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1 REVIEW ARTICLE pissn: eissn: Int J Thyroidol 2019 May 12(1): 한국임상현장에서갑상선의행동양식불명또는미상의신생물이해 가톨릭대학교의과대학병원병리학교실 1, 암연구소 2 정찬권 1,2 Understanding Neoplasm of Uncertain or Unknown Behavior of the Thyroid in Korean Clinical Practice Chan Kwon Jung 1,2 Department of Hospital Pathology 1, Cancer Research Institute 2, College of Medicine, The Catholic University of Korea, Seoul, Korea Thyroid tumors include a heterogeneous group of entities with variable clinical behavior and histology, mostly classified as benign or malignant. Neoplasm of uncertain or unknown behavior in thyroid gland was newly adopted by the 2017 edition of World Health Organization (WHO) classification of endocrine organs. The borderline thyroid tumors include a hyalinizing trabecular tumor and three encapsulated follicular-patterned thyroid tumors (follicular tumor of uncertain malignant potential, well-differentiated tumor of uncertain malignant potential, and non-invasive follicular thyroid neoplasm with papillary-like nuclear features). This review summarizes the changes in the 2017 WHO classification of thyroid tumors, highlights their implications for clinical practice in Korea, and briefly discusses National Health Insurance system, cancer insurance policies, and their associated benefits in Korea. Key Words: Borderline tumor, Non-invasive follicular thyroid neoplasm with papillary-like nuclear features, Thyroid neoplasm, Cancer insurance 서론 신생물은행동양식에따라양성신생물 (benign neoplasm), 행동양식불명또는미상의신생물 (neoplasm of uncertain or unknown behavior), 악성신생물 (malignant neoplasm) 로구분된다. 행동양식불명또는미상의신생물은경계성종양 (borderline tumor) 으로도불린다. 가장널리사용되고있는신생물의분류는세계보건기구 (World Health Organization, WHO) 에서발표하는국제질병사인분류 (International Statistical Classification of Diseases and Related Health Problems, ICD) 이며, 제2장에서신생물을다루고있다 ( 국제질병사인분류 (ICD) 에서신생물분류체계는행동양식과각장기의위치에따라고유의상병코드를부여한다. 한국표준질병ㆍ사인분류 (Korean Standard Classification of Diseases, KCD) 는 ICD 분류를바탕으로한국의실정에맞게개정한것이며, 현재사용되고있는제7차개정판 (KCD-7) 은 ICD-10을근간으로하고있다 ( KCD-7과 ICD-10에따른신생물의분류는조직병리학적진단명을나타낼수없기때문에갑상선암은병리학적진단명과상관없이모두 Received May 14, 2019 / Revised May 21, 2019 / Accepted May 21, 2019 Correspondence: Chan Kwon Jung, MD, PhD, Department of Hospital Pathology, Seoul St. Mary s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: , Fax: , ckjung@catholic.ac.kr Copyright c 2019, the Korean Thyroid Association. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 1

2 Borderline Thyroid Tumor Table 1. Updates in nomenclature and classification of the 2017 World Health Organization (WHO) Classification of thyroid tumors 2017 WHO classification Korean terminology ICD-10 & KCD-7 code ICD-O histology and behavior code Update Follicular adenoma 소포샘종, 소포선종, 여포선종 D /0 No change Hyalinizing trabecular tumor 유리질소주형종양 D /1 ICD-O behavior code change Follicular tumor of uncertain malignant potential 악성도불명소포종양, 악성도불명여포종양 D /1 New term and Well-differentiated tumor of uncertain malignant potential Non-invasive follicular thyroid neoplasm with papillary-like nuclear features 악성도불명고분화종양 D /1 New term and 유두암종유사핵모양비침습소포종양 D /1 New term and Papillary thyroid carcinoma 갑상샘유두암종, 갑상선유두암 ( 종 ) C /3 No change Follicular variant of PTC 소포형갑상샘유두암종, C /3 New 여포형갑상선우두암 ( 종 ) Encapsulated variant of PTC 피막형성형갑상샘유두암종, 피막형성갑상선우두암 ( 종 ) C /3 New term and Papillary microcarcinoma 유두미세암종 C /3 New Columnar cell variant of PTC 원주세포형유두암종 C /3 New Oncocytic variant of PTC 호산성형유두암종, C /3 New 호산성유두암 ( 종 ) Follicular thyroid carcinoma, 갑상샘소포암종, 갑상선여포암 ( 종 ) C /3 No change NOS Minimally invasive FTC 미세침습소포암종, C /3 New 미세침습여포암 ( 종 ) Encapsulated angioinvasive FTC 피막형성형혈관침습소포암종, 피막형성형혈관침습여포암 ( 종 ) C /3 New term and Widely invasive FTC 광범위침습소포암종, C /3 No change 광범위침습여포암 ( 종 ) Hürthle cell adenoma Hürthle 세포샘종, Hürthle 세포선종 D /0 New term and Hürthle cell carcinoma Hürthle 세포암종, Hürthle 세포암 ( 종 ) C /3 New term and Poorly differentiated thyroid carcinoma 갑상샘저분화암종, 갑상선저분화암 ( 종 ) C /3 New term and Anaplastic thyroid carcinoma 갑상샘역형성암종, C /3 New term 갑상선역형성암 ( 종 ) Squamous cell carcinoma 편평세포암종 C /3 No change Medullary thyroid carcinoma 갑상샘수질암종, 갑상선수질암 ( 종 ) C /3 No change Mixed medullary and follicular 수질소포혼합암종, C /3 Term change thyroid carcinoma 수질여포혼합암 ( 종 ) Mucoepidermoid carcinoma 점액표피모양암종 C /3 No change Sclerosing mucoepidermoid 호산구증가증동반경화성점액표피 C /3 No change carcinoma with eosinophilia 모양암종 Mucinous carcinoma 점액암종 C /3 No change Ectopic thymoma 딴곳가슴샘종 C /3 ICD-O behavior code change Spindle epithelial tumor with 방추상피흉선분화종양 C /3 Term change thymus-like differentiation Intrathyroid thymic carcinoma 갑상샘내흉선암종, C /3 Term change 갑상선내흉선암 ( 종 ) Paraganglioma 부신경절종 C /3 New term and Schwannoma 신경집종 D /0 No change 2 Int J Thyroidol

3 Chan Kwon Jung Table 1. Continued 2017 WHO classification Korean terminology ICD-10 & KCD-7 code ICD-O histology and behavior code Update Malignant peripheral nerve 악성말초신경집종 C /3 No change sheath tumor Hemangioma 혈관종 D /0 No change Cavernous hemangioma 해면혈관종 D /0 No change Angiosarcoma 혈관육종 C /3 No change Leiomyoma 평활근종 D /0 No change Leiomyosarcoma 평활근육종 C /3 No change Solitary fibrous tumor 단일섬유종양 D /1 ICD-O behavior code change Langerhans cell histiocytosis 랑게르한스세포조직구증 C /3 ICD-O behavior code change Follicular dendritic cell 소포가지세포육종 C /3 No change sarcoma Primary thyroid lymphoma 일차갑상샘림프종, 일차갑상선림프종 C /3, 9591/3, 9671/3, 9680/3, 9699/3, etc. No change ICD-O: International Classification of Diseases for Oncology, ICD-10: the 10th revision of the International Statistical Classification of Diseases and Related Health Problems, FTC: follicular thyroid carcinoma, KCD-7: the 7th revision of Korean Standard Classification of Diseases, NOS: not otherwise specified, PTC: papillary thyroid carcinoma C73으로만코딩된다. 따라서, 암환자의등록과통계를위해서는별도의분류체계가필요하였다. 세계보건기구는산하에암에관한연구및통계업무를전담하는국제암연구소 (International Agency for Research on Cancer, IARC) 를설립하여병리검사진단지에서얻을수있는종양의위치, 조직형태학적진단및행동양식을동시에표현할수있는국제종양분류 (International Classification of Diseases for Oncology, ICD-O) 를제정하였다 ( 현재 ICD-O는제3판 (ICD-O-3) 이사용되고있다. 갑상선결절은매우흔히발견되지만, 이들대부분은비종양성결절이다. 갑상선종양은그동안양성과악성으로만분류되어왔으나, 2017년에세계보건기구는새롭게경계성종양을포함하여내분비종양분류법제 4판을발표하였다. 1) 갑상선종양에서경계성개념을도입한것은갑상선암의과다진단과과잉치료의문제점을해결하고자하는노력과도관련이있다. 갑상선종양의병리학적진단명과국제종양분류 (ICD-O) 의변경사항에대해서는 Table 1에요약하였다. 갑상선의종양성결절의분류가 ICD-10과 KCD-7의신생물에서다뤄지는반면, 결절성고이터와단순갑상선결절과같은비종양성결절의질병분류는 ICD-10과 KCD-7 의내분비, 영양및대사질환에서다루고있다. 갑상선의장애는상병코드 E00-E07에해당하며, 결절형태로나타날수있는갑상선질병을 Table 2에요약하였다. 갑상선종양의한글용어사용을위해우선적으로 2017년에출판한대한병리학회교과서제8판을기준으로용어를선정하였다. 그러나새롭게생성된진단명과진단분류코드에대해서는적절한한글용어가없기때문에대한병리학회편찬위원회의한글용어제정지침에따라내분비병리학연구회에서새로운한글용어를생성한후대한병리학회암관리위원회의검토과정을거쳤다. 또한대한갑상선학회, 대한내분비학회, 대한갑상선내분비외과학회의의견을수렴하여흔히혼용하여사용되는한글용어에대해서는같이기술하였다. 한글용어가혼용되어사용되는대표적인예는갑상선과갑상샘, 여포와소포, 암과암종, 선종과샘종등이해당한다 (Table 1). 갑상선경계성종양 2017년에개정된제4판 WHO 내분비종양분류책에는유리질소주형종양, 악성도불명소포종양, 악성도불명고분화종양및유두암종유사핵모양비침습소포종양을갑상선경계성종양으로분류하고있다. 1,2) 유리질소주형종양을제외한나머지는현미경학적으로피막을형성하고소포구조를보이는종양을대상으로유두암종의세포핵모양과종양피막혹은혈관의침범여부에따라세분하여각기다른이름으로명명되었다 (Fig. 1). Vol. 12, No. 1,

4 Borderline Thyroid Tumor Table 2. ICD-10 and KCD-7 diagnosis codes for non-neoplastic thyroid nodules Diagnosis code Disease (ICD-10) Korean term (KCD-7) E01.1 Iodine-deficiency-related multinodular (endemic) goitre Iodine-deficiency-related nodular goitre 요오드결핍과관련된미만성 ( 풍토병성 ) 고이터요오드결핍과관련된결절성고이터 E01.2 Iodine-deficiency-related (endemic) goitre, unspecified Endemic goitre NOS 요오드결핍과관련된미만성 ( 풍토병성 ) 고이터풍토병성고이터 NOS E03.0 Congenital hypothyroidism with diffuse goitre Goitre (nontoxic) congenital: NOS Parenchymatous 미만성고이터를동반한선천성갑상선기능저하증선천성고이터 ( 비독성 ) NOS 선천성실질성고이터 ( 비독성 ) E04.0 Nontoxic diffuse goitre Diffuse (colloid) goitre, nontoxic Simple goitre, nontoxic 비독성미만성고이터비독성미만성 ( 콜로이드 ) 고이터비독성단순고이터 E04.1 Nontoxic single thyroid nodule Colloid nodule (cystic) (thyroid) Nontoxic uninodular goitre Thyroid (cystic) nodule NOS 비독성단순갑상선결절콜로이드결절 ( 낭성 ) ( 갑상선 ) 비독성단일결절성고이터갑상선 ( 낭성 ) 결절 NOS E04.2 Nontoxic multinodular goitre Cystic goitre NOS Multinodular (cystic) goitre NOS 비독성다결절성고이터낭성고이터 NOS 다결절성 ( 낭성 ) 고이터 NOS E04.8 Other specified nontoxic goitre 기타명시된비독성고이터 E04.9 Nontoxic goitre, unspecified Goitre NOS Nodular goitre (nontoxic) NOS 상세불명의비독성고이터고이터 NOS 결절성고이터 ( 비독성 ) NOS E05.0 Thyrotoxicosis with diffuse goitre Exophthalmic or toxic goitre NOS Graves disease Toxic diffuse goitre E05.1 Thyrotoxicosis with toxic single thyroid nodule Thyrotoxicosis with toxic uninodular goitre E05.2 Thyrotoxicosis with toxic multinodular goitre Toxic nodular goitre NOS 미만성고이터를동반한갑상선독증안구돌출성또는독성고이터 NOS 그레이브스병독성미만성고이터독성단일갑상선결절을동반한갑상선독증독성단일결절성고이터를동반한갑상선독증독성다결절성고이터를동반한갑상선독증독성결절성고이터 NOS ICD-10: the 10th revision of the International Statistical Classification of Diseases and Related Health Problems, KCD-7: the 7th revision of Korean Standard Classification of Diseases 유리질소주형종양 (hyalinizing trabecular tumor, ICD-O code: 8336/1) 진단명의동의어로 hyalinizing trabecular neoplasm 과 hyalinizing trabecular adenoma가알려져있다. 세포내외에유리질성분을가지는세포가기둥모양으로배열된소포세포기원의종양으로 WHO 내분비종양분류 2017년판에는행동양식불명또는미상의신생물로분류하였다. 임상적인예후는양성종양과같이매우좋으나한보고에따르면 119예중 1례에서원격전이를보였다. 3) 비록드물지만유리질소주형종양에서림프절전이를보인증례도보고되었다. 4) 유리질소주형종양은갑상선유두암종의세포핵과동일한모양을보여세침흡인세포검사에서종종유두암종으로오인되기도한다. 그러나 BRAF와 RAS 유전자 의돌연변이는유두암종에서흔히발견되지만, 유리질소주형종양에서는전혀발견되지않았다. 최근한연구는유리질소주형종양의 14예중에서 13예는 PAX8- GLIS3 유전자융합을, 1례는 PAX8-GLIS1 유전자융합을보인다는것을밝혀유두암종과는분명다른종양임을증명하였다. 5) 악성도불명소포종양 (follicular tumor of uncertain malignant potential, : 8335/1) 종양의경계가주변조직과명확히구분되고, 유두암종의세포핵을보이지는않으나종양의피막이나혈관의침범이의심되거나불확실한갑상샘소포종양이다. 소포샘종과소포암종의중간에해당한다. 재발이나원격전이의가능성은매우낮다. 4 Int J Thyroidol

5 Chan Kwon Jung Fig. 1. Schematic illustration of encapsulated follicularpatterned thyroid tumors on the basis of presence or absence of nuclear features of papillary thyroid carcinoma and capsular or vascular invasion by 2017 World Health Organization classification. EFVPTC: encapsulated follicular variant of papillary thyroid carcinoma, FT-UMP: follicular tumor of uncertain malignant potential, NIFTP: non-invasive follicular thyroid neoplasm with papillary-like nuclear features, WDC-NOS: well-differentiated carcinoma, not otherwise specified, WDT-UMP: well-differentiated tumor of uncertain malignant potential 악성도불명고분화종양 (well-differentiated tumor of uncertain malignant potential, : 8348/1) 종양의경계가주변조직과명확히구분되고, 유두암종의세포핵을보이며종양의피막이나혈관의침범이의심되거나불확실한갑상샘소포종양이다. 유두암종의소포변종과유사한분자병리학적특성을보인다. 재발이나원격전이의가능성은매우낮다. 유두암종유사핵모양비침습소포종양 (non-invasive follicular thyroid neoplasm with papillary-like nuclear features, : 8349/1) 종양의경계가주변조직과명확히구분되고, 유두암종의세포핵을보이며, 종양의피막이나혈관의침범이없는갑상샘소포종양이다. 과거에는유두암종의비침습소포변형으로불렸던종양으로 2016년국제전문가들그룹에의해새롭게명명되었다. 6) 유두암종의소포변형중에서피막이잘형성되어있고, 주변조직이나혈관으로침범하지않는유형은수술후재발이나전이가거의발생하지않아더이상의추가치료가필요하지않기때문에이러한유형은악성으로분류하지않기로하고, 유두암종유사핵모양비침습소포종양 (non-invasive follicular thyroid neoplasm with papillary- like nuclear features, NIFTP) 이라는새로운이름으로명명하게되었다. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features라는진단명은긴이름때문에줄여서 NIFTP라는약어로더흔히사용된다. NIFTP의진단은수술조직검체에서철저한병리학적검사를통해서만가능하며, 엄격한병리진단기준을모두만족할때에만가능하기때문에, 병리의사는 NIFTP로진단할때에는진단기준을숙지하여야한다. NIFTP는 2016년에처음논문으로발표된후, 실제사용경험이부족한상태로 WHO 내분비종양분류 2017년제4판에채택되었다. 1) 이로인해 NIFTP의진단기준을실제임상현장에적용함에있어서 NIFTP 진단기준과질환의특성에대해논란과한계점이다소발견되었다. NIFTP의진단기준에맞는종양임에도불구하고일부의 NIFTP는림프절전이, 원격전이, BRAF V600E, TERT promoter 돌연변이등이발견되었고, 진단기준을적용함에있어종양조직전체가철저히검사되지못하여 NIFTP로잘못분류되는경우도발생하였다. 7-9) 2016년에처음발표되었던 NIFTP의병리학적진단기준만으로는 NIFTP와갑상선유두암종을완벽히감별해내지못하게된것이었다. 이를보완하기위하여현재까지의사용경험을바탕으로 NIFTP Vol. 12, No. 1,

6 Borderline Thyroid Tumor 에대한진단기준은보다더엄격한기준으로개정되었다. 9) 조직학적으로종양내부에서보일수있는유두구조의허용범위가초기진단기준에는 1% 이하였으나, 개정된기준에는하나라도보이면 NIFTP로진단할수없다. 또한 BRAF V600E, TERT 프로모터돌연변이, TP53 돌연변이등과같이암과의관련성이높은돌연변이가발견된경우에는 NIFTP로진단할수없다. NIFTP는미국에서특히발생빈도가높았으며, 이로인한과다진단및과잉치료에따른사회적문제를해결하기위해미국을주축으로처음만들어졌다고볼수있다. 6) 그러나한국을비롯한아시아는 NIFTP 발생률이미국에비해현저히낮고, 이를진단하는병리의사들진단기준또한다른것이밝혀졌다 ) 따라서, NIFTP 진단을위해충분한병리학적검사를시행하지못하는상황에서는 NIFTP 진단용어사용은자제해야한다. 중증질환자산정특례대상 본인일부부담금산정특례에관한기준에따르면, 중증질환자산정특례대상이되는암환자가서식에따라등록하면등록일로부터 5년간해당상병 (C00-C97, D00-D09, D32-D33, D37-D48) 으로진료를받은경우에환자는외래또는입원진료 ( 질병군입원진료및고가의료장비사용포함 ) 시요양급여비용총액의 100분의 5에해당하는금액만부담한다 ( admrullsinfop.do?admrulseq= ). 중증질환자산정특례대상상병명코드는악성신생물 (C00-C97), 제자리암종 (D00-D09), 행동양식불명또는미상의신생물 (D37-D48), 일부양성신생물 ( 수막의양성신생물 [D32], 뇌및중추신경계통의기타부분의양성신생물 [D33]) 을포함한다. 따라서갑상선경계성종양의상명코드는 D44.0에해당하여중증질환자산정특례대상이된다 (Table 3). 2019년 3월 1일부터는암상병별산정특례등록기준을충족해야산정특례등록이가능하며, 갑상선암과부갑상선암의등록기준은조직학적검사혹은세포학적검사가필수검사항목이다. 악성암이아닌제자리암종, 행동양식불명또는미상의신생물인경우에는조직학적검사만등록기준에해당한다. 그러나조직 ( 세포 ) 학적검사를시행하기가어려운경우에는등록기준예외적용으로암산정특례등록신청도가능하다. 갑상선암과경계성종양에대한암보험금 우리나라에서암보험은 1988년생명보험사들이공동으로개발한상품인 21세기암보험 으로처음소개되었으며, 초기보험은암사망비가주요담보였으며암진단비는 1990년대부터추가되었다. 1990년후반기부터는기타피부암을소액화하고, 상피내암에대한보험급부를추가하였다. 2000년대부터암진단비가주요급부로자리잡아더많은보장을요구하는고액암에대해서는별도의진단비가추가되었고, 경계성종양보험급부도추가하였다. 보험사에서판매하는암보험은암의종류에따라암 Table 3. Copayment rates for the thyroid and parathyroid tumors according to disease severity in Korea Diagnostic code (ICD-10, KCD7) Neoplasm (ICD-10) Korean term (KCD-7) Copayment rate according to the health policy* D09.30 Carcinoma in situ of thyroid 갑상선의제자리암종 5% D09.38 Carcinoma in situ of other endocrine glands 기타내분비선의제자리암종 5% D34 Benign neoplasm of thyroid gland 갑상선의양성신생물 100% D35.1 Benign neoplasm of parathyroid gland 부갑상선의양성신생물 100% D44.0 Neoplasm of uncertain or unknown behavior 갑상선의행동양식불명또는미상의신생물 5% of thyroid gland D44.2 Neoplasm of uncertain or unknown behavior 부갑상선의행동양식불명또는미상의신생물 5% of parathyroid gland C73 Malignant neoplasm of thyroid gland 갑상선의악성신생물 5% C75.0 Malignant neoplasm of parathyroid gland 부갑상선의악성신생물 5% *Copayment rate for total health care costs covered by the National Health Insurance Program. ICD-10: the 10th revision of the International Statistical Classification of Diseases and Related Health Problems, KCD-7: the 7th revision of Korean Standard Classification of Diseases 6 Int J Thyroidol

7 Chan Kwon Jung 보험금의지급범위가달라진다. 치료비용이많이드는고액암은일반암보다보장급부가더크다. 특히암진단비에서소액암, 일반암, 고액암간의차이가크게난다. 예후가좋고, 치료비용이상대적으로낮은암은일반암보험금의 10-30% 수준으로보장되는것이일반적이다. 또한암보험은악성종양외에도경계성종양, 제자리암에대해서도암보험금의 10-30% 수준을보장하고있다. 현재보험사의보험약관에서 암 이란한국표준질병ㆍ사인분류에있어서악성신생물로분류되는질병 (C00-C97) 으로정의하지만, 예외적으로질병분류번호 C44 ( 피부의기타악성신생물 ) 와 C73 ( 갑상선의악성신생물 ), 대장점막내암및전암병변 ( 암으로변하기이전상태 ) 은암에서제외하고있다. 또한, 질환분류번호 C77-C80 ( 이차성악성신생물및상세불명부위의악성신생물 ) 의경우일차성악성신생물이확인되는경우에는원발부위 ( 최초발생한부위 ) 를기준으로분류하고있다. 그러나, 이러한기준이정립되기이전에는보험사별보험상품판매시기에따라약관에많은차이가있었다. 이로인해갑상선암의보험금지급에대한보험분쟁이많이발생하게되었다. 대개 2006년이전에판매된암보험상품은갑상선암에대한별도의규정을두지않아갑상선암을일반암으로취급하기때문에보험금지급에대한다툼은없었다. 그러나 2006년-2011년기간동안판매된암보험상품약관에서갑상선암의경우소액으로지급하는보험금지급기준만명시하였고, 갑상선암이경부림프절이나타장기로전이하여추가질병분류번호를진단받는경우에대한보험금지급기준은명확히하지않았다. 이로인해이기간동안암보험에가입한보험가입자들은갑상선암이경부림프절전이된경우상명코드 C73 ( 갑상선암 ) 과 C77 ( 경부림프절전이 ) 을함께진단받아일반암진단비추가지급을요구하는법적다툼이발생하기도하였다. 현재는우리나라에서판매되는암보험은갑상선암, 기타피부암, 대장점막내암, 제자리암, 경계성종양을 유사암 혹은 소액암 으로분류하여일반암에비해소액의보험금만을지급하고있다. 일반적으로생각하면갑상선암발생률은매우높고예후가아주좋아서암보험금을차등지급하는것은합리적으로보인다. 그러나갑상선에서발생한모든악성신생물 ( 암 ) 을질병분류번호 C73으로분류하고, 이에근거하여암보험금을동일하게지급하는데에는문제점이있다. 비록대부분의갑상선암환자의예후가좋다고할지라도, 일부환자는잦은재발과치료되지않는원격전이가발 생하여고액의치료비를부담할수도있고, 드물지만예후가일반암보다도더불량한역형성암종이발생할수도있다. 따라서, 병리학적으로다양한갑상선암을 C73 분류번호하나로갑상선암환자를분류하는것은치료과정이복잡하고, 예후가좋지않아암치료비가많이발생하는갑상선암환자를역차별하는결과를초래할수도있다. 갑상선경계성종양을가진환자는수술후재발을하는경우가거의없기때문에수술후추가적인치료를요하는경우는거의없다. 이러한임상적경과와치료원칙은양성종양과거의동일하다. 갑상선경계성종양과갑상선암의진단차이에따른암보험급지급범위는암보험상품가입시기에따라다르다. 대략 2006 년이전의보험가입자의경우에는갑상선암으로진단될경우일반암에준하는보험금을지급받을수있으나경계성으로진단될경우에는소액만지급받는다. 그러나, 그이후시기부터는대부분의보험상품은갑상선암과경계성종양에대한보험금지급기준을동일시하여, 최근암보험상품에가입한경우에는갑상선종양의진단이경계성이든악성이든보험금지급에는큰영향이없을것으로예상된다. 그러나, 암보험상품은판매하는보험사마다다르기때문에반드시보험약관을꼭확인하여야한다. 결론 세계보건기구는 2017년에내분비종양분류법을 4차개정발표하면서갑상선경계성종양개념을새롭게도입하였다. 유리질소주형종양은양성종양에서경계성종양으로재분류되었으며, 나머지 3종양 ( 악성도불명소포종양, 악성도불명고분화종양및유두암종유사핵모양비침습소포종양 ) 은새롭게채택된것이다. 이들종양의발생빈도는지역과기관마다차이가크게나고, 서양인에비해한국을비롯한아시아인에서는훨씬낮게보고되었다. 갑상선에서경계성종양은기존에없던새로운종양분류로서복잡한병리학적진단기준을바탕으로정의되었고, 진단명은길고다소생소한단어를포함하여이들종양을정확히이해하기어려울수있다. 유두암종유사핵모양비침습소포종양 (NIFTP) 의경우과거에는유두암종으로불렸으나현재는경계성으로재분류되는종양이기때문에, NIFTP 를정확히진단하기위해서는병리검사에추가적인물적자원, 노력과시간을더투입하여야한다. 경계성종양을수술전에세침흡인세포검사나조직생검을통 Vol. 12, No. 1,

8 Borderline Thyroid Tumor 해서진단할수는없다. 또한종양생물학적특성상악성으로진행할수있는질병이기때문에수술적절제를통해서만최종진단과치료가가능하다. 이러한경계성종양의특성을의사와환자가올바르게이해하여환자에게적정진료가이뤄질수있도록모두노력하여야할것이다. 중심단어 : 경계성종양, 유두암종유사핵모양비침습소포종양, 갑상선신생물, 암보험. References 1) Lloyd RV, Osamura RY, Klöppel G, Rosai J. WHO classification of tumours of endocrine organs. 4th ed. Lyon: IARC publication; ) Kakudo K, Bychkov A, Bai Y, Li Y, Liu Z, Jung CK. The new 4th edition World Health Organization classification for thyroid tumors, Asian perspectives. Pathol Int 2018;68(12): ) Gowrishankar S, Pai SA, Carney JA. Hyalinizing trabecular carcinoma of the thyroid gland. Histopathology 2008;52(4): ) Sambade C, Franssila K, Cameselle-Teijeiro J, Nesland J, Sobrinho-Simões M. Hyalinizing trabecular adenoma: A misnomer for a peculiar tumor of the thyroid gland. Endocr Pathol 1991;2(2): ) Nikiforova MN, Nikitski AV, Panebianco F, Kaya C, Yip L, Williams M, et al. GLIS rearrangement is a genomic hallmark of hyalinizing trabecular tumor of the thyroid gland. Thyroid 2019;29(2): ) Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: A paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol 2016;2(8): ) Parente DN, Kluijfhout WP, Bongers PJ, Verzijl R, Devon KM, Rotstein LE, et al. Clinical safety of renaming encapsulated follicular variant of papillary thyroid carcinoma: Is NIFTP truly benign? World J Surg 2018;42(2): ) Cho U, Mete O, Kim MH, Bae JS, Jung CK. Molecular correlates and rate of lymph node metastasis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive follicular variant papillary thyroid carcinoma: the impact of rigid criteria to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features. Mod Pathol 2017;30(6): ) Nikiforov YE, Baloch ZW, Hodak SP, Giordano TJ, Lloyd RV, Seethala RR, et al. Change in diagnostic criteria for noninvasive follicular thyroid neoplasm with papillarylike nuclear features. JAMA Oncol 2018;4(8): ) Bychkov A, Jung CK, Liu Z, Kakudo K. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features in Asian practice: Perspectives for surgical pathology and cytopathology. Endocr Pathol 2018;29(3): ) Bychkov A, Keelawat S, Agarwal S, Jain D, Jung CK, Hong S, et al. Impact of non-invasive follicular thyroid neoplasm with papillary-like nuclear features on the Bethesda system for reporting thyroid cytopathology: a multi-institutional study in five Asian countries. Pathology 2018;50(4): ) Liu Z, Bychkov A, Jung CK, Hirokawa M, Sui S, Hong S, et al. Interobserver and intraobserver variation in the morphological evaluation of noninvasive follicular thyroid neoplasm with papillary-like nuclear features in Asian practice. Pathol Int 2019;69(4): Int J Thyroidol

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.