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 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
MALT lymphoma
Macroscopy: often noncharacteristic Microscopy: Wotherspoon criteria - spectrum 0 normal mucosa 1chronic active gastritis 2chronic active gastritis with lymphoid follicles 3suspicious lymphoid infiltrate, probably reactive 4suspicious lymphoid infiltrate, probably lymphoma 5MALT lymphoma
B-cell monoclonality detection Imunohistochemistry Ig light chains Molecular 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 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
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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
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 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 CD8CD3
TCR gamma - PCR TGGE ABI PRISM Enteropathy assoc. T-cell lymphoma CGH marker: 9q gain (70%; Zettl 2007)
Molecular-genetic laboratory Dept. of Pathol., Plzeň, Czech Republic