Ken’s Pathology Guide

Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT)

Epidemiology / Etiology:

7-8% of B cell lymphomas
adults (median 61y)
Northeast Italy
Middle East (IPSID)
Cape region of South Africa (IPSID)
often history of chronic inflammatory or autoimmune disorder

H. pylori gastritis
Sjogren syndrome
Hashimoto’s thyroiditis (70x risk of developing primary thyroid lymphoma)
Lymphoepithelial sialadenitis (LESA)
Borrelia burgdorferi in some cases of cutaneous MALT

Common Sites:

GI tract (50% of MALTs)

stomach (50% of primary gastric lymphoma)
small intestine (immunoproliferative small intestinal disease – IPSID)
colon (IPSID)

lung
head and neck
ocular adnexae
skin
thyroid
breast
bone marrow (20% of MALT patients)

Gross features:

may be multifocal extranodal sites (up to 10%)

Histologic features:

reactive follicles

preserved mantle
expanded marginal zone that form confluent areas that eventually overrun some or most follicles
follicular colonization by lymphoma cells may be present (differentiate from follicular lymphoma)

lymphoepithelial lesions

epithelium invaded and destroyed

often with eosinophilic degeneration of epithelial cells

discrete aggregates of lymphoma cells (3 or more required)

marginal zone B cells (centrocyte like) :

small to medium
slightly irregular nuclei

moderately dispersed chromatin
inconspicuous nucleoli

relatively abundant pale cytoplasm (monocytoid appearance with more cytoplasm)

might not be present – may more closely resemble small lymphocytes

plasmacytic differentiation (33% of gastric, constant feature in thyroid and IPSID)
large transformed cells present (but minority)

not in solid or sheet-like formations (then it is DLBCL with MALT present)
centroblast-like
immunoblast-like

in gastric type:

small foci of lymphoma may be found throughout the gastric mucosa at various distances from the main confluent tumour mass and each other

1-4 lymphoid follicles surrounded by neoplastic marginal zone B cells

This may contribute to local relapse when resection margins are negative

lymph nodes:

expansion of marginal zone
interfollicular expansion
monocytoid B cells in a parafollicular and perisinusoidal distribution

grading:

low-grade:
high-grade:

with or without a low-grade component

Immunophenotype:

Marker:	Sensitivity:	Specificity:
sIg
IgM > IgA > IgG restriction	“typically” not in IPSID (no light chain)
sIgD (neg)
cIg	-/+
Pan-B (CD20, CD79a, etc)
CD5 (neg)	Some are +
CD10 (neg)
CD23 (neg)
CD43	-/+	Note: CD43 may be expressed in normal marginal zone B-cells in reactive lesions of the terminal ileum (Peyer’s patches), tonsils, myo/lymphoepithelial sialoadenitis, atypical marginal zone hyperplasia (children).
CD11c	+/-
CCND1 (neg)
Bcl-2

Molecular features:

Rearrangement of immunoglobulin heavy (IgH) and light chain genes (IgL)

Somatic hypermutation of variable regions

trisomy 3 (30%) (intestinal, salivary gland, orbital especially)

nonspecific
also rearrangements leading to gains of 3q

trisomy 18 (30%) (intestinal, salivary gland, orbital especially) (poor prognosis maybe)

nonspecific
also rearrangements leading to gains of 18q

rearrangements leading to gains of 9q
del(6)(q_q_) involving TNFAIP3 (A20) (ocular)
all recurrent translocations target the same cellular complex that links B-cell receptor signaling to activation of NFKB
t(11;18)(q21;q21) (API2-MALT1) (25-50%) (pulmonary/gastric mainly)(specific)

API2 / MALT1 fusion gene
API2 is an apoptosis-inhibitor
Imparts RESISTANCE to anti-H.pylori therapy in gastric MALT
Hardly ever associated with cytogenetically detectable secondary aberrations
Restricted to low-grade MALT, i.e. not transformed

t(14;18)(q32;q21) (IGH-MALT1) (11%) (ocular/orbit/salivary mainly) (same cytogenetic bands as IGH/BCL2)

dysregulates MALT1 gene by juxtaposing it next to IGH
may be found in transformed or high-grade lymphomas involving MALT

t(1;14)(p22;p32) (IGH-BCL10) (< 2%)

highly conserved set of secondary events associated:

+3, +12, +18

may be found in transformed or high-grade lymphomas involving MALT
may lower probability of response to antibiotics

t(3;14)(p14.1;q32) (IGH-FOXP1) (thyroid/ocular adnexae/orbit/skin mainly)

DLBCL and other B cell neoplasms

NEGATIVE for t(14;18) (IGH/BCL2), t(11;14)
Progression associated changes:

8q amplifications involving MYC
Del(17p) involving TP53
Del(9p) involving CDKN2A

Other features:

majority present with stage I or II disease
indolent course

transformation to DLBCL may occur

H. pylori therapy may induce protracted remissions in gastric MALT

T(11;18) is RESISTANT to this therapy

Broad-spectrum antibiotics may induce remissions of IPSID
serum paraprotein is rare except in IPSID
most IPSID patients have alpha heavy chain in peripheral blood
radiosensitive
multiple sites and bone marrow involvement do not confer a worse prognosis
extragastric MALT is more likely to recur

References:

WHO Blue Book (2001, 2008)
Heim & Mitelman, Cancer Cytogenetics (2009)
Garcia CF, Swerdlow SH. Best Practices in Contemporary Diagnostic Immunohistochemistry: Panel approach to hematolymphoid proliferations. Arch Pathol Lab Med 2009;133:756-764.
Lee PS, Beneck D, Weisberger J, Gorczyca W. Coexpression of CD43 by benign B-cells in the Terminal Ileum. Applied Immunohistochemistry & Molecular Morphology 2005;13(2):138-141.