Extranodal Marginal Zone B-cell Lymphoma (MALT Lymphoma)



Extranodal Marginal Zone B-cell Lymphoma (MALT Lymphoma)


Pei Lin, MD





Key Facts


Etiology/Pathogenesis



  • Infectious agents are implicated in pathogenesis of MALT lymphomas at specific sites



    • Helicobacter pylori: Stomach


    • Campylobacter jejuni: Intestine


    • Chlamydia psittaci: Ocular adnexa


    • Borrelia burgdorferi: Skin


  • Autoimmune diseases are implicated in pathogenesis of MALT lymphomas at specific sites



    • Sjögren syndrome: Salivary glands and lung


    • Hashimoto thyroiditis: Thyroid gland


Microscopic Pathology



  • MALT lymphomas share common features



    • Marginal zone pattern surrounding reactive follicles


    • Heterogeneous cell population


    • ± lymphoepithelial lesions


Ancillary Tests



  • CD20(+), CD22(+), CD79a(+), pax-5(+)


  • Monotypic Ig(+), Bcl-2(+), CD43(+/-), Ki-67 low


  • Recurrent translocations identified in 30-40% of MALT lymphomas


  • 4 common translocations



    • IAP2-MALT1/t(11;18)(q21;q21)


    • IgH-MALT1/t(14;18)(q32;q21)


    • FOXP1-IgH/t(3;14)(p14.1;q32)


    • BCL10-IgH/t(1;14)(p22;q32)


Top Differential Diagnoses



  • Reactive hyperplasia


  • Mantle cell lymphoma


  • Follicular lymphoma


  • Plasmacytoma







MALT lymphoma involving small intestine. The neoplastic infiltrate is diffuse. A few residual germinal centers image are present. The villi are blunted.






MALT lymphoma involving small intestine. The neoplastic cells are predominantly small, and many cells have pale, monocytoid cytoplasm.


TERMINOLOGY


Abbreviations



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


Synonyms



  • Low-grade B-cell lymphoma of MALT


  • MALToma


Definitions



  • Low-grade B-cell lymphoma arising at extranodal sites, presumably in marginal zone of reactive follicles


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • Implicated in pathogenesis of MALT lymphomas



    • Helicobacter pylori



      • Gastric marginal zone lymphoma


    • Campylobacter jejuni



      • Immunoproliferative small intestinal disease; also known as α heavy chain disease


    • Chlamydia psittaci



      • Ocular adnexal marginal zone lymphoma


    • Borrelia burgdorferi



      • Cutaneous marginal zone lymphoma


      • More common in Europe


Autoimmune Disorders



  • 2 autoimmune diseases have been implicated in pathogenesis of MALT lymphomas



    • Sjögren syndrome



      • MALT lymphomas of parotid gland and lung


    • Hashimoto thyroiditis



      • Thyroid MALT lymphoma


Chromosomal Translocations



  • Identified in 30-40% of MALT lymphomas


  • Result in NF-κB pathway activation resulting in enhanced cell survival and proliferation and impaired apoptosis


MALT Lymphomas Without Chromosomal Translocations



  • Possible role for antigen drive



    • Chronic antigen stimulation via infection or autoimmune disease



      • Leads to accumulation of extranodal lymphoid tissue


      • Polyclonal B-cell population evolves to oligoclonal and then monoclonal B-cell population


  • No central role for NF-κB activation


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 7-8% of all B-cell non-Hodgkin lymphomas


  • Age



    • Median: 61 years


  • Gender



    • Female predominance


Presentation



  • Subset of patients are asymptomatic


  • Symptoms are related to organ involved



    • Stomach: Anemia, weight loss, and pain are common


    • Lung: ± cough and dyspnea


    • Mass and related symptoms in other locations


Treatment



  • Stomach MALT lymphoma: Antibiotics to eradicate H. pylori



    • Chemotherapy ± radiation if transformed to large B-cell lymphoma or disseminated


  • Ocular adnexa




    • MALT lymphoma often stage IE and is treated by radiation alone


  • Other sites



    • Chemotherapy &/or radiation therapy depending on



      • Site, size, and stage


Prognosis



  • Stomach MALT lymphoma



    • Lymphoma can regress after eradication of H. pylori by antibiotics; true in ˜ 75% of cases


    • t(11;18)(q21;q21) is associated with resistance to antibiotics


    • < 10% of cases transform to diffuse large B-cell lymphoma


    • 5-year overall survival is ˜ 90%


    • 25-35% relapse rate in stomach or other extranodal sites


  • Other sites of MALT lymphoma



    • Disseminated disease is more common


    • Higher relapse rate


IMAGE FINDINGS


Radiographic Findings



  • Single or multiple masses


  • Lung(s) involved by MALT lymphoma ± consolidation


Endoscopic Findings



  • Gastric or intestinal MALT lymphoma: ± mass, ulcer, or bleeding


MICROSCOPIC PATHOLOGY


Histologic Features



  • Diffuse or nodular pattern of growth


  • Expansion of marginal zone by cytologically heterogeneous cell population



    • Predominantly centrocyte-like cells with small irregular nuclei


    • Monocytoid appearance with distinct rim of clear cytoplasm


    • Scattered large cells (centroblasts or immunoblasts) are present; up to 10% of all cells


    • ± plasmacytoid differentiation; ± Dutcher bodies


  • Hyperplastic lymphoid follicles are common



    • ± colonized by lymphoma imparting nodular pattern


  • Lymphoepithelial lesions are common in epithelial tissues involved by MALT lymphoma



    • Infiltration and distortion of epithelial structures by 3 or more neoplastic lymphoid cells


    • Epithelial degeneration and glandular structure destruction


    • Most prominent in thyroid and parotid glands


  • Transformation to diffuse large B-cell lymphoma



    • Large cells form sheets or large clusters of > 20 cells


    • May coexist with MALT lymphoma at initial presentation


  • Multifocal disease



    • ˜ 25% of patients have > 1 extranodal site of involvement


Cytologic Features



  • FNA smears show polymorphous cell population



    • Small round or irregular lymphocytes, variable numbers of large cells &/or plasma cells


Lymph Nodes



  • Involvement is indistinguishable from nodal marginal zone B-cell lymphoma



    • Usually lymph nodes draining primary site of disease are involved


    • Distant lymph nodes involved in < 10% of patients


Bone Marrow



  • 10-20% of patients with MALT lymphoma have bone marrow disease at staging


  • Paratrabecular &/or nonparatrabecular aggregates



    • Follicular dendritic cells commonly present in aggregates


  • Sinusoidal pattern highly unusual



Skin



  • Most common B-cell lymphoma of skin


  • Follicular colonization can be prominent; these lesions closely mimic follicular lymphoma


Ocular Adnexal Region



  • Includes orbital soft tissue, conjunctiva, and lacrimal gland


  • MALT is most common type of lymphoma at this location


Lung



  • Lymphoepithelial lesions common in MALT lymphoma and lymphocytic interstitial pneumonitis


  • Circumscribed mass supports diagnosis of MALT lymphoma


Salivary Gland



  • Arises in background of myoepithelial sialadenitis (MESA)


  • Lymphoepithelial lesions (epithelial-myoepithelial islands) common in MALT lymphoma and MESA


  • Concentric zones of pale cells around ducts are helpful clue for MALT lymphoma


Thyroid Gland



  • Arises in background of Hashimoto thyroiditis


  • Lymphoepithelial lesions common in both MALT lymphoma and Hashimoto thyroiditis


  • Lymphoma cells within follicles tend to be centrocyte-like cells


  • Lymphoma cells outside follicles often are extremely plasmacytic


Breast



  • Lymphoepithelial lesions are uncommon at this site


  • Can arise in or be disseminated to breast


Other MALT Lymphoma Sites



  • Very wide range of body sites can be involved



    • Dura, soft tissues, thymus, gallbladder, kidney, bladder


ANCILLARY TESTS


Immunohistochemistry



  • CD19(+), CD20(+), CD22(+), CD79a(+), pax-5(+)


  • IgM(+) > IgA(+) > IgG(+)


  • Monotypic Ig light chain(+); best seen in plasmacytoid cells


  • Bcl-2(+), CD43(+/-), Bcl-10(+/-)


  • Ki-67(MIB-1) is low; high in residual reactive germinal centers


  • IgD(-) but demonstrates intact follicular IgD(+) mantle zones


  • CD21 highlights follicular dendritic cell (FDC) meshworks in follicles



    • Meshworks are disrupted by follicular colonization


  • Cytokeratin(-); useful for highlighting lymphoepithelial lesions


  • CD10(-), Bcl-6(-), Cyclin-D1(-)


  • T-cell antigens(-), EBV-LMP1(-)


Flow Cytometry



  • Monotypic surface Ig light chain(+)


  • FMC7(+), CD11c(+/-), CD23(-/+), CD25(-), CD103(-)


Cytogenetics

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Extranodal Marginal Zone B-cell Lymphoma (MALT Lymphoma)

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