<div>Abstract: Objectives</div><div>The objectives of this study are to describe the incidence and age range
of presentation of lateral neck cysts, to evaluate a management
algorithm for adults presenting with lateral neck cystic lesions and to
report the age incidence at which malignant cystic lesions in the neck
have clinically presented as lateral neck cysts.</div><div>Design</div><div>A retrospective review of histologically diagnosed branchial cysts
between 1995 and 2014 at a single centre.</div><div>Setting</div><div>XXX University Hospitals NHS Foundation Trust.</div><div>Participants</div><div>A single senior head and neck pathologist and the ENT head and neck
team.</div><div>Main outcome measures</div><div>Does a dedicated pathway help to identify malignancy in lateral neck
cysts earlier in the diagnostic pathway?</div><div>Results</div><div>When using a random investigative pathway the sensitivity in
distinguishing malignant from non-malignant was 93%, specificity 12%
with a PPV of 83% and NPV 28%. When using a defined investigative
protocol, the sensitivity was 94%, specificity 67%, PPV of 85% and
NPV 86%.</div><div>Conclusions</div><div>This study conveys that using a structed pathway when working up
patients with a lateral neck cyst results in a greater sensitivity,
specificity, PPV and NPV in distinguishing malignancy compared to an
unstructured workup.</div><div>Key points</div><div>1) Establishing a lateral neck cyst as a benign structure is a diagnosis
of exclusion</div><div>2) There is no established protocol for this pathway.</div><div>3) The need for a diagnostic pathway is important given the impact of
COVID-19</div><div>4) The diagnostic challenge is differentiating benign from malignant</div><div>5) For lateral neck cysts a cut off age of 35 may not be appropriate</div><div>Introduction</div><div>Benign lateral neck cysts are recognised to present most commonly in
children and young adults with the majority classified as branchial
cleft cysts<sup>1</sup>. While recognised to occur in adults,
little is known about their incidence. In adults,the diagnostic
challenge is to differentiate benign lateral neck cysts from other
pathology, commonlycystic nodal metastasis of squamous cell
carcinoma<sup>2</sup>.</div><div>Head and neck cancers (HNC) represent the sixth most common cancer
worldwide with approximately 630,000 new patients diagnosed annually.
The incidence of HNC has increased significantly over the last 30 years
and is this rise is predicted to continue. In part this is due to a
significant increase in oropharyngeal cancers associated with the human
papilloma virus (HPV). HPV associated squamous cell carcinoma commonly
presents with cystic neck metastasis. For this reason, many protocols
mandate that above the age of 35 years, a cystic mass is considered
malignant until proven otherwise<sup>3</sup>. However, with the
increasing incidence of HNC associated with HPV, a cut off age of 35 may
not be appropriate<sup>4</sup>.</div><div>Establishing a lateral neck cyst as a benign structure is a diagnosis of
exclusion, but there is no established protocol for this
pathway<sup>5</sup>. The need for a diagnostic pathway has never
been more prescient given the impact of COVID-19 and the deferral of a
high number of elective operations.</div><div>The aims of this study are to describe the incidence and age range of
presentation of lateral neck cysts, to evaluate a management algorithm
for adults presenting with lateral neck cystic lesions and to report the
age incidence at which malignant cystic lesions in the neck have
clinically presented as lateral neck cysts.</div><div>Patients and Methodology</div><div>A retrospective review of histologically diagnosed branchial cysts
between 1995 and 2014 at a single centre (XXX University Hospitals NHS
Foundation Trust) was undertaken to establish the incidence at different
ages. This data was reviewed by a single senior head and neck
pathologist.</div><div>A retrospective review into management of patients presenting through
the XXX head and neck cancer MDT with lateral neck cystic between
2012-2019 was undertaken. Data collected included all diagnostic
investigations and the final diagnosis. Patients with clinically
apparent primary malignancy, history of head and neck cancer or
irradiation, and incomplete radiological and/or cytological workup were
excluded from the study.</div><div>Patients were stratified into two pathways, an ad-hoc diagnostic pathway
with a decision to treat based on the available test results. The other
pathway was a defined protocol based on age of presentation.
Sensitivity, specificity, positive predictive and negative predictive
values for the pathways were calculated.</div><div>Results</div><div>Between 1995 and 2018, 205 patients with histologically confirmed
branchial cysts were identified. These cases ranged in age from 11
months to 88 years.</div><div>Most branchial cysts were noted in patients between the ages of 26 and
40 years, with peak incidence between age 31-35 years (Figure 1). A
total of 87 branchial cysts were identified over the age of 35,
representing 42% of the overall cohort.</div><div>Between 2012-2019, 102 patients presented to the XX Head and Neck team
with a lateral neck cyst; for 5 patients follow up records were not
available, and these were excluded. Of the remaining 97, there were 50
male and 47 female patients with an age range of 0-77 years and a mean
age of 30 years. The diagnostic pathway was reviewed for this cohort.</div><div>During this period some patients were referred having completed an
ad-hoc set of investigations, which included ultrasound and/or MRI
imaging and fine needle aspiration cytology. Decision recommendations
were based on the best available evidence.</div><div>For those patients over 35 referred early in their pathway they followed
a pre-agreed diagnostic pathway. Figure 2. This involved an incremental
number of investigations; clinical examination, USS guided FNAC, PET-CT,
surgical excision. If any of these investigations indicated malignancy,
then the patient was transferred to an appropriate care pathway.</div><div>For those patients investigated under the ad-hoc pathway 71 patients
were identified, 35 males and 36 females, with a. mean age of 38 (range
18-75).</div><div>Following a review of the available investigations 50 patients had a
pre-operative diagnosis of a branchial cyst or other benign lateral neck
cyst that was subsequently confirmed based on final histology. 14
patients had a pre-operative diagnosis of branchial cyst or other benign
lateral neck cyst but at final histology were confirmed to have a
diagnosis of metastatic SCC or other malignant lateral neck cyst. 5
patients had a pre-operative diagnosis of highly probable metastatic SCC
or other cystic malignant lesion but on final histological assessment
had a benign branchial cyst or other benign lateral neck cyst. 2
patients had a pre-operative diagnosis of metastatic SCC or another
malignant cystic lesion and this was confirmed histologically. The
results for this combined (clinical/imaging/cytology) pathway indicated
that the sensitivity 93%, specificity 12% with a PPV of 83% and NPV
of 28%.</div><div>27 patients were identified having been referred with a cystic lesion in
the neck and followed the defined pathway, Figure 2. 15 males and 12
females with a mean age of 58 (range 34-82).</div><div>Following a review of the available investigations 17 patients had a
pre-operative diagnosis of a branchial cyst or other benign lateral neck
cyst that was subsequently confirmed based on final histology. 3
patients were identified with a pre-operative diagnosis of branchial
cyst or other benign lateral neck cyst that at final histology was
metastatic SCC or other malignant lateral neck cyst. 1 patient had a
presumptive diagnosis of a malignant cystic lesion in the neck that on
final histology was a reported as a branchial cyst or other benign
lateral neck cyst. 6 patients were identified with a pre-operative
diagnosis of metastatic SCC or another malignant cystic lesion and this
was confirmed on final histology. Using this investigative pathway, the
sensitivity was 94%, specificity 67%, PPV of 85% and NPV of 86%.</div><div>Of the 97 patients in this cohort 25 had a final diagnosis of metastatic
squamous cell carcinoma. The age distribution is shown in Figure 3. 1
patient (6%) was under the age of 35. Of those under the age of 35 the
age presentation of malignant cystic metastasis was at 21 years old.</div><div>Discussion</div><div>There remains some debate regarding the cause for benign lateral neck
cysts. They are recognised to be a common a common presentation in
children and young adults<sup>3</sup>. This study found that 58%
of histologically confirmed branchial cysts occurred in patients under
the age of 35. While the incidence deceased with increasing age, this
study found that 42% of branchial cysts occurred over the age of 35,
with the oldest patient being 78 years old. The most frequent age
bracket for occurrence of branchial cysts was 31-35 years.</div><div>While in children a lateral neck cyst is almost certainly benign in
nature, in adults the important differentiation is from cystic
metastasis,and in particular metastatic HPV associated oropharyngeal
carcinoma<sup>6</sup>. This has become an important consideration
due to the increasing incidence of oropharyngeal cancer.</div><div>There are no convincing cases documenting origin of squamous cell
carcinoma from branchial cysts and another possibility is of an unknown
primary in the upper aerodigestive tract<sup>6</sup>. In
adults,the diagnosis of benign branchial cysts and exclusion of
malignancy requiresimaging and cytology, though ultimately histology
from an excision biopsy may be needed<sup>7</sup>.</div><div>The ability to have a diagnosis of a malignant or benign lesion as early
as possible has many advantages. Avoiding an excision biopsy of a
malignant cystic lesion in the neck allow for appropriate planning and
treatment of malignancy. This study indicates an 8% prevalence of
malignancy in a lateral neck cyst. Other studies have reported a rate of
malignancy between 9 to 14% with malignant tumours found more frequent
in patients older than 40 years of age<sup>7</sup>. The disparity
in findings in this study may be a reflection of a more aggressive
diagnostic pathway or potentially earlier referrals for neck masses in
all younger age groups which are subsequently excised before malignant
transformation can potentially occur. The diagnostic accuracy of
preoperative fine needle aspiration for cytology has been reported to
have a sensitivity of 88.8% and a specificity of
60.0%<sup>2</sup>. It is the authors opinion that a dedicated
head and neck cytopathologist linked into a multidisciplinary review of
the history and diagnostic imaging is an advantage.</div><div>This study aimed to compare two pathways that have been utilised. It
suggests that there is an advantage in having a defined pathway. In
particular being able to increase the specificity and negative
predictive value of the testing. This has important implications in
particular following on from the recent Covid-19 pandemic. During this
time procedures on benign lesions have been deferred due to the
peri-operative risk of Covid-19 infection and reduced recourses. A
failure to recognised malignancy in this period could result in a delay
in treatment and a worse prognosis.</div><div>The age at which malignancy is actively screened for is frequently
quoted as 35 years. This study shows that 6% percentage of malignancies
were detected in under 35s. This suggests that a cut off of 35 may not
be appropriate and that this could be lowered to 20 which would cover
6% of patients</div><div>These findings need to be interpreted due to the limitations of the
study design; retrospective and a small cohort.</div><div>References</div><div>1. Franzen et al. (2019). Cystic Lateral Neck Lesions: Etiologic and
Differential Diagnostic Significance in a Series of 133 Patients.
Anticancer Research, 39(9), 5047–5052.</div><div>2. Yehuda et al. The incidence of malignancy in clinically benign cystic
lesions of the lateral neck: our experience and proposed diagnostic
algorithm. Eur Arch Otorhinolaryngology. March 2018.</div><div>3. Grønlund et al. The true malignancy rate in 135 patients with
preoperative diagnosis of a lateral neck cyst. Laryngoscope
investigative otolaryngology. 2016.</div><div>4. Stefanickaet al. Incidence and clinical predictors of cystic squamous
cell carcinoma metastases in lateral cervical cysts. J LaryngolOtol
2019;1–6</div><div>5. P. J. Andrews&amp; C. E. B. Giddings. Management of lateral cystic
swellings of the neck, in the over 40s’ age group. The Journal of
Laryngology &amp; Otology. 2003, Vol. 117, pp. 318–320.</div><div>6. Regauer et al. Cystic lymph node metastases of squamous cell
carcinoma of Waldeyer’s ring origin. British Journal of Cancer (1999)
79(9/10), 1437–1442</div><div>7.Koch et al. Cystic masses of the lateral neck – Proposition of an
algorithm for increased treatment efficiency. Journal of
Craniomaxillofacial Surg. Sept 2018.</div>