What is the likely diagnosis for a middle-aged adult with a history of occasional alcohol and tobacco use, presenting with persistent bilateral lymphadenopathy, night sweats, and pain upon neck movement 6 months post-treatment completion, with no known comorbidities, a family history of primary hypertension, and a negative TB GeneXpert result?

Lymphoma is the Most Likely Diagnosis

Given the persistent bilateral lymphadenopathy with night sweats, negative TB testing, and lack of response to antibiotics in a patient with tobacco and alcohol use, lymphoma—particularly Hodgkin lymphoma or non-Hodgkin lymphoma—is the most likely diagnosis, and the planned fine needle aspiration should be upgraded to excisional lymph node biopsy for definitive diagnosis. 1, 2

Critical Diagnostic Considerations

Why Lymphoma is Most Likely

The clinical presentation strongly suggests lymphoma based on multiple high-risk features:

• Bilateral supraclavicular lymphadenopathy is highly suspicious for malignancy, as supraclavicular nodes are abnormal and warrant immediate investigation 1, 3, 4
• Night sweats represent a classic B symptom that indicates systemic involvement and is highly suggestive of lymphoma, particularly Hodgkin lymphoma 2, 5
• Persistent lymphadenopathy beyond 4 weeks despite antibiotics indicates a non-infectious etiology requiring tissue diagnosis 1, 6, 3
• Tobacco and alcohol use are established risk factors for head and neck malignancies and lymphoma 1
• Firm, movable lymph nodes >1.5 cm meet criteria for possible malignancy 1

B Symptoms and Their Significance

The presence of night sweats is particularly important:

• Night sweats alone can mandate treatment initiation in certain lymphomas, even without other high tumor burden criteria 2
• B symptoms (fever >38°C, drenching night sweats, weight loss >10% in 6 months) indicate systemic involvement and more advanced disease 2, 5
• The absence of weight loss does not exclude lymphoma, as not all B symptoms need to be present 2

Critical Error in Current Plan: FNA is Insufficient

The planned fine needle aspiration must be changed to excisional lymph node biopsy:

• Excisional lymph node biopsy is mandatory for reliable lymphoma diagnosis, and fine needle aspiration alone is insufficient 2, 5
• Core needle biopsy is acceptable only when surgical biopsy is impractical or poses excessive risk 2
• Histology must follow WHO classification with immunophenotyping 2
• The right paracervical node (2x3 cm, movable, firm, tender) would be the optimal target for excisional biopsy 1

Differential Diagnosis to Consider

Hodgkin Lymphoma

• Most consistent with the clinical presentation given B symptoms (night sweats) and bilateral cervical/supraclavicular involvement 5
• Painless lymphadenopathy is typical in >60% of cases, though this patient has some tenderness 5
• Requires CD30+/CD15+ immunophenotyping for diagnosis 5

Non-Hodgkin Lymphoma

• Also highly possible given the presentation 2
• Multiple subtypes exist with varying aggressiveness
• B symptoms indicate need for immediate treatment regardless of stage in aggressive subtypes like diffuse large B-cell lymphoma 2

Less Likely Alternatives

Kikuchi-Fujimoto disease can present with cervical lymphadenopathy, fever, and night sweats but typically has a self-limiting course and would be unusual to persist this long without fever 7

Chronic lymphocytic leukemia/small lymphocytic lymphoma typically presents differently, with lymphadenopathy ≤1.5 cm being normal in some contexts, and this patient's nodes exceed this threshold 1

Immediate Next Steps

Required Workup Before Biopsy

• HIV, hepatitis B, and hepatitis C screening should be performed for all patients with suspected lymphoma and B symptoms 2
• Complete blood count to evaluate for cytopenias or circulating abnormal cells 2, 3
• LDH and β2-microglobulin levels (tumor burden markers) 2
• Comprehensive metabolic panel 3

Post-Biopsy Staging (If Lymphoma Confirmed)

• PET/CT scan is the gold standard for staging and should be performed in all patients with confirmed lymphoma and B symptoms 2
• MRI is recommended for suspected CNS involvement 2
• Bone marrow biopsy may be necessary depending on lymphoma subtype 5

Critical Pitfalls to Avoid

Do not proceed with FNA alone - this is the single most important error to correct, as it will delay definitive diagnosis and appropriate treatment 2, 5

Do not start corticosteroids empirically - they can mask the histologic diagnosis of lymphoma or other malignancy 3, 4

Do not dismiss the significance of supraclavicular nodes - these are abnormal in adults and highly associated with malignancy, particularly thoracic or abdominal malignancies draining to this region 1, 3, 4

Do not delay biopsy - lymphadenopathy persisting beyond 4 weeks with systemic symptoms requires tissue diagnosis to rule out malignancy 6, 3