Lymphangioleiomyomatosis - a wolf in sheep's clothing.

Nov 2012

Henske EP, McCormack FX.

Abstract

Lymphangioleiomyomatosis (LAM) is a rare progressive lung disease of women. LAM is caused by mutations in the tuberous sclerosis genes, resulting in activation of the mTOR complex 1 signaling network. Over the past 11 years, there has been remarkable progress in the understanding of LAM and rapid translation of this knowledge to an effective therapy. LAM pathogenic mechanisms mirror those of many forms of human cancer, including mutation, metabolic reprogramming, inappropriate growth and survival, metastasis via blood and lymphatic circulation, infiltration/invasion, sex steroid sensitivity, and local and remote tissue destruction. However, the smooth muscle cell that metastasizes, infiltrates, and destroys the lung in LAM arises from an unknown source and has an innocent histological appearance, with little evidence of proliferation. Thus, LAM is as an elegant, monogenic model of neoplasia, defying categorization as either benign or malignant.

Journal of Clinical Investigation

The role of vascular endothelial growth factor-D in diagnosis of lymphangioleiomyomatosis (LAM).

Nov 2012

Xu KF, Zhang P, Tian X, Ma A, Li X, Zhou J, Zeng N, Gui YS, Guo Z, Feng R, Zhang W, Sun W, Cai B.

Source

Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: kaifeng.xu@gmail.com.

Abstract

BACKGROUND:

Definite diagnosis of lymphangioleiomyomatosis (LAM) depends on either transbronchial lung biopsy or video-assisted thoracic surgery, unless there is a history of chylothorax, kidney angiomyolipoma (AML), or tuberous sclerosis complex (TSC). Vascular endothelial growth factor-D (VEGF-D) was recently considered as a novel diagnostic marker for LAM. Herein, we evaluated diagnostic value of serum VEGF-D in LAM patients.

METHODS:

Serum samples were obtained from 78 cases of LAM (50 definite and 28 probable LAM based on European Respiratory Society guidelines), and 40 healthy female volunteers. VEGF-D was measured using enzyme-linked immunosorbant assay according to product instruction (R&D).

RESULTS:

Serum VEGF-D was significantly increased in definite LAM group, compared with that of health control (median: 3841.9 pg/mL vs 405.5 pg/mL respectively, p < 0.001). The optimal cut-off point for definite LAM diagnosis was 850.7 pg/mL. In probable LAM group, the majority of patients (92.9%) had serum VEGF-D level over 850.7 pg/mL. The serum levels of VEGF-D in LAM patients with pulmonary cystic lesions only were lower than that in patients with any of evidences of AML, chylous effusions, adenopathy, lymphangioleiomyomas, or TSC, but higher than that in the health control. In addition, VEGF-D levels were correlated with disease severity measured as LAM CT grade, and presentations of chylous effusions and/or lymphatic involvement (p < 0.05).

CONCLUSION:

Serum VEGF-D should be added to the current diagnosis algorithm to enhance definitive diagnosis for LAM.

Elsevier

Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis.

Sept 2012

Glasgow CG, El-Chemaly S, Moss J.

Source

Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1590, USA.

Abstract

The primary function of the lymphatic system is absorbing and transporting macromolecules and immune cells to the general circulation, thereby regulating fluid, nutrient absorption and immune cell trafficking. Lymphangiogenesis plays an important role in tissue inflammation and tumour cell dissemination. Lymphatic involvement is seen in lymphangioleiomyomatosis (LAM) and idiopathic pulmonary fibrosis (IPF). LAM, a disease primarily affecting females, involves the lung (cystic destruction), kidney (angiomyolipoma) and axial lymphatics (adenopathy and lymphangioleiomyoma). LAM occurs sporadically or in association with tuberous sclerosis complex (TSC). Cystic lung destruction results from proliferation of LAM cells, which are abnormal smooth muscle-like cells with mutations in the TSC1 or TSC2 gene. Lymphatic abnormalities arise from infiltration of LAM cells into the lymphatic wall, leading to damage or obstruction of lymphatic vessels. Benign appearing LAM cells possess metastatic properties and are found in the blood and other body fluids. IPF is a progressive lung disease resulting from fibroblast proliferation and collagen deposition. Lymphangiogenesis is associated with pulmonary destruction and disease severity. A macrophage subset isolated from IPF bronchoalveolar lavage fluid (BALF) express lymphatic endothelial cell markers in vitro, in contrast to the same macrophage subset from normal BALF. Herein, we review lymphatic involvement in LAM and IPF.

European Respiratory

Lymphatic involvement in lymphangioleiomyomatosis.

Lymphatic involvement in lymphangioleiomyomatosis.

Ann N Y Acad Sci. 2008 May
Glasgow CG, Taveira-Dasilva AM, Darling TN, Moss J.
PhD., Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 10, Rm. 6D03 MSC 1590, Bethesda, MD 20892-1590. mossj@nhlbi.nih.gov.

Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease affecting primarily premenopausal women. The disease is characterized by cystic lung disease, at times leading to respiratory compromise, abdominal tumors (in particular, renal angiomyolipomas), and involvement of the axial lymphatics (e.g., adenopathy, lymphangioleiomyomas).

Disease results from the proliferation of neoplastic cells (LAM cells), which, in many cases, have a smooth muscle cell phenotype, express melanoma antigens, and have mutations in one of the tuberous sclerosis complex genes (TSC1 or TSC2). In the lung, LAM cells found in the vicinity of cysts are, at times, localized in nodules and may be responsible for cyst formation through the production of proteases.

Lymphatic channels, expressing characteristic lymphatic endothelial cell markers, are found within the LAM lung nodules. LAM cells may also be localized within the walls of the axial lymphatics, and, in some cases, penetrate the wall and proliferate in the surrounding adipose tissue. Consistent with extensive lymphatic involvement in LAM, the serum concentration of VEGF-D, a lymphangiogenic factor, is higher in LAM patients than in healthy volunteers.

Annals of the New York Academy of Sciences

A case of lymphangioleiomyomatosis found due to chylous ascites, pleural effusion and pelvic lymphadenopathy

A case of lymphangioleiomyomatosis found due to chylous ascites, pleural effusion and pelvic lymphadenopathy

Nihon Kokyuki Gakkai Zasshi. 2007

Yano T, Hasizume I, Kasamatsu N, Kato T, Shibata M, Ashinuma N, Kobayashi K, Yasuda T, Nakamura A.
Department of Respiratory Medicine, Hamamatsu Medical Center.

We report a case of lymphangioleiomyomatosis, complaining initially of abdominal distension due to massive chylous ascites. The patient was a 28-year-old woman in whom abdominal ultrasound had strongly suggested the existence of both pelvic lymphadenopathy and massive ascites, the latter subsequently turning out to be chylous. Pelvic lymph node biopsy yielded a diagnosis of lymphangioleiomyomatosis. High-resolution computed tomography (HRCT) of the chest showed no remarkable findings except for very few cystic changes in the lung parenchyma.

Pulmonary function had remained normal except for a temporary constrictive pattern when chylous pleural effusion developed. No airflow obstruction was detected on pulmonary function tests.

Although lymphangioleiomyomatosis is often associated with pulmonary symptoms, we should bear in mind the possibility of lymphangioleiomyomatosis even in the absence of such symptoms when facing any woman of child-bearing age with abdominal chylous ascites of unknown etiology.

PMID: 17554983 [PubMed - indexed for MEDLINE]