Fine Needle Aspiration and Medullary Thyroid Carcinoma: The Risk of Inadequate Preoperative Evaluation and Initial Surgery when Relying upon Fnab Cytology Alone

ObjectivesTo evaluate the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) to preoperatively diagnose medullary thyroid cancer (MTC) among multiple international centers and evaluate how the cytological diagnosis alone could impact patient management.MethodsWe performed a retrospective chart review of sporadic MTC (sMTC) patients from 12 institutions over the last 29 years. FNAB cytology results were compared to final pathologic diagnoses to calculate FNAB sensitivity. To evaluate the impact of cytology sensitivity for MTC according to current practice and to avoid confounding results by local treatment protocols, changes in treatment patterns over time, and the influence of ancillary findings (e.g., serum calcitonin), therapeutic interventions based on FNAB cytology alone were projected into 1 of 4 treatment categories: total thyroidectomy (TT) and central neck dissection (CND), TT without CND, diagnostic hemithyroidectomy, or observation.ResultsA total of 313 patients from 4 continents and 7 countries were included, 245 of whom underwent FNAB. FNAB cytology revealed MTC in 43.7% and possible MTC in an additional 2.4%. A total of 113 (46.1%) patients with surgical pathology revealing sMTC had FNAB findings that supported TT with CND, while 37 (15.1%) supported TT alone. In the remaining cases, diagnostic hemithyroidectomy and observation were projected in 32.7% and 6.1%, respectively.ConclusionFNAB is an important diagnostic tool in the evaluation of thyroid nodules, but the low sensitivity of cytological evaluation alone in sMTC limits its ability to command an optimal preoperative evaluation and initial surgery in over half of affected patients. (Endocr Pract. 2013;19:920-927)     

Predictive Value of Calcium Test for Preoperative Diagnosis of Medullary Thyroid Carcinoma in Patients With Moderately Elevated Basal Calcitonin

ObjectiveMedullary thyroid carcinoma (MTC) can be very aggressive, and early diagnosis is based on routine measurement of serum calcitonin (CT) and RET genetic testing for hereditary forms. Basal serum CT (bCT) concentrations are useful in the early detection of MTC, although it is still unclear whether they can also be used for the differential diagnosis between MTC and C-cell hyperplasia (CCH). Since false-positive results can be obtained with the basal measurement of CT, a provocative test to evaluate stimulated CT (sCT) is often needed. The objective of this study was to investigate the utility of a calcium gluconate test for CT in distinguishing MTC from CCH, a precancerous condition in hereditary forms of MTCs but with unclear significance in sporadic MTCs.MethodsA total of 74 patients underwent the calcium loading test before thyroidectomy, and bCT and sCT levels were compared with histologic results by receiver operating characteristic plot analyses.ResultsA peak CT level of 388.4 pg/mL after stimulation with calcium gluconate was able to significantly distinguish patients with MTC from those with CCH and those without C-cell pathology, with 81.8% sensitivity and 36.5% specificity. A bCT level of 16.1 pg/mL was able to distinguish between these 2 groups of patients with a sensitivity of 90%.ConclusionHigh-dose calcium test is an effective procedure that can be applied for differential diagnosis of MTC and CCH. Reference ranges for calcium sCT levels and CT thresholds in different groups of patients have been identified.     

ProGRP as a Novel Biomarker for the Differential Diagnosis of Medullary Thyroid Carcinoma in Patients with Thyroid Nodules

Objective: To investigate the release of progastrin-releasing peptide (ProGRP) in patients with thyroid nodules and the value of ProGRP in fine-needle aspirate washout fluid (FNA-ProGRP) in the differential diagnosis between medullary thyroid carcinoma (MTC) and non-MTC thyroid nodules.Methods: We investigated 2,446 healthy persons and 212 patients with 235 thyroid nodules. They were classified into healthy, nodular goiter, chronic thyroiditis, thyroid follicular neoplasm, papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma. The serum ProGRP and FNA-ProGRP were measured.Results: The serum ProGRP median concentration in MTC was 124.40 pg/mL, significantly higher than in other groups. The cutoff value of serum ProGRP was 68.30 pg/mL, leading to 53.85% sensitivity, 96.98% specificity, and 0.51 kappa value in MTC. The FNA-ProGRP median concentration in MTC nodules was 2,096.00 pg/mL, significantly higher than in other groups. A receiver operating characteristic analysis of MTC nodules and non-MTC nodules indicated that the cutoff value was 22.77 pg/mL, leading to 94.12% sensitivity, 98.27% specificity, and 0.85 kappa value.Conclusion: FNA-ProGRP measurement could be served as an ancillary method for the differential diagnosis between MTC and non-MTC thyroid nodules.Abbreviations: CEA = carcinoembryonic antigen; CT = calcitonin; FNAC = fine-needle aspiration cytology; FNA-CT = calcitonin in fine-needle aspirate washout fluid; FNA-ProGRP = ProGRP in fine-needle aspirate washout fluid; MTC = medullary thyroid carcinoma; ProGRP = progastrin-releasing peptide; SCLC = small-cell lung cancer; TM = tumor marker     

Autoimmune Thyroid Disease: A Risk Factor for Thyroid Cancer

ObjectiveTo examine the relationship between clinical markers of autoimmune thyroid disease and the risk of thyroid cancer in patients with thyroid nodules.MethodsA retrospective cohort analysis was performed in a single clinical practice. In 2, 500 consecutive patients, fine-needle aspiration biopsy (FNAB) was performed on all 3, 658 ultrasonography-positive thyroid nodules that were ≥ 1.0 cm in diameter or ≥ 0.5 cm in diameter with ultrasound features suspicious for thyroid cancer. Serum concentrations of thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies, and thyroid-stimulating hormone were measured before FNAB. Diagnosis of thyroid cancer was based on pathologic analysis of thyroidectomy tissue. Associations of thyroid cancer with the independent variables were determined by multivariate logistic regression analysis and reported as the adjusted odds ratio (OR) with the 95% confidence interval (CI).ResultsThere were 202 patients with malignant thyroid nodules, 51 patients with microscopic unsuspected thyroid cancer distal to the nodule under investigation (found at thyroidectomy), and 2, 247 patients with benign thyroid nodules. To evaluate the association of clinical markers for autoimmune thyroid disease with thyroid cancer, we included all 253 patients with thyroid cancer in the malignant cohort. Thyroid cancer was associated with elevated levels of TgAb (OR = 1.57; CI = 1.11 to 2.23) and age < 55 years (OR = 2.01; CI = 1.45 to 2.78), and a strong trend was demonstrated for association with male sex (OR = 1.45; CI = 0.99 to 2.12). Thyroid cancer was not associated with elevated levels of thyroid peroxidase antibodies.ConclusionIn patients who have thyroid nodules with indications for FNAB, elevated levels of TgAb are associated with thyroid cancer. (Endocr Pract. 2011;17: 201-209)     

The Risk of Thyroid Cancer in Patients with Thyroid Nodule 3 Cm Or Larger

Objective: There are conflicting data on the risk of thyroid cancer in thyroid nodules 3 cm or larger, and few such studies on this issue have been conducted in Asia. This study aimed to examine the risk of thyroid cancer in patients with thyroid nodules 3 cm or larger.Methods: This was a 7-year retrospective study conducted in a tertiary referral hospital in Taiwan. All patients with a thyroid nodule measuring ≥3 cm who underwent thyroid operation with or without fine-needle aspiration biopsy (FNAB) were included. The prevalence rate of thyroid cancer, as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false-negative rate of FNAB for thyroid nodule ≥3 cm were also examined.Results: A total of 132 patients were included in this study. Thyroid cancer was detected in 19 of 132 (14.4%) thyroid nodules measuring ≥3 cm. The performance of FNAB for detecting cancer in nodules 3 cm or larger without considering other ultrasonography parameters was relatively poor with a sensitivity of 50%, but the specificity (100%), PPV (100 %), and NPV (93.4 %) were excellent.Conclusion: The risk of thyroid cancer for thyroid nodules ≥3 cm in this study was low. The PPV and NPV of FNAB were high for the detection of cancer in large nodules. The decision to perform thyroidectomy should not be solely based on nodule size and should include other factors, such as ultrasound characteristics and surgical risk.     

Rendimiento diagnóstico de los hallazgos ecográficos de los nódulos tiroideos en la detección de lesiones malignas

ObjetiveTo evaluate the diagnostic efficiency of sonographic findings (nodule size, the presence of microcalcifications and echogenicity) compared with the results of fine-needle aspiration biopsy (FNAB) of thyroid nodules.MethodsThe results of cytology and the ultrasound characteristics of 341 thyroid nodules were analyzed.ResultsA total of 25.5% of the FNAB were inadequate, 65.1% were benign and 7.9% were suspicious or malignant. The percentage of inadequate samples was clearly larger in nodules smaller that 15 mm but that of malignant cytologies was also larger in this group of nodules (11.1 versus 2.8%: p=0.04). The percentage of inadequate samples among nodules smaller than 10 mm was 66.7% and no malignancies were detected. A notable finding was the absence of suspicious or malignant FNAB in hyperechogenic and anechogenic nodules. In contrast, the echogenic feature most frequently associated with malignancy was hypoechogenicity, although echogenicity, as a whole, was not significantly associated with malignancy (p=0.313). Most cases with microcalcifications (6 of 10) were malignant compared with four of the 239 nodules (1.7%) without calcifications (p<0.001). Multivariate logistic regression revealed that the only variable maintaining a significant association with malignancy was the presence of microcalcifications.ConclusionsThyroid cytology is an efficient method to evaluate thyroid nodules larger than 10 mm. The presence of nodule microcalcifications is significantly associated with malignancy, while hyperechogenicity and anechogenicity are associated with benign nodules.     

Preoperative and Postoperative Evaluation of Thyroid Disease in Patients Undergoing Surgical Treatment of Primary Hyperparathyroidism

ObjectiveTo evaluate the occurrence of thyroid disease in patients undergoing parathyroidectomy for primary hyperparathyroidism.MethodsIn this case series, records of all patients with a diagnosis of primary hyperparathyroidism who underwent parathyroidectomy between January 2005 and December 2008 in our clinic were analyzed retrospectively. Preoperatively, all patients were evaluated with ultrasonography and parathyroid scintigraphy; when needed, thyroid scintigraphy and ultrasound-guided fine-needle aspiration biopsy (FNAB) were used. All patients underwent standard neck exploration. Postoperative histopathologic findings of thyroid tissue were classified as nodular/ multinodular hyperplasia, Hashimoto thyroiditis, papillary thyroid carcinoma, or normal.ResultsFifty-one women and 9 men were included. In the 60 patients, preoperative ultrasonography revealed thyroiditis (without nodules) in 13 (22%), a solitary nodule in 9 (15%) (coexistent with thyroiditis in 7 patients), multinodular goiter in 24 (40%) (coexistent with thyroiditis in 5 patients), and normal findings in 14 (23%). Rates of thyroiditis and nodular goiter were 42% and 55%, respectively. Collectively, prevalence of thyroid disease was 77%. Total thyroidectomy was performed in 27 patients, and hemithyroidectomy was performed in 15 patients. Indications for total thyroidectomy were nondiagnostic or suspicious FNAB results in 5 patients, hyperthyroidism in 4 patients, ultrasonography findings in 11 patients, and intraoperatively recognized suspicious nodularity in 7 patients. Postoperatively, thyroid carcinoma was diagnosed in 9 patients (15%).ConclusionsThyroid disease, particularly thyroid carcinoma, is common in patients with primary hyperparathyroidism. This association should be considered when selecting the surgical procedure. Intraoperative evaluation of the thyroid is as important as preoperative evaluation with ultrasonography and FNAB in patients with thyroid disease and primary hyperparathyroidism. (Endocr Pract. 2010;16:7-13)     

Comparison of Ultrasound-Guided Fine-Needle Aspiration Biopsy with Core-Needle Biopsy in the Evaluation of Thyroid Nodules

ObjectiveTo compare the diagnostic rate of ultrasound-guided fine-needle aspiration biopsy (FNAB) with the diagnostic rate of combined FNAB and core-needle biopsy in the evaluation of nodular thyroid disease.MethodsWe performed a retrospective case-control study by reviewing charts of patients who underwent ultrasound-guided FNAB and core-needle biopsy of the thyroid at a tertiary referral center from January 1999 to December 2001. Results were classified as diagnostic (negative, suspicious, or positive for malignancy) or nondiagnostic. These findings were compared with an age- and sex-matched control group who underwent only FNAB. Complications between the groups were reviewed.ResultsThe patient group consisted of 320 patients who underwent 340 ultrasound-guided fine-needle aspiration and core-needle biopsies of the thyroid; the control group consisted of 311 patients who underwent 340 FNABs. There was no significant difference in the nondiagnostic rates between groups—12.9% in patients who had FNAB–only compared with 10.9% in patients who had both procedures (proportion difference, -2.1%; 95% confidence interval, -7.0% to 2.9%; P = .41). There was a trend towards an increased incidence of hematoma and infection in the core biopsy group. In the group that underwent FNAB and core-needle biopsies, 10 patients (3.1%) developed biopsy-specific complications (hematomas in 8 patients, biopsy site infections in 2 patients). In the FNAB only group, 3 patients (1.0%) developed hematomas; there was no incidence of infection.ConclusionsIn the evaluation of thyroid nodules, the addition of core-needle biopsies to FNAB confers little benefit in decreasing the nondiagnostic rates and may be associated with increased complications. Core-needle biopsies should not be routinely performed in the evaluation of thyroid nodules, but rather, patient selection for the more invasive core biopsy should be done judiciously. (Endocr Pract. 2008;14:426-431)     

Overview of Molecular Biomarkers for Enhancing the Management of Cytologically Indeterminate Thyroid Nodules and Thyroid Cancer

ObjectiveTo provide information on molecular bio markers that can help assess cytologically indeterminate thyroid nodules.MethodsPublished studies on immunohistologic, somatic mutation, gene expression classifier, microRNA, and thyrotropin receptor messenger RNA biomarkers are reviewed, and commercially available molecular test pan els are described.ResultsThyroid nodules are common, and clinical guidelines delineate an algorithmic approach including serum thyroid-stimulating hormone measurement, diagnostic ultrasound examination, and, when appropriate, fine-needle aspiration (FNA) biopsy for determination of a benign versus malignant status. In clinical practice, approximately 20% of FNA-derived cytology reports are classified as “indeterminate” or follicular nodules that do not fulfill either benign or malignant criteria. In this set ting, the actual risk for malignancy of a cytologically indeterminate nodule ranges from approximately 15% to 34%. Research describing molecular biomarkers from thyroid cancer tissue has been applied to FNA-derived thyroid nodule material. There is also a serum molecular marker that has been reported with goals similar to those for the FNA-derived molecular markers: to enhance the preoperative diagnosis of thyroid cancer and reduce the large number of patients who have a diagnostic surgical procedure for benign thyroid nodules.ConclusionProgress toward the foregoing goals has been made and continues to evolve with the recent appearance of molecular biomarker tests that can be selectively applied for further assessment of cytologically indeterminate thyroid nodules. (Endocr Pract. 2012;18:611-615)     

Predicting Malignant Involvement in a Thyroid Nodule: Role of Ultrasonography

ObjectiveTo assess how ultrasonography can contribute during the evaluation of a thyroid nodule and whether this technique can have a role in predicting malignant involvement.MethodsIn this retrospective study, data were analyzed on 220 consecutive patients (with 348 thyroid nodules) who underwent thyroidectomy and had previously undergone assessment by high-resolution thyroid ultrasonography. Nodule size, echogenicity, regularity of margins, halo sign, presence or absence of calcifications, and invasion of surrounding tissues were evaluated. The nodules were classified as low, medium, or high risk for malignant involvement on the basis of nodule characteristics found on ultrasonography. All nodules were submitted to cytologic examination by fine-needle aspiration (FNA) before thyroidectomy. Ultrasound, FNA, and pathologic postoperative results were compared.ResultsAmong the 348 thyroid nodules, 56 were ultrasonographically classified as low risk, 268 as medium risk, and 24 as high risk for malignant potential. Fifty of 56 (89.3%) low-risk nodules and 213 of 268 (79.5%) medium-risk nodules were diagnosed as benign at pathologic postoperative examination. In contrast, however, only 6 of 24 (25%) high-risk nodules were diagnosed as benign. Among the 18 high-risk nodules of 1-cm diameter or larger, FNA showed a 20% false-negative result.ConclusionHigh-risk classification of a thyroid nodule on ultrasonography had a positive predictive value for malignant involvement of 75%. Nodule characteristics analyzed by ultrasonography should be considered at the time of surgical intervention. (Endocr Pract. 2007;13: 219-224)     

Unusual Case of Multiple Endocrine Neoplasia Type 2A Syndrome Without Medullary Thyroid Carcinoma

ObjectiveTo present an unusual case of multiple endocrine neoplasia type 2A (MEN 2A) syndrome and to describe how this case differs from the typical clinical features and usual genetic variations seen in classic MEN 2A syndrome.MethodsWe describe the work-up, diagnosis, and treatment course of a patient who presented with multifocal pheochromocytomas, parathyroid adenoma, thyroid abnormalities, and a RET mutation.ResultsA 65-year-old man with previously treated pheochromocytoma presented with a parathyroid adenoma, multiple thyroid nodules, and a RET polymorphism. C-cell hyperplasia (CCH) or medullary thyroid carcinoma (MTC) occurs with nearly 100% penetrance in patients with MEN 2A syndrome. Our patient did not have CCH or frank MTC, but he expressed the other manifestations of the MEN 2A syndrome.ConclusionMEN 2A syndrome is characterized by the occurrence of MTC, pheochromocytomas, and parathyroid hyperplasia or adenomas. It is inherited in an autosomal dominant fashion, and more than 80% of patients with MEN 2A have a specific substitution on codon 634 of the RET proto-oncogene. Despite the nearly 100% penetrance of MTC or CCH in patients with MEN 2A, our patient did not have this. Additionally, he exhibited a RET mutation that is uncommonly seen in classic MEN 2A syndrome. Our patient may have a MEN 2A variant or a pseudo-MEN 2A syndrome. (Endocr Pract. 2011;17:e4-e7)     

Assay of Free Thyroxine and Free Triiodothyronine in Fine-Needle Aspiration of Thyroid Nodules: a Useful and Low-Cost Assessment

ObjectiveTo evaluate whether analysis of thyroid hormones in fine-needle aspiration (FNA) of thyroid nodules can provide information about the functional status and the nature of the nodules.MethodsWe studied 4 groups of patients: group 1, 17 patients with autonomous hyperfunctioning thyroid nodules; group 2, 52 patients with cold nonfunctioning thyroid nodules; group 3, 12 patients with malignant thyroid nodules; and group 4 (control group), 10 patients with nonthyroid nodular lesions (enlarged parathyroid glands or lymph nodes). The assay of thyroid hormones was performed in FNA after the washing of needles and, with patient consent, also in normal thyroid parenchyma.ResultsThe free thyroxine (FT₄) and free triiodothyronine (FT₃) values were remarkably high in group 1 (mean, 5.5 ± 0.53 ng/dL and 27.6 ± 3.1 pg/mL, respectively; P < 0.05 versus group 2 and group 4, the control group). The levels of FT₄ and FT₃ were very low in group 3 (< 0.2 ng/dL and < 1.0 pg/mL, respectively; P < 0.05 versus group 2). Thyroglobulin values in FNA specimens were much higher than the normal range in human serum, but no significant differences were found between the various groups. The control group had low levels of FT₄ and FT₃ (< 0.2 ng/dL and < 1.0 pg/mL, respectively) in conjunction with low levels of thyroglobulin, whereas parathyroid hormone levels were high in parathyroid nodules.ConclusionThese results show that assay of FT₄ and FT₃ in FNA can yield information about the functional status of thyroid nodules and, indirectly, about the nature of nodules. In this era of sophisticated new molecular markers in FNA cytology, this low-cost diagnostic method can be readily performed in every laboratory. (Endocr Pract. 2004;10:311-316)     

A Retrospective Study of Clinicopathologic Outcomes of Nodules With Hürthle Cell Cytology and the Thyroid Nodule App (TNAPP) Ultrasound Recommendations

ObjectivesHürthle cells are a common finding on thyroid fine-needle aspiration, but when they are the predominant cytology, they represent a difficult diagnostic challenge. The Thyroid Nodule App (TNAPP) is a new, publicly available web application utilizing ultrasound (US) features based on the updated 2016 American Association of Clinical Endocrinologists clinical practice guidelines for thyroid nodule management. This pilot study was performed to assess the TNAPP recommendations and surgical pathology outcomes of Hürthle cell-predominant thyroid nodules.MethodsA retrospective review of nodules with Bethesda III (atypia of undetermined significance with Hürthle cells) or Bethesda IV (suspicious for Hürthle cell neoplasm) cytology, for which surgery was performed between 2017 and 2021, was conducted. TNAPP US categories 1, 2, and 3 (low, intermediate, and high risk, respectively) were assigned based on nodule characteristics, and clinical management recommendations were recorded. Results were compared with histology-proven diagnoses.ResultsFifty-nine nodules in 57 patients where surgical pathology was available were analyzed with the TNAPP algorithm. Of the 59 nodules, 4 were US category 1 (low risk/suspicion), 40 were US category 2 (intermediate risk/suspicion), and 15 were US category 3 (high risk/suspicion). All US category 1 nodules were benign, while 30% of the US category 2 and 40% of the US category 3 nodules were malignant. Of the patients who had molecular marker testing with ThyroSeq, 22 out of 29 (76%) were positive, indicating either an intermediate or high risk of malignancy, 7 of which were malignant.ConclusionThis preliminary study suggests that TNAPP is a useful clinical tool for sonographic assessment of thyroid nodules with Hürthle cell cytology.     

甲状腺结节的现代诊疗进展

绝大多数甲状腺结节都是经影像学检查无意间发现的,即使是良性甲状腺结节,也有必要进行治疗。临床医生需要综合患者的病史、体格检查及实验室、影像学或细胞学穿刺活检等检查结果尽可能明确诊断结节的良恶性。非手术微创治疗方法对于多数的良性结节行药物或放射性碘治疗如无水酒精注射(PEI)、激光光凝(ILP)、放射性碘消融(RFI)和微波消融(MWA)效果较好;而恶性或高度怀疑恶性及部分较大良性结节需行外科手术切除,根据结节的具体类型并结合各高危因素选择适当的切除范围,某些恶性结节术后还需进一步辅助碘131放射治疗并跟踪随访。本文综述了有关甲状腺结节的最新诊断和治疗进展,重点阐述了美国甲状腺协会关于甲状腺结节和分化型甲状腺癌的诊治指南的相关主张。     

VEGF-C Is a Thyroid Marker of Malignancy Superior to VEGF-A in the Differential Diagnostics of Thyroid Lesions

Introduction

Thyroid nodular goiter is one of the most common medical conditions affecting even over a half of adult population. The risk of malignancy is rather small but noticeable–estimated by numerous studies to be about 3–10%. The definite differentiation between benign and malignant ones is a vital issue in endocrine practice. The aim of the current study was to assess the expression of vascular endothelial growth factor A (VEGF-A) and VEGF-C on the mRNA level in FNAB washouts in case of benign and malignant thyroid nodules and to evaluate the diagnostic value of these markers of malignancy.

Materials and Methods

Patients undergoing fine-needle aspiration biopsy (FNAB) in our department between January 2013 and May 2014 were included. In case of all patients who gave the written consent, after ultrasonography (US) and fine-needle aspiration biopsy (FNAB) performed as routine medical procedure the needle was flushed with RNA Later solution, the washouts were frozen in -80 Celsius degrees. Expression of VEGF-A and VEGF-C and GADPH (reference gene) was assessed in washouts on the mRNA level using the real-time PCR technique. Probes of patients who underwent subsequent thyroidectomy and were diagnosed with differentiated thyroid cancer (DTC; proved by post-surgical histopathology) were analyzed. Similar number of patients with benign cytology were randomly selected to be a control group.

Results

Thirty one DTCs and 28 benign thyroid lesions were analyzed. Expression of VEGF-A was insignificantly higher in patients with DTCs (p = 0.13). Expression of VEGF-C was significantly higher in patients with DTC. The relative expression of VEGF-C (in comparison with GAPDH) was 0.0049 for DTCs and 0.00070 for benign lesions, medians – 0.0036 and 0.000024 respectively (p<0.0001).

Conclusions

Measurement of expression VEGF-C on the mRNA level in washouts from FNAB is more useful than more commonly investigated VEGF-A. Measurement of VEGF-C in FNAB washouts do not allow for fully reliable differentiation of benign and malignant thyroid nodules and should be interpreted carefully. Further studies on larger groups are indicated. However, measurement of VEGF-C on mRNA level can bring important information without exposing patient for additional risk and invasive procedures.     

The value of 99mTc-MIBI scan in the detection of malignancy potential of hypermetabolic thyroid incidentalomas of 18F-FDG PET/CT

Aim of the studyIncreasingly use of PET/CT leads to discovery of incidental findings. Hypermetabolic thyroid nodules are one of the unexpected lesions in PET/CT imaging with an increased risk of thyroid cancers. Our study aims to determine the malignant potential of incidentally detected 18F-FDG avid thyroid nodules by using Tc-99m MIBI imaging.Materials and methodsPET/CT scans were performed for nonthyroidal purposes and were evaluated for the presence of hypermetabolic thyroid nodules. Tc-99m MIBI scans and ultrasonography-guided fine needle aspiration biopsies were subsequently performed for all patients.ResultsPrimary thyroid malignancies were identified in 25% of patients with increased focal FDG uptake at definitive diagnosis. Among the patients with FDG avid thyroid nodules, Tc-99m MIBI scan showed true-positive results in all thyroid carcinomas (n:7) with a 36.3% (4/11) false-positivity rate. In three patients with indeterminate cytology results, Tc-99m MIBI scan findings were also negative. The sensitivity, specificity, positive predictive value of Tc-99m MIBI scan in predicting the malignancy of FDG-positive thyroid nodules were 100%, 77%, 63.6%, respectively.ConclusionThe implementation of ^99mTc-MIBI scan performed by dual phase and SPECT/CT modality might be a helpful cost-effective approach in addition to FNAB in patients with ¹⁸F-FDG-positive thyroid nodules and indeterminate cytology to improve the patients’ prognosis and reduce unnecessary thyroid operations with associated use of FNAB.     

Feasibility of Immediate Assessment of Fine Needle Aspirates of Thyroid Nodules by Telecytopathology

ObjectiveIn this study we discuss the diagnostic accuracy and unsatisfactory rate of onsite evaluation of ultrasound-guided fine needle aspiration (USGFNA) of thyroid nodules using telecytopathology and compare it to that of a control group without telecytopathology.MethodsThis was a retrospective analysis of USGFNA of thyroid nodules over a 9-month period with and without telecytopathology. There was no randomization for selection of the groups with and without telepathologist. A single provider performed all the procedures. Real-time images of Diff Quik-stained cytology smears were obtained with an Olympus Digital camera attached to an Olympus CX41 microscope and transmitted via the Internet by a cytotechnologist to a pathologist, who communicated the preliminary diagnosis and sample adequacy. The unsatisfactory specimen rate was compared between a group whose images were transmitted (n = 45) and another group without onsite adequacy assessment (nontransmitted) (n = 47).ResultsA total of 92 nodules in 67 patients were aspirated with ultrasound guidance. The unsatisfactory sample rate in the transmitted group was 13% (6 out of 45) and that of the non-transmitted group was 23% (11 out of 47). In the transmitted group, the cytology specimens of 3 patients that were initially deemed inadequate by the pathologist were considered adequate after 2 additional passes. In the transmitted group, preliminary diagnosis concurred with the final diagnosis in 96% of cases. Four passes were made in the non-transmitted group, versus 2 passes in the transmitted group.ConclusionImmediate assessment of USGFNA via telecytopathology assures adequacy of the cytology sample and may reduce number of passes per nodule. Preliminary onsite telecytopathology diagnosis was highly accurate when compared to final diagnosis. (Endocr Pract. 2013; 19:14-18)     

A Literature Review of Factors Associated With Pain From Fine Needle Aspiration Biopsy of Thyroid Nodules

ObjectiveThyroid nodules are common, being detected in 19% to 67% of the population. A fine needle aspiration biopsy (FNAB) is recommended for suspicious thyroid nodules to rule out malignancy; however, the procedure can be painful for subsets of patients. It remains unclear what factors are more likely to be associated with pain during FNAB. This literature review aimed to investigate patient-, procedure-, and analgesic-related factors that affect pain levels during thyroid nodule FNAB.MethodsPredefined inclusion and exclusion criteria were set to search the Embase, MEDLINE, CINAHL, and Cochrane databases. The articles evaluating the factors affecting pain during FNAB were assessed for inclusion. The primary outcome of interest was scores evaluating pain level during FNAB.ResultsTwenty-two studies were included. The studies were a mix of cohort studies, randomized controlled trials, and clinical controlled trials. Under patient-related factor, nodule calcification was associated with increasing pain. The procedure-related factors potentially increasing pain included the number of needle passes and utilization of the aspiration technique (as opposed to capillary action), perpendicular needle placement (as opposed to parallel), and not using safety devices. Larger needle size, type of biopsy, operator expertise, and patient education did not appear to be correlated with pain. Subcutaneous lidocaine appeared to provide better pain relief than a topical analgesic.ConclusionWith increasing use of FNAB as the diagnostic test of choice for assessing thyroid nodules, understanding patient-, procedure-, and analgesic-related factors associated with optimal patient satisfaction is imperative.     

Thyroseq®V2.0 Molecular Testing: A Cost-Effective Approach for the Evaluation of Indeterminate Thyroid Nodules

Objective: Approximately 15 to 30% of thyroid nodules have indeterminate cytology. Many of these nodules are treated surgically, but only 5 to 30% are malignant. Molecular testing can further narrow the risk of malignancy of these nodules. Our objective was to assess the cost effectiveness of ThyroSeq®V2.0 compared to diagnostic thyroidectomy for the evaluation of indeterminate nodules.Methods: Cytology and histopathology slides of Bethesda category III and IV (suspicious for follicular neoplasia [SFN]) nodules obtained between January 1, 2014 and November 30, 2016 were re-reviewed by 2 endocrine cytopathologists. Costs for a diagnostic approach using ThyroSeq® were calculated and compared to those of diagnostic thyroidectomy.Results: We included 8 Bethesda category III nodules that underwent ThyroSeq® and 8 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 4 were positive for mutations and underwent thyroid surgery. The average cost per nodule evaluated was $14,669 using ThyroSeq®, compared to $23,338 for diagnostic thyroid surgery. The cost per thyroid cancer case detected was $58,674 using ThyroSeq® compared to $62,233 for diagnostic thyroid surgery. We included 13 nodules Bethesda category IV that underwent ThyroSeq® and 11 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 6 were positive for mutation and underwent thyroid surgery. The average costs per nodule evaluated were $14,641 using ThyroSeq® and $24,345 using diagnostic thyroidectomy. The cost per thyroid cancer case detected was $31,721 when using ThyroSeq® compared to $53,560 for diagnostic thyroidectomy.Conclusion: The use of ThyroSeq® in our institution is cost effective compared to diagnostic thyroid surgery for the evaluation of Bethesda categories III and IV (SFN) nodules.Abbreviations: FNA = fine-needle aspiration; GEC = gene expression classifier; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid cancer; SFN = suspicious for follicular neoplasia     

Papillary Hyperplastic Nodule: Pitfall in the Cytopathologic Diagnosis of Papillary Thyroid Carcinoma

ObjectiveTo identify the pitfalls of overdiagnosing papillary formation as papillary thyroid carcinoma (PTC) in thyroid cytology specimens.MethodsPatients with papillary hyperplastic nodules who had preoperative fine-needle aspiration biopsy (FNAB) were selected for this study. All patients had been diagnosed as having either PTC or lesions suggestive of PTC on preoperative FNAB. Pathology reports, surgical reports, and cytopathology slides were reviewed and analyzed for demographic data, nature of surgery, and pathologic features.ResultsSix women and 2 men with a mean age of 49 years (range, 16-79 years) were included. The lesion size ranged from 1.0 to 3.5 cm. Four patients were diagnosed as having PTC and 4 as having lesions suspicious for PTC. FNAB specimens were available for review in 6 cases. Surgical pathology slides were reviewed in all cases. When cytologic material was evaluated for the morphologic features that led to the misdiagnosis of PTC by comparing it with FNAB specimens of classic variant of PTC, the specimens from these patients showed follicular cells arranged in short, nonbranching papillae in a background of watery colloid and macrophages. The follicular cells were round and demonstrated oncocytic change with nuclear enlargement, prominent central nucleoli, nuclear chromatin clearing, and intranuclear grooves.ConclusionsCaution should be exercised rendering the diagnosis of PTC on FNAB samples when a thyroid lesion shows papillary configurations and oncocytic cells and if convincing nuclear features of PTC are not present. Furthermore, some morphologic features on thyroid aspiration can help differentiate these cases from true PTC. (Endocr Pract. 2008;14:863-868)