Prospective ultrasonographic surveillance study for incidence and recovery period of COVID-19 vaccination-related axillary lymphadenopathy

ABSTRACT

Background: COVID-19 vaccination-related lymphadenopathy is a frequent imaging finding which may be indistinguishable from malignant nodal involvement and lead to diagnostic difficulties in patients with cancer or healthy individuals on cancer screening. An expert panel of the leading cancer centers in United States recommended routine imaging examinations should be scheduled at least 6 weeks after the final vaccination to allow for any reactive lymphadenopathy to resolve. However, there were no prospective trials regarding COVID-19 vaccination-related lymphadenopathy and the evidence was so limited. The purpose of this study was to determine the incidence and imaging characteristics of COVID-19 vaccination-related axillary lymphadenopathy and assess the recovery period. Methods: We prospectively enrolled healthy women working at the St. Luke's International Hospital who received Pfizer COVID-19 vaccination within 8 weeks before enrollment between May 10th and 27th, 2021. Women with a history of any type of cancer or axillary surgery, active atopic dermatitis and auto-immune disease were excluded. Participants underwent ultrasound examinations for bilateral axilla at the enrollment. Lymphadenopathy was defined as demonstrating an enlarged node(s) with more than 5mm in short axis by ultrasound imaging in this trial. As for imaging characteristics, status of cortical thickening, echogenic hilus and vascularity of lymph nodes were evaluated. Other side effects by vaccination were assessed by a questionnaire. If lymphadenopathy was detected, we followed the participant by ultrasound examination every three weeks until the lymphadenopathy was resolved. We evaluated theincidence rate and imaging characteristics of lymphadenopathy detected by ultrasound examination, and the recovery period required for improvement of the lymphadenopathy. We also validated the association of the lymphadenopathy with the participant characteristics and other side effects. Results: A total of 135 women were enrolled in this study. Participants' median age was 37 years (range 23-63). Median time from the latest vaccination to the enrollment was 45 days (range 8-56). In the ultrasound examination at enrollment, axillary lymphadenopathy was observed in 67 participants (50%) on the injected (ipsilateral) side. In the contralateral axilla, 13 participants (10%) showed lymphadenopathy. In the ipsilateral axilla, the number of enlarged node(s) was 1 node in 25 cases (19%), 2 nodes in 24 cases (18%), 3 nodes in 13 cases (10%), 4 nodes in 4 cases (3%) and 5 nodes in 1 case (1%). Regarding the ipsilateral enlarged lymph node, focal cortical thickening was observed in 58 cases (43%) and the absence of the echogenic hilus was observed in 15 cases (11%). Hypervascularity was observed in 15 cases (11%). Incidence of the lymphadenopathy was not statistically correlated with participant's age or incidence of fever due to vaccination. At 6 weeks after the latest vaccination, the rate of ipsilateral axillary lymphadenopathy was 48%, 40% at 8 weeks, and 6% at 12 weeks. In participants with lymphadenopathy, median recovery period to resolve the lymphadenopathy was 75 days from the latest vaccination. Conclusion: A half of participants showed COVID-19 vaccination-related axillary lymphadenopathy and the imaging characteristics were often indistinguishable from malignant nodal involvement. Therefore, patients with breast cancer should be vaccinated on the contralateral arm to the cancer side to avoid diagnostic conundrum. The lymphadenopathy was commonly observed even in 8 weeks, and mostly resolved after 12 weeks from the vaccination. Therefore, non-urgent imaging examinations such as screening would be recommended to be scheduled at least 12 weeks following the latest vaccination.