Fine needle aspiration in COVID-19 vaccine-associated lymphadenopathy.

AIMS: With ongoing intensive vaccination programme against COVID-19, numerous cases of adverse reactions occur, some of which represent rare events. Enlargement of the injection site’s draining lymph nodes is increasingly reported, but is not yet widely recognised as being possibly associated with recent vaccination. As patients at risk of a severe course of COVID-19, indicated by their medical history such as a previous diagnosis of malignancy, receive priority vaccination, newly palpable lymph nodes raise concerns of disease progression. In this case series, we report on five patients who presented with enlarged lymph nodes after COVID-19 vaccination. METHODS: Sonography guided fine needle aspiration (FNA) was performed in five patients presenting with PET-positive and/or enlarged lymph nodes after COVID-19 vaccination with either the Pfizer-BioNTech or Moderna vaccine. RESULTS: COVID-19 vaccination had been carried out in all cases, with an interval of between 3 and 33 days prior to FNA. Three of five patients had a history of neoplasms. The vaccine was administered into the deltoid muscle, with subsequent enlargement of either the cervical, supra-, infra- or retroclavicular, or axillary lymph nodes, in four out of five cases ipsilaterally. In all cases, cytology and additional analyses showed a reactive lymphadenopathy without any sign of malignancy. CONCLUSIONS: Evidence of newly enlarged lymph nodes after recent COVID-19 vaccination should be considered reactive in the first instance, occurring owing to stimulation of the immune system. A clinical follow-up according to the patient’s risk profile without further diagnostic measures is justified. In the case of preexisting unilateral cancer, vaccination should be given contralaterally whenever possible. Persistently enlarged lymph nodes should be re-evaluated (2 to) 6 weeks after the second dose, with additional diagnostic tests tailored to the clinical context. Fine needle aspiration is a well established, safe, rapid and cost-effective method to investigate an underlying malignancy, especially metastasis. Recording vaccination history, including date of injection, site and vaccine type, as well as communicating this information to treating physicians of different specialties is paramount for properly handling COVID-19 vaccine-associated lymphadenopathy.

Bilateral Lymphadenopathy After COVID Vaccine in 18F-Choline PET/MRI Performed for Hyperparathyroidism.

ABSTRACT: We describe a case of a 56-year-old woman with primary hyperparathyroidism. 18F-Choline PET/MRI revealed incidental bilateral axillary lymphadenopathy with mild-moderate increased 18F-choline uptake. The patient had her first and third doses of COVID-19 vaccines from the left arm and second dose of vaccine from the right arm before PET examination.

Eosinophilic lymph node abscesses following a COVID-19 vaccination: A case report.

In this paper, we reported a 37-year-old man who developed several lymphadenopathies after using the second dose of Pfizer-BioNtech vaccination against SARS-CoV-2. The excisional lymph node biopsy showed eosinophil-rich inflammation with micro-abscesses. Although eosinophilic dermatosis and eosinophilic myocarditis have been described previously following COVID-19 vaccinations, eosinophilic lymph node abscess was not reported in the literature. In our case, all lesions were completely recovered with steroid treatment. The patient has been doing well and no recurrence has been observed for six months.

The location of unilateral axillary lymphadenopathy after COVID-19 vaccination compared with that of metastasis from breast cancer without vaccination.

PURPOSE: Unilateral axillary lymphadenopathy is known to occur after coronavirus disease (COVID-19) vaccination. Post-vaccination lymphadenopathy may mimic the metastatic lymph nodes in breast cancer, and it is challenging to distinguish between them. This study investigated whether the localization of axillary lymphadenopathy on magnetic resonance imaging (MRI) could be used to distinguish reactive lymphadenopathy after COVID-19 vaccines from metastatic nodes. MATERIALS AND METHODS: We retrospectively examined preoperative MRI images of 684 axillae in 342 patients who underwent breast cancer surgery from June to October 2021. Lymphadenopathy was defined as cortical thickening or short axis ≥ 5 mm. The axilla was divided into ventral and dorsal parts on the axial plane using a perpendicular line extending from the most anterior margin of the muscle group, including the deltoid, latissimus dorsi, or teres major muscles, relative to a line along the lateral chest wall. We recorded the presence or absence of axillary lymphadenopathy in each area and the number of visible lymph nodes. RESULTS: Of 80 axillae, 41 and 39 were included in the vaccine and metastasis groups, respectively. The median time from the last vaccination to MRI was 19 days in the vaccine group. The number of visible axillary lymph nodes was significantly higher in the vaccine group (median, 15 nodes) than in the metastasis group (7 nodes) (P < 0.001). Dorsal lymphadenopathy was observed in 16 (39.0%) and two (5.1%) axillae in the vaccine and metastasis groups, respectively (P < 0.001). If the presence of both ventral and dorsal lymphadenopathy is considered indicative of vaccine-induced reaction, this finding has a sensitivity of 34.1%, specificity of 97.4%, and positive and negative predictive values of 93.3％ and 58.5%, respectively. CONCLUSION: The presence of deep axillary lymphadenopathy may be an important factor for distinguishing post-vaccination lymphadenopathy from metastasis. The number of axillary lymph nodes may also help.

Tender cervical lymphadenitis as a herald of multi-system inflammatory syndrome in COVID-19 infection of children and adolescents: a report of two cases.

BACKGROUND: Post-COVID-19 multisystem inflammatory syndrome (MIS) has been increasingly recognized but fever with isolated tender cervical lymphadenitis as the initial presentation has been rarely reported. We present 2 female patients one a child and the other an adolescent. CASE PRESENTATION: Case 1 was a 13-year-old girl who presented with tender cervical lymphadenopathy and fever 3-weeks post-COVID-19, and then developed features of MIS 5 days later. Case 2, also female, was 18 years old. She had no history of COVID-19 infection or immunization but had a serologic diagnosis of COVID-19. She similarly presented with fever and tender cervical lymphadenopathy, and then progressed rapidly to develop features of MIS. Both patients responded well to treatment with immunosuppressants and intravenous immunoglobulin. CONCLUSION: Tender cervical lymphadenopathy could be the herald of multi-system inflammatory syndrome following COVID-19 infection among children and adolescents, which the clinicians must have a good suspicion about.

Kikuchi-Fujimoto-like lymphadenopathy following COVID-19 vaccine: diagnosis and management.

A woman in her mid 40s presented for breast imaging after 1 week of painful and enlarged right axillary lymphadenopathy. She denied history of fever, weight loss, night sweats fatigue, cat scratch or other trauma. She received the second dose of Pfizer COVID-19 vaccine 3 months previously on the contralateral arm. A mammogram demonstrated a single, asymmetric, large and dense right axillary lymph node. Ultrasound confirmed a 2.5 cm lymph node with cortical thickening of 0.6 cm. Ultrasound-guided core biopsy showed necrotising lymphadenitis with associated aggregates of histiocytes and plasmacytoid dendritic cells. Potential causes of necrotising adenitis including Bartonella, tuberculosis, Epstein-Barr Virus, herpes simplex virus, systemic lupus erythematosus and lymphoma were excluded. In the absence of any identifiable infectious or autoimmune causes, and given the temporal relatedness with vaccine administration, it was determined that the Kikuchi-Fujimoto-like necrotising lymphadenitis was likely secondary to the COVID-19 vaccine. To date, there has been no casual association made between the COVID-19 vaccine and KFD necrotising lymphadenitis.

Multispectral optoacoustic tomography to differentiate between lymph node metastases and coronavirus-19 vaccine-associated lymphadenopathy.

INTRODUCTION: Worldwide mass vaccination for COVID-19 started in late 2020. COVID-19 vaccines cause benign hypermetabolic lymphadenopathies. Clinical stratification between vaccine-associated benign lymphadenopathies and malignant lymphadenopathies through ultrasound, MRI or FDG PET-CT is not feasible. This leads to unnecessary lymph node biopsies, excisions and even radical lymph node dissections. Therefore, to avoid unnecessary surgeries, we assessed whether noninvasive multispectral optoacoustic tomography (MSOT) enables a better differentiation between benign and malignant lymphadenopathies. PATIENTS AND METHODS: All patients were vaccinated for COVID-19. We used MSOT to image deoxy- and oxyhaemoglobin levels in lymph nodes of tumour patients to assess metastatic status. MSOT imaging results were compared with standard ultrasound and pathological lymph node analysis. We also evaluated the influences of gender, age and time between vaccination and MSOT measurement of lymph nodes on the measured deoxy- and oxyhaemoglobin levels in patients with reactive lymph node changes. RESULTS: Multispectral optoacoustic tomography was able to identify cancer-free lymph nodes in vivo without a single false negative (33 total lymph nodes), with 100% sensitivity and 50% specificity. A statistically significant higher deoxyhaemoglobin content was detected in patients with tumour manifestations in the lymph node (p = 0.02). There was no statistically significant difference concerning oxyhaemoglobin (p = 0.65). Age, sex and time between vaccination and MSOT measurement had statistically non-significant impact on deoxy- and oxyhaemoglobin levels in patients with reactive lymph nodes. CONCLUSION: Here, we show that MSOT measurement is an advantageous clinical approach to differentiate between vaccine-associated benign lymphadenopathy and malignant lymph node metastases based on the deoxygenation level in lymph nodes.

Non-Hodgkin Lymphoma Developed Shortly after mRNA COVID-19 Vaccination: Report of a Case and Review of the Literature.

We report on a 66-year-old man who presented with a right axillary lymphadenopathy approximately 10 days after receiving the third dose of the BNT162b2 vaccine. The lymphadenopathy gradually enlarged, and physical examination and ultrasound (US) revealed one right axillary 6.99 cm and one right supraclavicular 2.36 cm lymphadenopathy. Histologic examination of the right axillary nodule revealed anaplastic large-cell lymphoma that was ALK negative and CD30 positive. A total body computerized tomography (CT) scan, positron emission tomography (PET) and bone-marrow biopsy showed a stage-II non-Hodgkin lymphoma (NHL). The patient was treated with chemotherapy and a scheme of Brentuximab Vedotin, Cyclophosphamide, Doxorubicin and Prednisone (BV-CHP) for six cycles and is now well and in complete remission. The revision of the literature revealed eight additional cases of NHL developed shortly after COVID-vaccination. There were four cases of diffuse large-B-cell lymphoma (DLBCL) (one in a patient who was a heart transplant recipient and developed an Epstein-Bar-virus-positive DLBCL), one case of extranodal NK/T-cell lymphoma, one patient with subcutaneous panniculitis-like T-cell lymphoma, one case of marginal zone B-cell lymphoma and one primary cutaneous anaplastic large-cell lymphoma (PC-ALCL). In five cases, the lymphoma developed after BNT162b2 mRNA vaccination, including one case after ChAdOx1 nCOV-19, one case after the adenovirus type 26 (Ad26) vaccine and one after mRNA-1273/Spikevax (ModernaTX). We are aware that the link between COVID-19 vaccination and lymphoma most likely is a chance phenomenon, and that COVID-19 vaccines represent very efficient products for many people around the world. However, we believe that clinical events, even if only temporally associated with novel treatments or novel vaccines, should be reported for the benefit of the patients and the scientific community.

Kikuchi-Fujimoto disease following SARS-CoV-2 vaccination.

A previously healthy Japanese woman in her 20s was admitted to our hospital with a 2-week history of fever (39.0°C) and a 1-week history of painful cervical lymphadenopathy. The day before fever onset, she had received her first Pfizer-BioNTech SARS-CoV-2 vaccine in her left arm. She had previously been treated with empirical antibiotics with no improvement. Physical examination revealed painful lymphadenopathy in both posterior cervical regions. CT showed symmetrical lymphadenopathies in the neck, supraclavicular, axillary and inguinal regions as well as hepatosplenomegaly. We suspected lymphoma and performed a lymph node biopsy in the right inguinal region, which revealed necrotising histiocytic lymphadenitis. The patient was, therefore, diagnosed with Kikuchi-Fujimoto disease (KFD). She improved after the corticosteroid therapy. This report highlights the importance of including KFD as a differential diagnosis of lymphadenopathy after SARS-CoV-2 vaccination. Additionally, lymph node biopsy is helpful for diagnosing KFD because it rules out other entities.

Hypermetabolic lymphadenopathy following the administration of COVID-19 vaccine and immunotherapy in a lung cancer patient: a case report.

BACKGROUND: Given the current climate of the pandemic, lung cancer patients are especially vulnerable to complications from severe acute respiratory syndrome coronavirus 2 infection. As a high-risk population group, these patients are strongly advised to receive coronavirus disease 2019 vaccination in accordance with Center for Disease Control and Prevention guidelines to minimize morbidity and mortality. In recent years, immunotherapy has taken a preeminent role in the treatment of non-small cell lung cancer with dramatic improvement in overall survival. Reactive lymphadenopathy following the administration of a coronavirus disease 2019 vaccination can confound the radiographic interpretation of positron emission tomography-computed tomography or computed tomography scans from lung cancer patients receiving immunotherapy. CASE PRESENTATION: Here, we present a case of a 61-year-old Caucasian female and former smoker who developed cervical, hilar, supraclavicular, mediastinal, and left retroauricular lymphadenopathy following her coronavirus disease 2019 booster vaccination. At the time, she had been receiving long-term immunotherapy for the treatment of advanced lung adenocarcinoma. Biopsy was pursued owing to concerns of treatment failure and confirmed recurrent malignancy. CONCLUSION: This case report highlights the importance of lymph node biopsies in lung cancer patients who present with contralateral lymphadenopathy following coronavirus disease 2019 vaccination to rule out tumor recurrence in this deserving patient population.

COVID-19 Vaccine-Associated Lymphadenopathy Mimicking Regrowth of Axillary Lymph Node Metastasis of Lung Adenocarcinoma.

We encountered a woman with re-enlarged axillary lymph nodes during a computed tomography (CT) scan for surveillance of lung adenocarcinoma with axillary lymph node metastasis at the initial diagnosis that had shrunk with standard chemotherapy. We first suspected cancer recurrence and considered a change in the chemotherapeutic regimen. However, after careful history taking regarding the timing of her Coronavirus Disease 2019 (COVID-19) vaccination, and subsequent careful, close follow-up, radiological shrinkage suggested a strictly benign cause. Especially in lung cancer with a medical history of axillary lymph node involvement, cliniciansshould be aware that vaccine-associated lymphadenopathy can mimic cancer recurrence and sometimesprompt serious misjudgment regarding a current treatment course and strategy.

Axillary lymph node characteristics in breast cancer patients versus post-COVID-19 vaccination: Overview of current evidence per imaging modality.

BACKGROUND: Axillary lymph node characteristics on axillary ultrasound (US), breast MRI and 18F-FDG PET/CT are relevant at breast cancer diagnosis. Axillary lymphadenopathy after COVID-19 vaccination has been frequently reported. This may cause a diagnostic dilemma, particularly in the ipsilateral axilla in women who have a either a recent diagnosis of breast cancer or a history of breast cancer. This review provides an overview of the current evidence regarding axillary lymph node characteristics at breast cancer diagnosis versus "post-COVID-19 vaccination". METHODS: A non-systematic narrative review was performed. Studies describing axillary lymph node characteristics per imaging modality (axillary US, breast MRI and 18F-FDG PET/CT) in breast cancer patients versus post-COVID-19 vaccination were selected and used for the current study. RESULTS: The morphologic characteristics and distribution of abnormal nodes on US may differ from the appearance of metastatic adenopathy since diffuse cortical thickening of the lymph nodes is the most observed characteristic after vaccination, whereas metastases show as most suspicious characteristics focal cortical thickening and effacement of the fatty hilum. Current evidence on MRI and 18F-FDG on morphologic characteristics of axillary lymphadenopathy is missing, although it was suggested that vaccine related lymphadenopathy is more likely to be present in level 2 and 3 nodes than metastatic nodes. Reported frequencies of lymphadenopathy post-COVID-19 vaccination range from 49% to 85% (US), 29% (breast MRI) and 14.5% to 53.9% (18F-FDG PET/CT). Several factors may impact the presence or extent of lymphadenopathy post-COVID-19 vaccination: injection site, type of vaccine (i.e., mRNA versus vector), time interval (days) between vaccination and imaging, previous history of COVID-19 pneumonia, and first versus second vaccine dose. CONCLUSION: Although lymph node characteristics differ at breast cancer diagnosis versus post-COVID-19 vaccination, clinical information regarding injection site, vaccine type and vaccination date needs to be documented to improve the interpretation and guide treatment towards the next steps of action.

Axillary adenopathy detected on breast MRI following COVID-19 vaccination: outcomes and follow-up recommendations.

This retrospective study presents 110 patients with suspected COVID-19 vaccine-related axillary adenopathy on breast MRI. Our study aimed to assess the outcomes of axillary adenopathy detected on breast MRI performed within one year after COVID-19 vaccination. The median time between the COVID-19 vaccine and breast MRI was shorter in patients with detected adenopathy compared to patients without detected adenopathy (6 weeks [2-17] versus 15 [7-24] weeks, p < 0.001). Unilateral axillary adenopathy detected on breast MRI had a low malignancy rate (3.3%), and no cases of malignant axillary adenopathy were diagnosed without a known breast cancer in the ipsilateral breast. Our findings suggest that unilateral axillary adenopathy identified on breast MRI ipsilateral to a recent COVID-19 vaccination can be considered benign in the absence of a suspicious breast finding or known breast cancer. Regardless of vaccine status and timing, unilateral axillary adenopathy detected on MRI evaluation with a known malignancy or suspicious breast finding should be considered suspicious. This will avoid unnecessary scheduling constraints, patient anxiety, and cost, without delaying diagnosis of metastatic breast cancer.

FDG PET/CT radiomics as a tool to differentiate between reactive axillary lymphadenopathy following COVID-19 vaccination and metastatic breast cancer axillary lymphadenopathy: a pilot study.

OBJECTIVES: To evaluate if radiomics with machine learning can differentiate between F-18-fluorodeoxyglucose (FDG)-avid breast cancer metastatic lymphadenopathy and FDG-avid COVID-19 mRNA vaccine-related axillary lymphadenopathy. MATERIALS AND METHODS: We retrospectively analyzed FDG-positive, pathology-proven, metastatic axillary lymph nodes in 53 breast cancer patients who had PET/CT for follow-up or staging, and FDG-positive axillary lymph nodes in 46 patients who were vaccinated with the COVID-19 mRNA vaccine. Radiomics features (110 features classified into 7 groups) were extracted from all segmented lymph nodes. Analysis was performed on PET, CT, and combined PET/CT inputs. Lymph nodes were randomly assigned to a training (n = 132) and validation cohort (n = 33) by 5-fold cross-validation. K-nearest neighbors (KNN) and random forest (RF) machine learning models were used. Performance was evaluated using an area under the receiver-operator characteristic curve (AUC-ROC) score. RESULTS: Axillary lymph nodes from breast cancer patients (n = 85) and COVID-19-vaccinated individuals (n = 80) were analyzed. Analysis of first-order features showed statistically significant differences (p < 0.05) in all combined PET/CT features, most PET features, and half of the CT features. The KNN model showed the best performance score for combined PET/CT and PET input with 0.98 (± 0.03) and 0.88 (± 0.07) validation AUC, and 96% (± 4%) and 85% (± 9%) validation accuracy, respectively. The RF model showed the best result for CT input with 0.96 (± 0.04) validation AUC and 90% (± 6%) validation accuracy. CONCLUSION: Radiomics features can differentiate between FDG-avid breast cancer metastatic and FDG-avid COVID-19 vaccine-related axillary lymphadenopathy. Such a model may have a role in differentiating benign nodes from malignant ones. KEY POINTS: • Patients who were vaccinated with the COVID-19 mRNA vaccine have shown FDG-avid reactive axillary lymph nodes in PET-CT scans. • We evaluated if radiomics and machine learning can distinguish between FDG-avid metastatic axillary lymphadenopathy in breast cancer patients and FDG-avid reactive axillary lymph nodes. • Combined PET and CT radiomics data showed good test AUC (0.98) for distinguishing between metastatic axillary lymphadenopathy and post-COVID-19 vaccine-associated axillary lymphadenopathy. Therefore, the use of radiomics may have a role in differentiating between benign from malignant FDG-avid nodes.

Post-vaccination SARS-CoV-2 axillary adenopathy. Differences with axillary metastases from breast cancer.

The differential diagnosis of the metastatic axillary lymphadenopathies of breast cancer with which they occur secondary to the Pfizer-BioNTech vaccine against COVID-19, is imperative. In a series of cases, we analyzed the characteristics of unilateral axillary lymphadenopathy in patients after Pfizer-BioNTech vaccination. Axillary lymphadenopathy were observed ipsilateral to the vaccination arm. The axillary ultrasound defined these as reactive and that they disappeared in 3 weeks. The pathological findings were benign. The anamnesis, the place and date of vaccination and the radiological findings, play an essential role to carry out a correct differential diagnosis and follow-up of these adenopathies.

El diagnóstico diferencial de las adenopatías axilares metastásicas del cáncer de mama con las que se producen secundarias a la vacuna de Pfizer-BioNTech contra la COVID-19 es imperioso. Analizamos una serie de casos con las características de las adenopatías axilares unilaterales tras la administración de la vacuna de Pfizer-BioNTech. Se observaron adenopatías axilares homolaterales al brazo de vacunación. La ecografía axilar las definió como reactivas y que desaparecían en 3 semanas. Los hallazgos anatomopatológicos fueron de benignidad. La anamnesis, el lugar y la fecha de vacunación, así como los hallazgos radiológicos, desempeñan un papel esencial para realizar un correcto diagnóstico deferencial y el seguimiento de estas adenopatías.