What is the appropriate workup for axillary lymphadenopathy?

Workup for Axillary Lymphadenopathy

Begin with ultrasound as the primary imaging modality, combined with diagnostic mammography (or digital breast tomosynthesis) for patients ≥30 years or ultrasound alone for patients <30 years, followed by ultrasound-guided core needle biopsy if morphologically abnormal lymph nodes are identified. 1, 2, 3

Initial Imaging Strategy

Age-Based Approach

• For patients ≥30 years: Perform diagnostic mammography (or digital breast tomosynthesis) plus targeted axillary ultrasound at the same visit 1, 2, 3
• For patients <30 years: Perform ultrasound alone as the initial imaging modality 2
• Complete all imaging studies before any tissue biopsy, as biopsy-related changes will confound subsequent image interpretation 3

Ultrasound Assessment

• Ultrasound serves as the best modality to assess axillary involvement and can identify morphologically abnormal lymph nodes not detected on physical examination 1, 3
• Look for the characteristic "snowstorm" appearance that indicates silicone adenitis from ruptured breast implants 1, 4
• Evaluate whether nodes are solid or cystic and characterize their morphology 1, 3

Mammography Role

• Mammography may identify a breast cancer that has metastasized to the axilla or detect silicone within low axillary nodes 1
• Provides comprehensive breast assessment and evaluates for additional suspicious findings such as microcalcifications 2

Tissue Diagnosis Protocol

Core Needle Biopsy

• Core needle biopsy is strongly preferred over fine needle aspiration because it provides adequate tissue for histologic diagnosis, immunohistochemical staining (ER/PR, HER2), and other ancillary studies 2, 3
• Proceed with ultrasound-guided core biopsy if imaging demonstrates morphologically abnormal lymph nodes, especially in the absence of any breast abnormality on mammography and ultrasound 1
• Core biopsy correctly establishes malignancy in 96% of haematological malignancies and 100% of metastatic carcinomas, with no false positives or false negatives 5

When to Biopsy

• Biopsy morphologically abnormal lymph nodes without characteristic findings of silicone adenitis 1
• If axillary lymphadenopathy persists for more than 3 months after COVID-19 vaccination, perform sonographic follow-up after another 3 months; biopsy if nodes are persistent, progressive, or suspicious 6
• In patients with histologically confirmed breast cancer, perform core biopsy without a follow-up interval regardless of vaccination history 6

Advanced Imaging Considerations

MRI Indications

• If mammography and ultrasound show no breast primary but lymph nodes appear suspicious, proceed to breast MRI, which identifies occult breast cancer in approximately 70% of patients with suspicious axillary lymphadenopathy and negative conventional imaging 3
• MRI provides better evaluation of the chest wall and level II and III nodes compared to ultrasound 1
• MRI without contrast is of limited value for unexplained axillary adenopathy, as silicone in lymph nodes can be more readily diagnosed with ultrasound 1

PET/CT Role

• For staging in patients with locally advanced breast cancer and suspected metastatic disease, either whole-body PET/CT or bone scan combined with contrast-enhanced abdominal CT remains the standard 1
• PET/CT detects distant metastasis with sensitivity of 50-100% and specificity of 50-97% in women with advanced breast cancers 1
• Avoid FDG-PET/CT as initial imaging for evaluating axillary masses, as it has low yield and is not cost-effective in this setting 2

Differential Diagnosis Framework

Unilateral Axillary Lymphadenopathy

• Metastatic breast cancer is the most common malignant cause when cancer is identified in axillary nodes 3, 4
• Occult breast cancer can present with isolated axillary masses, occurring in less than 1% of breast cancers 4
• Reactive lymphadenopathy from infections is the most common benign etiology 4
• Silicone adenitis from ruptured breast implants produces characteristic "snowstorm" appearance on ultrasound 1, 4

Bilateral Axillary Lymphadenopathy

• Non-Hodgkin's lymphoma frequently presents with bilateral nodal involvement 4
• Autoimmune diseases can produce bilateral reactive adenopathy 4
• Systemic infections or inflammatory conditions should be considered 4

Common Pitfalls to Avoid

• Do not delay preoperative staging of breast cancer with follow-up intervals; suspicious lymph nodes should be histologically examined in a minimally invasive procedure regardless of vaccination status 6
• Document vaccination history (vaccine, date, place of application) when evaluating suspicious lymph nodes, as vaccine-associated lymphadenopathy can persist for more than 100 days after COVID-19 vaccination 6
• Avoid extensive investigations hoping to discover an occult primary tumor; once malignancy is confirmed, limit further investigations to a search for treatable malignancies only 7
• Do not perform routine cytokeratin immunohistochemistry to define node involvement in clinical decision-making; use it only for equivocal cases on H&E staining 1