What initial labs and tests should be ordered for a patient with large cervical lymphadenopathy, neck pain, and fatigue?

Initial Diagnostic Workup for Large Cervical Lymphadenopathy, Neck Pain, and Fatigue

For a patient with large cervical lymphadenopathy, neck pain, and fatigue, a thorough diagnostic workup should include excisional lymph node biopsy, complete blood count, contrast-enhanced CT scan of neck/chest/abdomen/pelvis, and PET/CT scan to rule out malignancy, particularly lymphoma.

Initial Assessment and Risk Stratification

Concerning Features for Malignancy

• Size >1.5 cm - Lymph nodes larger than 1.5 cm in the cervical region are suspicious for malignancy 1
• Firm consistency - Non-tender, firm lymph nodes increase suspicion for malignancy 1
• Fixed to adjacent tissues - Reduced mobility suggests malignancy 1
• Duration ≥2 weeks without fluctuation 1
• Absence of infectious symptoms 1
• Systemic symptoms - Fatigue is particularly concerning when combined with lymphadenopathy 1

Laboratory Tests

1. Complete blood count with differential 1

   • Assess for leukocytosis, lymphocytosis, anemia
   • Look for atypical lymphocytes

2. Inflammatory markers

   • Erythrocyte sedimentation rate (ESR) 1
   • C-reactive protein (CRP) 1
   • Lactate dehydrogenase (LDH) - elevated in lymphoma 1

3. Liver and renal function tests 1

   • Alkaline phosphatase (AP)
   • Albumin
   • Liver enzymes

4. Infectious disease screening

   • HIV testing 1
   • Hepatitis B and C serology 1
   • EBV serology (if infectious mononucleosis suspected) 2

Imaging Studies

First-line Imaging

1. Contrast-enhanced CT scan of neck, chest, abdomen, and pelvis 1

   • Evaluates extent of lymphadenopathy
   • Identifies potential primary malignancy
   • Assesses for hepatosplenomegaly

2. PET/CT scan (skull base to midthigh) 1

   • Essential for initial staging if lymphoma is suspected
   • Should be obtained within 1 month before treatment initiation
   • Helps identify disease extent and metabolic activity
   • Can guide biopsy site selection

Additional Imaging Considerations

• Chest X-ray - Recommended in cases with suspected mediastinal mass 1
• MRI - May be considered in select cases, particularly for evaluating soft tissue involvement 1

Tissue Diagnosis

Biopsy Options

1. Excisional lymph node biopsy 1

   • Gold standard for diagnosis of lymphoma
   • Provides adequate tissue for histopathology, immunohistochemistry, and molecular studies
   • Preferred over core needle biopsy when possible

2. Core needle biopsy 1

   • May be adequate if diagnostic
   • Less invasive than excisional biopsy

3. Fine-needle aspiration (FNA) 1

   • Generally insufficient for definitive diagnosis of lymphoma
   • May be used initially to rule out metastatic carcinoma or infection

Immunohistochemical Studies

For suspected Hodgkin lymphoma, immunostaining should include 1:

• CD3, CD15, CD20, CD30, CD45, CD79a, and PAX5
• Reed-Sternberg cells typically express CD30 and CD15

Special Considerations

When to Suspect Lymphoma

• Combination of large cervical lymphadenopathy and fatigue
• Absence of infectious symptoms
• Firm, non-tender lymph nodes
• Presence of B symptoms (fever >38°C, night sweats, weight loss >10% in 6 months) 1

Pitfalls to Avoid

1. Inappropriate antibiotic use - Antibiotics should not be routinely prescribed unless there are clear signs of bacterial infection 1
2. Delayed diagnosis - Lymphadenopathy >2 weeks without fluctuation warrants prompt evaluation 1
3. Inadequate biopsy - FNA alone is usually insufficient for lymphoma diagnosis 1
4. Missing systemic disease - Complete imaging workup is essential even with localized lymphadenopathy 1

Diagnostic Algorithm

1. Assess for risk factors and concerning features for malignancy
2. Order initial laboratory tests (CBC, ESR, CRP, LDH, liver/renal function)
3. Obtain contrast-enhanced CT of neck/chest/abdomen/pelvis
4. Proceed with PET/CT if lymphoma is suspected
5. Perform excisional lymph node biopsy of the most accessible abnormal node
6. Consider additional testing based on initial results

By following this comprehensive diagnostic approach, clinicians can efficiently evaluate patients with cervical lymphadenopathy, neck pain, and fatigue to identify potentially serious conditions like lymphoma and guide appropriate management.