Nasopharyngeal carcinoma is a prevalent malignancy in Southeast Asia. External beam radiation therapy is the primary treatment, but recurrent disease remains challenging. Salvage nasopharyngectomy is used in some institutions for recurrent NPC after failed radiation. The nasopharynx has a complex anatomy near critical structures like the carotid artery. Staging involves imaging like CT and MRI to determine tumor extent and involvement of surrounding areas. Prognosis depends on staging, with 5-year survival rates from 24-95% depending on stage.
2. 2
History of the Procedure
• external beam radiation therapy - primary mode of therapy for
previously untreated NPC
• recurrent or persistent disease remains a challenge to clinicians
• in some institutions, salvage nasopharyngectomy is used for the
treatment of recurrent disease
• 1998 - Fee and Tu published results of salvage nasopha-
ryngectomy in a series of patients with recurrent NPC that failed
previous treatment with radiation
inspired other investigators to start using surgery in the treatment of
patients with recurrent NPC
since then, various surgical approaches to the nasopharynx have been
proposed
3. 3
these include the transpalatal-maxillary-cervical, maxillary
swing, transmandibular, transcervico-mandibulo-palatal, infratemporal
fossa, lateral temporal, and endoscopic approaches
4. 4
Anatomy of Nasopharynx
• 4cm high, 4cm wide and 3cm in
length
• anterior -choanal orifice and
posterior margin of nasal septum
• floor - upper surface of the soft
palate
• roof and posterior wall
Body of the sphenoid,
Basiocciput
First two cervical vertebrae
• lateral wall
Eustachian Tube orifice
Fossa of ROSSENMULLER
8. 8
Histology
3 types of epithelium
• pseudostratified columnar ciliated epithelium - near the
choanae and the adjacent part of the roof of the nasopharynx
• transitional epithelium - roof and the lateral walls
• stratified squamous epithelium - along the posterior and
inferior portions of the nasopharynx
9. 9
Epidemiology & Frequency
Geographical and race
• is a prevalent malignancy in Southeast Asia
• southern China, Hong Kong, Singapore, Malaysia, and Taiwan -
10-53 cases per 100,000 persons per year
• eskimos in Alaska and Greenland and in Tunisians - 15-20 cases
per 100,000 persons per year
• relatively uncommon in Western countries (<1 case per 100,000
persons)
however, prevalence rate for people of Asian descent in the United
States is 3.0-4.2 cases per 100,000 persons.
10. 10
Aetiology
Environmental factors
• geographical clustering in Southern China
• time trend - High risks among Chinese in Southern China
incidence in Hong Kong, Singapore virtually remained unchanged 50 yrs
2nd and 3rd generation born in USA shows decline
• NPC constitute 16% of all malignant tumors among the
chinese
11. 11
Smoking and Alcohol consumption
Occupational
• exposure to nickel, chromium
• radioactive metal
• inhalation of chemical fumes
Ingestions
• salted fish - Nitrosamine
• smoked food
12. 12
Drugs
• chinese herbal medicine
Cooking habits
• household smoke and fumes
Religious practice
• incense and joss stick smoke
Socioeconomic status
• nutritional deficiencies eg. Vitamin A & C
13. 13
Aetiological role of Epstein-Barr virus in
NPC
• more than 90% of patients having elevated antibody titres to
Epstein-Barr virus are those who have NPC of the
undifferentiated / poorly differentiated forms
• moderate to well differentiated NPC are devoid of Epstein-Barr
virus antigen
• thus the role of virus in NPC is still controversial
14. 14
Immunogenetics of NPC
prominent genetic susceptibility
high risk among southern Chinese population
differential high risk in emigrant Chinese compared to
indigenous population
family clustering of NPC in Chinese
elevated risk in people having genetic admixture with
Chinese
low risk in other racial groups despite living in high-risk
countries eg. Indians in Malaysia / Singapore
15. 15
Classification
• WHO classes
based on light microscopy findings
• 3 histological types
type I – Keratinizing SCC
type II – Nonkeratinizing Differentiated Carcinoma
type III – Nonkeratinizing Undifferentiated Carcinoma
Type I
• 25 % of NPC
• moderate to well differentiated cells similar to other keratinizing SCC
(keratin, intercellular bridges)
16. 16
Type II
• 12 % of NPC
• variable differentiation of cells ( mature to anaplastic)
• minimal if any keratin production
• may resemble transitional cell carcinoma of the bladder
Type III
• 60 % of NPC, majority of NPC in young patients
• difficult to differentiate from lymphoma by light microscopy requiring
special stains & markers
18. 18
• Differences between type I and types II & III
5 year survival
• Type I - 10%
• Types II, III - 50%
Long-term risk of recurrence for types II & III
Viral associations
• Type I - HPV
• Types II, III – EBV - full EBV genome present in all NPC epithelial cells
19. 19
Pathology
• Grossly the tumour presents in 3 forms
Proliferative growth causing nasal obstruction
Ulcerative causing epistaxis
Infiltrative which causes cranial nerve involvement
20. 20
Clinical Features
• bimodal peak incidence - 30-40 years and 50-60 years
• male:female – 3:1
• early symptoms - nasal obstruction, blood-tinged sputum or
nasal discharge, tinnitus, headache, ear fullness, and unilateral
conductive hearing loss from serous otitis media or recurrent
acute otitis media
• advanced cases - cranial nerve involvement (III-VI), including
diplopia and numbness of the face
23. 23
Cervical Lymphadenopathy (60%)
• tendency for early lymphatic spread
• commonest palpable node - jugulodiagastric, L2/L3/L5 level
• contralateral lymph nodes metastasis (nasopharynx is midline
structure)
24. 24
Aural Symptoms
• NPC leads to eustachian tube occlusion
sensation of a blocked ear
impaired hearing
tinnitus
serous otitis media
“Adult Chinese patients with unresolving unilateral serous otitis media
have to be presumed to have nasopharyngeal carcinoma until proven
otherwise”
25. 25
Epistaxis and Nasorespiratory Symptoms
• blood stained nasal discharge
• blood stained saliva on hawking
• profuse epistaxis
• nasal obstruction
• ozanea due to tumor necrosis
26. 26
Neurological Palsies
• Most frequently involved are:
VI - Lateral rectus palsy - Diplopia & squint
III, IV, VI - are commonly affected together (opthalmoplegia)
V - High neck & pacial pain & paraesthesia
IX, X & XI - Jugular Foramen Syndrome (involvement of the IX, X, and
XI CN)
• Isolated single C.N. palsy common with nerves V & VI
• Horner’s syndrome – due to involvement to cervical sympathetic chain
ptosis, miosis, dilation lag, enophthalmos (the impression that the eye is
sunk in), anhydrosis (decreased sweating), loss of ciliospinal reflex and
blood shot conjunctiva
27. 27
Pain and Headache
• Hallmark of terminal disease
Erosion of skull base (intracranial extension)
Sepsis - sphenoidal sinusitis
• Trismus
Inviltration of pterygoid muscles
28. 28
Diagnostic Evaluation
• Anterior Rhinoscopy Examination
blood stain nasal discharged
tumour extending into nasal cavity
• Post-Nasal Examination
post nasal mirror - can assess NP space and tumour
difficult to perform in sensitive patients
• Head and Neck Examination
Lymph node
• Level 2/3/5
• Progressively enlarging, hard, fixed, painless swelling
29. 29
• Aural Examination
Otoscopy
Examination under microscope
• retracted tympanic membrane
• fluid in the middle ear
• Cranial Nerve Examination
30. 30
• Rigid Nasal Endoscope
Inspection of the nasopharynx space
Localisation and extent of tumour
Biopsy under vision
• Shanmugaratnam et al - found that 26.4% of NPCs had features of
more than 1 histologic type
• Fee et al - encountered similar findings in 35% of recurrent NPC cases
• Diagnostic Nasal Endoscopy
Flexible Nasal Endoscope
• Fine Needle Aspiration Cytology of the neck lymph node
34. 34
• MRI – radiologic modality of choice
to determine if any intracranial extension of the tumor involves the brain
parenchyma or the cavernous sinus
intracranial spread can occur through foramen ovale, the foramen
spinosum, the foramen lacerum, the carotid canal, and the jugular
foramen that are in close proximity to the nasopharynx
to detect any tumor extension into the retropharyngeal, parapharyngeal,
and pterygomaxillary spaces, as well as the infratemporal fossa and the
sinuses
35. 35
Seroepidemiologic Studies
• demonstrated that 80-90% of patients with WHO type 2 NPC
and WHO type 3 NPC have elevated levels of immunoglobulin A
(IgA) antibodies to viral capsid antigen (VCA) and early antigen
(EA)
• however, only 10-20% of patients with WHO type 1 NPC have
elevated levels of IgA antibodies to VCA
• elevated EBV titers may also be associated with other disease
entities, such as sinonasal undifferentiated carcinoma (SNUC),
sinonasal lymphoma, and tongue cancer
36. 36
Distant Metastasis
• Incidence rate is about 30%
• Sites commonly involved:
skeletal - thoracolumbar spine > 50%
lung metastasis
liver metastasis
• 90% of patients die within the 1st year of diagnosis of the first
metastasis
38. 38
Treatment
• External Beam Radiotherapy
primary mode of management of NPC
at the primary site and in the neck
mainly because of tumor's high degree of sensitivity to radiation as well
as the anatomical constraints for surgical access
recent advances in imaging capabilities and improved radiotherapy
techniques have helped to improve the locoregional control rate
• Chemotherapy
can be delivered before (neoadjuvant), during (concurrent), or following
(adjuvant) radiation therapy
active chemotherapeutic - cisplatin, 5-fluorouracil (5-
FU), doxorubicin, epirubicin, bleomycin, mitoxantrone, methotrexate, an
d vinca alkaloids
39. 39
Chan et al - demonstrated that for patients with stage II and III NPC, the
5-year overall survival rate is better in patients treated with concurrent
chemoradiotherapy (70.3%) than for patients treated with radiation
alone (58.6%)
also for distant metastases
complications of radiotherapy
• brain - Pituitary dysfunction, brainstem encephalopathy, temporal
lobe necrosis, cranial nerve palsy
• ear - Sensorineural hearing loss, otitis media with
effusion, eustachian tube dysfunction
• eye - Dry eye syndrome, ischemic retinopathy
• thyroid - Hypothyroidism
40. 40
• gastrointestinal system - Severe
mucositis, xerostomia, nausea, vomiting, dysphagia, dehydration, eso
phageal stricture
• musculoskeletal system - Excessive fibrosis, trismus, radiation
myelitis, osteoradionecrosis, soft tissue necrosis, osteomyelitis
• vascular system - Stenosis of common carotid artery or internal
carotid artery
41. 41
• Surgery
only for treatment of recurrent NPC with limited disease
contraindicated in involvement of the cavernous sinus
clear appreciation of the tumor in relation to the internal carotid artery is
essential
approaches
• Fee - transpalatal, transmaxillary, and transcervical approach
– provides excellent exposure to both sides of the nasopharynx with
minimal morbidity to the patient
– minimal risk to the internal carotid artery and the cranial nerves
42. 42
• Fisch - infratemporal fossa approach; Gross and Panje - lateral
temporal approach
– both provide excellent exposure of tumors that extend into the
infratemporal fossa and the parapharyngeal space
– disadvantage - difficult if the tumor extends to the contralateral
nasopharynx
– morbidity - sensorineural hearing loss, CSF leak, unilateral laryngeal
paralysis, and facial nerve deficit
• Biller and Krespi - transcervico-mandibulo-palatal approach
– a wide-field exposure of the nasopharynx and excellent protection of
internal carotid artery
– Morton et al - 67% local control rate at 2 years with this approach
43. 43
Follow Up
• 1st year: once a month
• 2nd year: every 2nd month
• 3rd year: every 3 months
• 4th year: every 6 months
• >5years: Once a year
44. 44
Prognosis
• prognostic factors
extent of the primary tumor (ie, skull base invasion, cranial nerve
involvement, parapharyngeal infiltration)
level of the disease in the neck
histologic subtype
age and the sex of the patient
type and technique of radiotherapy
• 5-year overall survival (OS) rate (radiotherapy alone)
• 85-95% in stage I
• 70-80% in stage II
• 24-80% in stage III and IV
45. 45
• 5-year overall survival (OS) rate
60-80% in WHO type III NPC - high degree of radiosensitivity
20-40% in WHO type I NPC - low degree of radiosensitivity
46. 46
“ALWAYS a challenging problem, both
from diagnostic and therapeutic
standpoint, malignant lesions of the
nasopharynx are perhaps most
commonly misdiagnosed, most poorly
understood, and most pessimistically
regarded of all tumors of the upper part
of the respiratory tract”