key: cord-0720911-o7lrd77u
authors: Moy, Linda; Kim, Eric
title: Follow-up of COVID-19 Vaccine–related Axillary Lymphadenopathy before 12 weeks is Unnecessary
date: 2022-04-26
journal: Radiology
DOI: 10.1148/radiol.220962
sha: 6d840622d728effdf5709549d344ba613f112ba4
doc_id: 720911
cord_uid: o7lrd77u

nan

At the time of writing, there have been almost one million COVID-19-related deaths in the United States [1] and over six million globally [2] . To reduce the risk of severe infection, developers created vaccines effective against SARS-CoV-2 infection at an unprecedented pace. In December 2020, the U.S. Food and Drug Administration first issued emergency use authorization for the messenger RNA (mRNA) vaccines, BNT162b2

(Pfizer/BioNTech) and mRNA-1273 (Moderna), only one year after the first reported cases of COVID-19 [3] . Currently, three COVID-19 vaccines are approved for use in the United States, and other vaccines are in use around the world, including the vector ChAdOx1 nCoV-19 vaccine (AstraZeneca). Due to widespread vaccination efforts and increasing availability worldwide, 65% of the world population has received at least one dose of a COVID-19 vaccine, with over 11 billion doses administered [4] .

Aided by unprecedented media coverage, side effects of the COVID-19 vaccines have become well recognized. Different vaccines elicit different immune responses, but one of the more common findings after vaccination is reactive lymphadenopathy. It is often seen in the axilla ipsilateral to the side of vaccine administration, may also extend beyond the axilla, and can be seen on different imaging modalities [5] . Radiologists realized that vaccine-related axillary lymphadenopathy may be a diagnostic dilemma. While bilateral axillary lymphadenopathy is often benign due to reactive, infectious, or systemic etiologies, unilateral axillary lymphadenopathy is concerning due to the possibility of metastatic disease from underlying breast cancer. Up to 1% of all breast cancers initially present as isolated lymph node metastasis even in the absence of other suspicious breast findings on conventional imaging [6] . Therefore, radiologists do not want to miss a potential sign of breast cancer and have struggled with confidently stating that unilateral axillary lymphadenopathy in the setting of recent COVID-19 vaccination is benign. Instead, short-term follow-up imaging and/or biopsy of the suspicious lymphadenopathy are performed. weeks was recommended, with biopsy to be considered for any persistent axillary adenopathy on a follow-up imaging examination [7] . The European guidelines varied based on patient history, clinical presentation, history of breast cancer, vaccination delivery, and imaging findings [8] . The management of axillary adenopathy, presumably secondary to COVID-19 vaccinations, remains debated. It has evolved as more data and evidence on the incidence and duration of vaccine-related adenopathy became available.

In this issue of Radiology, Ha and colleagues assess the temporal changes of axillary lymphadenopathy after COVID-19 vaccination in 88 healthy women who underwent serial US [9] . This paper is the first prospective study that evaluates COVID-19 vaccine-related axillary lymphadenopathy. The prospective design reduces potential bias and confounding, which may be seen in retrospective studies. The authors recruited asymptomatic women without breast cancer who underwent an axillary US after COVID-19 vaccination at a single academic institution in South Korea. Patients received either one of the mRNA vaccines, BNT162b2 or mRNA-1273, or the ChAdOx1 nCoV-19 (recombinant) vaccine. All participants had a negative I n p r e s s or benign screening examination within six months of recruitment. Participants who demonstrated axillary lymphadenopathy on imaging, defined as focal or diffuse cortical thickening >3 mm with partial or complete loss of fatty hilum or rounded nodes with non-hilar or diffuse flow, were included for analysis. Follow-up US examinations were recommended at 4-6 weeks intervals for persistent lymphadenopathy.

Among the 88 women who exhibited axillary lymphadenopathy on US and had subsequent follow-up US examinations, only 26% (n=23) had complete resolution of axillary lymphadenopathy within six weeks of vaccination [9] . Of the 49 women with a follow-up US performed 10-12 weeks after vaccination, 51% (n=25) had persistent lymphadenopathy.

Interestingly, patients who received the mRNA vaccines had higher cortical thickness values and more suspicious appearing lymph nodes than those who received the vector vaccines. Of note, no patients were diagnosed with malignancy during the study period. Based on their results, the authors conclude that follow-up US in 12 or more weeks may be appropriate for cases of COVID-19 vaccine-associated axillary lymphadenopathy.

It is important to recognize the limitations of this study. This is a single-center study with a small sample size. Unfortunately, only three patients had follow-up US more than 12 weeks after vaccination. Considering that a large percentage of patients with follow-up US at 10-12 weeks demonstrated persistent lymphadenopathy, even longer follow-up would be helpful to get a better understanding of the duration of lymphadenopathy in this population. Finally, the reported 70% incidence of lymphadenopathy within one week of vaccination (in 35 of 50 women who volunteered for screening purposes) was higher than in prior studies. One reason for this higher incidence was because the study sample was enriched with patients for whom lymphadenopathy had been detected. As more studies with long-term data are being published and radiologists continue to gain more clinical experience, it is becoming clear that both the incidence and duration of vaccine-related adenopathy are greater than initially expected. With this in mind, the SBI recently published revised recommendations on the management of axillary adenopathy in patients with recent COVID-19 vaccination. They recommend that patients with unilateral axillary lymphadenopathy on screening without other suspicious findings be given a benign (BI-RADS 2) assessment. For those undergoing short-term follow-up imaging for probably benign (BI-RADS 3) assessment, a follow-up interval of 12 or more weeks is recommended rather than the shorter follow-up time previously recommended [7] . This recommendation is likely conservative because the mean doubling time of breast cancers is 212 days and a three-months delay in diagnosis is unlikely to impact prognosis.

In conclusion, this is the first prospective study to look at temporal changes in axillary lymphadenopathy after COVID-19 vaccination. The high incidence of adenopathy and the fact that no breast cancers were found suggest that adenopathy is a widespread and benign side effect of COVID-19 vaccinations. Therefore, the recommendation by Ha and colleagues to increase the follow-up imaging interval from 4-12 weeks to more than 12 weeks seems reasonable to reduce the number of follow-up examinations. I n p r e s s

GA: US Department of Health and Human Services

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