Dong Eun Song

Thyroid Nodules with Initially Nondiagnostic Cytologic Results: The Role of Core-Needle Biopsy

PURPOSE To evaluate the role of core-needle biopsy (CNB) in thyroid nodules with nondiagnostic results at previous fine-needle aspiration (FNA). MATERIALS AND METHODS From October 2008 to July 2011, 155 nodules from 155 patients (37 men, 118 women) with a mean age of 51.8 years (age range, 22-76 years) with nondiagnostic results at previous FNA were reviewed retrospectively. The Bethesda system for reporting thyroid cytopathologic results was used to assign FNA and CNB findings. Malignant nodules (n = 37) were diagnosed after surgery. Benign nodules (n = 79) were diagnosed either after surgery, with benign findings after FNA and/or CNB that had been repeated at least twice, or after benign cytology findings at FNA or CNB with a stable size at follow-up. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ultrasonographically guided CNB were evaluated. RESULTS At CNB, two nodules (1.3%) showed nondiagnostic results, and 135 nodules (87.1%) had conclusive diagnoses. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of core biopsies for the detection of malignancy were 94.6% (35 of 37), 100% (79 of 79), 100% (35 of 35), 97.5% (79 of 81), and 98.3% (114 of 116), respectively. For 28 nodules, nondiagnostic results were found after two or more FNA procedures; however, diagnostic surgery was performed in only one patient. CONCLUSION CNB of the thyroid nodule demonstrates high rates of conclusive and accurate diagnoses in patients for whom previous FNA results were nondiagnostic, thereby reducing the need for unnecessary diagnostic surgery.

Obesity is a risk factor for thyroid cancer in a large, ultrasonographically screened population

OBJECTIVE Obesity is a well-known risk factor for many cancers, including those of the esophagus, colon, kidney, breast, and skin. However, there are few reports on the relationship between obesity and thyroid cancer. We conducted this study to determine whether obesity is a risk factor for thyroid cancer by systematically screening a selected population by ultrasonography. DESIGN AND METHODS We obtained data from 15,068 subjects that underwent a routine health checkup from 2007 to 2008 at the Health Screening and Promotion Center of Asan Medical Center. Thyroid ultrasonography was included in the checkup, and suspicious nodules were examined by ultrasonography-guided aspiration. Those with a history of thyroid disease or family history of thyroid cancer were excluded from this study. RESULTS In total, 15,068 subjects, 8491 men and 6577 women, were screened by thyroid ultrasonography. Fine-needle aspiration cytology was performed in 1427 of these patients based on the predefined criteria and thyroid cancer was diagnosed in 267 patients. The prevalence of thyroid cancer in women was associated with a high BMI (per 5 kg/m(2) increase) (odds ratios (OR)=1.63, 95% CI 1.24-2.10, P<0.001), after adjustment for age, smoking status, and TSH levels. There was no positive correlation between the prevalence of thyroid cancer in men and a high BMI (OR=1.16, 95% CI 0.85-1.57, P=0.336). There was no association between age, fasting serum insulin, or basal TSH levels and thyroid cancer in either gender. CONCLUSIONS Obesity was associated with a higher prevalence of thyroid cancer in women when evaluated in a routine health checkup setting. This association between risk factor and disease was unrelated to serum insulin and TSH levels. Additional studies are needed to understand the mechanism(s) behind the association of obesity with thyroid cancer risk.

Pathology Reporting of Thyroid Core Needle Biopsy: A Proposal of the Korean Endocrine Pathology Thyroid Core Needle Biopsy Study Group

In recent years throughout Korea, the use of ultrasound-guided core needle biopsy (CNB) has become common for the preoperative diagnosis of thyroid nodules. However, there is no consensus on the pathology reporting system for thyroid CNB. The Korean Endocrine Pathology Thyroid Core Needle Biopsy Study Group held a conference on thyroid CNB pathology and developed guidelines through contributions from the participants. This article discusses the outcome of the discussions that led to a consensus on the pathology reporting of thyroid CNB.

Sonographically Suspicious Thyroid Nodules with Initially Benign Cytologic Results: The Role of a Core Needle Biopsy

PURPOSE To evaluate the diagnostic role of core needle biopsy (CNB) in sonographically suspicious thyroid nodules with initially benign cytologic results through a histologic analysis of CNB specimens. METHODS Between October 2008 and July 2011, 88 patients underwent ultrasound (US)-guided CNB for initially benign cytologic results with suspicious US features at our institution. In all, 85 patients with 85 focal thyroid nodules were included in the study after surgery or concordant benign readings following fine-needle aspiration biopsy (FNAB) and CNB. We evaluated the risk of malignancy, diagnostic performance of CNB, and histologic findings for these nodules. RESULTS Of the 85 nodules, 28 (32.9%) were histologically upgraded on CNB specimens including one case of atypia of undetermined significance (AUS), seven cases of follicular neoplasm, one case of suspicious for malignancy, and 19 cases of malignancy. Of these, 27 (31.8%) were finally confirmed as malignant, and one as follicular adenoma at surgery. The 27 malignant nodules included 21 papillary thyroid carcinomas (PTCs), five follicular thyroid carcinomas, and one Hürthle cell carcinoma. All PTCs were diagnosed from CNB readings of AUS suspicious for malignancy or malignancy. Follicular thyroid carcinomas and Hürthle cell carcinoma were diagnosed from CNB readings of follicular neoplasm. Histologic analysis of benign CNB specimens revealed severe fibrosis (96.4%), hemosiderin (21.4%), calcification (17.9%), granulation tissue (12.5%), and focal lymphocytic thyroiditis (12.5%). CONCLUSIONS The histologic information obtained by analysis of CNB specimens may enable more confident diagnosis for benign nodules with suspicious US features and reduce the need for repetitive FNABs or diagnostic surgery.

NRAS codon 61 mutation is associated with distant metastasis in patients with follicular thyroid carcinoma.

BACKGROUND Known factors related to distant metastases in follicular thyroid carcinoma (FTC) included age, primary tumor size, and invasiveness. Distant metastasis is a main cause of death in FTC patients. Several studies showed that the presence of RAS mutations is also associated with poor clinical outcomes. We analyzed RAS mutations in FTC with distant metastases, FTC without a distant metastasis, follicular adenoma (FA), and nodular hyperplasia (NH). Furthermore, we elucidated the relationship between RAS mutations and clinical outcomes in FTC patients. METHODS We selected patients who underwent a thyroidectomy for FTC with distant metastases (n=28), size matched FTC specimens without a distant metastasis (n=28), FA (n=17), and NH (n=12). NRAS, HRAS, and KRAS mutations were assessed using direct sequencing. RESULTS Among 85 patients, 39 patients (46%) had RAS mutations. The NRAS codon 61 mutation (n=21; 25%) was the most common point mutation. HRAS codon 61, KRAS codon 12/13, and KRAS codon 61 mutations were found in 7, 6, and 4 patients, respectively. A NRAS codon 12/13 mutation was found in only 1 patient, and a HRAS codon 12/13 mutation was not found. RAS mutations were significantly more common in the FTC than FA or NH groups. Especially, the NRAS codon 61 mutation was associated with distant metastasis in patients with FTC. CONCLUSIONS The presence of a RAS mutation, especially a NRAS codon 61 mutation, was significantly associated with the distant metastasis. The NRAS codon 61 mutation status might be a potential prognostic factor in FTC patients.

The prognostic value of the metastatic lymph node ratio and maximal metastatic tumor size in pathological N1a papillary thyroid carcinoma

OBJECTIVE The presence of central neck lymph node (LN) metastases (defined as pN1a according to Tumor Node Metastasis classification) in papillary thyroid cancer (PTC) is known as an independent risk factor for recurrence. Extent of LN metastasis and the completeness of removal of metastatic LN must have an impact on prognosis but they are not easy to measure. Moreover, the significance of the size of metastatic tumors in LNs has not been clarified. This study was to evaluate the impact of the extent of LN metastasis and size of metastatic tumors on the recurrence in pathological N1a PTC. DESIGN This retrospective observational cohort study enrolled 292 PTC patients who underwent total thyroidectomy with central neck dissection from 1999 to 2005. LN ratio was defined as the number of metastatic LNs divided by the number of removed LNs, which was regarded as variable reflecting both extent of LN metastasis and completeness of resection, and LN size as the maximal diameter of tumor in metastatic LN. RESULTS The significant risk factors for recurrence in univariate analysis were large primary tumor size (defined as larger than 2 cm), high LN ratio (defined as higher than 0.4), and presence of macrometastasis (defined as larger than 0.2 cm). Age, sex, clinical node status, and microscopic perithyroidal extension had no effect on recurrence. In multivariate analysis, high LN ratio and presence of macrometastasis were independent risk factors for recurrence. CONCLUSION LN ratio and size of metastatic nodes had a significant prognostic value in pathological N1a PTC. We suggest that risk stratification of pathological N1a PTC according to the pattern of LN metastasis such as LN ratio and size would give valuable information to clinicians.

Serum antithyroglobulin antibodies interfere with thyroglobulin detection in fine-needle aspirates of metastatic neck nodes in papillary thyroid carcinoma.

CONTEXT It is recommended to measure thyroglobulin (Tg) levels in the needle washout fluids from fine-needle aspirations (FNAs) in patients with papillary thyroid carcinoma (PTC) who have ultrasonographically suspicious metastatic lymph nodes (LNs). However, it is not clear whether serum anti-Tg antibodies (TgAbs) interfere with the detection of Tg in needle washout fluids from FNAs (FNA-Tg). OBJECTIVE The objective of the study was to evaluate the influence of serum TgAbs on FNA-Tg detection. DESIGN AND SETTINGS This retrospective observational cohort study enrolled 207 patients with conventional PTC in whom FNA-Tg values had been measured. All patients initially underwent total thyroidectomy and remnant ablation. FNA-Tg levels were measured from ultrasonographically suspicious metastatic LNs of 0.5 cm or greater in the longest diameter. RESULTS From 207 patients, 263 LNs were evaluated. Final histopathology was available for 92 LNs, of which 88 (96%) were malignant. FNA-Tg levels were lower in the LNs from serum TgAb-positive patients than in those from TgAb-negative patients (P < 0.001). In four of 13 metastatic LNs from TgAb-positive patients, the FNA-Tg levels were below 10 μg/liter including one in which both FNA-Tg and serum-stimulated Tg levels were below 1 μg/liter and stained positively for Tg in pathology. There was also one malignant LN with negative for FNA-Tg, serum-stimulated Tg, and serum TgAb but that nonetheless stained intensely for Tg. However, there were no malignant LNs with both negative cytology and negative FNA-Tg. A diagnosis based on FNA-Tg had a lower sensitivity and negative predictive value in the TgAb-positive group than in the TgAb-negative group. CONCLUSION FNA-Tg measurement is highly reliable in the diagnosis of neck metastases in PTC patients, even in cases of negative-stimulated Tg or positive TgAb. However, high-serum TgAb levels could interfere with FNA-Tg measurements and thereby result in falsely low FNA-Tg levels.

Adenocarcinoma Arising in Gastric Heterotopic Pancreas: A Case Report

A heterotopic pancreas in the gastrointestinal tract is mostly found incidentally and its malignant transformation is extremely rare. We describe the second case of adenocarcinoma arising in a gastric heterotopic pancreas of an asymptomatic 35-yr-old man in Korea. Esophagogastroduodenoscopy revealed a submucosal tumor with an irregular central umbilication in the gastric antrum. A wedge resection specimen demonstrated a submucosal oligolocular cystic mass (1.7×1.4×1.2 cm) with a solid portion. Microscopically, the cystic portion was composed of dilated pancreaticobiliary type ducts with adjacent small foci of periductal glandular structures. The adenocarcinoma components in the solid area infiltrated the proper muscle and the overlying mucosa of the stomach. The transitional area between the benign ductal structures and the adenocarcinoma component was found. The follow-up course was uneventful 5 months postoperatively.

Effects of Low-Dose and High-Dose Postoperative Radioiodine Therapy on the Clinical Outcome in Patients with Small Differentiated Thyroid Cancer Having Microscopic Extrathyroidal Extension

BACKGROUND It is unclear whether differentiated thyroid cancer (DTC) patients classified as intermediate risk based on the presence of microscopic extrathyroidal extension (ETE) should be treated with low or high doses of radioiodine (RAI) after surgery. We evaluated success rates and long-term clinical outcomes of patients with DTC of small tumor size, microscopic ETE, and no cervical lymph node (LN) metastasis treated either with a low (1.1 GBq) or high RAI dose (5.5 GBq). METHODS This is a retrospective analysis of a historical cohort from 2000 to 2010 in a tertiary referral hospital. A total of 176 patients with small (≤2 cm) DTC, microscopic ETE, and no cervical LN metastasis were included. Ninety-six patients were treated with 1.1 GBq (LO group) and 80 patients with 5.5 GBq (HI group). Successful RAI therapy was defined as (i) negative stimulated thyroglobulin (Tg) in the absence of Tg antibodies, and (ii) absence of remnant thyroid tissue and of abnormal cervical LNs on ultrasonography. Clinical recurrence was defined as the reappearance of disease after ablation, which was confirmed by cytologically or pathologically proven malignant tissue or of distant metastatic lesions. RESULTS There was no significant difference in the rate of successful RAI therapy between the LO and HI groups (p=0.75). In a subgroup analysis based on tumor size, success rates were not different between the LO group (34/35, 97%) and the HI group (50/56, 89%) in patients with a tumor size of 1-2 cm (p=0.24). In patients with smaller tumor size (≤1 cm), there was no significant difference in success rates between the LO (59/61, 97%) and HI groups (22/24, 92%; p=0.30). No patient had clinical recurrences in either group during the median 7.2 years of follow-up. CONCLUSIONS Low-dose RAI therapy is sufficient to treat DTC patients classified as intermediate risk just by the presence of microscopic ETE.

Recent Changes in the Clinical Outcome of Papillary Thyroid Carcinoma With Cervical Lymph Node Metastasis

CONTEXT The prognosis of papillary thyroid cancer (PTC) with cervical lymph node (LN) metastasis has changed with increased detection of subclinical metastatic LNs. The number and size of metastatic LNs were proposed as new prognostic factors in PTC with cervical LN metastasis (N1). OBJECTIVE The objective of the study was to evaluate changes in N1 PTC characteristics and clinical outcome over time and to confirm the prognostic value of the number and size of metastatic LNs. DESIGN AND PATIENTS This study included 1815 N1 PTC patients diagnosed between 1997 and 2011. Patients were classified into three risk groups according to the number and size of metastatic LNs: very low risk, five or fewer and 0.2 cm or less; low risk, five or fewer and 0.2 cm or greater; and high risk, more than five. MAIN OUTCOME MEASURES Response to initial therapy and disease-free survival (DFS) was measured. RESULTS Metastatic LNs became smaller, and the ratio of metastatic LNs, which represents the extent of LN involvement and the completeness of surgery, decreased significantly over time. The proportion of patients with excellent response significantly increased from 33% to 67% over time (P < .001). These improvements were more evident in the low- and high-risk groups than in the very low-risk group. The DFS 5 years after initial surgery was also significantly increased from 73% to 91% over time (P < .001). The new LN classification was strongly associated with outcome. Patients in the very low-risk group had longer DFS than those in the low- and high-risk groups during the study period. CONCLUSIONS The clinical outcome of N1 PTC has significantly changed over time with the earlier detection of thyroid cancers with less extensive LN involvement. More complete surgical neck dissection also might be responsible for these changes. The number and size of metastatic LNs are important prognostic factors of recurrence in N1 PTC.