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1 Korean Journal of Oral and Maxillofacial Pathology 2017;41(2): ISSN: (Print); (Online) Available online at 좌측경부상방에발생한비전형지방종선종양 - 증례보고및문헌고찰 - 송두헌 1)#, 엄찬용 1)#, 임영관 2), 김병국 2), 김혜은 1), 조혜중 1), SUN QIOACHU 1), 안규현 1), SHI SHUHAN 1), 김옥준 1)* 1) 전남대학교치의학전문대학원구강병리학교실 2) 전남대학교치의학전문대학원구강내과학교실 <Abstract> Atypical Lipomatous Tumor Occurred in Upper Left Cervical Region - Case Report and Its Literature Review - Du Hun Song 1)#, Chan Yong Eum 1)#, Yeong Gwan Im 2), Byung Gook Kim 2), Hye Eun Kim 1), Hye Joung Cho 1), SUN QIAOCHU 1), Kyu Hyeon Ahn 1), SHI SHUHAN 1), Ok Joon Kim 1)* 1) Dental Research Institute, Department of Oral Pathology, 2) Department of Oral medicine School of Dentistry, Chonnam National University. The occurrence of atypical lipomatous tumor of the head and neck is rare, and clinical and histologically differential diagnosis of the tumor is needed for other similar diseases. Herein we report atypical lipomatous tumor arising in neck area. And literature review was done. Complete excision with negative margins followed by long-term follow-up is recommended as the treatment of choice for these uncommon entities. Key words: Atypical lipomatous tumor, Upper left cervical, Differential diagnosis Ⅰ. INTRODUCTION 지방육종은연조직에서흔하게발생하는종양중의하나로, 악성종양과중간형악성종양으로구분한다. 악성종양으로는탈분화성지방육종, 점액성지방육종, 다형성지방육종, 혼합 # These authors contributed equally to this work. * Correspondence: Ok-Joon Kim, D.D.S, Ph.D, Department of Oral Pathology, College of Dentistry, Chonnam National University, Bug-Gu, Gwangju, , Korea Tel: , Fax: js3894@chonnam.ac.kr ORCID : Received: Mar ; Revised: Apr ; Accepted: Apr 성지방육종으로나뉜다 1,15). 중간형악성종양에는비전형지방종성종양, 고분화지방육종이있으며, 중간형악성종양의아류형으로는지방종유사형, 염증형, 경화형, 탈분화형으로분류된다 2,10,13,14). 본증례에서는비전형지방종성종양의염증형이호발한환자의증례에대해서보고하였다. 비전형지방종성종양은신체에서흔하게발병하기는하지만두경부에서는발병률이낮다. 또한감별진단해야할질환들이많기에진단이쉽지않다. 비전형지방종성종양은지방종과유사한임상적특성을가지고있기때문에두질환간의감별이필요하다 3). 본증례에서도병소의재발이없고적출된

2 종괴의경계가뚜렷하고성장속도가느린특징을나타내고있었다. 조직학적소견상비전형방추상세포지방종, 점액성지방육종그리고탈분화성지방육종의조직학적소견과유사하기때문에감별진단이필요하였다 4). 또한염증세포의침윤이관찰되었기에 IgG 4 관련질환과염증성근섬유아세포종과의감별진단도필요하였다. 중간형지방육종의조직학적특징은다양한크기의성숙한지방세포와섬유격막으로구성되어있으며이형성, 비전형성기질세포들이존재한다. 이들기질세포들은과염색성을나타내고다공포성형태의지방아세포가존재한다. 진단을위해서술전에미세바늘흡인법, 경부 CT, 초음파검사을진행하였고, 술후헤마톡실린염색과면역조직화학염색법을사용하였다. 본연구에서는 38세의환자의좌측경부에발생된종괴에대해서보고하려고한다. 두경부에서발생한비전형지방종성종양과다른질환과의감별진단에대해서고찰해보고, 다양한연령대의비전형지방종성종양이발생한증례들을토대로발병부위, 연령대, 재발여부에대해서알아보고자한다. 전남대학교중앙도서관학술자료를온라인검색을통해 1998년이후총 22개의논문에서의증례를기록하였다. 진단을위한검사로미세바늘흡인법, 경부 CT, 초음파, 헤마톡실린염색, 면역조직화학염색법을사용하였다. 초진시에낭종 이의심되어미세바늘흡입법을이용하였다. 경부 CT는조영제주입후종괴의형태및전이여부, 크기, 위치를알아보기위해시행하였고, 초음파검사는염증성, 양성종양, 악성종양여부를알아보기위해시행하였다. 통상적인헤마톡실린염색법을이용하였으며, 면역조직화학검사법을시행하였다. 헤마톡실린염색법은파라핀이첨가된조직을 xylene 을사용하여파라핀을녹인후에, 이를제거하였다. 그리고재수화를일으킨후헤마톡실린으로핵을염색하고이오신으로세포질을염색한다. 이후에탈수를하여염이유지되도록해준다. 종양세포의기원을알아보기위해서면역조직화학염색법을진행하였고이때사용된항체들은 IgG (Immunoglobulin G), IgG4 (Immunoglobulin G4), Actin, S-100, CD138 (Cluster of differentiation 138), ALK (Anaplastic lymphoma kinase), MDM-2 (Mouse double minute 2 homolog), CD34 (Cluster of differentiation 34) 이다. Ⅱ. CASE 2014 년 9월 26일 38세남자환자가좌측경부의종물을주소로전남대학교이비인후과외래를방문하였다. 환자가내원 Fig. 1. Neck CT finding before operation. A 2.4 x 2.2 x 1.8 cm well-defined heterogeneously enhancing mass in subcutaneous layer of left anterior neck. No significantly enlarged lymph node in both lateral necks. Fig. 2. A lesion is elliptical, well-defined, it abutts to muscle. No calcification/cystic changes are noted. Centrally the lesion is hyperechoic and hypoechoic peripherally. 98

3 하기 8개월전부터경부의전방부에종괴를발견하였으나, 그동안지켜보다가최근크기가증가하여치료를위해전남대학교병원을방문하였다. 이환자는다음과같은과거력을가지고있었다. 고혈압, 결핵, 간염, 암은없으나당뇨는있었고, 1999년광주소재병원에서혈관종으로수술한경력이있었다. 과거약물부작용은없었다. 흡연은하루 0.5갑씩 15년동안피웠고 2012년도부터금연을하였다. 초진시유피낭종이의심되어미세바늘흡인법을진행하였지만유피낭종은아닌것으로판별되었다. 술전경부의방사선전산화단층촬영 (Neck CT) 에서는 Neck Level VI에 2.4 x 2.2 x 1.8 cm 크기의종괴가좌측경부상방에위치하였고, 광경근 (Platysma muscle) 하방으로낭종성덩어리가견장근육 (Strap muslce) 에부착되어있는형태로확인되었다 (Fig. 1). 초음파도시행하였다 (Fig. 2). 2014년 11월전신마취하에좌측경부의종괴를절제하였다. 수술결과 Neck level VI의광경근의하방에견장근육부위에부착되어있는 2.4 x 2.2 x 1.8 cm 크기의종괴를관찰할수있었다. 수술하기전영상학적검사를통해지방종양성소견을보인병소에대해술후조직병리학적검사를시행하였다. H&E 염색하에저배율의광학현미경으로관찰했을때, 경계가명확하고지방세포와염증세포의침윤을관찰할수있었다 (Fig. 4). 고배율의광학현미경소견에서는성숙한지방세포와섬유격막이관찰되었다. 지방세포는다양한크기로존재하였고사멸된지방세포도존재하였다 (Fig. 5). 진단의학검사결과 WBC, Hgb, AST, ALS, BUN, LDH 등모든수치가정상이었고수술후현재까지병소가재발되지않았다. 면역조직화학염색결과에는 IgG(+), IgG4(+), Fig. 3. Gross finding of the excised tumor (cut surface). Well-demarcated tumor of yellowish cut surface resembling lipoma. Fig. 4. Pathologic findings (H&E 20). It showed mature adipose tissue and chronic inflammatory cell infiltrates. Fig. 5. Pathologic findings (H&E 200). The tumor was composed of mature adipocytes and fibrous septa. The mature adipocytes varied in size. 99

4 Fig. 6. Pathologic findings (H&E). It showed multivacuolated lipoblast, mature adipose tissue and inflitrate by inflammatory cells, which compose of lymphocyte and plasma cells. Fig. 7. Immunohistochemical stain findings. The tumor showed immunoreactivity for IgG, IgG4, CD138, S-100. No reactivity to ALK, Actin, MDM-2, CD-34. CD138(+), S-100(+), ALK(-), Actin(-), MDM-2(-), CD34(-) 으로나타났다 (Fig. 7). 진단자료들을토대로비전형지방종성종양의염증형으로최종진단하였다. Ⅲ. DISCUSSION 지방육종은연조직에서발생하는흔한종양중의하나로, 지방종에서발달되기보다는단독적으로생기는편이다 1). 하 100

5 지만지방육종이두경부에발생하는경우는흔치않으며전체지방육종의발생에서 5~9% 정도만두경부에서발생한다고알려져있다 5). 발병연령은 40~60 대까지가가장많고여자보다남자에서호발한다 5). 지방육종은어디부위에서건중배엽조직세포나지방조직이있는곳에서생길수있다 6). 지방육종이가장호발하는부위는넓적다리, 복막후강, 서혜부부위이다. 지방육종이두경부에서적게발생하는이유는두경부의지방조직이상대적으로다른부위보다적고근육이많이분포하여종양의성장에제한을가할수있기때문으로사료된다. 본증례의현미경학적소견으로는다양한크기의지방세포가존재하고섬유격막에이형성된기질세포가국소적으로존재하였다. 형질세포와림프구의침윤이나타나있었으며다공포성의지방아세포도존재하였다. 지방아세포는과염색성의핵을가지고다수의세포질공포를가지고있는세포로정의된다. H&E염색을통한지방아세포의검출이지방육종진단시주요소견이긴하지만이소견만으로는바로지방육종으로진단할수가없다. 이는지방아세포종증, 연골성지방종등의양성종양에서도지방아세포가관찰되기때문이다 13). 비전형방추상세포지방종, 점액성지방육종그리고탈분화형지방육종의조직소견에서도본증례와유사한소견을보이기때문에감별이필요하다. 비전형방추상세포지방종의주된소견은지방세포의크기가정상세포와유사한일반적인지방종과는달리지방세포의크기가다양하고다공포성의지방아세포도존재하고있다. 점액성지방육종과탈분화형지방육종도또한유사한조직소견을나타낸다. 두질환의주요소견도다양한크기의성숙지방세포, 지방아세포, 방추상세포가관찰이된다. 따라서세질환모두조직소견만으로는비전형지방종성종양과구분이쉽지않고감별을위해서면역조직화학검사가추가적으로필요하다. 본증례에서비전형지방종성종양으로진단하기위해사용된항체들은 IgG, IgG4, CD138, ALK, Actin, S-100, MDM-2, CD34이다. 염색법으로는면역조직화학염색법을시행하였다. 면역조직화학염색법은종양세포의기원을증명하기위해항체를사용하여염색하는방법으로종양세포의진단시에많이사용하는방법이다. 특정항체를단계별로사용하기보다는임의대로다수의항체를동시에사용하여검출한 단. 진단결과는 Table. 1에나타나있다. 먼저 IgG 4 관련질환과의감별이다. 비전형지방종성종양염증형의경우 B세포의표현형이다수존재한다. 마찬가지로 IgG 4 관련질환에서도 B세포가검출되는데, 형질세포를검출하기위해사용된항체는 IgG, IgG 4, CD138 로써각각양성으로나타났다. 이에조직학적소견을서로비교하였고 IgG 4 관련질환의경우염증세포의침윤과불규칙적소용돌이모양의섬유화를나타내지만본소견에서는발견되지않았기에제외하였다. 두번째는염증성근섬유아세포종과의감별이다. 근육조직기원여부를알아보기위해서 actin을사용하였고음성으로나타났다. 염증성근섬유아세포종에서만발견되는효소인 ALK도음성으로나타났기에, 이두결과를토대로염증성근섬유아세포종은감별진단에서제외되었다. 세번째는비전형방추상세포지방종, 점액형지방육종그리고탈분화형지방육종과의감별이다. 면역조직화학염색시사용한 CD34 항체는점액형종양과방추상세포지방종에주로검출되는항체이며본증례에서음성으로나타났기에두질환을제외하였다 9). 탈분화형지방육종은전이가잘되는것으로알려져있지만본증례에서전이가발생되지않았기때문에제외하였다. 네번째는지방종과의감별이다. 지방종의경우구강내에서발생율이낮고협측점막부위에발생된다고알려져있다. 또한일반적인지방종의조직소견은정상세포와유사하게관찰되는반면, 본증례에서의조직소견에선지방세포의크기가다양하기때문에제외하였다. S-100 단백질은양성으로나타났다. 이는지방아세포의검출에사용되는항체로써, 이세포는비전형지방종성종양에특징적으로존재하는세포이다 7). MDM-2 (12q14-15 염색체구간 ) 의검출은중간형악성종양의진단에주요한인자로알려져있으나본증례에서는음성으로나타났다. 이는 MDM-2 염색체구간은전체지방육종의증례에서 50% 정도만발현된다고알려져있기에본증례에서는발현이안된것으로사료된다 8). 본연구에서는두경부영역에서발생된비전형지방종성종양에관한문헌들을조사하고, 본교의중앙도서관학술자료를온라인검색을통해 1998년이후총 22개의논문에서 101

6 Table. 1. Immunohistochemical stain findings. IgG IgG4 CD138 ALK Actin S-100 MDM-2 CD Table. 2. Atypical lipomatous tumor in head and neck. Author Year Age/Sex Size Site Diagnosis Diagnostic method 1 William N. (18) /M 3.0cm Tongue WD H, I, M 2 Hattori (9) /M 1.2cm Lower lip ALT/WD H, I 3 S Capodiferro (19) /F 2.5 Tongue WD H 4 Angeles (20) /M 0.5cm Tongue ALT H, I, C 5 Georges Z. (21) /M 9cm Face ALT H, M 6 Gul O. A. (14) /F 15cm Hemi-facial ALT H, I, M 7 Ali T. (7) /M 4cm Submental ALT H, I, C 8 DeWitt (11) /F 0.6cm Tongue ALT/WD H 9 A Coca P. (10) /M 7cm Neck ALT/WD H, C 10 Jan Laco (8) /F 1.1cm Tongue ALT H, I 11 Chapman M. (22) /M 1.5cm Pharynx ALT H, I, C 12 Norifumi M. (23) /M 1.2cm Tongue ALT H, M 13 Shi, H. Y. (15) /F 3cm Larynx ALT H, I 14 H. Nouri (24) /W 5cm Hypopharynx WDLS H, I, C 15 Hakan B. (25) /M 25cm Neck ALT/WD H, I, C 16 Andrea B. (26) /M 14cm Esophagus ALT H, I, C 17 Ayman FA (27) /M 1.5cm Tongue ALT/WD H, I, C 18 Evangelia P. (13) /F 0.8cm Lower lip ALT/WD H, I 19 Jie Cheng (28) /F - Buccal area ALT/WD H, I, M 20 Dariusz K. (29) /F 3cm Cheek ALT/WD H, I, M 21 Y.B. Kim (5) /M 1.5cm Gingiva ALT/WD H, I, M 22 G. Priyal (2) /F 3.6cm Maxillary antrum ALT H, I, C (ALT=Atypical lipomatous tumor, WD, WDLS=Well differentiated liposarcoma, H=Hematoxylin-eosin stain, I=Immunohistochemistry, C=Computed tomography, M=Magnetic resonance imaging) 'Atypical lipomatous tumor of neck', 'liposarcoma of neck', 'liposarcoma of oral cavity', atypical lipomatous tumor case report' 의키워드를이용하여 22개의증례를조사했다 (Table. 2). 중간형지방육종이발생한평균연령대는 56.3세로, 총 22 명의증례중에서 50대이후의연령대가 14명으로써가장많이조사되었고그다음으로는 30~50 대연령대가 6명, 30대미만이 2명으로나타났다. 이를통해서중간형지방육종이연령이증가함에따라발생율이증가한다는것을알수있다. 이는노화로인한세포의비정상적인분열및암관련유전자가증가하는것때문으로사료된다. 본연구의증례에서는 38세의비교적젊은나이에서호발하였는데이는환자의 15 년동안의흡연습관이종괴의발생에기여한원인으로사료된다. 중간형지방육종을조사한증례에서성별은각각남성은 13명, 여성은 9명으로, 남성에서더호발하는것으로관찰됐다. 신체전체에서발생한지방육종은대개성인에서발생하며여성보다남성에서더많이호발한다고알려져있다 10). 102

7 남성이여성에비해서더높은흡연과음주성향그리고더잦은외상으로인해서더많이발생되는것으로보인다. 종양의진단을위해사용한영상진단방법들중에서는 CT를사용한경우가 9개, MRI 는 7개의증례에서사용되었다. 대부분의증례에서 H&E 염색과면역조직화학염색을시행하였다. 두경부에서발생한중간형지방육종의호발부위를 3부위 ( 경부, 구강및안면부 ) 로나누어서조사하였다. 결과는총 22 명의환자중에서 13명이구강에서발생되어구강이가장높은호발부위 (60%) 로나타났다. 그다음순서로는경부 6명 (27%), 안면부 3명 (13%) 로나타났다. 본연구통계에서는특히구강부위중혀부위에서높은호발율을보였는데, 이는협측점막에서호발율이제일높다는기존의연구들과다른결과가도출됐다 11). 이는저자가조사한증례위주로통계분석을한결과로사료된다. Table. 1의중간형악성종양증례들중 6개의증례를제외한나머지증례들에서평균 follow-up 기간은 18.3 개월이었으며수술후에재발했다는증례는없었다. 본증례에서도재발은관찰되지않았다. 지방육종의치료는완전한절제이다. 그러나두경부에발생한지방육종을완전한절제로제거할시에주변에위치하고있는여러해부학적인구조물이나신경, 혈관등의손상에대한우려로제한적으로절제해야한다. 하지만완전한절제가이루어지지않을경우재발의위험성이존재하고전이도발생될수있다 12). 지방육종의발생에기여하는원인에대해서는아직까지알려져있지않다. 지금까지알려진바로는다른암들과유사하게음주, 흡연, 유전인자, 지속적인외상등이있다. 현재의연구결과로는양성지방종이악성으로변한다는주장보다는다능성의지방아세포혹은간엽세포등에의해서발생된다고알려져있다 10). 여러원인들가운데간엽세포에의해서지방육종이발생된다는두가지연구는다음과같다. 첫번째는 EWSR1-DDIT3 결합단백질이다능성간엽세포에선택적으로결합한후전사과정을제어하여점액성지방육종을발생시킨다는연구가있다 16). 두번째는 Syndecan-1 이미분화성지방세포의간세포증식을촉진하고지방세포화분화를억제시켜서지방육종을유도한다는연구가있다 17). 하지 만정확한원인규명의부족과중간형악성종양이두경부에서발생한사례가충분히많지않기때문에이에대한연구가많이필요할것으로사료된다. REFERENCES 1. Choi MH, Choi JE, Kim SN: A Case of Atypical Lipomatous Tumor. Korean Journal of Dermatology 2007;45: Priyal G, Shakil M, Jose M, Hussain A: Liposarcoma of the maxillary antrum: A case report. J Cancer Res Ther 2015;11: Moritani N, Yamada T, Iida S: Atypical Lipomatous Tumor of the Tongue: Report of a Case. Acta Med Okayama 2010;8;64: Yamamoto H, Yamaguchi H, Tsuneyoshi M: Inflammatory Myofibroblastic Tumor Versus IgG4-related Sclerosing Disease and Inflammatory Pseudotumor A Comparative Clinicopathologic Study. Am J Surg Pathol 2009;9;33: Kim YB, Leem DH, Baek JA, Ko SO: Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma of the Gingiva: A Case Report and Review of Literature. J Oral Maxillofac Surg 2014;2;72: Choi JY, Kim JE, Baik SY: A Case of Pleomorphic Liposarcoma Originating from Mesentery. Korean J Gastroenterol 2015;64: Titiz A, Yilmaz YF, Ceyhan S, Unal T: Atypical Lipomatous Tumor in Submental Region. J Craniofac Surg 2008; 19: Laco J, Mentzel T, Ryska A: Atypical lipomatous tumor of the tongue: report of 6 cases. Virchows Arch 2009;10; 455: Hattori H: Atypical lipomatous tumor of the lip with pleomorphic lipoma-like myxoid area, clinically simulating mucocele. J Oral Pathol Med 2002;31: Pelaz AC, Batalla FN, Nieto CS: Giant neck liposarc oma with pathological clavicular fracture. Auris Nasus Larynx 103

8 2010;37: DeWitt J, Heidelman J, Summerlin DJ, Tomich C: Atypical Lipomatous Tumor of the Oral Cavity A cases J Oral Maxillofac Surg 2008;66: Nagano S, Yokouchi M, Komiya Sl: Differentiation of lipoma and atypical lipomatous tumor by a scoring system: implication of increased vascularity on pathogenesis of liposarcoma. Nagano et al. BMC Musculoskeletal Disorders 2015;16: Piperi E, Tosios KI, Sklavounou A: Well-Differentiated Liposarcoma/Atypical Lipo -matous Tumor of the Oral Cavity: Report of Three Cases and Review of the Literature. Head and Neck Pathol 2012;6: Acar GO, Cansiz H, Dervisoglu S: Atypical lipomatous tumor of the head and neck region with dyspnea and dysphagia a case report. Eur Arch Otorhinolaryngol 2007;264: Shi HY, Wei LX, Wang HT, Sun L: Clinicopathological feature of atypical lipomatous tumors of the laryngopharynx. J Zhejiang Univ-Sci B 2010;11: Suzuki K, Matsui Y, Kimura T: Myxoid Liposarcoma- Associated EWSR1-DDIT3 Selec-tively Represses Osteoblastic and Chondrocytic Transcription in Multipotent Mesenchymal Cells. PLoS One 2012;7:e Zaragosi LE, Dadone B, Bianchini L: Syndecan-1 regulates adipogenesis new insights in dedifferentiated liposarcoma tumorigenesis. Carcinogenesis 2015;36: Nelson W, Chuprevich T, Galbraith DA: Enlarging tongue mass. J Oral Maxillofac Surg 1998;56: Capodiferro S, Scully C, Favia G: Liposarcoma circumscriptum (lipoma-like) of the tongue: report of a case. Oral Dis 2004;11;10: Angeles RM, Vasquez J, Kim O: Pathologic quiz case: an 86-year-old man with a painless right tongue mass. Atypical lipomatous tumor of the tongue. Arch Pathol Lab Med 2005;2;129: Zaytoun G, Sabra O, Zaatari G: Atypical lipomatous tumors of the face: a controversial issue. Eur Arch Otorhinolaryngol 2006;12;263: McQueen C, Montogomery E, Illei PB: Giant hypopharyngeal atypical lipomatous tumor. Adv Ant Pathol 2010;17: Moritani N, Yamada T, Iida S: Atypical lipomatous tumor of the tongue: report of a case. Acta Med Ikayama 2010;64: Nouri H, Hassani R, Aderdour L, Raki A: The well-differentiated liposarcoma of the hypopharynx. Eur Ann Otorrhinolaryngol Head Neck Dis 2011;6;128: Bulus H, Gunbey E, Morkavuk B: Giant atypical lipomatous tumor/well-differentiated liposarcoma of the neck. J Craniofac Surg 2011;5;22: Boni A, Lisovsky M, Srivastava A: Atypical lipomatous tumor mimicking giant fibrovascular polyp of the esophagus. Hum Pathol 2013;6;44: Ayman FA, Mohammed TM: A case repor of atypical lipomatous tumor of the tongue and literature review. Sudan Med J 2012;12;48: Cheng J, Yu H, Wang X, Shen G: Primay oral and maxillofacial liposarcoma a clinicopathological and immunohistochemical study of 11 cases. Arch Med Sci 2012;8: Kaczmarczyk D, Jesionek-Kupnicka D, Morawiec- Sztandera A: Atypical lipomatous tumor of the cheek case report. Otolaryngol Pol 2013;67:

388 The Korean Journal of Hepatology : Vol. 6. No COMMENT 1. (dysplastic nodule) (adenomatous hyperplasia, AH), (macroregenerative nodule, MR

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