Chapter 106. Plasma Cell Disorders (Part 2)

Representative patterns of serum electrophoresis. The upper panel illustrates the normal pattern of serum protein on electrophoresis. Since there aremany different immunoglobulins in the serum, their differing mobilities in an electric field produce a broad peak. In conditions associated with increases in polyclonal immunoglobulin, the broad peak is more prominent (middle panel). In monoclonal gammopathies, the predominance of a product of a single cell produces a "church spire" sharp peak, usually in the γ globulin region (bottom panel).The nature of the M component is variable in plasma cell disorders. It may be an intact antibody molecule of any heavy...
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Chapter 106. Plasma Cell Disorders (Part 2) Chapter 106. Plasma Cell Disorders (Part 2) Figure 106-1 Representative patterns of serum electrophoresis. The upper panelillustrates the normal pattern of serum protein on electrophoresis. Since there aremany different immunoglobulins in the serum, their differing mobilities in anelectric field produce a broad peak. In conditions associated with increases inpolyclonal immunoglobulin, the broad peak is more prominent (middle panel). Inmonoclonal gammopathies, the predominance of a product of a single cellproduces a church spire sharp peak, usually in the γ globulin region (bottompanel). The nature of the M component is variable in plasma cell disorders. It maybe an intact antibody molecule of any heavy chain subclass, or it may be an alteredantibody or fragment. Isolated light or heavy chains may be produced. In someplasma cell tumors such as extramedullary or solitary bone plasmacytomas, used interchangeably. The tumor, its products, and the host response to it result ina number of organ dysfunctions and symptoms of bone pain or fracture, renalfailure, susceptibility to infection, anemia, hypercalcemia, and occasionallyclotting abnormalities, neurologic symptoms, and manifestations ofhyperviscosity. Etiology The cause of myeloma is not known. Myeloma occurred with increasedfrequency in those exposed to the radiation of nuclear warheads in World War IIafter a 20-year latency. A variety of chromosomal alterations have been found inpatients with myeloma; 13q14 deletions, 17p13 deletions, and 11q abnormalitiespredominate. The most common translocations are t(11;14)(q13;q32) andt(4;14)(p16;q32), and evidence is strong that errors in switch recombination—thegenetic mechanism to change antibody heavy chain isotype—participate in thetransformation pathway. Overexpression of myc or ras genes has been noted insome cases. Mutations in p53 and Rb-1 have also been described, but no commonmolecular pathogenesis has yet emerged. Myeloma has been seen more commonly than expected among farmers,wood workers, leather workers, and those exposed to petroleum products. Theneoplastic event in myeloma may involve cells earlier in B cell differentiation thanthe plasma cell. Circulating B cells bearing surface immunoglobulin that share theidiotype of the M component are present in myeloma patients. Interleukin (IL) 6may play a role in driving myeloma cell proliferation; a large fraction of myelomacells exposed to IL-6 in vitro respond by proliferating. The IL-6 dependency ofmyeloma is controversial. It remains difficult to distinguish benign from malignantplasma cells on the basis of morphologic criteria in all but a few cases (Fig. 106-2). Figure 106-2 Multiple myeloma (marrow). The cells bear characteristic morphologicfeatures of plasma cells, round or oval cells with an eccentric nucleus composedof coarsely clumped chromatin, a densely basophilic cytoplasm, and a perinuclearclear zone (hof) containing the Golgi apparatus. Binucleate and multinucleatemalignant plasma cells can be seen.