Myeloma Immunohisto-chemistry : MUM-1

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Image Description

MUM-1/IRF4 (MUltiple Myeloma-1/Interferon Regulatory Factor 4 protein) is a myeloma-associated oncogene that is expressed late in the differentiation of post-germinal center B-cells. Antigenically stimulated B-cells that differentiate into plasma cells express MUM-1/IRF4. It has been identified as a partner gene involved in t(6;14)(p25;q32) translocation of multiple myeloma. This translocation results in juxtaposition of MUM-1 gene on 6p25 to the immunoglobulin heavy chain gene (IgH) locus on 14q32.

Immunohistochemically, MUM-1 shows strong nuclear staining in myeloma cells. MUM-1 has been found to be a useful marker for identification of transition from germinal center B-cells (Bcl-6 positive, CD10 positive, MUM-1 negative) to post-germinal center cells such as immunoblasts and plasma cells (Bcl-6 negative, CD10 negative, MUM-1 positive, CD138 positive). Image courtesy of: Genevieve Crane, MD, PhD, Johns Hopkins Hospital, Baltimore, Maryland, USA.

About the Disease

Plasma cell disorders are B-cell neoplasms composed of plasma cells or lymphocytes that secrete a monoclonal immunoglobulin (Ig) or Ig fragment. They are responsible for about 15% of deaths caused by lymphoid malignancies in the US. The monoclonal Ig, usually identified by serum or urine protein electrophoresis, is known as the M component. Sometimes the M component consists of only light chains or heavy chains. Free light chains are referred to as Bence-Jones proteins when they are excreted in urine. The WHO Classification (2008) of plasma cell neoplasms includes the following: Monoclonal Gammopathy of Undetermined Significance (MGUS): MGUS refers to an asymptomatic patient with an M component (<3 gm/dl) in their blood. It is the most common plasma cell disorder and is seen in about 5% of individuals >70 years of age. About 1% of MGUS patients per year develop multiple myeloma, amyloidosis, macroglobulinemia, or other lymphoproliferative disorder. The median interval between the diagnosis of MGUS and the development of malignancy is about 10.5 years. Plasma Cell Myeloma: Multiple myeloma (MM) is a plasma cell neoplasm of older individuals that is characterized by scattered tumorous masses causing lytic bone lesions in the axial skeleton, hypercalcemia, renal damage, and acquired immune abnormalities. Solitary Plasmacytoma: About 3% to 5% of patients with plasma cell disorders present with solitary bone or soft tissue mass. An M component may be found in serum or urine in a small percentage of cases. Solitary bone plasmacytoma slowly progresses to multiple myeloma in most cases. Extraosseous plasmacytomas involve lungs, nasopharynx, oropharynx, or nasal sinuses and can often be cured by resection. Immunoglobulin Deposition Diseases: This group includes primary amyloidosis (PA) and light- or heavy- chain deposition disease. Immunoglobulins are deposited in various tissues eventually leading to organ failure. About 20% of PA patients have multiple myeloma (MM). The remainder don't meet the criteria for MM but have a small M component and increased plasma cells in bone marrow. Osteosclerotic Myeloma (POEMS Syndrome): Osteosclerotic myeloma is usually associated with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin lesions (POEMS syndrome). Some patients also develop Castleman's disease, serous effusions, and thrombocytosis.

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