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OBJECTIVE. Compared with other guidelines, the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) has decreased the number of nodules for which fine-needle aspiration is recommended. The purpose of this study was to evaluate the characteristics of malignant nodules that would not be biopsied when the ACR TI-RADS recommendations are followed. MATERIALS AND METHODS. We retrospectively reviewed a total of 3422 thyroid nodules for which a definitive cytologic diagnosis, a definitive histologic diagnosis, or both diagnoses as well as diagnostic ultrasound (US) examinations were available. All nodules were categorized using the ACR TI-RADS, and they were divided into three groups according to the recommendation received: fine-needle aspiration (group 1), follow-up US examination (group 2), or no further evaluation (group 3). RESULTS. Of the 3422 nodules, 352 were malignant. Of these, 240 nodules were assigned to group 1, whereas 72 were assigned to group 2 and 40 were included in group 3. Sixteen of the 40 malignant nodules in group 3 were 1 cm or larger, and, on the basis of analysis of the sonographic features described in the ACR TI-RADS, these nodules were classified as having one of five ACR TI-RADS risk levels (TR1-TR5), with one nodule classified as a TR1 nodule, eight as TR2 nodules, and seven as TR3 nodules. If the current recommendation of no follow-up for TR2 nodules was changed to follow-up for nodules 2.5 cm or larger, seven additional malignant nodules and 316 additional benign nodules would receive a recommendation for follow-up. If the current size threshold (1.5 cm) used to recommend US follow-up for TR3 nodules was decreased to 1.0 cm, seven additional malignant nodules and 118 additional benign nodules would receive a recommendation for follow-up. CONCLUSION. With use of the ACR TI-RADS, most malignant nodules that would not be biopsied would undergo US follow-up, would be smaller than 1 cm, or would both undergo US follow-up and be smaller than 1 cm. Adjusting size thresholds to decrease the number of missed malignant nodules that are 1 cm or larger would result in a substantial increase in the number of benign nodules undergoing follow-up.

Polarization-sensitive second harmonic generation (SHG) microscopy is an established imaging technique able to provide information related to specific molecular structures including collagen. In this investigation, polarization-sensitive SHG microscopy was used to investigate changes in the collagen ultrastructure between histopathology slides of normal and diseased human thyroid tissues including follicular nodular disease, Grave's disease, follicular variant of papillary thyroid carcinoma, classical papillary thyroid carcinoma, insular or poorly differentiated carcinoma, and anaplastic or undifferentiated carcinoma ex vivo. The second-order nonlinear optical susceptibility tensor component ratios, χ (2) zzz '/χ (2) zxx ' and χ (2) xyz '/χ (2) zxx ', were obtained, where χ (2) zzz '/χ (2) zxx ' is a structural parameter and χ (2) xyz '/χ (2) zxx ' is a measure of the chirality of the collagen fibers. Furthermore, the degree of linear polarization (DOLP) of the SHG signal was measured. A statistically significant increase in χ (2) zzz '/χ (2) zxx ' values for all the diseased tissues except insular carcinoma and a statistically significant decrease in DOLP for all the diseased tissues were observed compared to normal thyroid. This finding indicates a higher ultrastructural disorder in diseased collagen and provides an innovative approach to discriminate between normal and diseased thyroid tissues that is complementary to standard histopathology.

Background: Current classification systems for thyroid nodules are very subjective. Artificial intelligence (AI) algorithms have been used to decrease subjectivity in medical image interpretation. One out of 2 women over the age of 50 years may have a thyroid nodule and at present the only way to exclude malignancy is through invasive procedures for those that are suspicious on ultrasonography. Hence, there exists a need for noninvasive objective classification of thyroid nodules. Some cancers have benign appearance on ultrasonogram. Hence, we decided to create an image similarity algorithm rather than image classification algorithm. Materials and Methods: Ultrasound images of thyroid nodules from patients who underwent either biopsy or thyroid surgery from February 2012 to February 2017 in our institution were used to create AI models. Nodules were excluded if there was no definitive diagnosis of it being benign or malignant. A total of 482 nodules met the inclusion criteria and all available images from these nodules were used to create the AI models. Later, these AI models were used to test 103 thyroid nodules that underwent biopsy or surgery from March 2017 to July 2018. Results: Negative predictive value (NPV) of the image similarity model was 93.2%. Sensitivity, specificity, positive predictive value (PPV), and accuracy of the model were 87.8%, 78.5%, 65.9%, and 81.5%, respectively. Conclusions: When compared with published results of ultrasound thyroid cancer risk stratification systems, our image similarity model had comparable NPV with better sensitivity, specificity, and PPV. By using image similarity AI models, we can decrease subjectivity and decrease the number of unnecessary biopsies. Using image similarity AI model, we were able to create an explainable AI model that increases physician's confidence in the predictions.

Objective: The current paradigm in the treatment of patients with non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a diagnostic lobectomy rather than complete thyroidectomy and postoperative radioiodine treatment. Consequently, preoperative diagnosis of NIFTP is considered to be important., Methods: We performed the comprehensive analysis for diagnosis of preoperative 20 NIFTPs in comparison with 41 invasive encapsulated follicular papillary thyroid carcinomas (I-EFVPTCs) using the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and molecular analysis for BRAF and RAS mutations., Results: K-TIRADS 3 was identified as the most common sonographic diagnosis in both NIFTP and I-EFVPTC. Unlike I-EFVPTC, K-TIRADS 5 was not identified in NIFTP. AUS/FLUS was the most common cytopathological diagnosis and none of the cases were classified as malignant category in both groups, although the difference in distribution was not significant between the groups. BRAF mutation was not found in NIFTP but was present in 9.8% of cases in I-EFVPTC. The frequency of RAS mutation in I-EFVPTCs was twice as high as that of NIFTP. Wild-type BRAF and RAS in NIFTP was significantly higher than I-EFVPTC., Conclusion: The existence of overlapping features between the groups was evident, hence conclusive distinction between radiology, cytology and molecular analysis could not be achieved. Apparently, the diagnosis of NIFTP based on comprehensive analysis was not confirmable but could perceive or at least favor the diagnosis of NIFTP., Competing Interests: The authors have declared that no competing interests exist.

Objective: Hürthle cell carcinomas (HCCs) of the thyroid have been recently reclassified as a separate entity due to their distinct clinical and molecular profiles. Few studies have assessed the ability of preoperative characteristics in differentiating HCCs from Hürthle cell adenomas (HCAs) due to the low prevalence of both lesions. This study aimed to compare the preoperative features of HCCs and HCAs and evaluate the diagnostic performance of ultrasound in distinguishing between both., Subjetcs and Methods: Retrospective study including 101 patients (52 HCCs and 49 HCAs) who underwent thyroid surgery from 2000 to 2016. Clinical, ultrasonographic, and histological data were reviewed. Diagnostic performance of suspicious sonographic features was analyzed in 51 cases (24 HCCs and 27 HCAs)., Results: Hürthle cell neoplasms were predominant in females. Subjects ≥ 55 years represented 58% of the cases of HCCs and 53% of those of HCAs. Carcinomas were significantly larger (p < 0.001), and a tumor size ≥ 4 cm significantly increased the risk of malignancy (odds ratio 3.67). Other clinical, cytologic, and sonographic data were similar between HCCs and HCAs. Among the HCCs, the lesions were purely solid in 54.2%, hypoechoic in 37.5%, and had coarse calcifications in 12.5%, microcalcifications in 8.3%, irregular contours in 4.2%, and a taller-than-wide shape in 16.7%. Predominantly/exclusive intranodular vascularization was observed in 52.6%. Overall, 58% of the HCCs were classified as TI-RADS 4 or 5 compared with 48% of the HCAs. TI-RADS 4 or 5 had a specificity of only 51.8% and a positive likelihood ratio of 1.21., Conclusions: Apart from the lesion size, no other preoperative feature adequately distinguished HCCs from HCAs. Sonographic characteristics raising suspicion for malignancy, which are mostly present in papillary carcinomas, were infrequent in HCCs. New tools must be developed to improve preoperative diagnosis and deferral of surgery in cases of adenomas.

Context: In adults, noninvasive follicular variant of papillary thyroid carcinoma (FVPTC) is considered a low risk for metastasis and persistent/recurrent disease., Objective: The goal of this study was to assess the clinical, sonographic, and histopathologic features of FVPTC in a pediatric cohort., Design: A retrospective review of subjects <19 years of age with papillary thyroid carcinoma (PTC) who underwent thyroidectomy between January 2010 and July 2015., Setting: Multidisciplinary academic referral center., Patients: Patients with FVPTC, defined as a tumor ≥1 cm in the largest dimension with predominant follicular growth, complete lack of well-formed papillae, and nuclear features of PTC., Main Outcome Measures: Tumor size and location, presence of a tumor capsule, capsule and vascular invasion, lymph node invasion, and distant metastasis., Results: Eighteen patients with FVPTC were identified from a case cohort of 110 patients with PTC. On histopathology, 13 (72%) had unifocal nodules and 14 (78%) had completely encapsulated FVPTC. Capsule invasion was frequent (nine of 14; 64%), and vascular invasion was found in one-third of patients (six of 18; 33%). No lymph node metastases were found in the 13 patients (72%) who had a central neck lymph node dissection. One patient with vascular invasion had distant metastases., Conclusion: When strictly defined, FVPTC in pediatric patients has a low risk for bilateral disease and metastasis. Prospective studies are needed to confirm whether lobectomy with surveillance is sufficient to achieve remission in pediatric patients with low-risk FVPTC.

Background: The noninvasive encapsulated follicular variant of papillary carcinoma (nEFVPTC) has recently been reclassified to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)," removing this entity from the malignant category. This re-categorization has had major implications for clinical management. NIFTP has overlapping cytohistologic features with papillary thyroid carcinoma (PTC) and with follicular adenomas (FA), but sonographic data comparing NIFTP to PTC and FA is lacking. Our study examines the sonographic features of NIFTP as compared with PTC and FA., Methods: Ultrasound scans and Doppler blood flow from subjects who had pre-surgical sonograms and fine needle aspiration biopsies with final surgical pathology diagnoses of NIFTP/nEFVPTC, classical PTC, and FA between 01/2013-08/2016 were assessed. Sonographic and Doppler features as well as Bethesda System (TBS) diagnoses were recorded and analyzed., Results: 40 NIFTP, 58 classical PTC, and 23 FA cases were included. The most common NIFTP pre-surgical TBS cytology diagnosis was Atypia of Undetermined Significance (AUS/FLUS) (40%). NIFTP cases predominantly displayed wider-than-tall shape (100%), smooth borders (75%), occurrence in multinodular glands (82.5%), heterogeneous echogenicity (50%), both perinodular and intranodular Doppler flow patterns (70%), minimal Doppler flow grade (62.5%), and no calcifications (90%)., Conclusions: Our study demonstrates that NIFTP, PTC, and FA display several distinguishing and overlapping sonographic and Doppler features. Sonographic features appear to complement cytology findings and may help raise pre-operative concern for NIFTP in the proper clinical setting, potentially leading to a more conservative management approach., (© 2017 Wiley Periodicals, Inc.)

Background: This study aims to analyze changes in characteristics, practice and outcomes of pediatric differentiated thyroid cancer (DTC) at our tertiary care institution., Methods: Patients <21 years of age diagnosed between 1973 and 2013 were identified. Clinicopathological data, treatment and outcomes were obtained by a retrospective review., Results: Thirteen males and 68 females were divided into Group A (n=35, diagnosed before July 1993) and Group B (n=46, diagnosed after July 1993). Group B was more likely to undergo neck ultrasound (US) (70% vs. 23%, p<0.0001) and fine-needle aspiration (FNA) biopsy (80% vs. 26%, p<0.0001). Patients in Group B more often underwent total thyroidectomy as a definitive surgical treatment (87% vs. 69%, p=0.04). There was no difference in radioactive iodine use. Recurrence-free survival was similar., Conclusions: Increased use of US and FNA has affected initial surgical management in the latter part of the study, possibly due to extension of adult DTC guidelines. The effects of the new pediatric DTC guidelines need further study.

Background: Follicular variant of papillary thyroid carcinoma (FVPTC) is traditionally divided into infiltrative and encapsulated types. Adding to this classification, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a reclassification of a subset of cases (encapsulated tumors without lymphovascular or capsular invasion). The purpose of this study was to assess the role of ultrasound (US) in predicting tumor invasiveness in FVPTC., Methods: From January 2014 to May 2016, preoperative US examinations were performed on 151 patients with 152 FVPTCs who underwent surgery. Based on a pathologic analysis, the FVPTCs were categorized into three groups: NIFTP, invasive encapsulated FVPTC (iE-FVPTC), or infiltrative FVPTC (I-FVPTC). Each nodule was categorized based on the US pattern according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American Thyroid Association (ATA) guidelines. The correlation between tumor invasiveness and the K-TIRADS or ATA category was investigated using Spearman's rank correlation coefficient., Results: Among the 152 FVPTCs, there were 48 (31.6%) NIFTPs, 60 (39.5%) iE-FVPTCs, and 44 (28.9%) I-FVPTCs. US characteristics of the FVPTCs differed significantly according to tumor invasiveness (p ≤ 0.030). Tumor invasiveness showed a significant positive correlation with K-TIRADS (tumors of all sizes: r = 0.591, p < 0.001; tumors ≥1.0 cm: r = 0.427, p < 0.001) and ATA categories (tumors of all sizes: r = 0.532, p < 0.001; tumors ≥1.0 cm: r = 0.466, p < 0.001). According to both K-TIRADS and ATA guidelines for all-sized tumors, the most common subtype was NIFTP in low-suspicion nodules (52.6% and 51.6%), iE-FVPTC in intermediate-suspicion nodules (52.7% and 54.2%), and I-FVPTC in high-suspicion nodules (82.5% and 69.4%). After surgery, lymph node metastases were confirmed in two (4.2%) NIFTP cases, three (5.0%) iE-FVPTC cases, and eight (18.2%) I-FVPTC cases (p = 0.001). The results of the BRAF mutation analysis were not significantly different between the groups (p = 0.507)., Conclusions: Increasing tumor invasiveness from NIFTP to iE-FVPTC to I-FVPTC is positively correlated with the level of suspicion on US using both K-TIRADS and ATA guidelines.

The purpose of this prospective study was to determine the incremental diagnostic value of single photon emission computed tomography/computed tomography with iodine-131 over planar whole body scan in the staging of patients with differentiated thyroid carcinoma. A total of 365 patients (270 female, 95 male) with differentiated thyroid carcinoma were treated with radioiodine therapy for thyroid remnant ablation with radical intent after thyroidectomy between January 2013 and November 2014. In addition to planar whole body scan, single photon emission computed tomography/computed tomography of neck and chest were performed. Each radioactive focus at whole body scan was classified as positive or equivocal with respect of specific territories: thyroid bed, cervical lymph nodes and distant metastases.Whole-body scan detected focal uptake in 353 patients and no uptake in 12. The location was considered equivocal in 100. Single photon emission computed tomography/computed tomography detected focal uptake in 356 patients and no uptake in nine. In three patients with negative wholebody scan, single photon emission computed tomography/computed tomography provided information about residual activity in the thyroid bed. By single photon emission computed tomography/computed tomography the location was equivocal in 18 patients only. Single photon emission computed tomography/computed tomography was helpful in 82 out of 100 patients with equivocal findings by whole body scan allowing a correct identification of the uptake sites. In a great number of equivocal whole body scan, due to high remnant activity, single photon emission computed tomography/computed tomography was able to differentiate between thyroid remnant and lymph nodes uptake. In 22 out of 100 patients with doubtful whole body scan, single photon emission computed tomography/computed tomography correctly identified nodal or distant metastases, and in 2/100 patients, focal uptake classified as metastatic by whole body scan was reclassified as para-physiological by single photon emission computed tomography/computed tomography. The TNM classification changed in 13 out of 22 patients. Single photon emission computed tomography/computed tomography improves detection and localization of the iodine-131 uptake after thyroidectomy in patients with differentiated thyroid carcinoma and it is more accurate than whole body scan to evaluate lymph nodes and to identify and characterize distant metastases. Single photon emission computed tomography/computed tomography aids assessment of lower/upper stage in a significant number of patients with differentiated thyroid carcinoma and it can affect therapy decision-making and patient management.

A 68-year-old man underwent adjuvant radioiodine therapy for follicular variant papillary thyroid carcinoma. Post-therapeutic whole-body I scan showed abnormal radioiodine uptake on the right side of back. SPECT/CT localized this abnormal activity from a small subcutaneous lesion with fat density between the right 10th and 11th rib. Under ultrasound-guided autopsy, the lesion was confirmed as lipoma.

Follicular variant papillary thyroid cancer (FVPTC) is the second most common subtype after conventional PTC. We compared ultrasonographic (US) features of FVPTC to those of conventional PTC according to tumor size. We reviewed US findings, pathologic reports, and medical charts of 249 PTC patients with surgically proven disease (83 FVPTCs, 166 conventional PTCs) at our institution from January 2007 to December 2012. FVPTCs were divided into PTC-like and follicular neoplasm (FN)-like based on sonographic characteristics. PTC-like features were defined as having at least one malignant feature (taller-than-wide shape, infiltrative margin, marked hypoechogenicity, and micro-calcifications), whereas FN-like cancers showed oval solid features without malignant features. FVPTCs showed a higher rate of FN-like features than conventional PTCs. Of 166 conventional PTCs, 13 (7.8%) had FN-like features and 153 (92.2%) had PTC-like features, whereas of the 83 FVPTCs, 31 (37.3%) had FN-like features and 52 (62.7%) had PTC-like features. Macro-FVPTCs showed a higher rate of FN-like features than micro-FVPTCs (P < 0.001). Of 21 macro-FVPTCs, 18 (85.7%) had FN-like features and 3 (14.3%) had PTC-like features, whereas of the 62 micro-FVPTCs, 13 (21%) had FN-like features and 49 (79%) had PTC-like features. There were no differences in multifocality, extrathyroidal invasion, and lymph node metastasis between PTC-like FVPTCs and FN-like FVPTCs. FVPTCs showed fewer sonographic malignant features than conventional PTCs. In particular, FVPTCs larger than 1 cm had a more frequent benign sonographic appearance. Therefore, if fine-needle aspiration result is suspicious for PTC in a nodule larger than 1 cm with no suspicious US features, the possibility of FVPTC might be considered.

Objective: The follicular variant of papillary thyroid carcinoma (FVPTC) has multiple histological subtypes. Clinical outcomes of FVPTC are variable depending on the subtypes. This study evaluated the association of pre-operative ultrasonographic (US) findings and clinico-pathological features of FVPTC., Patients: This retrospective study enrolled patients with FVPTC (n = 70), size-matched classical variant of papillary thyroid carcinoma (CPTC, n = 328), follicular carcinoma (n = 85) and follicular adenoma (FA, n = 120). We defined the histological subtypes of FVPTC as infiltrative (I-FVPTC; n = 19) or encapsulated (E-FVPTC; n = 51) according to the presence of a fibrous capsule. Pre-operative US was reviewed using a US scoring system and classified into low US score (n = 42) and high US score (n = 28)., Results: The median US score for FVPTC was lower than CPTC (2 vs 7, P < 0·001), but higher than FA (2 vs 0, P < 0·001). The median US score for I-FVPTC was significantly higher than E-FVPTC (4 vs 2, P = 0·009). I-FVPTC was more likely to be diagnosed as a malignancy or suspicious for malignancy on cytology than E-FVPTC (P = 0·002). The cumulative risks of cervical lymph node (LN) or distant metastasis according to tumour size were significantly higher in I-FVPTC than E-FVPTC (all P < 0·001). The cumulative risks for cervical LN metastasis or capsular invasion according to tumour size were significantly higher in FVPTC with high US score than FVPTC with low US score (P = 0·005, P < 0·001, respectively)., Conclusions: Pre-operative US findings of thyroid nodules were associated with not only histological subtypes, but also the clinical behaviour in FVPTC., (© 2014 John Wiley & Sons Ltd.)

Objective: Follicular variant of papillary thyroid carcinoma (FVPTC) is a common variant of papillary thyroid carcinoma (PTC), but the association between BRAF mutation and the clinicopathological and ultrasonographical characteristics of FVPTC has not been well studied. The aim of this study was to determine the significance of BRAF mutation in FVPTC., Patients: The medical records of the 137 patients with >5 mm FVPTCs and known BRAF mutation status in the interested nodule were reviewed. BRAF mutation analysis was performed routinely and prospectively by Sanger sequencing. Clinicopathological and ultrasonographical characteristics were compared between BRAF mutation-positive and BRAF mutation-negative groups., Results: BRAF mutation was detected in 35 (25·5%) patients. The BRAF mutation-positive group was associated with smaller tumour size (P = 0·022), extrathyroidal extension (P = 0·001), multifocality (P = 0·046) and higher (III/IV) TNM stages (P = 0·005). In multivariable analysis, higher (III/IV) TNM stage was an independent predictive factor for BRAF mutation-positive status (adjusted OR 2·966, 95% CI 1·321-6·663). In diagnosis of FVPTC, the presence of BRAF mutation was associated with malignant features on ultrasonography (P < 0·001) and higher incidence of suspicious for malignancy or malignant diagnosis on the fine needle aspiration cytology (P = 0·023). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of US for detecting BRAF mutation were 82·9%, 57·8%, 40·3%, 90·8% and 64·2%, respectively. Conclusions BRAF mutation in FVPTC is associated with unfavourable clinicopathological characteristics and malignant features on ultrasonography and may be a potential prognostic factor as it is in classical PTC., (© 2014 John Wiley & Sons Ltd.)

Context: Published studies of thyroid stunning due to preablation (131)I scanning in the treatment of differentiated thyroid cancer after thyroidectomy had shown inconsistent clinical impact., Objective: The objective of the study was to evaluate the clinical outcome in patients who were given a low diagnostic (131)I activity (1.1 mCi or 40 MBq) 6 days prior to radioiodine ablation (RAI)., Design/setting: Two cohorts of patients were treated in a cancer referral center in 2004-2011. The eligibility criteria were as follows: 1) diagnosis of differentiated thyroid cancer; 2) total or near total thyroidectomy; 3) no distant metastasis; and 4) receiving 82.4 mCi or greater (3050 MBq) therapeutic (131)I activity., Patients/interventions: Three hundred five consecutive patients treated in 2004-2008 (group A) had a diagnostic activity 1.1 mCi of (131)I prior to RAI. The second cohort treated in 2009-2011 (group B) consisted of 237 patients who did not undergo diagnostic (131)I scanning prior to RAI., Main Outcome Measures: The tumor recurrence rate at 3 years and quantitative assessment using diagnostic whole-body radioiodine scans and TSH-stimulated thyroglobulin levels at 3-12 months after RAI were measured., Results: The 3-year recurrence-free survival rates were 96.4% in both groups, with 4.3% in group A and 3.4% in group B having tumor recurrence (P = .91). The ablation success rates measured by diagnostic whole-body radioiodine scans were 97.6% and 100% and by stimulated thyroglobulin were 85.3% and 85.8% in group A and B, respectively (P = .62)., Conclusions: The use of low diagnostic (131)I activity (1.1 mCi) given 6 days prior to RAI was safe and convenient without adversely affecting the long-term clinical outcome.

Background: Follicular variants of papillary thyroid carcinoma (FVPTCs) have dichotomous ultrasonographic (US) features. We investigated the differences in the biologic behavior of FVPTC according to US features., Methods: We reviewed the US findings, pathologic reports, and medical charts of 75 consecutive patients with FVPTC who underwent surgery at our institution from January 2006 to December 2008. FVPTCs were divided into PTC-like and follicular neoplasm (FN)-like based on US findings. PTC-like nodules were defined as having at least one accepted malignant feature (a taller-than-wide shape, an infiltrative margin, marked hypoechogenicity, and micro- or macrocalcifications), whereas FN-like nodules showed oval solid features without malignant features. The prognostic factors were compared., Results: Of the 75 FVPTCs, 42 (56%) were PTC-like and 33 (44%) were FN-like. The mean tumor size of PTC-like FVPTC was significantly smaller than that of FN-like FVPTC (p=0.0483). PTC-like FVPTC showed a significantly higher rate of multifocality than FN-like FVPTC (48% and 15% respectively; p=0.0031). Extrathyroidal extension occurred in 55% of PTC-like FVPTCs compared to 12% of FN-like FVPTCs (p=0.0001). Lymph node metastasis was more frequent in PTC-like FVPTC than in FN-like FVPTC (36% vs. 12%; p=0.0197). PTC-like FVPTC had a higher stage than FN-like FVPTC (p=0.0001). These significant factors persisted in multivariate analysis. Only one recurrence and one distant metastasis were identified, and both occurred in PTC-like FVPTC., Conclusions: FVPTC with malignant US features seems to behave in a more aggressive fashion than FVPTC without malignant US features. US can help predict the behavior of FVPTC.

Thyroid diseases are frequently seen in patients with acromegaly. The aim of this study is to evaluate thyroid diseases and thyroid cancer in acromegalic patients followed in a single institution. The data of 92 acromegalic (43 male, 49 female) patients followed over 12 years were retrieved retrospectively from the hospital recordings. All available data for gender, age, body weight and height, duration of acromegaly, age at diagnosis of acromegaly, treatment methods for acromegaly and history of thyroid disease, serum GH, IGF-1, thyroid function tests, thyroid ultrasonography (US), thyroid scintigraphy and thyroid fine needle aspiration biopsy (FNAB) results were recorded for the patients. The mean age of the patients was 43.9 ± 10.8 years and the mean disease duration was 12 ± 6.9 years. Thyroid US was performed in 64 patients who had nodular or diffuse goiter on palpation during the post-treatment follow-up and nodules were found in 44 (47.8 %) patients. Final diagnosis in 64 patients with thyroid US results and thyroid function tests including 26 patients with FNAB were as follows: 31 (48.4 %) benign multinodular goiter (MNG), 6 (9.4 %) simple nodular goiter, 1 (1.6 %) toxic MNG, 1 (1.6 %) Hurthle cell adenoma, and 5 (7.8 %) differentiated thyroid cancer. In addition, 9 (14.1 %) patients had diffuse goiter. One of the patients with diffuse goiter had amiodarone induced thyrotoxicosis. Eleven (17.1 %) patients had normal thyroid US and no other thyroid disease. Patients with nodules had longer disease duration than patients without nodules (14.2 ± 6.6 vs. 9.4 ± 3.4 years, p = 0.043). Thyroid volume was positively correlated with post-treatment GH and post-treatment IGF-1 levels (r = 0.309, p = 0.041 and r = 0.423, p = 0.004), respectively. We found that 7.8 % of our acromegalic patients with thyroid US results were diagnosed with thyroid cancer. Therefore, acromegalic patients must be considered as a high risk group for the development of thyroid cancer and must be closely followed for thyroid nodules and tumors.

Background: Follicular variant of papillary thyroid carcinoma (FV-PTC) has been increasingly diagnosed in recent years. However, little is known about its clinical behavior. The purpose of this study was to determine the disease characteristics of FV-PTC, and to compare it with classical papillary thyroid carcinoma (C-PTC) and follicular thyroid carcinoma (FTC)., Methods: All cases of C-PTC, FV-PTC, and FTC larger than 1 cm in the Surveillance, Epidemiology and End Results (SEER) Cancer Database from 1988 to 2007 were identified. Tumor behavior and patient survival were compared among these three groups. Different risk factors for disease-specific mortality in each group were evaluated by multivariate analysis., Results: More than 36,000 surgical cases were identified, including 21,796 C-PTCs, 10,740 FV-PTCs, and 3958 FTCs. Extrathyroidal extension and lymph-node metastases were more common in FV-PTC than in FTC, but significantly less common than in C-PTC (p<0.0001). Distant metastasis rates were present in 2% of patients with FV-PTC, in 1% with C-PTC, and in 4% with FTC (p<0.0001). The 10-year disease-specific survival for patients with FV-PTC was 98%, similar to C-PTC (97%) but better than FTC (94%, p<0.0001). Being over the age of 45 years remained a strong risk factor for disease-specific mortality in both FV-PTC and C-PTC, while the presence of extrathyroidal extension and distant metastases were stronger predictors of disease-specific mortality in FV-PTC than in C-PTC., Conclusions: FV-PTC is a common variant of PTC. Its clinical behavior is unique and represents an intermediate entity with clinical features that are between C-PTC and FTC. Interestingly, despite the variations in clinical behavior, the long-term outcome of these patients remains excellent and similar to C-PTC.

Background: The most important side effect of radioiodine ((131)I) therapy is sialoadenitis and xerostomy., Aim: To evaluate by ultrasound (US) parotid and submandibular glands after (131)I therapy for differentiated thyroid cancer (DTC)., Patients: Seventy-six subjects thyroidectomized for DTC submitted to salivary glands US examination. Forty-three of them had been previously treated with (131)I: 22 with 1.11 GBq (30 mCi) for remnant ablation, and 21 with higher doses [up to 44.4 GBq (1200 mCi)] for metastases. Thirty-three subjects studied before (131)I therapy served as controls. Parotid and submandibular volume, homogeneity, and echogenicity were determined. (131)I-treated patients filled a questionnaire about sialoadenitis symptoms., Results: Parotid gland volume was significantly higher in treated patients (28.3±16.2 ml) than in untreated patients (20.7±10.4 ml, p=0.0154) and related to the time from last (131)I therapy. Three had parotid volume <1.5 ml and complained severe xerostomy. Submandibular gland volume was similar in treated (11.2±7.6 ml) and untreated patients (8.6±4.2 ml, p=0.0602). Homogeneity and echogenicity were similar in treated and untreated patients. Sialoadenitis symptoms were reported in 26% and were related to the (131)I cumulative dose. Symptoms were not related to gland volume. Hypoechogenicity and inhomogeneity of the parotids were more frequent in patients with salivary stickiness., Conclusion: Parotid, but not submandibular, volume is increased after (131)I treatment depending on the received activity and the time from irradiation but not on sialoadenitis symptoms. Xerostomy is associated to gland atrophy at US., (©2013, Editrice Kurtis)

Background: Distant metastases of differentiated thyroid cancers are exceptionally localized in the soft tissues and the pelvic cavity. This last event complicates diagnosis, especially in female patients because of false positive nuclear imaging and unrelated iodine uptakes. False positive due to body secretions, urinary and fecal iodine retention and iodine uptake by non-thyroid tissues or ectopic thyroid tissue and bone metastasis of differentiated thyroid carcinoma., Methods: We present two cases of metastasectomy, guided by a peroperative gamma probe and intraoperative frozen sections of the specimens. In females patients because of potentially false positive nuclear imaging and iodine uptakes unrelated to pathology, it is very difficult to identify a pelvic metastasis. Our experience of two cases underlines these pitfalls and the possibilities to avoid them: the use of 131 Iodine SPECT/CT whole body scan, peroperative gamma probe and intraoperative frozen sections of specimen., Conclusion: Preoperative localization needs a precise 3D imaging and the surgical treatment must be guided by a peroperative gamma probe and frozen sections., (Celsius.)

Objective: The encapsulated follicular variant of papillary carcinoma (FVPC) was recently reported to have genetic alterations and biological behavior closer to follicular adenoma/carcinoma than classic papillary carcinoma and unencapsulated FVPC. The objective of this study is to alert cytologists to this new subtype and to report our experience., Study Design: Cytology of 41 cases of surgery-proven encapsulated FVPC was reviewed and correlated with histopathology and ultrasound findings. These cases were collected over 19 years from 188 aspirates reported as 'suspicious or atypical, cannot exclude FVPC' and from 245 aspirates reported as follicular neoplasm., Results: Thirteen aspirates had diffusely atypical nuclei, 20 aspirates had mixed normal and atypical nuclei, and 8 aspirates had no atypical nuclei. On histology, papillary nuclei were distributed focally in the second and third groups. Crowded, oval, clear nuclei occurred in nearly 80% of the cases, nuclear grooves occurred in 12.2%, and nuclear pseudoinclusions occurred in 4.9%. Capsular invasion without angioinvasion was present in 30% of encapsulated FVPCs, with angioinvasion in 17.5% and lymph node metastasis in 7.5%. Most encapsulated FVPCs were benign-appearing on ultrasound with round-to-oval, circumscribed nodules with a hypoechoic rim., Conclusions: Encapsulated FVPC is more difficult to recognize on fine-needle aspiration and ultrasound than unencapsulated FVPC., (Copyright © 2012 S. Karger AG, Basel.)

Diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) by ultrasound-guided fine-needle aspiration (FNA) is challenging. In this retrospective review, we evaluated triage efficacy (i.e., potential for triggering surgical intervention) in 44 archived FNA biopsies of surgically confirmed FVPTC obtained between December 2006 and December 2008. We compared the original FNA diagnoses with reclassified diagnoses based on 2007 National Cancer Institute (NCI)/Bethesda recommendations, and reviewed FNA cytologic features. Original FNA diagnoses included colloid nodule (7%, 3/44), atypical follicular cells (5%, 2/44), follicular lesion (11%, 5/44), follicular neoplasm (16%, 7/44), suspicious for malignancy/PTC (27%, 12/44), and papillary thyroid carcinoma (34%, 15/44). Reclassified diagnoses included indeterminate (5%, 2/44), colloid nodule (7%, 3/44), atypical cells of undetermined significance [ACUS] (7%, 3/44), Hurthle cell neoplasm (2%, 1/44), follicular neoplasm (7%, 3/44), suspicious for malignancy/PTC (25%, 11/44), and PTC (48%, 21/44). Triage efficacy was 77% (34/44) for original diagnoses versus 82% (36/44) for reclassified FNA diagnoses. We frequently observed cytologic features of PTC, such as nuclear grooves and fine chromatin; conversely, intranuclear inclusions, though present in 77% cases, were scant. Our review findings suggest that lack of characteristic cytologic features of PTC,coexistence with other thyroid lesions, and small tumor size arethe major obstacles to FNA diagnosis of FVPTC. Reclassification of thyroid FNA diagnoses does not significantly improve triage efficacy. Furthermore, FNA diagnoses of follicular neoplasm and suspicious for malignancy are valuable in patients with FVPTC because they trigger triage toward surgical intervention., (Copyright © 2011 Wiley Periodicals, Inc.)

Context: Thyroid hormone transport across the plasma membrane depends on transmembrane transport proteins, including monocarboxylate transporter 8 (MCT8). Mutations in MCT8 (or SLC16A2) lead to a severe form of X-linked psychomotor retardation, which is characterised by elevated plasma triiodothyronine (T(3)) and low/normal thyroxine (T(4)). MCT8 contributes to hormone release from the thyroid gland., Objective: To characterise the potential impact of MCT8-deficiency on thyroid morphology in a patient and in Mct8-deficient mice., Design: Thyroid morphology in a patient carrying the A224V mutation was followed by ultrasound imaging for over 10 years. After thyroidectomy, a histopathological analysis was carried out. The findings were compared with histological analyses of mouse thyroids from the Mct8(-/y) model., Results: We show that an inactivating mutation in MCT8 leads to a unique, progressive thyroid follicular pathology in a patient. After thyroidectomy, histological analysis revealed gross morphological changes, including several hyperplastic nodules, microfollicular areas with stromal fibrosis and a small focus of microfollicular structures with nuclear features reminiscent of papillary thyroid carcinoma (PTC). These findings are supported by an Mct8-null mouse model in which we found massive papillary hyperplasia in 6- to 12-month-old mice and nuclear features consistent with PTC in almost 2-year-old animals. After complete thyroidectomy and substitution with levothyroxine (l-T(4)), the preoperative, inadequately low T(4) and free T(4) remained, while increasing the l-T(4) dosage led to T(3) serum concentrations above the normal range., Conclusions: Our results implicate peripheral deiodination in the peculiar hormonal constellation of MCT8-deficient patients. Other MCT8-deficient patients should be closely monitored for potential thyroid abnormalities.

Differentiated thyroid cancer (DTC) is usually indolent with good prognosis and long-term survival. However, DTC distant metastasis is often a grave event and accounts for most of its disease-specific mortality. The major sites of distant metastases are the lung and bone. Metastases to the brain, breast, liver, kidney, muscle, and skin are rare or relatively rare. Nevertheless, recognizing rare metastases from DTC has a significant impact on the clinical decision making and prognosis of patients. (131)I single photon emission computed tomography/computed tomography ((131)I-SPECT/CT) can provide both metabolic and anatomic information about a lesion; therefore, it can better localize and define the (131)I-WBS findings in DTC patients. In this pictorial review, the imaging features of a range of rare metastases from DTC are demonstrated, with a particular emphasis on the (131)I-SPECT/CT diagnostic aspect.

(131)I is given in differentiated thyroid cancer (DTC) without taking into account thyroglobulin (Tg) levels at the time of ablation, whereas 6-18 months later it is a major criterion for cure. This single-center retrospective study assessed the frequency and risk factors for persistent disease on postablation whole body scan (WBS) and postoperative neck ultrasonography (n-US) and for recurrent disease during the subsequent follow-up, in patients with DTC and undetectable TSH-stimulated Tg level (TSH-Tg) in the absence of Tg antibodies (TgAb) at the time of ablation. Among 1031 patients ablated, 242 (23%) consecutive patients were included. Persistent disease occurred in eight cases (3%) (seven abnormal WBS and one abnormal n-US), all with initial neck lymph node metastases (N1). N1 was a major risk factor for persistent disease. Among 203 patients with normal WBS and a follow-up over 6 months, TSH-Tg 6-18 months after ablation was undetectable in the absence of TgAb in 173 patients, undetectable with TgAb in 1 patient and equal to 1.2  ng/ml in 1 patient. n-US was normal in 152 patients and falsely positive in 3 patients. After a mean follow-up of 4 years, recurrence occurred in two cases (1%), both with aggressive histological variants. The only risk factor for recurrence was an aggressive histological variant (P = 0.03). In conclusion, undetectable postoperative TSH-Tg in the absence of TgAb at the time of ablation is frequent. In these patients, repeating TSH-Tg 6-18 months after ablation is not useful. (131)I ablation could be avoided in the absence of N1 and aggressive histological variant.

The risk of malignancy in a "hot" thyroid nodule detected by radioiodine scintigraphy is rare. We report a case of a 63-year-old man with a hyperfunctioning nodule demonstrated by radioiodine scintigraphy and cytology suspicious for follicular variant of papillary thyroid carcinoma (FVPTC). There were no locoregional or distant metastases at initial diagnosis. Histopathologic examination following thyroidectomy confirmed the presence of an encapsulated FVPTC. A year into follow-up, his I-131 whole body scan performed following the withdrawal from exogenous thyroid hormone was negative, whereas his serum thyroglobulin (Tg) levels were intermediate. A subsequent PET/CT scan revealed a small, but stable, metabolically active pretracheal lymph node, which on biopsy was confirmed to be stage III FVPTC. In conclusion, the presence of hyperfunctioning thyroid nodule(s) does not preclude malignancy and, therefore, proper cytohistologic evaluation in such patients may help to exclude a coexistent thyroid carcinoma. Patients treated for localized PTC may benefit from serial PET/CT follow-up in the early detection and management of recurrence or distant metastases.

Background: Our aim in this study was to assess the relevance of (99m)Tc-sestaMIBI (MIBI) scan in the diagnostic evaluation of thyroid nodules with nondiagnostic cytology., Methods: In all, 74 patients with a single nodule and repeatedly nondiagnostic ultrasound-guided fine-needle aspiration cytology (US-FNAC) were enrolled. In all cases thyroid nodules were cold in (99m)Tc-pertechnetate (Tc) scans. Thyroid scans were also acquired 30 and 120 minutes after intravenous administration of MIBI. Nodules that concentrate MIBI were considered as positive (ie, suspicious for malignancy). Histologic findings were obtained after surgery in all patients., Results: No differences occurred in early and late MIBI images. None of 63 patients with a negative MIBI scan had a final histologic diagnosis of malignancy (ie, no false-negative results). Two patients with a final histologic diagnosis of papillary thyroid carcinoma (PTC) and 1 with follicular thyroid carcinoma (FTC) had a positive MIBI scan. Eight patients with a final histologic diagnosis of benign lesions (3 with follicular adenomas) also had MIBI-positive scans. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 100%, 88%, 89%, 27%, and 100%., Conclusions: A negative MIBI scan in a cold nodule accurately excludes malignancy when US-FNAC is reported as nondiagnostic. This avoids the need for more invasive diagnostic procedures (ie, surgery) and positively influences the cost-effectiveness profile. A MIBI scan may be performed by acquiring images 30 minutes after tracer administration alone. Histology is still necessary to distinguish benign from malignant disease in a MIBI-positive nodule but unnecessary surgery could have been reduced from 71 to 8 cases in our series.

Objective: The objective of this study was to determine whether the use of recombinant human TSH (rhTSH) to stimulate radioiodine uptake after thyroidectomy is as efficacious as a period of withholding thyroid hormones, while at the same time avoiding hypothyroidism, reducing sick leave time and shortening the hospital stay., Design: Our aim was to compare the standard procedure of differentiated thyroid cancer treatment, which consists of thyroidectomy followed by 4 weeks of hypothyroidism and a conclusive ablative activity of (131)iodine, with a new shortened treatment in which l-thyroxine (T(4)) medication is initiated a day after thyroidectomy, followed by application of rhTSH stimulation and subsequent ablation a few days after surgery. We presumed our treatment to represent the most sophisticated strategy for the reduction in sick leave days overall without any reduction in safety or the efficacy of ablative therapy., Methods: Patients (n=25) were randomized either for surgery and rhTSH stimulation or surgery and l-T(4) abstinence before the first application of radioiodine. Ablation success was determined by neck ultrasound and serum thyroglobulin during follow-up. RhTSH receivers were monitored for an average of 635 days (s.d.+/-289) and patients in l-T(4) abstinence for an average of 624 days (s.d.+/-205). Both groups were statistically compared for significant differences in treatment efficacy, safety and overall time of sick leave., Results and Conclusions: Our shortened treatment proved to be equally efficacious and safe in comparison with the conventional therapy regimen. At the same time, it showed economic advantages through the reduction in average sick leave time from approximately 29 days (l-T(4) abstinence) down to approximately 6 days (rhTSH stimulation) as well as sustaining the patient's quality of life by the complete avoidance of hypothyroidism.

Introduction: Certain surgeon-performed ultrasound (SUS) features may predict differentiated thyroid cancer (DTC). The purpose of this study was to determine the SUS characteristics that are strongly associated with DTC in patients with solitary thyroid nodules., Methods: A retrospective review of 115 patients with solitary thyroid nodules who had SUS before thyroid surgery was performed. Patients were subdivided into two groups based on final pathology results: patients with DTC(n=61) and those with benign disease (BD) (n=54). SUS characteristics of thyroid nodules were studied, including size, type, calcifications, borders, shape, and echogenicity. For SUS features, odds ratio (OR), confidence interval (CI), and P values are presented., Results: Of 115 operated patients with solitary thyroid nodules, 53% (61/115) had DTC [papillary, 59%; follicular variant/papillary, 34%; Hürthle cell, 5%; and follicular, 2%] and 47% (54/115) had BD [hyperplastic, 56%; follicular adenoma, 31%; lymphocytic thyroiditis, 7%; and Hürthle cell adenoma, 6%]. Univariate analysis showed that hypoechogenicity, irregular borders, and microcalcifications were associated with an increased risk for DTC compared to hyper/isoechogenicity, regular borders, and coarse/no calcifications. Association strength was confirmed using a multivariate model, including the five SUS characteristics. Hypoechogenicity (OR=4.27; 95% CI, 1.74-10.47; P<0.002), irregular borders (OR=3.10; 95% CI, 1.25-7.7; P<0.015), and microcalcifications (OR=2.65; 95%CI, 1.04-6.76; P<0.05) had a greater association with DTC after adjustment for the other four SUS features. Additionally, the combination of hypoechogenicity, irregular borders, and microcalcifications had the strongest association with DTC (OR=30.1; 95% CI, 7.76-119.2; P<0.0001)., Conclusions: Hypoechogenicity, irregular borders, and microcalcifications were most strongly associated with an increased risk for DTC. These SUS characteristics may have additional clinical value in predicting DTC in patients with solitary thyroid nodules.

Patients with poorly differentiated thyroid cancers (PDTC), anaplastic thyroid cancers (ATC), and radioactive iodine-refractory (RAIR) differentiated thyroid cancers have a high mortality, particularly if positive on [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET). To obtain comprehensive genetic information on advanced thyroid cancers, we designed an assay panel for mass spectrometry genotyping encompassing the most significant oncogenes in this disease: 111 mutations in RET, BRAF, NRAS, HRAS, KRAS, PIK3CA, AKT1, and other related genes were surveyed in 31 cell lines, 52 primary tumors (34 PDTC and 18 ATC), and 55 RAIR, FDG-PET-positive recurrences and metastases (nodal and distant) from 42 patients. RAS mutations were more prevalent than BRAF (44 versus 12%; P = 0.002) in primary PDTC, whereas BRAF was more common than RAS (39 versus 13%; P = 0.04) in PET-positive metastatic PDTC. BRAF mutations were highly prevalent in ATC (44%) and in metastatic tumors from RAIR PTC patients (95%). Among patients with multiple metastases, 9 of 10 showed between-sample concordance for BRAF or RAS mutations. By contrast, 5 of 6 patients were discordant for mutations of PIK3CA or AKT1. AKT1&#95;G49A was found in 9 specimens, exclusively in metastases. This is the first documentation of AKT1 mutation in thyroid cancer. Thus, RAIR, FDG-PET-positive metastases are enriched for BRAF mutations. If BRAF is mutated in the primary, it is likely that the metastases will harbor the defect. By contrast, absence of PIK3CA/AKT1 mutations in one specimen may not reflect the status at other sites because these mutations arise during progression, an important consideration for therapies directed at phosphoinositide 3-kinase effectors.

Context: There is a high prevalence of thyroid nodules on ultrasonographic (US) examination. However, most of them are benign. US criteria may help to decide cost-effective management., Objective: Our objective was to develop a standardized US characterization and reporting data system of thyroid lesions for clinical management: the Thyroid Imaging Reporting and Data System (TIRADS)., Design: This was a prospective study using the TIRADS, which is based on the concepts of the Breast Imaging Reporting Data System of the American College of Radiology., Materials: A correlation of the US findings and fine needle aspiration biopsy (FNAB) results in 1959 lesions biopsied under US guidance and studied histologically during an 8-yr period was divided into three stages. In the first stage, 10 US patterns were defined. In the second stage, four TIRADS groups were defined according to risk. The percentages of malignancy defined in the Breast Imaging Reporting and Data System were followed: TIRADS 2 (0% malignancy), TIRADS 3 (<5% malignancy), TIRADS 4 (5-80% malignancy), and TIRADS 5 (>80% malignancy)., Results: The TIRADS classification was evaluated at the third stage of the study in a sample of 1097 nodules (benign: 703; follicular lesions: 238; and carcinoma: 156). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 88, 49, 49, 88, and 94%, respectively. The ratio of benign to malignant or follicular FNAB results currently is 1.8., Conclusions: The TIRADS has allowed us to improve patient management and cost-effectiveness, avoiding unnecessary FNAB. In addition, we have established standard codes to be used both for radiologists and endocrinologists.

Objective: To evaluate the effectiveness of gamma probe performed with technetium Tc 99m-labeled pertechnetate in patients who underwent completion thyroidectomy after pathologic detection of incidental thyroid cancer following subtotal thyroidectomy., Methods: In this prospective study, we evaluated findings from patients with multinodular goiter who underwent gamma probe-guided lateral approach completion thyroidectomy after the pathologic detection of incidental thyroid cancer following subtotal thyroidectomy where partial thyroid tissue was left unilaterally or bilaterally. Patients who underwent the procedure between January 2003 and January 2007 were included. Thyroid scintigraphy; thyroid and neck ultrasonography examinations; and concentrations of thyroid hormones, thyrotropin (TSH), thyroglobulin, and thyroglobulin antibodies were evaluated before the second operation. Patients were administered 3 mCi technetium Tc 99m pertechnetate during anaesthetic induction, and we extracted suspicious thyroid tissue and tissue with activity above background activity levels according to gamma probe. Extracted tissues were evaluated pathologically., Results: Completion thyroidectomy was performed in 23 patients. Seventy-nine tissue samples were extracted; 49 were thyroid tissue and 30 were nonthyroid tissue. Mean thyroid tissue to background activity ratio (T:B) was 6.4 +/- 3.9 (range, 2-14.3), and mean thyroid bed (after excision) to background activity ratio (Tbed:B) was 1.2 +/- 0.2 (range, 0.8-1.7) (P = .001). Mean T:B and Tbed:B ratios of the nonthyroid tissue were 1.2 +/- 0.3 (range, 0.2-1.7) and 1.1 +/- 0.2 (range, 0.4-1.4), respectively (P = .001). The thyroid tissue T:B ratio was significantly higher than that of non-thyroid tissue (P<.001). Gamma probe labeling contributed to extraction of small amounts of thyroid tissue that could not be viewed by scintigraphy in 43% of patients., Conclusions: Using gamma labeling, thyroid tissue shows significantly more activity than nonthyroid tissue. Gamma probe helps detect small, residual thyroid tissue that is buried in the scar tissue that cannot be distinguished by scintigraphy; therefore, it assists in the extraction of the maximum amount of thyroid tissue.

Background: Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid neoplasia that have lost radioiodine (131I) uptake with heterogeneous results., Aim: Retrospective analysis of the recovery rate of 131I uptake after RA treatment in patients from 11 Spanish hospitals., Methods: Twenty-seven patients (14 men, 13 women) with papillary [21], follicular [4], and oncocytic [2] thyroid cancer initially treated with total thyroidectomy plus 131I, and with 131I negative metastatic disease, were given 13-cis RA (0.66-1.5 mg/kg for 5-12 weeks) followed by a therapeutic 131I dose (3700-7400 MBq); 3 months later thyroglobulin levels and computed tomography imaging were performed., Results: In 9 out 27 cases (33%) (8 papillary, 1 follicular) optimal positive 131I scan was observed after RA treatment; in the remaining 18, 10 had a suboptimal uptake (7 papillary, 2 follicular, 1 oncocytic) and in the rest there was no 131I uptake recovery (6 papillary, 1 follicular, 1 oncocytic). In 17 positive responses to RA (either optimal or suboptimal) in which image follow-up was available, decrease or stabilization of metastatic growth was observed in 7, while tumor mass increased at short term in the remaining 10. No major side effects were detected., Conclusion: Quite a high rate of 131I uptake recovery after RA treatment may be obtained in advanced differentiated thyroid cancer, but the potential modification of the natural course of the disease is uncertain. A better biological characterization of these tumors allowing the identification of potential responders to RA may improve the outcome of RA coadjuvant therapy.

Unlabelled: Thyroglobulin (Tg) is a specific marker of residual thyroid cancer or tumor recurrence. In patients with elevated Tg levels and negative diagnostic radioiodine (131I) whole-body scans (dWBS), administration of a therapy dose may reveal foci that were not initially apparent. The aim of this study was to identify factors, other than 131I activity, which might explain why a post-therapy 131I whole-body scan is sometimes positive despite a negative dWBS., Patients and Methods: We reviewed data on all patients with elevated Tg levels and negative dWBS with 185 MBq 131I off-T4 at followup, who subsequently received an empiric therapy dose of 3700 MBq of 131I. During a 5-yr period, 22 patients met these criteria. 131I therapy could be given immediately after negative dWBS in 9 patients, with an average of 8 extra days of hypothyroidism. In the other 13 patients, therapy was given an average of 8 months later., Results: The therapy scan was negative in 16 patients, while it showed uptake in the thyroid bed in 5 patients and distant metastases in two. In the latter two patients, the TSH level was suboptimal at the time of dWBS (9 and 25 microIU/ml), and had risen to 34 and 70 microIU/ml respectively at the time of therapy. Overall, a positive scan following therapy occurred in 7 patients (6/9 patients treated immediately and 1/13 patients treated in a separate setting; p<0.01). In patients with positive therapy scans, the mean TSH level was 73 microIU/ml at the time of dWBS and 103.5 microIU/ml at the time of therapy (41% increase; p<0.05). In patients with negative therapy scans the mean TSH level was 84 microIU/ml at dWBS and 86 microIU/ml at the time of the therapy scan (2% increase)., Conclusions: Our study suggests that interval increase in TSH level with a longer period of stimulation may have contributed to making the whole-body scan positive at the time of therapy. Nowadays, patients with elevated Tg are directly given a therapy dose of 131I. Special care should be taken when preparing patients who have been on suppressive levothyroxine therapy for a long time, in order to avoid misclassifying the tumor as non-functioning.

In this study, the characteristic sonographic textural feature that represents the major histopathologic components of the thyroid nodules was objectively quantified to facilitate clinical diagnosis and management. A total of 157 regions-of-interest thyroid ultrasound image was recruited in the study. The sonographic system used was the GE LOGIQ 700), (General Electric Healthcare, Chalfant St. Giles, UK). The parameters affecting image acquisition were kept in the same condition for all lesions. Commonly used texture analysis methods were applied to characterize thyroid ultrasound images. Image features were classified according to the corresponding pathologic findings. To estimate their relevance and performance to classification, ReliefF was used as a feature selector. Among the various textural features, the sum average value derived from co-occurrence matrix can well reflect echogenicity and can effectively differentiate between follicles and fibrosis base thyroid nodules. Fibrosis shows lowest echogenicity and lowest difference sum average value. Enlarged follicles show highest echogenicity and difference sum average values. Papillary cancer or follicular tumors show the difference sum average values and echogenicity between. The rule of thumb for the echogenicity is that the more follicles are mixed in, the higher the echo of the follicular tumor and papillary cancer will be and vice versa for fibrosis mixed. Areas with intermediate and lower echo should address the possibility of follicular or papillary neoplasm mixed with either follicles or fibrosis. These areas provide more cellular information for ultrasound guided aspiration

Context: Childhood cancer survivors need regular monitoring into young adulthood and beyond, because they are at risk for developing late-onset complications of cancer therapy, including second malignancies., Objective: This study focuses on the use of thyroid ultrasound to screen for thyroid carcinoma in a population of childhood cancer survivors., Patients: A total of 129 subjects who had received radiotherapy to the head, neck, or upper thorax for a pediatric cancer were studied in the setting of a long-term follow-up unit., Design: Thyroid ultrasound usually began 5 yr after radiotherapy and was repeated every third year, if negative. Median follow-up time since childhood cancer diagnosis was 15.8 yr (range 6.1-34.8 yr). Solid thyroid nodules were found in 35 patients. Fine-needle aspiration was performed in 19 patients, of which 14 had nodules above 1 cm., Main Outcome Measure: The main outcome measure was the finding of not palpable thyroid cancers., Results: Cytological examination of specimens diagnosed papillary carcinoma in five patients who underwent surgery. The cytological diagnosis of papillary thyroid carcinoma was confirmed in all cases by histological examination. Notably, only two of these patients had palpable nodules; the other three were smaller than 1 cm and were detected only by ultrasound. However, histological examination showed nodal metastases in two of these., Conclusions: Although ultrasound screening for thyroid cancer in the general population is not cost effective and could lead to unnecessary surgery, due to false positives, we believe that in childhood cancer survivors who received radiotherapy involving the head, neck, or upper thorax, it would be worthwhile.

For more than a decade, positron emission tomography (PET) has had an important role in the management of thyroid cancer patients. It may be involved in initial, sometimes inadvertent, diagnosis; in postoperative evaluation; in detection of occult metastases; in the evaluation of thyroid nodules; and in prognostication of metastatic disease. In this review we will update the advances in the application of PET scanning to optimal patient management. The majority of the published studies to date have used 18F-fluoro-deoxyglucose (FDG) as the PET isotope, and unless specifically noted, all references to PET scanning will imply that this tracer has been used.

A 60-year-old woman consulted a medical specialist for numbness of the chin. A bilateral mental nerve affection was found. A PET-scan with fluodeoxyglucose revealed a localised process in the right thyroid gland. She was operated for a localised thyroid cancer. At follow-up, 6 years later, she was in good health without any symptoms apart from numbness of the chin.

Background: Certain ultrasound features can predict malignancy in patients with thyroid nodules. The purpose of this study was to determine the value of surgeon-performed ultrasound (SUS) in predicting thyroid malignancy in patients with indeterminate fine-needle aspiration (FNA) cytology., Methods: 477 consecutive patients with dominant thyroid nodules were referred to our institution from 2002 to 2007. Of these, 180/477(38%) were judged to have indeterminate cytology: follicular neoplasm (FN, n = 108), Hürthle neoplasm (HN, n = 29), and suspicious for papillary thyroid cancer (SPTC, n = 43). SUS characteristics for thyroid nodules were recorded in a prospective database prior to thyroidectomy. Variables analyzed included patients' age and sex, nodule size, shape, echogenicity, consistency, borders, multiplicity/multicentricity, and presence of microcalcifications. SUS features of thyroid nodules were correlated with final pathology. The accuracy of individual SUS features as well as the presence of two or more adverse features in predicting malignancy was also examined., Results: There were 144 females and 36 males. Mean age was 52 years (range 17-87 years). Mean tumor size was 2.7 cm (range 0.65-6.6 cm). Overall, final pathology revealed cancer in 92/180 (51%) patients. Malignancy was present in 40/108 (37%) FN, 12/29 (41%) HN, and 40/43 (93%) SPTC. Nodule borders (irregular), shape (height > width), hypoechogenicity, and presence of microcalcifications were significantly associated with malignancy. The presence of 2 or >/=3 adverse SUS thyroid nodule features was associated with a >/=55% or >/=78% risk of malignancy, respectively., Conclusion: Adverse thyroid nodule features seen on SUS may predict malignancy and help determine the initial extent of thyroidectomy in patients with indeterminate FNA cytology.