Laboratory Findings in Lymphoma
Patients with lymphoma typically demonstrate elevated lactate dehydrogenase (LDH), cytopenias (anemia and thrombocytopenia), and abnormal flow cytometry showing clonal lymphocyte populations, with specific findings varying by lymphoma subtype. 1
Essential Initial Laboratory Tests
Complete Blood Count Abnormalities
- Anemia is common and may result from bone marrow infiltration, autoimmune hemolysis (particularly in chronic lymphocytic leukemia), or chronic disease 2, 3
- Thrombocytopenia occurs frequently, either from marrow replacement or immune-mediated destruction with increased platelet-bound IgG 4, 3
- Leukopenia may be present, though some patients maintain normal absolute neutrophil counts 3
- Lymphocytosis (absolute lymphocyte count >4000/μL) is characteristic of leukemic subtypes, particularly chronic and acute forms 2
- Circulating abnormal lymphocytes can be detected on peripheral blood smears in aggressive nodal T-cell lymphomas, correlating with bone marrow involvement 5
Biochemical Markers
- Elevated LDH serves as a critical prognostic marker, with levels >2× normal indicating particularly aggressive disease 1
- Hypercalcemia occurs specifically in certain T-cell lymphomas, especially adult T-cell leukemia/lymphoma, and should be measured in all patients 2, 1
- Elevated uric acid indicates high tumor burden and tumor lysis risk 1
- Hypoalbuminemia represents a strong independent negative prognostic factor, particularly in aggressive lymphomas 6
Comprehensive Metabolic Panel
- Liver and renal function tests are mandatory for initial evaluation and treatment planning 1
- Electrolytes must be assessed given the risk of tumor lysis syndrome 2
Critical Diagnostic Testing
Flow Cytometry Analysis
Flow cytometry is essential for distinguishing reactive from neoplastic lymphocytosis and determining lymphoma subtype. 1
B-Cell Lymphoma Panel
- Minimum markers include CD19, CD20, CD23, and surface immunoglobulin light chains (kappa/lambda) to assess clonality 1
- Additional markers CD5, CD10, BCL2, and BCL6 are required for specific B-cell subtypes 1
- Immunophenotypic studies reveal at least 2-3 distinct groups: CD20+ CD5+, CD20+ CD5- CD10+, and CD20+ CD5- CD10 unknown 3
T-Cell Lymphoma Panel
- Minimum panel includes CD2, CD3, CD4, CD5, CD7, CD8, and CD25 2, 1
- Adult T-cell leukemia/lymphoma typically shows CD4-positive cells with CD2, CD5, CD25, CD45RO, CD29, and HLA-DR expression 2
- Most cases are CD7-negative and CD26-negative with low CD3 expression 2
Infectious Disease Serology
- HIV, hepatitis B, and hepatitis C testing is mandatory for all lymphoma patients, as these infections influence treatment decisions and prognosis 1, 7
- HTLV-1 serology (enzyme-linked immunosorbent assay and Western blot) is required when adult T-cell leukemia/lymphoma is suspected 2
Inflammatory Markers
- Erythrocyte sedimentation rate (ESR) should be measured as part of initial evaluation 1
Advanced Molecular and Cytogenetic Testing
Essential FISH and Cytogenetic Studies
Genetic testing through FISH, conventional cytogenetics, and molecular analysis is critical for diagnosis, risk stratification, and treatment selection. 1
Subtype-Specific Testing
- Mantle cell lymphoma: t(11;14)(q13;q32) CCND1-IGH translocation 1
- Follicular lymphoma: t(14;18)(q32;q21) BCL2-IGH and immunoglobulin light chain variants 1
- Diffuse large B-cell lymphoma: MYC, BCL2, and BCL6 rearrangements assessment 1
- Adult T-cell leukemia/lymphoma: Monoclonal integration of HTLV-1 provirus by Southern blot or inverted polymerase chain reaction 2
Prognostic Markers
- Complex karyotypes and TP53 loss in mantle cell lymphoma indicate unfavorable prognosis 1
- Genomic complexity detected by chromosomal microarray represents an independent marker of aggressive disease 1
Subtype-Specific Laboratory Patterns
Adult T-Cell Leukemia/Lymphoma Classification
The Shimoyama classification distinguishes subtypes based on specific laboratory criteria 2:
- Smoldering: Normal lymphocyte count, >5% abnormal cells, no hypercalcemia, LDH <1.5× normal 2
- Chronic: Elevated lymphocyte count, >5% abnormal cells, no hypercalcemia, LDH <2× normal 2
- Acute: Elevated lymphocyte count, >5% abnormal cells, hypercalcemia present, LDH >2× normal 2
- Lymphoma: Normal lymphocyte count, <1% abnormal cells, hypercalcemia present, LDH >2× normal 2
Common Pitfalls to Avoid
- Do not rely solely on peripheral blood findings—bone marrow biopsy may be necessary when peripheral blood is non-diagnostic, though it is not routinely required 2, 3
- Do not overlook immune-mediated cytopenias—thrombocytopenia and anemia may be autoimmune rather than infiltrative, requiring different management approaches 4
- Do not miss circulating tumor cells—careful examination of peripheral blood smears can reveal lymphoma cells even when not suspected clinically 3
- Do not interpret LDH in isolation—correlate with other markers and clinical context, as levels >2× normal have specific prognostic significance 2, 1
- Do not forget infectious workup—HTLV-1, HIV, and hepatitis serology are not optional tests but mandatory components of lymphoma evaluation 2, 1