3.

5 Sign and Symptoms

Clinical manifestations of nasopharyngeal carcinoma can be classified

based on symptoms:

1. Cervical mass

Metastases to the neck glans also often occur in the form of nodes in the

neck (cervical mass) is the most common presenting symptom prompting the

patient to seek medical evaluation. Nodes that appear most often are unilateral but

not infrequently occur in bilateral necks. The cervical node enlargement is usually

painless unless it is accompanied by concurrent inflammatory or infectious

process.15,16

2. Nasal symptoms

Patients may experience of nasal symptoms including nasal discharge

include blood coming out of the anterior or posterior nose and unilateral or

bilateral nasal obstruction. Patients sometimes speak with a nasal twang because

of the nasal blockage so many of these symptoms can be confused with those

caused by sinusitis or rhinitis. If this symptoms occurs, it is very important to have

a thorough evaluation of the nasopharyngeal condition. This is because symptoms

usually do not exist while the tumor has grown or the tumor is not visible because

it is still under the mucosa (creeping tumor).15,16

3. Ear symptoms

Ear symptoms are the earliest symptoms that occur in patient. The patient

feels unilateral hearing loss (conductive deafness) caused by the blockage of the

Eustachian tube that results in effusion otitis media. These symptoms in normal is
relatively rare in adults population, so this condition can be a possible sign sign

for nasopharyngeal carcinoma. Therefore, a thorough examination of the

nasopharynx is necessary if serious otitis media does not clear out in 2–3 weeks in

an adult patient. Other common symptoms include unilateral tinnitus and severe

unilateral otalgia can occur where there is infiltration of the

glossopharyngeal.15,16,17

4. Neurologic symptoms

Neurological symptoms are usually indicative of locally advanced disease.

The most commonly involved cranial nerves are the V and the VI cranial nerves.

Impairment of the function of these nerves will result in paresthesia or numbness

of the face and diplopia, respectively. Other cranial nerves such as the III nerve

may be involved in more advanced cases but an isolated III nerve palsy will never

occur alone without associated involvement of the V and the VI nerves.

Trigeminal neuralgia is a symptom that is often found by neurologists if there are

no other significant symptoms.15,16

Carcinoma process will further affect the nerves of the brain to IX, X, XI,

and XII if the transmission through the jugulare foramen. This disorder is often

called Jakson’s syndrome. When it involvement all the nerves of the brain it is

called unilateral syndrome and can also be accompanied by destruction of the

skull.15,16

5. Eye symptoms
 Eye symptomps that often occur is diplopia. Diplopia is a common

manifestation of VI nerve palsy. In very rare circumstances, proptosis can occur

as a result of tumor infiltration of the orbit through the orbital fissures.16

6. Headache

Headache is usually unilateral and associated with intracranial

involvement are a sign that the disease has a severe stage.16

7. Paraneoplastic syndrome

Patient come with skin lesions consist of distinctive hyperkeratotic,

follicular, erythematous papules. The first lesions usually appear on the face and

eyelids and eventually, the neck, shoulders, and upper extremities are involved. 16

It can be seen in figure 3.2 above.

Figure 3.2 Patient diagnosed with NPC who presented with dermatomyositis.16

3.6 Diagnosis
 The stage of disease is the most important determinant of prognosis in

NPC. The early presenting symptoms of NPC can be confused with benign

conditions such as upper respiratory tract infection, sinusitis, and allergies and the

most common presenting symptoms is a neck mass as a result of cervical nodal

metastasis.16,18

A good understanding of the epidemiology of NPC and its presenting

symptoms and signs and a high index of suspicion in individuals with high risk of

developing NPC are necessary for a prompt diagnosis. In all patients with

symptoms and signs suspicious for NPC, a very thorough examination of

nasopharynx is necessary such as Rosenmüller's fossa biopsy is necessary to

provide pathologic diagnosis and further diagnostic tests including diagnostic

imaging studies and serology test.16

3.6.1 Physical examination

In all patients suspected to have nasopharyngeal carcinoma, a full head

and neck examination including a nasopharyngoscopy should be performed. On

the general head and neck examination, the neck is carefully palpated to detect

any cervical nodal involvement. It is also important to document whether the

cervical lymphadenopathy is mobile, partially fixed, or fixed. The oral cavity and

oral pharynx should be inspected to look out for tumor invasion of the oral

pharynx and trismus. The nasal cavity is inspected with a nasal speculum to detect

any tumor extension to the nasal cavity. The cranial nerves and cervical

sympathetic nerves should be examined systematically and any deficit present

should be carefully documented.16

 The nasopharynx is best examined using a flexible fiberoptic endoscope

under local anesthesia. An indirect mirror examination may be used if an

endoscope is not available. Most NPC arise from the fossa of Rosenmüller.

However, owing to the variation of its anatomy, some early tumors may be

obscured. In more advanced tumors, as a result of more extensive involvement of

the nasophar ynx, it may not be possible to determine where the tumor arises from

locally. Most tumors are pale-looking and have moderate vascularity. The

mucosal surface of the nasopharynx may appear to be normal despite involvement

by NPC (submucosally) and the only sign of involvement may just be some

asymmetry in the nasopharynx.16 It can be seen in figure 3.3

(a) (b)

Figure 3.3 (a). This is an endoscopic view of a normal nasopharynx; (b). This is

an endoscopic view of a nasopharyngeal carcinoma.16

The examiner should be thoroughly familiar with the variety of forms the

nasopharyngeal mucosa and know which parts should be evaluated or expected

there is a lesion. If the complaint is suspected in the direction of nasopharyngeal

carcinoma then the appropriate imaging examination and biopsy of the

nasopharyngeal mucosa is recommended even though the surface of the

nasopharyngeal mucosa looks normal. General examination is very important to

detect distant metastases, such as the chest and bones.16

3.6.2 Supporting investigation

3.6.2.1 Biopsy and histopathology

A biopsy of the nasopharyngeal tumor is necessary in the definitive

diagnosis of NPC. With direct visualization of the nasopharynx under the

endoscope, it is possible to obtain representative biopsies from suspicious areas. 15

Biopsies are usually performed under local anesthesia. The endoscopy should

enter through the nostril opposite to the site of the suspected tumor to allow clear

passage for the biopsy forceps.2 It is important to obtain adequate tissue for

microscopic examination. The specimens obtained should be sent fresh for

microscopic examination. The biopsy is usually painless if it is directed at the

tumor, which is friable and without sensation. However, if the biopsy is taken

from the normal mucosa, the patient may experience some discomfort. Although

some degree of bleeding may occur from the biopsy sites, massive hemorrhage is

seldom seen.19

A repeat biopsy can be performed under the conditions described in Figure

3.4.In patients where there is a clinical suspicion of NPC but with no tumor

visible or in patients with a negative biopsy under local anesthesia, a repeat biopsy

of the nasopharynx under general anesthesia is recommended by taking several

specimens from bilateral Rossenmuller fossa and from the superior / posterior

nasopharyngeal wall.19
 Figure 3.4 Diagnostic algorithm for carcinoma nasopharyng.16

Reporting the diagnosis of nasopharyngeal carcinoma based on WHO

criteria, namely:2,18,19

1. Keratinizing squamous cell carcinoma (WHO 1)

Keratinizing squamous cell carcinoma (SCC) is uncommon in NPC-

endemic regions areas such as Singapore, it constituted between 1% and 20% of

all cases of carcinoma nasopharyng and the proportion of this subtype in non-

endemic western populations has been reported in up to 67% of cases.19

Histologically, the tumor shows prominent features of keratinization,

including presence of squamous pearl formation and evident intercellular bridges.

It can be seen in figure 3.5. This subtype of NPC has been described to have the

most guarded prognosis of all NPC subtypes, probably contributed by its relative

radioresistance. The 5-year survival is reportedly 20%–40% as compared with

about 65% for nonkeratinizing NPC subtypes.19

 Figure 3.5 Keratinizing squamous cell carcinoma.19

2. Differentiated nonkeratinizing squamous cell carcinoma (WHO 2)

Differentiated nonkeratinizing NPC is very similar histopathologically to

undifferentiated carcinoma, except that the tumor cells have a stratified with cell

borders being readily discernable. It can be seen in figure 3.6. Apart from

histological similarities, differentiated nonkeratinizing NPC and undifferentiated

NPC have comparable prognosis and their distinction is not thought to have

clinical significance.19

Figure 3.6 Differentiated nonkeratinizing squamous cell carcinoma.19

3. Undifferentiated squamous cell carcinoma (WHO 3)

 Undifferentiated carcinoma is characterized microscopically by tumor

cells with spindle-to-oval vesicular or hyperchromatic nuclei bearing prominent

nucleoli and which also feature scattered mitotic activity. It can be seen in figure

3.7. This type of undifferentiated carcinoma is rarely found in non-endemic areas,

but conversely in endemic areas this type is the most frequent than non-endemic.19

Figure 3.7 Undifferentiated squamous cell carcinoma.19

4. Basaloid squamous carcinoma

Basaloid SCC is the most unusual variant of NPC with only a handful of

cases reported in the literature. It is histologically very similar to other basaloid

SCCs that occur in the rest of the upper aerodigestive tract and displays tumor

cells with hyperchromatic nuclei, increased nuclear–cytoplasmic ratio with

peripheral palisading of tumor nuclei.19

3.6.2.2 Radiology

Radiological examination in the form of CT scan / MRI of the coronal,

axial and sagittal nasopharyngeal sections, without and with contrast is useful for

viewing primary tumors and spreading to surrounding tissues and spread of lymph

nodes. Bone erosion at the base of the skull can be easily detected by a CT scan
using a bone window. However, MRI is more sensitive than CT scans in detecting

tumors at the base of the skull. CT scans can also detect perineural tumor

extension and intracranial. 15,16,18

In patients who present with cranial nerve deficits, attention should be

directed to the relevant area of the skull base to evaluate the extent of disease. 18

FDG PET/CT is increasingly used in the diagnosis of carcinoma nasopharyng.

Several studies show that 18 FDG–PET/CT is superior to other conventional

studies in terms of detection of cervical nodal and distant metastases. In the

advance metastases can be done by chest X-ray examination, bone scans, and

ultrasound abdomen.16

Nasoendoskopy examination with NBI (Narrow Band Imaging) is a

radiological examination which is best used for follow-up therapy in cases with

suspected residue and residif.16

The figure of CT scan carcinoma nasopharyng can be seen in figure 3.8

(a) (b)

Figure 3.8 A series of three axial contrast-enhanced CT images from inferior to

superior. Image (a) shows a nasopharyngeal carcinoma invading the left

pterygopalatine fossa and masticator space (asterisk) through an enlarged

sphenopalatine foramen (arrow); (b) Shows that the tumor (asterisk) extends via

the superior orbital fissure into the intracranial cavity and involves the left

cavernous sinus (arrow).20

3.6.2.3 Serology

Serological examination of IgA anti EA (early antigen) and IgA anti VCA

for Epstein Barr virus infection shows progress in detecting nasopharyngeal

carcinoma, although this examination is not routinely performed.The IgA

antibody to the viral capsid antigen (VCA) of EBV is a highly sensitive diagnostic

test for NPC although it has a much lower specificity and approximately 75%–

100%. The IgA antibody to the early antigen (EA) has a high specificity (100%)

and a raised titer almost certainly indicated the presence of NPC. Patients in

nasopharyngeal carcinoma will experience elevated levels of IgA VCA. In

patients with an apparently normal clinical examination but with raised titers of

IgA antibodies to VCA and EA, further detailed examination of nasopharynx is

warranted to avoid a missed diagnosis of NPC.16,17

3.7 Differential Diagnosis

The differential diagnosis of nasopharyngeal carcinoma is malignant

lymphoma, non-malignant processes (glandular TB), and metastases (secondary

tumors).2

3.8 Staging
 Classification of nasopharyngeal carcinoma based on TNM, can be

determined by assessing the characteristics of tumor mass, involved on lymph

nodes, and metastases to another organs.2

Primary tumor (T) TX Primary tumor cannot be assessed

T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumour confined to nasopharynx or extends
to oropharynx and/or nasal cavity
T2 With parapharyngeal extension
T3 Tumor invades bony structures and/or
paranasal sinuses
T4 Tumour with intracranial extension and/or
involvement of cranial nerves, infratemporal
fossa, hypopharynx, orbit or masticator
space
Regional lymph node NX Regional lymph nodes cannot be assessed
metastases (N)
N0 No regional lymph node metastasis
N1 Unilateral metastasis in lymph nodes, 6 cm
or less in the greatest dimension, above the
supraclavicular fossa
N2 Bilateral metastasis in lymph nodes, 6 cm or
less in the greatest dimension, above the
supraclavicular fossa.
N3 Metastasis in a lymph node greater than 6
cm in dimension or extension to the
supraclavicular fossa
N3a Greater than 6 cm in dimension
N3b Extension to the supraclavicular fossa
Distant metastasis (M) MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis

Based on the TNM classification above, the clinical stage of

nasopharyngeal carcinoma can be determined:2

Stage T N M
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T1 N1 M0
T2 N0-N1 M
Stage III T1-T2 N2 0
T3 N0-N2 M
Stage IV T4 N0-N2 0
Stage IV T1-T4 N3 M0
Stage IV T1-T4 N0-N3 M1