What is the workup for a patient with a lymph node enlargement and overlying skin discoloration, considering potential causes such as infection (e.g. tuberculosis, cat-scratch disease) or malignancy (e.g. lymphoma, metastatic cancer)?

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Workup for Lymph Node with Overlying Skin Discoloration

Immediate Priority: Exclude Malignancy

A lymph node with overlying skin discoloration requires urgent evaluation for malignancy, as skin ulceration overlying a neck mass indicates metastatic cancer that has broken through the lymph node capsule and directly invaded the skin, or represents a cutaneous malignancy with direct extension into the neck. 1


High-Risk Features Requiring Immediate Action

The presence of skin discoloration/ulceration is itself a red flag that mandates aggressive workup. Additional concerning features include:

  • Size >1.5 cm 1
  • Firm or hard consistency 1
  • Fixation to adjacent tissues (reduced mobility) 1
  • Duration ≥2 weeks 1
  • Age >40 years 1
  • Tobacco and/or alcohol use 1

Algorithmic Workup Approach

Step 1: Confirm Tissue Diagnosis

  • Fine-needle aspiration (FNA) is strongly preferred over open biopsy for initial tissue sampling 1, 2, 3
  • Open biopsy should be avoided as it can complicate subsequent treatment and delay definitive care 1
  • Send tissue for:
    • Histopathology with immunophenotyping 3
    • Cytogenetic/molecular analysis if lymphoma suspected 3
    • Mycobacterial culture if granulomatous disease present 4

Step 2: Imaging Studies

  • Contrast-enhanced CT of neck (or MRI) is mandatory to assess extent of disease and identify primary tumor 1, 2, 3
  • PET-CT should be considered to identify occult primary malignancy and assess for distant metastases 1, 2
  • For melanoma specifically: chest imaging and consideration of brain MRI if any neurologic symptoms 1

Step 3: Targeted Physical Examination

  • Direct visualization of upper aerodigestive tract including larynx, base of tongue, and pharynx by otolaryngologist 3
  • Complete skin examination to identify primary melanoma or other cutaneous malignancy 1
  • Examination of all lymph node basins 1, 3

Step 4: Laboratory Testing

  • Complete blood count, comprehensive metabolic panel 3
  • Lactate dehydrogenase (LDH) - prognostic marker for lymphoma and melanoma 1, 3
  • Hepatitis B, C, and HIV serology if malignancy confirmed and treatment planned 3
  • Tuberculosis testing (PPD or IGRA) if granulomatous disease suspected 4

Critical Differential Diagnoses

Malignancy (Most Likely)

  1. Metastatic squamous cell carcinoma from head/neck primary 1, 2
  2. Melanoma with in-transit metastases or direct skin invasion 1
    • Skin discoloration may represent melanoma pigmentation
    • Requires complete dermatologic examination 1
  3. Cutaneous lymphoma (CD30+ lymphoproliferative disorders, anaplastic large cell lymphoma) 1
  4. Lymphoma with extranodal extension 3

Infectious Causes (Less Likely but Important)

  1. Nontuberculous mycobacterial (NTM) infection 4
    • More common in children 1-5 years old
    • Typically unilateral, may have violaceous skin discoloration
    • Excisional biopsy is treatment of choice (95% success rate) 4
  2. Tuberculosis 4
    • Requires PPD/IGRA testing
    • Critical to distinguish from NTM for public health tracking 4
  3. Cat-scratch disease (Bartonella henselae) 5, 6, 7
    • History of cat exposure (though not always present)
    • Can present with persistent lymphadenopathy and skin changes
    • Serology and PCR on tissue for diagnosis 6, 7

Common Pitfalls to Avoid

  • Never prescribe empiric antibiotics without clear signs of acute bacterial infection (fever, rapid onset, tenderness, erythema), as this delays cancer diagnosis 1, 2
  • Do not assume cystic appearance on imaging is benign - HPV-positive oropharyngeal cancer frequently presents as cystic cervical metastases mimicking branchial cleft cysts 2
  • Avoid corticosteroids - they mask histologic diagnosis of lymphoma and other malignancies 8, 9
  • Do not rely on normal laboratory values - they provide false reassurance and do not exclude malignancy 2
  • Partial resolution after antibiotics does not exclude malignancy - infection can coexist with underlying cancer 2, 3

Urgent Specialist Referral

Immediate referral to otolaryngology (head/neck surgery) or surgical oncology is mandatory for any lymph node with overlying skin changes 1, 2, 3. This is not a "wait and see" scenario - skin involvement indicates advanced local disease requiring urgent evaluation and treatment planning.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Evaluation and Management of Persistent Upper Neck Lumps

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Evaluation and Management of Persistent Cervical Lymphadenopathy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Nontuberculous Mycobacterial Lymphadenitis in Children

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Disseminated cat-scratch disease during abatacept therapy for rheumatoid arthritis in an older patient: A case report and review of the literature.

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 2025

Research

Lymphadenopathy: Evaluation and Differential Diagnosis.

American family physician, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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