How does lymphoma present on complete blood counts (CBC) and other blood work?

How Lymphoma Presents on Blood Work

Lymphoma frequently shows nonspecific abnormalities on complete blood counts, with anemia being the most common finding (present in 42%-66% of cases), followed by leukocytosis (26%), thrombocytopenia (13%), and less commonly leukopenia (6%), though normal blood counts do not exclude the diagnosis. 1, 2

Complete Blood Count Abnormalities

Most Common Findings

• Anemia is the predominant hematologic abnormality, occurring in 42%-66% of patients at diagnosis, and carries prognostic significance with shorter survival times regardless of bone marrow involvement 1, 2
• One or more abnormal counts are present in approximately 85% of patients, meaning completely normal CBCs are uncommon but possible 2
• Leukocytosis occurs in 26% of cases; when the white blood cell count exceeds 20 × 10⁹/L in patients without marrow involvement, it predicts shorter survival 1
• Thrombocytopenia is found in 13% of patients and correlates with poor prognosis specifically when bone marrow is involved by lymphoma 1
• Leukopenia is relatively uncommon (6%) and more likely when bone marrow is infiltrated by lymphoma 1

Specific Patterns by Lymphoma Subtype

• Lymphoblastic lymphoma commonly shows peripheral atypical lymphocytes and diffuse marrow involvement 2
• Peripheral T-cell lymphoma frequently demonstrates lymphocytopenia (41.3% of all NHL cases), which is a notable finding 2
• Diffuse large B-cell lymphoma often presents with lymphocytopenia and occasionally peripheral myeloid precursors or nucleated red blood cells 2
• Burkitt's lymphoma typically shows diffuse marrow involvement and eosinophilia 2

Critical Laboratory Tests Beyond CBC

Essential Initial Workup

• Lactate dehydrogenase (LDH) is the single most important serologic prognostic marker, reflecting tumor burden and incorporated into the International Prognostic Index 3, 4
• Beta-2-microglobulin provides additional prognostic information and should be measured at diagnosis 3, 4
• Uric acid is essential for assessing tumor lysis syndrome risk, particularly in high tumor burden cases 3, 4
• Comprehensive metabolic panel including liver enzymes, alkaline phosphatase, albumin, and renal function is mandatory 3, 4
• Immunoglobulin levels should be checked as part of the initial workup 3

Mandatory Infectious Disease Screening

• HIV serology is compulsory as it affects prognosis and treatment selection 3, 4
• Hepatitis B and C screening is required before initiating immunochemotherapy, particularly rituximab-containing regimens, as reactivation can be fatal 3, 4

Bone Marrow Findings

• Bone marrow involvement occurs in approximately 47% of patients at diagnosis 2
• When marrow is involved, diffuse infiltration is the pattern in 71% of cases 2
• Multiple cytopenias (bone marrow failure) are present in 8% of patients and predict short survival 1
• Leukoerythroblastosis (peripheral myeloid precursors and nucleated red cells) occurs in only 2% but indicates poor prognosis 1

Circulating Lymphoma Cells

• Circulating lymphoma cells are detectable in peripheral blood smears in 9.5% of cases 1
• In intravascular large B-cell lymphoma specifically, lymphoma cells may be present in small groups or single file, and can be detected in both peripheral blood and bone marrow aspirate smears 5
• The presence of circulating lymphoma does not independently alter survival when compared with other patients who have bone marrow involvement 1

Important Caveats

The absence of blood count abnormalities does not exclude lymphoma—approximately 15% of patients have entirely normal CBCs at diagnosis, making tissue biopsy essential for diagnosis rather than relying on blood work alone 2. Excisional lymph node biopsy providing adequate tissue is strongly preferred over fine-needle aspiration for accurate diagnosis 3, 4.

Routine blood work is not recommended for lymphoma screening or early detection in asymptomatic patients, even in high-risk populations, as there is no evidence supporting benefit for early detection of lymphoma through serial CBCs 3. However, prompt evaluation with complete workup should occur when signs or symptoms develop 3.