Casus 2
• Een 40 jarige man bezoekt de huisarts i.v.m.
sinds een half jaar bestaande klachten van
zuurbranden en pijn midden in de bovenbuik,
vooral na de maaltijd.
• De huisarts schrijft een protonpomp remmer
voor. Dit resulteert wel in enige verbetering,
maar de klachten blijven bestaan.
• Patiënt wordt verwezen voor een
gastroscopie. In het antrum wordt een
ulcererende zwelling gezien van 1,5x 2 cm.
Er worden multipele biopten genomen
HE kleuring
Immunohistochemische kleuring
met anti CD20 antistoffen.
Casus 2
Vragen:
• Welke diagnose overweegt U en wat zijn
hiervoor belangrijke argumenten?
• Welk micro-organisme speelt een belangrijke
rol in de pathogenese?
• Wat is de behandeling?
Gastric MALT lymphoma
key messages
• Distinct disease entity
• Pivotal role of chronic antigenic
stimulation by H. pylori
• Can be cured by antibiotic treatment
• Good prognosis (5 yrs OS 82-93%)
MALT Lymphoma
• MALT: Mucosa-Associated Lymphoid Tissue
– Can be induced/expanded by chronic antigenic
stimulation
• Lymphomas of MALT-type : ~8% of all NHL
• Two subgroups
– Gastric MALT Lymphomas (70%)
– Non-Gastric MALT Lymphomas (30%)
Gastric MALT Lymphoma:
History
• 1991 Wotherspoon et al.
– Association H.Pylori gastritis and Gastric MALT
lymphoma
• 90% H.Pylori infection,
• 98% H.Pylori positive serology
• 1993 Wotherspoon et al.
– Remission of MALT lymphoma after H.pylori
eradication
• 1996 Hussell et al.
– H.Pylori strain specific T-cells involved in
lymphomagenesis
Gastric MALT Lymphoma:
Gastroscopy
Gastric MALT Lymphoma:
Histology
• LEL’s
(Lymphoepithelial lesions)
• monoclonal small/meduim sized B
cells (“marginal zone cells”)
• CD20+,CD79a+,CD5-,CD10-,
CD23-, CD21+, CD35+,IgM+
•Plasmacytoid differentiation
Translocations in MALT lymphoma
13.5%
10.8%
1.6%
All result in antigen-independent NFkB
activation74.1%
- proliferation
n=252
- Inhibition of apoptosis
t(11;18)
t(14;18)
t(1;14)
Unknown!
Streubel et al., Leukemia 2004
Pathogenesis Gastric MALT Lymphoma:
HP Infection acquired MALT
HP-specific
T-cell
APC
HP dependent
B-cell
NFkB activation of B cells
- proliferation
- Inhibition of apoptosis
MALT lymphoma
Chromosomal translocations → HP independent NFkB
activation
Gastric MALT Lymphoma:
assessment of localisations
• Gastroscopy with multiple biopsies (H.Pylori culture)
• Endosonography of the stomach
• CT-chest and abdomen (gastric protocol)
• Ophthalmologic and ENT-examination
• Bone Marrow investigation
25 % also
extragastric
localisation !
• Further Investigation of GI-tract depending on
symptoms
Gastric MALT Lymphoma
Therapy local disease
• H.Pylori eradication with strict Follow-Up
• Omeprazole 20 mg bid d1-7,
• Amoxycillin 1000 mg bid d1-7,
• Clarithromycin 500 mg bid d1-7
 CR 70-80%
• Similar OS with different treatments : 5yrs OS 82%
• chemotherapy, surgery, surgery with additional
chemotherapy or radiation therapy or H.Pylori eradication
Effect of eradication of H.Pylori
Before Hp
eradication
2 weeks
post-eradication
10 months
post-eradication
Dr Naomi Uemura, Hiroshima Japan
Gastric MALT Lymphoma
Therapy II
• Radiotherapy:
• Chemotherapy (mild, oral)
• Immunotherapy: Rituximab
Advanced disease:
• Comparable with follicular lymphoma:
– CVP-R or FCR
Non Gastric MALT lymphomas:
Primary site:
Percentage:
Antigen:
Head & Neck
30
Sjögren Syndrome
Ocular Adnexa
24
Chlamydia Psittaci
Lung
12
Skin
12
Borrelia Burgdorferi
Intestinal tract
8
IPSID: Campylobacter Jejuni
Thyroid
7
Hashimoto’s thyreoiditis
Breast
2
Genitourinary tract
1
Pathogenesis non-gastric MALT ymphoma
Bacterial Infection
Auto-antigen
APC
T-cell
B-cell
MALT lymphoma
Multistage development of
gastric MALT lymphoma
Isaacson et al. Nature Rev. Cancer 2004:4;644-653
Paris Staging system of Gastric
MALT Lymphoma
mucosa
m.mucosa
submucosa
m.propria
serosa
T1
T2
N1
regional
N2
intra-abdominal
N3
extra-abdominal
T3
T4
B0
BM neg
B1
BM pos
Adjacent structures or organs
M1
separate
GI site
M2
separate nonGI site
Predictors of response to
Helicobacter Pylori eradication
•
•
•
•
Depth of invasion of gastric wall
Helicobacter status at diagnosis
Presence/absence of large cell component
Immunocytochemistry
• nuclear bcl-10
• nuclear NF-kB
• Molecular abnormalities
• API-2/MALT-1 fusion t(11;18)
• t(1;14)
• Trisomy 3
Non Gastric MALT Lymphoma:
Therapy and Prognosis
No randomized controlled trials 
Patient tailored therapy
•Local disease:
•Radiotherapy
•Chemotherapy, Immunotherapy, Surgery
•Advanced disease: “indolent lymphomas”
•Prognosis: 5 year survival 82-93%