What is the appropriate workup and diagnosis for an 11-year-old child with cervical lymphadenopathy and a negative Interferon-Gamma Release Assay (IGRA) result, suspected of having lymphoma?

Lymphoma Workup and Diagnosis in an 11-Year-Old with Cervical Lymphadenopathy and Negative IGRA

For an 11-year-old child with persistent cervical lymphadenopathy and negative IGRA, proceed directly to excisional biopsy if the lymph node is >2 cm, supraclavicular, or has persisted >10 weeks with suspicious ultrasound features (round shape, irregular margins, abnormal vascularity), as these are strong predictors of malignancy or serious pathology requiring definitive diagnosis. 1, 2, 3, 4

Initial Clinical Assessment

The negative IGRA result effectively rules out tuberculosis in this age group, shifting focus to other etiologies including lymphoma, nontuberculous mycobacterial (NTM) infection, or reactive causes. 1, 5

Key clinical features to assess immediately:

• Lymph node characteristics: Size >2 cm, supraclavicular location, firmness, fixation, and ulceration are highly suspicious for malignancy 2, 3
• Systemic symptoms: B symptoms (fever, night sweats, weight loss >10% body weight) strongly suggest lymphoma, particularly Hodgkin lymphoma 6
• Duration: Lymphadenopathy persisting >10 weeks without resolution warrants excisional biopsy 4
• Distribution: Unilateral cervical adenopathy in a child aged 1-5 years suggests NTM infection (95% unilateral), but at age 11, consider lymphoma more strongly 5

Essential Diagnostic Workup

Laboratory studies required before biopsy:

• Complete blood count with differential, platelet count 1
• Comprehensive metabolic panel including LDH (elevated in lymphoma), uric acid, liver function tests 1
• Hepatitis B surface antigen and core antibody (required before any potential rituximab-based therapy) 1
• Hepatitis C testing if high-risk 1

Imaging studies:

• Chest X-ray is mandatory to evaluate for mediastinal mass, which is common in Hodgkin lymphoma and lymphoblastic lymphoma 1, 6
• Ultrasound of the cervical lymph node should assess architecture, margins, shape, and vascularity—round shape, irregular margins, and abnormal vascularity predict malignancy 2, 3, 4
• PET/CT scan if lymphoblastic lymphoma is suspected based on clinical presentation 1

When to Proceed to Biopsy

Absolute indications for excisional biopsy:

• Lymph node >2 cm persisting >10 weeks 2, 3, 4
• Supraclavicular location (high malignancy risk) 2, 3
• Multiple levels of cervical adenopathy 2
• Fixed, firm, or ulcerated nodes 5
• Ultrasound showing round shape, irregular margins, or abnormal vascularity 3, 4
• Presence of B symptoms 6
• Abnormalities on chest X-ray 3
• Abnormal complete blood count 3

Surgical biopsy is the gold standard for lymphoma diagnosis—excisional or incisional biopsy is required, NOT fine-needle aspiration alone. 1, 6 Fine-needle aspiration has variable sensitivity in children and cannot reliably exclude malignancy. 3

Tissue Processing Requirements

The biopsy specimen must be sent to a reference hematopathology laboratory with expertise in:

• Morphological interpretation 1
• Immunophenotyping (mandatory for all suspected lymphomas) 1
• Flow cytometry for B-cell and T-cell markers 1
• Molecular studies including FISH for specific translocations if lymphoma is confirmed 1

For Hodgkin lymphoma specifically, immunostaining must include CD3, CD15, CD20, CD30, CD45, CD79a, and PAX5, with classical Hodgkin showing CD15+/CD30+/CD20- Reed-Sternberg cells. 6

Additional Staging if Lymphoma Confirmed

Once lymphoma is diagnosed, complete staging workup includes:

• PET/CT from skull base to mid-thigh 6
• Bone marrow biopsy (essential for most lymphomas, though may be deferred if PET/CT shows bone involvement indicating stage III/IV disease) 1
• Lumbar puncture for CNS evaluation in high-risk cases 1
• Echocardiogram or MUGA scan (required before anthracycline-based chemotherapy) 1
• CT or MRI of head if neurologic symptoms present 1

Critical Pitfalls to Avoid

• Do not treat empirically with antibiotics in the absence of acute bacterial infection signs (rapid onset, fever, tenderness, erythema), as this delays diagnosis and can mask underlying malignancy 5
• Do not rely on fine-needle aspiration alone to exclude lymphoma in children 1, 3
• Do not delay biopsy if clinical and ultrasound features are suspicious—all malignancies in pediatric series were diagnosed within 14 days of presentation 7
• Do not assume reactive hyperplasia based on partial resolution with antibiotics, as infection can occur in an underlying malignancy 5

Alternative Diagnosis Consideration

If biopsy reveals granulomatous inflammation rather than lymphoma, consider NTM lymphadenitis (particularly Mycobacterium avium complex), which accounts for 80% of culture-proven mycobacterial cervical lymphadenitis in children. 5 However, at age 11, this is less likely than in the 1-5 year age group. Treatment for NTM is complete surgical excision with 95% success rate. 5