What is the role of PET (Positron Emission Tomography) CT scan with 18F-FDG (fluorodeoxyglucose) in evaluating lymphadenopathy?

Role of PET/CT in Evaluating Lymphadenopathy

PET/CT with 18F-FDG is strongly recommended for staging and response assessment of lymphoma, particularly in FDG-avid lymphomas such as Hodgkin's lymphoma and diffuse large B-cell lymphoma, as it provides critical metabolic information that impacts treatment decisions and patient outcomes. 1

Indications for PET/CT in Lymphadenopathy

• PET/CT is indicated for assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities 2
• PET/CT has become the standard for staging and assessment of treatment response for lymphomas that are FDG-avid at baseline or at the time of recurrence 1
• PET/CT should be performed from skull base to mid-thigh to ensure complete evaluation of potential lymphomatous involvement 1
• PET/CT is particularly valuable for distinguishing between viable tumor and necrosis or fibrosis in residual masses often present after treatment 1

Diagnostic Performance in Lymphadenopathy

• PET/CT demonstrates significantly superior accuracy compared to CT alone for loco-regional lymph node staging, with a negative predictive value equal or even superior to mediastinoscopy 1
• PET/CT improves extrathoracic staging through detection of lesions missed at conventional imaging or characterization of lesions that remain equivocal on conventional imaging 1
• In lymphoma staging, PET/CT has shown sensitivity of 100% and specificity of 96.4% for detecting distant metastases, compared to 61.5% and 99.2% respectively for conventional imaging 1
• For cervical lymphadenopathy, mean SUV ≥2.5 (or maximum SUV ≥3.5), nodular FDG uptake pattern, specific nodal locations, size ≥1.5 cm, and vague margins are important predictive factors of malignancy 3

Timing of PET/CT for Response Assessment

• PET/CT after completion of therapy should be performed at least 3 weeks, and preferably at 6 to 8 weeks, after chemotherapy or chemoimmunotherapy 1
• For patients who received radiation or chemoradiotherapy, PET/CT should be performed 8 to 12 weeks after completion of treatment 1
• If PET/CT is performed during a course of therapy (interim assessment), it should be done as close as possible to the subsequent cycle (within 4 days) 1

Interpretation Criteria

• Visual assessment alone is adequate for interpreting PET findings as positive or negative when assessing response after completion of therapy 1
• Mediastinal blood pool activity is recommended as the reference background activity to define PET positivity for a residual mass ≥2 cm in greatest transverse diameter 1
• A smaller residual mass or normal-sized lymph node (≤1 cm) should be considered positive if its activity is above that of the surrounding background 1
• Use of attenuation-corrected PET is strongly encouraged for accurate interpretation 1

Limitations and Pitfalls

• PET/CT has limited specificity in differentiating infections or inflammatory diseases from tumors 4, 5
• False-positive findings can occur due to rebound thymic hyperplasia, infection, inflammation, sarcoidosis, or brown fat 1
• False-negative results may occur due to equipment resolution limitations, technique issues, or variable FDG avidity among histologic subtypes 1
• Normal and hyperplastic thymus can be FDG-avid, which can be a confounder in PET/CT assessment of the prevascular mediastinum 1, 6
• A negative surveillance PET/CT is reassuring of a good outcome, but a positive PET/CT can be misleading as it does not always indicate residual or recurrent lymphoma 1

Special Considerations

• For HIV-infected patients with lymphadenopathy, SURmax (lesion-to-liver SUVmax ratio) >3.1 and lymph node SUVmax >8.0 are helpful in distinguishing malignant lymphoma from inflammatory lymphadenopathy 7
• Combined use of PET/CT and dynamic contrast-enhanced MRI has been shown to be helpful to distinguish prevascular mediastinal solid tumors from one another 1, 6
• Higher SUVs on PET/CT are more frequently found in high-risk thymoma, thymic carcinoma, and lymphoma than in low-risk thymoma 1, 6
• PET/CT appears to be more sensitive than CT alone for detection of mediastinal recurrence of thymoma 1, 6

Algorithm for PET/CT Use in Lymphadenopathy

1. Initial Evaluation:

   • For patients with suspected lymphoma: Perform baseline PET/CT from skull base to mid-thigh before treatment initiation 1
   • For indeterminate lymphadenopathy: Consider PET/CT to help characterize metabolic activity and guide biopsy 1, 3

2. During Treatment (if clinically indicated):

   • Perform interim PET/CT assessment only in clinical trial settings or as part of a prospective registry 1
   • Schedule scan within 4 days before the next treatment cycle 1

3. Post-Treatment Assessment:

   • For chemotherapy/chemoimmunotherapy: Perform PET/CT at 6-8 weeks after completion 1
   • For radiation/chemoradiation: Perform PET/CT at 8-12 weeks after completion 1
   • Use visual assessment with mediastinal blood pool as reference for interpretation 1

4. Surveillance (if indicated):

   • CT and MRI can be used for surveillance of lymphadenopathy when the metabolic activity is not of interest 1
   • Consider alternating PET/CT with other modalities based on clinical context and initial lymphoma subtype 1