Plasma cell neoplasms

• Plasma cell dyscrasias are neoplastic proliferations of plasma cells that secrete monoclonal intact immunoglobulin (Ig) or Ig fragments (free light chain)
• Classification of plasma cell neoplasms includes multiple myeloma, smoldering multiple myeloma, solitary myeloma (plasmacytoma), monoclonal gammopathy of undetermined significance, and Waldenstrom’s macroglobulinemia
• Multiple myeloma is characterized by multifocal bone marrow disease with malignant proliferation of plasma cells, leading to skeletal destruction
• In multiple myeloma, monoclonal B cells produce a single type of Ig, with IgG being the most common
• High-risk cytogenetics in multiple myeloma include t(4;14), t(14;16), or del 17p, identified from FISH test results
• The pathogenesis of multiple myeloma involves myeloma cells binding to bone marrow stromal cells via adhesion molecules
• Serum and urine analysis in multiple myeloma show monoclonal globulin spike on serum electrophoresis and proteinuria in urine
• Clinical features of multiple myeloma include the CRAB tetrad: Calcium (elevated), Renal (kidney) failure, Anemia, and Bone lesions
• Diagnosis of multiple myeloma involves bone marrow examination, radiology, serum and urine electrophoresis, and immunoglobulin level testing
• Radiological findings in multiple myeloma show multifocal destructive lesions in the axial skeleton with 'punched out' lytic lesions
• Pathogenesis of multiple myeloma involves decreased levels of osteoprotegerin (OPG), allowing osteoclasts to resorb bone unchecked
• Anaemia can be normocytic and normochromic, caused by:

  • Replacement of normal bone marrow by tumour cells
  • Inhibition of normal red blood cell production by cytokines
  • Decrease in erythropoietin production
• A notable feature of anaemia is the decrease in charge on red blood cells, leading to Rouleaux formation on blood smear
• Clinical features of bleeding in multiple myeloma include:

  • Monoclonal immunoglobulin interfering with normal coagulation
  • Infiltration of the bone marrow leading to thrombocytopenia
• Hyperviscosity in multiple myeloma is characterized by a high volume of monoclonal protein, leading to increased blood viscosity and potential complications like stroke, myocardial ischemia, or infarction
• Sepsis in multiple myeloma is associated with recurrent infections, often caused by decreased production of normal immunoglobulin, leading to recurrent bacterial infections, especially by encapsulated organisms like Staphylococcus, Streptococcus, and E. coli. It can also result in leucopenia
• Renal failure in multiple myeloma occurs in up to 50% of patients and is the second most common cause of death. It can be multifactorial, with causes like myeloma kidney (myeloma cast nephropathy), Bence-Jones proteins toxic to renal tubular epithelial cells, amyloidosis (AL type), light chain nephropathy, hypercalcemia, hyperuricemia, pyelonephritis, and drug-induced factors
• Neurological symptoms in multiple myeloma can be attributed to hyperviscosity, hypercalcemia, and nerve compression
• The prognosis of multiple myeloma is typically 6-12 months if untreated, with a median survival of 4-7 years. Common causes of death include infection and renal failure
• Treatment of multiple myeloma is currently not curable, but new therapies like immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, bisphosphonates, and bone marrow transplantation (autologous and allogeneic, rarely used) are employed
• Classification of plasma cell neoplasms includes:

  • Multiple myeloma
  • Smoldering multiple myeloma
  • Solitary myeloma (plasmacytoma)
  • Monoclonal gammopathy of undetermined significance
  • Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia)
  • Other rare entities
• Solitary plasmacytoma can involve osseous (bone) or extra-osseous (extra-medullary-soft tissue) lesions. Serum immunoglobulin concentrations are usually within normal limits
• Solitary plasmacytoma of bone typically affects younger patients and often involves the spine, pelvis, or femur. It presents as a single symptomatic area of bone destruction and may progress to multiple myeloma in 10-20 years
• Extra-medullary plasmacytoma can involve sites like the lung, oro-nasopharynx, and nasal sinuses. Extra-osseous lesions can be cured by local resection or radiotherapy, with progression to multiple myeloma being less common
• Monoclonal gammopathy of undetermined significance (MGUS) is the most common cause of monoclonal gammopathy, often asymptomatic with specific criteria for diagnosis. Progression to multiple myeloma occurs at a rate of 1% per year
• Lymphoplasmacytic lymphoma typically affects the elderly, with neoplastic cells producing monoclonal IgM (macroglobulin=Waldenstrom’s macroglobulinemia). The mean survival is 4-5 years
• Clinical features of lymphoplasmacytic lymphoma include:

  • Weakness, weight loss
  • Lymphadenopathy, hepatosplenomegaly
  • Increased serum protein with M spike (IgM)
  • Autoimmune hemolysis (IgM binds to RBC)
  • Hyperviscosity syndrome
• Hyperviscosity syndrome in lymphoplasmacytic lymphoma can lead to visual impairment, neurological symptoms, bleeding (due to interference with platelet function), and cryoglobulinemia, which can cause Raynaud’s phenomenon
• Treatment of hyperviscosity syndrome may involve plasmapheresis if urgently required, along with treating the underlying condition