Bilateral Axillary Nodal Uptake on ^99mTc–White Blood Cell Study Secondary to COVID-19 mRNA Vaccination

Abstract

A 77-year-old man with a history of chronic lower back pain, and prior spinal fusion surgery X2 was referred for ^99mTc-WBC Study for evaluation of worsening back pain and cervical radiculopathy to rule out any signs of infection. The patients white blood cells were tagged with ^99mTc-HMPAO (hexamethylpropylene amine oxime), and planar and SPECT/CT imaging was performed at 4 and 24 hours. ^99mTc-WBC Study showed no abnormal isotope localization in the spine; however, there was an incidental finding of bilateral increased soft tissue uptake in axillary lymph nodes. Medical history revealed intramuscular injection of second and third dose of Moderna mRNA COVID-19 vaccine in bilateral deltoids approximately 11 and 5 months before scan.

FIGURE 1.

Patient's white blood cells (WBCs) were tagged with ^99mTc-HMPAO (hexamethylpropylene amine oxime) followed by planar and SPECT/CT images performed approximately at 4 and 24 hours after injection. We have shown planar images 24 hours after injection in anterior and posterior views. There was no abnormal isotope localization in the C2, C3, C4, and C5 vertebral bodies and L3–L4 vertebral bodies. There is uptake in bilateral axillary lymph nodes.

FIGURE 2.

Shown are SPECT/CT images at 4 hours after injection. Transaxial CT shows spinal fusion in the cervical and lumbar region with no associated increased uptake of ^99mTc-WBC. Coronal views show bilateral increased soft tissue uptake found in the axillary lymph nodes. Medical history revealed that the most recent vaccination was the COVID-19 Moderna mRNA vaccine injected into the left deltoid 5 months before WBC scan and second dose injected into the right deltoid 11 months before scan. Differential diagnosis for bilateral axillary lymph node uptake can include a systemic process such as lymphoma¹ or autoimmune inflammatory condition,² metastatic breast cancer to axillary nodes,³ infectious process of viral or bacterial etiology, local infection, and reactive lymphadenopathy secondary to vaccination. However, our patient did not have any history of breast malignancy, laboratory findings, or clinical findings that would suggest metastasis, malignancy, infection, recent viral illness, or autoimmune inflammatory conditions. The only notable laboratory findings included chronically elevated creatinine kinase; therefore, COVID-19 vaccination was thought to be the most likely cause. Literature has shown incidental COVID-19 vaccination–related uptake on FDG PET/CT.^4–9 Several cases have been published discussing vaccine-related nodal and splenic FDG uptake, but minimal reports of increased ^99mTc-WBC uptake have been published. According to the Centers for Disease Control and Prevention, in patients older than 65 years, axillary lymphadenopathy was reported in 8.4% of patients after the second dose of the Moderna mRNA COVID-19 vaccine.¹⁰ In another study, authors found ¹⁸FDG PET/CT hypermetabolic axillary lymph nodes were detected in 25.8% of patients after a third dose of COVID-19 vaccination with a higher incidence of positive lymph nodes after the third dose.⁷ The exact mechanism of how the COVID-19 vaccine may cause lymphadenopathy and increased WBC uptake is unclear, although it is postulated that the increased immune response following vaccination causes an immune mediated inflammatory response in the area surrounding the vaccination site, and immune cells in the nearby nodes may proliferate as they become exposed to the vaccine. This type of reactive lymphadenopathy has been seen in multiple other vaccines in the past including measles, anthrax, H1N1, bacille Calmette-Guérin, and human papillomavirus vaccines.^11,12 Post-COVID reactive axillary lymphadenopathy has been reported to persist longer than 6 months and up to 43 weeks after vaccination.^11,12 The Moderna mRNA vaccine was also significantly more associated with lymphadenopathy compared with Pfizer.¹² Awareness of potential lymphadenopathy post–COVID-19 vaccine is important as it can be confused with metastasis or other false-positive results.