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Original article

Vol. 151 No. 2930 (2021)

Fine needle aspiration in COVID-19 vaccine-associated lymphadenopathy

Cite this as:
Swiss Med Wkly. 2021;151:w20557



With ongoing intensive vaccination programme against COVID-19, numerous cases of adverse reactions occur, some of which represent rare events. Enlargement of the injection site’s draining lymph nodes is increasingly reported, but is not yet widely recognised as being possibly associated with recent vaccination. As patients at risk of a severe course of COVID-19, indicated by their medical history such as a previous diagnosis of malignancy, receive priority vaccination, newly palpable lymph nodes raise concerns of disease progression. In this case series, we report on five patients who presented with enlarged lymph nodes after COVID-19 vaccination.


Sonography guided fine needle aspiration (FNA) was performed in five patients presenting with PET-positive and/or enlarged lymph nodes after COVID-19 vaccination with either the Pfizer-BioNTech or Moderna vaccine.


COVID-19 vaccination had been carried out in all cases, with an interval of between 3 and 33 days prior to FNA. Three of five patients had a history of neoplasms. The vaccine was administered into the deltoid muscle, with subsequent enlargement of either the cervical, supra-, infra- or retroclavicular, or axillary lymph nodes, in four out of five cases ipsilaterally. In all cases, cytology and additional analyses showed a reactive lymphadenopathy without any sign of malignancy.


Evidence of newly enlarged lymph nodes after recent COVID-19 vaccination should be considered reactive in the first instance, occurring owing to stimulation of the immune system. A clinical follow-up according to the patient’s risk profile without further diagnostic measures is justified. In the case of preexisting unilateral cancer, vaccination should be given contralaterally whenever possible. Persistently enlarged lymph nodes should be re-evaluated (2 to) 6 weeks after the second dose, with additional diagnostic tests tailored to the clinical context. Fine needle aspiration is a well established, safe, rapid and cost-effective method to investigate an underlying malignancy, especially metastasis. Recording vaccination history, including date of injection, site and vaccine type, as well as communicating this information to treating physicians of different specialties is paramount for properly handling COVID-19 vaccine-associated lymphadenopathy.


  1. Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020;91(1):157–60.
  2. World Health Organization. WHO Coronavirus (COVID-19) Dashboard. 2021 [cited 2021 June 19]; Available from:
  3. Mehta S, Machado F, Kwizera A, Papazian L, Moss M, Azoulay É, et al. COVID-19: a heavy toll on health-care workers. Lancet Respir Med. 2021;9(3):226–8. doi:.
  4. Rawat K, Kumari P, Saha L. COVID-19 vaccine: A recent update in pipeline vaccines, their design and development strategies. Eur J Pharmacol. 2021;892:173751. doi:.
  5. Izda V, Jeffries MA, Sawalha AH. COVID-19: A review of therapeutic strategies and vaccine candidates. Clin Immunol. 2021;222:108634. doi:.
  6. Noor R. Developmental Status of the Potential Vaccines for the Mitigation of the COVID-19 Pandemic and a Focus on the Effectiveness of the Pfizer-BioNTech and Moderna mRNA Vaccines. Curr Clin Microbiol Rep. 2021:1–8. Online ahead of print. doi:.
  7. Batty CJ, Heise MT, Bachelder EM, Ainslie KM. Vaccine formulations in clinical development for the prevention of severe acute respiratory syndrome coronavirus 2 infection. Adv Drug Deliv Rev. 2021;169:168–89. doi:.
  8. Dai L, Gao GF. Viral targets for vaccines against COVID-19. Nat Rev Immunol. 2021;21(2):73–82. doi:.
  9. Soleimanpour S, Yaghoubi A. COVID-19 vaccine: where are we now and where should we go? Expert Rev Vaccines. 2021;20(1):23–44. doi:.
  10. Vaccine Centre London School of Hygene & Tropical Medicine. COVID-19 Vaccine Tracker. 2021 [cited 2021 June 19]; Available from:
  11. Our World in Data. Coronavirus (COVID-19) Vaccinations. 2021 [cited 2021 June 19]; Available from:
  12. Bundesamt für Gesundheit BAG. COVID-19 Switzerland. [cited 2021 June 19]; Available from:
  13. Our World in Data. Coronavirus (COVID-19) Vaccinations. 2021 [cited 2021 May 14]; Available from:
  14. Bundesamt für Gesundheit BAG. COVID-19 Switzerland. [cited 2021 May 14]; Available from:
  15. Li H, Burm SW, Hong SH, Ghayda RA, Kronbichler A, Smith L, et al. A Comprehensive Review of Coronavirus Disease 2019: Epidemiology, Transmission, Risk Factors, and International Responses. Yonsei Med J. 2021;62(1):1–11. doi:.
  16. Desai A, et al. Mortality in hospitalized patients with cancer and coronavirus disease 2019: A systematic review and meta-analysis of cohort studies. Cancer. 2021;127(9):1459–68. doi:.
  17. Meo SA, Bukhari IA, Akram J, Meo AS, Klonoff DC. COVID-19 vaccines: comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines. Eur Rev Med Pharmacol Sci. 2021;25(3):1663–9. doi:.
  18. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al.; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384(5):403–16. doi:.
  19. Centers for Disease Control and Prevention. Local Reactions, Systemic Reactions, Adverse Events, and Serious Adverse Events: Moderna COVID-19 Vaccine. 2021 [cited 2021 March 14]; Available from:
  20. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al.; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603–15. doi:.
  21. Centers for Disease Control and Prevention. Local Reactions, Systemic Reactions, Adverse Events, and Serious Adverse Events: COVID-19 Vaccine Centers for Disease Control and Prevention. 2021 [cited 2021 March 14]; Available from:
  22. Barroca H, Bode-Lesniewska B, Cozzolino I, Zeppa P. Management of cytologic material, preanalytic procedures and biobanking in lymph node cytopathology. Cytopathology. 2019;30(1):17–30. doi:.
  23. Schmid S, Tinguely M, Cione P, Moch H, Bode B. Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas. Cytopathology. 2011;22(6):397–406. doi:.
  24. van Dongen JJ, Langerak AW, Brüggemann M, Evans PA, Hummel M, Lavender FL, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17(12):2257–317. doi:.
  25. Khanna R, Sharma AD, Khanna S, Kumar M, Shukla RC. Usefulness of ultrasonography for the evaluation of cervical lymphadenopathy. World J Surg Oncol. 2011;9(1):29. doi:.
  26. Monaco SE, Khalbuss WE, Pantanowitz L. Benign non-infectious causes of lymphadenopathy: A review of cytomorphology and differential diagnosis. Diagn Cytopathol. 2012;40(10):925–38. doi:.
  27. Hartsock RJ. Postvaccinial lymphadenitis. Hyperplasia of lymphoid tissue that simulates malignant lymphomas. Cancer. 1968;21(4):632–49. doi:.<632::AID-CNCR2820210415>3.0.CO;2-O
  28. Toy H, Karasoy D, Keser M. Lymphadenitis caused by H1N1 vaccination: case report. Vaccine. 2010;28(10):2158–60. doi:.
  29. Studdiford J, Lamb K, Horvath K, Altshuler M, Stonehouse A. Development of unilateral cervical and supraclavicular lymphadenopathy after human papilloma virus vaccination. Pharmacotherapy. 2008;28(9):1194–7. doi:.
  30. Pereira MP, Flores P, Neto AS. Neck and supraclavicular lymphadenopathy secondary to 9-valent human papillomavirus vaccination. BMJ Case Rep. 2019;12(11):e231582. doi:.
  31. Atalar H, Sarifakioglu E, Dener C, Yanik B, Koktener A, Bayrak R. Cutaneous lymphoid hyperplasia and reactive lymphadenopathy induced by hepatitis B vaccination. Eur J Dermatol. 2008;18(2):188–9.
  32. Dorfman RF, Herweg JC. Live, attenuated measles virus vaccine. Inguinal lymphadenopathy complicating administration. JAMA. 1966;198(3):320–1. doi:.
  33. Davis RL, Marcuse E, Black S, Shinefield H, Givens B, Schwalbe J, et al., The Vaccine Safety Datalink Team. MMR2 immunization at 4 to 5 years and 10 to 12 years of age: a comparison of adverse clinical events after immunization in the Vaccine Safety Datalink project. Pediatrics. 1997;100(5):767–71. doi:.
  34. Dos Santos BA, Ranieri TS, Bercini M, Schermann MT, Famer S, Mohrdieck R, et al. An evaluation of the adverse reaction potential of three measles-mumps-rubella combination vaccines. Rev Panam Salud Publica. 2002;12(4):240–6. doi:.
  35. Sukumaran L, McNeil MM, Moro PL, Lewis PW, Winiecki SK, Shimabukuro TT. Adverse Events Following Measles, Mumps, and Rubella Vaccine in Adults Reported to the Vaccine Adverse Event Reporting System (VAERS), 2003-2013. Clin Infect Dis. 2015;60(10):e58–65. doi:.
  36. White CK, Al-Saleem T, Skarbnik AP, Smith MR. Tetanus toxoid reactive lymphadenopathy masquerading as T-cell lymphoma. Future Oncol. 2012;8(5):631–4. doi:.
  37. Frey SE, Couch RB, Tacket CO, Treanor JJ, Wolff M, Newman FK, et al.; National Institute of Allergy and Infectious Diseases Smallpox Vaccine Study Group. Clinical responses to undiluted and diluted smallpox vaccine. N Engl J Med. 2002;346(17):1265–74. doi:.
  38. Suliman OM, Ahmed MJ, Bilal JA. Clinical characteristics and needle aspiration management of Bacillus Calmette-Guérin lymphadenitis in children. Saudi Med J. 2015;36(3):280–5. doi:.
  39. Hendry AJ, Dey A, Beard FH, Khandaker G, Hill R, Macartney KK. Adverse events following immunisation with bacille Calmette-Guérin vaccination: baseline data to inform monitoring in Australia following introduction of new unregistered BCG vaccine. Commun Dis Intell Q Rep. 2016;40(4):E470–4.
  40. Wang TC, Wu HJ, Yong SB. Bacillus Calmette-Guérin vaccination-associated axillary lymphadenopathy in a 2-year-old girl: Case report. J Formos Med Assoc. 2019;118(1):533–4. doi:.
  41. 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;48(8):2659–60. doi:.
  42. Cellina M, Irmici G, Carrafiello G. Unilateral Axillary Lymphadenopathy After Coronavirus Disease (COVID-19) Vaccination. AJR Am J Roentgenol. 2021;216(5):W27. doi:.
  43. Hiller N, Goldberg SN, Cohen-Cymberknoh M, Vainstein V, Simanovsky N. Lymphadenopathy Associated With the COVID-19 Vaccine. Cureus. 2021;13(2):e13524.
  44. Mehta N, Sales RM, Babagbemi K, Levy AD, McGrath AL, Drotman M, et al. Unilateral axillary Adenopathy in the setting of COVID-19 vaccine. Clin Imaging. 2021;75:12–5. doi:.
  45. Mitchell OR, Dave R, Bekker J, Brennan PA. Supraclavicular lymphadenopathy following COVID-19 vaccination: an increasing presentation to the two-week wait neck lump clinic? Br J Oral Maxillofac Surg. 2021;59(3):384–5. doi:.
  46. Mortazavi S. Coronavirus Disease (COVID-19) Vaccination Associated Axillary Adenopathy: Imaging Findings and Follow-Up Recommendations in 23 Women. AJR Am J Roentgenol. 2021;AJR.21.25651. doi:.
  47. Özütemiz C, Krystosek LA, Church AL, Chauhan A, Ellermann JM, Domingo-Musibay E, et al. Lymphadenopathy in COVID-19 Vaccine Recipients: Diagnostic Dilemma in Oncologic Patients. Radiology. 2021;300(1):E296–300. doi:.
  48. Washington T, Bryan R, Clemow C. Adenopathy Following COVID-19 Vaccination. Radiology. 2021;299(3):E280–1. doi:.
  49. Brewer KD, DeBay DR, Dude I, Davis C, Lake K, Parsons C, et al. Using lymph node swelling as a potential biomarker for successful vaccination. Oncotarget. 2016;7(24):35655–69. doi:.
  50. Youn H, Hong KJ. Non-invasive molecular imaging of immune cell dynamics for vaccine research. Clin Exp Vaccine Res. 2019;8(2):89–93. doi:.
  51. Williams G, Joyce RM, Parker JA. False-positive axillary lymph node on FDG-PET/CT scan resulting from immunization. Clin Nucl Med. 2006;31(11):731–2. doi:.
  52. Sheehy N, Drubach L. (18)F-FDG uptake at vaccination site. Pediatr Radiol. 2008;38(2):246. doi:.
  53. 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):1251–3. doi:.
  54. 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):848–53. doi:.
  55. Mingos M, Howard S, Giacalone N, Kozono D, Jacene H. Systemic Immune Response to Vaccination on FDG-PET/CT. Nucl Med Mol Imaging. 2016;50(4):358–61. doi:.
  56. Ayati N, Jesudason S, Berlangieri SU, Scott AM. Generalized Lymph Node Activation after Influenza Vaccination on 18F FDG-PET/CT Imaging, an Important Pitfall in PET Interpretation. Asia Ocean J Nucl Med Biol. 2017;5(2):148–50. doi:.
  57. Coates EE, Costner PJ, Nason MC, Herrin DM, Conant S, Herscovitch P, et al.; VRC 900 Study Team. Lymph Node Activation by PET/CT Following Vaccination With Licensed Vaccines for Human Papillomaviruses. Clin Nucl Med. 2017;42(5):329–34. doi:.
  58. Pektor S, Hilscher L, Walzer KC, Miederer I, Bausbacher N, Loquai C, et al. In vivo imaging of the immune response upon systemic RNA cancer vaccination by FDG-PET. EJNMMI Res. 2018;8(1):80. doi:.
  59. Doss M, Nakhoda SK, Li Y, Yu JQ. COVID-19 Vaccine-Related Local FDG Uptake. Clin Nucl Med. 2021;46(5):439–41. doi:.
  60. Eifer M, Eshet Y. Imaging of COVID-19 Vaccination at FDG PET/CT. Radiology. 2021;299(2):E248. doi:.
  61. Hanneman K, Iwanochko RM, Thavendiranathan P. Evolution of Lymphadenopathy at PET/MRI after COVID-19 Vaccination. Radiology. 2021;299(3):E282. doi:.
  62. Moghimi S, Wilson D, Martineau P. FDG PET Findings Post-COVID Vaccinations: Signs of the Times? Clin Nucl Med. 2021;46(5):437–8. doi:.
  63. 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;48(8):2655–6. doi:.
  64. 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;48(8):2657–8. doi:.
  65. Xu G, Lu Y. COVID-19 mRNA Vaccination-Induced Lymphadenopathy Mimics Lymphoma Progression on FDG PET/CT. Clin Nucl Med. 2021;46(4):353–4. doi:.
  66. Katal S, Pouraryan A, Gholamrezanezhad A. COVID-19 vaccine is here: practical considerations for clinical imaging applications. Clin Imaging. 2021;76:38–41. doi:.
  67. Habermann TM, Steensma DP. Lymphadenopathy. Mayo Clin Proc. 2000;75(7):723–32. doi:.
  68. Tandon S, Shahab R, Benton JI, Ghosh SK, Sheard J, Jones TM. Fine-needle aspiration cytology in a regional head and neck cancer center: comparison with a systematic review and meta-analysis. Head Neck. 2008;30(9):1246–52. doi:.
  69. Frederiksen JK, Sharma M, Casulo C, Burack WR. Systematic review of the effectiveness of fine-needle aspiration and/or core needle biopsy for subclassifying lymphoma. Arch Pathol Lab Med. 2015;139(2):245–51. doi:.
  70. Al-Abbadi MA, Barroca H, Bode-Lesniewska B, Calaminici M, Caraway NP, Chhieng DF, et al. A Proposal for the Performance, Classification, and Reporting of Lymph Node Fine-Needle Aspiration Cytopathology: The Sydney System. Acta Cytol. 2020;64(4):306–22. doi:.
  71. Fijten GH, Blijham GH. Unexplained lymphadenopathy in family practice. An evaluation of the probability of malignant causes and the effectiveness of physicians’ workup. J Fam Pract. 1988;27(4):373–6.
  72. Bettini E, Locci M. SARS-CoV-2 mRNA Vaccines: Immunological Mechanism and Beyond. Vaccines (Basel). 2021;9(2):147. doi:.
  73. Buschmann MD, Carrasco MJ, Alishetty S, Paige M, Alameh MG, Weissman D. Nanomaterial Delivery Systems for mRNA Vaccines. Vaccines (Basel). 2021;9(1):65. doi:.
  74. Castells MC, Phillips EJ. Maintaining Safety with SARS-CoV-2 Vaccines. [Reply]. N Engl J Med. 2021;384(10):e37. doi:.
  75. Mellet J, Pepper MS. A COVID-19 Vaccine: Big Strides Come with Big Challenges. Vaccines (Basel). 2021;9(1):39. doi:.
  76. Wu Z, Li T. Nanoparticle-Mediated Cytoplasmic Delivery of Messenger RNA Vaccines: Challenges and Future Perspectives. Pharm Res. 2021;38(3):473–8. doi:.
  77. Society of Breast Imaging. SBI Recommendations for the Management of Axillary Adenopathy in Patients with Recent COVID-19 Vaccination. 2021 [cited 2021 March 20]; Available from:
  78. Shirone N, Shinkai T, Yamane T, Uto F, Yoshimura H, Tamai H, et al. Axillary lymph node accumulation on FDG-PET/CT after influenza vaccination. Ann Nucl Med. 2012;26(3):248–52. doi:.
  79. Fernández-Prada M, Rivero-Calle I, Calvache-González A, Martinón-Torres F. Acute onset supraclavicular lymphadenopathy coinciding with intramuscular mRNA vaccination against COVID-19 may be related to vaccine injection technique, Spain, January and February 2021. Euro Surveill. 2021;26(10):2100193. doi:.
  80. Gaddey HL, Riegel AM. Unexplained Lymphadenopathy: Evaluation and Differential Diagnosis. Am Fam Physician. 2016;94(11):896–903.
  81. Kuderer NM, Hill JA, Carpenter PA, Lyman GH. Challenges and Opportunities for COVID-19 Vaccines in Patients with Cancer. Cancer Invest. 2021;39(3):205–13. doi:.
  82. Hwang JK, Zhang T, Wang AZ, Li Z. COVID-19 vaccines for patients with cancer: benefits likely outweigh risks. J Hematol Oncol. 2021;14(1):38. doi:.
  83. Desai A, Gainor JF, Hegde A, Schram AM, Curigliano G, Pal S, et al. COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials. Nat Rev Clin Oncol. 2021;18:313–9. doi:.
  84. 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):894–8. doi:.
  85. 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. AJR Am J Roentgenol. 2021;AJR.21.25688. doi:.
  86. McIntosh LJ, Bankier AA, Vijayaraghavan GR, Licho R, Rosen MP. COVID-19 Vaccination-Related Uptake on FDG PET/CT: An Emerging Dilemma and Suggestions for Management. AJR Am J Roentgenol. 2021;AJR.21.25728. doi:.
  87. Lehman CD, D’Alessandro HA, Mendoza DP, Succi MD, Kambadakone A, Lamb LR. Unilateral Lymphadenopathy After COVID-19 Vaccination: A Practical Management Plan for Radiologists Across Specialties. J Am Coll Radiol. 2021;18(6):843–52. doi:.
  88. Becker AS, Perez-Johnston R, Chikarmane SA, Chen MM, El Homsi M, Feigin KN, et al. Multidisciplinary Recommendations Regarding Post-Vaccine Adenopathy and Radiologic Imaging: Radiology Scientific Expert Panel. Radiology. 2021:210436. Online ahead of print. doi:.
  89. Edmonds CE, Zuckerman SP, Conant EF. Management of Unilateral Axillary Lymphadenopathy Detected on Breast MRI in the Era of Coronavirus Disease (COVID-19) Vaccination. AJR Am J Roentgenol. 2021. Online ahead of print. doi:.