대한내과학회지 : 제 80 권제 6 호 2011 림프구성전이암으로오인된 Erdheim Chester Disease 1 예 이화여자대학교의학전문대학원 1 내과학교실, 2 병리학교실 심윤수 1 박진경 1 이진화 1 송동은 2 장중현 1 Case of Erdheim-Chester Disease Mimicking Systemic Lymphangitic Metastasis Yun Su Sim 1, Jin Kyeong Park 1, Jin Hwa Lee 1, Dong Eun Song 2, and Jung Hyun Chang 1 Departments of 1 Internal Medicine and 2 Pathology, Ewha Womans University School of Medicine, Ewha Medical Research Institute, Seoul, Korea Erdheim-Chester disease (ECD) is non-langerhans cell histiocytosis that leads to multi-organ involvement with unknown etiology. We report a 64-year-old woman with a dry cough and dyspnea. She had interlobular septal thickening and ground-glass opacity in both lungs, suggesting lymphangitic lung metastasis. However, she was diagnosed with ECD after a long bone and immunohistological evaluation. (Korean J Med 2011;80:712-717) Keywords: Erdheim-Chester disease; Lung; Retroperitoneal fibrosis 서론 Erdheim-Chester disease (ECD) 는황색육아종이다발성장기에침범되는매우드문질환이다. 과거에는랑게르한스조직구증으로오인되기도하였으나장골에특징적인경화병변과조직학적으로세포질내에랑게르한스과립이존재하지않으면서 S100 항체가결여된포말조직구염색으로감별된다 [1,2]. 병태생리기전은단세포군증식을보여종양성질환으로제시되었던증례 [3] 가있었으나현재로서는원발성포식세포장애라는것외에는정확하게밝혀진것은없다 [1]. ECD는뼈, 간, 비장, 후복막강등에조직구가침착해다양한증상을나타나게되며폐를침범하는경우는비교적드문것으로알려져있다 [1]. 이에저자들은림프관성폐전이및복강전이로오인되어원발암진단을위한검사중에후복강과폐를동시에침범한 ECD로밝혀진 1예를경험하였기에문헌고찰과함께보고하는바이다. 증례고혈압과당뇨가있으며비흡연자인 64세의여자가 1년 Received: 2010. 4. 24 Revised: 2010. 5. 28 ccepted: 2010. 6. 4 Correspondence to Jung Hyun Chang, M.D. Respiratory Center, Department of Internal Medicine, Ewha Womans University School of Medicine, 911-10 Mok-dong, Yangcheon-gu, Seoul 158-710, Korea Tel: +82-2-2650-5686, Fax: +82-2-2655-2076, E-mail: hs1017@ewha.ac.kr - 712 -
- Yun Su Sim, et al. Erdheim-Chester disease mimicking - 간의근육통과전신쇠약감, 8 kg의체중감소와최근에심화된기침과호흡곤란을주소로내원하였다. 신체활력징후는정상이었으며양측폐에서건성수포음이청진되었다. 동맥혈산소포화도는 68.5 mm Hg, 적혈구침강속도는 36 mm/h였고, 혈액에서 ImmunoglobulinG (IgG) 는 1,030 mg/dl ( 정상범위, 700-1,600 mg/dl), IgG4는 51.4 mg/dl ( 정상범위, 0-185 mg/dl) 였다. ntinuclear antibody (N), double- stranded DN, C4 등은정상범위였으나 C3는 80.4 mg/dl ( 정상범위, 90-180 mg/dl) 로약간감소하였으며 perinuclear NC (p-nc) 는양성이었다. 단순흉부촬영은양측에림프관성전이나림프종의폐침범이의심되는미만성망상형음영을보였다 (Fig. 1). 흉부전산화단층촬영에서는양측폐에광범위한소엽사이막비후와간유리성음영이 (Fig. 2) 보이고, 대동맥궁에서시작되어 Figure 1. () chest radiograph shows reticular opacities in both lungs before treatment. () The reticular opacities disappeared after prednisolone therapy. Figure 2. () Chest computed tomography shows extensive interlobular septal thickening and ground-glass opacities in both lungs. () soft tissue mass is seen encircling the aortic arch, descending thoracic aorta, and cardiophrenic angle (arrow). - 713 -
- 대한내과학회지 : 제 80 권제 6 호통권제 610 호 2011 - Figure 3. Whole body computed tomography reveals a soft tissue mass encircling the aorta and involving both renal hila. () Coronal view. () Sagittal view. Figure 4. bone scan shows intense radioactivity in the right acetabulum and distal metadiaphyses of the right femur and both tibiae. 하행대동맥을감싸고심늑막간에위치한연조직성종괴 (Fig. 2) 및종격동에림프절들이관찰되어악성종양의전신적전이가의심되었다. 전신전산화단층촬영에서는대동맥과양측신장을감싸는연조직이관찰되었고 (Fig. 3) 양전자방출단층촬영에서는우측심늑막연과양측폐, 늑막에섭취가보였다. 뼈스캔에서는우측관골구 (acetabulum), 양측대퇴골의원위부골간단 (metadiaphysis) 과경골 (tibia) 에강한방사능이관찰되었다 (Fig. 4). 흉강경수술을통해우측폐와심늑막연에위치한연조직 으로부터조직을얻어병리학적검사를시행하였다. 병리소견에는섬유화를동반한방추세포 (spindle cell) 의증식과염증세포, 포식조직구와 (Fig. 5) IgG4염색에양성을보인배중심 (germinal center) (Fig. 5) 이관찰되었고, 조직구는 CD68에양성 (Fig. 5C) CD1a (Fig. 5D) 와 S100에음성을보여 ECD를시사하였다. 환자는경구스테로이드요법을시작하였고단순흉부방사선사진과증상이호전되었다 (Fig. 1). - 714 -
- 심윤수외 4 인. 전이암으로오인된 Erdheim Chester disease - C D Figure 5. In the thickened interstitium of the lung, () aggregated foamy histiocytes (H&E stain, 200) and () occasional lymphoid follicles (H&E stain, 200) are observed. The histiocytes show (C) positive immunoreactivity for CD68 ( 200) (D) but negative immunoreactivity for CD1a ( 200). 고찰 ECD는주로 40-60대의남자에게호발하며국내에서발생한 ECD 환자 10명 [4-12] 중에 7명이남자환자였고, 평균 47 세였으며 26세와 37세에 ECD가진단된두환자외에는모두 40세이상이었다 (Table 1). ECD는뼈, 후복강, 안와, 신경계, 피부, 림프절과종격동등다양한장기에조직구가침범하여증상이나타나게되며 [1,13]. 본증례와같이장골골간단 (metaphysic) 에경화성병변을보이면서하지의관절통을호소하는경우가특징적이다 [1,13]. 랑게르한스조직구증과구별되는 ECD의특징은장골의병변과함께면역조직염색에서 CD68 염색양성, CD1a, S-100항체음성소견과 irbeck 과립이보이지않는것이며 본증례의폐조직과대동맥을감싸는연조직에서시행한면역염색에서이에합당한소견을보여 ECD를확진할수있었다. 후복막섬유화 (retroperitoneal fibrosis, RF) 는 ECD의약 25% 에서동반되며후신후성신부전이나신장피막염등으로신기능의감소를가져오기도한다 [14]. 약 30-40% 에서종양, 약물, 출혈, 외상, 감염, 동맥경화, 면역관련질병등의알려진원인에의해발생하는경우가있으며 [14] 최근에는 RF는다양한병태생리기전을가진것으로이해되고있어 NC 양성과함께혈관염을보이거나, 혈중 IgG4증가, 조직에 IgG4 염색, 스테로이드에좋은반응을특징으로하는 IgG4 관련경화성질환에한범주로설명되기도한다 [15,16]. 본증례에서도 p-nc 양성, 조직염색에서배중심 (germinal - 715 -
- The Korean Journal of Medicine: Vol. 80, No. 6, 2011 - Table 1. Summary of the cases of Erdheim-Chester disease seen in Korea Case No. ge Gender Chief complaint Long bones Retro-peritoneum Orbit Lungs Other 1 [12] 26 M Elevated liver function + - - + Liver, kidney 2 [11] 37 F xilla mass + - - - xilla, brain 3 [10] 59 M Chest pain + + - - - 4 [9] 45 M General weakness + + + + - 5 [8] 53 F Headache + - - - rain 6 [7] 46 M Visual dimness + + + - - 7 [7] 70 F Visual dimness + - + - - 8 [6] 48 M Edema + + - - - 9 [5] 42 M Fever + + + - rain 10 [4] 46 M Night fever + + - - - center) 를보이면서 IgG4 염색에양성소견을보여 RF와 ECD 의우연한병발가능성에대한감별이필요하였으나흉강경을통한조직검사에서후복막종괴와연결된대동맥과심막사이의연조직에서특징적인 ECD의소견을보였다. 현재까지 ECD가원발성포식세포장애라는것외에정확한병태생리가밝혀져있지않고경화의진행이예후와관계가있어 [5] 추후 ECD와동반된후복막섬유화에서의면역학적염색과혈관염에대한혈액학적검사에대한면밀한검토가 ECD의병태생리와효과적인치료에도움이될수있을것이다. ECD가폐를침범하는경우는비교적드물어 59예의 ECD 를분석한보고 [1] 에서단 8명만이폐를침범하였고, 국내에보고된 10개의 ECD 증례 [4-12] 에서는폐를침범한경우는단 2예였다 (Table 1). 조직구가폐간질에침착하게되면서림프선, 기관지혈관, 늑막하에동시에침범하는경우가많다. 본증례에서양측폐에광범위한소엽사이막비후와간유리성음영이존재하면서종격동의림프절들이커져있어림프구성폐전이로오인되었다. ECD는매우드문질병이지만원발암을찾을수없는림프구성폐전이나후복막에전이환자에서는 ECD를고려하여면역조직염색이나장골의병변의확인이필요할수있다. 진단후에평균생존기간이 32개월이며폐섬유화로인한호흡부전, 심부전, 신부전등이동반될경우에는 6개월이내에 36%, 3년이내 50% 가사망하게되어폐를침범하게되면예후가불량하다. 치료는염증과전신증상완화를위한스테로이드나 cyclosphosphamide, vinblastine, adryamycin, azathioprine 등의항암제를병합하여사용하지만아직까지 확립된치료법은없다. 본증례의환자는스테로이드에초기반응이좋아현재감량하면서추적관찰중이다. 요 저자들은호흡곤란으로내원한환자에서폐실질과종격동림프절, 후복막종괴등을동반한병변을발견하여전신의림프구성전이로오인하여원발암을찾는과정에서 Erdheimchester disease를진단하였다. 이에문헌고찰과함께보고하는바이다. 약 중심단어 : Erdheim-Chester disease; 폐 ; 후복막섬유화 REFERENCES 1. Veyssier-elot C, Cacoub P, Caparros-Lefebvre D, et al. Erdheim- Chester disease: clinical and radiologic characteristics of 59 cases. Medicine (altimore) 1996;75:157-169. 2. assou D, El Kharras, Taoufik T, et al. Cardiac Erdheim- Chester. Intern Med 2009;48:83-84. 3. Chetritt J, Paradis V, Dargere D, et al. Chester-Erdheim disease: a neoplastic disorder. Hum Pathol 1999;30:1093-1096. 4. Hong JR, Lee HG, Ko YH, hn JM, Choi YH, Kim T. case of Erdheim-Chester disease with periodic fever and knee pain. Korean J Med 1999;56:542-546. 5. Park YK, Ryu KN, Huh, Kim JD. Erdheim-Chester disease: a case report. J Korean Med Sci 1999;14:323-326. 6. Lee W, Park NC. case of Erdheim-Chester disease with bilateral hydronephrosis. Korean J Urol 2001;42:453-456. 7. Kim YJ, Kim YD. Erdheim-Chester disease: two cases of orbital - 716 -
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