대한내과학회지 : 제 78 권제 1 호 2010 증례 09-190 초음파기관지경침흡인술로진단된신세포암의종격동림프절전이 1예 고신대학교의과대학복음병원 1 내과, 2 병리과, 3 메리놀병원내과 이송주 1 이규진 1 정현주 1 장태원 1 허방 2 최익수 3 A case of renal cell carcinoma with mediastinal lymph node metastasis diagnosed by EBUS-TBNA Song Ju Lee, M.D. 1, Gyu Jin Lee, M.D. 1, Hyun Joo Jung, M.D. 1, Tae Won Jang, M.D. 1, Bang Hur, M.D. 2, and Ik Su Choi, M.D. 3 Departments of 1 Internal Medicine and 2 Clinical Pathology, Gospel Hospital, Kosin University College of Medicine; 3 Department of Internal Medicine, Maryknoll Hospital, Busan, Korea Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a new method of sampling mediastinal lymph nodes to aid in diagnosing lymphadenopathy and in staging metastatic cancers. This paper describes a case of renal cell carcinoma with mediastinal and hilar lymph nodes metastasis that was diagnosed using EBUS-TBNA. A 17-year-old woman who had mediastinal lymphadenopathy and a right renal mass underwent imaging studies. The results of a first EBUS-TBNA suggested malignancy, but the type of tumor and exact site of the primary tumor were uncertain. Therefore, we repeated EBUS-TBNA with a lower pressure on the vacuum syringe. We successfully diagnosed the mediastinal lymph node metastasis from renal cell carcinoma. (Korean J Med 78:117-121, 2010) Key Words: Aspiration biopsy; Clear cell renal carcinoma; Lymphadenopathy; Staging 서론단순흉부방사선에서종격동병변을보이는질환으로는생식세포종양, 신경성종양, 흉선종양등의원발성종양과낭종등의양성질환, 종격동림프절종대를동반한질환등이있다 1). 종격동림프절은염증, 감염혹은악성전이등의다양한이유로커질수있으므로치료를결정하기전에정 확한진단및악성의경우원발암확인및병기설정이중요하다 2). 최근종격동림프절종대에대한진단수단으로초음파기관지경 (endobronchial ultrasonography) 및초음파기관지경침흡인술 (endobronchial ultrasonography guided transbronchial needle aspiration, 이하 EBUS-TBNA) 을통한조직및세포습득이각광받고있다 2-4). 특히, 폐암의병기결정에있어흉강경보다덜침습적인진단수단으로중요성이강조되고 Received: 2009. 6. 25 Accepted: 2009. 8. 3 Correspondence to Tae Won Jang, M.D., Department of Internal Medicine, Kosin University College of Medicine, 34 Amnam-dong, Seo-gu, Busan 602-702, Korea E-mail: jangtw@ns.kosinmed.or.kr - 117 -
- The Korean Journal of Medicine: Vol. 78, No. 1, 2010 - 있다 3,4). 또한폐내병변이보이지않는종격동질환이나종격동림프절전이를동반한원발암을알기어려운악성질환의경우 EBUS-TBNA 로종격동림프절조직검사가가능하다 5). 본연구는원발암이불분명했던신세포암으로부터의종격동림프절전이환자에서 EBUS-TBNA 를통해얻은조직의조직학적및면역조직화학적접근을통해성공적으로진단된예이다. 증 례 환자 : 이, 여자, 17세주소 : 한달간의기침, 가래현병력 : 내원한달전부터기침, 가래등상기도감염증상발생하였다. 내원 2주전지역병원방문후폐렴의심하여치료했으나증상지속되어시행한흉부컴퓨터단층촬영 ( 이하 CT) 에서종격동림프절및용골하림프절종대소견보여상급병원권유받아본원내원하였다. 과거력및가족력 : 6세경실신했던과거력및내원 4년전의식소실로지역병원신경과에서추적관찰중이었고, 그외다른특이병력은없었다. 이학적소견 : BMI 27.5 kg/m 2 였고, 청진상잡음은없었으며그외특이소견없었다. 검사실소견 : 말초혈액검사에서혈색소 11.2 g/dl, 헤마토크릿 33.6%, 백혈구수 7,500/mm 3, 혈소판수 251,000/mm 3 이었고, 적혈구침강속도는 20 mm/hr이었다. 혈청생화학검사에서크레아티닌 1.2 mg/dl, 나트륨 141 meq/l, 칼륨 4.1 Figure 1. Chest computed tomography (CT) shows both hilar lymphadenopathy and a large subcarinal lymph node. meq/l, 염소 109 meq/l, 칼슘 9.3 mg/dl, 인 2.6 mg/dl, 마그네슘 2.2 mg/dl, 총단백질 7.1 g/dl, 알부민 4.1 g/dl, AST 16 IU/L, ALT 3 IU/L, alkaline phosphatase 56 IU/L이었으며, 암표지자는 CEA 0.96 ng/ml, NSE 19.97 ng/ml이었다. 방사선검사소견 : 단순흉부방사선상양측종격동림프절이종대되어있었고, CT상종격동림프절과용골하림프절종대소견보였다 ( 그림 1). 그러나폐실질내병변은보이지않았으며, 기관지경검사에서도기관지내병변이보이지않아조직학적진단을위해 EBUS-TBNA 시행하였다. 검사방법및경과 : CT상병변이의심되는부위에초음파기관지경 (BF-UC260F-OL8, Olympus, Tokyo, Japan) 을위치하고, 기관지경끝에부착된풍선을생리식염수주입으로부 A B Figure 2. (A) The EBUS-Doppler image shows a hypervascular tumor. (B) The EBUS-imaging shows a needle within the subcarinal lymph node. - 118 -
- Song Ju Lee, et al. Renal cell carcinoma wiht mediastinal lymphadenopathy diagnosed by EBUS-TBNA - Figure 3. A huge bulging mass is seen at the right upper pole of the kidney, abutting the liver. Heterogeneous soft tissue densities are observed at the lower portion of the inferior vena cava (IVC) and right renal vein. IVC and right renal vein invasion is suspected. 풀려초음파영상을얻었다. 병변이보이면도플러영상으로주변혈관의주행및병변내혈류상태를확인했다. 본환자는병변내혈관이과다발달되어있었다 ( 그림 2A). 22G 기관지경침흡인용바늘 (NA-201SX-4022, Olympus, Tokyo, Japan) 을기관지경채널을통해삽입한뒤, 초음파유도하에병변내로바늘을찔러넣었다. 초음파상바늘이병변내에들어간것이확인되면 ( 그림 2B) 진공관주사기를 20 mmhg 까지당기고연결하여음압을가했다. 진공관연결후병변내에서바늘을 10회왕복하여흡인된검체로슬라이드에바름표본을만들고조직검체는포르말린에담갔다. 이러한술기를 3~4회반복하였다. EBUS-TBNA 를통해얻은조직슬라이드염색상크고둥근핵과뚜렷한핵인, 뚜렷한세포질을특징으로하는세포가다소느슨한덩어리형태로관찰되었으나적혈구가많이섞여있고세포수가적어정확한진단이어려웠다. CT상종격동림프절종대외에우측신장종양관찰되어복부자기공명영상 ( 이하 MRI) 검사시행하였으며, 방사선학적으로신세포암이의심되었다 ( 그림 3). 양전자방출컴퓨터단층촬영 ( 이하 PET-CT) 상우측신장및복부대동맥, 하대정맥주위림프절에당대사증가소견보였으나, 양측폐문부림프절에는당대사증가소견이관찰되지않았다. 정확한조직학적진단및치료를위해우측신종양의절제술을보호자에게권유하였으나수술거절하여조직학적확진및치료방향결정을위해 EBUS-TBNA 재시행하였다. 7번림프절을겨냥하여침흡인술시행하였으며, 도플러영상에과다혈관양상보여진공관의흡인압력을 20 mmhg 에서 5 mmhg 로감압하여흡인하였다. 이전흡인시에비해혈액이보다덜섞여나왔으며총 4회에걸쳐흡인한조직을얻었다. 재확인한조직슬라이드 H & E 염색에서이전검사에 A B Figure 4. This compares the high (A) and low (B) vacuum samples. The sample taken with a vacuum of 5 mmhg is better than that taken with a vacuum of 20 mmhg (H&E, 400). - 119 -
- 대한내과학회지 : 제 78 권제 1 호통권제 593 호 2010 - Figure 5. Immunohistochemical staining for CD10 shows that the epithelial tumor cells stained brown. It was ultimately diagnosed as clear cell carcinoma of the kidney, metastatic ( 200). 비해적혈구가적고세포수가많아적절한검체로확인되었다 ( 그림 4). 특수염색, 면역염색시행결과 EMA (epithelial membrane antigen) 에국소적약양성, vimentin ( 상피세포의중간섬유일종 ) 에약양성, TTF-1 (thyroid transcription factor) 에음성및 CD 10 (neutral endopeptidase) 에강양성으로확인되어신세포암의전이성병변 (clear cell carcinoma of kidney, metastatic) 으로최종진단되었다 ( 그림 5). 치료경과 : 신세포암및종격동림프절전이로진단후혈액종양내과에서독소루비신 -시스플라틴항암화학요법시행하였으며현재까지혈액종양내과에서경과관찰및항암화학요법시행중이다. 추적 CT상신장내종양크기는감소소견보이고있으며, 종격동및용골하림프절크기는큰변화가없는상태다. 폐문림프절을동반할경우예후가불량하다 8). 폐실질내전이가없는종격동림프절은상대적으로빈도가적지만, 예후와관련이있으므로전이에대한확인이필요하다 9). 근래에악성종양의병기설정에필수적으로시행하는검사인 PET-CT는 CT보다민감도와특이도가높으나위음성, 위양성이각각 84%, 89% 로정확한진단을위해서는세포및조직검사가필요하다 10,11). 폐암환자에있어종격동의조직획득에절대표준 (golden standard) 으로간주되었던흉강경은민감도가 81%, 특이도가 100% 이지만, 침습적이고전신마취가요구되어이에따른합병증이발생할수있다 2,11). 흉강경보다비침습적으로조직획득이가능하다는장점을가진통상적인맹검기관지경침흡인술 (blind TBNA) 은시술자의술기에영향을받는단점이있어보고에따라 39~89% 로민감도가다양하다 2,5,12). 이에반해실시간 EBUS-TBNA (realtime EBUS-TBNA) 는초음파영상으로병변을확인하면서시술하기때문에보다정확하게종격동병변에접근할수있는새로운최소침습적검사방법이다 12). Yasufuku 등 13) 은종격동과폐문림프절전이에대한 CT, PET와 EBUS-TBNA 사이의정확도를조사한연구에서각각의민감도에대해 76.9%, 80.0%, 92.3%, 특이도에대해 55.3%, 70.1%, 100% 로보고하였다. 따라서 EBUS-TBNA 의정확도는 98% 에달했다. 하지만 EBUS-TBNA 는양성예측률이 100% 인반면, 음성예측률은 97.4% 로위양성은검체오염이없는한발생하지않으나위음성이가능하다 12-14). 본증례와같이혈류가풍부한병변의경우혈액으로인해정확한진단이어려울수있다. 이등 15) 이 EBUS-TBNA 의적절한흡인횟수에대해보고한바있으나적절한흡인압력에대해서는현재까지정형화된보고가없다. 본증례를통해도플러영상으로혈류를확인하여혈관형성이풍부한경우진공관흡인압력을낮춰서조직을습득하는것이위음성을줄일수있음을알수있었다. 이에대해서는추가적인연구가필요하다. 고 찰 요 약 신세포암은병기에따라예후가달라지며, 수술이우선적이지만원격전이가있을경우항암화학요법을고려해야한다. 따라서정확한진단및병기결정이필수적이다 6). 신세포암의원격전이는폐가 60% 이상으로가장많고, 다음으로전이환자의 40% 이상이뼈전이를보인다 7). 신세포암의폐전이는병변크기가클수록, 양측성인경우, 종격동이나 EBUS-TBNA 는원인을모르는림프절종대의진단과전이성악성종양의병기결정에유용한최소침습적인종격동림프절조직검사방법이다. 저자들은 EBUS-TBNA 를통해신세포암으로부터의종격동림프절전이환자를진단한 1예를경험하였기에문헌고찰과함께보고하는바이다. - 120 -
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