Genetic Heterogeneity in Cellular Angiofibromas.

BACKGROUND: Cellular angiofibroma, a rare benign mesenchymal neoplasm, is classified within the 13q/RB1 family of tumors due to morphological, immunohistochemical, and genetic similarities with spindle cell lipoma. Here, genetic data reveal pathogenetic heterogeneity in cellular angiofibroma. METHODS: Three cellular angiofibromas were studied using G-banding/Karyotyping, array comparative genomic hybridization, RNA sequencing, and direct cycling sequencing. RESULTS: The first tumor carried a del(13)(q12) together with heterozygous loss and minimal expression of the RB1 gene. Tumors two and three displayed chromosome 8 abnormalities associated with chimeras of the pleomorphic adenoma gene 1 (PLAG1). In tumor 2, the cathepsin B (CTSB) fused to PLAG1 (CTSB::PLAG1) while in tumor 3, the mir-99a-let-7c cluster host gene (MIR99AHG) fused to PLAG1 (MIR99AHG::PLAG1), both leading to elevated expression of PLAG1 and insulin growth factor 2. CONCLUSION: This study uncovers two genetic pathways contributing to the pathogenetic heterogeneity within cellular angiofibromas. The first aligns with the 13q/RB1 family of tumors and the second involves PLAG1-chimeras. These findings highlight the diverse genetic landscape of cellular angiofibromas, providing insights into potential diagnostic strategies.

Cellular angiofibroma of the female pelvic cavity: a case report.

BACKGROUND: Cellular angiofibroma is a rare benign mesenchymal tumor that mostly occurs in the genital area. Its occurrence outside this region, particularly in the pelvis, is extremely rare. To our knowledge, this study reports the first case of cellular angiofibroma occurring in the pelvic cavity, except for one case reported in the retroperitoneum. CASE PRESENTATION: A 25-year-old female patient with chronic, intermittent, dull pain in the lower abdomen that lasted for several months was referred to our clinic. Imaging studies revealed a tumor in the pelvic cavity anterior to the bladder. The radiographic characteristics of this tumor indicated a hypervascular nature, suggesting the possibility of a pheochromocytoma or a neuroendocrine tumor. The patient underwent surgical excision of the lesion. To date, no recurrence has been observed four months after excision. CONCLUSIONS: Cellular angiofibroma, although rare in the pelvic cavity, should be considered in the differential diagnosis of hypervascular pelvic space-occupying lesions. Immunohistochemical staining can help confirm the diagnosis of this condition. Treatment is generally straightforward, involving local excision of the tumor followed by postoperative monitoring.

BiZact-Assisted Endoscopic Resection of a Sinonasal Tumor.

The BiZact device, a bipolar electrosurgical scissor designed for tonsillectomy, minimizes thermal tissue damage and seals blood vessels <3 mm in diameter while dividing the soft tissue. This study describes the authors' experience with sinonasal tumor surgery using a BiZact and discusses its clinical utility and advantages. The authors analyzed BiZact-assisted endoscopic sinonasal tumor surgery cases between January 2021 and May 2023. Data were collected on patients' demographics, histopathology, extent of tumor involvement, surgical records, and postoperative medical records. Clinical utility was assessed using the success rate of complete tumor excision, estimated blood loss during surgery, device-related complications, and operation time. A survey of the surgeons' BiZact experience was also conducted. The diagnoses of the 20 patients in this study included squamous cell carcinoma (n = 2), malignant melanoma (n = 1), sarcoma (n = 1), natural killer cell lymphoma (n = 1), inverted papilloma (n = 12), angiofibroma (n = 2), and schwannoma (n = 1). This pilot study demonstrated a shortened operative time, with a median of 0.8 hours and <100 mL of intraoperative blood loss. In addition, no BiZact-related complications were observed. The BiZact device allows efficient sinonasal surgery because it has the unique advantage of one-step sealing and cutting. BiZact-assisted endoscopic sinonasal tumor surgery is a beneficial and safe procedure that reduces blood loss during surgery, shortens the operative time, and minimizes postoperative complications.

Clinicopathologic and genetic characterization of angiofibroma of soft tissue: a study of 12 cases including two cases with AHRR::NCOA3 gene fusion.

AIMS: Angiofibroma of soft tissue (AFST) is a benign tumour characterised by prominent arborizing blood vessels throughout the lesion. Approximately two-thirds of AFST cases were reported to have AHRR::NCOA2 fusion, and only two cases have been reported to have other gene fusions: GTF2I::NCOA2 or GAB1::ABL1. Although AFST is included in fibroblastic and myofibroblastic tumours in the World Health Organization's 2020 classification, histiocytic markers, especially CD163, have been reported to be positive in almost all examined cases, and it still remains the possibility of a fibrohistiocytic nature of the tumour. Therefore, we aimed to clarify the genetic and pathological spectrum of AFST and identify whether histiocytic marker-positive cells were true neoplastic cells. METHODS AND RESULTS: We evaluated 12 AFST cases, which included 10 cases with AHRR::NCOA2 and two with AHRR::NCOA3 fusions. Pathologically, nuclear palisading, which has not been reported in AFST, was detected in two cases. Furthermore, one tumour resected by additional wide resection revealed severe infiltrative growth. Immunohistochemical analysis indicated varying levels of desmin-positive cells in nine cases, whereas CD163- and CD68-positive cells were diffusely distributed in all 12 cases. We also performed double immunofluorescence staining and immunofluorescence in situ hybridisation in four resected cases with >10% desmin-positive tumour cells. The results suggested that the CD163-positive cells differed from desmin-positive cells with AHRR::NCOA2 fusion in all four cases. CONCLUSION: Our findings suggested that AHRR::NCOA3 could be the second most frequent fusion gene, and histiocytic marker-positive cells are not genuine neoplastic cells in AFST.

Novel EWSR1::GFI1B gene fusion in angiofibroma of soft tissue.

AIMS: Angiofibroma of soft tissue is a benign soft tissue tumour characterised by bland spindle cells and a distinct branching vascular network. The majority of soft tissue angiofibromas harbour AHRR::NCOA2 gene fusions. Here we present three cases of EWSR1::GFI1B-fused soft tissue tumours that are morphologically most reminiscent of soft tissue angiofibroma. METHODS AND RESULTS: All three cases presented in male patients with an age range of 35-78 years (median = 54 years). Two cases presented as subcutaneous nodules on the trunk (posterior neck and chest wall); one was an intramuscular foot mass. The tumours were unencapsulated nodules with infiltrative margins ranging from 2.2 to 3.4 cm in greatest dimension. Histologically, the tumours contained uniformly bland fibroblastic spindle cells with ovoid to fusiform nuclei and delicate cytoplasmic processes embedded in a myxoid to myxocollagenous stroma. All three cases were characterised by a thin-walled, branching vascular network evenly distributed throughout the tumour. Overt cytological atypia or conspicuous mitotic activity was absent. The spindle cells had an essentially null immunophenotype. By targeted RNA sequencing, an in-frame gene fusion between EWSR1 exons 1-7 and GFI1B exons 6-11 or 7-11 was detected in all three cases. The tumours were marginally excised. For all three cases, there were no documented local recurrence or distant metastases during a limited follow-up period of 6-10 months. CONCLUSIONS: We propose that EWSR1::GFI1B may represent a novel fusion variant of soft tissue angiofibroma.

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.

Metastatic melanoma involving a genetically confirmed angiofibroma of soft tissue: A previously unreported type of tumor-to-tumor metastasis.

Tumor-to-tumor metastases are an uncommon phenomenon and are very rare in the context of malignant melanoma. This case report describes a 73-year-old male who underwent an excision of a melanoma from his forehead. Six months later, he developed metastatic disease, including metastasis to a genetically confirmed angiofibroma of soft tissue of the abdominal wall. Angiofibroma of soft tissue is a relatively recently described benign fibrovascular soft tissue tumor, and there appear to be no previous reports of it being a recipient tumor for a metastasis. Awareness of the phenomenon of tumor-to-tumor metastasis and of the distinctive morphologic and molecular genetic features of angiofibroma are critical to avoid misdiagnosis of this very rare event as "dedifferentiated" melanoma.

Extramammary myofibroblastoma of the oral cavity.

Myofibroblastoma is a rare, benign mesenchymal tumor first described as a neoplasm of the breast. Extramammary myofibroblastoma is a histopathologically and genetically identical lesion occurring outside the breast. Herein is presented a case of extramammary myofibroblastoma arising in the oral cavity. A 59-year-old woman presented with a 1.5 cm nodule on the buccal surface of the lower lip. Wide local excision was performed. Histopathologic examination revealed haphazard fascicles of monomorphic spindle cells with hyalinized collagen bundles without fat. The spindled cells were diffusely positive for CD34, and focally for progesterone receptor. Desmin, smooth muscle actin, estrogen receptor, androgen receptor, S100, and STAT6 were negative. Rb1 expression was lost in tumor cells. Thus, the diagnosis of extramammary myofibroblastoma was made. Differential diagnoses include spindle-cell lipoma and angiofibroma. All three tumors are members of the 13q14 deletion/RB1 loss family. Indolent but locally aggressive (solitary fibrous tumor, desmoid fibromatosis) and frankly malignant (low-grade peripheral nerve sheath tumor, dermatofibrosarcoma protuberans) entities can be excluded by immunohistochemistry and careful microscopic examination. Extensive sampling extramammary myofibroblastoma is important to exclude the possibility of malignancy. Clinicians and pathologists alike should be aware of this entity and its potential to arise rarely in unusual locations.

Combined endoscopic endonasal and sublabial transmaxillary approaches for resection of intracranially extended juvenile nasopharyngeal angiofibroma.

BACKGROUND: Juvenile nasopharyngeal angiofibromas (JNAs) are rare, benign, and locally invasive nasopharyngeal tumors. Endoscopic endonasal resection is effective, non-invasive, with low complication rates. Until recently, endoscopic resection was not suitable for intracranially invasive tumors. PURPOSE/METHOD: We describe resection steps of an intracranially extending JNA with a combined endoscopic endonasal and endoscopic-assisted sublabial transmaxillary approaches. Indications, advantages, and approach-specific complications are also discussed. The main surgical steps are shown in an operative video. CONCLUSION: Surgical excision of JNAs by a combined endoscopic endonasal and sublabial transmaxillary approaches represents a safe and effective treatment for selected intracranially invasive JNA.

Endoscopic, endoscopic-assisted and open approaches in the treatment of juvenile angiofibroma: what has been new in the past decade (and 1586 cases)?

PURPOSE: Juvenile angiofibroma (JA) is a benign, but locally invasive tumor of the nasopharynx. Surgical resection of JA is performed through endoscopic (EA), endoscopic-assisted (EAA), or open approaches (OA). The management of these tumors is constantly evolving. We aimed to compare the surgical efficiency and morbidity of EA, EAA, and OA in JA treatment by conducting a systematic review of the literature published over the last 10 years. METHODS: A systematic review of the English literature on surgical cases of JA published between 2012 and 2022 was performed. Eligible articles were analyzed for individual patient data (IPD) and aggregate patient data (APD). The primary predictor variable was the surgical approach. The primary outcome variable was recurrence rate. RESULTS: The search retrieved 75 articles reporting 1586 JA surgical cases; 129 in IPD, and 1457 in APD data sets. Within the IPD data set, recurrence rates were significantly lower in cases completed by EA than that by OA (p < 0.05). There was no significant difference in recurrence rates between the EA and EAA groups (p > 0.05). EAA had a lower recurrence rate than that of OA (p < 0.05). For the APD data set, the recurrence rate following EA was significantly lower than that following OA (p < 0.05). There was no significant difference in recurrence between the EA and EAA groups (p > 0.05), and between the EAA and OA groups (p > 0.05). CONCLUSIONS: EA represents the method of choice for mild and moderately advanced JA. EAA and OA still play important roles in the treatment of advanced-stage JA.

Harmonic Scalpel-Assisted Endonasal Endoscopic Resection of the Vascular Tumors of the Anterior Skull Base.

Vascular tumors represent a challenging pathologic subset for surgical treatment as they show a propensity for profuse bleedings. This is especially applicable to the skull base region, where surgical access is difficult due to its complex anatomy. To overcome this problem, the authors introduced the use of a harmonic scalpel in endoscopic skull base surgery for vascular tumors. Here, the authors report the outcomes of endoscopic harmonic scalpel-assisted surgery in 6 juvenile angiofibromas and 2 hemangiomas. All surgeries were performed using Ethicon Endo-Surgery HARMONIC ACE 5 mm Diameter Shears. The median intraoperative blood loss was 400 mL (range: 200-1500 mL). The median length of hospital stay was 7 days (range: 5-10 days). Recurrence was recorded in 1 patient with juvenile angiofibroma, which was successfully resolved with revision surgery. In this institutional experience, ultrasonic technology showed precise cutting with minimal bleeding, resulting in reduced surgical morbidity compared with conventional endoscopic instruments.

Cytology of angiofibroma of soft tissue of the inguinal region.

Angiofibroma of the soft tissue is a recently described benign fibroblastic/myofibroblastic tumour. This report describes the cytology of an angiofibroma of soft tissue occurring in a 30-year-old lady which showed bland spindle cells, occasional polygonal cells with nuclear grooving, prominent vessels, frayed stroma around the blood vessels, and scattered lymphocyte-rich inflammatory cells in the background.

Preoperative emobilisation of juvenile nasopharyngeal angiofibroma.

INTRODUCTION: Juvenile nasopharyngeal angiofibroma(JNA) are highly vascular benign tumours originating in the sphenopalatine fossa and may extend to the pterygopalatine fossa, paranasal sinuses, and nasal cavity. The management of JNA has evolved greatly with development of endoscopy. Treatment modality has changed from open approach to endoscopic approach due to various advantages offered by the endoscopic approach. Bleeding during the surgery can compromise the exposure and surgical excision of JNA endoscopically. There have been many techniques to decrease intraoperative bleeding including external carotid ligation, hypotensive anaesthesia and more recently embolization of the feeding vessels. Embolization of the tumour has made the endoscopic excision of JNA easier because of less bleeding. This study was taken to find out the outcomes of surgical excision of JNA after embolization. METHODOLOGY: We retrospectively reviewed 22 histopathological proven JNA cases that underwent preoperative embolization followed by resection during the period of June 2015 to December 2020 in our tertiary care hospital. From the records demographic, clinical, radiological imaging (CECT nose and PNS), angiographic, pre-operative embolization and operative details were evaluated. RESULT: In the present study a total of 22 cases of angiofibroma were taken up for surgical excision after embolization. A complete endonasal endoscopic resection could be done in 21/22 cases with average operative time of 141 minutes (80 minutes-190 minutes range). The mean blood loss during surgery was 1163 ml (Range 500 ml- 1900 ml). In 7/22 (31.81%) subjects required intraoperative blood transfusion. No perioperative surgical complications occurred. CONCLUSION: Endoscopic excision of JNA has now become the primary operative technique and pre operative embolization in such cases can reduce the intraoperative time, blood loss and tumour relapse rate. It is a relatively safe procedure in a hand of an expert and must be done where ever available.

Neural Crest Stem Cells in Juvenile Angiofibromas.

The etiology of juvenile angiofibroma (JA) has been a controversial topic for more than 160 years. Numerous theories have been proposed to explain this rare benign neoplasm arising predominately in adolescent males, focusing mainly on either the vascular or fibrous component. To assess our hypothesis of JA's being a malformation arising from neural crest cells/remnants of the first branchial arch plexus, we performed immunohistochemical analyses of neural crest stem cells (NCSC) and epithelial-mesenchymal transition (EMT) candidates. Immunoexpression of the NCSC marker CD271p75 was observed in all investigated JA's (n = 22), mainly around the pathological vessels. Close to CD271p75-positive cells, high MMP3-staining was also observed. Additionally, from one JA with sufficient material, RT-qPCR identified differences in the expression pattern of PDGFRß, MMP2 and MMP3 in MACS®-separated CD271p75positive vs. CD271p75 negative cell fractions. Our results, together with the consideration of the literature, provide evidence that JA's represent a malformation within the first branchial arch artery/plexus remnants deriving from NCSC. This theory would explain the typical site of tumor origin as well as the characteristic tumor blood supply, whereas the process of EMT provides an explanation for the vascular and fibrous tumor component.

Potential pathogenetic link between angiomyofibroblastoma and superficial myofibroblastoma in the female lower genital tract based on a novel MTG1-CYP2E1 fusion.

Angiomyofibroblastoma and superficial myofibroblastoma are distinctive benign mesenchymal tumors occurring in the female lower genital tract. Despite their significant overlapping clinicopathologic features, including the presence of bland-looking spindle or oval cells with myofibroblastic or myoid differentiation, the tumors have been regarded as separate entities. Although subepithelial, hormone-sensitive mesenchymal cells of the female lower genital tract are considered as their potential common progenitor cells, their potential kinship or pathogenetic similarities remain elusive. Based on the identification of a novel RNA sequencing-based MTG1-CYP2E1 fusion transcript in an angiomyofibroblastoma index case, we investigated an additional ten samples of the tumor and its site-specific histological mimics, including eight superficial myofibroblastomas, four deep angiomyxomas, four cellular angiofibromas, three fibroepithelial stromal polyps, and eight non-site-specific mesenchymal tumors occurring in the female lower genital tract. Using reverse transcription-polymerase chain reaction, we showed that the MTG1-CYP2E1 fusion transcripts were consistently detectable in angiomyofibroblastomas (5/5, 100%) and often in superficial myofibroblastomas (3/5, 60%) but were not detected in the other examined site-specific or non-site-specific mesenchymal tumors. Our immunohistochemical experiments showed that CYP2E1, an isoenzyme belonging to the cytochrome P450 superfamily, exhibited increased positivity in tumors with MTG1-CYP2E1 than was observed in fusion-negative tumors (RR = 6.56, p = 0.001). The results of our study provide further evidence supporting the assertion that angiomyofibroblastoma and superficial myofibroblastoma represent phenotypic variants of site-specific mesenchymal tumors and share a common oncogenic mechanism.

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.

Clinical and histopathological evaluation of cutaneous angiofibromas.

BACKGROUND: Angiofibromas are common benign skin lesions that are diagnosed clinically and histopathologically. Fibrous papule (FP) is one of the clinical types of angiofibromas located primarily on the nose. METHODS: The cases with the confirmed diagnosis of angiofibroma were enrolled. Demographic features of the patients and clinical characteristics of the lesions were extracted. Moreover, histopathological features of the available slides were microscopically reviewed. RESULTS: From 83 cases of cutaneous angiofibromas, 57 (69%) had lesions consistent with FP. The mean age at diagnosis was 37.7 ± 16.3 years and the most common site of involvement was the nose (53% of cases). Regarding the histopathological evaluation of 71 slides, most cases represented vascular changes (97%) and dermal fibroplasia (87%). Melanin incontinence (41%), acanthosis (31%), and lichenoid features (25%) were other common histopathological findings. Moreover, a sparse inflammatory cell infiltrate was present in 68% of cases. The most prevalent inflammatory cells were lymphocytes (61%) and histiocytes (34%). CONCLUSION: This study presented the histopathological findings of a series of cutaneous angiofibromas. Dermatopathologists should be aware of these features, especially those that are less common, to better diagnose and differentiate them from malignant neoplasms.

Histopathological characteristics and CD163 immunostaining pattern in fibrous papule of the face.

BACKGROUND: Signs of inflammation including epidermal interface changes, spongiosis, and dermal inflammation as well as pagetoid dyskeratosis are rarely described in fibrous papule (FP). We aimed to describe the inflammatory parameters, the rate of pagetoid dyskeratosis, along with CD163 immunohistochemical staining as an adjunctive diagnostic tool in FP. METHODS: Histopathology samples of all biopsy-proven FP cases were retrieved from archives and investigated for inflammatory parameters, presence of pagetoid dyskeratosis, as well as CD163, CD10, and CD34 immunostaining pattern of dermal spindle/stellate or multinucleate cells (graded from 0 to 4). RESULTS: Thirty-two cases of FP were identified. A high rate of inflammatory parameters including interface changes (20/32), spongiosis (31/32), and dermal lymphocytic inflammation (31/32) were detected. Pagetoid dyskeratosis was identified in eight out of 32 cases (25%). A grade 4 staining revealing a strong dendritic pattern was confirmed in all FP cases with CD163 immunohistochemistry including atypical variants such as granular FP, compared with CD10 (11/32) and CD34 (3/32). CONCLUSION: The dendritic cellular proliferation in FP may represent an inflammatory response to various stimuli; pagetoid dyskeratosis is a relatively common and underrecognized epidermal feature and CD163 immunostaining may be used as an adjunctive diagnostic tool in unusual histopathological subtypes.

EBV-Positive Plasmacytomas Involving a Nasopharyngeal Angiofibroma in an Adolescent.

We report comprehensive characterization of an unusual collision tumor comprising extramedullary plasmacytomas and nasopharyngeal angiofibroma in a pediatric patient, which has yet to be reported. Histologically, the nasopharyngeal angiofibroma showed typical morphology with a diffuse, dense plasmacytic infiltrate in the stroma. The neoplastic plasma cells showed a spectrum of well-differentiated, plasmablastic, and anaplastic morphology, Epstein-Barr virus encoded RNA (EBER) positivity, and aberrant immunophenotype. Fluorescence in situ hybridization using a plasma cell myeloma targeted panel detected gains of 1q21.3 (CKS1B, x3), 3q27 (BCL6, x4), and 11q22.3 (ATM, x3), but no rearrangement of ALK and MYC. A 50-gene next generation sequencing lymphoma panel failed to detect any pathogenic mutation. Plasmacytoma with EBER positivity and plasmablastic morphology must be distinguished from plasmablastic lymphoma due to different clinical management and prognosis. This case highlights the importance of a thorough pathological evaluation of a mass lesion with synchronous neoplastic processes.

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.