Juvenile Nasopharyngeal Angiofibroma (JNA)

Definition

Site of Origin

• Medially through the sphenopalatine foramen into the nasopharynx and nasal cavity
• Superiorly along the vidian nerve into the floor of the sphenoid sinus
• Laterally through the pterygomaxillary fissure into the infratemporal fossa
• Anteriorly, pushing the posterior wall of the maxillary sinus forward
• Intracranially via the inferior/superior orbital fissure, or along the maxillary nerve to the parasellar region (less common)

Endoscopic view: JNA appearing as a polypoid, hypervascularized mass behind the middle turbinate (Cummings Fig. 50.8)

Pathogenesis

Hormonal Theory

Branchial Arch / Vascular Malformation Theory

Molecular Pathogenesis

• β-catenin (CTNNB1) mutations are found in the majority of sporadic JNAs - Robbins & Cotran, p. 690
• JNA can also occur syndromically in familial adenomatous polyposis (FAP) via germline APC gene mutations, also leading to β-catenin activation
• Upregulation of VEGFA and activation of VEGF/FGFR signaling pathways implicated in angiogenesis
• Additional markers studied: bFGF, H-Ras, IL-6, c-Kit, c-Myc, PDGFa, TP53 - Cummings Otolaryngology, p. 988

Histopathology

Gross Pathology

• Sessile, lobulated, rubbery mass; dark red to tan-gray in color
• Can be large; unencapsulated
• Admixture of vascular tissue and fibrous stroma
• Mucosal ulceration is not a feature - Cummings Otolaryngology, p. 1768

Microscopic Features

Histopathology (Robbins Fig. 16.11): Thin-walled vessels lined by single-layer endothelium, set in dense collagenous stroma

• Vascular component: Thin-walled, irregular vascular channels of varying caliber - some large sinusoidal spaces, some smaller capillary-type vessels
• Key feature: Vessel walls lack elastic fibers and have incomplete or absent smooth muscle - this explains the tendency for profuse, uncontrolled bleeding when incised (vessels cannot contract)
• The endothelial lining is a single layer; no muscle layer in larger sinusoidal spaces
• Stromal component: Dense collagenous stroma containing bland spindle-shaped fibroblasts/myofibroblasts; no atypia or mitoses
• Scott-Brown's describes vascular cavities with endothelial layer but no muscle layer, mixed with a more conventional arteriocapillary tree with muscle layers - Scott-Brown's Vol. 1, p. 2889-2893
• Robbins: "numerous vessels embedded in a dense collagenous stroma" - Robbins & Cotran, p. 690

Clinical Features

• Age and sex: Typically adolescent males, ages 10-25 years; rare in females and older patients - Cummings Otolaryngology, p. 1768
• Unilateral nasal obstruction (most common presenting symptom)
• Epistaxis - recurrent, often severe; may lead to anemia - Scott-Brown's Vol. 1, p. 2903
• Blood-stained sputum
• Serous otitis media (Eustachian tube obstruction)

Symptoms with Advanced Disease

• Facial swelling / cheek swelling - infratemporal fossa involvement
• Proptosis and diplopia - orbital involvement
• Headache - cranial fossa involvement
• Nasal discharge, anosmia, sinusitis

Examination Findings

• Endoscopy: smooth, hypervascularized polypoid mass originating behind the middle turbinate, which is laterally displaced; choana may be completely obstructed
• The lesion bleeds readily on contact
• A clinical presentation of nasal obstruction + epistaxis in a teenage boy with an endoscopic hypervascular nasopharyngeal mass is virtually diagnostic

Fisch Staging Classification

Other Staging Systems

• Chandler (1984): 4-stage system - Stage I (nasopharynx only) → Stage II (nasal cavity/sphenoid) → Stage III (maxillary sinus, ethmoid, infratemporal fossa, orbit, cavernous sinus) → Stage IV (intracranial)
• Andrews-Fisch (1980): The standard Fisch I-IV classification above
• Snyderman/UPMC (2010): Emphasizes residual vascularization from the internal carotid artery after embolization and route of intracranial growth as predictors of endoscopic resectability - Cummings Otolaryngology, p. 990

Differential Diagnosis

1. Antrochoanal polyp - benign, non-vascular; arises from maxillary sinus; pale, non-pulsatile; occurs in both sexes
2. Lobular capillary hemangioma (pyogenic granuloma) - vascular but different location and age group; does not involve pterygopalatine fossa
3. Hemangiopericytoma - different age group; does not involve pterygopalatine fossa
4. Schwannoma / neurofibroma - enhances on imaging but lacks flow voids; different origin
5. Nasopharyngeal carcinoma - older age group; lymphadenopathy; ulceration common
6. Rhabdomyosarcoma - pediatric malignancy; rapid growth; destructive imaging features
7. Lymphoma - systemic features, lymphadenopathy
8. Chordoma - midline origin from clivus, different age/presentation

Management

Investigations

Imaging

1. CT with contrast (primary initial investigation):
   • Shows enhancing soft tissue mass arising from nasopharynx/lateral wall
   • Classically demonstrates widening of the pterygopalatine fossa
   • "Antral sign" / Holman-Miller sign: anterior bowing of posterior maxillary sinus wall
   • Bone expansion with diffuse/patchy enhancement suggests invasion
   • Dural enhancement suggests intracranial extension
   • Bone erosion is uncommon in early disease
2. MRI with contrast (gadolinium):
   • T1 and T2 sequences show multiple flow voids (signal voids from large feeding vessels) - pathognomonic
   • Better delineates soft tissue extent, intracranial spread, orbital involvement
   • Preferred for postoperative surveillance - Cummings Otolaryngology, p. 1769
3. Digital Subtraction Angiography (DSA):
   • Shows enlarged intratumoral vessels; intense inhomogeneous blush in venous phase
   • Maps vascular supply: primarily external carotid artery (internal maxillary artery, ascending pharyngeal artery) - internal carotid involvement in ~35% of cases
   • Essential before embolization
   • Shows connections with ICA, vertebral artery, and contralateral carotid
4. MR Angiography: Less invasive vascular mapping option

Biopsy

• Biopsy is avoided due to extremely high risk of hemorrhage. Diagnosis is established clinically and radiologically. Final histologic proof is obtained from the surgical specimen. - Cummings Otolaryngology, p. 1769

Treatment

Pre-operative Embolization

• Standard adjunct performed 24-48 hours before surgery
• Dramatically reduces intraoperative blood loss and improves surgical access; improves visualization of tumor borders
• Particles (polyvinyl alcohol - PVA) or liquid agents (NBCA, Onyx) via transarterial approach
• Direct tumor puncture with Onyx is increasingly used, especially when ICA supply is present
• Devascularization is more complete with Onyx direct puncture than traditional transarterial techniques
• Not without controversy - some authors note increased likelihood of residual disease at tumor periphery after embolization, and advocate clipping the maxillary artery early in small tumors instead
• Complications: facial dull ache (common), transient facial numbness/hemiparesis; rare: blindness, permanent neurologic deficit - Scott-Brown's Vol. 1, p. 2926-2940

Surgery (Primary Treatment)

• Dissection in the subperiosteal plane with bipolar coagulation
• Extensive drilling of the basisphenoid where the tumor grows in digitations - reduces recurrence rates
• Early control of the maxillary artery reduces bleeding in small tumors

Non-surgical (Adjuvant) Options

• Radiotherapy: Reserved for unresectable tumors, extensive intracranial involvement, or recurrent disease not amenable to re-resection with acceptable morbidity. Dose typically 30-45 Gy.
• Gamma Knife / CyberKnife radiosurgery: Alternatives with low morbidity for small residual lesions
• Hormonal therapy: Flutamide (androgen antagonist) has shown tumor reduction in some reports and may serve as a preoperative adjunct; not standard practice
• Anti-angiogenic/targeted therapy: Under investigation (VEGF, FGFR pathway targeting)

Post-operative Surveillance

• Periodic endoscopy and contrast-enhanced CT or MRI for minimum of 3 years
• MRI is preferred as residual lesions tend to grow submucosally
• Imaging in the immediate postoperative period best detects residual disease before inflammatory changes develop
• Residual/recurrent disease rate: 6-39%; more likely with preoperative skull base involvement and residual ICA vascularization after embolization
• Most residual lesions diagnosed within 1 year
• Residual disease: monitored with MRI; treatment scheduled only when clear progressive growth is demonstrated - Cummings Otolaryngology, p. 991

Complications

Tumor-Related Complications

• Severe epistaxis and anemia from tumor vascularity
• Intracranial extension (Fisch Stage IIIb-IV) - uncommon but reported
• Visual impairment / blindness from orbital involvement
• Eustachian tube obstruction → serous otitis media, conductive hearing loss
• Cranial nerve compression in advanced disease
• Malignant transformation: Very rare; reported cases of transformation to fibrosarcoma (Makek, Andrews, Fisch) - Cummings references
• Fatality: Recurrence rates approach 20%; approximately 9% of cases can be fatal (usually due to massive hemorrhage or intracranial invasion) - Robbins & Cotran, p. 690

Treatment-Related Complications

• Facial pain/dull ache (most common)
• Transient facial numbness
• Transient hemiparesis
• Blindness (rare case reports)
• Permanent neurological deficit (rare) - Scott-Brown's Vol. 1, p. 2936-2940

• Massive intraoperative hemorrhage (major risk)
• Residual disease (6-39%)
• CSF leak (in operations for intracranial lesions)
• Meningitis
• Cranial nerve injury
• Facial scarring (with open approaches)
• Orbital injury/diplopia
• Nasal obstruction/synechiae

• Radiation-induced malignancy (osteosarcoma, fibrosarcoma) - long-term risk
• Growth disturbance in skeletally immature patients
• Cataracts, dry eye
• Pituitary dysfunction