How common are renal angiomyolipomas in patients with pulmonary lymphangiomyomatosis?

Bernstein, Steven M.; Newell, John D.; Adamczyk, Darcy L.; Mortenson, Rebecca L.; King, Talmadge E.; Lynch, David A.

doi:10.1164/ajrccm.152.6.8520787

Cited by 114 publications

(62 citation statements)

References 23 publications

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“…Up to 63% of women with lymphangioleiomyomatosis also have renal angiomyolipoma (3,5). Angiomyolipomas are benign tumors consisting of smooth muscle cells, fibrous tissue, adipose tissue, and abnormally formed vascular channels (6).…”

Section: Introductionmentioning

confidence: 99%

Estrogen Enhances whereas Tamoxifen Retards Development of Tsc Mouse Liver Hemangioma: A Tumor Related to Renal Angiomyolipoma and Pulmonary Lymphangioleiomyomatosis

2005

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Pulmonary lymphangioleiomyomatosis and abdominal angiomyolipoma are related lesions for which there is no authentic animal model. Both of these proliferative lesions occur in sporadic patients, and at much higher frequency in patients with tuberous sclerosis, which is due to mutations in the TSC1 and TSC2 genes. Tsc1 +/À À and Tsc2 +/À À mice frequently develop liver hemangioma. We found that the Tsc mouse liver hemangioma are composed predominantly of endothelial cells but with a smooth muscle component, and express HMB45 antigen, estrogen receptor, and progesterone receptor, similar to lymphangioleiomyomatosis and angiomyolipoma. Estrogen treatment significantly accelerated the development of liver hemangioma in Tsc1 +/ À À female mice, with 91% having liver hemangioma and 55% having severe lesions by 7 months of age. Similarly, an increased frequency and severity of liver hemangiomas was seen in Tsc1 +/ À À males treated with estrogen. In contrast, tamoxifen treatment for 9 months significantly reduced the frequency and severity of hemangiomas in Tsc1 +/ À À female mice. In addition, estrogen treatment significantly increased serum vascular endothelial growth factor levels in Tsc1 +/ À À mice, whereas tamoxifen reduced vascular endothelial growth factor levels. These mouse model observations indicate the importance of estrogen signaling in vivo for the growth of tuberous sclerosis lesions, suggesting the possible benefits of tamoxifen therapy for the treatment of angiomyolipoma and lymphangioleiomyomatosis. (Cancer Res 2005; 65(6): 2474-81)

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Section: Introductionmentioning

confidence: 99%

Estrogen Enhances whereas Tamoxifen Retards Development of Tsc Mouse Liver Hemangioma: A Tumor Related to Renal Angiomyolipoma and Pulmonary Lymphangioleiomyomatosis

2005

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“…The pathologic features of sporadic and TSC-associated pulmonary LAM are identical (10). Sixty percent of women with sporadic LAM have renal angiomyolipomas (11,12), leading to speculation that LAM and TSC are related diseases (13,14).…”

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confidence: 99%

Mutations in the tuberous sclerosis complex geneTSC2are a cause of sporadic pulmonary lymphangioleiomyomatosis

Carsillo

Astrinidis

Henske

2000

Proc. Natl. Acad. Sci. U.S.A.

598

460

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Lymphangioleiomyomatosis (LAM) is a progressive and often fatal interstitial lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. LAM is of unusual interest biologically because it affects almost exclusively young women. LAM can occur as an isolated disorder (sporadic LAM) or in association with tuberous sclerosis complex. Renal angiomyolipomas, which are found in most tuberous sclerosis patients, also occur in 60% of sporadic LAM patients. We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis. In this study, we report the identification of somatic TSC2 mutations in five of seven angiomyolipomas from sporadic LAM patients. In all four patients from whom lung tissue was available, the same mutation found in the angiomyolipoma was present in the abnormal pulmonary smooth muscle cells. In no case was the mutation present in normal kidney, morphologically normal lung, or lymphoblastoid cells. Our data demonstrate that somatic mutations in the TSC2 gene occur in the angiomyolipomas and pulmonary LAM cells of women with sporadic LAM, strongly supporting a direct role of TSC2 in the pathogenesis of this disease.

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“…But the cause and pathogenesis of LAMare not known yet. There is a significant overlap between LAM, angiomyolipoma, and the syndrome of tuberous sclerosis (14). It has been shown that the smooth muscle found in PLAMis similar histologically and immunohistochemically to that found in angiomyolipoma (1 1).…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Lymphangioleiomyomatosis; Unusual Radiological Manifestation of Multiple Large Nodules.

et al. 2002

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A 44-year-old womanwas admitted to our hospital in August 1999 for multiple large nodules detected on chest roentgenogram in an annual health check. Chest CTscans showed bilateral large nodules (>10 mmin diameter) with irregular margins and multiple thin walled cystic lesions. Fromthese radiologic examinations, we suspected pulmonary Langerhans cell histiocytosis.Histological examination of the biopsy specimen by video-assisted thoracoscopy revealed a marked proliferation of the spindle cells, which were immunologically positive for alpha-smooth muscle actin and HMB-45,in the cyst walls and lung parenchyma. The large nodules consisted of proliferation of the smooth muscle cells surrounded by a dense layer of hemosiderinladen macrophages. During the two years subsequent to these 1999 examinations, the opacities have gradually diminished and the patient was found to have pulmonary lymphangioleiomyomatosis. This case exhibited rare radiologic manifestations of multiple large nodules mimicking Langerhans cell histiocytosis. (Internal Medicine 41: 879-882, 2002)

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How common are renal angiomyolipomas in patients with pulmonary lymphangiomyomatosis?

Cited by 114 publications

References 23 publications

Estrogen Enhances whereas Tamoxifen Retards Development of Tsc Mouse Liver Hemangioma: A Tumor Related to Renal Angiomyolipoma and Pulmonary Lymphangioleiomyomatosis

Estrogen Enhances whereas Tamoxifen Retards Development of Tsc Mouse Liver Hemangioma: A Tumor Related to Renal Angiomyolipoma and Pulmonary Lymphangioleiomyomatosis

Mutations in the tuberous sclerosis complex geneTSC2are a cause of sporadic pulmonary lymphangioleiomyomatosis

Pulmonary Lymphangioleiomyomatosis; Unusual Radiological Manifestation of Multiple Large Nodules.

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