[repeated Fine-needle Aspiration Cytology For The Diagnosis And Follow-up Of Thyroid Nodules].

The recently-proposed Bethesda reporting system has offered clinical recommendations for each category of reported thyroid cytology, including repeated fine-needle aspiration (FNA) for non-diagnostic and atypia/follicular lesions of undetermined significance, but there are no sound indications for repeated examination after an initial benign exam. To investigate the clinical validity of repeated FNA in the management of patients with thyroid nodules. The present study evaluated 412 consecutive patients who had repeated aspiration biopsies of thyroid nodules after an initial non-diagnostic, atypia/follicular lesion of undetermined significance, or benign cytology. The majority of patients were female (93.5%) ranging from 13 to 83 years. Non-diagnostic cytology was the most common indication for a repeated examination in 237 patients (57.5%), followed by benign (36.8%), and A/FLUS (5.6%) cytology. A repeated examination altered the initial diagnosis in 70.5% and 78.3% of the non-diagnostic and A/FLUS patients, respectively, whereas only 28.9% of patients with a benign cytology presented with a different diagnosis on a sequential FNA. Repeat FNA is a valuable procedure in cases with initial non-diagnostic or A/FLUS cytology, but its routine use for patients with an initial benign examination appears to not increase the expected likelihood of a malignant finding.

Comparative analysis of the new guidelines and consensuses for the management of hypothyroidism, thyroid nodules, and differentiated thyroid cancer

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Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus

Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.

Predictive value for malignancy in the finding of microcalcifications on ultrasonography of thyroid nodules

Background. The am of this study was to determine the predictive value for malignancy of microcalcifications determined by ultrasonography in thyroid nodules. Methods. One hundred seventy-seven nodules were prospectively studied by ultrasonography and compared with their fine-needle aspirative biopsy. The association between the presence and type of calcification and cytologic findings was verified through the chi-square test or likelihood ratio. Results. Thirty nodules showed calcification, of which 17 had fine calcifications, 3 had fine and gross calcifications, and 10 had only coarse calcification. Seven (41.18%) of 17 fine calcified nodules were malignant on cytology, 8 (47.06%) were benign, 1 (5,88%) was indeterminate, and 1 was suspect for malignancy. We found statistical significance between the presence of fine calcifications and malignancy (p =.001) and, in the 13 malignant nodule group, 8 (61.50%) had fine calcifications. Conclusion. This study suggests that microcalcifications were highly specific for malignancy and were present in 61% of the malignant nodules. (c) 2008 Wiley Periodicals, Inc.

Association of low sodium-iodide symporter messenger ribonucleic acid expression in malignant thyroid nodules with increased intracellular protein staining

Context: The expression of sodium iodide symporter (NIS) is required for iodide uptake in thyroid cells. Benign and malignant thyroid tumors have low iodide uptake. However, previous studies by RT-PCR or immunohistochemistry have shown divergent results of NIS expression in these nodules. Objective: The objective of the study was to investigate NIS mRNA transcript levels, compare with NIS and TSH receptor proteins expression, and localize the NIS protein in thyroid nodules samples and their surrounding nonnodular tissues (controls). Design: NIS mRNA levels, quantified by real-time RT-PCR, and NIS and TSH receptor proteins, evaluated by immunohistochemistry, were examined in surgical specimens of 12 benign and 13 malignant nodules and control samples. Results: When compared with controls, 83.3% of the benign and 100% of the malignant nodules had significantly lower NIS gene expression. Conversely, 66.7% of the benign and 100% of malignant nodules had stronger intracellular NIS immunostaining than controls. Low gene expression associated with strong intracellular immunostaining was most frequently detected in malignant (100%) than benign nodules (50%; P = 0.005). NIS protein was located at the basolateral membrane in 24% of the control samples, 8.3% of the benign, and 15.4% of the malignant nodules. The percentage of benign nodules with strong TSH receptor positivity (41.6%) was higher than malignant (7.7%). Conclusion: We confirmed that reduced NIS mRNA expression in thyroid malignant nodules is associated with strong intracellular protein staining and may be related to the inability of the NIS protein to migrate to the cellular basolateral membrane. These results may explain the low iodide uptake of malignant nodules.

Ultrasound-guided fine-needle aspiration of thyroid nodules: assessment of the ideal number of punctures

OBJECTIVE: To determine the number of punctures in fine-needle aspiration biopsies required for a safe cytological analysis of thyroid nodules. MATERIALS AND METHODS: Cross-sectional study with focus on diagnosis. The study population included 94 patients. RESULTS: The mean age of the patients participating in the study was 52 years (standard-deviation = 13.7) and 90.4% of them were women. Considering each puncture as an independent event, the first puncture has showed conclusive results in 78.7% of cases, the second, in 81.6%, and the third, in 71.8% of cases. With a view to the increasing chance of a conclusive diagnosis at each new puncture, two punctures have showed conclusive results in 89.5% of cases, and three punctures, in 90.6% of cases with at least one conclusive result. CONCLUSION: Two punctures in fine-needle aspiration biopsies of thyroid nodules have lead to diagnosis in 89.5% of cases in the study sample, suggesting that there is no need for multiple punctures to safely obtain the diagnosis of thyroid nodules.

[Thyroid nodules: which further investigations should be done]

Thyroid nodules are a very common clinical finding with an age-related increase in prevalence. The clinical detection of thyroid nodules is outnumbered by the ultrasonographic assessment of thyroid nodules. The clinical challenge is to exclude thyroid cancer and clinical or subclinical hyperthyroidism. Ultrasonography is the first imaging study in all patients with palpable nodules; their size and TSH determine further diagnostic evaluations. Fine-needle aspiration (cytology) is recommended in euthyroid patients of nodules measuring more than 1-1.5 cm in diameter. Nodules more than 4 cm in diameter have to be removed surgically without preceding cytological examination. Without risk factors thyroid nodules are followed by clinical examination and ultrasonography every 6-12 months, in case of symptoms or rapid growth a follow-up assessment should be done earlier.

A Putative Otu Domain-containing Protein 1 Deubiquitinating Enzyme Is Differentially Expressed In Thyroid Cancer And Identifies Less-aggressive Tumours.

This study aimed to identify novel biomarkers for thyroid carcinoma diagnosis and prognosis. We have constructed a human single-chain variable fragment (scFv) antibody library that was selected against tumour thyroid cells using the BRASIL method (biopanning and rapid analysis of selective interactive ligands) and phage display technology. One highly reactive clone, scFv-C1, with specific binding to papillary thyroid tumour proteins was confirmed by ELISA, which was further tested against a tissue microarray that comprised of 229 thyroid tissues, including: 110 carcinomas (38 papillary thyroid carcinomas (PTCs), 42 follicular carcinomas, 30 follicular variants of PTC), 18 normal thyroid tissues, 49 nodular goitres (NG) and 52 follicular adenomas. The scFv-C1 was able to distinguish carcinomas from benign lesions (P=0.0001) and reacted preferentially against T1 and T2 tumour stages (P=0.0108). We have further identified an OTU domain-containing protein 1, DUBA-7 deubiquitinating enzyme as the scFv-binding antigen using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. The strategy of screening and identifying a cell-surface-binding antibody against thyroid tissues was highly effective and resulted in a useful biomarker that recognises malignancy among thyroid nodules and may help identify lower-risk cases that can benefit from less-aggressive management.

Diagnosis, Treatment, And Follow-up Of Medullary Thyroid Carcinoma: Recommendations By The Thyroid Department Of The Brazilian Society Of Endocrinology And Metabolism.

Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. MTC should be suspected in individuals who present with thyroid nodules and family histories of MTC, associations with pheochromocytoma and hyperparathyroidism, and/or typical phenotypic characteristics such as ganglioneuromatosis and Marfanoid habitus. Fine-needle nodule aspiration, serum calcitonin measurements, and anatomical-pathological examinations are useful for diagnostic confirmation. Surgery represents the only curative therapeutic strategy. The therapeutic options for metastatic disease remain limited and are restricted to disease control. Judicious postoperative assessments that focus on the identification of residual or recurrent disease are of paramount importance when defining the follow-up and later therapeutic management strategies.

Ratio of Metalloproteinase 2 to Tissue Inhibitor of Metalloproteinase 2 in Medullary Thyroid Carcinoma

Objectives: To develop an index for the ratio of metalloproteinase 2 (MMP-2) to its tissue inhibitor (TIMP-2) in immunostained medullary thyroid carcinoma specimens and to correlate it with clinical and pathologic prognostic factors. Metalloproteinases, enzymes related to the degradation of the extracellular matrix, take part in carcinogenesis and have been associated with the prognosis of neoplasias. Nevertheless, medullary carcinoma is rarely considered in research analysis. Researchers tend to favor the ratio of enzymes to their inhibitors over the absolute concentrations of these enzymes. Design: Retrospective study of surgical samples. Setting: Head and Neck Surgery and Endocrinology Departments, Universidade de Sao Paulo Medical School Hospital. Patients: Surgical specimens from 33 patients who had been observed for a mean of 76.8 months (range, 4-201 months) were immunohistochemically stained for MMP-2 and TIMP-2. Only patients whose clinical and pathologic data were complete and whose specimens were preserved were included in the study. Main Outcome Measures: The ratio between the expressions of MMP-2 and TIMP-2 was based on a staining index (immunostaining extent and intensity) of each of the markers. Results: Proportionally large expressions of TIMP-2 over MMP-2 correlated with low occurrences of positive findings on initial cervical examination for the presence of thyroid nodules and/or lymphadenopathy (P = .02) and cervical lymph node metastases (P < .001), conditions correlated with prognosis. A correlation with cure at the end of follow-up (P = .01) was also observed. (P < .05 was considered statistically significant.) Conclusion: The ratio of MMP-2 to TIMP-2 expression is an additional and novel prognostic predictor of the outcome of medullary carcinoma treated surgically.

Thyroid metastasis as initial presentation of clear cell renal carcinoma.

INTRODUCTION Metastatic tumors account for 1.4-2.5% of thyroid malignancies. About 25-30% of patients with clear cell renal carcinoma (CCRC) have distant metastasis at the time of diagnosis, being the thyroid gland a rare localization [5%]. PRESENTATION OF THE CASE A 62-year woman who underwent a cervical ultrasonography and a PAAF biopsy reporting atypical follicular proliferation with a few intranuclear vacuoles "suggestive" of thyroid papillary cancer in the context of a multinodular goiter was reported. A total thyroidectomy was performed and the histology of a clear cell renal carcinoma (CCRC) was described in four nodules of the thyroid gland. A CT scan was performed and a renal giant right tumor was found. The patient underwent an eventful radical right nephrectomy and the diagnosis of CCRC was confirmed. DISCUSSION Thyroid metastasis (TM) from CCRC are usually apparent in a metachronic context during the follow-up of a treated primary (even many years after) but may sometimes be present at the same time than the primary renal tumor. Our case is exceptional because the TM was the first evidence of the CCRC, which was subsequently diagnosed and treated. CONCLUSION The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was) is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of "de novo" thyroid nodules in oncologic patients must be always considered and studied.

Chirurgie viscérale. Chirurgie thyroïdienne et parathyroïdienne: place de la chirurgie minimale invasive [Update in thyroid and parathyroid surgery: the role for minimally invasive surgery].

Thyroid and parathyroid surgery takes an important place in general surgery. Preservation of essential cervical structures and cosmetic of outcomes of cervical incisions are major concern. Several minimally invasive strategies have been developed recently but their acceptance in the surgical community is low. Their main advantages are focused tissue dissection and improved cosmetics. In this review, management and surgical indications of thyroid nodules and parathyroid adenomas are discussed. The various minimally invasive techniques are described and their current indications are reviewed.

Previous thyroid disease and risk of thyroid cancer in Switzerland

A hospital-based case-control study of 86 cases of thyroid cancer and 317 controls was done in the Swiss Canton of Vaud. Patients with thyroid cancer tended to be better educated (odds ratio [OR] 2.1 for greater than or equal to 14 vs. less than or equal to 8 years of education 95% CI 1.1-4.1) and of higher social class than controls. Cases more often had a history of benign thyroid nodules (OR 25.2, 95% CI 7.6-83.6) and non-toxic goitre (OR 5.3, 95% CI 2.5-11.2). Furthermore, patients with thyroid cancer were more likely to have resided in endemic goitre areas (OR 1.7, 95% CI 1.0-3.0) and to have had first-degree relatives affected by benign thyroid disease (OR 3.9, 95% CI 2.1-7.1). Therefore, this study offers quantitative evidence of the association between various thyroid diseases and the risk of thyroid cancer which, despite difficulties in the classification of benign and malignant thyroid diseases, is remarkably consistent in studies from different countries.

Use of fine-needle aspirate calcitonin to detect medullary thyroid carcinoma: A systematic review.

BACKGROUND: The measurement of calcitonin in washout fluids of thyroid nodule aspirate (FNA-calcitonin) has been reported as accurate to detect medullary thyroid carcinoma (MTC). The results from these studies have been promising and the most updated version of ATA guidelines quoted for the first time that "FNA findings that are inconclusive or suggestive of MTC should have calcitonin measured in the FNA washout fluid." Here we aimed to systematically review published data on this topic to provide more robust estimates. RESEARCH DESIGN AND METHODS: A comprehensive computer literature search of the medical databases was conducted by searching for the terms "calcitonin" AND "washout." The search was updated until April 2015. RESULTS: Twelve relevant studies, published between 2007 and 2014, were found. Overall, 413 thyroid nodules or neck lymph nodes underwent FNA-calcitonin, 95 were MTC lesions and 93 (97.9%) of these were correctly detected by this measurement regardless of their cytologic report. CONCLUSIONS: The present study shows that the above ATA recommendation is well supported. Almost all MTC lesions are correctly detected by FNA-calcitonin and this technique should be used to avoid false negative or inconclusive results from cytology. The routine determination of serum calcitonin in patients undergoing FNA should improve the selection of patients at risk for MTC, guiding the use of FNA-calcitonin in the same FNA sample and providing useful information to the cytopathologist for the morphological assessment and the application of tailored ancillary tests.

Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in The Bethesda System for Reporting Thyroid Cytopathology.

BACKGROUND: Recent discussions have focused on redefining noninvasive follicular variant of papillary thyroid carcinoma (NI-FVPTC) as a neoplasm rather than a carcinoma. This study assesses the potential impact of such a reclassification on the implied risk of malignancy (ROM) for the diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). METHODS: The study consisted of consecutive fine-needle aspiration biopsy (FNAB) cases collected between January 1, 2013 and June 30, 2014 from 5 academic institutions. Demographic information, cytology diagnoses, and surgical pathology follow-up were recorded. The ROM was calculated with and without NI-FVPTC and was presented as a range: all cases (ie, overall risk of malignancy [OROM]) versus those with surgical follow-up only. RESULTS: The FNAB cohort consisted of 6943 thyroid nodules representing 5179 women and 1409 men with an average age of 54 years (range, 9-94 years). The combined average ROM and OROM for the diagnostic categories of TBSRTC were as follows: nondiagnostic, 4.4% to 25.3%; benign, 0.9% to 9.3%; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 12.1% to 31.2%; follicular neoplasm (FN), 21.8% to 33.2%; suspicious for malignancy (SM), 62.1% to 82.6%; and malignant, 75.9% to 99.1%. The impact of reclassifying NI-FVPTC on the ROM and OROM was most pronounced and statistically significant in the 3 indeterminate categories: the AUS/FLUS category had a decrease of 5.2% to 13.6%, the FN category had a decrease of 9.9% to 15.1%, and the SM category had a decrease of 17.6% to 23.4% (P < .05), whereas the benign and malignant categories had decreases of 0.3% to 3.5% and 2.5% to 3.3%, respectfully. The trend of the effect on the ROM and OROM was similar for all 5 institutions. CONCLUSIONS: The results from this multi-institutional cohort indicate that the reclassification of NI-FVPTC will have a significant impact on the ROM for the 3 indeterminate categories of TBSRTC. Cancer Cytopathol 2016;124:181-187. © 2015 American Cancer Society.