Journal of Digestive Cancer Research

Korean Society of Gastrointestinal Cancer Research (대한소화기암연구학회)
권호 표지

Diagnosis and Treatment of Gastric MALT Lymphoma

위 MALT 림프종의 진단 및 치료에 대한 고찰

  • Tae Ho Kim (Subdivision of Gastroenterology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • 김태호 (가톨릭대학교 의과대학 부천성모병원 소화기내과)
  • Received : 2015.11.20
  • Accepted : 2015.12.18
  • Published : 2015.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Gastric lymphoma comprises 1-6% of all gastric malignant neoplasms and among them 50% is gastric MALT lymphoma. The 60-70% of MALT lymphomas is diagnosed at early, localized diseased state. Gastric MALT lymphoma is assumed that it progress slowly with indolent course. It presents nonspecific symptoms such as epigastric pain, dyspepsia, nausea and vomiting. It is rarely associated with serious complication such as gastrointestinal bleeding or perforation. The definite diagnosis of gastric MALT lymphoma should be made with histopathologically. Wotherspoon score is used to differential diagnosis with Helicobacter pylori associated gastric inflammatory change. Gastric MALT lymphoma is associated with Helicobacter pylori infection with supported by epidemiologic and histopathologic studies. Gastric MALT lymphoma is characterized with genetic aberrations such as trisomy 3, trisomy 18, chromosomal translocations t(11;18), t(1;14), t(14;18), t(3;14). Appropriate clinical staging is essential to determine the optimal treatment strategy for gastric MALT lymphoma. Lugano International Conference classification has been applied widely. Helicobacter pylori eradication is used as the first line treatment for gastric MALT lymphoma independent of the stage. The complete remission has been achieved in 60-90% of the stage I/II1 patients with Helicobacter pylori eradication only. The treatment options for the patients with refractory to eradication are radiotherapy, chemotherapy and/or immunotherapy with the complete remission rate of 75% to 100%. The incidence of gastric MALT lymphoma can be expected to down by virtue of the decrease of Helicobacter pylori infection rate. Further basic and clinical research is necessary to advance in determine the pathogenesis and management.

위에 발생하는 암 중 위 림프종이 1-6% 가량을 차지하고 있고, 이 중 50% 가량이 MALT 림프종이다. MALT 림프종의 60-70% 가량은 조기, 국소병기에서 진단된다. 위 MALT 림프종은 일반적으로 그 진행이 매우 느리며 상복부 통증, 소화불량, 오심, 구토 등의 비특이적인 증상을 보인다. 진단은 조직학적으로 진단하며, 헬리코박터필로리 연관 만성 위염에서 보이는 염증성 병변과의 감별을 위해 Wotherspoon score를 이용한다. 여러 연구를 통해 위 MALT 림프종이 헬리코박터필로리 감염과 관련이 있다는 것이 밝혀져 있고, 3세염색체증, 18세염색체증, t(11;18), t(1;14), t(14;18), t(3;14) 등 여러 유전적 이상을 가질 수 있는 것으로 알려져 있다. 적절한 치료 방침을 결정하기 위해 병기를 결정하는 것은 매우 중요하며, Lugano International Conference classification을 주로 사용한다. 위 MALT 림프종의 1차 치료는 헬리코박터필로리 감염 유무 및 병기와 관계없이 헬리코박터필로리 제균치료이다. Stage I/II1 환자의 경우 제균치료로 60-90%의 완전 완화율을 보인다. 제균치료에 반응이 없는 경우에는 방사선치료, 항암화학요법, 면역치료 등을 시행해 볼 수 있고, 75-100%의 완전완화율을 보인다. 향후 헬리코박터필로리의 감염율이 감소하면서 위 MALT 림프종의 발생도 감소할 것으로 기대된다. 또한 향후 치료방침 확립을 위해 지속적인 연구가 필요할 것으로 생각한다.

Keywords

References

  1. Nakamura S, Matsumoto T. Gastrointestinal lymphoma: recent advances in diagnosis and treatment. Digestion 2013;87:182-188.
  2. Nakamura S, Matsumoto T, Iida M, et al. Primary gastrointestinal lymphoma in Japan: a clinicopathologic analysis of 455 patients with special reference to its time trends. Cancer 2003;97:2462-2473.
  3. Jaffe E, Harris N, Stein H, et al. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery. Blood 2008;112:4384-4399.
  4. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. Journal of Clinical Oncology 1998;16:2780-2795.
  5. Thieblemont C, Berger F, Dumontet C, et al. Mucosa-associated lymphoid tissue lymphoma is a disseminated disease in one third of 158 patients analyzed. Blood 2000;95:802-806.
  6. Montalban C, Castrillo JM, Abraira V, et al. Gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. Clinicopathological study and evaluation of the prognostic factors in 143 patients. Annals of Oncology 1995;6:355-362.
  7. Taal BG, Boot H, van Heerde P, et al. Primary non-Hodgkin lymphoma of the stomach: endoscopic pattern and prognosis in low versus high grade malignancy in relation to the MALT concept. Gut 1996;39:556-561.
  8. Fischbach W, Dragosics B, Kolve Goebeler ME, et al. Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group. Gastroenterology 2000;119:1191-1202.
  9. Bertoni F, Coiffier B, Salles G, et al. MALT lymphomas: pathogenesis can drive treatment. Oncology 2011;25:1134-1147.
  10. Nakamura S, Ye H, Bacon C, et al. Clinical impact of genetic aberrations in gastric MALT lymphoma: a comprehensive analysis using interphase fluorescence in situ hybridisation. Gut 2007;56:1358-1363.
  11. Nakamura S, Ye H, Bacon C, et al. Translocations involving the immunoglobulin heavy chain gene locus predict better survival in gastric diffuse large B-cell lymphoma. Clinical Cancer Research 2008;14:3002-3010.
  12. Wotherspoon AC, Doglioni C, Diss TC, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. The Lancet 1993;342:575-577.
  13. Ferreri AJM, Govi S, Ponzoni M. Marginal zone lymphomas and infectious agents. Seminars in cancer biology 2013;23:431-40.
  14. Wotherspoon AC, Ortiz Hidalgo C, Falzon MR, et al. Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. The Lancet 1991;338:1175-1176.
  15. Parsonnet J, Hansen S, Rodriguez L, et al. Helicobacter pylori infection and gastric lymphoma. The New England Journal of Medicine 1994;330:1267-1271.
  16. Nakamura S, Yao T, Aoyagi K, et al. Helicobacter pylori and primary gastric lymphoma. A histopathologic and immunohistochemical analysis of 237 patients. Cancer 1997;79:3-11.
  17. D'Elios MM, Amedei A, Manghetti M, et al. Impaired T-cell regulation of B-cell growth in Helicobacter pylori-related gastric low-grade MALT lymphoma. Gastroenterology 1999;117:1105-1112.
  18. Schmees C, Prinz C, Treptau T, et al. Inhibition of T-cell proliferation by Helicobacter pylori gamma-glutamyl transpeptidase. Gastroenterology 2007;132:1820-1833.
  19. Cheng T-Y, Lin J-T, Chen L-T, et al. Association of T-cell regulatory gene polymorphisms with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma. Journal of Clinical Oncology 2006;24:3483-3489.
  20. Nakamura S, Matsumoto T. Treatment Strategy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma. Gastroenterology clinics of North America 2015;44:649-6460.
  21. Du M-Q. MALT lymphoma: many roads lead to nuclear factor-κb activation. Histopathology 2011;58:26-38.
  22. Hussell T, Isaacson PG, Crabtree JE, et al. Helicobacter pylori-specific tumour-infiltrating T cells provide contact dependent help for the growth of malignant B cells in low-grade gastric lymphoma of mucosa-associated lymphoid tissue. The Journal of pathology 1996;178:122-127.
  23. Chuang S-S, Lee C, Hamoudi R, et al. High frequency of t(11; 18) in gastric mucosa-associated lymphoid tissue lymphomas in Taiwan, including one patient with high-grade transformation. British Journal of Haematology 2003;120:97-100.
  24. Honma K, Tsuzuki S, Nakagawa M, et al. TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas. Blood 2009;114:2467-2475.
  25. Chan JK, Ng CS, Isaacson PG. Relationship between highgrade lymphoma and low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) of the stomach. The American Journal of Pathology 1990;136:1153-1164.
  26. de Jong D, Boot H, van Heerde P, et al. Histological grading in gastric lymphoma: pretreatment criteria and clinical relevance. Gastroenterology 1997;112:1466-1474.
  27. Rohatiner A, d'Amore F, Coiffier B, et al. Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Annals of Ooncology 1994;5:397-400.
  28. Nakamura S, Matsumoto T. Helicobacter pylori and gastric mucosa-associated lymphoid tissue lymphoma: recent progress in pathogenesis and management. World Journal of Gastroenterology 2013;19:8181-8187.
  29. Zullo A, Hassan C, Cristofari F, et al. Effects of Helicobacter pylori eradication on early stage gastric mucosa-associated lymphoid tissue lymphoma. Clinical Gastroenterology and Hepatology 2010;8:105-110.
  30. Nakamura S, Sugiyama T, Matsumoto T, et al. Long-term clinical outcome of gastric MALT lymphoma after eradication of Helicobacter pylori: a multicentre cohort follow-up study of 420 patients in Japan. Gut 2012;61:507-513.
  31. Ruskone Fourmestraux A, Lavergne A, Aegerter PH, et al. Predictive factors for regression of gastric MALT lymphoma after anti-Helicobacter pylori treatment. Gut 2001;48:297-303.
  32. Liu H, Ye H, Ruskone Fourmestraux A, et al. T(11;18) is a marker for all stage gastric MALT lymphomas that will not respond to H. pylori eradication. Gastroenterology 2002;122:1286-1294.
  33. Ye H, Liu H, Attygalle A, et al. Variable frequencies of t(11; 18)(q21;q21) in MALT lymphomas of different sites: significant association with CagA strains of H. pylori in gastric MALT lymphoma. Blood 2003;102:1012-1018.
  34. Sumida T, Kitadai Y, Hiyama T, et al. Antibodies to Helicobacter pylori and CagA protein are associated with the response to antibacterial therapy in patients with H. pylori-positive API2-MALT1-negative gastric MALT lymphoma. Cancer Science 2009;100:1075-1081.
  35. Ruskone Fourmestraux A, Fischbach W, Aleman BMP, et al. EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT. Gut 2011;60:747-758.
  36. Fischbach W, Goebeler ME, Ruskone Fourmestraux A, et al. Most patients with minimal histological residuals of gastric MALT lymphoma after successful eradication of Helicobacter pylori can be managed safely by a watch and wait strategy: experience from a large international series. Gut 2007;56:1685-1687.
  37. Copie Bergman C, Gaulard P, Lavergne Slove A, et al. Proposal for a new histological grading system for post-treatment evaluation of gastric MALT lymphoma. Gut 2003;52:1656.
  38. Zullo A, Hassan C, Ridola L, et al. Eradication therapy in Helicobacter pylori-negative, gastric low-grade mucosa-associated lymphoid tissue lymphoma patients: a systematic review. Journal of Clinical Gastroenterology 2013;47:824-827.
  39. Asano N, Iijima K, Koike T, et al. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review. World Journal of Gastroenterology 2015;21:8014-8020.
  40. Nakamura S, Matsumoto T, Ye H, et al. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: a clinicopathologic and molecular study with reference to antibiotic treatment. Cancer 2006;107:2770-2778.
  41. Raderer M, W?hrer S, Kiesewetter B, et al. Antibiotic treatment as sole management of Helicobacter pylori-negative gastric MALT lymphoma: a single center experience with prolonged follow-up. Annals of Hematology 2015;94:969-973.
  42. Teckie S, Qi S, Lovie S, et al. Long-term outcomes and patterns of relapse of early-stage extranodal marginal zone lymphoma treated with radiation therapy with curative intent. International Journal of Radiation Oncology, Biology, Physics 2015;92:130-137.
  43. Zullo A, Hassan C, Andriani A, et al. Treatment of low-grade gastric MALT-lymphoma unresponsive to Helicobacter pylori therapy: a pooled-data analysis. Medical Oncology 2010;27:291-295.
  44. Aguiar Bujanda D, Llorca Martinez I, Rivero Vera J, et al. Treatment of gastric marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue with rituximab, cyclophosphamide, vincristine and prednisone. Hematological Oncology 2014;32:139-144.
  45. Levy M, Copie Bergman C, Gameiro C, et al. Prognostic value of translocation t(11;18) in tumoral response of low-grade gastric lymphoma of mucosa-associated lymphoid tissue type to oral chemotherapy. Journal of Clinical Oncology 2005;23:5061-5066.
  46. Salar A, Domingo Domenech E, Estany C, et al. Combination therapy with rituximab and intravenous or oral fludarabine in the first-line, systemic treatment of patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type. Cancer 2009;115:5210-5217.
  47. Kiesewetter B, Mayerhoefer M, Lukas J, et al. Rituximab plus bendamustine is active in pretreated patients with extragastric marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma). Annals of hematology 2014;93:249-253.