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

Authors: Dorukhan Bahceci, M.D., Kwun Wah Wen, M.D., Ph.D.

Editorial Board Member: Catherine E. Hagen, M.D.

Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.

Last author update: 22 April 2021

Last staff update: 13 December 2023

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Table of Contents

Cite this page: Bahceci D, Wen KW. Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stomachMALT.html. Accessed April 26th, 2024.

Definition / general

Extranodal lymphoma composed of morphologically heterogeneous small B cells, including marginal zone (centrocyte-like) cells, cells resembling monocytoid cells, small lymphocytes and scattered immunoblasts and centroblast-like cells (Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017)

Essential features

Stomach is the most common site involved by MALT lymphoma
Most gastric MALT lymphomas associated with gastritis caused by Helicobacter pylori infection
Microscopic features: centrocyte-like cells, monocytoid cells, plasma cells, occasional large transformed lymphocytes, lymphoepithelial lesions, adjacent nonneoplastic germinal centers
Atypical features of lymphoid infiltrate help distinguish MALT lymphoma from reactive conditions, such as H. pylori gastritis (J Clin Pathol 2007;60:361)

Terminology

Also called MALToma

ICD coding

ICD-10: C88.4 - Extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma)

Epidemiology

7 - 8% of all B cell non-Hodgkin lymphomas (Leuk Lymphoma 2013;54:1891)
Median age: seventh decade
M:F = ~1:1
Up to 50% of primary gastric lymphomas
85 - 90% of all GI MALT lymphomas

Sites

Stomach (35%) is most common site of extranodal marginal zone lymphoma (Blood 2016;127:2082)
Ocular adnexa (13%)
Lung (9%)
Skin (9%)
Salivary glands (8%)

Etiology

Related to chronic inflammatory disorders driven by infectious agents or autoimmune stimuli (Blood 2016;127:2082)
Stomach: H. pylori associated gastritis
- H. pylori infection attracts B cells, T cells and neutrophils to the gastric mucosa; B cell proliferation is driven by reactive T cells, as well as by cytokines
- Chronic proliferative state of these B cells, as well as neutrophil mediated release of reactive oxygen species in areas of chronic inflammation, induces additional oncogenic events that eventually make lymphoproliferation independent of antigenic stimulation
- Additional genetic alterations can ultimately result in transformation to clinically aggressive diffuse large B cell lymphoma (Nat Rev Gastroenterol Hepatol 2010;7:336)

Clinical features

Can be asymptomatic or cause epigastric pain, anorexia, weight loss, anemia, early satiety, occasionally fever and night sweats
Most are low stage (stage I and II) at presentation
23 - 40% of patients may present with disseminated disease, involving other mucosal sites, lymph nodes or bone marrow (Blood 2000;95:802)
> 75% of cases will regress with successful treatment for H. pylori
Increased risk has been reported in patients with chronic hepatitis C virus (HCV) infection (Blood 2016;127:2082)

Diagnosis

Diagnostic workup includes endoscopic findings, histology with immunohistochemistry and molecular analysis

Prognostic factors

Indolent
Lugano staging system: most widely accepted staging system (UpToDate: Treatment of Extranodal Marginal Zone Lymphoma of Mucosa Associated Lymphoid Tissue (MALT Lymphoma) [Accessed 10 February 2021])
Recurrences may involve other extranodal sites
BIRC3-MALT1 translocation is associated with H. pylori treatment resistance
Histologic transformation, defined as an infiltration of 50% or more of large B cells, occurs in 8% of patients during the course of the disease (Mod Pathol 2013;26:182)

Case reports

32 year old man presented with epigastric pain of 6 months duration (BMC Gastroenterol 2002;2:6)
58 year old woman was referred with epigastric pain and 10 kg weight loss (Histopathology 1995;27:89)
72 year old woman presented with a 10 month history of intermittent epigastric discomfort without vomiting, anorexia or weight loss (J Clin Pathol 2002;55:548)

Treatment

H. pylori eradication - first line therapy (Gut 2012;61:507)
- Curative in majority of gastric MALT lymphomas
- Resolution can take up to 24 months
- Some primary gastric diffuse large B cell lymphomas may also respond to antibiotic eradication therapy alone
If H. pylori eradication therapy fails → second line therapy (Med Oncol 2010;27:291)
- Chemotherapy
- Radiation
Surgery: only necessary if complications (perforation, obstruction, bleeding) occur

Gross description

Large mass with or without ulcer
Diffusely thickened gastric wall
Polypoid lesions

Microscopic (histologic) description

Mass lesion with the following features
Sheets of neoplastic small lymphocytes
- Irregular / angulated nuclear contours with inconspicuous nucleoli (centrocyte-like)
- Relatively abundant pale cytoplasm (monocytoid appearance)
- Cells with plasmacytic differentiation
  - Clonally related to the small lymphocytes
  - ~33% of gastric lymphomas
  - Intranuclear (Dutcher bodies) or intracytoplasmic (Russell bodies) immunoglobulin inclusions can be seen
  - Nuclear polymorphism may be noted
- May see occasional transformed lymphocytes resembling centroblasts and immunoblasts
  - Larger nuclei with more open chromatin and prominent nucleoli
  - If solid or sheet-like proliferations of transformed cells → diffuse large B cell lymphoma (Arch Pathol Lab Med 2018;142:44)
Lymphoepithelial lesions (specific but not sensitive)
- Infiltration of gastric glands by neoplastic lymphocytes (> 3 centrocyte-like cells causing epithelial damage)
- Residual gastric glands are separated by the neoplastic lymphocytes
- Oxyphilic change (eosinophilic degeneration) of epithelial cells
- May lead to destruction of glands
Adjacent reactive germinal centers
- Neoplastic cell colonization may resemble follicular lymphoma
Amyloid deposition can be seen (Am J Clin Pathol 2012;137:51)
H. pylori gastritis associated changes can often be present in biopsies from patients
- Active or chronic inflammation
- Diffuse chronic monocytic infiltrate, microerosions, large lymphoid follicles and regenerative foveolar hyperplasia

Microscopic (histologic) images

Contributed by Kwun Wah Wen, M.D., Ph.D.

Dense lymphoplasmacytic infiltrate

Destruction of gastric glands

Focus of active inflammation

Marked plasmacytic differentiation

Lymphoepithelial lesion

Cytologic features of lymphoma cells

Diffusely positive for CD20

Numerous kappa restricted cells (κ:λ = > 8:1)

Rare lambda positive cells (κ:λ = > 8:1)

Low proliferative index

Positive stains

Neoplastic cells of MALT lymphoma: CD19, CD20, CD22, CD79a, CD43 variable, BCL2 (Arch Pathol Lab Med 2018;142:44)
Kappa / lambda: can be useful to demonstrate light chain restriction (especially if there are abundant neoplastic plasma cells)
Staining for CD21, CD23 and CD35 typically reveals disrupted and occasionally expanded meshwork of intermixed follicular dendritic cells, which may help to recognize colonized follicles
Keratin: can accentuate lymphoepithelial lesions
Congo red: can highlight amyloid deposition present in a subset of cases
MNDA staining: MALT (61 - 75%) versus follicular (< 10%) lymphoma (Am J Clin Pathol 2019;151:337)
IRTA1 antibody: potential MALT specific antibody

Negative stains

CD5, CD10 (rarely can be positive), BCL6, BCL1 / cyclin D1 (rules out mantle cell lymphoma) (Arch Pathol Lab Med 2018;142:44)

Molecular / cytogenetics description

PCR can help confirm clonally rearranged immunoglobulin genes in challenging cases (those that show no aberrant expression of CD43 and BCL2)
t(11;18)(q21;q21): BIRC3 (API2)-MALT1 (6 - 26%) (Haematologica 2019;104:e558)
- Associated with resistance to H. pylori eradication therapy
t(14;18)(q32;q21): IGH-MALT1 (1 - 5%)
t(1;14)(p22:q32): BCL10-IGH (not seen in gastric cases)
t(3;14)(p13;q32): FOXP1-IGH (not seen in gastric cases)
Trisomy 3 (11%)
Trisomy 18 (6%)
TNFAIP3 deletion / hypermethylation
Point mutations in Ig genes

Molecular / cytogenetics images

Images hosted on other servers:

t(11;18)(q21;q21) translocation

Sample pathology report

Gastric ulcers, biopsy:
- Extranodal marginal zone lymphoma (MALT lymphoma) (see comment)
- Comment: H&E sections of the biopsy show patchy involvement by a dense and atypical lymphoplasmacytic infiltrate with lymphoepithelial lesions. The background stomach shows chronic active gastritis. No carcinoma, dysplasia, Helicobacter organisms or intestinal metaplasia is present.
- Immunostains were performed and evaluated with the following results:
  - CD3: Highlights background small reactive T cells.
  - CD20: Highlights diffuse sheets of neoplastic B cells in some fragments.
  - CD21: Highlights rare residual dendritic cell meshworks underlying one lymphoid follicle.
  - Kappa: Highlights B cells and plasma cells with kappa restriction (kappa:lambda ratio > 8:1).
  - Lambda: Highlights a rare subset of B cells and plasma cells (kappa:lambda ratio > 8:1).
  - H. pylori: Negative.
  - CD5: Negative in B cells; positive in background T cells.
  - CD10: Negative in B cells.
  - CD43: Negative in B cells; positive in T cells.
  - BCL1: Negative for mantle cell lymphoma.
  - BCL2: Positive in B cells and T cells.
  - CD23: Negative in B cells.
  - Ki67: Low proliferative index.
  - AE1 / AE3: Negative for carcinoma.
- The above findings support the interpretation of extranodal marginal zone lymphoma in the stomach.

Differential diagnosis

Severe H. pylori gastritis / reactive lymphoid hyperplasia:
- No clonal B cell populations demonstrated by light chain restriction
- No sheets of monocytoid or monomorphous cell populations
- No abnormal plasma cells with nuclear irregularities
- No lymphoepithelioid lesions
CLL / SLL:
- May involve stomach, lymphocytosis and generalized lymphadenopathy
- Stains: CD5+, CD23+, LEF1+
Mantle cell lymphoma:
- Lymphocytes intermediate in size with irregular contours
- Stains: CD5+, cyclin D1 / BCL1+, SOX11+
Follicular lymphoma:
- Reactive germinal centers colonized by MALT can mimic follicular lymphoma (Surg Pathol Clin 2017;10:1021)
- Stains: CD10+, BCL6+, BCL2 variable
Lymphoplasmacytic lymphoma:
- Histologic and immunohistochemical features overlap; monocytoid B cells and centrocyte-like neoplastic cells are more common in gastric MALToma
- MYD88 L265P mutation, serum protein study
Russell body gastritis (J Clin Pathol 2006;59:1316):
- Polyclonal immunoreactive pattern to immunoglobulin light chains

Board review style question #1

You are asked to consult on a 55 year old patient with mucosa associated lymphoid tissue (MALT) lymphoma of the stomach. She is H. pylori positive. PET-CT does not show any other evidence of disease outside the stomach. The lesion is 5 - 6 cm and confined to fundus. A bone marrow biopsy is negative. Which of the following statements about MALT lymphoma is true?

Combination chemotherapy is used as the first curative approach
Gastric MALT may progress into diffuse large B cell lymphoma
H. pylori infection is associated with gastric MALT in a minority of cases
Most patients present with multi-organ involvement

Board review style answer #1

B. Gastric MALT may progress into diffuse large B cell lymphoma

Comment Here

Reference: MALT lymphoma

Board review style question #2

Which cytogenetic / molecular abnormality of gastric MALT lymphoma is associated with resistance to H. pylori antibiotic treatment?

t(11;18)(q21;q21): BIRC3-MALT1
t(14;18)(q32;q21): IGH-MALT1
TNFAIP3 deletion / hypermethylation
Trisomy 3

Board review style answer #2

A. t(11;18)(q21;q21): BIRC3-MALT1

Comment Here

Reference: MALT lymphoma

Board review style question #3

Which of the following is true regarding MALT lymphoma of the stomach?

Evidence of H. pylori infection should only be sought in the presence of symptoms, such as dyspepsia, bloating, nausea
Lymphomas with sheets of large cells should be diagnosed as high grade MALT lymphoma
Neoplastic lymphocytes are positive for CD5 and cyclin D1
Neoplastic lymphocytes ranging from small lymphocytic to monocytoid cells infiltrating into epithelial structures are characteristic for gastric MALT lymphoma

Board review style answer #3

D. Neoplastic lymphocytes ranging from small lymphocytic to monocytoid cells infiltrating into epithelial structures are characteristic for gastric MALT lymphoma

Comment Here

Reference: MALT lymphoma

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