Multiple Myeloma Overview

Multiple Myeloma

• A neoplastic disease, characterized by plasma cell accumulation in the bone marrow.
• Plasma cells undergo immunoglobulin (Ig) class switching and somatic hypermutation, secreting paraprotein in the serum.
• Monoclonal protein (M protein) is present in serum and/or urine.
• Related organ or tissue damage frequently occurs.
• Unknown cause, but common in Afro-Caribbean populations.
• Peaks in individuals 40 years and older, with incidence in the 70-80 age range.
• Often asymptomatic initially, with no noticeable organ or tissue damage.
•  Bone marrow displays abnormal plasma cells.
•  Diagnostic tools may include bone scans exhibiting osteoporosis/vertebral collapse, hypercalcemia, and low serum albumin levels .
•  Serum protein electrophoresis (SPEP) and immunofixation (IFE) are important for identifying monoclonal proteins.
• Increased plasma cells in bone marrow (over 20%).
• Elevated serum calcium, creatinine, and/or abnormal immunoglobulins, and lowered serum albumin.
• Light chain proteins (e.g., Bence Jones proteins) may be excreted into the urine.
•  Treatment options include stem cell transplants (for younger patients), intensive chemotherapy (for younger patients), and non-intensive chemotherapy (for older patients). The latter often involves several courses of chemotherapy using drugs like Prednisolone, Thalidomide, Lenalidomide, and Bortezomib. Radiotherapy may also be used for pain or spinal cord compression.

Pathophysiology

• Multiple myeloma cells produce an excess of monoclonal proteins and free light chains.
• These M proteins can be different types (IgA, IgD, IgG, IgE, IgM) depending on their heavy chain class.
• The excess M proteins cause hyperviscosity syndrome, which hinders fibrin aggregation and impairs platelet function.
• Light chains (kappa or lambda) can precipitate and deposit, causing organ damage.

Clinical Features

• Symptoms may include bone pain (backache due to vertebral collapse and fracture).
• Bleeding may occur due to problems with platelets.
• Infections occur frequently due to impaired antibody production and cell-mediated immunity.
• Anemia, characterized by symptoms like lethargy, weakness, dyspnea, and pallor, is also observed.
• Renal failure and hypercalcemia are also possible, presenting with symptoms such as polydipsia, polyuria, anorexia, vomiting, constipation, and mental disturbance.

Laboratory Findings

• Bone lesions on X-rays are often observed in conjunction with osteoporosis and vertebral collapse.
• Elevated serum calcium levels in the blood are common.
• Elevated creatinine levels are also frequently seen due to proteinaceous deposits from heavy light chain proteinuria.
• A severely lowered serum albumin level is an advanced stage indicator.
• A raised ESR (erythrocyte sedimentation rate) reflects the inflammation associated with abnormal immunoglobulins.
• Genetic abnormalities, such as hyperdiploidy, translocations, and 13q monoallelic loss, are frequently seen.
• Increased plasma cells detected in the bone marrow (BM) exeed 20%.
• Identification of Bence Jones proteins in the urine and abnormal monoclonal proteins (M protein) on serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) are also used for diagnosis.

Bone Marrow

• Normal bone marrow histology shows a mix of cell types, while Multiple Myeloma shows an increase in abnormal plasma cells
•  Immunostaining with CD138 can help differentiate abnormal plasma cells.

Serum Protein Electrophoresis (SPEP) and Immunofixation (IFE)

• SPEP separates serum proteins based on size and electrical charge, showing a prominent spike in the gamma region in the presence of monoclonal proteins (M protein).
• IFE identifies the type of immunoglobulin (Ig) the M protein belongs to (e.g., IgG).