Axillary lymph node characteristics in breast cancer patients versus post-COVID-19 vaccination: Overview of current evidence per imaging modality

Abstract

Background: Axillary lymph node characteristics on axillary ultrasound (US), breast MRI and 18F-FDG PET/CT are relevant at breast cancer diagnosis. Axillary lymphadenopathy after COVID-19 vaccination has been frequently reported. This may cause a diagnostic dilemma, particularly in the ipsilateral axilla in women who have a either a recent diagnosis of breast cancer or a history of breast cancer. This review provides an overview of the current evidence regarding axillary lymph node characteristics at breast cancer diagnosis versus "post-COVID-19 vaccination".

Methods: A non-systematic narrative review was performed. Studies describing axillary lymph node characteristics per imaging modality (axillary US, breast MRI and 18F-FDG PET/CT) in breast cancer patients versus post-COVID-19 vaccination were selected and used for the current study.

Results: The morphologic characteristics and distribution of abnormal nodes on US may differ from the appearance of metastatic adenopathy since diffuse cortical thickening of the lymph nodes is the most observed characteristic after vaccination, whereas metastases show as most suspicious characteristics focal cortical thickening and effacement of the fatty hilum. Current evidence on MRI and 18F-FDG on morphologic characteristics of axillary lymphadenopathy is missing, although it was suggested that vaccine related lymphadenopathy is more likely to be present in level 2 and 3 nodes than metastatic nodes. Reported frequencies of lymphadenopathy post-COVID-19 vaccination range from 49% to 85% (US), 29% (breast MRI) and 14.5% to 53.9% (18F-FDG PET/CT). Several factors may impact the presence or extent of lymphadenopathy post-COVID-19 vaccination: injection site, type of vaccine (i.e., mRNA versus vector), time interval (days) between vaccination and imaging, previous history of COVID-19 pneumonia, and first versus second vaccine dose.

Conclusion: Although lymph node characteristics differ at breast cancer diagnosis versus post-COVID-19 vaccination, clinical information regarding injection site, vaccine type and vaccination date needs to be documented to improve the interpretation and guide treatment towards the next steps of action.

Keywords: Axilla; Breast cancer; COVID-19 vaccination; Lymphadenopathy.

Fig. 1

Example of a 51-year old woman who presented with a palpable lump in her left breast. After mammography and ultrasound with tissue sampling, invasive lobular cancer (ER+,PR+,HER2+) was confirmed. Axillary ultrasound demonstrated no suspicious lymph nodes, a lymph node (green arrow) with a maximum cortical thickness of 1.4 mm was observed and considered benign (Fig. 1a). Breast MRI demonstrated a multicentric mass of approximately 7 cm in her left breast (red arrow). No suspicious axillary, internal mammary or periclavicular lymph nodes were detected bilateral (Fig. 1b). 18F-FDG PET/CT was requested by the clinician to rule out distant metastasis. Yet, six days prior to 18F-FDG PET/CT, after ultrasound and breast MRI, the patient received COVID-19 Vaccine Janssen in her right arm. 18F-FDG PET/CT demonstrated hypermetabolic axillary lymph nodes in the contralateral axilla (orange arrows), which were considered lymphadenopathy post-COVID-19 vaccination (Fig. 1c). Patient was treated with neoadjuvant systemic therapy (9 cycles of TCHP regimen (docetaxel, carboplatin, trastuzumab and pertuzumab). Breast MRI, performed mid-way and after neoadjuvant systemic therapy prior to surgical treatment, demonstrated no suspicious axillary lymph nodes bilateral (Fig. 1d). Patient underwent a left-sided mastectomy with sentinel lymph node biopsy. Three ipsilateral sentinel lymph nodes were removed, demonstrating no lymph node metastases at final histopathology. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Example of a 57-year old woman who presented with a palpable lump in her right axillary region. Patient underwent a right sided mastectomy and autologous breast reconstruction six years earlier because of breast cancer diagnosis. After recent ultrasound examination of the reconstructed breast with tissue sampling, invasive carcinoma of no special type (ER+,PR-,HER2-) was confirmed. Axillary ultrasound demonstrated a suspicious lymph node with a diffuse enlarged cortical thickness of 5,1 mm (green arrow; Fig. 2a). Ultrasound-guided tissue sampling was performed, axillary lymph node metastasis was confirmed. Breast MRI demonstrated an unifocal mass in the upper outer quadrant of the reconstructed breast (blue arrow) and multiple suspicious axillary lymph nodes in the right axillary region (red arrow; Fig. 2b). 18F-FDG PET/CT was requested by the clinician to rule out distant metastasis. Four days prior to 18F-FDG PET/CT, after ultrasound and breast MRI, the patient received Spikevax in her (contralateral) left arm. 18F-FDG PET/CT demonstrated bilateral hypermetabolic lymph nodes (orange arrows; Fig. 2c). Ultrasound-guided biopsy of the most suspicious axillary lymph node in the left axillary region after 18F-FDG PET/CT demonstrated no metastasis with visible lymphoid tissue after histopathological evaluation. Patient is currently treated with neoadjuvant systemic therapy (8 cycles of dose-dense AC-P (doxorubicine, cyclofosfamide and paclitaxel). Mid-way neoadjuvant systemic therapy breast MRI was performed. The axillary lymph nodes in the left axillary region were normalized, which can be explained by normalization of lymphadenopathy post-COVID-19 vaccination. The axillary lymph nodes in the right axillary region remained suspicious, though a reduced cortical thickness was observed when compared to the previous breast MRI, which can be explained by lymphadenopathy due to breast cancer diagnosis (red arrow; Fig. 2d). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)