Diseases Nasopharynx

Nasopharyngeal carcinoma
• You must know some anatomy and better to study it early
as background reading.
• Core lecture only 9, so must try to attend all.
• For any absence, need to submit application/MC.
• Very soon you can sign in lms.aimst.edu.my online
Otolaryngology. I’ve put some important notes and PDF version
of my lectures in LMS portal.
• Anytime you can access and review.
• For hospital posting, show your utmost respect to all doctors,
staffs and patients. You may find it difficult to adjust there but
it’s also a quality to manage a new and unfamiliar environment
in a tactful way to become successful as a clinician.
*Physicians should press the message on 5 Fronts:
* Quality of Diet
* Caloric intake
* Daily Exercise
* Serenity
* Smoking cessation
WHO (2005) definition of NPC

“A carcinoma arising in the

nasopharyngeal mucosa that shows light
microscopic or ultrastructural evidence of
squamous differentiation.”
 BEHAVIOURAL ABERRATIONS IN CANCER CELLS: what extra
Power cancer cells achieve which is not present in a normal cell?

• Proliferative signal------ • Sustaining

• Cell death------------------ • Resist
• Replicative immortality- • Enabling
• Angiogenesis------------- • Induce
• Growth suppression---- • Evading
• Invasion and metastasis • Inducing

10/8/2019 DR KISHORE
 The main categories of cancer (exam)
• Carcinoma (epithelium) - cancer that begins in the skin
or in tissues that line or cover internal organs.
• Sarcoma (CT)- connective or supportive tissue.
• Leukemia - cancer that starts in blood-forming tissue
• Lymphoma and myeloma - cancers that begin in the cells
of the immune system.
• Central nervous system cancers - cancers that begin in the
tissues of the brain and spinal

21/03/14
 What is N PC ?

A malignant tumour 1. Spread Upwards: nose(nose block),

of Nasopharynx brain ( fatigue, CN problem, Motor
arising from
problem, blur vision)
the epithelium
2. Downward: difficult in respiration
 Posterior of this opening is
Fossa of rosenmuller_ common
site of NPC!!

Anatomy_Nasopharynx
• Anteriorly -- nasal cavity
• Posteriorly -- skull base
and vertebral bodies
• Inferiorly -- oropharynx
and soft palate
• Laterally --
– Eustachian tubes and tori
– Fossa of Rosenmuller -
most common location
for NPC
10/8/2019 DR KISHORE
 Fossa of Rosenmüller (FOR)
When there is NPC, the eustachian tube will be blocked, pt will experience ear blocks
EXAM: Summarize how pt with NPC will present?

A recess behind the tubal elevation

10/8/2019 DR KISHORE
• Close association with skull base foramina
• Mucosa
– Epithelium - tissue of origin of NPC
• Stratified squamous epithelium
• Pseudostratified columnar epithelium, cilliated
– Salivary, Lymphoid structures

Tumor extension, affect CN

 Common nasopharyngeal lesions

Inflammator - non-specific Specific (chronic inflammatory d/s)

y
• Acute nasopharyngitis • TB,
• Chronic nasopharyngitis • Syphilis,
• Atrophic nasopharyngitis • Leprosy,
• Lymphiod • sarcoidosis,
Adenoids hypertrophy • wegener’s
– Adenoiditis granulomatosis etc
 • Presented with features of
Rhinitis- nose block, nasal
discharge, but
F / 17
• no
haemoptysis/epistaxis/cough Findings
• Nasal congestion and small
post-nasal mass &
• Incidental finding of lungs lesions
(slight opacities on CXR).
• So, Is it NPC ?

• Biopsy from nasopharynx

showed TB !!!!!!!
• I followed up, Repeat biopsy
became –Ve after ATT
06/20/13
10/8/2019 DR KISHORE
C XR TB minimal change
 What are the tumours in Nasopharynx ?

BENIGN MALIGNANT
•- Angiofibroma- commonest -• Nasopharyngeal
-youngpeople,severesuddennosebleeding, Carcinoma
• Lymphoepithelioma
benign but very dangerous • Adenocarcinoma
• Craniopharyngioma • Adenoid cystic ca
• Chondroma • Lymphoma
• Chordoma For younger
• Myxoma •group-
Rhabdomyosarcoma
• Lymphoma
• Olfactory
neuroblastoma
• Nasopharyngeal carcinoma (NPC) is a
rare malignancy in most parts of the
world
• but is one of the most common cancers
in Southeast Asia.
• This disease was initially reported in 1901,
and characterized clinically in 1922
• ------------------------------------------------------
A new century gift !
 WHY NPC IS A TOPIC TODAY ?
• Nasopharynx cancer is the 5th most
common cancer in Malaysia ( 4.5%)
• Nasopharyngeal cancer is the third most
common cancer among men.(7.5%)
• CHINESE-10%, MALAY- 4.7%
• INCIDENCE: 10 PER 100,000 population
• AMONG CHINESE MALES 16 PER 100,000
• UK 1 in 1400 cancer Pts.
National Cancer registry 2006
• In 2002, it was the 23rd most common new cancer in the world;
in contrast,
• NPC was the fourth most common new malignancy in Hong
Kong .
• NPC comprises the vast majority of nasopharyngeal cancers
in both high- and low-incidence populations.
• 0.7 % of the global cancer burden
• High incidence includes the Singapore Chinese,
• Malaysian Sarawak Bidayuh, and the Southern Chinese
• from Hong Kong and Guangdong.

• NPC is not registered in the list of top 10 in females, but you must
take care of your partner
C ANCER REGISTRY-2006 (males)
West Malaysia
The top 5 cancers affecting both male and
female in Malaysia are: (2003 – 2005
report)
• Breast
• Colorectal
(bowel)
• Lung
• Cervical
• Nasopharyngeal *
NCSM
 W HO classification 1991
(histological)

• Well/ moderate/ poorly differentiated sq.

• keratinizing – WHO type-1 (less
common)

Differentiated –WHO Type 2

• Non-keratinizing (more common)
Undifferentiated

WHO type-3
*Morning Headaches
* In Malaysia could
2nd group indicate
is most cerebral metastases
common
06/20/13
 Age , Sex & race Our
finding
This was the picture of a Malaysian district hospital
in one year time period
YEAR 2010
• Out of 15 cases
• Chinese - 7
• Others – 8 ( Kadazan, dusun, Sungai, Bajau, )
• No Malay case was detected.
• 1 case – 12 years old
• 4 cases 15 – 49 yrs
• 10 cases 50 – 70 yrs common group
 Known risk
• factors
Multifactorial etiology
• Environmental and
• Genetic components/Race

• First-degree relatives of NPC patients have

a fourfold to ten-fold elevated risk of
developing NPC, compared
to those without a family history
. (1999). "Clinical hereditary characteristics in
Zhang F, Zhang J

nasopharyngeal carcinoma through Ye-Liang's family cluster".

 What is more ?
• A viral component
• Epstein-Barr virus (EBV)
• Also called human herpes virus 4
(HHV4)
• A relatively complex virus, EBV is not yet fully understood.
• EBV is nearly always present in NPC
 Risk factors Nitrosamines
• High temperature in frying can increase the
formation of nitrosamines
• Cured meats, primarily cooked bacon; beer;
some cheeses; nonfat dry milk; and sometimes
fish.
• Nitrites used to prevent food contamination
changed to nitrosamine in acidic environment like
stomach, which is carcinogenic.
• ? McDonalds , KFC and Fun-fries
• Evaluation of Risk Factors for
Nasopharyngeal Carcinoma in High-
Risk Nasopharyngeal Carcinoma
Families in Taiwan.
• salted fish consumption during childhood,
exposure to wood, and betel nut
consumption were all associated with
elevated NPC risk
 Risk
factors
• The use of • Smoking,
nasal oils and cooking, and
balms for nose working
and throat under poor
problems ventilation,

Lester D. R. Thompson Update on Nasopharyngeal Carcinoma Head Neck Pathol. Sep 2007
 Genetic factors
associated
• HLA-A2, HLA-8SIN2, HLA-A8, HLA-B 14,17,46 HLA- Bw46
are usually found in chinese- it doubles the risk.
• Multiple aberrations found in chromosome
1,3,9.11.12.14
• Oncogenic gamma-herpesvirus
(hepB, HPV also)
• a ubiquitous virus carried in a
latent, non-pathogenic state
by 80–90 % of all humans.
• Mostly sub-clinical infection-
• Can act like a silent killer
• Transmitted by saliva
• Invades oro-pharyngeal
epithelial cells
mucosa/
• Replication occures there
• In f e c t B-lymphocytes – target cell
06/ 2 0/1 3
 • Type 1 Type 2
• High titres of Epstein-bar
virus is usually found to be
associated . But the exact
etiological role is unknown.
• IgG is found to be +VE
in almost all cases
including common
people.
• But high titre of
IgA class(IgA-VCA,IgA-EA)
is more important. (then IgG)
06/20/13
• In adolescence and teenagers it may
cause Infectious mononeucleosis (flu like
syndrome)
• Its infection is associated with certain
cancers like – Hodgkin’s Lymphoma
Burkitt’s Lymphoma
Nasopharyngeal
carcinoma
And also-
Multiple sclerosis

Lymphomatoid Granulomatosis
 HUMAN PAPILLOMA VIRUS
• ANOTHER ONCOGENIC AND
EPITHELIOTROPHIC VIRUS
• SUBTYPE p16 FOUND TO BE ASSOCIATED
WITH NPC. Usually in White people and
mostly as an oro-pharyngeal extension.
• 16/18 SUBTYPES ARE FOR Ca Cervix
• Double stranded DNA

Singhi et al Head Neck. 2012 Feb;34(2):213-8. doi: 10.1002/hed.21714. Epub 2011 Apr 11.20/13
 Association between allergic
rhinitis and nasopharyngeal
carcinoma: A population-
based study.
This study demonstrated an association
between NPC and prior AR. We recommend
physicians and patients with AR to keep this
potential risk of subsequent NPC
development in mind.

2013 The American Laryngological, Rhinological, and Otological Society, Inc .

 Smokers !!
• Independent Effect of EBV and Cigarette Smoking on
Nasopharyngeal Carcinoma: A 20-Year Follow-Up Study
on 9,622 Males without Family History in Taiwan
• The longer and heavier the cigarette smoking
habit, the higher was the nasopharyngeal
carcinoma risk.
• It is an important environmental pollutant and it
contains Nytrosamin.

06/20/13
 Clinical types

• Proliferative/exophytic (75%) – Patient

primarily
present with signs of blockage (grow into big size).
• Ulcerative(10%) – with bleeding .
• Infiltrative – Neuro-ophthalmological sign (hiding
and slowly spread via tissue)
 How does ?
it
• Direct Local spread to sorroundings
• Regional Lymphatics -- 85% of NPC
cases presented with
lymphadenopathy.
• Retropharyngeal (69%) and
• level II lymph nodes (70%).
• The overall probability of levels III, IV, and
V nodal involvement are 45%, 11%, and
27%, respectively
06/20/13 Dr kishore
Cervical Lymph
nodes • Retropharyngeal
69% 70
• Level II %
• Level III 45
%
 Common distant
•metastasis
Bones,
• Distant lymph nodes,
• Liver, and
• Lungs : most common sites of distant metastases

J Surg Oncol. 1986 Nov;33(3):194-7

Symptoms of local invasion
• Trotter’s triad:
1. Conductive deafness
(Eustachian tube opening
being blocked)
2. Elevation and immobility of homolateral soft
Palate
3. Pain in the side of head – from
involvement of Vth nerve-Trigeminal
nerve, causing pain at the left side of hea.
via foramen lacerum (upward extension).
Pain also may be in ear, upper/lower jaw
and tongue.
 Other neuro-
ophthalmological
• symptoms of invasion
Internal strabismus: involvement of VI th CN
(the most commo n nerve)
• Exopthalmos: from orbital invasion via
superior orbital fissure→ paralysis of 2nd, 3rd
and 4th cranial nerves
• Jugular foramen syndrome( posterolatera
l
extension): paresis of IX, X and XI cranial
nerves. (because these 3 neres pass through
the foramen)
 Base of the skull: Just think, what may happen if a
tumour extends from here in various directions

06/20/13
56
Ref. P L Dhingra
Epistaxis / Nasal
blockage

Neck gland or mass

Ocular palsy/ double

vision diplopia

Unilateral hearing
loss

Facial
numbness
Conductive deafness
Unilateral Why?
EPISTA INTERNAL
XIS STRABISMUS
6th nerve palsy
 VI CN PALSY
Looking to her right
N ECK MAS S
 What is important ?
When to refer?
• Male Patient
• Definite Family Hx of NPC
• with one or more of these symptoms
• Neck mass,
• Unilateral Hearing Loss,
• Epistaxis,
• Chr. rhinitis

•• should be refd. to ENT.

 Nasoendosco
py
• White light image Narrow band image
(WLI) (NBI)

15/03/14 http://www.entpractice.sg/thyroid-cancer-nose-npc.html
 NB
I
• Selecting Blue and Green light at
wavelengths of 415 and 540 nm,
epithelial and subepithelial microvascular
patterns in the nasopharynx can be
visualised.

• Non-exophytic lesion which may be missed

on white-light imaging may be picked up on
NBI, thus improving sensitivity. Joshua (2013)
STAGIN - American Joint Committee on
G Cancer (AJCC)
• DONE ON TNM spread status of tumour
• TX,T0,Tis,T1,T2,T3,T4
• NX,N0,N1,N2,N3
• MX,M0,M1
• Stage 0 : Tis, N0, M0 almost undetectable
• Stage 1 : T1,N0, M0
• Stage IIA T2a,N0 M0

• Stage IIB T2b, N0/N1, M0 or This is just to

get yourself
• Stage IIIT1 or 2, N2, M0, T3, N0-2, M0 familiar but no
need to
• Stage IVA, IVB,IVC T4--,/ N3--, /M1 memorize.
• Radiotherapy (main): External beam
radiation
– Dose: 6500-7000 cGy over 6 weeks
– Primary, upper cervical nodes, pos. lower
nodes
– Consider 5000 cGy prophylactic tx of
clinically negative lower neck
• Adjuvant brachytherapy
– mainly for residual/recurrent disease
• CHEMOTHERAPY: commonly used drugs
are Cisplatin, 5 FU
• CONCURRENT (with DXT) – both radio and
chemo given at same time
• ADJUVENT (post DXT)
• NEOADJUVENT (Pre DXT)
• EXAM: External beam radiation -
complications
– More severe when repeat treatments required
– Include
• xerostomia, tooth decay
• ETD - early (SOM), later (patulous ET)
• Endocrine disorders - hypopituitarism,
hypothyroidism, hypothalamic disfunction
• Soft tissue fibrosis including trismus
• Ophthalmologic problems
• Skull base necrosis Complications are less in
IMRT
 For irradiation in head-neck
• region
We need to ensure a good oral hygiene
before initiating the therapy.
• Pt should be referred to dental dept. for a
dental clearance which may need enough
time, involving dental extraction and
healing.

• Next slide showing how we plan which area

to include
Intensity-Modulated Radiation Therapy
 Treatment
Surgical management
• Mainly diagnostic - Biopsy
– consider clinic bx if cooperative patient
– must obtain large biopsy
– clinically normal NP - OR for panendos- and bx
• Surgical treatment
– primary lesion (radio-resistant, locally
recurrent)
– regional failure with local control
– ETD
• For Primary lesion (take sample for
Nasopharynx)
– Can be considered for residual or recurrent
disease
– approaches
• infratemporal fossa
• transparotid temporal bone approach
• transmaxillary
• transmandibular
• transpalatal
• Endoscopic Nasopharyngectomy
• Has a good prospect.
 Neck Dissection
For selected cases
rarely
• Radical
• Modified
radical
• Selective
 PROGNOSIS (Hongkong
study)
• DEPENDS ON STAGE OF DISEASE
5 YEAR survival (who died
only)
• I 91%
• II 95%
A 82%
• IIB 67%
• III 46-
• IV 50%
 Can we prevent this disease?
• General measures
• No definite • *Smoking
specific Cessation
prevention. * Quality of Diet
• Just to improve your * Caloric intake
overall health status * Daily Exercise
to boost your • * Serenity
immunity.
• SPECIFIC etc
PREVENTION
GENETIC : DEPENDS ON OUR FUTURE GENETIC REASERCH IF WE CAN
• CORRECT
THE CULPRIT CHROMOSOMAL
• LESIONS.
EB VIRUS: POSSIBLE TO VACCINATE IN EARLY CHILDHOOD. Still in trial.
• ENVIRONMENTAL : Our modern life style is full of carcinogens. CAN
CONTROL BUT
how?
 Like many other
cancers
• Early detection can play an
important
role to improve the quality of
life.

* Early detection of NPC reduces the morbidity of

treatment, as early stage disease is treated with
radiation therapy alone.
 Screening
• Endemic areas, high risk families
• Difficulties:
• Some patients may show normal looking
mucosa.
• No clear pre-malignant stage like
Dysplasia, carcinoma-in-situ.
• No single blood test has managed to
achieve sufficiently high sensitivity and
specificity
21/3/14
 Antibody
• EBV VCA IgAtitre Good sensitivity
• ≥C1:40
EBV Ea IgA ≥ >90%
• EBV DNase antibody. Good specificity
C1:10
• >95%
EBV IgA antibodies especially may be elevated
in the years before diagnosis (sometimes up to
10 years before diagnosis).
• It is especially important because of long
sojourn time (duration between symptomatic
and clinical phase of disease) >3years
Choi et al (2010)
 Targeted therapy
• Drugs that target specific parts of cancer
cells may prove to be useful against NPC
and have fewer side effects than standard
chemotherapy drugs.
• The drug cetuximab (Erbitux), which
targets the EGFR protein, is already being
used in some cases of NPC

12/3/14
 Immunotherapy
• To boost the immune system or help it better
target EBV-infected cells.
• One way to do this is to remove T
lymphocytes (immune system cells) from the
blood of patients with NPC and alter them in
the lab to increase their numbers and their
power to kill EBV.

12/3/14
 • EBV-specific cytotoxic T-
infusio coming
lymphocyte
up.
n

Recent development ( HK
& Queensland )
• Vaccine is made from specially trained T-
cells which attack the EBV-infected cancer
cell.
• Increase the survival 2 times.
 Gene therapy
• A clinical trial using a virus to replace the
damaged tumor suppressor gene p53 in
the cancer cells had some promising
results.

• This approach is still being

studied.
Diagnose
?