NDRG1 protein overexpression in malignant thyroid neoplasms

OBJECTIVES:

The aim of this study was to examine the expression of the N-myc downstream-regulated gene 1 protein in benign and malignant lesions of the thyroid gland by immunohistochemistry.

INTRODUCTION:

N-myc downstream-regulated gene 1 encodes a protein whose expression is induced by various stimuli, including cell differentiation, exposure to heavy metals, hypoxia, and DNA damage. Increased N-myc downstream-regulated gene 1 expression has been detected in various types of tumors, but the role of N-myc downstream-regulated gene 1 expression in thyroid lesions remains to be determined.

METHODS:

A tissue microarray paraffin block containing 265 tissue fragments corresponding to normal thyroid, nodular goiter, follicular adenoma, papillary thyroid carcinoma (classical pattern and follicular variant), follicular carcinoma, and metastases of papillary and follicular thyroid carcinomas were analyzed by immunohistochemistry using a polyclonal anti- N-myc downstream-regulated gene 1 antibody.

RESULTS:

The immunohistochemical expression of N-myc downstream-regulated gene 1 was higher in carcinomas compared to normal thyroid glands and nodular goiters, with higher expression in classical papillary thyroid carcinomas and metastases of thyroid carcinomas (P < 0.001). A combined analysis showed higher immunohistochemical expression of NDRG1 in malignant lesions (classical pattern and follicular variant of papillary thyroid carcinomas, follicular carcinomas, and metastases of thyroid carcinomas) compared to benign thyroid lesions (goiter and follicular adenomas) (P  =  0.043). In thyroid carcinomas, N-myc downstream-regulated gene 1 expression was significantly correlated with a more advanced TNM stage (P  =  0.007) and age, metastasis, tumor extent, and size (AMES) high-risk group (P  =  0.012).

CONCLUSIONS:

Thyroid carcinomas showed increased immunohistochemical N-myc downstream-regulated gene 1 expression compared to normal and benign thyroid lesions and is correlated with more advanced tumor stages.     

Enzymatic activity of type 1 iodothyronine deiodinase in selected liver tumors

Introduction

Type 1 iodothyronine deiodinase (D1) converts thyroxin (T4) into tri-iodothyronine (T3). Strong evidence indicates that thyroid hormone metabolism is disturbed in neoplasms such as thyroid and breast cancer. However, there is limited data concerning the function of the D1 enzyme in liver tumors. We aimed to estimate the enzymatic activity of D1 in two different common liver tumors.

Material and methods

We obtained 20 tumor samples from patients who had undergone a liver resection. Of the tissue samples, there were 13 benign lesions of focal nodular hyperplasia (FNH) and 7 malignant lesions of hepatocellular carcinomas (HCC). The D1 activity was assessed by measuring the amount of radioactive iodine released in reaction to D1-catalysed deiodination. Groups were compared by the Mann-Whitney non-parametrical test for independent trials, and the Kruskal Wallis test.

Results

The enzymatic activity of D1 was not significantly altered in the FNH group (median = 536 fmol/mg of protein/min; p = 0.972) and HCC group (367 fmol/mg; p = 0.128) when compared to matched normal liver parenchyma controls (546 fmol/mg and 556 fmol/mg, respectively).

Conclusions

Liver parenchyma expresses high levels of D1. The results clearly revealed that D1 activity was not significantly different between benign and malignant tumors (FNH and HCC) compared to healthy liver parenchyma cells.     

Total thyroidectomy as the single surgical option for benign and malignant thyroid disease: a surgical challenge

Introduction

Total thyroidectomy has been the treatment of choice for patients with malignant thyroid disease. However, the efficacy and safety of this procedure for patients with benign disease is still a matter of debate. The aim of this study is to show that total thyroidectomy can be safely performed for both malignant and benign disease.

Material and methods

A retrospective study on 216 patients was conducted. Once an indication for surgery was established, our single surgical treatment was total thyroidectomy. Age, sex, nature of thyroid disease, final pathology and postoperative complications were recorded.

Results

For both benign and malignant disease, total thyroidectomy resulted in no permanent laryngeal nerve injury and no permanent hypoparathyroidism. Temporary laryngeal nerve palsy occurred in 0.9% and 3% of patients with benign and malignant disease respectively (p = 0.245). Six percent of patients with benign and 10.0% of patients with malignant thyroid disease suffered temporary hypoparathyroidism (p = 0.280). Immediate reoperation for postoperative hemorrhage was performed in 1.7% of patients with benign disease and in 1.0% of patients with malignancy with an uneventful outcome (p = 0.650).

Conclusions

When performed by surgeons experienced in endocrine surgery, total thyroidectomy may be considered as the treatment of choice for both malignant and benign thyroid disease requiring surgical treatment. Total thyroidectomy virtually eliminates the requirement of completion thyroidectomy for incidentally diagnosed thyroid carcinoma and significantly reduces the rate of reoperation for recurrent disease, as it provides an immediate and permanent cure for all benign thyroid diseases, with a low incidence of postoperative complications.     

Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas

OBJECTIVES:

Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3⁺ lymphocyte infiltration in differentiated thyroid carcinoma cells.

METHODS:

We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues.

RESULTS:

We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3⁺ lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion, and in patients with concurrent chronic lymphocytic thyroiditis.

CONCLUSIONS:

We demonstrated FoxP3 expression in differentiated thyroid carcinoma cells and found evidence that this expression may exert an important influence on several features of tumor aggressiveness.     

Endoscopic thyroidectomy via an axillo-breast approach without gas insufflation for benign thyroid nodules and micropapillary carcinomas: preliminary results

Purpose

To examine the feasibility of endoscopic thyroidectomy (ET) via an axillo-breast approach without gas insufflation for large thyroid tumors and micropapillary carcinomas.

Materials and Methods

The patients in the benign group were separated into groups 1 (n=95, <4 cm in tumor diameter) and 2 (n=37, ≥4 cm in tumor diameter). Also, 57 patients in the micropapillary carcinoma group underwent an endoscopic hemithyroidectomy (HT) (group 3) and were compared with 60 patients who received conventional open HT (group 4). Postoperative functional outcome, local complications, surgical outcomes, and pathological outcomes were compared between the groups.

Results

In the benign group, there was no significant difference in mean operating time, hospital stay, or overall perioperative complications between the two groups. In the micropapillary carcinoma group, mean operating time and hospital stay in group 3 were significantly longer than in group 4 (p=0.015 and p≤0.001). The overall perioperative complications did not differ significantly between the groups. The postoperative cosmetic result was better in groups 1-3 (endo group) than in group 4 (open group).

Conclusion

ET via a gasless axillo-breast approach seems to be a safe procedure even for benign thyroid lesions ≥4 cm and micropapillary carcinomas. Although it has the advantage of better cosmetic results over open thyroidectomy, there is room for improvement in terms of lessening its invasiveness and shortening the operative time.     

Prevalence of thyroid cancer at a medical screening center: pathological features of screen-detected thyroid carcinomas

Purpose

To assess the incidence of thyroid malignancy in an adult population screened by high-resolution ultrasonography at a medical screening center and to compare the clinical and pathological features of screen-detected thyroid carcinomas to symptomatic overt thyroid carcinomas.

Materials and Methods

We calculated the prevalence of screen-detected thyroid cancer at a medical screening center using high-resolution ultrasonography and fine needle aspiration. We then compared the clinical and pathological features of screen-detected thyroid cancers (n = 46) to clinical symptomatic thyroid cancers (n = 157). We evaluated age, gender, size, perithyroidal extension, lymphovascular extension, stage, histological lymph node metastasis, and the type of cancer. We also compared the above findings of micropapillary carcinomas to papillary thyroid carcinomas that were larger than 1 cm in diameter.

Results

Screen-detected thyroid nodule patients were 2,747 (37%) of 7,491 patients. Nodules selected for fine needle aspiration were 658 and cytology confirmed malignancy were 79 (12%) nodules. When screen-detected thyroid cancers (n = 46) were compared to symptomatic overt thyroid cancers (n = 157), only statistically significant factor was size (p = 0.002). Papillary thyroid carcinomas that were larger than 1 cm had more frequent capsular invasion (p = 0.000) and a higher stage (p = 0.027), and a higher prevalence of lymph node metastases (p = 0.002).

Conclusion

Screen-detected thyroid cancers should be managed as same as symptomatic thyroid cancers in respect to size, and an assessment should strictly be based on the ultrasound features and fine needle aspiration biopsy findings.     

23-year experience on diagnosis and surgical treatment of benign and malignant cardiac tumors

Introduction

Although myxoma is the most frequent cardiac tumor, other conditions should be taken into consideration in the differential diagnosis. Transthoracic echocardiography (TTE), followed by transesophageal echocardiography (TEE) remain the principal methods for cardiac tumor screening and visualizing. The aim of the study was to compare the diagnostics, surgical treatment and prognosis of malignant and benign cardiac tumors.

Material and methods

From 1986 to 2009 there were 121 patients with cardiac tumors operated on in the Cardiac Surgery Clinic of the Medical University in Lodz. Patients were referred to surgery mainly on the basis of the TTE and TEE image. In 4 cases valvular prosthesis implantation or valve repair were carried out. Patients remained under long-term observation in the Cardiac Surgery Outpatient Clinic.

Results

Myxoma was diagnosed in 114 cases. Malignancies were discovered in 7 cases. The left atrium was the most frequent localization. The echocardiographic image differed significantly in benign and malignant tumors. The postoperative period was complicated by embolic events or myocardial infarctions. Only malignant tumors were associated with mortality due to cardiovascular events. The survival for malignant tumors was significantly shorter.

Conclusions

Short and long-term results of operative treatment are very good for benign tumors in contrast to cardiac malignancies. The TTE and TEE image can be very significant in the final diagnosis.     

Development of Thyroid-Associated Ophthalmopathy in Patients Who Underwent Total Thyroidectomy

Purpose

To report clinical characteristics of thyroid-associated ophthalmopathy (TAO) in patients who previously underwent total thyroidectomy for thyroid cancer or a benign mass of the thyroid.

Materials and Methods

Of the patients who were diagnosed with TAO from March 2008 to March 2012, we performed a retrospective chart review on those who had undergone total thyroidectomy for thyroid cancer or a benign mass of the thyroid before the occurrence of ophthalmopathy.

Results

Of the 206 patients diagnosed with TAO, seven (3.4%) met the inclusion criteria. The mean age of the subjects was 47.4 years, and all were female. Six patients were diagnosed with papillary thyroid cancer, and one was diagnosed with a benign mass. The duration between total thyroidectomy and onset of TAO ranged from 3-120 months (median 48 months). Ophthalmic manifestations varied among cases. Except for the patient who was diagnosed with a benign mass, all patients showed hyperthyroid status and were under Synthroid hormone treatment at the time of TAO development. Five of these six patients had positive levels of thyroid-stimulating hormone (TSH) receptor autoantibodies.

Conclusion

TAO rarely develops after total thyroidectomy, and the mechanism of TAO occurrence is unclear. However, most patients showed abnormalities in thyroid function and TSH receptor autoantibodies.     

Assessment of the argyrophilic nucleolar organizer region area/nucleus ratio in ovarian serous epithelial adenomas,borderline tumors and cancers

Introduction

There is a need to assess the value of the novel potentially useful biomarkers in ovarian tumors. The aim of study was to assess the value of sAgNOR analysis in ovarian serous epithelial tumors.

Material and methods

The analysis was performed in ovaries from 113 patients treated operatively due to serous ovarian tumors (30 adenomas, 14 borderline tumors and 69 cancers). After silver staining of paraffin specimens from surgery, sAgNOR in tumor cells was analyzed. Additionally, the value of the argyrophilic nucleolar organizer region area/nucleus ratio (sAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in 52 patients with serous ovarian cancer with complete follow-ups in November 2009 was evaluated. Age, grading, radicality of surgery and FIGO staging were analyzed as additional factors.

Results

sAgNOR in adenomas, borderline tumors and cancers was in the following ranges: (0.73 ±0.23) × 10⁶, (0.81 ±0.18) × 10⁶ and (0.96 ±0.33) × 10⁶ [AgNOR/cm²] respectively. In cancers from G1 to G3 sAgNOR was (1.02 ±0.32) × 10⁶ (G1), (0.98 ±0.37) × 10⁶ (G2) and (0.82 ±0.24) × 10⁶ (G3) [AgNOR/cm²] respectively. In univariate analysis, but not in multivariate analysis, staging negatively correlated with better DFS and OS. sAgNOR, age of patients, grading and radicality of surgery were not associated with DFS or OS in either univariate or multivariate analysis.

Conclusions

sAgNOR analysis is not sufficient to precisely characterize cellular kinetics in serous ovarian tumors, and the analysis of sAgNOR, mAgNOR and pAgNOR should be performed commonly. The prognostic significance of sAgNOR in patients with serous ovarian cancer was not proven.     

The impact of lesion vascularisation on tumours detection by electrical impedance scanning at 200 Hz

Objective:

Cancer cells exhibit altered local dielectric properties compared to normal cells. These properties are measurable as a difference in electrical conductance using electrical impedance scanning (EIS). EIS is at present not sufficiently accurate for clinical routine despite its technological advantages. To modify the technology and increase its accuracy, the factors that influence precision need to be analysed and identified. While size, depth, localisation and invasiveness affect sensitivity, vascularisation might show an increased conductance and thus might affect specificity.

Subjects and Methods:

All patients were investigated with EIS (TransScan TS 2000, Migdal Ha Emek, Israel) Planned DCE-MRI prior to histological clarification were included (295 lesions). Dynamic enhancements were assigned scores after analysis of subtracted images after application of Gd-DTPA. D1: strong enhancement of >100% from initial signal obtained on native T1weighted sequence; D2: moderate enhancement 50-100%; D3: enhancement similar to glandular tissue, <50%; D4: subtle or no enhancement, less then surrounding glandular tissue.

Results:

89/113 malignant and 107/182 benign findings were visible by a focal increased conductance and/or capacitance using EIS (Sensitivity 79%, Specificity 59%). DCE-MRI was aborted due to claustrophobia in 17/295 cases. MR was used and out of 278 completed MR examinations, 101/104 malignant and 141/174 benign lesions were correctly diagnosed as benign or malignant leading to a sensitivity of 97% and a specificity of 81%. D1 benign lesions were positive in EIS in 33/55 cases suggesting a specificity of 44.4%. This value increases significantly with decreased vascularity to 68.9% (D2-4; 82/119). Out of 60 fibroadenomatous lesions, 10/23 fibroadenomas in class 1 had no focal increased conductance or capacitance and were thus considered as non-suspicious in EIS. The same result was applicable for the 29/37 benign lesions with a D2-4 contrast uptake (43.5% vs. 78.4%, p<.01).

Conclusion:

Vascularisation influences the measurable conductance at low frequency and therefore partially causes the insufficiently low specificity of EIS. Impedance measurements at frequencies in a range of 0.1 KHz to 1 MHz are required . According to theoretical and in vitro studies this might increase the accuracy of EIS technology. © 2007 Biomedical Imaging and Intervention Journal. All rights reserved.     

Prognostic role of phospho-PRAS40 (Thr246) expression in gastric cancer

Introductions

Phospho-PRAS40^Thr246 (phosphorylated proline-rich Akt substrate of 40 kilodaltons at Thr246) is a biomarker for phosphatidylinositol 3-kinase (PI3K) pathway activation and AKT inhibitors sensitivity.

Material and methods

In this study, we immunohistochemically investigated the expression of phospho-PRAS40^Thr246 in 141 gastric cancer tumors, and evaluated its clinicopathological and prognostic significance.

Results

Sixty-four cases (45.4%) were defined as phospho-PRAS40^Thr246 positive. Phospho-PRAS40^Thr246 correlated positively with lymph node metastasis, lymphatic infiltration, vascular infiltration and shorter survival. Furthermore, phospho-PRAS40^Thr246 is an independent prognostic factor for gastric cancer.

Conclusions

Our data suggest that phospho-PRAS40^Thr246 was frequently expressed in gastric cancers, and correlated with malignant progression and poor prognosis of patients. PI3K pathway-targeted therapies should be considered in the future treatment of gastric cancers.     

Trends of cancer incidence and mortality in Cali,Colombia. 50 years experience

Purpose :

The Population-based Cancer Registry of Cali aims to report all new cases in permanent residents within the limits of the city of Cali. Time trends of cancer incidence and mortality are described. The registry has been in continuous operation for 50 years.

Methods:

Cancer cases reports are obtained actively by visiting all sources of information: hospitals, pathology departments, hematology laboratories, radiotherapy centers, government offices where death certificates are processed and physician''s offices. It is estimated that the reporting is at least 95% complete.

Results:

Drastic decreases are documented in rates for tumors causally related to infectious agents, especially cancers of the uterine cervix and the stomach. Gradual increases are documented in rates of tumors linked to affluence and the metabolic syndrome, especially cancers of the colon and the female breast. An unexpected increase in the incidence of papillary carcinoma of the thyroid gland in women is reported. Tobacco-related cancers, especially cancer of the lung, showed marked increase in incidence rates around 1970, apparently the beginning of an epidemic similar to the one reported in Western societies. But the increase in incidence stopped around 1980, resulting from a strong anti-smoking campaign launched in Colombia in the 1970s.

Conclusions:

The findings have influenced prevention strategies implemented by public health authorities, specially the establishment of a city-wide program to prevent cervix cancer via widespread use of vaginal cytology and anti-smoking campaigns. Also, new population-based cancer registries have been established in other Colombian cities as well as in Ecuador.     

Role of cytological characteristics of benign thyroid nodules on effectiveness of their treatment with levothyroxine

Introduction

Levothyroxine (LT4) therapy has been used for the treatment of euthyroid nodular goiter, but there are controversial results about its usefulness. We aimed to evaluate the possible role of benign nodules’ cytological characteristics in response to LT4 therapy.

Material and methods

In total, 93 patients with 128 nodules were included in the study; 74 of the nodules were treated with LT4 (group 1), and 54 of them had no medication (group 2). The subgroups consisted of adenomatous nodules, colloid nodules and cystic nodules.

Results

In group 1, mean thyroid volume and mean nodule volume were reduced significantly (p = 0.002 and p = 0.022, respectively) with low-normal level thyrotropin (TSH) suppression (between 0.3 mIU/ml and 1.0 mIU/ml), while there were no significant changes in group 2. When we evaluated changes of the initial and last nodule volumes in cytological subgroups, only colloid nodules in group 1 had significant reduction (p = 0.040) and the others had no significant changes. By omitting the colloid nodules, when the other nodules were revaluated, there were no significant changes in either group.

Conclusions

On the basis of these results, obtained from a large sample of Anatolian patients, it is possible that LT4 therapy leads to significant reductions of both thyroid volume and nodule size in colloid nodules, but not in other kinds of benign nodules.     

Cystic breast lesions by conventional ultrasonography: sonographic subtype-pathologic correlation and BI-RADS Assessment

Introduction

Appropriate categorization is very important because the clinical management of each subtype of cystic breast lesions (CBLs) differs. The purpose was to evaluate the sonographic subtype-pathologic correlation, and to identify the effectiveness of the Breast Imaging Reporting and Data System (BI-RADS)-ultrasound (US) for differentiation of benign and malignant CBLs.

Material and methods

A database from December 1, 2007 and November 30, 2009 was identified in the Department of Diagnostic Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, China. Those patients with palpable or clinical symptomatic breast masses were associated with a cystic component in lesions on breast US. All patients underwent a subsequent fine-needle/core-needle biopsy or surgical excision. The sonographic findings were analyzed according to the BI-RADS-US, and were categorized by two different methods of subtype categorization compared with the pathologic results.

Results

Ninety-nine breast cystic lesions in 83 women were included, among whom 16 patients were identified with bilateral cystic lesions. The total malignancy rate of CBLs was 14.1% (95% confidence interval 7.3–21.0%). Among 99 CBLs, 14 malignant lesions were associated with sonographic appearances of complex cystic lesions, while the remaining subtypes were benign. Shape, margin, echo pattern, orientation, calcification, and vascularity were statistically significantly different between the benign and malignant lesions (p = 0.010, p = 0.004, p < 0.001, p < 0.001, p = 0.036, and p < 0.001, respectively) (degrees of freedom = 1).

Conclusions

By comparison of the two different methods of subtype categorization of CBLs, the appropriate 5-variety classification should be suggested. The BI-RADS-US was useful for differentiating benign from malignant cystic lesions.     

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in invasive breast cancer in women

Introduction

Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression are crucial in the biology of breast carcinoma. HER-2/neu gene is amplified and overexpressed in 15-30% of invasive breast cancers. HER-2-positive breast cancers have worse prognosis than HER-2 negative tumors and possess distinctive clinical features. The aim of this study was to assess the expression of HER2 in cancer tissue of patients with invasive breast cancer in correlation with tumor type, histological grade, tumor size, lymph node status, and expression of estrogen receptor and progesterone receptor.

Material and methods

Formalin-fixed, paraffin-embedded tissues from 40 patients with invasive HER-2-positive breast cancer and from 191 patients with HER-2-negative breast cancer were used in this study. HER2 expression was determined using the test HerceptTest™ DAKO.

Results

Among 231 cases of breast cancer, 18 invasive lobular carcinomas and 213 invasive ductal carcinomas were diagnosed. Sixty percent of HER-2-positive breast cancers were ER-positive compared with 77% in the HER-2-negative group (p = 0.002). The expression of PR was observed in 43% of HER-2-positive breast cancers and in 72% of HER2-negative tumors (p = 0.003). Excessive expression of HER2 protein was detected in 60% of patients positive for estrogen receptors, which may worsen prognosis in these patients.

Conclusions

Determination of HER2 overexpression in breast cancer patients, allows for a determination of a group of patients with a worse prognosis.     

Detection of Plasma BRAFV600E Mutation Is Associated with Lung Metastasis in Papillary Thyroid Carcinomas

Purpose

The BRAF^V600E mutation represents a novel indicator of the progression and aggressiveness of papillary thyroid carcinoma (PTC). The purpose of this study was to determine the clinical significance of free circulating mutant BRAF^V600E in predicting the advanced disease of PTC.

Materials and Methods

Seventy seven matched tumor and plasma samples obtained from patients with both benign and PTC were analyzed for BRAF^V600E mutation using a peptide nucleic acid (PNA) clamp real-time polymerase chain reaction (PCR).

Results

The BRAF^V600E mutation was absent in tumor DNA samples obtained from patients with benign follicular adenomas or adenomatous goiter. In contrast, 49 of 72 (68.1%) PTC tumors were positive for the BRAF^V600E mutation. Among them, 3 (6.1%) patients with PTC were positive for BRAF^V600E mutation in plasma and tumor. However, all 3 patients (100%) had lateral lymph node and lung metastasis.

Conclusion

These findings suggest that the BRAF^V600E mutation can be detected using a PNA clamp real-time PCR in the blood of PTC patients with lung metastasis. Future studies are warranted to determine clinical significance of serum BRAF^V600E mutation in large prospective studies.     

Comparison of metabolic ratios of urinary estrogens between benign and malignant thyroid tumors in postmenopausal women

Background

Estrogen metabolism may be associated with the pathophysiological development of papillary thyroid carcinoma (PTC).

Methods

To evaluate the differential estrogen metabolism between benign and malignant PTCs, estrogen profiling by gas chromatography–mass spectrometry was applied to urine samples from postmenopausal patients with 9 benign tumors and 18 malignant stage I and III/IV PTCs.

Results

The urinary concentration of 2-methoxyestradiol was significantly lower in the stage I malignant patients (3.5-fold; P?<?0.025) than in the benign group. The metabolic ratios of 16α-OH-estrone/estrone and estriol/estradiol, which are responsible for 16α-hydroxylase activity, were increased more than 2.5-fold in the advanced-stage malignant PTC (P?<?0.02 each). The more than 6.2-fold decrease in the urinary 2-/16α-hydroxylase ratio in stage III/IV malignant PTC was consistent with the ratio in postmenopausal patients with endocrine gland cancers. In addition, reductive 17β-hydroxysteroid dehydrogenase (17β-HSD; estradiol/estrone or estriol/16α-OH-estrone) was present at significantly higher levels in subjects with stage III/IV malignant PTCs than in benign subjects (>3.5-fold difference; P?<?0.002). In particular, the estriol/16α-OH-estrone ratio differentiated between the benign and early-stage malignant patients (P?<?0.01).

Conclusions

Increased 16α-hydroxylation and/or a decreased 2-/16α-ratio, as well increased reductive 17β-HSD, with regard to estrogen metabolism could provide potential biomarkers. The devised profiles could be useful for differentiating malignant thyroid carcinomas from benign adenomas in postmenopausal women.

     

One-step nucleic acid amplification testing in medullary thyroid cancer lymph nodes: a case series

Introduction

Locoregional relapse in medullary thyroid cancer (MTC) may be caused by nodal micrometastases. Medullary thyroid cancer lymph nodes have not yet been evaluated by one-step nucleic acid amplification (OSNA). Therefore, the aim of this study was to detect MTC cells by OSNA in cervical lymph nodes and compare the obtained outcomes with conventional histopathology.

Material and methods

Twenty-one randomized, unenlarged lymph nodes from 5 patients with MTC were examined by histopathology and OSNA. Lymph nodes were divided into four representative blocks by a sterile, single use, special cutting device in the same way as in the clinical protocol study performed by Tsujimoto et al. Two blocks were used for histopathology and immunohistochemistry, 2 for OSNA.

Results

Positive results of histopathology and OSNA were revealed in 4 patients. The outcomes of OSNA and histopathology were corresponding in 3 patients. Positive histopathology results of 2 lymph nodes from 2 patients were confirmed by OSNA. In 1 patient there were only negative results of both examinations. One-step nucleic acid amplification failed to detect metastasis in 1 lymph node in 2 patients although it did not change the TNM status in these patients. There were no false positive results in the OSNA test.

Conclusions

One-step nucleic acid amplification may be an alternative method to histopathology in detecting nodal involvement in MTC. Further studies should evaluate the sensitivity and specificity of OSNA and the impact on staging in MTC.     

Focal Lymphocytic Thyroiditis Nodules Share the Features of Papillary Thyroid Cancer on Ultrasound

Purpose

It is often difficult to discriminate focal lymphocytic thyroiditis (FLT) or adenomatous hyperplasia (AH) from thyroid cancer if they both have suspicious ultrasound (US) findings. We aimed to make a predictive model of FLT from papillary thyroid cancer (PTC) in suspicious nodules with benign cytologic results.

Materials and Methods

We evaluated 214 patients who had undergone fine-needle aspiration biopsy (FNAB) and had shown thyroid nodules with suspicious US features. PTC was confirmed by surgical pathology. FLT and AH were confirmed through more than two separate FNABs. Clinical and biochemical findings, as well as US features, were evaluated.

Results

Of 214 patients, 100 patients were diagnosed with PTC, 55 patients with FLT, and 59 patients with AH. The proportion of elevated thyrotropin (TSH) levels (p=0.014) and thyroglobulin antibody (Tg-Ab) or thyroid peroxidase antibody (TPO-Ab) positivity (p<0.001) in the FLT group was significantly higher than that in the PTC group. Regarding US features, absence of calcification (p=0.006) and "diffuse thyroid disease" (DTD) pattern on US (p<0.001) were frequently seen in the FLT group. On multivariate analysis, Tg-Ab positivity, presence of a DTD pattern on US, and absence of calcification in nodules were associated with FLT with the best specificity of 99% and positive predictive value of 96%. In contrast, a taller than wide shape of nodules was the only variable significant for differentiating AH from PTC.

Conclusion

Suspicious thyroid nodules with cytologic benign results could be followed up with US rather than repeat FNAB, if patients exhibit Tg-Ab positivity, no calcifications in nodules, and a DTD pattern on US.     

Anaplastic Thyroid Cancer: Ultrasonographic Findings and the Role of Ultrasonography-Guided Fine Needle Aspiration Biopsy

Purpose

To investigate the ultrasonographic (US) features of anaplastic thyroid cancer (ATC) and the diagnostic performance of US-guided fine needle aspiration biopsy (FNAB) therein.

Materials and Methods

Eighteen cases of ATC diagnosed between January 2001 and May 2011 were included. FNAB was performed in all cases. Initial FNAB results were divided into three groups: 1) the cytological ATC group, cytological diagnosis of ATC; 2) the underestimated group, cytological diagnoses of malignancy other than ATC; and 3) the false negative group, cytological diagnoses of atypical, benign and non-diagnostic lesions. We retrospectively reviewed US findings and compared treatment modalities between each group.

Results

Among the 18 patients, there were nine in the initially cytological ATC group, four in the underestimated group and five in the false negative group. The most common US features of ATC were a solid (64.7%) and irregular shaped (88.2%) mass with lymph node involvement (76.4%). However, except for lymph node involvement (p=0.003), US findings for each group were not statistically different. The initial cytological diagnostic accuracy of ATC was 50% (9/18). Surgery was performed less in the ATC group (11%) and the false negative group (20%) than the underestimated group (75%).

Conclusion

The US features of ATC were not especially different from other types of aggressive thyroid cancer. A correct diagnosis of ATC by initial US-FNAB was made in 50% of the patients, which is significant in that therapeutic surgery can be undertaken in lower numbers if correctly diagnosed.