What are the typical laboratory findings for lymphoma?

Laboratory Findings of Lymphoma

The typical laboratory findings in lymphoma include complete blood count abnormalities (anemia in 42%, thrombocytopenia in 13%, leukopenia in 6%, leukocytosis in 26%), elevated lactate dehydrogenase, and specific cytogenetic abnormalities detected through FISH, flow cytometry, and chromosomal analysis that are essential for diagnosis, subtype classification, and prognostication. 1, 2

Initial Laboratory Evaluation

Complete Blood Count and Peripheral Blood Findings

• Anemia is present in approximately 42% of patients at diagnosis and is associated with shorter survival regardless of bone marrow involvement 1
• Thrombocytopenia occurs in 13% of cases and correlates with poor prognosis when bone marrow is involved by lymphoma 1
• Leukopenia is found in 6% of patients and is more common when bone marrow is infiltrated by lymphoma 1
• Leukocytosis (>20 × 10⁹/L) occurs in 26% and indicates poor prognosis in patients without marrow involvement 1
• Multiple cytopenias (bone marrow failure) are present in 8% of cases and strongly predict short survival 1
• Circulating lymphoma cells can be detected in 9.5% of patients, with atypical lymphocytes appearing as cells with polylobated nuclei, condensed chromatin, and basophilic cytoplasm ("flower cells" in adult T-cell leukemia/lymphoma) 2, 3

Essential Chemistry and Serology Tests

• Lactate dehydrogenase (LDH) is elevated in many lymphomas and serves as a prognostic marker; levels >2× normal are particularly significant in aggressive subtypes 2, 3
• Serum calcium should be measured, as hypercalcemia occurs in certain T-cell lymphomas, particularly adult T-cell leukemia/lymphoma 2
• Comprehensive metabolic panel including liver and renal function tests is required 3, 2
• Uric acid levels should be obtained to assess tumor lysis risk 4
• HIV, hepatitis B (HBs antigen, anti-HBs, anti-HBc), and hepatitis C serology are mandatory 2
• Erythrocyte sedimentation rate (ESR) should be measured 2

Specialized Diagnostic Testing

Flow Cytometry Immunophenotyping

Flow cytometry is essential for distinguishing reactive from neoplastic lymphocytosis and determining lymphoma subtype. 3, 2

B-Cell Lymphoma Markers

• Minimum panel for B-cell lymphomas: CD19, CD20, CD23, surface immunoglobulin light chains (kappa/lambda) to assess clonality 3
• Additional markers: CD5 (positive in CLL/SLL and mantle cell lymphoma), CD10 (positive in follicular lymphoma and Burkitt lymphoma), BCL2, BCL6 2

T-Cell Lymphoma Markers

• Minimum panel for T-cell lymphomas: CD2, CD3, CD4, CD5, CD7, CD8, CD25 2, 3
• Adult T-cell leukemia/lymphoma: CD4+, CD25+, CD7-, CD26- with low CD3 expression 2
• CD30 expression should be evaluated for anaplastic large cell lymphoma 3

Cytogenetic and Molecular Testing

Genetic testing through FISH, conventional cytogenetics, and molecular analysis is critical for diagnosis, risk stratification, and treatment selection. 2

Essential FISH Testing by Lymphoma Subtype

Mantle Cell Lymphoma:

• t(11;14)(q13;q32) CCND1-IGH and variants involving CCND2 or CCND3 2
• MYC and BCL6 rearrangements for prognostication 2
• TP53 deletion (17p13) associated with unfavorable prognosis 2

Follicular Lymphoma:

• t(14;18)(q32;q21) BCL2-IGH and immunoglobulin light chain variants 2
• BCL6 rearrangements (3q27) 2
• IRF4 rearrangements (6p25) and TNFRSF14 loss (1p36) in BCL2-negative cases 2

Diffuse Large B-Cell Lymphoma (DLBCL):

• "Double-hit" or "triple-hit" assessment: MYC (8q24), BCL2 (18q21), and BCL6 (3q27) rearrangements 2
• MYC rearrangements occur in 10% of DLBCL and confer poor prognosis, especially when combined with BCL2 rearrangements 2
• BCL10 (1p22) rearrangements 2

Burkitt Lymphoma:

• t(8;14) MYC-IGH and immunoglobulin light chain variants, with absence of BCL2 or BCL6 involvement or complex karyotype 2

MALT Lymphoma:

• t(11;18)(q21;q21) BIRC3-MALT1 2
• t(14;18)(q32;q21) MALT1-IGH (cytogenetically identical to BCL2-IGH, requiring FISH differentiation) 2
• t(1;14)(p22;q32) BCL10-IGH and t(3;14)(p14.1;q32) FOXP1-IGH 2
• Trisomy 3 and/or trisomy 18 2

Anaplastic Large Cell Lymphoma:

• ALK-positive: t(2;5)(p23;q35) NPM1-ALK and other ALK rearrangements 2
• ALK-negative: DUSP22-IRF4 rearrangement t(6;7)(p25.3;q32.3) (good prognosis) or TP63 rearrangements (adverse prognosis) 2

T-Cell Prolymphocytic Leukemia:

• inv(14)(q11;q32.1) or t(14;14)(q11;q32.1) TRA/D-TCL1A/B 2
• t(X;14)(q28;q11) TRA/D-MTCP1 2

Chromosomal Analysis Requirements

• G-banded chromosome analysis is recommended for all involved fresh tissues, preferably lymph node or biopsy material 2
• At least 100 selected cells should be scored for FISH analysis 2
• Positive cutoff levels: 10% for fusion or break-apart probes, 20% for numerical abnormalities 2
• Conventional cytogenetics can identify complex karyotypes and genomic complexity, which are independent markers of aggressive disease 2

Molecular Genetic Testing

• T-cell receptor (TCR) gene rearrangement demonstrates clonality in T-cell lymphoproliferative disorders 3
• HTLV-I serology and provirus integration (Southern blot or inverted PCR) for adult T-cell leukemia/lymphoma 2
• Mutation screening for hairy cell leukemia and Waldenström macroglobulinemia/lymphoplasmocytic lymphoma (no disease-specific chromosomal abnormalities) 2

Bone Marrow Evaluation

Indications for Bone Marrow Biopsy

• Not routinely required if PET/CT demonstrates bone or marrow involvement indicating advanced-stage disease 2
• Indicated when: PET/CT is negative but results would change prognosis and treatment, especially when shortened immunochemotherapy cycles are proposed 2
• Required for: persistent unexplained cytopenias, multiple cytopenias, or when peripheral blood findings are insufficient for diagnosis 4, 3
• Bone marrow involvement is an independent poor prognostic factor and more likely with leukopenia and thrombocytopenia 1

Bone Marrow Analysis Components

• Morphologic evaluation 4
• Cytochemical studies 4
• Conventional cytogenetic analysis 4
• Flow cytometry immunophenotyping 4
• Molecular genetic testing 4

Common Pitfalls and Caveats

• False-negative FISH results can occur without reliable plasma cell selection methods; totally normal results must be qualified 2
• PET/CT can be positive in sites of infection or inflammation even without lymphoma; additional clinical or pathologic evaluation is needed for atypical presentations 2
• Immunohistochemistry for cell-of-origin classification (germinal center vs. non-germinal center) has reproducibility issues and should not routinely guide clinical decisions 2
• MYC and BCL2 protein expression ("double expressors") by immunohistochemistry is only partly correlated with genetic rearrangements but indicates poor prognosis 2
• Fine-needle aspiration alone is insufficient for diagnosis except in unusual circumstances when combined with immunohistochemistry and judged diagnostic by an expert hematopathologist 2
• Atypical lymphocytes in patients receiving CAR-T therapy may represent reactive T cells at peak expansion rather than lymphoma 3
• CD30+ small cells with preserved T-cell antigens (CD2, CD3, CD5, CD7) suggest reactive T cells rather than lymphoma 3

Risk Stratification Laboratory Markers

• Anemia at presentation predicts shorter survival independent of bone marrow involvement 1
• Leukocytosis >20 × 10⁹/L without marrow lymphoma indicates poor prognosis 1
• Thrombocytopenia with bone marrow involvement predicts short survival 1
• Multiple cytopenias or leukoerythroblastosis strongly predict short survival 1
• Complex karyotypes and TP53 loss in mantle cell lymphoma indicate unfavorable prognosis 2
• Genomic complexity detected by chromosomal microarray is an independent marker of aggressive disease 2