Casus 2 Een 40 jarige man bezoekt de huisarts i.v.m. sinds een half jaar bestaande klachten van...
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Transcript of Casus 2 Een 40 jarige man bezoekt de huisarts i.v.m. sinds een half jaar bestaande klachten van...
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
Immunohistochemische kleuring met anti CD20 antistoffen.
HE kleuring
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 lymphomakey 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
t(11;18)t(11;18)
t(14;18)t(14;18)
t(1;14)t(1;14)
Unknown!Unknown!n=252
13.5%
10.8%
1.6%
74.1%
Translocations in MALT lymphomaTranslocations in MALT lymphoma
Streubel et al., Leukemia 2004
All result in antigen-independent NFkB activation- proliferation- Inhibition of apoptosis
Pathogenesis Gastric MALT Lymphoma:
B-cell
MALT lymphoma
HP Infection acquired MALT
HP-specificT-cell
APC
HP dependent NFkB activation of B cells- proliferation- Inhibition of apoptosis
Chromosomal translocations → HP independent NFkB activation
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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
• Further Investigation of GI-tract depending on
symptoms
25 % also extragastric localisation !
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, CR 70-80%• Clarithromycin 500 mg bid d1-7
• 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 LymphomaTherapy 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
B-cell
MALT lymphoma
Bacterial Infection
T-cell
Auto-antigenAPC
Multistage development of gastric MALT lymphoma
Isaacson et al. Nature Rev. Cancer 2004:4;644-653
Paris Staging system of Gastric MALT Lymphoma
m.mucosa
submucosa
mucosa
m.propria
T1T2
T3 T4
Adjacent structures or organs
N1 regional
N2 intra-abdominal
N3 extra-abdominal M1 separate GI site
M2 separate non-GI site
serosa
B0
B1
BM neg
BM pos
Predictors of response toHelicobacter 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%