Myeloma : Bone Marrow

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Image Description

The findings in bone marrow trephine biopsies correlate with the tumor burden in multiple myeloma. The pattern of plasma cell infiltration may be interstitial, focal, or diffuse. The extent of marrow involvement ranges from a small increase in the number of plasma cells to complete replacement by sheets of plasma cells. In early stages of the disease, the infiltrates are focal or interstitial and there is sparing of normal hematopoiesis. In advanced stages of myeloma, there is diffuse marrow involvement and hematopoiesis is suppressed resulting in cytopenias.

Staging of Myeloma: Based on the extent of bone marrow involvement on trephine biopsies, a staging system has been proposed. Stage I: less than 20% of marrow replaced by neoplastic plasma cells; Stage II: 20%-50% involvement; Stage III: greater than 50% involvement.

In this trephine biopsy of bone marrow from a myeloma patient, the plasma cells make up approximately 50% of the cells and the pattern of infiltration is interstitial. 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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