Thyroid Neoplasms

Background: The purpose of this study is to evaluate the suitability of lobectomy with isthmusectomy (LwI) in treatment of Follicular Thyroid Neoplasms (FTN), considering malignancy incidence and postoperative complications. Methods: 192 patients (165 females; 27 males) who underwent LwI for FTN from 01/2005 to 12/2007 were retrospectively evaluated: clinical and pathological features, surgical complications and five year outcome of the remnant lobe. Inclusion criteria were cytological Bethesda category III and IV or histological follicular architecture. Patients with metastatic follicular carcinoma or previous thyroid surgery were excluded. Results: Mean age was 48,68±14,93yrs. Overall malignancy occurred in 88 patients (45,83%) and 80 (41,67%) underwent thyroidectomy completion (TC), mainly by index lesion's malignancy. Forty-one (21,35%) in LwI and 31 (38,75%) in TC specimens had associated malignancy, mainly papillary microcarcinomas. High preoperative Thyroid-Stimulating Hormone (TSH), histological multinodularity and, in cytology category IV, younger age, were significantly associated to malignancy. Permanent recurrent laryngeal nerve lesion occurred in 0,58% in Lwl and 1,52% in TC, and temporary dysphonia occurred in 9,25% and 6,06% (LwI and TC respectively). No LwI patients presented hypoparathyroidism and 3,03% in TC had temporary symptoms. In LwI, 36,70% developed hypothyroidism. Higher preoperative TSH was associated with hypothyroidism development. Conclusions: LwI was inappropriate in 40,10% patients with malignancy who required TC and 23,12% had no functional benefit because post-LwI hypothyroidism. Nodular relapse was reported in at least 23/113 LwI patients (20,35%). We propose total thyroidectomy for patients with FTN preoperative TSH higher than 2,16 mU/L and, in Bethesda category IV, less than 39,5yrs.

Long non-coding RNAs (lncRNAs) regulate pathological processes, yet their potential roles in papillary thyroid carcinoma (PTC) are poorly understood. To profile transcriptionally dysregulated lncRNAs in PTC and identify lncRNAs associated with clinicopathological characteristics. We performed RNA sequencing of 12 paired PTC tumors and matched noncancerous tissues and correlated the expression of lncRNAs with clinical parameters. The 2 most significantly dysregulated lncRNAs were studied in an Ohio PTC cohort (n=109) and in PTC data (n=497) from TCGA. A combination of laboratory-based studies and computational analysis using clinical data and samples and a publically available database. Correlation between expression values and clinical parameters. We identified 218 lncRNAs showing differential expression in PTC (fold change ≥2.0, p value <0.01). Significant correlation was observed between the expression of two lncRNAs (XLOC_051122 and XLOC_006074) and (i) lymph node metastasis (...

A 61-year-old male patient presented with hoarseness and a painless swelling in the anterior aspect of the neck. Imaging Findings: A 61-year-old man presented with a history of hoarseness over the past several months, and the presence of a painless swelling, present since 4 years, in the anterior aspect of the neck. A physical examination showed a solid mass located in the region of the right thyroid cartilage wing. A laryngoscopy showed reduced mobility of the right vocal cord. A CT imaging of the neck was performed and plain thin sections (2.4 mm) were obtained, before and after the injection of a contrast medium. This showed a swelling of the right thyroid cartilage, measuring 4x5 cm in dimension, with irregular borders and inhomogeneous appearance, containing calcifications. The mass, which did not reach the median line, compressed the adjacent structures, in particular the vocal cord, which was medially dislocated but probably not invaded, by the lesion. Inferiorly, the lesion reached to the level of the cricoid cartilage. There was no evidence of a cervical lymph node enlargement. The patient underwent a total laryngectomy. A gross examination of the surgical specimen demonstrated the presence of a hard neoformation, measuring 5x4x3 cm in dimensions. The histological diagnosis was that of a Grade 1 chondrosarcoma. The surgical margins, marked with ink, were free of tumour.

Ultrasound is the most commonly used imaging technique for the evaluation of thyroid nodules. Sonographic findings are often not specific, and definitive diagnosis is usually made through fine-needle aspiration biopsy or even surgery. In reviewing the literature, terms used to describe nodules are often poorly defined and inconsistently applied. Several authors have recently described a standardized risk stratification system called the Thyroid Imaging, Reporting and Data System (TIRADS), modeled on the BI-RADS system for breast imaging. However, most of these TIRADS classifications have come from individual institutions, and none has been widely adopted in the United States. Under the auspices of the ACR, a committee was organized to develop TIRADS. The eventual goal is to provide practitioners with evidence-based recommendations for the management of thyroid nodules on the basis of a set of well-defined sonographic features or terms that can be applied to every lesion. Terms were chosen on the basis of demonstration of consistency with regard to performance in the diagnosis of thyroid cancer or, conversely, classifying a nodule as benign and avoiding follow-up. The initial portion of this project was aimed at standardizing the diagnostic approach to thyroid nodules with regard to terminology through the development of a lexicon. This white paper describes the consensus process and the resultant lexicon.

The increased use of diagnostic and therapeutic procedures that involve radiation raises concerns about radiation effects, particularly in children and to the radio-sensitive thyroid gland. Evaluation of relative risk (RR) trends for thyroid radiation doses <0.2 gray; evidence of a threshold dose; and possible modifiers of the dose-response, e.g., sex, age at exposure, time since exposure. Pooled data from nine cohort studies of childhood external radiation exposure and thyroid cancer with individualized dose estimates, ≥1,000 irradiated subjects or ≥10 thyroid cancer cases, with data limited to individuals receiving doses <0.2 gray. Cohorts included: childhood cancer survivors (n=2); children treated for benign diseases (n=6); and children who survived the atomic bombings in Japan (n=1). There were 252 cases and 2,588,559 person-years in irradiated individuals and 142 cases and 1,865,957 person-years in non-irradiated individuals. There were no interventions. Incident thyroid...

Nigeria is the most populous black nation in the world with her population estimated to be about 140 million (2006 population census). In Nigeria, health care is provided through 53 tertiary health institutions; numerous secondary, primary, and private health care entities; and many private clinics and hospitals [1], yet there is no com-prehensive health insurance. This is unlike in the developed countries such as Europe and the US where health insurance is with a history of about 700 years [2, 3].The lack of a comprehensive health insurance has led to a high default rate in thyroid cancer management among other cancers, in Nigeria. Thyroid malignancy is an uncom-mon disease with a uniform world incidence of 40 per mil-lion and accounts for less than 1% or approximately 1% of all malignancies [4-6]. Although seen from childhood to old age, the peak incidence is the 6

Between 1966 and 1974, France performed 41 atmospheric nuclear weapon tests in the Mururoa and Fangataufa atolls in French Polynesia. We performed a geographic analysis of thyroid cancer incidence, using data from the cancer registry of French Polynesia, medical evacuation files, insurance records and hospital and pathology laboratory files. A total of 153 thyroid cancers were diagnosed between 1985 and 1995 in the population born before 1976 and residing in French Polynesia. The incidence of thyroid cancer was 2-3 times larger in French Polynesia than in Maoris of New Zealand and Hawaiians of Hawaii. Based on few cases, a nonsignificant (p = 0.1) increase with decreasing distance between Mururoa and the birth place was observed in women born between 1950 and 1975 for thyroid cancer. Because the difference between Polynesian and reference populations was not larger for Polynesians who were children during the tests than for Polynesians born earlier; as would be expected in the case ...

A 46-year-old woman with history of radioiodine-refractory follicular thyroid carcinoma (FTC) presented with locally recurrent, high-risk, invasive disease. She was treated with paclitaxel/carboplatin concomitant chemoradiotherapy (CRT), which was well tolerated, resulting in complete remission and freedom from residual or recurrent FTC for longer than 5 years until her last follow-up at age 52. This case highlights the possibility of combining taxane-based chemotherapy with definitive radiotherapy (as CRT) for the management of locally aggressive recurrences in poorly differentiated thyroid carcinoma, thereby resulting in rapid and persistent disease eradication. Even in the light of recent data on the potential benefit of novel targeted therapy agents in poorly differentiated thyroid carcinoma, this approach in similar clinical settings deserves future investigation.

Shape and size of the nucleus, coupled with changes in chromatin amount and distribution, still remain the basic microscopic criteria for cytological diagnoses. Diagnostic recognition of the nuclear shape in pathological histology and cytology has been always based on the assumption that it is the content in nucleic acids, which determines the nuclear shape. The present review challenges this opinion, focuses on the structure, and functions of the nuclear envelope and on how these features can be exploited in diagnostic pathology. In particular, we will present the contribution of thee-dimensional modeling to the understanding of nuclear irregularities in breast cancer and papillary thyroid carcinomas. Specifically, it will be shown how tagging the nuclear membrane with anti-Emerin antibodies can represent an additional and valuable tool in the differential diagnosis of thyroid lesions. Finally, the prognostic importance of detecting irregularities of the nuclear shape in breast car...

Purpose: Fine-needle aspiration (FNA) cytology, a standard method for thyroid nodule diagnosis, cannot distinguish between benign follicular thyroid adenoma (FTA) and malignant follicular thyroid carcinoma (FTC). Previously, using expression profiling, we found that a ...

A patient with an invasive thyroid carcinoma located within a hot thyroid nodule is reported. Only four similar cases have been described in the literature. It is emphasized that a hot thyroid nodule per se should not be used as an argument against the diagnosis of thyroid carcinoma.

During the pathologic examination of neck dissection specimens, unexpected findings within lymph nodes may occasionally be uncovered. Such findings may include the presence of a second primary tumor or inflammatory disease, the discovery of which may have implications on management and prognosis. Incidental papillary thyroid carcinoma and necrotizing granulomatous inflammation were found in addition to squamous cell carcinoma metastasis in the pathological study of the neck dissection specimen in a 70-year-old male patient with laryngeal squamous cell carcinoma. The diagnostic, therapeutic and prognostic features of this rare association were discussed in the light of the current literature.

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management

Case presentation: a 75-year-old man with a 10-year history of nodular goitre was referred for clinical evaluation. The ultrasound scan revealed enlarged thyroid right lobe almost fully filled with a heterogeneous nodule with numerous calcifications. Fine-needle aspiration biopsy suggested medullary thyroid carcinoma (MTC). Before the surgery the patient was referred to the nuclear medicine department and somatostatin receptor imaging (SRS; 68 Ga-DOTATATE) with PET/CT was performed. The scan demonstrated an increased uptake within the right thyroid mass. Subsequent PET/CT with 68 Ga-gastrin analogue (MG48) revealed the same indications as the SRS: an increased alveolar uptake in the right thyroid mass without the signs of lymph node metastases. The patient underwent total thyroidectomy and central lymph nodes dissection. Histopathology examination confirmed the presence of MTC with vascular invasion, but without lymph node metastases (pT3NoMx according to the 7 th edition of the AJCC Cancer Staging Manual). Immunohistochemical staining revealed positive reaction to calcitonin and CD56, whereas the reaction to thyroglobulin remained negative. The Ki-67 was 1%. Staining for SSTR2 and CCK2 showed high cytoplasmic expression in both cases. Knowledge of the presence of CCK2 receptor in MTC patients may be an important indication for the choice of diagnostic and therapeutic procedures. The presence of both the receptor types, cholecystokinin-2/gastrin and somatostatin, is possibly an interesting combination as far as the therapeutic target is concerned.

BACKGROUND: Thyroid nodules are common, and of those biopsied by fine-needle aspiration (FNA), the majority will be benign colloid nodules (BCN). Current guidelines suggest these BCN should be followed by ultrasonographic examination (US) every 3 years, with no endpoint specified. This study evaluated if long-term follow-up of benign thyroid nodules was associated with change in treatment or improvement in diagnosing a missed malignancy compared with short-term follow-up. STUDY DESIGN: All patients with FNA-based diagnosis of BCN at our institution from 1998 to 2009 were identified. Patients observed after the diagnosis were divided into short-term follow-up (<3years) and long-term follow-up (3years). Rates of repeat FNA, thyroidectomy, and malignancy detection were compared. RESULTS: Of 738 patients with BCN, 92 patients underwent thyroid resection after the initial US. Six hundred forty-six patients were observed, of which 366 returned for 1 or more follow-up US: 226 in the short-term group (median 13 months) and 140 in the long-term group (median 57 months). There were more follow-up US in long-term vs short-term (medians 4 vs 2, p < 0.01), more repeat FNAs in the long-term group (18 of 140 vs 8 of 226, p < 0.01); but no difference in interval thyroidectomies (13 of 140 vs 31 of 226, p ¼ 0.25) or malignant final pathology (0 of 13 vs 2 of 31, p > 0.99). For all patients undergoing surgery, pathology was malignant in 2 of 136 (1.5%). CONCLUSIONS: Long-term follow-up of patients with BCN is associated with increased repeat FNA and US without improvement in the malignancy detection rate. After 3 years of follow-up, consideration should be given to ceasing long-term routine follow-up of biopsy-proven BCN.

Background: Our aim was to evaluate predictive factors of malignancy in patients with cytologically suspicious for Hurthle cell neoplasm (HCN) of thyroid nodules. Materials and methods: We searched cases with cytologically suspicious for HCN from 11,569 ultrasoundguided fine-needle aspirations (US-FNA) performed at our institution. Nodules that were confirmed surgically or followed-up for at least 2 years were compared with respect to age, gender, tumor size, US diagnosis, and US findings to predict malignancy. Results: The incidence of cases with cytologically suspicious for HCN was 1.2% (143 of 11,569). Of 75 nodules that underwent sufficient follow-up or surgery, malignancies were found in 11 (14.7%). Malignant histological examination revealed oncocytic variants of papillary thyroid carcinoma (PTC) in 3 cases, classic PTC in 1, Hurthle cell carcinoma in 3, follicular carcinoma in 3 and an unclassified carcinoma in 1. In univariate analysis, tumor size was significantly larger in malignant nodules compared to benign nodules (p ¼ 0.026). The best cutoff value of tumor size in predicting malignancy was 2.5 cm. (p ¼ 0.006, sensitivity: 63.6%, specificity: 79.7%). The incidences of hypoechogenicity and malignant US diagnoses were higher in malignant nodules than in benign nodules (p < 0.001). In multivariate analysis, tumor size was an independent factor in predicting malignancies. (p ¼ 0.037, odd ratio: 2.09, confidence interval: 1.046e4.161). Conclusion: Preoperative US provides predictive factors of malignancy in thyroid nodules with cytologically suspicious for HCN. Predictive factors include tumor size of 2.5 cm or greater, hypoechoic nodule and malignant US diagnosis.

Germ-line point mutations of the RET gene are responsible for multiple endocrine neoplasia (MEN) type 2A and 2B that develop medullary thyroid carcinoma and pheochromocytoma. We performed a differential display analysis of gene expression using NIH 3T3 cells expressing the RET-MEN2A or RET-MEN2B mutant proteins. As a consequence, we identified 10 genes induced by both mutant proteins and eight genes repressed by them. The inducible genes include cyclin D1, cathepsins B and L, and cofilin genes that are known to be involved in cell growth, tumor progression, and invasion. In contrast, the repressed genes include type I collagen, lysyl oxidase, annexin I, and tissue inhibitor of matrix metalloproteinase 3 (TIMP3) genes that have been implicated in tumor suppression. In addition, six RET-MEN2A-and five RET-MEN2B-inducible genes were identified. Among 21 genes induced by RET-MEN2A and/or RET-MEN2B, six genes including cyclin D1, cathepsin B, cofilin, ring finger protein 11 (RNF11), integrin-␣6, and stanniocalcin 1 (STC1) genes were also induced in TGW human neuroblastoma cells in response to glial cell line-derived neurotrophic factor stimulation. Because the STC1 gene was found to be highly induced by both RET-MEN2B and glial cell line-derived neurotrophic factor stimulation, and the expression of its product was detected in medullary thyroid carcinoma with the MEN2B mutation by immunohistochemistry, this may suggest a possible role for STC1 in the development of MEN 2B phenotype.

Background and Objective: Thyroid nodules are common among the general population and they increase the risk of thyroid malignancies. This study was done to evaluate the correlation of findings of ultrasound based on Thyroid Imaging and Reporting Data System (TIRADS) and cytology of fine needle aspiration (FNA) based on Bethesda system to evaluate of thyroid nodules.
Methods: This descriptive-analytical study, was performed on 165 patients (152 females and 13 males) referred to the sonography center of Sayyad Shirazi Educational Hospital, Gorgan, northern Iran during 2018. Ultralosonographic features of nodules were recorded in the pre-filled checklist. According to TIRADS and endocrinologist clinical suspicion, couple of patients was eligible for FNA under the ultrasound guidance. The cytology of FNAs was reported based on the Bethesda system classification.
Results: The mean age was significantly lower in patients with malignant nodules (35.4 vs 44.8; P<0.05). Frequency of malignancy was 8 times higher among females than males (16 vs. 2). TIRADS 3 and 4 were the most common categories among the others with the prevalence of 44.4% and 32.3%, respectively. Bethesda 2 and 4 were the most prevalent categories with prevalence of 58.8% and 20.6%, respectively. The strongest agreement was observed between TIRADS 2 and Bethesda 2 that showed benign findings. Kappa index was 0.061 between TIRADS and Bethesda (P<0.05). Echogenicity, echogenic foci, shape, and margin of nodules were seen significantly more in malignancy.
Conclusion: The most accurate prediction of TIRADS belongs to benign nodules. The correlation between TIRADS and Bethesda was evaluated to be significant overall and the maximum level of correlation was at benign findings. Therefore, these two systems can efficiently be used in order to rule out malignancies and reduce the rate of invasive interventions.
Keywords: Thyroid Nodule [MeSH], Thyroid Neoplasms [MeSH], Ultrasonography [MeSH], Fine Needle Aspiration [MeSH], TIRADS , Bethesda System ,

OBJECTIVE To study the clinical significance of stimulated high serum thyroglobulin (sTg) and of normal whole body imaging (WBI) in differentiated thyroid cancer (DTC) patients during their first follow-up and in a 5 years follow-up or till recurrence. SUBJECTS AND METHODS Sixty four DTC patients were retrospectively studied and were divided into two groups. Group 1, of 35 patients with disease free status on their first follow-up and group 2, of 29 patients with high sTg (&gt;2 μg/mL), but with normal WBI, iodine-131 (¹³¹I) findings. Patients were categorized into low, intermediate and high risk patients based on the ¹³¹I WBS findings. Histology, stage and risk-categories of both groups were statistically correlated. Best sTg cut-off for predicting recurrence was generated by receiver operating characteristic (ROC). Odd ratio for sTg trend was also analyzed for risk of recurrence in group 2. Independent t test was used for progression free survival (PFS) comparison of the two group...

Thyroid disease in pregnancy is a common clinical problem. Since the American Thyroid Association&#39;s (ATA&#39;s) guidelines for the management of these disorders were first published in 2011, significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid disease in women during pregnancy, preconception and the postpartum period. The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English-language articles were eligible for inclusion. The American College of Physicians Guideline Gradin...

Nuclear DNA measurements were performed on thyroid carcinomas from 36 patients aged 20 years or less. Histologic material from the tumors were stained according to the Feulgen technique and measured with slide cytophotometry. Thirty-two of the 36 tumors were of papillary type, 3 were medullary carcinoma and 1 was a follicular carcinoma. Of the 32 papillary carcinomas, 6 tumors (19%) were aneuploid and 26 (81 %) were diploid, including 2 cases with lung metastases at diagnosis. Of the 3 medullary carcinomas, 2 were diploid and 1 aneuploid. The only follicular carcinoma was aneuploid. The patients were followed between 10 and 35 years, and 34 were alive at the end of the study. Two patients died, both had medullary carcinomas. One patient, with a diploid tumor, died during surgery. The other patient, with an aneuploid tumor, died 5 years after diagnosis of metastatic disease. Six patients had recurrences, all within 7 years. All the primary tumors and the corresponding recurrences showed a diploid DNA content. The results show that the majority of thyroid carcinomas in young patients exhibit diploid DNA profdes which is in agreement with the overall good prognosis in this patient category. However, since also patients with aneuploid tumors exhibited a similar good prognosis it seems that DNA measurements do not contribute additional prognostic information in young patients.

Introduction-The aim of this study was to evaluate a new thyroidectomy difficulty scale (TDS) for its inter-rater agreement, correspondence with operative times, and correlation with complications. Methods-We developed a four item, 20-point TDS. Following cases where two board-certified surgeons participated, each surgeon completed a TDS, blinded to the other's responses. Paired sets of TDS scores were compared. The relationship between operative time and TDS scores was analyzed with linear regression. Multiple regression evaluated the association of TDS scores and other clinical data with operative times. Results-A total of 119 patients were scored using TDS. In this cohort, 22.7% suffered from hyperthyroidism, 37.8% experienced compressive symptoms, and 58.8% had cancer. The median total TDS score was 8, and both surgeons' total scores exhibited a high degree of correlation. 87.4% of both raters' total scores were within one point of each other. Patients with hyperthyroidism received higher median scores compared to euthyroid patients (10 vs. 8, p<0.01). Similarly, patients who suffered a complication had higher scores compared to those patients without complications (10 vs. 8, p= 0.04). TDS scores demonstrated a linear relationship with operative times (R 2 = 0.36, p<0.01, Figure 1). Cases with a score of 14 or greater took 41.0% longer compared to cases with scores of five or less (p<0.01). In multiple regression analysis, TDS scores independently predicted operative time (p<0.01). Conclusion-The TDS is an accurate tool, and scores correlate with more difficult thyroidectomies as measured by complications and operative times.

The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors, 2) encapsulated tumors with invasion, 3)...

The translocator protein (TSPO), formerly known as a peripheral benzodiazepine receptor, exerts pro-apoptotic function via regulation of mitochondrial membrane potential. We examined TSPO expression in human thyroid tumors (25 follicular adenomas (FA), 15 follicular cancers (FC), and 70 papillary cancers (PC)). The role of TSPO in the regulation of cell growth, migration, and apoptosis was examined in thyroid cancer cell lines after TSPO knockdown with siRNA and after treatment with TSPO antagonist (PK11195). Compared with normal thyroid, the level of TSPO expression was increased in FA, FC, and PC in 24, 26.6, and 55.7% of cases respectively. Thyroid cancer cell lines demonstrated variable levels of TSPO expression, without specific association with thyroid oncogene mutations. Treatment with inhibitors of PI3K/AKT or MEK/ERK signaling was not associated with changes in TSPO expression. Treatment with histone deacetylase inhibitor (valproic acid) increased TSPO expression in TSPO-de...

We report the case of a 59-year-old man with a two-month history of a fast-growing, left-sided neck mass and a 5 mm nodule over a thyroid mass at the site of fine needle aspiration cytology performed four weeks earlier. Histopathological studies confirmed anaplastic carcinoma of the thyroid and cutaneous needle track seeding of the primary tumour. The patient succumbed to extensive disease 10 weeks after initial diagnosis. To our knowledge, this is a rare report of implantation of anaplastic thyroid carcinoma along the track of fine needle aspiration. Some factors involved in needle track seeding are: needle size; number of passes; withdrawing the needle without releasing suction; injecting the tumour at time of biopsy; and inherent characteristics of the lesion (e.g. number of cells dislodged, adhesiveness of cells, amount of stroma present, enzymes released and immunologic characteristics).

Background. Human pituitary adenomas express folate receptors (FR); therefore, we hypothesized that parathyroid (PT) tumors also might express FR, whereas normal human thyroids might not. The purpose of our study was to characterize the functionality of FRs on human PT tumors, with the goal of developing an imaging tool that would concentrate in PT more than in the thyroid. Methods. Human PTs and thyroids were evaluated for FR expression by immunohistochemistry. Expression of genes for FRa and FRb was measured with the Illumina Human HT-12 Expression Bead Chips and verified by quantitative reverse-transcription polymerase chain reaction. Folate incorporation by PT cells versus normal thyroid cells was determined by incubation with 99m Technetium (99m Tc)(CO) 3-folate and 99m Tc-Etarfolatide, and uptake was determined by gamma counting. Specific targeting of FRs was demonstrated by blocking with cold folate. A549 cells and Jurkat cells served as FR-negative controls, and KB cells and HeLa cells were FR-positive controls. Results. On immunohistochemistry and Western blotting, human PT cells expressed FRs, whereas human thyroid cells did not. The FRa gene was expressed in all PTs analyzed, and the FRb gene was expressed by most. Uptake of 99m Tc(CO) 3-folate was increased in PT cells versus thyroid cells. There was dose-dependent uptake of 99m Tc-etarfolatide, and uptake was inhibited by preincubation with cold folate, confirming FR-mediated binding. Conclusion. This is the first report of the expression and functionality of FRs on human PT cells. These findings suggest that 99m Tc-folate holds potential for localization of PT tumors preoperatively and their treatment. (Surgery 2013;154:1385-93.

Background: Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-producing C-cell tumor. In hereditary cases, a germline RET mutation is found in 98% of families. Because MTC is cured only if intrathyroidal, prophylactic thyroidectomy is recommended in the gene carrier (GC). Aims: The aim was to determine whether thyroidectomy performed when stimulated CT becomes detectable is as safe as prophylactic thyroidectomy and to identify the serum CT cutoff able to distinguish intrathyroidal from extrathyroidal MTC. Patients: Eighty-four GC were prospectively enrolled; 53 of the 84 underwent total thyroidectomy, one refused surgery, and 30 with normal basal and stimulated CT were under surveillance. The follow-up ranged from 2 to 18 yr. Results: GC operated on for elevated stimulated CT included 27 GC with a positive peak CT at the screening and four cases who became positive after 4 yr. All of them had intrathyroidal MTC and no node metastases; all were cured after a mean follow-up of 7.5 yr. Among those operated on for detectable basal CT, intrathyroidal tumors were found when CT was below 60 pg/ml, whereas either node metastases or larger tumors were observed when CT was above 60 pg/ml. No correlation among serum CT, age, and type of RET mutation was observed. Thirty GC were still biochemically negative at the annual control. Conclusions: The time of thyroidectomy in GC with negative CT could be personalized and safely planned when stimulated CT becomes positive, independent of the type of RET mutation and patient's age. In this series, a basal CT below 60 pg/ml was always associated to an intrathyroidal localization of MTC.

The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered.

Significant advances have been made in thyroid can-cer research in recent years, therefore relevant clinical guidelines need to be updated. The current Polish guidelines &quot;Diagnostics and Treatment of Thyroid Carcinoma&quot; have been formulated at the &quot;Thyroid Cancer and Other Malignancies of Endocrine Glands&quot; conference held in Wisła in November 2015 [1].

Ectopic thyroid tissue (ETT) is an uncommon entity that may be found anywhere along the line of the obliterated thyroglossal duct, usually from the tongue to the diaphragm. We performed a retrospective analysis of patients undergoing surgical treatment for thyroid disease between January 2000 and December 2013, seeking for ETT All patients with prior neck surgery or trauma were excluded. The clinic-pathologic features, prevalence and diagnosis of the lesions were collected and analyzed. Out of 3092 included patients, 28 ETT were identified (0.9%). The anatomical site of ETT was as follows: lateral cervical in 6 (21.4%), along the thyroglossal duct in 6 (21.4%), mediastinal in 5 (17.9%), lingual in 5 (17.9%), sublingualin 3 (10.7%), and submandibular in 3 (10.7%). Histopathology revealed 27 benign lesions and 1 (3.6%) papillary carcinoma. ETT is found in less than 1% of patients receiving thyroid surgery. Diagnosis of ETT requires clinical imaging. Surgery is a prudent choice due to ...

Percutaneous ethanol injection (PEI) is an alternative therapy for thyroid nodules (TN). However, some concern is raised on its carcinogenic effects. To evaluate the cytological and clinical changes caused by PEI in patients with benign TN. Thirty-nine patients with TN (23.1% hyperfunctioning) were submitted to a median of three PEI sessions. After a median of 17 months, patients were reassessed. A new ultrasound-guided fine needle biopsy (US-FNB) was performed, and the smears were analyzed after May-Grünwald-Giemsa staining. The diagnostic findings and the cellular characteristics were compared before and after treatment. There was an increase in the proportion of nondiagnostic/unsatisfactory results (from 2.5% to 18.9%). No malignant cases were observed. The proportion of moderate/intense macrophage infiltration decreased from 60% to 15%. Before treatment, 23.1% patients had hyperthyroidism, which was completely or partially resolved in 66.7%. By ultrasound, the percentage of homogeneous nodules decreased from 64.0% to 38.4% (p=0.0235), and the mean nodule volume decreased from 13.4±12.2 to 5.3±5.1 cm 3. We demonstrate that PEI increases the proportion of nondiagnostic/unsatisfactory results from US-FNB. Therefore, cytological findings after PEI must be evaluated with caution. Our results also suggest that PEI is an efficacious and safe therapeutic option, with no carcinogenic effects observed on cytological evaluations. Safety and efficacy must be evaluated in larger studies with longer follow-up periods.

INTRODUCTION-Follicular variant of papillary thyroid cancer (FVPTC) is the most common and fastest growing subtype of papillary thyroid cancer (PTC) with features of both PTC and follicular thyroid cancer (FTC). The purpose of this study was to determine the patient and tumor features associated with lymph node metastases (LNM) in FVPTC. METHODS-This was a retrospective review of adult (≥18) patients with histologically confirmed diagnoses of FVPTC within the SEER database between 1988 and 2009. LNM were defined by at least two lymph nodes with metastatic disease. To determine factors associated with LNM, we constructed a multivariate logistic regression model from significant variables (p<0.05) identified on univariate analysis. Similarly, we used a Cox proportional hazards model to understand the relative importance of LNM in determining disease specific mortality (DSM). RESULTS-Of the 20,357 cases of FVPTC with lymph node data available, 1,761 (8.7%) had LNM. 61.1% of these LNM were located in the central neck and 38.9% were in the lateral neck. Extrathyroidal extension (OR 2.6, 95% C.

The accident at Chernobyl nuclear power plant (CNPP) was the worst industrial accident of the last century that involved radiation. The unprecedented release of multiple different radioisotopes led to radioactive contamination of large areas surrounding the accident site. The exposure of the residents of these areas was varied and therefore the consequences for health and radioecology could not be reliably estimated quickly. Even though some studies have now been ongoing for 25 years and have provided a better understanding of the situation, these are yet neither complete nor comprehensive enough to determine long term risk. A true assessment can only be provided after following the observed population for their natural lifespan. In this article, we review technical aspects of the accident and provide relevant information on radioactive releases that resulted in exposure of this large population to radiation. A number of different groups of people were exposed to radiation: workers involved in the initial clean-up response, and members of the general population who were either evacuated from the settlements in the CNPP vicinity shortly after the accident, or continued to live in the affected territories of Belarus, Russia and Ukraine. Through domestic efforts and extensive international cooperation, essential information on radiation dose and health status for this population has been collected. This has permitted the identification of high-risk groups and the use of more specialized means of collecting information, diagnosis, treatment and follow-up. Since radiationassociated thyroid cancer is the one of the major health consequences of the Chernobyl accident, a particular emphasis is placed on this malignancy. The initial epidemiological studies are reviewed, as are the most significant studies and/or aid programs in the three affected countries.

Patients with celiac disease have an increased rate of malignancies that are not limited to lymphomas. Thyroid carcinoma has not previously been associated with celiac disease. However, among a cohort of patients with celiac disease, we identified an increased risk of papillary carcinoma of the thyroid, standard morbidity ratio of 22.52 (95% confidence interval 14.90-34.04; P < .001), compared to United States national surveillance data. These patients were on a gluten-free diet. Only 1 had Hashimoto's thyroiditis, suggesting that mechanisms apart from autoimmune thyroiditis contribute to the increased risk of carcinoma of the thyroid in celiac disease.

The accident at the Chernobyl nuclear power plant on April 261986, released approximately 2 EBq of "'1 and other radiaiodine isotopes that heavily contaminated southern Belarus. An increase in thyroid cancer reported in 1992 and attributed to the Chernobyl accident was challenged as possibly the result of intensive screening. We began a case-control study to test the hypothesis that the Chernobyl accident caused the increase in thyroid cancer. Records of childhood thyroid cancer in the national therapy centers in Minsk in 1992 yielded 107 individuals with confirmed pathology diagnoses and available for interview. Pathways to diagnosis were (1) routine endocrinological screening in 63, (2) presentation with enlarged or nodular thyroid in 25 and (3) an incidental finding in 19. Two sets of controls were chosen, one matched on pathway to diagnosis, the other representing the area of heavy fallout, both matched on age, sex and rural/urban residence in 1986. The "'I dose to the thyroid was estimated from ground deposition of "'Cs. ground deposition of "'I, a data bank of 19Rfi thyroid radiation measurements, questiunnaires and interviews. Highly significant differences were observed between cases and controls (both sets) with respect to dose. The differences persisted within pathway to diagnosis, gender, age and year of diagnosis, and level of iodine in the soil, and were most marked in the southern portion of the Gomel region. The case<ontrol comparisons indicate a strong relationship between thyroid cancer and estimated radiation dose from the Chernobyl accident. o 1~98 b RNI~* w tirnty

Brief Communications Conclusion The management of fungal keratitis after PRK depends on many factors: In our experience, the decision of performing a prompt keratoplasty was aimed at reducing the corneal infection in the first occurrence, and to solve it in the second manifestation. Finally the use of intracameral antifungal medication proved to be very effective in avoiding the recurrence of infection.

Background-Hürthle cell neoplasms (HCNs) are rare tumors of the thyroid gland. The definitive treatment for Hürthle cell carcinoma (HCC) is total thyroidectomy, while thyroid lobectomy is adequate for Hürthle cell adenoma (HCA). However, differentiating HCC from HCA either before or during surgery is a challenge. The purpose of this study was to identify factors that predict malignancy in patients with HCN. Methods-Between May 1994 and January 2007, 1,199 patients underwent thyroid surgery at an academic medical center. Medical records of 55 consecutive patients who underwent thyroid resections for the preoperative diagnosis of HCN were reviewed. Results-Of the 55 patients with HCN, 46 (84%) had adenomas and 9 (16%) had carcinomas. Patients with HCC were significantly older than those with HCA (66 ± 6 years versus 53 ± 2 years, P = 0.01). Patients with carcinoma also had significantly larger thyroid nodules (4.5 ± 0.7 cm versus 2.5 ± 0.2 cm, P < 0.001). All HCNs less than 2 cm in diameter were benign. The malignancy rate increased with nodule size: 18% of nodules measuring 2-4 cm, and 44% of those larger than 4 cm were HCC. One patient with HCC had recurrence of the disease, but there were no disease-related deaths. Conclusion-Advanced patient age and larger nodule size are two important factors that predict malignancy in patients with HCN. In patients with these and other known risk factors for HCC, total thyroidectomy should be considered.

BACKGROUND: To date, thyroid fine-needle aspiration (FNA) has been used by clinicians as the screening test of choice to determine whether surgery is required and this is what the pathology report should communicate. Standard terminology for reporting thyroid FNA has not been implemented yet, and pathologists have used various reporting systems to communicate results. A significant source of confusion among both pathologists and clinicians has been the use of the indeterminate category. On the basis of an analysis of 1150 thyroid FNAs in 2000, this institution modified the reporting of thyroid biopsy results into 6 categories, including unsatisfactory. The indeterminate category was separated into 3 subroups: 1) indeterminate for neoplasia (IND), 2) follicular neoplasm (FN), and 3) suspicious for malignancy (SUSP). Repeat FNA in 6 months to 12 months was recommended for IND and surgery for FN and SUSP categories. METHODS: To determine the validity of this approach, the outcomes of this reporting system from July of 2000 to December of 2006 were analyzed. The IND category was used for 2 subsets of cases: (a) those that morphologically fall into the gray zone between adenomatoid nodule (AN) and FN, for Hurthle cell nodule (hyperplasia vs neoplasm), and chronic lymphocytic thyroiditis with concern for neoplasia; and (b) for suboptimal specimens due to low epithelial cellularity or collection artifacts. RESULTS: Among 5194 thyroid nodules, the IND category comprised 18%. FNA follow-up was done in 21% of IND cases: 58% were benign/negative and did not require surgery based on cytology alone. Surgical follow-up in 46% of IND showed 52% were benign/negative, and 42% were follicular/Hurthle cell adenomas. The surgical yield of malignancy in IND was low (6%) when compared with the FN category, which was 14% (more than 2Â that of the IND category), and the SUSP category, which was 53% (almost 9Â that of the IND category). CONCLUSIONS: A 6-tier reporting system for thyroid FNA was effective for determining which patients needed surgery versus follow-up FNA and also guided the clinician on the

Macrofollicular variant of papillary thyroid carcinoma (PTC) is an uncommon, recently described thyroid tumor. By frozen section it can be confused easily with goiter or macrofollicular adenoma. A 41-year-old female presented with a huge mass in the right thyroid lobe, cold on scintigraphy. By fine needle aspiration fluid was obtained. Smears of the sediment of the fluid showed epithelial cells with morphologic features diagnostic of PTC. Frozen section diagnosis was benign. This is the first reported case of macrofollicular variant of PTC diagnosed preoperatively by cytology. In our case the cytology was similar to that of cystic PTC.

Clinicians have long sought to characterize biological markers of neoplasia as objective indicators of tumor presence, pathogenicity, and prognosis. Armed with data that correlate biomarker activity with disease presence and progression, clinicians can develop treatment strategies that address risks of disease recurrence or persistence and progression. The B-type Raf kinase (BRAF V600E) mutation in exon 15 of the BRAF gene has been noted to be a putative prognostic marker of the most prevalent form of thyroid cancer, papillary thyroid cancer (PTC)Va tumor type with high proclivity for recurrence or persistence. There has been a remarkable interest in determining the association of BRAF mutation with PTC recurrence or persistence. Using many new studies that have been published recently, we performed a meta-analysis to investigate correlations of BRAF mutation status with PTC prognosis, focusing on the recurrence or persistence of the disease after initial treatment. The study was based on published studies included in the PubMed and Embase databases addressing the BRAF mutation and the frequency of recurrence of PTC. We selected studies with data that enabled measurement of the risk ratio for recurrent disease. We also analyzed the factors that are classically known to be associated with recurrence. These factors included lymph node metastasis, extrathyroidal extension, distant metastasis, and American Joint Committee on Cancer (AJCC) stages III/IV. We used 14 articles that included an analysis of these factors as well as PTC recurrence data, with a total of 2470 patients from 9 different countries. The overall prevalence of the BRAF mutation was 45%. The risk ratios in BRAF mutation-positive patients were 1.93 (95% confidence interval ECI^, 1.61Y2.32; Z = 7.01; p G 0.00001) for PTC recurrence, 1.32 (95% CI, 1.20Y1.45; Z = 5.73; p G 0.00001) for lymph node metastasis, 1.71 (95% CI, 1.50Y1.94; Z = 8.09; p G 0.00001) for extrathyroidal extension, 0.95 (95% CI, 0.63Y1.44; Z = 0.23; p = 0.82) for distant metastasis, and 1.70 (95% CI, 1.45Y1.99; Z = 6.46; p G 0.00001) for advanced stage AJCC III/IV. Thus, in this meta-analysis, the BRAF mutation in PTC was significantly associated with PTC recurrence, lymph node metastasis, extrathyroidal extension, and advanced stage AJCC III/IV. Patients with PTC harboring mutated BRAF are likely to demonstrate factors that are associated with an increased risk for recurrence of the disease, offering new prospects for optimizing and tailoring initial treatment strategies to prevent recurrence.

Signet ring cells (SRCs) can be seen in a variety of thyroid tumors and can pose a diagnostic pitfall on cytology. This study describes the cytologic, histomorphologic, and molecular aspects of a cohort of primary thyroid tumors with SRCs. A search was performed of the Massachusetts General Hospital and Brigham and Women&#39;s Hospital (Boston, MA) pathology archives for the keywords thyroid, signet, and signet ring features between 2000 and 2014. Seven thyroidectomy specimens with corresponding thyroid fine-needle aspiration (FNA) were obtained. Cytology and histopathology slides were evaluated. Molecular analysis was performed using anchored multiplex polymerase chain reaction (AMP). The cohort consisted of four follicular adenomas (FAs), two noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), and one secretory carcinoma (SC). The FNA diagnoses were atypia of undetermined significance (n = 3), suspicious for follicular neoplasm (n = 3), and susp...

Obesity and thyroid diseases are common disorders in the general population and they frequently occur in single individuals. Alongside a chance association, a direct relationship between &#39;thyroid and obesity&#39; has been hypothesized. Thyroid hormone is an important determinant of energy expenditure and contributes to appetite regulation, while hormones and cytokines from the adipose tissue act on the CNS to inform on the quantity of energy stores. A continuous interaction between the thyroid hormone and regulatory mechanisms localized in adipose tissue and brain is important for human body weight control and maintenance of optimal energy balance. Whether obesity has a pathogenic role in thyroid disease remains largely a matter of investigation. This review highlights the complexity in the identification of thyroid hormone deficiency in obese patients. Regardless of the importance of treating subclinical and overt hypothyroidism, at present there is no evidence to recommend pha...

Introduction.-Dyshormonogenetic goiter is a genetically determined thyroid hyperplasia due to an enzyme defect in thyroid-hormone synthesis. Malignant transformation is one of the most serious complications, rarely reported in the literature. Observation.-We report a new case of a 13-year-old boy with goitrous hypothyroidism who consulted for a voluminous goiter. Total thyroidectomy was performed. Histopathological examination revealed multiple foci of papillary carcinoma with a lymph node metastasis. Conclusion.-Dyshormonogenetic goiter is a rare entity, representing one of the causes of congenital hypothyroidism. It is morphologically characterized by architectural and cellular pleomorphism that may mimic thyroid malignancy and cause difficulties in differential diagnosis.

Radioactive iodine (131 I) targets the thyroid gland and has been proven to play an effective role in the treatment of differentiated papillary and follicular cancers. Simultaneously, this radioisotope hones in on the salivary glands where it is concentrated and secreted into the saliva. Dose related damage to the salivary parenchyma results from the 131 I irradiation. Salivary gland swelling and pain, usually involving the parotid, can be seen. The symptoms may develop immediately after a therapeutic dose of 131 I and/or months later and progress in intensity with time. In conjunction with the radiation sialadenitis, secondary complications reported include xerostomia, taste alterations, infection, increases in caries, facial nerve involvement, stomatitis, candidiasis, and neoplasia. Prevention of the 131 I sialadenitis may involve the use of sialogogic agents to hasten the transit time of the radioactive iodine through the salivary glands. However, studies are not available to delineate the efficacy of this approach. Recently, amifostine has been advocated to prevent the effects of irradiation. Treatment of the varied complications that may develop encompass numerous approaches and include gland massage, sialogogic agents, duct probing, antibiotics, mouthwashes, good oral hygiene, and adequate hydration.