Tumours of nasopharynx (2) itp class dr.davis - 03.06.16

1. TUMOURS OF
NASOPHARYNX

2. SYNONYMS
Epipharynx
Post nasal space
Retro nasal cavity

3. WHO CLASSIFICATION
 EPITHELIAL TUMOURS
› BENIGN MALIGNANT
Papilloma NPC
Pleomorphic Adenoma Adenocarcinoma
Oncocytoma Papillary adenocarcinoma
Ectopic pituitary Adenoma Basal Cell Ca
Muco-epidermoid carcinoma
Adenoid cystic Ca
Polymorphous low grade Adenocarcinoma

4. SOFT TISSUE TUMOURS
BENIGN MALIGNANT
Angiofibroma Fibrosarcoma
Haemangioma Rhabdomyosarcoma
Haemangio-pericytoma Angiosarcoma
Neurilemmoma Kaposi Sarcoma
Neurofibroma Malignant Haemangio-pericytoma
Paraganglioma Synovial Sarcoma.

5. TUMOURS OF BONE AND CARTILAGE
MALIGNANT LYMPHOMAS
NHL
Extra medullary palsmacytoma
Midline malignant reticulosis
Histocytic lymphoma
Hodgkin’s disease

6. MISCELLANEOUS TUMOUR
BENIGN MALIGNANT
Meningioma Malignant Melanoma
Craniopharyngioma Germ Cell Tumour
Teratoma Chordoma
SECONDARY TUMOURS
UNCLASSIFIED TUMOURS
TUMOUR LIKE LEISIONS – cysts / maningocele /
meningoencephalocele / granuloma / amyloid deposits

7. JUVENILE
NASOPHARYNGEAL
ANGIOFIBROMA
(NASOPHARYNGEAL FIBROMA)

8. JUVENILE NASOPHARYNGEAL
ANGIOFIBROMA
 Commonest of all benign tumours of
nasopharynx.
 Locally invasive, but histologically benign
vascular tumour.
 Seen in young adolescent males . It regresses
after adolescense.
 It is considered as “HAMARTOMA”

9. PATHOGENESIS
 Exact etiology is not known.
 Various theories include:
 Ringert’s theory.
 Som & Neffson.
 Huges-Craniopharyngeal duct.
 Bensch & Ewing-Embryonic fibrocartilage
 Brunner.
 Girgis & Fahmy-Chemodectoma.
 Osborn.
 Willis-Inflammatory immune response

10.  Ringertz (1938) – tumor arose from the
periosteum of nasopharyngeal vault.
 Som and Neffson – inequalities in the growth of
bones of skull base results in hypertrophy of
underlying periosteum,in response to hormonal
influence.
 Bensch and Ewing – tumor probably arose from
embryonic fibrocartilage between basiocciput and
basisphenoid.
 Brunner – origin from conjoined pharyngobasilar
and buccopharyngeal fascia.

11.  Osborn – possibility of the swelling to be
hamartomatous or residues of fetal erectile tissue
which were subject to hormonal influences.
 Girgis and Fahmy – noted cell nests of
undifferentiated epitheloid cells (zellballen) at the
growing edge of angiofibromas,likely to that of
paragangliomas.
 Marten et al – hormonal theory suggesting that
these tumors resulted from deficiency of androgen
and overactivity of estrogen.

12. SITE OF ORIGIN AND GROWTH
 Posterior part of nasal cavity close to the margin of
sphenopalatine foramen.
 From here the tumour grows into the nasal cavity,
nasopharynx and into the pterygopalatine fossa.
 Dumb-bell Shaped.

13. BLOOD SUPPLY OF THE TUMOUR
 Maxillary artery.
 Ascending pharyngeal artery
 Un named branches from internal carotid artery.

14. SPHENOPALATINE
FORAMEN
It is formed by:
 Orbital & Sphenoidal process of the
perpendicular plate of palatine bone.
 Horizontal ala of the vomer.
 Root of the pterygoid process of the sphenoid
bone.

15. PATHOLOGY
 Angiofibroma, as the name implies, is made up of
vascular and fibrous tissues
 Mostly, the vessels are just endothelium-lined spaces
(foetal type of blood vessels) with no muscle coat.
 This accounts for the severe bleeding as the vessels
lose the ability to contract.

16. SPREAD OF TUMOUR
 Nasal cavity
 Paranasal sinuses
 Pterygomaxillary fossa, infratemporal fossa
and cheek
 Orbits giving rise to proptosis and “frog-face
deformity” through the inferior orbital fissure
Cranial cavity
 There are two routes of entry:
1) By erosion of floor of middle cranial fossa
anterior to foramen lacerum.
2) Through sphenoid sinus

17. CLINICAL FEATURES
 Profuse and recurrent epistaxis.
 Progressive nasal obstruction.
 Hyponasal Voice.
 Conductive hearing loss and serous otitis
media due to obstruction of eustachian tube.
 Mass in the nasopharynx
 Broadening of nasal bridge, Proptosis, swelling
of cheek,
 Involvement of IInd, IIIrd, IVth, VIth cranial
nerves will depend on the extent of tumour.

18. Anterior rhinoscopy:
-- abundant mucopurulent secretions.
-- bowing of the septum to the uninvolved side.
Posterior rhinoscopy:
-- pink or red mass filling the nasopharynx.

19.  Gross physical signs are evident when the tumor
has involved the infratemporal fossa.
 Swelling in the cheek and temple
 Intraoral palpation in the area between the
ascending ramus of mandible and the side of
maxilla – fullness because of tumor that has
crept around the back of the antrum

20. PECULIARITIES
 More common in young adolescent males.
 Benign but locally invasive.
 It has got diffuse attachment and takes blood
supply whereever it goes.
 No capsule, No pedicle.
 Recurrences more common.

21. FISCH CLASSIFICATION
I-confined to Nasopharynx & Nasal
cavity without bone destruction.
II-Pterygopalatine fossa & Sinuses
with bone destruction.
III-Infratemporal fossa & Orbit.
IV-Intracranial extension.

22. FISCH STAGING CLASSIFICATION
 Done for prognosis and therapeutic approaches
 Stage I: Tumor limited to the nasal cavity
 Stage II: Tumor extension into the pterygopalatine fossa, or
maxillary, sphenoid or ethmoid sinuses.
 Stage IIIa: Tumor extension into the orbit or infratemporal
fossa without intracranial involvement.
 Stage IIIb: Stage IIIa with extradural (parasellar)
intracranial involvement
 Stage IVa: Intradural without cavernous sinus, pituitary, or
optic chiasm involvement
 Stage IVb: Involvement of the cavernous sinus, pituitary, or
optic chiasm

23. RADKOWSKI
CLASSIFICATION
 Stage Ia: limited to the nose and nasopharyngeal
area.
 Stage Ib: extension into 1 or more sinuses.
 Stage IIa: minimal extension into
pterygopalatine fossa
 Stage IIb: occupation of pterygopalatine fossa
without extension to orbit.
 Stage IIc: infratemporal fossa extension without
cheek or pterygoid plate involvement.
 Stage IIIa: erosion of skull base(middle cranial
fossa)
 Stage IIIb: erosion of skull base with intracranial
extension with or without cavernous sinus
involvement

24. DIFFERENTIAL DIAGNOSIS
 Enlarged Adenoids.
 Infected AC Polyp.
 Haemangiomas.
 Rhinosporidiosis.
 Inverted Papilloma.
 Malignancy.
 Craniopharyngioma.

25. INVESTIGATIONS
 X-ray Soft tissue lateral view of nasopharynx.
 X-ray of paranasal sinuses and base of skull.
 C.T. Scan - Plain & Contrast to know the
Intracranial extension.
 Carotid angiography.
 MR Angiography.

26. Brown’s Sign
 CT findings:
 A Vascular mass located posterior to the
maxillary antrum with anterior displacement of
the posterior wall of the maxillary sinus.
 X-Ray Findings:
 Holman Millar Antral Sign – Anterior
bowing of the posterior wall of the Maxillary
sinus.

27. HOLMAN MILLAR SIGN
 1) JNA
 2) Schwanoma
 3) Fibrous dysplasia
 4) Nasopharyngeal Carcinoma
 5) Tumours of infratemporal fossa.

28. TRIPLE LINE OF BACLESSE
Submento Vertical View of X-Ray PNS
 1) S-Shaped line represents the Posterior wall of the
Maxillary sinus. Erosion – into the Subtemporal fossa.
 2) Upper curvilinear line represents lateral wall of
orbit. Erosion – into the orbit.
 3) Lower curvilinear line represents lesser wing of the
Sphenoid. Erosion – Skull base.

29. DIAGNOSIS
 It is mostly based on clinical picture, Biopsy
is avoided.
 EMBOLISATION
 TREATMENT
 Surgical excision is now the treatment of
choice
1. Wilson’s Transpalatine
2. Transpalatine + Sublabial (Sardana’s
approach)
3. Extended lateral rhinotomy.
4. Midfacial degloving.
5. Endoscopic approach.
6. Maxillary swing.

30. Recurrent angiofibroma:
 Difficult if it occurs after initial surgical removal
 Facial disassembly approach.
 Stereotactic radiosurgery for small intracranial
recurrences.
 Doxorubicin and decarbazine.

31. MATERIALS USED FOR
EMBOLISATION
 Autologous substances like fat, blood clot, or chopped
muscle fragments.
Artificial materials: Gelfoam, Oxidised cellulose,
Tantalum powder, glass beads, polyvinyl alcohol etc.
 Embolisation should always be preceded by
angiography.
 Immediate complications of embolisation are pain,
embolisation of normal vessels, hypersensitivity.
 Delayed complications include fever, pain and
infections.

32. RADIOTHERAPY
 Radiotherapy can produce some amount of tumor
regression by radiation vasculitis and occlusion of
vessels by perivascular fibrosis.
 Radiotherapy should be reserved for selected
patients such as those with inoperable
intracranial extensions and recurrent tumors.
 External beam radiation is delivered in low dose
of 30 – 55 Gy in 15 fractions over 3 wks.
 Regression of angiofibromas after radiotherapy is
very slow, like 2 to 3 yrs to reduce the tumor size
but residual tumor remains.

33.  Disadvantages of radiotherapy:
a. If the child is exposed to large doses i.e.
above 5000-6000 rads, there may be damage to
eyes, spinal cord and brain.

b. Small doses are ineffective in reducing the
blood supply or the size of the mass.

c. Radiotherapy may cause fibrosis retardation of
facial growth and adhesions of surrounding
tissue. Later surgery upon these patients becomes
difficult.

d. Sarcomatous changes can occur in the mass as a
result of irradiation.

34. HORMONAL THERAPY
 Oestrogens - induces shrinkage,collagen
formation,reduces vascularity.
Disadvantages – feminizing effects
(breast size)
 Nonsteroidal androgen receptor blocker,
Flutamide – tumor shrinkage upto 44%
was reported.
Disadvantages - breast tenderness,
nausea, gynaecomastia.
 Hormones by themselves are carcinogens

35. OTHER BENIGN TUMOURS OF NASOPHARYNX
 Teratomas
 Pleomorphic adenoma
 Chordoma
 Hamartoma
 Choristoma
 Paraganglioma

36. NASOPHARYNGEAL
CARCINOMA

37. NASOPHARYNGEAL CANCER
 More common among Chinese & South-east
Asians.
 Male: Female ratio – 3 : 1
 15-19 years of age, 35-65 years of age

38. PREDISPOSING FACTORS
 Genetic Factors.
 Viral – EB Virus.
 Environmental factors
1) Tobacco Smoking.
2) Salted fish & Preserved Vegetables.
3) Incense Stick Smoke.
4) Household & Industrial fumes.
5) Wood dust.

39. EPIDEMIOLOGY
Chinese native > Chinese immigrant >
North American native
Both genetic and environmental factors
Genetic
HLA histocompatibility loci possible markers

40. Environmental
Viruses
EBV- well documented viral “fingerprints” in tumor cells
and also anti-EBV serologies with WHO type II and III
NPC
HPV - possible factor in WHO type I lesions
Nitrosamines - salted fish ( Cantonese type salted
fish )
Vitamin C deficiency
Others - polycyclic hydrocarbons, chronic nasal
infection, poor hygiene, poor ventilation

41. Immunology
Is an epithelial tumour , having antibody
response to
Viral Capsid Antigen ( VCA )
Early Antigen ( EA )
Epstein Barr Nuclear Antigen
( EBNA )
Antibody dependent Cellular
Cytotoxicity ( ADCC )

42.  Genetics ( Related to Oncogens & Tumour supressor genes )
 Human Leucocyte Antigen ( HLA )
 Chromosomal deletions and translocations
 Short arm of chromosome 6 has six loci
HLAA , B , C , DR , DQ , DS
 HLAAW19 , B17 – Short term survival
 HLAA2 BW46 – Intermediate term survival
 HLAA2 without BW46 or B17 – Long term survival

43. AGE & SEX DISTRIBUTION
AGE SEX
Bimodal distribution M : F = 3:1 in chinese
Peak age : 4th
decade in chinese 2:1 in non-chinese
6th
decade in non-chinese

44. WHO classification and relation to EB virus and
radiotherapy.
WHO nameWHO name IncludesIncludes EB virusEB virus
titretitre
Response toResponse to
radiationradiation
II Squamous cellSquamous cell
carcinomacarcinoma
Well andWell and
moderately diffmoderately diff
sq cell casq cell ca
LowLow poorpoor
IIII Non-Non-
KeratinisingKeratinising
carcinomacarcinoma
Transitonal cellTransitonal cell
caca
HighHigh RadioRadio
sensitivesensitive
IIIIII UndifferentiatUndifferentiat
ed carcinomaed carcinoma
LymphoepithLymphoepith
eliomaelioma
AnaplasticcaAnaplasticca
Spindle cellSpindle cell
caca
Clear cell caClear cell ca
HighHigh Radio -Radio -
sensitivesensitive

45. CLASSIFICATION
 Type I - “SCCA”
25 % of NPC
moderate to well differentiated cells similar to other SCCA
 Keratin pearls, intracellular bridges, and increased
nuclear-to-cytoplasmic ratios but consistent sizes of
the nuclei.

46.  Type II - “non-keratinizing” carcinoma
12 % of NPC
variable differentiation of cells ( mature to anaplastic)
minimal if any keratin production
may resemble transitional cell carcinoma of the bladder
 Decreased level of differentiation characterized by
increased nuclear pleomorphism
 Increasing inflammatory infiltrate compared with type
I tumors.

47.  Type III - “undifferentiated” carcinoma
 60 % of NPC, majority of NPC in young patients
Classic appearance of a lymphoepithelioma with difficult to
distinguish squamous cancer cells in a background of
lymphocytes
 Diverse group
 Lymphoepitheliomas, spindle cell, clear cell and anaplastic
variants

48. 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

49. CLINICAL FEATURES
1)Painless cervical lymphadenopathy 60%
2)Epistaxis
3)Aural symptoms 30%
4)Neurological Symptoms 20%

50.  NPC has a tendency for early lymphatic spread.
 Retropharyngeal node of Rouviere is the first
echelon node.
 Commonest first palpable node is the J.D. node
and the apical node under sternomastoid muscle.
 46 % - unilateral 22 % - bilateral

51. AURAL SYMPTOMS
Serous otitis media is common
Hearing loss
Pain in the ear
Aural block
Tinnitus

52. OPHTHALMIC
SYMPTOMS
Ptosis
Epiphora
Loss of corneal reflex
EOM – impaired
Enophthalmos
Diplopia
Xerophthalmia
Rarely optic nerve is involved.

53. Jacod`s triad Trotter’s triad
 Trigeminal neuralgia Trigeminal neuralgia
 Amaurosis bulbi Palatal Palsy
 Ophthalmoplegia Conductive HL

54. PAIN & HEADACHE
 This is an ominous symptom
 Severe pain is hallmark of terminal disease.
 Signifies tumour erosion into skull base.
 If accompanied by trismus, the disease is very
advanced and has extended into pterygopalatine
fossa.

55. SYNDROMES
 Tapia 9,12
 Avellis 9,10
 Schmidt 10,11
 Vernet 9,10,11
 Hughlings Jackson 10,11,12
 Collet sicard 9,10,11,12
 Villaret 9,10,11,12+ Cervical Sympathetic
Chain
 Horner’s syndrome , Gradenigo’s Syndrome , Garcin
Syndrome

56. DISTANT METASTASIS
Incidence is 30%
Skeletal metastasis account for more than
one half.
Thoraco lumbar spine is the commonest
site followed by the lung and liver.

57. SPREAD OF TUMOUR
Ca
Nx
Foramen lacerum
and Ovale
Eust tube
Nose and
Orbit
Distant
metastases
Serous O.M
Nasal obst,
Epistaxis
proptosis
Secondaries
Lung, Liver,
bone
Parapharyngeal
Space
Retro-
pharyngeal
nodes
Cervical
Nodes
Upper jugular & Posterior Δ
Nodes enlargement
Cranial nerve
palsies IX, X,
XI, XII,
Horner’s
syndrome
Pterygoid
muscles
Trismus
Neck pain
and stiffness

58. BRODER’S CLASSIFICATION
 Grade I – 25 % of cells are lacking
differentiation
 Grade II – 25 – 50 % of cells are undifferentiated
 Grade III – 50 – 75 % of cells are
undifferentiated
 Grade IV – More than 75 % of cells are
undifferentiated

59. TNM CLASSIFICATION
 T1- within Nasopharynx
 T2-Nasal cavity/oropharynx
a)without Parapharyngeal extension
b)with Parapharyngeal extension
 T3-Invasion of surrounding bony structures &
Paranasal Sinuses.
 T4-Intracranial extension.

60. Regional lymph nodes
Nx and No
 N1- Unilateral 6cm or less above supra clavicular fossa
 N2- bilateral 6cm or less above supra clavicular fossa
 N3a - >6cm above supra clavicular fossa
 N3b – extends into supra clavicular fossa

61.  Neel and Taylor System
› Extensive primary tumor +0.5
› Sx’s present < 2 months before dx - 0.5
› Seven or more sx’s +1.0
› WHO type I +1.0
› Lower cervical node dx +1.0

62. Neel and Taylor System
 Stage A = < 0
 Stage B = 0 to 0.99
 Stage C = 1 to 1.99
 Stage D = > 2

63. Grossly the tumour presents in three
forms.
Proliferative
Ulcerative
Infiltrative
The commonest site of origin is fossa of
Rosenmuller in the lateral wall of
nasopharynx.

64. INVESTIGATIONS
 Special diagnostic tests (for types II & III)
IgA antibodies for viral capsid antigen (VCA)
IgG antibodies for early antigen (EA)
 Special prognostic test (for types II & III)
antibody-dependent cellular cytotoxicity (ADCC)
assay
 higher titers indicate a better long-term prognosis
 CBC, ESR, chemistry profile, LFT’s
 Audiological Tests , Field test & other
Ophthalmic tests

65. Angiography
Contrast CT with bone and soft tissue windows
imaging tool of choice for NPC ( Erosion of
med.pterygoid plate , lateral extension into ITF ,
invasion of the middle fossa, by orbit / Sup.orbit
fissure )
Involvement of sphenoid sinus (70%) , ITF (60%) ,
Orbit (30%) , MCF (20%)
MRI - soft tissue involvement, recurrences
X rays, Skeletal Scintigraphy ,
CXR , USG - Abdomen
Chest CT, bone scans

66. TREATMENT
Radiotherapy is the definitive
treatment.
Chemotherapy is used to supplement
R.T. in advanced cases with cervical
metastasis
Role of surgery is only to take biopsy
or to deal with cervical metastasis
after the primary has been sterilized.

67. Mega Voltage External Radio-theraphy
Two lateral opposing and one anterior field
 Dose: 6500-7000 cGy , Consider 5000 cGy prophylactic tx
of clinically negative lower neck
 Five / six daily sessions per week for a total of six
weeks.
 Early disease ( stage I / II ) – conventional
radiotheraphy alone
 Locally advanced non-metastatic disease ( stage III /
IVB ) – Chemotheraphy + CRT
Adjuvant brachytherapy
mainly for residual/recurrent disease

68. COMPLICATIONS OF RT
 Mucositis
 Xerostomia
 Dental caries
 Radiation myelitis
 Optic atrophy
 Early intranasl adhesions
 Otitis externa with
osteoradionecrosis
 ETD - early (SOM), later
(patulous ET)
 Endocrine disorders -
hypopituitarism,
hypothyroidism,
hypothalamic disfunction
 Soft tissue fibrosis
including trismus
 Temporal lobe necrosis
 Hypoglossal nerve palsies

69. Chemotherapy ( Neoadjuvant / Concurrent /
Adjuvant )
Variety of agents - Bleomycin / Methotrexate /
Hydroxyurea / 5-Fluorouracil / Cisplatin
Chemotherapy + XRT - no proven long term benefit
Mainly for palliation of distant disease
Immunotherapy
Future treatment ??
Vaccine ??
Use of EBV structural antigens / Cytotoxic T –
Lymphocytes epitopes.

70. SURGICAL
APPROACHES
Anterior approaches Inferior approaches
Lateral rhinotomy Transpalatal
Transnasal transmaxillary Mandibular swing
Midfacial degloving
Le fort 1 osteotomy
Maxillary swing

71. PHOTODYNAMIC THERAPY
 Salvage for recurrent / residual NPC
 Tumouricidal effect – laser activation of photosensitizer – selectively taken up and
retained by the tumour
 1st
gen PDT – combination of HPD (Hemato-porphyrin derivatives) & laser light of
630mm red light from a gold vapour / pumped dye laser.
 2nd
gen PDT - combination of m-THPC
(m-tetrahydroxyphenylchlorin ) &
activated by 652mm red light from
diode laser

72. PROGNOSIS
5 - Year survival rate
Stage I – 90%
Stage II – 70%
Stage III – 60%
Stage IV – 40% without metastasis
0% with metastasis

73. THANK YOU