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Gastrointestinal Lymphomas. „Extranodal Lymphomas“. Definition: „....presenting with the main disease bulk at an extranodal site....“ Incidence: 24 – 48% of all lymphomas Considerable geographic variation. Extranodal Lymphomas: Incidence. USA: 24% Canada: 27% Hong Kong: 29% - PowerPoint PPT Presentation
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Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Gastrointestinal Lymphomas
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
„Extranodal Lymphomas“
Definition:
„....presenting with the main disease bulk at an extranodal site....“
Incidence:»24 – 48% of all lymphomas»Considerable geographic variation
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Extranodal Lymphomas: Incidence
• USA: 24%• Canada: 27%• Hong Kong: 29%• Israel: 36%• Denmark: 37%• Holland: 41%• Lebanon: 44%• Italy: 48%
Zucca et al, Ann Oncol 1997
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
MALT: Mucosa Associated Lymphoid
Tissue
• GALT: Gut associated......a priori: Peyer’s patches
• BALT: Bronchus associated• Salivary glands, thyroid gland, skin
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Histological Classification
• B-Cell:Mucosa associated lymphoid tissue Diffuse large B-cell lymphoma (+/- MALT-component)Mantle cell lymphoma (Lymphomatous polyposis)Burkitt‘s lymphomaOther types corresponding to nodal equivalents (follicular,
lymphocytic)Immunodeficiency related lymphomas• T – Cell:Enteropathy type T-cell lymphomaOther types not associated with enteropathy
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Frequency of gastric lymphoma:Vienna Lymphoma Registry 1997 – 9/2002
• Initial diagnosis:
MALT lymphoma: n = 100
Diffuse large B-cell lymphoma: n = 113 (18)
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Predominant sites of MALT-lymphoma
• Stomach
• GI-Tract
• Lung
• Salivary Glands
• Ocular Adnexa
• Skin
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Standardized staging:
• Ophthalmologic investigation• Ear, nose and throat (incl Sono/MR)• Endosonography + Gastroscopy (multiple biopsies)• Enteroklysma (-CT)• Colonoskopy• CT-Thorax + Abdomen• Bone marrow biopsy (?)
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Gastric Lymphoma
• Resected patients: n = 1609
Perioperative deaths: n = 75 (4.7 %)
• Unresected patients: n = 587
Major complications: n = 27 (4.6 %)
Gobbi et al; Haematologica 2000
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Conservative management plus surgery vs conservative alone
Koch et al, J Clin Oncol 2001
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Warren JR, Marshall B.Unidentified curved bacilli on gastric epithelium in active chronic gastritis.
Lancet 1983; 1: 1273-5
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Factors associated with acquired MALT
• Helicobacter pylori • Helicobacter Heilmanii• Chronic infection /
inflammation• Borrelia Burgdorferi• Autoimmune conditions:
Sjögren’s SyndromeHashimoto’s Thyroiditis........................................
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Time to Remission after HP-Eradication
• Isaacson et al.: 4 weeks – 14 months• Sackmann et al.: 6 – 14 months• Neubauer et al.: 4 – 18 months• Montalban et al.: 2 – 7 months
„The cases of late remission encourage us to wait for at least one year after eradication of H. pylori.“
A. Savio, Recent Results Cancer Res 2000
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Factors predicitive of response
• Staging / Endosonographic assessment:
Stage EI1 vs more advanced stages
Probability of complete response stage EI1 (n=22):
6 mos 60%
12 mos 79%
14 mos 100%
Sackmann et al, Gastroenteroloy 1997
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
t(11;18) (q21;q21)
• Characteristic translocation for MALT-lymphomas
found in up to 50% of gastric MALT-lymphomas
• Not detected in other MZBL and extranodal DLBCL
• Fusion of the apoptosis inhibitor gene API2 (11q21) and the novel MALT1 gene (18q21)
• Fusion product inhibits apoptosis by caspase pathways
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
t(11;18) translocation
in gastric MALT-lymphoma
• Number of patients: 111
• Response to eradication: 48
• t(11;18) positive: 2 / 48 responders 42 / 63 non-responders
Liu et al, Gastroenterology 2002
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Helicobacter eradication: Facts .....
• HP is a major factor in the development of MALT-lymphoma.• Eradication leads to durable remissions in about 80% of
selected patients.• t(11;18)+ patients seem to be unresponsive to HP eradication.• Relapse triggered by re-infection with HP remains sensitive to
eradication.• A high percentage of patients (-50%) remain PCR-positive
even in case of pathological complete remission.
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
................ and speculations
• Role of HP-eradication following extragastric spread of the lymphoma?
• Benefit of additional therapy following eradication?
• Does underlying autoimmune disease impair response to HP-eradication?
• Is persisting positive PCR an indicator for relapse?
• Regression of DLCL following eradication?
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Non-surgical management of gastric lymphoma
• Radiotherapy (stage I – II1):
„Low grade“: – 100% CR 5-year-survival: > 90%
„High grade“: 80% CR 5-year-survival: > 60%
• Chemotherapy (stages II2 – IV):
„Low grade“: - 75% CR 5-year-survival: > 80%
„High grade“: - 80% CR 5-year-survival: 40 – 93%
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Treatment for gastric lymphoma: MALT-type
• Stage I1: HP-eradication• Stage I2 – II2: HP eradication + radiation?
HP-eradication + chemotherapy?• Stage III/IV: HP-eradication + chemotherapy
• Chemotherapeutic options: Cyclophosphamide, Chlorambucil, 2 CdA, MCP
Surgery as an emergency procedure (bleeding, perforation)
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
Treatment for gastric lymphoma: Difuse large cell lymphoma
• Stage I - IV: HP-eradication + chemotherapy
• Stage I – II2:
HP eradication + chemotherapy (+ radiation?)
• Chemotherapeutic options:
CHOP, R-CHOP, ......?
Clinical Division of OncologyDepartment of Medicine I
Medical University ofVienna, Austria
“...for all gastric lymphomas, surgery probably belongs to the history of
medicine...”
E. Roggero et al. J Natl Cancer Inst 1997; 89:1328-30