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The New England Journal of Medicine May 2017
Topics: Aged; Angiofibroma; Face; Humans; Male; Nails; Renal Insufficiency, Chronic; Skin Neoplasms; Tuberous Sclerosis
PubMed: 28514607
DOI: 10.1056/NEJMicm1610501 -
Frontiers in Endocrinology 2023Multiple Endocrine Neoplasia type 1 is a rare genetic syndrome mainly caused by mutations of gene and characterized by a combination of several endocrine and...
BACKGROUND
Multiple Endocrine Neoplasia type 1 is a rare genetic syndrome mainly caused by mutations of gene and characterized by a combination of several endocrine and non-endocrine manifestations. The objective of this study was to describe cutaneous lesions and other non-endocrine manifestations of in a cohort of patients with familial (F) and sporadic (S) , compare the prevalence of these manifestations between the two cohorts, and investigate the correlation with mutation status.
METHODS
We collected phenotypic and genotypic data of 185 patients with F- and S- followed from 1997 to 2022. The associations between F- and S- or mutation-positive and mutation-negative patients and non-endocrine manifestations were determined using chi-square or Fisher's exact tests or multivariate exact logistic regression analyses.
RESULTS
The prevalence of angiofibromas was significantly higher in F- than in S- in both the whole (p < 0.001) and index case (p = 0.003) cohorts. The prevalence of lipomas was also significantly higher in F- than in S- (p = 0.009) and in mutation-positive than in mutation-negative (p = 0.01) index cases. In the whole cohort, the prevalence of lipomas was significantly higher in mutation-positive compared to mutation-negative patients (OR = 2.7, p = 0.02) and in F- than in S- (p = 0.03), only after adjustment for age. No significant differences were observed for the other non-endocrine manifestations between the two cohorts. Hibernoma and collagenoma were each present in one patient (0.5%) and meningioma and neuroblastoma in 2.7% and 0.5%, respectively. Gastric leiomyoma was present in 1.1% of the patients and uterine leiomyoma in 14% of women. Thyroid cancer, breast cancer, lung cancer, basal cell carcinoma, melanoma, and colorectal cancer were present in 4.9%, 2.7%, 1.6%, 1.6%, 2.2%, and 0.5% of the whole series, respectively.
CONCLUSIONS
We found a significantly higher prevalence of angiofibromas and lipomas in F- compared with S- and in mutation-positive compared to mutation-negative patients. In patients with one major endocrine manifestation of , the presence of cutaneous lesions might suggest the diagnosis of and a possible indication for genetic screening.
Topics: Humans; Female; Multiple Endocrine Neoplasia Type 1; Angiofibroma; Genetic Testing; Mutation; Lipoma
PubMed: 37484956
DOI: 10.3389/fendo.2023.1191040 -
Indian Journal of Otolaryngology and... Dec 2022Angiofibroma arising from sites other than nasopharynx is rare and termed as Extra nasopharyngeal angiofibroma (ENA). ENAs commonly arise from nasal septum, maxillary...
Angiofibroma arising from sites other than nasopharynx is rare and termed as Extra nasopharyngeal angiofibroma (ENA). ENAs commonly arise from nasal septum, maxillary sinus, and inferior turbinate. But angiofibroma arising from oropharynx have not been frequently reported. We present here a case of middle-aged male who presented with a large pedunculated oropharyngeal mass attached to palatopharyngeal fold. Endoscopic radiofrequency assisted transoral excision of mass was done. Histopathological features were consistent with angiofibroma arising from oropharynx. Patient recovered well with no evidence of recurrence till 18 months of follow up. In this report, we have tried to emphasize the diagnostic workup for oropharyngeal mass. This report also provides an insight into the clinical and pathological behavior of extra nasopharyngeal angiofibroma.
PubMed: 36742930
DOI: 10.1007/s12070-021-02956-4 -
Journal of the European Academy of... May 2021Tuberous sclerosis complex (TSC) is a hamartoma syndrome characterized by multiple skin lesions, such as angiofibromas, shagreen patch and miliary fibromas (MiF).
BACKGROUND
Tuberous sclerosis complex (TSC) is a hamartoma syndrome characterized by multiple skin lesions, such as angiofibromas, shagreen patch and miliary fibromas (MiF).
OBJECTIVE
To determine the clinical and histological features of MiF.
METHODS
A retrospective analysis was conducted on 133 adults with TSC. Photography was used to characterize the appearance and location of MiF. Histological features in five skin samples from four individuals were evaluated by a board-certified dermatopathologist.
RESULTS
MiF were observed in 19 of 133 (14%) individuals with TSC. MiF were 1- to 3-mm skin-coloured, sessile papules scattered on the back and rarely buttocks or thighs. Most were scattered in a bilaterally symmetric distribution, but others were asymmetric or associated with a shagreen patch. Histological features of MiF included expansion of the papillary and periadnexal dermis with variable hamartomatous abnormalities involving adjacent epithelial components.
CONCLUSIONS
MiF are distinct from other cutaneous lesions in TSC such as shagreen patches and angiofibromas. Recognition of this entity is important in defining the spectrum of TSC disease and reassuring individuals with TSC that these lesions are benign.
Topics: Adult; Angiofibroma; Fibroma; Humans; Nevus; Retrospective Studies; Tuberous Sclerosis
PubMed: 33565654
DOI: 10.1111/jdv.17161 -
Journal of Oral and Maxillofacial... 2016Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor arising predominantly in the nasopharynx of adolescent males. It is an aggressive neoplasm and shows a...
Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor arising predominantly in the nasopharynx of adolescent males. It is an aggressive neoplasm and shows a propensity for destructive local spread often extending to the base of the skull and into the cranium. Clinically, however, it is obscure with painless, progressive unilateral nasal obstruction being the common presenting symptom with or without epistaxis and rhinorrhea. Diagnosis of JNA is made by complete history, clinical examination, radiography, nasal endoscopy and by using specialized imaging techniques such as arteriography, computer tomography and magnetic resonance imaging. Histopathology reveals a fibrocellular stroma with spindle cells and haphazard arrangement of collagen interspersed with an irregular vascular pattern. A case report of JNA with rare intra-oral manifestation in a 17-year-old male patient is presented in the article. JNA being an aggressive tumor may recur posttreatment. Thus, early diagnosis, accurate staging, and adequate treatment are essential in the management of this lesion.
PubMed: 27601836
DOI: 10.4103/0973-029X.185908 -
Orphanet Journal of Rare Diseases Sep 2022Facial angiofibroma is the most predominant cutaneous manifestation of tuberous sclerosis complex (TSC), a rare autosomal dominant genetic disorder impacting the...
BACKGROUND
Facial angiofibroma is the most predominant cutaneous manifestation of tuberous sclerosis complex (TSC), a rare autosomal dominant genetic disorder impacting the mechanistic target of rapamycin (mTOR). Facial angiofibroma can bleed spontaneously, impair eyesight, and cause aesthetic disfiguration causing psychological and social stress. To date, there is little or no evidence on the demographics, and other TSC features associated with facial angiofibroma or the use of mTOR inhibitor for the management of facial angiofibroma. This is a retrospective study of TSC Alliance's Natural History Database aimed to characterize facial angiofibroma and to evaluate features associated with a higher risk of facial angiofibroma or the use of topical mTOR inhibitors for the management of facial angiofibroma. Data in the NHD was obtained from 18 clinical sites in the US since 2006.
RESULTS
Of the 2240 patients, 2088 patients were enrolled in the US and data from 2057 patients were included in this analysis. The mean (median) age of overall TSC patients was 22.4 (19.0) years. A total of 69 patients were ≤ 5 years of age. Facial angiofibroma was noted in 1329 (64.6%) patients with TSC. Patients with facial angiofibroma were older on average (Mean: 25.9 [median, 23.0] vs. 16.0 [12.4 years] years, p < 0.0001). In patients with vs. without facial angiofibroma, TSC2 mutation (38.9% vs. 34.8%) was more common than TSC1 mutation (12.3% vs. 18.1%), and the incidence rate of most of the other TSC-related manifestations was significantly higher in patients with facial angiofibroma. Majority of patients had focal seizures (72.8% vs. 60.7%), followed by angiomyolipoma (63.7% vs. 21.8%) and renal cysts (59.4% vs. 33.5%). The age groups, 11-17 (odds ratio [OR], 2.53) and 18-45 years (5.98), TSC2 mutation (1.31), focal seizures (1.50), ADHD (1.47) angiomyolipoma (2.79), and renal cysts (2.63) were significantly associated with a higher risk of facial angiofibroma based on multivariate logistic regression. Abrasive or laser therapy was used by 17.1% and 2.6% patients, respectively. Topical mTOR inhibitor use was noted for 329 (24.8%) patients with facial angiofibroma. Overall systemic mTOR inhibitor use was observed in 399 (30.0%) patients for management of one or more TSC manifestations. Use of systemic mTOR inhibitor for facial angiofibroma was noted for 163 (12.3%) patients, among whom only 9 (0.7%) patients used exclusively for the management of facial angiofibroma. Of the patients with facial angiofibroma, 44.6% did not receive any treatment. Significantly higher use of topical mTOR inhibitor was associated with the 11-17 years age group (OR, 1.67), anxiety (1.57), angiomyolipoma (1.51), and renal cysts (1.33).
CONCLUSIONS
The presence of TSC2 mutations and most other TSC-related manifestations was significantly higher in patients with facial angiofibroma. About one-fourth of patients with facial angiofibroma used a topical mTOR inhibitor and use of systemic mTOR inhibitor for the management of facial angiofibroma or for the other manifestations was noted for 30.0%. About 44.6% of patients did not receive any treatment for the management of facial angiofibroma.
Topics: Adult; Humans; Young Adult; Angiomyolipoma; Immunosuppressive Agents; Kidney Diseases, Cystic; Kidney Neoplasms; MTOR Inhibitors; Retrospective Studies; Seizures; Sirolimus; Tuberous Sclerosis; United States
PubMed: 36104799
DOI: 10.1186/s13023-022-02496-2 -
American Journal of Human Genetics Jun 2023Tuberous sclerosis complex (TSC) is a neurogenetic disorder due to loss-of-function TSC1 or TSC2 variants, characterized by tumors affecting multiple organs, including...
Tuberous sclerosis complex (TSC) is a neurogenetic disorder due to loss-of-function TSC1 or TSC2 variants, characterized by tumors affecting multiple organs, including skin, brain, heart, lung, and kidney. Mosaicism for TSC1 or TSC2 variants occurs in 10%-15% of individuals diagnosed with TSC. Here, we report comprehensive characterization of TSC mosaicism by using massively parallel sequencing (MPS) of 330 TSC samples from a variety of tissues and fluids from a cohort of 95 individuals with mosaic TSC. TSC1 variants in individuals with mosaic TSC are much less common (9%) than in germline TSC overall (26%) (p < 0.0001). The mosaic variant allele frequency (VAF) is significantly higher in TSC1 than in TSC2, in both blood and saliva (median VAF: TSC1, 4.91%; TSC2, 1.93%; p = 0.036) and facial angiofibromas (median VAF: TSC1, 7.7%; TSC2 3.7%; p = 0.004), while the number of TSC clinical features in individuals with TSC1 and TSC2 mosaicism was similar. The distribution of mosaic variants across TSC1 and TSC2 is similar to that for pathogenic germline variants in general TSC. The systemic mosaic variant was not present in blood in 14 of 76 (18%) individuals with TSC, highlighting the value of analysis of multiple samples from each individual. A detailed comparison revealed that nearly all TSC clinical features are less common in individuals with mosaic versus germline TSC. A large number of previously unreported TSC1 and TSC2 variants, including intronic and large rearrangements (n = 11), were also identified.
Topics: Humans; Tumor Suppressor Proteins; Tuberous Sclerosis; Tuberous Sclerosis Complex 2 Protein; Mutation; Tuberous Sclerosis Complex 1 Protein; Phenotype
PubMed: 37141891
DOI: 10.1016/j.ajhg.2023.04.002 -
Diagnostics (Basel, Switzerland) Nov 2022Non-endocrine findings in patients with MEN1 (multiple endocrine neoplasia) syndrome also include skin lesions, especially tumor-type lesions. This is a narrative review... (Review)
Review
Non-endocrine findings in patients with MEN1 (multiple endocrine neoplasia) syndrome also include skin lesions, especially tumor-type lesions. This is a narrative review of the English-language medical literature including original studies concerning MEN1 and dermatological issues (apart from dermatologic features of each endocrine tumor/neuroendocrine neoplasia), identified through a PubMed-based search (based on clinical relevance, with no timeline restriction or concern regarding the level of statistical significance). We identified 27 original studies involving clinical presentation of patients with MEN1 and cutaneous tumors; eight other original studies that also included the genetic background; and four additional original studies were included. The largest cohorts were from studies in Italy (N = 145 individuals), Spain (N = 90), the United States (N = 48 and N = 32), and Japan (N = 28). The age of patients varied from 18 to 76 years, with the majority of individuals in their forties. The most common cutaneous tumors are angiofibromas (AF), collagenomas (CG), and lipomas (L). Other lesions are atypical nevi, basocellular carcinoma, squamous cell carcinoma, acrochordons, papillomatosis confluens et reticularis, gingival papules, and cutaneous T-cell lymphoma of the eyelid. Non-tumor aspects are confetti-like hypopigmentation, café-au-lait macules, and gingival papules. gene, respective menin involvement has also been found in melanomas, but the association with MEN1 remains debatable. Typically, cutaneous tumors (AF, CG, and L) are benign and are surgically treated only for cosmetic reasons. Some of them are reported as first presentation. Even though skin lesions are not pathognomonic, recognizing them plays an important role in early identification of MEN1 patients. Whether a subgroup of MEN1 subjects is prone to developing these types of cutaneous lesions and how they influence MEN1 evolution is still an open issue.
PubMed: 36428828
DOI: 10.3390/diagnostics12112768 -
Ear, Nose, & Throat Journal Nov 2022Significance StatementExtranasopharyngeal angiofibromas (ENA) are rare vascular tumors that do not conform to the clinical characteristics of typical nasopharyngeal...
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.
Topics: Angiofibroma; Diagnosis, Differential; Humans; Nasopharyngeal Neoplasms; Nose Neoplasms; Respiratory Tract Neoplasms
PubMed: 33226849
DOI: 10.1177/0145561320972600 -
Korean Circulation Journal Sep 2013Cardiac Angiofibroma is an uncommon intracardiac tumor. Thus far, only 4 cases of the rare intracardiac tumor have been reported. The present case-report describes an...
Cardiac Angiofibroma is an uncommon intracardiac tumor. Thus far, only 4 cases of the rare intracardiac tumor have been reported. The present case-report describes an intracardiac angiofibroma in a 57-year-old healthy female. The patient was incidentally diagnosed with a left ventricle mass during echocardiography. We performed cardiac imaging, surgical excision and histological evaluation of the mass. The angiofibroma demonstrated features different from the relatively common cardiac tumors such as fibroma, myxoma and angiosarcoma. The cardiac MRI showed slightly high signal intensity on both T1 and T2, with the central core of lower signal intensity. The resected tumor was a whitish and rubbery mass. Histologically, the tumor showed the benign vascular proliferations associated with the surrounding collagen deposition.
PubMed: 24174966
DOI: 10.4070/kcj.2013.43.9.636