Chapter 106. Plasma Cell Disorders (Part 5)

Anemia occurs in ~80% of myeloma patients. It is usually normocytic and normochromic and related both to the replacement of normal marrow by expanding tumor cells and to the inhibition of hematopoiesis by factors made by the tumor. In addition, mild hemolysis may contribute to the anemia. A larger than expected fraction of patients may have megaloblastic anemia due to either folate or vitamin B12 deficiency. Granulocytopenia and thrombocytopenia are very rare. Clotting abnormalities may be seen due to the failure of antibody-coated platelets to function properly or to the interaction of the M component with clotting factors I,...
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Chapter 106. Plasma Cell Disorders (Part 5) Chapter 106. Plasma Cell Disorders (Part 5) Anemia occurs in ~80% of myeloma patients. It is usually normocytic andnormochromic and related both to the replacement of normal marrow byexpanding tumor cells and to the inhibition of hematopoiesis by factors made bythe tumor. In addition, mild hemolysis may contribute to the anemia. A larger thanexpected fraction of patients may have megaloblastic anemia due to either folateor vitamin B12 deficiency. Granulocytopenia and thrombocytopenia are very rare.Clotting abnormalities may be seen due to the failure of antibody-coated plateletsto function properly or to the interaction of the M component with clotting factorsI, II, V, VII, or VIII. Deep venous thrombosis is also observed with use ofthalidomide or lenalidomide in combination with dexamethasone. Raynaudsphenomenon and impaired circulation may result if the M component formscryoglobulins, and hyperviscosity syndromes may develop depending on thephysical properties of the M component (most common with IgM, IgG3, and IgAparaproteins). Hyperviscosity is defined on the basis of the relative viscosity ofserum as compared with water. Normal relative serum viscosity is 1.8 (i.e., serumis normally almost twice as viscous as water). Symptoms of hyperviscosity occurat a level of 5–6, a level usually reached at paraprotein concentrations of ~40 g/L(4 g/dL) for IgM, 50 g/L (5 g/dL) for IgG3, and 70 g/L (7 g/dL) for IgA. Although neurologic symptoms occur in a minority of patients, they mayhave many causes. Hypercalcemia may produce lethargy, weakness, depression,and confusion. Hyperviscosity may lead to headache, fatigue, visual disturbances,and retinopathy. Bony damage and collapse may lead to cord compression,radicular pain, and loss of bowel and bladder control. Infiltration of peripheralnerves by amyloid can be a cause of carpal tunnel syndrome and othersensorimotor mono- and polyneuropathies. Sensory neuropathy is also a sideeffect of thalidomide and bortezomib therapy. Many of the clinical features of myeloma, e.g., cord compression,pathologic fractures, hyperviscosity, sepsis, and hypercalcemia, can present asmedical emergencies. Despite the widespread distribution of plasma cells in thebody, tumor expansion is dominantly within bone and bone marrow and, forreasons unknown, rarely causes enlargement of spleen, lymph nodes, or gut-associated lymphatic tissue. Diagnosis and Staging The classic triad of myeloma is marrow plasmacytosis (>10%), lytic bonelesions, and a serum and/or urine M component. Bone marrow plasma cells areCD138+ and monoclonal. The most important differential diagnosis in patientswith myeloma involves their separation from individuals with monoclonalgammopathies of uncertain significance (MGUS). MGUS are vastly morecommon than myeloma, occurring in 1% of the population over age 50 and in upto 10% individuals over age 75. The diagnostic criteria for MGUS, smolderingmyeloma, and myeloma are described in Table 106-2. When bone marrow cellsare exposed to radioactive thymidine in order to quantitate dividing cells, patientswith MGUS always have a labeling index < 1%; patients with myeloma alwayshave a labeling index > 1%. With long-term follow-up, ~1% per year of patientswith MGUS go on to develop myeloma. Non-IgG subtype, abnormalkappa/lambda free light chain ratio, and serum M protein > 15 g/L (1.5 g/dL) areassociated with higher incidence of progression of MGUS to myeloma. Typically,patients with MGUS require no therapy. Their survival is ~2 years shorter thanage-matched controls without MGUS. There are two important variants ofmyeloma, solitary bone plasmacytoma and extramedullary plasmacytoma. Theselesions are associated with an M component in plasmacytosis. Both tumors are highly responsive to local radiation therapy. If anM component is present, it should disappear after treatment. Solitary boneplasmacytomas may recur in other bony sites or evolve into myeloma.Extramedullary plasmacytomas rarely recur or progress. Table 106-2 Diagnostic Criteria for Multiple Myeloma, MyelomaVariants, and Monoclonal Gammopathy of Unknown Significance Monoclonal gammopathy of undetermined significance (MGUS) M protein in serum < 30 g/L Bone marrow clonal plasma cells < 10% No evidence of other B cell proliferative disorders No myeloma-related organ or tissue impairment (no end organ damage,including bone lesions)a Asymptomatic myeloma (smouldering myeloma) M protein in serum ≥30 g/L and/or Bone marrow clonal plasma cells ≥10% No myeloma-related organ or tissue impairment (no end organ damage,including bone lesions)a or sympt ...