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Stains

MUM1 / IRF4


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 27 September 2012, last major update September 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

Definition
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● Transcriptional factor (MUM1/IRF4, MUltiple Myeloma 1 / Interferon Regulatory Factor 4 protein) expressed in final step of intra-germinal center B cell differentiation and in post-germinal center (late centrocyte) B cells (Blood 2000;95:2084, Appl Immunohistochem Mol Morphol 2010;18:301)
● Antigen stimulated B cells with the capacity to differentiate toward plasma cells express MUM1/IRF4
● Has critical role in lymphoid development and in regulating immune response (Proc Natl Acad Sci USA 2012;109:8664)
● Usually mutually exclusive with BCL6 in nonneoplastic tissue: germinal center cells are MUM1- BCL6+ CD10+ and post-germinal (non germinal center) cells are MUM1+ BCL6- CD10-; mantle cells are MUM1- BCL6- CD10-
● Note: in botany, refers to mucilage modified mutant of seed coat epidermal cells

Uses by pathologists
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● Nuclear stain
● Helps divide diffuse large B cell lymphomas into germinal center (MUM1-) and non-germinal center (post-germinal center or activated B-like, MUM1+) phenotypes; germinal center phenotypes have superior outcomes (Am J Surg Pathol 2009;33:1815)
● FISH for IRF4 favors cutaneous anaplastic large cell lymphoma versus other cutaneous T cell lymphoproliferative disorders (Mod Pathol 2011;24:596)
● As part of panel, may help differentiate nodular lymphocyte predominant Hodgkin lymphoma (MUM1/IRF4 negative) from classical Hodgkin lymphoma (positive, Rom J Morphol Embryol 2011;52:69)
● Helps differentiate double hit lymphomas (MUM1+ in 45%) from Burkitt and diffuse large B cell lymphoma (usually MUM1- if germinal center phenotype, Am J Surg Pathol 2010;34:327)

Micro images
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Normal lymph node


Normal tonsil


Lymphoma, Burkitt: MUM1+


Lymphoma, cutaneous anaplastic large cell

           
       
Lymphoma, diffuse large B cell


Lymphoma, double hit: MUM1+ (fig F)


Lymphoma: Ig/IRF4 translocation positive cases


Lymphoma, mantle cell (fig 2B)


Lymphoma, plasmablastic


Lymphoma, primary CNS (fig c)


Lymphoma, primary effusion (HIV+)


Lymphomas (various) and myeloma


Polymorphic PTLD (EBV+)

Positive staining - normal
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● B cells (some), plasma cells

Positive staining - disease
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● Infectious mononucleosis (atypical lymphoid infiltrate with numerous MUM1+ CD10- BCL6- immunoblasts, Mod Pathol 2012;25:1149)
● B-ALL and Burkitt lymphoma (occasionally, Am J Clin Pathol 2010;133:41)
● Diffuse large B cell lymphoma (50%, Arch Pathol Lab Med 2010;134:759)
● Extranodal NK/T-cell lymphoma, nasal type (variable, Am J Surg Pathol 2012;36:481)
● Hodgkin lymphoma (classical)
● Intravascular large B cell lymphoma (95%, Arch Pathol Lab Med 2012;136:333)
● ALK+ large B cell lymphoma
● Mantle cell lymphoma (35%, Appl Immunohistochem Mol Morphol 2010;18:103)
● Primary mediastinal large cell lymphoma (45%, Leuk Lymphoma 2011;52:1495)
● Post transplant lymphoproliferative disorders (EBV+); age related EBV-associated B-cell lymphoproliferative disorders
● Primary CNS lymphoma (84%, Clin Cancer Res 2006;12:1152)
● Pyothorax associated lymphoma
● Melanocytic tumors (Nordiqc)

Negative staining
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● T-ALL

Molecular description
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● FISH detection of MUM1 / IRF4 translocation (DUSP22-IRF4) favors cutaneous anaplastic large cell lymphoma (Mod Pathol 2011;24:596)
● FISH detection of IG/IRF4 fusion detects lymphomas associated with younger patient age and favorable outcome (Blood 2011;118:139)
● t(6;14)(p25;q32), causing MUM1/IRF4-IgH, present in 20% of myeloma (Leukemia 1999;13:1812)

Molecular images
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IRF4 / MUM1 FISH abnormalities in cutaneous CD30+ T cell lymphoproliferative disorders


IG Kappa /IRF4 fusion

End of Stains > MUM1 / IRF4


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