A-III. 위장관림프종 Room A 국립암센터위암센터 Diagnosis and Staging of Gastrointestinal Lymphoma Soo-Jeong Cho Center for Gastric Cancer, National Cancer Center, Goyang, Korea 서론 프종 (diffuse large B-cell lymphoma) 이 35.1% 였다. 3,4 림프종은전통적으로크게호지킨림프종 (Hodgkin s lymphoma) 과비호지킨림프종 (non- Hodgkin s lymphoma) 으로나눈다. 호지킨림프종이비교적동질성을지닌질환군임에반해비호지킨림프종은다양한질환의집합체이다. 발생위치에따라서림프절림프종 (nodal lymphoma) 과림프절외림프종 (extranodal lymphoma) 으로나누는데, 림프절외림프종은위장관에서가장흔하다. 원발성위장관림프종은촉지되는림프절이없고, 간이나비장비대가없으며, 단순흉부촬영에서림프절비대가없고, 말초혈액백혈구가정상이면서위장관및국소림프절에국한될경우로정의한다. 1 원발성위장관림프종은발병위치와조직학적종류가다양하여그경과와예후도다양하다. 원발성위장관림프종 371예를분석한보고에서 74.8% 가위에서발생하였으며, 이어서소장 (8.6%), 회맹부 (7.0%), 위장관의다발성침범 (6.5%), 직장 결장 (2.4%) 순서였다. 림프종은최근우리나라에서지속적으로발생이증가하고있는악성종양으로주로림프절외림프종의증가에기인하고있다. 이전의연구에의하면, 우리나라에서림프절외림프종은전체비호지킨림프종의 63.3% 이며, 이중원발성위장관림프종이차지하는비중이 20.7% 로가장높았다. 2 2011년도에발표된국내림프종발생현황을살펴보면전체림프종중비호지킨림프종이 95.4% 였고림프절외림프종이 69.6% 였다. 림프절외림프종중위림프종이가장많았는데, 세포형으로는 MALT 림프종 (extranodal marginal zone B-cell lymphoma of MALT type) 이 56.1%, 미만성거대 B-세포림 본론 1. 분류 여러질환의집합체인림프종을정확히파악하고분류하려는노력은크게병리학적인분류와원발부위에따른구분의두가지방향으로이루어져왔다. 병리학적접근법은역사적으로 Rappaport의분류방식 5 이널리이용되어오다가, 미국국립암연구소의분류체계 (National Cancer Institute Working Formulation) 6 로대체되었다. 이체계는병리학적인악성도를임상적인소견과연계시켜, 크게 3등급으로분류하면서임상의사들이치료방침을결정하는데도움을주지만림프종이발생한세포의근원을제대로반영하지못하는단점이있었다. 이를보완하여 1994년 Revised European American Lymphoma (REAL) 분류법 7 이제안되었고, 2001 년세계보건기구 (World Health Organization, WHO) 에서 REAL 분류법을발전시켜형태학적소견, 세포의기원, 임상소견과유전자형까지고려한새로운분류를제안하기에이르렀고, 8 가장널리사용되는분류체계가되었다. 현재 2008 년도에발표된 4차개정판이사용되고있다 (Table 1). 9 2. 진단 위장관림프종은 40-60대에호발하며남녀모두에서비슷하게분포한다. 초기에는별다른증상을갖지않아위림프종의경우건강검진을목적으로시행한내시경에서발견되는경우가많다. 최근의국내보고 10 에따르면, 검진자 105,194 제 55 회대한소화기내시경학회세미나 47
Table 1. WHO Classification of Lymphoid Neoplasms, 4th Edition 9 B cell neoplasms Precursor B-cell neoplasm B-lymphoblastic leukemia/lymphoma Mature (peripheral) B-cell neoplasms Chronic lymphocytic leukemia/small lymphocytic lymphoma B-cell prolymphocytic leukemia Lymphoplasmacytic lymphoma Splenic marginal zone B-cell lymphoma Hairy cell leukemia Splenic lymphoma/leukemia, unclassifiable Plasma cell myeloma/plasmacytoma Heavy chain diseases Extranodal marginal zone B-cell lymphoma of MALT type a) Nodal marginal zone B-cell lymphoma Follicular lymphoma a) Primary cutaneous follicle center lymphoma Mantle cell lymphoma a) Diffuse large B-cell lymphoma (DLBCL) a) Burkitt lymphoma a) B-cell lymphoma, unclassifiable T-cell and NK-cell neoplasms Precursor T-cell neoplasm T- lymphoblastic leukemia/lymphoma Mature (peripheral) T/NK-cell neoplasms T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Aggressive NK-cell leukemia Systemic EBV positive T-cell lymphoproliferative disease of childhood Hydra vacciniforme-like lymphoma Adult T-cell lymphoma/leukemia (HTLV 1+) Extranodal NK/T-cell lymphoma, nasal type a) Enteropathy-type T-cell lymphoma a) Hepatosplenic T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Mycosis fungoides/sezary syndrome Primary cutaneous anaplastic large cell lymphoma Primary cutaneous aggressive epidermotropic CD8 positive cytotoxic T-cell lymphoma Primary cutaneous gamma-delta T-cell lymphoma Primary cutaneous small/medium CD4 positive T-cell lymphoma Peripheral T-cell lymphoma, not otherwise characterized a) Angioimmunoblastic T-cell lymphoma Anaplastic large cell lymphoma, ALK-positive Anaplastic large cell lymphoma, ALK-negative a) Gastrointestinal lymphomas. 명중내시경으로발견된위림프종은 52예 (0.049%) 로, 외래에서진단된위림프종에비해 MALT 림프종의빈도가높고 (98.1% vs. 60.0%), 헬리코박터균제균치료로치료된예가많았으며 (98.1% vs. 48.1%), 5년생존율도유의하게높았다 (100.0% vs. 89.3%). 이외에도초기에는비특이적인소화불 Fig. 1. Gastric MALT lymphoma. Fig. 2. Gastric diffuse large B-cell lymphoma. 량, 속쓰림등의상부위장관증상을호소할수있고, 소장또는대장에발생한림프종의경우초기에는대변잠혈반응검사에서양성을보일수있다. 대개림프종에특징적인 B 증상 ( 발열, 야간발한, 체중감소 ) 을호소하는경우는매우드물고, 병변이진행하는경우복통, 위장관출혈, 체중감소, 복부종괴등으로나타날수있으며, 천공이발생하는경우는상대적으로드문것으로알려져있다. 내시경에서는모든위치에서다양한형태로나타날수있다. 위림프종의경우주로전정부에호발하지만체부및분문에서도발생할수있다. MALT 림프종의경우주로미란, 48 Korean Society of Gastrointestinal Endoscopy
궤양등의점막변형형태로나타나나 (Fig. 1), 미만성거대 B-세포림프종의경우에는종괴를형성하는경향이있다 (Fig. 2). MALT 림프종에서의궤양또는미란은일반적인양성위궤양또는조기위암과달리불규칙하거나지도상모양을갖는경우가많으며, 다양한형태의궤양또는미란이다발성으로발생하는것이특징적이다. 이외에도불규칙한점막의요철이나색조변화만을보이는경우도있어의심되는경우조직검사로확인하는것이필요하다. 침범과진행정도에따라서용종또는상피하종양, 종괴를형성할수있다. 미만성거대 B-세포림프종은진행성위암또는상피하종양과유사한형태를보일수있다. 그러나미만성거대 B-세포림프종의경우진행형위선암과는달리궤양또는종괴의심한정도에비해위신전도가비교적유지되며, 선암과달리주위점막에침습에의한변화가적다는것이차이점이다. 위림프종의침범범위가넓은경우에는위주름의비후를보이기도하여보만 4형위암과의감별이중요하다. 면역염색을포함한조직검사에서림프종이확인되면병기설정을위해적절한문진과신체검진이필수적이다. 검사실검사로는일반혈구검사, 일반화학검사, 간기능및신기능검사, ESR, CRP, 혈청 LDH 등을시행한다. 면역결핍과관련된림프종감별을위해 HIV 검사, 향후 rituximab 등의치료를위해 Hepatitis B serology 검사를시행해야한다. 내시경초음파를이용하여침윤깊이를알아볼수있다. 림프종의침윤깊이에대한내시경초음파의민감도, 특이도, 정확도는각각 89%, 97%, 95% 정도로알려져있으며, T, N 병기결정에있어 CT보다우수하다. 11,12 림프종의주위림프절및주변장기의침범여부는목, 흉부, 복부를포함한전산화단층촬영으로확인할수있고, 이외에골수검사가필요하다. 미만성거대 B-세포림프종, 소포성림프종 (follicular lymphoma), 외투세포림프종 (mantle cell lymphoma) 의경우 fludeoxyglucose (FDG)-PET가도움이된다. 13,14 최근 International Harmonization Project에의해림프종에서치료반응평가방법으로서의 PET 사용권고안이발표되었으며, 14 FDG-PET 및 PET-CT을포함한림프종병기설정과치료반응평가방법의표준화시도도이루어지고있다. 15 한편, 골수검사가모든환자에대해필요한지에관해서는아직까지논란의여지가있다. 미만성거대 B-세포림프종의경우골수침범범위가넓지않을때에 PET-CT가골수검사에비해더민감하다는보고들이있고, 초기림프종의경우골수침범이드물기때문에 PET 양성일경우에만골수검사를하자는주장도있다. 16,17 PET-CT와골수검사를시행한 130명의미만성거대 B-세포림프종을분석하였을때, PET-CT의골수침범진단에대한민감도와특이도는각각 94% 와 100% 로골수검사의 40% 와 100% 에비해높았으며, PET-CT 양성 (focal-uptake) 환자는골수침범이없는 IV기환자의생존율과유사하였으므로골수검사가필요하지않고, PET-CT 양성 (diffuse uptake) 이면서다른나쁜예후인자가없을때에골수검사를하는것이진단적도움이된다고주장하였다. 18 또한, PET-CT 양성환자는이미다른검사에서대개진행된병기를가지기때문에골수검사로병기가달라지지않는다고주장하였다. 18 최근국내보고 19 에따르면위 MALT 림프종으로진단받은 105명중 1명에서만골수검사에서골수침범이있었으며, 점막이나점막하층에국한된위 MALT 림프종 91명에서는골수침범이없었다. 19 그러나임상에서행해지는 standard practice를바꾸기위해서는보다많은데이터와논의가필요하겠다. 3. 병리진단 진단의기본은조직검사를통한병리학적진단이다. 특히위 MALT 림프종의경우내시경소견이위염과감별이어려워조직검사를시행하지않는경우에는진단이어렵다. 림프종이점막하층에국한된경우에는조직생검에서위음성을보일수있기때문에가급적큰겸자를이용하거나경우에따라점막절제술과같은보다적극적인조직생검을시도하는것도필요하다. 20 MALT 림프종은주로작은크기의림프구가모여이루어진종양으로, 중심구유사세포 (centrocyte-like cell) 증식, 형질세포침윤, 주위조직과분비선에침투하여파괴하는특징적인림프상피병변 (lymphoepithelial lesion) 이동반된다. 중심모세포 (centroblast) 나면역모세포 (immunoblast) 처럼보이는거대세포가증식된소견이있으면미만성거대 B-세포림프종으로진단한다. WHO classification 9 에서는 MALT 림프종에서거대세포가보이면미만성거대 B-세포림프종으로진단하도록권고하며, MALT 림프종동반여부를반드시기입하도록하고있다. 이전에많이사용되던고등급 MALT 림프종은혼란의여지가있어서더이상사용하지않고미만성거대 B-세포림프종으로진단한다. MALT 림프종에서가장흔하게발견되는유전변이는 t(11;18)(q21;q21)/ API2 MALT1, t(14;18)(q32;q21)/igh MALT1, t(1;14)(p22;q32)/ IGH BCL10이며, 헬리코박터제균치료에반응하지않는림프종과연관있다고알려져있다. 여기에 p53 불활성화및 p16 결손등과같은추가적유전자손상이발생하는경우미만성거대 B-세포림프종으로발전하는것으로알려져있다. 21,22 Wotherspoon 등 23 이발표한 5등급체계가 MALT 림프종 제 55 회대한소화기내시경학회세미나 49
Table 2. Histologic Scoring of Lymphoid Infiltrations in the Stomach 23 Score Diagnosis Histological features 0 Normal Scattered plasma cells in lamina propria. No lymphoid follicles 1 Chronic active gastritis Small clusters of lymphocytes in lamina propria. No lymphoid follicles. No lymphoepithelial lesions 2 Chronic active gastritis with florid lymphoid follicle formation Prominent lymphoid follicles with a surrounding mantle zone and plasma cells. No lymphoepithelial lesions 3 Suspicious lymphoid infiltrate, probably reactive Lymphoid follicles surrounded by small lymphocytes that infiltrate diffusely in lamina propria and occasionally into the epithelium 4 Suspicious lymphoid infiltrate, probably lymphoma Lymphoid follicles surrounded by marginal zone cells that infiltrate diffusely in lamina propria and into the epithelium in small groups 5 MALT lymphoma Presence of dense diffuse infiltrate of marginal zone cells in lamina propria with prominent lymphoepithelial lesions MALT, mucosa-associated lymphoid tissue. Table 3. Groupe d'etude des Lymphomes de l'adulte (GELA) Histological Grading System for Post Treatment Evaluation of Gastric MALT Lymphoma 24 Score Lymphoid infiltrate LEL Stomach changes CR Absent or scattered plasma cells and small lymphoid cells in the LP Normal or empty LP and/or fibrosis pmrd Aggregates of lymphoid cells or lymphoid nodules in the LP/MM and/or SM Empty LP and/or fibrosis rrd Dense, diffuse or nodular extension around glands in the LP /+ Focal empty LP and/or fibrosis NC Dense, diffuse or nodular + No changes CR, complete histological remission; LEL, lymphoepithelial lesions; LP, lamina propria; MM, muscularis mucosa; NC, no change; pmrd, probable minimal residual disease; rrd, responding residual disease; SM, submucosa. 의진단에필요한조직기준으로널리사용되며, score 3, 4 병변은중합효소연쇄반응 (PCR) 을이용하여 B세포단클론성이증명되어야 MALT 림프종으로진단할수있다 (Table 2). 보다공격적인미만성거대 B-세포림프종에비해 MALT 림프종은위에많이발생하고초기인경우가많아치료반응평가에있어서영상의학또는핵의학적진단보다병리적진단이중요할때가많다. 특히제균치료에반응하는위 MALT 림프종의경우림프구침윤과림프상피병변이줄어들고 lamina propria가없어지거나섬유화된다. 최근치료반응평가에대한객관적지표를위해 Groupe d'etude des Lymphomes de l'adulte (GELA) histological grading system이사용되고있다 (Table 3). 24 이시스템에서 probable minimal residual disease (pmrd) 카테고리는기본적으로림프종이활성화되지않고 remission이진행되는상태로보기때문에다른치료를시작하기보다는적절한 follow-up을권유하고있다. 21 4. 병기결정 위장관림프종병기는다양한방법으로표현할수있다. 임상에서림프종병기에널리쓰이는 Ann Arbor system 25 은해부학적분류법으로서병기를 stage I-IV까지분류하며, stage I은한개의림프절이나림프기관만침범했을때, stage II는횡경막을기준으로한쪽에두개이상의림프절그룹을침범했을때, stage III은횡경막을기준으로흉부와복부의림프절그룹을동시에침범했을때, stage IV는골수, 뇌, 간, 척수, 흉막등의원격전이가있을때로분류하며, 림프절밖의장기 (extranodal organ) 를침범하면 stage 옆에 E를붙여표기하도록한다. 예를들면, 점막에국한된 MALT 림프종의경우 stage IE로표기한다. 그러나 Ann Arbor system은원래호지킨림프종의분류를위해개발된병기체계로서비호지킨림프종, 특히림프절외비호지킨림프종인원발성위장관림프종의병기설정에사용되는것은한계가있다. 내시경초음파검사로평가한림프종침윤도가헬리코박터균제균치료후예후를예측하는중요인자임에도불구하고 Ann Arbor system에는포함되어있지않다. 이러한단점을극복하고자 Ann Arbor system을개정하여 the Musshoff modified Ann Arbor system 26 이발표되었으나주변조직침범등을고려하지못하는병기시스템이었다. 장막침범등의위장관의해부학적측면을고려한 Lugano system 27 이이역시제안되었으나임상의사들에게혼선을주어지지를얻지못하였다. 이후제안된것이 Paris staging system 28 이다 (Table 4). Paris staging system은원 50 Korean Society of Gastrointestinal Endoscopy
Table 4. Paris Staging System for Primary Gastrointestinal Lymphoma 28 Stage TX TO T1 T1m T1sm T2 T3 T4 NX NO N1 N2 N3 MX MO M1 M2 BX B0 B1 TNM ptnmb pn Gastrointestinal lymphomas Lymphoma extent not specified No evidence of lymphoma Lymphoma confined to the mucosa/submucosa Lymphoma confined to mucosa Lymphoma confined to submucosa Lymphoma infiltrates muscularis propria or subserosa Lymphoma penetrates serosa (visceral peritoneum) without invasion of adjacent structures Lymphoma invades adjacent structures or organs Involvement of lymph nodes not assessed No evidence of lymph node involvement Involvement of regional lymph nodes Involvement of intra-abdominal lymph nodes beyond the regional area Spread to extra-abdominal lymph nodes Dissemination of lymphoma not assessed No evidence of extranodal dissemination Non-continuous involvement of separate site in gastrointestinal tract (eg, stomach and rectum) Non-continuous involvement of other tissues (eg, peritoneum, pleura) or organs (eg, tonsils, parotid gland, ocular adnexa, lung, liver, spleen, kidney, breast etc.) Involvement of bone marrow not assessed No evidence of bone marrow involvement Lymphomatous infiltration of bone marrow Clinical staging: status of tumour, node, metastasis, bone marrow Histopathological staging: status of tumor, node, metastasis, bone marrow The histological examination will ordinarily include 6 or more lymph nodes Table 5. Comparison of Lugano stage, 27 modified Ann Arbor stage, 26 and Paris classification 28 Stage Lugano system modified Ann Arbor system Paris classification Extent of lymphoma Stage I Stage I IE1 T1 N0 M0-1 B0 Mucosa, submucosa IE2 T2 N0 M0-1 B0 Muscularis propria, subserosa IE2 T3 N0 M0-1 B0 Serosa penetration Stage II Stage II1 IIE1 T1-4 N1 M0-1 B0 Regional lymph nodes Stage II2 IIE2 T1-4 N2 M0-1 B0 Intra-abdominal distant lymph nodes Stage IIE IE2 T1-4 N0 M0-1 B0 Invasion of neighboring organ Stage IV Stage IV IIIE T1-4 N3 M0-1 B0 Extra-abdominal lymph nodes IVE T1-4 N0-2 M2 B0 Diffuse/disseminated spread IVE T1-4 N0-2 M01-2 B1 Bone marrow involvement 발장기의심달도와림프절침범뿐만아니라원격장기의침윤양상도자세히분류하고있으며임상의들에게익숙한상피암분류체계인 TNM staging을근간으로하여보다익숙한점이장점이다. Table 5는여러병기시스템을비교하여보여준다. 5. 예후예측위 MALT 림프종의경우내시경초음파검사로평가한침윤도가헬리코박터균제균치료후치료반응을예측하는중요인자이다. 또한, 점막이나점막하층에국한된 MALT 림프종에서헬리코박터균이양성일때에제균치료만으로약 80% 의 관해에도달하는것으로알려져있다. 전통적으로림프종의예후예측인자로유명한것이 international prognostic index (IPI) 29 이다 (Table 6). 예후가좋고전신질환이거의없는위 MALT 림프종에적용할필요는없지만, 위장관미만성거대 B-세포림프종에서는적용가능하다. 국내의한보고에따르면원발성위장관미만성거대 B- 세포림프종 76명을대상으로 IPI를적용하였을때 5년생존율이 low risk, low-intermediate, high-intermediate, high risk 순서로각각 78.4%, 63.7%, 30.0%, 0% 로 IPI가강력한예후인자라고보고하였다. 30 제 55 회대한소화기내시경학회세미나 51
Table 6. Internaional prognostic index for non-hodgkin lymphoma 29 Prognostic factors Risk category Complete remission rate (%) 5-year overall survival (%) Age 60 years Low (0 or 1) 87 73 Reduced performance status (ECOG 2) Low-intermediate (2) 67 51 Elevated LDH High-intermediate (3) 55 43 2 Extranodal sites High (4 or 5) 44 26 Ann Arbor stage III or IV ECOG 2; Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. ECOG, eastern cooperative oncology group; LDH, lactate dehydrogenase. 결론 최근 20여년동안위장관림프종의진단, 병기, 치료에있어많은변화가있었다. 최근내시경건수의증가로인해증상이거의없는위장관림프종의발견율이더증가할것으로예상되며, 진단기기의발전으로임상접근방법의변화가예측된다. 참고문헌 1. Dawson IM, Cornes JS, Morson BC. Primary malignant lymphoid tumours of the intestinal tract. Report of 37 cases with a study of factors influencing prognosis. Br J Surg 1961;49: 80-89. 2. Ko YH, Kim CW, Park CS, et al. REAL classification of malignant lymphomas in the Republic of Korea: incidence of recently recognized entities and changes in clinicopathologic features. Hematolymphoreticular Study Group of the Korean Society of Pathologists. Revised European-American lymphoma. Cancer 1998;83:806-812. 3. Kim JM, Ko YH, Lee SS, et al. WHO classification of malignant lymphomas in Korea: report of the third nationwide study. Korean J Pathol 2011;45:254-260. 4. Lee Y, Lee J. Gastrointestinal Lymphoma. Korean J Helicobacter Up Gastrointest Res 2012;12:158-165. 5. Rappaport H. Atlas of tumor pathology. Tumors of the hematopoietic system. Washington DC: Armed Forces Institute of Pathology, 1966. 6. National Cancer Institute sponsored study of classifications of non-hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer 1982;49: 2112-2135. 7. Harris NL, Jaffe ES, Stein H, et al. A revised European- American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994;84:1361-1392. 8. Jaffe ES, Harris NL, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. 9. Swerdlow SH, Campo E, Harris NL, et al. WHO classification of Tumours of Haematopoietic and lymphoid tissues, 4th edition. Lyon: IARC Press; 2008. 10. Yang HJ, Lee C, Lim SH, et al. The clinical characteristics of primary gastric lymphoma detected during screening for gastric cancer in Korea. J Gastroenterol Hepatol 2016 [Epub ahead of print]. 11. Caletti G, Ferrari A, Brocchi E, et al. Accuracy of endoscopic ultrasonography in the diagnosis and staging of gastric cancer and lymphoma. Surgery 1993;113:14-27. 12. Palazzo L, Roseau G, Ruskone-Fourmestraux A, et al. Endoscopic ultrasonography in the local staging of primary gastric lymphoma. Endoscopy 1993;25:502-508. 13. Isasi CR, Lu P, Blaufox MD. A metaanalysis of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography in the staging and restaging of patients with lymphoma. Cancer 2005;104:1066-1074. 14. Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the imaging subcommittee of international harmonization project in lymphoma. J Clin Oncol 2007;25:571-578. 15. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014;32:3059-68. 16. Carr R, Barrington SF, Madan B, et al. Detection of lymphoma in bone marrow by whole-body positron emission tomography. Blood 1998;91:3340-6. 17. Pelosi E, Penna D, Douroukas A, et al. Bone marrow disease detection with FDG-PET/CT and bone marrow biopsy during the staging of malignant lymphoma: results from a large multicentre study. Q J Nucl Med Mol Imaging 2011;55:469-75. 18. Khan AB, Barrington SF, Mikhaeel NG, et al. PET-CT staging of DLBCL accurately identifies and provides new insight into the clinical significance of bone marrow involvement. Blood 2013;122:61-7. 19. Park JY, Kim SG, Kim JS, et al. Bone marrow involvement is rare in superficial gastric mucosa-associated lymphoid tissue lymphoma. Digestive and Liver Disease 2016;48:81-86. 20. Choi M, Kim G. Diagnosis and Treatment of Gastric MALT Lymphoma. Korean J Gastroenterol Vol. 57 No. 5, 272-280. 21. Bacon CM, Du MQ, Dogan A. Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists. J Clin Pathol 2007;60:361-72. 52 Korean Society of Gastrointestinal Endoscopy
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