Histopathology

Peripheral Blood and Bone Marrow

Hairy cells are mononuclear cells with nuclei that are eccentric or central.11 Nuclear morphology is variable, the nuclei being round, ovoid, reniform, or convoluted (Figure 8-1A). The cells with round and ovoid nuclei are the smallest, those with convoluted nuclei are intermediate in size, and those with indented nuclei are largest, often with nucleoli. Nuclear forms tend to have a fine reticular chromatin pattern. Hairy cells have variable amounts of cytoplasm, which is blue-gray in appearance, exhibiting thin cytoplasmic projections. Rarely, granules or broad-shaped inclusions can be seen in the cytoplasm, which correspond to the ribosomal lamellar complex seen on electron microscopy.12 The peripheral blood usually demonstrates pancytopenia; the leukopenia is associated with severe monocytopenia in 80 percent of patients.11

Because of marrow reticulin fibrosis, the marrow is frequently difficult or impossible to aspirate.13-15 Occasional cases will, however, reveal typical hairy cells on the aspirated sample and/or on touch preparation of the marrow core biopsy. The hairy cells in the marrow aspirate tend to have a slightly coarser reticular chromatin staining pattern than those found in the peripheral blood. The marrow biopsy specimens usually demonstrate hairy cell infiltrates, which in some patients may be patchy and difficult to discern. The most subtle pattern of HCL infiltration to appreciate is that of a hypocellular marrow with scant infiltration by hairy cells admixed with residual hematopoietic tissue.11,13-15

Marrow involvement may be diffuse or focal. The hairy cells have monotonous round, oval, or spindle-shaped nuclei, which are separated by abundant quantities of pale-staining cytoplasm in a fine fibrillar network. This separation of individual hairy cells is characteristic and referred to as the "fried-egg" appearance (Figure 8-2). Fibroblast infiltration has never been noted in the marrow, and it has been demonstrated that hairy cells synthesize and assemble a fibronectin matrix, which is likely responsible for the marrow fibrosis so characteristic of the disease.16 The pale and delicate network of fibrils between individual hairy cells is usually recognizable but is often better appreciated with the periodic acid-Schiff stain. Among the hairy cells are varying numbers of small lymphocytes, plasma cells, mast cells, and extravasated red blood cells. Cells with round or ovoid nuclei predominate at higher magnification. Occasionally, dilated sinuses with extravasated erythrocytes, similar to the red blood cell lakes seen in the spleen, are present. Rarely, hairy cells may have a peritrabec-ular distribution.

Spleen and Other Sites

The spleen is usually enlarged with a median weight of 1,300 g.17 When sectioned, the spleen has a dark red, smooth surface. On light microscopy the hairy cells involve the splenic red pulp, and later the white pulp atrophies and is replaced. Initial HCL involvement is by the focal infiltration of trabeculae and suben-dothelial infiltrates within trabecular veins.18 Red cell lakes,

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