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Background
Juvenile angiofibroma (JNA) is a benign tumor that tends to bleed and occurs in the nasopharynx
of prepubertal and adolescent males.
Coronal CT scan of the lesion filling the left nasal cavity and ethmoid sinuses, blocking the
maxillary sinus and deviating the nasal septum to the right side.
Epidemiology
Frequency
Juvenile nasopharyngeal angiofibroma (JNA) accounts for 0.05% of all head and neck tumors. A
frequency of 1:5,000-1:60,000 in otolaryngology patients has been reported.
Sex
Juvenile nasopharyngeal angiofibroma (JNA) occurs exclusively in males. Females with juvenile
nasopharyngeal angiofibroma (JNA) should undergo genetic testing.
Age
Onset is most commonly in the second decade; the range is 7-19 years. Juvenile nasopharyngeal
angiofibroma (JNA) is rare in patients older than 25 years.
Etiology
The lesion originates in close proximity to the posterior attachment of the middle turbinate, near
the superior border of the sphenopalatine foramen.
A hormonal theory has been suggested because of the lesion's occurrence in adolescent males.
Other theories include a desmoplastic response of the nasopharyngeal periosteum or the
embryonic fibrocartilage between the basiocciput and the basisphenoid.
Etiology from nonchromaffin paraganglionic cells of the terminal branches of the maxillary
artery has also been suggested. Comparative genomic hybridization analysis of these tumors
revealed deletions of chromosome 17, including regions for the tumor suppressor gene p53 as
well as the Her-2/neu oncogene.
Pathophysiology
The tumor starts adjacent to the sphenopalatine foramen. Large tumors are frequently bilobed or
dumbbell-shaped, with one portion of the tumor filling the nasopharynx and the other portion
extending to the pterygopalatine fossa.
Anterior growth occurs under the nasopharyngeal mucous membrane, displacing it anteriorly and
inferiorly toward the postnasal space. Eventually, the nasal cavity is filled on one side, and the
septum deviates to the other side. Superior growth is directed toward the sphenoid sinus, which
may also be eroded. The cavernous sinus may become invaded if the tumor advances further.
Lateral spread is directed toward the pterygopalatine fossa, bowing the posterior wall of the
maxillary sinus. Later, the infratemporal fossa is invaded. Occasionally, the greater wing of the
sphenoid may be eroded, exposing the middle fossa dura. Proptosis and optic nerve atrophy
result if orbital fissures are encroached upon by the tumor. Extranasopharyngeal angiofibroma is
extremely rare and tends to occur in older patients, predominately in females, but the tumor is
less vascular and less aggressive than juvenile nasopharyngeal angiofibroma (JNA).
Presentation
Symptoms
Epistaxis (45-60%) - Mostly unilateral and recurrent; usually severe epistaxis that
necessitates medical attention; diagnosis of angiofibroma in adolescent males to be ruled
out
Signs
Proptosis (10-15%)
Other signs include serous otitis due to eustachian tube blockage, zygomatic swelling,
and trismus that denote spread of the tumor to the infratemporal fossa, decreasing vision
due to optic nerve tenting (rare)
Differentials
Other causes of nasal obstruction, (eg, nasal polyps, antrochoanal polyp, teratoma,
encephalocele, dermoids, inverting papilloma, rhabdomyosarcoma, squamous cell
carcinoma)
Nasal Endoscopy
Given the presenting symptoms, the patient should be examined by nasal endoscopy which
usually shows a large, lobulated mass behind the middle turbinate filling the choana with a
smooth surface and clear signs of hypervascularization.
Imaging Studies
Plain radiography views of the sinuses may demonstrate nasopharyngeal polyp. Bowing of the
posterior wall of the maxillary sinus and maxillary sinus opacification is very suggestive of
juvenile nasopharyngeal angiofibroma (JNA). Newer radiographic modalities have surpassed
plain films in usefulness.
CT scan images below demonstrate the extent of the tumor. Extension to the sphenoid sinus,
erosion of the greater sphenoidal wing, or invasion of the pterygomaxillary and infratemporal
fossae is usually visualized, as in the images below.
Coronal CT scan of the lesion filling the left nasal cavity and ethmoid sinuses, blocking the
maxillary sinus and deviating the nasal septum to the right side. Axial CT scan of lesion
involving the right nasal cavity and paranasal sinuses.
Magnetic resonance imaging (MRI) is indicated to delineate and define the extent of the tumor,
especially in cases of intracranial involvement. Coronal MRI scan showing extension of the
lesion to the cavernous sinus is seen in the image below.
Coronal MRI scan showing extension of the lesion to the cavernous sinus.
Angiography shows the branches of the external carotid system to be the primary feeders (94%).
The main supply comes from the internal maxillary artery, but ascending pharyngeal or vidian
arteries may contribute to the blood supply. Unnamed branches from the internal carotid artery
contribute to vascularity in rare instances. Bilateral vascular supply may be an underappreciated
factor in JNA, and thorough radiographic investigation via angiography of bilateral carotid
systems should be routinely performed preoperatively.[1] An angiofibroma before and after
embolization can be seen in the images below.
Histologic Findings
On gross examination, the tumor is usually sessile, lobulated, rubbery, and red-pink to tan-gray
in appearance. In rare cases, the tumor is polypoid or pedunculated.
Nasopharyngeal angiofibroma is usually encapsulated and composed of vascular tissue and
fibrous stroma with coarse or fine collagen fibers. Vessels are thin-walled, lack elastic fibers,
have absent or incomplete smooth muscle, and vary in appearance from stellate or staghorn to
barely conspicuous because of stromal compression. Stromal cells have plump nuclei and tend to
radiate around the vessels. An abundance of mast cells in the stroma and a lack of other
inflammatory cells exist. Localized areas of myxomatous degeneration may be observed in the
stroma.
When examined under electron microscope, stromal cells are mostly fibroblasts and show
intensive immunostaining for vimentin. However, myofibroblasts may occur focally in
connection with fibrotic areas and are characterized by the coexpression of vimentin and smooth
muscle actin.
(a)
(b)
Angiofibroma; Staghorn-shaped blood vessels (arrows) with endothelial cells but no smooth muscle are
compressed by fibrous tissue
Staging
Different staging systems exist for nasopharyngeal angiofibroma. There are
many classification described although none is universally accepted. There
are a variety of staging criteria developed for evaluating JNAs which include
those developed by Radkowski, Fisch, Andrews, Chandler, Johns, Onerci and
Sessions although none is universally accepted. In several staging systems
that of Andrews (1989) is the most robust and practical for exclusively
endoscopic surgery for JNAs17. Another staging system is Radkowski (1996)
that is the most recently developed staging system and appears most
commonly in recent literature on JNAs.
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Stage III
(a) Invading the infratemporal fossa or orbital region without
intracranial involvement
(b) Invading the infratemporal fossa or orbit with intracranial
extradural (parasellar) involvement
Stage IV
(a) Intracranial intradural without infiltration of the cavernous
sinus, pituitary fossa or optic chiasm
(b) Intracranial intradural with infiltration of the cavernous sinus,
pituitary fossa or optic chiasm
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Stage I
(A) Limited to posterior nares and/or nasopharyngeal vault
(B) Involving the posterior nares and/or nasopharyngeal vault
with involvement of at least one paranasal sinus
Stage II
(A) Minimal lateral extension into the pterygopalatine fossa
(B) Full occupation of pterygopalatine fossa with or without
superior erosion orbital bones
(C) Extension into the infratemporal fossa or extension posterior
to the pterygoid plates
Stage III
(A) Erosion of skull base (middle cranial fossa/base of pterygoids)
minimal intracranial extension
(B) Extensive intracranial extension with or without extension
into the cavernous sinus
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o Stage III - Deep extension into the cancellous bone at the base of the pterygoid or
the body and the greater wing of sphenoid, significant lateral extension to the ITF
or to the pterygoid plates posteriorly or orbital region, cavernous sinus
obliteration
o Stage IV - Intracranial extension between the pituitary gland and internal carotid
artery, tumor localization lateral to ICA, middle fossa extension, and extensive
intracranial extension
Medical Therapy
Hormonal therapy
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The testosterone receptor blocker flutamide was reported to reduce stage I and II tumors to 44%.
Despite tumor reduction with hormones, this approach is not routinely used. Schuon et al
reported on the immunohistochemical analysis of growth mechanisms in juvenile
nasopharyngeal angiofibroma. They concluded that juvenile angiofibroma (JNA) growth and
vascularization are driven by factors released from stromal fibroblasts. Therefore, inhibition of
these factors might be beneficial for the therapy of inoperable juvenile nasopharyngeal
angiofibroma (JNA).
Radiotherapy
Some centers have reported 80% cure rates with radiation therapy. However, concerns regarding
potential effects of radiation make radiation therapy a nonuseful modality in most cases.
The use of radiotherapy for the primary treatment of angiofibroma has been advocated in recent
publications. External beam radiation is generally reserved for larger and/or unresectable tumors
and tumors that are life threatening due to their location. Studies by Briant et al. and Cummings
et al. both reported an 80% control rate with moderate dose primary radiotherapy (30 to 35 Gy
given in 15 fractions over a 3 week period). Additional other authors have reported good results
after radiotherapy for surgically inaccessible intracranial extension or for recurrences following a
primary procedure. Long-term severe complications of radiation therapy are encountered
including growth retardation, panhypopituitarism, temporal lobe necrosis, cataract, and radiation
keratopathy. Also others reported remote secondary malignancy of the head and neck such as
thyroid carcinoma and sarcomas of bone-soft tissue a serious adverse effect of radiation therapy
on JNA.
Stereotactic radiotherapy (ie, Gamma Knife) delivers a lower dose of radiation to surrounding
tissues. However, most authorities reserve radiotherapy for intracranial disease or recurrent
cases.
Conformal radiotherapy in extensive juvenile nasopharyngeal angiofibroma (JNA) or intracranial
extension provides a good alternative to conventional radiotherapy regarding disease control and
radiation morbidity, even with advanced disease.
Surgical Therapy
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face because of the use of a sub labial incision, but needs extensive removal of bones from the
anterior, posterior, medial and lateral walls of maxillary antrum
The facial translocation approach is combined with Weber-Ferguson incision and coronal
extension for a frontotemporal craniotomy with midface osteotomies for access.
An extended anterior subcranial approach facilitates en bloc tumor removal, optic nerve
decompression, and exposure of the cavernous sinus.
Endoscopic Surgery
Improvements in endonasal technique and knowledge of the intranasal anatomy enable the use of
nasal endoscopic surgery to remove some JNA tumors. The decision to perform JNA resection
endoscopically should be based on the experience and skill of the surgeon as well as the extent of
the tumor. Endoscopic sinonasal surgery and embolize these tumors preoperatively is to allow
atraumatic dissection, minimizing bleeding and more precise tumor resection, thus minimizing
the possibility of residual tumor. Patient selection for endoscopic resection is of paramount
importance for a successful outcome. It has been suggested that tumors involving the ethmoid,
maxillary, or sphenoid sinus, the sphenopalatine foramen, nasopharynx, pterygomaxillary fossa
and have limited extension into the infratemporal fossa are amenable to endoscopic resection.
Onerci et al. reported no recurrence for tumors extension into infratemporal fossa.
Some authors advocate the use of intranasal endoscopic surgery for lesions with limited
extension to the infratemporal fossa. Endoscopic surgery has a great advantage because it
preserves both the anatomy and physiology of the nose, requires less rehabilitation days after
surgery, requiring less days of hospitalization and is less subject to hospital infections. The
push-pull technique involves an incision of about 1 inch in the upper bucco-gingival sulcus,
one more step in the evolution of endoscopic surgery for JNA. It is now possible to excise
tumors with large lateral extensions in the infratemporal and parapharyngeal regions without
resorting to an open approach. Image-guided, endoscopic, laser-assisted removal has also
recently been used. Hackman et al (2009) reviewed 31 cases of JNA at the University of
Pittsburgh Medical Center from 1995 to 2006. Most tumors were completely excised using the
expanded endonasal approach (EEA) alone or in combination with minor sublabial incisions,
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avoiding the morbidity associated with larger open approaches or postoperative radiation
therapy.
Radical removal of a large JNA may be difficult because of its extreme vascularity and extension
to the cavernous sinus, orbit, middle fossa, and anterior fossa. Nevertheless, most of JNAs with
intracranial extension can be resected in the first operation with minimal morbidity through a
facial degloving and further combination of expanded endoscopic endonasal approaches.
Preoperative Details
Preoperative embolization has typically been performed via a transarterial route using a variety
of embolic materials. It is accomplished using reabsorbable microparticulate substances (eg,
Gelfoam, polyvinyl alcohol, dextran microspheres) or nonabsorbable microparticulates (eg,
Ivalon, Terbal). Limiting blood loss during surgery is essential. Endoscopic assistance has been
used for direct transnasal tumor puncture and intratumoral embolization using the liquid embolic
agent Onyx.
Postoperative Surveillance
Based on the experience by Kania et al., Lund et al., and Nicolai et al.,
recommended postoperative MR imaging after removal of the nasal packing
and until 72 hours for early identification of any suspicious residual disease.
The reason for this is the presence of minor inflammatory changes, typically
observed
3-4
months
after
treatment,
which
frequently
challenge
Preoperative angiography and embolization minimize intraoperative blood loss, and the current
shift in the treatment to endoscopic excision in selected cases reduces perioperative morbidity.
Low-grade consumption coagulopathy may complicate small juvenile nasopharyngeal
angiofibroma (JNA) and implies that preoperative coagulation screening may have a role in
perioperative hemostasis.
Malignant transformation has been reported in 6 cases; 5 of these patients were treated with
radiotherapy, according to a study by Makek et al.
Transient blindness has been reported as a result of embolization, but it is a rare occurrence.
Osteoradionecrosis and/or blindness due to optic nerve damage may occur with radiotherapy.
Fistula of the palate at the junction of the soft and hard palate may occur with the transpalatal
approach but is prevented by preservation of the greater palatine vessels during flap elevation.
Anesthesia of the cheek is a frequent occurrence with the Weber-Ferguson incision.
Outcome and Prognosis
The presence of tumor in the pterygoid fossa and basisphenoid, erosion of the clivus, intracranial
extension, feeders from the internal carotid artery, a young age, and a residual tumour were risk
factors associated with the recurrence of juvenile nasopharyngeal angiofibroma.
RESOURCES:
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Allergic Rhinitis
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Allergic rhinitis is a symptomatic disorder of the mucous membrane of the nose induced after
allergen exposure due to an IgE-mediated infl ammation of the membranes lining the nose. It
was defi ned in 1929: The three cardinal symptoms in nasal reactions occurring in allergy are
sneezing, nasal obstruction and mucous discharge.
Allergic rhinitis is a global health problem that affects patients of all ages and ethnic groups.
It causes major illness and disability worldwide. Allergic rhinitis affects social life, sleep, and
performance at school and work, and its economic impact is substantial. However, rhinitis is still
underdiagnosed and undertreated. Over 600 million patients suffer from this disease, but there
are still differences between rural and urban areas, both in developed and developing countries,
possibly due to differences in immune reactions.
In 1999, during the ARIA (Allergic Rhinitis and its Impact on Asthma) World Health
Organization (WHO) workshop, an evidence-based document was produced using an extensive
review of the literature available up to December 1999. The statements of evidence for the
development of ARIA followed WHO rules and the recommendations of Shekelle et al. The
ARIA document presented the state-of-the-art for the specialist, general practitioner, and other
health care professionals. Its aims were as follows:
To update knowledge of allergic rhinitis
To highlight the impact of allergic rhinitis on asthma
To provide an evidence-based documented review of diagnostic methods
To provide an evidence-based review of the treatments available
To propose a stepwise approach to the management of the disease
The ARIA update began in 2004 and was published earlier this year. Several chapters were
extensively reviewed using the Shekelle evidence-based model, and papers published in peerreviewed journals. These papers cover the area of tertiary prevention of allergy, complementary
and
alternative
medicine,
pharmacotherapy
and
anti-IgE
treatment,
allergenspecific
immunotherapy, links between rhinitis and asthma, and mechanisms of rhinitis. The need arose
for a global document to highlight the interactions between the upper and the lower airways
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efficacious and combined strategy should be adopted to treat diseases of the upper and lower
airway.
Aria Recommendations
1. Allergic rhinitis is a major chronic respiratory disease due to its:
- Prevalence
- Impact on quality-of-life
- Impact on work/school performance and productivity
- Economic burden
- Links with asthma
2. In addition, allergic rhinitis is associated with sinusitis and other co-morbidities such as
conjunctivitis.
3. Allergic rhinitis should be considered as a risk factor for asthma along with other known risk
factors.
4. A new subdivision of allergic rhinitis has been proposed:
- Intermittent (IAR)
- Persistent (PER)
5. The severity of allergic rhinitis has been classified as mild or moderate/severe depending
on the severity of symptoms and quality-of-life outcomes.
6. Depending on the subdivision and severity of allergic rhinitis, a stepwise therapeutic approach
has been proposed.
7. The treatment of allergic rhinitis combines:
- Allergen avoidance (when possible)
- Pharmacotherapy
- Immunotherapy
- Education
8. Patients with persistent allergic rhinitis should be evaluated for asthma by means of a medical
history, chest examination, and, if possible and when necessary, the assessment of airflow
obstruction before and after bronchodilator.
9. Patients with asthma should be appropriately evaluated (history and physical examination) for
rhinitis.
10. Ideally, a combined strategy should be used to treat the upper and lower airway diseases to
optimize efficacy and safety.
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RESOURCES:
1. ARIA At-A-Glance Pocket Reference. 2007. Based On The Allergic Rhinitis And Its
Impact On Asthma Workshop Report In Collaboration With The World Health
Organisation,Ga2len, And Allergen
2. Allergic Rhinitis and its Impact on Asthma Update (ARIA 2008) The Perspective From
Spain. 2008. J Investig Allergol Clin Immunol 2008; Vol. 18(5): 327-334.
3. Rhinitis. 2010. J Investig Allergol Clin Immunol 2010; Vol. 20, Suppl. 1: 37-42.
4. David M. Quillen, M.D., And David B. Feller, M.D. 2006. Diagnosing Rhinitis: Allergic
Vs. Nonallergic, American Family Physician.
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