Chapter 57: Hairy Cell Leukemia

DEFINITION

• B-lymphocyte malignancy that principally involves the marrow and spleen.

• Reactive marrow fibrosis and blood cytopenias are frequent features.

• Irregular cytoplasmic projections on neoplastic B lymphocytes (which gives the disease its name), most striking when examined as a wet preparation by phase microscopy.

EPIDEMIOLOGY

• Estimated that about 700 cases per year occur in the United States (approximately 2% of all leukemias).

• Male:female ratio approximately 4:1.

• Median age at presentation approximately 50 to 55 years.

ETIOLOGY AND PATHOGENESIS

• No exogenous causes established.

• Disease is rare in persons of African or Asian descent.

• Hairy cells are B cells in a late (pre-plasma cell) stage of development.

• B cells have clonal immunoglobulin gene rearrangements.

• Express pan-B–cell markers (e.g., CD19, CD20, and CD22) and the plasma cell marker Prostate Cancer Antigen-1.

• Express additional surface antigens that are uncommon on B lymphocytes (e.g., CD11c, CD25, and CD103).

• Secrete cytokines that may impair normal hematopoiesis (e.g., tumor necrosis factor-α).

CLINICAL FEATURES

• Abdominal fullness/discomfort caused by massive splenomegaly (25%).

• Fatigue, weakness, weight loss (25%).

• Bleeding or infection (25%).

• Found incidentally to have abnormal blood count and/or splenomegaly (25%).

• Painful bony lesions (3%).

• Splenomegaly in 90 percent of patients (median splenic weight approximately 1300 g).

• Infections with common bacteria, viruses, fungi, Mycobacterium kansasii, Pneumocystis jiroveci, aspergillus, histoplasma, cryptococcus, Toxoplasma gondii or other opportunistic organisms, once common, are less frequent because of more effective initial therapy.

• Unusual findings include: cutaneous vasculitis, leukoclastic angiitis, erythema nodosum, polyarthritis, and Raynaud phenomenon.

LABORATORY FEATURES

• Eighty percent of patients have absolute neutropenia and monocytopenia.

• Severe neutropenia (< 0.5 × 10⁹/liter) in 30 percent of patients.

• Severe monocytopenia is hallmark of the disease.

• Anemia is present in three-quarters of patients.

• Moderate to severe pancytopenia found in 67 percent.

• Thrombocytopenia in about 75 percent of patients.

• Careful examination of the blood by light microscopy identifies hairy cells in 80 percent of patients (Fig. 57–1) and in > 90 percent of patients with flow cytometry.

• Liver function test abnormalities in 19 percent, azotemia in 27 percent, and hyperglobulinemia in 18 percent, which may be monoclonal.

• Occasionally leukocytosis is present as a result of circulating hairy cells. Extreme leukocytosis (>100 × 10⁹/L) can occur very infrequently, most often seen in the "hairy cell leukemia variant" (see below).

• Hairy cells comprise less than 20 percent of lymphocytes in patients with low white blood cell counts, but are the predominant cell in patients whose white blood cell count is greater than 10 × 10⁹/L.

• Marrow biopsy shows focal or diffuse infiltrate of leukemic cells with characteristic surrounding halo of pale-staining cytoplasm (the "fried-egg" appearance) and a diffuse fine fibrillar network best appreciated with the periodic acid–Schiff stain (Fig. 57–1).

• Marrow is usually hypercellular, but occasionally hypocellular, mimicking aplastic anemia.

• Immunohistochemistry ...