Chyloperitoneum, chylothorax and lower extremity lymphedema in woman with sporadic lymphangioleiomyomatosis successfully treated with sirolimus: A case report

Department of Internal Medicine, Wroclaw Medical University, Wroclaw, Poland.
Lymphology (Impact Factor: 1.45). 06/2012; 45(2):53-7.
Source: PubMed


Lymphangioleiomyomatosis (LAM) is a rare disease characterized by diffuse thin-walled cysts throughout the lungs on computed tomography and diffuse proliferation of abnormal smooth muscle-like cells (LAM cells) on lung biopsy. LAM affects women almost exclusively, predominantly in their reproductive age. The most typical presenting symptoms include dyspnea, spontaneous pneumothorax, cough and chylothorax. Abdominal findings represent less common initial manifestations of the disease and may pose diagnostic difficulties. The treatment of LAM has not been fully established. Recent studies report effectiveness of sirolimus in LAM patients. We report the case of a 45-year-old woman with sporadic LAM, successfully treated with sirolimus, in whom the first manifestation of the disease was chyloperitoneum and after three and nine years, respectively, lymphedema of the left lower extremity and right sided chylothorax occurred.

Download full-text


Available from: Mariusz Chabowski, Mar 02, 2014

  • Lymphatic Research and Biology 12/2012; 10(4):211-9. DOI:10.1089/lrb.2012.1042 · 1.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a key regulator of the PI3K/AKT/mTOR pathway, one of the downstream pathways activated by different intracellular mediators which control cell proliferation, differentiation, motility, survival, and metabolism. PTEN along with phosphoinositide 3-kinase makes up a regulatory hub which strictly controls the pool of the second lipid messenger, PtdIns(3,4,5)P3, an activator of the AKT/mTOR pathway. A genomic analysis of breast and other cancers revealed that this regulatory hub is vulnerable to cancer-driving mutations causing a constant activation of AKT signal. It was established that PTEN is a haploinsufficient tumor suppressor gene with one functional allele being insufficient to maintain wild-type function of PTEN which leads to cancer initiation in mice and humans. The observed PTEN dose-dependence of cancer susceptibility strongly indicates that PTEN is under strict control at both translational and post-translational levels. Haploinsufficiency at the PTEN gene is suggested to synergistically interact with post-translation inactivation of PTEN. More than 15 proteins regulate/inhibit PTEN activity through phosphorylation, ubiquitination, and acetylation via more than 15 PTEN regulatory sites. PTEN-modifier proteins form a PTEN regulatory network connecting the PI3K/AKT/mTOR pathway with multiple pathways relevant to cancer development. Heterozygous PTEN mutations were observed to cooperatively interact with genetic aberrations events in this regulatory network providing selective benefits in cancer progression. The PTEN regulatory network has been revealed to be a druggable target in cancer personalized therapy through restoration of PTEN activity in PTEN-deficient cancers.
    PTEN: Structure, Mechanisms-of-Action, Role in Cell Signaling and Regulation, Protein Science and Engineering edited by Ke Xu, 01/2013: chapter Role of Post-translational Regulation of PTEN Activity in Cancer Cell Addiction to Heterozygous PTEN Mutations: pages 173-210; Nova Publishers., ISBN: 978-1-62808-049-0
  • [Show abstract] [Hide abstract]
    ABSTRACT: PTEN's nodal role in a significant number of different metabolic pathways was revealed both by direct analysis, but also through the study of the pathologic features present in its absence. Majority of times the experiments are performed in vitro and are subjected to technical imperfections. For the PTEN mutations that result in loss of function, a specific clinical entity entitled PTEN Hamartoma Tumor Syndrome (PHTS) was described allowing in vivo study. One of the main characteristics of PHTS is the presence of vascular anomalies requiring acute and chronic medical management. In this chapter we will focus on describing the role of PTEN in vascular organization via clinical studies on pediatric patients with PHTS. We will start by a review of PTEN's activity in angiogenesis control proven as the PTEN mutation allows uninhibited angiogenesis stimulation by Akt/mTOR pathway. To integrate basic science findings into clinical picture, the characteristics of PTEN Hamartoma Tumor Syndrome with emphasis on the radiologic and histological description of typical vascular anomalies prevalent in PHTS will follow. We will analyze the current trends in therapeutic management including interventional radiology procedures and medical therapies. Data supporting the rationale of administration of oral rapamycin will be presented as the medication restores the lost inhibitory control of PTEN over mTOR and significantly improves acute symptomatology, decreases vascularity in the irregular vascular network and presumably prevents more vascular anomalies development with chronic use. Understanding the mechanism of action of PTEN can be done through one of the rare translational models where a real-life knock-off of a specific gene (as it happens in PHTS patients) dramatically influences the structure of the whole mTOR pathway, explaining the clinical findings that a directed therapy (already available) is restoring, at least partially, to the normal pattern.
Show more