What is the best approach for a patient with a triple phase computed tomography (CT) scan of the abdomen showing lymphadenopathy suggestive of Tuberculous lymphadenitis, metastatic disease, or lymphoma?

Diagnostic Approach to Abdominal Lymphadenopathy with Differential of Tuberculous Lymphadenitis, Metastatic Disease, or Lymphoma

The next step is tissue diagnosis through image-guided core needle biopsy or excisional biopsy of the most accessible lymph node, with concurrent tuberculosis testing (tuberculin skin test or interferon-gamma release assay) and assessment for primary malignancy sites. 1, 2, 3

Immediate Diagnostic Workup

Tissue Acquisition Strategy

• Obtain histologic confirmation through excisional biopsy or core needle biopsy of the most abnormal/accessible node, as this provides the best architectural assessment for distinguishing between tuberculosis, lymphoma, and metastatic disease 1, 2, 4
• Fine-needle aspiration (FNA) is less reliable than excisional biopsy for lymphoma diagnosis but can be highly effective for tuberculous lymphadenitis when acid-fast bacilli smears are performed on the aspirate 5, 6
• Request the following on biopsy specimens: routine histology, acid-fast bacilli staining, mycobacterial culture, flow cytometry (for lymphoma), and immunohistochemistry as needed 1, 5

Concurrent Laboratory and Imaging Studies

• Obtain tuberculin skin test or interferon-gamma release assay immediately, as 94% of patients with tuberculous lymphadenitis have positive tuberculin skin tests 7
• Complete blood count, lactate dehydrogenase (LDH), erythrocyte sedimentation rate, and HIV testing are essential 1, 7
• For suspected lymphoma: PET-CT from skull base to mid-thigh is the gold standard for staging FDG-avid lymphomas including diffuse large B-cell lymphoma 1
• Chest radiograph or chest CT to evaluate for pulmonary tuberculosis (present in 38% of tuberculous lymphadenitis cases) or primary lung malignancy 7, 5

Distinguishing Features on Imaging and Clinical Presentation

Tuberculous Lymphadenitis Characteristics

• Typically presents with insidious onset over weeks to months without systemic symptoms in many cases 8, 5
• In adults, tuberculous lymphadenitis accounts for >90% of culture-proven mycobacterial cervical lymphadenitis, though abdominal involvement follows similar patterns 8, 7
• Nodes may show rim enhancement with central necrosis on contrast-enhanced CT 5, 6

Lymphoma Characteristics

• PET-CT demonstrates focal FDG uptake in involved nodes and can identify bone marrow involvement, potentially eliminating the need for bone marrow biopsy in some cases 1
• Systemic B symptoms (fever, night sweats, weight loss) are common but not universal 1
• Multiple nodal regions involved (generalized lymphadenopathy) suggests lymphoma or systemic disease 2, 3

Metastatic Disease Characteristics

• Search for primary malignancy sites: supraclavicular nodes have highest malignancy risk; axillary nodes often indicate breast cancer metastases; abdominal/retroperitoneal nodes may indicate GI, GU, or gynecologic primaries 2, 3, 6
• Nodes >2 cm, hard consistency, or matted/fused to surrounding structures suggest malignancy 3, 4
• Elevated LDH has prognostic significance in metastatic disease 1

Critical Decision Points

If Tuberculosis is Confirmed

• Initiate 4-drug anti-tuberculosis therapy immediately: isoniazid 5 mg/kg (max 300 mg daily), rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4-7 additional months 7, 9, 10
• Surgical excision plus chemotherapy may be considered for localized disease, particularly if nodes are large or in difficult anatomical locations 7, 5
• Mandatory public health notification as tuberculosis is a reportable disease 8, 7

If Lymphoma is Confirmed

• Complete staging with PET-CT if not already performed 1
• Bone marrow biopsy is only needed if PET-CT is negative and identifying discordant histology would change management 1
• Treatment depends on lymphoma subtype, stage, and International Prognostic Index (IPI) score; for DLBCL, R-CHOP chemotherapy is standard for most patients 1

If Metastatic Disease is Confirmed

• Identify the primary malignancy through additional imaging: chest/abdomen/pelvis CT, mammography for women, colonoscopy, upper endoscopy, or other site-specific studies based on clinical suspicion 1
• Biopsy confirmation of metastatic disease is preferred before initiating systemic therapy 1

Common Pitfalls to Avoid

• Never use corticosteroids before obtaining tissue diagnosis, as they can mask histologic features of lymphoma or malignancy 7, 2, 3
• Avoid incisional biopsy or drainage alone for suspected mycobacterial lymphadenitis, as this frequently leads to sinus tract formation and chronic drainage 7
• Do not treat empirically with antibiotics for presumed bacterial lymphadenitis when lymphadenopathy has persisted >4 weeks without clear infectious source 2, 3
• Do not use anti-TB drugs without proper confirmation, as inappropriate treatment can lead to drug resistance and treatment failure 7, 9
• If considering FNA, ensure acid-fast bacilli smears are specifically requested, as this is the most reliable indicator of mycobacterial infection (positive in all but 3 patients in one series) 5