58 pissn : 1226-2102, eissn : 2005-8918 Original rticle J Korean Orthop ssoc 2018; 53: 58-65 https://doi.org/10.4055/jkoa.2018.53.1.58 www.jkoa.org 기괴방골성골연골종류증식의진단과치료 신덕섭 양한석 나호동 류승민 영남대학교병원정형외과 Diagnosis and Treatment of izarre Parosteal Osteochondromatous Proliferation Duk-Seop Shin, M.D., Ph.D., Han Seok Yang, M.D., Ho Dong Na, M.D., and Seung Min Ryu, M.D., Ph.D. Department of Orthopedic Surgery, Yeungnam University Medical Center, Daegu, Korea Purpose: There have been a few reports of bizarre parosteal osteochondromatous proliferation (POP) in Korea to date. The purpose of this study was to investigate the etiology, diagnosis, treatment, and prognosis of POP and to report the clinical outcomes from a single institution. Materials and Methods: etween 1999 and 2016, six patients who were diagnosed and treated operatively at Yeungnam University Medical Center were reviewed retrospectively. The analysis was performed using medical records, simple radiographs, magnetic resonance imaging (MRI), and pathology results, based on clinical and oncological results. ll patients underwent surgical treatment for complete resection. We also analyzed one patient who was initially diagnosed with POP, showing different clinical features during the follow-up period. Results: The age of patients ranged from 17 to 60 years. ll patients did not show a history of trauma. ll patients showed localized edema on the tumor lesion, and three patients also showed tenderness. The tumor lesions were distributed to the femur, tibia, and humerus. ll patients underwent marginal resection or wide resection. The mean follow-up period was 50.3 months. There was a malignant change in one patient, but no recurrence or metastasis. Conclusion: In this study, there was no difference in the incidence of POP in accordance with sex. Moreover, there was no significant relationship between trauma and onset of POP. Unlike previous reports, no recurrence occurred after complete resection. If POP is diagnosed, it is necessary to consider the possibility of malignant change and distinguish it from other malignant tumors. Key words: bizarre parosteal osteochondromatous proliferation, Nora s lesion 서론 기괴방골성골연골종류증식 (bizarre parosteal osteochondromatous proliferation, POP) 은 1983년 Nora 등 1) 이보고하면서알려지기시작하여일명 Nora씨병변으로불려지기도하는드문양성골병변이다. 2,3) Received March 8, 2017 Revised May 8, 2017 ccepted June 26, 2017 Correspondence to: Seung Min Ryu, M.D., Ph.D. Department of Orthopedic Surgery, Yeungnam University Medical Center, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea TEL: +82-53-620-3640 FX: +82-53-628-4020 E-mail: karaz101@ynu.ac.kr POP는피질골의바깥에경계가명확한고착성골병변소견 (exophytic osseous mass) 을보이며, 연골, 뼈, 그리고섬유화조직의혼합으로구성된다. 4) 호발연령은 20-30대성인으로알려져있고, 40대여성에서약간높은유병률을보이기도한다. 2) POP는매우드문골종양으로보고사례가많지않아질병의진단및치료, 치료후경과, 예후등이잘알려져있지않다. 국내에서는단편의증례보고는있지만증례를모아서한기관에서정리한연구는지금까지는없었다. 본연구에서는영남대학교병원에서 POP로진단하고절제술을시행하고조직학적으로최종확진후재발없이추적관찰중인 6예를통하여 POP의진단과치료및예후등을조사하여임상적결과를분석하고자한다. The Journal of the Korean Orthopaedic ssociation Volume 53 Number 1 2018 Copyright 2018 by The Korean Orthopaedic ssociation This is an Open ccess article distributed under the terms of the Creative Commons ttribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
59 izarre Parosteal Osteochondromatous Proliferation 대상및방법 1999년부터 2016년까지본원에서수술하여조직학적으로 POP 로진단되고, 1년이상추시관찰중인 6예의환자를대상으로하였다. 환자의성별, 평균연령, 발생원인, 종양의발생부위, 재발여부에대해후향적으로분석하여임상적및종양학적결과를분석하고자하였다. 단순방사선촬영, 자기공명영상 (magnetic resonance imaging, MRI) 을사용하여종양의위치, 주변조직으로의침범양상등을확인하였다. 수술은전체예에서동일한술자가시행하였고변연부절제또는광범위절제에해당하는정도의절제술을시행하였다. 절제술뒤에는절삭기 (burr) 를이용하여조금더경계를제거하였다. 또한동일한검사자가조직학적검사를시행하였다. 조직학적검사를시행할때에는종양의크기및경계확인을위해절제편의여러곳에서검사를시행하였으며조직검사의결과가모호한경우검체를외부에의뢰하였다. 조직검사는헤마톡실린및에오신 (H&E) 염색을통해세포핵과골모세포의분포양상등을확인하였으며종양의해부학적발생위치, 분포, 특징및임상경과에대해분석하였다. 앞에서언급한 6예외에수술전조직검사에서는 POP로진단받았지만수술후조직검사소견상방골성골육종 (parosteal osteosarcoma) 으로진단된 1예도함께비교분석하였다. 결과 총 6예의환자들중성별분포는남자 2명, 여자 4명이었으며, 평균연령은 29.1세 ( 범위, 17-60세 ) 였다 (Table 1). 발생부위는수지 2 예 (Fig. 1), 대퇴골원위부 1예, 경골근위부 1예, 비골원위부 1예, 그리고족지 1예등으로다양하게분포하였다 (Table 1). 모든환자에서병변부위에국소종창을확인할수있었으며, 3명의환자에서병변부위동통을확인할수있었다. 전체예에서병변부에대한과거외상력은없었다. 추시기간은평균 50.3개월 ( 범위, 18-108 개월 ) 이었고, 수술후최소 1년 6개월추시관찰기간중재발은없었다. 방사선적으로경계가분명한골화된덩이가골피질의표면에위치하고있었고골수강과연결성은발견되지않았다. 조직학적으로기괴연골세포, 유골세포, 방추상세포등이관찰되는소견을보였다. Table 1. Demographic Data of the izarre Parosteal Osteochondromatous Proliferation Case No. Sex ge (yr) Location Trauma history Margin Local recurrence Malignant change Follow-up period (mo) 1 F 19 Rt. ankle lateral malleolous - Negative - + 96 2 F 22 Lt. 4th finger proximal phalanx - Negative - - 22 3 M 36 Rt. 3rd toe middle phalanx - Negative - - 36 4 F 60 Rt. 2nd finger middle phalanx - Negative - - 22 5 M 21 Lt. distal femur - Negative - - 18 6 F 17 Rt. proximal tibia - Negative - - 108 F, female; M, male; Rt., right; Lt., left. Figure 1. () Preoperative radiographs of a 60-year-old female. The tumor was grown in the ulnar aspect of the middle phalangeal head of the index finger. () Postoperative radiographs.
60 Duk-Seop Shin, et al. 대상환자군중 19세여자환자 1예 (Table 1; Case No. 1) 는 2년동안지속된오른쪽발목외과부위에골종괴로내원하였고이학적검사소견상단단하고고정된덩이양상을보였으며외상과의연관성은발견되지않았다. 단순방사선적으로는비골원위부피질골의바깥에경계가명확한고착성골병변소견이관찰되었다. 병변의중심부와수질강사이에연속성은관찰되지않았다. 수술전진단은 POP 또는골연골종 (osteochondroma) 이었다. 외과적절제를시행하였고, 절제된조직은두개의특징적인영역을가지고있었다. 먼저연골모와수질골에 4.7 3.5 cm의골연골성부분이있었고, 변연부에는 2.3 2.0 cm의회백색연조직부분이있었다 (Fig. 2). 조직학적으로골연골성부위는조직화되지않은연골조직의불규칙한소엽이뼈로성숙하는모습을보였다 (Fig. 3). 조직학적소견과방사선적소견을종합하여골연골성부분은전형적인 POP로진단되었다. 하지만회백색연조직부분은오늬무늬배열 (herringbone arrangement) 의비정형방추세포의증식이관찰되었다. 이세포들은과염색핵을가지고있었고핵의다형성은경미했으며유사분열이때때로나타났다. 면역조직화학염색에서비정형의방추세포들은데스민 (desmin) 과 S-100 단백질에음성이었다. 이러한결과는 POP의 2등급섬유육종 (fibrosarcoma) 로의악성변화로평가되었다 (Fig. 4). 연구대상환자군 6예외에 24세남자환자 1예의 MRI 검사에서우측상완골하단 35 33 36 mm 3 크기의 POP 또는골연골종으로진단을하고경과관찰을하였다. 추적관잘중처음진단 후 2년뒤에단순방사선촬영과 MRI 소견상크기가 44 42 50 mm 3 로증가하여오진의가능성을염두에두고전신마취하절개생검을시행하였다. 면역조직화학검사소견상방추세포에서 p53 antibody는관찰되지않았고, Ki-67 labelling index가 5% 미만으로나타났다. 조직학적소견에서는유리연골과골소주의분절이관찰되었고, 골소주사이간질에서는저세포성방추세포가약간의이형성을보였다. 종합적으로 POP 또는저등급방골성골육종으로판단되나정확한진단을위해절제술을계획하였다. 종괴의크기가증가한점을고려하여저등급방골성골육종으로진단하고절개생검을시행한지 10일뒤에상완골원위부광범위절제술및종양인공관절대치물삽입술을시행하였다 (Fig. 5). 광범위절제술및종양인공관절대치물삽입술후절제된조직검사결과 1등급방골성골육종으로확인되었다. 광범위절제술및종양인공관절대치물삽입술후 2달뒤추시관찰중, 폐의좌상엽과좌하엽으로의전이가발견되어쐐기절제술을시행하였고, 현재까지재발이나추가전이없이경과관찰중이다. 고찰 POP는국소적으로빠르게성장하는매우드문양성골종양으로 1983년에처음보고되었다. 1) 어느연령에서나발생가능하지만평균적으로 30-33세에서발생한다고알려져있다. 5) 성별에따른빈도는비슷하며주로손과발의작은골에서발생하는것 Figure 2. () Radiographs of the right ankle. The anteroposterior (left) and oblique (right) views demonstrate a well-defined, exophytic bony mass attached to the lateral cortex of the metaphysis of the distal fibula. Continuity between the central part of the lesion and the medullary cavity of the fibular is absent. () The excised mass revealed two distinctive areas (left): n area resembling osteochondroma with a cartilaginous cap and medullary bone, as well as an unusual, gray-white, fleshy soft tissue mass (arrows) in the periphery. Note a broad base (arrowheads) attached to the cortical surface of the distal fibula. The whole mount section of the excised mass (H&E) shows an osteochondromatous area with a cartilaginous cap and medullary bone, and a fibrosarcomatous area in the periphery (right).
61 izarre Parosteal Osteochondromatous Proliferation Figure 3. () low-magnification view shows a cartilaginous cap maturing into the bony trabeculae (H&E, 40). () higher-magnification view shows cartilage with bizarre, enlarged nuclei and a blue tinctorial quality in the woven bone spicules (H&E, 200). (C) highermagnification view shows loosely arranged spindle cells between the bony trabeculae, rimmed by osteoblasts (H&E, 200). C Figure 4. () The lower part of the photomicrograph shows an osseous element of the bizarre parosteal osteochondromatous proliferation. The fibrosarcomatous area can be seen above. () The fibrosarcomatous area is moderately cellular with mild nuclear pleomorphism and occasional mitotic figures (, : H&E, 200).
62 Duk-Seop Shin, et al. C D Figure 5. () Initial radiographs of a 24-year-old male. The exophytic osteoblastic tumor in the antero-medial aspect of the distal humerus (arrows). () The tumor had grown up for 3 years (arrows). (C) Postoperative radiographs and intraoperative photographs. The right distal humerus mass was excised (arrows). The biopsy result was parosteal osteosarcoma, grade 1. (D) Distal humerus was excised and tumor prosthesis inserted. Radiographs were taken postoperatively. 으로보고되었으나최근에는장골, 두개골등다양한부위에서 POP가보고되고있다. 1,5-7) 국내에서는드물게족부, 수부, 장골에발생한경우들이보고된적이있다. 8-10) 본연구에서는 17세에서 60세에이르기까지다양한연령대에발생하였고손과발의지골뿐만아니라경골및대퇴골등의장골에서도발생하였다. 발병원인으로는반복되는외상등으로인한골막의자극이나허혈로인한증식반응등이알려져있다. 11) 하지만본연구에서는기존외상력과의상관관계와는달리, 2,12) 모든환자에서과거외상력은확인할수없었다. 방사선적으로경계가뚜렷하고골수변화없이골막에서발생하는것을확인할수있었다. 3) 조직학적으로는비정형세포가동반되지않는석회화성, 골성, 연골성종양으로보고되고있고, 2,13,14) 혼돈이쉬워진단시에오류가잘생긴다. 단순방사선촬영소견에서골면에경계가분명한덩이형태로보이며종종연부조직으로방사되는형태를보인다. MRI와컴퓨터단층촬영은골연골종과감별에유용하다. 유전학적으로 t(1:17)(q32;q21) 와연관이있다고알려져있다. 15) 임상적으로는특이한소견을보이지않는경우가많고대부
63 izarre Parosteal Osteochondromatous Proliferation 분수주혹은수개월에걸쳐크기가커지는통증이동반된덩이가주된증상이며관절주변의경직등이동반된경우도있다. 2) 악성변화가없다고알려져절제술로치료가가능한것으로보고되고있으나 2년재발률이 29%-55% 에이르고, 1-3) Meneses 등 2) 에따르면재발률이 55% 에이른다고보고되고있다. 본연구에서도 6 예모두에서병변부위에국소종창을확인할수있었으며, 3명의환자에서병변부위동통을확인할수있었다또한모든환자에서절제술로치료하였지만국소재발률이매우높다는이전의결과와는상반되게재발은발생하지않았다. 1-3) 이전의보고에의하면 POP는악성변화나전이가보고된적이없는양성질환이었다. 2,16) 하지만본연구의 1예에서초기에족관절외과의 POP를진단받았으나절제된조직편에서종양의경계부에섬유육종로악성변화가확인되었다. 기존에 POP는재발률은높은반면악성변화는하지않는다고알려져있었지만본연구의 1예의경우에서섬유육종으로처음으로악성변화를한경우를확인하고보고하였다. 17,18) 이질환과유사한소견을보이는질환으로는골연골종, 조갑하외골종증 (subungual exostosis), 방골성골육종, 탈분화형연골육종 (dedifferentiated chondrosarcoma), 탈분화형방골성골육종 (dedifferentiated parosteal osteosarcoma), 그리고전이성방추세포육종 (metastatic spindle cell sarcoma) 등이있다. 초기에 POP로진단되었으나임상증상의진행으로시행한조직검사결과방골성골육종으로진단된증례에서영상및조직학적진단에서 POP가방골성골육종과비슷한양상을보이기때문에진단시감별이반드시필요할것으로생각된다. 또한병변이골표면에위치하고있는영상학적소견과연골성분이포함되어있다는조직학적소견에서골연골종과도감별이필요할것으로생각된다. 5) 본연구에서 POP로확인된조직편의경계부에서악성변화가발견된 1예와임상양상, 영상학적및조직학적유사성으로인해 POP로오진되었다가추시관찰중방골성골육종으로진단된 1 예를통해 POP 진단시악성변화가능성과다른악성종양과의세밀한감별을염두에두어야할것으로생각된다. 이때문에초기치료시완전절제를목표로하여야하고주기적인경과관찰이중요할것으로생각된다. 본연구는국내에서처음으로 POP 증례를모아서연구를진행하였다. 총 6예를비교분석하였으며 POP로확인된조직편의경계부에서악성변화가발견된 1예와임상양상, 영상학적및조직학적유사성으로인해 POP로오진되었다가추시관찰중방골성골육종으로진단된 1예를보고함으로써진단시에악성변화의가능성과다른악성종양과의감별의필요성을제시하였다는점에의의가있다. 결론 본연구에서는환자의성별에따른발병차이는없는것으로생각된다. 또한외상과발병과의유의한관계를발견할수없었다. 기존에보고되었던것과는달리변연부절제이상의절제연으로수술한경우후재발은 1예도발생하지않았다. POP로진단된경우악성변화가능성을염두에두어야한다. 또한다른악성종양과감별에유의하여야한다. CONFLICTS OF INTEREST The authors have nothing to disclose. REFERENCES 1. Nora FE, Dahlin DC, eabout JW. izarre parosteal osteochondromatous proliferations of the hands and feet. m J Surg Pathol. 1983;7:245-50. 2. Meneses MF, Unni KK, Swee RG. izarre parosteal osteochondromatous proliferation of bone (Nora's lesion). m J Surg Pathol. 1993;17:691-7. 3. Dhondt E, Oudenhoven L, Khan S, et al. Nora's lesion, a distinct radiological entity? Skeletal Radiol. 2006;35:497-502. 4. Fechner RE, Mills SE. Tumors of bones and joints. In: Rosai J, Leslie H, ed. tlas of tumor pathology. Third series, Fascicle 8. Washington, DC: rmed Forces Institute of Pathology; 1993. 268-9. 5. Gruber G, Giessauf C, Leithner, et al. izarre parosteal osteochondromatous proliferation (Nora lesion): a report of 3 cases and a review of the literature. Can J Surg. 2008;51:486-9. 6. Torreggiani WC, Munk PL, l-ismail K, et al. MR imaging features of bizarre parosteal osteochondromatous proliferation of bone (Nora's lesion). Eur J Radiol. 2001;40:224-31. 7. Cooper PN, Malcolm J. bizarre parosteal osteochondromatous proliferation of the radius. Histopathology. 1993;22:78-80. 8. Kim SW, Suh JH, Shin SM, Cho K. izarre parosteal osteochondromatous proliferation (Nora's lesion) of the big toe. ( report of two cases and review). J Korean Foot nkle Soc. 2013;17:68-73. 9. Noh HK, Jeon HS, Jeon SJ, Moon CS, Kang SG, Song GS. izarre parosteal osteochondromatous proliferation in the proximal phalanx of the third toe: case report. J Korean one Joint Tumor Soc. 2011;17:91-4.
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65 pissn : 1226-2102, eissn : 2005-8918 Original rticle J Korean Orthop ssoc 2018; 53: 58-65 https://doi.org/10.4055/jkoa.2018.53.1.58 www.jkoa.org 기괴방골성골연골종류증식의진단과치료 신덕섭 양한석 나호동 류승민 영남대학교병원정형외과 목적 : 현재까지국내에서기괴방골성골연골종류증식 (bizarre parosteal osteochondromatous proliferation, POP) 에대한보고는 많지않았다. 이에본연구에서는단일기관에서진단하고수술을시행한 POP 의증례를모아서발생과진단, 치료및예후등을조사하여임상적경과를살펴보고자한다. 대상및방법 : 영남대학교병원에서 1999년부터 2016년까지 POP 로진단하고수술한 6명의환자를대상으로후향적분석을시행하였다. 분석은의무기록, 단순방사선촬영, 자기공명영상및병리결과를통해시행하였으며임상적결과와종양학적결과를토대로시행하였다. 모든환자군에서완전절제를목표로수술적치료를시행하였다. POP 로초기에진단되었다가추시관찰중임상적으로다른양상을보인 1예도함께분석하였다. 결과 : 환자의나이는 17세에서 60세까지분포하였다. 모든환자에서병변부에대한과거외상력은확인할수없었다. 모든환자에서병변에국소적으로부종이있었으며, 3명의환자에서는압통도있었다. 발생부위는대퇴골원위부, 경골근위부및수족부의지골등다양하게분포하였다. 모든환자에서변연부절제술또는광범위절제술을시행하였다. 평균 50.3개월간추시관찰하였으며추시기간중한명의환자에서악성변화가있었지만재발이나전이가있었던환자는없었다. 결론 : 본연구에서는환자의성별에따른발병차이는없는것으로생각된다. 또한외상과발병과의유의한관계를발견할수없었다. 기존에보고되었던것과는달리절제술후재발은 1예도발생하지않았다. POP 로진단된경우악성변화가능성을염두에두어야한다. 또한다른악성종양과감별에유의하여야한다. 색인단어 : 기괴방골성골연골종류증식, Nora 병변 접수일 2017 년 3 월 8 일수정일 2017 년 5 월 8 일게재확정일 2017 년 6 월 26 일책임저자류승민 42415, 대구시남구현충로 170, 영남대학교병원정형외과 TEL 053-620-3640, FX 053-628-4020, E-mail karaz101@ynu.ac.kr 대한정형외과학회지 : 제 53권제 1호 2018 Copyright 2018 by The Korean Orthopaedic ssociation This is an Open ccess article distributed under the terms of the Creative Commons ttribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.