{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:46:26Z","timestamp":1761864386193,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Several authors have reported cervical and axillary lymphadenopathies as known side effects following anti-COVID-19 vaccine administration. Few data are available about atypical locations of post-anti-COVID-19 vaccine lymphadenopathy. In this investigation, we evaluated the incidence and prevalence of postvaccine lymphadenopathy ultrasound (US) features in atypical sites. Materials and Methods: In this retrospective study, we retrospectively selected 64 patients on whom US was performed between January and October 2021 due to COVID-19 vaccine-related lymphadenopathy. We investigated lymph node anatomical sites, presence, number, size, shape, cortical profile, hilum outline, superb microvascular imaging (SMI), and elastosonography. Results: A total of 170 nodes were assessed. Atypical location was demonstrated in 5\/64 patients (7.8%). In all these cases, atypical nodal involvement was associated with lymphadenopathy in a typical site (axillary, supraclavicular) ipsilateral to the vaccine injection site. Two patients presented lymphadenopathy in the infraclavicular station (3.1%), one in the pectoralis major muscle (1.6%), one in the left arm (1.6%), and one in the nuchal site (1.6%). All lymphadenopathies were oval-shaped, with a median size of 0.9 \u00b1 0.2 cm. US features included a symmetric cortex with hilum evidence (4\/6, 60%), vascular signal at SMI in both the hilar region and periphery of lymph node (5\/6, 83.3%), and a US elastography pattern resembling that of adjacent tissues (5\/6, 83.3%). The median age of patients with lymphadenopathies in an atypical location was 23 years. The main type of vaccine associated with lymph node appearance in atypical sites was Moderna\u2019s mRNA-1273 (60% of patients, 4\/6 lymph nodes accounting for 66.7% among atypical locations). Conclusion: Post-COVID-19 vaccine administration lymphadenopathies in an atypical location represent an intense immune response to antigenic stimuli and they may show alarming US traits superimposed on malignant pathologies, which may complicate the patient\u2019s clinical and diagnostic pathway. Despite no distinctive US features between reactive post-COVID-19 vaccination and malignant lymph nodes being available, careful examination of atypical lymph node locations associated with accurate knowledge of patients\u2019 clinical background and delay of US exam to four to six weeks after vaccine injection should be considered.<\/jats:p>","DOI":"10.3390\/medicina58020197","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T22:00:56Z","timestamp":1643320856000},"page":"197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Atypical Sites of Lymphadenopathy after Anti-COVID-19 Vaccine: Ultrasound Features"],"prefix":"10.3390","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3458-5468","authenticated-orcid":false,"given":"Giulio","family":"Cocco","sequence":"first","affiliation":[{"name":"Unit of Ultrasound in Internal Medicine, Department of Medicine and Science of Aging, \u201cG. d\u2019Annunzio\u201d University, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Delli Pizzi","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine and Dentistry, \u201cG. d\u2019Annunzio\u201d University, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Taraschi","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine and Dentistry, \u201cG. d\u2019Annunzio\u201d University, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-7790","authenticated-orcid":false,"given":"Andrea","family":"Boccatonda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Bentivoglio Hospital, AUSL Bologna, 40010 Bentivoglio, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Corvino","sequence":"additional","affiliation":[{"name":"Motor Science and Wellness Department, University of Naples \u201cParthenope\u201d, 80133 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5866-3849","authenticated-orcid":false,"given":"Claudio","family":"Ucciferri","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Medicine and Science of Aging, \u201cG. d\u2019Annunzio\u201d University, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Falasca","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Medicine and Science of Aging, \u201cG. d\u2019Annunzio\u201d University, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Caulo","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine and Dentistry, \u201cG. d\u2019Annunzio\u201d University, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacopo","family":"Vecchiet","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Medicine and Science of Aging, \u201cG. d\u2019Annunzio\u201d University, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_2","unstructured":"(2021, October 13). WHO Coronavirus (COVID-19) Dashboard. Available online: https:\/\/covid19.who.int\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/S0140-6736(20)30633-4","article-title":"Clinical course and mortality risk of severe COVID-19","volume":"395","author":"Weiss","year":"2020","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/his.14180","article-title":"Diffuse alveolar damage (DAD) resulting from coronavirus disease 2019 Infection is Morphologically Indistinguishable from Other Causes of DAD","volume":"77","author":"Konopka","year":"2020","journal-title":"Histopathology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"585354","DOI":"10.3389\/fimmu.2020.585354","article-title":"A Review of the Progress and Challenges of Developing a Vaccine for COVID-19","volume":"11","author":"Sharma","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1056\/NEJMoa2101765","article-title":"BNT162b2 mRNA COVID-19 Vaccine in a Nationwide Mass Vaccination Setting","volume":"384","author":"Dagan","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Granata, V., Fusco, R., Setola, S., Galdiero, R., Picone, C., Izzo, F., D\u2019Aniello, R., Miele, V., Grassi, R., and Grassi, R. (2021). Lymphadenopathy after BNT162b2 COVID-19 Vaccine: Preliminary Ultrasound Findings. Biology, 10.","DOI":"10.3390\/biology10030214"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e210038","DOI":"10.1148\/rycan.2021210038","article-title":"COVID-19 Vaccination\u2013related Lymphadenopathy: What to be Aware of","volume":"3","author":"Tu","year":"2021","journal-title":"Radiol. Imaging Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.clinimag.2021.01.016","article-title":"Unilateral axillary Adenopathy in the setting of COVID-19 vaccine","volume":"75","author":"Mehta","year":"2021","journal-title":"Clin. Imaging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s40336-021-00441-0","article-title":"Ultrasound and shear-wave elastography patterns of COVID-19 mRNA vaccine-related axillary, supra and subclavicular lymphadenopathy","volume":"9","author":"Fulgione","year":"2021","journal-title":"Clin. Transl. Imaging"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cocco, G., Pizzi, A.D., Fabiani, S., Cocco, N., Boccatonda, A., Frisone, A., Scarano, A., and Schiavone, C. (2021). Lymphadenopathy after the Anti-COVID-19 Vaccine: Multiparametric Ultrasound Findings. Biology, 10.","DOI":"10.3390\/biology10070652"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E323","DOI":"10.1148\/radiol.2021210436","article-title":"Multidisciplinary Recommendations Regarding Post-Vaccine Adenopathy and Radiologic Imaging: Radiology Scientific Expert Panel","volume":"300","author":"Becker","year":"2021","journal-title":"Radiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s40477-020-00458-7","article-title":"Thoracic ultrasound and SARS-COVID-19: A pictorial essay","volume":"23","author":"Sofia","year":"2020","journal-title":"J. Ultrasound"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s40477-021-00575-x","article-title":"One year of SARS-CoV-2 and lung ultrasound: What has been learned and future perspectives","volume":"24","author":"Boccatonda","year":"2021","journal-title":"J Ultrasound."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17237","DOI":"10.1038\/s41598-021-96755-0","article-title":"Radiomics-based machine learning differentiates \u201cground-glass\u201d opacities due to COVID-19 from acute non-COVID-19 lung disease","volume":"11","author":"Pizzi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ferrari, C., Nappi, A.G., Santo, G., Mammucci, P., Rubini, D., Tucci, M., and Pisani, A.R. (2021). The Day after Mass COVID-19 Vaccination: Higher Hypermetabolic Lymphadenopathy Detection on PET\/CT and Impact on Oncologic Patients Management. Cancers, 13.","DOI":"10.3390\/cancers13174340"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13244-021-01062-x","article-title":"Axillary lymphadenopathy at the time of COVID-19 vaccination: Ten recommendations from the European Society of Breast Imaging (EUSOBI)","volume":"12","author":"Schiaffino","year":"2021","journal-title":"Insights Imaging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.rcl.2019.01.005","article-title":"Ultrasonography of Cervical Lymph Nodes","volume":"57","author":"Wagner","year":"2019","journal-title":"Radiol. Clin. N. Am."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/jcu.23068","article-title":"Seeing the unseen with superb microvascular imaging: Ultrasound depiction of normal dermis vessels","volume":"50","author":"Corvino","year":"2021","journal-title":"J. Clin. Ultrasound"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"32","DOI":"10.5114\/pjr.2018.73293","article-title":"Evaluation of diagnostic value of conventional and color Doppler ultrasound with elastography strain ratios in differentiation between benign and malignant lymph nodes","volume":"83","author":"Zel","year":"2018","journal-title":"Pol. J. Radiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/j.acra.2021.04.007","article-title":"Lymphadenopathy Following COVID-19 Vaccination: Imaging Findings Review","volume":"28","author":"Keshavarz","year":"2021","journal-title":"Acad. Radiol."},{"key":"ref_23","unstructured":"(2021, October 13). Moderna COVID-19 Vaccine\u2019s Reactions and Adverse Events|CDC, Available online: https:\/\/www.cdc.gov\/vaccines\/covid-19\/info-by-product\/moderna\/reactogenicity.html."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Palladino, R., Ceriotti, D., De Ambrosi, D., De Vito, M., Farsoni, M., Seminara, G., and Barone-Adesi, F. (2021). A Quantitative Benefit\u2013Risk Analysis of ChAdOx1 nCoV-19 Vaccine among People under 60 in Italy. Vaccines, 9.","DOI":"10.1101\/2021.05.07.21256826"},{"key":"ref_25","first-page":"e13524","article-title":"Lymphadenopathy Associated with the COVID-19 Vaccine","volume":"13","author":"Hiller","year":"2021","journal-title":"Cureus"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1007\/s00259-021-05389-x","article-title":"Correlation between BNT162b2 mRNA COVID-19 vaccine-associated hypermetabolic lymphadenopathy and humoral immunity in patients with hematologic malignancy","volume":"48","author":"Cohen","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1592\/phco.28.9.1194","article-title":"Development of Unilateral Cervical and Supraclavicular Lymphadenopathy After Human Papilloma Virus Vaccination","volume":"28","author":"Studdiford","year":"2008","journal-title":"Pharmacotherapy"},{"key":"ref_28","first-page":"199","article-title":"BCG-induced axillary lymph-adenitis in the adult","volume":"119","author":"Newfield","year":"1990","journal-title":"Harefuah"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3879","DOI":"10.1016\/j.radcr.2021.09.042","article-title":"Rare case of contralateral supraclavicular lymphadenopathy after COVID-19 vaccination: Computed tomography and ultrasonography findings","volume":"16","author":"Park","year":"2021","journal-title":"Radiol. Case Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E296","DOI":"10.1148\/radiol.2021210275","article-title":"Lymphadenopathy in COVID-19 Vaccine Recipients: Diagnostic Dilemma in Oncologic Patients","volume":"300","author":"Krystosek","year":"2021","journal-title":"Radiology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.jacr.2021.03.001","article-title":"Unilateral Lymphadenopathy After COVID-19 Vaccination: A Practical Management Plan for Radiologists Across Specialties","volume":"18","author":"Lehman","year":"2021","journal-title":"J. Am. Coll. Radiol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/2\/197\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:09:19Z","timestamp":1760134159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/2\/197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,27]]},"references-count":31,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["medicina58020197"],"URL":"https:\/\/doi.org\/10.3390\/medicina58020197","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2022,1,27]]}}}