Serum cholesterol levels are inversely associated with the risk of malignancy in subjects with Bethesda category IV thyroid nodules.

INTRODUCTION: Some epidemiological data suggest that there may be an inverse relationship between cholesterol levels and the risk of thyroid cancer in the overall population. The present study was aimed to evaluate the lipid profile specifically in subjects with Bethesda category IV thyroid nodules, and compare whether there were any differences between those with benign and malignant nodules. METHODS: Single-centre, retrospective study on 204 subjects treated by partial or total thyroidectomy for excision of a Bethesda category IV thyroid nodule, who had undergone a blood lipid profile test in the 12 months prior to surgery. In addition to lipid measures, other demographic, clinical, biochemical and ultrasound data were collected. RESULTS: Seventy-five subjects (36.8%) were diagnosed with thyroid carcinoma in the definitive histopathological examination. Patients with thyroid cancer had lower levels of total cholesterol, LDL-cholesterol and non-HDL-cholesterol than subjects with benign thyroid diseases. There were no differences in HDL-cholesterol, triglycerides or total cholesterol/HDL-cholesterol ratio. There were no differences either between groups in other clinical, biochemical and ultrasound variables, including the use of lipid-lowering drugs. In multivariate analysis, only LDL-cholesterol was independently associated with malignancy. Subjects with follicular carcinoma showed the lowest cholesterol levels, while those with papillary carcinoma had intermediate values between the group with follicular carcinoma and the group with benign thyroid diseases. CONCLUSIONS: In subjects with cytologically indeterminate Bethesda category IV thyroid nodules, levels of total cholesterol, non-HDL-cholesterol and, particularly, LDL-cholesterol are lower among those with malignant nodules.

Cytologic features of differentiated high-grade thyroid carcinoma: A multi-institutional study of 40 cases.

BACKGROUND: Differentiated high-grade thyroid carcinoma (DHGTC) is recently recognized by the World Health Organization (WHO) as a subgroup of thyroid carcinomas with high-grade features while retaining the architectural and/or cytologic features of well-differentiated follicular-cell-derived tumors. The cytomorphology of DHGTC is not well documented despite potential implications for patient triage and management. METHODS: The pathology archives of six institutions were searched for cases diagnosed on resection as "high-grade thyroid carcinoma" using WHO criteria. The fine-needle aspiration (FNA) cohort represents a 10-year period (2013-2023); all were reviewed to confirm DHGTC classification. The corresponding FNAs were assessed for 32 cytomorphologic features. RESULTS: Forty cases of DHGTC with prior FNA were identified. The mean patient age was 64.2 years. The average lesion size was 4.9 cm, and the majority demonstrated a TI-RADS score of 4 or 5 (95.2%). Three main high-grade subsets of DHGTC based on corresponding histology included papillary thyroid carcinoma (65%), follicular carcinoma (22.5%), and oncocytic carcinoma (12.5%). Over 97% of FNA cases were classified as Bethesda category IV or above. Approximately 25% of DHGTC showed cytologic features that included marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, or necrosis (p < .05); 68% of DHGTC cases were associated with high-risk molecular alterations. TERT mutations occurred in 41%, of which 89% of these were associated with a second mutation, usually RAS or BRAF p.V600E. CONCLUSIONS: Cytology has a low sensitivity for DHGTC, although a subset of DHGTCs have cytologic features raising the possibility of a high-grade thyroid carcinoma. Other findings include high-risk molecular changes and clinicopathologic features such as older patient age and larger lesion size.

Single Institution Experience in the Management of Locally Advanced (pT4) Differentiated Thyroid Carcinomas.

BACKGROUND: Locally infiltrating (T4) differentiated thyroid carcinomas (DTC) represent a challenge. Surgical strategy and adjuvant therapy should be planned balancing morbidity and oncologic outcome. A series of patients with T4 DTC who underwent multidisciplinary evaluation and treatment is reported. The main study endpoints were the oncologic outcome, complication rates, and risk factors for tumor recurrence. PATIENTS AND METHODS: All DTC cases operated between 2009 and 2021 were reviewed and T4 DTC cases were identified. En bloc resection of inferior laryngeal nerve (ILN), tracheal, and/or internal jugular vein (IJV) was performed in cases of massive infiltration. In cases of pharyngoesophageal junction (PEJ) invasion, the shaving technique was always applied. RESULTS: Among 4775 DTC cases, 60 were T4. ILN infiltration was documented in 45 cases (en bloc resection in 9), tracheal infiltration in 14 (tracheal resection in 2), PEJ invasion in 11 (R0 resection in 7 cases and < 1 cm residual tissue in 4 cases), IJV resection in 6, and laryngeal in 2. In total, 11 postoperative ILN palsy, 23 transient hypoparathyroidisms, and 2 hematomas requiring reoperation were registered. Final histology showed 7 pN0, 22 pN1a, and 31 pN1b tumors. Aggressive variants were observed in 47 patients. All but 1 patient underwent radioiodine treatment, 12 underwent adjuvant external beam radiation therapy (EBRT), and 2 underwent chemotherapy. At a median follow-up of 58 months, no tumor-related death was registered, and seven patients required reoperation for recurrence. Tracheal invasion was the only significant factor negatively impacting recurrence (p = 0.045). CONCLUSIONS: A multidisciplinary approach is essential for the management of T4 DTC. Individualized and balanced surgical strategy and adjuvant treatments, in particular EBRT, ensure control of locally advanced disease with acceptable morbidity.

Palliative treatment of generalized metastatic follicular carcinoma of thyroid after operation: A case report and literature review.

RATIONALE: Follicular carcinoma of thyroid is a rare pathological type of thyroid carcinoma, accounting for 4.5% of the total. At present, the main treatment methods include surgery, iodine therapy, thyroid hormone inhibitors, etc. Targeted drug therapy is very important for distant metastasis and iodine-refractory differentiated thyroid cancer. PATIENT CONCERNS: This clinical case is a 51-year-old male patient with follicular carcinoma of thyroid. DIAGNOSES: After 7 years of total thyroidectomy, multiple distant metastasis occurred to bilateral lungs, bones, multiple lymph nodes, etc. INTERVENTION: After multidisciplinary consultation in the department of oncology, thoracic surgery, nuclear medicine and other departments, he received targeted drug therapy of Lenvatinib. OUTCOMES: After 3 months, his condition was partially relieved, and his quality of life was significantly improved. After 11 months of treatment, the evaluated efficacy was still in remission. LESSON: Late metastatic thyroid cancer is faced with dilemma of radioiodine refractory after traditional treatment. This will provide further evidence for therapeutic intervention in similar patients in the future.

Incidentally detected follicular thyroid carcinoma mimicking parathyroid adenoma on Tc-99m MIBI scan: A case report.

RATIONALE: Primary hyperparathyroidism, though relatively prevalent among endocrine disorders, affecting 1% of the general population, often presents diagnostic challenges. Given its potential to precipitate severe complications including nephrolithiasis and fractures, timely diagnosis, and effective management are crucial. PATIENT CONCERNS: A 38-year-old woman with hypercalcemia was referred to the Department of Nuclear Medicine for a Tc-99m MIBI scan. DIAGNOSES: Tc-99m MIBI scan showed focal increased uptake in the left thyroid gland area, initially suggesting a parathyroid adenoma. Further examination using SPECT/CT revealed a nodular lesion within the left thyroid gland showing high Tc-99m MIBI uptake. INTERVENTIONS: Left thyroid lumpectomy confirmed the lesion as follicular thyroid carcinoma. On the second Tc-99m MIBI scan conducted after total thyroidectomy, a parathyroid adenoma was eventually detected in the right lower area, enabling the subsequent appropriate treatment, a right lower parathyroidectomy. OUTCOMES: Thirteen days after the parathyroidectomy, serum levels of total calcium and parathyroid hormone returned to normal. Furthermore, bone mineral density evaluated using DEXA remained within the expected range for her age even after 14 months. LESSONS: When interpreting the Tc-99m MIBI scan, it is essential to keep in mind that various tumors rich in mitochondria, such as thyroid carcinoma, could show a high uptake of Tc-99m MIBI.

Follow-up and Outcomes of 186 Patients With Follicular Cell-Derived Thyroid Cancer Seen at a Referral Center by One Thyroidologist in 2015.

OBJECTIVE: To study the profile, management, and outcomes of follicular cell-derived thyroid cancer (FCDTC) before publication of the 2016 American Thyroid Association guidelines recommending less-aggressive thyroid cancer procedures. METHODS: Patients with FCDTC were seen by one thyroidologist at Mayo Clinic during the 2015 calendar year. Patients underwent surgical procedures for FCDTC in 2015 or earlier at Mayo Clinic or another institution. Follow-up data were collected from January 1, 2016, through July 20, 2022. Outcomes measured included tumor characteristics, treatment methods, adverse effects, diagnostic imaging methods, and primary tumor/metastasis status at the last follow-up. RESULTS: Of 186 included patients, 85 had total or near-total thyroidectomy. Bilateral disease was present in 35.5% of these patients, and contralateral involvement would have been missed by lobectomy for 9 (10%) patients with low-risk thyroid cancer. Additionally, 57% had positive neck lymph nodes identified during their surgical procedure, 25% (21% in central compartment) of which were undetected by preoperative ultrasonography. At the last follow-up, 65.6% of patients had no evidence of disease and 10.7% had distant metastases. CONCLUSION: This report outlines the profile and outcomes of patients with FCDTC who were treated at a referral center before the revised 2016 American Thyroid Association guidelines. Lobectomy for low-risk FCDTC may miss some cancer in the contralateral lobe. However, the clinical importance of these missed microcarcinomas is unclear. Preoperative ultrasonography effectively predicts lateral, but not central compartment, nodal metastases.

Incidental thyroid carcinoma in an endemic goiter area in Italy: histopathological features and predictors of a common finding.

PURPOSE: The occurrence and histopathological features of incidental thyroid carcinoma (ITC) vary considerably among populations from different geographical regions. The aim of this study is to assess the prevalence and histopathological characteristics of ITC in patients who underwent thyroid surgery for apparently benign thyroid diseases in an endemic goiter area in Italy. METHODS: A total of 649 consecutive patients (531 females and 118 males; mean age, 52.9 ± 11.0 years), who underwent thyroid surgery at the Endocrine Surgery Unit of the tertiary care "Renato Dulbecco" University Hospital (Catanzaro, Italy) in the period between years 2017 and 2022, were included in this retrospective study. A comprehensive histopathological examination was performed on surgically excised thyroid tissue. Logistic regression analysis was employed to identify potential predictors of ITC. RESULTS: The histopathological examination revealed the presence of ITC in 81 patients, accounting for 12.5% of the total study population. The female to male ratio was found to be 6.4 to 1. Among the patients with ITC, 72 had papillary carcinoma (PTC), with 53 of these tumors being microcarcinomas (microPTC). Additionally, 5 patients had follicular thyroid carcinoma, 2 patients had low-risk follicular cell-derived thyroid neoplasms, 1 patient had an oncocytic carcinoma, and 1 patient had a medullary thyroid carcinoma. Logistic regression analysis demonstrated a significant association between female sex and incidental microPTC. CONCLUSIONS: These findings provide further evidence of the common occurrence of ITC, typically in the form of microPTC, among individuals who undergo thyroid surgery for apparently benign thyroid diseases.

Use of the Afirma Xpression Atlas for cytologically indeterminate, Afirma Genomic Sequencing Classifier suspicious thyroid nodules: Clinicopathologic analysis with postoperative molecular testing.

OBJECTIVES: Afirma has recently introduced its Xpression Atlas (XA) as an adjunct to its Genomic Sequencing Classifier (GSC) for risk stratification of cytologically indeterminate thyroid nodules. We evaluated the performance of Afirma XA and associated pathologic findings for Afirma GSC suspicious nodules. METHODS: Intradepartmental records of thyroid fine-needle aspirations (FNAs) from January 2021 to December 2022 were identified and reviewed for patient and nodule characteristics, FNA findings, molecular test results, and final surgical pathology, if available. RESULTS: Material for Afirma GSC testing was collected in 624 thyroid FNAs, and 148 (24%) were classified as cytologically indeterminate. Afirma GSC testing was successful in 132 (89%) of those cases, of which 35 (27%) were Afirma GSC suspicious. Afirma XA testing was positive in 11 cases (11/35 [31%]). Eight (73%) patients underwent surgery that revealed 7 patients with papillary thyroid carcinoma and 1 patient with noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (risk of malignancy: 100% [8/8]). Among the 24 patients with negative Afirma XA results, 19 (79%) underwent surgery, revealing 5 patients with malignancy and 3 patients with NIFTP (risk of malignancy: 42% [8/19]). Overall, the risk of malignancy for Afirma GSC suspicious nodules was 59% (16/27). CONCLUSIONS: Afirma XA improved risk stratification of thyroid disease with a high risk of malignancy in Afirma GSC suspicious nodules. A negative Afirma XA result, however, should not be used as a rule-out test.

Malignancy Risk of Follicular Neoplasm (Bethesda IV) With Variable Cutoffs of Tumor Size: A Systemic Review and Meta-Analysis.

CONTEXT: The decision on diagnostic lobectomy for follicular neoplasms (FN) is challenging. OBJECTIVE: This meta-analysis investigates whether an appropriate size cutoff exists for recommending surgery for thyroid nodules diagnosed as FN by fine needle aspiration. METHODS: The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched for studies reporting the malignancy rate of FN/suspicious for FN (FN/SFN) according to tumor size, using search terms "fine needle aspiration," "follicular neoplasm," "lobectomy," "surgery," and "thyroidectomy." RESULTS: Fourteen observational studies comprising 2016 FN/SFN nodules with postsurgical pathologic reports were included, and 2 studies included malignancy rates with various tumor sizes. The pooled malignancy risk of FN/SFN nodules according to size was: odds ratio (OR) 2.29 (95% CI, 1.68-3.11) with cutoff of 4 cm (9 studies), OR 2.39 (95% CI, 1.45-3.95) with cutoff of 3 cm (3 studies), and OR 1.81 (95% CI, 0.94-3.50) with cutoff of 2 cm (5 studies). However, tumors ≥2 cm also showed a higher risk (OR 2.43; 95% CI, 1.54-3.82) based on the leave-one-out meta-analysis after removal of 1 influence study. When each cutoff size was evaluated by summary receiver operating characteristic (sROC) curves, the cutoff of 4 cm showed the highest summary area under the curve (sAUC, 0.645) compared to other cutoffs (sAUC, 0.58 with 2 cm, and 0.62 with 3 cm), although there was no significant difference. CONCLUSION: Although the risk of malignancy increases with increasing tumor size, the risk remains significant at all tumor sizes and no cutoff limit can be recommended as a decision-making parameter for diagnostic surgery in Bethesda IV thyroid nodules.

Impact of the 3rd Edition of the Bethesda System for Reporting Thyroid Cytopathology on Grey Zone Categories.

INTRODUCTION: Thyroid Bethesda Reporting System is a six-tiered system that aims to bring uniformity in reporting thyroid cytology and improve the communication with clinicians. The system has achieved its goal as a presurgical diagnostic method; however, it remains a screening method in the grey zone categories, namely atypia of undetermined significance (AUS) and follicular neoplasm (FN). The book recently released the 3rd edition, following the recent changes in thyroid pathology. One of the most important novelties is subgrouping AUS category and FN to be able to make a better risk stratification in these categories. Our group aims to retrospectively analyze a large dataset based on the new TBSRTC, with a focus on the grey zone categories. METHODS: Only patients who underwent lobectomy or total thyroidectomy were included, allowing for direct comparison between cytological and histopathological results. Cytological evaluations, based on the TBSRTC 3rd edition, were methodically compared with their respective histopathological results, enabling a comprehensive analysis. RESULTS: Of the 244 patients (female:male ratio = 8.8:1, mean age = 56), a total of 252 nodules were evaluated. A distinction was noted with 79 nodules (31%) diagnosed as AUS and 173 nodules (69%) as FN. Intriguingly, the risk of malignancy (ROM) for AUS-overall stood at 44.3%, with AUS-nuclear atypia at 50% and AUS-other at 43.2%. Although the AUS subdivisions did not demonstrate statistical significance, a significant disparity was observed in their distribution, with 15% as AUS-nuclear atypia compared to 85% as AUS-other. This disparity raises the question: Could AUS-other be considered the new waste-basket category in the TBSRTC 3rd edition? Using the TBSRTC 3rd edition as a base, we added a subclassification for FN nodules based on the presence or absence of papillary thyroid carcinoma (PTC) nuclear features. Our findings showed that differentiating FN with oncocytic characteristics correlated well with histological outcomes and ROMs. Though retrospective in design with inherent bias potential, our data suggest a possible improvement in PTC case segregation in the FN category when differentiating between FN nodules with and without PTC nuclear features. CONCLUSION: Our retrospective study sheds light on the potential advantages of the TBSRTC 3rd edition, particularly in refining the AUS and FN categories for thyroid nodules. The clear disparity in AUS subcategories raises important questions about their classification and potential future refinements. Moreover, the differentiation of FN nodules based on PTC nuclear features holds a promising approach for better risk stratification.

Risk factors for death of follicular thyroid carcinoma: a systematic review and meta-analysis.

BACKGROUND: There are conflicting reports on the factors that increase the likelihood of patients dying from follicular thyroid carcinoma (FTC). Therefore, it is critical to identify risk factors of patients with FTC. This study aimed to identify the factors that increase the risk of death of patients with FTC and help clinicians make better treatment and follow-up decisions. METHODS: A systematic literature review was conducted in PubMed and Web of Science databases for relevant studies published before January 31, 2023. Their reference lists were also analyzed. Two reviewers extracted data and evaluated the quality of eligible studies independently. Studies on patients who had open thyroidectomy procedures with or without neck dissection were included in this review. The RevMan 5.3 software was used to analyze the data. RESULTS: This meta-analysis included thirteen studies with a total of 2075 patients. The following variables were associated with an increased risk of death in FTC patients: age > 45 years, male, tumor diameter > 4 cm, multifocality, extrathyroidal extension (ETE), widely invasive (WI), cervical lymph node metastasis (CLNM), distant metastases (DM) and non-radical resection tumor. Lobectomy and no radioactive iodine (RAI) treatment was not associated with the death of FTC patients. CONCLUSION: Clinicians should pay closer attention to the following significant risk factors associated with the death of FTC patients: age (> 45), male, multifocality, tumor diameter > 4 cm, ETE, WI, non-radical resection tumor, CLNM, and DM. Individualized initial treatment and close follow-up are needed FTC patients who have these risk factors.

Thyroid surgery in children and adolescents: results from a multi-institutional German and Austrian database.

BACKGROUND: Outcomes of paediatric thyroid surgery have only been reported in smaller series or over long intervals. The aim of this multicentre study was to describe the recent outcomes of paediatric thyroid surgery in Germany and Austria. METHODS: Patients aged less than or equal to 18 years who underwent thyroid surgery and were prospectively documented in the StuDoQ|Thyroid registry between March 2017 and August 2022 were studied. RESULTS: In total, 604 patients from 90 institutions were included. The mean age was 15.4 years and 75 per cent of patients were female. The most frequent benign pathologies were nodular goitre (35.6 per cent), follicular adenoma (30.1 per cent), and Graves' disease (28.5 per cent). Among 126 thyroid malignancies, papillary thyroid carcinoma was diagnosed in 77.8 per cent of patients, follicular thyroid carcinoma was diagnosed in 10.3 per cent of patients, and medullary thyroid carcinoma was diagnosed in 8.7 per cent of patients. Lymph node metastases were found in 45.9 per cent of patients with papillary thyroid carcinoma and in 36.4 per cent of patients with medullary thyroid carcinoma. Vascular invasion was found in 62.9 per cent of patients with follicular thyroid carcinoma. The mean tumour diameters were 18, 42, and 13 mm in patients with papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma respectively. Early postoperative recurrent laryngeal nerve injury was seen in 27 of 556 patients (4.9 per cent) (22 of 617 (3.6 per cent) nerves at risk with intermittent intraoperative nerve monitoring and 5 of 237 (2.1 per cent) nerves at risk with continuous intraoperative nerve monitoring). Persistent recurrent laryngeal nerve injury was documented in 4 of 556 patients (0.7 per cent). Early postoperative hypoparathyroidism correlated with Graves' disease, thyroid carcinoma, and lymph node dissection. CONCLUSION: Papillary thyroid carcinoma and follicular thyroid carcinoma in children were often advanced at presentation. Persistent or recurrent lymph node metastases were mainly seen in papillary thyroid carcinoma. Overall survival was excellent, but longer follow-up is needed.

Radioactive iodine therapy strategies for distinct types of differentiated thyroid cancer: a propensity score-matched analysis.

Background: The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However, in distinct types DTC, differences in RAI avidity and response existed and the effect of RAI therapy could not be equated. Methods: DTC patients' data in SEER database were extracted to perform retrospective analysis. The differences between case group and control group were compared by chi-square tests. We used Kaplan-Meier statistics and Cox regression analyses to investigate cancer-specific survival (CSS). Propensity score-matched was performed to make 1:1 case-control matching. Results: 105195 patients who receiving total thyroidectomy were identified in SEER database. Compared to papillary thyroid carcinoma (PTC) (52.3%), follicular thyroid carcinoma (FTC) (63.8%) and oncocytic carcinoma of thyroid (OCA) (64.4%) had higher rates of RAI therapy. In the multivariable Cox regression model, RAI therapy was independent prognosis factor in PTC but not in OCA and FTC. In subgroup analysis, RAI therapy could improve prognosis in PTC when gross extrathyroidal extension or lymph node metastases or early survival when distant metastases (DM) were presented. However, OCA and FTC patients with DM rather than regional lesions only could benefit from RAI therapy. High-risk patients receiving RAI therapy showed a better prognosis in PTC but not in OCA and FTC. Conclusion: RAI therapy was an effective treatment for DTC and should be considered individually in PTC, OCA and FTC patients. Our results provided further guideline for treatment selection in DTC.

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

OBJECTIVE: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFT-P) is an encapsulated follicular variant of papillary thyroid carcinoma (PTC) with nonaggressive 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, little information is available about its ability in identifying NIFT-P. DESIGN: 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. METHODS: We retrospectively evaluated 403 consecutive patients submitted to thyroid surgery, with positive histology for at least 1 nodule being NIFT-P, follicular variant of PTC (FV-PTC), follicular thyroid carcinoma (FTC), or follicular adenoma (FA). RESULTS: The US features of NIFT-P (n = 116), FV-PTC (n = 170), FTC (n = 76), and FA (n = 90) were reported. Follicular variant of PTC and FTC more frequently showed irregular margins, presence of calcifications, "taller than wide" shape, and the absence of halo compared with NIFT-P. Furthermore, FTC and 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 with FV-PTC and FTC. CONCLUSIONS: Ultrasound features of NIFT-P are frequently superimposable to those of nodules with low suspicion of malignancy. The NIFT-P is almost never classified in the high-suspicious category according to the main US RSS. Therefore, although the preoperative 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.

Cytological and Ultrasound Features of Thyroid Nodules Correlate With Histotypes and Variants of Thyroid Carcinoma.

CONTEXT: Prognosis is excellent for papillary thyroid carcinoma (PTC), noninvasive follicular thyroid neoplasia with papillary-like nuclear features (NIFT-P), and follicular thyroid carcinoma (FTC) but is poor for poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC). Among PTCs, the prognosis is more favorable for follicular (FV-PTC) and classic (CV-PTC) than for tall cell (TCV-PTC), and solid (SV-PTC) variants. OBJECTIVE: To associate histotypes and variants of thyroid carcinoma with ultrasound and cytological features. METHODS: Histology of 1018 benign tumors and 514 PTC (249 CV, 167 FV, 49 TC, 34 SV, and 15 other variants), 52 NIFT-P, 50 FTC, 11 PDTC, and 3 ATC was correlated with fine-needle aspiration biopsy categories (Italian classification: TIR1, TIR2, TIR3A, TIR3B, TIR4, and TIR5) and ultrasound features at the Endocrinology Unit, University Hospital of Pisa. In total, 1117 patients with thyroid nodule(s) who underwent thyroidectomy were included. RESULTS: Of PTC, 36.3% had indeterminate cytology (TIR3A or TIR3B), 56.6% were suspicious for malignancy or malignant (TIR4 or TIR5); 84.0% FTC and 69.3% NIFT-P were TIR3A or TIR3B; 72.5% FV-PTC and 73.6% SV-PTC were TIR3A or TIR3B; 79.9% CV-PTC and 95.9% TCV-PTC were TIR4 or TIR5. The association of a hypoechoic pattern, irregular margins, and no microcalcifications was more frequent in TCV-PTC than in CV-PTC (P = .02, positive predictive value = 38.9%; negative predictive value = 85.5%). CONCLUSION: At cytology, most FTC, NIFT-P, FV-PTC, and SV-PTC were indeterminate, most CV-PTC and TCV-PTC were suspicious for malignancy or malignant. Ultrasound can be helpful in ruling out TCV-PTC.

Risk of malignancy and diagnostic accuracy of fine-needle aspiration biopsy in thyroid nodules with diameters greater than 4 centimeters.

Objective: The risk of malignancy and diagnostic accuracy of fine-needle aspiration biopsy (FNAB) of thyroid nodules (TN) with diameters ≥ 3-4 cm remains controversial. However, some groups have indicated surgical treatment in these patients regardless of the FNAB results. We aimed to evaluate the diagnostic accuracy of the FNAB in systematically resected ≥4 cm TN and if the risk of malignancy is higher in these patients. Subjects and methods: We retrospectively evaluated 138 patients (142 nodules) with TN with diameters ≥4 cm who underwent thyroidectomy. Results: The FNAB results were nondiagnostic/unsatisfactory (ND/UNS) in 2.1% of the cases and benign in 51.4%. They indicated atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in 23.9% of cases, follicular neoplasia/suspicious for a follicular neoplasm (FN/SFN) in 9.2%, suspicion of malignancy (SUS) in 8.5%, and malignant in 4.9%. The histopathological analysis after thyroidectomy revealed a thyroid cancer rate of 100% in the FNABs classified as malignant, 33.3% in SUS cases, 7.7% in FN/SFN, 17.6% in AUS/FLUS, and 4.1% in benign FNABs. None of the ND/UNS FNABs were malignant. The global malignancy diagnosis was 14.8% (n = 21). However, the rate of false negatives for FNAB was low (4.1%). Conclusion: We showed that the risk of malignancy in nodules with diameters ≥4 cm was higher compared to the risk of thyroid cancer in TN in general. However, we found a low rate of false-negative cytological results; therefore, our data do not justify the orientation of routine resection for these larger nodules.

Intratumoural metastasis of primary lung adenocarcinoma to non-invasive follicular thyroid neoplasm with papillary-like nuclear features.

Metastasis to the thyroid gland is very uncommon with an incidence of 2-3% of all thyroid malignancies. A higher incidence is noted in autopsy studies indicating incidental detection. However, tumour-to-tumour metastasis is extremely uncommon with a handful of cases published in the literature to date. Also, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFT-P) is a rare neoplasm; diagnosis requires meticulous sampling of the entire capsule and fulfilment of other diagnostic criteria. We report a case of primary adenocarcinoma of lung in a 57-year-old female who additionally had a left thyroid nodule which appeared suspicious on ultrasonography. Histology of lung tumour was conventional papillary adenocarcinoma while aspiration cytology from the thyroid raised suspicion of metastatic adenocarcinoma. On hemithyroidectomy, the thyroid nodule showed metastatic adenocarcinoma in the centre of the nodule, while the peripheral portion showed non-invasive follicular thyroid neoplasm with papillary-like nuclear features; the diagnosis of which was confirmed with complete sampling of the thyroid capsule. The immunoprofile also supported the above dual histology. This is an extremely uncommon occurrence and metastasis within a NIFT-P has not been reported to the best of our knowledge.

Evaluation of Risk Factors for Malignancy Obtained by Means of Fine Needle Aspiration Biopsies in Thyroid Nodules and Surgical Outcomes of Patients with Bethesda Category III (AUS/FLUS).

Background: The nodules diagnosed as the "atypia of undetermined significance" category are a heterogenous group with an indeterminate risk of malignancy. This study aimed to perform a detailed cytological examination of the preparations to determine the cytomorphological criteria that may be useful to distinguish benign cases from malignant ones, correlate them with ultrasonographic findings, and compare them with the final pathological result in surgically treated patients. Methods: The preparations of patients classified as Bethesda 3 were re-evaluated; presence or absence of one of 11 parameters (hypochromasia, oval nucleus, colloid, intra-nuclear pseudoinclusions, nuclear grooving, nuclear moldering, isolated nuclear enlargement, nuclear irregularity, nuclear size, microfollicular pattern, distinct nucleoli) and correlating with surgical outcomes by adding ultrasonographic findings to statistically significant parameters. Results: Two hundred and six fine needle aspirations (FNA) procedures were classified as Bethesda 3. A total of 53 patients underwent surgery; 28 (52.8%) of them were benign, and 25 (47.1%) were malignant. Thirty-two (15.5%) accepted direct surgery; 53 patients underwent repeat FNA at 3-6 month intervals and those with malignancy and repeated Bethesda 3 interpretation were operated. One hundred twenty-one (69.5%) patients who did not undergo biopsy were invited for ultrasonographic controls at 3-6 month intervals. Among the 11 cytomorphologic parameters evaluated, 7 were found to be statistically significant (p 0.05) with malignancy. When at least 3 of these parameters were positive, the malignancy rate was 92%. Malignancy was present in 19 (61.3%) of the patients with high risk nodules (TIRADS = 4), compared to only 6 (35.8%) of the low-risk (TIRADS = 3); there was a significant correlation between the presence of malignancy and TIRADS score (p=0.015). The preparations that displayed nucleus atypia were closely associated with the ultrasonographically high-risk group. Conclusion: The parameters indicating nuclear atypia, presence of more than 3 cytomorphological factors, TIRADS score 4 were significantly associated with malignancy; nuclear atypia were closely associated with the ultrasonographically high TIRADS. No significant correlation was found between the presence of "microfollicular pattern" and malignancy.

Percutaneous cryoablation of follicular thyroid carcinoma metastasis to the pancreas

The following is a technical report of the successful cryoablation of pancreatic metastasis originating from follicular thyroid carcinoma. The patient was a 72-year-old female who underwent total thyroidectomy and radioiodine ablation for follicular carcinoma. One year after surgery, a positron emission tomography-computed tomography (PET-CT) examination, performed to demonstrate the source of the increased thyroglobulin, showed a fluorodeoxyglucose (FDG) avid mass located in the body of the pancreas. A percutaneous tru-cut biopsy was performed that revealed follicular thyroid carcinoma metastasis to the pancreas. Because of the patient's comorbidities, the patient underwent percutaneous cryoablation and made a successful recovery over the following 13 months. At the most recent follow-up, the thyroglobulin level was undetectable, and a PET-CT scan showed no FDG avid mass in the pancreas. To our knowledge, follicular carcinoma metastasis of the pancreas is extremely rare, and this is the first report of successful cryoablation of a metastatic tumor in the pancreas.

A Comprehensive Study on the Diagnosis and Management of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features.

Background: Since the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) was introduced in 2016, most retrospective studies have included cases diagnosed as encapsulated follicular variant of papillary thyroid carcinoma. We investigate a cohort diagnosed with NIFTP at resection. Methods: Retrospective institutional cohort of NIFTP from 2016 to 2022, including clinical, cytological, and molecular data for 319 cases (6.6% of thyroid surgeries, 183 cases as NIFTP-only). Results: The patient cohort had unifocal or multifocal thyroid nodules. Female:male ratio was 2.7:1, mean age was 52 years and median NIFTP size was 2.1 cm. NIFTP was associated with multiple nodules in 23% patients (n = 73) and 12% of NIFTP were multifocal (n = 39). Fine needle aspiration (FNA) of NIFTP (n = 255) were designated as nondiagnostic = 5%, benign = 13%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) = 49%, follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) = 17%, suspicious for malignancy = 12%, or malignant = 4%. Molecular alterations were identified in 93% (n = 114), RAS or RAS-like. Thyroid Imaging Reporting and Data System (TI-RADS) score 4 was recorded in 50% of NIFTP, followed by scores 3 and 5 (26% and 20%, respectively). We also investigated the factors associated with extent of surgery. In our NIFTP-only group (n = 183), 66% were identified after hemithyroidectomy (HT) and 34% after total thyroidectomy (TT). On univariate analysis, TT patients demonstrated higher Bethesda category by FNA, more often had aberrant preoperative thyroid function, and/or underwent an FNA of additional nodule(s). With multivariable regression, Bethesda V NIFTP, in the presence of other nodules being evaluated by FNA and aberrant preoperative thyroid function, independently predicts TT. Bethesda II NIFTP correlated significantly with HT. Fifty-two patients (28%) with NIFTP-only had at least one postoperative surveillance ultrasound. In the NIFTP-only cohort, no HT patients had completion thyroidectomy or received postoperative radioactive iodine. No recurrence or metastases were recorded with median follow-up of 35 months (6-76 months; n = 120). Conclusions: Given this large cohort of NIFTP, including a large subset of isolated NIFTP-only, some with >6 years of follow-up and no tumor recurrences, consensus practical guidelines are needed for adequate postoperative management. Given the American Thyroid Association (ATA) provides guidelines for management of low-risk malignancies, guidance regarding that for borderline/biologically uncertain tumors, including NIFTP, is a reasonable next step.