BACKGROUND: Juvenile Nasopharyngeal Angiofibroma (JNA) is a fibrovascular tumor of the nasopharynx that classically presents in adolescent males. The reported mean age of onset is between 13 and 22 years old [1-6]. Significant androgen stimulation is hypothesized to explain the strong predisposition for JNA to present in young adolescent males. However, considerable variability in age at diagnosis exists with rare involvement of very young patients incongruent with typical male pubertal growth patterns.
OBJECTIVE: The purpose of this systematic review is to identify cases of early-onset JNA (EOJNA), (defined as age < 10 years) in the literature and to examine the disease characteristics and treatments used in this patient group. A case of a 7 year old boy with EOJNA at our institution is also described and presented.
METHODS: We searched Embase, Cochrane database and MEDLINE from 1996 to February 2021 for studies that reported cases of EOJNA. Relevant clinico-demographic data, disease severity and treatment outcomes were recorded and analyzed using descriptive statistics. We compared our findings with reported means for JNA in all ages.
RESULTS: We identified 29 studies containing a total of 34 cases of EOJNA. The vast majority (31/34) of patients were males and the mean age of diagnosis was 8.15 years old. The most common presenting symptoms were nasal obstruction (65.2%) and epistaxis (60.9%). Patients were most commonly Radkowski stage II (39.4%) and III (39.4%). Primary treatment modalities included open surgery (66.7%), endoscopic surgery (24.2%), and radiotherapy (9.1%). Recurrence was evident in 30%. Radkowski stage and type of treatment did not differ significantly within the EOJNA group (p = 0.440 and p = 0.659, respectively).
CONCLUSIONS: This systematic review suggests that rare cases of EOJNA have distinct disease characteristics. Patients in this cohort appeared to have more advanced disease and higher recurrence rates when compared with reported averages. We hope that this review prompts increased clinical awareness of this potentially more aggressive subtype of JNA. As more cases of EOJNA are reported, a more powered statistical analysis of this cohort would be feasible.

To comprehensively summarize the radiological characteristics of sinonasal tract angiofibroma (STA) (commonly known as juvenile nasopharyngeal angiofibroma).
Forty-four lesions from 41 cases provided by 33 study articles identified through a systematic review and 13 lesions from 13 cases from our institution associated with patients with STA who underwent MRI were included in the review study, carried out by two board-certified experienced radiologists.
The study participants were all male patients with a mean age of 15.6 years at the time of diagnosis. All of them presented with nasal cavity lesions (100%), predominantly in the nasopharynx (98.2%). The sphenopalatine foramen/pterygopalatine fossa was involved in 76.0%, and compressive shift of the posterolateral wall of the maxillary sinus was present in more than half (57.9%). T2-weighted imaging signal intensity was heterogeneous with mixed high and iso intensities as compared to skeletal muscle (100%). T1-weighted imaging showed partial high signal intensity in 61.1% of the cases. Flow void and intense enhancement were present in almost all cases. Cystic/nonenhancement changes on contrast-enhanced MRI were relatively common (40.8%). The mean apparent diffusion coefficient value (2.07 × 10-3  mm2 /second) and some quantitative dynamic contrast-enhanced MRI parameters were high. There was a significant difference in the frequency of residual/recurrent lesions based on the presence of MRI findings of skull base invasion (p = .017) and intracranial extension (p = .003).
We summarized the MRI findings of STA that can facilitate timely diagnosis and appropriate management.

Juvenile nasopharyngeal angiofibromas are one of the most enigmatic, bloody tumors encountered by otorhinolarygnologists, head and neck surgeons, neurosurgeons, and anesthesiologists. Juvenile nasopharyngeal angiofibromas are rare, benign, highly vascular tumors with a propensity towards aggressive local invasion. Surgery, open or endoscopic, to remove the growth is the primary treatment of choice for Juvenile nasopharyngeal angiofibromas. Historically, surgical resection was associated with massive, rapid blood loss, traditionally managed by blood product transfusion and deliberate hypotension. Preventative management employing multimodal blood conservation strategies should be an essential standard of perioperative care for patients with Juvenile nasopharyngeal angiofibromas.
We describe a contemporary and comprehensive approach in the management of patients with high grade Juvenile nasopharyngeal angiofibromas. This includes surgical strategies such as preemptive external carotid artery embolization, endoscopic surgical approach, and staged operations, as well as anesthetic strategies including antifibrinolytic therapy and acute normovolemic hemodilution. These surgeries, once synonymous with massive transfusion, may potentially be performed without allogeneic blood transfusion, or deliberate hypotension.
Using a case series, the authors introduce a contemporary approach to multimodal, multidisciplinary blood conservation strategies for Juvenile nasopharyngeal angiofibromas surgery.
Here in the authors report on an updated contemporary perioperative clinical approach to patients with Juvenile nasopharyngeal angiofibromas. From an anesthetic perspective, we describe the successful use of normal hemodynamic goals, restrictive transfusion strategy, antifibrinolytic therapy, autologous normovolemic hemodilution, and early extubation in the care of three adolescent males with highly invasive tumors. We demonstrate that new surgical and anesthetic strategies have yielded a significant decrease in intraoperative blood loss and eliminated the need for transfusion of autologous red blood cells, which enable improved outcomes.
The perioperative approach to elective surgery for Juvenile nasopharyngeal angiofibromas management is presented from a multidisciplinary patient blood management perspective.

Preoperative embolization has proven beneficial in the surgical treatment of juvenile nasopharyngeal angiofibromas (JNA). However, the consensus for the best embolization practices remains unclear. This systematic review seeks to characterize the reporting of embolization protocols throughout the literature and to compare differences in surgical outcomes.
PubMed, Embase, and Scopus.
Studies investigating embolization in the treatment of JNA from 2002 to 2021 were selected from defined inclusion criteria. All studies underwent a 2-stage blinded screening, extraction, and appraisal process. Embolization material, time to surgery, and embolization route were compared. Embolization complications, surgical complications, and rate of recurrence were pooled.
Of 854 studies, 14 retrospective studies with 415 patients met the criteria for inclusion. A total of 354 patients underwent preoperative embolization. A total of 330 patients (93.2%) underwent transarterial embolization (TAE) and 24 patients had a combination of direct puncture embolization and TAE. Polyvinyl alcohol particles were the most used embolization material (n = 264, 80.0%). The most common reported time to surgery was 24 to 48 hours (n = 8, 57.1%). Pooled results showed an embolization complication proportion of 3.16% (95% confidence interval [CI]: 0.96-6.60) (n = 354), a surgical complication proportion of 4.96% (95% CI: 1.90-9.37) (n = 415), and a recurrence proportion of 6.30% (95% CI: 3.01-10.69) (n = 415).
The current data on JNA embolization parameters and their effect on surgical outcomes remains too heterogenous to provide expert recommendations. Future studies should use uniform reporting to allow for more robust comparisons of embolization parameters, which, in turn, may lead to optimized patient outcomes.

To compare outcomes of juvenile nasopharyngeal angiofibroma (JNA) resection between embolized and non-embolized cohorts, and between transarterial embolization (TAE) and direct puncture embolization (DPE).
Per PRISMA guidelines, PubMed, Embase, Web of Science, Scopus, and Cochrane databases were searched for publications prior to or in 2021.
Original English manuscripts investigating the resection of JNA with and without preoperative embolization were included. Embolization type, recurrence rate, complication rates, blood loss, and transfusions were extracted. Risk of bias was assessed by the Risk of Bias in Non-randomized Studies-of Interventions method.
There were 61 studies with 917 patients included. Preoperative embolization was performed in 79.3% of patients. Of those embolized, 75.8% (N = 551) underwent TAE and 15.8% (N = 115) underwent DPE. JNA recurrence in embolized patients was lower than in non-embolized patients (9.3% vs. 14.4%; odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.35, 1.06). DPE resulted in lower rates of disease recurrence (0% vs. 9.5%; OR: 0.066, 95% CI: 0.016, 0.272) and complications (1.8% vs. 21.9%; OR: 0.07, 95% CI: 0.02, 0.3) than TAE. A random effects Bayesian model was performed to analyze the difference in mean blood loss in 6 studies that included both embolized and non-embolized patients. This analysis showed a mean reduction in blood loss of 798 mL in the embolized group.
We found embolization decreases blood loss in JNA resection. DPE led to improved recurrence and complication rates when compared to TAE, but future prospective studies are needed to further evaluate which embolization technique can optimize outcomes in JNA.
NA Laryngoscope, 133:1529-1539, 2023.

Juvenile Nasopharyngeal Angiofibroma is a rare and locally aggressive benign tumor. It is characterized by high vascularization leading to spontaneous bleeding or massive hemorrhage. We reported a case of 13 years old boy with a swollen at the right face, nasal congestion, recurrent nose bleeding, hyposmia, headache, breathing difficulty, and a nasopharyngeal mass at CT scan. Angiography examination showed a highly vascularized mass which was successfully occluded through preoperative embolization procedures. It is suggested that imaging modalities is not only playing an important role in diagnostic process, but also as an adjunct treatment approach in patient with Juvenile Nasopharyngeal Angiofibroma.

BACKGROUND: The molecular profile of juvenile nasopharyngeal angiofibroma (JNA) is extremely variable. In absence of established molecular signature the molecular targeting seems difficult for this heterogeneous disease. To establish a basic molecular signature, this paper analyses the interaction of 7 markers according to their ranks as per the decreasing scale of molecular expression.
METHODS: Fourteen samples of JNA were obtained following surgical excision and mRNA expressions were established through real-time polymerase chain reaction (RT-PCR) for vasculoendothelial growth factor (VEGF), fibroblastic growth factor (FGF), c-Kit, c-myc, Ras, platelet-derived growth factor (PDGF) and tumor suppressor gene p53. Nasal polyp was taken as control. The quantitative expressions for every marker were ranked on a decreasing scale and were compared by Spearman\'s rank correlation test to define the statistically significant interaction. An attempt was also made to overview the basic clinical parameters (age, duration of symptoms, radiological staging, intraoperative haemorrhage and tumor-volume/weight) associated with enhanced molecular expressions for every marker.
RESULTS: Five significant molecular interactions were identified on the basis of rank-correlation: (1) FGF/VEGF (p < 0.01); (2) Ras/FGF (p < 0.01); (3) Ras/VEGF (p < 0.001), (4) FGF/c-Kit (p < 0.05); (5) c-Myc/p53 (p < 0.05). These basic \'molecular signatures\' suggested a preliminary \'molecular classification\'. The implication of the interactions between FGF, VEGF and Ras were the most outstanding observation that not only revealed a direct relationship but were also consistent with the clinical behaviour. In addition, a non-significant interaction was identified with c-Myc/PDGF and also an inverse relationship between FGF/c-Kit.
CONCLUSIONS: FGF, VEGF, and Ras being significantly interrelated seemed to be the \'most soft\' molecular targets for JNA. The other targets observed included FGF/c-Kit and c-Myc/p53 interactions that seemed equally important but only after VEGF/FGF/Ras complex per se. These preliminary signatures are likely to provide a background for further expansion of the molecular classification of JNA.

OBJECTIVE: To examine the expression of hypoxia-inducible factor-1α (HIF-1α) and its related molecules (cellular repressor of E1A-stimulated genes [CREG], osteopontin [OPN], proto-oncogene tyrosine-protein kinase Src [c-Src], and vascular endothelial growth factor [VEGF]) in juvenile nasopharyngeal angiofibroma (JNA) and explore the correlation between clinical prognosis and HIF-1α expression.
METHODS: The study performed a retrospective review of the clinical records of patients with JNA treated between 2003 and 2007. Specimens were analyzed by immunohistochemistry for HIF-1α, CREG, OPN, c-Src, and VEGF expression, and microvessel density (MVD) was assessed by tissue microarray. The correlation between expression levels and clinicopathological features including age, tumor stage, intraoperative blood loss, and recurrence was analyzed.
RESULTS: HIF-1α, CREG, OPN, c-Src, and VEGF were upregulated in endothelial cells (ECs) of patients with JNA, and strong correlations in the expression of these molecules were observed. HIF-1α expression was higher in young patients ( P = .032) and in recurrent cases ( P = .01). Survival analysis showed that low HIF-1α levels in ECs predicted longer time to recurrence (log rank test P = .006). Receiver operating characteristic curve analysis showed that HIF-1α was a prognostic factor for recurrence (area under the curve = 0.690, P = .019). No correlation was found between the expression of molecules and Radkowski stage or intraoperative blood loss.
CONCLUSIONS: In cases of JNA treated surgically, HIF-1α expression in ECs is a useful prognostic factor for tumor recurrence.

Vascular patterns of juvenile nasopharyngeal angiofibroma (JNA) are poorly defined. We performed both institutional and systematic literature reviews to characterize the relationship between arterial supply patterns of JNA with intraoperative blood loss and tumor recurrence.
A retrospective review of 26 patients with JNA treated at our institution from 1995 to 2015 with available angiograms, and systematic reviews and meta-analyses of 828 JNA cases undergoing angiographic embolization published between 1995 and 2015 were completed per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
The systematic review (828 cases) found internal carotid artery (ICA) supply in 35.6% of tumors, and 30.8% of tumors received bilateral vascular supply. Our institutional data (n = 26) indicated 69% had bilateral supply. Meta-analysis of data from 5 studies demonstrated ICA/bilateral arterial supply is predictive of increased operative blood loss (P < .01).
Complex vascular contributions to JNA are frequent, underreported, and portends increased blood loss. This information can justifiably be included in staging systems to enhance prognostic counseling of patients.

Juvenile nasopharyngeal angiofibroma is a locally aggressive benign vascular neoplasm, composed of vasogenic and myofibroblastic elements, accounts for 0.05-0.5% of all the head and neck neoplasms. There are very few case reports of nasopharyngeal angiofibroma involving the oral cavity; we report a case involving both the maxilla and mandible in a 17-year-old patient who reported with a large firm swelling on right side of face with recurrent epistaxis and headache. Magnetic resonance angiography revealed a large lobulated enhancing soft tissue mass, which was hypointense on T1-weighted image and heterogeneously hyperintense on T2-weighted image causing expansion of pterygopalatine fossa and sphenopalatine foramen with extension into the sphenoid sinus, ethmoid air cells, right nasal cavity, right infratemporal fossa and right maxillary sinus with remodeling of right zygomatic arch and part of body and ramus of mandible. It was supplied by the right external carotid artery. Patient was referred to the department of neurosurgery for further management. The diagnosis at an early stage is important because it is associated with high risk of morbidity, but advances in imaging, and surgical methods of treatment have changed the sites associated with high risk of morbidity.