age groups were included. The selected patients were subjected to clinical examination, routine hematological investigation, thyroid hormone test, USG, thyroid Scan, FNAC and histopathological examinations of the thyroidectomy specimens. Correlation between FNAC and histopathology reports were done in those patients.&#x0D; Results: In this study, age range of the patients were 11 years to 70 years. Out of 80 patients of thyroid swelling, the most of the patients 28(35%) were 31-40 years of age groups. out of 80 patients of thyroid swelling, 26(26.25%) were male and 59(73.75%) were female and male female ratio was1:2.81. On FNAC 64(80%) were non neoplastic and 16(20%) were neoplastic. Out of 64(80%) of non neoplastic lesions, 62(77.50%) were nodular goitre and 2(2.5%) were lymphocytic thyroiditis and out of 16(20%) neoplastic thyroid swelling, 2(2.50%) were follicular lesion, 12(15%) were papillary carcinoma, 1(1.25%) was follicular carcinoma and 1(1.25%) was suspicious for malignancy. On histopathology, out of 80 patients of thyroid swelling 60(75%) were non neoplastic and 20(25%) were neoplastic. out of 60(75%) non neoplastic, 59 (73.75%) were nodular, 1(1.25%) was Lymphocytic thyroiditis and out of 20(25%) neoplastic lesions, 3(3.75%) were follicular adenoma,13(16.25%) were papillary carcinoma,3(3.75%) were follicular variant of papillary carcinoma and 1(1.25%) was follicular carcinoma.&#x0D; Conclusion: It is concluded from the present study that female are more affected in our region. Non neoplastic lesions of the thyroid were more common (Nodular goitre being the commonest) than neoplastic lesions (Papillary carcinoma being the commonest). FNAC is essential diagnostic tool for thyroid swelling but final diagnosis to rule out thyroid cancer is surgical excision and histopathology.&#x0D; Chatt Maa Shi Hosp Med Coll J; Vol.22 (1); January 2023; Page 19-22

Radiofrequency ablation for autonomously functioning nodules as treatment for hyperthyroidism: subgroup analysis of toxic adenoma and multinodular goitre and predictors for treatment success

PurposeTreatment of hyperthyroidism caused by autonomously functioning thyroid nodules (AFTN) with 131I often leads to undesirable hypothyroidism. Radiofrequency ablation (RFA) has emerged as a promising alternative. This retrospective analysis aimed to examine the efficacy of, and postprocedural hypothyroidism after, RFA for AFTN.MethodsPatients with hyperthyroidism caused by AFTN and treated with RFA were included if follow-up of at least 1 year was available. Cure was defined as thyroid medication–free biochemical euthyroidism. To predict cure, patient and treatment factors were analysed. A distinction was made between solitary toxic adenoma (STA) and toxic multinodular goitre (TMG).ResultsForty-eight patients (36 STA, 12 TMG) were included. One year post-RFA cure rate was 72% in STA versus 25% in TMG (p = 0.004). One patient developed hypothyroidism. In 11 patients that remained hyperthyroid, a second RFA was successful in 83% of STA and 40% of TMG patients. At last available follow-up, this amounted to a total cure rate of 81% in STA and 33% in TMG (p = 0.002). In STA, cured patients had a higher baseline TSH and a lower FT3 than non-cured patients (p = 0.026 and 0.031). Cure was observed in 91% of patients when > 2.1 kJ/mL was delivered during RFA, compared to 44% when less energy was administered.ConclusionThe efficacy of RFA was nearly 3 times higher in STA patients compared to TMG. Severity of hyperthyroidism and kJ/mL delivered during RFA predicts cure. Direct comparison to the current standard of care is needed to implement RFA in treatment of hyperthyroidism caused by AFTN.

Papillary thyroid carcinoma coexisting with benign thyroid and parathyroid pathology: clinical and pathomorphological features

Background. Papillary thyroid carcinoma (PTC) is the most frequent malignant neoplasm originating from follicular cells of thyroid gland. PTC is often coexisting with other benign thyroid pathology such as chronic lymphocytic thyroiditis, follicular thyroid adenoma, toxic thyroid adenoma, Graves’ disease, non-toxic multinodular goiter. PTC can be diagnosed in patients undergoing surgical treatment for hyperparathyroidism. However, the clinical and pathomorphological features of PTC in the presence of other benign thyroid or parathyroid pathology, as well as possible differences in surgical tactics, remain relevant as evidenced by previously published reports. The purpose of the study is to assess the prevalence and determine the differences in the clinical and pathomorphological parameters of PTC in the presence of benign thyroid and parathyroid pathology. Materials and methods. There were identified 91 patients with PTC, who underwent surgical treatment at the clinical bases of the Department of Surgery of the NSC “Institute of Biology and Medicine” of Taras Shevchenko National University of Kyiv. Results. In the studied PTC cohort, 31 (35 %) patients were without coexisted benign thyroid pathology and 60 (35 %) patients had it (PTC/coexisted). A statistically significantly higher number of mitoses per 10 high power fields in the PTC group were identified in 3 (10 %) patients, as compared to the absence of this pathohistological parameter in the PTC/coexisted (p = 0.037). Further analysis of these 3 cases showed that 4 mitotic figures were found in one PTC, and one mitotic figure in the other two cases per 10 high power fields (400×). Conclusions. Papillary thyroid carcinoma in patients with other benign thyroid pathology is associated with lower biological aggressiveness than PTC without comorbidity as evidenced by a lower frequency of mitotic figures per 10 high power fields. The presence of concomitant benign thyroid pathology can be considered as a favorable prognostic factor for patients with PTC.

An interesting case of papillary thyroid carcinoma with heterotrophic ossification

Calcification in thyroid gland is associated with both benign and malignant lesion. However calcification is most frequently seen in malignant lesions. Calcification can give rise to metaplasia and bone containing marrow tissue. Papillary carcinoma with heterotrophic ossification has been associated with high incidence extrathyroidal invasion, multifocality, lymphnode metastsasis and older age group than in those without heterotrophic ossification. It has not been described as a specific entity in WHO classification because of its rarity. Expression of both basic fibroblast growth factor and bone morphogenetic protein was highest in papillary carcinoma with intratumoral heterotrophic ossification. In this case report we described a 71-year-old female patient who sought medical care for swelling in the neck for the past 4 years. The cervical ultrasound showed a 2 well defined nodules measuring 2x2 cms and 4mm in the right lobe with larger lesion showing peripheral rim of calcification and left lobe and isthumus shows well defined lesions measuring 5mm and 4 mm each. The clinical diagnosis was multinodular goitre. Patient subsequently underwent thyroidectomy. On histopathological investigation right lobe showed follicular adenoma and papillary carcinoma thyroid with extensive heterotrophic ossification and calcification within the tumor. The margins were free of neoplasia and there was no extrathyroidal extension. No preineural/ vascular invasion noted. One lymphnode was identified which was free of tumor. pTNM staging was pT1bNxMx.

Detection and yield of thyroid cancer surveillance in adults with PTEN Hamartoma Tumour Syndrome.

Thyroid cancer surveillance (TCS) with ultrasound (US) is advised for PTEN Hamartoma Tumour Syndrome (PHTS) patients due to increased thyroid cancer (TC) risk. However, data supporting TCS guidelines are scarce. We aimed to assess the detection and yield of annual TCS with US in adult PHTS patients without a TC history, and to evaluate the impact of a reduced US interval on the TCS yield. A retrospective cohort study including adult PHTS patients and medical record data between 2005-2021. The yield from annual TCS was compared with hypothetical biennial and triennial TCS after two initial US with annual interval by counting delayed detection of nodular growth, thyroid adenoma and TC. During 279 follow-up years, 84 patients (median age 40 years) underwent 349 US. Thyroidectomy was performed in 6/84 (7%) patients, revealing a minimally invasive follicular TC in one patient aged 22 and a thyroid adenoma in two patients aged 21 and 53. Multiple thyroid nodules were diagnosed in 73/84 (87%) patients (median age 36 years). Nodular growth was detected in 9/56 (16%) patients, and its detection would have been delayed in 4-7% US rounds with biennial TCS, and in 2-6% US rounds with triennial US. US-based thyroiditis and indeterminate non-malignant lymph nodes were found in 8/74 (11%) and 7/72 (10%) patients, respectively. Following our findings combined with literature, we propose starting TCS before age 18, and reducing the follow-up frequency after the initial two US from annual to biennial if no suspicious findings are detected.