DOI: 10.4046/trd.2010.69.2.129 ISSN: 1738-3536(Print)/2005-6184(Online) Tuberc Respir Dis 2010;69:129-133 CopyrightC2010. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved. 다발성골수종의관해후발생한다발성폐형질세포종 1 예 Case Report 가톨릭대학교의과대학내과학교실 성필수, 송준호, 박종원 A Case of Multiple Pulmonary Plasmacytomas after Complete Remission of Multiple Myeloma Pil Soo Sung, M.D., Joon Ho Song, M.D., Chong Won Park, M.D., Ph.D. Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea Extramedullary plasmacytoma (EMP) is a rare disorder that typically occurs in the upper airway. Although the condition rarely arises in the lungs, a few cases have been reported. Here, we report a case of pulmonary plasmacytoma in 66-year-old man, who had been treated with VAD (vincrestine, adriamycin, dexamethasone) chemotherapy for multiple myeloma. The patient had been declared clear of multiple myeloma after 4 cycles of chemotherapy. Three months later, the patient had multiple masses visible on computed tomography (CT) and on positron emission tomography-computed tomography (PET-CT) with hot uptake. Subsequent studies using CT-guided needle biopsy and immunohistochemical stain showed pulmonary plasmacytoma. Bone marrow biopsy, serum, and urine M protein tests were repeated, showing no evidence of multiple myeloma. Pulmonary plasmacytomas, as extramedullary plasmacytomas, were considered an isolated manifestation of multiple myeloma recurrence. We treated the patient with concurrent chemoradiotherapy and the pulmonary plasmacytomas regressed dramatically. Key Words: Multiple Myeloma; Plasmacytoma; Lung 서 수질외형질세포종은드문질환으로이중 80% 이상이두경부및상기도에서발생되며, 3 13% 정도가위장관에서발생하고폐실질및하기도에서발생하는경우는매우드문것으로알려져있다 1-3. 폐실질에서발생하는형질세포종은대부분단일폐결절로발견되는데, 드물게다발성결절이나경화성병변, 미만성침윤등으로나타나기도한다 4. 현재까지보고된바에의하면전세계적으로 25여증례 Address for correspondence: Jong Won Park, M.D., Ph.D. Department of Internal Medicine, Seoul St. Mary Hospital, The Catholic University of Korea College of Medicine, 505, Banpo-dong, Seocho-gu, Seoul 137-701, Korea Phone: 82-2-2258-2900, Fax: 82-2-599-3589 E-mail: cwp@catholic.ac.kr Received: Dec. 20, 2009 Accepted: Mar. 18, 2010 론 만이조직검사를통해폐형질세포종으로진단되었다 5,6. 그중에서항암치료로원발골수종이완전관해소견을보인후, 추적관찰도중원발골수종의재발로의심되는다발성폐형질세포종이골수조직검사및 M 단백검사에서재발소견없이단독으로나타난경우는현재까지문헌에보고된바가없다. 이에저자들은문헌고찰과함께증례로보고하는바이다. 증례환자 : 강, 66세, 남자주소 : 3일동안지속된좌측흉막성흉통현병력 : 66세남환, IIIa기다발성골수종 (IgG, kappa type) 진단후총 4차례 vincristine, adriamycin, dexamethasone (VAD) 항암화학요법시행후골수조직검사및혈청과소변의 M 단백검사에서완전관해판정받은자로, 관해판정 3개월후추적관찰도중좌측흉막성 129
PS Sung et al: Multiple pulmonary plasmacytomas after complete remission of multiple myeloma 흉통및마른기침있어입원하였다. 과거력 : 5년전진단받은고혈압병력외에는당뇨, 결핵, 간염없었으며수술받은적없었다. 사회력및가족력 : 흡연의과거력없었고, 1주일에 1차례소주 1병가량음주하였고, 가족력상특이사항없었다. 이학적소견 : 혈압 130/80 mm Hg, 맥박 78회 / 분, 체온 36.5 o C, 호흡수 20회 / 분이었다. 급성병색을보였고결막창백이나공막황달소견은없었으며경부와액와부에만져지는종물이나림프절비대는없었다. 흉부청진상심음은규칙적이고심잡음은들리지않았으며호흡음은우하엽으로마른수포음을동반한거친호흡음이청진되고있었다. 복부촉진상간, 비장종대는관찰되지않았고사지부종은관찰되지않았다. 검사소견 : 내원당시말초혈액검사상혈색소 10.4 mg/dl, 헤마토크리트는 31.1%, 백혈구 4,910/μL, 혈소판 402,000/μL 이었다. BUN과 Cr는각각 16.6 mg/dl와 0.93 mg/dl 소견을보였으며전해질은 Na 141 mmol/l, K 4.0 mmol/l, Ca 8.2 mg/dl 로정상범위내에있었다. 간기능검사상 AST, ALT는정상소견을보였고단백질은 6.4 g/dl, 알부민은 3.97 g/dl의소견을보였다. ESR, CRP는각각 66 mm/hr, 32.2 mg/dl 로증가된소견을보였으며혈액응고검사는모두정상범위안에있었다. 방사선학적소견 : 내원당시단순흉부촬영에서 (Figure 1A) 좌측폐의다발성결절음영이관찰되고있었으며, 전산화단층촬영에서는 (Figure 2A) 좌측폐야에장경 4 cm, 2.5 cm, 2 cm의결절음영이관찰되었고크기가작은다발성결절이양폐야에관찰되어진균성폐렴, 패혈성색전혹은다발성폐형질세포종이의심되었다. 상기병 Figure 1. (A) Chest radiograph on admission showed multifocal mass-like consolidations in left lung field. (B) Follow-up of chest radiograph obtained after chemoradiotherapy showed marked shrinkage of multiple masses in left lung filed. Figure 2. (A) Initial chest CT scan displayed three nodules up to 4 cm were in left lung, and multiple disseminated small nodules were in both lung fields. (B) Chest CT scan after chemoradiotherapy showed much regression of previous lung masses. 130
Tuberculosis and Respiratory Diseases Vol. 69. No. 2, Aug. 2010 변에대한양전자방출전산화단층촬영소견으로는 (Figure 3) 염증성병변보다종양성병변이의심되는소견이었다 (SUV, 6.4 7.2). 진단을위해가장크기가큰결절에대해전산화단층촬영을이용한피부경유침생검을시행하였다. 병리조직학적소견 : 종괴는거의대부분비정상적인성숙형질세포로구성되어있었다 (Figure 4A). 면역조직화학염색에서 kappa 단쇄에 (Figure 4B) 양성이었고, CD56a 에는음성소견을보여형질세포종에합당한소견이었으며원발골수종과같은면역조직화학염색소견을보였다. 치료및경과 : 우선전신적인골수종의재발을감별하 기위해골수조직검사를다시실시하였으나여전히관해소견이었으며, 다시실시한혈청과소변의 M 단백검사또한모두음성소견을보여상기폐결절이수질외형질세포종의정의에합당한소견이었다. 조직검사는가장큰결절에대해서만실시하였으나 PET-CT 소견을감안하여좌폐야의세결절이모두형질세포종이라고판단하였다. 원발골수종과무관하게발생한폐형질세포종의가능성도완전히배제할수는없었으나, 원발골수종의관해후 3개월만에발생했다는점과, 원발골수종과같은유형의 IgG, kappa 단쇄에양성이라는점은원발골수종이다른부위에재발없이폐형질세포종이라는독특한형태로재발한사실을시사하였다. 폐형질세포종에대한치료로세결절에대한방사선치료를시작하였으며, 영상검사상작은결절성음영들은폐형질세포종의파종으로생각되어 2차항암치료로 bortezomib 과 dexamethasone 의병용요법을시작하였다. 항암치료 2회및방사선치료종료 1개월후, 추적관찰한단순흉부촬영 (Figure 1B) 및흉부전산화단층촬영 (Figure 2B) 사진에서폐형질세포종들의크기는절반이하로감소하였으며중심부위에괴사성음영이관찰되었다. 이후환자는특별한합병증없이 bortezomib 과 dexamethasone 항암치료지속중이며, 다른부위에서의골수종소견은아직까지관찰되고있지않다. 고 찰 Figure 3. PET CT showed multiple hot uptakes (SUV, 6.4 7.2) in both lung fields. 형질세포종 (plasmacytoma) 은다발성골수종, 단발성 Figure 4. (A) Photomicrograph of the lung biopsy demonstrated many aggregates of plasma cells, suggestive of plasmacytoma (H&E stain, 400). (B) Immunohistochemical staining of kappa light chain (H&E stain, 200). 131
PS Sung et al: Multiple pulmonary plasmacytomas after complete remission of multiple myeloma 골형질세포종 (solitary bone plasmacytoma), 수질외형질세포종 (extramedullary plasmacytoma), 형질세포성백혈병 (plasma cell leukemia) 네가지로분류된다. 이중수질외형질세포종은다음다섯가지조건을만족하는경우에진단된다 7. 1) 조직검사에서형질세포의집합이증명될것, 2) 골수에서의형질세포가차지하는비율이 5% 이상을넘지않을것, 3) 골용해성병변이존재하지않을것, 4) 고칼슘혈증및신부전이존재하지않을것, 5) 혈청 M 단백의수치가낮거나 M 단백이존재하지않을것이다. 수질외형질세포종은대략 80% 가상기도에서발생하며폐실질에발생하는경우는매우드물다 3. 현재까지보고된바에의하면전세계적으로 25여증례만이조직검사를통해폐형질세포종으로진단되었다 5,6. 폐형질세포종의분포양상은다발성병변보다단일폐병변이더욱흔하게관찰되었으며, 좌측폐와우측폐가동일하게침범되었다. Adam 등 8 은골수종및형질세포종의진단및치료방향설정에있어서 PET-CT 의유용성을보고하였다. 그들은 PET-CT 가단순촬영에서골용해성병변이존재하지않았던다발성골수종및형질세포종의초기병기설정및추적관찰에유용하다고보고하였다 8. 본증례에서도 CT 촬영후시행한 PET-CT 촬영소견에서폐형질세포종의발생이강력히의심되었다. 폐에결절성병변이있고, 병변에대한조직검사를시행하여형질세포의집합이관찰되는경우폐형질세포종을진단하기위해서는우선전신적인골수종의증거가없어야하며, 또한반응성형질세포종, 형질세포육아종및림프종등이감별되어야한다 9. 폐형질세포종은종종침윤성병변을형성하며또한파종성병변을수반하는경우가있으며이들은폐를침범하는기타형질세포질환과의영상검사상감별점이된다. Luh 등 9 이보고한증례에서는 2 cm 이상의형질세포종이우측폐에존재하였으며, 다발성파종성병변이동반되었고본증례에서도이와유사하게형질세포종과파종성폐병변이동반되었다. 수질외형질세포종과기타형질세포질환과의가장정확한감별점은수질외형질세포종이 CD38 및단클론성단쇄를이용한면역조직화학염색에양성을보인다는점이다. 본증례에서도피부경유침생검을이용한면역조직화학염색에서 kappa 단쇄에양성소견을보였다. 본증례에서발생한다발성폐형질세포종은원발골수종관해후 3개월만에발생했다는점과면역조직화학검사에서원발골수종과같은유형의 IgG, kappa 단쇄에 양성소견을보인점등을고려할때, 원발골수종이폐형질세포종이라는독특한형태로재발한것으로추정된다. 원발골수종의재발이라할지라도본증례에서는다발성폐형질세포종이발견될당시골수조직검사및혈청, 소변 M 단백검사에서전신적인골수종재발의증거가없었으므로수질외형질세포종의정의에는합당하다. 이와같이다발성골수종의완치후수질외형질세포종이발생한경우를국내외문헌에서보고하였다. Kim 등 10 은다발성골수종완치후신형질세포종이발생한경우를보고하였으며, Vande Broek 등 11 은다발성골수종완치후해면정맥동에형질세포종이발생한경우를보고하였다. 수질외형질세포종은방사선치료에반응이좋은것으로알려져있으며, 수술을하는경우에도방사선치료를병행하는경우가많다. 방사선은 4 5주에걸쳐서총 40 50 Gy를조사하며, 치료후 5% 미만의국소재발률을나타낸다 12-14. 만약진단과정에서수술적완전절제가이루어진경우추가적인방사선치료의적응이되지않는다. 수술이나방사선치료후보조항암치료의효과는증명되지않았다. 결과적으로수질외형질세포종은비교적양호한예후를보이며, 10년생존율이 70% 이상에이른다. 수질외형질세포종의예후는향후다발성골수종의발생여부와직접적으로관련되므로지속적인추적관찰이필요하다 15. 폐형질세포종의경우, 현재까지보고된증례중단일결절의대부분은수술혹은방사선요법만으로치료했거나수술과방사선요법의병용요법을사용하였으며, 한증례에서만항암화학요법만으로치료하였다. 다발성결절에대해서는항암화학요법으로부분반응이상의성적을보고한경우가보고되고있는데, melphalan, prednisolone (MP) 항암화학요법이일차치료로사용되었다 7,16,17. 현재까지의문헌보고중, 본증례와같이항암치료로원발골수종이완전관해소견을보인후, 추적관찰도중다발성폐형질세포종이나타난경우는보고된바가없다. 본증례의경우, 조직검사는가장크기가큰결절에서만시행하였으나, 임상적으로형질세포종이다발성으로발생한것으로생각, 모든다발성종괴에대해방사선치료를시행하였으며, 영상검사상작은결절성음영들이좌측폐야에서관찰되어형질세포종의파종성병변으로판단하여 bortezomib 과 dexamethasone의병합항암화학요법을병행하였고부분반응이상의성적을얻을수있었다. 이상으로저자들은항암치료로원발골수종이완전관해소견을보인후, 추적관찰도중다발성폐형질세포종 132
Tuberculosis and Respiratory Diseases Vol. 69. No. 2, Aug. 2010 이나타난증례를문헌과더불어보고하는바이다. 폐형질세포종은적절한치료시예후가양호한것으로밝혀져있으므로다발성골수종환자가완전관해되었다하더라도원인불명의폐결절이나타나면반드시조직검사및면역조직화학염색을시행하여폐형질세포종을감별해야한다. 참고문헌 1. Corwin J, Lindberg RD. Solitary plasmacytoma of bone vs. extramedullary plasmacytoma and their relationship to multiple myeloma. Cancer 1979;43:1007-13. 2. Woodruff RK, Whittle JM, Malpas JS. Solitary plasmacytoma. I: Extramedullary soft tissue plasmacytoma. Cancer 1979;43:2340-3. 3. Knowling MA, Harwood AR, Bergsagel DE. Comparison of extramedullary plasmacytomas with solitary and multiple plasma cell tumors of bone. J Clin Oncol 1983; 1:255-62. 4. Thoennissen NH, Schliemann C, Hungermann D, Bremer J, Juergens KU, Semik M, et al. Solitary plasmacytoma of the lung with coexisting sarcoid-like lesions. Ann Hematol 2008;87:417-20. 5. Koss MN, Hochholzer L, Moran CA, Frizzera G. Pulmonary plasmacytomas: a clinicopathologic and immunohistochemical study of five cases. Ann Diagn Pathol 1998;2:1-11. 6. Goździuk K, Kedra M, Rybojad P, Sagan D. A rare case of solitary plasmacytoma mimicking a primary lung tumor. Ann Thorac Surg 2009;87:e25-6. 7. Hayes-Lattin B, Blanke CD, Deloughery TG. Pulmonary and intracerebral plasmacytomas in a patient without multiple myeloma: a case report. Am J Hematol 2003; 73:131-4. 8. Adam Z, Bolcák K, Stanícek J, Pour L, Hájek R, Krejcí M, et al. The value of fluorodeoxyglucose positron emission tomography in multiple myeloma. Vnitr Lek 2006;52:207-14. 9. Luh SP, Lai YS, Tsai CH, Tsao TC. Extramedullary plasmacytoma (EMP): report of a case manifested as a mediastinal mass and multiple pulmonary nodules and review of literature. World J Surg Oncol 2007;5:123. 10. Kim SH, Kim ES, Hur JW, Lee JH, Chang SH, Kim YS, et al. A case of relapsed renal plasmacytoma after complete remission of multiple myeloma. Korean J Med 2003;64:114-8. 11. Vande Broek I, Stadnik T, Meurs A, Maes J, Van Camp B, Schots R. Extramedullary plasmacytoma of the cavernous sinus. Leuk Lymphoma 2002;43:1691-3. 12. Liebross RH, Ha CS, Cox JD, Weber D, Delasalle K, Alexanian R. Clinical course of solitary extramedullary plasmacytoma. Radiother Oncol 1999;52:245-9. 13. Mayr NA, Wen BC, Hussey DH, Burns CP, Staples JJ, Doornbos JF, et al. The role of radiation therapy in the treatment of solitary plasmacytomas. Radiother Oncol 1990;17:293-303. 14. Creach KM, Foote RL, Neben-Wittich MA, Kyle RA. Radiotherapy for extramedullary plasmacytoma of the head and neck. Int J Radiat Oncol Biol Phys 2009;73: 789-94. 15. Dimopoulos MA, Kiamouris C, Moulopoulos LA. Solitary plasmacytoma of bone and extramedullary plasmacytoma. Hematol Oncol Clin North Am 1999;13:1249-57. 16. Wise JN, Schaefer RF, Read RC. Primary pulmonary plasmacytoma: a case report. Chest 2001;120:1405-7. 17. Wang J, Pandha HS, Treleaven J, Powles R. Metastatic extramedullary plasmacytoma of the lung. Leuk Lymphoma 1999;35:423-5. 133