Myeloma : Bone Marrow

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Image Description

Role of Bone Marrow Examination: Examination of the bone marrow plays a central role in the diagnosis and management of plasma cell myeloma. The findings in bone marrow provide information about prognosis as well as patient response to therapy. Bone marrow aspirate smears and trephine biopsy specimen provide material for immunophenotyping, cytogenetics, and molecular studies.

Plasma Cell Numbers:The aspirate smears show increased number of plasma cells (20% to 35%) in most cases. In about 5% of symptomatic myeloma patients, the number of plasma cells is below 10%. This may be due to suboptimal specimen or uneven distribution of tumor in the bone marrow.

Plasma Cell Morphology: The morphology of plasma cells ranges from mature normal-appearing cells to highly atypical plasmablasts with dispersed chromatin and a single prominent nucleolus. This image shows several immature plasma cells in the center. The neoplastic plasma cells are usually larger in size with a bigger nucleus than normal plasma cells. The chromatin is less condensed and nucleoli are variably prominent. The cytoplasm is basophilic, moderate to abundant in quantity, and often contains vacuoles, granules, crystals, or inclusions (additional details in later slides). In 1%-2% of plasma cell myelomas, the neoplastic cells may show unusual features, including multinucleation, convoluted nuclei, and lymphoid morphology. 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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