Juvenile Nasopharyngeal Angiofibroma
Dr. T. Balasubramanian M.S.
Synonyms: angiofibroma, juvenile
angiofibroma, juvenile nasopharyngeal angiofibroma, (JNA)
Definition: Juvenile nasopharyngeal
angiofibroma (JNA) is a histologically benign , but locally
invasive neoplasm occuring almost exclusively in adolescent
males. These tumors are highly aggressive and are associated
with significant morbidity and mortality due to its tendency to
History: Juvenile nasopharyngeal
angiofibroma has been documented since the time of Hippocrates (4
BC). Infact Hippocrates goes on to describe a polyp in
the nose which weeped blood. In 1906 Chareau revived
the interest in the study of juvenile nasopharyngeal
angiofibroma. Shaheen in 1930 reported the first female
patient with juvenile nasopharyngeal angiofibroma.
Hondousa recorded the youngest JNA patient (8 years). Figi and
Davis (1950) emphasised the role of surgery in the management of
JNA. They also suggested that subperiosteal
dissection of the mass reduced bleeding to a great
Histopathological studies of JNA tissue was
extensively done by Harma (1959).
Nasopharynx: Since JNA involves the nasopharynx, a complete
understanding of nasopharyngeal anatomy is a must for the safe
management of the problem. This area has been considered
as an antomical blind spot (a virtual no man's land) because of its
relative inaccessibility. It is very difficult to visualise
completely the entire nasopharynx. Cawthorne (1953)
remarked "I am never sure whether I will be able to get a really
satisfactory view of the whole nasopharynx". The advent
of endoscopes have made the task of examination of nasopharynx
simpler these days. The recent imaging modalities like CT scan
and MRI has further simplified non invasive ways of examining the
Location: Nasopharynx is located at
the confluence of nasal, aural and pharyngeal air passages. It
is an unyielding irregular cuboidal box containing
4 x 3 x
2 cm air space ar the base of middle cranial
Nasopharynx is located
immediatly behind the nasal cavities and below the body of the
sphenoid and basi occiput above the level of soft palate as
illustrated in the figure. Posteriorly it is limited by the
first two cervical vertebrae. The posterior wall
of nasopharynx is about 8 cm from the pyriform aperture
along the floor of the nose.
orifice and posterior margin of nasal septum.
formed by the upper surface of soft palate in its anterior 2/3 while
the posterior 1/3 is formed by nasopharyngeal isthumus.
and posterior wall: is formed by the continuous sloping surface of
the body of the sphenoid, the basiocciput and the first two cervical
vertebrae up to the level of the soft palate. The upper
portion of the posterior wall lies in front of the anterior arch of
atlas with a mass of lymphoid tissue embedded in the mucous membrane
(adenoid). The prevertebral fascia and muscles separate the
adenoid from the vertebrae.
Lateral wall: is dominated by the
pharyngeal end of eustachean tube. It is located in the middle
of the lateral wall, it is about 1.5 cm equidistant from the roof,
posterior wall, choana and the floor. The tubal elevation
created by the elastic cartilage of the tube is particularly
prominent in its upper and posterior lip. Behind the posterior
margin of torus, between it and the posterior wall lies the lateral
pharyngeal recess or the fossa of Rosenmuller. Aggregates
of lymphoid tissue (Gerlachs tonsil) of variable sizes surround
the tubal orifice. This is alsl known as the tubal
Fossa of Rosenmuller is situated
at a corner between the lateral and dorsal walls. This recess
is not obvious in infants, and can measure up to 1.5 cm in depth in
adults. It opens into the nasopharynx at a point below the
foramen lacerum related to the internal carotid artery.
Boundaries of Fossa of Rosenmuller:
Eustachean tube and levator veli palati muscle.
Pharyngeal wall mucosa overlying the pharyngobasilar fascia and
retro pharyngeal space, containing the retropharyngeal lymph nodes
Medial: Nasopharyngeal cavity.
Foramen lacerum and floor of the carotid canal.
lateral (apex): Carotid canal opening and petrous apex posteriorly,
foramen ovale and spinosum laterally.
Lateral: Tensor palati
muscle, mandibular nerve and the prestyloid compartment of the para
Nasopharynx as seen through nasal endoscope.
Epithelial lining of nasopharynx:
The mucosal lining of nasopharynx is thrown into numerous folds
and crypts. The surface area of mucosal llining of nasopharynx
is about 50 cm 2 in adults. The mucosa abutting the choanae
and immediate nasopharyngeal roof is completely lined by ciliated
columnar epithelium. The nasopharyngeal mucosa differs from
the rest of the upper respiratory tract in that the subepithelial
connective tissue is rich in lymphoid tissue.
the clinical features of mass lesions involving the
nasopharynx, a clear understanding of the roof of the fossa
of Rosenmuller is important. As already mentioned
the roof of fossa of Rosenmuller is formed by the Foramen
Lacerum. Through this foramen lacerum passes:
Internal carotid artery
b. Greater superficial petrosal
c. The ascending palatine artery sometimes passes through
It is through this foramen tumors from fossa of
Rosenmuller invades intracranial structures. The 3rd,
4th, 5th and 6th cranial nerves are in juxtaposition of
the foramen. These nerves are commonly involved when tumors
invade intracranial structures via the foramen
Blood supply of nasopharynx:
Ascending pharyngeal artery
b. Ascending palatine branch of
c. Branches of internal maxillay artery
Veins form a plexus which communicate above with the
pterygoid plexus and drains into the common facial and internal
Lymphatics: Nasopharynx is richly endowed
with lymphatics. They mainly originate in the pharyngeal
tonsil and runs laterally and downwards on the pharyngeal
aponeurosis, some of them terminating in the median and lateral
veins. The collecting trunks terminate for the most part in
the upper nodes of the spinal accessory chain, which lie under
the upper end of sternomastoid muscle, and also into the
jugulodigastric node of the internal jugular chain. From these
nodes efferent branches run down to the middle and lower group of
nodes of the internal jugular and spinal accessory
Nerve supply: is derived mainly from the
pharyngeal plexus which is formed by branches of the 9th and
10th cranial nerves together with sympathetic
This relatively rare tumor
occurs in the second decade. Almost exclusively adolescent
males are affected. The reported rate of incidence varies from
1/6000 (Harma 1959) to 1/50,000 (Hondousa etal 1954). The
exact nature of the tumor and its etiology is not well known.
Various theories have been propounded to explain the
etiopathogenesis of JNA.
Theories of etiopathogenesis of
Ringertz theory: This theory
was proposed by Ringertz in 1938. He believed that JNA always
arose from the periosteum of the skull base.
Som & Neffson (1940): believed that
inequalities in the growth of bones forming the skull base resulted
in hypertrophy of the underlying periosteum in response to hormonal
Bensch & Ewing
(1941): thought that the tumor probably arose from embryoninc
fibro cartilage between the basi occiput and basi
Suggested an origin from conjoined pharyngobasilar and
Marten et al
(1948): Proposed a hormonal theory suggesting that these
tumors resulted from deficiency of androgens or over activity of
estrogens and that the hormonal stimulation is responsible for
angiomatous components seen in JNA tissue.
Sternberg (1954): Proposed that JNA could be a
type of haemangioma like a cutaneous haemangioma seen in children
which regresses with age.
(1959): Considered two alternatives to explain the
etiology of JNA. They proposed that the swelling could be due
to either a hamartoma or residual fetal erectile tissue which were
subject to hormonal influences.
& Fahmy (1973): Observed cell nests of undifferentiated
epitheloid cells or "Zell ballen" at the growing edge of
angiofibromas. This appearance was more or less similar to
that of paraganglioma. They considered JNA to be a
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
Pathophysiology: The proposed origin of the JNA is
located along the posterior-lateral wall in the roof of the
nasopharynx, usually in the region of the superior margin of the
sphenopalatine foramen and the posterior aspect of the middle
turbinate. Fetal histology confirms large areas of endothelial
tissue in this region. Rather than invading surrounding tissue, this
tumor displaces and distorts, relying on pressure necrosis to
destroy and push through its bony confines. Intracranial extension
is noted in 10-20% of cases.
JNA are seldom seen in children
below the age of 8. The rate of growth of tumor and period of
maximum development coincides with rate of erectile tissue of
penis, both increasing in size during the period of sexual
Grossly, angiofibromas appear as firm slightly spongy lobulated
swelling with presence of nodules. The nodularity increases
with age. Their color varies from pink to white. The
part which is seen in the nasopharynx and which is covered by mucous
membrane is invariably pink, where as those parts which have escaped
to adjacent extra pharyngeal areas are often white or
On section the
tumor is reticulated, whorled or spongy in appearence lacking a true
capsule. The edges of the tumor are however, sharply
demarcated and easily distinguishable from the surrounding
tissues. Hence to reduce bleeding during surgical excision of
the tumor the mass should be peeled off from its attachments and the
mass should not be broken into.
appearance: Microscopically the picture is of vascular spaces
of varying shapes and sizes within a stroma of fibrous tissue.
The relative proportions of the vascular and the stromal components
change with the age of the swelling. In earlier lesions the
vascular component stands out as an all pervasive feature, whereas
in the more long standing tumors collagen predominates. It
could also be seen that, as one strays away from the heart of the
tumor the fibrous tissue element overshadows vascular element.
The tumor is covered by squamous epithelium. In some
cases pseudostratified columnar epithelium is seen side by side
with the metaplastic squamous
Cellular infiltration is a
common feature, particularly in the superficial parts of the tumor,
underneath the epithelium. the infiltrates include, plasma
cells, lymphocytes, polymorphs and eosinophils in varying
The structure of the tumor
is made up of fibrous tissue elements and vascular channels.
The fibrous tissue element is made up of cells which are spindle
shaped, oval or round cells. In between these cells, the
bundles of collagen fibres are seen running in different
The vascular channels of the
tumor may be divided into 2 main types. One type which is
seen in all cases is made up of spaces lined with one layer of
endothelium and is free of any muscular coating. In the other
type the vascular channels are made up of arteries with thick
Mucous glands may be
seen in the superficial parts of the tumor underneath the epithelial
covering. In some patients nerve bundles could also
be seen. In long standing tumors, there is a
tendency towards gradual compression of the sinusoids so that the
lining endothelial cells are pushed against each other like cords,
where in others intravascular thrombosis occur.
showing histologic features of JNA
features: Signs and
symptoms are present for an average of 6 months prior to the
diagnosis, commonly with extension beyond the
cardinal symptoms of angiofibroma are nasal obstruction and
intermittent unprovoked epistaxis. Epistaxis may vary in
severity from an occasional show to an alarming sometimes
threatening torrent. Chronic anaemia is thus a feature of an
The nasal obstruction
is so complete causing stasis of secretions and sepsis become
inevitable. Patients may even have hyposmia or
of a patient with JNA showing nasal mass
voice of the patient acquires a nasal intonation. If the
swelling enlarges to force the soft palate down, the voice may
Blockage of eustachean tube orifice is also
common causing deafness and otalgia. Headache is not uncommon
in long standing cases. If present it could be attributable to
chronic sinusitis in some patients. Intracranial extension of
the mass could also be the cause
for headache in these patients.
Diplopia may occur
secondary to the erosion of the mass into the cranial cavity and
causing pressure on the optic chiasma. Failing vision has been
attributed by Shaheen to the tenting of the optic nerveby the
Anterior rhinoscopy shows the presence of
abundant purulent nasal secretions together with bowing of
nasal septum to the uninvolved side. Posterior rhinosocpy in a
cooperative patient shows a pink or red mass filling the
nasopharynx. Due to the bulk of the lesion it may not be
always possible to ascertain the site of origin accurately.
Gross physical signs become evident when extensive
disease involves the nose and infra temporal fossa. The nasal
bones become spayed out and there may be obvious swelling in the
temple and cheek. Intra oral palpation in the interval between
the ascending ramus of the mandible and the side of the maxilla may
reveal the tell tale thickening of disease which has crept around
the back of the antrum. Impaction of bulky mass in the infra
temporal fossa results in extreme signs, such as trismus and bulging
of the parotid gland. Proptosis is a definite sign that the
orbital fissures have been penetrated. The classic frog face
seen in patients with extensive disease is due to massive escape of
As growth enlarges it
has to follow the lines of least resistance.
a. It hangs down
in the cavity of nasopharynx and when large enough, it may depress
the soft palate and may even peep below it.
b. It can work its
way in to the corresponding nasal passage towards the anterior
nares. It can cause pressure on the outer wall as well as on
the septum bending it to the opposite side. The corresponding
turbinates and ethmoidal air cells and the related antral wall may
suffer pressure atrophy. The most common deformity referred to
as the "frog face" is due to the forward spread involving the
ethmoidal region. Lateral spread in to the maxillary sinus may
be responsible for the cheek swelling.
c. The mass
commonly arises from the sphenopalatine foramen area. It may
have two components, one filling the nasopharynx and the other
extending out into the pterygopalatine and infratemporal
fosse. The central stalk joining the two components occupy the
sphenopalatine foramen at the upper end of the vertical plate of
d. It can encroach into the orbit by passing
through the infra orbital fissure.
e. It can erode the skull base
and cause intracranial problems.
Blood supply of JNA: is from
1. Enlarged maxillary artery
2. Ascending pharyngeal
3. Unnamed branches from internal carotid
Staging of the tumor: Staging of the tumor has
been done to for prognosis and
therapeutic approaches. The currently accepted
staging has been devised by Andrews.
Stage I: Tumor limited to the nasal
Stage II: Tumor extension into the pterygopalatine fossa,
or maxillay, sphenoid or ethmoid sinuses.
Stage IIIa: Tumor
extension into the orbit without intracranial involvement.
IIIb: Stage IIIa with extradural (parasellar) intracranial
Stage IVa: Intradural without cavernous sinus, pituitary,
or optic chiasm involvement
IVb:Involvement of the cavernous
sinus, pituitary, or optic chiasm
Surgery is usually recommended for
stages up to IVa while for stage IVb radiotherapy is
Investigations: Standard X-rays of paranasal
sinuses may reveal opacity in the nose and sinus areas. Xray
skull lateral view may show the mass inside the nasopharynx.
CT scan has replaced the preferred imaging modality in these
patients. Both plain and contrast CT scans must be performed
to clinch the diagnosis. It also reveals the extent of the
lesion and also helps in staging of the disease. MRI reveals
the precise extent of the mass.
Carotid angiogram may be
performed to identify the feeder vessel and also to embolise the
feeder to reduce bleeding during surgery.
diagnosis: JNA should be differentiated from:
3. Angiomatous polyp
scan contrast (axial cuts) showing JNA mass in the nasopharynx
and sphenoid area.
Carotid angiogram showing tumor blush
mainly on the extent of the lesion. Surgery is the preferred
modality of treatment for all stages of the mass up to stage IVa
while radiotherapy is used for stage IVb. Mainly three lines
of treatment are available:
Hormonal (purely supportive in nature)
Complete excision of an extensive JNA mass is a desirable goal but
is a surgical challenge because of the limited field of work,
inadequate visualisation and profuse bleeding during surgery.
Besides the deformity, scars and adhesions as a result of prior
surgery adds to this problem. Currently several approaches are
available to access the neoplasm. They are:
removal - via naturalis:
This approach is preferred for very
small tumors confined to nasopharynx. The tumor can be removed
by subperiosteal dissection after soft palate retraction.
Access is limited in this approach.
Wilson in 1951 described this approach. This
approach gives exposure to nasopharynx as well as extensions into
the sphenoid sinus and choana. It gives no visible scar and
post op healing is good. This approach is useful in dealing
with masses in the nasopharynx with minimal extension into the
choana and sphenoid sinus.
Procedure: Patient is put
in tonsillectomy position. A forward curved
incision is made just in front of the junction of hard and soft
palate. Mucoperiosteum is separated either way.
Posterior spine of the hard palate is removed. Incision is
extended laterally and downwards on either side along the
pterygomandibular raphe. The mucosa of the lateral pharyngeal
wall is not divided and care is taken not to damage the greater
palatine vessels. A good view of nasopharynx is achieved in
this procedure. The mucous membrane on the side of the growth
is incised with a blunt knife. Thus with blunt dissection the
periosteum is elevated, growth is separated and finally avulsed in
showing Wilson's transpalatal approach
Lateral rhinotomy approach: This approach is suited for
smaller growth restricted to the nasal cavity. It is
contraindicated for larger masses and whose extensions and
attachements cannot be ascertained.
showing lateral rhinotomy approach
hyoid approach: This is suitable for tumors localised to
nasopharynx without any extension into the surrounding
structures. The major disadvantage is that it requires a
Incision is made vertically infront
of the ear and carried down the neck anterior to the sternomastoid
muscle. Dissection is started in the neck by exposing the
carotid bifurcation at which level the external carotid artery is
ligated. Lower pole of parotid is dissected free. The
insertions of masseter muscle is severed from the mandible.
Lateral aspect of the mandible is exposed by elevation of the
periosteum. Transection of mandible is done with a giglisaw at
a point 1 cm below the notch formed by coronoid and condyloid
processes. Separation of mandible exposes the tube muscular
wall of nasopharynx which is incised longitudinally on its lateral
wall so that its lumen is entered. Tumor is exposed and
VI. Sublabial midfacial degloving approach
(Conley 1979): It is a bilateral extended trans nasal
maxillary approach. There is no visible scarring, adequate
exposure of nasal complex, nasopharynx and middle third of the face
is obtained. Sublabial incision is performed from one
maxillary tuberosity to the other. Intercartilagenous
incisions are given to separate soft tissue of the nose from the
upper lateral cartilages. Incisions along the pyriform
aperture connects the circumferential septal vestibular incisions to
the sublabial incision. This allows total mid facial degloving
up to the roof of the nose and infra orbital foramen. The
complication of this procedure is vestibular
showing midfacial degloving approach
Transzygomatic approach (Sami & Girgis 1965): This
approach is useful for removal of tumor involving the temporal and
infra temporal regions.
the size and extent of the mass a combination of various approaches
can be attempted to extripate the mass in toto.
Transpalatal sublabial approach (Saldana 1965): This approach
is useful for tumors extending into pterygoid and infratemproal
fossa. A sublabial incision 'S' shaped is made extending to
the maxillay tuberosity. After elevation of mucoperiosteal
flap, the greater palatine neurovascular pedicle is preserved.
The surgeon's index finger is inserted into the pterygopalatine
fossa and blunt dissection is used to free the tumor from its
lateral attachement. The mass can be deliverd via the
II. Combined transpalatal and lateral rhinotomy
approach: This approach is indicated for larger mass,
recurrent JNA, and when attachement and extensions of the tumor are
not predetermined. This approach gives excellent exposure and
so the chances of recurrence are minimal.
approach of Hiranandani (1968): In this approach transpalatal
and lateral rhinotomy are combined along with caldwel luc.
Complete exposure of pterygopalatine fossa is possible by removal of
posterior wall of the maxillary antrum, after opening the antrum
through caldwel luc incision. Chances of recurrence are
minimised. Ligation of internal maxillary artery is done to
reduce the bleeding.
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
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
c. Radiotherapy may cause fibrosis and adhesions of
surrounding tissue. Later surgery upon these patients becomes
d. Sarcomatous changes can occur in the mass as a
result of irradiation.
Since JNA has been postulated as an endocrine tumor testosterone
receptor blocking drugs / estrogens have been tried to reduce the
mass. These hormones cause disaggreable side effects such as
increased breast size. Hormones could even act as
Was first attempted by Robertson in 1972. This was not meant
to be therapeutic measure. After embolisation bleeding is
minimised during surgery. It is ideally carried out a few days
before surgery. Hence it is a valuable preliminary to
surgery. The feeding vessels to the tumor is identified.
It is then deliberatly occluded by means of materials injected
through a selectively placed catheter.
Autologous substances like fat, blood clot, or chopped
Artifical materials: Gelfoam, Oxidised
cellulose, Tantalum powder, glass beads, polyvinyl alcohol
Embolisation should always be preceded by angiography.
Subtraction films may be helpful in areas containing complex bony
Immediate complications of embolisation are
pain, embolisation of normal vessels, hypersensitivity.
Delayed complications include fever, pain and
Cryosurgery and Lasers can also be used during
surgery to minimise
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