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\begin{document}

\title{Irreversible facial nerve palsy as a revelator of parotid gland cancer}



\author[1]{Joanna Marszał}%
\author[1]{Anna Bartochowska}%
\author[1]{Hanna Klimza}%
\author[1]{Piotr Nogal}%
\author[1]{Małgorzata Wierzbicka}%
\affil[1]{Poznan University of Medical Sciences}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\begin{abstract}
Aim of the study. The goal of the study was to assess the frequency of
malignancies hidden under the diagnosis of ``Bell's palsy''. We aimed to
create diagnostic algorithm to avoid failures concerning patients whose
only symptom of parotid gland cancer was irreversible FNP. Materials and
methods. We analyzed 253 consecutive patients with FNP treated in our
department in the last 5 years. All patients with irreversible FNP were
reassessed in 6-12 months. We underlined all shortcomings in the
diagnostics of those in whom malignancies were found out in MRI of the
neck and presented the proposal of diagnostic algorithm to avoid missing
such an entity. Results. Bell's palsy was observed in 157 / 253 patients
(62.06\%), in 36 / 157 (22.92\%) it remained permanent. In 4 / 36
patients (11.11\%) with irreversible FNP, which constituted 2.54\% of
all ``Bell's palsy'' cases, parotid gland deep lobe mass was found out
in MRI. In one patient infiltration of the skull base was diagnosed.
Adenoid cystic carcinoma was confirmed in final histopathology in all
cases. Conclusions. Our experience has shown that irreversible FNP can
be a revelator of the malignant tumor located in the deep lobe of the
parotid gland. Contrast-enhanced MRI covering intra- and extracranial
segments of facial nerve should be ordered in all cases of FNP without
recovery after 4 months. The main point of our study is to underline
that the assessment of the deep lobe of the parotid gland with MRI
should be included in the standard diagnostic protocol in all
irreversible ``Bell's palsy'' cases. Key words: Bell's palsy, facial
nerve palsy, parotid gland cancer%
\end{abstract}%



\sloppy


\emph{I} \emph{rreversible facial nerve palsy as a revelator of parotid
gland cancer}

\emph{Abstract}

\textbf{Aim of the study} . The goal of the study was to assess the
frequency of malignancies hidden under the diagnosis of ``Bell's
palsy''. We aimed to create diagnostic algorithm to avoid failures
concerning patients whose only symptom of parotid gland cancer was
irreversible FNP.

\textbf{Materials and methods} . We analyzed 253 consecutive patients
with FNP treated in our department in the last 5 years. All patients
with irreversible FNP were reassessed in 6-12 months. We underlined all
shortcomings in the diagnostics of those in whom malignancies were found
out in MRI of the neck and presented the proposal of diagnostic
algorithm to avoid missing such an entity.

\textbf{Results} . Bell's palsy was observed in 157 / 253 patients
(62.06\%), in 36 / 157 (22.92\%) it remained permanent. In 4 / 36
patients (11.11\%) with irreversible FNP, which constituted 2.54\% of
all ``Bell's palsy'' cases, parotid gland deep lobe mass was found out
in MRI. In one patient infiltration of the skull base was diagnosed.
Adenoid cystic carcinoma was confirmed in final histopathology in all
cases.

\textbf{Conclusions} . Our experience has shown that irreversible FNP
can be a revelator of the malignant tumor located in the deep lobe of
the parotid gland. Contrast-enhanced MRI covering intra- and
extracranial segments of facial nerve should be ordered in all cases of
FNP without recovery after 4 months. The main point of our study is to
underline that the assessment of the deep lobe of the parotid gland with
MRI should be included in the standard diagnostic protocol in all
irreversible ``Bell's palsy'' cases.

\emph{Key words:} Bell's palsy, facial nerve palsy, parotid gland cancer

\emph{Key points:}

All patients with irreversible facial nerve palsy require further
diagnostics to exclude organic, infectious, metabolic and
autoimmunological cause of such a process.

Clinicians should pay special attention to patients with new or
worsening neurologic findings at any point, ocular symptoms developing
at any point, or incomplete facial recovery 3 months after initial
symptom onset.

The differential diagnosis should put emphasis on expansive processes,
including cancers.

Depending on the suspected localization of the lesion, high-resolution
CT of the temporal bone and MRI with contrast enhancement are
recommended for the evaluation of the facial nerve.

In selected undiagnosed cases, repeated imagings or even explorative
surgery with biopsy of tissues adjacent to the facial nerve should be
considered.

\emph{Introduction}

Bell's palsy accounts for approximately 65\% of acute facial
palsies.\textsuperscript{1} Diagnosis of Bell's palsy is still one of
exclusion. Its etiology has been the subject of debates for years
.\textsuperscript{2-4} Nowadays, most authors refer to the theory of
inflammatory demyelinating neuritis caused by reactivated latent viral
infection (herpex simplex virus 1, herpes zoster virus) or other
pathogens like Coxsackie virus, adenovirus or Epstein-Barr virus. Among
non-infectious causes atherosclerosis and autoimmunological disorders
(like Hashimoto or Sjogren disease) leading to facial nerve edema are
listed.\textsuperscript{3} Facial nerve palsy (FNP) has occasionally
been reported as a complication following the administration of some
vaccinations, including mRNA vaccines (BNT162b2 and mRNA-1273) against
coronavirus disease 2019 (COVID-19).\textsuperscript{5-6} Most
researchers show that over 70\% of patients with Bell's palsy make a
full recovery in one week to six months.\textsuperscript{2,4} In some
groups, involving people over 60, patients with severe pain or pregnant
at onset, with complete paralysis, suffering from diabetes and high
blood pressure, the course of the disease may be more severe, even with
cases of permanent FNP.\textsuperscript{2,4}All patients with
irreversible palsy need further diagnostics to exclude organic,
infectious, metabolic and autoimmunological cause of such a process. The
detailed evaluation should be based on in-depth history, clinical
neurological and otolaryngological examination, laboratory tests and
imagings to check for any viral (HIV, human herpesvirus 6, mumps virus,
cytomegalovirus, and rubella virus), bacterial (Borrelia burgdorferi,
Rickettsia, otogenic process), autoimmunological / metabolic
(sarcoidosis, Sjogren's syndrome, sclerosis multiplex, GPA), and organic
(tumors in the region of cerebellopontine angle, parotid gland, petrous
bone, brainstem) pathologies.\textsuperscript{2-4}

The goal of the study was to assess the frequency of malignancies hidden
under the diagnosis of ``Bell's palsy''. We aimed to create diagnostic
algorithm to avoid failures concerning patients whose only symptom of
parotid gland cancer was irreversible FNP. One can use the algorithm for
daily clinical practice and initiation of further studies.

\emph{Materials and methods}

We analyzed 253 consecutive patients with FNP treated in our department
in the last 5 years. The STROBE guidelines has been followed. The
subject of the study were patients with Bell's paresis who were
evaluated in detail. We reassessed all cases with permanent FNP and
extended the diagnostics to exclude organic, infectious and
autoimmunological cause of the disease. Contrast-enhanced magnetic
resonance imaging (MRI) of the head and neck, laboratory tests for HIV
infection, Lyme disease, autoimmune disorders including Sjogren's
syndrome (if not available or already performed) were ordered. We
describe four under-diagnosed patients with permanent FNP and
malignancies found out in MRI and point out all deficiencies and
shortcomings in their diagnostic process. Descriptive statistics~was
used to evaluate the study group. We also present a proposal of
diagnostic algorithm for patients with irreversible FNP.

The study was approved by an institutional ethics committee (KB-175/20).
All patients provided written informed consent to participate in the
study.

\emph{Results}

Bell's palsy (idiopathic FNP) was observed in 157 out of all 253
patients with FNP (62.06\%) who had reported to the outpatient
department and emergency unit. Other reasons of FNP included: head
trauma with skull base fracture, facial trauma, complication of acute or
chronic ear infection, facial nerve schwannoma, middle ear squamous cell
cancer (Table 1).

In Bell's palsy group 121 / 157 patients (77\%) achieved a complete or
partial regression of the face paralysis within 3 months, in 36
(22.92\%) it remained permanent, despite typical treatment. In all
patients with irreversible FNP, HIV infection and Lyme disease were
excluded and the level of antinuclear antibodies was within normal
limits. In 32 out of 36 cases the reason of permanent FNP was not found.
In 4 patients (2.54\% of all ``Bell's cases'' and 11.11\% of
irreversible ``Bell's cases''), in MRI of the neck there was found a
mass in the deep lobe of the parotid gland, in one patient infiltrating
the skull base. The largest size of the tumor was 1.5, 2.0, 2.1 and 2.3
cm, respectively. Fine-needle aspiration biopsy confirmed malignant
process while final histopathology adenoid cystic carcinoma in all
analyzed cases.

The patients' details are presented in Table 2. In all cases the first
symptom of parotid gland and skull base cancer was FNP, diagnosed as
``Bell's paresis''. In all patients, there was no palsy regression,
therefore, further diagnostics was implemented. It included high
resolution computed tomography (HRCT) of the temporal bone to exclude
masked ear infection, ultrasound examination of the neck and salivary
glands with linear probe and neurological consultation with head imaging
(in 3 cases computed tomography (CT) while in 1 case both CT and MRI).
When all results were within normal limits, diagnostic procedures were
discontinued. In the above 4 cases, after 6 to 12 months of observation,
reassessment with contrast-enhanced MRI of the head and neck was
conducted. In all patients malignant process in the deep lobe of the
parotid gland with infiltration of the main nerve trunk was revealed, in
the absence of other symptoms and finally with a relatively low tumor
mass volume. All patients were treated surgically - in 3 cases total
parotidectomy with facial nerve resection was performed, while in
patient with infiltration of the skull base lateral petrosectomy was
necessary. All patients had adjuvant irradiation and are still under
control. In 2 patients there are no signs of local, regional or distant
dissemination of the disease. In other 2 metastases to the lungs have
been detected in the 11\textsuperscript{th} and
28\textsuperscript{th}month of follow-up.

A proposal of diagnostic algorithm for patients with irreversible FNP
was presented in Fig.1.

\emph{Discussion}

Typically, Bell's palsy does not progress and it is rather unilateral
and self-limiting. In fact, the majority of cases recover spontaneously
within 3 weeks, even if untreated \textsuperscript{7}, or remit within
4-6 months, but nearly always remission is complete by 1
year.\textsuperscript{8} In 2013 the specialists' panel made
recommendations that diagnostic imaging for patients with new-onset
Bell's palsy should not be performed routinely. However, clinicians
should reassess or refer to a facial nerve specialist those Bell's palsy
patients with (1) new or worsening neurologic findings at any point, (2)
ocular symptoms developing at any point, or (3) incomplete facial
recovery 3 months after initial symptom onset.\textsuperscript{9}

The differential diagnosis of permanent FNP, with particular emphasis on
expansive processes, including cancers, is mostly discussed in the
literature basing on case reports.\textsuperscript{10-12} We present a
set of patients with irreversible FNP and under-diagnosed malignancies
finally found out in the deep lobe of the parotid gland. All of them
were primarily misdiagnosed with Bell's palsy. While detailed
diagnostics implemented 3 to 8 months after FNP onset excluded masked
ear infection and head pathology, as well as did not reveal pathology in
ultrasound examination of the neck and laboratory tests, further
examinations were discontinued.

The most common imaging techniques used in the assessment of salivary
glands are ultrasound, CT and MRI. Ultrasound is a quick and relatively
inexpensive method that can accurately depict most salivary gland
neoplasms.\textsuperscript{13}However, it should be underlined that it
provides limited visualization of the deep lobe of the parotid gland.
Moreover, penetration of ultrasound can be hindered in case of high
content of fat in the parenchyma.\textsuperscript{14} CT is frequently
used as a more precise tool, but, due to relatively poor soft-tissue
contrast, sometimes the accurate assessment of the tumor extent and
differentiation of its malignancy potential can be
impossible.\textsuperscript{13} Nowadays MRI is a gold standard in
evaluation of parotid gland.\textsuperscript{15}Our study shows that it
is very important to include MRI in the diagnostics of all patients with
irreversible FNP and, what important, even to repeat the imaging in
uncertain / untypical clinical picture of the disease. MRI should cover
all anatomical segments of facial nerve, both intra- and extratemporal.
In 3 out of 4 presented patients with malignancies of the parotid gland,
MRI of the head and neck was not included in the diagnostic algorithm.
In one patient MRI scanning did not cover the region of parotid gland
where the malignant tumor was located, which was an obvious shortcoming.
Adenoid cystic carcinoma of the deep lobe of the parotid gland, which
was finally confirmed in all presented cases, is a slow-growing but very
aggressive tumor characterized, among others, by perineural
spread.\textsuperscript{16}It is estimated that FNP is an initial
symptom in about 60\% of cases.\textsuperscript{17} Referring to our
study group, early diagnosis with MRI of the neck could have improved
oncological results in all of the analyzed patients, especially those
with the distant spread of the disease.

Zimmerman et al \textsuperscript{18} concluded that MRI is a useful tool
for exclusion of otogenic and neoplastic processes with a sensitivity of
83\% and 88\%.~Quesnel et al \textsuperscript{19} indicate imaging of
parotid gland, brain and temporal bone at 4 months for patients with
irreversible idiopathic facial paralysis. They support that
recommendation by the natural history of Bell's palsy, in which early
signs of recovery are seen in the majority of cases by this time. We
strongly agree with such an algorithm. In case of no lesion identified,
they suggest to repeat the imaging in 3 months or even to consider
explorative surgery and biopsy of tissues adjacent to the facial nerve.
In our opinion, surgical procedures, due to the potential complications
and difficulties, should be performed only in selected cases.

Although there are a few papers on magnetic resonance (MRI) protocols
for the malignancies manifesting as facial palsy\textsuperscript{20-22},
they are universally suboptimal and thus may fail to reliably
differentiate neoplastic from inflammatory process even when interpreted
by experienced radiologists. Chhabda et al\textsuperscript{23} underline
that selected segments of the nerve are better evaluated on certain
imaging modalities, so radiologists should try to combine clinical
picture with specific facial nerve pathologies to tailor the imaging
test to best answer the clinical question. Gupta el al
\textsuperscript{24} recommend contrast-enhanced MRI as the first
imaging in cases when the palsy cannot be definitively localized. They
indicate high-resolution temporal bone CT to evaluate the fallopian
canal if the lesion can be localized in the region of the mastoid,
tympanic, or labyrinthine segments of the facial nerve and
contrast-enhanced MRI if the cisternal or intracanalicular segments of
the facial nerve or the pontine nuclei should be assessed. In our
opinion, such recommendations are very good. The intraparotid facial
nerve is best evaluated by gadolinium-enhanced MRI, with T1-weighted
gadolinium-enhanced images.\textsuperscript{12} In the inner ear
pathologies the combined non-contrast and postcontrast T1-weighted and
T2-weighted sequences are mostly used.\textsuperscript{24}

Our paper has strong points and some limitations. Our attempt to create
diagnostic algorithm in irreversible Bell's palsy to avoid missing a
parotid gland cancer is unique. The main limitation is a small sample
size. Nevertheless, deep lobe adenoid cystic carcinoma is a rare disease
and it is difficult to expand the study group. The algorithm can be used
for clinical practice and initiation of further studies.

\emph{Conclusions}

Neoplastic etiology should always be considered as a cause of
irreversible FNP that originally seemed Bell's. Our experience shows
that FNP can be a revelator of the malignant tumor located in the deep
lobe of the parotid gland. Contrast-enhanced MRI covering intra- and
extracranial segments of facial nerve should be ordered in all cases of
FNP without recovery after 4 months. Repeated imaging should be
considered in undiagnosed cases. The main point of our study is to
underline that the assessment of the deep lobe of the parotid gland with
MRI should be included in the standard diagnostic protocol in all
irreversible ``Bell's palsy'' cases.

\emph{List of tables and figures}

\textbf{Table 1.} Etiology of facial nerve palsy in all patients treated
in our department in the last 5 years

\textbf{Table 2.} Patients with facial nerve (FN) palsy, diagnosed as
``Bell's'', without regression, which turned out to be a parotid gland
cancer

\textbf{Figure 1.} A proposal of diagnostic algorithm for patients with
irreversible FNP

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