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1 ORIGINAL ARTICLE pissn: eissn: Int J Thyroidol 2016 November 9(2): 임신중진단된갑상선유두암의외과적치료시기 미래여성병원외과 1, 산부인과 2 김윤석 1, 이창훈 1, 제은애 2, 이영진 2, 정주은 2, 김수선 2, 김미향 2, 이은숙 2, 박천숙 2, 박재묵 2, 정현우 2, 박무실 2, 이재준 2, 안준모 2, 이수 2 Timing of Surgical Management of Papillary Thyroid Cancer Diagnosed during Pregnancy Yoonseok Kim 1, Changhoon Lee 1, Eunae Jae 2, Youngjin Lee 2, Jueun Jung 2, Susun Kim 2, Mihyang Kim 2, Eunsuk Lee 2, Chunsuk Park 2, Jaemook Park 2, Hyunwoo Jung 2, Musil Park 2, Jaejun Lee 2, Junmo Ahn 2 and Soo Lee 2 Departments of Surgery 1 and Obstetrics & Gynecology 2, Mirae Woman s Hospital, Busan, Korea Background and Objectives: Although the thyroid cancer occurs in every one of 1000 pregnant women, the optimal timing of surgery is still uncertain. The aim of this study is to propose the timing of surgical management of papillary thyroid cancer in pregnant woman. Materials and Methods: The authors reviewed the medical records of papillary thyroid cancer patients diagnosed during pregnancy in our hospital from May 1st, 2013 to April 30th, We analyzed the changes of radiologic and pathologic findings during prenatal and postpartum period. Results: 17 of 4978 patients were diagnosed with papillary thyroid cancer. 10 of 17 patients enrolled in this study. Each size of thyroid cancer in 1st trimester, in 2nd trimester, in 3rd trimester, and after delivery was 11.30±6.01 mm, 12.74±7.79 mm, 13.82±9.93 mm, and 13.82±8.19 mm, respectively. No patient showed the recurrence or death after surgery. Conclusion: There was no statistical significance on the prognosis of papillary thyroid cancer during prenatal and postpartum period. The authors propose that the surgical treatment of papillary thyroid cancer diagnosed during pregnancy could be delayed after delivery. Key Words: Pregnancy, Thyroid neoplasms, Timing of surgery 서론 최근한국인의암발생통계에서갑상선암은전체암중 19.6% 를차지하여우리나라에서가장호발하는암으로알려졌으며, 특히여성에서가장높은빈도를차지하는암으로보고되고있다. 1) 2013년 Cho 등 2) 의보고에의하면한국인의갑상선암은대부분분화갑상선암이차지하고있으며, 이는예후가매우양호하여 10년생존율이 96% 이상에이르는것으로알려져있 다. 2,3) 가임기여성에서발견되는암은대부분분화갑상선암이며, 임산부약 1000명당 1명꼴로발생한다고알려져있다. 4,5) 임신중갑상선암의수술적치료는임신2기에해야한다는주장과출산후수술을해야한다는의견으로대비되고있다. 6-9) 이러한논란은임신중갑상선암수술에명확한방침이없다는것이외에도모체와태아에발생할수있는합병증의위험에의한것이라고할수있다. 9,10) 이에저자들은최근 2년간본원에서출산한산모들중외과에서임신중갑상선유두암을진단받고, 수술 Received October 31, 2015 / Revised 1st May 12, 2016, 2nd May 26, 2016 / Accepted May 26, 2016 Correspondence: Changhoon Lee, MD, PhD, Department of Surgery, Mirae Woman s Hospital, 459 Gaya-daero, Busanjin-gu, Busan 47268, Korea Tel: , Fax: , gschlee@naver.com Copyright c 2016, 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. 168

스크리닝초음파를한환자들의갑상선초음파소견은 TIRADS (Thyroid Image Reporting and Data System) 분류 11) 에따랐으며, 이중 TIRADS 4a 이상인환자를대상으로하였다. TIRADS 4a 이상이지만종양의크기가 0.5 cm 미만인경우는추적관찰을하였으며 (Fig. 1), 0.

2 Timing of Surgery of PTC Diagnosed during Pregnancy 한환자를대상으로후향적분석을통해임산부에서갑상선유두암의수술적치료를임상적으로고찰하여, 적합한외과적치료시기를알아보고자하였다. 대상및방법 2013년 5월 1일부터 2015년 4월 30일까지만 2년간미래여성병원산부인과에서시행한총분만 4978건중, 임신진단을위해본원외래를첫방문하여스크리닝유방 / 갑상선초음파를시행한 1863예의환자를대상으로하였다. 스크리닝초음파를한환자들의갑상선초음파소견은 TIRADS (Thyroid Image Reporting and Data System) 분류 11) 에따랐으며, 이중 TIRADS 4a 이상인환자를대상으로하였다. TIRADS 4a 이상이지만종양의크기가 0.5 cm 미만인경우는추적관찰을하였으며 (Fig. 1), 0.5 cm 이상의경우에한해초음파유도하세침흡인세포검사를시행하였다. 이중병리학적소견상갑상선유두암으로진단받은환자 17명을대상으로후향적의무기록조사를시행하였으며, 갑상선암진단환자중임신또는분만후에갑상선절제술을시행한 10명을최종대상으로선정하였다. 환자의의무기록을통해갑상선암진단시임신주수및환자의나이, 진단초음파상크기와경부임파선전이여부, 수술시기, 진단시기와수술시기의시간간격, 수술방법및술후방사성요오드치료여부, 수술후최종조직결과, 임신분기당초음파상병변의크기변화를분석하였고, 술후재발여부를확인하였다. 환자의임신주수평가는규칙적인월경력을가진경우최종월경일을기준으로하였고, 불규칙적인월경력을가진환자는임신초기혹은초진초음파소견을참고로교정한예정일을기준으로하였다. 통계분석은 SPSS 19 (SPSS Inc., Chicago, IL, USA) 를이용하여양측검정을시행하였으며, Student t-test 를이용하여 95% 신뢰구간을기준으로 p값이 0.05 미만인경우를통계적으로유의하다고판정하였다. 결과 환자군의특징연구기간중미래여성병원산부인과에서시행한분만건수는총 4978건이었으며, 이중임신확인을위해첫외래방문시스크리닝유방 / 갑상선초음파를시행한경우는 1863예였다. 이중병리학적소견상갑상선유두암으로진단받은환자는 17명이었고, 갑상선절제술을시행한경우는최종 10명으로, 본원에서 7명, 타원에서 3명을시행하였으며나머지 7명중 6명은연구기간내에분만전이었고 1명은분만후수술받지않고추적조사만하고있었다. 수술환자 10명의수술시기는임신 2분기 1예를제외한 9명의환자가출산후 6개월이내에수술을받았으며, 진단시기와수술시기의시간간격은평균 5.87± 4.91개월이었다. 17명의갑상선암진단환자의나이는평균 34.80±3.01세였고, 진단당시임신태령은임신 1분기 16예, 3분기 1예로평균임신 9.06±8.04주였다 (Table 1). 전체 17명의환자중수술을시행한환자는 10명이었으며, 본연구에최종대상으로선정되었다. 10명의수술환자모두가갑상선전절제및중앙경부림프절곽청술을시행하였으며, 2명의환자에서변형근치적경부곽청술이추가되었다. 수술후방사성요오드치료를시행한경우는 4예였으며, 모든환자의수술전세침흡인검사와술후조직검사결과갑상선유두암으 Fig. 1. TIRADS 4a mass which sized less than 0.5 centimeters. (A) Transverse view, (B) Longitudinal view. TIRADS: Thyroid Image Reporting and Data System. 169 Int J Thyroidol

3 Yoonseok Kim, et al 로확인되었다 (Table 2). 최종선정된환자각각의데이터는 Table 3과같다. 수술전후종괴크기의변화및술후경과 전체수술환자 10명중 1명은임신 3분기에초음파진단되어총 9명의환자에서임신중크기변화를확인 Table 1. Characteristics of patients (n=17) No. of patients (%) Time of ultrasonographic diagnosis 1st trimester 16 (94.1%) 3rd trimester 1 (5.9%) Time of FNA* diagnosis 1st trimester 5 (29.4%) 2nd trimester 3 (17.6%) After delivery 9 (52.9%) Ultrasonographic findings Location Right 4 (23.5%) Left 5 (29.4%) Isthmus 2 (11.8%) Both 6 (35.3%) Size <1 cm 8 (47.1%) 1 cm 9 (52.9%) Central neck node metastasis Yes 4 (23.5%) No 13 (76.5%) Lateral neck node metastasis Yes 2 (11.1%) No 15 (88.9%) *FNA: fine needle aspiration 할수있었다. 1분기초음파상종괴의크기는평균 11.30±6.01 mm였으며, 임신 2분기와 3분기종괴의크기는각각평균 12.74±7.79 mm, 13.82±9.93 mm였다. 수술후최종병리검사상종괴의크기는평균 13.84± 8.19 mm로약간의크기증가가있었으나진단당시와비교하면통계적으로차이는없었다 (Table 4, Fig. 2). 전체수술환자에서수술후합병증은관찰되지않았으며, 특별한징후또한보이지않았다. 수술후경과관찰기간은평균 16.50±4.48개월이었고, 이기간동안병변의재발및환자사망은관찰되지않았다. 고찰 한국인의갑상선암은인구 10 만명당 명으로 Table 2. Characteristics of patients who received thyroid surgery (n=10) No. of patients (%) Timing of surgery 2nd trimester 1 (10.0%) After delivery 9 (90.0%) Surgical procedure TT c CCND* 8 (80.0%) TT c mrnd 2 (20.0%) RAI Yes 4 (40.0%) No 6 (60.0%) *Bilateral total thyroidectomy with central compartment neck dissection; Bilateral total thyroidectomy with modified radical neck dissection; Radioactive iodine Table 3. Data of patients who enrolled in this study (n=10) No. Age (yr) Location Size* (mm) Node metastasis status Time of surgery Surgical procedure RAI 1 32 Right 28.0 Negative S TT c CCND No 2 39 Both 26.0 Negative P TT c CCND Yes 3 35 Both 11.9 Central P TT c mrnd** Yes Lateral 4 32 Left 10.7 Negative P TT c CCND No 5 39 Left 10.0 Negative P TT c CCND No 6 34 Left 3.0 Central P TT c CCND No 7 34 Both 10.0 Negative P TT c CCND No 8 36 Right 9.0 Negative P TT c CCND No 9 37 Both 16.0 Negative P TT c CCND Yes Both 35.0 Central Lateral P TT c mrnd Yes *Largest mass size at ultrasonographic diagnosis, Pathologic finding, Radioactive iodine, Second trimester, Bilateral total thyroidectomy with central compartment neck dissection, Postpartum period, **Bilateral total thyroidectomy with modified radical neck dissection Vol. 9, No. 2,

Timing of Surgery of PTC Diagnosed during Pregnancy Table 4. Change in tumor size during prenatal and postpartum period (n=9) 1st trimester 2nd trimester 3rd trimester Final pathology Size* (mm) 11.

Ultrasonographic findings which shows an increase in the size of tumor. (A) 1st trimester, (B) 2nd trimester and (C) 3rd trimester. 알려져있고, 일반적으로임산부 1000명당한명꼴로발견되는것으로보고되고있다.

4 Timing of Surgery of PTC Diagnosed during Pregnancy Table 4. Change in tumor size during prenatal and postpartum period (n=9) 1st trimester 2nd trimester 3rd trimester Final pathology Size* (mm) 11.30± ± ± ±8.19 p value Reference standard *Mean±standard deviation, Statistical value compared with 1st trimester Fig. 2. Ultrasonographic findings which shows an increase in the size of tumor. (A) 1st trimester, (B) 2nd trimester and (C) 3rd trimester. 알려져있고, 일반적으로임산부 1000명당한명꼴로발견되는것으로보고되고있다. 1,4,5) 본원에서진단된임산부갑상선암의경우만 2년간의분만환자 4978명중 17명이진단되어외국사례의유병률보다약 3배정도높은것으로확인되었다. 일반적인갑상선암의첫번째치료는수술적치료와방사성동위원소를이용한치료로나뉜다. 이런치료원칙하에수술이임산부의경우임신시정상적인생리적변화이외에도수술합병증이산모뿐아니라태아에도치명적인영향을줄수있다는점에서좀더신중한치료결정이필요하다 ) 특히방사성동위원소치료는일반인의경우와달리임신시태아에많은양의방사선을노출시켜, 그로인한후유증으로임산부의갑상선암치료에는금기이며, 모유에다량의방사선이축적되어분비되므로수유부에게도금기되는치료법이다. 따라서임산부갑상선암치료는수술적치료가유일한치료법으로알려져있다 ) 임산부의갑상선암수술시기에대한의견은크게임신중과출산후로나뉜다. 임신중수술을해야한다는측의주장은임신에의한여러가지생리학적변화가갑상선에자극을주기때문이다. 임신중갑상선자극호르몬과구조적으로유사한사람융모성고나도트로핀의증가로인해갑상선암조직의자극이증가되고이는임신중갑상선암의급격한크기증가와관련이있다고주장한다. 19) 반대로출산후로수술시기를연기해야한다는주장의근거는다음과같다. 첫째, 임신 2분기때의수술적치료는모체의갑상선기능저하를 가져오고, 이는저체중아및기형아출산과신생아의인지능력저하등을유도하기때문이다. 둘째, 전신마취제에의한태아의기관형성 (organogenesis) 장애유발및자연유산, 조산등의위험성이증가되기때문이다. 14) 이상과같은이유로임신중갑상선암의수술은그시기에있어많은논란이있다. 6-9,20,21) 본원에서는임신중분화갑상선암이발견된환자에서경부림프절전이가없거나공격적인병의진행을보이지않는경우는수술적치료를분만후로연기하고있다. 이에본연구는임신중과출산후기간동안의갑상선병변크기의변화및술후최종병변의크기를비교분석하여임신이병변의변화에어떠한영향을미치는지알아보고, 수술후추적검사를통해예후를분석하여그수술시기를출산후로연기하는것이옳은것인지에대한방침을제시하고자한다. 이전의여러연구를통하여보면 Messuti 등 22) 은임신이분화갑상선암의예후에부정적인영향을준다고하였으나, 에스트로겐수용체, 프로게스테론수용체, 아로마타제, NIS유전자, BRAF V600E 변이가모두병변의병태생리에관여하지않아그에대한연구가필요하다하였고, Hirsch 등 23) 은출산후갑상선암수술기간과임신과의상관관계를연구한결과임신시병변의진행을의심할수있는소견이관찰되나임신자체가갑상선암의재발을유도하지않는다고하였다. 그들이관찰한생물학적 / 방사선학적으로병변의진행을보이는환자들은이미임신전부터공격적인성향을지닌종양이었다고하며, 질병자체의과거력이더욱 171 Int J Thyroidol

5 Yoonseok Kim, et al 중요하다하였다. Yasmeen 등 24) 의연구에서는임신자체가갑상선암의예후에영향을주지않는다고하며, 임신중갑상선절제술이산모 / 태아에악영향을주지않는다고하였다. Vini 등 7) 은평균 28세의산모를대상으로한연구에서갑상선암이진단된지 1년이후에수술을하는경우 1년이내에하는것에비해나쁜예후를가진다고하였으며, 초기임신에진단된경우임신 2분기, 임신후반기에진단된경우출산후로그수술시기를정해야한다고하였다. 그에반해, Moosa 등 9) 은동일한연령대환자들의경우임산부와비임산부의예후는차이가없어수술시기를출산후로연기하는것이옳다고하였다. 또한 Shindo 등 25) 은미세유두암임산부환자중 44% 에서임신중크기의증가가관찰되어비임산부환자에비해통계적으로의미있는차이를나타내었으나, 예후에는관련이없다는보고를하였으며, Nam 등 26) 도임신 2분기때나유산후수술하는경우에비해출산후로수술을연기하는경우가종양의크기를약간증가시키지만수술시간, 수술관련합병증, 치료결과등이차이를나타내지않아출산후수술을권장한다고하였다. 본연구에서도마찬가지로임신중종양의크기는증가되는양상을보였으나, 통계적으로유의하지않아임신자체가병의예후에영향을주지않는다고할수있었다. 본연구에서관찰된임상적변화와수술결과의비교분석을통해임신중갑상선유두암의변화는통계적인의미를나타내지않았다. 또한수술후추적검사에서전신재발혹은갑상선암에의한사망은단한예도나타나지않아전체생존기간에는영향을미치지않았다. 따라서, 임신중발견된갑상선유두암의수술적치료는모체와태아에합병증을발생시킬수있다는점에서볼때수술시기를출산후로연기하는것을고려할수있겠으며, 좀더많은환자를대상으로한추가적인연구가필요할것으로생각된다. 결론 본연구를통해임신중진단된갑상선유두암의수술을출산후로연기한예에서종양의크기는약간증가하였지만예후에는변화가없었고, 임신중수술에의한합병증을피할수있으므로, 출산이후로수술을연기하는것이좋을것으로생각된다. 중심단어 : 임신, 갑상선암, 수술시기. References 1) Jung KW, Won YJ, Kong HJ, Oh CM, Cho H, Lee DH, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in Cancer Res Treat 2015;47(2): ) Cho BY, Choi HS, Park YJ, Lim JA, Ahn HY, Lee EK, et al. Changes in the clinicopathological characteristics and outcomes of thyroid cancer in Korea over the past four decades. Thyroid 2013;23(7): ) Machens A, Holzhausen HJ, Dralle H. The prognostic value of primary tumor size in papillary and follicular thyroid carcinoma. Cancer 2005;103(11): ) Donegan WL. Cancer and pregnancy. CA Cancer J Clin 1983;33(4): ) Akslen LA, Haldorsen T, Thoresen SO, Glattre E. Incidence of thyroid cancer in Norway Population review on time trend, sex, age, histological type and tumour stage in 2625 cases. APMIS 1990;98(6): ) Hod M, Sharony R, Friedman S, Ovadia J. Pregnancy and thyroid carcinoma: a review of incidence, course, and prognosis. Obstet Gynecol Surv 1989;44(11): ) Vini L, Hyer S, Pratt B, Harmer C. Management of differentiated thyroid cancer diagnosed during pregnancy. Eur J Endocrinol 1999;140(5): ) Herzon FS, Morris DM, Segal MN, Rauch G, Parnell T. Coexistent thyroid cancer and pregnancy. Arch Otolaryngol Head Neck Surg 1994;120(11): ) Moosa M, Mazzaferri EL. Outcome of differentiated thyroid cancer diagnosed in pregnant women. J Clin Endocrinol Metab 1997;82(9): ) Yoshimura M, Hershman JM. Thyrotropic action of human chorionic gonadotropin. Thyroid 1995;5(5): ) Horvath E, Majlis S, Rossi R, Franco C, Niedmann JP, Castro A, et al. An ultrasonogram reporting system for thyroid nodules stratifying cancer risk for clinical management. J Clin Endocrinol Metab 2009;94(5): ) Mazzaferri EL. Approach to the pregnant patient with thyroid cancer. J Clin Endocrinol Metab 2011;96(2): ) Owen RP, Chou KJ, Silver CE, Beilin Y, Tang JJ, Yanagisawa RT, et al. Thyroid and parathyroid surgery in pregnancy. Eur Arch Otorhinolaryngol 2010;267(12): ) Fanarjian N, Athavale SM, Herrero N, Fiorica J, Padhya TA. Thyroid cancer in pregnancy. Laryngoscope 2007;117(10): ) Gibelli B, Zamperini P, Proh M, Giugliano G. Management and follow-up of thyroid cancer in pregnant women. Acta Otorhinolaryngol Ital 2011;31(6): ) American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19(11): ) Gorman CA. Radioiodine and pregnancy. Thyroid 1999;9(7): Vol. 9, No. 2,

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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.