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. 2022 Jul 3;36(4):1977–1981. doi: 10.21873/invivo.12921

Axillary Lymph Node Swelling After COVID-19 Booster Vaccination: Japanese Case Report and Literature Review

NOBUYASU YOSHIMOTO 1,2, AKEMI YANAGI 3, SATORU TAKAYAMA 4, MASAKI SAKAMOTO 4, KEISUKE TOMODA 4, KEN ISHIKAWA 4, AKIFUMI KAWATE 4, SHORYU TAKAYAMA 4, MASAKATSU YAMASHITA 4, SHINYA YAMAMOTO 4, KIOTO YOKOYAMA 4, HIROTO SUZUKI 4, HISANORI KANI 4
PMCID: PMC9301409  PMID: 35738594

Abstract

Background/Aim: COVID-19 has been a global pandemic for more than 2 years, and vaccination against COVID-19 using an mRNA vaccine is widespread. The COVID-19 vaccination can cause specific side-effects, such as axillary lymph node swelling; therefore, breast oncologists should pay attention to such occurrences. Initially, only two COVID-19 vaccinations were planned; however, in some countries third or fourth vaccines have been administered. Here, we present a female case who developed axillary lymph node swelling after her third vaccination. We have also reviewed the literature regarding this side-effect after a third or fourth COVID-19 vaccination.

Case Report: A 64-year-old woman who came to our clinic regarding a mammography abnormality in her left breast. She had no palpable mass, but a left breast mass was shown by mammography, and ultrasonography and magnetic resonance imaging indicated a hamartoma. At 2 months after her second COVID-19 vaccination when she underwent these tests, she had no axillary lymph node swelling. We planned a follow-up after 6 months. At her next visit, by chance, she underwent ultrasonography 14 days after she received a third COVID-19 vaccination, and a swollen axillary lymph node was observed.

Conclusion: Axillary lymph node swelling can occur after a third COVID-19 vaccination. Therefore, breast oncologists will have to consider this side-effect of COVID-19 vaccination when diagnosing breast tumors.

Keywords: COVID-19 booster vaccine, axillary lymph node swelling, side-effect

Pneumonia caused by the novel coronavirus, called Coronavirus Disease 2019 (COVID-19), was first reported in Wuhan, China in December 2019 (1). Two years later and the pandemic has become global. During this pandemic, COVID-19 vaccines, such as the BNT162b2 vaccine (Pfizer) (2) and mRNA-1273 vaccine (Moderna) (3), have been developed rapidly, and in many countries, including Japan, vaccination with these vaccines has been performed. BNT162b2 and mRNA-1273 are mRNA vaccines and this is the first time this type of vaccine has been used in a clinical setting.

When these vaccinations were started, clinical trials of BNT162b2 and mRNA-1273 (2,3) were designed to administer two doses. However, this pandemic has continued for 2 years, and therefore booster vaccinations have been required to prevent COVID-19 infection because antibody levels to the virus decrease within several months. In Japan, the third vaccination started in December 2021 (4). Currently, a third vaccination is indicated for those who received a second vaccination more than 6 months previously, and further vaccination might be needed. Indeed, Japan is planning to administer a fourth COVID-19 vaccination (5).

These vaccines have characteristic side-effects including fever, general fatigue, injection-site pain, and swelling (2). In addition, local lymph node swelling can also occur after these vaccinations (3). In cases of axillary lymph node swelling, breast oncologists should consider whether these swellings are metastases of breast cancer or a side-effect of the vaccine. Here, we present a case with axillary lymph node swelling, observed by ultrasonography (US), which was thought to be related to a third COVID-19 vaccination. We also present a literature review of studies of cases receiving a third or fourth COVID-19 vaccination.

Case Report

A 64-year-old woman came to our breast surgery clinic after a screening mammography abnormality in July 2021. She had undergone resection of an ascending colon carcinoma 6 years previously, partial liver resection due to metastatic colon cancer 3 years previously, and partial resection of the right lung assisted with a thoracoscope due to metastatic colon cancer 2 years previously. There was no palpable abnormality in either breast or axilla. A mass, which seemed to be a hamartoma, was present in her left upper area on mammography (Figure 1); a mass was present in the left superolateral quadrant, which also seemed to be a hamartoma on US (Figure 2). We also performed magnetic resonance imaging (Figure 3), which was also compatible with a hamartoma. Both US and magnetic resonance imaging indicated no swollen axillary lymph nodes. These imaging studies had been performed 2 months after the second COVID-19 vaccination with Pfizer BNT162b2 in her left arm. We decided to continue follow-up without aspiration biopsy cytology. At the 6-month follow up, no palpable abnormality was observed, and almost the same left breast mass as before was present. In addition, an axillary lymph node with a thickened cortex was observed on US (Figure 4). This was 14 days after her third COVID-19 vaccination in her left arm. It was thought that the swelling was related to the third COVID-19 vaccination. We decided to follow-up 3 months later. In May 2022, she came to our clinic and underwent US again; and she had no swelling of the axillary lymph node was found.

Figure 1. Mammography in July 2021, showing a round, circumscribed mass in the upper left breast in mediolateral oblique (MLO) (A) and ipsilateral craniocaudal (CC) (B) views.

Figure 1

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Figure 2. Ultrasonography in August 2021, 2 months, and 2 weeks after the second COVID-19 vaccination. A mass in the left superolateral quadrant (suspected hamartoma) is shown and there were no swollen lymph nodes in the axilla.

Figure 2

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Figure 3. Magnetic resonance imaging in August 2021, 2 months, and 3 weeks after a second COVID-19 vaccination. There were no swollen lymph nodes in the axilla.

Figure 3

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Figure 4. Ultrasonography in February 2022, 14 days after the third COVID-19 vaccination. A lymph node with a thick cortex in the patient’s left axilla is shown.

Figure 4

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Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. This was a case report and therefore we did not require additional permission from our review board.

Discussion

When BNT162b2 and mRNA-1273 were developed, they were designed for two vaccinations. Davit et al. reported the need for an additional vaccination for immunocompromised individuals and seniors in Israel (6). Werbel et al. reported the efficacy of increased antibody levels by the third vaccination in solid-organ transplant recipients (7). Albach et al. reported a case with higher antibody levels achieved by a third vaccination with immunosuppressive medication for rheumatoid arthritis (8). Therefore, it was reported that insufficient efficacy was achieved after two doses of the vaccines for particular immunological cases, such as those with specific immunological conditions.

Because the COVID-19 pandemic remains globally, a third vaccination for the general public was discussed. Flaxman et al. reported that in 18- to 55-year-olds, antibody levels increased after a third vaccination (9). Bar-On et al. reported the efficacy of a third vaccination to protect people aged ≥60 years against COVID-19 (10). Spitzer et al. reported the efficacy of a third vaccination in people aged ≥18 years (11). A third vaccination has become popular, and similar to other countries, a third vaccination was offered in December 2021 in Japan.

There are some reports about two dose COVID-19 vaccine-induced axillary lymph node swelling (12-14). Raj et al. reported this side-effect on screening mammography (15), and Romeo et al. reported it in a prospective study (16). However, there have been few reports about the side-effects of a third COVID-19 vaccination. Dicks et al. reported a rare case of leukocytoclastic vasculitis after a third BNT162b2 COVID-19 vaccination (17). Aviram et al. reported four cases of myocarditis after a third dose of the BNT162b2 COVID-19 vaccine (18). David et al. reported side-effects caused by a third BNT162b2 vaccination in a relatively large cohort, and these included fatigue, myalgia, fever, and lymphadenopathy, similar to that reported after the second vaccination (6). In our case, axillary lymph node swelling was observed 14 days after the third COVID-19 vaccination. Therefore, axillary lymph node swelling might be induced after the first, second, or third COVID-19 vaccination. In our case, although there seemed to be no axillary lymph node swelling after the second vaccination (imaging was conducted 2 months after the second vaccination), swelling was observed after the third. We previously reported axillary lymph node swelling as a side-effect of the first or second COVID-19 vaccination (19); therefore, this side-effect observed after the third vaccination can be considered similar to that after the first or second COVID-19 vaccinations.

Axillary lymph node swelling as a side-effect of COVID-19 vaccination can influence breast cancer screening. The Japan Association of Breast Cancer Screening presented guidelines on the effects of COVID-19 on breast cancer screening (20). It suggested that breast cancer screening should be conducted before vaccination or 6-10 weeks after the second COVID-19 vaccination in case reactive axillary lymph node swelling occurs.

A major limitation of this report was that only one case was presented, and some of the image analyses were conducted 2 months after the second vaccination. Axillary lymph node swelling due to COVID-19 vaccination might occur after the first or second vaccination, or after the third vaccination. Therefore, further case studies are needed.

Conclusion

Axillary lymph node status is very important in breast oncology. It was thought that after two doses of COVID-19 vaccination were administered, axillary lymph node swelling would have reduced some months after the second vaccination. However, under the present situation, third and possibly fourth vaccinations might be required. Therefore, breast oncologists should continue to be aware of axillary lymph node swelling related to COVID-19 vaccinations when diagnosing a breast tumor. Further research on the side-effects of COVID-19 vaccinations, especially axillary lymph node swelling, is required.

Conflicts of Interest

The Authors report no conflicts of interest in relation to this study.

Author’s Contributions

Research design: N. Yoshimoto; collection and analysis of data: N. Yoshimoto and A Yanagi; all Authors contributed to reviewing the article. All Authors approved the final article.

Acknowledgements

The Authors express their appreciation to Ms. Haruna Hashio for her preparation of the reference papers.

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