Korean J Hematol Vol. 42, No. 4, December, 2007 Case Report 골수에침윤된원발불명의소세포암종 1 예 경희대학교의과대학동서신의학병원 1 진단검사의학교실, 2 내과학교실, 3 병리학교실 조선영 1 ㆍ강소영 1 ㆍ이재진 2 ㆍ임성직 3 ㆍ이우인 1 A Case of Small Cell Carcinoma of Unknown Primary Sun Yong Cho, M.D. 1, So Young Kang, M.D. 1, Jae Jin Lee, M.D. 2, Sung Jig Lim, M.D. 3 and Woo In Lee, M.D. 1 Departments of 1 Laboratory Medicine, 2 Internal Medicine and 3 Pathology, East-West Neo Medical Center, Kyung Hee University College of Medicine, Seoul, Korea Small cell carcinoma with unknown primary (SCUP) is an uncommon cancer. Histologically, SCUP has been included with extrapulmonary small cell carcinoma (EPSCC) that is defined as a biopsy proven small cell carcinoma in a nonpulmonary primary site. SCUP is usually diagnosed in the lymph nodes, liver, brain, or bone. This tumor is a distinct clinicopathologic entity from small cell carcinoma of the lung. Generally, the clinical course is aggressive and often recurrent, and it has poor prognosis. The identification and differential diagnosis of this tumor can be made with the morphology of neuroendocrine features, immunohistochemistry with chromogranin A, neuron-specific enolase, synaptophysin and CD56, and cytogenetic findings. We treated a case of aggressive SCUP diagnosed by bone marrow biopsy in a 68-year-old man. There was no evidence of tumor in the lung. The patient died one month after without receiving any therapy. (Korean J Hematol 2007;42:404-408.) Key Words: Small cell carcinoma of unknown primary (SCUP), Extrapulmonary small cell carcinoma (EPSCC), CD56 서 원발불명의소세포암종 (small cell carcinoma of unknown primary, SCUP) 은매우드문암종으로폐에는병소가없이다른기관에서원발성으로진단되는폐외소세포암종 (extrapulmonary small cell carcinoma, EPSCC) 의한종류이다. 1-3) SCUP은주로림프절, 골수, 뇌, 간등에서발견되며정확한발생빈도는알려져있지않다. 1) 폐외소세포암종으로정의하려면흉부단순촬영및흉부컴퓨터단층촬영등에서소세포암종이발견되 론 지않을뿐아니라객담및기관지경검사에서도소세포암종의증거가없어야한다. 4) 폐외소세포암은전체소세포암종의약 2.5% 의빈도를차지하며임상적특징은폐에서발생하는소세포암종과는임상경과나예후등에서차이를나타내는것으로알려져있다. 2,5) 즉종양이발견되는부위와크기에따라예후도매우다양하게나타나지만일반적으로는나쁜예후를보이는것으로알려져있다. 1,3) 폐외소세포암종의진단은형태학적으로는분화도가좋지않은신경내분비암종의조직학적특성을보이나다양한면역조직화학염색법, 유전학적검사소견등을이용하여일차성, 전이성혹은다 접수 :2007 년 8 월 3 일, 수정 :2007 년 9 월 10 일승인 :2007 년 9 월 16 일교신저자 : 이우인, 서울시강동구상일동 149 134-727, 경희대학교의과대학동서신의학병원진단검사의학과 Tel: 02-440-7190, Fax: 02-440-7195 E-mail: wileemd@khu.ac.kr 404 Correspondence to:woo In Lee, M.D., Ph.D. Department of Laboratory Medicine, East-West Neo Medical Center, Kyung Hee University College of Medicine 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Korea Tel: +82-2-440-7190, Fax: +82-2-440-7195 E-mail: wileemd@khu.ac.kr
조선영외 : 골수에침윤된원발불명의소세포암종 1 예 405 Fig. 1. Bone marrow aspiration smears show small to medium sized malignant cells which were clustering, with high N/C ratio and scanty cytoplasm (Wright stain, x1,000). Fig. 2. Bone marrow entire spaces are replaced into malignant cells which were squeezed and desmoplastic reaction (HE stain, x100). 른신경내분비암종들과의감별이필요하다. 2-4,6) 저자들은최근소세포암종이원발병소없이골수에만침윤된 SCUP 1예를경험하였기에문헌고찰과함께보고하고자한다. 증례환자 : 이, 68세, 남자주소 : 허리및둔부통증현병력 : 내원 2주전부터시작된허리및둔부의통증으로다른병원을방문하여시행한요추엑스선촬영및자기공명영상검사에서 1번요추의골절과다수의종양세포골전이소견을보여본원으로전원되었다. 과거력및가족력 : 3년전담낭절제술을받았고협심증약을복용중이었다. 신체검사소견 : 내원시활력징후는정상이었고의식은명료하였으며특이소견은관찰되지않았다. 검사실소견 : 내원당시시행한일반혈액검사에서백혈구 7,100/μL, 혈색소 12.5g/dL, 혈소판 3,000/μL 이었으며말초혈액바른표본에서중등도크기의종양세포와백적혈구모세포반응소견이관찰되었다. 혈액생화학적검사상알칼리인산분해효소 584IU/L, 칼슘 11.1IU/L, C 반응성단백 11.8mg/dL, LDH 1163IU/L이었다. 객담검사및기관지내시경검사에서는특이소견이관찰되지않았다. 방사선소견 : 흉부단순촬영에서양쪽폐하부의무기폐소견이있었고흉부컴퓨터단층촬영에서종격동림프절병증소견이관찰되었으며흉추및요추자기공 명영상검사에서 1번요추의골절과종양의골전이소견이관찰되었다. 뼈스캔과전신양전자단층촬영에서도종양의파종성골전이소견과혈액암의심소견이관찰되었다. 소화기계및비뇨생식계통의종양유무를평가하기위한내시경검사및초음파검사에서는모두음성소견이었다. 골수흡인및생검소견 : 골수흡인검사에서작거나중등도크기의종양세포가집락화한소견으로관찰되었으며분포는전체골수세포의 85% 로관찰되었다 (Fig. 1). 골수생검소견에서는골수전체가종양세포로대체되었으며부분적인섬유화현상과세포의찌그러짐및결합조직형성소견이관찰되었다 (Fig. 2). 골수흡인세포를이용한유세포분석에서 CD45, HLA- DR, CD3, CD5, CD7, CD20, CD13 등에비특이적으로양성소견을보였으며 CD56에 57.4% 의강양성소견을나타내어반응성 T, B 림프구증가와 CD56 양성인전이성종양에의한소견으로판단했다. 골수생검조직에면역조직화학염색을한결과 neuron specific enolase (NSE), chromogranin A, CD56에양성소견을나타냈으며 cytokeratin, melanosome, CD45, vimentin에는음성소견을, synaptophysin과 epithelial membrane antigen (EMA) 에는부분적으로양성소견을나타냈다 (Fig. 3). 종양세포의세포유전학적검사에서는 44,X, -Y,t(3;6)(q27;q23),-5,del(10)(q22),-16,del(17)(p11.2), +20[4]/46,XY[15] 의복합이상소견을나타냈다 (Fig. 4). 치료및경과 : 이상의소견등으로소세포암의전이를의심하고원발병소를찾았으나폐를포함한다른
406 Korean J Hematol Vol. 42, No. 4, December, 2007 Fig. 3. Immunohistochemical findings on the BM biopsy section. Negative reaction for CD45 (A) & cytokeratin (D), and positive reaction for chromogranin A (B) & CD56 (C). 부위에서는병소부위를발견하지못하여최종적으로 SCUP으로진단되었다. 그러나환자는더이상의치료를받지않았으며진단후한달뒤사망하였다. 고찰소세포암종은폐에서가장흔하게발견되는암종으로임상경과가나쁜종양이다. 5,7) 그러나폐에는병소없이다른기관에서소세포암종이발견되기도하는데이를폐외소세포암종이라하며 1930년 Duguid와 Kennedy에의해처음으로보고되었다. 8) 폐에서생기는소세포암종과는달리폐외소세포암종은아직까지도종양의자연경과가명확히밝혀지지않아적정한치료지침을결정하기어려울뿐아니라환자의예후도폐소세포암종과차이를보여폐소세포암종과는다른임상질환으로구분한다. 2,5) 폐외소세포암은임상경과가매우나쁘고종종재발하는특성이있으며가장흔히발 견되는장기는소화기계통과비뇨기계통의장기이다. 3) 이외에도골조직, 림프절, 간, 뇌등에서진단되는경우도있으나종양이발생된원발병소를찾을수없는경우가있는데이를 SCUP이라한다. 1) SCUP 의병리기전에대해서는두가지가설이있는데원발병소가자연퇴행되어소세포암을발견하지못하는경우와원발병소의종양세포가초기전이를일으키는특성을갖고있어원발병소의종양세포가발견되기전에전이된곳에서증식을보여전이된장기에서먼저진단되는경우가있을수있다고한다. 9) 매년보고되고있는폐외소세포암종중에서원발병소를찾지못하는경우는정확한빈도를측정하기어려우나폐외소세포암중 0 50% 까지보고되고있다. 4,10,11) 소세포암종의진단은종양세포의형태학적특징에기초하여진단되며이에면역조직화학염색결과를추가하여감별및확진하고있다. 12,13) 특히기관지경등으로얻은검체의경우소세포암세포의형태를감별하
조선영외 : 골수에침윤된원발불명의소세포암종 1 예 407 Fig. 4. Cytogenetic analysis result of bone marrow. The karyotyping shows complex abnormalities: 44,X,-Y,t(3;6)(q27;q23), -5,del(10)(q22),-16,del(17)(p11. 2),+20[4]/46,XY[15]. 기어려울정도로세포의형태가찌그러져있는경우가많아진단및감별에어려움을겪는경우도종종있다. 13) 그러므로진단적예민도를높이기위해다양한항체를이용한면역조직학화학염색이동원되는데일반적으로이용되는항체로는 cytokeratins, chromogranin A, CD57 (Leu-7), synaptophysin, neuron specific enolase 등이있다. 12,14) 최근에는소세포암종의진단시종양세포가찌그러진경우라할지라도양성을나타내는 CD56의유용성에대한보고가있다. 12) CD56 표지자는다른표지자와더불어소세포암의진단시도움이될것으로생각한다. 본증례의경우도골수흡인도말표본에서집락을형성하고있는작거나중등도크기의종양세포가관찰되었으며유세포분석기로 CD56 측정을시행한결과 57.4% 에서강양성소견을나타냈고 CD56을이용한면역조직화학염색에서도다른염색과는달리확연히대별되는소견을보여주었다. 종양세포의유전학적검사소견에있어서는폐에생기는소세포암종과폐외소세포암종에서나타나는유전학적변이에는다소차이가있는데 3번단암혹은 10번장암의소실, 13번염색체의일부결실등은폐소세포암에서는비교적흔하나폐외소세포암에서는드물게나타나는소견이며 5번장암을포함한염색체변이나 17 번염색체의변화, 그리고 1번과 3번장암의획득등은 두군모두에서흔히나타나는소견이다. 1,9) 본증례에서도 5번장암의일부가결실되고 17번단암의일부가결실된소견을보였다. 이와같이소세포암종에서나타나는염색체변이는일정한방식을갖고반복적으로나타나는변이임을알수있다. 15) 그러므로폐외소세포암종의진단에는형태학적진단및다양한면역조직화학염색법, 유전학적검사소견등이고려되어야할것이다. 요약원발불명의소세포암종은폐외소세포암종의일종으로폐에서발견되는소세포암종과는임상적으로구분되는암종이다. 이에대한임상적경과나예후, 치료방침등에대해서는아직까지도많은연구가진행되고있는상태이다. 진단에는형태학적인진단이외에도다양한기법을동원하여진단및확진에이용할수있다. 저자들은최근에둔부의통증으로내원한 68세남자에서원발병소없이전이된소견만을보인폐외소세포암종 1예를경험하여형태학적특징과다양한면역조직화학염색및조직이찌그러진부분에서도양성으로나타나진단에도움을주는 CD56항체염색과염색체검사를시행하여진단하였기에보고하는바이다.
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