What is the diagnosis and treatment for a patient with persistent lymphadenopathy, extreme fatigue, and dysregulation of body temperature for 6 months?

Diagnostic Workup for Persistent Lymphadenopathy with Fatigue and Temperature Dysregulation

This patient requires urgent evaluation for lymphoma or other hematologic malignancy given the 6-month duration of lymphadenopathy with constitutional symptoms, and should undergo immediate laboratory testing followed by excisional lymph node biopsy if initial workup suggests malignancy.

Initial Laboratory Assessment

The first step is obtaining a peripheral blood film with complete blood count, as this can rapidly identify lymphocytosis, abnormal lymphocytes, or circulating blasts indicating leukemia or lymphoma 1. This single test can establish the diagnosis of chronic lymphocytic leukemia without requiring bone marrow examination initially 1.

Priority Laboratory Tests

• Complete blood count with differential to evaluate for cytopenias or abnormal cells 1
• Lactate dehydrogenase (LDH) as an elevated level strongly suggests lymphoma or lymphoproliferative processes 2, 1
• β2-microglobulin for prognostic assessment if lymphoproliferative disorder is suspected 2
• Erythrocyte sedimentation rate (ESR) to screen for inflammatory or malignant processes 2
• Thyroid function tests (TSH, free T4) as hypothyroidism causes fatigue in 66% of cases and commonly presents with temperature dysregulation 2, 3

Additional Screening Tests

• Morning cortisol and ACTH levels to evaluate for adrenal insufficiency, which commonly presents with fatigue 2
• EBV serology (VCA-IgG, EA-IgG) and quantitative EBV PCR to assess for chronic active EBV infection, which can present with persistent lymphadenopathy and fatigue 2, 1
• Hepatitis B and C, HIV testing as these are mandatory before potential chemotherapy 4, 1

Imaging Studies

Contrast-enhanced CT scan of chest, abdomen, and pelvis is mandatory to evaluate the extent of lymphadenopathy and identify potential primary sites of malignancy 1. A baseline PET-CT scan should be performed when lymphoma is suspected, as it has high sensitivity for staging and can eliminate the need for bone marrow biopsy 4, 1.

Critical Red Flags for Malignancy

The following features strongly suggest malignant lymphadenopathy and warrant urgent tissue diagnosis:

• Duration >4 weeks (this patient has 6 months) 5, 6
• Constitutional B symptoms: The combination of extreme fatigue and temperature dysregulation likely represents fever/night sweats, which are classic B symptoms 4, 1
• Lymph nodes >2 cm are considered abnormal and concerning for malignancy 5, 6
• Supraclavicular location is the most worrisome for malignancy 6, 7

Tissue Diagnosis

Excisional lymph node biopsy is the gold standard for definitive diagnosis when lymphoma is suspected 1, 8. This should be pursued when:

• The blood film shows abnormal lymphocytes requiring characterization 1
• Clinical suspicion remains high despite non-diagnostic initial tests 1
• Immunophenotyping and histologic architecture are needed for classification 1

Fine-needle aspiration or core needle biopsy have lower diagnostic yield for lymphoma and should be avoided when lymphoma is the primary concern 8. Excision of an entire lymph node is essential for proper lymphoma workup 9.

Common Pitfalls to Avoid

• Do not wait beyond 4 weeks for persistent lymphadenopathy—this patient is already at 6 months 5, 6
• Do not use corticosteroids before establishing a diagnosis, as they can mask the histologic diagnosis of lymphoma 5, 6
• Do not rely solely on fine-needle aspiration when lymphoma is suspected 8
• Do not assume benign etiology in adults with generalized lymphadenopathy, as this frequently indicates hematological systemic disease 9

Specific Lymphoma Considerations

If Hodgkin lymphoma is suspected based on age and presentation:

• 26% of Hodgkin lymphoma patients have fatigue lasting ≥6 months 4
• Temperature dysregulation may represent the fever component of B symptoms 4
• The presence of B symptoms significantly impacts staging and prognosis 4

Treatable Contributing Factors

While pursuing malignancy workup, assess for:

• Sleep disturbances and sleep apnea, which are present in 30-75% of patients with cancer-related fatigue 4
• Depression, which correlates moderately with fatigue (r=0.41) in lymphoma patients 4
• Anemia, which commonly accompanies lymphoproliferative disorders 4
• Pain and emotional distress, which frequently cluster with fatigue 4

The diagnostic algorithm priority is: (1) peripheral blood film and CBC with differential, (2) LDH and β2-microglobulin, (3) contrast-enhanced CT imaging, (4) excisional lymph node biopsy if malignancy suspected 2, 1.