Transcript Gastrointestinal MALT Lymphoma

GASTROINTESTINAL
MALT LYMPHOMA
Scott R. Owens, M.D.
[email protected]
Unique to GI
Or at least things that make it interesting….
• Our “gross” is often the endoscopist’s description
• We are often (usually) dealing with very small
pieces of tissue
• The GI tract is rife with inflammatory conditions
that can result in lymphoproliferative disorders…
and confound our diagnosis of them
• The GI tract is also rife with normal populations of
lymphoid tissue that can give rise to
lymphoproliferative disorders…and confound our
diagnosis of them!
Why lymphoma?
• Primary GI lymphoproliferative disorders are fairly
uncommon
• About 1-4% of GI tumors
• But…the GI tract is the most common extranodal site of
lymphoma
• 4-20% of non-Hodgkin lymphoma
• B-cell lymphoma most common
• And…the development of lymphoma can complicate other
disorders
GI Lymphoma Facts
• Distribution
• Stomach
• Primary site in 55-65%
• 1-7% of all gastric malignancies
• Small intestine
• Primary site in 20-35%
• About 25% of small intestinal malignancies
• Large intestine
• Primary site in 7-20%
• About 0.5% of colonic malignancies
• Other sites
• Liver
• Appendix
Distribution of GI Lymphoma
55-65%
20-35%
7-20%
Courtesy of Dr. Alyssa Krasinskas
What is MALT?
• Definition:
• Extranodal marginal zone lymphoma of mucosa-associated
lymphoid tissue (MALT)
• Heterogeneous, predominantly small B-lymphocytes
• Includes centrocyte-like cells, monocytoid cells, scattered larger cells
(immunoblast- and/or centroblast-like)
• Some cases have plasma cell differentiation
• The lymphoepithelial lesion (LEL) is a hallmark
MALT Mania
• Epidemiology
• About 7-8% of all B-cell lymphomas
• GI tract is most common site
• About 50% of primary gastric lymphomas
• 85% of GI MALTs are in the stomach
• Median age 61 years
• Females > males (1.2:1)
• Associated with chronic inflammatory conditions
• Autoimmune, infectious
• Often seen with Helicobacter pylori in the stomach
• A lymphoma of acquired MALT (as opposed to preexisting MALT like Peyer’s patches)
More MALT
• Clinical features
• Majority present with low-stage disease
• Bone marrow often uninvolved in GI cases
• M-proteins are rare, despite relatively frequent
plasmacytic differentiation
• In immunoproliferative small intestinal disease (IPSID), a
subtype of MALT, a paraprotein is usually found
• Etiology
• Activated T-cells (e.g., by H. pylori antigens) are thought
to be essential to B-cell proliferation
Marginal zone
MALT Morphology
Mantle zone
Germinal center
• Morphology
• Reactive B-cell follicles with surrounding, expanded
“marginal zones” of neoplastic cells (analogous to
Peyer’s patches)
• Neoplastic cells infiltrate mucosa widely, creating LELs
• Defined as at least three neoplastic cells, causing epithelial
damage
• While usually easily found, LELs are not (on their own)
diagnostic of MALT lymphoma/EMZL
• Small/medium-sized lymphocytes with irregular nuclei
(resembling centrocytes) and relatively abundant cytoplasm
• More cytoplasm gives a “monocytoid” appearance
More MALT Morphology
• Morphology (cont.)
• Cells may also be smaller, with less abundant
cytoplasm
• Plasma cell differentiation present (in varying
degree) in about 1/3 of cases
• Often most pronounced in the “superficial” (i.e.,
luminal) part of the mucosa
• Can be focal/scattered, or predominant (raising the
differential diagnosis of extramedullary plasmacytoma
and/or lymphoplasmacytic lymphoma (LPL)
• While plasmacytic differentiation is fairly common,
paraproteins are not
MALT Madness
• Morphology (cont.)
• May colonize follicles, mimicking FL, or be
diffuse
• Large/transformed (centroblast- or
immunoblast-like) cells can vary in number
• If infiltrate is diffuse and predominantly large cells, the
appropriate diagnosis is DLBCL
• Report low-grade MALT lymphoma component, if present
• IPSID
• Similar, but usually with more pronounced plasma cell
component (and a paraprotein, often)
MALT Markers
• Immunophenotype
• IgM (less often IgG or IgA) positive with lightchain restriction (on flow cytometry)
• Immunohistochemical evidence of light chain
restriction mostly associated with plasmacytic
differentiation
• IPSID has α-heavy chain expression
• Positive: CD20, CD79a, CD43+/-, CD21, CD35
• CD43 + in about 1/3-1/2 of cases
• Negative: CD5, CD10, CD23
• Bottom line: no specific MALT/EMZL marker
Molecular MALT
• Genetics
• t(11;18)(q21;q21)
• API2/MALT1 gene fusion
• ~25% of gastric MALT lymphomas
• t(1;14)(p22;q32)
• BCL10 deregulated by coming under control of Ig gene
• Some intestinal MALT lymphomas
• t(14;18)(q32;q21)
• MALT1/Ig fusion
• <5% of gastric MALT lymphomas
• Trisomy 3, 12, 18 (often associated with t(1;14)
• p53 mutation; methylation of p15 and p16 promoters
• Mutations of fas
• Owens SR, Smith LB. Molecular aspects of H. pylori-related MALT lymphoma. Patholog
Res Int. 2011 Jan 24;2011:193149.
Lymphoepithelial lesions
Near total destruction of gland
Infiltration by few neoplastic lymphocytes
“Monocytoid” B-cells
“Naked” germinal centers
“Naked” germinal center
surrounded by lymphoma
cells
Dutcher body
MALT lymphoma with extensive
plasmacytic differentiation