JNA

angiofibroma

1. Dr. SANJAY MAHARJAN PG, ENT-HNS. MANIPAL TEACHING HOSPITAL. Juvenile nasopharyngeal angiofibroma :

2. Introduction: Nasopharynx is an embryologic confluence of end of nasal structures and beginning of pharynx Symptoms generally arise late because of capacity for tumor growth and expansion Diagnostic inaccessibility of nasopharyngeal (NP) area, tumors can be difficult to detect

3. DIAGNOSTIC APPROACH FOR NASOPHARYNGEAL MASSES Presentation of an NP tumor is variable and ranges from ear, nose, and throat symptoms to neck masses and cranial nerve palsies Age and gender are important in D/D Usually due to adenoidal hypertrophy in pediatric but JNA should be strongly considered in teenage boys In adults, NP malignancy should be default diagnosis In several Asian regions it is common and usually of epstein-barr virus (EBV)–related, undifferentiated carcinoma

4. Imaging studies before biopsy of mass. Histology of the NP mass dictates the management

5. THORNWALDT CYST OR BURSA : Next to adenoidal hypertrophy, it is m/c epithelial growth in NP area Result of a cleavage line between nasal and pharyngeal embryologic processes ( Rathke pouch) Usually asymptomatic D/D should include Meningocele or meningoencephalocele Generally do not need to be removed , nor is biopsy necessary if diagnosis is apparent

6. Juvenile nasopharyngeal angiofibroma :

7. Introduction : Usually occurs in adolescent boys , thus commonly called juvenile nasal angiofibroma (JNA) <1% of all head and neck tumors Benign but Locally infiltrative Sarcomatous , malignant transformation is extremely rare and attributable to prior radiotherapy Slow-growing vascular tumor, arises in area of S phenopalatine foramen at root of pterygoid process on lateral nasal wall Maxillary sinus is m/c site for extra-NP angiofibroma , occur most often in females

8. Main blood supply : Internal maxillary artery Others : Ascending pharyngeal artery, vidian artery, inferomedial trunk or inferior hypophyseal artery ( br of ICA) rarely vertebral artery

9. Spread: Tumor migrate beneath mucus membrane of NP, displacing it downward in the process Grows in adjacent anatomical sites that offer less resistance and invade cancellous bone of basisphenoid Medially  nasopharynx , nasal fossa, and eventually towards contralateral side Laterally  infratemporal fossae, via an enlarged pterygo -maxillary fissure  typical anterior displacement of posterior maxillary wall  contact with masticatory muscles and cheek Posteriorly  ICA via vidian canal, cavernous sinus via foramen rotundum and orbital apex via inferior orbital fissure

10. White dotted line : spread into cancellous bone of basisphenoid along vidian canal White arrowheads : spread deep into pterygomaxillary fossa toward masticatory muscles, with ant. Displacement of post. Maxillary wall Black arrows : right vidian nerve

11. Bone involvement occurs via two main mechanisms: Resorption by direct pressure of preexisting bony structures with osteoclastic activation Direct spread along perforating arteries into cancellous root of pterygoid process In advanced cases Extends posteriorly towards upper-middle of clivus Laterally within greater wing of sphenoid Erosion of the inner table of middle cranial fossa I nfiltration of dura is very rare

12. Pathologic features: Gross pathology usually shows a sessile, lobulated, rubbery, dark red to tan gray mass that can be large Color varies from pink to white On section  reticulated, whorled or spongy appearance, lacks true capsule but sharply demarcated edges Microscopically, Composed of an admixture of vascular tissue and fibrous stroma Vessel walls lack elastic fibers and have incomplete or absent smooth muscle -- tendency to bleed

13. Factors that play a role in the growth : Chromosomal abnormalities: gains at chromosomes 4, 6, 8, and X and losses on chromosomes 17, 22, and Y are most frequent Increased prevalence of JA (25 times) in patients with familial adenomatous polyposis (FAP) , condition that is associated with mutations of adenomatous polyposis coli ( APC) gene This gene regulates beta-catenin pathway which influences cell to cell adhesion. Mutations of beta-catenin have been found in sporadic and recurrent JAs.

14. Angiogenic growth factor, vascular endothelial growth factor (VEGF) has been found localized on both endothelial and stromal cells Overexpression of insulin-like growth factor II (IGFII ) Hormonal factors: controversial

15. Theories associated with its aetiopathogenesis : Ringertz theory (1938) – JNA arose from the periosteum of NP vault Som & Neffson (1940) – inequalities in the growth of bones forming skull base resulted in hypertrophy of the underlying periosteum in response to hormonal influence. Bensch & Ewing (1941) – tumour probably arose from embryonic fibro cartilage between basi -occiput and basi -sphenoid. Brunner (1942) – suggested origin from conjoined pharyngobasilar and buccopharyngeal fascia.

16. Sternberg (1954) – proposed that JNA could be a type of hemangioma like a cutaneous hemangioma seen in children which regresses with age Osborn (1959) – it could be due to either a hamartoma or residual fetal erectile tissue which were subjected to hormonal influence Girgis & fahmy (1973) – observed cell nests of undifferentiated epitheloid cells or “ zellballen ” at the growing edge of angiofibromas and so considered it as a paraganglioma

17. ‘ Branchial arch artery’ theory: Tumour origin is based on an incomplete regression of the first branchial arch artery Able to explain different aspects of JNA: During embryological development, it finally recedes close to pterygoid base and sphenopalatine foramen regions Vascular remnants of this artery are incorporated into sphenopalatine and maxillary arteries themselves

18. Its connection to c4-segment of ICA accounts for vascular supply from ICA, despite an anatomical distance between this vessel and the JA Elucidates common finding of residual tumour at pterygoid base and clivus

19. Clinical features: Ages : 10 and 25 in males Cardinal symptoms : nasal obstruction and intermittent epistaxis Others: Chronic anaemia Hyposmia or anosmia Nasal intonation of voice Deafness and otalgia Headache

20. In extensive lesions  Nasal bones become splayed out Swelling in temple and cheek Intraoral palpation between ascending ramus of mandible and side of maxilla may reveal thickening of disease which has crept around back of the antrum Trismus and bulging of parotid if Impaction of bulky mass in infratemporal fossa Proptosis if orbital fissures are penetrated Frog face appearance if massive escape of diseases

21. Diagnosis: Endoscopic examination: Rubbery vascular mass that protrudes into anterior nasal space May have excessive bleeding on contact Since epidemiologic and endoscopic findings are typical, biopsy is absolutely contraindicated because of a considerable and undue risk of massive hemorrhage

22. Diagnosis on imaging is based on three factors Site of origin Hypervascularization after contrast enhancement Patterns of growth CT scan with contrast: Enhancing soft tissue mass arising from NP or lateral wall of nose. Pterygopalatine fossa may be widened by tumor , bone erosion not present in general MRI: Vascular tumor with flow voids within mass that enhance on gadolinium imaging

23. Signs in CECT: HOLMAN MILLER SIGN: 80% Anterior bowing of posterior wall of maxillary antrum HONDOUSA SIGN: Widening of gap between ramus of mandible & maxillary body

24. RAM HARAN SIGN: Quadrilateral appearance of pterygoid wedge CHOP STICK SIGN: Post op appearance of medial & lateral pterygoid plates as two separate sticks due to drilling & removal of pterygoid wedge

25. Pathognomonic sign : erosion of upper medial pterygoid plate which is found in 98 % Differential diagnosis includes other hypervascularized lesions: Hemangiopericytoma Lobular capillary hemangioma Paraganglioma

26. Rich vascularity of tumour gives rise to typical small dotted flow voids (salt pepper appearance)

27. Angiography: b/l vascular supply is around 36% hence both carotid systems require angiographic evaluation Assess vascular supply of JA Allow embolization of feeding vessels prior to surgery More as a surgical treatment adjuvant via possibility of embolization rather than diagnostic tool MR angiography is least invasive form of vascular imaging that will show size feeding vessels Vascular blush seen in postnasal space and adjacent areas is diagnostic

28. However, final proof of diagnosis is histologic.

29. Staging: Several staging systems have been proposed – Fisch Chandlers Andrews Radkowski Fisch  most robust and practical. Defines clearly which surgical approach is required Radkowsk i  appeals to those involved with management of smaller tumours as there are more subdivisions

30. Chandler’s staging of JNA: Stage 1 : Tumor is confined to nasopharynx Stage 2 : Extends into nasal cavity or sphenoid Stage 3 : Tumor involves maxillary sinus, ethmoid sinus, infratemporal fossa, orbit, cheek, and cavernous sinus Stage 4 : Tumor is intracranial

31. General surgical principles: The surgical approach is dependent on Tumour location and extent Pattern of vascular supply Effectiveness of embolisation Facial skeletal maturity Experience of the surgical team JNAs may be resected by endoscopic, open or combined (endoscopic & open) techniques

32. Endoscopic sinus surgery techniques Mainstay of surgical resection in present era Advantages: Magnified view of lesion and related anatomical structures from multiple angles  better identification of interface between lesion and soft tissues or adjacent bone strs Allows more accurate and complete dissection and better control of bleeding

33. Indications: Tumours involving nasal cavity, paranasal sinuses, and nasopharynx Tumours with only medial infratemporal fossa involvement or extradural parasellar involvement with limited intracranial extension Facilitation of open approaches Relative contraindications: Lateral infratemporal fossa involvement, Extensive parasellar extension, Encasementof the optic nerve, Intradural spread, or cavernous sinus involvement

34. Complications: Pain B leeding Infection Hyposmia Synechiae Orbital Injury, loss of vision Cerebrospinal fluid leak I ntracranial injury Tumour recidivism if margins are not cleared

35. Open approaches: Tumours that extend to infra-temporal fossa Tumours with intradural extension In centres that lack endo-scopic expertise In conjunction with endo-scopic resection e.g. Anterior antrostomy ( caldwell-luc ) may be employed to gain access to, and clip, internal maxillary artery

36. Includes: Medial maxillectomy Le fort 1 osteotomy Transpalatal Maxillary swing Infratemporal fossa Facial translocation

37. Intraoral transpalatal approach: (Wilson’s) Allows for access to NP (for small lesions)

38. Medial maxillectomy approach: For tumors extending to pterygopalatine fossa Soft tissue elevation preferably with a midfacial degloving incision. Advantages are: Excellent exposure of lesion Direct control of internal maxillary artery in pterygopalatine fossa Very satisfactory cosmetic outcome Commonest complication – Vestibular stenosis, Infraorbital N. Injury lateral rhinotomy only required when superior parts of ethmoids are to be dissected

39. Midfacial degloving approach:

40. Lateral rhinotomy :

41. Le fort type 1 osteotomy: Will allow an inferior approach to maxillary and ethmoid sinuses and to pterygopalatine canal For extension outside NP into paranasal sinuses Complication – Malocclusion, Necrosis of maxilla

42. Facial translocation approach: Affords a large window of access For lesions that involve infratemporal fossa or large lesions that involve majority of sinuses

43. Adjuvant Therapies:

44. Preoperative embolization: Reduces intra-operative bleeding May shrink the tumor Enables better visualization of surgical field (endoscopic setting), facilitates dissection However, risk of recurrence increased Tumour shrinkage makes borders ill-defined leads to inadequate resection Done 24–72 hours pre-operatively Stroke, visual loss, facial paralysis, or carotid dissection may occur if feeders from ICA embolized

45. Gelfoam Polyvinyl alcohol foam Coils Micro-particles or Liquid glue Ethylene–vinyl alcohol co-polymer (Onyx ®): shows deep penetration into tumor more extensive tumor necrosis embolization of large portions of tumor via fewer catheterizations safe withdrawal of catheter

46. Limiting factors for successful embolization: Vessel tortuosity Vasospasm Prior sacrifice of internal maxillary artery or external carotid artery Most serious complication : loss of vision secondary to occlusion of central retinal artery direct intra- tumoral embolization under, radiographic control if feeder not accessible

47. Hormonal Therapy: Tumor enlargement with administration of testosterone and shrinkage with estrogen therapy Flutamide (2-methyl-n-[4-nitro-3{ trifluoromethyl }phenyl] propanamide ), orally active non-steroidal androgen antagonist Gates et al .  tumor reduction of 44% in 4 of 5 cases receiving 6 week treatment course Labra et al.  tumor reduction of only 11.1% in 6 cases receiving 3 week treatment course Current recommendation  6 week course of flutamide as adjuvant therapy in post-pubertal patient

48. Radiation: For tumors that recur after surgery and those with intracranial extension , where clearance of margins may be difficult 3000 – 5500 cGy in 15 -18# over 3 - 3.5 wks Tumour regression is very slow (over 2-3 year ) and is by radiation vasculitis and occlusion of vessels by perivascular fibrosis Intensity-modulated radiotherapy: Creates conformal dose distribution to minimize dose to adjacent tissues Has been used to deliver 3,400–4,500 cGy to patients with extensive disease involving cavernous sinus and skull base

49. Proton RT  Creates even tighter dose distribution Further reduce risk of late effects Stereotactic radiosurgery  For minimal, well-defined residual tumor following incomplete resection Disadvantages : Risk of marginal miss because of necessarily tight dose distribution Higher risk of late complications

50. Complications of radiotherapy: Up to 33% Growth retardation Panhypopituitarism Temporal lobe necrosis Cataracts Radiation keratopathy Thyroid and nasopharyngeal malignancies

51. Hypotensive Anesthesia: Provide a relative bloodless field  tumor removal is easier, quicker and satisfactory

52. Complications: Recurrence  Most common complication (25 %) More likely in patients with advanced disease and in those treated by inexperienced surgeons Younger patient Usu. Develop as a consequence of invasion of basisphenoid Disease-free status five years after primary surgery probably represents cure

53. Infraorbital nerve sensory deficits and nasal vestibular stenosis  complication of mid-facial degloving ,. Prolonged nasal crusting  may develop into ozaena (regular nasal douching with saline and the use of glucose in glycerine drops can alleviate) Ocular problems with more extensive resections Displacement of globe caused by loss of bony support, Ophthalmoplegia Visual loss

54. Trigemino -cardiac reflex: Characterized by – 1. Bradycardia / Asystole 2. Hypotension 3. Apnea 4. Gastric Hypermotility Incidence – 4 % Cause – Manipulation of PPF, ITF, NP Mucosa To prevent – 4% Xylocaine pack in PPF , ITF If occurs – Stop all manipulation, IV Crystalloids, wait for 10-15 min

55. Management of ICA injury: Don’t panic Don’t pack Use 2 suctions 1 – 2 cm 3 muscle harvested from thigh or abdomen Crushed & placed over bleeding point for at least 3-5 min → activates platelet fibrin plug Reinforce with surgicel If still not controlled → Endovascular intervention by angiography team

56. References: Scott browns ORL & HNS 6 th , 7 th and 8 th edition. Cummings ORL & HNS 6 TH edition. López , Fernando, et al. "Nasal juvenile angiofibroma : Current perspectives with emphasis on management."  2017 Nicolai P, Schreiber A, Bolzoni Villaret A. “Juvenile angiofibroma : evolution of management .” 2011 Open atlas. JUVENILE NASOPHARYNGEAL ANGIOFIBROMA SURGERY.