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Nasopharyngeal Cancer
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AishaLarem, EmadAl Duhirat, andHassanOmer
41
41.1 Introduction
The nasopharynx is the space behind the nasal
cavity and above the oropharynx. As it is deep
space, it makes it difcult to be examined during
regular examination, the presentation of any
pathology will be late due to this position, and the
surgical excision of any pathology will be difcult and incomplete. The proximity of this space
to multiple vital structures like the ear through
the Eustachian tube, skull base, and cranial
nerves gives it a crucial functional and pathological importance.
41.2 Anatomy
The nasopharynx is bounded.
• Inferiorly by the lower surface of the soft
palate.
• Anteriorly by the choana (nasal cavity).
• Superiorly the oor of the sphenoid which
slopes down to become the posterior wall
formed by the clivus bone.
• Laterally by the opening of the Eustachian
tubes superiorly and the upper part of the
superior constrictor muscle inferiorly.
The fossa of Rosenmuller (the most common
area of nasopharyngeal carcinoma) [1]: Is a
recess extends postero-laterally on both sides of
the posterior wall of the nasopharynx to form the
lateral recess which has variable depths and
bounded anteriorly by the opening of the
Eustachian tube (Fig.41.1).
The nasopharynx is lined by pseudostratied squamous epithelium, the lymphatic drainage mainly to the lymph nodes in the
retropharyngeal space (nodes of Rouvière) and
into the deep cervical nodes. The cranial nerves
IX, X, XI, and XII, the carotid sheath and the
sympathetic trunk traverse the parapharyngeal
space which is lateral to the superior constrictor muscle.
Blood supply to the nasopharynx is through
branches of the internal maxillary artery while
venous drainage is to the pterygoid plexus, then
to the facial and internal jugular veins.
The area with the highest incidence of
nasopharyngeal carcinoma (NPC) is in
Southern China [2]. The male to female ratio
of the disease is 3 to 1. The peak age group of
presentations of NPC in endemic areas is
50–55 years old, and it decreases with increasing age.
A. Larem (*) · E. Al Duhirat · H. Omer
Hamad Medical Corporation, Doha, Qatar
e-mail: alarem@hamad.qa; EAIDuhirat@hamad.qa
© Springer Nature Switzerland AG 2021
A. Al-Qahtani et al. (eds.), Textbook of Clinical Otolaryngology,
https://doi.org/10.1007/978-3-030-54088-3_41
41.3 Etiologies
– Genetic factors
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480
Fig. 41.1 Endoscopic view of normal postnasal space compared to nasopharyngeal tumor, Rosenmiller fossa (arrow)
A. Larem et al.
– Environmental factors: salted sh, preserved
foods may be due to the high nitrosamine content [3–6]
– Epstein-Barr virus in endemic areas
41.4 Pathology
Nasopharyngeal cancer is a squamous cell carcinoma which arises from the epithelium.
The World Health Organization (WHO) originally categorized the epithelial malignancies
from the nasopharynx into three subtypes:
1. Well-differentiated keratinizing squamous
cell carcinoma (WHO type 1)
2. Nonkeratinizing carcinoma (WHO type 2)
3. Undifferentiated carcinoma (WHO type 3) [7]
The classication was later revised to two
subtypes:
• Keratinizing squamous cell carcinoma
• Combining type 2 and type 3 into nonkera-
tinizing carcinoma. The nonkeratinizing carci-
noma can be further subclassied as
differentiated and undifferentiated types [7].
Only the nonkeratinizing class is associated
with Epstein-Barr virus (EBV) infection. This
classication shows prognostic signicance.
The undifferentiated NPC have a higher local
tumor control rate with therapy although the
possibility of distant metastasis is also higher
(Fig.41.2) [8, 9].
41.5 Clinical Manifestations
• A painless mass in the neck: About 70% of
patients have an enlarged lymph node in the
neck on presentation. The most frequently
involved nodes are level II (upper jugular) and
upper level V (apex of posterior triangle) [10].
• Otological symptoms: Eustachian tube dysfunction secondary to tumor bulk and/or invasion. Unilateral secretory otitis media in an
adult patient is an alarming symptom for nasopharyngeal cancer.
• Nasal symptoms: Blood-stained nasal discharge, postnasal drip and blockage.
• Neurological symptoms: Headache or presentation related to cranial nerve involvement.
The prevalence of cranial nerve palsy on presentation is around 20% [11]. When the tumor
extends superiorly to affect the lateral wall of
the cavernous sinus, then the cranial nerves III
to VI might be affected and with lateral
extension of the tumor into the parapharyngeal
space, cranial nerves IX–XII might be affected.
41 Nasopharyngeal Cancer
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Fig. 41.2 Nonkeratinizing nasopharyngeal carcinoma, undifferentiated, high magnication and low magnication
respectively. (Photo credits, Dr. Adham A.Ammar—Senior Consultant Pathology—HMC)
481
The cranial nerves most frequently affected are
the third, fth, sixth, and twelfth [12].
Common sites of distant metastases are liver,
lung, and bone, with brain metastasis being rare.
41.5.1 Diagnosis
• Thorough history
• Physical exam
Full ENT exam concentrating on the follow-
ing points:
• Endoscopy of the post nasal space, attention
showed be made to the submucosal NPC
• Neck exam looking for lymph nodes
• Ears exam looking for secretory otitis media
(Unilateral)
• Cranial nerves examination
• Fine needle biopsy: With the addition of
immunohistochemical staining for EBV RNA
(EBER), a denitive diagnosis of NPC with
neck lymph node metastasis can be made
• Biopsy, Gold standard
• Blood tests
41.5.1.1 EBV Antibodies Serology
In NPC, the level of IgA in response to early
intracellular antigen (EA) and viral capsid anti-
gen (VGA) are much higher than those detected,
in the general population [
13].
The IgA anti-EA has been shown to be more
specic while IgA anti-VCA is more sensitive for
the diagnosis of NPC [14].
41.5.2 Imaging Studies
41.5.2.1 CT Scan
See Fig.41.3.
41.5.2.2 MRI
MRI’s superiority in soft tissue pathology detection makes it the preferred modality in nasopharyngeal cancer. For assessment of tumor extent,
MRI can better delineate parapharyngeal extension of tumor, perineural spread and marrow
inltration. MRI can also differentiate between
tumor inltration from secretions in the paranasal
sinuses, and can dene better the limits of the
optic chiasma, optic nerves, and brainstem
(Fig.41.4) [15].
41.5.2.3 Positron Emission
Tomography (PET)
PET-CT can detect distant metastases in addition
to locoregional disease extent. PET-CT is very
useful in assessing residual and recurrent disease
after treatment (Fig.41.5).
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482
A. Larem et al.
Fig. 41.5 FDG PET Axial CT scan, of patient with naso-
pharyngeal cancer noted by the increase uptake in the scan
noted by increase uptake of glucose in affected areas
Fig. 41.3 Axial postnasal space CT scan shows a naso-
pharyngeal mass completely obstructing the post nasal
space with features suspicious of malignancy
Fig. 41.4 T1 MRI scan with contrast showing a nasopha-
ryngeal mass (arrow) with contrast enhancement
41.6 Staging andTNM
Classication [16]
T
Category T Criteria
TX Primary tumor cannot be assessed
T1 Tumor conned to nasopharynx, or extends
to oropharynx and/or nasal cavity without
parapharyngeal space involvement
T2 Tumor with extension to parapharyngeal
space and/or inltration of the medial
pterygoid, lateral pterygoid, and/or
prevertebral muscles
T3 Tumor invades bony structures of skull base
cervical vertebra, pterygoid structures, and/
or paranasal sinuses
T4 Tumor with intracranial extension and/or
involvement of cranial nerves, hypopharynx,
orbit, parotid gland and/or inltration
beyond the lateral surface of the lateral
pterygoid muscle
N
Category N Criteria
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Unilateral metastasis, in cervical lymph
node(s), and/or unilateral or bilateral
metastasis in retropharyngeal lymph nodes,
6cm or less, above the caudal border of
cricoid cartilage
41 Nasopharyngeal Cancer
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483
N
Category N Criteria
N2 Bilateral metastasis in cervical lymph
N3 Metastasis in cervical lymph node(s) greater
M category M criteria
M0 No distant metastasis
M1 Distant metastasis
Stages
I T1 N0 M0
II T1
III T1, T2
I VA T4
IVB Any T Any N M1
node(s), 6cm or less above the caudal
border of cricoid cartilage
than 6cm in dimension and/or extension
below the caudal border of cricoid cartilage
T2
T3
Any T
N1
N0, N1
N2
N0, N1, N2
N0, N1, N2
N3
M0
M0
M0
M0
M0
M0
41.7 Treatment
even in clinically node-negative patients due to
the high incidence of neck relapse in the absence
of prophylactic nodal irradiation [
17].
A dose of 65–70Gy is normally given to the
primary tumor, 65–70Gy to the involved neck
nodes, and 50–60Gy to the node-negative neck.
41.7.1 Chemotherapy
Current evidence indicates that concurrent
chemoradiotherapy has a major role in advanced
stage nasopharyngeal carcinoma. Combined
induction and concurrent chemotherapy may
have the added benet of tumor shrinkage prior
to radiotherapy, and excellent control can be
achieved using this approach in advanced T stage
NPC [18].
Stage I and low-risk stage II, can be treated
with radical radiotherapy alone.
Stage II disease with higher tumor load and
stage III, IV disease require combination chemotherapy and radiotherapy.
• Radiotherapy (primary treatment)
• Concurrent chemoradiotherapy (for advanced
cases)
• Surgery (salvage surgery for failure of primary treatment)
Radiotherapy is the mainstay treatment for
primary NPC (radiosensitive) and surgical
treatment is reserved for salvage of radiation
failures [15].
Intensity-modulated radiotherapy (IMRT)
allows different dose levels to different regions to
be applied in the same treatment.
Nasopharyngeal carcinoma has a tendency of
early spread to paranasopharyngeal and cervical
lymphatics, hence prophylactic nodal treatment
is mandatory and radiotherapy can cover these
areas adequately.
For effective treatment of nasopharyngeal car-
cinoma, the radiation target volume includes the
nasopharynx and also the parapharyngeal space,
oropharynx, base of skull, sphenoid sinus, posterior ethmoid sinus and posterior half of maxillary
antrum. Cervical nodal irradiation is mandatory
41.7.2 Surgery
Surgical resection of the nasopharynx, is only
reserved for salvaging radiation failures. Neck
dissection is considered as the standard of care
for management of nodal failures [19].
41.7.3 Follow-up
Regular examination of the nasopharynx by
endoscopy should be performed as part of
follow-up.
• Every 3 months rst year
• Every 6 months during the second and third
years after treatment
• Follow-up is necessary every year afterward
• CT and/or MR imaging of the nasopharynx
should also be performed every 6 months
Complications of radiotherapy:
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484
Although radiotherapy is the main treatment
of nasopharyngeal cancer, many complications
can affect the quality of life of patients post
radiotherapy.
1. Xerostomia is almost always present after
conventional radiotherapy which causes dry
mouth, poor oral hygiene, and dental caries
(1).
2. Hearing impairment is also seen either due to
direct radiation trauma to the hearing organs,
Eustachian tube dysfunction or ototoxicity
due to chemotherapy (2).
3. Radiotherapy may induce soft tissue brosis
and rigidity that might affect the neck move-
ment and mouth opening (3).
T
4. CN
IX, X, XI, and XII) can also be damaged
by radiation (4).
5. Cranial nerve palsies, dryness or pharyngeal
stricture can contribute to the dysphagia (5).
6. Hormonal insufciency and disturbance can
develop due to damage to the hypothalamicpituitary axis or organs like the thyroid gland
(6).
7. Carotid artery stenosis is a possibility following neck irradiation and may cause cerebral
ischemia (7).
8. Neurological sequelae like memory loss, cognitive dysfunction, and neuropsychological
dysfunction can happen after radiotherapy
(8–10).
The advent of conformal radiotherapy such as
IMRT has the potential of reducing late radiation
problems by reducing the dose delivered to critical structures.
41.8 Prognosis
Stage I and II disease treated with radiotherapy
have a 5 years survival rate up to 80% and more,
Stage III and IV with concurrent chemoradiation
have 5 years survival around 70% [20].
A. Larem et al.
Take Home Messages
• As an otolaryngologist a complete ENT
exam involves the postnasal space.
• Any adult patient presenting with unilateral secretory otitis media should
have his post nasal space examined with
focus on the fossa of Rosenmuller.
• Radiotherapy is the main treatment
modality for nasophargeal cancer, with
less side effects when using the IMRT.
• Epstein-Barr virus is a main pathogen in
nasopharyngeal cancer.
Acknowledgment Authors of this chapter appreciate
the help of Dr. Adham A. Ammar—Senior Consultant
Pathology, Dr. Khalid Murshed—Pathology Resident,
HMC, Qatar, and the help of Dr. Adham Aljariri, an ENT
resident in HMC of his effort in editing the chapter.
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