Association between a high-expressing interferon-gamma allele and a lower frequency of kidney angiomyolipomas in TSC2 patients.
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Tuberous sclerosis complex (TSC) is a familial hamartoma syndrome in which renal involvement is common and, at times, life threatening. We have investigated the potential effect of a non-TSC gene on renal disease in a cohort of 172 TSC patients with TSC2 mutations. Patients were genotyped for an interferon-gamma (IFN-gamma) microsatellite polymorphism, within intron 1, for which one common allele (allele 2, with 12 CA repeats) has been shown to have a higher expression of IFN-gamma. A chi(2) analysis was used to examine the association between IFN-gamma allele 2 and the development of kidney angiomyolipomas (KAMLs) in this TSC2 cohort. Because of the age-dependent development of KAMLs in TSC, we initially focused on the 127 patients who were >5 years old. Additional subgroup analyses were done to investigate the influence of age and gender. The transmission/disequilibrium test (TDT) was also performed in a subset of this cohort (46 probands) for whom parent and/or sibling samples were available for analysis. Both chi(2) analysis and TDT suggested an association between IFN-gamma allele 2 and the absence of KAMLs in patients who have known TSC2 mutations. Among the 127 patients who were >5 years old, KAMLs were present in 95 (75%) and were absent in 32 (25%). In the group with KAML present, the frequency of IFN-gamma allele 2 was 56%; in the group with KAML absent, the frequency of IFN-gamma allele 2 was significantly higher, at 78% (P=.02, by chi(2) analysis). The family-based TDT analysis gave similar results, with a TDT statistic (TDT chi2=5.45) corresponding to a P value of.02. Subgroup analyses show that both age and gender may influence the impact of this association. Although these results should be replicated in other populations with TSC, the present study suggests that modifier genes play a role in the variable expression of TSC and also suggests a potential therapy for KAMLs in patients with TSC. (+info)
Renal angiomyolipomas from patients with sporadic lymphangiomyomatosis contain both neoplastic and non-neoplastic vascular structures.
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Renal angiomyolipomas are highly vascular tumors that occur sporadically, in women with pulmonary lymphangiomyomatosis (LAM), and in tuberous sclerosis complex (TSC). The goal of this study was to determine whether the distinctive vessels of angiomyolipomas are neoplastic or reactive. We studied angiomyolipomas with loss of heterozygosity (LOH) in the TSC2 region of chromosome 16p13 from patients with LAM. We found that angiomyolipomas contain five morphologically distinct vessel types: cellular, collagenous, hemangiopericytic, glomeruloid, and aneurysmatic. Using laser capture microdissection, we determined that four of the vessel types have TSC2 LOH and are therefore neoplastic. One vessel type, collagenous vessels, did not have LOH, and is presumably reactive. Recently, activation of S6 Kinase and its target S6 ribosomal protein (S6) was demonstrated in cells lacking TSC2 expression. We found that angiomyolipoma vessel types in which LOH were detected were immunoreactive with anti-phospho-S6 antibodies. Angiomyolipoma cells without LOH, including the endothelial component of the vessels, were not immunoreactive. To our knowledge, angiomyolipomas are the first benign vascular tumor in which the vascular cells, rather than the stromal cells, have been found to be neoplastic. Angiomyolipomas appear to reflect novel vascular mechanisms that may be the result of activation of cellular pathways involving S6 Kinase. (+info)
Association of angiomyolipoma and oncocytoma of the kidney: a case report and review of the literature.
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AIM: The association between renal carcinoma and angiomyolipoma is rare. Only 14 cases have been reported in the literature. The purpose of this paper is to present an additional case and review the literature on this association. PATIENT AND METHODS: A healthy 42 year old woman was found to have a left flank mass incidentally when she presented for a Papanicolaou smear. The computerised tomography scan revealed a left lower pole renal mass consistent with a renal cell carcinoma. A nephrectomy was performed and the patient recovered uneventfully. The nephrectomy specimen was processed routinely. In addition to haematoxylin and eosin staining, immunohistochemistry for CAM 5.2, vimentin, CD34, antismooth muscle actin, and HMB45 was carried out. Transmission electron microscopy was also performed. RESULTS: Macroscopically, the lower pole of the kidney contained a well circumscribed, non-encapsulated, tan coloured tumour with a large area of central haemorrhage measuring 10.5 cm. In addition, there was a 0.4 cm poorly circumscribed unencapsulated yellow nodule adjacent to the tumour. Microscopically, the larger tumour showed characteristic features of an oncocytoma. Numerous mitochondria were seen on electron microscopy. The smaller yellow nodule was an angiomyolipoma. CONCLUSIONS: This paper presents an additional case of oncocytoma associated with angiomyolipoma. Of the 15 cases described in the literature, three were associated with the tuberous sclerosis complex, all from a single study. In tuberous sclerosis, angiomyolipomas are more commonly associated with renal cell carcinoma. If angiomyolipomas are found incidentally in nephrectomy specimens together with other tumours, it is important to exclude tuberous sclerosis retrospectively. (+info)
Bilateral giant renal angiomyolipoma associated with hepatic lipoma in a patient with tuberous sclerosis.
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OBJECTIVE: To report a case of bilateral giant renal angiomyolipoma associated with tuberous sclerosis, with successful treatment, and to review the literature concerning angiomyolipoma treatment. CASE REPORT: Patient with tuberous sclerosis and angiomyolipoma diagnosed by ultrasonography during her pregnancy. At that time, the angiomyolipoma on the right side was 9 cm in diameter. Conservative management was selected during her pregnancy. The patient returned 7 years later, with a 24.7 x 19.2 x 10.7 cm tumor on the right side and another of 13 x 11.5 x 6.5 cm on the left side, in addition to multiple small angiomyolipomas. A nephron-sparing surgery with tumoral enucleation was performed on the right side, and after 3 months, the tumor on the left side was removed. Renal function in the post-operative period was preserved, and contrast medium progression was uniform and adequate in both kidneys. CONCLUSION: We conclude that an angiomyolipoma larger than 4 cm should be removed surgically, since they have a greater growth rate and pose a risk of hemorrhage. Resection of smaller tumors is safe and has decreased morbidity. Tumoral enucleation is an effective treatment method that preserves kidney function. (+info)
Diagnosis and treatment of hepatic angiomyolipoma in 26 cases.
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AIM: To summarize the experience of the diagnosis and treatment of hepatic angiomyolipoma (HAML). METHODS: The clinical, imaging and pathological features, and treatment strategies of 26 patients with HAML treated at the authors' institute between October 1998 and January 2003 were retrospectively analyzed. All the patients received liver resection and were followed up till the study. Immunohistochemical assays were performed with a panel of antibodies. RESULTS: There was an obvious female predominance (21:5), and most of the patients (18/26) had no symptoms. Heterogeneous high echo was found in ultrasonography and punctiform or filiform vascular distribution pattern was found in color Doppler-sonography in most of the lesions (21/26). All of the 5 lesions further enhanced with Levovist showed early and prolonged enhancement. At contrast-enhanced spiral CT, the soft-tissue components of 24 lesions were markedly enhanced in the arterial phase and 18 lesions remained enhanced in the portal venous phase. MRI was performed in 9 patients, and showed hypointensity or hyperintensity on T1-weighted images and heterogeneous hyperintensity on T2-weighted images. Histopathologically, all lesions were composed of adipose tissues, smooth muscle and blood vessels with different proportions. Most lesions showed positive immunohistochemical staining for HMB45 (26/26), A103 (24/26) and SMA (24/26). All of the 26 patients showed a benign course with no sign of recurrence. CONCLUSION: Preoperative radiological diagnosis of HAML is possible. The demonstration of intratumoral fat and central vessels is helpful in the diagnosis. HMB45, A103 and SMA are promising markers for pathologic diagnosis of HAML, and surgical resection is effective for the treatment of HAML. (+info)
Estradiol and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways.
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Lymphangioleiomyomatosis (LAM) is a progressive lung disease affecting almost exclusively women. The reasons for this strong gender predisposition are poorly understood. Renal angiomyolipomas occur in 50-60% of sporadic LAM patients. The smooth muscle cells of pulmonary LAM and renal angiomyolipomas are nearly indistinguishable morphologically. Here, we report the first successful cell culture of a LAM-associated renal angiomyolipoma. The cells carried inactivating mutations in both alleles of the TSC2 gene and expressed estrogen receptor , estrogen receptor , and androgen receptor. To elucidate the cellular pathways through which steroid hormones influence LAM pathogenesis, we treated the cells with both estradiol and tamoxifen. Cell growth was stimulated by estradiol, associated with phosphorylation of p44/42 MAPK at 5 min and an increase in c-myc expression at 4 h. Tamoxifen citrate also stimulated cell growth, associated with increased phosphorylation of p44/42 MAPK and expression of c-myc, indicating that tamoxifen has agonist effects on angiomyolipoma cells. This response to tamoxifen in human angiomyolipoma cells differs from prior studies of Eker rat leiomyoma cells, possibly reflecting cell type or species differences in cells lacking tuberin. Our data provide the first evidence that estradiol stimulates the growth of angiomyolipoma cells, that tamoxifen has agonist effects in angiomyolipoma cells, and that estradiol and tamoxifen impact both genomic and nongenomic signaling pathways in angiomyolipoma cells. The responsiveness of angiomyolipoma cells to estradiol may be related to the underlying reasons that LAM affects primarily women. (+info)
Renal angiomyolipoma with lymph node involvement: a case report and literature review.
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Renal angiomyolipomas (AMLs) are relatively common tumors containing fatty tissue, blood vessels, and muscular cells in various proportions. Typical AMLs can be diagnosed without histological confirmation by a combination of ultrasound and computed tomography imaging in up to 95% of cases. In contrast, simultaneous involvement of the kidney, renal vein, or lymph nodes is uncommon and might be confused with a metastasizing malignant tumor. We present a pathologically proven case of the very uncommon simultaneous involvement of the kidney and the lymph nodes in AML. (+info)
Juxta-caval hepatic angiomyolipoma masquerading as hepatocellular carcinoma.
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Hepatic angiomyolipoma is an uncommon primary benign epithelial liver neoplasm. Most patients with angiomyolipomas are middle-aged women who commonly present with epigastric fullness or pain. Angiomyolipomas are tumors consisting of three tissue types: blood vessels, smooth muscle, and fat. Hepatic angiomyolipomas may be difficult to differentiate from other liver neoplasms by noninvasive imaging. We report a 58-year-old asymptomatic woman with a mass in the right lobe of the liver, found incidentally on routine abdominal sonography. Preoperative radiographic evaluation revealed a 6.5-cm hypervascular lesion abutting the inferior vena cava. Preoperative histologic study demonstrated an epithelial neoplasm suspicious for hepatocellular carcinoma. Metastatic workup was negative. At resection, the tumor was found to be an angiomyolipoma composed of lipoid, vascular and smooth muscle cells. Further staining was positive for HMB-45. Resection margins were negative. The woman had an uneventful recovery and was discharged on postoperative day seven. She currently remains well several months after her right hepatectomy. (+info)