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