What is the diagnosis for an elderly man with lymphadenopathy, leukocytosis with mature lymphocytes, and a negative Tartrate-Resistant Acid Phosphatase (TRAP) stain?

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Diagnosis: Chronic Lymphocytic Leukemia (CLL)

The diagnosis is CLL (option b), as this elderly patient presents with the classic triad of lymphadenopathy, leukocytosis with mature lymphocytes, and normal platelets—all consistent with early-stage CLL. The negative TRAP stain effectively excludes hairy cell leukemia, which characteristically stains positive for tartrate-resistant acid phosphatase 1.

Diagnostic Reasoning

Why CLL is the Correct Answer

  • CLL is the most common leukemia in elderly patients, with a median age at diagnosis of 72 years and incidence increasing to >30:100,000/year in patients over 80 years 1.

  • The clinical presentation matches CLL diagnostic criteria: peripheral blood lymphocytosis (15,000 WBC with mature lymphocytes exceeds the diagnostic threshold of ≥5,000 monoclonal B lymphocytes/µL), lymphadenopathy, and normal platelet count 1, 2.

  • Mature lymphocyte morphology is characteristic of CLL, appearing as small, mature-appearing lymphocytes with narrow cytoplasm borders and dense nuclei lacking discernible nucleoli 1.

  • Normal platelets indicate early-stage disease (Binet stage A or B, or Rai stage 0-II), which is common at presentation 1, 2.

Why Other Options Are Incorrect

Hairy cell leukemia (option a) is definitively excluded:

  • Hairy cell leukemia characteristically stains positive for TRAP, whereas this patient's cells are TRAP-negative 1.
  • Hairy cell leukemia typically presents with pancytopenia (low blood counts), not leukocytosis 1.
  • Lymphadenopathy is uncommon in hairy cell leukemia, making this presentation atypical 1.

CML (option c) is unlikely:

  • CML presents with leukocytosis but shows a left shift with immature myeloid cells (myelocytes, metamyelocytes, blasts), not mature lymphocytes 3, 4.
  • CML patients typically have splenomegaly rather than prominent lymphadenopathy 3.
  • The mature lymphocyte predominance points away from a myeloid disorder 1.

Polymorphic leukemia (option d) is not a recognized diagnostic entity in standard hematologic classification systems 1, 3, 4.

Confirmatory Testing Required

To definitively establish the CLL diagnosis, the following must be performed:

  • Flow cytometry is mandatory to confirm B-cell clonality and demonstrate the characteristic immunophenotype: CD5+, CD19+, CD20+ (low), CD23+, surface immunoglobulin (low), CD79b (low), FMC7- 1, 2.

  • Monoclonal light chain restriction (either kappa or lambda) must be demonstrated 1.

  • Physical examination should document the number of involved lymph node regions for Binet staging 1, 2.

Common Pitfall to Avoid

Do not confuse TRAP staining results: TRAP-positive cells are pathognomonic for hairy cell leukemia, while TRAP-negative mature lymphocytes with lymphadenopathy in an elderly patient strongly suggest CLL 1. The negative TRAP stain in this case is a critical discriminating feature that rules out hairy cell leukemia and supports the CLL diagnosis.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Diagnostic Approach for Chronic Lymphocytic Leukemia (CLL)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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