Invited Commentary: Evolving Management of COVID-19 Vaccine–related Axillary Adenopathy

See also the article by Zhang et al in this issue.

In 2020, the world was disrupted by the impact of COVID-19, and we still continue to feel its repercussions today. We are still dealing with supply chain issues, and we continue to grapple with the impact of the Great Resignation, with a record number of people choosing to leave their jobs. Like the rest of the economy, health care was significantly impacted.

During the height of the pandemic, elective surgeries and procedures were deferred, as well as routine screening examinations. At the University of Pennsylvania, the breast imaging center remained open only for patients who needed diagnostic imaging, but similar to other centers, screening was deferred during the height of the pandemic. With the reopening and resumption of mammographic screening, it was estimated that there was a deficit of almost 4 million screening episodes (1). The reason for this may be multifactorial, such as health concerns about entering a medical facility, limited access, mixed messages, and financial hardship.

The pandemic led to the shutdown of the economy, with massive layoffs resulting in financial hardship for patients and loss of employer-sponsored health insurance. Health care gradually reopened with social distancing guidelines, yet the cessation of screening for months resulted in backlogs, and we have yet to close the gap. The delay in screening has also resulted in a backlog of biopsies, as patients present with more advanced cancers. The access issues have been exacerbated by a national shortage of breast imagers and technologists, as some chose to leave their professions as part of the Great Resignation.

The U.S. Food and Drug Administration (FDA) granted emergency use authorization (EUA) for the Pfizer-BioNTech and Moderna vaccines in 2020 and the Johnson & Johnson vaccine in 2021. Soon after, reports of unilateral axillary adenopathy detected clinically and at mammography began to surface. The authors of “Axillary Lymphadenopathy in the COVID-19 Era: What the Radiologist Needs to Know” (2) expertly review the imaging findings and summarize the varying society guidelines that ensued.

Various societies and groups began to issue recommendations, resulting in mixed messages to the public. Between January 2021 and March 2022, the Society of Breast Imaging, Radiological Society of North America (RSNA), and Massachusetts General Hospital each issued management guidelines (3–5). The recommendations ranged from recalling patients with unilateral adenopathy for follow-up imaging to issuing a Breast Imaging Reporting and Data System (BI-RADS) category 2 at screening, if there was a documented clinical history of ipsilateral vaccine administration. The European Society of Breast Imaging did not issue its risk-stratified recommendations until August 2021 (6).

In addition to the mixed messages about management, there were mixed messages regarding the timing of the screening examination relative to the vaccine administration. Some recommended screening before administration of the first dose or waiting at least 6–12 weeks after the second dose, while others did not think that such “timing” of imaging was warranted (3–6). At the time these recommendations were made, the impact and duration of axillary adenopathy after administration of messenger RNA (mRNA)–based vaccine still needed to be better elucidated; it was all new territory.

New data continue to emerge. Wolfson and colleagues (7) reported findings from the largest cohort to date. The authors reported the presence of vaccine-related lymphadenopathy as early as 1 day and as long as 71 days after vaccination. In their cohort, all four patients diagnosed with metastatic breast cancer to the axilla had suspicious mammographic findings. Short-term follow-up yielded no malignancy.

On the basis of these results, the authors concluded that short-term follow-up should not be recommended for unilateral axillary adenopathy in the context of vaccine administration with no suspicious findings in the ipsilateral breast. During the study period, 407 follow-up examinations were performed. Eliminating the need for the follow-up examinations will open up much-needed examination slots, help alleviate some of the backlog, and decrease patient anxiety.

As new COVID-19 variants arise, additional boosters will likely be needed. There is talk of annual boosters as new variants emerge, similar to the flu vaccine. As of now, we do not fully know the impact of each additional booster that the patient receives in regard to the degree and duration of adenopathy. Therefore, continued documentation of the vaccination date and the side of administration should be obtained from the patient for every patient undergoing mammography.

The mammographic interpretation should be made in the context of this information as well as the knowledge that extended persistence of the lymphadenopathy may occur in some patients. The society guidelines, which are now better aligned, give us general guidelines on management of vaccine-related adenopathy. Thus armed with the latest scientific data, we should interpret the mammograms taking into consideration the patient’s personal history and risk factors, while minimizing harm to the patient.