Nodal Marginal Zone B Cell Lymphoma
Definition
B cell neoplasm composed of small and medium sized cells that involves the mantle and marginal zones of peripheral lymph nodes
Alternate/Historical Names
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
Small B Cell Lymphomas
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%
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
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+
Clinical
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
Lists
Types of small B cell lymphoma
Bibliography
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.