1.Translational Medicine Branch, NHLBI, NIH, Building 10, Room 6D05, MSC 1590, Bethesda, Maryland 20892-1590, USA
Radiologic Imaging: Retroperitoneal lymphangioleiomyomas have a distinctive radiologic appearance (Figures 3-7), and diurnal variation in size of the tumor masses can be demonstrated by ultrasonography or computed tomography scans (Figure 8). Lymphangioleiomyomas are well characterized by either ultrasonography or computed tomography scanning, appearing as well-circumscribed lobular, thin or thick-walled masses without evidence of necrosis or hemorrhage. Masses greater than 3 cm in diameter are usually cystic in appearance and many contain fluid, presumably chyle. Lesions as large as 20 cm in diameter have been observed. In patients with LAM, the lesions most often occur in the retroperitoneal region.
Sirolimus: The TSC1 and TSC2 genes encode respectively, hamartin and tuberin. Although Hamartin and tuberin may have individual functions, they are also known to interact in a cytosolic complex. Hamartin may play a role in the reorganization of the actin cytoskeleton. Tuberin has roles in pathways controlling cell growth and proliferation. It is a negative regulator of cell cycle progression, and loss of tuberin function shortens the G1 phase of the cell cycle. Tuberin binds p27KIP1, a cyclin-dependent kinase inhibitor, thereby preventing its degradation and leading to inhibition of the cell cycle. Tuberin also integrates signals from growth factors and energy stores through its interaction with mTOR (mammalian target of rapamycin). Tuberin has Rheb GAP (Ras homolog enriched in brain GTPase-activating protein) activity, which converts active Rheb-GTP to inactive Rheb-GDP. Rheb regulates mTOR, a serine/threonine kinase that phosphorylates at least two substrates: 4E-BP1, allowing cap-dependent translation, and S6K1, leading to translation of 5 TOP (terminal oligopyrimidine tract)-containing RNAs. Phosphorylation of tuberin by Akt, which is activated by growth factors, leads to inhibition of tuberin, resulting in cell growth and proliferation. Phosphorylation of tuberin by AMPK (AMP-activated kinase) activates tuberin and further promotes inhibition of cell growth in conditions of energy deprivation. Sirolimus, an inmmunosuppressive agent, inactivates mTOR. Sirolimus has been shown to induce apoptosis of tumors in rodents and decrease the size of renal angiomyolipomas in patients with lymphangioleiomyomatosis or TSC. Further, sirolimus was effective in decreasing the size of chylous effusions and lymphangioleiomyomas in one patient with LAM and improved chylous effusions in another patient who underwent lung transplantation.
Connie G Glasgow ; Angelo M Taveira-DaSilva ; Joel Moss
Soft Tissues: Lymphangioleiomyoma
Atlas Genet Cytogenet Oncol Haematol. 2009-04-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5868/soft-tissues-lymphangioleiomyoma