Periungual Fibromas Research Articles

Multiple unilateral angiofibromas with a hypopigmented patch as a possible presentation of tuberous sclerosis complex (TSC)

Tuberous sclerosis complex (TSC), known as Bourneville’s disease or epiloia, is an autosomal dominant inherited disorder that may affect numerous organ systems. TSC has many forms of clinical presentation. The cutaneous features of TSC include facial angiofibromas, shagreen patches, ash leaf hypopigmented macules, periungual fibromas, forehead fibrous plaques, confetti hypopigmentation, and poliosis. Rarely, the angiofibromas in TSC have a segmental distribution. It has been suggested that the segmental expression of tuberous sclerosis may result from a postzygotic mutation. The aim of this concise communication was to describe a patient with unilateral angiofibromas associated with a hypopigmented patch. No other features of TSC were present. We think this could have been a rare presentation of TSC. Key words: Angiofibroma, Hypopigmented patch, Loss of heterozygosity (LOH), Tuberous sclerosis complex (TSC)

Cutaneous manifestations of tuberous sclerosis in the foot: A case study

Tuberous sclerosis is a neurocutaneous syndrome that can manifest in many different ways. One of the major criteria is the presence of periungual or subungual fibromas in the toes. This article presents two cases of recurrent periungual fibromas and multiple options for treatment.

Case report on tuberous sclerosis

Patient M., 23 years old, consulted a dermatologist with complaints of rashes on the face, which had bothered since childhood. On objective examination, skin lesions were widespread. A visual examination revealed spots of hypopigmentation, angiofibromas of the face, shagreen fate of the skin, periungual fibromas. She was diagnosed with tuberous sclerosis. Further examination revealed a neoplasm in the brain and right kidney, damage to the lungs, tubular bones, lymphadenopathy. The patient continues to be monitored by a neurologist and therapist. Based on the results of CT scan of the chest organs, an oncologist's consultation was scheduled to conduct an oncology search. Thus, with skin manifestations characteristic of this disease, it is necessary to conduct a comprehensive examination to identify concomitant pathology and early diagnosis of complications.

Retinal Hamartomas in a case of Tuberous Sclerosis

A 21 year old male patient suffering from epilepsy came for fundoscopic evaluation. Right eye showed a flat, smooth surfaced well circumscribed, non-calcified translucent lesion of 1 disc dioptre size, inferior to the optic disc, obscuring underlying vessels & an opaque, calcified,yellow white lesion having irregular surface & margins with mulberry appearance, elevated, supero-nasal to the disc, obscuring the underlying vessels. Adenoma sebaceum, periungual fibromas, Ash leaf macules were seen on general physical examination suggestive of tuberous sclerosis. MRI brain revealed subependymal nodules & subcortical tubers. OCT showed an optically hyper reflective mass with retinal disorganization and moth eaten spaces. 2D echo showed mild LVH , diastolic dysfunction, trivial mitral and tricuspid regurgitation .USG showed fatty liver and Renal angiomyolipoma. It was interesting to note cardiac & hepatic involvement in addition to the standard TSC major & minor diagnostic criteria.

Dermoscopic findings in a case of multiple subungual fibromas

Periungual and subungual fibromas, also known as Koenen tumors, are diagnostic findings of tuberous sclerosis. The clinical appearance and histological features that characterize ungual fibromas are well defined. However, dermoscopic findings of these benign tumors have not been reported previously. Here we report a rare presentation of multiple subungual fibromas of all fingers in a developmentally delayed patient with tuberous sclerosis along with the dermoscopic features of the ungual tumors.

Masquerading case of a lumpy bumpy face

Masquerading case of a lumpy bumpy face

Dermoscopy of subungual red comets associated with tuberous sclerosis complex.

We report here our experience on the use of dermoscopy for the detection of subungual red comets, which are sometimes present in the nails of patients affected by tuberous sclerosis complex. Dermoscopy allowed us to visualize, with better resolution than the naked eye, very tortuous capillaries surrounded by a whitish halo and close parallel binary tortuous capillaries. In some cases, subungual red comets are associated with the presence of periungual or subungual fibromas, but their exact pathogenesis remains unknown.

Fibroma-like PEComa: A Tuberous Sclerosis Complex-related Lesion.

Perivascular epithelioid cell tumor (PEComa), mesenchymal tumors morphologically characterized by epithelioid cells, coexpress melanocytic and muscle markers. Herein, we describe a heretofore-undescribed tuberous sclerosis complex (TSC)-related neoplasm, morphologically resembling a soft tissue fibroma-like lesion, but showing an immunophenotype resembling PEComa. We identified 3 soft tissue fibroma-like lesions in individuals with TSC. We also evaluated 6 TSC-related periungual fibroma as well as a range of non-TSC fibroma-like lesions (n=19). Immunohistochemistry for HMB-45, desmin, smooth muscle actin, TFE3, and S100 was performed on the TSC-related fibromas. Periungual fibromas and non-TSC fibroma-like lesions were also stained for HMB-45. All 3 TSC patients were female, ranging in age from 4 to 51 years (mean, 26.7 y). Two tumors were located in extremities and 1 on the chest wall. The tumors showed elongated to stellate spindle-shape cells, prominent collagenous background, and lacked mitotic activity and cytologic atypia. Immunohistochemically, all 3 tumors were positive for HMB-45; smooth muscle actin or desmin was positive in both tumors tested. TFE3 was negative. All patients were alive with no evidence of disease with median follow-up of 55 months (range, 6 to 131 mo). Non-TSC fibroma-like lesions and oral and periungual fibromas were negative for HMB-45. Fibroma-like PEComa, a newly recognized soft tissue tumor with a strong association with TSC, mimics soft tissue fibroma but shows reactivity with melanocytic markers.

Tuberous sclerosis: a case report

An 11-year-old girl, from a consanguineous family. With history of suspected akinetic seizures and normal intelligence. Physical examination revealed several small-scattered facial angiofibromas that were histologically determined by skin biopsy. Hypomelanotic macules, shagreen patches on her back. Periungual fibromas were not seen. CT brain showed multiple calcified sub ependymal nodules and cortical tubers. Cardiological consult and ECG were normal. Neurological consult shows: normal status of conscience, without meningeal signs of irritation, cranial nerves without deficit, and no ataxia. No hamartomas or retinal achromic patches was noticed by ophthalmologic evaluation. Radiography of the chest, truncal CT was without abnormality. So with the above clinical findings, a diagnosis of Tuberous sclerosis was made, and the patient is under regular monitoring. Tuberous Sclerosis, also known as Bourneville's disease, is an autosomal dominant syndrome with variable clinical expression. The dermatologist plays an essential role in the history of the disease, since skin manifestations represent the most prevalent clinical features, enabling early diagnosis and intervention in its natural course.

401 Dermal fibroblasts with loss of TSC2 express increased galectin-3, a potential biomarker for tuberous sclerosis complex

400 Amlexanox: Efficacy and mechanism for potential therapy for RDEB V Atanasova, Q Jiang, J Uitto and A South Thomas Jefferson University, Philadelphia, PA Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin blistering disorder caused by loss-of-function mutations in the COL7A1 gene, which encodes type VII collagen (ColVII). ColVII is the main, if not exclusive, component of anchoring fibrils that adhere the epidermis to the dermal layer of the skin. Mutations in COL7A1 lead to defective anchoring fibrils and subsequent perturbed adhesion between the two skin layers resulting in severe skin fragility and constant wounding without ability to heal. A subgroup of RDEB patients harbors nonsense mutations in COL7A1 which create premature termination codons (PTCs) of translation in the mRNA molecule. This leads to mRNA instability and lack of functional protein synthesized. A group of drugs have been reported for their ability to induce “readthrough” and allow for insertion of an amino acid at the site of PTC, thus producing fulllength protein. The mechanism by which these drugs act is currently not known. Here we focus on a PTC read-through drug, amlexanox, previously approved by the FDA for mouth ulcers. Our data show that amlexanox is able to induce full-length synthesis of ColVII in HpV immortalized RDEB patient derived keratinocytes and fibroblasts, as shown by western blotting. After 48 hours of treatment keratinocytes showed up to 14 fold increase in full-length ColVII protein synthesis as compared to non-treated controls. The same treatment in HpV fibroblasts led up to 3 fold increase in ColVII as compared to non-treated controls, or 25% of normal human fibroblasts. While the mechanism by which amlexanox is able to recover protein synthesis from the PTC containing COL7A1 gene is currently unclear, activation of UPF1 by its phosphorylation has been shown to be required for assembly of mRNA degradation machinery. Our data show that amlexanox treatment increases UPF1 phosphorylation, which may be part of the PTC read-through mechanism. In conclusion, we present data to support amlexanox as a read-through agent for the treatment of RDEB in cases with PTC in COL7A1. 401 Dermal fibroblasts with loss of TSC2 express increased galectin-3, a potential biomarker for tuberous sclerosis complex P Klover, R Thangapazham, J Kato, J Wang, S Li, C Dalgard, M Wilkerson, E Mccart, J Moss and T Darling 1 Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD, 2 Cardiovascular and Pulmonary Branch, NIH/NHLBI, Bethesda, MD and 3 Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD Tuberous sclerosis complex (TSC) is an autosomal genetic disorder in which tumors form in multiple organs due to biallelic inactivating mutations in TSC1 or TSC2 and increased mTORC1 signaling. In order to discover biomarkers for TSC, we studied our mouse model of TSC with conditional deletion of Tsc2 in dermal mesenchyme (Tsc2cKO), testing the potential clinical relevance of findings using human TSC skin tumors. RNA-sequencing analysis of cultured Tsc2-null and wild-type mouse dermal fibroblasts identified galectin-3 as overexpressed by the mutant cells. Levels of both intracellular and secreted galectin-3 protein were approximately 3-fold greater in Tsc2-null fibroblasts than wild-type fibroblasts. Tsc2-null cells incubated in the presence of 20 nM sirolimus, an mTORC1-inhibitor, showed decreased galectin-3 expression but not to the level of wild-type fibroblasts, suggesting that overexpression of galectin-3 is only partially mTORC1-dependent. Serum levels of galectin-3 were 68% greater (p1⁄40.0015) in Tsc2 cKO than wild-type mice and sirolimus treatment for 4 weeks decreased galectin-3 serum levels 25% (p1⁄40.036) in the Tsc2cKO. Fibroblast-like cells grown from human TSC skin tumors, including angiofibromas, fibrous cephalic plaque, and periungual fibromas, showed greater intracellular and secreted galectin-3 levels than patient normal fibroblasts. Immunohistochemical analysis showed abundant galectin-3 positive dermal cells in TSC skin tumors but nearly absent dermal staining in paired samples of patient normal-appearing skin. Our results demonstrate that loss of TSC2 in dermal fibroblasts is associated with increased galectin-3 and suggest that this molecule should be investigated as a biomarker for TSC and possibly other diseases associated with increased mTORC1 activation.

A subtle case of tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is known to cause severe intractable epilepsy and mental retardation; however, diagnosis can be delayed in milder cases. We report a 26-year-old right-handed female patient who started having convulsions at age 7 days. She had several focal seizures per year that were intractable to treatment with carbamazepine or phenytoin. Her two sisters had several episodes of suspected epileptic seizures but had no symptoms related to TSC. Seizure semiology of the patient comprised of visual hallucination, loss of consciousness, and convulsive movements predominantly on the right. Physical examination revealed several small scattered angiofibromas over the nose that were histologically determined by skin biopsy. Hypomelanotic macules, shagreen patches, or periungual fibromas were not seen. Neurological examination showed mental retardation (MMSE: 23/30, WAIS-III: VIQ63, PIQ59, FIQ58) and decreased vibration sensation in both legs. Interictal EEG showed slow waves and epileptiform discharges broadly over the anterior quadrants bilaterally. Brain imaging showed multiple cortical tubers and malformation of cortical development but no subependymal nodules. Interictal IMP-SPECT showed hypoperfusion in the left frontal lobe. Cardiac rhabdomyoma was not noticed by cardiac echography. Truncal CT showed sclerosis of the bilateral lumbosacral joints. There was no abnormality in the lung, major arteries, liver, or kidneys. No hamartomas or retinal achromic patches were noticed by ophthalmologic evaluation. Administration of lamotrigine was effective for her seizures. This patient fulfilled two major features of diagnostic criteria for TSC and was diagnosed as definite TSC. Patients with mental retardation and epilepsy should be carefully evaluated for the possible diagnosis of TSC.

Tuberous sclerosis with giant internal carotid artery aneurysm resulting left third nerve palsy: A case report

Tuberous sclerosis is an autosomal dominant hereditary condition with many varied forms of clinical presentation. The most frequent cutaneous findings in tuberous sclerosis include multiple angiofibromas, hypopigmented macules, periungual fibromas and shagreen patch. It is characterized by the development of hamartomatous growths in many organs. We present a case of tuberous sclerosis with a giant left internal carotid artery aneurysm causing pulsatile proptosis, left sided ptosis, anisocoria and papillary mydriasis indicative of left third cranial nerve palsy. DOI: http://dx.doi.org/10.3329/bmj.v43i2.21393 Bangladesh Med J. 2014 May; 43 (2): 103-105

TREATMENT OF FACIAL ANGIOFIBROMAS OF TUBEROUS SCLEROSIS WİTH RADIOFREQUENCY DESSICATION AND COAGULATION

Tuberous sclerosis is an autosomal dominant neurocutaneous disorder with an incidence of approximately 7/100 000. Inheritance is autosomal dominant, but up to 70% of cases are new mutations. Tuberous sclerosis is mainly characterized by a triad of epilepsy, learning difficulties and skin lesions including angiofibromas, hypopigmented macules, connective tissue naevi and periungual fibromas. Angiofibromas are a common presentation of tuberous sclerosis. They cause considerable cosmetic and hygienic morbidity for patients. Treatments of angiofibromas have included curettage, cryosurgery, chemical peeling, dermabrasion, shave excision, lasers and 13-cis retinoic acid. Traditional methods of treating angiofibromas are not entirely successful as they frequently lead to scarring and pigmentary changes. We report the successful use of radiofrequency dessication and coagulation in treating multiple angiofibromas of four patients. The technique is easy to use and very cost effective. Key words: tuberous sclerosis, angiofibroma, ambulatory surgical procedures. Cite this article : Ulas Guvenc, Anil Gunsel Bahali, Umit Tursen, Tamer Irfan Kaya, Guliz Ikizoglu, Erdinc Terzi. Treatment of facial angiofibromas of tuberous sclerosis with radiofrequency dessication and coagulation. RoJCED 2017;3(4):182-185 https://doi.org/10.26574/rojced.2017.4.3.182

Tuberous Sclerosis in Pregnancy

Tuberous sclerosis is an autosomal dominant neurocutaenous disorder or neuroectodermatosis affecting multiple organ systems with variable clinical manifestations. We are reporting a case of a 26 years old female with history of epilepsy with mental retardation presented with fever and convulsions following an episode of stillbirth on first time with normal fetal outcome on second time. She had facial angiofibromas, shagreen patch, ash-leaf macules, periungual and subungual fibromas. She also had bilateral renal angiomyolipomas with haemorrhages and sub ependymal cortical tubers in brain. We report such a unique case having all clinically diagnostic physical sings of tuberous sclerosis with complicated obstetric history.

Ventriculomegaly and Intracranial Masses

A newborn presents with ventriculomegaly and multiple intracranial masses. (Figure 1) Figure 1. Figure 2. ### Prenatal and Birth Histories ### Presentation The infant was active and fed well for the first 48 hours after birth. Postnatal head ultrasonography was performed again because of prenatally diagnosed bilateral ventriculomegaly. Ultrasonography revealed 2 periventricular or intraventricular solid masses and dilatation of the occipital horn, primarily of the left lateral ventricle. Magnetic resonance imaging of the brain revealed multiple intracranial masses and cortical enhancing lesions. The infant was transferred to our neonatal intensive care unit 3 days after birth for further care and monitoring. ### Vital Signs

Coexistence of tuberous sclerosis complex and malignant melanoma

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder characterised by widespread hamartomas in organs such as the skin, brain, heart, lung, liver and kidney. Although associations of TSC with hamartomas, angiomyolipomas and fibromas have been reported, there has been no report of its association with malignant melanoma. Herein, we describe a 31-year-old man with malignant melanoma associated with TSC. The patient had a history of epilepsia, multiple hypomelanotic macules, periungual fibromas and multiple hepatic lesions. Malignant melanoma was diagnosed by hepatic biopsy. To the best of our knowledge, this is the first report of malignant melanoma coexisting with TSC in the literature. We also present and discuss the imaging findings, prognosis, underlying mechanisms and practical approaches in relation to the disease.

Abstract 5510: Tranilast inhibits growth of skin tumor cells in a xenograft mouse model of tuberous sclerosis complex.

Abstract Pharmacological approaches for treating tumors in patients with tuberous sclerosis complex (TSC) are inadequate. Although mTORC1 inhibitors such as rapamycin represent a major new avenue for treatment, we and others have shown that rapamycin improves but does not eradicate TSC skin tumors. We tested the effects of tranilast, an antiallergic and antifibrotic drug with antiproliferative effects, on fibroblasts grown from angiofibromas, forehead plaques, periungual fibromas, and normal-appearing skin from 5 patients with TSC. Tumor cells showed loss of TSC2 expression and hyperactivation of the mTORC1 signaling pathway. Tranilast (5, 10, 20, 40 μM) inhibited the viability of TSC skin tumor cells from five patients in an MTT assay. These effects on cell viability appeared to be independent of mTORC1 activity, since tranilast did not inhibit phosphorylation of ribosomal protein S6. Four paired samples of RNA from tumor and normal cells, treated with or without tranilast, were studied using gene expression arrays, revealing that tranilast significantly altered the expression of at least 36 genes, of which 12 are involved in transcription. In a xenograft model in which dermal-epidermal constructs comprising normal human keratinocytes with either TSC angiofibroma cells or TSC normal fibroblasts from a TSC patient were grafted to nude mice (6-8 mice per group), tranilast treatment (300 mg/kg/day) reduced the number of skin tumor cells compared to vehicle control group (P< 0.05). Tranilast treatment did not block angiogenesis or lymphangiogenesis in the xenograft model. These results indicate that tranilast has antiproliferative effects independent of mTORC1 and suggest that tranilast may be useful as an adjunctive agent for the treatment of TSC skin tumors. Citation Format: Shaowei Li, Ji-an Wang, Rajesh L. Thangapazham, Peter Klover, Joel Moss, Thomas N. Darling. Tranilast inhibits growth of skin tumor cells in a xenograft mouse model of tuberous sclerosis complex. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5510. doi:10.1158/1538-7445.AM2013-5510

TS or not TS?

A 47-year-old woman had first presented in her late twenties with complex partial seizures and became seizure-free on carbamazepine. She re-presented 13 years later with migrainous headaches. MR scan of...

Angiofibromas with multiple epidermoid cysts in tuberous sclerosis: new mutation or post‐traumatic?

Tuberous sclerosis is a genetic multisystem disorder characterized by widespread hamartomas in several organs. Clinically, more than 90% of affected patients have skin lesions including facial angiofibromas, periungual fibromas, hypomelanotic macule, etc. Periungual fibroma is one of the major diagnostic criteria of tuberous sclerosis and has the same pathology (angiofibroma) as the facial papules. We herein describe an interesting histologic variant of angiofibromas coupled with multiple epidermoid cysts in a 33-year-old patient with tuberous sclerosis.

Unilateral multiple facial angiofibromas: A case report with brief review of literature

Tuberous sclerosis (TSC) is an autosomal dominant hereditary condition with many varied forms of clinical presentation. The most frequent cutaneous findings in TSC include multiple angiofibromas, hypopigmented macules, periungual fibromas, and shagreen patch. Rarely, unilateral multiple facial angiofibromas have been reported. We report a case of unilateral multiple facial angiofibromas without any other manifestations of TSC. Although rare, unilateral multiple facial angiofibromas may be a mosaic form of TSC.