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1 대한내과학회지 : 제 72 권부록 2 호 2007 유전자형검사를통해진단된자궁경부암의기관지내전이 1 예 포천중문의과대학교내과학교실, 부인암센터 2, 병리학교실 3 시계동 김주영 이지현 김인호 2 안희정 3 김은경 =bstract= case of endobronchial metastasis from cervix cancer that was diagnosed by genotyping Kyeh-Dong Shi, M.D., Joo-Young Kim, M.D., Ji-Hyun Lee, M.D., In-Ho Kim, M.D. 2, Hee-Jung n, M.D. 3 and Eun Kyung Kim, M.D. Departments of Internal Medicine, Gynecologic oncology 2, and pathology 3, College of Medicine, Pochon CH University, Seongnam, Korea The lung is the most common site for metastasis from extrapulmonary malignancies. However, endobronchial metastases have rarely been reported. The major contributors include breast, colorectal and renal cell carcinoma. Endobronchial metastasis from cervix cancer is very rare and it is difficult to diagnose. It is defined as a bronchoscopically visible metastasis to the bronchus and it is histologically identical to cervix cancer. We experienced a case of endobronchial metastasis from cervix cancer, and this was pathologically confirmed by fiberoptic bronchoscopic biopsy. n 80-year-old woman was admitted to the hospital with chief complaints of cough and dyspnea. She was diagnosed as having cervix cancer two years ago. The bronchoscopic biopsy showed squamous cell carcinoma identical to the previously diagnosed cervix cancer. Human Papilloma Virus (HPV) genotyping from the specimen of the right middle lobar bronchus showed strongly positive high risk 16, which was identical to the HPV genotyping from the cervical brushing specimen. We report here on this case along with a literature review.(korean J Med 72:S298-S303, 2007) Key Words : Endobronchial metastasis, Cervix cancer 서론폐는폐외악성종양이전이되는흔한장소이다. 악성종양의폐전이는대부분은폐실질, 흉막, 림프절로의전이이며드물게기관지내전이를하기도한다. 기관지내전이는원발성종양과조직학적으로동일한병변이기관지내시경상분절기관지근위부이상에서관찰되는것으로정의할수있는데 1), 종괴에의해기관지가폐쇄되지않는한단순흉부방사선검사에서발견이어렵고, 또한발견되는경우에도원발성폐암으로오인하기쉽다. 그빈도는보고자들마다차이가있으며부검시조사된내용에따르면육안적으로진단할수있는병변을갖는빈도가 2~5% 로알려져있다 2-5). 기관지내전이를일으키는원발종양은유방암, 대장암, 신세포암이비교적많은것으로알려져있고 4, 6, 7), 그외에방광암, 악성흑색종, 육종, 갑상선암등과같은다양한종양에서기관지내전이가보고되었다 1, 4, 6). 하지만자궁경부암의기관지내전이는매우드물어국내에서는 2001년김등에의해 Received : ccepted : Correspondence to : Eun Kyung Kim, M.D., Division of Pulmonology & Critical Care Medicine, Department of Internal Medicine, undang CH Hospital, College of Medicine, Pochon CH University, #351 Yatap-dong, undang-gu, Seongnam, Kyeonggi-do , Korea imekkim@cha.ac.kr - S298 -

- 시계동외 5 인 : 유전자형검사를통해진단된자궁경부암의기관지내전이 1 예 - Figure 1. Chest P () and lateral view () show diffuse increased densities in both lower lung zones. 2예가보고되었을뿐이다 8).

2 - 시계동외 5 인 : 유전자형검사를통해진단된자궁경부암의기관지내전이 1 예 - Figure 1. Chest P () and lateral view () show diffuse increased densities in both lower lung zones. 2예가보고되었을뿐이다 8). 저자들은자궁경부암을진단받은기왕력이있는환자에서호흡곤란과기침으로내원하여기관지내종양에대해기관지내시경검사및조직생검을시행하여자궁경부암의기관지내전이로진단된예에서조직에서인간유두종바이러스유전자형검사를시행하여국내에서는처음으로유전자형검사를통해자궁경부암의기관지내전이로진단하였기에이를문헌고찰과함께보고하는바이다. 증례환자 : 김, 여자 80세주소 : 기침, 호흡곤란현병력 : 내원 2년전질출혈을주소로내원하여자궁경부암 (Stage II, 편평상피세포암 ) 을진단받은후 cisplatin과 etoposide 복합항암화학요법과골반외부에 5,000 cgy, 질내부에 2,400 cgy의방사선요법을시행받았다. 이후국소재발없이외래에서추적관찰하고있던중, 내원 3개월전부터기침과호흡곤란이발생하여내원하였다. 개인력 : 흡연력과음주력없음. 주부과거력 : 자궁경부암진단받은이외에폐결핵이나기관지천식의과거력은없음. 가족력 : 특이소견없음. 이학적소견 : 내원당시혈압은 150/90 mmhg, 맥박 수는분당 100회, 호흡수는분당 22회, 체온은 36.6 이었고, 만성병색소견을보였다. 흉부에서는양측하폐야에서흡기성기관지호흡음과호기성천명음이청진되었다. 부인과적진찰에서는이상소견이발견되지않았다. 검사실소견 : 내원당시시행한말초혈액검사상혈색소 12.6 g/dl, 백혈구 8,500개 ( 호중구 88%, 임파구 7%, 단핵구 5%), 혈소판 189,000/mm 3 이었고, 혈청생화학검사와소변검사는정상소견이었으며심전도는정상동율동소견을보였다. 동맥혈가스검사는실내공기흡입상태에서 ph 7.489, PaCO mmhg, PaO mmhg, HCO meq/l 였으며 SaO 2 96% 이었다. 객담항산균도말및배양검사는음성이었다. 객담세포진검사에서는비정형적인편평상피세포가검출되었다. 방사선소견 : 흉부 X-선검사상양측하엽의음영증가소견이관찰되었다 ( 그림 1). 흉부전산화단층촬영상우측주기관지및우하엽기관지의협착소견과좌하엽기관지의협착소견이관찰되었다 ( 그림 2). 복부-골반전산화단층촬영에서는종양의국소재발증거는없었다. 기관지내시경소견 : 우중엽과우하엽기관지사이의돌기가둔감되어있었으며불규칙한점막표면이관찰되어조직검사를시행하였다. 좌하엽기관지의입구에서기관지내시경의진입이어려울정도의부종소견이관찰되었으나점막병변은관찰되지않았다 ( 그림 3). - S299 -

- 대한내과학회지 : 제 72 권부록 2 호 2007 - Figure 2.

peribronchial increased densities in the right lobar and segmental bronchi and an irregularly lobulated soft tissue mass

() The post-enhanced mediastinal setting of the chest CT at the subcarinal level shows diffuse and multifocal

() ronchoscopy shows irregular mucosal nodularity at the orifice of the right middle lobe and a blunted spur between the

3 - 대한내과학회지 : 제 72 권부록 2 호 Figure 2. () Post-enhanced mediastinal setting of chest CT at the level of the left inferior pulmonary vein shows diffuse peribronchial increased densities in the right lobar and segmental bronchi and an irregularly lobulated soft tissue mass in the mediastinum. () The post-enhanced mediastinal setting of the chest CT at the subcarinal level shows diffuse and multifocal discontinuous peribronchial increased densities in the left lower lobar and segmental bronchi. Figure 3. () ronchoscopy shows irregular mucosal nodularity at the orifice of the right middle lobe and a blunted spur between the right middle lobe and the right lower lobe. () ronchoscopy shows diffuse edematous bronchial mucosa at the left lower lobar bronchus. 병리소견 : 우중엽에서시행한조직검사소견은편평상피세포암이었다. 원발성폐암과자궁경부암의기관지내전이를감별하기위해이전의자궁경부암조직과비교하였을때두조직의세포병리학적소견이같음을 관찰하였다. 또한, 이전자궁경부암종의찰과세포진표본과기관지내에서생검된조직에서인체유두종바이러스유전자형검사를시행하였으며두조직모두에서자궁경부암과연관이높은 9) 인체유두종바이러스유전자 - S300 -

- 시계동외 5 인 : 유전자형검사를통해진단된자궁경부암의기관지내전이 1 예 - C Figure 4. () Microscopic findings from the bronchoscopic biopsy of the right middle lobar bronchus show squamous cell carcinoma.

4 - 시계동외 5 인 : 유전자형검사를통해진단된자궁경부암의기관지내전이 1 예 - C Figure 4. () Microscopic findings from the bronchoscopic biopsy of the right middle lobar bronchus show squamous cell carcinoma. The cytoplasm of the cells is eosinophilic, suggesting keratin production, and there is squamous pearl formation. Cytologically, the nuclei are pleomorphic (they vary in size and shape) and hyperchromatic (increased chromatin and darker staining). (H&E stain, 200). () HPV genotyping by HPVDNChip R from the cervical brushing specimen shows strongly positive high risk 16 (white arrow head) and weakly positive high risk 52 (red arrow head). (C) HPV genotyping of the biopsy of the right middle lobar bronchus using the HPVDNChip R shows strongly positive high risk 16. 형 16이동일하게확인되었다 ( 그림 4). 임상경과 : 고식적치료위해항암화학요법계획하였으나고령이어서환자와보호자더이상의치료를거절하여퇴원하였으며추적관찰소실되었다. 고찰악성종양의폐전이의빈도는 20~50% 정도로흔하게관찰되나기관지내전이는드문것으로알려져있다. 발생빈도는보고자들마다차이가있어, King 등 2) 은폐외악성종양 109명의환자를부검한결과 18% 에서 Rosenblatt 등 3) 은 29.5% 에서기관지내전이를발견했다고보고하였으나, raman 등 4) 은폐외악성종양환자 244명의부검예중단 5명 (2%) 에서기관지내전이가있었다고보고하였다. 이러한현저한차이는기관지내전이를정의하는기준이다르기때문으로 King과 Rosenblatt 등은육안적전이뿐아니라현미경적침범까지도기관지내전이로규정하였으나, raman 등은주기관지와폐엽기관지근위부의중심성기관지에육안적전이가확인된경우만을포함시켰기때문이며최근에는후자의개념만을인정하고있다. 이와같은정의에근거하여현재까지의보고들을종합해볼때기관지내악성종양중전이암이차지하는비율은 2~5% 정도일것으로여겨진다 2-6). 현재까지다양한종양의기관지내전이가보고되었으며, 1966년부터 2002년까지보고된증례들을분석한 Srensen 의연구에의하면유방암, 신장암, 대장암이기관지내전이를일으키는흔한원발종양이었고 5), 김등 의국내보고에서는대장암이가장흔한원발종양이었다 10). 기관지내전이의진단을위해서는기관지내병변의조직을얻는것이중요하며이를원발종양의조직과비교하는것이필수적이다 3). 기관지내전이와기관지내원발종양을구분하는것또한중요한데, 편평상피세포암이나선암과같이다른조직에서도흔히발생하는암종의경우간혹생검결과만으로는전이암과원발암을구분하는것이어려울수있다. Salud 등은임상적양상과함께면역조직화학적방법이원발암과전이암을구분하는지표가될수는있으나이를구분하는명확한병리적기준은없다고하였다 6). 또한 aumgartner 등은인접한기관지점막에상피내암종 (carcinoma in situ) 의병변이존재할경우원발성폐암을강력히시사하므로감별에도움을받을수있다고보고하였다 7). 최근면역조직화학적방법과함께이형접합의소실과같은유전자차이를비교하는분자유전학적방법을사용할경우전이암과원발암의구분이보다용이하다는보고가있었으나 6), 1980년대이후보고된 4예에서면역조직화학적방법을감별에이용하였을뿐 11-14) 으로그사용이제한되어있는형편이다. 본증례의경우편평상피세포암으로진단된예로원발성폐암과기존의자궁경부암의기관지내전이간의감별이어려운상태였다. 저자들은이의감별을위해자궁경부암의발병과정에서는중요한역할을담당하나폐암의발병과정에서는그역할이아직은제한된것으로알려진 9, 15) 인간유두종바이러스에대한유전자형 - S301 -

5 - 대한내과학회지 : 제 72 권부록 2 호 검사를시행하여감별진단에도움을받을수있었다. 이전에국내에서보고되었던자궁경부암의기관지내전이 2예는기관지내병변과자궁경부암조직의병리소견을비교한것에근거하고있다. 이경우에원발암과전이암의구분이쉽지않은데저자들은이의구분을위한지표로서두조직소견의비교및세포의특성에근거하여이를진단한바있다 8). 본증례에서는원발성자궁경부암과기관지내병변의조직을비교하여같은조직소견을확인하였을뿐아니라, 인체유두종바이러스에대한유전자형을비교하여동일한유전자형을확인함으로서보다쉽고정확하게자궁경부암의기관지내전이를진단할수있었다. 기관지내전이암의증상은기관지내원발종양과차이가없는데대표적인증상은기침, 객혈, 호흡곤란등이다. 그러나증상없이발견되는경우도약 20~50% 에이르는것으로보고되고있으며 1, 10) 이러한경우에조기진단과치료가늦어져나쁜예후를보일수있다. 따라서악성종양의추적과정에서증상이없더라도정기적인흉부 X-선검사를시행하는것이필수적일것이다. 원발종양의진단에서부터기관지내전이를발견하기까지의기간은 41개월 16) 에서 65개월까지 1) 의시간간격을보이는데, 평균약 4년정도가소요되는것으로알려져있다 5). 본증례에서는그기간이 2년정도로비교적빨리발견되었는데그이유는호흡곤란과기침과같은임상증세외에흉부 X-선검사상이상소견이있었기때문에기관지내시경검사를바로시행하여기관지내전이를발견할수있었다. 치료는원발종양의생물학적성상, 병변의해부학적위치, 다른전이병변의유무, 환자의수행능력을고려하여결정되어야하는데치료방법으로는수술적치료, 항암화학요법 7), 체외방사선치료 7, 16) 등이있다. 그외에도근접조사방사선치료, 광선역학요법, Nd-Yag laser를이용한용적축조술, 스텐트삽입술등을치료방법으로고려해볼수있으나본증례는환자의나이가 80세로고령이어서환자와보호자가모든치료를거절하여더이상의치료를하지않았으며추적관찰소실되었다. 평균생존기간은 12~18개월로불량한예후를보이고있는데기관지내전이가원격전이의하나로종양의진행된상태를보이기때문이고 5, 10), 또한적극적인치료가예후에좋은영향을미친다는보고도 17) 있으나대부분의경우전신상태불량등의이유로보존적치료가많은 것도예후가불량한이유중의하나라고생각된다 1, 7, 10, 17). 기관지내전이암은드문질환이며, 임상적인증상, 방사선학적소견, 기관지내시경소견등으로는원발성폐암과구별이어렵다. 따라서악성종양의병력이있으면서만성적인호흡기증상을호소하거나흉부방사선소견상이상이있는경우, 기관지내시경상육안적으로원발성폐암이의심된다고하더라도전형적인원발성폐암의병리소견을보이지않는경우에는면역조직화학적방법, 유전자형검사등분자유전학적방법을동원하여기관지내전이암의가능성을염두에두고환자에대해접근해야하겠다. 요약 저자들은자궁경부암을진단받은기왕력이있는환자에서호흡곤란과기침으로내원하여비교적조기에기관지내시경검사, 조직검사및조직의유전자형검사를시행하여자궁경부암의기관지내전이로진단된예를경험하였기에문헌고찰과함께보고하는바이다. 중심단어 : 기관지내전이, 자궁경부암 REFERENCES 1) Kiryu T, Hoshi H, Matsui E, Iwata H, Kokubo M, Shimokawa K, Kawaguchi S. Endotracheal/Endobronchial metastases: clinicopathologic study with special reference to developmental modes. Chest 119: , ) King DS, Castelman. ronchial involvement in metastatic pulmonary malignancy. J Thorac Surg 12: , ) Rosenblatt M, Lisa JR, Trinidad S. Pitfalls in the clinical and histologic diagnosis of bronchogenic carcinoma. Chest 49: , ) raman SS, Whitcomb ME. Endobronchial metastasis. rch Intern Med 135: , ) Sorensen J. Endobronchial metastases from extrapulmonary solid tumors. cta Oncol 43:73-79, ) Salud, Porcel JM, Rovirosa, ellmunt J. Endobronchial metastatic disease: analysis of 32 cases. J Surg Oncol 62: , ) aumgartner W, Mark J. Metastatic malignancies from distant sites to tracheobronchial tree. J Thorac Cardiovasc Surg 79: , ) Kim YS, Chang J, Kim YS, Shin DH, Kim HS, Kim SK. Endobronchial metastasis of uterine cervix cancer: a two case reports and a review of the - S302 -

6 - 시계동외 5 인 : 유전자형검사를통해진단된자궁경부암의기관지내전이 1 예 - literature. Yonsei Med J 43: , ) n HJ, Cho NH, Lee SY, Kim IH, Lee C, Kim SJ, Mun MS, Kim SH, Jeong JK. Correlation of cervical carcinoma and precancerous lesions with human papillomavirus (HPV) genotypes detected with the HPV DN chip microarray method. Cancer 97: , ) Kim DH, Park MS, Chung JH, Cheong JH, Kim SK, Chang J, Kim YS. Endobronchial metastasis of extrapulmonary malignancies. Tuberc Respir Dis 53: , ) Jackisch C, Gast, ankfalvi, Diallo R, Lerchenmuller C, Kiesel L. Endobronchial mucosal metastases in breast cancer: a rare metastatic pattern. Lancet Oncol 3: , ) Ohno T, Nakayama Y, Kurihara T, Ichikawa H, Tsuda K, Ishida T, Hirato J, Suzuki Y. Endobronchial metastasis of breast cancer 5 years after breastconserving therapy. Int J Clin Oncol 6: , ) Scoggins WG, Witten J Jr, Texter JH Jr, Hazra T. Endobronchial metastasis from prostatic cancer in patient with renal cell carcinoma. Urology 12: , ) Takahashi Y, Nakashima T, Kobayashi T, Ohmasa M, Tamada J. Endobronchial metastasis from prostate cancer. Jpn J Thorac Cardiovasc Surg 49: , ) Clavel CE, Nawrocki, osseaux, Poitevin G, Putaud IC, Mangeonjean CC, Monteau M, irembaut PL. Detection of human papillomavirus DN in bronchopulmonary carcinomas by hybrid capture II: a study of 185 tumors. Cancer 88: , ) Katsimbri PP, amias T, Froudarakis ME, Peponis I, Constantopoulos SH, Pavlidis N. Endobronchial metastases secondary to solid tumors; report of eight cases and review of the literature. Lung Cancer 28: , ) Froudarakis ME, ouros D, Siafakas NM. Endoluminal metastases of the tracheobronchial tree: is there any way out? Chest 119: , S303 -

Kjtcs324( ).hwp

Kjtcs324( ).hwp 과오종과유사한폐상피모양혈관내피종 -1 예보고 - Pulmonary Epithelioid Hemangioendothelioma Mimicking Hamartoma -A case report- Epithelioid hemangioendothelioma, originating from the vascular endothelium, is a very rare and