Juvenile angiofibroma

Juvenile Nasopharyngeal Angiofibroma

Juvenile angiofibroma is a unique tumour presenting almost exclusively in adolescent males. Angiofibromas are non-encapsulated fibrovascular tumours that arise in the region of the sphenopalatine foramen. Despite being benign, these tumours exhibit aggressive growth, spreading through foramina and fissures. The vascular component of juvenile angiofibroma consists of endothelial-lined spaces lacking muscular layers, contributing to their propensity for profuse bleeding. As a result, these tumours tend to bleed profusely and patients may present with epistaxis. While rare, juvenile angiofibroma is the most common benign tumour of the nasopharynx.

Aetiology

The precise cause of juvenile angiofibroma remains unknown. However, two primary theories have been proposed to explain its origin:

1. Testosterone Dependency Theory: This theory suggests that the tumour’s prevalence in adolescent males during their second decade of life indicates a dependence on testosterone. According to this theory, individuals with a hamartomatous nidus of vascular tissue in the nasopharynx experience the activation of this tissue to form angiofibroma upon the presence of male sex hormones.
2. Branchial Arch Artery Theory: This theory proposes that the tumour’s origin is linked to the incomplete regression of the first branchial arch artery. This explanation is appealing because it addresses several aspects of juvenile angiofibroma:
   • Embryological Development: The first branchial arch artery recedes near the pterygoid base and sphenopalatine foramen regions during embryonic development.
   • Vascular Remnants: The remnants of this artery become part of the sphenopalatine and maxillary arteries.
   • Tumour Location and Blood Supply: The close proximity of the tumour origin to the sphenopalatine foramen and its main blood supply from the sphenopalatine and maxillary arteries in the early stages of juvenile angiofibroma can be explained by this theory.
3. A primary aberration of pituitary-gonadal axis is suggested but not proved.

Site of origin and growth

The exact site of origin of juvenile angiofibroma has been a subject of debate. Initially, it was thought to arise from the roof of the nasopharynx or the anterior wall of the sphenoid bone. However, current understanding suggests that juvenile angiofibroma originates from the lateral wall of the posterior part of the nasal cavity, near the superior margin of the sphenopalatine foramen and the pterygoid base.

Due to its early submucosal expansion towards the nasopharynx, juvenile angiofibroma is often called “nasopharyngeal angiofibroma.” From this initial site, the tumour typically grows into the nasal cavity and the pterygopalatine fossa, causing the posterior wall of the maxillary sinus to be pushed forward as the tumour enlarges. The tumour can also extend laterally into the pterygomaxillary fossa and further into the infratemporal fossa and cheek. This growth pattern reflects the tumour’s aggressive nature and its tendency to spread through anatomical spaces and foramina. Although the tumour is histopathologically classified as a benign lesion, bony erosions of the pterygoid, the clivus and the sphenoid sinus floor are common hallmarks of juvenile angiofibroma.

Angiofibromas: Composition and Surgical Considerations

Angiofibromas are benign fibrovascular tumours composed of varying proportions of vascular and fibrous tissues. Typically, the vessels within these tumours are irregularly shaped and lined solely by endothelial cells, lacking an elastic or muscle coat. This structural peculiarity results in significant bleeding during surgical dissection, as the vessels are incapable of contracting. The bleeding cannot be effectively controlled with the application of adrenaline, complicating the surgical procedure.

Despite being benign, angiofibromas do not possess a capsule, which further complicates their removal. The amount of fibrous tissue and vessel density within juvenile angiofibroma can vary greatly, presenting a significant challenge for surgeons. The highest density of vessels, particularly those with characteristic irregular shapes, is usually found beneath a pseudocapsule at the tumour’s surface. To minimize bleeding, surgeons should always aim to dissect along this pseudocapsule.

Blood Supply of Nasopharyngeal Fibroma

• External carotid artery (majority) – Internal maxillary artery, ascending pharyngeal artery, palatine arteries
• Internal carotid artery (less common), usually in larger tumours – Sphenoidal branches, ophthalmic artery.

Blood Supply of Nasopharyngeal Fibroma according to the site of the extension

• Nasopharyngeal fibromas receive their blood supply primarily from the internal maxillary artery and its branches, including the sphenopalatine and pterygovaginal arteries. These vessels provide blood to the tumour at its origin in the anterior nasopharynx and posterior nasal cavity. 
• As the tumour grows larger and extends into areas such as the sphenoid sinus, infratemporal fossa, or parapharyngeal space, it acquires additional blood supply from other branches of the ECA, such as the accessory meningeal, ascending pharyngeal, and ascending palatine arteries.
• In advanced stages, the tumour’s blood supply becomes more complex, with contributions from the internal carotid arteries (ICAs) and, in some cases, the vertebral arteries. This bilateral blood supply is a characteristic of more advanced tumours, especially large juvenile angiofibromas.

Extensions of Nasopharyngeal Fibroma

Nasopharyngeal fibroma, while benign, is a locally invasive tumour that tends to spread through anatomical spaces and foraminae, destroying adjoining structures. The tumour may extend into various areas, resulting in distinct symptoms and complications:

• Anteriorly into the nasal Cavity: When the tumour extends into the nasal cavity, it can cause nasal obstruction, epistaxis (nosebleeds), and nasal discharge.
• Posteriorly into the nasopharynx.
• Paranasal Sinuses: The tumour can invade the maxillary, sphenoid, and ethmoid sinuses, contributing to further complications and obstruction.
• Laterally into the pterygomaxillary and Infratemporal Fossae: The tumour may spread laterally through the sphenopalatine foramen into the pterygomaxillary fossa, and from there into the infratemporal fossa and cheek.
• Orbit: The tumour can reach the orbit via the inferior orbital fissure, leading to proptosis (bulging of the eye), “frog-face deformity,” and/or optic nerve compression, which can cause visual disturbances. Additionally, the tumour can destroy the apex of the orbit or enter the orbit through the superior orbital fissure.
• Superiorly into the cranial Cavity: The tumour can extend into the cranial cavity in several ways:
  – Anterior Cranial Fossa: Through the roof of the ethmoids or the cribriform plate.
  – Middle Cranial Fossa: By eroding the floor of the middle cranial fossa or indirectly by invading the sphenoid sinus and sella turcica. In the former case, the tumour lies lateral to the internal carotid artery; in the latter case, medial to the artery.

In cases of intracranial tumour growth, juvenile angiofibromas are primarily located in the extradural space. Dural infiltration or brain involvement is rare but can occur.

Clinical Features

The patient usually presents with nasal obstruction (80%) but also epistaxis (50%), headache (25%) and facial swelling (15%). He can also have eye symptoms and signs (diplopia, proptosis) and unilateral otological symptoms (OME).

1. Age and Sex: This tumour predominantly affects males aged 10-20 years. It is rarely seen in older persons and females.
2. Epistaxis: Profuse, recurrent, and spontaneous nasal bleeding are the most common symptoms. Patients often become markedly anaemic due to repeated blood loss.
3. Nasal Obstruction and Speech Changes: Progressive nasal obstruction caused by the tumour mass in the postnasal space leads to denasal speech.
4. Hearing Loss and Otitis Media: Conductive hearing loss and otitis media with effusion occur due to the obstruction of the eustachian tube by the tumour.
5. Nasopharyngeal Mass: The tumour appears as a sessile, lobulated, or smooth mass in the nasopharynx, obstructing one or both choanae. It is pink or purplish and has a firm consistency. Digital palpation should be avoided until the time of operation.
6. Other Clinical Features: Depending on the extent of the tumour, other features may include broadening of the nasal bridge, proptosis, swelling of the cheek or infratemporal fossa, and involvement of the second, third, fourth, and sixth cranial nerves.

Diagnosis and Investigations of Nasopharyngeal Fibroma

The diagnosis of nasopharyngeal fibroma is primarily based on its typical clinical and radiological findings. Biopsy of the tumour is generally avoided due to the high risk of severe bleeding. If a biopsy is necessary to differentiate it from other tumours, it should be performed under general anaesthesia with all arrangements in place to control bleeding and provide blood transfusions if needed.

Nasal Endoscopy: This procedure reveals a sessile, lobulated, or smooth reddish mass in the nasal cavity.

Contrast-Enhanced Computed Tomography (CT) Scan: It is the investigation of choice, replacing conventional radiographs. It provides detailed information on the extent of the tumour, bony destruction, or displacement. The anterior bowing of the posterior wall of the maxillary sinus (antral sign or Holman-Miller sign) is pathognomonic of angiofibroma. The scan also shows the widening of the pterygomaxillary fissure, pterygopalatine fossa, and sphenopalatine foramen.

Magnetic Resonance Imaging (MRI): MRI is superior for defining orbital and intracranial soft tissue extensions. T2 images may display flow void loops, creating a “salt-and-pepper” appearance (salt = punctate hyperintense regions, pepper = small flow voids). This appearance, though classically seen in paragangliomas on T1 images, is more commonly observed in juvenile angiofibroma on T2 images.

Carotid Angiography: This imaging technique shows the extent of the tumour, its vascularity, and feeding vessels, which mostly originate from the external carotid artery system. For advanced tumours, it is essential to evaluate the ipsilateral and contralateral external and internal carotid arteries, as well as both vertebral arteries. Contrast angiography is often reserved for presurgical planning and embolization of the tumour’s blood supply.

X-ray soft tissue nasopharynx lateral view: Soft tissue mass in the nasopharynx and anterior bowing of posterior wall of maxillary sinus (antral sign) is pathognomic.

X-rays of paranasal sinuses and base of skull: Displacement of nasal septum, opacity of sinuses, destruction of medial antral wall, erosion of greater wing or pterygoid plates of sphenoid or widening of lower lateral margin of superior orbital fissure.

Blood Transfusion Arrangements: While successful embolization may reduce the need for blood during surgery, it is prudent to have 2–3 units of blood available and reserved after proper grouping and cross-matching.

Treatment of Juvenile Nasopharyngeal Angiofibroma. Surgical excision is the treatment of choice though radiotherapy and chemotherapy singly or in combination have also been used.

Surgery

Surgical excision is the primary treatment of choice for juvenile nasopharyngeal angiofibroma. Spontaneous regression of the tumour does not occur and no wait-and-watch policy should be adopted. Various surgical approaches have been described, including:

1. Transpalatine
2. Transpalatine + Sublabial (Sardana’s approach)
3. Lateral rhinotomy with medial maxillectomy
   a. Via facial incision
   b. Via degloving approach
4. Endoscopic removal
5. Transmaxillary (Le Fort I) approach
6. Maxillary swing approach or facial translocation approach, or Wei’s operation
7. Infratemporal fossa approach
8. Intracranial–extracranial approach

The specific approach depends on the origin and extensions of the tumour. Endoscopic resection has become the preferred technique for most juvenile angiofibroma in the hands of experienced sinonasal surgeons.

Extent of angiofibroma	Surgical approach
1. Nasal cavity and nasopharynx area involved	Transpalatal approach or endoscopic approach
2. Nasal cavity, nasopharynx, maxillary antrum and pterygopalatine fossa area involved	Lateral rhinotomy with medial maxillectomy approach or  Endoscopic approach or Le Fort I approach
3. B + Infratemporal fossa area involved	Extended lateral rhinotomy approach or Infratemporal fossa approach or Maxillary swing approach
4. C + Cheek involved	Extended lateral rhinotomy approach
5. B + C + Intracranial extension	Combined intracranial and extracranial approach (craniotomy + one of the extracranial approaches) or Radiation if the intracranial part is inaccessible
6. Residual or recurrent disease (extracranial)	Observation or repeat surgery or radiation if inaccessible
7. Intracranial residual or recurrent disease	Stereotactic radiation (X or gamma knife)

Preoperative embolization of the tumour’s blood supply 24-48 hours prior to surgery. It is an important tool to reduce intraoperative bleeding and surgery should not be delayed beyond 24–48 hrs of embolization to avoid revascularization from the contralateral side. Average intra-operative blood loss was reported to be approximately 2000mL; this has now been reduced to less than 1000mL by the routine use of embolization. Angiography is used to identify feeding vessels, which are then embolized. However, some surgeons prefer to ligate the vessels during surgery to avoid embolization complications and to detect possible tumour remnants by bleeding.

Radiotherapy

Radiotherapy has been used as a primary treatment or for recurrent or surgically inaccessible tumours. A dose of 3000 to 3500 cGy in 15–18 fractions is delivered over 3–3.5 weeks. The tumour regresses slowly over about a year. Radiotherapy is also used for intracranial extension when the tumour derives its blood supply from the internal carotid system. The use of radiotherapy is controversial. Some reserve it for large tumours with intracranial extension or recurrent inoperable tumours, while others believe it should be avoided due to the risk of malignancy development in the young nasopharynx.

Hormonal Therapy

Since juvenile nasopharyngeal angiofibroma occurs in young males at puberty, likely due to testosterone activation, hormonal therapy has been used. Diethylstilbestrol and flutamide (an androgen blocker) have been tried but have not shown significant tumour regression.

Chemotherapy

Very aggressive recurrent tumours and residual lesions have been treated with chemotherapy, using combinations of doxorubicin, vincristine and dacarbazine. Chemotherapy can arrest growth and cause some regression but does not achieve complete tumour eradication. Recurrence of juvenile nasopharyngeal angiofibroma is not uncommon, occurring in up to 35% of cases. Management options for recurrence include observation, revision surgery, radiotherapy, hormonal therapy, and chemotherapy.

——– End of the chapter ——–

Reference Textbooks.

• Scott-Brown, Textbook of Otorhinolaryngology-Head and Neck Surgery.
• Cummings, Otolaryngology-Head and Neck Surgery.
• Stell and Maran’s, Textbook of Head and Neck Surgery and Oncology.
• Ballenger’s, Otorhinolaryngology Head And Neck Surgery
• Susan Standring, Gray’s Anatomy.
• Frank H. Netter, Atlas of Human Anatomy.
• B.D. Chaurasiya, Human Anatomy.
• P L Dhingra, Textbook of Diseases of Ear, Nose and Throat.
• Hazarika P, Textbook of Ear Nose Throat And Head Neck Surgery Clinical Practical.
• Mohan Bansal, Textbook of Diseases of Ear, Nose and Throat Head and Neck Surgery.
• Hans Behrbohm, Textbook of Ear, Nose, and Throat Diseases With Head and Neck Surgery.
• Logan Turner, Textbook of Diseases of The Nose, Throat and Ear Head And Neck Surgery.
• Arnold, U. Ganzer, Textbook of  Otorhinolaryngology, Head and Neck Surgery.
• Ganong’s Review of Medical Physiology.
• Guyton & Hall Textbook of Medical Physiology.

Author:

Dr. Rahul Bagla
MBBS (MAMC, Delhi) MS ENT (UCMS, Delhi)
Fellow Rhinoplasty & Facial Plastic Surgery.
Renowned Teaching Faculty
Mail: msrahulbagla@gmail.com
India

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