Ultrasound Features to Differentiate COVID-19 Vaccine-Induced Benign Adenopathy from Breast Cancer Related Malignant Adenopathy

Abstract

Rationale and objective: To identify nodal features used to distinguish coronavirus disease 2019 (COVID-19) vaccine-Induced benign reactive adenopathy from malignant adenopathy.

Materials and methods: This IRB-approved, single-institution, retrospective study compared features of 77 consecutive patients with benign adenopathy secondary to a messenger RNA COVID-19 vaccine with 76 patients with biopsy-proven malignant adenopathy from breast cancer. Patient demographics and nodal features were compared between the two groups using univariate and multivariate logistic regression models. A receiver operating characteristic analysis with the maximum value of Youden's index was performed for the cutoff value of cortical thickness for predicting nodal status.

Results: The mean cortical thickness was 5.1 mm ± 2.8 mm among benign nodes and 8.9 mm ± 4.5 mm among malignant nodes (p < 0.001). A cortical thickness ≥3.0 mm had a sensitivity of 100% and a specificity of 21% (area under the curve [AUC] = 0.60, 95% confidence interval [CI]: 0.52-0.68). When the cutoff for cortical thickness was increased to ≥5.4 mm, the sensitivity decreased to 74%, while the specificity increased to 69% (AUC = 0.77, 95% CI: 0.70-0.84).Cortical thickness correlated with nodal morphology type (r² = 0.57). An axillary node with generalized lobulated cortical thickening had a 7.5 odds ratio and a node with focal cortical lobulation had a 123.0 odds ratio compared to one with diffuse, uniform cortical thickening only (p < 0.001).

Conclusion: Cortical thickness and morphology are predictive of malignancy. Cortical thickness cutoff of ≥5.4 mm demonstrates higher specificity and improved accuracy for detecting malignant adenopathy than a cutoff of ≥3.0 mm.

Keywords: COVID-19; cortical thickness, ultrasound; lymphadenopathy; vaccine.

Figure 1

Area under the curve for cortical thickness of 5.4 mm.

Figure 2

Cortical thickness and morphologic type.

Figure 3

A 62-year-old woman with benign reactive adenopathy after COVID-19 vaccination. (a) Longitudinal AUS, 17 days after COVID-19 vaccination, demonstrates a type 3 node measuring 27 mm in long axis in the axilla. Diffuse, uniform cortical thickening measures 5.3 mm (arrows) on the ipsilateral side of vaccination. (b) Longitudinal AUS, 5 months later, demonstrates a decrease in cortical thickness to 2.4 mm (arrows). AUS, axillary ultrasound; COVID-19, coronavirus disease 2019.

Figure 4

A 49-year-old woman with benign reactive adenopathy after COVID-19 vaccination. Longitudinal AUS demonstrates a node with generalized lobulated cortical thickening, with a maximum cortical thickness of 4.5 mm (solid arrows). Fine needle aspirate biopsy confirmed a benign reactive node. AUS, axillary ultrasound; COVID-19, coronavirus disease 2019.

Figure 5

A 41-year-old woman with malignant metastatic adenopathy due to breast cancer. Longitudinal AUS demonstrates a type 5 node measuring 37 mm in long axis, with focal cortical lobulation. At the focal cortical thickening, the cortex measures 15 mm (arrows) while the remainder of the node shows a thin cortex (arrowheads). Fine needle aspiration biopsy performed on the focal hypoechoic lobulation confirmed metastatic adenopathy from breast cancer.

Figure 6

A 53-year-old woman with benign reactive adenopathy after COVID-19 vaccination. (a) Longitudinal AUS, 6 days after receipt of COVID-19 vaccination, demonstrates a type 5 node measuring 29 mm in long axis, with focal cortical lobulation measuring 18 mm (solid arrows) and displacement of the hilum (dashed arrow). (b) Longitudinal AUS, 5 months later, demonstrates a decrease in the cortical thickness (arrows) from 18 mm to 7.6 mm at the thickest portion of the cortex. The cortex surrounds the now centrally located hilum (dashed arrow). AUS, axillary ultrasound; COVID-19, coronavirus disease 2019.

Figure 7

A 61-year-old woman with malignant metastatic adenopathy due to breast cancer. Longitudinal AUS demonstrates a type 4 node measuring 36 mm in long axis with generalized lobulated cortical thickening (arrows) measuring 12 mm. Core needle biopsy of the node confirmed malignant adenopathy. AUS, axillary ultrasound.