Breast cancer screening is an essential component of preventive care, but when a scheduled mammogram overlaps with the receipt of a COVID-19 vaccine, enlarged lymph nodes have been identified in some cases. Here to offer clarity on these abnormal mammograms and screening recommendations in light of this recent finding is Dr. Hector Chapa.
Hector O. Chapa, M.D., F.A.C.O.G.
The saying is, “Every rose has its thorn.” Such is the case with the COVID-19 vaccines.
Thankfully, the rapid creation, manufacturing, and distribution of vaccines effective against COVID-19 are resulting in victories in the battle against the pandemic. However, the vaccine is having an unexpected side effect for some women: abnormal breast cancer screening mammograms.
This is due to enlarged lymph node in the axilla of the ipsilateral (same-sided), immunized arm. This vaccination reaction of subclinical unilateral lymphadenopathy was first reported on imaging in January 2021 which was documented as an incidental finding in 2 women during screening breast ultrasound and in 1 woman on short-interval follow-up ultrasound of bilateral breast masses.
Axillary adenopathy in women with an otherwise normal screening mammogram is a rare occurrence, reported in 0.02%-0.04% of screening mammograms. The differential diagnosis for unilateral axillary adenopathy is broad, including both benign and malignant conditions. It is imperative to exclude malignancy by thoroughly examining the ipsilateral breast, both clinically by physical examination as well as radiologically. Radiologists have long known that a recent dose of vaccine for shingles, tetanus or flu can cause lymph nodes to appear slightly enlarged. But these were rather “random” cases in the general population.
That said, this current COVID-19 vaccine adenopathy seems much more robust than in historical vaccines. As mass vaccination is well underway, these abnormal, enlarged lymph node findings on screening mammograms are becoming much more prevalent.
The Data on Post-Vaccination Lymphadenopathy
Post-vaccination ipsilateral axillary lymphadenopathy is not a new finding, however, as they were reported in the original vaccination trials. Hyperplastic axillary adenopathy is more common after a vaccine that evokes a strong immune response, including the most recently FDA-approved Pfizer-BioNTech and Moderna COVID-19 vaccines.
In the initial Moderna COVID-19 vaccine trial, axillary swelling or tenderness (lymphadenopathy) was a reported adverse event reported in 11.6% of patients following the first dose and occurred in 16.0% following dose 2. This was a “solicited“ adverse event, meaning that the researchers specifically asked about this occurrence in patients receiving the vaccine.
In the Pfizer-BioNTech COVID-19 vaccine trial, lymphadenopathy was reported as an “unsolicited” adverse event with 58 more cases in the vaccine group than the placebo group (64 versus 6 respectively). Lymphadenopathy occurred in the arm and neck within 2-4 days of vaccination and lasted for a mean of 10 days. It is important to note that this was unsolicited complaints, meaning that the patients volunteered that information without being asked specifically for it. Because of this, the true incidence rate is likely higher.
This post-COVID vaccination concern resulted in an editorial in the Radiological Society of North America (RSNA) journal, Radiology: Imaging Cancer. In that April 9, 2021 release, the authors confirmed that vaccine-induced lymphadenopathy can present a diagnostic dilemma for radiologists interpreting these examinations. As stated, “With mass vaccination rollout, lymphadenopathy ipsilateral to the injected deltoid muscle has become an important manifestation of an immune response” and can mimic pathological findings in the axillary lymph nodes.
This report also noted that as of March 2021, at least 20 articles have been published illustrating or discussing COVID-19 vaccine-related lymphadenopathy, with 18 of these articles published in imaging journals with more reports and data sure to come.
Screening Recommendations Relating to COVID-19 Vaccines & the Bi-Rads System
To mitigate the diagnostic dilemma of vaccine-induced lymphadenopathy, the Society of Breast Imaging (SBI) recommends that patients should “consider scheduling screening exams prior to the first dose of a COVID-19 vaccination or 4-6 weeks following the second dose of a COVID-19 vaccination.” This screening recommendation has been followed by a similar guideline published in the journal Radiology, authored by a multidisciplinary panel from oncologic centers. The panel recommends that non-urgent indications for breast cancer screenings or surveillance be scheduled prior to vaccination or to postpone imaging at least 6 weeks after final vaccination dose.
Currently, unilateral lymphadenopathy at initial screening would be given a mammogram interpretation of BI-RADS category of 0. BI-RADS stands for the “Breast Imaging-Reporting and Data System”. This is a risk assessment and quality assurance tool developed by American College of Radiology and provides a widely accepted reporting scale and schema for imaging of the breast. It applies to mammography, ultrasound, and MRI.
In this system, the categories are as follow:
- BI-RADS 0: incomplete. need additional imaging evaluation (additional mammographic views or ultrasound) and/or comparison to prior results
- BI-RADS 1: negative (symmetrical and no masses, architectural distortion, or suspicious calcifications)
- BI-RADS 2: benign (0% probability of malignancy)
- BI-RADS 3: probably benign (<2% probability of malignancy; short interval follow-up suggested)
- BI-RADS 4: suspicious for malignancy (2-94% probability of malignancy)
- BI-RADS 5: highly suggestive of malignancy (>95% probability of malignancy; appropriate action should be taken)
- BI-RADS 6: known biopsy-proven malignancy
Proposed Plan of Care
Hospitals and diagnostic centers are quickly establishing their own protocols for screening mammograms in light of this post vaccination finding. At the Cleveland Clinic, for example, once lymphadenopathy is identified on screening mammogram, then an ultrasound is performed to establish a baseline. Then, the patient is brought back several weeks after the second dose to compare the imagining to ensure that the nodes have returned to back to normal.
Here are some important diagnostic and clinical guidelines from the SBI for healthcare professionals to keep in mind:
- Consider obtaining the following information prior to obtaining patient mammograms: COVID-19 vaccination status, timing, and side (left vs. right arm) of vaccination. To minimize patient anxiety, consider including this introductory statement: Vaccines of all types can result in temporarily enlarged lymph nodes, which may be a sign that the body is making antibodies in response as intended.
- Unilateral axillary adenopathy on screening exams warrants a BI-RADS category 0 assessment to allow for further assessment of the ipsilateral breast and documentation of medical history, including COVID-19 vaccination.
- Following appropriate diagnostic work up for unilateral axillary adenopathy in women who received a COVID-19 vaccine in the ipsilateral upper extremity within the preceding 4 weeks, consider a short term follow up exam in 4-12 weeks (BI-RADS category 3) following the second vaccine dose.
- If axillary adenopathy persists after short term follow up, then consider lymph node sampling to exclude breast and non-breast malignancy.
In closing, the following statement by the Cleveland Clinic’s provider website, ConsultqD, captures the essence of the current clinical situation very well: “It’s important for physicians to stress that screening mammograms should not be postponed. Asymptomatic patients seeking routine screening may wish to schedule their mammogram 4-6 weeks following the COVID-19 vaccine. However, we do not want to discourage patients from receiving the vaccine. If patients are offered the opportunity for vaccination, they should take it. Lymphadenopathy does not occur in a majority of patients, and if it does, we will follow up as needed.”