Dermatology: Practical and Conceptual Letter to the Editor | Dermatol Pract Concept. 2022;12(4):e2022171 1 Lymphadenopathy After COVID-19 Vaccine Mimicking Lymph-Node Progression in a Patient With Metastatic Melanoma Julia Verdaguer-Faja1, José Luis Manzano2, Sofía España2, Paula Cecilia Notta3, Raul Vicente Rodriguez Iniesta4, Aram Boada1,5 1 Dermatology Department. Hospital Universitari Germans Trias i Pujol. Universitat Autònoma de Barcelona. Badalona, Barcelona, España. 2 Medical Oncology Department. Hospital Universitari Germans Trias i Pujol. Universitat Autònoma de Barcelona. Badalona, Barcelona, España. 3 Nuclear Medicine-PET Department. Hospital Universitari de Bellvitge. Universitat de Barcelona. Hospitalet de Llobregat, Barcelona, España. 4 Radiology Department. Hospital Universitari Germans Trias i Pujol. Universitat Autònoma de Barcelona. Badalona, Barcelona, España. 5 Institut Investigació Germans Trias i Pujol (IGTP). Badalona, Barcelona, España. Citation: Verdaguer Faja J, Manzano JL, España S, Notta PC, Rodriguez Iniesta RV, Boada A. Lymphadenopathy After COVID-19 Vaccine Mimicking Lymph Node Progression in a Patient With Metastatic Melanoma. Dermatol Pract Concept. 2022;12(4):e2022171. DOI: https://doi.org/10.5826/dpc.1204a171 Accepted: February 19, 2022; Published: October 2022 Copyright: ©2022 Verdaguer Faja et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Julia Verdaguer Faja, MD, Dermatology Department. Hospital Universitari Germans Trias I Pujol. Carretera de Canyet s/n. 08916. Badalona (Barcelona), Spain. Phone: 0034934978813, E-mail: verdaguer.ju@gmail.com Introduction COVID-19 vaccination has been rapidly implemented worldwide, especially among patients with cancer. Local reactions with ipsilateral lymphadenopathy are among the most common side effects. A few cases of false- positive 18-fluorodeoxyglucose (18FDG) PET/computed tomog- raphy (CT) scan after COVID-19 vaccination have been reported [1,2]. This is especially important in oncologic patients, such as in cutaneous melanoma, where these findings might pose difficulties during their follow-up and management. Case presentation A 47-year-old male with BRAF mutant melanoma of the back and right axillar adenopathies underwent wide ex- cision and lymphadenectomy and started adjuvant treat- ment with nivolumab. One month later, he presented disease relapse with satellitosis and a contralateral ade- nopathy in the left axilla, the latter detected by PET-CT. Treatment was changed to targeted therapy (dabrafenib and trametinib), reaching complete remission. An FDG- PET/CT from February 2021 showed no active disease. In May 2021, after eight months of targeted therapy, a 2 Letter to the Editor | Dermatol Pract Concept. 2022;12(4):e2022171 routine FDG-PET/CT showed substantial 18F-FDG avidity in the left axilla, with multiple malignant-appearing lymph nodes; no other foci were identified (Figure 1A). Given this finding, up to two ultrasound-guided biopsies were performed on the left axilla, describing at least one clearly malignant-appearing adenopathy in the ultrasound exam- ination (Figure 1, B and C), and showing histologically lymphoid hyperplasia with no evidence of microscopic disease. Further questioning of the patient revealed that he had received the second dose of the COVID-19 mRNA vaccine (Moderna) in the left deltoid muscle 5 days prior to the routine PET/CT scan. Finally, a new PET/CT was performed 4 months later and revealed complete resolu- tion of the hypermetabolic left axillary nodes (Figure 2), suggesting the diagnosis of reactive lymphadenopathy due to COVID-19 vaccine. Figure 1. Imaging tests performed in May 2021. (A-D) Routine ¹⁸F-FDG-PET/TC: hypermetabolic lymphadenopathy in the left axillary re- gion, the largest and with most metabolism of 13 mm (SUVmax: 3.9), suggestive of malignancy. (E) Sonographic exam of the left axilla after PET/CT findings: left axillary lymphadenopathy of rounded morphology with displacement of the central fatty hilum at the expense of great hypoechoic cortical thickening, sonographically suspicious. Core needle biopsy was taken from it. Figure 2. (A-D) 4-month control 18F-FDG-PET/TC, September 2021: normalization of hypermetabolic lymphadenopathies in the left axillary region: resolution of the pathologic nodal uptake. Letter to the Editor | Dermatol Pract Concept. 2022;12(4):e2022171 3 Discussion Transient FDG uptake in normal or enlarged lymph nodes (mainly axillary, supraclavicular and cervical nodes) has already been described after administration of several types of vaccines [3,4]. This issue has also been observed now with the COVID-19 vaccination [1,2], being more frequently seen in pa- tients vaccinated with Moderna, compared to Pfizer-BioNTech (72% versus 43%), and more intensely after the booster administration. Furthermore, it has been most frequently seen on day 1–7 after vaccination (71% of patients) and showed a negative correlation with time after vaccination [2]. This FDG avid axillary lymphadenopathy may confound interpretation in oncologic patients and change patient man- agement (eg excessive follow-up imaging studies, unneces- sary biopsies, treatment delays), besides causing additional patient anxiety [2]. This is the case of cutaneous melanoma, where misinterpretation in tumor staging or disease response during treatment may lead to deeply important differences in terms of disease prognosis and treatment algorithm. In order to avoid misinterpretation, it is therefore im- portant in oncologic patients to perform vaccination contra- lateral to the tumor expected nodal drainage, to ask patients about recent vaccination, and to perform FDG PET/CT be- fore or at least 2 weeks after (optimally 4–6 weeks after) vaccine administration, if possible [2,4,5]. Conclusions As COVID-19 vaccination has been rapidly implemented worldwide, clinicians should be aware of the transient appearance of hypermetabolic regional lymph nodes after its injection. Keeping this etiology in mind and following some recommendations for scheduling the PET-CT is espe- cially important when evaluating oncologic patients to avoid misinterpretation. References 1. Cohen D, Krauthammer SH, Wolf I, Even-Sapir E. 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