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1 대한내과학회지 : 제 72 권제 5 호 2007 항암화학요법으로장기생존을보인원발성난소소세포암 1예 계명대학교의과대학내과학교실 김진영 김용진 성희진 박우영 홍윤석 도영록 송홍석 =Abstract= Primary small cell carcinoma of the ovary and the long-term survival after systemic chemotherapy Jin Young Kim, M.D., Yong Jin Kim, M.D., Hee Jin Seong, M.D., Woo Young Park, M.D., Yoon Seok Hong, M.D., Young Rok Do, M.D. and Hong Suk Song, M.D. Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea Ovarian small cell carcinoma is a rare type of ovarian carcinoma with a poor prognosis.the hypercalcemic type is a tumor of unknown histogenesis, and small cell carcinoma of the pulmonary type may be a component of a typical ovarian surface epithelial-stromal tumor. We experienced a case of primary ovarian small cell carcinoma and lung metastasis. The patient was a 65-year old woman who complained of rectal heaviness. The chest x-ray and chest CT scan revealed multiple pulmonary metastases. Abdominal MRI showed a well defined heterogenous solid mass with central necrosis arising from the right ovary and hydronephrosis of the right kidney. Biopsy of the ovarian mass showed small cell carcinoma of the pulmonary type. After 4 cycles of cisplatin (80 mg/m 2, on day 1, iv), etoposide (100 mg/m 2, on day 1 to 3, iv), the patient achieved a complete response. The follow up chest CT scan 5 years after treatment revealed no evidence of disease. We report here in a case of primary small cell carcinoma of the ovary with lung metastasis and we include a review of the literature.(korean J Med 72: , 2007) Key Words : Carcinoma, Ovary 서론폐소세포암은전체폐암의약 1/4~1/3 정도를차지하며임상적으로진행속도가빠르고조기에전신으로전이되며치료하지않을경우생존기간은진단후수개월을넘지못한다 1). 원발성폐외소세포암은폐소세포암과조직학적으로감별이어려우며소세포암의 2.5~ 4% 를차지한다 2). 원발성폐외소세포암은두경부, 식도, 위, 췌장, 담낭, 자궁경부, 신장, 방광, 전립선에잘발생한다 3). 폐외소세포암은임상경과가일반적으로진행이빠르며다른장기로전이도잘되고재발이잦은것으로알려져있다 3). 원발성난소소세포암은매우드문경우이며치료및자연경과가잘알려져있지않다. 한편소세포암의경우원발부위와관계없이항암화학치료에폐소세포암과유사하게폐외소세포암에서도유사한반응을나타내는것으로보고되고있다 4). Received : Accepted : Correspondence to : Hong Suk Song, M.D., Department of Internal Medicine, Dongsan Medical Center, Keimyung University School of Medicine, 194 Dongsan-dong, Jung-gu, Daegu , Korea shs7436@dsmc.or.kr

-The Korean Journal of Medicine : Vol. 72, No. 5, 2007 - A B Figure 1.

from right ovary. (B) Follow CT scan of 5year after treatment revealed no evidence of disease. Figure 2.

Chest CT scan reveals variable sized calcified and non-calcified nodules on both lung fields.

증례환자 : 도 미, 여자, 65세주소 : 직장중압감현병력 : 6개월전직장중압감이발생하였으나특별한검사가없었고, 2개월전개인의원에서시행한초음파검사에서난소부위에종괴가관찰되어검사위해내원하였다.

2 -The Korean Journal of Medicine : Vol. 72, No. 5, A B Figure 1. (A) 7 5 9cm sized, relatively well defined heterogeneous solid mass with central necrosis and strong enhancement arising from right ovary. (B) Follow CT scan of 5year after treatment revealed no evidence of disease. Figure 2. Abdominal CT scan showed right hydronephrosis and hydroureter. Figure 3. Chest CT scan reveals variable sized calcified and non-calcified nodules on both lung fields. 최근저자들은 65세여자환자에서원발성난소소세포암 1예를경험하였기에이를문헌고찰과함께보고하는바이다. 증례환자 : 도 미, 여자, 65세주소 : 직장중압감현병력 : 6개월전직장중압감이발생하였으나특별한검사가없었고, 2개월전개인의원에서시행한초음파검사에서난소부위에종괴가관찰되어검사위해내원하였다. 과거력및가족력 : 20년전폐결핵으로치료받았으 며가족력에서특이소견은없었다. 이학적소견 : 입원당시혈압은 120/80 mmhg, 맥박수 85회 / 분, 호흡수 20회 / 분, 체온 36.8 였고, 공막에서황달소견은관찰되지않았으며경부에서비정상적으로촉지되는종괴는없었다. 폐와심음은정상소견이었고복부에서자궁내진검사상오른쪽자궁벽면에서약 8 cm 크기의단단히만져지는종괴가관찰되었다. 검사실소견 : 입원당시말초혈액검사에서혈색소 11.1 g/dl, 헤마토크리트 34.6%, 백혈구 7,750/µL, 혈소판 355,000/µL였으며, 뇨검사상뇨비중 1.015, 뇨단백음성, 뇨당음성, 고배율시야에서백혈구 2-3개가보였고뇨침검사상원주는없었다. 생화학검사상칼슘

-Jin Young Kim, et al : Small cell carcinoma of the ovary - Figure 4. The tumor cells have scanty cytoplasm and hyperchromatic nuclei with stippled chromatin and inconspicuous nucleoli.

3 -Jin Young Kim, et al : Small cell carcinoma of the ovary - Figure 4. The tumor cells have scanty cytoplasm and hyperchromatic nuclei with stippled chromatin and inconspicuous nucleoli. There are foci of large nests of small cells with containing central necrosis (H&E stain, 400). mg/dl, 혈액뇨소질소 18 mg/dl, 크레아티닌 1.2 mg/dl, 혈청나트륨 142 meq/l, 혈청칼륨 4.9 meq/l, 총단백 8.4 g/dl, 알부민 4.8 mg/dl, 총빌리루빈 0.5 mg/dl, ALP 97 U/L, AST 17 U/L, ALT 13 U/L, 총콜레스테롤 200 mg/dl, 요산 5.4 mg/dl, LDH U/L, 프로트롬빈시간 11.1초, 활성부분트롬보플라스틴시간 30.1초였다. 종양표지자는 CA U/mL, CA U/mL 로증가되었고, CEA 4.43 ng/ml, NSE 27.4 ug/l로정상범위이었다. 방사선학적소견 : 복부초음파에서오른쪽자궁부속기에불균질한음영의종괴가관찰되었다. 복부자기공명촬영에서오른쪽자궁부속기에 cm 크기의비교적경계가좋은불균질음영의단단한종괴가관찰되었으며조영증강시내부에괴사가관찰되었으며 ( 그림 1A), 우측원위부수뇨관의압박에의해우측수신증이관찰되었다 ( 그림 2). 흉부단순촬영에서다발성종괴가양측폐야에서관찰되었으며, 흉부전산화단층촬영에서양측폐야원위부에다양한크기의석회성및비석회성종괴가관찰되었으나양측폐문부및종격동에서병적림프절은관찰되지않았다 ( 그림 3). 조직병리학적소견 : 오른쪽난소종괴는육안적으로 cm였으며무게는약 100 gm이었다. 외부는소엽성으로이루어졌고부드러운양상의분홍색의단단한종괴양상을보였다. 광학현미경하에서각개의종양세포는작은크기의둥글며방추형의모양을보였 고세포질은적고과염색된핵과눈에잘띄지않는핵소체가관찰되었다 ( 그림 4). Cytokeratin, chromogranin A, Grimelius 염색에서양성을보였으며 synaptophysin, vimentin 염색에서는음성을보였다. 치료및경과 : Cisplatin (80 mg/m 2, on day1, iv) and etoposide (100 mg/m 2, on day 1~3, iv) 병용항암화학요법을 2000년 2월 17일부터 2000년 5월 10일까지 4 차례시행하여완전관해가되었다. 2004년 11월 5일시행한복부전산단층촬영상재발의증거는없으며 ( 그림 1B) CA 125 치는 U/mL에서 U/mL로감소된상태로치료후 6년간재발의근거없이건강하게외래에서주기적으로경과관찰중에있다. 고찰 1926년 Barnard 5) 는소세포암이원발성폐종양임을밝혀내고수질성암종이라하였다. 폐소세포암은전체폐암의약 1/4~1/3 정도를차지하며평균나이는다른폐암보다적고남자가약 85% 를차지한다 6). 증상발현기간이약 3개월정도로상피세포암의 8개월에비해매우짧고임상적으로진행속도가빠르고진단당시약 2/3에서원격전이가있으며특히뇌, 골격계, 간및림프절로잘전이한다. 흉부단순촬영소견상약 65% 정도에서중심부종괴를보이고종격동의확장은약 12% 에서나타나며폐문부림프절종대는약 60% 에서동반된다 6). 폐소세포암은 APUD (Amine precursor uptake and decarboxylation) 세포에서원발하는것으로보며 7) SIADH-(syndrome of inappropriate antidiuretic hormone), 쿠싱증후군등과같은부종양증후군이나타날수있다 1). 치료하지않을시생존기간은평균 2.8개월정도로알려져있으나방사선요법이나화학요법에대한반응이좋으며최근에는제한병기의경우복합항암화학요법과동시에방사선요법을하는동시병용요법이좋은결과를보인다고한다 8). 1930년 Duguid와 Kennedy 9) 가일차적인폐질환의증거없이종격동에서발생한폐외소세포암을처음으로보고하였고, 이러한폐외소세포암은주로두경부, 식도, 위, 췌장, 담낭, 자궁경부, 신장, 방광, 전립선에서호발한다. 대부분의환자가남자이며 60~70대에호발하고초기에전이를잘한다 10). 원발성폐외소세포암의정의는첫째, 조직학적으로소세포암이고둘째, 흉부단순촬영및흉부단층촬영상에서정상소견이어야하고셋

4 - 대한내과학회지 : 제 72 권제 5 호통권제 561 호 째, 정상적인객담세포검사또는정상적인기관지내시경결과가있어야하며조직학적기준은폐소세포암과동일한즉치밀한핵, 뚜렷하지않은핵인과빈약한세포질을가진균일한소세포이어야한다 11). 그러나이러한기준이있지만여전히원발성폐외소세포암은폐소세포암의전이와많은혼동이있다. 이환자의경우에서도폐에병변이있는것으로확인되었으나원발성난소암으로진단한이유는흉부단층촬영상에서양측폐야의원위부에혈행성전이소견에해당하는다양한크기의종괴들이관찰되며종격동과양측폐문부에병적림프절종대소견이없어폐부위의질환을전이소견으로판단한것이다. 원발성폐외소세포암이나폐소세포암에관계없이조직화학적및초미세구조는 APUD 세포와비슷하다는보고 7) 가있으며전자현미경하에서 APUD 세포의특징적인신경분비과립을포함하고있고이런종양에서이소성호르몬이생성되므로 APUD 세포기원으로생각되나모든예의폐외소세포암에서신경분비과립이보이는것은아니다 12). 폐외소세포암은치명적질환으로 5년생존율이 13% 정도로알려져있다. 종양의크기가매우작고원발부위에국한된경우라면수술로치료가가능하지만소세포암의경우예후가그리좋지않기때문에수술후보조적항암화학요법이권장된다. 제한병기에서항암화학치료와방사선치료의병합요법은수술과비슷한효과를보인다. 대부분의폐외소세포암의치료에서폐소세포암과같은항암화학치료에반응이있다 13). Lo Re 등 14) 의연구에서 cisplatin 과 etoposide를 13명에서사용하여컴퓨터전산단층촬영으로관찰한결과 3명이완전관해를보였고, 6명에서부분관해를얻어 69.2% 의치료반응율을보였으며, 평균생존율은 13~24개월을보였다. Etoposide는폐소세포암의치료에단일제제로효능이있는약제이며 15) etoposide와 cisplatin은체외에서서로상승작용이있어폐소세포암에효과적인것으로알려져있다 16). 따라서폐소세포암및폐외소세포암에서비슷한조직학적상태와양상이결국약물치료에대한비슷한감수성을나타낸다고할수있다 17). 소세포암의치료는원발장기에관계없이화학요법에잘반응하므로임상적으로원발부이는큰문제가되지않는다는보고도있으며 4), 현재는전신적복합화학요법이가장추천되고치료약제는폐소세포암에서사용하는것과동일한것으로알려져있다 11). 원발성난소소세포암은젊은여자에서주로발생하며매우드문질환으로알려져있으며매우진행이빠르고예후및장기생존율이낮다 18). Harrison 등 18) 의보고에서 FIGO stage I 10명, stage III 6명을수술이후 cisplatin 을포함한보조항암화학요법을모두에서시행하였다. 7명은방사선치료를병행하였는데조사부위는골반과대동맥주위혹은골반과전체복부에조사하였다. 생존중앙기간은 stage III의경우 6개월을보였다. Stage I에서 6명은보조적방사선요법을받아 5명은현재생존중이며, 보조적방사선요법을받지않은 4명중 1명이생존된것으로보고되었다 18). 요약 저자들은 65세여자환자가직장중압감을주소로내원하여복부단층촬영상에서난소에종괴가확인되어시행한조직검사상소세포암으로판명되었으며, 4차례의 cisplatin+etoposide 복합항암화학요법시행후완전관해된뒤약 5년간재발의증거가없는경과가매우양호한진행병기의원발성난소소세포암 1예를경험하였기에이에문헌고찰과함께보고하는바이다. 중심단어 : 원발성난소소세포암 REFERENCES 1) Johnson BE, Grayson J, Makuch RW, Linnoila RI, Anderson MJ, Cohen MH, Glatstein E, Minna JD, Ihde DC. Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. J Clin Oncol 8: , ) Remick SC, Ruckdeschel JC. Extrapulmonary and pulmonary small-cell carcinoma: tumor biology, therapy and outcome. Med Pediatr Oncol 20:89-99, ) Sengoz M, Abacioglu U, Salepci T, Eren F, Yumuk F, Turhal S. Extrapulmonary small cell carcinoma: multimodality treatment result. Tumori 89: , ) Fer MF, Levenson RM, Cohen MH, Greco FA. Extrpulmonary small cell carcinoma. In: Greco FA, Oldham RK, Bunn PA, eds. Small cell lung cancer. p. 301, New York, Grune and Stratton, ) Barnard WG. The nature of the oat-celled sarcoma of the mediastinum. J Pathol Bacteriol 29: , ) Shamelian SO, Nortier JW. Extrapulmonary small

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( )Jkstro011.hwp 비인강암의방사선치료결과및생존율에관한예후인자분석 2005 2 1 2005 3 28. :, Tel: 053)250-7665, Fax: 053)250-7984 E-mail: jhkim@dsmc.or.kr 정영연외 2 인 : 비인강암의예후인자분석 정영연외 2 인 : 비인강암의예후인자분석 Carcinoma of the nasopharynx treated by radiotherapy