What is the management approach for a single enlarged lymph node?

Management of a Single Enlarged Lymph Node

A single enlarged lymph node requires immediate tissue diagnosis via fine-needle aspiration (FNA) if it exhibits high-risk features (hard, fixed, >1.5 cm), with excisional biopsy if FNA is non-diagnostic, as malignancy must be excluded to prevent mortality from delayed diagnosis of cancer or lymphoma. 1

Initial Risk Stratification

The physical examination characteristics determine urgency and approach:

High-Risk Features Requiring Immediate Biopsy

• Hard consistency and reduced mobility are specific indicators of increased malignancy risk 1
• Fixation to adjacent tissues indicates capsular violation by metastatic cancer invading surrounding structures 1
• Size >1.5 cm combined with firm texture significantly increases malignancy probability 1, 2
• Duration ≥2 weeks or uncertain timeline constitutes a red flag for malignancy 1
• Supraclavicular location warrants immediate investigation regardless of other features 2

Additional Concerning Features

• Age >40 years, particularly with tobacco/alcohol use 1
• Constitutional symptoms including unexplained weight loss, night sweats, fever 1
• Absence of recent infection makes reactive etiology unlikely 1
• Ulceration of overlying skin suggests capsular breakthrough and advanced malignancy 1

Diagnostic Algorithm

Step 1: Tissue Diagnosis

FNA is the standard initial approach for accessible nodes per American Academy of Otolaryngology-Head and Neck Surgery guidelines 1:

• Ultrasound-guided FNAC achieves 93% sensitivity and 91% specificity for palpable nodes 3
• If FNA is negative but high-risk features persist, proceed immediately to excisional biopsy 1
• Surgical excisional biopsy should be considered when FNA is non-diagnostic or lymphoma is suspected 3

Step 2: Concurrent Imaging

CT with IV contrast should be obtained concurrently to evaluate disease extent 1:

• CT is the imaging method of choice, using >15 mm short axis as the size criterion 3
• PET/CT may be useful for suspected lymphoma (88% sensitivity, 98% specificity) 3

Step 3: Laboratory Evaluation

• Complete blood count with differential 3
• Lactate dehydrogenase (LDH) 3
• Flow cytometry if hematologic malignancy suspected 3

Location-Specific Malignancy Considerations

The anatomic location guides differential diagnosis:

• Cervical nodes: Head/neck squamous cell carcinoma, lymphoma, or metastatic disease 1
• Axillary nodes: Breast cancer, lymphoma, or melanoma from upper extremity 1
• Inguinal nodes: Genitourinary malignancies, melanoma from lower extremity, or lymphoma 1
• Supraclavicular nodes: Always consider malignancy regardless of other features 2

Observation Strategy (Low-Risk Nodes Only)

Observation for 2-4 weeks is appropriate ONLY for nodes with benign clinical features 2:

• Soft consistency
• Mobile
• <1 cm diameter
• Associated with recent infection
• Age <40 years without risk factors

Any node that persists beyond 4 weeks requires tissue diagnosis 2.

Critical Pitfalls to Avoid

• Never rely solely on negative FNA in high-risk nodes—confirm with excisional biopsy 1
• Do not delay biopsy for prolonged observation in nodes with concerning features—surgical biopsy reduces investigation time from 3 months to 1.25 months compared to sequential needle biopsies 4
• Normal-sized nodes may contain malignant cells, and morphological criteria beyond size improve diagnostic accuracy 3
• Needle biopsy sensitivity for lymphoma is only 67-68%, necessitating surgical confirmation when clinical suspicion remains high 4

Response Assessment (If Lymphoma Diagnosed)

For diffuse large B-cell lymphoma, complete response requires regression to ≤1.5 cm greatest transverse diameter in nodes >1.5 cm before therapy 5.