What is the differential diagnosis for an 8-year-old with subclavian lymph node enlargement?

Differential Diagnosis of Subclavian Lymph Node Enlargement in an 8-Year-Old

In an 8-year-old with subclavian lymph node enlargement, the differential diagnosis includes infectious causes (viral infections like EBV, bacterial lymphadenitis, nontuberculous mycobacteria), malignant causes (lymphomas including Burkitt lymphoma, diffuse large B-cell lymphoma, and Hodgkin lymphoma), and less commonly, autoimmune or metabolic conditions. 1, 2

Primary Diagnostic Categories

Infectious Etiologies (Most Common)

• Viral infections are the most frequent cause of lymphadenopathy in children, with EBV-associated infectious mononucleosis presenting with constitutional symptoms, cervical/supraclavicular lymphadenopathy, and splenomegaly 3
• Bacterial lymphadenitis typically presents with tender, warm, erythematous nodes, often unilateral, and may be mistakenly treated with antibiotics when the true cause is nontuberculous mycobacteria 4
• Nontuberculous mycobacterial (NTM) lymphadenitis occurs most commonly in children aged 1-5 years, with approximately 80% of cases due to Mycobacterium avium complex; these nodes are typically unilateral, non-tender, and may progress to violaceous discoloration 4
• Tuberculosis must be considered, particularly with positive PPD tuberculin skin testing and granulomatous disease on biopsy 4

Malignant Etiologies (Critical to Exclude)

• Burkitt lymphoma presents with rapidly growing masses, often with extranodal involvement, fever, night sweats, and potential oncologic emergencies like tumor lysis syndrome; cells are intermediate-sized with "starry sky" appearance on histology and >95% Ki-67 positivity 5
• Diffuse large B-cell lymphoma (DLBCL) shows large lymphoid cells with variable nuclear contours and typically lacks the "starry sky" pattern; both express CD20, CD10, and surface immunoglobulin 5
• Hodgkin lymphoma should be considered, particularly in older children and adolescents, with EBV detected in approximately 40% of classical cases 3

Other Considerations

• Autoimmune conditions and metabolic diseases can affect lymph nodes but are less common in this age group 6
• Post-transplant lymphoproliferative disorders are relevant only in immunocompromised patients 5

Critical Diagnostic Approach

History Must Include:

• Duration and progression of lymph node enlargement (rapid growth suggests malignancy) 7
• Constitutional symptoms: fever, night sweats, unintentional weight loss, fatigue (B symptoms suggest lymphoma) 5
• Infectious exposures: sick contacts, animal exposures, travel history, soil/water contact (NTM risk) 4, 2
• Respiratory or gastrointestinal symptoms: cough, dyspnea, abdominal pain (extranodal involvement) 5
• Family history of lymphoma or immunodeficiency 7

Physical Examination Must Assess:

• Node characteristics: size (>2 cm supraclavicular is concerning), consistency (hard/rubbery suggests malignancy, fluctuant suggests abscess), mobility (fixed nodes suggest malignancy), tenderness (suggests infection) 7, 6
• Location: supraclavicular/subclavian nodes have higher malignancy risk than cervical nodes 1, 7
• Regional examination: check for hepatosplenomegaly, other lymph node regions 5
• Skin changes: violaceous discoloration suggests NTM, erythema suggests bacterial infection 4

Initial Diagnostic Workup:

• Complete blood count with differential to assess for atypical lymphocytosis (viral), leukemia, or cytopenias 3, 7
• Tuberculosis testing with PPD or interferon-gamma release assay, particularly if node is unilateral and non-tender 4
• Ultrasound imaging is the first-line imaging modality to characterize node size, vascularity, and internal architecture 1, 7
• Chest radiograph to evaluate for mediastinal masses or pulmonary involvement 1

When to Pursue Tissue Diagnosis:

• Excisional biopsy is indicated for: supraclavicular location, node >2 cm persisting >4-6 weeks, hard/fixed consistency, absence of infectious symptoms, or concerning imaging features 1, 7
• For suspected NTM lymphadenitis, excisional biopsy without chemotherapy is the treatment of choice with 95% success rate 4
• For suspected malignancy, fresh tissue should be sent in saline for flow cytometry, immunohistochemistry (CD20, CD10, Ki-67), and cytogenetics 5
• Fine-needle aspiration has limitations but may be used for initial evaluation in select cases 4

Critical Pitfalls to Avoid

• Do not dismiss supraclavicular/subclavian lymphadenopathy as benign without thorough evaluation, as this location carries higher malignancy risk than cervical nodes 1, 7
• Do not treat presumed bacterial lymphadenitis with prolonged antibiotics without response assessment; lack of improvement after 2 weeks suggests alternative diagnosis like NTM or malignancy 4, 2
• Do not delay biopsy in children with painless, progressive lymph node enlargement, B symptoms, or nodes >2 cm persisting beyond 4-6 weeks 7
• Recognize that EBV infection carries long-term lymphoma risk, requiring patient education about warning signs and consideration of follow-up every 6-12 months for 2-3 years 3
• In children with strongly positive PPD and granulomatous disease, consider anti-TB therapy while awaiting culture results 4