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

2021; Radiological Society of North America; Volume: 300; Issue: 3 Linguagem: Inglês

10.1148/radiol.2021210886

1527-1315

Yael Eshet, Noam Tau, Yousef Alhoubani, Nayroz Kanana, Liran Domachevsky, Michal Eifer,

Colorectal and Anal Carcinomas

HomeRadiologyVol. 300, No. 3 PreviousNext Original ResearchFree AccessResearch LetterPrevalence of Increased FDG PET/CT Axillary Lymph Node Uptake Beyond 6 Weeks after mRNA COVID-19 VaccinationYael Eshet , Noam Tau, Yousef Alhoubani, Nayroz Kanana, Liran Domachevsky, Michal EiferYael Eshet , Noam Tau, Yousef Alhoubani, Nayroz Kanana, Liran Domachevsky, Michal EiferAuthor AffiliationsFrom the Department of Diagnostic Imaging, Chaim Sheba Medical Center, Sheba Road 2, 52621 Ramat Gan, Israel (Y.E., N.T., Y.A., N.K., L.D., M.E.); and Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel (Y.E., N.T., L.D., M.E.).Address correspondence to Y.E. (e-mail: [email protected]).Yael Eshet Noam TauYousef AlhoubaniNayroz KananaLiran DomachevskyMichal EiferPublished Online:Apr 27 2021https://doi.org/10.1148/radiol.2021210886MoreSectionsPDF ToolsAdd to favoritesCiteTrack Citations ShareShare onFacebookXLinked In IntroductionAs 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 MethodsWe 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.ResultsAmong 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 IndicationsOverall, 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: 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.Figure 1:Download as PowerPointMost 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: 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.Figure 2:Download as PowerPointDiscussionThis 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 ContributionsAuthor 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.References1. Eifer M, Eshet Y. Imaging of COVID-19 Vaccination at FDG PET/CT. Radiology 2021;299(2):E248. Google Scholar2. Özütemiz C, Krystosek LA, Church AL, et al. Lymphadenopathy in COVID-19 Vaccine Recipients: Diagnostic Dilemma in Oncology Patients. Radiology 2021. 10.1148/radiol.2021210275. Published online February 24, 2021. MedlineGoogle Scholar3. Cohen D, Krauthammer SH, Wolf I, Even-Sapir E. Hypermetabolic lymphadenopathy following administration of BNT162b2 mRNACovid-19 vaccine: incidence assessed by [18F]FDG PET-CT and relevance to study interpretation. Eur J Nucl Med Mol Imaging 2021. https://doi.org/10.1007/s00259-021-05314-2. Published online March 27, 2021. Google Scholar4. Becker AS, Perez-Johnston R, Chikarmane SA, et al. Multidisciplinary Recommendations Regarding Post-Vaccine Adenopathy and Radiologic Imaging: Radiology Scientific Expert Panel. Radiology 2021. https://doi.org/10.1148/radiol.2021210436. Published online February 24, 2021. Google Scholar5. Tu W, Gierada DS, Joe BN. COVID-19 Vaccination-Related Lymphadenopathy: What To Be Aware Of. Radiol Imaging Cancer 2021;3(3):e210038. Google Scholar6. Thomassen A, Lerberg Nielsen A, Gerke O, Johansen A, Petersen H. Duration of 18F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination. Eur J Nucl Med Mol Imaging 2011;38(5):894–898. MedlineGoogle ScholarArticle HistoryReceived: Apr 05 2021Revision requested: Apr 16 2021Revision received: Apr 21 2021Accepted: Apr 22 2021Published online: Apr 27 2021Published in print: Sept 2021 FiguresReferencesRelatedDetailsCited ByAnalysis of clinical factors and ultrasound features associated with COVID-19 vaccine-related axillary lymphadenopathy: A large group studyJiheLim, Eun KyungKhil, Seun Ah.Lee, Jung-AhChoi, Kyoung YeonLee, Sang WonJo, JangheeLee2024Jan1 | Clinical Imaging, Vol. 105Comparison of post-COVID-19 vaccination hypermetabolic lymphadenopathy on 18F-fluorodeoxyglucose PET/CT between virus-vector vaccine and mRNA vaccineMeng-TingChiang, Jann-TayWang, Wan-YuLin, Ruoh-FangYen, Jei-YieHuang, Ching-ChuLu15 November 2023 | European Journal of Medical Research, Vol. 28, No. 1COVID-19 Vaccination Safety Profiles in Patients With Solid Tumour Cancers: A Systematic ReviewS.L.Shear, K.Shams, J.Weisberg, N.Hamidi, S.C.Scott2023Jul1 | Clinical Oncology, Vol. 35, No. 7Coronavirus disease 2019 (COVID-19) vaccination-induced unilateral axillary lymphadenopathy: case series with follow-up and literature reviewJeong JaeKim, Su YeonKo2023Jun30 | Journal of Medicine and Life Science, Vol. 20, No. 2[18F]FES PET Resolves the Diagnostic Dilemma of COVID-19-Vaccine-Associated Hypermetabolic Lymphadenopathy in ER-Positive Breast CancerMunenobuNogami, TetsuyaTsujikawa, HiroyukiMaeda, NobuyukiKosaka, MizuhoTakahashi, NaokiKinoshita, TetsuyaMori, AkiraMakino, YasushiKiyono, TakamichiMurakami, TakanoriGoi, HidehikoOkazawa25 May 2023 | Diagnostics, Vol. 13, No. 11FDG–PET findings associated with various medical procedures and treatmentsChioOkuyama, TatsuyaHigashi, KoichiIshizu, TsuneoSaga28 December 2022 | Japanese Journal of Radiology, Vol. 41, No. 5COVID-19 Vaccine-related Lymphadenopathy in Lung Cancer Patients: a Presentation of Three Cases with Suggestions for ManagementYuukiKou, NobuhisaYamazaki, YasutoSakaguchi, HirokazuTanaka, MakotoSonobe2023Apr20 | Haigan, Vol. 63, No. 2ACE2 PET to reveal the dynamic patterns of ACE2 recovery in an infection model with pseudocorona virusXiaoLi, WeiYin, AoLi, DanniLi, XiaolongGao, RuizhiWang, BinCui, ShuangQiu, RouLi, LinaJia, ChangjingZuo, LanZhang, MingLi18 January 2023 | Journal of Medical Virology, Vol. 95, No. 2Post‐COVID‐19 Vaccine Imaging FindingsShadiAsadollahi, Liesl S.Eibschutz, SanazKatal, VoradaSakulsaengprapha, YasaswiVengalasetti, NikooSaeedi, Sean K.Johnston, Jennifer H.Johnston30 December 2022Axillary Lymphadenopathy after Pfizer-BioNTech and Moderna COVID-19 Vaccination: MRI EvaluationTakeharu Yoshikawa, Soichiro Miki, Takahiro Nakao, Saori Koshino, Naoto Hayashi, Osamu Abe, 13 September 2022 | Radiology, Vol. 306, No. 1The Clinical Utility of Molecular Imaging in COVID-19: An UpdateAhmedElsakka, RandyYeh, JeebanDas2023Jan1 | Seminars in Nuclear Medicine, Vol. 53, No. 1COVID-19 vaccination, implications for PET/CT image interpretation and future perspectivesMargaritaKirienko, MatteoBiroli, CristianoPini, FabriziaGelardi, MartinaSollini, ArturoChiti16 August 2022 | Clinical and Translational Imaging, Vol. 10, No. 6COVID-19 vaccine-induced lymphadenopathies: incidence, course and imaging features from an ultrasound prospective studyValeriaRomeo, ArnaldoStanzione, DivinaD'Auria, LudovicaFulgione, FabioGiusto, SimoneMaurea, ArturoBrunetti4 May 2022 | Journal of Ultrasound, Vol. 25, No. 4The role of Israeli researchers in the scientific literature regarding COVID-19 vaccinesBruceRosen, NadavDavidovitch, GabrielChodick, AviIsraeli23 November 2022 | Israel Journal of Health Policy Research, Vol. 11, No. 1PET/CT variants and pitfalls in malignant melanomaNicolasAide, AmirIravani, KevinPrigent, DianeKottler, RaminAlipour, Rodney J.Hicks4 January 2022 | Cancer Imaging, Vol. 22, No. 1Hypermetabolic Ipsilateral Supraclavicular and Axillary Lymphadenopathy: Optimal Time Point for Performing an 18F-FDG PET/CT after COVID-19 VaccinationKwadwoAntwi, FedericoCaobelli, KenKudura, Hans-GeorgBuchholz, MartinHoffmann, MathiasSchreckenberger6 December 2022 | Diagnostics, Vol. 12, No. 12Axillary Lymphadenopathy in the COVID-19 Era: What the Radiologist Needs to KnowMeng Zhang, Richard W. 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