CLINICAL FEATURES

• Rare, ~ 600 cases per year in the United States and accounting for only 2% of all leukemias

• Affects predominantly middle-aged men, mean age 54 years, male-to-female ratio 4:1

• Most patients present with symptoms related to cytopenia, splenomegaly and uncommon lymphadenopathy

PERIPHERAL BLOOD FINDINGS

• Leukopenic or pancytopenia

• Rarely leukocytosis (>10,000 × 10⁹/L), 10 - 15% of cases

• Monocytopenia seen in almost all cases, one of the most sensitive markers of disease

• Hairy cells

• 1.5 - 2 times the size of small lymphocytes

• Oval to bean-shaped nuclei, moderately dispersed chromatin

• Absent or inconspicuous small nucleoli

• Cytoplasm: moderately abundant, pale blue, and often flocculent, with ill-defined or ruffled borders with “wispy” projections

BONE MARROW FINDINGS

• Mainly interstitial or diffuse, no well-defined aggregates

• Hypercellular marrow in most cases with diffuse sheets of hairy cells. In early stages of the disease the bone marrow may be hypocellular or may have a subtle interstitial infiltrate

• Leukemic cells with “fried egg” appearance:  round and monotonous, oval to indented to occasionally convoluted nuclei, abundant clear cytoplasm; lack of large cells

• Often reduction in normal hematopoietic cells, particularly myeloid lineage

• Significant reticulin fibrosis

SPLEEN FINDINGS

• Spleen always involved, preferentially the red pulp

• Blood lake: microscopic areas of hemorrhage, characteristic but not specific for HCL

• Not uncommonly involves abdominal and retroperitoneal lymph nodes, particularly after splenectomy or in patients with long-standing disease
• Paracortical distribution and may surround germinal centers in a pattern mimicking nodal marginal zone lymphoma

FLOW CYTOMETRY

• Hairy cells often fall outside of the usual lymphocyte region within the monocyte gate

• Positive: CD45 (bright), CD19, CD20 (bright), FMC-7, CD22, and CD79a

• Positive: CD11c, CD25,CD103, CD123,

• Negative: CD5, CD10, and CD79b

IMMUNOPROFILE

• Positive: CD20, CD79a, DBA.44, Annexin 1, CD11c, CD103, CD25, CD123, TRAP, and HC2

• Cyclin D1 is overexpressed in HCL, but  usually weak or focal

VARIANTS: Hairy cell leukemia variant (HCL-v)

• 10% HCL cases, morphologic, immunophenotypic, and clinical features that deviate significantly from typical HCL

• Older than typical HCL patients, median age, 71 years

• Massive splenomegaly at presentation

• Periperal blood:

  • Usually marked leukocytosis (median WBC 116 × 109/L)

  • No monocytopenia

  • Leukemic cells resemble classic hairy cells but have prominent central nucleoli that are not typically seen in classic HCL

• Bone marrow

  • Interstitial and sinusoidal infiltration, similar to classic HCL

  • Minimal myelosuppression

  • Relatively little marrow fibrosis

• Immunoprofile

  • CD103+

  • Usually negative for CD25, TRAP, CD123, and Annexin A1

• >50% cases express IgG heavy chain

• Clinically more aggressive, ~50% of patients resistant to purine analogues

DIFFERENTIAL DIAGNOSES

• Myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasms, primary myelofibrosis, acute myeloid leukemia: do CD20 stain when MDS or aplastic anemia is considered but HCL remains a possibility

• Systemic mast cell disease, monocytic leukemias, and large granular lymphocyte leukemia

• SMZL:

  • Nodular and intrasinusoidal  marrow infiltration

  • In peripheral blood, circulating SMZL cells have less prominent, blunter and polarized hairy projections

  • Negative for CD103, CD25, CD11c, CD123, ANXA1 and cyclin D1

TREATMENT AND PROGNOSIS

• The purine analogues 2-chlorodeoxyadenosine (2-CdA) and deoxycoformycin (pentostatin, DCF) represent highly effective therapies for HCL and have replaced interferon-α and splenectomy

• The long-term survival of HCL treated with 2-CdA is excellent (96% at 13 years), and death due to HCL is now uncommon

• Hematopathology, 2011. By Elaine Sarkin Jaffe, MD, Nancy Lee Harris, James Vardiman, MD, Elias Campo, MD and Daniel MD Arber, MD