GASTROINTESTINAL LYMPHOMAS

1
GASTROINTESTINAL LYMPHOMAS

• Boudová, Fakan, Mukenšnabl, Daum
• Vanecek, Šíma, Nemcová, Michal
• PLZEN

2
Primary GI lymphomas

• Most common extranodal lymphomas
• Heterogeneous

Extranodal lymphomas 1/3 of all lymphomas GIT,
skin CNS, testis, bone, soft tissue salivary
glands, thyroid, Waldeyer ring, lung kidney,
liver, spleen, female genital tract
3
GI lymphomas

• Type
• B
• DLBCL, MALT
• MCL, FL
• T
• EATL

• Site
• Stomach
• Intestines
• (ileocaec., jejunum, duodenum)

4
MALT lymphoma

• stomach, intestine (IPSID)
• chronic antigenic stimulation
• - Helicobacter pylori
• Regulation specific activated T-cells
• Slow progression- 90 stage IE, IIE
• (bone marrow involvement rare, 10)

5
MALT lymphoma
Different sites common features Architecture Cyt
ology Immunophenotype
6
MALT lymphomamonocytoid B-cells(centrocyte-like,
small lymphocytes) plasma cells, Dutcher bodies
7
MALT lymphomaLEL
8
MALT lymphoma epithelium LEL, eosinophilic
change
9
MALT lymphoma - LEL (CD20)
10
MALT lymphoma

• Immunohistochemistry
• No specific MALT lymphoma marker
• Positivity CD20, CD79a Ig light chains Ig
  heavy chains IgM CD43
• Negativity CD5, CD10, bcl6, IgD, cyclin D1
• CD21, CD10, Ki-67 residual lymphoid follicles

11
MALT lymphomadiagnostic problems

• Large blasts (lt 10)
• Follicular colonization
• B-cell monoclonality

12
MALT lymphoma - diagnostic problems

• Large blasts (lt 10)

Ki-67
13
MALT lymphoma - diagnostic problemsFollicular
colonization
Bacon J Clin Path 06
14
MALT lymphoma

• Differential diagnosis
• HP gastritis
• other lymphomas DLBCL, MCL, FL

• Integrated approach
• favoring MALT lymphoma
• dense lymphoid infiltrate
• prominent LEL
• Dutcher bodies
• infiltration of muscularis mucosae
• atypia of lymphoid cells
• B - cell monoclonality

15
MALT lymphoma
16
Macroscopy often noncharacteristic

• Microscopy Wotherspoon criteria - spectrum
• 0 normal mucosa
• 1 chronic active gastritis
• 2 chronic active gastritis with lymphoid
  follicles
• 3 suspicious lymphoid infiltrate,
• probably reactive
• 4 suspicious lymphoid infiltrate,
• probably lymphoma

5 MALT lymphoma
17
B-cell monoclonality detection

• Imunohistochemistry
• Ig light chains
• Molecular biology
• PCR
• IgH rearrangement

CDR III
18
B-cell monoclonality detection
Polyclonal IgH rearrangement
Monoclonal IgH rearrangement
19
It is often not possible to establish a clear
diagnosis in a single biopsy.

• repeat the biopsy sampling
• MALT lymphoma/gastritis?
• Large cell component?

20
Correct diagnosis and treatment

• Interdisciplinary communication
• Repeated biopsies
• Specialized methods

21

• MALT lymphoma after therapy
• Response regression of lymphoid infiltrate and
  LEL
• Gastric mucosa atrophy, intestinal metaplasia,
  empty, fibrotic, basal lymphoid aggregates
• Always assess Helicobacter pylori
• B-cell clonality assessment by PCR not clear

22
Gastric MALT lymphoma

• Recurrent genetic abnormalities
• t(1118)(q21q21)/ API2-MALT1
• usually the sole genetic abnormality, 25 of g.
  MALT l., H. p. neg., no response to ATB
• t(1418)(q32q21)/ IgH-MALT1
• non-gastric
• t(114)(p22q32)/ IgH-BCL10 t(12)(p22p12)

23
MALT lymphoma versus DLBCL

• Gastric DLBCL
• de novo
• transformation of a low-grade lymphoma
• clonal progression in time
• Independent coexistence of 2 clones
• low /high grade component
• DO NOT USE HIGH-GRADE MALT LYMPHOMA

24
Diffuse large B-cell lymphoma of the stomach
25

Diffuse large B-cell lymphoma of the stomach
26
Multiple lymphomatous polyposis

• Mantle cell lymphoma
• Follicular lymphoma
• MALT lymphoma

27
Mantle cell lymphoma

• Multiple lymphomatous polyposis
• M?60
• bad prognosis
• imunohistochemistry
• genetics

WHO 2001
28
Mantle cell lymphoma
29
Mantle cell lymphoma
Cyclin D1
CD5
30
MALT? MCL? FISH t(1114)(q13q32)
31
Lymphomatous polyposisfollicular lymphoma g. 1
of the colon
M, 55, 2 polyps stage IE, no therap, no disease
3 ys after the diagnosis
32
Follicular lymphoma of the colon
CD10
33
Follicular lymphoma of the colon
Ki-67
Bcl-2
34
F, 53-ys,ileocaecal carcinoma follicular
lymphoma stage IV, 7x CHOP no disease detected
4 ys after the diagnosis
appendix
Bcl-2
ileum
35
Follicular lymphoma, ileocaecal
36
Enteropathy-associated T-cell lymphoma

• Proximal jejunum
• Very rare x most common GI T-cell lymphoma
• Acute abdomen (40) emergency surgery
• Obstruction/perforation, peritonitis, sepsis,
  death
• Non-acute pain, weight loss, malabsorption
• Age 60, MF

37
Enteropathy-associated T-cell lymphoma
Multifocal ulcers
38
Enteropathy-associated T-cell lymphoma

• Striking association with celiac disease
• Histology and immunomorphology
• Anaplastic/pleomorphic (80)
• Cel., enteropathy , CD56-
• Monomorphic (20)
• Cel.-, enteropathy/-, CD56
• Half of the patients die soon after the
  manifestation

39
Enteropathy-associated T-cell lymphoma
Anaplastic/pleomorphic
T-cells, plasma cells, eosinophils
40
Enteropathy-associated T-cell lymphoma
CD8
CD3
41
TCR gamma - PCR
ABI PRISM
TGGE
Enteropathy assoc. T-cell lymphoma CGH marker
9q gain (70 Zettl 2007)
42
Molecular-genetic laboratory Dept. of Pathol.,
Plzen, Czech Republic