Reactive lymphadenopathy due to Pfizer-BioNTech COVID-19 vaccine: a case report / Linfadenopatía reactiva por vacuna Pfizer-BioNTech para COVID-19: reporte de un caso

Uno de los efectos secundarios encontrados en pacientes con antecedente de vacunación por COVID-19, especialmente con la vacuna Pfizer-BioNTech, es la aparición de múltiples adenopatías hiperplásicas, principalmente en los ganglios linfáticos axilares, supraclaviculares e infraclaviculares ipsilaterales al sitio de vacunación. Presentamos el caso de una paciente femenina de 33 años, con aparición de masa dolorosa supraclavicular izquierda, quien una semana antes había sido vacunada con la primera dosis de la vacuna Pfizer-BioNTech en región deltoidea izquierda. Los hallazgos citológicos fueron sugestivos de una enfermedad linfoproliferativa, y el estudio histopatológico reveló linfadenopatía reactiva con proliferación de inmunoblastos B activados, secundaria a la vacunación contra COVID-19. Aportamos a la literatura con la caracterización de los hallazgos histopatológicos de la linfadenopatía posvacunación contra COVID-19. Es importante que los médicos tratantes y radiólogos estén familiarizados con este diagnóstico diferencial, para brindar recomendaciones adecuadas basadas en un seguimiento a corto plazo, en lugar de realizar biopsias, intervenciones y conductas inmediatas innecesarias en el manejo de los pacientes

One of the side effects found in patients with a history of vaccination for COVID-19, especially with the Pfizer-BioNTech vaccine, is the appearance of multiple hyperplastic adenopathies, mainly axillary, supraclavicular and infraclavicular lymph nodes ipsilateral to the vaccination site. We present the case of a 33-year-old female patient, with the appearance of a painful left supraclavicular mass, who was vaccinated a week earlier with the first dose of the Pfizer-BioNTech vaccine in the left deltoid region. The cytological findings were suggestive of a lymphoproliferative disease, and the histopathological study revealed reactive lymphadenopathy with proliferation of activated B immunoblasts, secondary to vaccination against COVID-19. We contribute to the literature with the characterization of the histopathological findings of COVID-19 post-vaccination lymphadenopathy. It is important for treating physicians and radiologists to be familiar with this differential diagnosis, in order to provide appropriate recommendations based on short-term follow-up, instead of performing unnecessary immediate biopsies or interventions in patient management.

COVID-19 vaccine-induced lymphadenopathies: incidence, course and imaging features from an ultrasound prospective study.

AIMS: lymphadenopathy can occur after COVID-19 vaccination and when encountered at ultrasound examinations performed for other reasons might pose a diagnostic challenge. Purpose of the study was to evaluate the incidence, course and ultrasound imaging features of vaccine-induced lymphadenopathy. METHODS: 89 healthy volunteers (median age 30, 76 females) were prospectively enrolled. Vaccine-related clinical side effects (e.g., fever, fatigue, palpable or painful lymphadenopathy) were recorded. Participants underwent bilateral axillary, supraclavicular and cervical lymph node stations ultrasound 1-4 weeks after the second dose and then again after 4-12 weeks in those who showed lymphadenopathy at the first ultrasound. B-mode, color-Doppler assessment, and shear-wave elastography (SWE) evaluation were performed. The correlation between lymphadenopathy and vaccine-related side effects was assessed using the Fisher's exact test. RESULTS: Post-vaccine lymphadenopathy were found in 69/89 (78%) participants (37 single and 32 multiple lymphadenopathy). Among them, 60 presented vaccine-related side effects, but no statistically significant difference was observed between post-vaccine side effect and lymphadenopathy. Ultrasound features of vaccine-related lymphadenopathy consisted of absence of fatty hilum, round shape and diffuse or asymmetric cortical thickness (median cortical thickness of 5 mm). Vascular signal was mainly found to be increased, localized in both central and peripheral regions. SWE showed a soft cortical consistence in all cases (median value 11 Kpa). At follow-up, lymph-node morphology was completely restored in most cases (54/69, 78%) and in no case lymphadenopathy had worsened. CONCLUSION: A high incidence of vaccine-induced lymphadenopathy was found in a population of healthy subjects, with nearly complete regression within 4-12 weeks.

Frequency of Ipsilateral Axillary Lymphadenopathy After the Inactivated COVID-19 Vaccine.

OBJECTIVE: During COVID-19 vaccine development studies, vaccines' efficacy and safety profiles should be carefully investigated. Only a few studies have shown that the COVID-19 vaccine can cause axillary lymphadenopathy on the injection arm. This study aimed to investigate the incidence of axillary lymphadenopathy and imaging findings using B-mode and Doppler ultrasonography (US) examinations in volunteers who had recently been vaccinated against COVID-19. METHODS: The ipsilateral and contralateral axillae of 101 volunteers who received the COVID-19 vaccine were evaluated using B-mode and Doppler US examinations. The volunteers were asked when and to which arm the vaccine had been applied, and the type and dose of the vaccine were recorded. It was also questioned whether the individual experienced any side effects after vaccination, such as pain, tenderness, fever, and redness at the injection site. In addition, the demographic data of the participants, such as age and gender, were recorded. RESULTS: The B-mode US examinations revealed that the long- and short-axis diameters, size, cortical thickness, and asymmetric cortical thickening of the left axillary lymph nodes were significantly higher compared to the right side in individuals having received the CoronaVac vaccine (p<0.05). When the individuals were evaluated separately according to gender, the frequency of cortical thickness and asymmetric cortical thickening in the left axillary lymph nodes was higher than on the right side in both males and females (p=0.011). CONCLUSION: It should be kept in mind that ipsilateral reactive lymphadenopathy may develop after the COVID-19 vaccine. This knowledge can prevent unnecessary axillary lymph node biopsies.

Regional lymphadenopathy following COVID-19 vaccination: Literature review and considerations for patient management in breast cancer care.

PURPOSE: Over 1 billion doses of COVID-19 vaccines have been already administered across the United States, the United Kingdom and the European Union at the time of writing. Furthermore, 1.82 million booster doses have been administered in the US since 13th August, and similar booster programmes are currently planned or under consideration in the UK and the EU beginning in the autumn of 2021. Early reports showed an association between vaccine administration and the development of ipsilateral axillary and supraclavicular lymphadenopathy, which could interfere with the diagnosis, treatment and follow-up of breast cancer patients. In this paper, we review the available evidence on vaccine-related lymphadenopathy, and we discuss the clinical implications of the same on breast cancer diagnosis and management. METHODS: A literature search was performed - PubMed, Ovid Medline, Scopus, CINHAL, Springer Nature, ScienceDirect, Academic Search Premier and the Directory of Open Access Journals were searched for articles reporting on regional palpable or image-detected lymphadenopathy following COVID-19 vaccination. Separately, we compiled a series of case studies from the University Hospitals of Derby and Burton, United Kingdom and the Mayo Clinic in Minnesota, United States of America, to illustrate the impact that regional lymphadenopathy post-COVID-19 vaccination can have on the diagnosis and management of patients being seen in diagnostic and therapeutic breast clinics. RESULTS: From the literature search, 15 studies met the inclusion criteria (n = 2057 patients, 737 with lymphadenopathy). The incidence of lymphadenopathy ranged between 14.5% and 53% and persisted for >6 weeks in 29% of patients. CONCLUSIONS: Clinicians managing breast cancer patients should be aware that the COVID-19 vaccination may result in regional lymphadenopathy in a significant number of patients, which can result in unnecessary investigations, treatment and increased patient anxiety. An accurate COVID-19 vaccination history should be collected from all patients where regional lymphadenopathy is a clinical and/or an imaging finding and then combined with clinical judgement when managing individual cases.

Limiting Screening Mammography Recalls for Vaccine-Induced Adenopathy, a Single Institution Experience.

RATIONALE AND OBJECTIVES: Reported incidence of vaccine-induced adenopathy varies widely, with higher estimates in early reports and small series. Objective was to evaluate a large sample of vaccinated patients undergoing screening mammography, to determine callback rates associated with vaccine-induced adenopathy and their outcomes. MATERIALS AND METHODS: Single-institution retrospective review of patients who received at least 1 dose of a COVID-19 vaccine prior to presentation for screening mammography from January 15 through May 31, 2021. Patient-related vaccination information (dose, brand, arm, date) was obtained by mammography technologists and available for interpreting radiologists. Patients recalled for axillary adenopathy were included; other causes for recall were excluded. Follow-up imaging and outcomes were tracked. Wilcoxon rank-sum test, Fisher exact test, multivariable logistic regression modeling, and receiver operating characteristic curve analyses were utilized. All tests were two-sided; p < 0.05 considered statistically significant. RESULTS: Total of 2304 vaccinated patients underwent screening mammography; 24 (1.0%) recalled for ipsilateral adenopathy. There was no significant difference in presence of adenopathy associated with patient age, dose, or brand of vaccine. Presence of adenopathy significantly decreased as days from vaccination increased (p < 0.001). Receiver operating characteristic curve suggested 28.5 days as the best cutoff point to distinguish presence or absence of adenopathy on mammogram. Of 24 callbacks, 13 (54.2%) had benign results, 2 (8.3%) are still undergoing surveillance, and 9 (37.5%) are overdue for subsequent follow-ups. No cases resulted in biopsy or malignancy. CONCLUSION: Low recall rates related to vaccine-induced adenopathy are achievable and can limit unnecessary workups, improve access, and promote flexible timing of vaccinations and screening exams.

COVID-19 Vaccine-Related Axillary Adenopathy on Breast Imaging: Follow-Up Recommendations and Histopathologic Findings.

This study describes 94 patients who presented with suspected COVID-19 vaccine-related axillary adenopathy on breast imaging. All biopsies recommended within 12 weeks of the second vaccine dose were benign. Among women not recommended for biopsy, the median interval between the second vaccine dose and ultrasound follow-up was 15.9 weeks. Three biopsies yielding malignant diagnoses were recommended 12.0-13.1 weeks after the second vaccine dose. Lengthening imaging follow-up to 12-16 weeks after the second dose may reduce unnecessary biopsy recommendations.

Cervical lymphadenopathy following coronavirus disease 2019 vaccine: clinical characteristics and implications for head and neck cancer services.

OBJECTIVE: Patients with coronavirus disease vaccine associated lymphadenopathy are increasingly being referred to healthcare services. This work is the first to report on the incidence, clinical course and imaging features of coronavirus disease vaccine associated cervical lymphadenopathy, with special emphasis on the implications for head and neck cancer services. METHODS: This was a retrospective cohort study of all patients referred to our head and neck cancer clinics between 16 December 2020 and 12 March 2021. The main outcomes measured were the proportion of patients with vaccine-associated cervical lymphadenopathy, and the clinical and imaging characteristics. RESULTS: The incidence of vaccine-associated cervical lymphadenopathy referrals was 14.8 per cent (n = 13). Five patients (38.5 per cent) had abnormal-looking enlarged and rounded nodes with increased vascularity. Only seven patients (53.9 per cent) reported full resolution within an average of 3.1 ± 2.3 weeks. CONCLUSION: Coronavirus disease vaccine associated cervical lymphadenopathy can mimic malignant lymphadenopathy and therefore might prove challenging to diagnose and manage correctly. Healthcare services may encounter a significant increase in referrals.

COVID-19 Vaccine-Associated Subclinical Axillary Lymphadenopathy on Screening Mammogram.

BACKGROUND: Women who received a COVID-19 vaccination may display subclinical unilateral axillary lymphadenopathy on screening mammography, which can appear suspicious for malignancy, leading to additional diagnostic evaluation. PURPOSE: To evaluate the prevalence of subclinical unilateral axillary lymphadenopathy (sLAD) on screening mammogram in women who received either the first or second dose of the Pfizer-BioNTech (Pfizer) or Moderna COVID-19 vaccines compared to women who have not. MATERIALS AND METHODS: In this IRB-approved, HIPAA complaint study from 12/14/2020 to 4/14/2021, 1027 patients presented for screening mammography and met study inclusion criteria. Patients with history of baseline lymphadenopathy or prior cancer diagnosis were excluded. RESULTS: Of the 1027 women, 43 were recalled for unilateral sLAD. 34 women received a COVID-19 vaccination ipsilateral to the sLAD (Pfizer n=19, 44.2%; Moderna n=15, 34.9%), 9 did not (20.9%). Incidence of unilateral axillary sLAD was significantly higher (p-value<0.01) in those who received a COVID-19 vaccination within approximately 7 weeks preceding screening mammogram. 13.2% of patients who received the Pfizer vaccine and 9.5% of patients who received the Moderna vaccine developed sLAD. Moderna's vaccine elicited a more robust reaction in the elderly (Moderna 63.7 years vs. Pfizer 59.7 years). For both vaccines, sLAD resolved on average 46.5 days after the last COVID-19 vaccine (p=0.44). CONCLUSION: Women who have received either mRNA COVID-19 vaccines may benefit from scheduling their screening mammogram before vaccination or consider delaying screening mammography 8 weeks. While Pfizer may have an overall more robust immune response, Moderna may elicit a stronger immune response in elderly women. SUMMARY: Women who received a COVID-19 vaccination before screening mammography were significantly more likely to present with subclinical axillary lymphadenopathy than women who did not receive the vaccine. KEY RESULTS: 13.2% of women who received a Pfizer-BioNTech vaccine exhibited subclinical axillary lymphadenopathy compared to 9.5% of those who received the Moderna vaccine. Only 1.2 % of those who did not receive a vaccine presented with subclinical unilateral axillary lymphadenopathy. The average time of resolution of the lymphadenopathy on diagnostic mammogram was 46.5 days overall, with Pfizer-BioNTech taking 50.7 days and Moderna 41.5 days.

COVID-19 vaccine-related axillary lymphadenopathy in breast cancer patients: Case series with a review of literature.

PURPOSE: Lymphadenopathy (LAP) after COVID-19 vaccination in patients with a diagnosis of cancer has been challenging. We analyzed imaging and clinical features from early cases of axillary LAP in six COVID-19 vaccine recipients with a history of breast cancer. METHOD: Among the patients with a history of breast cancer and recent COVID-19 vaccine administration, six patients who showed isolated axillary LAP were gathered. Radiologic features were reviewed from breast ultrasound, chest computed tomography, and breast magnetic resonance imaging. Clinical and pathological information were obtained for analysis. RESULTS: The interval between ultrasound detection of LAP and last COVID-19 vaccine administration ranged from 14 to 28 days (mean 21.67 days). Round shape of the lymph node and irregular cortex were noted in 2 and 0 cases, respectively. Mean maximum cortical thickness, length to width ratio and interval aggravation in maximum cortical thickening were 4.2 mm, 1.34, and 2.81-fold with cut-off value of 3 mm, 1.5, 2.0-fold, respectively. CONCLUSION: We observed axillary LAP ipsilateral to a recent vaccine administration persisting longer than what the Centers for Disease Control and Prevention announced. In our patients, COVID-19 vaccine-related LAP tended to show increased cortical thickness without cortical irregularity. Oncologist as well as radiologist should be familiar with the fact that COVID-19 vaccines, regardless of vaccine type or dosage, can frequently cause ipsilateral axillary LAP, showing some suspicious features more often than others, and can persist longer than anticipated so that both over- and underdiagnosis can be avoided. We report our observations in six patients and provide an exhaustive review of the published literature.

Coronavirus disease 2019 vaccine mimics lymph node metastases in patients undergoing skin cancer follow-up: A monocentre study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has changed the lives of people around the world. Fortunately, sufficient vaccines are now available. Local reactions with ipsilateral lymphadenopathy are among the most common side effects. We investigated the impact of lymphadenopathy after COVID-19 vaccination on the value of ultrasound in tumour patients. PATIENTS AND METHODS: Patients with melanoma or Merkel cell carcinoma were included who underwent lymph node excision and received COVID-19 vaccination within 6 weeks before surgery. The consistency of the preoperative ultrasound findings with the histopathologic findings was investigated. RESULTS: Eight patients were included (two Merkel cell carcinoma and six melanoma patients) who underwent lymph node excision between 16th April 2021 and 19th May 2021 and had previously received COVID-19 vaccination. In three of the eight patients (one Merkel cell carcinoma and two melanoma patients), lymph node metastases were erroneously diagnosed preoperatively during tumour follow-up with physical examination, ultrasound, and or fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT). In these three patients, the suspected lymph node metastases were located in the left axilla after COVID-19 vaccination in the left upper arm, which resulted in selective lymph node removal in two patients and complete lymphadenectomy in one patient. CONCLUSION: COVID-19 vaccine-associated lymphadenopathy is expected to be observed much more frequently in the near future because of increasing vaccination rates. This cause of lymphadenopathy, which may in ultrasound as well as in FDG PET/CT resemble lymph node metastases, must be considered, especially in oncologic patients undergoing tumour follow-up. In addition, COVID-19 vaccination should be given as far away as possible from an underlying primary on the contralateral side to avoid oncologic misdiagnosis followed by malpractice.

Coordination and optimization of FDG PET/CT and COVID-19 vaccination; Lessons learned in the early stages of mass vaccination.

As the world embarks on mass vaccination for COVID-19, we are beginning to encounter unintended dilemmas in imaging oncology patients; particularly with regards to FDG PET/CT. In some cases, vaccine-related lymphadenopathy and FDG uptake on PET/CT can mimic cancer and lead to confounding imaging results. These cases where findings overlap with cancer pose a significant dilemma for diagnostic purposes, follow-up, and management leading to possible treatment delays, unnecessary repeat imaging and sampling, and patient anxiety. These cases can largely be avoided by optimal coordination between vaccination and planned imaging as well as preemptive selection of vaccine administration site. This coordination hinges on patient, oncologist, and radiologists' awareness of this issue and collaboration. Through close communication and patient education, we believe this will eliminate significant challenges for our oncology patients as we strive to end this pandemic.

COVID-19 Vaccination Induced Lymphadenopathy in a Specialized Breast Imaging Clinic in Israel: Analysis of 163 cases.

INTRODUCTION: Following vaccination of Israeli population with Pfizer-BioNTech COVID-19 Vaccine, an unusual increase in axillary-lymphadenopathy was noted. This study assesses the rate and magnitude of this trend from breast-imaging standpoint. MATERIALS AND METHODS: Participants undergoing breast-imaging, in whom isolated axillary-lymphadenopathy was detected were questioned regarding SARS-CoV-2 vaccine to the ipsilateral arm. Patients' and imaging characteristics were statistically compared. In order to perform a very short-term follow-up, twelve healthy vaccinated medical staff-members, underwent axillary-ultrasound shortly after the second dose, and follow-up. RESULTS: Axillary-lymphadenopathy attributed to vaccination was found in 163 women undergoing breast-imaging, including BRCA-carriers. During the study, number of detected lymphadenopathies increased by 394% (p = 0.00001) in comparison with previous 2 consecutive years. Mean cortical-thickness of abnormal lymph-nodes after second dose vaccination was 5 ± 2 mm. Longer lymph-node diameter after second vaccination was noted (from 15 ± 5 mm, to 18 ± 6 mm, p = 0.005). In the subgroup of medical staff members, following trends were observed: in patients with positive antibodies, lymph-node cortical-thickness was larger than patients with negative serology (p = 0.03); lymph-node cortical-thickness decreased in 4-5 weeks follow-up (p = 0.007). Lymphadenopathy was evident on mammography in only 49% of cases. DISCUSSION: Vaccine-associated lymphadenopathy is an important phenomenon with great impact on breast-imaging clinic workload. Results suggest the appearance of cortical thickening shortly after both doses. Positive serology is associated with increased lymph-node cortical-thickness. In asymptomatic vaccinated women with ipsilateral axillary-lymphadenopathy as the only abnormal finding, radiological follow-up is probably not indicated. BRCA-carriers, although at higher risk for breast-cancer, should probably receive the same management as average-risk patients.

Unilateral axillary adenopathy following COVID-19 vaccination: a multimodality pictorial illustration and review of current guidelines.

We present a multimodality pictorial review of axillary lymphadenopathy in patients recently vaccinated against COVID-19. As the mass vaccination programme continues to be rolled out worldwide in an effort to combat the pandemic, it is important that radiologists consider recent COVID-19 vaccination in the differential diagnosis of unilateral axillary lymphadenopathy and are aware of typical appearances across all imaging methods. We review current guidelines on the management of unilateral axillary lymphadenopathy in the context of recent COVID-19 vaccination.

Lymphadenopathy Following COVID-19 Vaccination: Imaging Findings Review.

RATIONALE AND OBJECTIVES: Despite all the benefits and effectiveness of the coronavirus disease 2019 (COVID-19) vaccines mentioned in recent clinical trials, some post-vaccination side effects such as lymphadenopathy (LAP) were observed. The present study reviewed all studies with imaging findings presentation of LAP after COVID-19 vaccination. MATERIALS AND METHODS: We conducted a literature search in online databases, including Scopus, Medline (PubMed), Web of Science, Embase (Elsevier), Cochrane library, and Google Scholar. RESULTS: A total of 19 studies (68 cases), including 60 (88.2%) females and eight (11.8%) males with a presentation of LAP after COVID-19 vaccination, were reviewed. LAP was identified after first or second dosages of three types of COVID-19 vaccines, including Pfizer-BioNTech (n = 30, 44.1%), Moderna (n = 17, 25%), and Oxford-AstraZeneca (n = 1, 1.5%). In 20 (29.4%) cases, vaccine type was not reported or only reported as mRNA COVID-19 vaccine. The median days of LAP presentation after the first and second dosages of COVID-19 vaccination, were 12 and 5 days, respectively. Most of the LAP imaging findings related to COVID-19 vaccination (n = 66, 97%) were seen from first day to 4 weeks after vaccination. However, LAP remained after 5 and 6 weeks of the first and second dosages of COVID-19 vaccination with decreased lymph nodes' size and residual cortical thickening in two cases. CONCLUSION: This review study of cases with LAP-associated COVID-19 vaccination guides radiologists and physicians to rely on patient's clinical context and updated resources to prevent potential disease upstaging and change in therapy.

DOTATATE -Avid Bilateral Axilla and Subpectoral Lymphadenopathy Induced From COVID-19 mRNA Vaccination Visualized on PET/CT.

ABSTRACT: A 64-year-old woman with malignant carcinoid tumor of the ileum received right ileocolectomy 9 years ago. Series follow-up imaging studies including most recent 68Ga-DOTATATE PET/CT scan in June 2020 have been negative for disease. Current 68Ga-DOTATATE PET/CT scan showed new cluster of bilateral axillary and subpectoral lymphadenopathy with normal CT morphology, but with avid DOTATATE uptake. There was no other abnormal DOTATATE-avid lesion or suspicious CT image findings. The medical history revealed that the patient received 2 doses of COVID-19 (coronavirus disease 2019) mRNA vaccine at bilateral upper arm deltoid muscles at 21 and 42 days prior to the PET/CT examination, respectively.

COVID-19 mRNA Vaccination-Induced Lymphadenopathy Mimics Lymphoma Progression on FDG PET/CT.

ABSTRACT: We present here a 72-year-old man with mantle cell lymphoma who has completed chemotherapy and achieved complete metabolic response to the therapy 10 months ago. Series follow-up FDG PET/CT scans have been negative for lymphoma. Current FDG PET/CT scan showed a new cluster of subcentimeter left axillary lymphadenopathy with avid FDG uptake. There was also focal FDG uptake in the left upper arm deltoid muscle and adjacent subcutaneous soft tissue, with no other abnormal FDG-avid lesion or suspicious CT image findings. The medical history revealed that the patient received COVID-19 mRNA vaccine 2 days before the FDG PET/CT examination.