Clinical importance of thoracal lymphadenopathy in COVID-19.

BACKGROUND: Thoracal lymphadenopathy may predict prognosis in patients with coronavirus disease 2019 (COVID-19), albeit the reported data is inconclusive. The aim of the present analysis was to analyze the affected lymph node stations and the cumulative lymph node size derived from computed tomography (CT) for prediction of 30-day mortality in patients with COVID-19. METHODS: The clinical database was retrospectively screened for patients with COVID-19 between 2020 and 2022. Overall, 177 patients (63 female, 35.6%) were included into the analysis. Thoracal lymphadenopathy was defined by short axis diameter above 10 mm. Cumulative lymph node size of the largest lymph nodes was calculated and the amount of affected lymph node stations was quantified. RESULTS: Overall, 53 patients (29.9%) died within the 30-day observation period. 108 patients (61.0%) were admitted to the ICU and 91 patients needed to be intubated (51.4%). Overall, there were 130 patients with lymphadenopathy (73.4%). The mean number of affected lymph node levels were higher in non-survivors compared to survivors (mean, 4.0 vs 2.2, p < 0.001). The cumulative size was also higher in non-survivors compared to survivors (mean 55.9 mm versus 44.1 mm, p = 0.006). Presence of lymphadenopathy was associated with 30-day mortality in a multivariable analysis, OR = 2.99 (95% CI 1.20 - 7.43), p = 0.02. CONCLUSIONS: Thoracal lymphadenopathy comprising cumulative size and affected levels derived from CT images is associated with 30-day mortality in patients with COVID-19. COVID-19 patients presenting with thoracic lymphadenopathy should be considered as a risk group.

COVID-19 vaccine related hypermetabolic lymph nodes on PET/CT: Implications of inflammatory findings in cancer imaging.

We observed several patients presenting 2-[18F]FDG uptake in the reactive axillary lymph node at PET/CT imaging, ipsilateral to the site of the COVID-19 vaccine injection. Analog finding was documented at [18F]Choline PET/CT. The aim of our study was to describe this source of false positive cases. All patients examined by PET/CT were included in the study. Data concerning patient anamnesis, laterality, and time interval from recent COVID-19 vaccination were recorded. SUVmax was measured in all lymph nodes expressing tracer uptake after vaccination. Among 712 PET/CT scans with 2-[18F]FDG, 104 were submitted to vaccination; 89/104 patients (85%) presented axillary and/or deltoid tracer uptake, related to recent COVID-19 vaccine administration (median from injection: 11 days). The mean SUVmax of these findings was 2.1 (range 1.6-3.3). Among 89 patients with false positive axillary uptake, 36 subjects had received chemotherapy due to lymph node metastases from somatic cancer or lymphomas, prior to the scan: 6/36 patients with lymph node metastases showed no response to therapy or progression disease. The mean SUVmax value of lymph nodal localizations of somatic cancers/lymphomas after chemotherapy was 7.8. Only 1/31 prostate cancer patients examined by [18F]Choline PET/CT showed post-vaccine axillary lymph node uptake. These findings were not recorded at PET/CT scans with [18F]-6-FDOPA, [68Ga]Ga-DOTATOC, and [18F]-fluoride. Following COVID-19 mass vaccination, a significant percentage of patients examined by 2-[18F]FDG PET/CT presents axillary, reactive lymph node uptake. Anamnesis, low-dose CT, and ultrasonography facilitated correct diagnosis. Semi-quantitative assessment supported the visual analysis of PET/CT data; SUVmax values of metastatic lymph nodes were considerably higher than post-vaccine lymph nodes. [18F]Choline uptake in reactive lymph node after vaccination was confirmed. After the COVID-19 pandemic, nuclear physicians need to take these potential false positive cases into account in daily clinical practice.

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.

Contrast-enhanced Ultrasound Using Intradermal Microbubble Sulfur Hexafluoride for Identification of Sentinel Lymph Nodes During Breast Cancer Surgery: A Clinical Trial.

BACKGROUND/AIM: Sentinel lymph node (SLN) procedures have gained popularity in early breast cancer thanks to the reduction of surgical side-effects. The standard SLN mapping procedure uses 99mTc-nanocolloid human serum albumin with/without blue dye; limitations include logistical challenges and adverse reactions. Recently, contrast-enhanced ultrasound (CEUS) using sulfur hexafluoride has emerged as a promising technique for SLN mapping. Our study aimed to compare the CEUS technique with the standard isotope method. MATERIALS AND METHODS: AX-CES, a prospective, monocentric, single-arm phase-3 study was designed (EudraCT: 2020-000393-20). Inclusion criteria were histologically diagnosed early breast cancer eligible for upfront surgery and SLN resection, bodyweight 40-85 kg, and no prior history of ipsilateral surgery or radiotherapy. All patients underwent CEUS prior to surgery and blue dye injection was performed in areas with contrast accumulation. After the experimental procedure, all patients underwent the standard mapping procedure and SLN frozen section assessment was performed. Data on the success rate, systemic reactions, mean procedure time, CEUS appearance, SLN number, and concordance with standard mapping procedure were collected. RESULTS: Among 16 cases, a median of two SLNs were identified during CEUS. In all cases, at least one SLN was identified by CEUS (100%). In six cases, SLNs were classified during CEUS as abnormal, which was confirmed by definitive staining in four cases. After the standard mapping technique, in 15 out of the 16 cases (87.50%), at least one SLN from the standard mapping procedure was marked with blue dye in the CEUS procedure. In our series, sensitivity and specificity of SLN detection by CEUS were 75% and 100%, respectively. CONCLUSION: CEUS is a safe and manageable intraoperative procedure. When compared with standard techniques, US appearance during CEUS may provide additional information when associated with histological assessment.

18F-Fluciclovine-Avid Axillary Lymph Nodes After COVID-19 Vaccination on PET/CT for Suspected Recurrence of Prostate Cancer.

Abnormally increased 18F-FDG avidity of axillary lymph nodes has become a frequent diagnostic dilemma on PET/CT in the current climate of global vaccinations directed against severe acute respiratory syndrome coronavirus 2. This avidity is due to the inflammatory response evoked by vaccines and the nonspecific nature of 18F-FDG uptake, which is increased in both malignant and inflammatory processes. Similarly, 18F-fluciclovine, an amino acid analog indicated for the assessment of biochemical recurrence of prostate cancer, may also demonstrate nonspecific inflammatory uptake. We report a case of 18F-fluciclovine PET/CT obtained for concern about prostate cancer. In this case, isolated avid lymph nodes were seen in the left axilla. A screening questionnaire revealed that the patient had recently received the second dose of the Pfizer-BioNTech coronavirus disease 2019 vaccine in his left shoulder, and hence, the uptake was determined to be reactive.

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.

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.

Prevalence of Adenopathy at Chest Computed Tomography After Vaccination for Severe Acute Respiratory Syndrome Coronavirus 2.

OBJECTIVE: This study aimed to determine the prevalence of axillary and subpectoral (SP) lymph nodes after ipsilateral COVID-19 vaccine administration on chest computed tomography (CT). METHODS: Subjects with chest CTs between 2 and 25 days after a first or second vaccine dose, December 15, 2020, to February 12, 2021, were included. Orthogonal measures of the largest axillary and SP nodes were recorded by 2 readers blinded to vaccine administration and clinical details. A mean nodal diameter discrepancy of ≥6 mm between contralateral stations was considered positive for asymmetry. Correlation with the side of vaccination, using a Spearman rank correlation, was performed on the full cohort and after excluding patients with diseases associated with adenopathy. RESULTS: Of the 138 subjects (81 women, 57 men; mean [SD] age, 74.4 ± 11.7 years), 48 (35%) had asymmetrically enlarged axillary and/or SP lymph nodes, 42 (30%) had ipsilateral, and 6 (4%) had contralateral to vaccination ( P = 0.003). Exclusion of 29 subjects with conditions associated with adenopathy showed almost identical correlation, with asymmetric nodes in 32 of 109 (29%) ipsilateral and in 5 of 109 (5%) contralateral to vaccination ( P = 0.002). CONCLUSIONS: Axillary and/or SP lymph nodes ipsilateral to vaccine administration represents a clinical conundrum. Asymmetric nodes were detected at CT in 30% of subjects overall and 29% of subjects without conditions associated with adenopathy, approximately double the prevalence rate reported to the Centers for Disease Control and Prevention by vaccine manufacturers. When interpreting examinations correlation with vaccine administration timing and site is important for pragmatic management.

CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice.

BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative disease, wherein aberrant immune cells target myelin-ensheathed nerves. Conventional magnetic resonance imaging (MRI) can be performed to monitor damage to the central nervous system that results from previous inflammation; however, these imaging biomarkers are not necessarily indicative of active, progressive stages of the disease. The immune cells responsible for MS are first activated and sensitized to myelin in lymph nodes (LNs). Here, we present a new strategy for monitoring active disease activity in MS, chemical exchange saturation transfer (CEST) MRI of LNs. METHODS AND RESULTS: We studied the potential utility of conventional (T2-weighted) and CEST MRI to monitor changes in these LNs during disease progression in an experimental autoimmune encephalomyelitis (EAE) model. We found CEST signal changes corresponded temporally with disease activity. CEST signals at the 3.2 ppm frequency during the active stage of EAE correlated significantly with the cellular (flow cytometry) and metabolic (mass spectrometry imaging) composition of the LNs, as well as immune cell infiltration into brain and spinal cord tissue. Correlating primary metabolites as identified by matrix-assisted laser desorption/ionization (MALDI) imaging included alanine, lactate, leucine, malate, and phenylalanine. CONCLUSIONS: Taken together, we demonstrate the utility of CEST MRI signal changes in superficial cervical LNs as a complementary imaging biomarker for monitoring disease activity in MS. CEST MRI biomarkers corresponded to disease activity, correlated with immune activation (surface markers, antigen-stimulated proliferation), and correlated with LN metabolite levels.

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.

Evaluation of clinically involved lymph nodes with deformable registration in breast cancer radiotherapy.

OBJECTIVES: Modern radiotherapy (RT) techniques require careful delineation of the target. There is no particular RT contouring guideline for patients receiving neoadjuvant chemotherapy (NACT). In this study, we examined the distribution of pre-chemotherapy clinically positive nodal metastases. METHODS: We explored the coverage rate of the RTOG breast contouring guideline by deformable fusion of 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan. We retrospectively evaluated neoadjuvant chemotherapy patients. All PET-CT images were imported into the planning software. We combined the planning CT and the CT images of PET-CT with rigid and then a deformable registration. We manually contoured positive lymph nodes on the CT component of the PET-CT data set and transferred them to planning CT after fusion. We evaluated whether previously contoured lymphatic CTVs, according to the RTOG breast atlas, include GTV-LNs. RESULTS: All breast cancer patients between October 2018 and February 2021 were evaluated from the electronic database. There were 142 radiologically defined positive lymph nodes in 31 patients who were irradiated after NACT. Most LNs (70%) were in the level I axilla. Only 71.1% (n:101) of the whole lymph nodes in 10 patients were totally covered, 22.5% (n:32) partially covered and 6.4% %(n:9) totally undercovered. CONCLUSIONS: The extent of regional nodal areas in the RTOG atlas may be insufficient to cover positive lymph nodes adequately. For patients with nodal involvement undergoing neoadjuvant chemotherapy, PET-CT image fusions can be helpful to be sure that positive lymph nodes are in the treatment volume. ADVANCES IN KNOWLEDGE: RTOG contouring atlas may be insufficient to cover all involved lymph nodes after NACT. For patients with nodal involvement undergoing neoadjuvant chemotherapy, PET-CT image fusions may help to be sure that positive lymph nodes are in the treatment volume.

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.

Vaccine-Related Lymph Nodes: The Emerging Pitfalls of 18F-Fluorocholine and 68Ga-PSMA-11 PET/CT in the Era of COVID-19 Vaccination.

PURPOSE: Vaccination against coronavirus disease 2019 (COVID-19) is currently under worldwide deployment. The consequences of this vaccination can be seen in radiology and nuclear medicine explorations with visualization of axillary lymph nodes (LNs), as observed on ultrasonography, MRI, or 18F-FDG PET/CT.We aimed to evaluate on PET/CT the incidence of vaccine-related LNs and their characteristics after COVID-19 vaccination, using several radiopharmaceuticals different from 18F-FDG. PATIENTS AND METHODS: Between February and July 2021, all consecutive patients undergoing a whole-body PET/CT for any indication using a different radiopharmaceutical from 18F-FDG were eligible for inclusion if they had received at least 1 dose of the COVID-19 vaccine. The radiopharmaceutical administered and vaccine type were recorded for each patient. The incidence of positive vaccine-related axillary and supraclavicular LNs on PET/CT was our primary finding, along with the nodes characteristics. Statistical analyses were performed for patients with prostate cancer (PCa) to determine certain interaction factors that were associated with the detection of vaccine-related LNs. RESULTS: Of the 226 patients in our cohort study, 120 patients underwent an 18F-fluorocholine PET/CT, 79 a 68Ga-PSMA-11 PET/CT, 6 an 18F-FDOPA PET/CT, and 21 a 68Ga-DOTATOC PET/CT. A total of 67.3% of patients (152/226) received BNT162b2mRNA (Pfizer-BioNTech), 26.5% (60/226) ChAdOx1-S (AstraZeneca), 4.9% (11/226) mRNA-1273 (Moderna), and 1.3% (3/226) Ad26.COV2.S (Janssen). The incidence of positive vaccine-related axillary and supraclavicular LNs was 42.5% (51/120 patients) on PET/CT using 18F-fluorocholine and 12.7% (10/79 patients) with 68Ga-PSMA-11. None of our patients undergoing 18F-FDOPA or 68Ga-DOTATOC PET/CT presented any vaccine-related lymphadenopathy. Vaccine-related LNs were statistically associated with the nature of the radiopharmaceutical (P < 10-4), with the number of vaccine doses received (P = 0.041), with a short delay between vaccination and PET/CT realization (P < 10-5), and with a higher prostate-specific antigen level for patients with PCa (P = 0.032), but not with age or vaccine type. The vaccine-related nodes appeared in 85% of the cases, in the 30 days after vaccine injection, were limited in size and uptake, and were most often limited to the axilla level 1 area. CONCLUSIONS: Detecting positive LNs after COVID-19 vaccination is not an exclusive 18F-FDG PET/CT pattern but is common on 18F-fluorocholine and possible on 68Ga-PSMA-11 PET/CT. Confronting PET/CT findings with clinical data (such as date and site of injection) seems essential in the current pandemic context, just as it does for the radiopharmaceuticals used in PCa to avoid PET/CT misinterpretation and incorrect patient treatment. For 18F-FDOPA or 68Ga-DOTATOC PET/CT, this seems to have a lesser impact.

Quantitative ultrasound image analysis of axillary lymph nodes to differentiate malignancy from reactive benign changes due to COVID-19 vaccination.

PURPOSE: The aim of this study is to assess the potential of quantitative image analysis and machine learning techniques to differentiate between malignant lymph nodes and benign lymph nodes affected by reactive changes due to COVID-19 vaccination. METHOD: In this institutional review board-approved retrospective study, we improved our previously published artificial intelligence model, by retraining it with newly collected images and testing its performance on images containing benign lymph nodes affected by COVID-19 vaccination. All the images were acquired and selected by specialized breast-imaging radiologists and the nature of each node (benign or malignant) was assessed through a strict clinical protocol using ultrasound-guided biopsies. RESULTS: A total of 180 new images from 154 different patients were recruited: 71 images (10 cases and 61 controls) were used to retrain the old model and 109 images (36 cases and 73 controls) were used to evaluate its performance. The achieved accuracy of the proposed method was 92.7% with 77.8% sensitivity and 100% specificity at the optimal cut-off point. In comparison, the visual node inspection made by radiologists from ultrasound images reached 69.7% accuracy with 41.7% sensitivity and 83.6% specificity. CONCLUSIONS: The results obtained in this study show the potential of the proposed techniques to differentiate between malignant lymph nodes and benign nodes affected by reactive changes due to COVID-19 vaccination. These techniques could be useful to non-invasively diagnose lymph node status in patients with suspicious reactive nodes, although larger multicenter studies are needed to confirm and validate the results.

Resolution of Misleading COVID-19 Vaccination-Related Nodal and Splenic FDG Uptake in the Follow-up Study.

ABSTRACT: Newly diagnosed low-grade bilateral breast lymphoma in 63-year-old woman demonstrated intense FDG uptake in the left axillary lymph nodes and the spleen, concerning for lymphomatous involvement. Subsequent ultrasound-guided biopsy did not demonstrate any pathologic left axillary lymph nodes. Further investigation revealed COVID-19 vaccination in the left arm, 5 days prior to the 18 F-FDG PET/CT study. Six-month follow-up 18 F-FDG PET/CT showed resolution of the intense FDG uptake in the left axillary lymph nodes and spleen without any treatment, suggesting a self-remitting acute local and systemic immune response to COVID-19 vaccination.

Utility of Esophageal Ultrasound-guided Biopsy of Mediastinal Lymph Nodes in Diagnosis of Childhood Tuberculosis.

A 6-year-old boy with autistic spectrum disorder was diagnosed with tuberculosis infection following contact tracing of his mother who had isoniazid-resistant pulmonary tuberculosis. He progressed to develop mediastinal lymphadenopathy causing a persistent cough. He was too small to undergo endobronchial ultrasound-guided biopsy. As an alternative, he underwent esophageal endoscopic ultrasound-guided biopsy, leading to confirmation of the diagnosis. We believe this approach to diagnostic biopsy is underrecognized in pediatric practice, and highlight its utility with this case and a brief literature review.

Intensity of hypermetabolic axillary lymph nodes in oncologic patients in relation to timeline following COVID-19 vaccination.

PURPOSE: First discovered in Wuhan, China in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is a highly contagious and deadly novel virus that quickly wreaked havoc throughout the world. As mass vaccination are now underway worldwide, clinicians have started to encounter a new clinical entity, COVID-19 vaccine-associated axillary lymphadenopathy. This presents a unique challenge to medical imagers, particularly in oncologic patients. METHODS: In this retrospective study, we assessed metabolic activity, size, and timeline of COVID-19 vaccine-associated axillary hypermetabolic lymph nodes in 202 oncologic patients post vaccination with 18-fluorodeoxyglucose positron emission tomography (18-FDG PET). RESULTS: When present, COVID-19 vaccine-associated hypermetabolic lymph nodes demonstrate a mean maximum standard uptake value (SUVmax) of 2.5 ± 0.3, and more common in younger patients. The metabolic activity is the most intense in the first two weeks post vaccination and diminishes over time. By approximately 5-6 weeks, only about half of the patients demonstrated appreciable, low grade uptake compared to background. CONCLUSION: Based on our preliminary results, we would recommend correlation with a history and time of vaccination and routine use of a pre-study patient questionnaire to guide interpretation to prevent over-diagnosis of axillary nodal metastases and/or unnecessary work-up in oncologic patients.