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
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.
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.
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
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
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.
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
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.
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