International Journal of Anesthesiology & Pain Medicine

Keywords

Mediastinal mass; Lymphadenopathy; COVID-19; SARS-CoV-2

Introduction

As of December 2019, a new highly infectious coronavirus (SARS-CoV-2) has begun spreading worldwide causing a wide variety of clinical manifestations, ranging from asymptomatic to extremely severe. Many studies in the past year have focused on the epidemiological, clinical, and radiologic characteristics of coronavirus disease 2019 (COVID-19) with the purpose of providing guidance for frontline medical workers facing this international emergency. The focus of this review is to summarize what little is known about a rather uncommon radiologic feature of COVID-19 that is the presence of a mediastinal mass with lymphadenopathy, in patients who are not critically ill.

Literature Review

Coronavirus disease (COVID-19) was first reported in Wuhan, China, in 2019, and has since spread throughout the world causing a global public health emergency. Based on the evidence gathered during this past year, although COVID-19 infection is mainly a respiratory illness, the virus is capable of spreading throughout the body affecting all organs; most patients commonly present with mild signs and symptoms, such as anosmia, ageusia, fever, dyspnea, dry cough, sore throat, and abdominal pain with or without diarrhea [1,2].

Among the possible complications, there can be neurological disorders, renal dysfunction, cardiac abnormalities, and gastrointestinal manifestations [3]. Another known complication of SARS-CoV-2 infection is a pro-thrombotic state [4], which may lead to either arterial or Venous Thromboembolism (VTE): the increased incidence of Pulmonary Embolism (PE) and ischemic stroke in COVID-19 affected patients has prompted an improvement in VTE diagnostic strategies as well as in its treatment since the first few months of the pandemic [4,5].

A 50-year-old woman, former smoker with a negative medical history, went to the emergency room in March 2020 for pain in the neck and left arm. No dyspnea or coughs were reported. At clinical examination the upper left arm and the neck showed swelling edema and redness. Blood tests showed leukocytosis, C-reactive Protein and D-dimer elevated SARS-CoV-2 and H1N1 nasal swabs were negative. An eco-color-doppler showed left upper extremity deep vein thrombosis (UEDVT). The anatomical extension of the thrombosis was up to the left axillary vein, left subclavian vein, left jugular vein. The patient was therefore treated with Low Molecular Weight Heparin (Enoxaparin) 8000 IU BID. The UEDVT was due to a mass in the upper anterior mediastinum compressing and displacing the left anonymous vein evident at a contrast medium Chest Computed Tomography (CT).

A surgical mediastinal mass biopsy by VATS was therefore planned, but a new SARS-CoV-2 nasal swab was positive. This, together to the pulmonary embolism, prompted us to delay the procedure. The patient was relocated in a dedicated SARS-CoV-2 department where she was treated with azithromycin and hydroxychloroquine for 10 days and long-term anticoagulation therapy. The patient was discharged in home isolation protocol 24 days after access (11 from positivity). After the execution of 2 negative SARS-CoV-2 control nasal swabs, respectively, 15 and 20 days after discharge, the patient was revaluated for the surgical procedure. Because the previous PET-CT dated back a couple of months before it was repeated. A complete regression of the mediastinal lesion was evident, confirmed also by a contrast medium CT, which showed also a resolution of the UEDVT.

According to a WHO report on SARS-CoV-2, the disease has no specific manifestation, and the presentation can range from completely asymptomatic to severe pneumonia and death. In our patient, the presenting symptom of the SARS-CoV-2 was a UEDVT due to a mass in the anterior mediastinum compressing and displacing the left anonymous vein. There was also some pulmonary embolism due to the well-known thrombotic complication of the disease. Interestingly, the mediastinal mass that was initially strongly suspected of lymphoproliferative disease disappeared after 2 months with the resolution of the SARS-CoV-2 without any specific therapy. It must therefore be considered as enormous mediastinal confluent lymphadenopathy.

In the specific case of patients with pulmonary manifestations, in addition to what reported above, patients may also present radiologically with signs ranging from mild opacification at chest X-ray to severe interstitial pneumonia at CT scan [6]. Chest CT scans are the most accurate radiologic examinations to evaluate COVID-19 in patients with respiratory illness, with isolated Ground-Glass Opacities (GGO) or a combination of GGO and consolidative opacities being some of the most common findings [7].

Other, less common radiologic signs include pleural and pericardial effusion, lymphadenopathy, cavitation, and CT halo sign; however, these seem to be mostly found in critically illpatients [3,7,8]. Currently, it seems that while it may be found in the more severe cases, lymphadenopathy is a rare manifestation [3,7-9].

Therefore, some authors believe that lymphadenopathy should not be considered an atypical characteristic of COVID-19 patients, particularly those who are severely ill, as it is probably a reactive phenomenon to viral disease and inflammation [10].

In our previous report [11], we presented the case of a 50- year-old woman, a former smoker with an otherwise silent medical history, who reported to the Emergency Department of our Hospital in March 2020 for pain in the neck and left arm. The eco-color Doppler revealed Left Extremity Deep Vein Thrombosis (UEDVT), for which she was treated with Low Molecular Weight Heparin (LMWH), and whose triggering factor was hypothesized to be a previously unknown mediastinal mass. The mediastinal mass was investigated via CT scan and shown to be compressing and displacing the left brachiocephalic vein.

FDG-PET examination also showed an intense contrast uptake by the mass, suggesting either a lymphoproliferative disease or a metastasis from a yet undiscovered malignancy. However, further investigation on the nature of the mass was halted when the patient’s nasal swab for SARS-CoV-2 came back positive. After the patient was discharged from the dedicated COVID-19 ward, she was re-evaluated for surgery, but the mediastinal mass had completely regressed along with the UEDVT. In the following months, another patient came to our department for the incidental discovery of a thoracic mass. CT images showed a suspicious mediastinal mass in this patient who had just been hospitalized for bilateral COVID-19 pneumonia.

Considering our previous experience, the case was discussed and it was ultimately decided to wait for the resolution of the COVID-19 infection and only then perform a FDG-PET scan to reevaluate the lesion. As with our previous case, the mass regressed with disease resolution, and glucose uptake at the level of the remaining lesion was mild. At the following radiologic follow-up, the mass had completely disappeared. Although there are few cases of mediastinal lymphadenopathies reported in literature, usually in critically ill COVID-19 patients, not much has been discussed about the diagnostic and therapeutic approach.

Based on our experience, we recommend to wait until disease resolution before proceeding with invasive diagnostic investigations. However, at the same time, it is of fundamental importance to monitor these patients over time to exclude either permanence or worsening of the mediastinal disease. In this latter case, it is obviously necessary to proceed with adequate diagnostic investigations, such as a guided CT needle biopsy or a surgical biopsy, regardless of COVID-19 resolution.

Discussion and Conclusion

Thanks to the data gathered since the beginning of 2020, the heterogeneity of clinical and radiologic manifestations of COVID-19 are now known. However, the association between SARS-CoV-2 and mediastinal lymphadenopathy is only just starting to be fully acknowledged in the literature. Our experience seems to suggest that in cases of mediastinal mass in SARS-CoV-2 patients, the radiological examination (FDG-PET and/or CT scan) should be repeated after the resolution of the infection and before performing the procedure. The repeated radiologic examinations are justified in this case in order to avoid unnecessary surgical procedures in lesions that may spontaneously regress with time.

Data Availability Statement

The original contributions presented in the study are included in the article/supplementary material further inquiries can be directed to the corresponding authors.

Ethics Statement

Ethical review and approval were not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author Contributions

All authors participated equally in the case and in the writing of the manuscript.

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