COVID-19 vaccination simulating lymph node progression in a patient with prostate cancer.

Several cases of cancer patients with 18-fluorodeoxyglucose (18FDG) Positron Emission Tomography/Computed Tomography (PET/CT) evidence of metabolically active axillary lymph nodes after COVID-19 vaccination have been described, creating a diagnostic dilemma and sometimes leading to further unnecessary examinations. A 62-year-old male, diagnosed with prostate cancer, treated with hormone-therapy and radiotherapy of the prostate 2 years before, underwent fluorine-18 choline (F-FCH) PET/CT for restaging purpose, less than 3 weeks after he had received the second dose of the Pfizer BioNTech-BNT162b2 mRNA COVID-19 vaccine. This exam showed an increased F-FCH uptake and an enlargement of the left axillary, paratracheal, para-aortic, subcarinal, and hilar bilateral lymph nodes. Fourteen weeks later, the patient underwent a new F-FCH PET-CT scan, displaying an almost complete regularization of the FCH uptake in all the previously involved regions. The patient was not treated after the first PET-CT scan, thus, the aforementioned PET/CT findings represented inflammatory vaccine-related lymph nodes. This case highlights the significance of knowing vaccination history to correctly interpret imaging findings and to avoid false-positive reports.

Introduction

World-wide healthcare systems have been profoundly affected by the COVID-19 virus pandemic, and in Italy a national mass vaccination using the Pfizer BNT162b2 mRNA vaccine initiated in December 2020, with early attempt to prioritize cancer patients. As soon as mass COVID-19 vaccination started worldwide, Vaccine-Associated Hypermetabolic Lymphadenopathy (VAHL) began to be noticed as a possible side effect [1].

Several authors reported cancer patients with 18-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) evidence of metabolically active axillary lymphnodes after COVID-19 vaccination. In all cases reported, in the clinical context of cancer history lymph node enlargement and metabolic uptake generate a diagnostic dilemma and might lead to further unnecessary examinations [2], [3], [4], [5].

Benign lymphadenopathy in the vaccine injection site nearest regions is considered a very common consequence, not only after COVID vaccination; it is also reported as an effect of H1N1 and human papillomaviruses vaccines [6,7]. Hypermetabolic lymphadenopathy is usually identified as an increased lymph nodes uptake on PET-CT occurring not only in cancer-related situations but also during an occurring inflammatory process [8].

Case report

A 62-year-old male, diagnosed with prostate cancer (Gleason 9) in 2019, with lymph nodes and bone metastasis, was initially treated with hormone-therapy and radiotherapy of the prostate (80 Gy) and pelvic lymph nodes (45 Gy), and thereafter started a regular follow-up, without evidence of recurrence for 2 years. Subsequently, the patient underwent a new follow-up F-FCH PET-CT, less than 3 weeks after he had received the second dose of the Pfizer BioNTech-BNT162b2 mRNA COVID-19 vaccine with an intramuscular left deltoid injection.

The PET-CT showed a slight F-FCH uptake and enlargement of the left axillary lymph nodes (Fig. 1), findings already reported by other authors following COVID-19 vaccine [16].

Fig. 1

June 2021. PET-CT axial images showing a slight F-FCH uptake and an enlargement of the left axillary (A), hilar bilateral (B) and subcarinal (C) lymph nodes. (D) Coronal PET-CT reconstruction better displaying the findings.

At the same time, the scan also revealed an increased F-FCH uptake in paratracheal, para-aortic, subcarinal, and hilar bilateral lymph nodes. This outcome was unexpected, considering the clinical history of the patient, without evidence of pulmonary disease.

There was no evidence of increase in the PSA levels (1.17 ng/mL) and the comparison of the imaging findings with the staging CT scan performed 2 years earlier (Fig. 2), revealed the morphological stability of lymph nodes.

Fig. 2

September 2019. Axial portal-phase CT scan, revealing the dimensional stability of the right hilar lymph node.

Thus, considering dimensional stability of lymph nodes and serum PSA level steadiness, no therapies were prescribed, and, 14 weeks later (Fig. 3), the patient underwent a new F-FCH PET-CT scan, displaying an important decrease of the FCH uptake in all the previously involved regions, proving that the hypermetabolic lymphadenopathy was a side effect of the COVID-19 vaccine, not associated with his oncological disease.

Fig. 3

September 2021. PET-CT axial images revealing a significant reduction of the F-FCH uptake in left axillary (A), hilar (B) and subcarinal (C) lymph nodes. (D) Coronal PET-CT reconstruction better displaying the findings. Compare findings with figure 1.

Discussion

It is established that vaccine administration leads to a local inflammatory response in a certain number of cases, involving injection site muscles and the lymphnodes afferent to the injection site. Therefore, this is responsible of the increased 18FDG uptake of axillary lymphnodes on the PET-CT [9].

As different studies show, this condition can be challenging when occurring in oncological patients: it is hard to define whether the lymphnodes uptake is due to a cancer recurrence or not [10,11], particularly when considering fluorine-18 choline (F-FCH) PET-CT increased uptake.

More recently, the association between choline phospholipid metabolism and macrophage immune responsiveness has been recognized and it is due to the increase of the choline transporter-like protein-1 (CTL1) which allows the uptake of choline in activated macrophages that populate the pneumonia-affected lungs [12]. 18F-Fluorocholine is a synthetic analog of the natural choline, and this may help understanding the evidence of COVID-19-induced lung lesions with an amplified uptake of 18F-fluorodeoxyglucose [13,14] and 18F-fluorocholine [15,16] but there are no reports of F-FCH increased uptake after COVID-19 vaccination.

To our knowledge this is one case of vaccine-associated hypermetabolic lymphadenopathy involving lymph nodes that are located far away from the injection site, especially mediastinal and pulmonary hilar locations, which can create a diagnostic challenge in patients with hitory of prostate cancer. This case highlights the significance of knowing vaccination history to correctly interpret the findings and to avoid false-positive reports.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.