What is relative lymphocytosis?

Relative Lymphocytosis: Definition and Clinical Significance

Relative lymphocytosis is defined as an increased percentage of lymphocytes (>15% of the total white blood cell differential count) without an elevation in the absolute lymphocyte count. 1

Distinguishing Relative vs. Absolute Lymphocytosis

• Relative lymphocytosis: Increased percentage of lymphocytes in the differential count without elevation in absolute lymphocyte count
• Absolute lymphocytosis: Increased absolute lymphocyte count (typically >4,000 lymphocytes/μL in adults)

Clinical Significance

Relative lymphocytosis commonly occurs in two main scenarios:

1. Normal lymphocyte count with decreased other white blood cells:

   • Most commonly due to neutropenia
   • The lymphocyte percentage appears increased because other cell lines are decreased

2. Response to specific infections:

   • Viral infections (particularly EBV, CMV, HIV)
   • Certain bacterial infections (pertussis, tuberculosis)
   • Parasitic infections

Diagnostic Evaluation

When relative lymphocytosis is identified:

1. Complete blood count with differential to confirm the finding and assess other cell lines 1

2. Peripheral blood smear review to evaluate lymphocyte morphology:

   • Normal-appearing lymphocytes suggest reactive process
   • Atypical lymphocytes (>10%) suggest viral infection 2
   • Abnormal morphology may suggest malignancy

3. Flow cytometry immunophenotyping if malignancy is suspected:

   • Essential for distinguishing between reactive and malignant lymphocytosis
   • Should include T-cell markers (CD3, CD4, CD8), B-cell markers (CD19, CD20, CD23), and clonality assessment 1

Common Causes of Relative Lymphocytosis

Infectious Causes

• Viral infections (EBV, CMV, hepatitis, HIV)
• Pertussis (whooping cough)
• Tuberculosis
• Brucellosis

Non-infectious Causes

• Recovery phase of acute infections
• Stress response with neutrophilia
• Certain medications
• Hypersplenism

Distinguishing from Chronic Lymphocytic Leukemia (CLL)

It's important to distinguish relative lymphocytosis from CLL:

• CLL diagnosis requires ≥5 × 10^9/L B lymphocytes in peripheral blood 3
• Flow cytometry showing CD5+/CD19+/CD23+ phenotype is diagnostic of CLL 1
• In CLL, lymphocytes appear mature but monoclonal 3

When to Suspect Malignancy

Consider malignancy when:

• Persistent lymphocytosis (>4 weeks)
• Presence of lymphadenopathy or organomegaly
• Abnormal lymphocyte morphology
• Age >50 years with persistent relative lymphocytosis ≥50% 4

Key Pitfalls to Avoid

1. Overlooking relative lymphocytosis: Even without absolute lymphocytosis, persistent relative lymphocytosis ≥50% in older individuals warrants investigation 4

2. Missing monoclonal B-cell lymphocytosis (MBL): Can occur with normal lymphocyte counts but shows decreased normal B-cell subsets 5

3. Age-related variations: Lymphocyte subpopulations vary significantly during childhood, requiring age-specific reference ranges 6

4. Focusing only on percentages: Absolute counts of lymphocyte subpopulations provide more valuable clinical information than percentages alone 6

By systematically evaluating relative lymphocytosis and understanding its various causes, clinicians can appropriately identify patients requiring further investigation for potential underlying conditions affecting morbidity and mortality.