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Case 217 - Discussion

Uploaded: 2011-10-08, Updated: 2011-10-08



Annexin A1




Hairy Cell Leukemia (HCL)


  • 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


  • 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


  • 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 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


  • 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


  • 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


  • 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


  • 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