key: cord-0758607-n66yoplf
authors: Adin, Mehmet Emin; Wu, Jennifer; Isufi, Edvin; Tsui, Edison; Pucar, Darko
title: Ipsilateral Malignant Axillary Lymphadenopathy and Contralateral Reactive Lymph Nodes in a COVID-19 Vaccine Recipient With Breast Cancer
date: 2022-03-15
journal: J Breast Cancer
DOI: 10.4048/jbc.2022.25.e12
sha: b73a3689384024a76d3f062c1a028209ed1ab6bb
doc_id: 758607
cord_uid: n66yoplf

Vaccine-related axillary nodal enlargement is a common benign condition that many mRNA vaccine receivers experience. However, a false attribution of axillary swelling to vaccination may result in delay in cancer care and potential disease progression, particularly in breast cancer patients presenting with ipsilateral axillary lymphadenopathy. We report the case of a 41-year-old pre-menopausal female who presented with suspicious axillary nodal enlargement and a right breast lump (triple-negative invasive ductal carcinoma) after recent administration of the second dose of Moderna mRNA coronavirus disease 2019 (COVID-19) vaccine. On imaging, bilateral axillary lymph nodes were detected. The ipsilateral right-sided node was proven to be metastatic, whereas contralateral nodes were related to a recent mRNA COVID-19 vaccination. Right-sided lymph node had intense uptake (maximum standardized uptake value [SUVmax] = 5), while the contralateral reactive nodes were mildly avid (SUVmax = 2.6). On magnetic resonance imaging, the right-sided node revealed asymmetric cortical thickening and marked cortical enhancement as opposed to normal-appearing left-sided nodes.

Vaccine related imaging findings including ipsilateral axillary lymphadenopathy can generate false alarms and cause patient anxiety, particularly in those with a known underlying malignancy. Occasionally this may prompt unnecessary interventions for an otherwise reactive process [1] . Conversely, false attribution of axillary lymphadenopathy to vaccination may result in delay in cancer treatment and the potential for disease progression. It has been previously reported that vaccine-related axillary nodal enlargement can occur in the setting of influenza and human papillomavirus vaccines [2, 3] . Recent reports have also reported ipsilateral reactive axillary lymph node enlargement in recipients of the coronavirus disease 2019 (COVID-19) mRNA vaccines [1, 4] . We report the case of a COVID-19 vaccine recipient with reactive and malignant axillary lymph node enlargement in the setting of breast cancer.

A 41-year-old pre-menopausal female presented with palpable right breast lump and ipsilateral axillary nodal enlargement on physical exam. This was subsequently confirmed on dedicated breast imaging as a 1.5 cm round right breast mass with a 0.8 × 0.8 × 0.7 cm ipsilateral axillary lymph node. Core biopsies of the right breast mass revealed triple negative invasive ductal carcinoma and enlarged lymph node demonstrated findings concerning for malignant involvement. Staging 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) (with tracer injected through an IV placed in the right antecubital fossa) showed an intensively FDG avid right axillary tail breast primary ( Figure 1E , shows a cluster of reactive lymph nodes in the left axilla with no significant enhancement or asymmetric cortical thickening (red arrow). An additional right axillary node with asymmetric cortical thickening is also seen, highly suspicious for metastatic disease (yellow arrow). 18F-FDG PET/CT = 18F-fluorodeoxyglucose positron emission tomography/computed tomography; 3D = three-dimensional; MIP = maximum intensity projection; SUVmax = maximum standardized uptake value; MRI = magnetic resonance imaging. https://ejbc.kr COVID-19 vaccine which was administrated to the left arm sixteen days previously. Contrastenhanced breast magnetic resonance imaging (MRI; MRI study was performed before and after IV gadolinium administration) approximately 5 weeks post-vaccination and prior to any treatment revealed stable bilateral axillary nodes. However, there were differences in imaging characteristics of lymph nodes. The right axillary lymph node demonstrated eccentric cortical thickening and contrast enhancement, whereas the left axillary lymph nodes showed clear delineation of fatty hila without discernable enhancement on post contrast images (Figure 1) . The latter is typically suggestive of a benign etiology such as inflammation/infection [5] .

The patient completed neoadjuvant chemotherapy for triple negative disease, and a follow-up 18F-FDG PET/CT at approximately 6-months from her last 18F-FDG PET/CT showed complete resolution of the previously hypermetabolic bilateral lymph nodes (Figure 2 ). She underwent a right mastectomy and complete axillary node dissection, the final surgical specimen demonstrated complete histopathological response to neoadjuvant systemic therapy with treatment-related changes.

The COVID-19 vaccines can result in reactive ipsilateral axillary and neck lymphadenopathy demonstrated on both anatomic and functional imaging that may need to be distinguished from malignancy, particularly in patients with current or a prior history of cancer [6, 7] . Vaccine related nodal reactivity or adenopathy can sometimes be seen or persist up to several months after vaccination [8] . Conclusive distinction between malignant or reactive lymphadenopathy remains challenging particularly in nodes with borderline activity and morphology on imaging. Imaging features such as asymmetric cortical thickening, significant enlargement, necrosis, indistinct contours, and conglomeration favor malignancy [9] . PET-CT is more sensitive, as it can detect metabolic activity in very small lymph nodes as well, regardless of its underlying condition. That said, there is no clear cut-off for a malignant or benign nodal enlargement, and the decision may be based upon multiple factors. For example, in the case we report here, the malignant node SUVmax (Deauville score = 5) value was higher than that of the reactive nodes (Deauville score = 3). On MRI, malignant nodes revealed abnormal findings such as asymmetric cortical thickening and cortical enhancement. To decrease reporting variability between PET-based imaging studies, the Deauville scoring system a globally agreed-upon approach for evaluation of treatment response in lymphoma was proposed to be used in the evaluation of vaccine-related nodal reactivity [1] . Deauville scores are more reproducible among different institutions as compared to SUV values given their individual PET protocols. In the case we report here, the reactive left-sided node had a Deauville score of 3, versus the malignant node, which had a Deauville score of 5. The Deauville activity score for the reactive node was in line with previously reported nodal activity in vaccinerelated nodal enlargement [1] . Nodal reactivity with mRNA vaccines is more common after the second dose [1, 10] . Moderna vaccines have shown to have slightly higher likelihood of nodal reactivity compared to Pfizer vaccine [1] . A recent retrospective study suggested that lymphopenia maybe associated with lower incidence of nodal reactivity, further supporting the link between nodal reactivity and vaccine immunogenicity [11] .

In conclusion, ipsilateral axillary nodal reactivity is a common observation after administration of the second dose of COVID-19 mRNA vaccines, with the potential persistence up to several months [12] . In the case we reported here, nodal enlargement persisted beyond 6 weeks. Current expert recommendations for follow-up are ongoing and include follow-up of the affected axilla at least 6-weeks after the second dose of the vaccination, with consideration for lymph node sampling if suspicion remains. The follow-up to resolution particularly in those with known underlying malignancies should warrant careful consideration, and documentation of vaccination should be included to assist the interpreting radiologist. The timing and location of the vaccination and imaging characteristics should all be considered [7] . Management in this context is case-specific in hopes of both reducing patient anxiety, costs, and unnecessary testing with delays in diagnosis or treatment.

Association of COVID-19 mRNA vaccine with ipsilateral axillary lymph node reactivity on imaging

Lymph node activation by PET/CT following vaccination with licensed vaccines for human papillomaviruses

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COVID-19 mRNA vaccination-induced lymphadenopathy mimics lymphoma progression on FDG PET/CT

Lymph node imaging in patients with primary breast cancer: concurrent diagnostic tools

Multidisciplinary recommendations regarding post-vaccine adenopathy and radiologic imaging: Radiology scientific expert panel

Unilateral lymphadenopathy after COVID-19 vaccination: a practical management plan for radiologists across specialties

COVID-19 vaccination-related lymphadenopathy: what to be aware of

Generalized lymph node activation after Influenza vaccination on 18F FDG-PET/CT imaging, an important pitfall in PET interpretation

Prevalence and significance of hypermetabolic lymph nodes detected by 2-[18F] FDG PET/CT after COVID-19 vaccination: a systematic review and a meta-analysis

Absolute lymphocyte count after COVID-19 vaccination is associated with vaccine-induced hypermetabolic lymph nodes on 18

CT: a focus in breast cancer care

Duration of 18F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination