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1 대한외과학회지 : 제74권제1호 Vol. 74, No. 1, January, 2008 원저 여포상갑상선암 : 임상병리적특징, 예후인자및치료전략 1 아주대학교의과대학외과학교실, 2 연세대학교의과대학외과학교실 이잔디 1 ㆍ윤지섭 2 ㆍ정종주 2 ㆍ남기현 2 ㆍ정웅윤 2 ㆍ소의영 1 ㆍ박정수 2 Follicular Thyroid Carcinoma: Clinicopathologic Features, Prognostic Factors, and Treatment Strategy Jandee Lee, M.D. 1, Ji Sup Yun, M.D. 2, Jong Ju Jeong, M.D. 2, Kee-Hyun Nam, M.D. 2, Wong-Youn Chung, M.D. 2, Euy-Young Soh, M.D. 1 and Cheong Soo Park, M.D. 2 Department of Surgery, 1 Ajou University College of Medicine, Suwon, 2 Yonsei University College of Medicine, Seoul, Korea Purpose: Follicular thyroid carcinoma (FTC) is a relatively rare form of thyroid carcinoma that often presents at a more advanced stage of disease with a higher incidence of distant metastases because of its propensity for vascular invasion. However, FTC and papillary thyroid carcinoma (PTC) have similar prognoses when they are matched for age and stage. Therefore, this study was conducted to evaluate the useful prognostic factors and determine the optimal management of FTC. Methods: This study was conducted on 216 patients with FTC who underwent thyroidectomy at our institutions between April 1986 and August The patients included 174 women and 42 men with a mean age of 41 (4 87) years, and patients underwent follow-up evaluation for a mean period of 114 (6 253) months. The potential risk factors for treatment outcome were calculated using multivariate analysis, and the prognostic accuracy of UICC/AJCC ptnm staging, AMES, AGES, MACIS, and Degroot classification for predicting survival were compared. Results: During the follow-up period, 13 (6.0%) patients developed locoregional recurrences and 8 patients (3.7%) showed distant metastases. In addition, cause specific mortality was seen in 8 patients (3.7%). The overall survival and cause-specific survival (CSS) rates at 10 years were 95.4% and 89.3%, respectively, and these cases were 책임저자 : 정웅윤, 서울시서대문구신촌동 134 번지 , 연세대학교의과대학외과학교실 Tel: , Fax: woungyounc@yumc.yonsei.ac.kr 접수일 :2007 년 6 월 16 일, 게재승인일 :2007 년 8 월 29 일중심단어 : 여포상갑상선암, 예후인자, 병기결정법, 치료범위 accurately predicted by the AMES and ptnm staging systems. The Cox proportional hazards revealed that gender (P=0.015), angioinvasion (P=0.013), invasion to adjacent structure (P=0.003), widely invasive carcinoma (P=0.028), and distant metastases at the time of presentation (P <0.001) were independent prognostic factors for survival. Conclusion: The extent of surgery in cases of FTC should be individualized based on the clinicopathologic findings; Conservative surgery should be adequate for cases of minimally invasive FTC without angioinvasion, however total or near-total thyroidectomy should be conducted in cases of widely invasive and minimally invasive FTC with angioinvasion. (J Korean Surg Soc 2008;74:34-41) Key Words: Follicular thyroid carcinoma, Prognostic factors, Staging system, Proper management 서 전체갑상선암의약 5 15% 를차지한다고알려져있는여포상갑상선암 (follicular thyroid carcinoma) 은병리조직검사상피막침범, 혈관침습, 림프절침범및임상적으로원격전이여부등에따라악성도가결정되므로, 유두상갑상선암과달리수술전세침흡인검사나수술중동결절편검사만으로정확한진단이불가능하다.(1,2) 즉, 수술후최종병리조직검사결과를통해서만악성여부가판단되고, 악성일경우일반적으로광범위침윤형 (widely invasive type) 과미세침윤형 (minimally invasive type) 으로대별되며, 적절한치료에대해서는아직확실하게알려진바가없다.(1,3,4,5-7) 여포상암의예후는유두상암과마찬가지로매우좋은것으로알려져있는데기존의분화갑상선암의병기결정법및예후인자가상대적으로발생빈도가높은유두상암에중점을두었기때문에여포상암이유두상암과상이한병태생리적특징을보인다는점을고려한다면이같은병기결정법과예후인자를그대로여포상암에적용시켜치료방향을결정할수있는지에대해서는논란의대상이되고있다.(8-10) 특히요오드섭취가풍부하여여포상갑상선이 론 34

2 Jandee Lee, et al:follicular Thyroid Carcinoma: Clinicopathologic Features, Prognostic Factors, and Treatment Strategy 35 매우드물게발생하는우리나라에서는이에대한연구가거의없었다. 이에저자들은진단방법, 수술술기, 추적관찰방법이동일한세군데의 3차의료기관에서임상자료를수집하여여포상갑상선암에대한임상병리적특징을알아보고예후인자에대한분석을통해적절한치료방향을제시하고자하였다. 방법 1) 대상군 1986년 4월부터 2006년 8월까지연세대학교세브란스병원 (160예) 및아주대학교병원 (56예) 에서수술적치료를받은여포상갑상선암환자 216예를대상으로의무기록을통한후향적조사를하였다. 최종조직검사상여포상갑상선암으로진단된경우만을포함하였고, 휘틀세포아형 (Hurthle cell carcinoma), 저분화형태 (poorly-differentiated type) 가혼합된경우및유두상우연암종 (occult papillary thyroid carcinoma) 이동시에발견된경우는대상군에서제외하였다. 병리조직검사에따라크게미세침윤형 (minimally invasive type) 및광범위침윤형 (widely invasive type) 으로구분하였다. 미세침윤형은종괴의육안적인피막침범은관찰되지않으나현미경적으로피막침습을보이지만완전한피막통과는보이지않는경우, 혹은육안적인피막침범없이미세한혈관침습 (angioinvasion) 을보이는경우로한정하였다.(11-13) 광범위침윤형은육안적혹은현미경적으로피막을완전히통과하는형태를보이며, 대개엽뿐아니라전체갑상선으로병소가침윤하는양상을보이는경우로정의하였다.(11,12) 2) 치료방법및추적관찰종괴의크기, 다발성여부, 세침흡인검사, 수술소견, 및 술중동결절편검사결과를통해수술범위를결정하였다. 즉, 엽절제술이나아전절제술등을시행한경우에최종조직검사결과상광범위침윤형으로진단된경우에는완결절제술을추가하였고, 미세침윤형의경우에는혈관침습여부및다른위험요소들을고려하여추가치료여부를결정하였다. 갑상선전절제술을받은대상군중고위험요인을가진환자의경우방사성요오드를잔여조직소멸또는치료목적으로투여하였으며, 치료후방사성요오드전신촬영을시행하였다. 이후모든환자들은갑상선자극호르몬 (thyroid stimulating hormone, TSH) 억제를위한갑상선호르몬제제를복용하였다. 대상환자들은수술후 3개월에서 6개월간격으로정기적인진찰및영상학적검사, 혈액검사와필요한경우핵의학검사등을통해암종의국소재발과원격전이여부를추적관찰하였다. 환자들의치료성적은혈청티로글로불린수치및영상학적검사결과에따라국소재발이나원격전이의증거가전혀없는무병생존과재발이나전이를보이지만생존해있는유병생존및질병관련사망등으로분류하였다. 추적기간은평균 114개월 (6 253) 이었다. 3) 병기결정법및예후인자분화갑상선암의기존의알려진병기결정법인 UICC/AJCC ptnm (Tumor size, Nodal status, presence of Metastasis) (2002),(14) AGES (Age, Grade, Extent, Size),(15) AMES (Age, Metastases, Extent, Size),(16) MACIS (Metastases, Age, Completeness of resection, Invasion, Size),(17) 및 Degroot (class I IV)(18) 등을대상군에적용시켜그효용성을알아보았다. 또한, 각각의임상적특징및병리학적특성을조사하여예후예측인자를조사하였다. 4) 통계학적분석방법통계학적분석은 SPSS 12.0 (2003 SPSS Inc. Chicago, Illi- Fig. 1. Overall survival (A) and cause-specific (B) survival curves for patients with follicular thyroid carcinoma.

3 36 J Korean Surg Soc. Vol. 74, No. 1 nois, USA) 을이용하였으며, 추적기간동안의전체생존율및질병특이생존율은 Kaplan-meier 방법으로구했으며, 각각의위험요소및병기에따른생존율의차이는 log rank test로검정하였다. 예후에영향을미치는예후인자들의다 변량분석은 Cox의비례위험모델 (proportional hazards regression model) 을이용하였으며, 단변량분석에서유의하다고판정된예후인자들을다시다변량분석으로검증하였다. P<0.05인경우를유의한것으로정하였다. Table 1. Univariate analysis of risk factor for cause-specific survival (CSS) Variables No. of cases 10-years OS* 10-years CSS 20-years CSS (n=216) (100%) (n=208) (95.4%) (n=197) (89.3%) (n=193) (81.9%) P Sex Female 174 (80.6) 170 (97.7) 163 (92.5) 159 (84.2) Male 42 (19.4) 38 (90.5) 34 (73.1) 34 (73.1) Age 45 yrs 61 (28.2) 53 (86.9) 46 (70.1) 44 (61.7) <45 yrs 155 (71.8) 155 (100) 151 (96.7) 149 (90.1) < Sex & Age Male 40 yrs 75 (34.7) 67 (89.3) 59 (72.2) 57 (64.3) & Female 50 yrs Male<40 yrs 141 (65.3) 141 (100) 138 (97.6) 136 (90.8) < & Female<50 yrs Clinical/Incidental carcinoma Clinical cancer 198 (91.7) 190 (96.0) 180 (89.5) 176 (82.1) Incidentaloma 18 (8.3) 18 (100.0) 17 (75.0) 17 (75.0) Size 4 cm 80 (37.0) 74 (92.5) 79 (83.5) 67 (68.9) <4 cm 136 (63.0) 134 (68.5) 128 (93.1) 126 (89.7) Size II >5 cm 21 (9.7) 18 (85.7) 14 (75.6) 14 (75.6) 5 cm 195 (90.3) 190 (97.4) 180 (90.8) 176 (82.4) Extrathyroidal extension Yes 43 (19.9) 37 (86.1) 29 (61.8) 28 (53.0) No 173 (80.1) 171 (98.8) 168 (96.3) 165 (89.1) < Invasion to adjacent structure Yes 8 (3.7) 5 (62.5) 2 (15.6) 2 (15.6) No 208 (96.3) 203 (97.6) 195 (92.2) 191 (84.6) < Subclassification Widely invasive 28 (13.0) 23 (81.5) 16 (52.4) 15 (43.7) Minimally invasive 188 (87.0) 185 (98.4) 181 (95.3) 178 (88.5) < Angioinvasion Yes 83 (38.4) 77 (92.8) 72 (82.7) 68 (64.5) No 70 (32.4) 70 (100.0) 67 (95.6) 67 (95.6) Initial distant metastasis Yes 11 (5.1) 7 (63.6) 3 (16.4) 3 (16.4) No 205 (94.9) 201 (98.5) 194 (93.4) 190 (85.6) < Extent of surgery Less than total 140 (64.8) 138 (98.5) 135 (95.4) 132 (88.1) Total 76 (35.2) 70 (92.1) 62 (77.5) 71 (66.3) Radioactive iodine therapy Yes 61 (28.2) 6 (90.2) 46 (70.3) 44 (53.7) No 155 (71.8) 153 (98.7) 151 (96.6) 149 (90.9) < *OS = overall survival.

4 Jandee Lee, et al:follicular Thyroid Carcinoma: Clinicopathologic Features, Prognostic Factors, and Treatment Strategy 37 결과 1) 임상적특징및진단방법진단당시평균연령은 41세 (4 87) 였으며, 남녀비는 42: 174였다. 진단당시경부갑상선종괴를주소로내원한경우는 187예 (86.6%), 측경부전이림프절종대를주소로내원한경우 1예 (0.5%), 호흡곤란이주증상인경우 1예 (0.5%) 및애성 1예 (0.5%) 였다. 그외최초원격전이부위의증상 ( 골통 6예, 두통 1예, 기침 1예, 두피종괴 1예 ) 을주소로내원하여역추적으로원발갑상선암이진단된경우는 8예 (3.7%) 였으며, 건강검진시우연히발견된경우는 18예 (8.3%) 였다. 진단방법중세침흡인검사를시행한 167예중확정적이지는않으나여포상종양 (follicular neoplasm) 이의심되거나진단된경우는 105예 (62.9%) 였으며, 동결절편검사를시행한 72예중에서악성이의심되는경우는 12예 (16.7%) 였다. 2) 병리조직학적특징종괴의평균크기는 3.0 (0.5 9) cm였으며, 최종조직검사상미세침윤형으로진단된경우가 188예 (87%), 광범위침윤형으로진단된경우가 28예 (13%) 였다. 혈관침습여부가조직검사결과지에기록되어확인이가능한경우는 153 예로이중한군데이상의혈관침습이발견된경우는 83예 (38.4%) 였다. 갑상선전절제술을시행한 76예에서다발성이 31예 (40.8%), 양측성 12예 (15.8%) 로확인되었다. 중앙경부림프절청소술을동시에시행한 48예중중앙경부림프절전이를보인경우는 10예였다. 3) 치료방법엽절제술후최종조직검사결과에따라완결절제술이시행된 34예를포함하여 76예 (35.2%) 에서갑상선전절제술 이시행되었고, 나머지 140예 (64.8%) 에서는엽절제술혹은아전절제술이시행되었다. 수술후방사성요오드치료를받은경우는저용량 (30 mci) 은 29예, 고용량 ( mci) 은 32예로모두 61예 (28.2%) 였다. 4) 예후및예후인자추적기간동안국소재발이 9예, 원격전이가 2예, 국소재발및원격전이를동시에보인경우 6예관찰되었으며, 질병관련사망이 8예였다. 10년및 20년전체생존율은각각 95.4%, 92.5% 였고, 무병생존율은각각 89.3%, 81.9% 였다 (Fig. 1). 단변량분석을통한예후인자분석상남성 (P= ), 45세이상의연령 (P<0.0001), 40세이상의남성및 50세이상의여성 (P<0.0001), 피막외침범 (P<0.0001), 주위조직침범 (P<0.0001), 광범위침윤형 (P<0.0001), 혈관침습 (P=0.0122), 최초원격전이 (P<0.0001) 등이재발을예측하는유의한지표였다. 또한, 전절제술을시행한경우이거나방사성요오드치료를시행한경우는위험요소가있거나병리조직검사상공격적인성향을보이는경우로대부분으로불량한예후를보였다 (Table 1). 다변량분석시남성 (P=0.015), 혈관침습 (P=0.013), 광범위침윤형 (P=0.028), 최초원격전이 (P<0.0001) 만이유의한예후예측인자였다 (Table 2). 5) 병리학적특징에따른예후인자의분석추적관찰기간중질병관련사망을보인 8예모두최초진단당시광범위침윤형이며다발성혈관침습을동반한경우였다. 추적기간중원격전이를보인 8예중 3예는미세침윤형이었으나혈관침습이동반된경우였으며, 5예는광범위침윤형이었다. 국소재발 15예중 7예가미세침윤형에서발견되었으며, 그중 5예는반대측갑상선, 2예는중앙구획림프절전이를보인경우였다. 또한반대측갑상선에서재발한 2예를제외한 5예의경우모두혈관침습이동반된 Table 2. Independent prognostic variables for cause-specific survival (CSS) using cox proportional hazards model Variables Hazard ratio Regression SE (95% confidence interval) coefficient (β) (standard error) P Sex Female 1 0 Male ( ) Angioinvasion No 1 0 Yes ( ) Subclassification Minimally invasive 1 0 Widely invasive ( ) Initial distant metastasis No 1 0 Yes ( ) <0.0001

5 38 J Korean Surg Soc. Vol. 74, No. 1 경우였다. 6) 병기결정법에따른예후예측기존의다양한병기결정법 (TNM, AGES, AMES, MACIS, DeGroot) 을이용하여대상군의병기를무병생존율에적용시켜보았을때 TNM 및 AMES score는모두예후예측에유용한방법이었다 (Fig. 2). 하지만, AGES, MACIS, DeGroot 병기법에서는저위험군 (I기및 II기 ) 에서장기추적관찰시 II기와 I기의예후가역전되는양상을보여저위험군에서는병기법이정확하게일치하지않았다. 고찰여포상갑상선암은전체갑상선암의약 10% 내외의빈 Fig. 2. Cause-specific survival curve for patients with follicular thyroid carcinoma classified using TNM (A), AGES (B), AMES (C), MACIS (D), DeGroot (E) category.

6 Jandee Lee, et al:follicular Thyroid Carcinoma: Clinicopathologic Features, Prognostic Factors, and Treatment Strategy 39 도를보인다고알려져있으나, 요오드섭취정도에따라서 4 39% 까지다양하게보고되고있다.(3,4,12) 대부분전경부종괴의촉지를주소로내원하는데, 양성과악성의감별은세침흡인검사로진단이불가능하며, 최종조직검사상피막침범, 혈관침습, 국소림프절전이, 원격전이등에의해결정된다.(1,2) 세침흡인검사상여포상종양이의심된경우최종조직검사에서여포상암으로진단되는경우는약 15 30% 정도로보고된다.(19-21) 저자들의경우에도여포상암의주증상은갑상선종괴의촉지 (86.6%) 가가장많았으며, 대부분의경우수술전세침흡인검사나동결절편검사가악성여부의진단에도움이되지않았다. 최근까지세침흡인검사의수술전진단방법의정확도를높이기위한분자유전학적분석및말초혈액에서암세포추출등많은연구들이있었다. 분자생물학적으로는 PAX8/ PPARŗ, 3개의유전자결합 (cyclin D2, protein convertase 2, prostate differentiagion factor), RAS 유전자변이와 retinoblastoma, p16ink4a, cyclin D1 및 c-erb Aβ 등에대한연구가진행된바있다.(22-24) 또한, 최근에는 thyrotropin 수용체, 티로글로불린 mrna 및 CEA (carcinoembryonic antigen) mrna의 RT-PTC (reverse transcriptase-polymerase chain reaction) 등으로말초혈액에서여포상암세포를감지하여술전진단을용이하게하고자하는노력들이시도되고있으나, 아직실험단계이다.(25-27) 여포상암의치료범위는광범위침윤형의경우완결절제술을포함한갑상선전절제술이필요하지만, 미세침윤형의경우에는엽절제술혹은아전절제술로충분하다고알려졌다.(1,3-7) 하지만일부에서는여포상암의혈행성전이및원격전이가능성으로여포상암으로진단된모든경우에서완결절제술을통한전절제술이치료에도움을준다는주장들도있다.(4,7,10-13) 전절제술을시행한경우방사성요오드치료의효용성에대해서도논란이있지만, 병리조직검사등에서공격적인형태를보이는경우에는대부분방사성요오드치료가권고되고있다.(1,4,7-10) 일반적으로여포상암은혈행성전이를통한원격전이가흔하며, 공격적인형태를보이는경우가많으므로유두상암에비해불량한예후를보인다고알려져왔다. 하지만최근에는연령및병기를고려하였을때여포상암및유두상암의예후에는큰차이가없다는보고도있다.(5,7,12) 분화갑상선의병기결정법인 TNM, AGES, AMES, MACIS, 및 DeGroot 병기법은모두여포상암의임상자료가소규모포함되었지만, 대부분유두상암의임상적치료결과를기초로하여고안되었다. 이러한병기결정법이대부분여포상암에도유용하다고보고되지만, 최근에는 MACIS 혹은 TNM staging이예후예측에가장정확하다는주장도있다.(9,10,28,29) 저자들의경우 TNM 및 AMES 병기법은대상군모두유의한결과를보였지만, AGES, MACIS, DeGroot 병기법에서는초기암에서 I기와 II기가추적기간이경과함 에따라예후의역전을보였다. 이같이본연구를포함한여러연구들이상이한결과를보였던이유는기존의분화갑상선암의병기결정법이여포상암의특징적인예후인자 ( 피막침범정도, 혈관침습등 ) 를포함하지않고, 유두상암의예후인자인암종의크기, 피막침윤여부등을중요하게간주하므로예후예측의정확도가떨어진것으로추정되나, 추후대규모의연구대상에대한장기추적관찰결과를분석한다면확실한결론을얻을수있으리라고생각한다. 여포상암에특징적인예후예측인자로는고령, 최초원격전이, 피막외침습, 림프절전이, 혈관침습, 광범위침윤형, 불완전절제등으로보고되고있으며, 일부에서는종괴의크기도치료결과와관계있다고주장되었다.(5,7,12,27-29) 병리조직학적아형에따라뚜렷한예후의차이를보이는데, 광범위침윤형이 40% 전후의재발률을보이는반면, 미세침윤형의경우장기간추적관찰시에도재발률 5% 이내의양호한치료결과를나타낸다.(12) 특히, 미세침윤형중에서혈관침습이없는경우에는사망률이나원격전이가거의발생하지않으므로, 양성종양과도예후에큰차이가없다는주장도있다.(30) 최근에는혈관침습여부가병리학적아형인피막침범유무와상관없이독립적인예후예측인자로판단되며, 혈관침습이있는경우에는광범위침윤형에비해서는예후가양호하지만, 혈관침습이없는미세침윤형과비교하여확연히불량한예후를보인다고보고된다.(12,13,31) 따라서미세침윤형중혈관침습을보인경우를중간침윤형 (moderately invasive, angioinvasive) 이라는새로운범주로구분하자는이론들이발표되고있으며, 수술범위에있어서도기존의미세침윤형에서다른위험요인뿐아니라혈관침습정도를기준으로완결절제술여부를결정하자는주장들이있다.(1,3,4,11-13,29) 저자들의경우에도혈관침습이독립적으로주요한예후예측인자였으며, 특히미세침윤형에서원격전이등의불량한예후를보이는경우에는대부분원발암에서혈관침습이동반되어있음을확인하였다. 즉, 미세침윤형의경우에도혈관침습등의독립적인예후인자를확인하여추가적인치료여부가고려되어야할것으로생각하며, 향후대상군이추가된다면적절한치료범위에대한지침을모색할수있을것이다. 저자들의경우다변량분석에의한독립적인예후인자는성별, 광범위침윤형, 혈관침습및최초원격전이였으며, 종괴의크기는예후와관계가없었다. 병리학적아형별로는미세침윤형및광범위침윤형의 10년무병생존율이각각 95.3% 및 52.4% 로뚜렷한예후의차이를보였다. 또한, 미세침윤형에서원격전이를보인 3예및국소재발 5예모두혈관침습이동반된경우로, 혈관침습이예후를결정하는주요한요소임을시사하였다. 하지만, 성별의경우국내에서여성들의상당수가유방검진과동시에시행하는정기적인경부초음파검진을통해초기의우연종의형태로발견되는반면, 남성들의경우대부분진행된상태에서발

7 40 J Korean Surg Soc. Vol. 74, No. 1 견되는임상암이므로성별을독립적인예후인자의하나로판단하기는어렵다. 따라서, 향후각각의대상군에서연령및병기를고려한추가적인분석이필요할것으로생각한다. 결 여포상갑상선암에대한치료방향을결정하기위해서는기존의병기결정법이기초가되지만, 여포상암의병태생리적특징에따른독립적인예후예측인자를고려하여유두상암과는차별화된치료가필요하다. 즉, 혈관침습이없는미세침윤형의경우엽절제술혹은아전절제술로충분하지만, 혈관침습을보이거나광범위침윤형의경우에는완결갑상선절제술및방사성동위원소치료와같은적극적인치료를결정해야할것으로생각한다. 론 REFERENCES 1) Hirokawa M, Carney JA, Goellner JR, DeLellis RA, Heffess CS, Katoh R, et al. Observer variations of encapsulated follicular lesions of the thyroid gland. Am J Surg Pathol 2002; 26: ) Chan JK. Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol 2002;117: ) Phitayakorn R, McHenry CR. Follicular and Hurthle cell carcinoma of the thyroid gland. Surg Oncol Clin N Am 2006; 15: ) Correra P, Chen VW. Endocrine gland cancer. Cancer 1995;75: ) DeGroot LJ, Kaplan EL, Shukla MS, Salti G, Straus FH. Morbidity and mortality in follicular thyroid cancer. Am J Surg 1995;80: ) Donohue JH, Goldfien SD, Miller TR, Abele JS, Clark OH. Papillary and follicular thyroid carcinoma. Am J Surg 1984; 148: ) Mazzaferri EL, Young RL, Oertel JE, Kemmerer WT, Page CP. Papillary thyroid carcinoma: the impact in 576 patients. Medicine 1977;56: ) Davis NL, Bugis SP, McGregor GI, Germann E. An evaluation of prognostic scoring system in patients with follicular thyroid cancer. Am J Surg 1995;170: ) D'Avanzo A, Ituarte P, Treseler P, Kebebew E, Wu J, Wong M, et al. Prognostic scoring systems in patients with follicular thyroid cancer: a comparison of different staging systems in predicting the patient outcome. Thyroid 2004;14: ) Passler C, Prager G, Scheuba C, Kaserer K, Zettinig G, Niederle B. Application of staging system for differentiated thyroid carcinoma in an endemic region with iodine substitution. Ann Surg 2003;237: ) Franssila KO, Ackerman LV, Brown CL, Hedinger CE. Follicular carcinoma. Semin Diagn Pathol 1985;2: ) Thompson LDR, Wieneke JA, Paal E, Frommelt RA, Adair CF, Heffess CS. A clinicopathologic study of minimally invasive follicular carcinoma of the thyroid gland with a review of the English literature. Cancer 2001;91: ) Baloch ZW, Livolsi VA. Pathology of the thyroid gland. In: Livolsi VA, Asa SL, editors. Endocrine Pathology. 1st ed. New York: Churchill Livingstone; p ) Hermanek P, Scheibe O, Spiessl B, Wagner G UICC: TNM classification of malignant tumors. In: ROFO Fortschr Geb Rongenstr Nuklearmed. 4th ed. Berlin: Springer-Verlag; p ) Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987;102: ) Caby B, Rossi R. An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 1988;104: ) Hay ID, Bergstralh EJ, Geollner JR, Ebersold JR, Grant CS. Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through Surgery 1993;114: ) DeGroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab 1990;71: ) McHenry CR, Sandoval BA. Management of follicular and Hurthle cell neoplasm of the thyroid gland. Surg Oncol Clin N Am 1998;7: ) Alaedeen DI, Khiyami A, McHenry CR. Fine needle aspiration biopsy specimens with a predominance of Hurthle cell: a dilemma in the management of nodular thyroid disease. Surgery 2005;138: ) De Jong SA, Demeter JG, Castelli M. Follicular cell predominance in the cytologic examination of dominant thyroid nodules indicates a sixty percent incidence of neoplasm. Surgery 1990;108: ) Ying H, Suzuki H, Zhao L, Willingham MC, Meltzer P, Cheng SY. Mutant thyroid hormone receptor β represses the expression and transcriptional activity of peroxisome proliferators-activated receptor ŗ during thyroid carcinogenesis. Cancer Res 2003;63: ) Weber F, Shen L, Aldred MA, Morrison CD, Frilling A, Saji M, et al. Genetic classification of benign and malignant thyroid follicular neoplasia based on a three-gene combination. J Clin Endocrinol Metab 2005;90: ) Challeton C, Bounacer A, Du Villard JA, Caillou B, De Vathaire F, Monier R, et al. Pattern of ras and gsp oncogene mutations in radiation-associated human thyroid tumors. Oncogene 1995;11: ) Segev DL, Umbricht C, Zeiger MA. Molecular pathogenesis of thyroid cancer. Surg Oncol 2003;12: ) Chinnappa P, Taguba L, Arciaga R, Faiman C, Siperstein A, Mehta AE, et al. Detection of thyrotropin-receptor messenger

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Kaes017.hwp

Kaes017.hwp 갑상선의 Poorly Differentiated (Insular) Carcinoma Insular Carcinoma: An Aggressive Subtype of Differentiated Thyroid Neoplasms Seok-Jin Nam, M.D., Sang-Dal Lee, M.D., Hal-lin Park, M.D., Young-Ryun Oh, M.D.