Analysis of Malignant Thyroid Nodules That Do Not Meet ACR TI-RADS Criteria for Fine-Needle Aspiration.

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.

Characterization of pathological thyroid tissue using polarization-sensitive second harmonic generation microscopy.

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.

Ultrasonographic Characteristics of the Follicular Variant Papillary Thyroid Cancer According to the Tumor Size.

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.

Association between neck ultrasonographic findings and clinico-pathological features in the follicular variant of papillary thyroid carcinoma.

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.

BRAF mutation in follicular variant of papillary thyroid carcinoma is associated with unfavourable clinicopathological characteristics and malignant features on ultrasonography.

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.

Salivary glands ultrasound examination after radioiodine-131 treatment for differentiated thyroid cancer.

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.

Encapsulated follicular variant of papillary thyroid carcinoma: fine-needle aspiration with ultrasound and histologic correlation of 41 cases.

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.

Peroperative detection with a gamma probe of pelvic metastasis after differentiated thyroid carcinoma in female patients: about two cases and management reflections.

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.

AIBx, Artificial Intelligence Model to Risk Stratify Thyroid Nodules.

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.

Surgeon-performed ultrasound can predict differentiated thyroid cancer in patients with solitary thyroid nodules.

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.

Thyrotropin variations may explain some positive radioiodine therapy scans in patients with negative diagnostic scans.

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.

Effectiveness of retinoic acid treatment for redifferentiation of thyroid cancer in relation to recovery of radioiodine uptake.

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.

Comprehensive analysis for diagnosis of preoperative non-invasive follicular thyroid neoplasm with papillary-like nuclear features.

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.

Diagnostic performance of thyroid ultrasound in Hürthle cell carcinomas.

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.

Limited value of repeat recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin testing in differentiated thyroid carcinoma patients with previous negative rhTSH-stimulated thyroglobulin and undetectable basal serum thyroglobulin levels.

CONTEXT: One year after initial treatment, low-risk differentiated thyroid cancer (DTC) patients undergo recombinant human (rh)TSH-stimulated serum thyroglobulin (Tg) (rhTSH-Tg) and neck ultrasound (US). OBJECTIVE: The need for more rhTSH-Tg in these patients is controversial. We evaluated the utility of a second rhTSH-Tg in DTC patients 2-3 yr after their first evaluation. RESULTS: At the first rhTSH-Tg, basal and stimulated serum Tg was undetectable in 68 of 85 patients. Neck US was unremarkable in all but one, who had evidence of lymph node disease. Seventeen of 85 patients had undetectable serum Tg that became positive after rhTSH, with negative imaging in 10 and evidence of disease in seven. Patients with no evidence of disease were reevaluated 2-3 yr later (second rhTSH-Tg). In patients in which the first stimulated Tg was undetectable, all had undetectable basal serum Tg, which remained undetectable after rhTSH in 66 of 67 patients (98.5%) and became detectable in one (1.5%) (positive neck US). In the 10 patients with detectable stimulated Tg in the first test, basal serum Tg and US were negative at the second test, but rhTSH-Tg became detectable in six. Compared with the first rhTSH-Tg, the second stimulated Tg in these six patients decreased in one, increased in three, and stabilized in two patients. CONCLUSIONS: The second rhTSH-Tg was informative in patients who had first stimulated Tg detectable but not in those who had undetectable Tg at the first test, in which the only patient with recurrence was diagnosed by neck US. Thus, rhTSH-Tg should be repeated only in patients who have had a positive first rhTSH-Tg and negative imaging.

Ultrasound screening for thyroid carcinoma in childhood cancer survivors: a case series.

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.

Role of surgeon-performed ultrasound in predicting malignancy in patients with indeterminate thyroid nodules.

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.

Does noninvasive follicular thyroid neoplasm with papillary-like nuclear features have distinctive features on sonography?

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.