Diagnostic Approach for Suspected Lymphoma
An excisional lymph node biopsy is the gold standard first step, followed by comprehensive staging with PET-CT, laboratory studies including complete blood count, chemistry panel with LDH, viral screening (HIV, hepatitis B and C), and bone marrow assessment only if PET-CT is unavailable. 1, 2, 3
Tissue Acquisition
Excisional biopsy of an entire lymph node is mandatory for initial diagnosis, providing adequate tissue for morphology, immunohistochemistry, flow cytometry, and molecular studies. 1, 2, 3
Fine-needle aspiration is inadequate and inappropriate for initial lymphoma diagnosis and should only be used in rare emergency situations requiring immediate treatment. 1, 3
Core needle biopsies are acceptable only when excisional biopsy is not feasible (inaccessible nodes) or to document relapse, but a nondiagnostic sample must be followed by excisional biopsy. 1, 3
Fresh-frozen tissue and cell suspensions should be stored with patient consent for future molecular analyses. 1
The specimen must be reviewed by an experienced lymphoma pathologist, with diagnosis according to WHO classification. 1, 3
Essential Laboratory Studies
Complete blood count with differential, comprehensive metabolic panel including LDH, and mandatory viral screening are required before treatment planning. 2, 3
- CBC with platelets and differential 1, 2
- Chemistry panel: LDH, uric acid, potassium, phosphates, calcium (tumor lysis panel), liver function tests, albumin, renal function 1, 2
- Mandatory screening for HIV, hepatitis B, and hepatitis C 1, 2, 3
- Erythrocyte sedimentation rate (ESR) 2
Imaging Studies for Staging
PET-CT is the standard imaging modality for staging and should include contrast-enhanced CT of neck, chest, abdomen, and pelvis. 1, 2, 3
PET-CT improves accuracy of staging compared to CT alone for both nodal and extranodal sites in FDG-avid lymphomas (Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma). 1, 4
PET-CT is particularly valuable for confirming localized stage I/II disease and identifying areas with high standardized uptake values suspicious for transformation. 2
For non-FDG-avid lymphomas (small lymphocytic lymphoma/chronic lymphocytic leukemia), contrast-enhanced CT alone is sufficient. 4
Bone Marrow Assessment
Bone marrow biopsy is no longer required if PET-CT is performed, as PET-CT has high sensitivity for bone marrow involvement. 2
Bone marrow aspirate and biopsy must be performed only if PET-CT is unavailable. 1, 2
In Hodgkin lymphoma specifically, PET-CT is sufficient to rule out bone marrow involvement without biopsy. 4
Pathology Requirements
The minimum immunohistochemistry panel must include: 1, 3
- CD45, CD20, CD3 (pan-T-cell and B-cell markers) 1, 3
- Additional markers as needed: CD10, BCL-2, BCL-6, MUM1, CD5, CD30, Ki-67 1, 3
- Flow cytometry alternative: CD45, CD3, CD5, CD19, CD10, CD20, CD30, CD4, CD8, CD7, CD2 1
Molecular studies for clonal T-cell receptor gene rearrangements and specific translocations (e.g., ALK gene rearrangements) may be useful in peripheral T-cell lymphomas. 1
Site-Specific Evaluations
Additional testing is required based on clinical presentation and lymphoma subtype: 1, 2
CNS evaluation: Lumbar puncture for CSF analysis and CT/MRI head with contrast if neurologic symptoms present or high-risk features (multiple extranodal sites, testicular involvement, HIV-positive status) 1, 2
Testicular evaluation: All male patients require assessment for testicular involvement; scrotal ultrasound if indicated 1, 2
Gastrointestinal evaluation: Endoscopy if GI involvement suspected 2
Skin examination: Full skin examination for cutaneous manifestations; punch biopsy (minimum 4mm diameter, full-thickness) if lesions present 3
Pre-Treatment Assessments
Cardiac and fertility evaluations are mandatory before initiating anthracycline-based chemotherapy: 1
- Echocardiogram or multigated acquisition scan (anthracyclines are backbone of most regimens) 1
- Electrocardiography 2
- Pulmonary function tests 2
- Pregnancy testing for females of reproductive age 1, 2
- Fertility counseling and preservation options for all patients 1
Staging and Risk Stratification
Stage according to Ann Arbor/Lugano classification system and calculate prognostic indices: 1, 2, 3
- Ann Arbor staging with notation of bulky disease (>10cm or >1/3 thoracic diameter) 1
- International Prognostic Index (IPI) for aggressive lymphomas 1, 3
- Follicular Lymphoma International Prognostic Index (FLIPI) for follicular lymphoma 1, 2
Common Pitfalls to Avoid
Never rely on fine-needle aspiration alone for initial diagnosis—this is the most common error and leads to inadequate tissue for complete characterization. 1, 3
Do not skip viral screening—HIV and hepatitis status fundamentally alter treatment approach and prognosis. 2, 3
Do not perform bone marrow biopsy if PET-CT is available—this represents unnecessary invasive testing with PET-CT's high sensitivity. 2
Do not forget cardiac assessment—anthracycline cardiotoxicity is a major cause of treatment-related morbidity. 1