Nasopharyngeal angiofibroma

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Causes & Risk Factors for Nasopharyngeal angiofibroma

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Treatment of Nasopharyngeal angiofibroma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2] Maria Fernanda Villarreal, M.D. [3]

Synonyms and keywords: Juvenile nasopharyngeal angiofibroma (JNA); angiofibroma of the nasopharynx, nasopharyngeal fibroma, bleeding fibroma of adolescence, fibroangioma

Overview

Nasopharyngeal angiofibroma was first described by Hippocrates, a Greek physician, in the 5th century BC. Nasopharyngeal angiofibroma may be classified according to Fisch classification into 4 groups. Nasopharyngeal angiofibroma is a histologically benign tumor. This tumor is located in the posterolateral wall of the nasal cavity. On gross pathology, characteristic findings of nasopharyngeal angiofibroma include tan to purple-red, rubbery-firm unencapsulated polypoid fibrous mass. Fibroblastic cells with plump (near cuboidal) nuclei and abundant capillaries are seen on microscopic histopathological analysis. The cause of Nasopharyngeal angiofibroma has not been identified, but it may be caused by hormonal effect. Incidence of juvenile nasopharyngeal angiofibroma is less than 0.5% of head and neck tumors. If left untreated, %9 of patients with nasopharyngeal angiofibroma may progress to develop hemorrhage and intracranial extension. The hallmark of Nasopharyngeal angiofibroma is the classic triad of epistaxis, unilateral nasal obstruction and a mass in the nasopharynx. Physical examination of patients with Nasopharyngeal angiofibroma is usually remarkable for nasal mass and rhinorrhea. Findings on an x-ray suggestive of nasopharyngeal angiofibroma include nasopharyngeal polyp and Antral sign or Holman-Miller sign (Forward bowing of the posterior wall of the maxillary sinus). CT scan and MRI demonstrate the extent of the tumor. The mainstay of treatment for nasopharyngeal angiofibroma is surgical resection.

Historical Perspective

  • Nasopharyngeal angiofibroma was first described by Hippocrates, a Greek physician, in the 5th century BC.[1]
  • In 1940, Friedberg was the first to use the term angiofibroma.
  • The first endoscopic resection of nasopharyngeal angiofibroma was done in 1996.

Classification

Nasopharyngeal angiofibroma may be classified according to Fisch classification into 4 groups: [2]

.

Pathophysiology

Nasopharyngeal angiofibroma is a histologically benign tumor. This tumor is located in the posterolateral wall of the nasal cavity. Nasopharyngeal angiofibroma may involve sphenoid sinuses, maxillary, ethmoid, pterygoid plate , orbit, base of the skull and extradural. In rare cases, nasopharyngeal angiofibroma may involve pituitary, cavernous sinus and/or optic chiasm and anterior fossa. [3]

  • Genetic alterations associated with the development of nasopharyngeal angiofibroma include:[4]
  • On gross pathology, characteristic findings of nasopharyngeal angiofibroma include:
  • On microscopic histopathological analysis, characteristic findings of nasopharyngeal angiofibroma include:

Causes

The cause of Nasopharyngeal angiofibroma has not been identified, but it may be caused by hormonal effect. [6] Nasopharyngeal angiofibroma express higher levels of vascular endothelial growth factor (VEGF) and hormone receptors.

Differentiating Nasopharyngeal angiofibroma from Other Diseases

  • Nasopharyngeal angiofibroma must be differentiated from other diseases that cause epistaxis, unilateral nasal obstruction, and rhinorrhea, such as:[7]

Epidemiology and Demographics

Incidence of juvenile nasopharyngeal angiofibroma is less than 0.5% of head and neck tumors. [8]

The incidence of juvenile nasopharyngeal angiofibroma is 0.6 per 100,000 individuals worldwide.[9]

Some reports suggest juvenile nasopharyngeal angiofibroma is more common in the indian subcontinent than in the west.[10]

Men are more commonly affected by juvenile nasopharyngeal angiofibroma than women.

Risk Factors

Common risk factors in the development of nasopharyngeal angiofibroma include:

Screening

There is insufficient evidence to recommend routine screening for nasopharyngeal angiofibroma.

Natural History, Complications, and Prognosis

  • If left untreated, %9 of patients with nasopharyngeal angiofibroma may progress to develop hemorrhage and intracranial extension.
  • Prognosis is generally good.

Diagnosis

Diagnostic Study of Choice

The diagnosis of nasopharyngeal angiofibroma is made when the following findings are met:

History and Symptoms

The hallmark of Nasopharyngeal angiofibroma is the classic triad of epistaxis, unilateral nasal obstruction and a mass in the nasopharynx. The most common symptoms of Nasopharyngeal angiofibroma include nasal obstruction, epistaxis and headache. Less common symptoms of Nasopharyngeal angiofibroma include conductive hearing loss, diplopia, proptosis, anosmia, recurrent otitis media and eye pain. [13]

Physical Examination

Physical examination of patients with Nasopharyngeal angiofibroma is usually remarkable for nasal mass and rhinorrhea.[13]

Rare physical examination include:

Laboratory Findings

There are no diagnostic laboratory findings associated with nasopharyngeal angiofibroma.

Electrocardiogram

There are no ECG findings associated with nasopharyngeal angiofibroma.

X-ray

An x-ray may be helpful in the diagnosis of nasopharyngeal angiofibroma. Findings on an x-ray suggestive of nasopharyngeal angiofibroma include:[14]

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with nasopharyngeal angiofibroma.

CT scan

CT scan demonstrate the extent of the tumor. Findings on CT scan suggestive of nasopharengeal angiofibroma include:[15]

MRI

Cronal MRI demonstrate the extent of the tumor especially in intracranial involvement. [16] Findings on MRI suggestive of nasopharengeal angiofibroma include:[17]

  • Largely isointense to muscle on T1-weighted images
  • Hyperintense on T2-weighted images
  • Internal signal-void regions
  • Intense enhancement after intravenous (IV) contrast injection

Other Imaging Findings

DSA (digital subtraction angiography) of carotid artery is helpful in the diagnosis extension of nasopharengeal angiofibroma and feeding vessel.[18]

Other Diagnostic Studies

Other diagnostic studies for nasopharengeal angiofibroma include nasal endoscopy, which demonstrates hypervascularized large, lobulated mass behind the middle turbinate.[19][20]

Medical Therapy

The mainstay of treatment for nasopharyngeal angiofibroma is surgical resection. Medical therapies for nasopharyngeal angiofibroma include: [21]

Surgery

Arteriography followed by preoperative embolization and surgical resection is the mainstay of treatment for nasopharyngeal angiofibroma. [22]

Surgical approaches for nasopharyngeal angiofibroma include: [23]

  • Transpalatal
  • Transmaxillary
  • Lateral rhinotomy
  • Mid-facial degloving
  • Extended sublabial Denker
  • Le Fort type I osteotomy
  • Endoscopic surgery

Primary Prevention

There are no established measures for the primary prevention of Nasopharyngeal angiofibroma.

Secondary Prevention

Once diagnosed and successfully treated, patients with nasopharyngeal angiofibroma are followed-up after surgery, and every 6 or 12 months, depending on the clinical progression.

References

  1. Moorthy PN, Ranganatha Reddy B, Qaiyum HA, Madhira S, Kolloju S (October 2010). "Management of juvenile nasopharyngeal angiofibroma: a five year retrospective study". Indian J Otolaryngol Head Neck Surg. 62 (4): 390–4. doi:10.1007/s12070-010-0097-2. PMC 3266082. PMID 22319699.
  2. Martins MB, de Lima FV, Mendonça CA, de Jesus EP, Santos AC, Barreto VM, Santos RC (January 2013). "Nasopharyngeal angiofibroma: Our experience and literature review". Int Arch Otorhinolaryngol. 17 (1): 14–9. doi:10.7162/S1809-97772013000100003. PMC 4423317. PMID 25991988.
  3. Pryor SG, Moore EJ, Kasperbauer JL (July 2005). "Endoscopic versus traditional approaches for excision of juvenile nasopharyngeal angiofibroma". Laryngoscope. 115 (7): 1201–7. doi:10.1097/01.MLG.0000162655.96247.66. PMID 15995507.
  4. McKnight CD, Parmar HA, Watcharotone K, Mukherji SK (2017). "Reassessing the Anatomic Origin of the Juvenile Nasopharyngeal Angiofibroma". J Comput Assist Tomogr. 41 (4): 559–564. doi:10.1097/RCT.0000000000000566. PMID 28632604.
  5. Liu Z, Wang J, Wang H, Wang D, Hu L, Liu Q, Sun X (January 2015). "Hormonal receptors and vascular endothelial growth factor in juvenile nasopharyngeal angiofibroma: immunohistochemical and tissue microarray analysis". Acta Otolaryngol. 135 (1): 51–7. doi:10.3109/00016489.2014.952774. PMID 25384380.
  6. Alimli AG, Ucar M, Oztunali C, Akkan K, Boyunaga O, Damar C, Derinkuyu B, Tokgöz N (June 2016). "Juvenile Nasopharyngeal Angiofibroma: Magnetic Resonance Imaging Findings". J Belg Soc Radiol. 100 (1): 63. doi:10.5334/jbr-btr.1090. PMC 5854277. PMID 30038985.
  7. Gullane PJ, Davidson J, O'Dwyer T, Forte V (August 1992). "Juvenile angiofibroma: a review of the literature and a case series report". Laryngoscope. 102 (8): 928–33. doi:10.1288/00005537-199208000-00014. PMID 1323003.
  8. Coutinho-Camillo CM, Brentani MM, Nagai MA (March 2008). "Genetic alterations in juvenile nasopharyngeal angiofibromas". Head Neck. 30 (3): 390–400. doi:10.1002/hed.20775. PMID 18228521.
  9. Biswas D, Saha S, Bera SP (May 2007). "Relative distribution of the tumours of ear, nose and throat in the paediatric patients". Int. J. Pediatr. Otorhinolaryngol. 71 (5): 801–5. doi:10.1016/j.ijporl.2007.01.021. PMID 17368816.
  10. Ponti G, Losi L, Pellacani G, Rossi GB, Presutti L, Mattioli F, Villari D, Wannesson L, Alicandri Ciufelli M, Izzo P, De Rosa M, Marone P, Seidenari S (March 2008). "Wnt pathway, angiogenetic and hormonal markers in sporadic and familial adenomatous polyposis-associated juvenile nasopharyngeal angiofibromas (JNA)". Appl. Immunohistochem. Mol. Morphol. 16 (2): 173–8. doi:10.1097/PAI.0b013e31806bee12. PMID 18227724.
  11. Roy Chowdhury S, Rajkumar K, Deshmukh T (March 2017). "Complications of Midface Swing for Management of Juvenile Nasopharyngeal Angiofibroma". J Maxillofac Oral Surg. 16 (1): 96–100. doi:10.1007/s12663-016-0947-x. PMC 5328877. PMID 28286392.
  12. 13.0 13.1 Enepekides DJ (December 2004). "Recent advances in the treatment of juvenile angiofibroma". Curr Opin Otolaryngol Head Neck Surg. 12 (6): 495–9. PMID 15548906.
  13. Ikubor JE, Okolugbo NE, Okhakhu AL (2013). "Radiological features of juvenile nasopharyngeal angiofibroma". J West Afr Coll Surg. 3 (4): 84–91. PMC 4437236. PMID 26046027.
  14. Mishra S, Praveena NM, Panigrahi RG, Gupta YM (2013). "Imaging in the diagnosis of juvenile nasopharyngeal angiofibroma". J Clin Imaging Sci. 3 (Suppl 1): 1. doi:10.4103/2156-7514.109469. PMC 3716018. PMID 23878770.
  15. Mishra S, Praveena NM, Panigrahi RG, Gupta YM (2013). "Imaging in the diagnosis of juvenile nasopharyngeal angiofibroma". J Clin Imaging Sci. 3 (Suppl 1): 1. doi:10.4103/2156-7514.109469. PMC 3716018. PMID 23878770.
  16. Alimli AG, Ucar M, Oztunali C, Akkan K, Boyunaga O, Damar C, Derinkuyu B, Tokgöz N (June 2016). "Juvenile Nasopharyngeal Angiofibroma: Magnetic Resonance Imaging Findings". J Belg Soc Radiol. 100 (1): 63. doi:10.5334/jbr-btr.1090. PMC 5854277. PMID 30038985.
  17. Giavroglou C, Constantinidis J, Triaridis S, Daniilidis J, Dimitriadis A (January 2007). "[Angiographic evaluation and embolization of juvenile nasopharyngeal angiofibroma]". HNO (in German). 55 (1): 36–41. doi:10.1007/s00106-006-1410-y. PMID 16775738.
  18. Makhasana JA, Kulkarni MA, Vaze S, Shroff AS (2016). "Juvenile nasopharyngeal angiofibroma". J Oral Maxillofac Pathol. 20 (2): 330. doi:10.4103/0973-029X.185908. PMC 4989574. PMID 27601836.
  19. Nicolai P, Schreiber A, Bolzoni Villaret A (2012). "Juvenile angiofibroma: evolution of management". Int J Pediatr. 2012: 412545. doi:10.1155/2012/412545. PMID 22164185.
  20. Enepekides DJ (December 2004). "Recent advances in the treatment of juvenile angiofibroma". Curr Opin Otolaryngol Head Neck Surg. 12 (6): 495–9. PMID 15548906.
  21. Nicolai P, Schreiber A, Bolzoni Villaret A (2012). "Juvenile angiofibroma: evolution of management". Int J Pediatr. 2012: 412545. doi:10.1155/2012/412545. PMC 3228400. PMID 22164185.
  22. Nicolai P, Schreiber A, Bolzoni Villaret A (2012). "Juvenile angiofibroma: evolution of management". Int J Pediatr. 2012: 412545. doi:10.1155/2012/412545. PMID 22164185.


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WikiDoc Resources for Nasopharyngeal angiofibroma

Articles

Most recent articles on Nasopharyngeal angiofibroma

Most cited articles on Nasopharyngeal angiofibroma

Review articles on Nasopharyngeal angiofibroma

Articles on Nasopharyngeal angiofibroma in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Nasopharyngeal angiofibroma

Images of Nasopharyngeal angiofibroma

Photos of Nasopharyngeal angiofibroma

Podcasts & MP3s on Nasopharyngeal angiofibroma

Videos on Nasopharyngeal angiofibroma

Evidence Based Medicine

Cochrane Collaboration on Nasopharyngeal angiofibroma

Bandolier on Nasopharyngeal angiofibroma

TRIP on Nasopharyngeal angiofibroma

Clinical Trials

Ongoing Trials on Nasopharyngeal angiofibroma at Clinical Trials.gov

Trial results on Nasopharyngeal angiofibroma

Clinical Trials on Nasopharyngeal angiofibroma at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Nasopharyngeal angiofibroma

NICE Guidance on Nasopharyngeal angiofibroma

NHS PRODIGY Guidance

FDA on Nasopharyngeal angiofibroma

CDC on Nasopharyngeal angiofibroma

Books

Books on Nasopharyngeal angiofibroma

News

Nasopharyngeal angiofibroma in the news

Be alerted to news on Nasopharyngeal angiofibroma

News trends on Nasopharyngeal angiofibroma

Commentary

Blogs on Nasopharyngeal angiofibroma

Definitions

Definitions of Nasopharyngeal angiofibroma

Patient Resources / Community

Patient resources on Nasopharyngeal angiofibroma

Discussion groups on Nasopharyngeal angiofibroma

Patient Handouts on Nasopharyngeal angiofibroma

Directions to Hospitals Treating Nasopharyngeal angiofibroma

Risk calculators and risk factors for Nasopharyngeal angiofibroma

Healthcare Provider Resources

Symptoms of Nasopharyngeal angiofibroma

Causes & Risk Factors for Nasopharyngeal angiofibroma

Diagnostic studies for Nasopharyngeal angiofibroma

Treatment of Nasopharyngeal angiofibroma

Continuing Medical Education (CME)

CME Programs on Nasopharyngeal angiofibroma

International

Nasopharyngeal angiofibroma en Espanol

Nasopharyngeal angiofibroma en Francais

Business

Nasopharyngeal angiofibroma in the Marketplace

Patents on Nasopharyngeal angiofibroma

Experimental / Informatics

List of terms related to Nasopharyngeal angiofibroma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [5]

Synonyms and keywords: Juvenile nasopharyngeal angiofibroma; angiofibroma of the nasopharynx; JNA

Overview

Nasopharyngeal angiofibroma (also called juvenile nasopharyngeal angiofibroma) is a locally aggressive, benign vascular neoplasm that grows in the pterygopalatine fossa. The most common symptoms of nasopharyngeal angiofibroma include one-sided nasal obstruction and recurrent bleeding. Nasopharyngeal angiofibroma may be classified according to Radkowski Classification System (severity) into 3 categories: I, II, and III. The majority of nasopharyngeal angiofibromas are irrigated by the external carotid artery. Genetic alterations associated with the development of nasopharyngeal angiofibroma include: overexpression of PDGF-B, bFGF, VEGF. Nasopharyngeal angiofibroma accounts for 0.05% of all head and neck tumors. Nasopharyngeal angiofibromas are more commonly observed among children and adolescents. Males are more commonly affected with nasopharyngeal angiofibroma than females. Common risk factors in the development of nasopharyngeal angiofibroma, include: presence of tumor in the pterygoid fossa and young age. Physical examination may be remarkable for smooth submucosal mass in the posterior nasal cavity. Computed tomography is the imaging modality of choice. On conventional radiography, findings of nasopharyngeal angiofibroma include: visualization of a nasopharyngeal mass, opacification of the sphenoid sinus, and anterior bowing of the posterior wall of the maxillary antrum. Surgery is the mainstay of therapy for nasopharyngeal angiofibroma. Surgical approach for nasopharyngeal angiofibroma will usually depend on the stage. The treatment of choice for early stage for nasopharyngeal angiofibroma is intranasal endoscopic surgery ( e.g. lateral rhinotomy). The treatment of choice for late stage nasopharyngeal angiofibroma include the infratemporal fossa approach, and the mid-facial degloving approach. Common complications of nasopharyngeal angiofibroma include transient blindness, optic nerve damage, and low-grade consumption coagulopathy.

Historical Perspective

  • Nasopharyngeal angiofibroma was first described by Hippocrates, a Greek physician, in the 5th century BC.

Classification

  • Nasopharyngeal angiofibroma may be classified according to Radkowski Classification System into 3 categories:[1]
  • Stage I
  • Stage II
  • Stage III
  • Stage IIIA: intracranial extension

Pathophysiology

  • The pathogenesis of nasopharyngeal angiofibroma is characterized by the following features:
  • Genetic alterations associated with the development of nasopharyngeal angiofibroma include:[2]
  • Overexpression PDGF-B
  • Overexpression bFGF
  • Overexpression bFGF
  • Deletion of chromosome 17
  • Tumor suppressor gene p53
  • Overexpression of Her-2/neu oncogene
  • On gross pathology, characteristic findings of nasopharyngeal angiofibroma include:
  • Unencapsulated
  • Polypoid fibrous mass
  • Bleeding on manipulation
  • On microscopic histopathological analysis, characteristic findings of nasopharyngeal angiofibroma include:
  • Fibroblastic cells with plump (near cuboidal) nuclei
  • Fibrous stroma
  • Abundant capillaries

Causes

  • There are no known causes of nasopharyngeal angiofibroma.

Differentiating Nasopharyngeal Angiofibroma from Other Diseases

  • Nasopharyngeal angiofibroma must be differentiated from other diseases that cause epistaxis, unilateral nasal obstruction, and rhinorrhea, such as:

Epidemiology and Demographics

  • Nasopharyngeal angiofibroma is a rare tumor.
  • Nasopharyngeal angiofibroma accounts for 0.05% of all head and neck tumors.
  • The prevalence of nasopharyngeal angiofibroma is approximately 0.4 per 100,000 individuals worldwide.[1]

Age

  • Nasopharyngeal angiofibroma is more commonly observed among patients aged 7-19 years.[1]

Gender

  • The male to female ratio for nasopharyngeal angiofibroma is approximately 4 to 1.[1]

Race

  • There is no racial predilection for nasopharyngeal angiofibroma.

Risk Factors

  • Common risk factors in the development of nasopharyngeal angiofibroma include:
  • Presence of tumor in the pterygoid fossa
  • Young age
  • Feeders from the internal carotid artery
  • Residual tumor

Natural History, Complications and Prognosis

  • The majority of patients with nasopharyngeal angiofibroma are symptomatic at diagnosis.
  • Early clinical features include epistaxis, facial pain, and headache.
  • If left untreated, the majority of patients with nasopharyngeal angiofibroma may progress to develop malignant transformation.
  • Common complications of nasopharyngeal angiofibroma include transient blindness, optic nerve damage, and low-grade consumption coagulopathy.
  • Prognosis is generally good, and the 5-year survival rate of patients with early stage nasopharyngeal angiofibroma is approximately 90%
  • Survival rate of patients with late stage nasopharyngeal angiofibroma is approximately 50% to 75%.

Diagnosis

Diagnostic Criteria

  • The diagnosis of nasopharyngeal angiofibroma is made when the following diagnostic criteria are met:
  • Clinical criteria
  • Positive physical exam
  • A smooth submucosal mass in the posterior nasal cavity
  • Positive imaging finding: visualization of a nasopharyngeal mass

Symptoms

  • Common symptoms of nasopharyngeal angiofibroma, may include:

Physical Examination

  • Patients with nasopharyngeal angiofibroma usually are well-appearing.
  • Physical examination may be remarkable for:
  • A smooth submucosal mass in the posterior nasal cavity

Laboratory Findings

  • There are no specific laboratory findings associated with the diagnosis of nasopharyngeal angiofibroma.

Imaging Findings

  • Computed tomography is the imaging modality of choice for nasopharyngeal angiofibroma.
  • On conventional radiography, findings of nasopharyngeal angiofibroma include:
  • Visualization of a nasopharyngeal mass
  • Opacification of the sphenoid sinus
  • Anterior bowing of the posterior wall of the maxillary antrum
  • Holman-miller sign: the anterior bowing of the posterior wall of the maxillary antrum which is seen on lateral skull film or cross-sectional imaging
  • Widening of the pterygomaxillary fissure and pterygopalatine fossa
  • Erosion of the medial pterygoid plate
  • On CT, findings of nasopharyngeal angiofibroma include:
  • Bony changes
  • Non-encapsulated soft tissue mass
  • Anterior bowing the posterior wall of the maxillary antrum
  • On MRI, findings of nasopharyngeal angiofibroma include:
  • T1: intermediate signal
  • T2: heterogeneous signal - flow voids appear dark
  • T1 C+ (Gd): shows prominent enhancement
  • The images below demonstrate findings of nasopharyngeal angiofibroma.

Other Diagnostic Studies

  • Nasopharyngeal angiofibroma may also be diagnosed using nasal endoscopy.

Treatment

Medical Therapy

  • Medical therapy for nasopharyngeal angiofibroma is divided into 2 categories:[3]
  • Hormonal therapy for nasopharyngeal angiofibroma includes:[3]
  • Medical treatment is usually given before surgery to reduce the blood loss
  • Radiotherapy for nasopharyngeal angiofibroma, include:
  • Stereotactic radiotherapy

Surgery

  • Surgery is the mainstay of therapy for nasopharyngeal angiofibroma.[3]
  • Preoperative embolization is highly suggested for nasopharyngeal angiofibroma.
  • Surgical approach for nasopharyngeal angiofibroma will depend on the stage.[3]
  • The treatment of choice for early stage for nasopharyngeal angiofibroma is intranasal endoscopic surgery. Lateral rhinotomy is the preferred surgical approach.
  • The treatment of choice for late stage for nasopharyngeal angiofibroma include the infratemporal fossa approach, and the mid-facial degloving approach.

Prevention

  • There are no primary preventive measures available for nasopharyngeal angiofibroma.
  • Once diagnosed and successfully treated, patients with nasopharyngeal angiofibroma are followed-up after surgery, and every 6 or 12 months, depending on the clinical progression.

References

  1. 1.0 1.1 1.2 1.3 Paris J, Guelfucci B, Moulin G, Zanaret M, Triglia JM (2001). "Diagnosis and treatment of juvenile nasopharyngeal angiofibroma". Eur Arch Otorhinolaryngol. 258 (3): 120–4. PMID 11374252.
  2. Coutinho-Camillo CM, Brentani MM, Nagai MA (2008). "Genetic alterations in juvenile nasopharyngeal angiofibromas". Head Neck. 30 (3): 390–400. doi:10.1002/hed.20775. PMID 18228521.
  3. 3.0 3.1 3.2 3.3 Nicolai P, Schreiber A, Bolzoni Villaret A (2012). "Juvenile angiofibroma: evolution of management". Int J Pediatr. 2012: 412545. doi:10.1155/2012/412545. PMC 3228400. PMID 22164185.


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