Gastrointestinal MALT Lymphoma

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Gastrointestinal MALT Lymphoma

• Scott R. Owens, M.D.
• srowens_at_med.umich.edu

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Unique to GIOr at least things that make it
interesting.

• Our gross is often the endoscopists
  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 disordersand confound our
  diagnosis of them!

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Why lymphoma?

• Primary GI lymphoproliferative disorders are
  fairly uncommon
• About 1-4 of GI tumors
• Butthe GI tract is the most common extranodal
  site of lymphoma
• 4-20 of non-Hodgkin lymphoma
• B-cell lymphoma most common
• Andthe development of lymphoma can complicate
  other disorders

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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

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Distribution of GI Lymphoma
Courtesy of Dr. Alyssa Krasinskas
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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

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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 gt males (1.21)
• Associated with chronic inflammatory conditions
• Autoimmune, infectious
• Often seen with Helicobacter pylori in the
  stomach
• A lymphoma of acquired MALT (as opposed to
  pre-existing MALT like Peyers patches)

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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

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MALT Morphology
Marginal zone
Mantle zone
Germinal center

• Morphology
• Reactive B-cell follicles with surrounding,
  expanded marginal zones of neoplastic cells
  (analogous to Peyers 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

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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

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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)

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MALT Markers

• Immunophenotype
• IgM (less often IgG or IgA) positive with
  light-chain restriction (on flow cytometry)
• Immunohistochemical evidence of light chain
  restriction mostly associated with plasmacytic
  differentiation
• IPSID has a-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

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Molecular MALT

• Genetics
• t(1118)(q21q21)
• API2/MALT1 gene fusion
• 25 of gastric MALT lymphomas
• t(114)(p22q32)
• BCL10 deregulated by coming under control of Ig
  gene
• Some intestinal MALT lymphomas
• t(1418)(q32q21)
• MALT1/Ig fusion
• lt5 of gastric MALT lymphomas
• Trisomy 3, 12, 18 (often associated with t(114)
• 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 242011193149.

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Lymphoepithelial lesions Near total destruction
of gland Infiltration by few neoplastic
lymphocytes
Monocytoid B-cells
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Naked germinal centers
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Naked germinal center surrounded by lymphoma
cells
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Dutcher body
MALT lymphoma with extensive plasmacytic
differentiation