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  • Surgical Pathology Criteria

    Nodal Marginal Zone B Cell Lymphoma


    • B cell neoplasm composed of small and medium sized cells that involves the mantle and marginal zones of peripheral lymph nodes

    Alternate/Historical Names

    • Monocytoid lymphoma

    Diagnostic Criteria

    • Biphasic population with mantle and marginal zone distribution
      • Small round lymphocytes surround and replace follicles
      • Medium sized cells with clear cytoplasm in surrounding marginal zone
        • Scattered large blasts may be intermixed
      • Occasional features
        • Plasmacytoid differentiation
        • Epithelioid histiocytes
    • Marginal zone type lymphocytes may be numerous
      • Small cells with clear cytoplasm
    • Marrow and peripheral blood may be involved
    • Lacks specific markers of other small cell lymphomas
      • Negative to infrequent for CD23, bcl1, CD5, CD10
      • Positive for B lineage markers and bcl2
      • No specific positive immunologic marker
        • Immunologically, a diagnosis of exclusion
    • Lacks involvement of extranodal tissues
    • Transformation to large B cell lymphoma may occur

    Yasodha Natkunam MD PhD
    Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting:: May 1, 2006

    Supplemental studies

    Immunohistology and Flow Cytometry

    • B lineage 100%
    • Immunoglobulin light and heavy chains variably detectable
      • More frequently detectable in plasmacytoid cases
      • IgD reported in some cases
    • CD23 8%
    • CD5 negative
    • CD43 35%
    • bcl1 negative
    • CD10 2%
    • bcl2 65-90%
    • bcl6 negative
    • Cases with transformation to diffuse large cell lymphoma maintain CD5 and CD10 negativity
    • CD138 can be extensive if plasmacytoid differentiation is prominent


    Differential Diagnosis

    Extranodal vs. Nodal vs. Splenic Marginal Zone Lymphomas

    • Extranodal involvement takes precedence in separation of the three types
      • Mixed types are designated as extranodal with nodal or splenic involvement
    • Nodal type must lack extranodal involvement
    • Splenic type must lack both extranodal and peripheral nodal involvement
      • Splenic hilar nodes may be involved
    • Genetic abnormalities are incompletely studied but support the above separation
      Extranodal Nodal Splenic
    7q21-32 loss rare rare 40%
    trisomy 3 60% rare 17%
    t(11;18) 25-50% rare 0%


    Small B Cell Lymphomas
      SLL/CLL Mantle Marginal Zone Lymphoplasmacytic Follicular
    CD23 85% 2% 8% 0-30% on immunohistology but up to 60% weak positive on flow 0-25%
    CD5 80% 80% 0% 5% 0%
    bcl1 2% 85% 0% 0% 0%
    CD10 0% 2% 2% 3% 85%
    CD43 80% 85% 35% 10-30% 7%
    bcl2 95% 95% 65-90% >50% 90%
    • CD23 staining refers to lymphoid staining
      • Follicular dendritic cells stain in many processes
    • bcl1
      • Blastic mantle cell lymphoma 100%
      • Hairy cell leukemia 41%
    • CD43 stains only 2% of splenic marginal zone lymphoma


    Nodal Marginal Zone Lymphoma SLL/CLL
    Nodular pattern with prominent marginal zone Diffuse effacement
    Polymorphous cell population Uniform small round lymphocytes
    May have residual germinal centers Proliferation centers frequent
    CD23 8% CD23 85%
    CD5 negative CD5 80%
    CD43 35% CD43 80%


    Nodal, Extranodal and Splenic Marginal Zone Lymphoma Lymphoplasmacytic Lymphoma
    Enlarged marginal zone Diffuse effacement
    Pale monocytoid cells No monocytoid population
    • No useful distinguishing immunologic markers
    • Marginal zone lymphomas are frequently plasmacytoid; this combined with the lack of a definitive marker can make this distinction difficult
    • The distinction is sometimes suggested by the propensity to involve mucosal sites by extranodal marginal zone lymphoma


    Nodal, Extranodal and Splenic Marginal Zone Lymphoma Mantle Cell Lymphoma
    Enlarged marginal and mantle zones Enlarged mantle zone frequent
    Polymorphous population Uniform small lymphocytes
    bcl1 negative bcl1 85%
    CD25 negative CD25 30%
    CD5 negative CD5 80%
    CD43 35% (Splenic 2%) CD43 85%
    • Both may involve the GI tract and other mucosal sites in extranodal cases.
    • Enlarged marginal and mantle zones may be hard to distinguish


    Nodal Marginal Zone Lymphoma Follicular Lymphoma
    Polymorphous population Uniform population of atypical small lymphocytes
    Centers of nodules may contain bcl2 negative residual germinal centers Centers of nodules composed of bcl2 positive small atypical lymphocytes
    Plasmacytoid differentiation frequent Plasmacytoid differentiation rare
    CD10 2% CD10 85%
    • Both usually express bcl2 in the neoplastic cells
    • Cases with combined features are occasionally seen


    Nodal, Extranodal and Splenic Marginal Zone Lymphoma Mast Cell Disease
    B lineage markers positive B lineage markers negative
    Toluidine blue, Giemsa stains negative Toluidine blue, Giemsa stains positive
    CD117, tryptase immuno stains negative CD117, tryptase immuno stains positive
    Pale marginal zone cells may simulate mast cells


    Nodal, Extranodal and Splenic Marginal Zone Lymphoma Marginal Zone Hyperplasia
    Monocytoid cells may be prominent No monocytoid population
    Light chain monotypia variably demonstrable No monotypia
    Clonal Ig gene rearrangement No clonal rearrangement
    Coexpression of CD43 by B cells 35% No CD43 coexpression
    Sheets of B cells Distinct B and T cell zones


    Nodal, Extranodal and Splenic Marginal Zone Lymphoma with Large Cell Transformation Sporadic Diffuse Large B Cell Lymphoma
    Prior or concurrent specimen with typical marginal zone lymphoma No evidence of typical marginal zone lymphoma
    CD5 negative CD5 10%
    CD10 2% CD10 25-50%
    bcl6 negative bcl6 60%
    Both may involve the GI tract and other mucosal sites


    Plasmacytoma / Myeloma Lymphoplasmacytic Lymphoma and Nodal, Extranodal and Splenic Marginal Zone Lymphomas
    Plasma cells may be pleomorphic or plasmablastic Plasma cell component usually not markedly atypical
    Uniform plasma cell morphology Plasma cells mixed with small lymphocytes
    IgG or IgA M component most common IgM or IgG M component most common
    CD20 often negative CD20 80%
    Uniformly CD138 positive Scattered CD138 positive cells
    Often CD56+, CD19-, CD45- CD56-, CD19+, CD45+


    • Mean age 60's, rare before 30
    • Involves peripheral lymph nodes
      • May involve marrow and peripheral blood
      • May involve spleen
    • Incidence
      • Approximately 1-3% of lymphomas
    • Few cases studied but appears to have indolent behavior

    Grading / Staging / Report

    • While staging is linked to prognosis, it does not generally determine therapy
      • Therapy generally determined by clinical signs and symptoms
    • Pathologic staging is usually limited to bone marrow biopsy and biopsies of other sites to confirm clinical evidence of involvement

    Ann Arbor Staging System

    • Stage I
      • I if involvement of a single lymph node region
      • IE if involvement of a single extralymphatic organ or site
    • Stage II
      • II if two or more lymph node regions on same side of diaphragm
      • IIE if localized involvement of an extralymphatic organ or site and one or more lymph node regions on the same side of the diaphragm
    • Stage III
      • III if Involvement of lymph node regions on both sides of the diphragm
      • IIIS if spleen involved
      • IIIE if extralymphatic site involved
    • Stage IV
      • Diffuse or disseminated involvement of one or more extralymphatic organs or tissues, with or without associated lymph node involvement
    • Systemic Symptoms in 6 months preceding admission
      • Fever, night sweats, 10% weight loss
      • A = absent
      • B = present
    • Extranodal sites are also designated
      • M+ = marrow
      • L+ = lung
      • H+ = liver
      • P+ = pleura
      • O+ = bone
      • D+ = skin and subcutaneous tissue
    • Although originally designed for Hodgkin lymphoma, the Ann Arbor System is also used for non-Hodgkin lymphomas.

    The pathology report should contain the following information:

    • Diagnosis in the World Health Organization (WHO) classification
      • Equivalent diagnosis in other classifications used by relevant clinicians
    • Results of supplementary studies if performed
    • Relationship to other specimens from the same patient
    • Information relevant to staging if available
    • If present, comment on transformation



    Types of small B cell lymphoma


    • Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF . Tumors of the Lymph Nodes and Spleen, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 14, 1995
    • Jaffe ES, Harris NL Stein H, Vardiman JW eds. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, World Health Organization Classification of Tumours 2001
    • Kojima M, Nakamura S, Murase T, Motoori T, Murayama K, Iijima M, Itoh H, Sakata N, Masawa N. Follicular colonization of nodal marginal-zone B-cell lymphoma resembling follicular lymphoma: report of 6 cases. Int J Surg Pathol. 2005 Jan;13(1):73-8.
    • Campo E, Miquel R, Krenacs L, Sorbara L, Raffeld M, Jaffe ES. Primary nodal marginal zone lymphomas of splenic and MALT type. Am J Surg Pathol. 1999 Jan;23(1):59-68.
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