What are the causes of axillary adenopathy with uptake on a Positron Emission Tomography (PET) scan?

Causes of Axillary Adenopathy with FDG Uptake on PET-CT

Axillary adenopathy with FDG uptake on PET-CT has a broad differential diagnosis that includes both benign and malignant etiologies, with the most common causes being metastatic breast cancer, lymphoma/leukemia, reactive lymphadenopathy from infectious or inflammatory processes, and less commonly, metastases from non-mammary malignancies. 1

Malignant Causes

Primary Breast Cancer and Metastases

• Metastatic breast cancer is the most common malignant cause of axillary adenopathy with FDG uptake, though less than 1% of breast cancers initially present as isolated axillary adenopathy. 1
• FDG-PET/CT demonstrates high specificity (90-100%) but variable sensitivity (48-87%) for detecting axillary lymph node metastases from breast cancer. 1
• Higher maximum standardized uptake value (SUV max) of axillary nodes may predict metastatic disease, though this finding is not universally reliable. 1
• When incidental axillary FDG uptake is detected on PET/CT, further evaluation with mammography, digital breast tomosynthesis, and ultrasound is required, followed by possible image-guided biopsy. 1

Hematologic Malignancies

• Lymphoma and leukemia are the most common non-mammary malignancies causing bilateral axillary adenopathy with FDG uptake. 1
• These systemic malignancies typically present with adenopathy in multiple nodal stations beyond just the axilla. 1

Metastases from Other Primary Sites

• Metastatic melanoma can present as FDG-avid axillary adenopathy, sometimes without an identifiable primary lesion. 2
• Other non-mammary malignancies can metastasize to axillary nodes, though this is less common. 1

Benign Causes

Reactive/Inflammatory Adenopathy

• Benign reactive lymphadenopathy from infectious and inflammatory processes is a common cause of FDG-avid axillary nodes. 1
• Infectious etiologies include mastitis, granulomas, and skin wound infections. 1, 3
• Autoimmune diseases can also cause reactive axillary adenopathy with FDG uptake. 1

Post-Vaccination Adenopathy

• COVID-19 vaccination causes ipsilateral axillary and cervical lymphadenopathy with FDG uptake that can persist for weeks to months after vaccination. 2, 4
• This vaccine-related adenopathy can be indistinguishable from nodal metastasis on imaging, creating a diagnostic challenge in oncology patients. 4
• Critical pitfall: Do not automatically attribute all axillary adenopathy to recent vaccination, as true malignancy can coexist or present shortly after vaccination. 2

Silicone-Related Adenopathy

• Silicone adenitis from breast implant leakage can cause hypermetabolic axillary lymph nodes that mimic metastatic disease on FDG-PET/CT. 5
• This is an important false-positive cause to consider in patients with a history of silicone breast implants. 5

Diagnostic Approach Algorithm

Initial Evaluation

• Axillary ultrasound is the primary modality of choice for initial evaluation, as it can determine if nodes are solid or cystic and assess morphologic features. 3
• Ultrasound-guided biopsy should be performed for suspicious nodes, providing definitive diagnosis with high specificity (98-100%). 3

Complementary Imaging

• Diagnostic mammography and/or digital breast tomosynthesis should complement axillary ultrasound to evaluate for potential breast primary lesions. 3
• If occult breast cancer is suspected with negative mammography, breast MRI can identify the primary lesion in approximately 70% of cases. 3

Staging for Confirmed Malignancy

• For confirmed breast cancer metastasis, complete breast imaging workup with MRI is recommended. 3
• For lymphoma or other non-breast malignancies, CT chest/abdomen/pelvis or PET/CT is appropriate for staging. 3

Important Clinical Caveats

• FDG uptake by an axillary node does not always represent true metastatic disease, as multiple benign causes exist. 1
• The SUV of the primary breast tumor cannot reliably predict axillary metastases, despite higher values often being associated with nodal spread. 6
• In patients with very low probability of axillary metastases (T1a tumors), the role of PET/CT should be carefully considered given radiation exposure and cost. 6
• Always obtain vaccination history, as post-vaccination adenopathy is increasingly common but should not lead to under-diagnosis of true malignancy. 2, 4
• Clinical context is essential, as the majority of enlarged lymph nodes have benign reactive changes. 3