International Journal of Nasopharyngeal Carcinoma (IJNPC) Vol. 03, No.

01, March, 2021 | 13-16

International Journal of
NASOPHARYNGEAL CARCINOMA
Journal homepage: https://talenta.usu.ac.id/IJNPC

Nasopharyngeal Carcinoma with a Complication of Facial Nerve Paresis

Nova Audrey Luetta Pieter*, Adi Matra Prawira
Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, Hasanuddin University Hasanuddin University Hospital, Makassar, Indonesia

Abstract Article Info

Introduction: One fifth of NPC patients have cranial nerve involvement at the time of diagnosis. The nearby Article history:
location of rossenmuller fossa to lacerum foramen and middle base of the cranium provide way for tumor to Received: 14th February 2021
extent directly to the cranium and adjacent cranial nerve. Facial palsy due to NPC does not happen very often, Received in revised form: 14th March 2021
with incidence only compromise less than 1% of all cases. Accepted: 16th March 2021
Case report: We reported a case of a 42 years old female with a complaint of blood stain rhinorea, mass in the
nasopharynx, and facial assymmetry. Based on his history of illness, physical examination, imaging, and Keywords:
histopathology, the working diagnosis was Nasopharyngeal Carcinoma Stage IVA (T4 N0 M0) with facial nerve Nasopharyngeal carcinoma, facial palsy,
paresis (Hause-Brackmann V). The intervention done for the patient was radiotherapy. diagnosis, radiotherapy
Conclusion: The patient refused to undergo chemotherapy, so the only therapy done in this case was
*Corresponding author:
radiotherapy. After undergoing 35 cycles of radiotherapy, a fair improvement was seen clinically on the patient.
Address: Jl. Sahabat Raya No.3, Tamalanrea Indah,
Kec. Tamalanrea, Kota Makassar, Sulawesi
Selatan 90245
e-mail: novapieter@gmail.com

1. CASE REPORT acids. Other than dietary factors, the environmental factors that is suspected to
play a role are oral hygiene, inhalation of wood dust, smoke, formaldehyde, and
Nasopharyngeal carcinoma (NPC) is the most common cancer found among chemical material [6, 7].
ENT malignancies in Indonesia with prevalence being on the highest 5th among
all cancer (along with cervical cancer, breast cancer, lymph node cancer, and skin
cancer). Not only being the most common found cancer on the head and neck,
NPC also compromise almost 60% of tumor in head and neck, followed by
cancer in the nose, paranasal sinus, throat, mouth, tonsil, and hypopharynx.
Nasopharyngeal carcinoma (NPC) is a cancer originated from the mucosal lining
of nasopharynx, with middle point most commonly located in fossa of
Rosenmüller, where the tumor invades the adjacent space or organ. The incidence
of NPC in Makassar, South Sulawesi, represented by NPC patient in Dadi
Regional Hospital and Wahidin Sudirohusodo Central General Hospital in a 10-
year period (1990-1999), was reported by Kuhuwael in 2001 with a finding of
274 cases (47.98% of all head and neck cancer) with man to woman ratio of 2.6:1.
Whereas from January 2004 to June 2007, NPC was found to compromise only
33% of all malignancy in ENT [1-3].
The etiology and risk factor of KNF is not yet known in exact, but there are
hypothesis of some factors that is suspected to increase the risk of NPC. Epstein-
Barr Virus (EBV) infection might be the most studied etiologic factor of NPC.
Using in-situ hybridization technique who targets EBV encoded RNA, the virus
is able to be detected only inside the tumor cell, but not in a normal epithelial cell
of the nasopharynx. In histopathological findings, EBV infection has a
correlation with non-keratinized carcinoma both in differentiated and non- Picture 1. The role of EBV in the pathogenesis of NPC [6].
differentiated subtypes, with differentiated types only correlates in high-risk
areas. The role of individual genetic susceptibility towards the pathogenesis of The symptoms of NPC are categorized in 4 groups, including
NPC is indicated by the high incidence of NPC in certain ethnic. This is most nasopharyngeal, ear, cranial nerve, and neck or its metastatic symptoms. The
noticeable on second and third generation of population coming from high-risk most common symptom is a lump on the neck, where this usually suggest a
areas in which after emigration and assimilation with different culture, the risk metastasis in neck lymph nodes. Hearing disturbance is one of the early
seemed to remain higher than the local population [4, 5]. symptoms due to the close position of tumor origin, fossa of Rosenmuller,
Large-scale epidemiological studies propose a correlation between dietary to the eustachian tube. Disturbance in the ear compromised of tinnitus,
and social behavior with the increased risk of NPC. The most common factor sensation of fullness in the ear, or ear pain (otalgia). It is not rare that hearing
mentioned is the history of salted fish (fish undergoing preservation process) disturbance in a patient later on found out to be NPC [1, 2, 8].
consumption. The carcinogen which plays a role found in salted fish is volatile Nasopharyngeal symptoms might be mild nosebleed or nasal
n-nitrosamines, which induces DNA damage and chronic inflammation in obstruction, therefore a thorough nasopharyngeal examination should be
mucosal lining of nasopharynx. Consumption of other food associated with the performed. If necessary, nasopharyngoscope should be performed due to
incidence of NPC are pickled vegetables, fermented food, herbal tea, slow- common cases of creeping tumor, which is a presence of tumor without any
cooked soup, alcohol, animal products, carbohydrates, and unsaturated fatty symptom or visibility on the mucosal lining. A few cranial nerve
disturbances may be found as a late symptom of NPC due to the adjacent

Copyright © International Journal of Nasopharyngeal Carcinoma Published by Talenta Publisher, ISSN: 2656-9027 e-ISSN: 2656-9035 DOI: 10.32734/ijnpc.v3i01.5608 13
International Journal of Nasopharyngeal Carcinoma (IJNPC) Vol. 03, No. 01, March, 2021 | 13-16

location of tumor origin and cranial space through a couple of holes.

Disturbance in the ear includes serous otitis media and conductive hearing
loss. Neurological disturbance includes diplopia, loss of sensation in the
cheek, decreased corneal reflex, and headache which involved cranial nerve
number II, III, IV, V, and VI. Disruption of cranial nerve number IX, X, XI,
and XII may cause dysphagia, soft palate hemiparesis, and tongue palsy.
Due to the high location, disruption of cranial nerve number VII and VIII
rarely occurs [4, 8].
Facial palsy is a weakness of facial muscles. A patient may not be able to
move the facial muscle completely, therefore the patient’s face will show
asymmetry. The causes of facial nerve palsy are congenital factor, infection,
tumor, trauma, vascular problem, idiopathic, or due to certain disease. Among
all cases of facial nerve palsy, 5% is reported due to tumor involvement with Picture 1. Clinical views of the patient with facial asymmetry
nasopharyngeal involvement only occurs in less than 1% [9].
A woman aged 42 years old was referred from regional hospital with a
The diagnosis of NPC requires history taking, physical examination, and
complaint of nosebleed in the last 5 months that predominant in the right
other additional examination. Early detection in primary health care through a
nasal cavity. The blood shed is in mild volume that it was able to be stopped
thorough history taking is required to increase the good prognosis in NPC by pinching the nose. Often, the blood flowed to the throat. There was no
patients. Nasoendoscopic examination plays a key role in early detection by complaint of runny nose, post nasal drip, facial pain, nor nasal obstruction
detecting mucosal lining with suspicion of NPC lesion, as a guide to locate biopsy in the other nose, but there were complaints of blood-stain rhinorrhea,
spot, and as a follow up for residual cases. Imaging modalities includes CT scan hyposmia, and intermittent headache.
of nasopharynx in the level of frontal sinus to clavicula with coronal, axial, and Mouth asymmetry had been complained since 4 months prior,
sagittal section, with or without contrast [1, 2, 8]. accompanied by inability to close the right eyelid which cause a painful and
A study found that EBV DNA analysis in plasma sample (pEBV) can watery eyes as well as sensation of thickness and stiffness in the right face.
be used as a screening tool for asymptomatic NPC. Marker of pEBC also There was no currently happening ear discharge at the time of presentation,
has prognostic value as pEBV is used in selection of patient with high-risk but there was history of ear discharge around 4 months prior. There was
NPC to receive adjuvant therapy. A definitive diagnosis is made based on hearing loss that predominant in the right ear, accompanied by tinnitus
without any pain nor vertigo. There was no complaint in the throat. There
histopathology finding with specimen taken through nasopharynx biopsy.
was no history of similar complaint in the family as well as any other
WHO classify histopathology specimen into 4 types, including keratinized comorbid diseases such as hypertension or diabetes. The patient underwent
(WHO type I), non-keratinized and differentiated (WHO type II), and non- a nasopharynx biopsy in the regional hospital 3 months prior.
keratinized and non-differentiated (WHO type III), and basaloid squamous The vital sign examinations were within normal value. On anterior
cell carcinoma (WHO type IV) [4, 6, 7]. rhinoscopy, a congested concha with hyperemic mucosal lining was found.
On nasoendoscopic examination, a mass on the right nasopharynx with
Table 1. TNM classificaton and saging of Nasopharyngeal Carcinoma of irregular surface and high susceptibility to bleed was found. Soft palate
AJCC/UICC 8 [10] phenomenon was not found on the right nasal cavity. Otoscopy examination
of right acoustic meatal was found normal with a moderate perforation on
the tympanic membrane. There was no discharge nor granulation and
TNM Clasification Stadium AJCC 8 (2016)
Tis Tumor is unidentified, but EBV status is 0 TisN0M0 retroauricular space showed no swelling nor hyperemic appearance.
positive on neck lymph node metastasis Oropharynx examination revealed normal findings and no enlargement of
T1 Tumor is limited in nasopharynx, or extend to I T1N0M0 lymph node was found.
oropharynx and/or nasal cavity without
parapharynx involvement
T2 Tumor with extension to parapharynx space, II T0N1M0 Table 3. Clinical Facial Nerve Examination
and/or involvement of adjacent soft tissue T1N1M0
Examination Right Left
(medial pterygoid muscle, lateral pterygoid T2N0M0
muscle, prevertebral muscle) T2N1M0 Frowning - +++
T3 Tumor infiltrate structures of cranial base, Closing the eye lid - +++
cervical vertebrae, pterygoid, and/or paranasal Showing the teeth - +++
sinus Whistling - +++
T4 Tumor with intracranial extension, Taste in 2/3 anterior of the tongue - +
involvement of cranial nerves, hypopharynx, Hyperacussis - -
orbita, parotid gland, and/or infiltration to soft Tear secretion + +
tissue extending to lateral border of lateral
pterygoid muscle There was obvious disfiguring difference between two sides, lack of
N0 No lymph node metastasis III T0N2M0
N1 Metastasis on neck lymph node unilaterally T1N2M0 movement of the right forehead and eyebrows. At rest asymmetry and
and/or metastasis on retropharynx lymph node T2N2M0 tone of facial muscles were present. Patient was unable to voluntarily
uni/bilaterally with a size of < 6 cm on the T3N0M0 close eyes completely with effort and reduced movement on forehead was
widest dimension, superior to caudal border of T3N1M0
cricoid cartilage. T3N2M0 seen on motion. The tip of the nose is drawn to the unaffected side. She
N2 Metastasis on neck lymph node bilaterally with had paraesthesia in 2/3 anterior of the tongue. No associated pain over
a size of < 6 cm on the widest dimension, ears and face.
superior to caudal border of cricoid cartilage
N3 Metastasis on neck lymph node uni/bilaterally
with a size of > 6 cm on the widest dimension
and/or extension to inferior to caudal border of
cricoid cartilage
M0 No distant metastasis IVA T4N0M0
M1 Distant metastasis T4N1M0
T4N2M0
T1-T4,N3M0
IVB T1-T4,N0-N3,M1

Modalities of therapy includes radiation, chemotherapy, combination of

both, and supported by symptomatic therapy.

Table 2. Modalities of therapy for NPC According to Its Stage

Graphic 1. Pure Tone Audiometry (PTA), Right: Moderate Severe Mix
Stage Modalities of Therapy Hearing Loss (57.5 dB); Left: Mild Conductive Hearing Loss (33.75 dB)
Stage I Radiotherapy
Stage II Chemoradiation
Stage III Chemoradiation
Stage IV with N <6 cm Chemoradiation
Stage IV with N >6 cm Full-dose chemotherapy followed by chemoradiation

14
International Journal of Nasopharyngeal Carcinoma (IJNPC) Vol. 03, No. 01, March, 2021 | 13-16
The patient had a hearing loss in both ear especially of the right ear. The
result of Pure tone Audiometry showed a moderate severe mix hearing loss
(57.5 dB) of the right ear and mild conductive hearing loss (33.75 db) of the
left ear.
Picture 2. CT scan of Nasopharynx in Coronal Section
Additional examination was done with CT scan of nasopharynx in
coronal section and a mass was found on the right side of nasopharynx with
a shallow fossa of rossenmuller with any extent on parapharyngeal space.
Bone survey and abdominal ultrasound showed no sign of metastatic sign.
Histopatology finding from biopsy of nasopharynx shows tendency to Non-
Keratinizing Squamous Cell Carcinoma.
Based on history taking, physical examination, and several additional
examinations performed, the working diagnosis was Nasopharyngeal
Carcinoma Stage IVA (T4 N0 M0) with facial nerve paresis (Hause-
Brackmann V). The intervention done for the patient was radiotherapy.
1.1 Follow up
The patient came to the ENT clinic for a control check-up after
undergoing 35 cycles of radiotherapy. There was no complaint of nosebleed,
runny nose, nasal obstruction, facial pain, nor headache. The intensity of
tinnitus decreased but the hearing loss persist. There was no pain in the ear
nor vertigo. Paresis of the face seemed to have a mild relief. Patient was
complaining of paresthesia, especially in both the hands and the feet.
Picture 3. Clinical views of the patient after undergoing radiotherapy
Table 4. Clinical Facial Nerve Examination
Examination Right Left
Frowning + +++
Closing the eye lid + +++
Showing the teeth + +++
Whistling + +++
Taste in 2/3 anterior of the tongue + +
Hyperacussis - -
Tear secretion + +
On clinical examination, paresis of the face seemed to have a mild relief.
Lack of movement of the right forehead and eyebrows still appeared. At
rest normal symmetry and tone of facial muscles were present. Patient was
able to voluntarily close eyes completely with effort. She had no change in
taste sensation or paraesthesia, no dry eyes or tearing on salivation, no
excessive facial sweating or sweating on salivation.
A control CT scan examination of nasopharynx with coronal section
found a thickness on mucosal lining of the right pharyngeal space with a
shallow fossa of rossenmuller. The finding concluded that there was a relief
compared to the initial CT scan finding before the patient underwent
radiotherapy. Besides, a CT Scan of Mastoid with axial section was done
with a finding of air cell mastoid opacification that predominant in the right
ear, concludes a finding of right otomastoiditis.
Picture 4. CT scan of Nasopharynx after Radiotherapy Session
Based on history taking, physical examination, and several additional
examinations performed, the working diagnosis after radiotherapy session
was Nasopharyngeal Carcinoma Stage IVA (T4 N0 M0) with facial nerve
paresis (Hause-Brackmann III). The proposed action for the patient was 500
mg of oral mecobalamin tablet every 12 hours and a referral to medical
rehabilitation department.
2. DISCUSSION
One fifth of NPC patients have cranial nerve involvement at the time of
diagnosis. The nearby location of rossenmuller fossa to lacerum foramen
and middle base of the cranium provide way for tumor to extent directly to
the cranium and adjacent cranial nerve. Involvement of trigeminal nerve is
the most common finding of all, followed by abducent nerve that causes
facial pain, paresthesia, and diplopia [11]. A group of symptoms caused by
disruption of anterior cranial nerves due to NPC metastasis is called
Petrosphenoid Syndrome. However, NPC can also affect cranial nerve
number IX, X, and XI in parapharyngeal space, causing palsy on the tongue,
palate, pharynx, throat, sternocleidomastoid muscle, and trapezius muscle.
This syndrome might cause trismus, aphonia due to vocal cord palsy,
dysphagia, and nerve palsy of sympathetic cervical nerve (Horner
Syndrome) [4, 8, 12].
Facial palsy is a weakness of facial muscle. The patient is unable to
move its face muscle completely, causing asymmetrical face. Among all
facial nerve palsy, 5% is reported to be caused by tumor, one of which is
NPC. Facial palsy due to NPC does not happen very often, with incidence
only compromise less than 1% of all cases. After arising from brainstem, the
facial nerve enters the cerebellopontine angle (CPA), temporal bone
(internal acoustic meatal, middle ear, and mastoid) and parotid gland before
then branching to innervate the facial muscles. Tumor involvement along
the pathway may cause facial palsy [9, 13].
Involvement of facial nerve in CPA is probably due to metastasis (via
hematogenous, CSF, or leptomeningeal spread), whereas involvement in
middle ear is probably due to direct invasion (through eustachian tube or
direct invasion from parapharyngeal space) or through metastasis. Indirect
invasion might due to tubal occlusion. The nearby location of eustachian
tube and fossa of rossenmuller might cause a negative pressure inside the
tympanic cavity leading to otitis media and if left untreated might cause
mastoiditis in the long run. Involvement of facial nerve due to disruption of
parotid gland might give a hint of lymphatic spread to the retropharynx
group of lymph node [8, 14].
On this patient, a sign of intratemporal complication was found. Facial
nerve paresis might be caused by indirect spread to middle ear through
eustachian tube. Moreover, CT Scan of Mastoid with axial section revealed
right otomastoiditis and moderate perforation on the right tympanic
membrane that might be caused by indirect mechanism of spread.
The ideal therapy on this patient is concurrent chemoradiation,
chemotherapy and radiation done at the same time. Tumor response towards
radiation generally increased on combination with chemotherapy
medications such as Cisplatin, 5 FU, Hydroxyurea, and Mytomkin. The
15
International Journal of Nasopharyngeal Carcinoma (IJNPC) Vol. 03, No. 01, March, 2021 | 13-16

advantage of concurrent chemoradiation is that both work in synergy to [15] Patil V, Joshi A, Noronha V, Talreja V, Shima V, Dhumal S, et al.
prevent resistance, kill hypoxic subpopulation of cancerous cell, and inhibit Palliative chemoteraphy in carcinoma nasopharynx. South Asian J
DNA recovery on sublethal cancerous cell [15]. However, the patient Cancer, 2019; 8: 173-7. DOI: https://doi/org/10.4103/sajc.sajc_230_18
refused to undergo chemotherapy, so the only therapy done in this case was [16] Wang S, Li S, and Shen L. Combined chemoradiation vs radiation
radiotherapy. Chemoradiation have contributed to improvements in therapy alone in stage-II nasopharyngeal carcinoma: A meta-analysis
of the published literature. Curr Probl Cancer. 2018; 42(3): 302-18.
functional organ preservation. The study by Wang et al (2018) reported that
DOI: https://doi/org/10.1016/j.currproblcancer.2018.03.004
compared with those threated with radiation therapy alone, chemoradiation
could significantly improve patients prognosis in terms of overall survival,
and progression free survival in nasopharyngeal carcinoma [16].
After undergoing 35 cycles of radiotherapy, a significant improvement
was seen clinically on the patient. Before undergoing radiotherapy, patient
was identified with Hause Brackmann grade V and after therapy it improved
to grade III.

3. CONCLUSION

We reported a case of 42 years old female with stage IVA

Nasopharyngeal Carcinoma (T4N0M0) with facial nerve paresis (Hause
Brackman V) who underwent radiotherapy with 35 cylces with fair
response. Facial palsy due to NPC does not happen very often, with
incidence only compromise less than 1% of all cases. Therefore, it is
important to understand the anatomy of nasopharynx structure and facial
nerve pathway to provide an accurate clinical evaluation for the patient.

REFERENCES

[1] Adham M, Kurniawan AN, Muhtadi AI, Roezin A, Hermani B,

Gondhowiardjo S, Tan IB. Nasopharyngeal carcinoma in Indonesia:
epidemiology, incidence, signs, and symptoms at presentation. Chin
J Cancer, 2012 ; 31(4) : 185-96. DOI: https://10.5732/ cjc.011.10328
[2] Jayalie VF, Paramitha MS, Jessica, Liu CA, Ramadianto AS,
Trimartani, Adham M. Profile of Nasopharyngeal Carcinoma in Dr.
Cipto Mangunkusumo National Hospital, 2010. eJKI, 2016 ; 4(3) :
156-62. DOI : https://doi/org/10.23886/ejki.4.7110.156-62
[3] Punagi AQ, Savitri E. Profil Karsinoma Nasofaring di Rumah Sakit
Pendidikan Unhas Periode Januari 2004 - Juni 2007. Bagian THT-
FK UH. 2007. 1-5 p
[4] Pieter N. Profil IgA (Vca- P18+ Ebna 1) dan Viral Load DNA EBV
Sebagai Faktor Resiko Keluarga Penderita Karsinoma Nasofaring
dengan EBV Positif. [Disertation]. Universitas Hassanuddin, 2013 :
8-22 p
[5] Tsao SW, Yip YL, Tsang CM, Pang PS, Lau VMY, Zhang G, Lo KW.
Etiological factors of nasopharyngeal carcinoma. Oral Oncol,
2014;50:330-8. DOI: https://doi/org/10.1016/j.oraloncology.
2014.02.006
[6] Young LS, Dawson CW. Epstein-Barr virus and nasopharyngeal
carcinoma. Chin J Cancer, 2014; 33(12): 581-90.
DOI: https://doi/org/10.5732/cjc.014.10197
[7] Zeng MS, Zeng YX. Pathogenesis and Etiology of Nasopharyngeal
Carcinoma. In: Lu JJ, Cooper JS, Lee AWM (Eds). Nasopharyngeal
Cancer Multidisciplinary Management. Berlin: Springer, 2010: 9-25
p. DOI: https://doi.org/10.1007/978-3-540-92810-2_2
[8] Thorneau C, Faivre S. Nasopharyngeal Cancer. In: Souza CD, Cruz
AD. Head and Neck Surgery Volume 2. New Delhi: Jaypee Brothers
Medical Publishers. 2009. 873-82 p
[9] Pasha R, Golub J.S. Otolaryngology Head and Neck Surgery Fifth
Edition. San Diego: Plural Publishing, 2018. 359-63 p
[10] American Joint Committee on Cancer. AJCC Cancer Staging Manual
Eight Edition. Chicago: Springer, 2017. 103-11 p
[11] Richardo T, Prattapong P, Ngernsombat C, Wisetyaningsih N, Iizasa
H, Yoshiyama H, Janvilisri T. Epstein-Barr virus mediated signaling
in nasopharyngeal carcinoma carcinogenesis. Cancers. 2020
Sep;12(9):2441. DOI: https:// 10.3390/cancers12092441
[12] Simo R, Robinson M, Lei M, Sibtain A, and Hickey S.
Nasopharyngeal carcinoma: United Kingdom National
Multidisciplinary Guidelines. J Laryngol Otol, 2016; 130(2): 97-103.
DOI : https://10.1017/S002221511600 0517
[13] Mavrikakis I. Facial nerve palsy: Anatomy, etiology, evaluation, and
management. Informa Healthcare, 2008; 27(6): 466-74. DOI:
https://doi/org/10.1080/01676830802352543
[14] Low W.K. Facial palsy from metastasic nasopharyngeal carcinoma at
various sites: three reports. Ear Nose Throat J, 2002; 81(2): 99-101.
PMID: 11868483. DOI: https://doi.org/10.1177/014556130208100214

16