Beware of False-Positive Lymph Nodes on PET Scans After COVID-19 Vaccination

COVID vaccination is followed in some people by swelling of lymph nodes in the neck, armpits, and groin, causing concern and sometimes unnecessary biopsies. This is known to occur more often with mRNA vaccines than with inactivated vaccines and to cause greater concern in cancer patients (see why should cancer patients get a COVID vaccine?).

BioNTech and Moderna COVID vaccines, both of which are mRNA vaccines, may trigger reactive lymphadenopathy and radiotracer uptake on PET imaging, which can lead to these lymph nodes being mistakenly interpreted as positive for cancer. This may be because mRNA vaccines trigger a stronger immune system response.

Findings from a recent study highlighting this situation were published on May 19, 2021, in the American Journal of Roentgenology journal.

False-Positive Lymph Nodes After Vaccination

The study reported false positivity due to radiotracer uptake in an axillary lymph node in 7 of 67 patients (10.4%) who underwent PET-CT within 24 days of a COVID vaccine.

In the five cases where the injection site was known, the positive nodes were on the same side as the vaccination.

Above: PET images showing axillary lymph node uptake on the same side as the vaccination, using two different radiotracers.

One of the 7 patients also had FDG (radiotracer) uptake in a supraclavicular (above the collarbone) lymph node, again on the same side as the vaccination.

Four patients received the Pfizer vaccine and three received the Moderna vaccine. They had no lymph node uptake on previous PET scans.

Nuclear medicine specialists and radiologists should be aware that this can occur when interpreting PET imaging.

Screening for Vaccination History Is "Mandatory"

Three of the seven positive cases in the review also had uptake in their deltoid (shoulder) muscles as a result of inflammation at the injection site. Therefore, if radiotracer uptake is present in both the deltoid and axilla on the same side, this may be related to a COVID vaccine.

False-positive lymph nodes in around 10% of patients undergoing PET imaging after vaccination were less common than in previous studies, where the figure reached up to one-third of patients. The authors attributed this to the patients' high average age (76) and therefore noted that people in this age group may not have reacted to vaccines as strongly as the younger people in earlier reports.

Given the findings, it may be reasonable to postpone PET imaging for 3-4 weeks after vaccination.

Also, because the reaction occurs on the same side as the injection, patients should, if possible, be vaccinated on the side opposite their tumors.

Doctors experienced in this area should now take care to screen patients for their COVID vaccination history and document it in the medical record system to help interpret images. Knowing which side the vaccine was given on and when can "really help".

The mean short-axis diameter of the positive axillary nodes in the study was only 8 mm, and only one was abnormally enlarged in diameter. The absence of substantial enlargement may be another clue that a vaccine reaction is responsible.

The team noted that the patient with supraclavicular uptake was receiving pembrolizumab (Keytruda) immunotherapy and may therefore have had a particularly strong reaction to the vaccine, leading to uptake outside the axilla.

The study's greatest limitation was that the positive nodes were not biopsied to rule out metastasis or infection. However, after careful review and consideration of previous negative PET scans, the team concluded that they were most likely a result of vaccine reactions.

The researchers noted that increased PET activity had previously been reported after other vaccines, but that there was an "even stronger association" with COVID-19 vaccination.