Impact of coronavirus disease 2019 pandemic on breast cancer surgery using the National Database of Japan.

Various countries have reported a decrease in breast cancer surgeries during the coronavirus disease 2019 (COVID-19) pandemic; however, inconsistent results have been reported in Japan. This study revealed changes in the number of surgeries during the pandemic using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) from January 2015 to January 2021, where insurance claims data from Japan as a whole are comprehensively accumulated. The number of breast-conserving surgeries (BCS) without axillary lymph node dissection (ALND) significantly decreased in July (- 846; 95% confidence interval (CI) - 1190 to - 502) and October 2020 (- 540; 95% CI - 861 to - 218). No decrease was observed for other types of surgery, BCS with ALND, and mastectomy with or without ALND. In the age-specific subgroup analysis, significant and transient reduction in BCS without ALND was observed in all age groups (0-49, 50-69, and ≥ 70 years). The number of BCS without ALND significantly decreased for a relatively short period in the early pandemic stages, suggesting reduced surgery for patients with a relatively low stage of cancer. Some patients with breast cancer might have been left untreated during the pandemic, and an unfavorable prognosis would be a concern.

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.

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.

Axillary Lymphadenopathy in the COVID-19 Era: What the Radiologist Needs to Know.

Axillary lymphadenopathy caused by the high immunogenicity of messenger RNA (mRNA) COVID-19 vaccines presents radiologists with new diagnostic dilemmas in differentiating vaccine-related benign reactive lymphadenopathy from that due to malignant causes. Understanding axillary anatomy and lymphatic drainage is key to radiologic evaluation of the axilla. US plays a critical role in evaluation and classification of axillary lymph nodes on the basis of their cortical and hilar morphology, which allows prediction of metastatic disease. Guidelines for evaluation and management of axillary lymphadenopathy continue to evolve as radiologists gain more experience with axillary lymphadenopathy related to COVID-19 vaccines. General guidelines recommend documenting vaccination dates and laterality and administering all vaccine doses contralateral to the site of primary malignancy whenever applicable. Guidelines also recommend against postponing imaging for urgent clinical indications or for treatment planning in patients with newly diagnosed breast cancer. Although conservative management approaches to axillary lymphadenopathy initially recommended universal short-interval imaging follow-up, updates to those approaches as well as risk-stratified approaches recommend interpreting lymphadenopathy in the context of both vaccination timing and the patient's overall risk of metastatic disease. Patients with active breast cancer in the pretreatment or peritreatment phase should be evaluated with standard imaging protocols regardless of vaccination status. Tissue sampling and multidisciplinary discussion remain useful in management of complex cases, including increasing lymphadenopathy at follow-up imaging, MRI evaluation of extent of disease, response to neoadjuvant treatment, and potentially confounding cases. An invited commentary by Weinstein is available online. ©RSNA, 2022.

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

BACKGROUND/AIM: COVID-19 has been a global pandemic for more than 2 years, and vaccination against COVID-19 using an mRNA vaccine is widespread. The COVID-19 vaccination can cause specific side-effects, such as axillary lymph node swelling; therefore, breast oncologists should pay attention to such occurrences. Initially, only two COVID-19 vaccinations were planned; however, in some countries third or fourth vaccines have been administered. Here, we present a female case who developed axillary lymph node swelling after her third vaccination. We have also reviewed the literature regarding this side-effect after a third or fourth COVID-19 vaccination. CASE REPORT: A 64-year-old woman who came to our clinic regarding a mammography abnormality in her left breast. She had no palpable mass, but a left breast mass was shown by mammography, and ultrasonography and magnetic resonance imaging indicated a hamartoma. At 2 months after her second COVID-19 vaccination when she underwent these tests, she had no axillary lymph node swelling. We planned a follow-up after 6 months. At her next visit, by chance, she underwent ultrasonography 14 days after she received a third COVID-19 vaccination, and a swollen axillary lymph node was observed. CONCLUSION: Axillary lymph node swelling can occur after a third COVID-19 vaccination. Therefore, breast oncologists will have to consider this side-effect of COVID-19 vaccination when diagnosing breast tumors.

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.

Axillary Lymph Node Swelling Mimicking Breast Cancer Metastasis After COVID-19 Vaccination: A Japanese Case Report and Literature Review.

BACKGROUND/AIM: COVID-19 started to spread as a pandemic in December 2019 and COVID-19 vaccination has been initiated worldwide. The efficacy of vaccination has been scientifically proven, but it might cause axillary lymph node swelling. To diagnose patients with axillary lymph node swelling caused by COVID-19 vaccination, we herein reviewed existing literature on this symptom. CASE REPORT: We report the case of a 70-year-old woman with a breast tumour. She had undergone cecum cancer surgery and regular computed tomography (CT). During breast tumour follow-up, she received scheduled CT that indicated severe axillary lymph node swelling mimicking breast cancer metastasis. We performed aspiration biopsy cytology of that lymph node, and determined this was not cancer metastasis but an effect of the COVID-19 vaccine. We confirmed this diagnosis at one month after computed tomography showed that the lymph node swelling had improved. CONCLUSION: Axillary lymph node swelling can occur after COVID-19 vaccination. Therefore, it is important to consider the effect of the COVID-19 vaccination on axillary lymph node swelling when diagnosing breast tumours.

SARS-CoV-2 mRNA Vaccination Causes Prolonged Increased Cortical Thickening and Vascularity in Ipsilateral Axillary Lymph Nodes.

OBJECTIVES: To describe the serial grey-scale and color Doppler appearance of ipsilateral axillary lymphadenopathy in response to the Pfizer-BioNTech Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) messenger RNA (mRNA) vaccine over 24 to 28 weeks. METHODS: The data for this study were collected during an observational study to determine whether mRNA vaccination induced a germinal center B cell reaction in blood and draining axillary lymph nodes. The current study evaluated the serial color Doppler and grey-scale sonographic appearance of these lymph nodes. Ten participants who each underwent 6 sonograms and FNAs over 24 to 28 weeks were included in the study. A total of 11 lateral lymph nodes were identified. Cortical thickness was measured and absence or presence of color Doppler flow in the hilum and lymph node cortex was graded (scale: 0-2). RESULTS: Eleven lateral axillary lymph nodes were biopsied over 24 to 28 weeks. Mean thickness varied through time (P < .001) and was greater weeks 2 to 7 compared to weeks 24 to 28 (mean differences of 2.6 to 1.3; P < .006), but weeks 14 to 17 mean thickness was not different from weeks 24 to 28 (0.57; P = .15). Cortical vascularity was increased in all 11 lymph nodes by week 5. Mean vascularity varied through time (P < .001) and was greater weeks 2 to 14 compared to weeks 24 to 28; mean differences ranged from 1.7 to 0.83 (P < .001). CONCLUSIONS: Serial grey-scale and color Doppler appearance of ipsilateral axillary lymph nodes after mRNA vaccination manifest as increased and prolonged cortical thickening and vascularity that diminishes and approaches normal by 24 to 28 weeks.

Metastatic melanoma in the breast and axilla: A case report.

Metastatic melanoma of the breast is rare, and demonstrates nonspecific imaging findings which may overlap with both benign and malignant pathology.1-3 Immunohistochemical stains are important to confirm the diagnosis, particularly combining S100, a sensitive marker for melanoma, with more specific tumor markers such as Melan-A and HMB-45, and lack of cytokeratin staining.4-7 We present a case of a 64-year-old female who presented for diagnostic imaging of a palpable abnormality in her right breast, with medical history notable for previously excised cutaneous melanoma, recent COVID-19 vaccination, and significant family history of breast cancer. Diagnostic mammogram of the right breast demonstrated a circumscribed mass in the lower inner quadrant corresponding to the area of palpable concern, as well as an additional non-palpable circumscribed mass in the lower inner quadrant. Targeted right breast ultrasound demonstrated corresponding circumscribed cystic versus solid masses as well as a morphologically abnormal right axillary lymph node. Pathologic results after tissue sampling of the two right breast masses and right axillary lymph node all yielded metastatic melanoma.

Ultrasound Features to Differentiate COVID-19 Vaccine-Induced Benign Adenopathy from Breast Cancer Related Malignant Adenopathy.

RATIONALE AND OBJECTIVE: To identify nodal features used to distinguish coronavirus disease 2019 (COVID-19) vaccine-Induced benign reactive adenopathy from malignant adenopathy. MATERIALS AND METHODS: This IRB-approved, single-institution, retrospective study compared features of 77 consecutive patients with benign adenopathy secondary to a messenger RNA COVID-19 vaccine with 76 patients with biopsy-proven malignant adenopathy from breast cancer. Patient demographics and nodal features were compared between the two groups using univariate and multivariate logistic regression models. A receiver operating characteristic analysis with the maximum value of Youden's index was performed for the cutoff value of cortical thickness for predicting nodal status. RESULTS: The mean cortical thickness was 5.1 mm ± 2.8 mm among benign nodes and 8.9 mm ± 4.5 mm among malignant nodes (p < 0.001). A cortical thickness ≥3.0 mm had a sensitivity of 100% and a specificity of 21% (area under the curve [AUC] = 0.60, 95% confidence interval [CI]: 0.52-0.68). When the cutoff for cortical thickness was increased to ≥5.4 mm, the sensitivity decreased to 74%, while the specificity increased to 69% (AUC = 0.77, 95% CI: 0.70-0.84).Cortical thickness correlated with nodal morphology type (r2 = 0.57). An axillary node with generalized lobulated cortical thickening had a 7.5 odds ratio and a node with focal cortical lobulation had a 123.0 odds ratio compared to one with diffuse, uniform cortical thickening only (p < 0.001). CONCLUSION: Cortical thickness and morphology are predictive of malignancy. Cortical thickness cutoff of ≥5.4 mm demonstrates higher specificity and improved accuracy for detecting malignant adenopathy than a cutoff of ≥3.0 mm.

Impact of the COVID-19 lockdown in France on the diagnosis and staging of breast cancers in a tertiary cancer centre.

OBJECTIVES: Due to COVID-19, a lockdown took place between March 17 and May 1, 2020, in France. This study evaluates the impact of the lockdown on the diagnosis and staging of breast cancers in a tertiary cancer centre. METHODS: Our database was searched for all consecutive invasive breast cancers diagnosed in our institution during the lockdown (36 working days), during equivalent periods of 36 working days before and after lockdown and a reference period in 2019. The number and staging of breast cancers diagnosed during and after lockdown were compared to the pre-lockdown and reference periods. Tumour maximum diameters were compared using the Mann-Whitney test. Proportions of tumour size categories (T), ipsilateral axillary lymph node invasion (N) and presence of distant metastasis (M) were compared using Fisher's exact test. RESULTS: Compared to the reference period (n = 40 in average), the number of breast cancers diagnosed during lockdown (n = 32) decreased by 20% but increased by 48% after the lockdown (n = 59). After the lockdown, comparatively to the reference period, breast cancers were more often symptomatic (86% vs 57%; p = 0.001) and demonstrated bigger tumour sizes (p = 0.0008), the rates of small tumours (T1) were reduced by 38%, locally advanced cancers (T3, T4) increased by 80% and lymph node invasion increased by 64%. CONCLUSION: The COVID-19 lockdown was associated with a 20% decrease in the number of diagnosed breast cancers. Because of delayed diagnosis, breast cancers detected after the lockdown had poorer prognosis with bigger tumour sizes and higher rates of node invasion. KEY POINTS: • The number of breast cancer diagnosed in a large tertiary cancer centre in France decreased by 20% during the first COVID-19 lockdown. • Because of delayed diagnosis, breast cancers demonstrated bigger tumour size and more frequent axillary lymph node invasion after the lockdown. • In case of a new lockdown, breast screening programme and follow-up examinations should not be suspended and patients with clinical symptoms should be encouraged to seek attention promptly.

COVID-19 post-vaccination lymphadenopathy: Report of cytological findings from fine needle aspiration biopsy.

The coronavirus COVID-19 pandemic has spurred the rapid development of vaccines, with vaccination programmes already underway in many countries. Regional lymphadenopathy is one of the documented side effects of vaccination. We document the fine needle aspiration cytological findings of an enlarged supraclavicular lymph node in a 34-year-old Asian female following the first dose of the Pfizer-BioNTech COVID-19 mRNA vaccine, which appears to be the first such report in a premorbidly well patient with no known history of malignancy. The cytological findings featured a reactive pattern in keeping with follicular hyperplasia, with prominent germinal centre elements including lymphohistiocytic aggregates and tingible-body macrophages. Despite an increased proportion of larger lymphocytes, the overall pattern was in keeping with a reactive pattern, bearing in mind the temporal and geographic relation to the vaccination injection. In instances of localised lymphadenopathy, particularly in supraclavicular or axillary locations, pathologists should be cognizant of the possibility of post-vaccination reactive lymphadenopathy, and seek clinical and radiological hints favouring a benign process, whilst recognising potential morphological overlaps with lymphoproliferative disorders. Awareness of this diagnostic pitfall is especially important as COVID-19 vaccination coverage is ramped up worldwide, leading to an expected increase in incidence of post-vaccination reactive lymphadenopathy.

Delay in Breast Cancer Treatments During the First COVID-19 Lockdown. A Multicentric Analysis of 432 Patients.

BACKGROUND/AIM: Extraordinary restrictions aimed to limit Sars-CoV-2 spreading; they imposed a total reorganization of the health-system. Oncological treatments experienced a significant slowdown. The aim of our multicentric retrospective study was to evaluate screening suspension and surgical treatment delay during COVID-19 and the impact on breast cancer presentation. PATIENTS AND METHODS: All patients who underwent breast surgery from March 11, 2020 to May 30, 2020 were evaluated and considered as the Lockdown group. These patients were compared with similar patients of the previous year, the Pre-Lockdown group. RESULTS: A total of 432 patients were evaluated; n=223 and n=209 in the Lockdown and Pre-lockdown-groups, respectively. At univariate analysis, waiting times, lymph-nodes involvement and cancer grading, showed a statistically significant difference (p<0.05). Multivariate analysis identified waiting-time on list (OR=1.07) as a statistically significant predictive factor of lymph node involvement. CONCLUSION: Although we did not observe a clinically evident difference in breast cancer presentation, we reported an increase in lymph node involvement.