Case of giant juvenile angiofibroma resected by external incision with temporary double balloon occlusion of the internal carotid artery by intraoperative endovascular treatment.

We report the first case of a juvenile nasal angiofibroma (JNA) fed by multiple arteries from the internal carotid artery (ICA), removed without complications by temporarily blocking the ICA with two balloons. An early adolescent with JNA underwent preoperative embolisation of feeding arteries arising from the external carotid artery (ECA) (University of Pittsburgh Medical Centre classification IV). Endoscopic resection was attempted once but discontinued due to massive bleeding (7000 mL). 17 months later, the JNA had grown to fill both nasal cavities. Repeated preoperative embolisation of the feeders from the ECA was performed, followed by surgery combined with endoscopic and external incision. Intraoperatively, two balloons were inserted into the right ICA, which were inflated at the proximal and distal sites of the feeder vessels to cut-off blood flow to the tumour. The tumour was almost completely resected with 6270 mL of blood loss and no postoperative neurological deterioration.

A survey of patients with facial angiofibromas associated with tuberous sclerosis complex: Short-, medium- and long-term efficacy and safety of topical rapamycin.

AIMS: Topical rapamycin is used to reduce facial angiofibromas in patients with tuberous sclerosis (TSC). In the absence of a commercially available preparation, numerous formulations have been tested clinically, although only in the short term. METHODS: The pharmacy at Angers University Hospital (France) produced a cream formulation that was administered to people presenting this genetic disease. We conducted a questionnaire-based survey among 79 patients with TSC about their perceptions regarding the short-, medium- and long-term efficacy and safety of a topical rapamycin preparation in relation to facial angiofibromas. RESULTS: This formulation was very well tolerated and its efficacy was sustained over the long term with a mean treatment duration of 33 months (extremes 1-60). Efficacy was rated ≥ 8/10 by 67.1% of patients while safety was rated ≥ 8/10 by 84.8% of patients. CONCLUSION: This survey supports the safety and efficacy of topical rapamycin in the short-, medium- and long-term in the treatment of facial angiofibromas in a cohort of 79 patients with TSC.

A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial.

BACKGROUND: Facial angiofibromas (FAs) are a major feature of tuberous sclerosis complex (TSC). Topical rapamycin can successfully treat FAs. A new stabilized cream formulation that protects rapamycin from oxidation has been developed in 0.5% and 1% concentrations. OBJECTIVES: To assess the efficacy and safety of a novel, stabilized topical rapamycin cream formulation. METHODS: This multicentre double-blind randomized placebo-controlled dose-response phase II/III study with a parallel design included participants aged 6-65 years with FAs of mild or moderate severity according to the Investigator's Global Assessment (IGA) scale. Participants were randomized to one of three treatment arms: topical rapamycin 0.5%, topical rapamycin 1% or placebo. Treatment was applied once daily for 26 weeks. Safety and efficacy measures were assessed at days 14, 56, 98, 140 and 182. The primary endpoint was the percentage of participants achieving IGA scores of 'clear' or 'almost clear' after 26 weeks of treatment. Secondary measures included Facial Angiofibroma Severity Index (FASI) and participant- and clinician-reported percentage-based improvement. Safety measures included the incidence of treatment-emergent adverse events and blood rapamycin concentration changes over time. RESULTS: Participants (n = 107) were randomized to receive either rapamycin 1% (n = 33), rapamycin 0.5% (n = 36) or placebo (n = 38). All treated participants were included in the final analysis. The percentage of participants with a two-grade IGA improvement was greater in the rapamycin 0.5% treatment group (11%) and rapamycin 1% group (9%) than in the placebo group (5%). However, this was not statistically significant [rapamycin 0.5%: odds ratio (OR) 1.71, 95% confidence interval (CI) 0.36-8.18 (P = 0.50); rapamycin 1%: OR 1.68, 95% CI 0.33-8.40 (P = 0.53)]. There was a statistically significant difference in the proportion of participants treated with rapamycin cream that achieved at least a one-grade improvement in IGA [rapamycin 0.5%: 56% (OR 4.73, 95% CI 1.59-14.10; P = 0.005); rapamycin 1%: 61% (OR 5.14, 95% CI 1.70-15.57; P = 0.004); placebo: 24%]. Skin adverse reactions were more common in patients following rapamycin application (64%) vs. placebo (29%). CONCLUSIONS: Both rapamycin cream formulations (0.5% and 1%) were well tolerated, and either strength could lead to clinical benefit in the treatment of FA.

Cellular angiofibroma in the retroperitoneal space during pregnancy: A case report.

BACKGROUND: Cellular angiofibroma (CA) is a rare, benign mesenchymal tumor first described by Nucci et al. (Am J Surg Pathol 21:636-644, 1997. 10.1097/00000478-199706000-00002). It affects both men and women, although it is more common in middle-aged women. CA is well circumscribed and usually observed on the body surface, primarily in distal genital regions. Aggressive angiomyxoma and angiomyofibroblastoma are clinically and histologically similar; therefore, it may be necessary to distinguish between CA and these similar tumors. We present a rare case of CA, with atypical features, in the retroperitoneal space during pregnancy. CASE PRESENTATION: The presence of a 130 mm tumor was detected in a 19-year-old woman. The tumor, located in the retroperitoneal space, was found during first pregnancy examination. At 16 weeks of gestation, the woman developed nausea and fever, and it was diagnosed with acute pyelonephritis. After a few days, the amniotic membranes prematurely ruptured, leading to a miscarriage. The woman underwent a tumor resection, after miscarriage. This case presented with atypical features of CA. This included the young age of the patient, and presence of a tumor in the retroperitoneal space. CONCLUSION: In this case, the diagnosis of CA was difficult due to the rarity of the disease and its atypical clinical features. From this experience, we recommend that the discussion on the efficacy of surgical treatment and pregnancy outcomes should be done based on individual case, and not generalized.

Analysis of current data on the use of topical mTOR inhibitors in the treatment of facial angiofibromas in tuberous sclerosis complex-An update.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome causing hamartomatous growths in multiple organs. Facial angiofibromas occur in up to 80% of patients and can be highly disfiguring. Treatment for these lesions is challenging. Recently, topical rapamycin has been proposed as an effective option to treat angiofibromas but a commercially available compound has not yet been developed in Europe. We conducted a retrospective review with the aim to update the current data on the use of topical rapamycin in the treatment of angiofibromas in TSC, focusing on the optimal concentration and trying to establish which vehicle should be preferred. Thirty-nine reports describing the use of topical rapamycin in the treatment of angiofibromas in TSC were considered, involving a total of 483 patients. An improvement of the lesions has been shown in over 90% of subjects, particularly if the treatment was started at early stages. Several different formulations (ointment, gel, solution and cream) with a wide range of concentrations (0.003%-1%) were proposed, of which a pharmacological analysis has also been performed. Topical rapamycin can be considered an effective and safe option for the treatment and the prevention of facial angiofibromas in younger patients, but the best formulation has yet to be established. Our review demonstrates that ointment and gel should be preferred, but it is not clear which concentration is optimal. However, according to this study, the 0.1% concentration represents the first choice. Long-term and comparative studies between topical rapamycin formulations are required in order to establish which treatment has a better outcome and lower recurrence rate.

The combination of photodynamic therapy and ultrapulse carbon dioxide laser for facial angiofibromas in tuberous sclerosis complex: A case report.

Facial angiofibromas are one of the dermatological hallmarks of tuberous sclerosis complex. Facial angiofibromas often lead to disfigurement and cosmetic concerns, which has a serious negative effect on the quality of life of the patients. There are no guidelines or consensus on the management of facial angiofibromas up to now. We report a patient with extensive facial angiofibromas treated with the combination of photodynamic therapy and ultrapulse carbon dioxide laser, achieving satisfying results. We suggest this might be a promising therapeutic option for facial angiofibromas in tuberous sclerosis complex.

Frontoethmoidal Extranasopharyngeal Angiofibroma With Orbital Pyocele.

Significance StatementExtranasopharyngeal angiofibromas (ENA) are rare vascular tumors that do not conform to the clinical characteristics of typical nasopharyngeal angiofibromas. We present the management of an angiofibroma in a rare site, within the frontal sinus with a concomitant orbital pyocele, which was completely excised via an endoscopic approach. ENAs should be considered as a differential diagnosis in patients with sinonasal mass and epistaxis. Awareness of this rare entity will avoid radical surgery thus decreasing postoperative morbidity.

Topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis: a systematic review based on evidence.

INTRODUCTION: facial angiofibromas of tuberous sclerosis are the most prevalent cutaneous manifestation, affecting 80% of patients, which cause facial lesions with negative psychosocial consequences. Newly, topical rapamycin has been established as an effective and safe therapy for this skin condition. PURPOSE: to analyze the available scientific evidence about the effectiveness and safety of topical sirolimus in the treatment of facial angiofibromas in tuberous sclerosis. METHODS: a literature search was conducted in PubMed and Cochrane. Effectiveness and safety were analyzed along with the main characteristics of each formulation in all included studies. RESULTS: thirty studies were included involving a total of 508 patients, developed in the last 20 years. Four randomized clinical trial, 17 case series and 9 single case reports were founded. Multiple topical rapamycin concentrations (0.003-1%) and formulations (gel, ointment, solution) were found in literature. Rapamycin demonstrated its effectiveness in all studies included, except for 5 patients in a 1 b study. Rapamycin was shown to be safe for the treatment of FA. CONCLUSIONS: Topical sirolimus can be considered an effective and safety option for the treatment of facial angiofibromas in tuberous sclerosis. However, further long-term studies need to establish an evidence-based therapeutic protocol.KEY MESSAGEUpdated review to date in topical rapamycin for facial angiofibromas, allowing support in therapeutic decisions.

CNS infection with a history of recurrent epistaxis: Streptococcal meningitis as a first presentation of juvenile nasopharyngeal angiofibroma.

An adolescent male with a history of recurrent epistaxis presented with headache and vomiting. Investigations revealed concurrent meningitis as well as the presence of a subarachnoid haemorrhage. Subsequent imaging identified a Juvenile Nasopharyngeal Angiofibroma; a rare but important cause of meningitis that should be considered in the young adult population.

Bronchial angiofibroma in tuberous sclerosis complex: A case report and literature review.

Cutaneous angiofibroma is part of the classic triad of tuberous sclerosis complex (TSC). Angiofibroma is rarely reported to affect the mucous membranes of the trachea and bronchus. Tracheobronchial angiofibroma is also a hamartomatous manifestation of TSC. Considering the paucity of literature describing tracheal lesions in TSC, more case reports are needed to guide treatment planning. This case report adds to the existing clinical literature and provides a reference for clinical diagnosis.

Crescentic postinfectious glomerulonephritis in an adult patient with juvenile nasopharyngeal angiofibroma.

Crescentic glomerulonephritis is usually associated with an acute nephritic syndrome with rapidly declining renal function. Postinfectious cases usually have a higher possibility of recovery. Juvenile nasopharyngeal angiofibroma (JNA) is a rare, locally aggressive tumour affecting mostly young men. A 28-year-old man presented with recurrent JNA initially excised 2 years prior. The patient was initially managed as a case of airway obstruction and pneumonia. He developed tea-coloured urine, oedema and acute kidney failure requiring dialysis while awaiting surgery. Urine and immunological studies (low C3, negative antineutrophil cytoplasmic antibody and antinucleosomal antibody and high antistreptolysin O) suggested a nephritic aetiology. Nasopharyngeal swab cultures of the mass revealed gram-negative organisms. Kidney biopsy showed diffuse proliferative glomerulonephritis compatible with a postinfectious glomerulonephritis with 77% cellular crescents. The mass was excised with histopathology consistent with JNA. The patient was eventually discharged off dialysis.

Nasal septal angiofibroma: less vascular behaviour than observed in radiological imaging, a rare case in a 51-year-old woman.

Angiofibroma of the head and neck is classically found in the nasopharynx of an adolescent male. We present a rare case where an angiofibroma was diagnosed in the anterior nasal septum of a 51-year-old woman, the eighth nasal septal angiofibroma reported in a female. This case highlights how an angiofibroma in an older woman has a less vascular behaviour than one in an adolescent male, even though radiological enhancement may suggest that the lesion is highly vascularised. Nasal septal angiofibromas can be managed by biopsy and removed by simple endoscopic resection with minimal haemorrhage. Although very rare, extranasopharyngeal angiofibroma/nasal septal angiofibroma should be included in the differential diagnosis when patients of all ages present with nasal obstruction secondary to a nasal mass, with or without epistaxis.

Rare case of angiofibroma presenting as perineal hernia.

Angiofibroma is a benign soft tissue tumour presenting as a gradually progressive swelling in the vulvovaginal area in women and in the inguinoscrotal region in men. Being a rare tumour, there are only a few case reports in the literature, and among them, presentation as perineal herniation is very rare. En bloc resection of angiofibroma either via laparoscopic or open approach is the choice of treatment to avoid recurrence. Detailed pathological examination and immunohistochemistry workup are imperative to distinguish it from various mesenchymal tumours. Perineal hernia is itself rare and may occur spontaneously or following abdominoperineal resection, sacrectomy or pelvic exenteration. Surgical repair via open transabdominal and transperineal approaches has been described. Here, we report a case of a young woman who presented with spontaneous reducible perineal hernia with a soft tissue tumour as its content, which on histopathological investigation was found to be an angiofibroma.

Early Postoperative Magnetic Resonance in the Diagnosis of Persistent Juvenile Angiofibroma.

OBJECTIVES/HYPOTHESIS: Despite improvements in the treatment of juvenile angiofibroma (JA), the rate of persistence (pJA) is still not negligible. In the present study, we assessed the value of early postoperative magnetic resonance imaging (MRI) in depicting unintentional pJAs and designed a MRI-driven decisional flow-chart for pJA management and follow-up. STUDY DESIGN: Observational study. METHODS: Patients undergoing early postoperative MRI after endoscopic resection of JA in the Unit of Otorhinolaryngology - ASST Spedali Civili, University of Brescia from 2007 to 2017 were enrolled. MRI was defined as negative or positive based on defined radiological criteria. The diagnostic performance of MRI was evaluated. RESULTS: The analysis included 26 patients, with a mean age of 16.5 years (range, 11-25). Early MRI was negative for pJA in 21 (80.8%) patients and positive in five (19.2%). No patient with a negative finding was found positive at subsequent follow-up MRIs. The accuracy of a positive finding was confirmed by pathologic examination (three cases) or follow-up MRIs (two cases). The diagnostic performance of MRI was excellent with sensitivity and specificity of 100%. An MRI-driven flow-chart for pJA management and follow-up was designed. CONCLUSIONS: Early postoperative MRI demonstrated a high diagnostic accuracy in the detection of unintentional pJA. Our MRI-driven strategy and decisional flow-chart could aid in the decision-making process in the management of pJA and definition of postoperative surveillance. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2436-E2441, 2021.

The Efficacy of Everolimus for Facial Angiofibromas in Tuberous Sclerosis Complex Patients Treated for Renal Angiomyolipoma/Subependymal Giant Cell Astrocytoma.

BACKGROUND: Facial angiofibromas may be present since early childhood in individuals with tuberous sclerosis complex (TSC), causing substantial cosmetic disfigurement. Current therapies are partially effective, but they are uncomfortable, produce scarring, and are especially expensive. OBJECTIVE: The aim of the present study was to evaluate the efficacy of oral everolimus for TSC-associated angiofibromas. METHODS: This retrospective study included TSC patients being treated with oral everolimus for subependymal giant cell astrocytomas (SEGAs) and angiomyolipomas (AMLs). We recorded the changes in facial angiofibromas. Changes in the Angiofibroma Grading Scale (AGS) indicators were recorded according to erythema, average lesion size, lesion density, and percent involvement on the forehead, nose, cheeks, and chin. The scores were recorded before and after the administration of oral everolimus. RESULTS: Twenty-one patients being treated with oral everolimus were enrolled in this study. The mean age was 20.5 years (range 11-44 years, 4 males, and 17 females). The mean dose of oral everolimus was 3.6 mg/day. Clinically meaningful and statistically significant improvement was observed in erythema (p = 0.001), average lesion size (p < 0.001), lesion density (p < 0.001), and percent involvement (p < 0.001). Changes in the AGS findings were statistically significant on the forehead (p = 0.001), nose (p < 0.001) cheeks (p < 0.001), and chin (p = 0.004). CONCLUSION: Everolimus shows evident improvement and is approved for TSC-associated SEGAs and AMLs. The current study demonstrated the efficacy of oral everolimus in reducing facial angiofibromas, showing the parallel benefits of the treatment protocol for TSC.