What is the recommended workup for a patient with suspected lymphoma?

Lymphoma Workup

An excisional lymph node biopsy is the gold standard for lymphoma diagnosis, followed by comprehensive staging with PET-CT imaging, complete laboratory evaluation including hepatitis B screening, and bone marrow assessment only if PET-CT is unavailable or shows specific indications. 1, 2

Tissue Diagnosis

Biopsy Approach

• Excisional lymph node biopsy is strongly preferred as it provides adequate tissue architecture for accurate subtype classification 1, 2
• Core needle biopsy may be adequate but should only be used when lymph nodes are not easily accessible 1, 2
• Fine needle aspiration is insufficient for proper diagnosis except in rare circumstances when combined with expert immunohistochemistry interpretation 1, 2
• Fresh frozen tissue should be stored when possible to allow for additional molecular analyses 2

Immunophenotyping

• Initial panel must include Pan-B and Pan-T cell antigens (CD3, CD15, CD20, CD30, CD45, CD79a, PAX5 for classical Hodgkin lymphoma) 1
• Additional B-cell and T-cell subset antigens should be added based on morphologic and clinical features 1
• For non-Hodgkin lymphoma, minimum panel should include CD20, CD10, CD5, and cyclin D1 to differentiate from other indolent lymphomas 1

Essential Laboratory Studies

Blood Work

• Complete blood count with differential and platelets 1, 2
• Comprehensive metabolic panel including renal and liver function 1, 2
• Lactate dehydrogenase (LDH) - critical prognostic marker 1, 2
• Hepatitis B testing (HBsAg and HBcAb) is mandatory before initiating anti-CD20 monoclonal antibody therapy due to reactivation risk 1
• Hepatitis C and HIV testing should be performed in high-risk patients 1
• Erythrocyte sedimentation rate (ESR) 2
• Beta-2 microglobulin (optional, depending on lymphoma type) 1

Additional Testing

• Pregnancy test in women of childbearing age before treatment 1
• Serum protein immunofixation for certain subtypes 1

Imaging Studies

Required Imaging

• PET-CT from skull base to mid-thigh is now the standard staging modality 1, 2
• Diagnostic contrast-enhanced CT of chest, abdomen, and pelvis if PET-CT unavailable 1, 2
• Chest radiograph particularly for patients with large mediastinal mass 1

PET-CT Advantages

• Superior for confirming localized stage I/II disease 2
• Identifies areas with high standardized uptake values suggesting transformation 2
• Serves as baseline for response assessment 2
• Has largely replaced routine bone marrow biopsy due to high sensitivity for bone marrow involvement 1, 2

Bone Marrow Assessment

Bone marrow biopsy is no longer routinely required if PET-CT is performed and shows negative or homogeneous uptake pattern 1, 2. However, bone marrow biopsy remains essential in these situations:

• PET-CT unavailable 2
• PET-CT shows multifocal (≥3) skeletal lesions suggesting involvement 1
• Cytopenias present 1
• Evaluation of potentially early-stage indolent lymphoma (stage I or II) 1
• Aggressive subtypes like primary cutaneous DLBCL, leg-type 1
• When treatment decisions depend on marrow status 1

A common pitfall: In patients with low-bulk indolent disease and radiographic stage III disease managed with observation, bone marrow biopsy can be deferred as it won't change management 1

Site-Specific Evaluations

Central Nervous System

• CT or MRI of head with contrast if neurologic symptoms present 1, 2
• Lumbar puncture for cerebrospinal fluid analysis in high-risk subtypes (mantle cell lymphoma, DLBCL with specific features) 1, 2

Gastrointestinal

• Esophagogastroduodenoscopy with multiple biopsies for gastric MALT lymphoma 1
• Endoscopic ultrasound to evaluate regional lymph nodes and gastric wall infiltration 1

Testicular

• Scrotal ultrasound as indicated for male patients, particularly with T-cell lymphomas 1, 2

Cardiac and Pulmonary Assessment

• Echocardiogram or MUGA scan is mandatory when anthracycline-containing regimens are planned 1
• Pulmonary function tests including DLCO for patients receiving bleomycin-based chemotherapy 1
• More frequent cardiac monitoring required if anthracyclines used in patients with impaired cardiac function 1

Pre-Treatment Considerations

Fertility Preservation

• Fertility counseling should be offered to all patients of reproductive age 1
• Sperm cryopreservation for males, oocyte or ovarian tissue cryopreservation for females 1
• Alkylating agent-based chemotherapy carries higher risk of premature ovarian failure 1
• Oophoropexy should be considered for premenopausal women receiving pelvic radiation 1

Vaccinations

• H. influenzae, pneumococcal, and meningococcal vaccines if splenic radiation contemplated 1

Common Pitfalls to Avoid

• Never rely solely on fine needle aspiration - inadequate tissue architecture leads to misdiagnosis 1, 2
• Don't skip hepatitis B testing - reactivation with rituximab can be fatal 1
• Don't routinely perform bone marrow biopsy if high-quality PET-CT available - unnecessary invasive procedure 1, 2
• Don't delay fertility counseling - must occur before chemotherapy initiation 1
• Ensure adequate tissue is obtained initially to avoid repeat biopsies 2
• In early-stage indolent lymphoma, bone marrow biopsy remains essential despite PET-CT availability 1