Juvenile Nasopharyngeal Angiofibroma

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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.

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.


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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 ri....

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

Signs

Differentials

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.


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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 ri....


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

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.


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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.


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Angiogram depicting angiofibroma before embolization. Courtesy of J Otolaryngol 1999;28:145.


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Angiogram depicting angiofibroma after embolization. Courtesy of J Otolaryngol 1999;28:145.

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.

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 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]

In a retrospective review, Battaglia et al (2014) evaluated the use of endoscopic endonasal surgery in the radical resection of benign or nonmetastatic malignant tumors that have either developed in or extended to the infratemporal fossa or upper parapharyngeal space.[7] According to the investigators, the results, derived from 37 patients, including 20 with JNA, suggested that purely endoscopic endonasal radical resection can be safely used to treat selected tumors involving these spaces.

In a review article, Cloutier et al (2012) reported on 72 patients operated on over a 10-year period.[8] They concluded that the progress in skull-base surgery allowed for expansion of the indications for endoscopic removal of JNA. This approach has a better outcome in terms of blood loss, hospital stay, and complications. Of course, an external approach should be considered only for selected cases due to massive intracranial extension or optic nerve or internal carotid artery entrapment by the tumor.

In a meta-analysis of the endoscopic surgical outcomes of JNA, covering 92 studies and a total of 821 patients, Khoueir et al (2014) calculated that the mean operative blood loss from endoscopic JNA surgery was 564.21 mL. Random effect estimates for recurrence, complications, and residual tumor were 10%, 9.3%, and 7.7%, respectively. The authors stated that endoscopic treatment is currently considered the treatment of choice for JNA but also commented that they could find no randomized, controlled studies for their analysis. They advised that future studies propose a new, endoscopic approach – based classification system.[9]

Yi et al (2013) described a simplified classification system and management option for juvenile nasopharyngeal angiofibroma, as follows[10] :

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.[11]

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.[12] 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.[13]

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.

A rare case of massive epistaxis from spontaneous rupture of the intracavernous tract of the internal carotid artery 20 days after resection of a giant JNA by midface degloving was recently reported.[14] Coils were selectively used to occlude the vessel and to stop the hemorrhage.

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.

Author

Ted L Tewfik, MD, Professor, Department of Otolaryngology-Head and Neck Surgery, Director of Continuing Medical Education of Otolaryngology; and Professor of Pediatric Surgery, McGill Faculty of Medicine, Senior Staff Montreal Children's Hospital, Montreal General Hospital and Royal Victoria Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Mohammed A Al Garni, MBBS, Assistant Professor, King Saud Bin Abdulaziz University for Health Sciences; Consultant, Department of Otolaryngology-Head and Neck Surgery, King Abdulaziz Medical City, Saudi Arabia

Disclosure: Nothing to disclose.

Specialty Editors

Ari J Goldsmith, MD, Chief of Pediatric Otolaryngology, Long Island College Hospital; Associate Professor, Department of Otolaryngology, Division of Pediatric Otolaryngology, State University of New York Downstate Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Gregory C Allen, MD, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine

Disclosure: Nothing to disclose.

Christopher L Slack, MD, Private Practice in Otolaryngology and Facial Plastic Surgery, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA, Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Disclosure: Medvoy Ownership interest Management position; Cerescan Imaging Honoraria Consulting

References

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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.

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. Courtesy of J Otolaryngol 1999;28:145.

Coronal MRI scan showing extension of the lesion to the cavernous sinus. Courtesy of J Otolaryngol 1999;28:145.

Angiogram depicting angiofibroma before embolization. Courtesy of J Otolaryngol 1999;28:145.

Angiogram depicting angiofibroma after embolization. Courtesy of J Otolaryngol 1999;28:145.

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. Courtesy of J Otolaryngol 1999;28:145.

Coronal MRI scan showing extension of the lesion to the cavernous sinus. Courtesy of J Otolaryngol 1999;28:145.

Angiogram depicting angiofibroma before embolization. Courtesy of J Otolaryngol 1999;28:145.

Angiogram depicting angiofibroma after embolization. Courtesy of J Otolaryngol 1999;28:145.

Preembolization lateral carotid angiogram of juvenile nasopharyngeal angiofibroma (JNA).

Postembolization angiogram.