The head and neck contain around 2/3rd of the lymph nodes in the body. Besides, the inflammatory or malignant process in any area can reach the neck through the lymphatic system. Therefore, there is a huge list of causes of cervical lymphadenopathy (enlargement of a node > 1 cm in diameter). Cervical lymphadenopathy is common in the pediatric population, and most of the cases are benign. The first systematic review about the causes of cervical lymphadenopathy in children of Deosthali et al. [7] reported that 67.8% of the 2687 cases are due to nonspecific benign causes, followed by Epstein-Barr virus (8.86%), malignancy (4.69%), and granulomatous disease (4.06%). In the presenting case, the histopathology and immunohistochemistry evaluations revealed the reactive benign nature of the supraclavicular lymph node. The high possible cause of this cervical lymphadenopathy was COVID-19 because the patient was diagnosed as COVID-19 by real-time PCR of the nasopharyngeal swab and high IgM as well as an absence of indicators of other pathologies in the history, examination, and investigations. Accordingly, COVID-19 can lead to reactive cervical lymph node enlargement.
Involvement of the axillary and/or supraclavicular lymph nodes on the same side is a frequent adverse effect of the vaccines against COVID-19. This is due to local activation of the immune response [8][9][10]. Moreover, Distinguin et al. reported 3 cases of cervical lymphadenopathy in group II (upper jugular group) on magnetic resonance imaging (MRI) in patients with COVID-19. All those patients have complained of otorhinological symptoms (anosmia, aguesia, nasal obstruction, rhinorrhea, and sore throat). These symptoms due to inflammation of the nose, nasopharynx, and oropharynx that caused by SARS-CoV-2. As a result of this inflammation, a local immune reaction occurs, resulting in lymph node enlargement of the Waldeyer’s ring, neck, and parotid regions [6]. Interestingly, we presented the first case in the world of unilateral supraclavicular enlargement in a patient with COVID-19. Although the mechanism of supraclavicular lymphadenopathy is obscure, it is of utmost importance to put the COVID-19 in the differential diagnosis of supraclavicular lymphadenopathy.
Identification of the possible ways of the transmission of the SARS-CoV-2 has a major role in understanding the mechanism of the infection with its further treatment options. The specific coronavirus receptor (ACE-2 receptor) is distributed in all body tissues, including the lymph nodes [11], therefore, it is possible to find the virus in the lymph node as in the presenting case, leading to inflammation and enlargement of the node. Another possible mechanism of getting enlargement of the supraclavicular lymph node is a local immune response in the lung.
According to the American College of Radiology (ACR) recommendations, chest X-ray and computerized tomography (CT) should not be used as a screening or first diagnostic tool of the COVID-19 owing to the similarity of the radiological signs among various lung conditions. However, radiological investigation in the pediatric population plays an essential tool for moderate and severe forms of COVID-19 (as a baseline, assessment of complications, and assessment of treatment response or progression of the disease). Moreover, chest X-ray is considered the first radiological investigation in children, and CT scan is reserved for suspicious cases of pulmonary embolism or worsening clinical condition [12]. Pulmonary abnormalities in children are unilateral in 55% and bilateral in 45% of affected children [13] and about 8% are affected the right upper lobe of the lung [14] which was a similar finding of our patient.
Cervical lymphadenopathy following COVID-19 is extremely rare. However, it can put on the long list of differential diagnoses which include infections and primary tumor (lymphoma) or secondary malignant lymph node. Radiological investigations in the form of sonography or MRI as a diagnostic tool should be performed when there are suspicious findings on physical examination.
As reported in the literature, supraclavicular lymphadenopathy after taking the COVID-19 vaccine affects mostly females and occurs in up to 24 days (mostly in the first 10–15 days). It gradually subsides within 4–6 weeks [15]. Our case presented with features of COVID-19 (fever, fatigue, cough, and loss of smell and taste) for 10 days, and the disease was confirmed by a real-time PCR test of the nasopharyngeal swab. Seven days following the resolution of the symptoms, there was an appearance of right-sided supraclavicular lymphadenopathy. Supraclavicular lymphadenopathy in children, particularly if persists for more than two weeks, carries a sinister pathology [16], therefore we subjected the child to an excisional biopsy which revealed a benign nature of the lesion on the histopathological and immunohistochemical evaluation. Accordingly, the supraclavicular lymphadenopathy in the presenting case was highly suspicious that the COVID-19 was a cause.