IMMUNOHISTOCHEMICAL MARKERS AND SPECT/CT SOMATOSTATIN-RECEPTOR (99MTC-TEKTROTYD) UPTAKE IN WELL AND MODERATELY DIFFERENTIATED NEUROENDOCRINE TUMORS.

Context: Diagnosis of primary NETs (neuroendocrine tumors) is challenging and often late due to tumor heterogeneity, and a wide variety of general symptoms. Low grade NETs are often indolent and have a good prognosis, especially in the early stages. Even so, some tumors are diagnosed using SPECT/CT either in the metastatic stage or directly as a metastasis with an unknown primary tumor. Objective: This study aims to characterize well and moderately differentiated NETs, using Tektrotyd SPECT/CT imaging as well as from the viewpoint of NET immunohistochemical biomarker expression. Design: Patients diagnosed with low grade neuroendocrine tumors (carcinoids) investigated over a period of 2 years, using SPECT/CT with 99mTc-EDDA/HYNIC-Tyr3-Octreotide (Tektrotyd) and confirmed through at least two immunohistochemical neuroendocrine markers were evaluated. Subjects and Methods: Twenty-seven cases with neuroendocrine tumors were analyzed. Four patients met the inclusion criteria. Staining intensity was scored using a weak, moderate, or strong scoring system. CD56 was quantified using criteria derived from Her2 cell membrane staining evaluations. Results: Patients included in the study had two well differentiated (G1) NETs and two moderately differentiated (G2) NETs. SPECT/CT with Tektrotyd showed variable intensity ranging from discreet to strong. All tumors expressed chromogranin A with at least moderate intensity, weak to moderate intensity for synaptophysin and variable CD56 intensity. Conclusions: Chromogranin A and synaptophysin staining patterns may aid in primary tumor identification. CD56 stain intensity showed an inverse correlation with Tektrotyd uptake in carcinoids. Additional studies merit further investigation for use in clinical settings.

FOLLICULAR THYROID CARCINOMA - CLINICAL AND DIAGNOSTIC FINDINGS IN A 20-YEAR FOLLOW UP STUDY.

CONTEXT: Follicular thyroid carcinomas (FTC) represent 6-10 % of all thyroid carcinomas; the evolution of FTC is quite controversial, partly due to frequent changes of the histopathological definition (minimally invasive-MIFTC or widely invasive carcinoma-WIFTC) and treatment strategies adjustments. OBJECTIVE: This research aims to examine the diagnostic procedure, therapeutic attitude and survival rates of patients with FTC, over a period of 16 years in the same institution, with a follow-up of at least 4 years, by analyzing correlations between histology subtype, treatments and the rate of recurrent disease. SUBJECTS AND METHODS: We have studied 5891 patients with thyroid carcinomas who have undergone surgical or oncological treatment within the institution, between 1st January 2000 - 31st December 2015; among them we found 133 patients (2.25%) with "pure" follicular thyroid carcinoma: 114 (86%) women and 19 (14%) men, with a female-male ratio of 6:1. The age of the patients ranged from 10 to 76 years, with an average of 47.8 years. Statistical analysis was done comparing differences among groups of MIFTC and WIFTC. RESULTS: There was an unexpected high percentage of WIFTC and also an increased number of biochemically persistent and/or recurrent disease in patients with MIFTC. A stronger correlation was observed with the tumour dimensions, rather than with the histopathological subtype. CONCLUSIONS: This research observed that overall survival was associated with tumour size rather than histopathological subtype and there is an important need to perform further studies to assess the effectiveness of treatment strategies.

18F-FDG PET/CT IN DIFFERENTIATED THYROID CARCINOMA.

AIM: Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) become an important tool in oncology by combining the metabolic information from 18F-FDG PET with the morphological information of CT. The main objective of this study was to assess the diagnostic value of PET/CT in patients with differentiated thyroid carcinoma (DTC). MATERIAL AND METHODS: We analyzed 173 PET/CT scans of patients with DTC presenting elevated thyroglobulin (Tg) levels, negative Tg-antibodies levels, negative Iodine-131 whole-body scanning (I-131 WBS) and without any signs of clinical or other imaging technique for tumor recurrence/metastases. RESULTS: PET/CT scans were positive in 38% of cases (65/173). The sensitivity, specificity, positive predictive values and the accuracy of PET/CT imaging were 88.09%, 98.6%, 93.1% respectively 96.53%. After the PET/CT scan 29 patients underwent surgery, 24 of them continued radio-iodine therapy, 5 patients initiated tyrosine kinase inhibitors treatment and external radiotherapy. CONCLUSION: 18F-FDG PET/CT is a valuable imaging technique which has the capability of identifying those cases of thyroid recurrence/metastases with elevated Tg levels and negative I-131 WBS. The treatment strategy was changed in 89.2% cases of positive PET/CT scans which shows us that 18F-FDG PET/CT imaging should be integrated into the follow-up programs for DTC patients.

CIRCULATING TUMOR CELLS IN MINIMALLY INVASIVE FOLLICULAR THYROID CARCINOMA AND BENIGN THYROID TUMORS WITH A FOLLICULAR PATTERN: PILOT EXPERIENCE.

PURPOSE: Minimally invasive follicular thyroid carcinomas (MIFCs) are uncommon; literature offers limited guidance on their natural history and management. Starting January 2015 we measured circulating tumor cells (CTCs) in patients with MIFC (n=22) or benign thyroid tumors with follicular features (n=4). METHODS: In a retrospective analysis, we assessed detectability of and serial changes in CTC, compared demographic/clinical differences between CTC-positive versus CTC-negative subgroups using Student's t-test, and examined correlations between CTC status and serum thyroglobulin using Spearman's test. CTCs were quantitated via immunomagnetic separation/microscopic inspection. RESULTS: Thirteen patients (50%: 12/22 MIFC, 1/4 benign tumor) were initially CTC-positive; 3 remained CTC-positive in ≥1 subsequent measurement. CTC-positive patients had larger tumors and more frequent multifocality and vascular invasion versus CTC-negative patients (n=13). However, no tested variable differed significantly between the subgroups. After 17.2±10.5 months, neither subgroup showed evidence of disease. Significant correlation was absent (p ≥ 0.263) between CTC and Tg negativity (r = 0.243; n=13 evaluable) or initial CTC positivity and Tg positivity (r = -0.418; n=9 evaluable). CONCLUSIONS: In the studied settings, CTC measurement is feasible, has unclear clinical/outcome implications, but may provide different information versus thyroglobulin testing. Lengthier assessment is warranted in larger series.

Iodine status and thyroid nodules in females: a comparison of Cyprus and Romania.

OBJECTIVES: The increased comparative prevalence rates of thyroid cancer in Cyprus (>EU average) led us to conduct this study on possible risk factors of thyroid nodules. Romania served as a reference with a comparative thyroid cancer prevalence < EU average. This study aimed to assess the association between urinary iodine (UI) and thyroid nodules in adult females (n = 208) from Cyprus and Romania. STUDY DESIGN: A case-control study (n = 208). METHODS: Cases were females with ultrasound-confirmed thyroid nodules and controls with confirmed absence of nodules. In both countries, subjects underwent ultrasound medical examinations, completed a questionnaire and offered a spot urine sample. RESULTS: Median UI level in Cyprus was 94 µg/L, whereas 32% of the Cypriot UI was < 50 µg/L, classifying the population as mildly iodine deficient. In Romania, both cases and controls were iodine sufficient. No significant differences (P > 0.05) in serum free thyroxin (fT4) and thyroid stimulating hormone (TSH) levels were found between cases and controls. Cases had lower median TSH levels compared with controls (1.4 mIU/L and 1.7 mIU/L, P = 0.060), but serum TSH and free thyroxin levels were within normal range. Albeit non-significant, participants with inadequate UI (<100 µg/L) had increased risk for thyroid nodules (odds ratio = 1.40, 95% confidence interval = 0.70, 2.81, P = 0.346), using multiple logistic regression after adjusting for age, body mass index, education, country and serum TSH. CONCLUSIONS: This was the first study to quantify UI levels in Cyprus. While the Romanian iodine fortification programme reflected onto its UI levels, a representative assessment of iodine status in Cyprus will address the necessity of an iodine fortification programme.

EVALUATION OF CARDIOVASCULAR RISK AND MYOCARDIAL PERFUSION IN PATIENTS WITH RADICALLY TREATED DIFFERENTIATED THYROID CARCINOMA AND REPEATED EPISODES OF IATROGENIC HYPOTHYROIDISM.

CONTEXT: Patients with radically treated differentiated thyroid carcinoma (DTC) undergo multiple episodes of iatrogenously-acquired hypothyroidism for the oncological follow-up. In some patients, this elevates high-sensitive C-reactive protein (hsCRP), a cardiovascular risk biomarker. OBJECTIVE: We wanted to determine if there is any correlation between repeated hypothyroidism episodes, elevated hsCRP and an increased cardiovascular risk as stated through myocardial perfusion. DESIGN: Between July 2014-January 2015, we analyzed serological levels of hsCRP for identifying our patients' cardiovascular risk; we performed a myocardial perfusion scintigraphy to observe the alterations. SUBJECTS AND METHODS: We included 27 patients (n=27), mean age of 52±10: CI (95%),14 female, all disease- free after thyroidectomy, radioiodine ablation and chronic thyroid hormone treatment. We assigned the cardiovascular risk category for each patient according to hsCRP levels; all patients underwent a myocardial perfusion scintigraphy in order to determine the cardiac perfusion index (CPI). RESULTS: hsCRP has been higher in > 65 years old male patients with more than 5 thyroid hormone withholdings. hsCRP is significantly associated with CPI (p=0.001). Spearman's rank correlation indicates a strongly positive linear correlation between these two parameters (r=0.745). CONCLUSIONS: Repeated thyroid hormonal withdrawals in patients with DTC during the long-term follow-up elevated hsCRP at cardiovascular risk levels, having an impact on myocardial perfusion.

Incidental papillary thyroid microcarcinoma: is completion surgery required?

BACKGROUND: The indications for completion surgery in patients with thyroid papillary microcarcinoma (PMC), incidentally found in thyroids removed for benign conditions, remains a subject of debate. METHODS: In a retrospective, transversal, cohort study of 187 incidental PMCs, found during histological examination of the thyroid gland in 2168 patients operated for benign thyroid conditions, we evaluated the influence of initial and completion surgery on pathological features associated to local recurrence and cancer-related mortality. RESULTS: In the patients with almost total or total thyroidectomy at the first operation, lymphadenectomy of lymph nodes with features suggestive of malignancy on postoperative ultrasound resulted in a statistically significant (p 0.01) increase of node positive patients in pathological examination. Completion surgery in 38 out of 42 patients who underwent less than a total thyroidectomy doesn't result in a significant increase of tumor size, number, multifocality, bilaterality, invasion or nodal metastases. There were no significant differences in postoperative complications between the two groups. CONCLUSIONS: In patients with less than total thyroidectomy and incidentally found PMC in resection specimens, 1-5 mm in greatest dimension and without extrathyroidal extension, completion surgery was not followed by a significant increase of pathological features associated to cancer related morbidity and mortality.

Highly-sensitive C-reactive protein, a biomarker of cardiovascular disease risk, in radically-treated differentiated thyroid carcinoma patients after repeated thyroid hormone withholding.

AIMS: In patients radically treated for differentiated thyroid carcinoma, we assessed the response of highly-sensitive C-reactive protein, an inflammatory biomarker for cardiovascular risk, after thyroid hormone withholding ("deprivation"), as well as factors potentially influencing this response. MATERIAL AND METHODS: We included 52 adults (mean age 45.6±14.0 years, 35 females) who were disease-free after total thyroidectomy, radioiodine ablation and chronic thyroid hormone therapy. They were lifelong non-smokers without apparent inflammatory comorbidity, cardiovascular history beyond pharmacotherapy-controlled hypertension, anti-dyslipidemic medication, or C-reactive protein >10 mg/L in any study measurement. The index deprivation lasted ≥2 weeks, elevating serum thyrotropin >40 mIU/L or ≥100 × the individual's suppressed level. We examined the relationship of age, number of prior deprivations, and gender with the magnitude of post-deprivation C-reactive protein concentration through multivariable statistical analyses using the F test on linear regression models. RESULTS: Post-deprivation, C-reactive protein reached intermediate cardiovascular risk levels (based on general population studies involving chronic elevation), 1-3 mg/L, in 44.2% of patients and high-risk levels, >3 mg/L, in another 17.3%. Mean C-reactive protein was 1.77±1.50 mg/L, differing significantly in females (2.12±1.66 mg/L) vs. males (1.05±0.69 mg/L, P <0.001). In multivariable analysis, patients ≤45 years old (odds ratio, 95% confidence interval 0.164 [0.049-0.548]) were less likely, and females, more likely (3.571 [1.062-12.009]) to have post-deprivation C-reactive protein ≥1 mg/L. CONCLUSIONS: Thyroid hormone withdrawal frequently elevated C-reactive protein to levels that when present chronically, were associated with increased cardiovascular risk in general population studies.