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 lymphomasType B

DLBCL, MALT

MCL, FL T

EATLSite 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

ArchitectureCytologyImmunophenotype

MALT lymphomamonocytoid B-cells

(centrocyte-like, small lymphocytes) plasma cells, Dutcher bodies

MALT lymphomaLEL

MALT lymphoma epithelium: LEL, eosinophilic change

MALT lymphoma - LEL (CD20)

MALT lymphoma

Immunohistochemistry

No specific MALT lymphoma markerPositivity: CD20, CD79a; Ig light chains; Ig

heavy chains: IgM; CD43Negativity: 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 problemsLarge blasts (< 10%)

Ki-67

MALT lymphoma - diagnostic problemsFollicular colonization

Bacon J Clin Path 06

MALT lymphoma

Differential diagnosis

HP gastritis

other lymphomas: DLBCL, MCL, FL…

Integrated approachfavoring MALT lymphoma:dense lymphoid infiltrate prominent LELDutcher bodiesinfiltration of muscularis mucosaeatypia of lymphoid cellsB - cell monoclonality

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 chainsMolecular biology

PCR

IgH rearrangement

CDR III

B-cell monoclonality detection

Monoclonal IgH rearrangement

Polyclonal 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 lymphomaRecurrent 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 novotransformation of a low-grade lymphoma

clonal progression in timeIndependent 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

M60 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

Bcl-2ileum

appendix

Follicular lymphoma, ileocaecal

Enteropathy-associated T-cell lymphoma

Proximal jejunum Very rare x most common GI T-cell lymphoma

Acute abdomen (40%) – emergency surgeryObstruction/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

TGGE

ABI PRISM

Enteropathy assoc. T-cell lymphoma

CGH marker: 9q gain (70%; Zettl 2007)

Molecular-genetic laboratoryDept. of Pathol., Plzeň, Czech Republic