Multiple myeloma is a plasma cell neoplasm that is usually associated with synthesis of a monoclonal immunoglobulin (paraprotein), a monoclonal immunoglobulin light chain (Bence-Jones protein) or both [1-4]. In a minority of cases, multiple myeloma is non-secretory. Disease is mainly medullary (i.e. within the bone marrow cavity) but extra-medullary lesions also occur (extra-medullary plasmacytoma). In the World Health Organization (WHO) classification, multiple myeloma is designated 'plasma cell myeloma'.
Clinical features can be the direct effect of the proliferation of plasma cells (e.g. pathological fracture, spinal cord compression) (Figure 21.1), can result from marrow infiltration (anaemia) or can be caused directly by the paraprotein (hyperviscosity) or the Bence-Jones protein (renal failure). Some cases are complicated by amyloidosis, the amyloid being formed from altered light chains.
Vertebral collapse in multiple myeloma.
Haematological and pathological features
Anaemia is usual. Thrombocytopenia occurs less often. A blood film characteristically shows increased rouleaux formation (Figure 21.2) and increased background staining (a blue tinge to the blood film), as a result of the presence of a paraprotein; patients with synthesis of Bence-Jones protein only or with non-secretory myeloma lack this feature. The erythrocyte sedimentation rate is characteristically elevated in patients with a serum paraprotein. Sometimes there are circulating neoplastic cells. When these are numerous the designation plasma cell leukaemia is used (Figure 21.3).
Peripheral blood film in multiple myeloma showing increased rouleaux formation. Romanowsky, x 50 objective.
Peripheral blood film in plasma cell leukaemia showing lymphocytes and pleomorphic plasmacytoid lymphocytes. Romanowsky, x 100 objective.
Biochemical tests often show renal impairment and hypercalcaemia. There may be hyperuricaemia. Serum β2-microglobulin is increased and this may relate to the myeloma activity or to renal impairment. A paraprotein is often present in the serum (Figures 21.4 and 21.5) and Bence-Jones protein in the urine. In patients with renal failure, Bence-Jones protein may be detected in the serum.
Serum protein electrophoretic pattern in multiple myeloma showing a prominent paraprotein band in the gamma region on an electrophoretic strip (top) and by densitometric scanning (middle). The < and=""> signs indicate if a percentage is above or below the reference range. With thanks to Miss Carol Hughes.
Serum protein electrophoresis showing a prominent paraprotein band in the gamma region (left) identified as an IgA κ paraprotein by immunofixation (right). With thanks to Miss Carol Hughes.