E

Figure 13.7 Plasma cells. Note basophilic cytoplasm and eccentric nucleus.

plasma cells. These include exposure to atomic radiation, work involving the use of organic solvents, work with toxins within the textile industries, and any occupation that may primarily or secondarily expose one to chemicals, pesticides, or herbicides.12 Additionally, chromosome abnormalities have been defined in 18% to 35% of patients with multiple myeloma.13 Aberrations in chromosome 13 have been particularly well studied and include monosomy, deletions, or translocations of the chromosome. Multiple myeloma patients with chromosomal damage have a worse prognosis, a higher rate of disease acceleration, and a decreased survival.14 Screening for chromosomal abnormalities seems a prudent course of action in monitoring disease progress (Table 13.5).

Pathophysiology in Multiple Myeloma

Disease and clinical symptoms in multiple myeloma follow along three distinct pathways:

1. Acceleration of plasma cells in the bone marrow

2. Activation of bone resorption factors or osteoclasts

3. Production of an abnormal monoclonal protein

Table 13.5 O A Simplified list of Chromosomal Aberrations in Multiple Myeloma

• 13q14 deletions

Figure 13.8 Sheets of plasma cells.

Figure 13.1G Plasma cell with inclusion.

To begin, plasma cells accelerate in multiple myeloma under the direction of the renegade cytokine interleukin (IL)-6. The plasma cells appear in clusters (Fig. 13.8) and may be morphologically normal, or they may appear binucleated and have a bizarre structure. Some may even develop colorless inclusions called Russell bodies or other crystalline inclusions (Figs. 13.9 and 13.10). Flame cells may also be visualized in IgA myelomas and appear as plasma cells with a striking deep pink cytoplasm (Fig. 13.11). Eventually, these clusters or sheets overtake the normal bone marrow structure, leading to the appearance of plasma cells in the peripheral smear as well as anemias, thrombocytopenia, and neutropenia. Plasma cell tumors may seed to other areas in the body, and plasmacytomas may occur in liver, spleen, gastrointestinal tract, or nasal cavities. Additionally, the increased plasma cell activity leads to commensurate increased osteoclast activity. Osteoclasts are large multinucleated cells in the bone marrow that absorb bone tissue. With increased activity, bone loss is inevitable and this pathology usually brings forward the single most frequent complaint from MM patients— bone pain. Pain usually develops due to compressed vertebrae in the back, ribs, or sternum. This compression may lead to loss of sensation, fractures, and paralysis. Serum calcium is also greatly increased due to bone loss, and this event may lead to kidney failure or the formation of kidney stones.

Increased plasma cell production results in increased immunoglobulin production and usually the advent of a monoclonal gammopathy, a purposeless proliferation of one particular antibody, usually IgG. On serum immunoelectrophoresis (see Fig. 13.11), this is seen as an M spike. This excess globulin production may lead to complications from hyperviscosity in the plasma such as blurred vision or headache. Subsequent

Figure 13.9 Russell bodies. These inclusions are derived from an accumulation of immunoglobulin.

Figure 13.11 Flame cell; a plasma cell with a pink cytoplasm.

Figure 13.9 Russell bodies. These inclusions are derived from an accumulation of immunoglobulin.

Figure 13.11 Flame cell; a plasma cell with a pink cytoplasm.

212 Part III • White Cell Disorders

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