Is an elevated white blood cell count normal in the absence of Hodgkin lymphoma?

Elevated WBC in Non-Hodgkin Lymphoma

An elevated white blood cell count can occur in non-Hodgkin lymphoma and is present in approximately 26% of patients at diagnosis, though it is not a universal or defining feature of the disease. 1

Frequency and Clinical Significance

• Leukocytosis (elevated WBC) occurs in roughly one-quarter of NHL patients at presentation, making it a common but not obligatory finding 1
• The presence of leukocytosis does not distinguish between lymphoma subtypes, as hematologic parameters are similar across B-cell and T-cell lymphomas 1
• Circulating lymphoma cells are detectable in approximately 9.5% of NHL cases at diagnosis 1

Prognostic Implications

Mild to moderate leukocytosis (WBC <20 × 10⁹/L) does not adversely affect survival in NHL patients. 1

However, important prognostic distinctions exist:

• In patients without bone marrow involvement, leukocytosis exceeding 20 × 10⁹/L is associated with significantly shortened survival 1
• In patients with bone marrow involvement, the degree of leukocytosis does not independently predict survival outcomes 1
• The presence of circulating lymphoma cells does not alter survival when compared to other patients with bone marrow involvement 1

Bone Marrow Involvement Patterns

The relationship between peripheral blood findings and marrow disease shows specific patterns:

• Leukopenia (6% of cases) and thrombocytopenia (13% of cases) are more strongly associated with bone marrow involvement than leukocytosis 1
• Anemia occurs in 42% of NHL patients at diagnosis but shows only a weak association with marrow involvement 1
• Multiple cytopenias (present in 8% of cases) indicate bone marrow failure and predict poor survival regardless of documented marrow involvement 1

Diagnostic Workup Requirements

When NHL is suspected, the NCCN guidelines mandate specific laboratory assessments:

• Complete blood count with differential and platelet count 2
• Comprehensive metabolic panel including LDH, which serves as a prognostic marker 2
• Peripheral blood flow cytometry to evaluate for circulating lymphoma cells 2
• Bone marrow biopsy (trephine) with or without aspiration for initial staging 2

Critical Distinction: Reactive vs. Malignant Leukocytosis

Manual examination of the peripheral blood smear is essential to distinguish benign reactive leukocytosis from lymphoproliferative disorders. 3

Key morphologic features to assess:

• Pleomorphic lymphocytes suggest reactive processes, while monomorphic lymphocyte populations favor lymphoproliferative neoplasms 3
• Flow cytometry should be performed on samples suspicious for lymphoproliferative disorders to confirm clonality 3
• Activated neutrophil changes with left shift suggest infection rather than malignancy 3

Common Pitfalls to Avoid

• Do not assume that normal or low WBC excludes NHL—74% of patients present without leukocytosis 1
• Do not rely solely on automated differentials; manual smear review is mandatory to identify circulating lymphoma cells and assess lymphocyte morphology 3
• Do not interpret leukocytosis in isolation—correlate with other cytopenias, bone marrow involvement, and clinical stage 1
• Do not overlook that leukocytosis >20 × 10⁹/L carries prognostic significance only in patients without bone marrow involvement 1