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\title{Supraclavicular Lymphadenopathy after COVID-19 vaccination}



\author[1]{Kelsey Larkin}%
\author[2]{Archana Sharma}%
\author[1]{Gratian Salaru}%
\author[1]{Richard Drachtman}%
\affil[1]{Robert Wood Johnson Medical School}%
\affil[2]{Cancer Institute of NJ}%


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  \date{June 08, 2024}


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Supraclavicular Lymphadenopathy after COVID-19 vaccination

Kelsey Larkin \textsuperscript{1}, Archana Sharma DO\textsuperscript{2,}
Richard Drachtman MD,\textsuperscript{2}, Gratian Salaru ,
MD\textsuperscript{3}

\textsuperscript{1} Robert Wood Johnson Medical School

\textsuperscript{2}Division of Pediatric Hematology, Rutgers Cancer
Institute, Robert Wood Johnson Medical School

\textsuperscript{3}Department of Pathology, Robert Wood Johnson Medical
School

Correspondence to Archana Sharma, DO, Rutgers Cancer Institute of NJ,
195 Little Albany Street, Room 3507, New Brunswick, NJ 08901.

Telephone: 732-235-8864

Sharmaar@cinj.rutgers.edu

Text Word Count: 974

Brief running title: Lymphadenopathy after COVID-19 vaccination.

Key words: lymphadenopathy, COVID-19, vaccine,

Images: 2\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Abbreviation &\tabularnewline
\midrule
\endhead
COVID-19 & Coronavirus Disease of 2019\tabularnewline
CDC & Center for Disease Control\tabularnewline
FDA & Food \& Drug Administration\tabularnewline
\bottomrule
\end{longtable}

The Coronavirus Disease of 2019 (COVID-19) pandemic has impacted the
lives of everyone, driving the need for mass vaccinations since February
2020. Rapid medical advances have brought about vaccination options for
the world, helping to ameliorate the devastating effects of this
pandemic. As of August 2021, the Center for Disease Control (CDC) has
approved vaccinations for children 12 years of age and older. As further
developments are made, the age requirement will eventually include
younger children, and it is critical to understand the potential side
effects of the vaccinations. These side effects, such as malignant
appearing lymphadenopathy, may lead to potential invasive diagnostic
measures.

This case report presents two pediatric cases of supraclavicular
lymphadenopathy following COVID-19 vaccinations. These cases highlight
the need to develop assessment guidelines to help prevent potentially
harmful diagnostic procedures in the pediatric population.

In general practice, less than 1\% of lymphadenopathies are malignant,
with that number being 0.4\% in patients under 40 years of age. In
referral centers, the percentage of malignant cases rises to 17\% and
40-60\% in patients presenting with related symptoms. However, the
location of lymphadenopathy brings about different prevalence rates with
the supraclavicular region having the highest risk, 90\% in those older
than 40 and 25\% in those younger. (Mohseni). Generally, it is standard
practice to biopsy true supraclavicular nodes in the absence of known
infectious causes. On the contrary, recent COVID vaccination may be an
indication for watchful waiting of enlarged supraclavicular lymph nodes
as we describe below.

We present two cases of patients who presented with supraclavicular
lymphadenopathy within weeks after receiving COVID-19 vaccination. The
patients underwent biopsies for the suspicion of a malignancy and both
biopsies showed reactive lymph nodes without evidence of malignancy. Of
note, the vaccine was given on the same side as the lymphadenopathy was
recognized. We highlight these cases to discuss the possibility that the
COVID-19 vaccines could potentially trigger an inflammatory response,
resulting in lymphadenopathy which can be mistaken for a malignancy.

The first patient, a 16-year-old male presented for left supraclavicular
adenopathy. The patient had noticed the mass two days prior to the visit
and notably 2 weeks after his first dose of the COVID-19 vaccine. The
patient did not present with any additional symptoms and denied any
fever, night sweats, unexplained weight loss or other notable lymph
nodes. The patient denied any travel or potential close COVID-19
contacts.

At the time of presentation, the lymph node was approximately 1 cm in
size and was freely movable, non-matted, ``rubbery,'' singular lymph
node in the left supraclavicular region. Due to the location, a surgical
excision was performed. The pathology report showed a final diagnosis of
reactive follicular hyperplasia and focal increased Epstein-Barr virus
positive cells. The EBV positive cells are of uncertain significance and
a diagnostic evaluation showed a serum negative EBV PCR. EBER in situ
hybridization on the collected specimen are suggestive of a prior
infection and the EBV IgG was positive in this patient.

The second patient, a 13-year-old male presented with left
supraclavicular adenopathy. The patient had noticed the mass a few weeks
prior and noted that it was transiently painful, but the pain had since
subsided. There were no other systemic complaints. The COVID vaccination
was given approximately 2 weeks prior to the appearance of the
supraclavicular lump. The lump was an approximately 1 cm, freely
moveable soft, non-matted, nontender, singular lymph node in the left
supraclavicular region. Due to the location of the lymph node and
suspicion of malignancy, the node was surgically removed. The pathology
showed florid, reactive follicular hyperplasia with foci of follicular
lysis, increased immunoblasts, and progressive transformation of
germinal centers. (See images 1-4)

During the COVID-19 pandemic, the Food and Drug Administration (FDA) has
approved

multiple vaccinations to combat the viral outbreak. This case report
presents two separate but

remarkably similar cases of supraclavicular adenopathy that arose within
2 weeks post-COVID-

19 vaccination. Lymphadenopathies corresponding with inflammation
inducing vaccinations

have been previously cited in the literature and are uncommon but
potential side effects. There is

literature supporting significant unilateral cervical and
supraclavicular lymphadenopathy

following human papilloma virus vaccination {[}1{]} . Furthermore, it
has been reported that bacille

Calmette-Guerin (BCG) lymphadenitis is the most common complication of
the tuberculosis

vaccine and has been found to either regress on its own, or become large
and suppurative {[}2{]}. With the current and extensive vaccination
efforts to combat COVID-19, it is increasingly important to recognize
and understand possible complications and how to effectively diagnose
without resulting in additional medical procedures.

There have been numerous publications about ipsilateral axillary
lymphadenopathy and management strategies {[}3{]}, {[}4{]}, {[}5{]},
{[}6{]}. In one publication by Mehta et. al, there were 4 reported cases
of unilateral axillary lymphadenopathy in female patients ranging from
ages 42 to 59. Our case discussion presents a unique situation due to
the location of lymphadenopathy and age of the patients. The
supraclavicular location of lymphadenopathy is less commonly reported
than the axillary finding, and it is especially interesting that two
cases presented similarly in a short time frame. As the FDA continues to
expand the qualifying age group for vaccination, it is exceedingly
important to develop an algorithm for potential similar cases. The need
for routine chest radiographs as well as procedures requiring surgery
and anesthesia it should be addressed in this setting. It can be
suggested that in the absence of ``B-symptoms'' such as fever, night
sweats and weight loss, the lymphadenopathy is to be closely monitored
for changes that would increase the suspicion of malignancy. While there
is always a risk-reward balance when it comes to testing for malignancy,
especially with invasive or radiation-exposure modalities, the novelty
of this virus and its vaccinations emphasizes a need for additional
guidelines. It is critical to identify and delineate risk factors that
would lead the clinician to aggressively pursue a biopsy as opposed to
observation.

1. Studdiford J, Lamb K, Horvath K, Altshuler M, Stonehouse
A:\textbf{Development of Unilateral Cervical and Supraclavicular
Lymphadenopathy After Human Papilloma Virus Vaccination}
.\emph{Pharmacotherapy: The Journal of Human Pharmacology and Drug
Therapy} 2008, \textbf{28} (9):1194-1197.

2. Goraya JS, Virdi VS: \selectlanguage{ngerman}\textbf{Bacille Calmette-Guérin lymphadenitis}
.\emph{Postgraduate Medical Journal} 2002, \textbf{78} (920):327-329.

3. Becker AS, Perez-Johnston R, Chikarmane SA, Chen MM, El Homsi M,
Feigin KN, Gallagher KM, Hanna EY, Hicks M, Ilica AT \emph{et al}
:\textbf{Multidisciplinary Recommendations Regarding Post-Vaccine
Adenopathy and Radiologic Imaging: Radiology Scientific Expert Panel}
.\emph{Radiology} 2021, \textbf{300} (2):E323-e327.

4. Edmonds CE, Zuckerman SP, Conant EF: \textbf{Management of Unilateral
Axillary Lymphadenopathy Detected on Breast MRI in the Era of
Coronavirus Disease (COVID-19) Vaccination} . \emph{AJR Am J
Roentgenol}2021.

5. Mehta N, Sales RM, Babagbemi K, Levy AD, McGrath AL, Drotman M,
Dodelzon K: \textbf{Unilateral axillary Adenopathy in the setting of
COVID-19 vaccine} . \emph{Clin Imaging} 2021, \textbf{75} :12-15.

6. Lehman CD, D'Alessandro HA, Mendoza DP, Succi MD, Kambadakone A, Lamb
LR: \textbf{Unilateral Lymphadenopathy After COVID-19 Vaccination: A
Practical Management Plan for Radiologists Across Specialties} . \emph{J
Am Coll Radiol} 2021, \textbf{18} (6):843-852.

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