Hypermetabolic lymphadenopathy following administration of BNT162b2 mRNA Covid-19 vaccine: incidence assessed by [18F]FDG PET-CT and relevance to study interpretation

Dan Cohen, Shir Hazut Krauthammer, Ido Wolf, Einat Even-Sapir, Dan Cohen, Shir Hazut Krauthammer, Ido Wolf, Einat Even-Sapir

Abstract

Purpose: Nationwide mass vaccination against Covid-19 started in Israel in late 2020. Soon we identified on [18F]FDG PET-CT studies vaccine-associated hypermetabolic lymphadenopathy (VAHL) in axillary or supraclavicular lymph nodes (ASLN) ipsilateral to the vaccination site. Sometimes, differentiation between the malignant and benign nature of the hypermetabolic lymphadenopathy (HLN) could not be made, and equivocal HLN (EqHL) was reported. The purpose of the study was to determine the overall incidence of VAHL after BNT162b2 vaccination and also its relevance to PET-CT interpretation in oncologic patients.

Methods: A total of 951 consecutive patients that underwent [18F]FDG PET-CT studies in our department were interviewed regarding the sites and dates of the vaccine doses. A total of 728 vaccinated patients (All-Vac group) were included: 346 received the first dose only (Vac-1 group) and 382 received the booster dose as well (Vac-2 group). Studies were categorized as no HLN, malignant-HLN (MHL), VAHL, or EqHL. In studies with VAHL, location, [18F]FDG-intensity uptake and nodes size were recorded.

Results: The incidences of HLN were 45.6%, 36.4%, and 53.9% in All-Vac, Vac-1, and Vac-2 groups, respectively. VAHL was reported in 80.1% of vaccinated patients with HLN. Lower incidences of VAHL were found during the first 5 days or in the third week after the first vaccine and beyond 20 days after the booster dose. In 49 of 332 (14.8%) vaccinated patients, we could not determine whether HLN was MHL or VAHL. Breast cancer and lymphoma were the leading diseases with EqHL.

Conclusion: VAHL is frequently observed after BNT162b2 administration, more commonly and with higher intensity following the booster dose. To minimize false and equivocal reports in oncological patients, timing of [18F]FDG PET-CT should be based on the time intervals found to have a lower incidence of VAHL, and choice of vaccine injection site should be advised, mainly in patients where ASLN are a relevant site of tumor involvement.

Keywords: Axillary lymph nodes; Covid-19; False-positive [18F]FDG uptake; Oncologic imaging; Vaccination.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Vaccine-associated hypermetabolic lymphadenopathy (VAHL) grades. Each row represents one patient and includes from left to right CT, PET, and fusion PET-CT trans-axial slices and a maximal intensity projection (MIP) image. From top to bottom: patient referred for staging of colon cancer imaged 9 days following the first vaccine dose, patient referred for follow-up of rectal cancer 13 days following the booster vaccine dose, patient with history of left breast cancer referred for follow-up study 10 days following the first vaccine dose, and a patient referred for staging of right upper lobe lung cancer 1 day following the booster vaccine dose. In all presented cases, HLN was identified in ASLN, attributed to the recent vaccination on the report, and graded in our data based on [18F]FDG-uptake intensity. SUVmax measured in the presented cases were 1.97, 3.39, 10.10, and 14.34 from top to bottom. On the bottom row, LN diameter was 14 mm. On the MIP images, brown arrows point hypermetabolism recognized at the vaccine injection site
Fig. 2
Fig. 2
Proportion of vaccinated patients with VAHL and the grade of VAHL in different time points after the first vaccine dose
Fig. 3
Fig. 3
Proportion of vaccinated patients with VAHL and the grade of VAHL in different time points after the booster vaccine dose
Fig. 4
Fig. 4
Proportion of vaccinated patients with VAHL and the grade of VAHL in different age groups after the first vaccine dose
Fig. 5
Fig. 5
Proportion of vaccinated patients with VAHL and the grade of VAHL in different age groups after the booster vaccine dose
Fig. 6
Fig. 6
Examples of cases with equivocal reports. Each row represents one patient and includes from left to right CT, PET, and fused PET-CT trans-axial slices and a maximal intensity projection (MIP) image. a A patient with newly diagnosed left breast cancer 7 days following the first vaccine dose. Green arrow points the primary tumor. b A follow-up study of a patient after resection of sarcoma from the left forearm, imaged 3 days following the booster vaccine dose. In both presented cases, HLN was identified in ASLN, but differentiation between MHL and VAHL could not be obtained, and the lymphadenopathy was reported as equivocal

References

    1. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED, Zerbini C, Bailey R. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–2615. doi: 10.1056/NEJMoa2034577.
    1. Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med. 2021. 10.1056/NEJMoa2101765.
    1. Panagiotidis E, Exarhos D, Housianakou I, Bournazos A, Datseris I. FDG uptake in axillary lymph nodes after vaccination against pandemic (H1N1) Eur Radiol. 2010;20(5):1251–1253. doi: 10.1007/s00330-010-1719-5.
    1. Burger IA, Husmann L, Hany TF, Schmid DT, Schaefer NG. Incidence and intensity of F-18 FDG uptake after vaccination with H1N1 vaccine. Clin Nucl Med. 2011;36(10):848–853. doi: 10.1097/RLU.0b013e3182177322.
    1. Coates EE, Costner PJ, Nason MC, Herrin DM, Conant S, Herscovitch P, Sarwar UN, Holman L, Mitchell J, Yamshchikov G, Koup RA. Lymph node activation by PET/CT following vaccination with licensed vaccines for human papillomaviruses. Clin Nucl Med. 2017;42(5):329–334. doi: 10.1097/RLU.0000000000001603.
    1. Becker AS, Perez-Johnston R, Chikarmane SA, Chen MM, El Homsi M, Feigin KN, Gallagher KM, Hanna EY, Hicks M, Ilica AT, Mayer EL. Multidisciplinary recommendations regarding post-vaccine adenopathy and radiologic imaging: radiology scientific expert panel. Radiology. 2021;24:210436. doi: 10.1148/radiol.2021210436.
    1. Mortazavi S. Coronavirus disease (COVID-19) vaccination associated axillary adenopathy: imaging findings and follow-up recommendations in 23 women. Am J Roentgenol. 2021. 10.2214/AJR.21.25651.
    1. Edmonds CE, Zuckerman SP, Conant EF. Management of unilateral axillary lymphadenopathy detected on breast MRI in the era of coronavirus disease (COVID-19) vaccination. Am J Roentgenol. 2021. 10.2214/AJR.21.25604.
    1. Lehman CD, Lamb LR, D'Alessandro HA. Mitigating the impact of coronavirus disease (COVID-19) vaccinations on patients undergoing breast imaging examinations: a pragmatic approach. Am J Roentgenol. 2021. 10.2214/AJR.21.25688.
    1. Özütemiz C, Krystosek LA, Church AL, Chauhan A, Ellermann JM, Domingo-Musibay E, Steinberger D. Lymphadenopathy in COVID-19 vaccine recipients: diagnostic dilemma in oncology patients. Radiology. 2021;24:210275. doi: 10.1148/radiol.2021210275.
    1. Mehta N, Sales RM, Babagbemi K, Levy AD, McGrath AL, Drotman M, Dodelzon K. Unilateral axillary adenopathy in the setting of COVID-19 vaccine. Clin Imaging. 2021;75:12–15. doi: 10.1016/j.clinimag.2021.01.016.
    1. Ahn RW, Mootz AR, Brewington CC, Abbara S. Axillary lymphadenopathy after mRNA COVID-19 vaccination. Radiology: Cardiothoracic Imaging. 2021;3(1):e210008. doi: 10.1148/ryct.2021210008.
    1. Eifer M, Eshet Y. Imaging of COVID-19 vaccination at FDG PET/CT. Radiology. 2021. 10.1148/radiol.2020210030.
    1. Society of Breast Imaging. SBI recommendations for managing axillary adenopathy post COVID vaccination. . Accessed 7 Feb 2021.
    1. Hanneman K, Iwanochko RM, Thavendiranathan P. Evolution of lymphadenopathy at PET/MRI after COVID-19 vaccination. Radiology. 2021;24:210386. doi: 10.1148/radiol.2021210386.
    1. Nawwar AA, Searle J, Singh R, Lyburn ID. Oxford-AstraZeneca COVID-19 vaccination induced lymphadenopathy on [18F] choline PET/CT—not only an FDG finding. Eur J Nucl Med Mol Imaging. 2021;4:1–2. doi: 10.1007/s00259-021-05279-2.
    1. Nawwar AA, Searle J, Hagan I, Lyburn ID. COVID-19 vaccination induced axillary nodal uptake on [18F] FDG PET/CT. Eur J Nucl Med Mol Imaging. 2021;26:1–2. doi: 10.1007/s00259-021-05274-7.
    1. Avner M, Orevi M, Caplan N, Popovtzer A, Lotem M, Cohen JE. COVID-19 vaccine as a cause for unilateral lymphadenopathy detected by 18F-FDG PET/CT in a patient affected by melanoma. Eur J Nucl Med Mol Imaging. 2021;6:1–2. doi: 10.1007/s00259-021-05278-3.
    1. Israel Ministry of health. COVID-19 in Israel - dashboard data. . Accessed 7 Mar 2021.
    1. Guedj E, Million M, Dudouet P, Tissot-Dupont H, Bregeon F, Cammilleri S, Raoult D. 18 F-FDG brain PET hypometabolism in post-SARS-CoV-2 infection: substrate for persistent/delayed disorders? Eur J Nucl Med Mol Imaging. 2021;48(2):592–595. doi: 10.1007/s00259-020-04973-x.
    1. Guedj E, Verger A, Cammilleri S. PET imaging of COVID-19: the target and the number. Eur J Nucl Med Mol Imaging. 2020;47(7):1636–1637. doi: 10.1007/s00259-020-04820-z.
    1. Morbelli S, Ekmekcioglu O, Barthel H, Albert NL, Boellaard R, Cecchin D, et al. COVID-19 and the brain: impact on nuclear medicine in neurology. 10.1007/s00259-020-04965-x.
    1. Guedj E, Campion JY, Dudouet P, Kaphan E, Bregeon F, Tissot-Dupont H, Guis S, Barthelemy F, Habert P, Ceccaldi M, Million M. 18 F-FDG brain PET hypometabolism in patients with long COVID. Eur J Nucl Med Mol Imaging. 2021;26:1–1. doi: 10.1007/s00259-021-05215-4.
    1. World Health organization. . Accessed 4 Mar 2021.
    1. Pfizer. COVID-19 mRNA VACCINE BNT162b2. . Accessed 4 Mar 2021.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner