대한초음파의학회지 2011; 30(3) 갑상선유두암의경부림프절전이의진단 : 전산화단층촬영의 조영증강양상이림프절전이의진단에도움이되는가? 신현주 김은경 문희정곽진영 연세의대영상의학교실 Diagnosis of Cervical Metastatic Lymph Nodes in Papillary Thyroid Carcinoma: Is CT Enhancement Useful for Diagnosing Lymph Node Metastasis? Hyun Joo Shin, MD, Eun-Kyung Kim, MD, Hee Jung Moon, MD, Jin Young Kwak, MD Department of Radiology, Yonsei University College of Medicine J Korean Soc Ultrasound Med 2011; 30: 187-191 Received March 22, 2011; Revised July 15, 2011; Accepted July 25, 2011. Address for reprints : Jin Young Kwak, MD, Department of Radiology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752, Korea. Tel. 82-2-2228-7400 Fax. 82-2-393-3035 E-mail: docjin@yuhs.ac Purpose: We wanted to determine the utility of CT enhancement for diagnosing metastatic lymphadenopathy in patients with papillary thyroid carcinoma (PTC), and especially in the lymph nodes (LNs) of the lateral neck level and that are not suspicious for metastasis on ultrasonography (US). Materials and Methods: Our study population included 34 consecutive LNs of 31 patients (25 females and 6 males, mean age: 46.7 yrs) with PTC and who had no suspicious metastatic lateral cervical LN on preoperative US, but enhancement of the lateral cervical LNs was seen on CT. To objectify the degree of enhancement, the difference of Hounsfield units between the suspicious LN and that of the ipsilateral SCM muscle was calculated. For the node-by-node analysis, marking of the corresponding LN with CT enhancement on the second look US was performed. The final assessment was attained by surgical dissection of the marked LNs. The medical records were reviewed for the patients age and gender and the size of the LNs. Results: Among the 34 LNs, 17 LNs were diagnosed as metastasis and 17 were benign. There was no difference in the size of the LNs between two the groups (benign and metastatic). The patients who had metastatic LNs were younger than those patients with benign LNs (p = 0.037). The incidence of metastatic LN was higher in the male patients than in the female patients (F:M = 38.5%:100%, p = 0.018). There was no statistical difference between the metastatic LNs and benign LNs according to the degree of enhancement (p = 0.953). Conclusion: The degree of CT enhancement is not feasible to use for diagnosing metastatic LNs in the lateral neck level in patients with PTC. Key words : Papillary thyroid carcinoma; Computed tomography (CT); Lymph node enhancement 서론유두암은갑상선에서가장흔한암으로국소림프절전이의빈도가높다 [1-3]. 이러한림프절전이는국소재발률과연관성이높고, 이는치료방법및수술범위결정, 또수술후예후 판정에중요한영향을미친다 [4, 5]. 그러므로수술전평가에있어국소림프절전이의정확한예측이중요하다 [6]. 수술전병기결정에서초음파는 American Thyroid Association guidelines에서권고하는가장유용한방법이다 [7]. 갑상선암의경부림프절전이를진단하는데초음파는민감도는 52-84%, 특이도는 95-97% 로보고되었다 [8, 9]. - 187-
대한초음파의학회지 2011;30(3) 전산화단층촬영 (Computed Tomography, CT) 은지금까지는갑상선암환자의수술전평가에있어서관례적으로시행되는검사는아니었으나, 최근몇몇연구에서수술전초음파와 CT가초음파단독시행보다뛰어난진단율을보였다 [10, 11]. CT에서갑상선유두암의림프절전이를시사하는소견은석회화, 낭성또는, 괴사성변성, 둥근모양 (round shape), 강한조영증강이다 [10, 11]. 이중, 림프절조영증강은 CT에서만평가가능한항목으로이에대한객관적인지표를제시한연구는거의없다. 기존연구에서는갑상선유두암의수술전평가로시행한초음파, CT 결과와수술결과를후향적으로비교하여각각의민감도, 특이도등을분석하였으나, 이번연구에서는갑상선유두암의림프절전이진단에 CT의조영증강이가지는유용성및 CT가초음파에더하여추가적인의미를가지고있는지를평가하기위하여, 초음파에서전이가의심되지않았으나 CT상조영증강이있었던림프절만을대상으로 CT의진단적가치를알아보고자하였다 [10, 11]. Siemens Healthcare, 3 mm reconstructed slice thickness) 을시행하고있다. 조영제는 90 ml의 iodinated contrast (iopromide, Ultravist 300, Bayer Schering Pharma) 를사용하였고, 3 ml/s의속도로주입되었다. 쇄골하정맥에서오는혈류에의한인공허상을최소화하기위하여조영제주입직후생리식염수를 3 ml/s의속도로주입하였다. Scan delay time은 40-60초였다. CT에서림프절전이가의심되는소견은석회화, 중심부괴사또는낭성변성, 주변근육보다높은조영증강을보이는경우였다. 이연구에서는초음파시행후 CT를시행하여, 초음파에서전이의심소견이없으나 CT에서다른의심스러운소견없이단지조영증강을보인병변에대하여이소견의진단정확도를평가하였다. 정성적으로조영증강이의심되는림프절을선택하여, 조영증강의객관적인정도를평가하기위하여해당림프절과동측흉쇄유돌근에서난원형의 region of interests (ROIs) 를그려이둘의차이값을구하였다. 림프절의 HU 값에서근육의 HU 값을뺀값을조영증강정도 (degree of enhancement; DOE) 로생각하였다. 대상및방법환자군본병원의생명윤리위원회가이연구에대하여승인하였고검사시행전환자에대한사전동의가이루어졌다. 2008년 4 월부터 2008년 9월까지본원에서갑상선유두암으로수술전병기결정목적으로시행한초음파에서경부림프절전이가의심되지않았으나 CT에서외측경부림프절의조영증강이관찰되었던 31명의환자에서 34개의림프절에대하여후향적으로연구를진행하였다. 의심되는림프절위치는 level Ⅰ (n = 1), level Ⅱ (n = 2), level Ⅲ (n = 20), level Ⅳ (n = 9), level Ⅴ (n = 1), level Ⅵ (n = 1) 였고, 장경은 4-17 mm ( 평균 7.62 mm) 였다. 여자는 25명 (80.6%), 남자는 6명 (19.4%) 이었으며평균연령은 46.7세였다. 수술전초음파에의한림프절평가수술전병기결정초음파는 7-15-MHz 선형탐촉자 (HDI5000; Philips Medical Systems, Bothell, WA) 또는 5-12-MHz 선형탐촉자 (iu22; Philips Medical Systems) 를이용하였다. 초음파는 11년, 7년, 5년의경험을가지고있는 3명중한명의영상의학과전문의 (K.E.K., K.J.Y., K.M.J) 가갑상선암이진단된것을알고병기결정의목적으로시행하였다. 초음파상림프절전이가의심되는소견은주변근육보다높은에코를보이거나, 낭성변성이나석회화가있거나, 구형 ( 종경 / 횡경비 <1.5) 의모양을보이는경우였다. 수술전평가를위해본원에서는일상적으로조영증강경부 CT (contrast-enhanced CT with an multidetector scanner, SOMATOM Sensation 16 또는 SOMATOM Sensation 64, 수술및병리보고초음파에서전이가의심되지않았으나이후시행한 CT에서조영증강이있는림프절에대하여다시한번초음파를시행하여그위치를수술직전경부에표시하였고, 이를토대로수술당시해당림프절을절제하였다. 수술을시행한림프절의최종병리보고를위하여, 6th edition AJCC/UICC TNM Classification system을기준으로삼았다. 통계분석최종진단은림프절의병리결과를토대로하였고이들의초음파와전단화단층촬영의조영증강소견, 그리고각환자의몇가지임상소견과악성과의연관성을알아보았다. 범주형변수는 Fisher s exact test, 연속형변수는 student t-test를이용하여구하였다. 모든값에서 p value가 0.05보다작을때그값이통계적으로유의하다고보았다. 통계분석은 SAS software (version 9.1.3; SAS Institute, Cary, NC) 를사용하였다. 결과병리결과에서 34개의림프절중 17개 (50%) 는갑상선유두암의림프절전이가있고, 나머지 17개 (50%) 는양성이었다 (Fig. 1). CT상에서전이림프절의평균장경은 7.65 mm ± 1.66 mm, 양성림프절은 8.12 mm ± 3.5 mm 이었다 (p value = 0.62). 림프절전이가있는환자군은평균 42.4 세 ± 12.2 세로, 전이가없는환자군 ( 평균 51 세 ± 10.1 세 ) 에비하여낮은연령을보였다 (p = 0.037). 또한남자환자 6명의림프절에서모두전이가있었고 (100%), 여자는 38% 에서전이가있어남자환자에게림프절전이가더많았다 (p = 0.018). - 188-
신현주외 : 갑상선유두암의경부림프절전이의진단 조영증강된림프절과근육의 HU 차이는, 전이림프절은평균 32.53 HU ± 14.66 HU, 양성림프절은 32.18 HU ± 19.49 HU로둘간의유의한차이는보이지않았다 (p = 0.953). 림프절과근육의조영증강차이가클수록전이가능성이높은지알기위해구해본 odds ratio는 1.001 (95% 신뢰구간 0.962, 1.042) (p value = 0.951) 로유의한결과를보이지않았다 (Table 1). 고찰갑상선유두암은국소림프절전이가흔하고, 재발이가장많이발생하는위치는경부림프절이다 [19, 20]. 반복되는림프절전이를가진환자는예후가나쁘다고생각하고있으며적절한림프절절제는재발위험을감소시킨다 [20]. 갑상선유두암의림프절전이의유무에따라수술범위및방법이달라지므로수술전림프절전이의정확한평가가중요하다. 지금까지초음파는갑상선유두암의림프절전이평가에중요한역할을하고있지만, 검사자의존도가높고검사가능범위의제한이있다는한계가있다. 초음파상갑상선유두암의경부림프절전이는내부에국소또는미만성의고에코부위가있거나, 석회화, 낭성변성, 둥근모양 ( 종경 / 횡경비 <1.5), 비정상적혈류양상 ( 주변부혈관분포등 ) 을띌때의다섯가지중하나이상의소견을보일때의심할수있다 [10, 12-16]. 림프절의위치별비교를통해갑상 선유두암의림프절전이를평가한연구들에따르면, 초음파의민감도는 52-84%, 특이도는 95-97% 로높았고, 진단정확도는 76-77% 로보고되었다 [17, 21, 22]. CT상갑상선유두암의경부림프절전이는내부에괴사또는낭성변성, 석회화를동반하거나주변근육보다높은정도의조영증강양상을보일때의심할수있다 [10, 11, 17, 18]. 이러한소견을이용한 CT의림프절전이평가가초음파단독검사보다진단적가치가높다는보고들이있다 [11, 23]. 이중, Table 1. Demographics of the Patients Included in This Study Metastatic LN Reactive LN P value Age (years) Mean 42.4 Mean 51 (21-65) (39-75) 0.0373 Gender ratio (M:F) 6:10 0:16 0.0177 Table 2. Characteristics of Included Lymph Nodes Metastatic LN Reactive LN P value Size (mm) Mean 7.6 Mean 8.1 0.6195 (6-11) (4-17) DOE difference (HU) Mean 32.5 Mean 32.2 0.9528 (10-64) (5-64) Note. Size : The longest diameter of LN in CT examination, HU : Hounsfield unit A B Fig. 1. CT and sonography of the 57-years-old female patient with papillary thyroid cancer. A. In neck CT scan with contrast administration, about 10 mm sized lymph node in neck level 3 showed enhancement pattern (81 HU, arrow), compared with ipsilateral SCM muscle (57 HU). B. Follow up sonography for lymph node marking was performed for surgical excision. The final pathology of the lymph node was proven to reactive lymph node. - 189-
대한초음파의학회지 2011;30(3) 림프절의조영증강양상에대한평가는초음파에서는가능하지않은 CT 고유의소견으로, 조영증강양상이진단에유용하다는몇가지연구들이있으나이에대한정량적평가를내린연구는없다 [10, 11, 23]. 이연구는초음파에서전이가의심되지않는림프절중 CT 에서조영증강의정도를객관적으로측정하여이소견이림프절전이의진단에진단적가치를가지는지알아보고자하였다. 총 34개의림프절중, 초음파에서전이가의심되지않았던림프절의주변근육과의조영증강정도차이는평균 32.176 HU (±19.485 HU), 전이림프절은 32.529 HU (±14.659 HU) 로둘간의유의한차이는없었고, 이는 CT에서조영증강정도를림프절전이예측소견으로사용하기어렵다는것을시사하고있다. 이는림프절전이외에도감염에따른반응성림프절등에서도마찬가지로조영증강양상이나타나기때문에조영증강양상만으로여러질환을감별하는것이어려운것으로추측해볼수있다. 갑상선암의재발과고위험인자로는남성환자, 종양의직경이 4 cm보다큰경우, 연령이 15세미만, 45세이상일경우이다 [24]. 이연구에서추가적으로시행한비교를통해, 림프절전이는남성에게더많았고림프절의직경과전이간에는상관관계가없는것으로나타났으며, 젊은연령에서전이가더많은것으로나타났다. 이번연구에는몇가지한계가있다. 첫째, 초음파상림프절전이가의심되지않았던환자중 CT를시행하여림프절조영증강이있었던환자를대상으로하여실제적으로모든림프절을대상으로하지않아대상군설정에한계가있다. 둘째, 수술전평가를위하여총3명중한명의영상의학과전문의가초음파검사를시행하였으나, 이에대한 interobserver variability 가평가되지않았다. 셋째, 총 32명의환자, 34개의림프절을대상으로시행하였기때문에, 더많은환자를대상으로연구를진행한다면 CT 소견뿐만아니라, 환자연령이나성별, 림프절직경에대해서도유의한결과를얻을수있을것이다. 넷째, 림프절의조영증강양상에중점을두었기때문에, 조영제주입양, 속도또 scan delay time에따라결과값이달라질수있다. 그러므로앞으로전이림프절의조영증강정도분석을위해많은수의환자에대해조영제주입양및속도, scan delay time 을각각독립적변수로지정하여진행하는연구도진행되어야할것이다. 이러한몇가지제한점에도불구하고, 이번연구에서 CT의외측경부림프절조영증강정도는갑상선유두암의경부림프절전이를진단하는데에유용한도움을주지못하였다. 이를통하여, CT의외측경부림프절의조영증강은갑상선유두암의경부림프절전이를진단하는데에유용하지않았으며, 림프절전이의정확한진단을위해초음파에추가하여 CT를시행하여도진단정확도의부가적인향상을기대하기는어렵다는결론을내릴수있었다. 요 목적 : 갑상선유두암의경부림프절전이진단에있어초음파상전이가의심되지않았던림프절에대하여전산화단층촬영의조영증강양상이가지는진단적유용성을보고자하였다. 방법 : 갑상선유두암을진단받은환자 31명 ( 여성 25명, 남성 6명, 평균연령 46.7세 ) 에서초음파상림프절전이가의심되지않았으나전산화단층촬영상조영증강양상이관찰된 34개림프절을대상으로하였다. 조영증강양상의정량적측정을위해동측의흉쇄유돌근과의심되는림프절의 Hounsfield unit 차이를비교하였다. 각림프절간의분석을위해전산화단층촬영상조영증강이된림프절을다시초음파를시행하여정확한위치표시를하였고, 이에대한수술적절제를통해병리결과를얻었다. 더불어, 각환자의연령, 성별, 림프절크기에대한분석을더하였다. 결과 : 수술후 34개의림프절중 17개는전이, 17개는양성림프절로진단받았다. 두환자군간림프절크기의차이는없었고림프절전이가있는환자군이그렇지않은환자군에비해연령이낮았고 (p = 0.037), 남성에게서림프절전이가더많이보고되었다 (F:M = 38.5%:100%, p = 0.018). 전산화단층촬영상림프절조영증강양상은전이가있는림프절과양성림프절간의유의한차이는없었다 (p = 0.953). 결론 : 갑상선유두암에서경부림프절의전산화단층촬영상조영증강양상은림프절전이를예측하는데에유용하지않았다. 약 References 1. Wunderbaldinger P, Harisinghani MG, Hahn PF, et al. Cystic lymph node metastases in papillary thyroid carcinoma. AJR Am J Roentgenol 2002;178:693-697 2. King AD, Ahuja AT, To EW, Tse GM, Metreweli C. Staging papillary carcinoma of the thyroid: magnetic resonance imaging vs ultrasound of the neck. Clin Radiol 2000;55:222-226 3. Lang W, Borrusch H, Bauer L. Occult carcinomas of the thyroid. Evaluation of 1,020 sequential autopsies. Am J Clin Pathol 1988;90:72-76 4. Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994;97:418-428 5. Noguchi S, Murakami N, Yamashita H, Toda M, Kawamoto H. Papillary thyroid carcinoma: modified radi- - 190-
신현주외 : 갑상선유두암의경부림프절전이의진단 cal neck dissection improves prognosis. Arch Surg 1998;133:276-280 6. Marshall CL, Lee JE, Xing Y, et al. Routine pre-operative ultrasonography for papillary thyroid cancer: effects on cervical recurrence. Surgery 2009;146:1063-1072 7. Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-1214 8. Kouvaraki MA, Shapiro SE, Fornage BD, et al. Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer. Surgery 2003;134:946-954; discussion 954-945 9. Stulak JM, Grant CS, Farley DR, et al. Value of preoperative ultrasonography in the surgical management of initial and reoperative papillary thyroid cancer. Arch Surg 2006;141:489-494; discussion 494-486 10. Kim E, Park JS, Son KR, Kim JH, Jeon SJ, Na DG. Preoperative diagnosis of cervical metastatic lymph nodes in papillary thyroid carcinoma: comparison of ultrasound, computed tomography, and combined ultrasound with computed tomography. Thyroid 2008;18:411-418 11. Ahn JE, Lee JH, Yi JS, et al. Diagnostic accuracy of CT and ultrasonography for evaluating metastatic cervical lymph nodes in patients with thyroid cancer. World J Surg 2008; 32:1552-1558 12. Choi JS, Kim J, Kwak JY, Kim MJ, Chang HS, Kim EK. Preoperative staging of papillary thyroid carcinoma: comparison of ultrasound imaging and CT. AJR Am J Roentgenol 2009;193:871-878 13. Kwak JY, Kim EK, Son EJ, et al. Papillary thyroid carcinoma manifested solely as microcalcifications on sonography. AJR Am J Roentgenol 2007;189:227-231 14. Sohn YM, Kwak JY, Kim EK, Moon HJ, Kim SJ, Kim MJ. Diagnostic approach for evaluation of lymph node metastasis from thyroid cancer using ultrasound and fine-needle aspiration biopsy. AJR Am J Roentgenol 2009;194:38-43 15. Miseikyte-Kaubriene E, Trakymas M, Ulys A. Cystic lymph node metastasis in papillary thyroid carcinoma. Medicina (Kaunas) 2008;44:455-459 16. Langer J, Mandel S. Sonographic imaging of cervical lymph nodes in patients with thyroid cancer. Neuroimaging Clin N Am 2008;18:479-489 17. Jeong HS, Baek CH, Son YI, et al. Integrated 18F-FDG PET/CT for the initial evaluation of cervical node level of patients with papillary thyroid carcinoma: comparison with ultrasound and contrast-enhanced CT. Clin Endocrinol (Oxf) 2006;65:402-407 18. Som PM. Detection of metastasis in cervical lymph nodes: CT and MR criteria and differential diagnosis. AJR Am J Roentgenol 1992;158:961-969 19. Ito Y, Miyauchi A, Jikuzono T, et al. Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping. World J Surg 2007;31:838-848 20. Ito Y, Miyauchi A. Lateral lymph node dissection guided by preoperative and intraoperative findings in differentiated thyroid carcinoma. World J Surg 2007;32:729-739 21. Machens A, Holzhausen HJ, Lautenschlager C, Thanh PN, Dralle H. Enhancement of lymph node metastasis and distant metastasis of thyroid carcinoma. Cancer 2003;98:712-719 22. Soler ZM, Hamilton BE, Schuff KG, Samuels MH, Cohen JI. Utility of computed tomography in the detection of subclinical nodal disease in papillary thyroid carcinoma. Archives of otolaryngology--head & neck surgery 2008;134:973-978 23. Park JS, Son KR, Na DG, Kim E, Kim S. Performance of preoperative sonographic staging of papillary thyroid carcinoma based on the sixth edition of the AJCC/UICC TNM classification system. AJR Am J Roentgenol 2009;192:66-72 24. Mazzaferri EL, Kloos RT. Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 2001;86:1447-1463 - 191-