Image Description
Myeloma is a neoplasm of post-germinal center B-cell derivation with plasmacytic differentiation. The tumor cells show strong expression of CD38, CD138 (syndecan-1) (shown here), CD79a, VS38c, and MUM-1/IRF4. There is strong cytoplasmic expression of light chains with kappa or lambda restriction. Almost 70% of multiple myelomas express CD56; however, almost 80% of plasma cell leukemias are CD56 negative. In typical cases, there is no expression of pan B-cell antigens such as CD19, CD20, Pax-5, nor CD45. Exceptions do occur. A small subset of myelomas expresses CD20. Some cases with t(11;14)(q13;q32) translocation resemble mantle cell lymphoma and express cyclinD1, CD19, CD20, and Pax-5 along with plasmacytic markers such as CD138 and MUM-1. In such cases, the diagnosis of myeloma rests on clinical presentation.
The image shows replacement of entire marrow by CD138 positive plasma cells. IHC stain. 40X. Courtesy of: Jian-Hua Qiao, MD, FCAP, Los Angeles, CA, 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.