Original ResearchFree Access

Prevalence of Increased FDG PET/CT Axillary Lymph Node Uptake Beyond 6 Weeks after mRNA COVID-19 Vaccination

Published Online:https://doi.org/10.1148/radiol.2021210886

Introduction

As the COVID-19 pandemic crosses the 1-year threshold, a growing number of countries are engaged in extended large-scale COVID-19 vaccination programs. Recently, there have been reports of unilateral axillary lymphadenopathy seen with various imaging modalities, in association with recent ipsilateral vaccination (1,2). A recent study estimated the prevalence of fluorodeoxyglucose (FDG) PET/CT axillary lymph node uptake to be 54% up to 3 weeks after a second mRNA-based vaccination dose (3).

Recommendations for vaccine lymphadenopathy after vaccination seen at imaging were published, advising scheduling routine imaging (such as screening) either before or at least 6 weeks after the final vaccination dose to eliminate false-positive results for cancer (4,5). However, information is still lacking regarding duration and prevalence of imaging findings after vaccination.

We aimed to assess the prevalence of FDG PET/CT–avid axillary lymph nodes beyond 6 weeks after the second dose of mRNA-based BNT162b2 COVID-19 vaccine.

Materials and Methods

We conducted a retrospective analysis of prospectively collected data in a single tertiary medical center. The study has been approved by the institutional ethics committee, and the need for patient informed consent was waived.

All consecutive adult patients older than 18 years referred for FDG PET/CT at our institution, who underwent the examination at least 42 days after the second dose of Pfizer-BioNTech (BNT162b2) COVID-19 vaccine, were evaluated for the presence of FDG-avid axillary lymphadenopathy ipsilateral to the injection site. Patients with underlying disease that was likely to involve the axilla (such as ipsilateral locally advanced breast cancer or lymphoma previously involving the axilla) and patients who were vaccinated in both arms were excluded.

Bilateral axillary lymph node uptake was measured by three board-certified radiologists (Y.E., M.E., and N.C., with 13, 2, and 3 years of experience, respectively) and a nuclear medicine resident (Y.A., with 1 year of experience). To overcome physiologic lymph node uptake, positive unilateral uptake was determined as maximum standardized uptake value ratio between the ipsilateral and contralateral axillary lymph nodes above 1.5, as previously used (6). Largest ipsilateral lymph node size was measured in short axis.

Results

Among 205 consecutive adults who underwent an FDG PET/CT examination 42–71 days (7–10 weeks) after a second dose vaccination, 37 were excluded: 21 had high probability of ipsilateral axillary lymph node involvement, one patient had only partial medical history information, and 15 patients had bilateral injection Our final cohort comprised a total of 169 patients (median age, 65 years 6±14 [standard deviation]; 49% women), scanned a median of 52 days 6±7 after the second vaccine dose (interquartile range, 47–57 days). The Table details PET/CT indications.

PET/CT Indications

Overall, 29% (49 of 169) had positive axillary uptake 7–10 weeks after second vaccination (median maximum standardized uptake value, 2.9± 1.3), divided to 42%, 31%, 25%, and 19% on 7th, 8th, 9th, and 10th weeks, respectively. The distribution number of patients with positive uptake on each week after vaccination can be seen in Figure 1. Immunotherapy did not contribute to persistent immune reactions, as four of 14 (28%) patients receiving immunotherapy had positive lymph node uptake, compared with 13 of 70 (19%) patients receiving other treatment, and 32 of 85 (38%) patients not receiving oncologic treatment.

Figure 1:

Figure 1: Graph shows axillary lymph node uptake prevalence by week after second vaccination dose. Darker area corresponds to positive axillary uptake, and brighter area to negative uptake.

Most FDG-avid lymph nodes were of normal size (mean, 0.5 cm; range, 0.1–1.6 cm). Figure 2 depicts an example of avid axillary FDG uptake in a patient 62 days after vaccination.

Figure 2:

Figure 2: Images in a 63-year-old patient with multiple myeloma and skeletal pain show new fluorodeoxyglucose-avid axillary lymphadenopathy 62 days (9 weeks) after second mRNA vaccination dose. Top row: maximum intensity projection and coronal PET multiplanar reconstruction. Bottom row: coronal noncontrast-enhanced CT and fusion images.

Discussion

This study shows that avid axillary lymph node uptake at FDG PET/CT can be detected in more than a quarter of our patient population even beyond 6 weeks after the second dose of the mRNA-based COVID-19 vaccination. Compared with a previous study showing normalization of FDG uptake within 40 days of receiving an inactivated H1N1 influenza vaccine (6), we found uptake persistence even at 70 days. Physicians should be aware of this potential pitfall.

Disclosures of Conflicts of Interest: Y.E disclosed no relevant relationships. N.T. disclosed no relevant relationships. Y.A. disclosed no relevant relationships. N.K. disclosed no relevant relationships. L.D. disclosed no relevant relationships. M.E. disclosed no relevant relationships.

Author Contributions

Author contributions: Guarantors of integrity of entire study, Y.E., M.E.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors; literature research, Y.E., L.D., M.E.; clinical studies, Y.E., N.T., Y.A., M.E.; statistical analysis, Y.E., Y.A., M.E.; and manuscript editing, Y.E., N.T., N.K., L.D., M.E.

References

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Article History

Received: Apr 05 2021
Revision requested: Apr 16 2021
Revision received: Apr 21 2021
Accepted: Apr 22 2021
Published online: Apr 27 2021
Published in print: Sept 2021