Hematology Oncology · Year 2 · from Hematology Oncology

Case 3: Hairy Cell Leukemia

Patient Presentation

Demographics: 55-year-old male

Chief Complaint: Recurrent infections, fatigue, and abdominal fullness

History of Present Illness: The patient has had 3 episodes of bacterial pneumonia over the past year. He reports progressive fatigue and early satiety with 15-pound weight loss. He has noticed increasing abdominal fullness on the left side. He has no lymphadenopathy, fevers, or night sweats. He is a non-smoker with no significant past medical history.

Physical Examination:

  • Vital signs: BP 118/72, HR 78, RR 16, Temp 36.9C
  • General: Pale, thin male
  • HEENT: Pallor, no lymphadenopathy
  • Cardiac: Regular rhythm, soft flow murmur
  • Lungs: Clear
  • Abdomen: Massive splenomegaly extending to the pelvis
  • No hepatomegaly, no peripheral lymphadenopathy

Workup and Results

Complete Blood Count:

  • WBC: 2,100/uL (low)
  • Absolute neutrophil count: 450/uL (neutropenia)
  • Absolute monocyte count: 80/uL (monocytopenia - characteristic)
  • Lymphocytes: 1,400/uL
  • Hemoglobin: 9.2 g/dL
  • Platelets: 68,000/uL
  • Pancytopenia with characteristic monocytopenia

Peripheral Blood Smear:

  • Occasional abnormal lymphocytes with oval nuclei
  • Fine, hair-like cytoplasmic projections
  • Abundant pale blue cytoplasm

Bone Marrow:

  • "Dry tap" on aspiration attempt
  • Biopsy: Diffuse infiltration by abnormal lymphocytes
  • "Fried egg" appearance due to cytoplasmic clearing
  • Reticulin fibrosis present

Immunophenotype (Flow Cytometry):

  • CD19+, CD20+, CD22+
  • CD11c+, CD25+, CD103+
  • Annexin A1+
  • CD5 negative, CD23 negative

Special Stains:

  • TRAP (tartrate-resistant acid phosphatase): Positive

Molecular Testing:

  • BRAF V600E mutation: Positive (present in >95% of HCL)

CT Imaging:

  • Massive splenomegaly (25 cm)
  • No lymphadenopathy

Clinical Image

Peripheral blood smear in hairy cell leukemia showing characteristic lymphocytes with oval/kidney-shaped nuclei and fine, hair-like cytoplasmic projections extending from the cell surface.

Diagnosis

Hairy Cell Leukemia (HCL)

Diagnostic criteria:

  • Characteristic "hairy" lymphocytes on smear
  • Immunophenotype: CD19+, CD20+, CD11c+, CD25+, CD103+, Annexin A1+
  • TRAP positive
  • BRAF V600E mutation positive
  • Monocytopenia (virtually diagnostic)
  • Massive splenomegaly without lymphadenopathy

Treatment Plan

  1. First-line therapy:
  • Cladribine (2-CdA) 0.1 mg/kg/day continuous infusion x 7 days
  • OR Pentostatin 4 mg/m2 every 2 weeks x 4-6 cycles
  • Single course achieves complete remission in >90%
  1. Expected course:
  • Initial pancytopenia may worsen transiently
  • Nadirs at 1-2 weeks
  • Recovery over 4-8 weeks
  • Durable remissions lasting years to decades
  1. Supportive care during treatment:
  • PJP prophylaxis (TMP-SMX)
  • Antiviral prophylaxis (acyclovir)
  • G-CSF if severe neutropenia with infection
  • Irradiated blood products (risk of TA-GVHD)
  1. Relapsed disease options:
  • Repeat purine analog if long remission
  • Rituximab with or without purine analog
  • Vemurafenib (BRAF inhibitor) for refractory disease
  • Moxetumomab pasudotox (anti-CD22 immunotoxin)
  1. Monitoring:
  • MRD assessment by flow cytometry
  • Long-term surveillance for relapse

Teaching Points

  1. Hairy cell leukemia has pancytopenia with characteristic monocytopenia
  2. "Dry tap" on bone marrow aspiration due to reticulin fibrosis
  3. The BRAF V600E mutation is present in >95% of cases and is a therapeutic target
  4. TRAP positivity helps confirm diagnosis
  5. Massive splenomegaly without lymphadenopathy is typical
  6. Purine analogs (cladribine, pentostatin) achieve excellent long-term remissions
  7. Atypical infections (Legionella, atypical mycobacteria) occur due to monocytopenia
  8. HCL has excellent prognosis with high cure rates

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