What is the appropriate diagnosis and management for a patient with congenital lymphadenopathy involving multiple cervical and supraclavicular lymph nodes?

Congenital Lymphadenopathy with Progressive Cervical and Supraclavicular Involvement

This patient requires urgent excisional biopsy of the supraclavicular lymph node to rule out malignancy, as supraclavicular lymphadenopathy carries a significantly higher risk for malignant disease compared to other cervical locations, and the progressive growth pattern since birth is highly concerning. 1, 2

Critical Risk Stratification

The supraclavicular location is a red flag that fundamentally changes the diagnostic approach:

• Supraclavicular nodes are abnormal by definition and warrant immediate investigation regardless of other features 1
• Supraclavicular or posterior cervical lymphadenopathy carries a much higher risk for malignancies than anterior cervical lymphadenopathy 2
• The progressive growth pattern over time, rather than spontaneous resolution, further elevates malignancy concern 1, 3

Immediate Diagnostic Workup

Proceed directly to excisional biopsy without delay, as observation is inappropriate for supraclavicular nodes:

• Excisional biopsy is indicated for supraclavicular location, nodes >2 cm, hard/fixed consistency, or absence of infectious symptoms 4
• Send fresh tissue in saline for flow cytometry, immunohistochemistry (CD20, CD10, Ki-67), and cytogenetics to evaluate for lymphoma 4
• Include tissue for mycobacterial culture and acid-fast bacilli staining, as tuberculosis and nontuberculous mycobacteria can present with cervical and supraclavicular involvement 5, 6

Pre-Biopsy Evaluation

While arranging urgent biopsy, obtain:

• Complete blood count with differential to assess for leukemia, cytopenias, or atypical lymphocytosis 4
• Tuberculosis testing (PPD or interferon-gamma release assay), as mycobacterial disease can involve supraclavicular nodes 4, 5
• CT chest and abdomen to evaluate for mediastinal, hilar, or intra-abdominal lymphadenopathy and assess for systemic disease 4
• Regional examination for hepatosplenomegaly and other lymph node regions 4

Differential Diagnosis Priority

Given the congenital onset with progressive growth, consider:

Malignant Etiologies (Highest Priority)

• Lymphoma (Hodgkin or non-Hodgkin): Progressive lymphadenopathy with supraclavicular involvement is characteristic 4, 1
• Burkitt lymphoma: Rapidly growing masses with potential for oncologic emergencies like tumor lysis syndrome 4
• Diffuse large B-cell lymphoma: Large lymphoid cells with variable nuclear contours 4

Infectious Etiologies (Lower Priority but Must Exclude)

• Tuberculosis: Can present with cervical and supraclavicular involvement, particularly with mediastinal node involvement 5
• Nontuberculous mycobacteria: Typically affects children 1-5 years old with unilateral cervical nodes, but supraclavicular involvement is atypical 6, 7
• EBV-associated lymphoproliferative disease: Can cause persistent lymphadenopathy with long-term lymphoma risk 8

Critical Pitfalls to Avoid

• Never observe supraclavicular lymphadenopathy for 2-4 weeks as you would with anterior cervical nodes—this location demands immediate tissue diagnosis 1, 2
• Do not treat empirically with antibiotics without tissue diagnosis, as this delays appropriate management and may mask malignancy 7, 4
• Avoid fine-needle aspiration as the sole diagnostic modality for supraclavicular nodes—excisional biopsy provides superior tissue architecture and diagnostic yield 4
• Do not dismiss the congenital history—while most congenital lymphadenopathy is benign, progressive growth indicates an active pathologic process requiring definitive diagnosis 1

Management Algorithm

1. Immediate referral to surgical oncology or pediatric surgery for excisional biopsy within 1-2 weeks 4
2. If tuberculosis testing is strongly positive and granulomatous disease is found on biopsy, consider anti-TB therapy while awaiting culture results 4
3. If lymphoma is diagnosed, immediate oncology referral for staging and treatment 4
4. If nontuberculous mycobacteria is confirmed, excisional surgery alone is curative in 95% of cases 7

The combination of supraclavicular location, progressive growth since birth, and involvement of multiple cervical regions creates a clinical picture that cannot be managed conservatively—tissue diagnosis is mandatory to guide appropriate treatment and prevent mortality from delayed malignancy diagnosis. 1, 2