• Korean Journal of Clinical Laboratory Science
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• v.47 no.1
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• pp.17-23
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• 2015

A fine needle aspiration biopsy (FNAB) is the primary means of distinguishing benign from malignant in thyroid nodules. However, between 10 and 30% of the FNABs of thyroid nodules are diagnosed as 'indeterminate'. A molecular method is needed to reduce unnecessary surgery in this group. In Korea, most thyroid cancer is classic papillary type and BRAFV600E mutation is highly prevalent. Thus, this study compared the pyrosequencing method with the conventional direct DNA sequencing and PCR-RFLP analysis and investigated the evaluation of preoperative BRAFV600E mutation analysis as an adjunct diagnostic method with routine FNABs. Sixty-five (78.3%) of 83 histopathologically diagnosed malignant nodule revealed positive BRAFV600E mutation on pyrosequencing analysis. In detail, 65 (83.8%) of 78 papillary thyroid carcinomas sample showed positive BRAFV600E mutation. None of 29 benign nodules had in pyrodequencing, direct DNA sequencing and PCR-RFLP. Out of 31 thyroid nodules classified as 'indeterminate' on cytological examination preoperatively, 28 cases turned out to be malignant: 24 papillary thyroid carcinomas. Among that, 16 (66.7%) classic papillary thyroid carcinomas had BRAFV600E mutation. Among 65 papillary thyroid carcinomas with positive BRAFV600E mutation detected by pyrosequencing analysis, each 3 cases and 5 cases did not show BRAFV600E mutation by direct DNA sequencing and PCR-RFLP analysis. Therefore, pyrosequencing was superior to direct DNA sequencing and PCR-RFLP in detecting the BRAFV600E mutation of thyroid nodules (p =0.027). Detecting BRAFV600E mutation by pyrosequencing was more sensitivity, faster than direct DNA sequencing or PCR-RFLP.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.23-29
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• 2002

Mutation of the P53 tumor suppressor gene playa major role in the development of many carcinomas, namely in the colon, breast and bladder, whereas the role played by such mutations in thyroid carcinogenesis remains controversial. Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule Expression of p53, VEGF and E-cadherin was assessed immunohistochemically in 19 tall columnar variant of papillary carcinoma, 24 common papillary carcinoma and 7 follicular carcinoma. The aim of this study was to evaluate the expression of P53,VEGF and E-cadherin as a potential maker for the prognosis of thyroid carcinomas. The results are as follows: 1) There were no significance in any clinical parameters examined among tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma. 2) The expression of P53 demonstrated low in tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma, but a significantly high in regional lymph node metastasis. 3) The expression of VEGF demonstrated a significantly high in regional lymph node metastasis than those without metastasis in papillary thyroid carcinoma. 4) The expression of E-cadherin demonstrated less often among papillary carcinomas with lymph node metastasis than in those without metastasis in papillary thyroid carcinoma. In conclusion, it is suggested that VEGF and E-cadherin will be useful for the diagnosis of thyroid carcinoma and serves as a biological marker for thyroid carcinoma lymph node metastasis.

• Korean Journal of Bronchoesophagology
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• v.12 no.2
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• pp.31-34
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• 2006

Simultaneous occurrence of medullary and papillary thyroid carcinomas in the same gland is very rare. In fact. there are only 18 cases of simultaneous occurrence of medullary and papillary thyroid carcinomas in the literature. We report a case of simultaneous medullary and papillary carcinoma of thyroid gland. A 67-year-old woman was diagnosed with medullary carcinoma of right lobe of thyroid gland and papillary carcinoma of left lobe of thyroid gland by fine needle aspiration cytology. Total thyroidectomy, anterior neck dissection, bilateral modified radical neck dissection and tracheotomy was undertaken. The tumor metastasized to regional lymph node and extrathyroidal muscle invasion of left papillary carcinoma was also revealed by pathological report. This report describes a case of thyroid carcinoma that demonstrated both medullary carcinoma and papillary components in the thyroid with lymph node metastasis.

• Korean Journal of Head & Neck Oncology
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• v.10 no.2
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• pp.102-105
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• 1994

The indolent course of most thyroid papillary carcinomas, even the presence of regional lymph node metastasis, make them unique among human malignant head and neck cancers. Age, sex, extracapsular invasion and anaplastic change are known to be correlated with prognosis. The purpose of this study is to clarify the significance of DNA content analysis as a prognostic factor. Twenty five thyroid papillary carcinomas were possible to be examined by flow cytometric analysis using fresh surgical specimens and three nodular hyperplasias and seven follicular adenomas were included as control group. The results were as follows: l) All of twenty five thyroid papillary carcinomas showed diploidy. 2) S-phase fraction was $1.94{\pm}2.77%$ in normal control group and $2.60{\pm}2.66%$ in papillary carcinoma group. The proliferation index was $8.44{\pm}3.89%$ in normal control and $7.70{\pm}3.63%$ in papillary carcinoma group with even low value. 3) Age, sex, extracapsular spread and lymph node metastasis showed no significant difference. In conclusion, low proliferative activity of thyroid papillary carcinomas are thought to be related with good prognosis.

• Korean Journal of Head & Neck Oncology
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• v.23 no.1
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• pp.50-53
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• 2007

Adrenal metastasis from papillary thyroid carcinoma is extremely rare. We present herein a patient with adrenal metastases from recurrent papillary carcinoma of the thyroid. A 54 year-old woman had received a total thyroidectomy and postoperative radioactive iodine therapy for locally advanced papillary thyroid carcinoma. One year after initial surgery, distant metastases to multiple organs including right cervical lymph nodes, left upper lung, left 2nd and 3rd ribs, 2nd thoracic vertebra and left adrenal gland were found by 18-FDG-PET-CT whole body scan. She underwent right modified neck dissection, partial resection of left 2nd and 3rd ribs, posterior arch of 2nd thoracic vertebra, left upper lobectomy of lung, and left adrenalectomy. On histologic examination, metastases to the left adrenal gland and cervical lymph nodes were papillary thyroid carcinomas, while other metastatic sites turned out to be anaplastic thyroid carcinomas. Despite aggressive surgery and postoperative adjuvant therapy, her general clinical conditions were getting worse day by day due to regrowing of the anaplastic thyroid carcinomas. To our knowledge, this is the first case reported in Korea.

• International journal of thyroidology
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• v.11 no.2
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• pp.123-129
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• 2018

Background and Objectives: Hypermethylation of the tumor suppressor gene RASSF1A and activating mutation of BRAF gene have been recently reported in thyroid cancers. To investigate the role of these two epigenetic and genetic alterations in thyroid tumor progression, methylation of RASSF1A and BRAF mutation were examined in thyroid tumors. Materials and Methods: During 2007 to 2017, 69 papillary carcinomas, 18 nodular hyperplasia, 3 follicular carcinomas, and 13 follicular adenomas were selected. The methylation-specific polymerase chain reaction (MSP) technique was used in detecting RASSF1A methylation and polymerase chain reaction (PCR)-single-stranded conformation polymorphism and sequencing were used for BRAF gene mutation study. Results: The hypermethylation of the RASSF1A gene was found in 84.6%, 100% and 57.9% of follicular adenomas, follicular carcinomas, and papillary carcinomas, respectively. Nodular hyperplasia showed a hypermethylation in 33.3%. The BRAF mutation at V600E was found in 60.7% of papillary carcinoma and 27.0% of nodular hyperplasia, but none of follicular neoplasms. The BRAF mutation was correlated with the lymph node metastasis and MACIS clinical stage. There is an inverse correlation between RASSF1A methylation and BRAF mutation in thyroid lesions. Conclusion: Epigenetic inactivation of RASSF1A through aberrant methylation is considered to be an early step in thyroid tumorigenesis, and the BRAF mutation plays an important role in the carcinogenesis of papillary carcinoma, providing a genetic marker.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.17 no.4
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• pp.442-446
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• 1995

Thyroid carcinomas are usually classified as papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and anaplastic thyroid carcinoma. Among the thyroid carcinomas, the incidence of medullary and anaplastic thyroid carcinoma is low, but the rate of lymph node & distant metastasis from them are more common compared to other types. Follicular thyroid carcinoma has a low rate of lymph node metastasis as 10% and has a high occurrence of hematogenous metastasis to lung, bone, brain and liver. Papillary thyroid carcinoma accounts for $60{\sim}70%$ of whole thyroid carcinomas and the cervical lymph node metastasis is $21{\sim}81%$ including micrometastasis, but the distant metastasis is rare. In the case of bone metastasis, follicular type reveals most frequent, and the rate is about 5%, and more likely to be found on vertebra, pelvis, ribs, femur, and skull. The clinical symptoms of bone metastasis are pain, swelling, pathological fracture and radiologically osteolytic lesions can be observed. But distant metastasis of papillary thyroid carcinoma is very rare and especially, bone metastasis has hardly been reported. The treatment modalities of metastatic thyroid carcinoma to mandible are known as follows : thyroidectomy to treat primary site, resection of the affected site of mandible, external beam radiotherapy and radioiodine therapy etc.

• The Korean Journal of Cytopathology
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• v.8 no.1
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• pp.52-56
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• 1997

Oxyphilic (Hurthle) cells have abundant eosinophilic granular cytoplasms and occur in both benign and malignant neoplasms of the thyroid gland. Most published studies described mainly oxyphilic tumors of follicular type, and reports on oxyphilic papillary thyroid carcinomas are rare. The oxyphilic variant of papillary carcinoma differs from the classic papillary carcinoma in its more aggressive biological behavior. We report a case of oxyphilic papillary carcinoma exhibiting exclusively oxyphilic cells in a follicular pattern without papillary structures. The pattern of papillary carcinoma was confirmed by fine needle aspiration material and lymph nodal metastasis, both of which revealed typicaled papillary structures with characteristic nuclear features, psammoma bodies, and oxyphilic cytoplasm.

• The Korean Journal of Nuclear Medicine
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• v.12 no.2
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• pp.33-40
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• 1978

Clinical features of 147 patients with biopsy-proven thyroid carcinomas were investigated from January, 1972 to April, 1978 at the Seoul National University Hospital with the following results. 1) The incidence of thyroid carcinomas according to their histopathological classification revealed 76.2% of papillary carcinoma, 19.0% of follicular carcinoma, and 3 cases of occult sclerozing carcinoma, 1 case of giant cell carcinoma and 1 case of metastatic melanoma. 2) The ratio of male to femle patients was 1:8.3 and showed no difference between papillary and follicular carcinomas. 3) The age distribution showed the peak incidence in the fourth decade (29.3%) followed by the fifth and sixth decades. 4) The average duration of illness from the onset of symptoms was about 5 years while it was 4.4 years and 7.6 years in the papillary and follicular carcinomas respectively. 5) The diameter of the thyroid masses was smaller than 5 cm in 53.6% of the patients, from 5 cm to 10 cm in 40.0% and larger than 10 cm in 6.4%. 6) In 36.4% of the patients with thyroid carcinomas the thyroid masses were fixed to adjacent tissues. 7) Metastasis to the regional lymph nodes was noted in 40.0% of the total cases, and in 45.2% and 17.6% of the papillary and follicular carcinomas respectively, while the lung and bone metastases were found in 10.0% and 4.4% in each type respectively. 8) 88.9% of the patients showed cold areas in the thyroid scans using $^{131}I$. 9) Typical psammoma bodies were observed in 21.3% of the cases in the microscopic examination of the pathological specimens. 10) The initial diagnosis of thyroid malignancy could be made before histological confirmation in 64.5% of the patients. 11) The clinical staging slightly modified from Schulz method revealed 43.6% of the patients in stage I, 26.4% in stage II, 20.9% in stags III and 9.1 % in stage IV. 12) The association with Hashimoto's thyroiditis was noted in 4 cases, with nodular goiter in 3 cases, and with follicular adenoma in 1 case.

• The Korean Journal of Cytopathology
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• v.9 no.2
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• pp.169-180
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• 1998

Fine needle aspiration cytology(FNAC) has been used effectively as the initial modality in evaluating various thyroid lesions. We correlated cytologic and histopathologic features to investigate the diagnostic pitfalls of FNAC of the thyroid. A total of 1,593 FNACs of the thyroid were diagnosed at the Department of Pathology, Hanyang University Hospital, from January 1993 to December 1997 There were 963 cytologically benign cases(60.5%), 97 suspicious cases(6.1%), and 75 malignant cases(4.71%). The remaining 458 cases(28.8%) were unsatisfactory. Subsequent surgical resection was done in 192 cases. Seventy-two cases(37.5%) were cytologically diagnosed as benign, 45 cases(23.4%) suspicious, 56 cases(29.2%) malignant, and 19 cases(9.9%) unsatisfactory. Histopathologically, 101 cases were benign(11 thyroidites, 52 adenomatous hyperplasias, 34 follicular adenomas, and four Hurthle cell adenomas), and 91 cases malignant(72 papillary carcinomas, 16 follicular carcinomas, one medullary carcinoma, one anaplastic carcinoma, and one granular cell tumor). After excluding 19 unsatisfactory cases, 63 were misdiagnosed. They included 17 benign(three thyroidites and 14 adenomatous hyperplasias), 27 suspicious(10 follicular adenomas, four Hurthle cell adenomas, and seven follicular carcinomas), and 19 malignant(16 papillary carcinoma, one medullary carcinoma, one anaplastic carcinoma. and one granular cell tumor) lesions. The accuracy rates in the benign, suspicious, and malignant categories were 54.9%, 49.8%, & 92.8%, respectively. The cytological pitfalls were as follows: (1) background, (2) crowded follicular cell clusters indistinguishable between follicular neoplasia and adenomatous hyperplasia, (3) papillary structure, irregular nuclear membrane and pleomorphism mimicking those of papillary carcinoma, (4) indistinct eosinophilia in follicular epithelial cells, (5) unusual cellular components not commonly seen in FNACS of the thyroid.