Hamartoma fibrovascular facial grave en paciente con esclerosis tuberosa (ET). Resolución de caso problema. Nuestra experiencia / Severe facial fibrovascular hamartoma in a patient with tuberous sclerosis (TS). Problem case resolution. Our experience

La ET es un trastorno multisistémico autosómico dominante que se caracteriza por displasia celular y tisular en varios órganos (cerebro, corazón, piel, ojos, riñones, pulmones) que constituyen una fuente importante de morbilidad y mortalidad. Las manifestaciones comunes incluyen tubérculos corticales, nódulos subependimarios, astrocitomas subependimarios de células gigantes, convulsiones, rabdomiomas cardíacos, AML renales, hamartomas retinianos, linfangioleiomiomatosis pulmonar, angiofibromas faciales, manchas de hojas de ceniza, parches de Shagreen, discapacidad intelectual y trastorno del espectro autista. Se presenta a continuación la resolución de un caso problema grave de una paciente que llega a la consulta al hospital público, con severa incapacidad para mantener la permeabilidad de la válvula nasal externa, a expensas de formación harmartomatosa grave, de años de evolución, fétida y sangrante, decidiéndose tomar conducta quirúrgica urgente y agresiva dada las condiciones de la lesión, la poca colaboración de la paciente y el contexto familiar de la misma que presenta además trastornos conductuales asociados a manifestaciones neurológicas de la enfermedad (retraso madurativo)

ET is an autosomal dominant multisystem disorder characterized by cellular and tissue dysplasia in several organs (brain, heart, skin, eyes, kidneys, lungs) that constitute a major source of morbidity and mortality. Common manifestations include cortical tubercles, subependymal nodules, subependymal giant cell astrocytomas, seizures, cardiac rhabdomyomas, renal AML, retinal hamartomas, pulmonary lymphangioleiomyomatosis, facial angiofibromas, ash leaf spots, shagreen patches, intellectual disability, and autism spectrum disorder. This paper presents the resolution of a serious problem case of a patient who attends the consultation of a public hospital, with severe inability to maintain the patency of the external nasal valve, at the expense of severe harmartomatous formation, of many years of evolution, fetid and bleeding, deciding to undertake urgent and aggressive surgical conduct given the conditions of the lesion, the lack of collaboration of the patient and the family context of the same, which also presents behavioral disorders associated with neurological manifestations of the disease (maturational delay).

Preoperative Transarterial Embolization of Advanced Juvenile Nasopharyngeal Angiofibroma Using n-Butyl Cyanoacrylate: Case-Control Comparison with Microspheres.

PURPOSE: To evaluate the efficacy and safety of transarterial embolization (TAE) with n-butyl cyanoacrylate (nBCA) for juvenile nasopharyngeal angiofibroma (JNA). MATERIALS AND METHODS: A retrospective review was performed on patients with JNA who underwent TAE and endoscopic resection between 2020 and 2022. Patients embolized with nBCA were identified, and those embolized with microspheres were set as the control group. Data on demographics, symptoms, tumor characteristics, blood loss, adverse events, residual disease, and recurrence were collected, and case-control analysis was performed for the 2 groups. Differences in characteristics between the groups were tested using the Fisher exact and Wilcoxon tests. A generalized linear model (GLM) was used to analyze the univariate and multivariate influences on blood loss. RESULTS: Twenty patients were included in this study: 13 in the microsphere group and 7 in the nBCA group. The median blood loss was 400 mL (interquartile range [IQR], 200-520 mL) in the nBCA group and 1,000 mL (IQR, 500-1,000 mL) in the microsphere group (P = .028). The GLM confirmed lower blood loss in the nBCA group (relative risk, 0.58 [0.41-0.83]; P = .01). A residual tumor was found in 1 patient in each group (7.7% vs 14.3%; P = 1.000). Recurrence was not observed in any patient. None of the patients experienced adverse events during embolization. CONCLUSIONS: TAE of advanced JNA with nBCA glue is safe and effective and can significantly reduce intraoperative blood loss compared with microspheres.

Pre-Operative Embolisation of an Aberrant Pharyngeal Arterial Branch Arising From the Internal Carotid Artery and Contributing Significantly to the Supply of a Large Juvenile Nasopharyngeal Angiofibroma.

Preoperative embolisation of juvenile nasopharyngeal angiofibromas (JNAs) is a well-established treatment that reduces intraoperative blood loss and improves surgical outcomes. While the bulk of arterial supply to the tumour is derived from the external carotid system, some degree of contribution from the internal carotid artery (ICA) is common. ICA branch embolisation in this setting has previously been avoided due to concerns over ischaemic neurological complications, possibly contributing to the increased intraoperative blood loss observed in patients with tumours with ICA supply. There is a marked paucity of reports of embolisation of ICA branches supplying JNA in the medical literature. We present a case of successful embolisation of an aberrant pharyngeal branch of the ascending pharyngeal artery arising from the proximal cervical ICA, which was making a significant contribution to tumour blood supply in a male adolescent with a very large JNA.

68 Ga DOTANOC PET/CT Scan in Primary Juvenile Nasopharyngeal Angiofibroma - A Pilot Study.

OBJECTIVES/HYPOTHESIS: Somatostatin receptors (SSTRs) are highly expressed in neuroendocrine tumors and is exploited for its imaging and treatment. SSTRs expression is also demonstrated in diverse benign and malignant tumor cell types and proliferating peri-tumoral vessels. Similarly, Juvenile Nasopharyngeal Angiofibroma (JNA) expresses different SSTRs and may be utilized for its imaging and treatment using DOTA, 1-Nal3-octreotide (DOTANOC)-PET/CT scan. STUDY DESIGN: Prospective cohort. METHODS: Nineteen clinico-radiologically diagnosed primary JNA patients underwent a 68 Ga-DOTANOC PET-CT scan. Using a dedicated PET/CT scanner, a low-dose head and neck spot CT scan was performed after 45 to 60 minutes of intravenous injection of 2 to 3 mCi(74-111 MBq) of DOTANOC. The primary objective was to assess the intensity and pattern of DOTANOC uptake in these patients. RESULTS: DOTANOC expression was noted in all cases (n = 19) of primary JNA (100%). The mean (SD) DOTANOC SUVmax ratio of tumor and background was 6.9+/-1.4(range, 3.8-9.5). Intra-cranial extension in all 13/19 patients was prominently visualized due to the absence of DOTANOC uptake in the brain. Compared to the background all stages of JNA showed significant DOTANOC uptake (P < .0001). No difference in uptake between advanced-stage tumors and early tumors was noted (P = .47). A statistically non-significant negative trend was noted for decreasing uptake with increasing age (Spearman correlation coefficient, r = -0.19). CONCLUSIONS: This first study of 68 Ga-DOTANOC-PET/CT scan in JNA demonstrates consistent and reliable uptake activity in all patients irrespective of age and stage. This opens up possibilities to physiological diagnostic imaging with a promise of greater specificity and sensitivity and may have applications in ambivalent diagnostic situations such as the detection of recurrence. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1509-1515, 2021.

Embolization of Internal Carotid Artery Branches in Juvenile Nasopharyngeal Angiofibroma.

OBJECTIVE: Preoperative embolization of juvenile nasopharyngeal angiofibroma (JNA) is usually performed by the occlusion of branches of the external carotid artery (ECA). However, a significant proportion of JNAs also receive blood from the internal carotid artery (ICA). The objective of this study was to report on the feasibility and clinical impact of superselective embolization of ICA branches in complex cases of JNA. METHODS: This was a single-center retrospective study of all patients operated on for JNA between 2000 and 2018. The patients treated with embolization of branches of the ICA were identified. The results in terms of complications, intraoperative blood loss, and rate of residual disease were analyzed and compared to those of a control group of patients treated only with embolization of ECA branches and matched by age, stage, angiographic pattern, surgical approach, and previous surgery. RESULTS: Ninety-two patients were included. Embolization of branches of the ICA was attempted in 14 cases of advanced or recurrent tumors and was ultimately possible in nine cases. There were no complications after embolization. The mean intraoperative blood loss was 1428 mL. Residual disease was found in three cases (33%). There was no significant difference compared with the control group (mean intraoperative blood loss = 1355 mL, residual disease = 4 (44%); all P > .05). CONCLUSION: In this retrospective study, we report the feasibility of superselective embolization of ICA branches in selected cases of JNA. There was no observed benefit of this technique in terms of intraoperative bleeding or decreased risk of residual disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E775-E780, 2021.

[Experience of transnazal endoscopic surgery of juvenile angiofibroma of the skull base and nasopharynx without performing preoperative embolization]. / Opyt transnazal'noi endoskopicheskoi khirurgii yuvenil'noi angiofibromy osnovaniya cherepa i nosoglotki bez vypolneniya predoperatsionnoi embolizatsii.

Juvenile nasopharyngeal angiofibroma (JNA) is a hypervascular, blood-supplied, benign tumour affecting the sinuses, nasal cavity, nasopharynx and the base of the skull. For intraoperative hemostasis, pre-operative embolism is a common and recommended procedure, but it has serious disadvantages, such as additional radiation exposure, anesthesia, and the risk of iatrogenic complications associated with the occlusion of the central artery of the retina, orbital and middle cerebral arteries. This article presents a report on successful radical removal of the widespread SAS without resorting to preoperative embolization, but with intraoperative transnazal endoscopic clipping of the internal maxillary artery (IMA).

Recurrent pterygo-palatal angiofibroma with intracranial extension: case report.

We report the case of a patient with recurrent pterygo-palatal angiofibroma and its treatment. A 21-year-old male patient had a long history of recurrent epistaxis with progressive nasal obstruction. He was diagnosed with an angiofibroma centered in the right pterygo-palatine fossa. Initially, he underwent surgical excision with removal of the entire tumor. The evolution was clinically good with no signs of recurrence on the cervico-facial scan of control (CT). Nine months after, he presented a reappearance of epistaxis. A cervico-facial MRI was performed and showed a recurrence of the tumor process, which this time was considered inextirpable, hence the decision to opt for radiotherapy with intensity modulated radiation therapy (IMRT). He has improved clinically with a clear reduction in tumor mass on CT scan. This technique represents an interesting alternative to overcome anatomical complexity of the region, cover the tumor and preserve the organs at risk.

Juvenile Nasopharyngeal Angiofibroma Outcomes and Cost: Analysis of the Kids' Inpatient Database.

OBJECTIVE: To report trends in Juvenile Nasopharyngeal Angiofibroma (JNA) hospitalizations and identify key factors affecting treatment outcomes and cost of care in JNA patients. METHODS: The Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database was queried for all cases of JNA between the years of 1997 and 2016. Key factors extracted were patient demographics, geographic region, hospital size, teaching status, elective admissions, and number of diagnoses and procedures performed during the hospitalization. These elements were correlated to length of stay (LOS) and cost-per-day (CPD) using a multiple linear regression (MLR). Regional variation in JNA diagnosis and changes in LOS and CPD trends over time were also analyzed. RESULTS: A total of 614 JNA patients were hospitalized in this time period, with a majority of patients identifying as male (98%) and Caucasian/White (55%). The average LOS has decreased by 0.14 day per year since 1997 (P = .0034) whereas the CPD has steadily increased by $2 380 per year (P < .001). MLR analysis revealed that while holding all other factors constant, patients who stayed at teaching hospitals had an increased LOS of 1.7 days (P = .026), but paid $11 961 less per day (P = .05). Regional variation in CPD was found in the Northeast region, where hospitalizations were more expensive by $9 801 per day compared to the South (P = .017). CONCLUSION: These results indicate hospital characteristics, such as teaching status and geographic region, may predict differences in JNA outcomes and cost. Healthcare providers should be cognizant of these variations to ensure optimal patient outcomes and expenditures.

Trimodal embolization of juvenile nasopharyngeal angiofibroma with intracranial extension.

OBJECTIVES/PURPOSE: 1. Understand three different techniques for embolization of juvenile nasal angiofibroma (JNA) and assess their combined efficacy. 2. Perform successful endoscopic intralesional embolization of highly vascular sinonasal neoplasms. METHODS: In this study, we present the case of a 10-year-old male patient diagnosed with juvenile nasal angiofibroma (JNA) who successfully underwent trimodal embolization and resection at a tertiary academic medical center after failed coil embolization in his home country. We examine the clinical details of the case and a review of pertinent literature. RESULTS: Preoperative embolization is common in the treatment of JNA, but there is little consensus as to the proper timeframe and techniques utilized. In our case, preoperative imaging revealed a vascular tumor with intracranial extension consistent with UPMC Stage V JNA. Diagnostic angiogram revealed significant arborization from the internal and external carotid systems. A trimodal embolization technique, utilizing transarterial, percutaneous, and direct endoscopic intralesional injection of n-Butyl Cyanoacrylate (n-BCA) was performed. A two-staged endoscopic and open resection was subsequently performed one week later with minimal blood loss. In our case, combining intralesional embolization with traditional transarterial techniques resulted in an improved operative field and a successful clinical result. CONCLUSION: Embolization of highly vascular sinonasal tumors with n-BCA is not limited to endovascular techniques, but can be safely combined with percutaneous and endoscopic intralesional embolization up to one week prior to surgical resection.

Locally Advanced Staged Juvenile Nasopharyngeal Angiofibroma Treated with Endoscopic Endonasal Approach and Angio-embolization at a Tertiary Institution in Jamaica / Angiofibroma nasofaríngeo juvenil en etapa localmente avanzada tratado con un enfoque endonasal endoscópico y angioembolización en una institución terciaria en Jamaica

ABSTRACT Locally advanced staged juvenile nasopharyngeal angiofibroma (JNA) traditionally treated with external approaches has been associated with significant morbidities such as blood loss with subsequent blood transfusions, scars, impaired speech, poor swallowing, recurrence and prolonged hospital stays. This case report describes our initial experience in a patient with a locally advanced JNA treated with endonasal endoscopic approach and angio-embolization at Kingston Public Hospital, Jamaica, with subsequent benefits.

RESUMEN El angiofibroma nasofaríngeo juvenil (ANJ) en etapa localmente avanzada, tratado tradicionalmente con enfoques externos, se ha asociado a morbilidades significativas, tales como pérdida de sangre con transfusiones subsecuentes de sangre, cicatrices, trastornos del habla, pobre deglución, recurrencia y estancias hospitalarias prolongadas. Este reporte de caso describe nuestra experiencia inicial con un paciente con ANJ localmente avanzada tratado con un enfoque endonasal endoscópico y angioembolización en el Hospital Público de Kingston, Jamaica, con beneficios subsiguientes.

Efficacy and safety of preoperative internal maxillary arterial embolization with gelfoam for nasopharyngeal angiofibroma.

PURPOSE: To investigate the efficacy and safety of preoperative internal maxillary arterial embolization with gelfoam particles in patients with nasopharyngeal angiofibroma. MATERIALS AND METHODS: We retrospectively reviewed a total of 27 consecutive patients with pathologically confirmed nasopharyngeal angiofibroma from August 2006 to September 2018. Of the 27 enrolled patients, 10 patients received surgical excision alone; 17 patients received preoperative internal maxillary arterial embolization followed by surgical excision. Embolic agents were gelfoam particles. RESULTS: The mean volume of intro-operative blood loss was 385.3 ml in patients with preoperative arterial embolization, which was significantly lower than 1215.0 ml in the patients without preoperative arterial embolization (P < 0.001). The mean surgical time was shorter in patients with preoperative arterial embolization than in the patient without preoperative arterial embolization, but the difference had no statistical significance (205.0 vs 264.5 min, P = 0.064). Neurological complications such as facial palsy or vision loss or hemiplegia were not observed in patients with preoperative arterial embolization. CONCLUSION: Internal maxillary artery embolization with gelfoam particles suffices to provide an effective and safe adjuvant procedure for surgical excision of nasopharyngeal angiofibroma.

Juvenile nasopharyngeal angiofibroma surgical treatment in paediatric patients. / Tratamiento quirúrgico del angiofibroma nasofaríngeo juvenil en pacientes pediátricos.

INTRODUCTION AND OBJECTIVES: The juvenile nasopharyngeal angiofibroma is a highly vascularised benign neoplasm of complex treatment in its surgical preparation, surgery to be performed, risks and recurrences. The aim of the study was to analyze the management and surgical treatment for the pathology of juvenile nasoangiofibroma. MATERIALS AND METHODS: We reviewed the clinical histories and images of the patients who underwent surgery with a pathology result of juvenile nasoangiofibroma in the period from January 2008 to December 2016. RESULTS: Sixty-one cases were treated; all of them treated using the same surgical access by means of a Le Fort I osteotomy. All of the patients were male, with an average age of 13.3 years. The Andrew-Fish classification was used for staging the cases, most were staged as grade II and I. CONCLUSIONS: The described approach provided extensive surgical access, which was adequate for the different stages of the tumour. It requires experience to be able to resect the tumour with the least possible bleeding.

Contemporary management of juvenile angiofibroma.

PURPOSE OF REVIEW: To illustrate the latest developments and trends in the management of juvenile angiofibroma. RECENT FINDINGS: Endoscopic surgery is currently the primary management strategy for juvenile angiofibroma. Recent reports on the use of multiportal approaches have contributed to further extend its indications. Studies from different countries suggest that the lesion can display variable growth rates not only in relation to patient age. The same concept applies to residual lesions. For this reason, retreatment of persistent juvenile angiofibromas is indicated when serial imaging clearly shows that the lesion is growing. When redo surgery is potentially associated with high morbidity for the critical relationships of the lesion with adjacent structures, stereotactic or intensity-modulated radiation therapy can be an alternative. Early use of MRI in the postoperative course is a highly effective way to detect residual lesions. SUMMARY: Contemporary management of juvenile angiofibroma should primarily rely on endoscopic surgery to obtain radical tumor resection. Recent evidence on the behavior of residual postoperative juvenile angiofibroma and the development of conformal RT techniques have helped to clarify the role of watchful waiting and radiotherapy (RT) as alternatives to aggressive procedures in cases with critical extension of the lesion. Although radical excision is the primary therapeutic objective, the benign nature of juvenile angiofibroma and the reported tendency of small residual lesions to remain stable or involute, especially in postpubertal patients, should always be kept in mind to avoid unnecessary morbidity. VIDEO ABSTRACT: In the video, two of the authors describe the content of the review and present the main topics discussed in the article. http://links.lww.com/COOH/A37.

Juvenile Nasal Angiofibroma on 68Ga-PSMA PET/CT: Opening New Frontiers.

The prostate-specific membrane antigen (PSMA) is highly expressed in prostatic cancer. However, PSMA expression is also noted in various benign and malignant nonprostatic neoplasms in the endothelial cells of tumor-associated neovasculature. We performed Ga-PSMA PET/CT in a 14-year-old boy with juvenile nasal angiofibroma (JNA) to explore its theranostic potential. The scan revealed high uptake in the lesion. Performance of PSMA PET/CT in JNA opens up new frontiers with respect to radiological staging, early recurrence identification, and perhaps even radioligand therapy of residual/recurrent JNAs in the future.

[The current trends and the tactical-technical approaches to the management of the neoplastic processes in the base of the skull]. / Sovremennye tendentsii i taktiko-tekhnicheskie podkhody pri opukholevykh protsessakh osnovaniia cherepa.

The neoplastic processes localized in the base of the skull and the surrounding region have until recently been considered as the inoperable condition. Juvenile angiofibroma of the base of the skull or angiofibroma of the base of the skull (ABS) is most frequently encountered in the otorhinolaryngological practice. In terms of the histological picture, ABS is a benign tumour having a very complicated structure. The multi-disciplinary approach and the application of up-to-date medical technologies made it possible to obtain an insight into the deepest-lying areas of the base of the skull. A total of 69 patients presenting with juvenile angiofibroma of the base of the skull were available for the examination in the present study. In all this cases, the presence of the tumour was confirmed by the histological studies. Apart from the routine medical examination, all the patients underwent X-ray investigations including computed tomography with 3D-reconstruction, angiography subtracted VRT-reconstruction, and magnetic resonance tomography with contrast enhancement. Moreover, the trans-maxillary-buccal approach was applied with the use of the endovideoscopic equipment. All the patients were discharged from the clinic in the satisfactory condition. Recurrent tumours were documented only in three patients, the lethal cases were altogether absent. The length of the period of follow-up observations amounted to five and more years. It is concluded that the application of the modern medical technologies in the combination with the 'teamwork' interdisciplinary approach greatly contributes to the successful surgical treatment of the pathological processes localized at the base of the skull and the surrounding region.

Juvenile nasopharyngeal angiofibroma: a single centre's 11-year experience.

OBJECTIVE: This study aimed to present the clinical features and surgical outcomes of juvenile nasopharyngeal angiofibroma patients who were surgically treated. METHODS: The medical records of 48 male patients histologically confirmed as having juvenile nasopharyngeal angiofibroma, who underwent transnasal endoscopic surgery between 2005 and 2016, were retrospectively reviewed. RESULTS: The overall recurrence rate was 20.8 per cent; however, the recurrence rate differed significantly between patients diagnosed aged less than 14 years (34.7 per cent) and more than 14 years (8 per cent) (p < 0.05). Advanced-stage tumours (Radkowski stage of IIC or more, and Önerci stage of III or more) were more aggressive than earlier stage tumours (p < 0.05 and p < 0.01, respectively). Pre-operative embolisation significantly prolonged mean hospitalisation duration, but had no effect on intra-operative blood loss in patients with advanced-stage tumours (p < 0.001 and p = 0.09, respectively). CONCLUSION: The findings show that transnasal endoscopic surgery could be considered the treatment of choice for juvenile nasopharyngeal angiofibroma. Patients diagnosed when aged less than 14 years and those with advanced-stage tumours are at risk of recurrence, and should be monitored with extreme care.

Facial angiofibromas treated by rapamycin 0.05% ointment and a combined laser therapy.

BACKGROUND: Tuberous sclerosis is an autosomal dominant genodermatosis characterized by nonmalignant hamartomas in multiple organs. Facial angiofibromas are most commonly located on the face and have the potential to cause disfigurement. Facial disfigurement negatively affects the quality of life of patients and their families, often leading to negative psychosocial outcomes. Nowadays there are no treatment guidelines for facial angiofibromas but due to the progressive nature of facial angiofibromas a safe technique offering good results is needed. OBJECTIVE AND RESULTS: We report the case of a 40-year-old female affected by tuberous sclerosis, whose facial angiofibromas were satisfactorily treated by rapamycin 0.05% ointment, and a combined laser therapy.

Cutaneous Manifestations of Tuberous Sclerosis.

Dear Editor, Tuberous sclerosis (TS) is an autosomal dominant multisystem disease, which occurs due to genetically determined hyperplasia of ectodermal and mesodermal cells. Clinical manifestations present on the skin and in the nervous system, kidneys, heart, and other organs. Recent studies estimate the incidence of TS at 1/6000 to 1/10,000 live births, and a prevalence in the general population of approximately 1 in 20,000 (1). There are two different genetic loci responsible for TS: 9q34 (TSC1-hamartin) and 16p13.3 (TSC2-tuberin) (2). Cutaneous manifestations occur in about 96% of patients (3). Neurological disorders occur in 50% of patients in the form of seizures and motor and psychomotor symptomatology (4). A 19-year-old male patient was hospitalized for clinical and diagnostic evaluation in February 2016 year in Clinic for Nephrology, Clinical Center of Montenegro, Podgorica, Montenegro. Polycystic kidney changes were verified by ultrasound when the patient was three years old, with the presence of several calcified nodules in lateral ventricles and supraventricularly in the brain as well as the existence of several hypopigmented maculae on the skin. During the last hospitalization in February 2016, the following tests were performed: cranial magnet resonance imaging (MRI) findings showed the existence of visible changes in the signal in the form of ectopic tuber tissue in the region of the cortex and subcortical white matter of the brain, but without neurological and psychomotor abnormalities; ultrasound of the urinary tract showed that both kidneys were enlarged with multiple cysts, with dominant cysts at the lower pole of the right kidney with a size of 55 mm and at the upper pole of the left kidney, approximately 40 mm. Reduced functional capacity of kidneys was found on dynamic scintigraphy, slightly more in the left kidney (41%) compared with the right (59%). Electroencephalography, X-ray of the lungs and heart, and echocardiography were also performed, but without any pathological findings. Dermatological examination found numerous fibroma up to 0.5 cm in diameter, the largest located nasolabially, periorally, and on the chin skin (Figure 1) at the age of seven, whereas a fibroma and several white maculae were present from birth on the skin of the forehead. They were now also present on the skin of the trunk and on the upper and lower extremities (Figure 2), accompanied by surrounding minor changes in the form of confetti-like maculae. A subungual fibroma was present on the third finger of the right hand. Collagen nevus (shagreen patch) (5), i.e. a subepidermal fibrosis as a mildly elevated, palm-sized area is also characteristic of TS, which is described in literature, in most cases in the lumbosacral region. In our case, such a fibrosis about 3 cm in diameter, and with the consistency of an orange peel, was discovered on the right shoulder. Subungual fibromas (Koenen tumors) (6), which can develop in adolescence, were present in our patient on the third finger of the right hand. The diagnosis of TS was established based on genetic testing, physical examination, ultrasound-verified polycystic kidney disease and reduced global renal functions, intracranial MRI, many hypomelanotic changes, and angiofibromas found with dermatological examination (7). There is no specific therapeutic approach for TS, and the treatment is symptomatic. Angiofibromas of the skin can be removed by dermabrasion or laser. Recent data show a good therapeutic effect of applying 0.1% rapamycin (8), which leads to a reduction of angiofibromas in patients with TS. On dermatological follow up after five weeks of application of tacrolimus, angiofibromas of the face were in regression. Some studies suggest the simultaneous topical applications of both of those drugs (9). In adolescents and adults of reproductive age, genetic counseling is recommended (10).

Hypoxia-Inducible Factor-1α (HIF-1α) Expression on Endothelial Cells in Juvenile Nasopharyngeal Angiofibroma: A Review of 70 cases and Tissue Microarray Analysis.

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. CONCLUSION: In cases of JNA treated surgically, HIF-1α expression in ECs is a useful prognostic factor for tumor recurrence.