Juvenile Nasopharyngeal Angiofibroma

Juvenile nasopharyngeal angiofibroma (JNA) is a rare, benign but locally aggressive and highly vascular tumour. It arises almost exclusively in adolescent males (peak age 14 to 18 years, range 9 to 25). It accounts for about 0.5 percent of head and neck tumours (incidence 1 in 150,000 to 1 in 1,500,000).

The tumour originates at the sphenopalatine foramen, at the posterolateral wall of the nasal cavity, where the pterygopalatine fossa meets the sphenoid, from the posterior part of the superior margin of the sphenopalatine foramen. It spreads submucosally along natural pathways of least resistance:

• the nasopharynx and nasal cavity
• the pterygopalatine and infratemporal fossae, through the pterygomaxillary fissure (the "anterior bowing of the posterior wall of the maxillary sinus", the Holman-Miller sign)
• sphenoid sinus and the middle cranial fossa
• the orbit, through the inferior orbital fissure
• intracranial extension, in 10 to 20 percent, usually extradural and later through the cavernous sinus

Histology shows a vascular stroma of thin walled vessels lacking a muscular layer and elastic lamina (hence the bleeding) in a fibrous stroma with stellate and multinucleated cells. Androgen receptors are expressed (hormonal influence), and beta catenin mutations (CTNNB1) are common.

Blood supply is mainly from the internal maxillary artery (via the sphenopalatine and the descending palatine arteries) and ascending pharyngeal artery. Advanced tumours have additional supply from the internal carotid artery branches (vidian, and the inferolateral trunk). There is an association with familial adenomatous polyposis (25 times higher risk) in males.

Staging uses the Radkowski (IA to IIIB) and Andrews-Fisch classifications. The Andrews-Fisch types are:

• type I: nasopharynx and nasal cavity
• type II: pterygopalatine fossa and paranasal sinuses
• type IIIa: infratemporal fossa and orbit
• type IIIb: intracranial extradural
• type IVa: intracranial intradural without involving the cavernous sinus, pituitary or optic chiasm
• type IVb: with involvement of the cavernous sinus, pituitary or optic chiasm

• Classic: a teenage boy with unilateral progressive nasal obstruction and recurrent, spontaneous, severe unilateral epistaxis (in about 60 to 90 percent), which can be life threatening.
• Nasal discharge (mucopurulent), hyponasal speech, anosmia, headache, and conductive hearing loss (Eustachian tube obstruction, secondary otitis media with effusion).
• Facial swelling or cheek fullness (from infratemporal extension), trismus, proptosis, diplopia, visual loss (orbital or optic canal involvement), and cranial nerve deficits in advanced disease.
• Examination (anterior rhinoscopy and endoscopy): a smooth, lobulated, reddish pink to purple, vascular mass in the posterior nasal cavity and nasopharynx, firm, which bleeds easily on touch; the soft palate may bulge downward.
• Biopsy must not be done in the clinic (risk of severe haemorrhage).

• Nasal endoscopy (flexible, gently): the vascular mass; no biopsy.
• Contrast enhanced CT of the skull base (axial and coronal): a soft tissue mass centred in the sphenopalatine foramen and pterygopalatine fossa, widening it, anterior bowing of the posterior wall of the maxillary sinus (Holman-Miller sign), bony erosion of the pterygoid plates, sphenoid, and the base of the skull, with intense enhancement; the diagnostic hallmark.
• MRI with gadolinium (the best for soft tissue extent, intracranial and cavernous sinus involvement, and perineural spread): intermediate signal on T1 and T2 with "salt and pepper" pattern (flow voids), and avid enhancement; differentiates tumour from retained secretions in the sinus.
• Digital subtraction angiography with selective external carotid injection: a hypervascular mass with the typical "tumour blush" fed by the internal maxillary artery, delineating feeding vessels (to plan embolisation), usually done 24 to 72 hours before surgery.
• Laboratory: full blood count (anaemia from chronic blood loss), group and cross match; genetic testing for familial adenomatous polyposis in selected cases.
• Differential diagnoses: antrochoanal polyp, nasopharyngeal carcinoma, lymphoma, rhabdomyosarcoma, haemangioma, encephalocele, inverted papilloma, adenoid hypertrophy, and juvenile hormonal polyps.

Surgical excision is the standard treatment and is curative in most patients.

• Preoperative embolisation of the feeding vessels (internal maxillary and ascending pharyngeal artery) with polyvinyl alcohol particles or Onyx, 24 to 72 hours before surgery, reduces blood loss by about 60 to 70 percent and eases dissection. Avoid embolisation of the internal carotid branches (risk of stroke and blindness).
• Surgical approach depends on the stage:
  • Endoscopic endonasal resection is the preferred approach for Radkowski stages I to IIIA, Andrews I to IIIa, even some IIIb. It uses a four handed technique. The sphenopalatine foramen is opened and the tumour is devascularised at the origin. It is then removed with the pterygopalatine fossa extension, with multi layered haemostatic control.
  • Endoscopic results are comparable to open surgery, with reduced blood loss (average 300 to 800 mL), shorter hospital stay, and recurrence rates of about 5 to 15 percent.
  • Open approaches: lateral rhinotomy (Weber-Ferguson), midfacial degloving, transpalatal, Le Fort I osteotomy, Denker approach for the maxillary extension, transmaxillary, and combined approaches for large tumours with infratemporal fossa involvement.
  • For intracranial extension (Andrews IIIb and IV), use the lateral infratemporal fossa approach (Fisch) or a combined craniofacial or craniotomy approach.
• Residual and recurrent disease: residual tumour in the skull base, especially at the basisphenoid, clivus and pterygoid canal. Recurrence is 10 to 40 percent in advanced stages. Options are surgical reintervention or stereotactic radiotherapy (30 to 36 Gy in 15 to 20 fractions, with local control of 85 to 90 percent).
• Radiotherapy is reserved for unresectable disease, residual intracranial tumour, and recurrences. Risks include growth retardation, cataract, hypopituitarism, and secondary malignancy in adolescents, so it is used with caution.
• Hormonal therapy (flutamide 250 mg three times daily for 6 to 12 weeks preoperatively) can shrink tumours by up to 40 percent.
• Other systemic therapies (tyrosine kinase inhibitors, sirolimus, bevacizumab and sorafenib) have been used for unresectable tumours with limited evidence. Chemotherapy (doxorubicin and dacarbazine, vincristine, and actinomycin) is used in rare cases of aggressive or unresectable residual disease.
• Intraoperative care: blood available (cross match 2 to 4 units), hypotensive anaesthesia, and tranexamic acid 10 to 15 mg/kg intravenously before surgery (and every 8 hours for 24 hours).
• Postoperatively, nasal packing is removed after 24 to 72 hours. Perioperative antibiotics are cefuroxime 1.5 g or amoxicillin clavulanate.
• Follow up: endoscopy and MRI at 3 to 6 months, then every 6 to 12 months for 3 to 5 years. Most recurrences present within the first 2 years (typically residual disease). Long term follow up for 5 years or more.
• Prognosis: excellent in early stage disease (cure in 85 to 95 percent), with reduced rates in intracranial extension. Spontaneous regression after adolescence is reported but cannot be relied upon.