Juvenile nasopharyngeal angiofibroma - current treatment modalities

1. JNA(Juvenile Nasopharyngeal
angiofibroma) current treatment
modalities and future
considerations
Presenter-
Dr. Sritama De

2. • Juvenile angiofibroma is an uncommon, benign and extremely vascular
tumour that arises in the tissues within the sphenopalatine foramen.
• Angiofibroma, nasopharyngeal fibroma, bleeding fibroma of adolescence,
fibroangioma
• Accounts for less than 0.5 percent of all head and neck tumours
• Develops almost exclusively in adolescent males, though there are reports
of this tumour being found in children, the elderly, young and even
pregnant women.
• Mean age at presentation is 14y ( 7 – 19y)

3. Surgical anatomy of
the Nasopharynx

6. ETIOPATHOGENESIS
• Many theories have been propounded but none is entirely convincing
1. Ringertz (1938) – Periosteum of nasopharyngeal vault
2. Som & Neffson (1940) – Inequalities in the growth of bones forming the skull base resulted in
hypertrophy of the underlying periosteum in response to hormonal influence
3. Bensch & Ewing (1941) – embryonic fibrocartilage between basiocciput and basisphenoid
4. Brunner (1942) – conjoined pharyngobasilar and buccopharyngeal fascia
5. Osborn (1959) – Swelling were either hamartomas or residue to fetal erectile tissue which were
subject to hormonal influence
6. Girgis & Fahmy (1973) – Paragangliomatous tissue around the terminal part of the maxillary
artery in the pterygopalatine fossa may be the forerunners of angiofibroma
The most accepted theory is that JNAs originate from sex steroid–stimulated
hamartomatous tissue located in the turbinate cartilage. The proposed hormonal
influence may explain why (rarely) some JNAs involute after puberty.

7. RECENTLY
1. Immunocytochemical techniques have been used to show that
a) Androgen receptors - present in at least 75 % of tumours (in both the vascular and stromal
elements)
b) Progesterone receptors - smaller proportion
c) Oestrogen receptors - not been demonstrated
2. Angiogenic growth factor (vascular endothelial growth factor (VEGF) - localized on both
endothelial and stromal cells
3. Proliferative marker Ki67 - Vessel density and both the expression and localization of VEGF
4. Overexpression of insulin-like growth factor II (IGFII) –
a. Short arm of chromosome 11
b. Expressing the paternal allele only
c. Might be associated with a tendency to recurrence and poorer prognosis

8. 5. Germline mutations in the APC gene on chromosome 5q
a) pathogenesis of sporadic juvenile angiofibromas.
b) 25 times more frequently in patients with familial adenomatous polyposis
c) This gene regulates the beta-catenin pathway which influences cell to cell adhesion.
d) sporadic and recurrent juvenile angiofibromas.
e) Localization of beta-catenin only to the nuclei of stromal cells hence suggested that
the stromal cells have a critical role in the development of these neoplasms.

9. PATHOLOGY
GROSS
1. Firm, slightly spongy lobulated
swelling
2. Nodularity increases with age
3. Colour- Pink to white
CUT SECTION
1. Reticulated, whorled or spongy
appearance
2. Lacks true capsule
3. Edges are sharply demarcated
Nasopharyngeal angiofibroma - The cut
surface shows the characteristic spongy
appearance and well-circumscribed outline

10. MICROSCOPIC
1. Proliferative irregular vascular
channels
2. Vascular channels of varying size and
shape abounding in a stroma of fibrous
tissue
3. Vascular pattern is
a) Large thin walled sinusoidal vessels
b) Lined by flattened epithelium
c) Lack smooth muscle and elastic fibres
4. Stroma
a) Coarse parallel or wavy interlacing
bundles of collagen in which stromal
cells are seen to radiate outward from
vessel
b) Stromal cells are plump cells which
may be spindle/ stellate in shape
c) Localised areas of myxomatous
degeneration

11. SITE OF ORIGIN
• Broad base
• Originate from the sphenopalatine foramen
• Some authors also suggest that they may arise from
the nasopharyngeal vault or choana.
• A recent study by Lloyd et al(1999); suggests that
angiofibroma takes origin in the pterygopalatine fossa
at the aperture of the pterygoid canal. [1]
[1] Lloyd, G, Howard, D, Phelps, P, and Cheesman, A. Juvenile angiofibroma: the lessons of 20 years of modern imaging.
J Laryngol Otol. 1999; 113(2): 127-34.

12. ROUTES OF SPREAD
• Medially, towards nasopharynx and nasal cavity
• Distorts the nasal septum, turbinates and the soft palate.
• It may erode the posterior ethmoidal and sphenoidal sinuses
allowing direct extension of tumour into the orbit, cavernous
sinus and the parasellar region
• Laterally, Sphenopalatine foramen -> Pterygopalatine fossa ->
Pterygomaxillary fissure -> Infratemporal fossa -> Cheek
• Can also extend along the inferior orbital fissure, across the apex
of the orbit into the superior orbital fissure.
• Continued tumour expansion –> pressure erosion of the base of
the pterygoid plate and greater wing of sphenoid -> tumour
comes against the dura of the middle cranial fossa

13. BLOOD SUPPLY
1. Enlarged maxillary artery – mainly
2. Ascending pharyngeal artery
3. Vidian artery
4. Unnamed branches of the internal carotid artery
5. Vertebral artery- rarely

14. CLINICAL FEATURES
SYMPTOMS
1. Progressive nasal obstruction
2. Recurrent severe epistaxis- profuse, painless,
unprovoked paroxysms of epistaxis
3. With tumour growth and extension –
 swelling of the cheek,
 Frog face deformity(proptosis+nasal bridge broadening),
 Trismus
 Hearing loss secondary to Eustachian tube obstruction,
 Hyposmia or anosmia
 Nasal intonation or plummy quality to the voice
4. More extensive tumour
 Proptosis - spread through orbital fissures
 Diplopia
 Visual loss
 Facial pain and headache

15. SIGNS
1. Anterior rhinosopy – abundant mucopurulent secretions with bowing of
nasal septum towards uninvolved side
2. Posterior rhinoscopy - pink or red mass filling the nasopharynx
3. Soft palate is often displaced inferiorly by the bulk of the tumour which
can be seen clearly as a pink or reddish mass that fills the nasopharynx.
4. Gross physical signs- seen in extensive disease
• Splaying of nasal bones (broadening of nasal bridge)
• Swelling in temple or cheek
• proptosis
5. Intraoral palpation – fullness in the interval
between the ascending ramus of mandible
and side of the maxilla
6. Endoscopy - smooth lobulated pink or
reddish mass in the nasopharynx.

16. ASSESMENT
1. Plain lateral skull radiographic - anterior bowing of
the posterior wall of the maxillary sinus
2. CT
• Images demonstrate extent of the tumor
• View of the sinuses may demonstrate nasopharyngeal
polyp
• Bowing of the posterior wall of the maxillary sinus
(Holman-Miller sign) and maxillary sinus
opacification is very suggestive of JNA.
• Erosion of roof of medial pterygoid plate.
3. Magnetic resonance imaging (MRI) –
• delineate and define the extent of the tumor especially
in cases of intracranial involvement/ cavernous sinus
• Improved detail of the cribiform plate and the
cavernous sinus is noted
4. Diagnostic angiography –
• evaluate the source of blood supply and as a prelude
to selective embolization
• extent of tumor
• tumour blush (due to increased vascularity)

17. Coronal MRI scan showing extension of the lesion to the
cavernous sinus

18. 1. Sessions et al, (1981)
2. Fisch (1983) - most robust and practical
3. Andrews et al ,1989
4. Radkowski et al in 1996 (Revised Sessions)
5. Chandler et al,1984.
STAGING SYSTEMS

19. FISCH STAGING SYSTEM OF JUVENILE ANGIOFIBROMAS
Type 1 - Tumour limited to the nasopharyngeal cavity; bone destruction
negligible or limited to the sphenopalatine foramen
Type 2 - Tumour invading the pterygopalatine fossa or the maxillary, ethmoid
or sphenoid sinus with bone destruction
Type 3 - Tumour invading the infratemporal fossa or orbital region:
(a) without intracranial involvement
(b) with intracranial extradural (parasellar) involvement
Type 4 - Intracranial intradural tumour:
(a) without infiltration of the cavernous sinus, pituitary fossa or optic chiasm
(b) with infiltration of the cavernous sinus, pituitary fossa or optic chiasm

21. DIFFERENTIAL DIAGNOSIS
1. Antrochoanal polyp
2. Large adenoids
3. Chordoma
4. Tumours of post nasal space
a. Teratoid – dermoid, teratomata, epignathi
b. Neuroectodermal - encephalocoele, brain
heterotopia, meningioma
c. Dysontogenetic - chordoma, craniopharyngioma,
d. Miscellaneous – cysts, haemangioma, hamartoma,
rhabdomyosarcoma

22. CURRENT TREATMENT MODALITIES

23. • Liston, at University College London performed the
first successful resection of an angiofibroma
• Liston removed the tumour by performing a total
maxillectomy through a Weber– Fergusson incision
without anaesthesia!
HISTORICAL

24. SURGICAL RESECTION
1. Transnasal maxillary approach
2. Transpalatal approach (Wilson’s approach)
3. Lateral rhinotomy
4. Sublabial mid-facial degloving approach
5. Infratemporal fossa approaches
6. Transmaxillary(Le fort-1)
7. Maxillary swing
8. Endoscopic resection (one or two surgeon techniques)
9. Combined approaches
• Combined craniofacial approaches
• Combined transpalatal and sublabial (Sardana’s approach)
• Combined transoral and transnasal endoscopic approach (recent concept)

25. TRANSNASAL MAXILLARY APPROACH
• Tumour in the maxillary antrum and anterior part of
the nose – removed through sublabial incision
• Preoperative ligation or clipping of the internal
maxillary artery – transantrally
• Denker’s extension of the Caldwell - Luc procedure
provides fair extension
• Use of lateral rhinotomy or Weber – Fergusson
incision improves exposure
• Often needs to be combined with transpalatal
approach to deliver the tumour completely

26. Wilson 1957
Exposes the nasopharynx and allows extension the sphenoidal and posterior nasal
fossa
U- shaped incision made about 2.5cm anterior to junction of soft and hard palate
Incision may be extended around the maxillary tuberosity to join the sublabial
incision– to reach extensions into pterygopalatine fossa
TRANSPALATAL APPROACH
Mucoperiosteal flap elevated (preserving the
greater palatine neurovascular pedicles) ->
bone from hard palate removed
 Contraindications
1. Tumours with significant dural and
intracranial extensions
2. Lesions that require a degree of lateral
access(parapharyngeal space,infratemporal
fossa )

27. For tumours which encroach on the nasal fossa
and just spill over into the pterygopalatine fossa –
lateral rhinotomy combined with resection of
medial antral wall (medial maxillectomy)
Indication
1. Tumours limited to
nasopharynx,ethmoid,sphenoid,maxillary
sinus
2. Tumours extending to orbit,pterygopalatine
fossa,infratemporal fossa(medial end)
 Contraindication
1. Larger masses
2. Masses whose extensions and attachments
cannot be ascertained
LATERAL RHINOTOMY

28. • For larger tumours which
invade the infra temporal
fossa access is improved
by combined transnasal
or transantral approach
• Weber Ferguson incision
(Shaheen, 1982) or facial
degloving approach
(Howard and Lund,
1992)

29. SUBLABIAL MID-FACIAL DEGLOVING
 A bilateral extended sublabial and transnasal- maxillary approach
 This approach allows the pterygopalatine and infratemporal fossa to be reached
 Advantages
• Adequate exposure to the nasal complex, nasopharynx and mid third of the face
•No visible scar
 Disadvantage
Vestibular stenosis

30. LE FORT OSTEOTOMY 1
Indication: Tumours extending into nasopharynx, nasal cavity, paranasal
sinuses,pterygopalatine fossa,minor extension into the infratemporal fossa
Sublabial incision and transverse maxillary osteotomy through both maxillary
sinuses
Hard palate & both inferior maxillae down
fractured
Access to nasopharynx and central skull base
No facial bones resected,no visible scar

31. MAXILLARY SWING
Described by Wei in 1991
Indication
Nasopharyngeal tumours with limited extension to anterior infratemporal region
Contraindication
Tumours extending into posterior infratemporal region or para sellar region
Incision: Weber-Fergusson Longmire
Advantages
• Exposes nasopharynx and surrounding areas from
antero-lateral aspect
• Entire maxilla separated from its bony foundations
• Sufficient exposure for dissection between both
carotid arteries

32. COMBINED APPROACHES
1.TRANSPALATAL SUBLABIAL approach(Saldana 1965)
Tumours extending into pterygoid and infratemporal fossa
2.TRANSPALATAL and LATERAL RHINOTOMY approach
• Larger tumours
• Recurrent JNA
• Tumour extensions not predetermined
3.TRIPLE APPROACH OF HIRANANDANI
• Transpalatal+Lateral rhinotomy+Caldwel Luc
• Complete exposure of pterygopalatine fossa
• Recurrences minimised
• Ligation of internal maxillary artery minimises bleeding
4.MIDFACIAL DEGLOVING and TRANSMAXILLARY approach
5.SUBTEMPORAL PRE-AURICULAR INFRATEMPORAL FOSSA approach+MODIFIED
MIDDLE FOSSA CRANIOCTOMY:Intradural/cavernous sinus extensions

33. ENDOSCOPIC ENDONASAL TECHNIQUES
 Stage Fisch 1, 2 and some type 3 tumours (limited medial invasion of the
infratemporal fossa)
 Preoperative embolization is usually undertaken

34. 1
2
3
4

35. Advantages
1. Incision avoided
2. Less haemorrhage
3. Osteotomies avoided
4. Decreased duration of hospitalisation
5. Can also handle intracranial extensions (image guided)
6. CSF leaks can be sealed
7. Laser assisted endoscopic resection
Disadvantages
1. Larger tumours >Fisch 3a

36. COMPLICATIONS
1. Recurrence
• Most common complication
• Reported in up to 25 % of patients regardless of the method of treatment
2. Surgically induced infraorbital nerve sensory deficits and nasal vestibular stenosis -
mid-facial degloving,
3. Prolonged nasal crusting which may develop into ozaena
4. With more extensive resections, ocular problems like displacement of the globe caused
by loss of bony support, ophthalmoplegia, ectropion and visual loss
5. Palatal fistula – if incision is directly over the junction of hard and soft palate
6. Weber - Fergusson approach – anaesthesia over cheek

37. PREOPERATIVE EMBOLIZATION
 Role is controversial
 Small tumours –
1. The blood supply is predictable, usually the terminal branches of the internal
maxillary artery, and these can be controlled easily at the time of surgery.
2. Embolization in such cases would seem to be unnecessary.
 More extensive tumours - acquire a blood supply from other vessels, branches of
both the external and internal carotid circulations.
1. Preoperative selective embolization, some days before surgery, is prudent at the
very least.
 Medium-sized tumours – benefits of preoperative embolization are doubtful.
Intraoperative blood loss after embolization is certainly less.
 Recurrence rates seem to be increased perhaps due to shrinkage of the tumour
makes it more difficult to define its entirety at the bottom of a deep and bloody
operative field

38. Before embolisation After embolisation

39. PREOPERATIVE HORMONAL THERAPY
OESTROGENS
• Have been reported to induce shrinkage in some but their
effect is variable
• Therapy delays surgery
• Side effects - secondary feminizing effects
FLUTAMIDE
• Nonsteroidal androgen receptor blocker,
• Side effects, nausea, breast tenderness and gynaecomastia,
• These effects were only temporary and disappear
completely at the end of therapy.
• Might have a role in the preoperative preparation of
patients with very advanced tumours, certainly those with
intracranial extension

40. RADIOTHERAPY
• External beam radiation
• Several fractions to achieve a total tumour dose of 30–55Gy
• Regression is very slow, often taking two to three years before ‘radiological stabilization’ is
achieved
• Residual tumour remains
• Local control rates of 80–85%
• Reserved for selected patients – inoperable intracranial extension or recurrent tumours
• Disadvantages
 Skin, thyroid and nasopharyngeal malignancies
 Growth retardation
 Temporal lobe radionecrosis
 Panhypopituitarism
 Cataracts
 Radiation induced keratopathy
LIFETIME MONITORING WITH INTERVAL MRIs – in patients with residual disease

41. FUTURE CONSIDERATIONS
1. Endoscopic removal of intracranial extradural angiofibroma
(Oncocerci et al and Baser et al)
2. Endoscopic intratumoural injection of ONYX
(Case report by Hira et al-lesser radiation exposure)
3. Radiotherapy
• Intense modulated conformational radiotherapy(IMRT)
• Robotic radiotherapy (CYBERKNIFE)(Deguchi et al)
3. Radiosurgery
4. Gammaknife stereotactic radiosurgery
5. Robotic surgery
6. Laser

42. THANK YOU