슬라이드 1

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1 Gastric MALT Lymphoma 성균관대학교의과대학내과이준행

2 모든사람은죽는다. 모든사람은세금을내야한다. 림프종분류는항상변한다.

3 Biologically rational classification morphology immunophenotype genetic features clinical features Clinically useful classification clinical features natural history prognosis treatment

4 Rappar- port 1966 Kiel 1978 Working Formulation 1982 REAL 1994 WHO 2001 Revised WHO 2008

6 Immunohistochemical markers B-cell: CD20, CD79a T-cell: CD3, CD45RO NK-cell: CD56 Ki-67: Burkitt lymphoma > DLBL > others Mantle cell lympoma: cyclin D1 HTLV-1 serology TdT, CD4, CD5, CD8, CD10, CD30, Bcl-2, cytokeratin AE1/AE3,etc

7 Marginal zone cells (IgM) Mantle zone cells (IgM+D) Follicle center cells (IgM, IgG, IgA or IgE, not IgD)

8 Molecular pathogenesis Br J Haematol. 2007;136:

9 Lymphoepithelial lesions Monocytoid B-cells

10 병리학적진단기준, MALToma MALT 림프종을진단하는데필요한형태학적인특징은 정상적인 Peyer s patch의림프조직을닮아반응성림프여포가있고 Marginal zone/monocytoid B 세포들이있으며 Lymphoepithelial lesion 즉 3개이상의 marginal zone cell이상피혹은위선에침범하여상피세포의호산성변성을보이는병변을보이며 소림프구와형질세포 (Dutcher 소체를가질수도있다 ) 침윤과함께 여포아세포 (centroblast) 와면역아세포 (immunoblast) 가출현하는 다섯가지소견을모두만족하면 CD5와 cyclin D1염색과관계없이 MALT 림프종으로진단할수있다. Kim. 대한내과학회지 2000;59:

11 과거의 High grade MALToma 는더이상 MALToma 가아니다. MALT lymphoma without high grade component Extranodal marginal zone B cell lymphoma of MALT MALT lymphoma with high grade component DLBCL with a MALT lymphoma component DLBCL DLBCL without a MALT lymphoma component

12 이렇게까지 over 할필요는없습니다. Gut 2011;60:

13 진단이애매한경우 성균관대학교의과대학내과이준행

14 Pseudolymphoma? Massive gastric infiltrate (A) from an archival case in a study from the late 1960s, labeled as pseudolymphoma. The diagnosis of pseudolymphoma most likely was based on the fact that the infiltrate is dominated by small, round lymphocytes with scattered germinal centers (B). With current criteria, this case likely would be labeled gastric marginal zone lymphoma of MALT type (hematoxylin-eosin, original magnifications 150 [A] and 300 [B]). Burke. Arch Pathol Lab Med 2011;135:

15 The criteria is analogue. Score Diagnosis 0 Normal 1 Chronic active gastritis Chronic active gastritis with florid lymphoid follicle formation Suspicious lymphoid infiltrate, probably reactive Suspicious lymphoid infiltrate, probably lymphoma 5 MALT lymphoma Histological features Scattered plasma cells in lamina propria. No lymphoid follicles. Small clusters of lymphocytes in lamina propria. No lymphoid follicle. No lymphoepithelial lesions. Prominent lymphoid follicles with surrounding mantle zone and plasma cells. No lymphoepithelial lesions. Lymphoid follicles surrounded by small lymphocytes that infiltrate diffusely in lamina propria and occasionally into epithelium. Lymphoid follicles surrounded by marginal zone cells that infiltrate diffusely in lamina propria and into epithelium in small groups. Presence of dense infiltrate of marginal zone cells in lamina propria with prominent lymphoepithelial lesions.

16 Wotherspoon grade 3

17 What for Wootherspoon 3 and 4???? Choi MK. Korean J Gastroenterol 2011;57:

18 의심정도였는데재판독 / 재검하면 MALToma 로나오는경우가많습니다. 암으로진단이바뀌는것말고는거의아무런이 슈가없습니다.

19 외부슬라이드리뷰 : MALToma 재검 : Hp gastritis with lymphoid follicle

21 재판독 : MALToma

22 내시경위체상부에서 "H. pylori-chronic gastritis, active, with intestinal metaplasia (incomplete type), lymphoid aggregates and suspicious lymphoepithelial lesion" 소견으로재검후추가치료방침결정예정 1 달후추적검사에서 MALToma 로나와서치료시작함

23 반대도있습니다. - 외부에서는 MALToma, 재판독및재검에서는 Hp gastritis, 혹은 suggestive, suspicious, possibility 등애매한진단 보험이슈가있습니다. Code 이슈입니다. Option 은두가지입니다. 1) 외부결과의거 C-code 를붙인다. 2) 본병원결과의거 K-code 를붙인상태로제 균치료를한다.

25 암보험이슈

26 위궤양추적검사에서 MALT 림프종나왔는데. 어떻게해석해야할까요? Biopsy: Chronic gastritis, active, with lymphoid follicles, Hp (+) HPE + PPI Biopsy: EXTRANODAL MARGINAL ZONE OF MALT, Hp (-)

27 Hp 검사에서우연히 MALToma 나온경우도있습니다. 위에는특이소견없었음.

28 위 MALT 림프종이의심되었는데첫조직검사에서 Hp (+) lymphoid aggregate 만나오면

29 선종의심이나조직검사에서 chronic gastritis with foveolar epithelial hyperplasia 소견 EMR 에서 MALToma 나와의뢰됨

30 Endoscopic Findings 성균관대학교의과대학내과이준행

31 MALToma

32 Endoscopic findings Gastritis-like Multifocal atrophic Multinodular Ulcerative Polypoid EGC-like

33 MALToma, mimicking EGC

34 Typical response to HPE - MALT lymphoma of the antrum anterior wall and high body Initial biopsy (2015/12) 1) H.pylori gastritis with lymphoid follicle 2) H.pylori gastritis with atypical lymphoid proliferation 2. 의뢰후재검 (2016/3): MALToma, Hp (+) 3. 제균후첫검사 (2016/6): rrd 4. 제균후두번째검사 (2016/12): pmrd 5. 제균후세번째검사 (2017/10): complete remission

35 Gastric neoplasm detected during the health screening examination (SNUH) Number Converted annaul incidence per 100,000(male:female) Adenocarcinoma :70.9 EGC :23.6 AGC :7.9 MALToma 7 3.9:9.8 Metastatic cancer 1 1.9:0.0 Adenoma :53.2 Park. Gut and Liver 2007;1:33-39

36 제균치료하기전에의뢰해주시기바랍니다. - 개업가에서진단 / 치료하다의뢰된 MALToma

37 Initial Treatment Options 성균관대학교의과대학내과이준행

38 Treatment of gastric MALToma: NCCN Gastric MALT Stage IE Others H pylori positive H pylori (-)ve or t (11:18) +ve Complications e.g. Bleeding/ perforation/ Bulky disease Uncomplicated * H pylori eradication Local Radiotherapy Surgery? Radiation + CCT* Recurrence / Failure * NCCN advocates observation in patients who have advanced stage IV but asymptomatic disease.

39 Personal protocol for MALToma Low-grade MALT lymphoma in the first endoscopic biopsy Staging work-up including CT (prn, EUS, BM) Stage E-I 2, II, III, IV or H. pylori (-) or high-grade HPE or ChemoRx H. pylori eradication (PCA 2 weeks ) + 2nd eradication, if necessary UBT 4-6 wks after completing antibiotic treatment Endoscopy, 3 months after completing eradication

41 Module 화진료

42 Typical response to HPE Initial EGC 2 months later 6 months later

43 Typical response to HPE (HPE 1 개월 ) (HPE 3 개월 ) (HPE 5 개월 )

44 Typical response to HPE

45 From HPE to complete remission Hong (AMC). Helicobacter 2006;11:

46 Outcome of H. pylori eradiation 김수진. 대한소화기학회지 2010;55:94-99

47 Hong (AMC). Helicobacter 2006;11:

48 HPE 반응 (-) RT 후호전

49 HPE 로호전되지않아 RT Hp 제균치료후 RT 후관해

50 제균하였으나용종없어지지않아서용종절제술후경과관찰함 Min (SMC). Clin Endosc 2013;46:

51 Histology after polypectomy Min (SMC). Clin Endosc 2013;46:

52 가장천천히좋아진위 MALT 림프종 3 년

53 Multifocal atrophic scars (s/p HPE for MALToma) MALToma White atrophic scar (MALToma remission)

54 MALToma 제균치료후 NC RT 거부하여 10 년관찰 1 년후 4 년후 10 년후

55 Post-treatment Patholgy 성균관대학교의과대학내과이준행

56 육안은좋은데조직이나쁘면 - 조직이정말나쁜것일까? 과잉진단이아닐까?

57 Post-therapy grading system Gut 2003;52:

58 Probable minimal residual = CR??? Copie-Bergman C. Gut 2003;52:1656

59 왜 NC 가나쁜이름인가? - physician assistant 가정리한의무기록

60 GELA 용어때문에생긴대혼란 1 년전 최근내시경

61 Recurrence 성균관대학교의과대학내과이준행

62 MALToma 8 년경과관찰중미란모양으로재발. 다시제균치료했는데계속 MALToma 나옴 방사선치료 (30Gy/15Fx's)

63 H. pylori-negative MALToma 성균관대학교의과대학내과이준행

64 H. pylori-negative MALToma 로의뢰 재검에서 Giemsa 에서 H. pylori (+)

65 H. pylori-negative MALToma 로의뢰 - 조직검사 (Giemsa), UBT: 음성, CLOtest: 양성

66 H. pylori-negative MALToma - Improvement after Helicobacter treatment Improvement after HPE

67 H. pylori-negative MALToma - improvement after radiation treatment RT

68 H. pylori-negative MALToma ESD

69 Bone Marrow Involvement 성균관대학교의과대학내과이준행

(cellularity 50 %) with three lineage hematopoiesis and

70 Bone marrow involvement - lymphoid aggregate, CD20(+) Bone marrow, left, biopsy: Normocellular marrow (cellularity 50 %) with three lineage hematopoiesis and involvement of malignant lymphoma (tumor volume: less than 5 %)

71 Bone marrow involvement - lymphoid aggregate

72 Bone marrow involvement - lymphoid aggregate, CD20 (+)

73 Won (AMC). Histopathology 2013;62:

74 Plasmacytoma-like MALToma 성균관대학교의과대학내과이준행

75 MALToma mimicking plasmacytoma

76 Follow-up 8 years later - MALToma mimicking plasmacytoma

77 MALT lymphoma simulating an extramedullary plasmacytoma of the stomach Approximately one third of all cases of gastric MALToma show variable degrees of plasma cell differentiation, occasionally plasma cells constitute the major population in the tumor. As surgical resection has been the standard treatment for gastric plasmacyotoma, this case highlights the need for caution. If H. pylori infection is found in a patient with a gastric plasmacytoma, it should be eradicated as a first line of therapy before surgery is considered. Kodama. Am J Med 1999;107:

78 Take home messages images Gastritis-like Multifocal atrophic Multinodular Ulcerative Polypoid EGC-like

79 경청해주셔서감사합니다.

슬라이드 1

슬라이드 1 Gastric MALT Lymphoma 성균관대학교의과대학내과이준행 모든사람은죽는다. 모든사람은세금을내야한다. 림프종분류는항상변한다. Biologically rational classification morphology immunophenotype genetic features clinical features Clinically useful classification