Background

Juvenile angiofibroma (JNA) is a benign tumor that tends to bleed and occurs in the nasopharynx of prepubertal and adolescent males.

History of the Procedure

Hippocrates described the tumor in the 5th century BC, but Friedberg first used the term angiofibroma in 1940. Other titles (eg, nasopharyngeal fibroma, bleeding fibroma of adolescence, fibroangioma) have also been used. The image below depicts a coronal CT scan.

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 Her2/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
Nasal obstruction (80-90%) - Most frequent symptom, especially in initial stages Epistaxis (45-60%) - Mostly unilateral and recurrent; usually severe epistaxis that necessitates medical attention; diagnosis of angiofibroma in adolescent males to be ruled out Headache (25%) - Especially if paranasal sinuses are blocked Facial swelling (10-18%) Other symptoms - Unilateral rhinorrhea, anosmia, hyposmia, rhinolalia, deafness, otalgia, swelling of the palate, deformity of the cheek

Signs
Nasal mass (80%) Orbital mass (15%) 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) Other causes of epistaxis, systemic or local Other causes of proptosis or orbital swellings

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. scan of lesion involving the right nasal cavity and paranasal sinuses. Courtesy of J Otolaryngol 1999;28:145.

Axial CT

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. Courtesy of J Otolaryngol 1999;28:145.

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.

Angiogram depicting angiofibroma before embolization. Courtesy of J Otolaryngol

1999;28:145. Otolaryngol 1999;28:145.

Angiogram depicting angiofibroma after embolization. Courtesy of J

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.

Staging
Different staging systems exist for nasopharyngeal angiofibroma. The 2 most commonly used are those of Sessions and Fisch. o o o o o o o o Classification according to Sessions Stage IA - Tumor limited to posterior nares and/or nasopharyngeal vault Stage IB - Tumor involving posterior nares and/or nasopharyngeal vault with involvement of at least 1 paranasal sinus Stage IIA - Minimal lateral extension into pterygomaxillary fossa Stage IIB - Full occupation of pterygomaxillary fossa with or without superior erosion of orbital bones Stage IIIA - Erosion of skull base (ie, middle cranial fossa/pterygoid base); minimal intracranial extension Stage IIIB - Extensive intracranial extension with or without extension into cavernous sinus Classification according to Fisch Stage I - Tumors limited to nasal cavity, nasopharynx with no bony destruction Stage II - Tumors invading pterygomaxillary fossa, paranasal sinuses with bony destruction

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Stage III - Tumors invading infratemporal fossa, orbit and/or parasellar region remaining lateral to cavernous sinus Stage IV - Tumors invading cavernous sinus, optic chiasmal region, and/or pituitary fossa

Medical Therapy
Hormonal therapy
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. [2] 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. 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.[3, 4]

Surgical Therapy
A lateral rhinotomy, transpalatal, transmaxillary, or sphenoethmoidal route is used for small tumors (Fisch stage I or II). The infratemporal fossa approach is used when the tumor has a large lateral extension. The midfacial degloving approach, with or without a LeFort osteotomy, improves posterior access to the tumor. 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. Some authors advocate the use of intranasal endoscopic surgery for lesions with limited extension to the infratemporal fossa. 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[5] . Most tumors were completely excised using the expanded endonasal approach (EEA) alone or in combination with minor sublabial incisions, 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.[6]

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. [7]

Complications
Preoperative angiography and embolization minimize intraoperative blood loss, and the current shift in the treatment to endoscopic excision in selected cases reduces perioperative morbidity. [8] 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.[9] 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.