Angiomyolipoma In Tuberous Sclerosis Research Articles

Large renal angiomyolipomas in tuberous sclerosis

Large renal angiomyolipomas in tuberous sclerosis

Ангиомиолипомы почек у детей при туберозном склерозе — современное состояние проблемы

Tuberous sclerosis is a rare multisystem disease with autosomal dominant inheritance, characterized by the formation of hamartomas in many organs and tissues, including skin, brain, kidneys, lungs and heart, with a variety of clinical manifestations. One of the largest problems in patients with tuberous sclerosis is renal angiomyolipomas, which are the most common manifestation of the disease. An important point in the course of tuberous sclerosis with kidney damage is the formation of secondary complications that occur against the background of the underlying disease. The present review shows the relevance of the problem of angiomyolipomas in tuberous sclerosis, considers the pathogenesis of the disease, and presents the basic principles of treatment.

Angiomyolipoma in Tuberous Sclerosis

Angiomyolipoma in Tuberous Sclerosis

Bilateral renal angiomyolipomas in tuberous sclerosis

BackgroundTuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign hamartomas in multiple organs of the body. Renal angiomyolipomas (AML) are commonly associated with TSC. They are mostly asymptomatic. But large and rapidly growing AMLs with the presence of an aneurysm cause symptoms and pose a life-threatening risk for hemorrhage.Case presentationOur patient is a 25-year-old female who presented to us as an undiagnosed case of tuberous sclerosis having a large abdominal mass. She fulfilled the clinical criteria required for the diagnosis of TSC. The CT scan revealed an 18 × 13 × 33 cm fat-containing lesion in the right kidney with an adjacent aneurysm measuring around 16 cm in diameter. Due to the large size of the AML and associated aneurysm, surgical exploration was mandated. On the contralateral kidney, multiple contrast-enhancing soft-tissue densities were present that appeared suspicious on radiology. So a percutaneous biopsy of those lesions was done. Fortunately, it had the same histopathology as an Angiomyolipoma. Nephrectomy of the right-sided kidney with AML has been done. The left-sided lesions that are less than 2 cm and asymptomatic are kept on close surveillance. Any change in size will prompt therapy with mTOR inhibitors.ConclusionWhen dealing with bilateral renal AML, it is important to adopt a conservative approach. When intervention is indicated, the least invasive strategy should be sought and enacted. Radical surgery should be the last resort.

Late Recurrence of Metastatic Pancreatic Angiomyolipoma in Tuberous Sclerosis Following Bilateral Nephrectomy and Transplant

ABSTRACTRecurrent angiomyolipomas are rare, particularly in the pancreas of patients with tuberous sclerosis (TSC). We report a 59-year-old woman with TSC who underwent bilateral nephrectomy for malignant, hemorrhagic angiomyolipomas with subsequent renal transplant. Almost 10 years after initial discovery of renal angiomyolipoma, the patient was found to have a pancreatic tail angiomyolipoma on endoscopic ultrasound performed for the evaluation of abnormal liver enzymes. The mass was not visualized on previous imaging. This case highlights the possible role of endoscopic ultrasound in continued surveillance for recurrent angiomyolipoma after nephrectomy in patients with TSC.

1387 Late Recurrence of Metastatic Pancreatic Angiomyolipoma in Tuberous Sclerosis Following Bilateral Nephrectomy and Transplant

INTRODUCTION: Angiomyolipomas are typically benign tumors often associated with tuberous sclerosis, most commonly occurring in the kidneys. Some variants have malignant potential. Surgical resection remains the most effective form of treatment; however, recurrence after nephrectomy is rare, especially in the pancreas. CASE DESCRIPTION/METHODS: We report a unique case of a 59-year-old female with tuberous sclerosis who underwent bilateral nephrectomy for malignant, hemorrhagic angiomyolipomas with subsequent renal transplant. Almost 10 years after initial discovery of renal angiomyolipoma, patient presented to gastroenterology clinic with elevated liver function tests and was subsequently referred for endoscopic ultrasound (EUS) to evaluate for biliary obstruction as the etiology. If no obstruction was found, an EUS guided liver biopsy was requested. The EUS showed a normal non-dilated common bile duct (CBD) with no evidence of obstruction. EUS guided liver biopsy was then performed using a 19G core biopsy needle. Incidentally, she was found to have pancreatic tail mass lesion which measured 13 mm in diameter. This was not visualized on her previous surveillance CT scans. EUS fine needle aspiration was performed on the pancreatic tail mass with a 25G needle. The liver biopsy showed mild iron overload and minimal macrovesicular steatosis. The cytology from the pancreatic lesion was reported as an angiomyolipoma. The patient was subsequently referred to surgical oncology for evaluation of distal pancreatectomy. DISCUSSION: This is the second reported case of a pancreatic angiomyolipoma in a tuberous sclerosis patient, however guidelines on surveillance are lacking. Radiological imaging has not been an effective form of detecting pancreatic angiomyolipomas. This case highlights the importance of continued surveillance, and the possible role of EUS in that surveillance, for recurrent angiomyolipoma following nephrectomy in patients with tuberous sclerosis.

Abnormal Neural Progenitor Cells Differentiated from Induced Pluripotent Stem Cells Partially Mimicked Development of TSC2 Neurological Abnormalities.

SummaryTuberous sclerosis complex (TSC) is a disease featuring devastating and therapeutically challenging neurological abnormalities. However, there is a lack of specific neural progenitor cell models for TSC. Here, the pathology of TSC was studied using primitive neural stem cells (pNSCs) from a patient presenting a c.1444-2A>C mutation in TSC2. We found that TSC2 pNSCs had higher proliferative activity and increased PAX6 expression compared with those of control pNSCs. Neurons differentiated from TSC2 pNSCs showed enlargement of the soma, perturbed neurite outgrowth, and abnormal connections among cells. TSC2 astrocytes had increased saturation density and higher proliferative activity. Moreover, the activity of the mTOR pathway was enhanced in pNSCs and induced in neurons and astrocytes. Thus, our results suggested that TSC2 heterozygosity caused neurological malformations in pNSCs, indicating that its heterozygosity might be sufficient for the development of neurological abnormalities in patients.

Renal angiomyolipomas in tuberous sclerosis

Renal angiomyolipomas in tuberous sclerosis

Angiographic and volumetric effects of mammalian target of rapamycin inhibitors on angiomyolipomas in tuberous sclerosis.

To investigate the angiographic and volumetric effects of mammalian target of rapamycin (mTOR) inhibitors on angiomyolipomas (AMLs) in a case series of patients with tuberous sclerosis complex. All patients who underwent catheter angiography prior to and following mTOR inhibitor therapy (n = 3) were evaluated. All cross-sectional imaging studies were analyzed with three-dimensional volumetrics, and tumor volume curves for all three tissue compartments (soft tissue, vascular, and fat) were generated. Segmentation analysis tools were used to automatically create a region of interest (ROI) circumscribing the AML. On magnetic resonance images, the "fat only" map calculated from the in- and opposed-phase gradient recalled echo sequences was used to quantify fat volume within tumors. Tumor vascularity was measured by applying a thresholding tool within the ROI on post-contrast subtraction images. On computed tomography images, volume histogram analysis of Hounsfield unit was performed to quantify tumor tissue composition. The angiography procedures were also reviewed, and tumor vascularity based on pre-embolization angiography was characterized in a semi-quantitative manner. Patient 1 presented at the age of 15 with a 6.8 cm right lower pole AML and a 4.0 cm right upper pole AML. Embolization was performed of both tumors, and after a few years of size control, the tumors began to grow, and the patient was initiated on mTOR inhibitor therapy. There was an immediate reduction in the size of both lesions. The patient then underwent repeat embolization and discontinuation of mTOR inhibition, after which point there was a substantial regrowth in both tumors across all tissue compartments. Patient 2 presented at the age of 18 with a right renal AML. Following a brief period of tumor reduction after embolization, she was initiated on mTOR inhibitor therapy, with successful reduction in tumor size across all tissue compartments. As with patient 1, however, there was immediate rebound growth following discontinuation of inhibitor therapy, without sustained control despite repeat embolization. patient 3 presented at the age of 5 with a left renal AML and underwent two embolization procedures without lasting effect prior to starting mTOR inhibition. As with patients 1 and 2, following discontinuation of therapy, there was immediate rebound growth of the tumor. Repeat embolization, however, was notable for a substantial reduction in intratumoral aneurysms and vascularity. AML volume reduction as well as post-treatment rebound growth due to mTOR inhibitors involves all three tissue components of the tumor.

Assessing the effectiveness of rapamycin on angiomyolipoma in tuberous sclerosis: a two years trial

BackgroundTuberous sclerosis (TS) is a rare autosomal dominant systemic disease with an estimated prevalence of 1/6000. Renal angiomyolipoma (AML) is a benign tumour with high morbidity frequently present in TS. The aim of the study was to test the effect of rapamycin in reducing the volume of AML in TS.MethodsTwenty four-month prospective open-label, single arm, unicentre Phases II andIII study. The primary endpoint was to evaluate the effect of treatment on the reduction of at least 50% AML volume from baseline at 24 months. The secondary endpoints were: average tumour reduction, surgical complications, skin lesions and drug safety.The study population comprised 17 patients, aged >10 years who were diagnosed with TS and had ≥1 renal AML >2 cm of diameter and had a serum creatinine < 2mg/dl and urine protein/creatinine ratio < 22.6 mg/mmol. The trial was conducted at Fundació Puigvert. Rapamycin was given to achieve stable plasma levels between 4 and 8 ng/ml. AML volume was estimated using orthogonal measurements by MRI at baseline, 6, 12 and 24 months.ResultsTen out of 17 patients were success responders for the main outcome −58.8%, 95%CI: 32.9% to 81.6%-. After 6 months of therapy, the mean volume decrease was 55.18% (5.01 standard error (SE); p<0.001) and 66.38% (4.41 SE; p<0.001) at year 1. There was no significant decrease between year 1 and 2. According to RECIST criteria, all patients achieved a partial response at year 1 and all but two had already achieved this partial response after 6 months.The main analysis was performed according to the intention-to-treat principle analysis. Tumour volume was analyzed over time by means of mixed models for repeated measurement analysis. We used the baseline tumour volume as a covariate for the absolute change and percentage change from baseline data. The analysis was performed using SAS version 9.2 software, and the level of significance was established at 0.05 (two-sided).ConclusionsThis study show that mTOR inhibitors are a relatively safe, efficacious and less aggressive alternative than currently available options in the management of AML in TS.Trial registrationEudraCT number: 2007-005978-30, ClinicalTrials.gov number: NCT0121712

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.

A giant aneurysm arising from renal angiomyolipoma in tuberous sclerosis

Angiomyolipomas are found in 40% patients with tuberous sclerosis; such lesions tend to bleed because of their hypervascularity and the presence of small aneurysms. Very large macroaneurysms are rarely seen...

Metastatic Breast Carcinoma to Renal Angiomyolipomas in Tuberous Sclerosis

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease manifesting as hamartomatous involvement of several organs, including brain, kidneys, skin, heart, lungs, and retina. We report the first case of a patient with TSC, with large bilateral renal angiomyolipomas (AML), who developed multiple soft tissue masses within her primarily fatty AMLs, resulting from metastatic breast cancer.

Wunderlich′s syndrome with hepatic angiomyolipoma in tuberous sclerosis

We present a patient of tuberous sclerosis complex with bilateral renal angiomyolipoma and hepatic angiomyolipoma with spontaneous retroperitoneal hemorrhage from right angiomyolipoma (Wunderlich's syndrome). Nephron preserving approach was tried but the right kidney could not be salvaged. Hepatic angiomyolipoma was managed conservatively. Wunderlich's syndrome has been found in around 10% of cases of renal angiomyolipomas. Hepatic Angiomyolipoma is a benign mesenchymal neoplasm of the liver which is rarely reported in literature.

Pseudoaneurysm After Spontaneous Rupture of Renal Angiomyolipoma in Tuberous Sclerosis: Successful Treatment with Percutaneous Thrombin Injection

We report a case of a large perinephric pseudoaneurysm due to spontaneous rupture of renal angiomyolipoma, occluded by percutaneous thrombin injection under ultrasound guidance in a young woman affected by tuberous sclerosis.

Massive renal angiomyolipoma in tuberous sclerosis

A massive renal angiomyolipoma, measuring 45 × 20 × 15 cm and weighing 3,500 g in a patient with tuberous sclerosis is presented. While renal angiomyolipomas may become quite large, this is one of the largest such tumors ever reported.

Hepatic angiomyolipoma: is fat in the liver friend or foe?

Angiomyolipoma (AML) of the liver is a very uncommon benign neoplasm composed of vessels, muscle, and variable amounts of fat (ranging from 5-90% of the tumor), indistinguishable histologically from renal angiomyolipoma [1]. For the majority of radiologists, knowledge of AML is based upon the renal variety. The radiologic appearance of AML in the kidney, its association with tuberous sclerosis, and its potential for rupture, causing massive retroperitoneal hemorrhage, are well known. However, the fact that AML can involve the liver either in association with tuberous sclerosis or spontaneously is not common knowledge. This is due to the rarity of hepatic AML, limited to only 5-10% of tuberous sclerosis cases and a few cases of spontaneous AML reported (approximately 45, primarily in the pathologic literature). The five papers on hepatic AML included in the current issue of Abdominal Imaging allow us to study with cross-sectional imaging a series of eight new cases, including six spontaneous AMLs and two in association with tuberous sclerosis. This almost doubles the number of published cases with cross-sectional imaging from 12 to 20 and adds three new cases with magnetic resonance imaging (MRI) to a single case [2-13]. If one combines the data from these five papers, there is interesting new information both in the clinical and imaging arenas. It appears that hepatic AMLs are predominately seen in women (all four cases of spontaneous AML and two out of three AMLs in tuberous sclerosis). The clinical picture is, as expected, related to size. Large AMLs are painful, while small ones are discovered incidentally. Interestingly enough, despite the enormous size of some of the AMLs described in this issue of Abdominal Imaging, no rupture has ever been recorded of a hepatic AML. In one of the cases, a patient with tuberous scle-

Coincidental Renal Cell Carcinoma and Renal Angiomyolipomas in Tuberous Sclerosis

We report a case of bilateral renal multiple angiomyolipomas associated with renal cell carcinoma on one side in a patient with tuberous sclerosis. The difficulties in diagnosis and management of such a condition are discussed.

Evaluation of renal angiomyolipoma by traditional and modern imaging in a case of tuberous sclerosis

Renal angiomyolipoma is known to affect mainly patients with tuberous sclerosis, although it can be found in a significant number of otherwise normal individuals. Few cases have been published in which angiomyolipoma and renal cell carcinoma occurred in the same kidney. In such cases the radiologist may be asked if it is possible to distinguish between the two tumors in the same kidney. The present case report describes systemic traditional and modern imaging of huge bilateral angiomyolipoma in tuberous sclerosis. The analysis of the data implies that, although the diagnosis of angiomyolipoma can be established with noninvasive techniques only, it is impossible to distinguish between the two mentioned tumors if they coexist in the same kidney, even if all available imaging techniques are used.