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Axillary lymphadenopathy following bivalent COVID-19 booster vaccination

Published:December 16, 2022DOI:https://doi.org/10.1016/j.clinimag.2022.12.003

      Highlights

      • Imaging features of axillary lymphadenopathy in the setting of ipsilateral bivalent COVID-19 vaccine booster are presented.
      • Resolution of the axillary lymphadenopathy was demonstrated in two cases and three cases were assessed at the outset as benign.
      • Radiologists will continue to encounter axillary lymphadenopathy following bivalent COVID-19 vaccines.

      Keywords

      1. Introduction

      With the recent FDA emergency use authorizations of the bivalent Pfizer-BioNTech and Moderna COVID-19 vaccines, in conjunction with documented lymphadenopathy in clinical trials, vaccine history should continue to be considered when encountering unilateral axillary lymphadenopathy. With the rise of the Omicron subvariants came a reduced effectiveness of the monovalent COVID-19 vaccines, leading to the development of the bivalent COVID-19 vaccines (Original and Omicron B.4/B.5) [
      • Chalkias S.
      • Harper C.
      • Vrbicky K.
      • et al.
      A bivalent omicron-containing booster vaccine against Covid-19.
      ]. The Moderna bivalent booster contains 25 μg of the nucleoside-modified mRNA that was used in the original vaccine that encodes the “prefusion stabilized Spike glycoprotein (S) of the SARS-CoV-2 Wuhan-Hu-1 strain” and 25 μg of mRNA that encodes “the pre-fusion stabilized S-protein of the SARS-CoV-2 Omicron variant lineages BA.4 and BA.5”. [
      Moderna HCP FS for bivalent booster for 6 years and older (Gray Label) 10122022. The U.S. Food and Drug Administration.
      ] Similarly, the Pfizer bivalent booster contains 15 μg of the original mRNA and 15 μg of the nucleoside-modified mRNA that encodes for BA.4 and BA.5 variants. [
      Pfizer HCP FS bivalent booster grey 10122022. The U.S Food and Drug Administration.
      ]. Although vaccine related adenopathy ipsilateral to the vaccination site following monovalent COVID-19 vaccination has been well documented in the literature [
      • Mehta N.
      • Sales R.M.
      • Babagbemi K.
      • et al.
      Unilateral axillary adenopathy in the setting of COVID-19 vaccine.
      ,
      • Lane E.G.
      • Eisen C.S.
      • Drotman M.B.
      • et al.
      Time for resolution of COVID-19 vaccine-related axillary lymphadenopathy and associated factors.
      ,
      • Wolfson S.
      • Kim E.
      • Plaunova A.
      • et al.
      Axillary adenopathy after COVID-19 vaccine: no reason to delay screening mammogram [published correction appears in Radiology. 2022 Sep;304(3):E57].
      ], reaction to bivalent COVID-19 vaccines is not well documented. Similar lymph node reactivity is suggested, given reports of lymphadenopathy in bivalent COVID-19 vaccine trials. [
      Centers for Disease Control and Prevention website. The Moderna COVID-19 vaccine's local reactions, systemic reactions, adverse events, and serious adverse events.
      ,
      Centers for Disease Control and Prevention website. Pfizer-BioNTech COVID-19 vaccine reactions & adverse events.
      ]
      In this case series, we present five patients with incidental axillary lymphadenopathy identified on breast ultrasound, PET-CT, or breast MRI, following the administration of the Pfizer or Moderna bivalent COVID-19 booster vaccine.

      2. Case descriptions

      2.1 Case 1

      46-year-old female presented for baseline screening mammogram and ultrasound. Bilateral mammogram was assessed as BI-RADS 1. Prominent left axillary lymph nodes were identified on screening ultrasound (Fig. 1a). The patient received the Moderna Bivalent Booster (50 MCG/0.5 mL) Sars-CoV-2-Vaccination to the left deltoid two days prior to breast imaging. The ultrasound was assessed as BI-RADS 0. The patient was recalled for a diagnostic, targeted ultrasound of the left axilla for further evaluation. Diagnostic breast ultrasound imaging, 21 days post-bivalent booster vaccination, demonstrated an interval decrease in the size of the previously prominent lymph nodes (Fig. 1b), and as such lymphadenopathy was attributed to reactive vaccine related etiology and assessed as BI-RADS 2. The patient had previously received three doses of the Pfizer COVID-19 vaccine, which included the initial series, and one monovalent booster.
      Fig. 1
      Fig. 1a. Transverse gray-scale static sonographic image of the left axilla demonstrates a lymph node (arrow) with diffusely thickened cortex.
      b. Follow up ultrasound performed 19 days subsequent to the initial screening ultrasound. Transverse gray-scale static sonographic image of the left axilla demonstrates interval resolution of cortical thickening of a previously noted axillary lymph node (arrow) compatible with benign reactive etiology.

      2.2 Case 2

      75-year-old female presented for bilateral diagnostic mammogram and ultrasound as a follow up of recent left lumpectomy for DCIS with positive margins. Patient received the Pfizer Bivalent Booster (30 MCG/0.3 mL) Sars-CoV-2-Vaccination to the right deltoid three days prior to mammogram and ultrasound. Bilateral prominent axillary lymph nodes were identified on ultrasound, the largest on the right, measuring 1.1 × 0.7 × 1.1 cm which, given history of recent vaccination with a bivalent booster were attributed to reactive vaccine related etiology (Fig. 2). Prominent left axillary lymph nodes were assessed as consistent with recent postoperative status. The ultrasound was assessed as BI-RADS 2. The patient had previously received four doses of the Pfizer COVID-19 vaccine, the initial series, and two monovalent booster vaccines. The patient did not demonstrate axillary lymphadenopathy on breast imaging performed within six months following the initial COVID-19 vaccine series.
      Fig. 2
      Fig. 2a. Transverse gray-scale static sonographic image of the left axilla demonstrates a lymph node (arrow) with diffusely mildly thickened cortex, assessed as reactive and compatible with recent lumpectomy.
      b. Transverse gray-scale static sonographic image of the right axilla demonstrates a lymph node (arrow) with diffusely thickened cortex and obliteration of the fatty hilum.

      2.3 Case 3

      73-year-old female with right-sided breast cancer status post bilateral mastectomy presented for surveillance PET-CT skull base to mid-thigh. The patient received the Moderna Bivalent Booster (50 MCG/0.5 mL) Sars-CoV-2-Vaccination to the left upper extremity, four days prior to imaging. Mildly FDG avid, non-enlarged, left supraclavicular and axillary lymph nodes were identified (Fig. 3). Lymphadenopathy ipsilateral to vaccination site was attributed to reactive vaccine related etiology. The patient had previously received four doses of the Moderna COVID-19 vaccine, the initial series, and two monovalent booster vaccines without enlarged or FDG avid axillary lymphadenopathy noted on prior surveillance PET-CTs performed within four and eight months of vaccination.
      Fig. 3
      Fig. 3a. Fused axial PET/CT image demonstrates FDG avid left axillary lymph nodes (arrow).
      b. Fused axial PET/CT image demonstrates FDG avid left supraclavicular lymph nodes (arrow).

      2.4 Case 4

      70-year-old female presented for routine screening mammogram and breast ultrasound. The patient received the Pfizer Bivalent Booster (30 MCG/0.3 mL) Sars-CoV-2-Vaccination to the left deltoid two days prior to mammogram and ultrasound. The ultrasound demonstrated multiple prominent left lymph nodes and was assessed as BI-RADS 0. The patient returned for additional imaging four days later. The subsequent diagnostic ultrasound demonstrated multiple left axillary lymph nodes with cortical thickening, up to 0.4 cm (Fig. 4). The diagnostic imaging was assessed as BI-RADS 3 and six month follow up sonographic evaluation was recommended. The patient had previously received four doses of the Pfizer COVID-19 vaccine, the initial series, and two monovalent booster vaccines. The patient did not demonstrate axillary lymphadenopathy on breast imaging performed one day after the first monovalent COVID-19 booster vaccine.
      Fig. 4
      Fig. 4Transverse gray-scale static sonographic image of the left axilla demonstrates multiple enlarged lymph nodes (arrow) with diffusely thickened cortices.

      2.5 Case 5

      62-year-old female with a history of right-sided breast cancer, status post lumpectomy, presented for bilateral, screening breast MRI. The patient received the Moderna bivalent booster (50 MCG/0.5 mL) Sars-CoV-2-vaccination to the left upper extremity 26 days prior to imaging. MRI demonstrated a mildly prominent left axillary lymph node (Fig. 5). The imaging was assessed as BI-RADS 2. The patient had previously received three doses of the Moderna COVID-19 vaccine, the initial series, and one monovalent booster vaccine. The patient did not demonstrate axillary lymphadenopathy on breast imaging performed within five months of the initial COVID-19 vaccine series.
      Fig. 5
      Fig. 5a. Axial T1-weighted fat suppressed post contrast subtracted sequence demonstrates a single left axillary lymph node (arrow) with obliteration of the fatty hilum.
      b. Sagittal T1-weighted fat suppressed post contrast sequence demonstrates a single left axillary lymph node (arrow) with obliteration of the fatty hilum.

      3. Discussion

      Lymphadenopathy has been reported in clinical studies investigating both the Pfizer and Moderna bivalent COVID-19 vaccines [
      Centers for Disease Control and Prevention website. The Moderna COVID-19 vaccine's local reactions, systemic reactions, adverse events, and serious adverse events.
      ,
      Centers for Disease Control and Prevention website. Pfizer-BioNTech COVID-19 vaccine reactions & adverse events.
      ]. In one study, 21.3% of participants (age 18 to 64) and 11.5% (65+) reported axillary swelling and tenderness within seven days of receiving a second booster dose (Moderna bivalent booster (Original and Omicron BA.1)) compared to 18.5% of participants (age 18 to 64) and 10.7% (65+) who received the monovalent Moderna vaccine as a second booster dose [
      Centers for Disease Control and Prevention website. The Moderna COVID-19 vaccine's local reactions, systemic reactions, adverse events, and serious adverse events.
      ]. In a study evaluating a Pfizer bivalent booster (Original and Omicron BA.1) 0.3% of participants (age 55+) reported lymphadenopathy [
      Centers for Disease Control and Prevention website. Pfizer-BioNTech COVID-19 vaccine reactions & adverse events.
      ]. One should note that the bivalent boosters in these studies contained the Omicron variant lineage BA.1, rather than BA.4/BA.5, variants, which are present in the current bivalent booster vaccines. As delay of screening mammography post COVID vaccination is no longer recommended [
      Revised SBI Recommendations for the Management of Axillary Adenopathy in Patients with Recent COVID-19 Vaccination. Society of Breast Imaging Patient Care and Delivery Committee.
      ] nor prudent, breast radiologists should be aware of the continued COVID-19 vaccine related adenopathy, in particular within a few days following bivalent COVID-19 booster. As with the monovalent COVID-19 vaccines, we expect to encounter large numbers of patients with axillary lymphadenopathy following the administration of the COVID-19 bivalent booster vaccines. This underscores the importance of continuing to collect “information on patient COVID-19 vaccination status including the date and side of vaccination on patient intake forms” as advised by the Society of Breast Imaging (SBI) guidelines [
      Revised SBI Recommendations for the Management of Axillary Adenopathy in Patients with Recent COVID-19 Vaccination. Society of Breast Imaging Patient Care and Delivery Committee.
      ]. Given appropriate vaccine related history, as per revised SBI guidelines [
      Revised SBI Recommendations for the Management of Axillary Adenopathy in Patients with Recent COVID-19 Vaccination. Society of Breast Imaging Patient Care and Delivery Committee.
      ], a follow-up of 12 or more weeks is recommended, or patients can be returned to the screening pool if lymphadenopathy is assessed as benign in the absence of other suspicious breast findings.

      Declaration of competing interest

      None.

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