Stains & CD markers
MEF2B
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PubMed Search: MEF2B stain
MEF2B
Editorial Board Members: Brandon Umphress, M.D., Anamarija M. Perry, M.D.
Last author update: 14 August 2023
Last staff update: 20 May 2024
Copyright: 2022-2024, PathologyOutlines.com, Inc.
PubMed Search: MEF2B stain
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Interpretation | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Sample pathology report | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Bosch-Schips J, Schürch CM. MEF2B. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsMEF2B.html. Accessed December 29th, 2024.
Definition / general
- MEF2B (myocyte specific enhancer factor 2B) is located on chromosome 19p13.11 and encodes a calcium regulated gene member of the MADS / MEF2 family of DNA binding proteins actively involved in regulation of gene expression
Essential features
- MEF2B (myocyte specific enhancer factor 2B) is a member of the MADS / MEF2 family of DNA binding proteins
- MEF2B lies in close relation to BCL6 in germinal center (GC) development and can act as an oncogene in lymphomagenesis
- MEF2B staining reliably distinguishes nodular lymphocyte predominant B cell lymphoma / NLPHL (MEF2B+) from classic Hodgkin lymphoma (MEF2B-)
Terminology
- MEF2B (myocyte specific enhancer factor 2B)
Pathophysiology
- Member of the MADS / MEF2 family of DNA binding proteins
- Involved in smooth muscle myosin heavy chain (SMMHC) gene regulation (Am J Respir Crit Care Med 1998;158:S100)
- Highly expressed in germinal center B cells (Cancer Cell 2018;34:453, Nat Rev Immunol 2015;15:137)
- MEF2B expression precedes the upregulation of BCL6 expression
- Involved with AP2α and BCL6 proteins in the formation of the BCL6 gene transcriptional complex
- Frequently mutated in diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL)
- MEF2B somatic mutations deregulate BCL6 transcriptional activity and may contribute to DLBCL lymphomagenesis (Nat Immunol 2013;14:1084)
- Role in histone acetylation in cooperation with CREBBP and EP300
Interpretation
- Nuclear expression
Uses by pathologists
- High sensitivity and specificity in differentiating nodular lymphocyte predominant B cell lymphoma / nodular lymphocyte predominant Hodgkin lymphoma (NLPHL; MEF2B+) from classic Hodgkin lymphoma (MEF2B-) (Hum Pathol 2017;68:47)
- Helpful in highlighting lymphocyte predominate (LP) cells
- Differentiates follicular lymphoma (MEF2B+) from marginal zone lymphoma (MEF2B-) (Am J Surg Pathol 2018;42:342)
- Particularly useful in cases of follicular lymphoma with plasmacytic differentiation
- Superior sensitivity and specificity compared with HGAL and LMO2
- Helps classify difficult lymphomas as part of a pan-germinal center B cell marker panel
Microscopic (histologic) images
Contributed by Leonie Frauenfeld, M.D.
Normal germinal center
Nodular lymphocyte
predominant
B cell lymphoma
/ NLPHL
Positive staining - normal
- Germinal center B lymphocytes in lymph nodes and tonsils
- Megakaryocytes
- Plasma cells
- Gastric chief cells
- Neuronal cells, Purkinje cells
- Endothelial cells
- Myocytes
- References: Lab Invest 2019;99:539, Virchows Arch 2015;467:345
Positive staining - disease
- Nodular lymphocyte predominant B cell lymphoma / NLPHL
- Follicular lymphoma and variants
- Burkitt lymphoma (Virchows Arch 2015;467:345)
- Mantle cell lymphoma
- Majority of DLBCL with germinal center differentiation, as well as a subset of non-GC DLBCLs
Negative staining
- Classic Hodgkin lymphoma
- Extranodal marginal zone lymphoma, nodal marginal zone lymphoma
- T follicular helper cells
- Peripheral T cell lymphoma
- References: Virchows Arch 2015;467:345, Hum Pathol 2017;68:47
Sample pathology report
- Lymph node, left cervical, excision:
- Nodular lymphocyte predominant Hodgkin lymphoma (comment)
- Comment: The lymph node architecture is replaced by a vaguely nodular expansion, consisting mostly of small lymphocytes with scant cytoplasm and sparse large cells with multilobular nuclei with small nucleoli, morphologically consistent with LP cells. Immunohistochemistry shows the large cells are positive for CD45, CD20, CD79a and BCL6, while also showing strong expression of OCT2 and MEF2B.
Board review style question #1
The image above shows MEF2B positivity in lymphocyte predominant (LP) cells of nodular lymphocyte predominant B cell lymphoma. Which of the following is true about MEF2B expression?
- Always negative in aggressive lymphomas, such as diffuse large B cell lymphoma
- Helpful to highlight follicular helper T cells in the germinal center
- Lost in all B cell lymphomas with plasmacytic differentiation
- Reliably distinguishes between nodular lymphocyte predominant Hodgkin lymphoma and classic Hodgkin lymphoma
- Typically stains the cell membrane of germinal center B cells
Board review style answer #1
D. Reliably distinguishes between nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and classic Hodgkin lymphoma. MEF2B has high sensitivity and specificity in differentiating nodular lymphocyte predominant B cell lymphoma / NLPHL (MEF2B+) from classic Hodgkin lymphoma (MEF2B-). Answer A is incorrect because MEF2B is positive in the majority of diffuse large B cell lymphomas (DLBCL) with germinal center (GC) differentiation, as well as a subset of non-GC DLBCLs. Answers B and E are incorrect because MEF2B typically stains the nucleus of GC B cells but not follicular T helper cells. Answer C is incorrect because MEF2B has superior sensitivity and specificity compared with other GC markers (HGAL and LMO2) in detecting GC origin, even in cases with marked plasmacytic differentiation.
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Reference: MEF2B
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Board review style question #2
Which of the following lymphomas is typically negative for MEF2B?
- Classic Hodgkin lymphoma
- Diffuse large B cell lymphoma
- Follicular lymphoma
- Follicular lymphoma with plasmacytic differentiation
- Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)
Board review style answer #2
A. Classic Hodgkin lymphoma. MEF2B has high sensitivity and specificity in differentiating nodular lymphocyte predominant B cell lymphoma / NLPHL (MEF2B+) from classic Hodgkin lymphoma (MEF2B-). The other answers are incorrect because MEF2B detects germinal center (GC) origin and is positive in follicular lymphoma (even in cases with plasmacytic differentiation) and in the majority of diffuse large B cell lymphomas (DLBCL) with GC differentiation, as well as a subset of non-GC DLBCLs.
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Reference: MEF2B
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