GASTROINTESTINAL LYMPHOMA

(For the Surgical Resident ) What is it? Is it a distinct clinical entity from regular lymphoma? First thing is to understand lymphoma. Lymphoma in basic terms is a clonal proliferation of lymphoid progenitor cells, ie. stem cell many steps mature T or B cells. Lymphomas have been described for every progenitor cell. GI lymphoma has had various definitions, a good one isA lymphoma presenting w/ the bulk of the disease in the GI tract +/- contiguous lymph nodes necessitating treatment in that area. Lymphomas that predominate in nodal areas but involve the GI tract are generally managed as the nodal disease would be alone and wont be discussed. Epidemiology1) 53,000 lymphomas diagnosed in 2002 in US- Extranodal in 40% of cases-GI tract most frequent (up to of extranodal sites) 2) Somewhere between 4-20% of all Non-Hodgkin Lymphoma Overview1) Lymphoid tissue of the gut- Mucosa Associated Lymphoid Tissue (MALT) basically lymph nodes of the intestine (including Peyers patches) 2) Site of GI lymphoma and estimated frequency in western countries (based on case reports and series) Stomach(48%)> Small Bowel (26%) > Colon (12%) > Pancreas (2%) > Esophagus (rare) *In the middle east small bowel is most common* Staging and Classification (Many Systems) Ann Arbor SystemI-Single nodal or extranodal site (surgeons involved) II-More than one nodal group on same side of diaphragm or single extranodal group w/ adjacent lymph nodes (surgeons involved) III- Multiple nodal sites on both sides of diaphragm (surgeons generally not involved) IV-Bone, CNS, diffuse visceral involvement (surgeons generally not involved) Classification- Several systems (6 in common use today) to attempt to define particular cell that is involved and its natural history- too many to discuss all of them we will discuss ones important from surgical standpoint. (MALT, diffuse B-cell etc) I) Gastric Lymphoma- (Gastric mucosa usually does not contain MALT) A) Marginal zone or MALT-(40% of gastric lymphoma) H. Pylori infection present in 9098%. Present with epigastric pain or dyspepsia, B symptoms and other GI symptoms unusual. Treatment: Early (mucosa or submucosa)-antibiotics and serial EGD (deep or through wall) Chemo (single agent) 75% remission, Radiation -100%, Surgery 82% -all with small numbers of patients. Late-think Ann Arbor stage 3 basically the optimal treatment is unknown. B) Diffuse Large B-cell (most common ~50%) Genesis is not entirely clear may arise from MALT lesions or may be its own high grade lesion. Present with abdominal pain, large tumors may present with obstruction, ulcerating lesions may cause GI bleeding.

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Treatment: Traditionally surgical with 70% 5 year survival for Stage I disease. However, with endoscopy, CT, & endoscopic sono, surgery is not needed for tissue diagnosis or staging. Nonprospective trials suggest that chemo/radiation is at least as effective as surgery. Morbidity/Mortality slightly less than surgery. II) Small Bowel A) Marginal Zone or MALT- (~20%) In small bowel no association with H Pylori. Generally present as elderly person with melena. Usually appear as single exophytic or annular tumor, usually confined to intestine and/or local nodes. Treatment- Surgical. Chemo can slow growth but not cure it. 5 year survival ~75% B) Diffuse Large B cell (~55%) Similar to gastric diffuse large b-cell in clinical appearance. Abdominal pain, weight loss, obstruction, mass, bleeding, perforation. Usually an exophytic or annular tumor. One half have local disease other have regional or distant nodes. Surgery usually required, chemo and radiation sometimes employed. Survival ~ 40% C) Mantle Cell (Uncommon) Surgery required for obstruction (Usually involves ileocecal region) Mainstay of therapy is chemo D) Enteropathy Associated T-Cell (Celiac Sprue/Gluten sensitivity)- Monoclonal T cell populations develop in 3 scenarios- 1) Loss of responsiveness to gluten free diet 2) ulcerative jejunitis 3) enteropathy associated T lymphoma. Presentation: Celiac sprue with 23% SB perforation, 19% SBO, abdominal pain, weight loss, n/v. Optimal treatment not defined but usually involves surgery and chemotherapy with resection of as much tumor as possible. 5 year survival ~ 20%. III) Colon A) Diffuse Large Cell (60%) B) MALT (15%) C) Burkitts (15%) Aggressive Chemo, same treatment as systemic burkitts IV) Future Directions 1) Prospective trials regarding advanced stages of gastric lymphoma 2) Changes in Chemotherapy regimens (CHOP is still main one used) 2nd and 3rd generation regimens have not shown a difference, improvements in radiation oncology techniques 3) Further advances in immunotherapy (Rituximab) V) Take Home Points 1) Gastric- When early=think antibiotics for H. Pylori, For more advanced disease the jury is still out but chemo, surgery, and radiation all have good results. 2) Small bowel- Predominately surgical treatment 3) Colon-pretty much the same as small bowel 4) Esophageal- 3 cases in 47 years from Mayo Marco Harmaty, M.D. September 11, 2003

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