What workup is required to exclude lymphoma in a patient presenting with enlarged cervical lymph nodes?

Workup to Exclude Lymphoma in Enlarged Cervical Lymph Nodes

The essential workup requires excisional lymph node biopsy for definitive tissue diagnosis, contrast-enhanced CT imaging of neck/chest/abdomen/pelvis, complete blood count, comprehensive metabolic panel, LDH, and hepatitis B/C and HIV screening. 1, 2

Immediate Tissue Diagnosis

Excisional or incisional lymph node biopsy is the gold standard and must be performed to definitively exclude or diagnose lymphoma. 3, 1 This provides adequate tissue for:

• Routine histology with WHO classification 3
• Immunohistochemistry including CD20, B-cell and T-cell markers 3
• Fresh frozen material for molecular studies when possible 3

Fine needle aspiration (FNA) can be used as an initial approach but has significant limitations—it may yield non-diagnostic results requiring repeat sampling and often provides insufficient tissue for complete immunophenotyping. 1, 2 If FNA shows only necrosis or is non-diagnostic, proceed immediately to excisional biopsy rather than repeating FNA. 2

Core needle biopsy may be acceptable only in emergency situations or when nodes are not easily accessible (e.g., retroperitoneal), but should not be the first choice for accessible cervical nodes. 3

Essential Imaging Studies

Obtain contrast-enhanced CT scan of neck, chest, abdomen, and pelvis immediately for any patient with enlarged cervical lymph nodes concerning for malignancy. 3, 1, 2 This evaluates:

• Extent of nodal disease and additional involved stations 2
• Mediastinal or abdominal involvement suggesting lymphoma 2
• Identification of occult primary tumors 2

A baseline chest X-ray is also required. 3

PET-CT should be considered after tissue diagnosis is confirmed for complete staging, as it has high sensitivity for detecting additional disease sites and bone marrow involvement. 3, 1, 2

Mandatory Laboratory Testing

Complete the following labs before any treatment:

Blood counts and chemistry:

• Complete blood count with differential to assess for cytopenias or leukocytosis 3, 1
• Comprehensive metabolic panel including liver enzymes and albumin 3, 1
• Lactate dehydrogenase (LDH)—critical prognostic marker and indicator of tumor burden 3, 1
• Uric acid level to assess tumor lysis risk if high tumor burden present 3, 1

Infectious disease screening (mandatory before treatment):

• Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb)—reactivation can occur with chemotherapy and anti-CD20 therapy 3, 1, 2
• Hepatitis C serology 3, 1
• HIV testing 3, 1

Additional markers if lymphoma suspected:

• β2-microglobulin as prognostic marker 3, 2
• Protein electrophoresis for B-cell lymphomas 3

Bone Marrow Evaluation

If PET-CT is performed, bone marrow biopsy may not be necessary. 1 However, if PET-CT is unavailable, bone marrow aspirate and biopsy are essential for complete staging. 3, 1

High-Risk Features Requiring Additional Workup

Perform lumbar puncture with prophylactic intrathecal chemotherapy in patients with more than two adverse International Prognostic Index (IPI) parameters, especially with bone marrow involvement, testicular involvement, or involvement of spine/base of skull. 3, 1

Specialized Physical Examination

The otolaryngologist must perform direct laryngoscopy to visualize the larynx, base of tongue, and pharynx to identify occult primary tumors in the upper aerodigestive tract that commonly metastasize to cervical nodes. 2

Measure all accessible peripheral lymph node groups, assess liver and spleen size, and document performance status. 3, 1

Critical Pitfalls to Avoid

Do not assume benignity based solely on imaging characteristics—tissue diagnosis is mandatory. 1

Do not prescribe empiric antibiotics without clear bacterial infection, as this delays malignancy diagnosis and provides false reassurance. 2

Do not accept inadequate tissue for diagnosis—if initial sampling is insufficient, proceed directly to excisional biopsy. 1, 2

Do not delay hepatitis B screening, as reactivation during treatment can be life-threatening. 3, 1, 2

Timeline for Completion

Urgent referral is required for any neck mass present ≥2 weeks, with imaging within days of presentation, tissue diagnosis within 1-2 weeks, and definitive diagnosis and treatment planning within 3-4 weeks of initial presentation. 2