For Follicular Thyroid Carcinoma Research Articles

The alternative value of thyroid stimulating hormone instead of thyroglobulin in differentiation of follicular thyroid neoplasm in Hashimoto's thyroiditis.

To provide novel aspects for the preoperative diagnosis and appropriate differentiation strategies for follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). Among 25,765 cases, a total of 326 patients with follicular thyroid neoplasms between 2013 and 2019 were enrolled. Patient demographics, perioperative parameters, surgical profiles and oncologic outcomes were collected and analyzed. There were no significant differences in preoperative ultrasound findings between FTA and FTC patients. The true positive rate (sensitivity) and true negative rate (specificity) of fine needle aspiration (FNA) for FTA patients were 0.6956 and 0.5000, respectively, and those for FTC patients were 0.0714 and 0.9348, respectively. Patients with FTC presented significantly higher serum thyroglobulin (TG) levels than patients with FTA. Preoperative TG level was positively related to tumor invasiveness and recurrence or distant metastases in FTC patients. There were 55 patients with Hashimoto's thyroiditis (HT), accounting for 16.87% of enrolled patients. HT patients had significantly lower serum TG concentrations than antibody-negative patients. Among HT patients, no significant differences were observed in TG levels between the FTA and FTC groups. Instead, FTA patients had significantly higher serum thyroid stimulating hormone (TSH) levels and lower serum T3 (Triiodothyronine) levels compared to FTC patients. Serum TSH level >1.736U/L was associated with benign follicular neoplasms in HT patients according to the receiver operating characteristic (ROC) curve. Distinguishing FTC from FTA remains a challenge for ultrasonography and FNA. Serum TG should be measured as a risk factor of FTC. However, in HT patients, serum TSH levels can serve as a more reliable indicator for differentiating FTC from FTA preoperatively.

Efficacy of color Doppler ultrasound signs combined with serum tumor-specific growth factor in the diagnosis of differentiated thyroid cancer.

To construct a diagnostic model for follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC), both subtypes of differentiated thyroid carcinoma (DTC), using color Doppler ultrasound signs in conjunction with serum laboratory markers. We conducted a retrospective analysis of patients with thyroid nodules who underwent ultrasonography at Yulin Hospital from February 2021 to March 2023. The cohort included 269 subjects: 105 with benign nodules and 164 with DTC (59 with FTC and 105 with PTC). We compared baseline demographics and laboratory indices between the groups. Diagnostic values of ultrasound features and laboratory markers were assessed using receiver operating characteristic (ROC) curves, and logistic regression was employed to pinpoint independent diagnostic factors for FTC. A predictive nomogram was subsequently developed based on these factors. There were significant differences between the benign and malignant groups regarding ultrasound signs (including border, morphology, echogenicity, calcification, blood flow, lymph node zoning) and laboratory indices (free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (Tg), thyroid-stimulating hormone (TSH), vascular endothelial growth factor (VEGF), tumor-specific growth factor (TSGF)), with all P-values <0.05. The areas under the curve (AUCs) for FT3, FT4, Tg, TSH, VEGF, and TSGF were all above 0.75, with Tg achieving the highest at 0.91. Logistic regression identified borders, morphology, echogenicity, VEGF, and TSGF as independent diagnostic factors for distinguishing between FTC and PTC, with significant P-values. The constructed nomogram demonstrated an AUC of 0.853, indicating high diagnostic accuracy. Both calibration and decision curve analysis (DCA) validated the model's stability and clinical utility. We successfully developed a nomogram combining ultrasound features and serum markers that enhances the diagnostic precision for FTC. This model offers a valuable tool for clinical diagnostics in differentiated thyroid cancer.

Role of the Degree of Vascular Invasion in Predicting Prognosis of Follicular Thyroid Carcinoma.

The present study investigated the prognostic factors for follicular thyroid carcinoma (FTC) with the incorporation of the histologic subtype and degree of vascular invasion (VI). The records of 474 patients with FTC confirmed by surgical specimens at Ito Hospital from January 2005 to December 2014 were reviewed in this retrospective cohort study. The Cox proportional hazard model was used to determine factors associated with disease-free survival (DFS) and distant metastasis-free survival. Of the 474 patients, 140 (30%) had minimally invasive FTC, 260 (55%) had encapsulated angio-invasive FTC, and 74 (16%) had widely invasive FTC. Among the 428 patients with M0 FTC, the 10-year DFS rates of patients with minimally invasive FTC (n = 133), encapsulated angio-invasive FTC (n = 247), and widely invasive FTC (n = 48) were 97.3%, 84.2%, and 69.9% (P < .001), respectively. A multivariate analysis identified aged ≥55 years (hazard ratio [HR], 2.204; 95% CI, 1.223-3.969; P = .009), histologic subtype (HR, 2.068; 95% CI, 1.064-4.021; P = .032), VI of ≥2 (HR, 6.814; 95% CI, 3.157-14.710; P < .001), and tumor size >40 mm (HR, 2.014; 95% CI, 1.089-3.727; P = .026) as independent negative prognostic factors for DFS. Our study results may enable us to stratify the prognosis of FTC more accurately by combining the histologic subtype with the degree of VI ≥2, aged ≥55 years, and tumor size >40 mm.

Clinical Implication of World Health Organization Classification in Patients with Follicular Thyroid Carcinoma in South Korea: A Multicenter Cohort Study.

BackgroundThe study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC).MethodsThis multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell’s C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS).ResultsIn total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (P<0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (P<0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (P<0.001) were independent risk factors for DSS.ConclusionWHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS.

Identification of CHEK1, SLC26A4, c-KIT, TPO and TG as new biomarkers for human follicular thyroid carcinoma.

The search for preoperative biomarkers for thyroid malignancies, in particular for follicular thyroid carcinoma (FTC) diagnostics, is of utmost clinical importance. We thus aimed at screening for potential biomarker candidates for FTC. To evaluate dynamic alterations in molecular patterns as a function of thyroid malignancy progression, a comparative analysis was conducted in clinically distinct subgroups of FTC and poorly differentiated thyroid carcinoma (PDTC) nodules. NanoString analysis of FFPE samples was performed in 22 follicular adenomas, 56 FTC and 25 PDTC nodules, including oncocytic and non-oncocytic subgroups. The expression levels of CHEK1, c-KIT, SLC26A4, TG and TPO were significantly altered in all types of thyroid carcinomas. Based on collective changes of these biomarkers which correlating among each other, a predictive score has been established, allowing for discrimination between benign and FTC samples with high sensitivity and specificity. Additional transcripts related to thyroid function, cell cycle, circadian clock, and apoptosis regulation were altered in the more aggressive oncocytic subgroups only, with expression levels correlating with disease progression. Distinct molecular patterns were observed for oncocytic and non-oncocytic FTCs and PDTCs. A predictive score correlation coefficient based on collective alterations of identified here biomarkers might help to improve the preoperative diagnosis of FTC nodules.

Intraoperative Frozen Section May Reduce the Need for Reoperative Thyroid Surgery in Patients with Follicular Neoplasm

Background: Follicular neoplasm (Bethesda IV cytology) requires thyroid lobectomy for diagnosis. Approximately 15-30% of cases are ultimately malignant, requiring reoperative completion thyroidectomy. We sought to reassess whether intraoperative frozen section (FS) reduces the need for reoperative thyroidectomy in these cases. Methods: A retrospective chart review of fine needle aspiration (FNA) results showing follicular neoplasm from 2003 to 2012 was performed. Our practice is to offer thyroid lobectomy with FS for these patients; with suspicious FS, surgery proceeded to total thyroidectomy. FS suspicious for papillary thyroid carcinoma (PTC) was based on nuclear features (nuclear grooves/atypia, pseudo-nuclear inclusions) and for follicular thyroid carcinoma (FTC) was based on capsular/vascular invasion. Results: A total of 148 patients with follicular neoplasm on FNA were identified, of which 79 underwent FS. Fifteen had suspicious FS with 12 having malignancy on final pathology, for a positive predictive value of 80%. Nine showed features suspicious for PTC, of which eight had PTC. Six showed features suspicious for FTC, of which four had malignancy on final pathology. Of the 64 patients with unremarkable FS, 49 had benign final pathology, for a negative predictive value of 77%. Twelve (19%) patients required reoperation. Seven of 19 patients (37%) with malignancy avoided reoperation due to FS. Risk of malignancy with follicular neoplasm diagnosis was 34% (51/148), while risk of malignancy with follicular neoplasm and suspicious FS was 80%. Conclusions: Risk of malignancy with follicular neoplasm and suspicious FS is 80%. FS may avoid reoperative completion thyroidectomy in up to a third of patients. J Curr Surg. 2016;6(1):1-5 doi: http://dx.doi.org/10.14740/jcs286w

Follicular Thyroid Carcinoma: Disease Response Evaluation Using American Thyroid Association Risk Assessment Guidelines

Objective: To evaluate the overall and progression-free survival for follicular thyroid carcinoma (FTC) based on the American Thyroid Association (ATA) staging system for recurrence risk assessment and the TNM staging system. Methods: A clinical review of FTC patients between 1995 and 2014 was conducted at a single center. The data was classified using the TNM staging system into low, intermediate, and high risk of recurrence as per the ATA risk assessment. Results: Over the course of 19 years, 114 (11.9%) of all of the thyroid cancer patients presenting to our hospital had FTC (i.e. 78 females and 36 males). The age range was 15-80 years. Ninety-four tumors were resectable and 18 were unresectable. Sixteen patients were excluded due to insufficient information on their recurrence risk. Based on the ATA categorization, 36 patients had a low recurrence risk. All patients were alive at the time of categorization, and 1 showed progressive disease. Thirty-eight patients had an intermediate recurrence risk. One patient died and 2 showed progression. Twenty-four had a high recurrence risk. Seven patients died and 6 showed progression. In terms of TNM stages, 2 (3.2%) stage I, 3 (17.6%) stage II, 1 (14%) stage III, and 2 (12.5%) stage IV patients died during follow-up. Both ATA risk classification and TNM staging were significant predictors of disease-free survival. On bivariate analysis, the ATA classification (HR 4.67; 95% CI 1.74-12.5, p = 0.002) was a better predictor of survival compared to the TNM classification (HR 1.26; 95% CI 0.98-1.62, p = 0.063). Conclusion: ATA risk stratification predicts the disease recurrence rate and survival better than TNM staging. Age does not have an association; the risk category with dynamic reassessment effectively better predicts the course of disease in FTC.

Differential miRNA expression defines migration and reduced apoptosis in follicular thyroid carcinomas

The objective of the study was to identify microRNAs (miRs) characteristic for follicular thyroid carcinoma (FTC) and to define their role in tumorigenesis. A miR-microarray study was conducted to identify miRs differentially expressed between FTCs and their surrounding tissues. Selection was further reinforced by a literature review. Four miRs were selected and confirmed by RT-qPCR: miR-146b, -183, -221 were up-regulated, whereas miR-199b down-regulated in FTCs. The influence of these miRs on cell proliferation, cell cycle, apoptosis and migration was studied in HTori and FTC-133 cells. Functional characterization suggests an impact of miR-183 and miR-146b in FTC development. Overexpression of both miRs significantly induces migration. Moreover, overexpression of miR-183 significantly represses apoptosis. MiR-199b and -221 do not have significant effects on proliferation, cell cycle, apoptosis or migration in HTori and FTC-133 cells. Our data suggest that miR-146b and miR-183 may influence FTC development through the induction of migration and apoptosis inhibition.

Thyroid Lobe Ablation with Radioactive Iodine as an Alternative to Completion Thyroidectomy After Hemithyroidectomy in Patients with Follicular Thyroid Carcinoma: Long-Term Follow-Up

Radioactive iodine lobe ablation (RAI-L-ABL) is a possible alternative to completion thyroidectomy (C-Tx) for follicular thyroid carcinoma (FTC), but no long-term outcome data are available after lobe ablation. We analyzed the long-term outcome of lobe ablation in a series of patients with FTC.This was a retrospective study of patients who were treated with lobe ablation between 1983 and 2008. Of 134 patients with FTC, 37 (27.6%) had lobe ablation with (131)I (30-32 mCi) (RAI-L-ABL), 68 (50.7%) had C-Tx, and 29 (21.6%) had initial total thyroidectomy (T-Tx). The main outcomes analyzed were (131)I uptake after lobe ablation, C-Tx or T-Tx, serum thyroglobulin (Tg), serum thyroid-stimulating hormone (TSH), long-term disease-specific mortality, and disease-free survival.After lobe ablation, radioiodine uptake was significantly lower for the RAI-L-ABL group (0.6%) than for the C-Tx group (2.0%, p<0.005) or T-Tx group (1.3%, p=0.054). Subsequent remnant ablation was performed in 12 of 37 (32%) patients in the RAI-L-ABL group, in 58 of 68 (85.3%) patients in the C-Tx group, and in 25 of 29 (86.2%) patients in the T-Tx group (p<0.01). With median follow-up of 95 months for the RAI-L-ABL group, 47 months for the C-Tx group, and 53 months for the T-Tx group, there was one death in the RAI-L-ABL group and one death in the T-Tx group. No other RAI-L-ABL patients had detectable disease, whereas patients in the C-Tx group and two patients in the T-Tx group had detectable disease (p=0.18). Long-term stimulated or suppressed Tg of <1 ng/mL were found in 87.5% of the RAI-L-ABL group (n=28), 86.3% of the C-Tx group (n=57), and 77.8% of the T-Tx group (n=21). Tg was detectable in 40.6% of the RAI-L-ABL group compared to 13.8% of C-Tx and 28.6% of T-Tx groups (p<0.05, between groups).RAI-L-ABL, C-Tx, and T-Tx are equally effective in achieving serum TSH concentrations of >25 mIU/L and preparing patients for conventional (131)I treatment and whole body scanning with similar long-term outcomes. However, persistent measurable Tg (range 0.2-2.2 ng/mL) is more common after RAI-L-ABL.

Conservative management of patients with intrathyroidal well-differentiated follicular thyroid carcinoma

Background. Total or near-total thyroidectomy is advocated as the treatment of choice for follicular thyroid carcinoma (FTC). The prognosis of patients with low-risk FTC, however, is excellent, and thus total thyroidectomy may not be justifiable in such patients. Methods. A retrospective review identified 61 patients diagnosed with intrathyroidal well-differentiated FTC between 1958 and 1991. Results. Median age at diagnosis was 42 years (range, 15-78 years). Most patients (90.2%) had a lobectomy or subtotal thyroidectomy. Median tumor size was 3.0 cm (range, 0.9-9.5 cm). Fifty-eight patients (95.1%) received thyroid hormone supplementation, and 5 (8.2%) received radioactive iodine ablation postoperatively. Median follow-up was 11 years (range, 3-35 years). Local recurrence, metastasis, or both developed in 3 patients (4.9%), and all subsequently died of thyroid cancer. The cumulative 10- and 15-year cancer-specific survival rate was 96.5%. Factors significantly related to worse survival were oxyphilic histology (log-rank, P =.00) and tumor size of more than 4 cm (P =.001). However, neither was found to be an independent predictor of outcome by Cox multivariate analyses (P =.7 and.9, respectively). The extent of initial operation (unilateral versus bilateral procedure) was not significantly related to survival (P =.52). Conclusion. Conservative management consisting mainly of lobectomy or subtotal thyroidectomy and thyroid hormone supplementation is associated with favorable outcome of patients with intrathyroidal well-differentiated FTC. (Surgery 2001;130:30-5.)