The Korean Journal of Pathology 2004; 38: 거대세포종과유사한역분화부분을가지는연골육종 - 1 예보고 - 황필규 원재경 김민아 김한수 1 이상훈 1 김종재 서울대학교의과대학병리학교실 1 정형외과학교실 접수 : 2004년 8월 26

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1 The Korean Journal of Pathology 2004; 38: 거대세포종과유사한역분화부분을가지는연골육종 - 1 예보고 - 황필규 원재경 김민아 김한수 1 이상훈 1 김종재 서울대학교의과대학병리학교실 1 정형외과학교실 접수 : 2004년 8월 26일게재승인 : 2004년 9월 22일 책임저자 : 김종재우 서울시종로구연건동 28 서울대학교의과대학병리학교실전화 : Fax: cjkim@plaza.snu.ac.kr Dedifferentiated Chondrosarcoma with Giant Cell-rich Sarcomatous Component Resembling Giant Cell Tumor - A Case Report - Pil Gyu Hwang, Jae Kyung Won, Min A Kim, Han Soo Kim 1, Sang Hoon Lee 1 and Chong Jai Kim Departments of Pathology and 1 Orthopedic Surgery, Seoul National University College of Medicine, Seoul, Korea Dedifferentiated chondrosarcoma is an uncommon bone tumor, defined as a tumor in which two components -a low-grade chondrosarcoma and a high-grade non-cartilaginous sarcomacoexist with abrupt interface. We report a rare case of giant-cell rich dedifferentiated chondrosarcoma occurred in the right distal femur shaft of a 60 year-old female. The plain X-ray film showed an irregular radiolucent mass. The T2-weighted MRI revealed a heterogeneous high signal intensity. It was an irregular mass composed of bluish-white, translucent chondroid elements and yellowish solid components with extraosseous invasion. Microscopically, a lowgrade chondrosarcoma and a giant-cell rich spindle cell sarcoma with areas resembling giant cell tumor were recognized with abrupt transition. Immunohistochemical staining revealed a S100 protein positivity in chondroid cells and a few spindle cells. CD68 was strongly positive in giant cells. Vimentin was positive in both components and smooth muscle actin was positive in some spindle cells. There was no cytokeratin, desmin and myogenin immunopositivity. It is important to be aware of this rare variant of dedifferentiated chondrosarcoma to avoid the misdiagnosis of more common bone tumors including giant cell tumors. Key Words : Chondrosarcoma-Giant Cells-Dedifferentiation-Immunohistochemistry 역분화연골육종은전체연골육종의 6-11% 를차지하는악성종양으로, 1971년 Dahlin과 Beabout에의해처음기술되었다. 1-6 호발부위는보통의연골육종과유사하며대퇴골, 골반뼈, 상완골이다. 2,5 다양한연령층에서발생하지만 50대와 60대에서많이발병하며, 남자에서여자보다 1.5-2배빈발한다. 2,3 방사선상으로는대개점모양의방사선비투과성부분이방사선투과성부분에둘러싸인형태를보인다. 1,6 그러나방사선학적인소견만으로진단하기어려운점이지적되기도하였다. 2,8 역분화연골육종의가장중요한특징은조직학적으로분화가나쁜육종과분화가좋은연골성병변이분명한경계를보이는것이다. 1-3,5,6,8-10 치료는광범위절제술과항암화학요법, 방사선치료등이있다. 2,12 예후는불량하며평균생존기간은 6개월이고, 5년생존율은 18% 이다. 2,5 역분화된부분은대개악성섬유조직구종, 섬유육종이며때때로골육종이나횡문근육종이기도하다. 2-5,9-11 매우드문경 우로역분화된부분에거대세포가풍부할수있는데이경우에는거대세포가많은악성섬유조직구종이나거대세포종과유사하다. 이런종양은전체를반영하지못한생검이나불충분하게슬라이드가제작된경우에거대세포종으로오진할수있다. 15,16 역분화된부분에거대세포가많은역분화연골육종은매우드물며국내에는보고되어있지않다. 저자들은최근에거대세포종과유사한부위를보이는역분화연골육종 1예를경험하였기에간단한문헌고찰과함께보고하고자한다. 증례 60세여자가 2개월전부터시작된오른쪽넓적다리의통증을주소로내원하였다. 환자는고혈압과당뇨로 3년간약물치료를 345

dimension, composed of bluish-white, translucent chondroid tissues

chondrosarcoma and a giant-cell rich portion resembling giant cell

(B) Cartilaginous areas show mild nuclear pleomorphism and

2 346 황필규 원재경 김민아외 3 인 Fig. 1. Plain X-ray film shows an irregular radiolucent mass in the diaphysis of femur. Fig. 2. Resected specimen shows an irregular mass measuring 7 4 cm in two dimension, composed of bluish-white, translucent chondroid tissues and yellowish solid area with extraosseous tumor invasion. A B C D Fig. 3. (A) The tumor shows sharp demarcation between low-grade chondrosarcoma and a giant-cell rich portion resembling giant cell tumor. (B) Cartilaginous areas show mild nuclear pleomorphism and hyperchromatism. (C) Multinucleated giant cells are evenly distributed in the dedifferentiated area. (D) Areas with increased atypism are frequently noted with mitoses (arrows). 받고있었으며, 갑상선에는 1 cm의작은결절이있었으나갑상선기능의이상은없었으며 15년간관찰을하고있었다. 그외 에흡연이나음주등은하지않았고기타과거력은없었다. 신체검진에서오른쪽넓적다리의압통을호소하였다. 방사선학적

거대세포종유사역분화부분을가지는연골육종 347 A B C D Fig. 4. (A) Chondrosarcoma cells are positive for S100 protein.

(D) Some spindle cells are positive for smooth muscle actin. 검사에서오른쪽원위대퇴골간에경계가뚜렷하지않은방사선투과성병변이있었으며, 군데군데방사선비투과성부분들이관찰되었다 (Fig. 1). 자기공명영상에서는 T2 강조영상에서비균질의고신호강도를가지는종괴가오른쪽원위대퇴골간에서관찰되었다.

현미경소견에서 1등급내지 2등급의연골육종부분과거대세포를많이가지고있는부분이명확한경계를가지고있었다 (Fig. 3A). 연골육종부분은저배율에서결절을이루고있었다. 일부에서는석회화되는곳이있었다. 연골육종의세포밀도는중간정도였으며연골세포방안에는 1개내지 2개의핵이들어있었다.

핵안에는 1개내지 2개의작거나중간정도의크기를가진핵소체가있었고, 염색질은비교적거친모습이었다. 유사분열이자주관찰되었으며 50개의고배율상에서 30개까지관찰되었다. 어떤부분에서는보통의거대세포종보다이형성이증가된부분이있었다 (Fig. 3D). 일부에서섬세한뼈가관찰되었으며, 반응성으로생각되었다.

3 거대세포종유사역분화부분을가지는연골육종 347 A B C D Fig. 4. (A) Chondrosarcoma cells are positive for S100 protein. (B) A few spindle cells show S100 positivity, whereas multinucleated giant cells are negative. (C) Giant cells and a few spindle cells are CD68 positive. (D) Some spindle cells are positive for smooth muscle actin. 검사에서오른쪽원위대퇴골간에경계가뚜렷하지않은방사선투과성병변이있었으며, 군데군데방사선비투과성부분들이관찰되었다 (Fig. 1). 자기공명영상에서는 T2 강조영상에서비균질의고신호강도를가지는종괴가오른쪽원위대퇴골간에서관찰되었다. 임상적으로연골육종으로진단하여광범위절제술을시행하였다. 육안검사상원위대퇴골간안에크기 7 cm의경계가불분명한푸른빛이도는하얀색의연골부분과부분적으로어두운노란빛을띠고있는종괴가관찰되었으며, 종괴는피질뼈를뚫고주변연부조직으로침윤하고있었다. 종괴의단면에서출혈이나괴사는관찰되지않았다 (Fig. 2). 종괴는육안으로확인할때무릎관절과절연면을침범하지않았다. 현미경소견에서 1등급내지 2등급의연골육종부분과거대세포를많이가지고있는부분이명확한경계를가지고있었다 (Fig. 3A). 연골육종부분은저배율에서결절을이루고있었다. 일부에서는석회화되는곳이있었다. 연골육종의세포밀도는중간정도였으며연골세포방안에는 1개내지 2개의핵이들어있었다. 연골육종의세포핵은과다염색성을보이고있었으며유사분열상을관찰할수 는없었다 (Fig. 3B). 종양의여러부분에위치한분화가나쁜부분에서는다수의핵을가진파골세포형거대세포가관찰되었으며거대세포는균질하게분포되어있었다. 거대세포주변으로는방추모양세포들이짧은다발을이루는부분도있었다 (Fig. 3C). 세포질은호산성으로비교적풍부하였다. 핵안에는 1개내지 2개의작거나중간정도의크기를가진핵소체가있었고, 염색질은비교적거친모습이었다. 유사분열이자주관찰되었으며 50개의고배율상에서 30개까지관찰되었다. 어떤부분에서는보통의거대세포종보다이형성이증가된부분이있었다 (Fig. 3D). 일부에서섬세한뼈가관찰되었으며, 반응성으로생각되었다. 대표적인절편에서 S100 단백 (Z311, 1:500, DAKO, Glostrup, Denmark), CD68 (PG-M1, 1:70, DAKO, Glostrup, Denmark), cytokeratin (MNF116, 1:400, DAKO, Glostrup, Denmark), vimentin (M0725, 1:100, DAKO, Glostrup, Denmark), smooth muscle actin (M0851, 1:150, DAKO, Glostrup, Denmark), desmin (D33, 1:150, DAKO, Glostrup, Denmark), myogenin (M3559, 1:70, DAKO, Carpinteria, CA, USA) 에대해면역조직화학염색을시행하였다. Vimentin은연골육종

4 348 황필규 원재경 김민아외 3 인 Table 1. Review of the previously reported cases including the present case Case Age/ Sex Presenting Symptom Symptom duration Location Radiologic finding Gross finding Initial treatment Follow-up (month) 1 51/F Elbow pain - Femur diaphysis Lytic - Curettage Died of disease (24) /F Shoulder pain 6 years Left proximal Lytic with foci of Pale lobulated Wide excision No evidence 15 humerus calcification cartilaginous of disease (92) mass surrounded by fleshy tissue 3 69/M Shoulder discomfort, Long Right proximal Lytic with punctate Bluish-white Wide excision Recurred (9) 16 pain, limitation standing humerus calcification cartilage surrounded of motion by reddish-brown soft tissue 4 30/F Shoulder discomfort, Long Left proximal Lytic Bluish-white Wide excision No evidence of 17 limitation of motion standing humerus cartilage surrounded disease (5) by reddish-brown soft tissue 5 60/F Thigh pain 2 months Right distal Lytic with multiple Bluish-white Wide excision No evidence This femur calcification cartilage with & radiation of disease (15) case yellowish solid part Reference 부분과방추세포부분모두에서양성이었다. 연골육종부분은 S100 단백에염색이잘되었으나 CD68 에는음성을보였다 (Fig. 4A). 분화가나쁜부분에서는방추세포의일부가 S100 단백과 CD68에양성을나타내었고, 거대세포는 S100 단백음성, CD68 강양성을나타내었다 (Fig. 4B, C). Smooth muscle actin은몇몇방추세포에서염색이되었으며 (Fig. 4D), desmin, myogenin, cytokeratin은음성이었다. 환자는수술후 7주에거쳐 61.2 Gy의방사선치료를받았으며방사선요법을받던중급성충수돌기염으로개복술을받았다. 적출된충수돌기에종양의전이소견은없었으며, 항암화학요법은받지않았다. 수술후 15개월이지난현재재발이나전이의증거는없다. 고찰 1971년에 Dahlin과 Beabout가보고한역분화연골육종은연골육종중 6-11% 정도를차지하는아형이다. 1-6 호발하는부위는보고자마다조금씩다른양상을보이고있다. Mitchell 등 2 은대퇴골, 골반뼈, 상완골순으로보고하고있으며, Johnson 등 3 은골반뼈, 대퇴골, 상완골순으로보고하고있다. 역분화연골육종은분화가좋은연골육종부분과분화가나쁜육종부분이명확한경계를이루며섞여있는종양이며, 악성섬유조직구종, 섬유육종, 골육종, 횡문근육종, 평활근육종등이나올수있다. 2-5,9-11,13 그렇지만거대세포종과유사하게거대세포가풍부하게나오는경우는소수의예만보고되었으며, 성별, 연령별발생빈도, 호발부위, 종양의기원이나예후등이산발적으로기술되어있다 이들은 false giant cell variant of dedifferentiated chondrosarcoma, 14 dedifferentiated chondrosarcoma with malignant fibrous histiocytoma initially resembling giant cell tumor, 15 dedifferentiated chondrosarcoma with giant cell-rich variant of malignant fibrous histiocytoma, 16 dedifferentiated chondrosarcoma with a noncartilagenous component mimicking a conventional giant cell tumor 17 등의병명으로기술되었다. 본증례의역분화성분은조직학적으로파골세포형거대세포가풍부하며악성섬유조직구종이나섬유육종보다거대세포종을연상시키지만, 거대세포종보다심한세포분열빈도와이형성이관찰된다. 이는보고된증례와유사한소견이다 현재까지기술된 4예와본증례의임상적특징을요약하면 Table 1과같다. 다른역분화연골육종보다여성에호발하는경향이외에특이한임상상은아직발견되지않았다. S100 단백이연골육종부분의대부분의세포와일부의방추세포에염색되는것은, 역분화연골육종의면역조직화학염색결과에부합하는소견이다. 4,17 대부분의거대세포와소수의방추세포가 CD68 양성을보인점은거대세포종과유사한소견이며, 거대세포들은조직구계통으로생각된다. Smooth muscle actin 이일부세포에서염색된것은방추세포가근육섬유모세포성의분화를보이는것으로생각된다. 이러한부분만이생검되었을경우거대세포종외에악성섬유조직구종, 연골모세포형골육종, 중간엽연골육종, 연골모세포종등으로오진될가능성이있다. 15 역분화연골육종의기원은아직확실하게알려져있지않다. 분화가좋은연골부분과분화가나쁜부분이같은기원세포를가진다는가설 10,18,19 이있는반면, 두부분은다른기원세포에서생긴다는가설도있다. 3,4 이증례의경우분화가좋은연골세포와일부의분화가나쁜방추세포에서 S100 단백이염색되었다. 이는이전보고와같은결과이며같은기원세포에서나왔음을지지하는결과로해석된다. 18 반면거대세포에서 CD68 양성, S100 단백음성인점은거대세포가악성세포이기보다반응성세포임을시사하며, 기원에대한더많은연구가요구된다. 역분화연골육종의예후는불량하며평균생존기간은 6개월,

5 거대세포종유사역분화부분을가지는연골육종 349 5년생존율은 18% 로보고되어있다. 2,5 본증례와유사한역분화연골육종의예후는아직확실하게알려져있지않다. Mirra 가보고한증례는수술후 3개월만에재발하였고구역절제술을시행한후절단하였으나 2년후사망하였다. 14 Sissons 등이보고한증례를추적관찰한결과, 5개월후수술한자리에서재발하였고절단후 8.5년을생존하였다. Ishida 등의증례에서는수술후 9개월에재발하였다. 15,16 이전에보고된증례에서모두재발이나전이된종괴는거대세포가있는부분들이었다 Estrada 등 17 의증례에서는수술후 5개월동안재발이나전이의증거는없었고, 이번증례는수술후 15개월이지난현재재발이나전이의증거는없다 (Table 1). 그러나이전증례에비추어볼때세심한추적관찰이필요하다고생각한다. 본증례와유사한역분화연골육종의치료방침은정립된바가없으며, 현재까지통상적인역분화연골육종의치료로는광범위한절제술이바탕이되며절연면에종양이없는환자에서는항암화학요법이효과가있었다고보고된바있다. 2 본증례는거대세포가풍부한역분화연골육종으로서아직까지국내에는증례가보고된바없고, 조직학적으로거대세포종과비슷한부분이있어진단의혼선을가져올가능성이있다. 이에그존재를인지하고감별진단에포함시켜야할질병단위로가치가있어보고하고자한다. 참고문헌 1. Dahlin DC, Beabout JW. Dedifferentiation of low-grade chondrosarcomas. Cancer 1971; 28: Mitchell AD, Ayoub K, Mangham DC, et al. Experience in the treatment of dedifferentiated chondrosarcomas. J Bone Joint Surg Br 2000; 82: Johnson S, Tetu B, Ayala AG, Chawla SP. Chondrosarcoma with additional mesenchymal component (dedifferentiated chondrosarcoma). I. A clinicopathologic study of 26 cases. Cancer 1986; 58: Tetu B, Ordonez NG, Ayala AG, Mackay B. Chondrosarcoma with additional mesenchymal component (dedifferentiated chondrosarcoma). II. An immunohistochemical and electron microscopic study. Cancer 1986; 58: Faquin WC, Pilch BZ, Keel SB, Cooper TL. Fine-needle aspiration of dedifferentiated chondrosarcoma of the larynx. Diagn Cytopathol 2000; 22: Sakai O, Curtin HD, Faquin WC, Fabian RL. Dedifferentiated chondrosarcoma of the larynx. Am J Neuroradiol 2000; 21: De Lange EE, Pope TL Jr, Fechner RE. Dedifferentiated chondrosarcoma: radiographic features. Radiology 1986; 161: Mecuri M, Picci P, Campanacci L, Rulli E. Dedifferentiated chondrosarcoma. Skeletal Radiol 1995; 24: Garcia RE, Gannon FH, Thompson LDR. Dedifferentiated chondrosarcoma of the larynx: a report of two cases and review of the literature. Laryngoscope 2002; 112: Bovee J, Cleton-Jansen A-M, Rosenberg C, et al. Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for histogenesis. J Pathol 1999; 189: Sakamoto A, Oda Y, Adachi T, et al. H-ras oncogene mutation in dedifferentiated chondrosarcoma: polymerase chain reaction-restriction fragment length polymorphism analysis. Mod Pathol 2001; 14: Bruns J, Elbracht M, Niggemeyer O. Chondrosarcoma of bone: an oncological and functional follow-up study. Ann Oncol 2001; 12: Munk PL, Connell DG, Quenville NF. Dedifferentiated chondrosarcoma of bone with leiomyosarcomatous mesenchymal component: a case report. Can Assoc Radiol J 1988; 39: Mirra JM. Bone tumors. Clinical, radiologic and pathologic correlations. Philadelphia: Lea & Febinger, 1989: Sissons HA, Matlen JA, Lewis MM. Dedifferentiated chondrosarcoma. Report of an unusual case. J Bone Joint Surg Am 1991; 73: Ishida T, Dorfman HD, Habermann ET. Dedifferentiated chondrosarcoma of humerus with giant cell tumor-like features. Skeletal Radiol 1995; 24: Estrada EG, Ayala AG, Lewis V, Czerniak B, Valerie L. Dedifferentiated chondrosarcoma with a noncartilagenous component mimicking a conventional giant cell tumor of bone. Ann Diagn Pathol 2002; 6: Wick MR, Siegal GP, Mills SE, et al. Dedifferentiated chondrosarcoma of bone. An immunohistochemical and lectin-histochemical study. Virchows Arch A Pathol Anat Histopathol 1987; 411: Park YK, Yang MH, Ryu KN, Chung DW. Dedifferentiated chondrosarcoma arising in an osteochondroma. Skeletal Radiol 1995; 24:

Jkbcs016(92-97).hwp

Jkbcs016(92-97).hwp Expression of bcl-2 and Apoptosis and Its Relationship to Clinicopathological Prognostic Factors in Breast Cancer - A Study with Long Term Follow-up correlated with the survival rate.(journal of Korean