Case Of Tuberous Sclerosis Research Articles

Well-differentiated Pancreatic Neuroendocrine Carcinoma in Tuberous Sclerosis—Case Report and Review of the Literature

Neuroendocrine tumors of the pancreas are rare in children. They usually occur in the setting of genetic syndromes such as multiple endocrine neoplasia type 1, von Hippel-Lindau disease, and neurofibromatosis 1. These tumors have also been reported in the tuberous sclerosis complex (TSC), but the incidence is low in comparison with other syndromes. Only 9 cases have been described to date, and it is not yet well understood if any connection exists between TSC and pancreatic endocrine tumors. TSC is characterized by mutations in TSC1 and TSC2 genes, which activate the AKT-mTOR oncogenic cascade. Recent molecular studies in pancreatic endocrine tumors showed activation of the same pathway, which points toward a common molecular pathway between these two entities. We present a case of well-differentiated neuroendocrine carcinoma of the pancreas in a child with TSC and discuss the genetic aspects of this disease.

Massive bilateral renal angiomyolipomatosis and multifocal micronodular pneumocytes hyperplasia associated with tuberous sclerosis: A case report

Tuberous sclerosis (TS) is an autosomal-dominant disorder characterized by a variety of hamartomatous lesions in various organs. Various organ involvements can be detected with radiology: neurologic involvement (cortical tubers, subependymal nodules and white matter abnormalities), renal involvement (angiomyolipoma) and pulmonary involvement (pulmonary lymphangioleiomyomatosis, multifocal micronodular pneumocyte hyperplasia). Here, we are reporting a case of tuberous sclerosis with multiple organ involvement and massive bilateral AMLs in a 49-year-old female patient.

Wunderlich's Syndrome in a Tuberous Sclerosis Patient

Spontaneous non-traumatic renal hemorrhage known as Wunderlich's syndrome is known to occur in renal angiomyolipoma and may be the first manifestation of the disease. Angiomyolipomas in tuberous sclerosis are usually bilateral and multicentric. A 25yr old female, a case of Tuberous sclerosis with bilateral renal angiomyolipomas presented with right loin pain of increasing severity. On evaluation she had acute abdomen with increasing abdominal distension. Investigations revealed large right perinephric hematoma with bilateral renal angiomyolipomas. Exploratory laparotomy and right nephrectomy was done. Spontaneous hemorrhage in renal angiomyolipoma in a case of tuberous sclerosis and management are discussed. The online version of this article (doi:10.1007/s12262-010-0231-0) contains supplementary material, which is available to authorized users.

Tuberous sclerosis: A novel approach to diagnosis

Tuberous sclerosis or tuberous sclerosis complex is a dominantly inherited neurocutaneous disorder that variably affects the brain, skin, kidneys, heart, and other organs. Diagnosis of tuberous sclerosis becomes difficult in the young individuals with subtle changes. At this point, a careful inquiry and examination of the accessible signs and symptoms can errand a possible diagnosis. We hereby report such a rare case of tuberous sclerosis in 14-year-old boy, which was diagnosed in a novel approach.

Anévrismes intracrâniens et sclérose tubéreuse de Bourneville : une association rare

Tuberous sclerosis is an autosomal dominant inherited phakomatosis. It is associated with a wide variety of central nervous system abnormalities, but intracranial aneurysms are rare. We report a 34-year-old patient fulfilling the diagnostic criteria of tuberous sclerosis in association with intracranial aneurysm. This association has been reported in only 17 other cases of tuberous sclerosis. We discuss the etiopathogenic mechanisms, preferential localizations and the various therapeutic propositions.

Two Different Renal Cell Carcinomas and Multiple Angiomyolipomas in a Patient with Tuberous Sclerosis

We report a case of tuberous sclerosis associated with two histologically different renal cell carcinomas (RCCs) and multiple angiomyolipomas (AMLs) in the same kidney. A 43-year-old female was admitted to our hospital with left flank pain and a huge palpable mass in the left flank area. Abdominal computed tomography revealed two concurrent RCCs and multiple AMLs in the left kidney. Because of the clinical suspicion of RCC, the patient underwent left radical nephrectomy. On gross examination, the total size of the resected left kidney was 30.5×17×8 cm. Microscopically, the upper pole tumor features were consistent with chromophobe RCC and the midpole tumor was a clear-cell RCC. The multifocal masses in the remaining remnant parenchyma were AMLs. Six months after surgery, the patient is healthy without signs of tumor recurrence.

Fibrofolliculoma/trichodiscoma and fibrous papule (perifollicular fibroma/angiofibroma): a revaluation of the histopathological and immunohistochemical features

The multiple facial lesions of fibrofolliculoma (FF)/trichodiscoma (TD) and those of fibrous papule (FP; perifollicular fibroma/angiofibroma, AF) are characteristic of Birt-Hogg-Dubé (BHD) syndrome and tuberous sclerosis, respectively. However, there was a recently reported case of BHD syndrome with multiple facial FP lesions and a case of tuberous sclerosis, in which one FF lesion was included among the multiple facial FPs. The histopathological and immunohistochemical features of FF/TD and FP lesions were revaluated to study the relationship between the two. This investigation evaluated 20 FF/TD lesions including two cases of BHD syndrome and 35 FP lesions including three cases of tuberous sclerosis. There are common histopathological features in the two lesions, such as the follicular and perifollicular elements, an angiofibromatous element and stellate fibrocytes. The similar immunohistochemical features between the two lesions included the expression patterns of CD34, factor XIIIa, nestin and c-kit in the stromal cells as well as abnormal CK15 expression in the hair follicles. Both FF/TD and FP are hamartomas composed of perifollicular or interfollicular connective tissue and a hair follicular epithelial component, which may be caused by an abnormal functioning of the hair follicle bulge cells.

Expression patterns of glial fibrillary acidic protein (GFAP)‐delta in epilepsy‐associated lesional pathologies

Aims: Glial fibrillary acidic protein (GFAP)‐δ is a novel isoform that differs in its C‐terminal sequence from other GFAP isoforms. Previous studies suggest restriction of expression to the subpial layer, subventricular zone and the subgranular zone astrocytes, with an absence in pathological conditions causing reactive gliosis. GFAP‐δ is speculated to have roles in regulation of astrocyte size and motility and a subpopulation of GFAP‐δ‐positive glia may be multipotent stem cells. The aim of this study was to investigate its expression in common causes of lesion‐related refractory epilepsy. Methods: Hippocampal sclerosis (HS), focal cortical dysplasia (FCD) type IIB, cortical tuberous sclerosis (TSC) lesions, gangliogliomas, grey matter heterotopias and hemimegalencephaly from a wide age range of patients using both surgical and post mortem tissue specimens were studied. Results: GFAP‐δ expression was observed in CA4 and CA1 astrocytes in HS with less frequent labelling in the granule cell layer, even where granule cell dispersion was present. No significant labelling was noted in the subiculum in HS cases or in any subfields in non‐HS epilepsy cases. Balloon cells in FCDIIB and hemimegalencephaly, giant cells in TSC and the astrocytic component of gangliogliomas showed immunoreactivity, colocalizing with conventional GFAP. No neuronal expression for GFAP‐δ was seen in any of the pathologies. Quantitative analysis in 10 FCDIIB and five TSC cases revealed greater numbers of GFAP‐δ‐positive balloon cells than conventional GFAP. There was no GFAP‐δ expression within nodular heterotopia. Conclusions: GFAP‐δ expression patterns in HS overall appears to mirror regional reactive gliosis. It is a useful marker for the demonstration of balloon cells in FCD and TSC, which may be relevant to their abnormal size and localization. The lack of GFAP‐δ within heterotopia supports their composition from cells destined for deeper cortical layers.

Medullary Thyroid Carcinoma and Tuberous Sclerosis

Medullary thyroid carcinoma (MTC) is a rare tumor and accounts for 5-10% of thyroid cancers. Tuberous sclerosis (TS) is a complex autosomal dominant neurocutaneous syndrome. In literature, a few endocrine neoplasias have been reported in association with TS, but never a case of TS associated with sporadic MTC. We describe a unique case, which has never been reported previously, of MTC associated with TS. The MTC up to today has been associated with other endocrine neoplasia, and TS increases risk of neoplasia in various organs. The case reported shows one more circumstance and suggests thyroid screening in patients with diagnosis of TS.

27. Psychoaffective crisis as a clinical onset in one case of tuberous sclerosis

27. Psychoaffective crisis as a clinical onset in one case of tuberous sclerosis

PO16.5 A Case of Tuberous Sclerosis with Cardiac Rhabdomyoma Diagnosed by Prenatal Ultrasound

PO16.5 A Case of Tuberous Sclerosis with Cardiac Rhabdomyoma Diagnosed by Prenatal Ultrasound

Autopsy findings in a case of tuberous sclerosis

Tuberous sclerosis is a neurocutaneous disorder with autosomal dominant inheritance. It is characterized by the triad of seizures, mental retardation, angiofibromas of the face though the triad is not always complete. We incidentally encountered a case of tuberous sclerosis in a case of hanging. He was an epileptic. Autopsy findings included unusual findings of myocardial and renal lipomata. He also had cortical thickening of bones, cortical tubers of brain, polycystic kidney disease.

Multiple bilateral renal oncocytoms in a known case of tuberous sclerosis: a case report

One of the rare patterns of renal involvement by tuberous sclerosis is oncocytoma. This is a report of a known male patient diagnosed with tuberous sclerosis. He was asymptomatic, but his periodic abdominal ultrasound examination revealed bilateral renal masses. CT and MRI confirmed the presence of these masses which were proven histopathologically to be multiple oncocytomas.

Expression patterns of glial fibrillary acidic protein (GFAP)-delta in epilepsy-associated lesional pathologies.

Glial fibrillary acidic protein (GFAP)-delta is a novel isoform that differs in its C-terminal sequence from other GFAP isoforms. Previous studies suggest restriction of expression to the subpial layer, subventricular zone and the subgranular zone astrocytes, with an absence in pathological conditions causing reactive gliosis. GFAP-delta is speculated to have roles in regulation of astrocyte size and motility and a subpopulation of GFAP-delta-positive glia may be multipotent stem cells. The aim of this study was to investigate its expression in common causes of lesion-related refractory epilepsy. Hippocampal sclerosis (HS), focal cortical dysplasia (FCD) type IIB, cortical tuberous sclerosis (TSC) lesions, gangliogliomas, grey matter heterotopias and hemimegalencephaly from a wide age range of patients using both surgical and post mortem tissue specimens were studied. GFAP-delta expression was observed in CA4 and CA1 astrocytes in HS with less frequent labelling in the granule cell layer, even where granule cell dispersion was present. No significant labelling was noted in the subiculum in HS cases or in any subfields in non-HS epilepsy cases. Balloon cells in FCDIIB and hemimegalencephaly, giant cells in TSC and the astrocytic component of gangliogliomas showed immunoreactivity, colocalizing with conventional GFAP. No neuronal expression for GFAP-delta was seen in any of the pathologies. Quantitative analysis in 10 FCDIIB and five TSC cases revealed greater numbers of GFAP-delta-positive balloon cells than conventional GFAP. There was no GFAP-delta expression within nodular heterotopia. GFAP-delta expression patterns in HS overall appears to mirror regional reactive gliosis. It is a useful marker for the demonstration of balloon cells in FCD and TSC, which may be relevant to their abnormal size and localization. The lack of GFAP-delta within heterotopia supports their composition from cells destined for deeper cortical layers.

Poliosis as the First Clue of Tuberous Sclerosis

Ash leaf hypopigment macules, until now, was known as earliest signs of tuberous sclerosis, unfortunately not always visible at birth. We reported herein a case of tuberous sclerosis presented with a tuft of white hair (poliosis) at birth for recommended poliosis as a useful earliest sign for detection of tuberous sclerosis in the newborn.

Renal Angiomyolipoma: Long-term Results Following Selective Arterial Embolization

BackgroundThe treatment for and long-term outcome of renal angiomyolipoma (AML) at high-risk for bleeding has not been determined. ObjectiveTo evaluate the complication rates and the long-term outcomes among patients treated by selective arterial embolization (SAE) for a large or symptomatic renal AML. Design, setting, and participantsForty-one patients with 48 kidneys containing AML were treated by SAE at a single tertiary academic center. InterventionAll patients were treated by SAE and followed in a single center. MeasurementsSAE was performed with a mixture of 96% ethanol and polyvinyl alcohol particles. The variables used for the analysis included age, gender, presence of tuberous sclerosis (TS), and maximal tumor size prior to SAE. The study end points were recurrence of symptoms or bleeding, the need for re-embolization or surgery, and disease-specific survival. The mean follow-up period for the entire group was 4.8 yr. Results and limitationsMean patient age was 51 yr (range: 24–82), and the mean initial tumor size was 10.3cm. Successful SAE was achieved in 40 patients (91%) with a minor complication rate of 11%. Avoidance of surgery was achieved in 96% of the kidneys. No retroperitoneal hemorrhage was noted during follow-up, and 98% of the kidneys were preserved during the follow-up period. No significant changes in creatinine levels were noted following SAE (P=0.27). The freedom from surgical treatment at 5 yr following SAE was 94% (95% CI, 89–99%). Disease-specific survival of the entire cohort was 100%. The study is a retrospective, and treatment was not given according to prospective protocol, and therefore sample bias may be present. ConclusionsSAE of renal AML has long-term efficacy in preventing hemorrhagic complications of renal AML, and preservation of the involved kidneys is amenable in both TS and sporadic cases.

Gingival Enlargement as a Manifestation of Tuberous Sclerosis: Case Report and Periodontal Management

Tuberous sclerosis is an autosomal-dominant inherited disease involving many organs of the body. Oral manifestations include gingival enlargement, fibromas, and dental enamel pitting. The report presents a case of tuberous sclerosis with gingival enlargement histologically consistent with angiofibroma, describes its successful periodontal management, and reviews the literature associated with oral manifestations of tuberous sclerosis. A 26-year-old white male presented to the Department of Periodontics and Implant Dentistry, New York University College of Dentistry, with a diagnosis of tuberous sclerosis and a chief complaint of gingival enlargement affecting mastication and esthetics. Following a complete medical history review, consultation with the patient's medical team at New York University Medical Center, and a thorough oral and periodontal examination, a treatment plan was developed that included oral hygiene instructions, mechanical debridement, and periodontal reevaluation. This was followed by gingivectomy, which provided improved function and esthetics. Excised tissue was submitted for histologic examination. The patient was followed every 2 months for assessment of the outcome of the surgical treatment. An extensive search of the dental and dermatologic literature was performed on MEDLINE. Histologic examination of the gingival tissue revealed features consistent with angiofibroma. Fifteen months following gingivectomy, the contours and gingival surface appearance remained normal. The gingival enlargement was histologically consistent with the characteristic angiofibromas of tuberous sclerosis. The gingival enlargement responded very well to gingivectomy and periodontal maintenance.

Two cases of tuberous sclerosis complicated by pulmonary lesions

自20世纪70年代以来,结节性硬化症(tuberous sclerosis complex,TSC)的肺病变:淋巴管平滑肌瘤病(lymphangioleiomyomatosis,LAM)引起临床注意,早期的流行病学统计认为其发生率不足TSC患者的4％[1]。

Multifocal pneumocyte hyperplasia in tuberous sclerosis

A 29-year-old woman, a known case of tuberous sclerosis, presented to our hospital with a 1-day history of multiple episodes of convulsions. This was associated with vague chest and abdominal...

Expression of drug resistance-associated proteins in brain of patients with refractory epilepsy

To study the expression of P-glycoprotein, multi-drug resistance associated protein and major vault protein in pathologic brain specimens, and to investigate their roles in the pathogenesis of refractory epilepsy. Immunohistochemical study was performed in pathology specimens from 18 cases of refractory epilepsy (including 5 cases of focal cortical dysplasia, 3 cases of tuberous sclerosis, 5 cases of ganglioglioma and 5 cases of dysembryoplastic neuroepithelial tumor). Both the P-glycoprotein and major vault protein were localized in microvascular endothelium of the lesions. Major vault protein was also seen in balloon cells and some neuronal cells. On the other hand, multi-drug resistance associated protein was mainly localized in the neuronal component of the lesions. In general, the expression of P-glycoprotein and major vault protein in tumoral tissue was higher than that in non-tumoral tissue. The expression of multi-drug resistance associated protein and major vault protein was also different in the neoplastic glial cells of ganglioglioma and dysembryoplastic neuroepithelial tumor. P-glycoprotein, multi-drug resistance associated protein and major vault protein contribute to the pathogenesis of refractory epilepsy. They may however have different roles, with different cellular localization.