Can a Positron Emission Tomography (PET) Computed Tomography (CT) scan differentiate between reactive lymphadenopathy and lymphoma?

From the Guidelines

PET-CT scans can help differentiate between reactive lymphadenopathy and lymphoma, but they are not always definitive. The scan works by detecting areas of high metabolic activity using a radioactive glucose tracer (typically 18F-FDG), which lymphoma cells typically absorb more readily than reactive lymph nodes. Lymphomas generally show higher standardized uptake values (SUVs) compared to benign reactive nodes. However, there is overlap in SUV values between these conditions, as some inflammatory processes can also show high metabolic activity 1. For this reason, a definitive diagnosis of lymphoma still requires tissue biopsy for histopathological examination, even after a suggestive PET-CT.

Key Considerations

• The Lugano classification recommends PET-CT for staging of FDG-avid lymphomas, and CT scan for other lymphomas 1.
• PET-CT is useful for assessing response in FDG-avid histologies using the 5-point scale, and for identifying the optimal site to biopsy for confirmation of discordant histology or malignant transformation 1.
• The scan is most valuable for staging known lymphoma, monitoring treatment response, and detecting residual or recurrent disease.
• When interpreting PET-CT results, physicians consider not only the SUV values but also the pattern of uptake, lymph node size, and clinical context.

Limitations of PET-CT

• False-positive findings due to rebound thymic hyperplasia, infection, inflammation, sarcoidosis, or brown fat 1.
• False-negative results relating to the resolution of the equipment, technique, and variability of FDG avidity among histologic subtypes 1.
• Variability among readers and equipment 1.

Clinical Implications

• While PET-CT provides valuable information, it should be considered a complementary tool rather than a replacement for histological confirmation in the initial diagnosis of lymphoma.
• A tissue biopsy is still required for a definitive diagnosis of lymphoma, even after a suggestive PET-CT scan.

From the Research

Differentiation between Reactive Lymphadenopathy and Lymphoma using PET CT

• The ability of Positron Emission Tomography (PET) Computed Tomography (CT) to differentiate between reactive lymphadenopathy and lymphoma has been explored in various studies 2, 3, 4, 5, 6.
• A study published in 2008 found that PET/CT accurately depicted the extent of lymphoma in 75% of patients' scans, but increased fluorodeoxyglucose uptake was noted in lymph nodes of normal CT appearance (PET+/CT-) in 25% of scans, which were later proven to be benign 2.
• Another study from 2008 suggested that the differing levels of FDG uptake in enlarged nodes may potentially distinguish reactive from malignant adenopathy, and that PET/CT can provide valuable information on the physiologic and anatomic characteristics of lymphoma lesions 3.
• A review published in 2016 noted that functional imaging with 18-F-fluorodeoxyglucose (FDG)-PET-CT is widely recognized as the most sensitive and specific imaging modality for patients with lymphoma, but also highlighted the potential for false positive results, particularly in indolent lymphomas 4.
• A study from 2007 compared the diagnostic performance of PET alone, CT alone, side-by-side reading, and fused images for restaging of non-Hodgkin lymphoma, and found that PET alone and fused images yielded higher diagnostic performance than CT alone 5.
• However, a case report from 2005 highlighted the importance of considering infectious etiologies in immunocompromised patients with a history of lymphoma and positive PET scan results, as a patient with T cell lymphoblastic lymphoma was found to have cat scratch disease rather than lymphoma relapse 6.

Limitations and Considerations

• The studies suggest that while PET/CT can be a valuable tool in differentiating between reactive lymphadenopathy and lymphoma, it is not always definitive and may require correlation with clinical, immunologic, and virological data 2, 3, 4.
• The potential for false positive results, particularly in indolent lymphomas, highlights the need for careful interpretation of PET/CT results and consideration of other diagnostic modalities 4, 6.
• The importance of considering infectious etiologies in immunocompromised patients with a history of lymphoma and positive PET scan results cannot be overstated, and lymph node biopsy may be necessary to confirm the diagnosis of relapse or refractory lymphoma 6.