Chapter 57: Hairy Cell Leukemia

DEFINITION

• A B-lymphocyte malignancy principally involving the marrow and spleen.

• Blood cytopenias and marrow reticulin fibrosis are frequent features.

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

EPIDEMIOLOGY

• It is estimated that about 1000 cases per year occur in the United States (~2% of all leukemias).

• The male-to-female ratio is approximately 4:1. This large difference is unexplained.

• The median age at presentation is approximately 55 years.

• There is a bimodal peak incidence by age with a mode at approximately age 30 and at age 55.

• More than 90% of patients are of European descent.

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

ETIOLOGY AND PATHOGENESIS

• No exogenous causes have been established.

• A mutation in BRAF (ie, BRAF V600E) is found in virtually all cases of classical hairy cell leukemia (HCL-c).

• BRAF V600E is present in the hemopoietic stem cells of individuals with HCL-c.

• This mutation is not found in cases of variant hairy cell leukemia (HCL-v).

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

• Neoplastic B cells have clonal immunoglobulin gene rearrangements.

• Neoplastic B cells express pan–B-cell markers (eg, CD19, CD20strong, CD22, and CD123) and the plasma cell marker prostate cancer antigen-1.

• Neoplastic B cells express additional surface antigens that are uncommon on B lymphocytes (eg, CD11c, CD25, and CD103).

• HCL-c cells do not express CD5, CD10, CD27, or CD43.

• Neoplastic B cells secrete cytokines that may impair normal hematopoiesis (eg, tumor necrosis factor-α).

CLINICAL FEATURES

• Fatigue and weakness, with or without weight loss, are the most common presenting symptom that occur (50%).

• Abdominal fullness/discomfort is caused by massive splenomegaly.

• Bleeding or infection may be present (25%).

• Some patients are found incidentally to have abnormal blood counts and/or splenomegaly (25%).

• Painful bony lesions rarely occur (3%).

• Splenomegaly exists in 90% of patients, but the incidence is falling due to earlier diagnosis.

• Infections with common bacteria, viruses, fungi, Mycobacterium kansasii, Pneumocystis jirovecii, 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.

• Paraneoplastic neurological syndromes occur rarely.

LABORATORY FEATURES

• Anemia is present in three-fourths of patients.

• Eighty percent of patients have absolute neutropenia and monocytopenia.

• Severe neutropenia (<0.5 × 10⁹/L) is found in 30% of patients.

• Severe monocytopenia is a hallmark of the disease.

• Thrombocytopenia was present at diagnosis in about 75% of patients in the cohorts reported several decades ago, but subsequent earlier diagnosis has reduced this frequency. The extent of thrombocytopenia is very variable but is rarely less than 20 × 10⁹/L.

• Moderate to ...