Transcript Bez nadpisu - Cytopathos

GASTROINTESTINAL
LYMPHOMAS
Boudová, Fakan, Mukenšnabl, Daum
Vaněček, Šíma, Němcová, Michal
PLZEŇ
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
GI lymphomas
Type
B
DLBCL, MALT
MCL, FL
T
EATL
Site
 Stomach
 Intestines
(ileocaec., jejunum,
duodenum)
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%)
MALT lymphoma
Different sites
common features
Architecture
Cytology
Immunophenotype
MALT lymphoma
monocytoid B-cells
(centrocyte-like, small lymphocytes)
plasma cells, Dutcher bodies
MALT lymphoma
LEL
MALT lymphoma
epithelium: LEL, eosinophilic change
MALT lymphoma - LEL (CD20)
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
MALT lymphoma
diagnostic problems
Large blasts (< 10%)
Follicular colonization
B-cell monoclonality
MALT lymphoma - diagnostic problems
Large blasts (< 10%)
Ki-67
MALT lymphoma - diagnostic problems
Follicular colonization
Bacon J Clin Path 06
MALT lymphoma
Differential diagnosis
HP gastritis
Integrated approach
favoring MALT lymphoma:
dense lymphoid infiltrate
prominent LEL
Dutcher bodies
infiltration of muscularis mucosae
atypia of lymphoid cells
B - cell monoclonality
other lymphomas: DLBCL, MCL, FL…
MALT lymphoma
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
B-cell monoclonality detection
Imunohistochemistry
Ig light chains
Molecular biology
PCR
IgH rearrangement
CDR III
B-cell monoclonality detection
Polyclonal IgH rearrangement
Monoclonal IgH rearrangement
It is often not possible to establish
a clear diagnosis in a single biopsy.
repeat the biopsy; sampling
MALT lymphoma/gastritis?
Large cell component?
Correct diagnosis and treatment
• Interdisciplinary communication
• Repeated biopsies
• Specialized methods
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
Gastric MALT lymphoma
Recurrent genetic abnormalities
• t(11;18)(q21;q21)/ API2-MALT1
usually the sole genetic abnormality, 25% of g.
MALT l., H. p. neg., no response to ATB
• t(14;18)(q32;q21)/ IgH-MALT1
non-gastric
• t(1;14)(p22;q32)/ IgH-BCL10; t(1;2)(p22;p12)
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“
Diffuse large B-cell lymphoma of the stomach
Diffuse large B-cell lymphoma of the stomach
;
Multiple lymphomatous polyposis
Mantle cell lymphoma
Follicular lymphoma
MALT lymphoma
Mantle cell lymphoma
 Multiple lymphomatous
polyposis
 M60
 bad prognosis
 imunohistochemistry
 genetics
WHO 2001
Mantle cell lymphoma
Mantle cell lymphoma
CD5
Cyclin D1
MALT? MCL?
FISH t(11;14)(q13;q32)
Lymphomatous polyposis:
follicular lymphoma g. 1 of the colon
M, 55, 2 polyps; stage IE, no therap, no disease 3 ys after the diagnosis
Follicular lymphoma of the colon
CD10
Follicular lymphoma of the colon
Bcl-2
Ki-67
F, 53-ys,“ileocaecal carcinoma“
follicular lymphoma stage IV,
7x CHOP; no disease detected
4 ys after the diagnosis
ileum
appendix
Bcl-2
Follicular lymphoma, ileocaecal
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, M=F
Enteropathy-associated T-cell lymphoma
Multifocal ulcers
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
Enteropathy-associated T-cell lymphoma
Anaplastic/pleomorphic
T-cells, plasma cells, eosinophils
Enteropathy-associated T-cell lymphoma
CD8
CD3
TCR gamma - PCR
ABI PRISM
TGGE
Enteropathy assoc. T-cell lymphoma
CGH marker: 9q gain (70%; Zettl 2007)
Molecular-genetic laboratory
Dept. of Pathol., Plzeň, Czech Republic