Lymphangioleiomyomatosis

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number of new cases each year is between 0.23 and 0.31/million women/year in the US, UK and Switzerland. The variation between countries and between adjacent states in the US, suggest that a significant number of women with LAM remain either undiagnosed or their symptoms are attributed to other diseases. Adult women with tuberous sclerosis are more likely to develop LAM than women without tuberous sclerosis. Cohorts of patients with tuberous sclerosis have been screened for LAM using CT scanning. In a retrospective study of adults with tuberous sclerosis, CT demonstrated lung cysts in 42% of 95 women and 13% of 91 men. In general, lung cysts were larger and more numerous in women than in men. In a further retrospective study of women with TSC who underwent CT scanning to detect LAM, 25% of those in their 20s had lung cysts whereas 80% of women in their 40s were affected, suggesting that the development of LAM is age dependent at least in tuberous sclerosis-related LAM. Although the prevalence of tuberous sclerosis at 1 in 6,000 births is much greater than that of LAM, most pulmonary clinics see more cases of sporadic than tuberous sclerosis–LAM: probably due to a combination of low levels of screening for LAM in tuberous sclerosis and in many, the absence of symptoms.

796:, and, often, estrogen and progesterone receptors. The cuboidal cells within LAM lesions also react with a monoclonal antibody called HMB-45, developed against the premelanosomal protein gp100, an enzyme in the melanogenesis pathway. This immunohistochemical marker is very useful diagnostically, because other smooth muscle-predominant lesions in the lung do not react with the antibody. The spindle-shaped cells of the LAM lesion are more frequently proliferating cell nuclear antigen positive than the cuboidal cells, consistent with a proliferative phenotype. Compared with cigar-shaped normal smooth muscle cells, spindle-shaped LAM cells contain less abundant cytoplasm and are less eosinophilic. Estrogen and progesterone receptors are also present in LAM lesions, but not in adjacent normal lung tissue. LAM lesions express lymphatic markers LYVE-1, PROX1, podoplanin and VEGFR-3. The smooth muscle-like cells of AMLs are morphologically and immunohistochemically similar to LAM cells, including reactivity with antibodies directed against actin, desmin, vimentin, and HMB-45 as well as estrogen and progesterone receptors. Unlike the dilated airspaces in emphysema, the cystic spaces found in LAM may be partially lined with hyperplastic type II cells. 732:

plethysmography, but was only 103% of predicted determined with gas dilution methods, suggesting significant air trapping in noncommunicating airspaces. Approximately 25% of patients with obstructive physiology may demonstrate bronchodilator responsiveness but may be less in more severe obstruction. The obstructive physiologic defect in LAM is primarily attributable to airflow obstruction. The earliest change in initial pulmonary function testing in various case series was abnormal gas transfer, as assessed by the diffusing capacity for carbon monoxide (DLCO), described in 82% to 97% of patients. It is not unusual for DLCO to be reduced out of proportion to forced expiratory volume in 1 second (FEV1). Reduction in DLCO and increase in residual volume are generally considered to be LAM's earliest physiologic manifestations.

642:(HRCT) chest scan is better than the chest radiograph to detect cystic parenchymal disease and is almost always abnormal at the time of diagnosis, even when the chest radiograph and pulmonary function assessments are normal. The typical CT shows diffuse round, bilateral, thin-walled cysts of varying sizes ranging from 1 to 45 mm in diameter. The numbers of cysts varies in LAM from a few to almost complete replacement of normal lung tissue. The profusion of cysts tends to be milder in patients with TSC-LAM than S-LAM, perhaps explained in part because TSC-LAM patients typically receive earlier screening. Pleural effusions are seen on CT in 12% of patients with S-LAM and 6% of patients with TSC-LAM. Other CT features include linear densities (29%), hilar or mediastinal 1072:

pneumothorax with pregnancy, consistent with an incidence of pneumothorax in pregnancy of at least 10% (38 of 318). In one third of patients, the pneumothorax during pregnancy led to the LAM diagnosis. Pneumothoraces were almost twice as frequent on the right as on the left, and four women presented with bilateral spontaneous pneumothorax. Most pneumothoraces took place during the second and third trimesters. This study and others suggest that pregnancy is associated with pleural complications in LAM patients. Few women with a known LAM diagnosis choose to become pregnant and patients in whom LAM is diagnosed during pregnancy rarely have baseline pulmonary function tests available, complicating resolution of this question.

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in patients who have abnormal lung function (i.e. FEV1<70% predicted). Whether the benefits of treatment outweigh the risks for asymptomatic LAM patients with normal lung function is not clear, but some physicians consider treatment for declining patients who are approaching the abnormal range for FEV1. Sirolimus also appears to be effective for the treatment chylous effusions and lymphangioleiomyomatosis. The benefits of sirolimus only persist while treatment continues. The safety of long term therapy has not been studied.

846:. Thoracic duct ligation can be considered, but since thoracic effusions sometimes originate from ascites that are siphoned into the chest by the bellows action of the thorax, it is important to rule out an abdominal source before considering this option. Pleural symphysis may be required to prevent nutritional and lymphocyte deficiencies that can result from repeated taps or persistent drainage. Chemical pleurodesis is generally an effective therapy for chylothorax, as is mechanical abrasion and talc poudrage. 181: 551: 825:

pneumothorax. The LAM Foundation Pleural Consensus Group advocated the use of a pleural symphysis procedure with the first pneumothorax, given the greater than 70% chance of recurrence. Chemical sclerosis, mechanical abrasion, talc poudrage and pleurectomy have been effective in patients with LAM, but mechanical abrasion is preferred for those who may require pulmonary transplantation in the future. About half of LAM patients who have undergone transplant have had a prior

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single pulmonary function laboratory at the NHLBI was 75 ± 9 mL, and 0.69 ± 0.07 mL/min/mm Hg, respectively. In other series from Europe, the rate of decline in FEV1 was considerably higher, estimated at approximately 100 to 120 mL/yr. In the MILES trial, patients in the placebo group lost 134 cc/yr. There was some evidence in these studies that rate of decline in lung function correlates with initial DLCO, with menopausal status and high baseline VEGF-D.

565: 153: 538:. VEGF-D binds to the receptor protein tyrosine kinases VEGFR-2 and VEGFR-349 in humans, and to VEGFR3 in mice. Surprisingly, knock-out of VEGF-D in mice has little effect on lymphatic system development. Nevertheless, during tumorigenesis VEGF-D promotes formation of tumor lymphatic vessels and facilitates metastatic spread of cancer cells. However, little is known about a role of abnormal lymphatics and VEGF-D in LAM 573:

20% of women have cystic change by age 20 and about 80% of women have cystic changes after age 40. LAM is sometimes revealed by chest CT in patients who present with an apparent primary spontaneous pneumothorax, but more often CT scanning is not ordered (in the United States) until recurrences occur. Progressive dyspnea on exertion without the exacerbations and remissions that are characteristic of asthma or

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32% of patients with S-LAM and 93% of patients with TSC-LAM. Hepatic AMLs were present in 2% of patients with S-LAM and 33% of patients with TSC-LAM. Ascites was uncommon, seen in fewer than 10% of patients with LAM. Abdominal lymphangiomatosis, often containing both cystic and solid components, were seen in 29% of patients with S-LAM and 9% of patients with TSC-LAM.

858:(AMLs) may require embolization or cauterization for control of bleeding, a complication that is thought to be more common when tumor diameter exceeds 4 cm. The extent of aneurysmal change may determine bleeding risk. Serial abdominal imaging should be performed to assess AML size at 6- to 12-month intervals, at least until trends in growth are clear. 653:(MMPH) made up of clusters of hyperplastic type II pneumocytes. MMPH may be present in males or females with TSC in the presence or absence of LAM, but not in patients with S-LAM. MMPH is not typically associated with physiologic or prognostic consequences, but one case of respiratory failure due to MMPH has been reported. 966:

Sirolimus is often effective as first-line management for chylothorax. If chylous leakage or accumulations persist despite treatment, imaging with heavy T2 weighted MRI, MRI lymphangiography or thoracic duct lymphangiography can be considered. Pleural fusion procedures can be considered in refractory

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and headache. Sirolimus pneumonitis and latent malignancy are more serious concerns, but occur infrequently. Sirolimus inhibits wound healing. It is important to stop therapy with the drug for 1–2 weeks before and after elective procedures that require optimal wound healing. Precautions must be taken

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Sirolimus is an mTOR inhibitor that stabilizes lung function and improves some measures of life in LAM patients. It is approved by the FDA for use in LAM, based on the results of the Multicenter International LAM Efficacy and Safety of Sirolimus (MILES) Trial. MILES data supports the use of sirolimus

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The LAM Foundation was founded in 1995 as a grassroots organization to provide patient advocacy and research funding. Today, the LAM Foundation provides support and education for women with LAM and their families, engages doctors and scientists to continue to learn more about the disease, and raises

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Patients typically develop progressive airflow obstruction. In a cohort of patients in the United Kingdom, 10 years after symptom onset, 55% of 77 patients were breathless walking on flat ground and 10% were housebound. The average annual rate of decline in FEV1 and DLCO in 275 patients studied in a

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If none of these clinical features are present, a biopsy may be necessary to make the diagnosis. Video-assisted thoracoscopic lung biopsy is the most definitive technique, but transbronchial biopsy has a yield of over 50% and can also be effective. The safety of the latter procedure in patients with

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LAM can come to medical attention in several ways, most of which trigger a chest CT. Thin-walled cystic change in the lungs may be found incidentally on CT scans of the heart, chest or abdomen (on the cuts that include lung bases) obtained for other purposes. HRCTs of TSC patients reveals that about

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LAM is almost completely restricted to women. While lung cysts consistent with LAM are reported in some men with tuberous sclerosis, very few of these men develop symptoms. The prevalence of LAM is estimated using data from registries and patient groups and is between 3.4 and 7.8/million women. The

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Lymphangioleiomyomatoses are fluid-filled hypodense structures present in the retroperitoneal regions of the abdomen and pelvis in about 30% of LAM patients. They generally do not require intervention. Biopsy or resection can lead to prolonged leakage. mTOR inhibitors are effective at shrinking the

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Grossly, LAM lungs are enlarged and diffusely cystic, with dilated air spaces as large as several centimeters in diameter. Microscopic examination of the lung reveals foci of smooth muscle-like cell infiltration of the lung parenchyma, airways, lymphatics, and blood vessels associated with areas of

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Pulmonary function testing in patients with LAM may be normal or may reveal obstructive, restrictive or mixed patterns. Obstructive physiology is the most common abnormality. Quality-controlled lung function data were collected prospectively by the NHLBI Registry, a five-year study of patients with

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of AMLs. AMLs are more prevalent and more frequently bilateral and large in patients with TSC-LAM than in patients with S-LAM. AML size correlates with the prevalence of pulmonary cysts in patients with TSC. One study CT imaged 256 patients with S-LAM and 67 with TSC-LAM. Renal AMLs were present in

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A variable percentage of cells within the LAM lesion contain mutational inactivation of the tuberous sclerosis complex (TSC1 or TSC2) tumor suppressor genes. TSC1 mutations cause a less severe clinical phenotype than TSC2 mutations. The discovery of TSC1/2 gene function as negative regulator of the

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gene mutations. Germline and somatic mutations in LAM include many types of mutations spread across the genes, with no clear "hot spots," including missense changes, in-frame deletions and nonsense mutations. Because of the large size of the genes (together they have more than 60 exons) and because

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Bissler, JJ; Kingswood, JC; Radzikowska, E; Zonnenberg, BA; Frost, M; Belousova, E; Sauter, M; Nonomura, N; Brakemeier, S; de Vries, PJ; Whittemore, VH; Chen, D; Sahmoud, T; Shah, G; Lincy, J; Lebwohl, D; Budde, K (2013). "Everolimus for angiomyolipoma associated with tuberous sclerosis complex or

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Mitani, K; Kumasaka, T; Takemura, H; Hayashi, T; Gunji, Y; Kunogi, M; Akiyoshi, T; Takahashi, K; Suda, K; Seyama, K (2009). "Cytologic, immunocytochemical and ultrastructural characterization of lymphangioleiomyomatosis cell clusters in chylous effusions of patients with lymphangioleiomyomatosis".

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Chyle does not generally cause pleural inflammation or fibrosis. Small stable chylous effusions rarely require intervention once the LAM diagnosis is made. Shortness of breath may mandate possibly repeated drainage. Sirolimus is effective for chylous effusions and most experts believe it should be

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is the most commonly used parameter to monitor disease progression. Although resting pulmonary hypertension appears to be unusual in LAM, pulmonary arterial pressure often rises with low levels of exercise, related in part to hypoxemia. One study reported an increase in intraparenchymal shunts in

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through Rho GTPases, and Rac1 is required for mTOR activation. In TSC2-null and human LAM cells, Rho GTPase activity is required for cell adhesion, motility, proliferation and survival. Loss of TSC1/TSC2 in LAM induces uncontrolled LAM cell growth and increases LAM cell viability. Upregulation of

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McCormack, FX; Inoue, Y; Moss, J; Singer, LG; Strange, C; Nakata, K; Barker, AF; Chapman, JT; Brantly, ML; Stocks, JM; Brown, KK; Lynch, JP, 3rd; Goldberg, HI; Young, LR; Kinder, BW; Downey, GP; Sullivan, EJ; Colby, TV; McKay, RT; Cohen, MM; Korbee, L; Taveira-DaSilva, AM; Lee, HS; Krischer, JP;

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Survival estimates vary, dependent on mode of presentation or ascertainment, and have generally trended upward, probably due to earlier recognition through more widespread use of CT scanning. In a recent population-based cohort survey, median survival was found to be 29 years. Data from earlier,

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van Slegtenhorst, M; de Hoogt, R; Hermans, C; Nellist, M; Janssen, B; Verhoef, S; Lindhout, D; van den Ouweland, A; Halley, D; Young, J; Burley, M; Jeremiah, S; Woodward, K; Nahmias, J; Fox, M; Ekong, R; Osborne, J; Wolfe, J; Povey, S; Snell, RG; Cheadle, JP; Jones, AC; Tachataki, M; Ravine, D;

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may be apparent. Preservation of lung volumes in the presence of increased interstitial markings is a radiographic hallmark of LAM that helps distinguish it from most other interstitial lung diseases, in which alveolar septal and interstitial expansion tend to increase the lung's elastic recoil

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may appear relatively normal, even late in the disease, or may suggest hyperinflation only. As the disease progresses, the chest radiograph often demonstrates diffuse, bilateral and symmetric reticulonodular opacities, cysts, bullae or a "honeycomb" (i.e., pseudo fibrotic) appearance. Pleural

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tumor cells. LAM cells appear to arise from an extrapulmonary source and migrate to the lung. Increased LAM cell migration and invasiveness is rescued by TSC2 re-expression. The cellular and molecular mechanisms of neoplastic transformation and lung parenchymal destruction by LAM cells remain

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Franz, DN; Brody, A; Meyer, C; Leonard, J; Chuck, G; Dabora, S; Sethuraman, G; Colby, TV; Kwiatkowski, DJ; McCormack, FX (2001). "Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous

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Goncharova EA, Goncharov DA, Chisolm A, Spaits MS, Lim PN, Cesarone G, Khavin I, Tliba O, Amrani Y, Panettieri RA, Krymskaya VP (March 2008). "Interferon beta augments tuberous sclerosis complex 2 (TSC2)-dependent inhibition of TSC2-null ELT3 and human lymphangioleiomyomatosis-derived cell

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Pregnancy has been reported to exacerbate LAM in some cases. However, the risk has not been rigorously studied. In a survey of 318 patients who indicated that they had had at least one pregnancy, 163 responded to a second survey focusing on lung collapse. A total of 38 patients reported a

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Pneumothoraces in LAM patients tend to recur, especially after conservative management such as observation, aspiration or simple tube thoracostomy. Over 65% of LAM patients develop pneumothorax during the course of their illness, averaging 3.5 pneumothoraces in those who have at least one

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revealed obstructive changes in about 57% of patients and normal results in 34%. Restriction, defined as a total lung capacity less than the lower limit of normal, was seen in 11%. Hyperinflation was present in about 6%. The average residual volume was 125% of predicted when measured by

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Mild cystic changes consistent with LAM have been described in 10–15% of men with TSC, but symptomatic LAM in males is rare. Sporadic LAM occurs exclusively in women, with one published exception to date. Both TSC-LAM and S-LAM are associated with mutations in tuberous sclerosis genes.

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Sampson, JR; Reeve, MP; Richardson, P; Wilmer, F; Munro, C; Hawkins, TL; Sepp, T; Ali, JB; Ward, S; Green, AJ; Yates, JR; Kwiatkowska, J; Henske, EP; Short, MP; Haines, JH; Jozwiak, S; Kwiatkowski, DJ (1997). "Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34".

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should be kept up to date. Pulmonary rehabilitation seems to be particularly rewarding in young, motivated patients with obstructive lung disease, but studies to assess this intervention's effect on exercise tolerance, conditioning and quality of life have not been done.

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Taveira-DaSilva, AM; Hedin, C; Stylianou, MP; Travis, WD; Matsui, K; Ferrans, VJ; Moss, J (2001). "Reversible airflow obstruction, proliferation of abnormal smooth muscle cells, and impairment of gas exchange as predictors of outcome in lymphangioleiomyomatosis".

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in 217 patients. Exercise-induced hypoxemia was found even in patients who did not have resting abnormalities in FEV1 and DLCO. In most patients, exercise was thought to be ventilation limited, owing to airflow obstruction and increased dead-space ventilation.

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Kumasaka, T; Seyama, K; Mitani, K; Souma, S; Kashiwagi, S; Hebisawa, A; Sato, T; Kubo, H; Gomi, K; Shibuya, K; Fukuchi, Y; Suda, K (2005). "Lymphangiogenesis-mediated shedding of LAM cell clusters as a mechanism for dissemination in lymphangioleiomyomatosis".

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Schiavina, M; Di Scioscio, V; Contini, P; Cavazza, A; Fabiani, A; Barberis, M; Bini, A; Altimari, A; Cooke, RM; Grigioni, WF; D'Errico-Grigioni, A (2007). "Pulmonary lymphangioleiomyomatosis in a karyotypically normal man without tuberous sclerosis complex".

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Diagram 1. Outlines a proposed algorithm for the diagnosis of LAM. CT: computed tomography; TSC: tuberous sclerosis complex; AML: angiomyolipoma; VEGF-D: vascular endothelial growth factor D; TBBx: transbronchial biopsy; VATS: video-assisted thoracoscopic

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Female sex and tuberous sclerosis are the only known risk factors. Although use of supplemental estrogen is not associated with development of LAM, one study suggested that use of estrogen-containing contraceptive pills was associated with earlier onset.

646:(9%), pneumothorax, lymphangiomyoma, and thoracic duct dilation. Ground-glass opacities (12%) suggest the presence of interstitial edema due to lymphatic congestion. In patients with TSC, nodular densities on HRCT may represent multifocal micronodular 1534:

Ryu, JH; Moss, J; Beck, GJ; Lee, JC; Brown, KK; Chapman, JT; Finlay, GA; Olson, EJ; Ruoss, SJ; Maurer, JR; Raffin, TA; Peavy, HH; McCarthy, K; Taveira-Dasilva, A; McCormack, FX; Avila, NA; Decastro, RM; Jacons, SS; Stylianou, M; Fanburg, BL (2006).

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Young L, Lee HS, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP, Goldberg HJ, Downey GP, Swigris JJ, Taveira-DaSilva AM, Krischer JP, Trapnell BC, McCormack FX (August 2013).

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Moss, J; Avila, NA; Barnes, PM; Litzenberger, RA; Bechtle, J; Brooks, PG; Hedin, CJ; Hunsberger, S; Kristof, AS (2001). "Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex".

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Gupta, N; Meraj, R; Tanase, D; James, LE; Seyama, K; Lynch, DA; Akira, M; Meyer, CA; Ruoss, SJ; Burger, CD; Young, LR; Almoosa, KF; Veeraraghavan, S; Barker, AF; Lee, AS; Dilling, DF; Inoue, Y; Cudzilo, CJ; Zafar, MA; McCormack, FX (2015).

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used as the first line of therapy. Imaging the source of the leak with heavy T2-weighted MRI or contrast lymphangiography is an advised for refractory effusions. Some leaks are amenable to embolization through catheters threaded from groin

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The average age of onset is the early-to-mid-30s. Exertional dyspnea (shortness of breath) and spontaneous pneumothorax (lung collapse) have been reported as the initial presentation of the disease in 49% and 46% of patients, respectively.

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Urban, T; Lazor, R; Lacronique, J; Murris, M; Labrune, S; Valeyre, D; Cordier, JF (1999). "Pulmonary lymphangioleiomyomatosis. A study of 69 patients. Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P)".

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Almoosa, KF; Ryu, JH; Mendez, J; Huggins, JT; Young, LR; Sullivan, EJ; Maurer, J; McCormack, FX; Sahn, SA (2006). "Management of pneumothorax in lymphangioleiomyomatosis: effects on recurrence and lung transplantation complications".

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LAM occurs in two settings: in the disease tuberous sclerosis complex (TSC-LAM) and in a sporadic form, in women who do not have TSC (sporadic LAM). In both settings, genetic evidence indicates that LAM is caused by inactivating or

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diffuse cystic disease and the profusion of cystic change that predicts an informative biopsy are incompletely understood, however. Cytology of chylous fluids, aspirated abdominal nodes or lymphatic masses can also be diagnostic.

4459:"Serum VEGF-D a concentration as a biomarker of lymphangioleiomyomatosis severity and treatment response: a prospective analysis of the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial" 4658:

Achen, MG; Williams, RA; Baldwin, ME; Lai, P; Roufail, S; Alitalo, K; Stacker, SA (2002). "The angiogenic and lymphangiogenic factor vascular endothelial growth factor-D exhibits a paracrine mode of action in cancer".

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Karnezis, T; Shayan, R; Caesar, C; Roufail, S; Harris, NC; Ardipradja, K; Zhang, YF; Williams, SP; Farnsworth, RH; Chai, MG; Rupasinghe, TW; Tull, DL; Baldwin, ME; Sloan, EK; Fox, SB; Achen, MG; Stacker, SA (2012).

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Karbowniczek, M; Astrinidis, A; Balsara, BR; Testa, JR; Lium, JH; Colby, TV; McCormack, FX; Henske, EP (2003). "Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism".

978:-containing medications can exacerbate LAM and are contraindicated. Agents that antagonize the effects of estrogen have not been proven to be effective for treatment, but no proper trials have been done. A trial of 6966:

Schiavina M, Contini P, Fabiani A, Cinelli F, Di Scioscio V, Zompatori M, Campidelli C, Pileri SA (March 2007). "Efficacy of hormonal manipulation in lymphangioleiomyomatosis. A 20-year experience in 36 patients".

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Zafar, MA; McCormack, FX; Rahman, S; Tencza, C; Wikenheiser-Brokamp, KA; Young, LR; Shizukuda, Y; Elwing, JM (2013). "Pulmonary vascular shunts in exercise-intolerant patients with lymphangioleiomyomatosis".

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Zhe X, Yang Y, Jakkaraju S, Schuger L (April 2003). "Tissue inhibitor of metalloproteinase-3 downregulation in lymphangioleiomyomatosis: potential consequence of abnormal serum response factor expression".

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Rossi, GA; Balbi, B; Oddera, S; Lantero, S; Ravazzoni, C (1991). "Response to treatment with an analog of the luteinizing-hormone-releasing hormone in a patient with pulmonary lymphangioleiomyomatosis".

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Hayashida, M; Seyama, K; Inoue, Y; Fujimoto, K; Kubo, K (2007). "The epidemiology of lymphangioleiomyomatosis in Japan: A nationwide cross-sectional study of presenting features and prognostic factors".

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Seyama, K; Kumasaka, T; Souma, S; Sato, T; Kurihara, M; Mitani, K; Tominaga, S; Fukuchi, Y (2006). "Vascular endothelial growth factor-D is increased in serum of patients with lymphangioleiomyomatosis".

669:, usually grossly matched. These authors also described an "unusual," "speckling pattern" on the perfusion images in 74% of patients, consisting of "small, often peripheral collections of radioisotope." 714:, are common in patients with TSC, including those with TSC-LAM, but are not found in women with S-LAM. Moss and associates reported that women with S-LAM and TSC-LAM may have an increased incidence of 502:-D, recruit lymphatic endothelial cells (LECs) that form lymphatic vessels and induce lung cysts. VEGF-D serum levels are increased in LAM compared to other cystic lung diseases, including pulmonary 297:

Cystic lymphangiomas or lymph nodes with hypodense centers, which mimic necrotizing lymphomas, ovarian or renal cancers, or other malignancies can occur in the retroperitoneum, pelvis or mediastinum.

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Sleiman, C; Mal, H; Jebrak, G; Darne, C; Meeus, E; Dubois, F; Luisetti, M; Fournier, M; Pariente, R; Andreassian, B (1992). "Pulmonary lymphangiomyomatosis treated by single lung transplantation".

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Adriaensen, ME; Schaefer-Prokop, CM; Duyndam, DA; Zonnenberg, BA; Prokop, M (2011). "Radiological evidence of lymphangioleiomyomatosis in female and male patients with tuberous sclerosis complex".

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Henske EP, Ao X, Short MP, Greenberg R, Neumann HP, Kwiatkowski DJ, Russo I (July 1998). "Frequent progesterone receptor immunoreactivity in tuberous sclerosis-associated renal angiomyolipomas".

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procedure, and more than 75% of those had had prior bilateral pleurodesis. Although pleurodesis is not a contraindication to transplantation, it can result in increased perioperative bleeding.

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Figure A shows the location of the lungs and airways in the body. The inset image shows a cross-section of a healthy lung. Figure B shows a view of the lungs with LAM and a collapsed lung (

467:(S6K1) and 4E-BP1. mTOR forms two physically and functionally distinct multiprotein complexes: the rapamycin-sensitive mTORC1 and the rapamycin-insensitive mTORC2. MTORC1 consists of five 5848:

Taveira-DaSilva, AM; Stylianou, MP; Hedin, CJ; Kristof, AS; Avila, NA; Rabel, A; Travis, WD; Moss, J (2003). "Maximal oxygen uptake and severity of disease in lymphangioleiomyomatosis".

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Strizheva, GD; Carsillo, T; Kruger, WD; Sullivan, EJ; Ryu, JH; Henske, EP (2001). "The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis".

6201:

Gao, L; Yue, MM; Davis, J; Hyjek, E; Schuger, L (2014). "In pulmonary lymphangioleiomyomatosis expression of progesterone receptor is frequently higher than that of estrogen receptor".

514:. VEGF-D levels correlate with the severity of LAM, evaluated as a measure of CT grade (the abundance of chylous effusions and lymphatic involvement). VEGF-D is a secreted homodimeric 290:(fatty kidney tumors) are present in about 30% of patients with sporadic LAM and up to 90% of patients with TSC-LAM. Angiomyolipomas can sometimes spontaneously bleed, causing pain or 6349:

Matsui K, K Riemenschneider W, Hilbert SL, Yu ZX, Takeda K, Travis WD, Moss J, Ferrans VJ (November 2000). "Hyperplasia of type II pneumocytes in pulmonary lymphangioleiomyomatosis".

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Serum VEGF-D concentration is useful, predictive and prognostic biomarker. Higher baseline VEGF-D levels predicts more rapid disease progression and a more robust treatment response.

6279:

Logginidou, H; Ao, X; Henske, EP (2000). "Frequent estrogen and progesterone receptor immunoreactivity in renal angiomyolipomas from women with pulmonary lymphangioleiomyomatosis".

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Muzykewicz, DA; Sharma, A; Muse, V; Numis, AL; Rajagopal, J; Thiele, EA (2009). "TSC1 and TSC2 mutations in patients with lymphangioleiomyomatosis and tuberous sclerosis complex".

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cells. LAM cells generally expand interstitial spaces without violating tissue planes but have been observed to invade the airways, the pulmonary artery, the diaphragm, aorta, and

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de la Fuente J, Páramo C, Román F, Pérez R, Masa C, de Letona JM (1993). "Lymphangioleiomyomatosis: unsuccessful treatment with luteinizing-hormone-releasing hormone analogues".

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Dabora, SL; Jozwiak, S; Franz, DN; Roberts, PS; Nieto, A; Chung, J; Choy, YS; Reeve, MP; Thiele, E; Egelhoff, JC; Kasprzyk-Obara, J; Domanska-Pakiela, D; Kwiatkowski, DJ (2001).

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Kerr, LA; Blute, ML; Ryu, JH; Swensen, SJ; Malek, RS (1993). "Renal angiomyolipoma in association with pulmonary lymphangioleiomyomatosis: forme fruste of tuberous sclerosis?".

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El-Hashemite, N; Walker, V; Zhang, H; Kwiatkowski, D (2003). "Loss of Tsc1 or Tsc2 induces vascular endothelial growth factor production through mammalian target of rapamycin".

3637:"Signal transducer and activator of transcription 3 is required for abnormal proliferation and survival of TSC2-deficient cells: relevance to pulmonary lymphangioleiomyomatosis" 2315:"Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis" 408:

genes, consistent with the "two-hit" tumor suppressor gene model. The second hit event in LAM cells is often loss of the chromosomal region containing the wild-type copy of the

6015:

Carrington CB, Cugell DW, Gaensler EA, Marks A, Redding RA, Schaaf JT, Tomasian A (December 1977). "Lymphangioleiomyomatosis. Physiologic-pathologic-radiologic correlations".

3544:"Perturbed IFN-gamma-Jak-signal transducers and activators of transcription signaling in tuberous sclerosis mouse models: synergistic effects of rapamycin-IFN-gamma treatment" 2604:

Goncharova, EA; Goncharov, DA; Eszterhas, A; Hunter, DS; Glassberg, MK; Yeung, RS; Walker, CL; Noonan, D; Kwiatkowski, DJ; Chou, MM; Panettieri, RA Jr; Krymskaya, VP (2002).

1203:

Kitaichi, M; Nishimura, K; Itoh, H; Izumi, T (1995). "Pulmonary lymphangioleiomyomatosis: A report of 46 patients including a clinicopathologic study of prognostic factors".

6069:

Matsumoto, Y; Horiba, K; Usuki, J; Chu, SC; Ferrans, VJ; Moss, J (1999). "Markers of cell proliferation and expression of melanosomal antigen in lymphangioleiomyomatosis".

2606:"Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation. A role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM)" 1081:

funds for the continued study of LAM. It seeks safe and effective treatments, and ultimately a cure, for lymphangioleiomyomatosis. It is headquartered in Cincinnati, Ohio.

7266:

Oberstein, EM; Fleming, LE; Gómez-Marin, O; Glassberg, MK (2003). "Pulmonary lymphangioleiomyomatosis (LAM): examining oral contraceptive pills and the onset of disease".

5304:

Lantuejoul, S; Ferretti, G; Negoescu, A; Parent, B; Brambilla, E (1997). "Multifocal alveolar hyperplasia associated with lymphangioleiomyomatosis in tuberous sclerosis".

866:

is sometimes required for tumors with intravascular extension or other reasons, but is rarely the approach of choice for AMLs that can be managed by less invasive means.

6790:

Oprescu, N; McCormack, FX; Byrnes, S; Kinder, BW (2013). "Clinical Predictors of Mortality and Cause of Death in Lymphangioleiomyomatosis: A Population-based Registry".

3153:

Jacinto, E; Loewith, R; Schmidt, A; Lin, S; Rüegg, MA; Hall, A; Hall, MN (2004). "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive".

6689: 2751: 498:

Clinical and histopathological evidence demonstrate the lymphatic involvement in LAM. The prevailing hypothesis is that LAM lesions secrete the lymphangiogenic factor

4404:

Young, LR; Vandyke R, Gulleman, PM; Inoue, Y; Brown, KK; Schmidt, LS; Linehan, WM; Hajjar, F; Kinder, BW; Trapnell, BC; Bissler, JJ; Franz, DN; McCormack, FX (2010).

1299:

Chu, SC; Horiba, K; Usuki, J; Avila, NA; Chen, CC; Travis, WD; Ferrans, VJ; Moss, J (1999). "Comprehensive evaluation of 35 patients with lymphangioleiomyomatosis".

8004: 2755: 923:

were reduced by treatment. Adverse events were generally consistent with those known to be associated with mTOR inhibitors, although some were serious and included

681:(PET) scanning. Other neoplasms (or sources of inflammation) should therefore be considered in known or suspected LAM cases in which FDG-PET results are positive. 495:(MMPs) and their endogenous inhibitors TIMPs. The invasive cell phenotype in LAM is associated with TIMP-3 downregulation and TSC2-dependent upregulation of MMPs. 3921:"Activation of the estrogen receptor contributes to the progression of pulmonary lymphangioleiomyomatosis via matrix metalloproteinase-induced cell invasiveness" 784:

There are two major cell morphologies in the LAM lesion: small spindle-shaped cells and cuboidal epithelioid cells. LAM cells stain positively for smooth muscle

6244:

Berger, U; Khaghani, A; Pomerance, A; Yacoub, MH; Coombes, RC (1990). "Pulmonary lymphangioleiomyomatosis and steroid receptors. An immunocytochemical study".

4947:

Johnson, SR; Cordier, JF; Lazor, R; Cottin, V; Costabel, U; Harari, S; Reynaud-Gaubert, M; Boehler, A; Brauner, M; Popper, H; Bonetti, F; Kingswood, C (2010).

5261:

Popper, HH; Juettner-Smolle, FM; Pongratz, MG (1991). "Micronodular hyperplasia of type II pneumocytes—A new lung lesion associated with tuberous sclerosis".

5183:

Yamauchi, M; Nakahara, H; Uyama, K; Tsujimoto, A; Tamai, M; Aozasa, K (2000). "Cytologic finding of chyloascites in lymphangioleiomyomatosis. A case report".

7908: 7828: 201:

destruction. It predominantly affects women, especially during childbearing years. The term sporadic LAM is used for patients with LAM not associated with

7138:

Harknett, EC; Chang, WY; Byrnes, S; Johnson, J; Lazor, R; Cohen, MM; Gray, B; Geiling, S; Telford, H; Tattersfield, AE; Hubbard, RB; Johnson, SR (2011).

2557:"Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs" 2769:

Bissler, JJ; McCormack, FX; Young, LR; Elwing, JM; Chuck, G; Leonard, JM; Schmithorst, VJ; Laor, T; Brody, AS; Bean, J; Salisbury, S; Franz, DN (2008).

7783: 459:

Rheb via the GTPase activating protein (GAP) domain of TSC2. Rheb binds to Raptor and controls the activity of mTOR complex 1 (mTORC1) that directly

7733: 2421:

Cai, X; Pacheco-Rodriguez, G; Fan, QY; Haughey, M; Samsel, L; El-Chemaly, S; Wu, HP; McCoy, JP; Steagall, WK; Lin, JP; Darling, TN; Moss, J (2010).

6166:

Colley, MH; Geppert, E; Franklin, WA (1989). "Immunohistochemical detection of steroid receptors in a case of pulmonary lymphangioleiomyomatosis".

5572:

Young, LR; Franz, DN; Nagarkatte, P; Fletcher, CD; Wikenheiser-Brokamp, KA; Galsky, MD; Corbridge, TC; Lam, AP; Gelfand, MJ; McCormack, FX (2009).

7893: 3684:

Parkhitko, A; Myachina, F; Morrison, TA; Hindi, KM; Auricchio, N; Karbowniczek, M; Wu, JJ; Finkel, T; Kwiatkowski, DJ; Yu, JJ; Henske, EP (2011).

919:, was reported in a small, open-label trial to be associated with improvement in FEV1 and six-minute walking distance. Serum levels of VEGF-D and 6629:

Goldberg, HJ; Harari, S; Cottin, V; Rosas, IO; Peters, E; Biswal, S; Cheng, Y; Khindri, S; Kovarik, JM; Ma, S; McCormack, FX; Henske, EP (2015).

431:

mutations as the original LAM, has led to the "benign metastasis" hypothesis that LAM cells can migrate or metastasize from one site to another.

5770:

Yen, KT; Putzke, JD; Staats, BA; Burger, CD (2005). "The prevalence of acute response to bronchodilator in pulmonary lymphangioleiomyomatosis".

3876:

Chang WY, Clements D, Johnson SR (September 2010). "Effect of doxycycline on proliferation, MMP production, and adhesion in LAM-related cells".

1589:

Avila, NA; Bechtle, J; Dwyer, AJ; Ferrans, VJ; Moss, J (2001). "Lymphangioleiomyomatosis: CT of diurnal variation of lymphangioleiomyomatosis".

8062: 4615:

Stacker, SA; Williams, SP; Karnezis, T; Shayan, R; Fox, SB; Achen, MG (2014). "Lymphangiogenesis and lymphatic vessel remodelling in cancer".

526:. Proteolytic processing of VEGF-D affects cognate binding to VEGFR3. Histopathologically, LAM lesions are surrounded by cells that stain for 7219:"Relation of pulmonary lymphangioleiomyomatosis to use of the oral contraceptive pill and fertility in the UK: a national case control study" 2655:"A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells" 1167: 222: 7301:

Costello, LC; Hartman, TE; Ryu, JH (2000). "High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex".

7861: 3962:"Rapamycin-insensitive up-regulation of MMP2 and other genes in tuberous sclerosis complex 2-deficient lymphangioleiomyomatosis-like cells" 1112: 229:, or lung collapse, precedes the diagnosis of LAM in 82% of patients. The consensus clinical definition of LAM includes multiple symptoms: 6887:

Zhe, X; Yang, Y; Schuger, L (2005). "Imbalanced plasminogen system in lymphangioleiomyomatosis: potential role of serum response factor".

5347:

Muir, TE; Leslie, KO; Popper, H; Kitaichi, M; Gagné, E; Emelin, JK; Vinters, HV; Colby, TV (1998). "Micronodular pneumocyte hyperplasia".

7062:

Aubry, MC; Myers, JL; Ryu, JH; Henske, EP; Logginidou, H; Jalal, SM; Tazelaar, HD (2000). "Pulmonary lymphangioleiomyomatosis in a man".

5226:

Muller, NL; Chiles, C; Kullnig, P (1990). "Pulmonary lymphangiomyomatosis: Correlation of CT with radiographic and functional findings".

4011:"Doxycycline inhibits matrix metalloproteinase-2 secretion from TSC2-null mouse embryonic fibroblasts and lymphangioleiomyomatosis cells" 3198:"Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton" 2275:

Yu, J; Astrinidis, A; Henske, EP (2001). "Chromosome 16 loss of heterozygosity in tuberous sclerosis and sporadic lymphangiomyomatosis".

7673: 639: 511: 2234:

Henske, EP; Scheithauer, BW; Short, MP; Wollmann, R; Nahmias, J; Hornigold, N; van Slegtenhorst, M; Welsh, CT; Kwiatkowski, DJ (1996).

100: 8113: 7945: 4508:"Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4)" 933:

infection. Escalating doses of everolimus were used, up to 10 mg per day; higher than what is typically used clinically for LAM.

689:

Abnormalities on abdominal imaging, such as renal AML and enlarged lymphatic structures, are also common in LAM. Fat density within a

499: 72: 8036: 7854: 3495:"Interferon-gamma-JAK-STAT signaling in pulmonary lymphangioleiomyomatosis and renal angiomyolipoma: a potential therapeutic target" 1027:

Estimates of median survival vary from 10 to 30 years, depending on whether hospital-based or population-based cohorts are studied.

119: 4751:

Baldwin, ME; Catimel, B; Nice, EC; Roufail, S; Hall, NE; Stenvers, KL; Karkkainen, MJ; Alitalo, K; Stacker, SA; Achen, MG (2001).

994:

should be considered in all patients who are immobilized and/or on antiestrogen therapies, and appropriate therapy instituted for

7888: 7833: 7597: 991: 340:

on exertion with daily activities by 10 years after symptom onset. Many patients require supplemental oxygen over that interval.

6752:

Shen, A; Iseman, MD; Waldron, JA; King, TE (1987). "Exacerbation of pulmonary lymphangioleiomyomatosis by exogenous estrogens".

79: 7838: 7813: 1750:

Ferrans, VJ; Yu, ZX; Nelson, WK; Valencia, JC; Tatsuguchi, A; Avila, NA; Riemenschn, W; Matsui, K; Travis, WD; Moss, J (2000).

452: 2423:"Phenotypic characterization of disseminated cells with TSC2 loss of heterozygosity in patients with lymphangioleiomyomatosis" 7898: 7843: 7823: 735:

Cardiopulmonary exercise testing in a much larger cohort of patients with LAM revealed a reduced maximal oxygen consumption (

57: 50: 6728: 5574:"Utility of [18F]2-fluoro-2-deoxyglucose-PET in sporadic and tuberous sclerosis-associated lymphangioleiomyomatosis" 6131:

McCarty, KS Jr; Mossler, JA; McLelland, R; Sieker, HO (1980). "Pulmonary lymphangiomyomatosis responsive to progesterone".

6104:

Hoon, V; Thung, SN; Kaneko, M; Unger, PD (1994). "HMB-45 reactivity in renal angiomyolipoma and lymphangioleiomyomatosis".

1711:

Matsui, K; Tatsuguchi, A; Valencia, J; Yu, Z; Bechtle, J; Beasley, MB; Avila, NA; Travis, WD; Moss, J; Ferrans, VJ (2000).

1626:"Sporadic lymphangioleiomyomatosis and tuberous sclerosis complex with lymphangioleiomyomatosis: comparison of CT features" 606: 7848: 7776: 4856:

Cudzilo, CJ; Szczesniak, RD; Brody, AS; Rattan, MS; Krueger, DA; Bissler, JJ; Franz, DN; McCormack, FX; Young, LR (2013).

503: 86: 6384:

Ussavarungsi, K; Hu, X; Scott, JP; Erasmus, DB; Mallea, JM; Alvarez, F; Lee, AS; Keller, CA; Ryu, JH; Burger, CD (2015).

4259:

Glasgow CG, Taveira-DaSilva A, Pacheco-Rodriguez G, Steagall WK, Tsukada K, Cai X, El-Chemaly S, Moss J (December 2009).

1673:

Avila, NA; Kelly, JA; Chu, SC; Dwyer, AJ; Moss, J (2000). "Lymphangioleiomyomatosis: abdominopelvic CT and US findings".

939:

Hormonal approaches to treatment have never been tested in proper trials. In the absence of proven benefit, therapy with

588:) in patients with typical cystic changes on high resolution CT scanning of the lung and findings of tuberous sclerosis, 7871: 5382:

Cancellieri, A; Poletti, V; Corrin, B (2002). "Respiratory failure due to micronodular type ii pneumocyte hyperplasia".

871: 678: 310: 4109:"Lymphangioleiomyoma cells and lymphatic endothelial cells: expression of VEGFR-3 in lymphangioleiomyoma cell clusters" 1059:

form of the disease (S-LAM), however, which is not associated with other manifestations of tuberous sclerosis complex.

8031: 4406:"Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases" 68: 1044: 662: 568:

CT scan of the lungs in a patient with lymphangioleiomyomatosis showing numerous thin walled cysts within the lungs

202: 2023:"Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis" 6586:

sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial".

4800:

Baldwin, ME; Halford, MM; Roufail, S; Williams, RA; Hibbs, ML; Grail, D; Kubo, H; Stacker, SA; Achen, MG (2005).

4163:"Changes in lung function and chylous effusions in patients with lymphangioleiomyomatosis treated with sirolimus" 577:

sometimes prompt a chest CT. A review of the CT by an expert familiar with LAM may increase diagnostic accuracy.

4571:"VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium" 1020:

large case series indicated that 38% to 78% of patients were alive at 8.5 years from the time of disease onset.

7987: 7769: 7684: 3196:

Sarbassov, DD; Ali, SM; Kim, DH; Guertin, DA; Latek, RR; Erdjument-Bromage, H; Tempst, P; Sabatini, DM (2004).

3057:"SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity" 3960:

Lee PS, Tsang SW, Moses MA, Trayes-Gibson Z, Hsiao LL, Jensen R, Squillace R, Kwiatkowski DJ (February 2010).

1100: 507: 423:

Angiomyolipomas and pulmonary LAM cells from women with the sporadic form of LAM carry identical mutations in

8118: 7940: 2908:

Kim, DH; Sarbassov, DD; Ali, SM; King, JE; Latek, RR; Erdjument-Bromage, H; Tempst, P; Sabatini, DM (2002).

2859:

Hara, K; Maruki, Y; Long, X; Yoshino, K; Oshiro, N; Hidayat, S; Tokunaga, C; Avruch, J; Yonezawa, K (2002).

2362:

Crooks, DM; Pacheco-Rodriguez, G; DeCastro, RM; McCoy, JP; Wang, JA; Kumaki, F; Darling, T; Moss, J (2004).

471:

including Raptor that positively regulate mTOR activity. MTORC2 consists of six proteins including mTOR and

46: 4753:"The specificity of receptor binding by vascular endothelial growth factor-d is different in mouse and man" 3919:

Glassberg MK, Elliot SJ, Fritz J, Catanuto P, Potier M, Donahue R, Stetler-Stevenson W, Karl M (May 2008).

2910:"mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery" 2508:"Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis" 8123: 8014: 7935: 7903: 2085:"Exonic mutations of TSC2/TSC1 are common but not seen in all sporadic pulmonary lymphangioleiomyomatosis" 2083:

Badri, KR; Gao, L; Hyjek, E; Schuger, N; Schuger, L; Qin, W; Chekaluk, Y; Kwiatkowski, DJ; Zhe, X (2013).

1090: 929: 7415:

Hughes E, Hodder RV (July 1987). "Pulmonary lymphangiomyomatosis complicating pregnancy. A case report".

7749: 6044: 2745: 7580: 751:

Disease progression is usually accompanied by a progressive obstructive ventilatory defect. Decline in

550: 397:

mutations can be located virtually anywhere within the genes, mutation detection is often challenging.

7442:

Yockey, CC; Riepe, RE; Ryan, K (1986). "Pulmonary lymphangioleiomyomatosis complicated by pregnancy".

7140:"Regional and national variability suggests underestimation of prevalence of lymphangioleiomyomatosis" 4949:"European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis" 3635:

Goncharova EA, Goncharov DA, Damera G, Tliba O, Amrani Y, Panettieri RA, Krymskaya VP (October 2009).

3345:"TSC2 modulates actin cytoskeleton and focal adhesion through TSC1-binding domain and the Rac1 GTPase" 261: 93: 7962: 7930: 7925: 7818: 5049:"The diagnosis of cystic lung diseases: a role for bronchoalveolar lavage and transbronchial biopsy?" 4519: 4321: 4009:

Moir LM, Ng HY, Poniris MH, Santa T, Burgess JK, Oliver BG, Krymskaya VP, Black JL (September 2011).

3697: 2653:

Kwiatkowski, DJ; Zhang, H; Bandura, JL; Heiberger, KM; Glogauer, M; el-Hashemite, N; Onda, H (2002).

2375: 2145: 2034: 3686:"Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent" 3397:"Modulation of cell migration and invasiveness by tumor suppressor TSC2 in lymphangioleiomyomatosis" 765:

thin-walled cystic change. LAM lesions often contain an abundance of lymphatic channels, forming an

180: 7883: 7654: 1887:"Lymphangioleiomyomatosis: calling it what it is: a low-grade, destructive, metastasizing neoplasm" 744: 337: 7738: 5142:

Ohara, T; Oto, T; Miyoshi, K; Tao, H; Yamane, M; Toyooka, S; Okazaki, M; Date, H; Sano, Y (2008).

4900:"Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseases" 4506:

Achen, MG; Jeltsch, M; Kukk, E; Mäkinen, T; Vitali, A; Wilks, AF; Alitalo, K; Stacker, SA (1998).

17: 7999: 7866: 7397: 6992: 6912: 6815: 6720: 6670: 6611: 6526: 6304: 6226: 5795: 5713: 5525:"The tuberous sclerosis complex regulates trafficking of glucose transporters and glucose uptake" 5407: 5329: 5286: 5208: 5124: 4988: 4929: 4782: 4684: 4640: 4089: 3901: 3768: 3617: 3573: 3227: 3178: 3086: 3037: 2988: 2939: 2890: 2635: 2537: 2506:

Sato, T; Seyama, K; Fujii, H; Maruyama, H; Setoguchi, Y; Iwakami, S; Fukuchi, Y; Hino, O (2002).

2216: 1864: 492: 266: 5008:"Clinical analysis of patients with pulmonary lymphangioleiomyomatosis (PLAM) in mainland China" 3008:"mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s" 998:

patients. Proper attention should be paid to cardiovascular health following natural or induced

3055:

Jacinto, E; Facchinetti, V; Liu, D; Soto, N; Wei, S; Jung, SY; Huang, Q; Qin, J; Su, B (2006).

895:

Potential side effects from mTOR inhibitors include swelling in the ankles, acne, oral ulcers,

8067: 8026: 7695: 7562: 7521: 7486: 7451: 7424: 7389: 7354: 7318: 7283: 7248: 7199: 7161: 7120: 7079: 7041: 6984: 6948: 6904: 6869: 6842: 6807: 6769: 6712: 6662: 6603: 6567: 6518: 6477: 6442: 6407: 6366: 6331: 6296: 6261: 6218: 6183: 6148: 6113: 6086: 6032: 5997: 5953: 5917: 5865: 5830: 5787: 5752: 5705: 5666: 5603: 5554: 5505: 5456: 5399: 5364: 5321: 5278: 5243: 5200: 5165: 5116: 5080: 5029: 4980: 4921: 4879: 4831: 4774: 4733: 4676: 4632: 4592: 4547: 4488: 4435: 4383: 4347: 4290: 4241: 4192: 4138: 4081: 4040: 3991: 3942: 3893: 3858: 3822: 3760: 3725: 3666: 3609: 3565: 3524: 3475: 3426: 3374: 3325: 3276: 3219: 3170: 3135: 3078: 3029: 2980: 2931: 2882: 2841: 2800: 2733: 2676: 2627: 2586: 2529: 2488: 2452: 2403: 2344: 2292: 2257: 2208: 2173: 2114: 2062: 1990: 1952: 1916: 1856: 1818: 1773: 1732: 1690: 1655: 1606: 1566: 1511: 1470: 1427: 1373: 1316: 1268: 1220: 1149: 1094: 519: 427:. This, together with the fact that recurrent LAM after lung transplantation carries the same 420:

and lymph nodes from women with LAM, and in circulating LAM cells (cells in blood and urine).

378: 169: 7629: 5813:

Burger, CD; Hyatt, RE; Staats, BA (1991). "Pulmonary mechanics in lymphangioleiomyomatosis".

4802:"Vascular endothelial growth factor D is dispensable for development of the lymphatic system" 4178: 4107:

Seyama K, Mitani K, Kumasaka T, Gupta SK, Oommen S, Liu G, Ryu JH, Vlahakis NE (April 2010).

2364:"Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis" 7915: 7552: 7513: 7478: 7381: 7346: 7310: 7275: 7238: 7230: 7191: 7151: 7112: 7071: 7031: 7023: 6976: 6940: 6896: 6799: 6761: 6704: 6652: 6642: 6595: 6557: 6508: 6469: 6460:

Ryu, JH; Doerr, CH; Fisher, SD; Sahn, SA (2003). "Chylothorax in lymphangioleiomyomatosis".

6434: 6397: 6358: 6288: 6253: 6210: 6175: 6140: 6078: 6024: 5987: 5945: 5907: 5899: 5857: 5822: 5779: 5744: 5697: 5656: 5593: 5585: 5544: 5536: 5495: 5487: 5446: 5438: 5391: 5356: 5313: 5270: 5235: 5192: 5155: 5108: 5070: 5060: 5019: 4970: 4960: 4911: 4869: 4821: 4813: 4764: 4723: 4715: 4668: 4624: 4582: 4537: 4527: 4478: 4470: 4425: 4417: 4375: 4337: 4329: 4280: 4272: 4231: 4223: 4182: 4174: 4128: 4120: 4073: 4030: 4022: 3981: 3973: 3932: 3885: 3850: 3812: 3804: 3752: 3715: 3705: 3656: 3648: 3601: 3555: 3514: 3506: 3465: 3457: 3416: 3408: 3364: 3356: 3315: 3307: 3266: 3258: 3209: 3162: 3125: 3117: 3068: 3019: 2970: 2921: 2872: 2831: 2790: 2782: 2723: 2715: 2666: 2617: 2576: 2568: 2519: 2480: 2442: 2434: 2393: 2383: 2334: 2326: 2284: 2247: 2200: 2163: 2153: 2104: 2096: 2052: 2042: 1982: 1944: 1906: 1898: 1848: 1808: 1800: 1763: 1724: 1682: 1645: 1637: 1598: 1556: 1548: 1537:"The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment" 1503: 1462: 1417: 1409: 1365: 1308: 1258: 1212: 1141: 1056: 924: 920: 665:

were abnormal in 34 of 35 LAM patients. The most common abnormality was nonspecific diffuse

621: 564: 326: 5886:

Taveira-DaSilva, AM; Hathaway, OM; Sachdev, V; Shizukuda, Y; Birdsall, CW; Moss, J (2007).

3444:

Goncharova, EA; Goncharova, DA; Li, H; Pimtong, W; Lu, S; Khavin, I; Krymskaya, VP (2011).

3006:

Frias, MA; Thoreen, CC; Jaffe, JD; Schroder, W; Sculley, T; Carr, SA; Sabatini, DM (2006).

2959:"TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function" 677:

LAM and AML lesions do not typically exhibit increased uptake of 18F-fluorodeoxyglucose on

7808: 7644: 6690:"A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis" 1099:, Spencer (Angela Gots) was diagnosed with LAM, though later it was found to be a case of 979: 813: 778: 774: 707: 643: 460: 287: 256: 152: 2236:"Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions" 313:. The consequences of vessel and airway obstruction include chylous fluid accumulations, 7217:

Wahedna, I; Cooper, S; Williams, J; Paterson, IC; Britton, JR; Tattersfield, AE (1994).

4523: 4325: 3701: 2771:"Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis" 2379: 2149: 2038: 584:

In some cases, a LAM diagnosis can be made with confidence on clinical grounds (without

8057: 7972: 7967: 7957: 7792: 7036: 7011: 5992: 5975: 5912: 5887: 5598: 5573: 5549: 5524: 5500: 5475: 5451: 5426: 5317: 5274: 4826: 4801: 4728: 4703: 4483: 4458: 4430: 4405: 4342: 4309: 4285: 4260: 4236: 4211: 4187: 4162: 4133: 4108: 4077: 4035: 4010: 3986: 3961: 3817: 3792: 3720: 3685: 3661: 3636: 3519: 3494: 3470: 3445: 3421: 3396: 3369: 3344: 3320: 3295: 3271: 3246: 3130: 3105: 2795: 2770: 2728: 2703: 2581: 2556: 2447: 2422: 2339: 2314: 2252: 2235: 2109: 2084: 1911: 1886: 1713:"Extrapulmonary lymphangioleiomyomatosis (LAM): clinicopathologic features in 22 cases" 1686: 1650: 1625: 1561: 1536: 1422: 1397: 983: 855: 589: 417: 413: 7659: 7243: 7218: 6599: 6386:"Mayo clinic experience of lung transplantation in pulmonary lymphangioleiomyomatosis" 5729: 5727: 4474: 2975: 2958: 2926: 2909: 2877: 2860: 2398: 2363: 2168: 2133: 483:

STAT1 and STAT3 and autophagy are known mediators of LAM cell viability and survival.

8107: 7982: 7598:

American Thoracic Society (US): Patient Information Series – Lymphangioleiomyomatosis

7557: 7540: 7517: 6562: 6545: 6513: 6496: 6179: 5826: 5783: 5701: 5523:

Jiang, X; Kenerson, H; Aicher, L; Miyaoka, R; Eary, J; Bissler, J; Yeung, RS (2008).

5395: 5360: 5160: 5143: 4542: 4507: 4026: 3743:

Henske, EP (2003). "Metastasis of benign tumor cells in tuberous sclerosis complex".

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dyspneic patients with LAM, which may contribute to resting and exercise hypoxemia.

217:

Diagnosis is typically delayed 5 to 6 years. The condition is often misdiagnosed as

8092: 8087: 8022: 7800: 7724: 6674: 6230: 5888:"Pulmonary artery pressure in lymphangioleiomyomatosis: An echocardiographic study" 5411: 5212: 5128: 4992: 4704:"Lymphatic endothelial differentiation in pulmonary lymphangioleiomyomatosis cells" 4644: 3231: 3041: 2943: 2894: 2313:

Smolarek, TA; Wessner, LL; McCormack, FX; Mylet, JC; Menon, AG; Henske, EP (1998).

1868: 1055:

in multiple tissues. Most LAM patients who present for medical evaluation have the

1052: 1003: 995: 944: 940: 904: 900: 766: 626: 539: 518:

and a member of the VEGF family of growth factors, is known for its role in cancer

515: 479: 366: 318: 226: 161: 3560: 3543: 3090: 1752:"Lymphangioleiomyomatosis (LAM) (A review of clinical and morphological features)" 558: 491:

unknown. Lung remodeling may be mediated by an imbalance between matrix degrading

7689: 7350: 7075: 6688:

Chang, WY; Cane, JL; Kumaran, M; Lewis, S; Tattersfield, AE; Johnson, SR (2014).

6362: 5748: 3311: 2288: 1986: 1948: 1507: 1216: 475:, which defines the activation level of mTORC2 and modulates the assembly of the 7992: 7878: 7727: 6144: 6028: 4916: 4899: 1880: 1878: 1263: 1246: 960: 948: 909: 863: 826: 770: 711: 650: 593: 578: 291: 251: 198: 174: 35: 7700: 7539:

Tazelaar, HD; Kerr, D; Yousem, SA; Saldana, MJ; Langston, C; Colby, TV (1993).

7279: 7195: 7116: 7012:"Survival and disease progression in UK patients with lymphangioleiomyomatosis" 6944: 6438: 6402: 6385: 6064: 6062: 6060: 5949: 5624:

Johnson, SR; Tattersfield, AE (1998). "Pregnancy in lymphangioleiomyomatosis".

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El-Hashemite, N; Zhang, H; Walker, V; Hoffmeister, KM; Kwiatkowski, DJ (2004).

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Crino, PB; Nathanson, KL; Henske, EP (2006). "The tuberous sclerosis complex".

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Taveira-DaSilva, AM; Steagall, WK; Moss, J (2006). "Lymphangioleiomyomatosis".

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on exertion, spaced by recurrent pneumothoraces and in some patients, chylous

314: 306: 302: 239: 7097: 7095: 7093: 6900: 6082: 5661: 5644: 4719: 3977: 3854: 3510: 3412: 3296:"Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size" 2861:"Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action" 2100: 2016: 2014: 2012: 2010: 2008: 2006: 2004: 1466: 1312: 1132:

McCormack FX (February 2008). "Lymphangioleiomyomatosis: a clinical update".

777:

fat, to destroy bronchial cartilage and arteriolar walls, and to occlude the

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had no effect on the rate of lung function decline in a double blind trial.

956: 952: 896: 809: 445: 441: 7761: 7393: 7358: 7322: 7287: 7203: 7165: 7156: 7139: 7124: 7083: 7057: 7055: 7045: 6988: 6908: 6846: 6811: 6765: 6716: 6666: 6607: 6571: 6522: 6481: 6446: 6411: 6370: 6300: 6292: 6222: 6090: 5957: 5921: 5869: 5791: 5756: 5709: 5670: 5607: 5558: 5509: 5460: 5403: 5204: 5169: 5120: 5084: 5033: 4984: 4925: 4883: 4835: 4778: 4769: 4752: 4737: 4680: 4636: 4596: 4492: 4439: 4387: 4379: 4351: 4294: 4245: 4196: 4142: 4085: 4044: 3995: 3946: 3897: 3862: 3826: 3764: 3729: 3670: 3652: 3613: 3605: 3569: 3528: 3479: 3430: 3378: 3329: 3280: 3223: 3174: 3139: 3082: 3033: 2984: 2935: 2886: 2845: 2804: 2737: 2680: 2671: 2654: 2631: 2622: 2605: 2590: 2533: 2492: 2456: 2407: 2296: 2212: 2118: 2066: 1994: 1920: 1860: 1822: 1777: 1736: 1694: 1659: 1610: 1570: 1515: 1474: 1431: 1377: 1320: 1153: 986:-responsive airflow obstruction. Oxygen should be administered to maintain 455:(mTOR) signaling complex by directly controlling the activity of the small 7566: 7525: 7490: 7455: 7428: 7252: 6952: 6873: 6773: 6335: 6265: 6187: 6152: 6117: 6001: 5903: 5834: 5589: 5368: 5325: 5282: 5247: 4874: 4857: 4551: 4532: 4421: 4276: 4212:"Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis" 3395:

Goncharova EA, Goncharov DA, Lim PN, Noonan D, Krymskaya VP (April 2006).

3360: 2719: 2348: 2261: 2177: 2158: 2078: 2076: 1956: 1272: 1224: 1145: 7744: 7234: 7010:

Johnson, SR; Whale, CI; Hubbard, RB; Lewis, SA; Tattersfield, AE (2004).

6036: 4702:

Davis JM, Hyjek E, Husain AN, Shen L, Jones J, Schuger LA (August 2013).

3937: 3920: 3461: 2786: 1852: 1488: 1486: 1484: 975: 789: 350: 271: 7612: 5881: 5879: 5619: 5617: 4058: 4056: 4054: 1768: 1751: 1529: 1527: 1525: 197:) is a rare, progressive and systemic disease that typically results in 8083: 7952: 6657: 5425:

Gupta N, Vassallo R, Wikenheiser-Brokamp KA, McCormack FX (June 2015).

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in clinical trials and FDA approval of sirolimus for treatment of LAM.

330: 322: 305:

smooth muscle-like cells that invade all lung structures including the

7177: 7175: 5474:

Gupta, N; Vassallo, R; Wikenheiser-Brokamp, KA; McCormack, FX (2015).

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McCormack FX, Travis WD, Colby TV, Henske EP, Moss J (December 2012).

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size of lymphangioleiomyomatosis, and can lead to total resolution.

862:

sparing partial resections may be considered for very large tumors.

301:

Lung destruction in LAM is a consequence of diffuse infiltration by

248:

Chylous complications arising from lymphatic obstruction, including

6425:

Itkin, M (2014). "Lymphatic intervention is a new frontier of IR".

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1834: 1832: 1240: 1238: 1236: 1234: 603:

Diagram 1 outlines a proposed algorithm for the diagnosis of LAM.

7678: 4161:

Taveira-DaSilva, AM; Hathaway, O; Stylianou, M; Moss, J (2011).

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should be considered in LAM patients, because up to 17–25% have

805: 752: 574: 205:(TSC), while TSC-LAM refers to LAM that is associated with TSC. 7765: 1584: 1582: 1580: 1391: 1389: 1387: 990:

saturations of greater than 90% with rest, exercise and sleep.

3343:

Goncharova, E; Goncharov, D; Noonan, D; Krymskaya, VP (2004).

2704:"Efficacy and safety of sirolimus in lymphangioleiomyomatosis" 1447: 1445: 1443: 1441: 1350: 29: 4851: 4849: 4847: 4845: 1348: 1346: 1344: 1342: 1340: 1338: 1336: 1334: 1332: 1330: 451:

TSC1 and TSC2 form a tumor suppressor complex that regulates

444:

complex 1 (mTORC1) led to successful use of rapamycin analog

361:

genes, which were cloned in 1997 and 1993, respectively. The

816:

remains the last resort for patients with advanced disease.

718:, but the significance of that finding has been challenged. 416:

or LOH. LOH can be detected in microdissected LAM cells, in

164:). The inset image shows a cross-section of a lung with LAM. 6785: 6783: 4399: 4397: 4308:

Glasgow CG, Taveira-Dasilva AM, Darling TN, Moss J (2008).

1398:"Clinical experience of lymphangioleiomyomatosis in the UK" 812:, is available for stabilization of lung function decline. 6497:"Management of renal angiomyolipoma: a report of 53 cases" 2134:"Mutation and cancer: statistical study of retinoblastoma" 1294: 1292: 1290: 1288: 1286: 1284: 1282: 1247:"Lymphangioleiomyomatosis. Clinical course in 32 patients" 2957:

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1047:(TSC-LAM), a heritable syndrome that is associated with 5643:

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The typical disease course displays progressive 6049:: CS1 maint: DOI inactive as of September 2024 ( 3493:El-Hashemite N, Kwiatkowski DJ (September 2005). 908:to avoid prolonged sun exposure due to increased 1624:Avila, NA; Dwyer, AJ; Rabel, A; Moss, J (2007). 8005:Intravascular papillary endothelial hyperplasia 2021:Carsillo, T; Astrinidis, A; Henske, EP (2000). 804:An FDA-approved drug for treatment of LAM, the 3786: 3784: 3782: 706:Central nervous system abnormalities, such as 7777: 6495:De Luca, S; Terrone, C; Rossetti, SR (1999). 5974:Corrin B, Liebow AA, Friedman PJ (May 1975). 4610: 4608: 4606: 4563: 4561: 8: 3294:Saci, A; Cantley, LC; Carpenter, CL (2011). 2750:: CS1 maint: multiple names: authors list ( 1093:", the fifth episode of the fifth season of 7784: 7770: 7762: 7603: 7581:"About Us | About the LAM Foundation" 5976:"Pulmonary lymphangiomyomatosis. A review" 3245:Zoncu, R; Efeyan, A; Sabatini, DM (2011). 2754:) CS1 maint: numeric names: authors list ( 377:(16p13). TSC-LAM occurs in women who have 179: 151: 134: 7556: 7242: 7155: 7035: 6656: 6646: 6561: 6512: 6401: 5991: 5911: 5660: 5645:"Meningiomas in lymphangioleiomyomatosis" 5597: 5548: 5499: 5450: 5159: 5074: 5064: 5023: 4974: 4964: 4915: 4873: 4825: 4768: 4727: 4586: 4541: 4531: 4482: 4429: 4341: 4284: 4235: 4186: 4132: 4034: 3985: 3936: 3816: 3791:Henske EP, McCormack FX (November 2012). 3719: 3709: 3660: 3559: 3518: 3469: 3420: 3368: 3319: 3270: 3213: 3129: 3072: 3023: 2974: 2925: 2876: 2835: 2794: 2727: 2670: 2621: 2580: 2523: 2446: 2397: 2387: 2338: 2251: 2167: 2157: 2108: 2056: 2046: 1910: 1812: 1767: 1706: 1704: 1649: 1560: 1421: 1262: 1043:It occurs in more than 30% of women with 899:, diarrhea, elevation of cholesterol and 727:LAM in centers around the United States. 120:Learn how and when to remove this message 4179:10.7326/0003-4819-154-12-201106210-00007 1124: 915:Treatment with another mTOR inhibitor, 630:properties and decreased lung volumes. 8063:Multifocal lymphangioendotheliomatosis 6042: 5476:"Diffuse Cystic Lung Disease. Part II" 3878:Am. J. Physiol. Lung Cell Mol. Physiol 2743: 1396:Johnson, SR; Tattersfield, AE (2000). 769:meshwork of slit-like spaces lined by 56:Please improve this article by adding 7541:"Diffuse pulmonary lymphangiomatosis" 5427:"Diffuse Cystic Lung Disease. Part I" 2820:"Defining the role of mTOR in cancer" 486:LAM cells behave, in many ways, like 412:gene; this is referred to as loss of 400:On a cellular basis, LAM cells carry 223:chronic obstructive pulmonary disease 7: 7862:Proliferating angioendotheliomatosis 1113:Perivascular epithelioid cell tumour 530:3, the lymphatic vessel endothelial 373:gene is located on the short arm of 6544:Bissler, JJ; Kingswood, JC (2004). 640:high-resolution computed tomography 365:gene is located on the long arm of 5318:10.1046/j.1365-2559.1997.4600811.x 5275:10.1111/j.1365-2559.1991.tb00856.x 4119:(4): 2051–2, author reply 2052–4. 4078:10.1097/01.pas.0000172192.25295.45 3104:Laplante, M; Sabatini, DM (2009). 2818:Guertin, DA; Sabatini, DM (2007). 1687:10.1148/radiology.216.1.r00jl42147 309:, airway walls, blood vessels and 25: 18:Pulmonary lymphangioleiomyomatosis 8037:Acquired progressive lymphangioma 6969:Sarcoidosis Vasc Diffuse Lung Dis 927:, pneumonia, cardiac failure and 850:Treatment of renal angiomyolipoma 581:can also bring LAM to attention. 6563:10.1111/j.1523-1755.2004.00838.x 6514:10.1046/j.1464-410x.1999.00932.x 6180:10.1097/00000478-198909000-00011 5784:10.1111/j.1440-1843.2005.00762.x 5702:10.1111/j.1440-1843.2007.01101.x 5396:10.1046/j.1365-2559.2002.01433.x 5361:10.1097/00000478-199804000-00012 5161:10.1016/j.athoracsur.2008.07.062 4027:10.1111/j.1476-5381.2011.01344.x 1756:Journal of Nippon Medical School 1370:10.1097/00005792-199909000-00004 878:Treatment of lymphangioleiomyoma 596:or serum VEGF-D > 800 pg/ml. 34: 7814:Blue rubber bleb nevus syndrome 5240:10.1148/radiology.175.2.2326457 4818:10.1128/mcb.25.6.2441-2449.2005 959:are not routinely recommended. 27:Progressive cystic lung disease 5827:10.1164/ajrccm/143.5_Pt_1.1030 5006:Ye, L; Jin, M; Bai, C (2010). 702:Central nervous system imaging 138:Lymphangioleiomyomatosis (LAM) 1: 7483:10.1164/ajrccm/145.4_Pt_1.964 6600:10.1016/s0140-6736(12)61767-x 5431:Am. J. Respir. Crit. Care Med 4475:10.1016/S2213-2600(13)70090-0 3966:Am. J. Respir. Cell Mol. Biol 3843:Am. J. Respir. Cell Mol. Biol 3561:10.1158/0008-5472.can-03-3609 3499:Am. J. Respir. Cell Mol. Biol 3401:Am. J. Respir. Cell Mol. Biol 2976:10.1016/s0960-9822(03)00329-4 2927:10.1016/s0092-8674(02)00808-5 2878:10.1016/s0092-8674(02)00833-4 1891:Am. J. Respir. Crit. Care Med 557:of lymphangioleiomyomatosis. 504:Langerhans cell histiocytosis 453:mammalian target of rapamycin 58:secondary or tertiary sources 7909:Immunosuppression-associated 7872:Infantile hemangiopericytoma 7558:10.1016/0046-8177(93)90265-i 7518:10.1016/0090-4295(93)90504-4 7351:10.1164/ajrccm.164.4.2101154 7076:10.1164/ajrccm.162.2.9911006 6363:10.5858/2000-124-1642-HOTIPI 5749:10.1164/ajrccm.164.6.2102125 5047:Torre, O; Harari, S (2010). 3312:10.1016/j.molcel.2011.03.017 3106:"mTOR signaling at a glance" 2289:10.1164/ajrccm.164.8.2104095 1987:10.1164/ajrccm.163.1.2005004 1949:10.1126/science.277.5327.805 1508:10.1164/ajrccm.164.4.2011025 1217:10.1164/ajrccm.151.2.7842216 872:Food and Drug Administration 679:positron emission tomography 673:Positron emission tomography 351:"loss of function" mutations 8032:Lymphangioma circumscriptum 6145:10.1056/nejm198012183032506 6029:10.1164/arrd.1977.116.6.977 4917:10.1183/13993003.00570-2015 1264:10.1056/nejm199011013231807 1051:, cognitive impairment and 820:Treatment of pneumothoraces 710:or subependymal tubers and 663:ventilation-perfusion scans 657:Ventilation-perfusion scans 8140: 7280:10.1089/154099903321154176 7196:10.1016/j.crad.2011.02.009 7117:10.1164/rccm.200610-1408cr 6439:10.1016/j.jvir.2014.06.004 6403:10.1016/j.rmed.2015.08.014 5950:10.1164/rccm.201304-0618le 5541:10.2353/ajpath.2008.070958 5492:10.1164/rccm.201411-2096ci 5443:10.1164/rccm.201411-2094CI 5066:10.1016/j.rmed.2010.03.021 5025:10.1016/j.rmed.2010.05.003 4125:10.2353/ajpath.2010.091239 3925:J. Clin. Endocrinol. Metab 3890:10.1152/ajplung.00437.2009 3074:10.1016/j.cell.2006.08.033 2439:10.1164/rccm.201003-0489oc 1903:10.1164/rccm.201205-0848OE 1805:10.1177/107327480601300405 1553:10.1164/rccm.200409-1298oc 1045:tuberous sclerosis complex 722:Pulmonary function studies 317:, airflow obstruction and 203:tuberous sclerosis complex 69:"Lymphangioleiomyomatosis" 8114:Lymphatic vessel diseases 7339:Am J Respir Crit Care Med 7268:J Womens Health (Larchmt) 7105:Am J Respir Crit Care Med 7064:Am J Respir Crit Care Med 6981:10.1007/s11083-007-9058-0 6889:Am J Respir Cell Mol Biol 6804:10.1007/s00408-012-9419-3 6709:10.1183/09031936.00167413 6648:10.1183/09031936.00210714 6215:10.1007/s00428-014-1559-9 6071:Am J Respir Cell Mol Biol 5938:Am J Respir Crit Care Med 5862:10.1164/rccm.200206-593oc 5850:Am J Respir Crit Care Med 5737:Am J Respir Crit Care Med 5626:Am J Respir Crit Care Med 5480:Am J Respir Crit Care Med 4966:10.1183/09031936.00076209 4673:10.1080/08977190290031969 4588:10.1016/j.ccr.2011.12.026 4228:10.1183/09059180.00009311 3215:10.1016/j.cub.2004.06.054 3025:10.1016/j.cub.2006.08.001 2837:10.1016/j.ccr.2007.05.008 2525:10.1007/s10038-002-8651-8 2485:10.1164/rccm.200208-969oc 2473:Am J Respir Crit Care Med 2427:Am J Respir Crit Care Med 2277:Am J Respir Crit Care Med 2089:Am J Respir Crit Care Med 1975:Am J Respir Crit Care Med 1642:10.1148/radiol.2421051767 1603:10.1148/radiol.2212001448 1541:Am J Respir Crit Care Med 1496:Am J Respir Crit Care Med 1414:10.1136/thorax.55.12.1052 1205:Am J Respir Crit Care Med 874:(FDA) for AML treatment. 781:of pulmonary arterioles. 159: 150: 146:lymphangiomyomatosis, LAM 8051:Lymphangioleiomyomatosis 7894:African lymphadenopathic 7793:Tumours of blood vessels 7739:lymphangioleiomyomatosis 6945:10.1164/ajrccm/143.1.174 6901:10.1165/rcmb.2004-0289oc 6546:"Renal angiomyolipomata" 6083:10.1165/ajrcmb.21.3.3693 5662:10.1001/jama.286.15.1879 4720:10.1369/0022155413489311 4512:Proc Natl Acad Sci U S A 3978:10.1165/rcmb.2009-0050OC 3855:10.1165/rcmb.2002-0124OC 3745:Genes Chromosomes Cancer 3690:Proc Natl Acad Sci U S A 3511:10.1165/rcmb.2005-0152RC 3413:10.1165/rcmb.2005-0374OC 2368:Proc Natl Acad Sci U S A 2138:Proc Natl Acad Sci U S A 2101:10.1164/ajrccm.187.6.663 2027:Proc Natl Acad Sci U S A 1467:10.1378/chest.129.5.1274 1313:10.1378/chest.115.4.1041 833:Treatment of chylothorax 534:receptor 1 (LYVE-1) and 191:Lymphangioleiomyomatosis 7386:10.1136/jmg.2008.065342 7028:10.1136/thx.2004.023283 6474:10.1378/chest.123.2.623 6031:(inactive 2024-09-12). 4334:10.1196/annals.1413.018 3711:10.1073/pnas.1104361108 2389:10.1073/pnas.0407971101 2132:Knudson, AG Jr (1971). 2048:10.1073/pnas.97.11.6085 1729:10.1053/hupa.2000.18500 592:, lymphangioleiomyoma, 512:Birt–Hogg–Dubé syndrome 7979:Universal angiomatosis 7946:Targeted hemosiderotic 7829:Endovascular papillary 6766:10.1378/chest.91.5.782 6351:Arch. Pathol. Lab. Med 6293:10.1378/chest.117.1.25 4770:10.1074/jbc.m100097200 4708:J. Histochem. Cytochem 4380:10.1089/lrb.2006.4.143 3653:10.1124/mol.109.057042 3606:10.1124/mol.107.040824 2623:10.1074/jbc.m202678200 930:Pneumocystis jirovecii 870:is approved by the US 612: 569: 561: 45:relies excessively on 6258:10.1093/ajcp/93.5.609 5904:10.1378/chest.07-1205 5821:(5 Pt 1): 1030–1033. 5590:10.1378/chest.09-0336 4875:10.1378/chest.12-2813 4533:10.1073/pnas.95.2.548 4422:10.1378/chest.10-0573 4277:10.1089/lrb.2009.0017 3361:10.1083/jcb.200405130 3251:Nat Rev Mol Cell Biol 2720:10.1056/nejmoa1100391 2702:Trapnell, BC (2011). 2159:10.1073/pnas.68.4.820 1146:10.1378/chest.07-0898 609: 567: 553: 7819:Hemangioendothelioma 7450:(10): 277–278, 293. 7235:10.1136/thx.49.9.910 7157:10.1093/qjmed/hcr116 6427:J Vasc Interv Radiol 6017:Am. Rev. Respir. Dis 4314:Ann. N. Y. Acad. Sci 3938:10.1210/jc.2007-1283 3462:10.1128/mcb.01061-10 3116:(Pt 20): 3589–3594. 2787:10.1056/nejmoa063564 2672:10.1093/hmg/11.5.525 1853:10.1056/nejmra055323 1358:Medicine (Baltimore) 1002:. Immunizations for 440:mammalian target of 404:inactivation of the 279:in vaginal discharge 7477:(4 Pt 1): 964–966. 6106:Arch Pathol Lab Med 4763:(22): 19166–19171. 4524:1998PNAS...95..548A 4326:2008NYASA1131..206G 3702:2011PNAS..10812455P 3696:(30): 12455–12460. 2616:(34): 30958–30967. 2380:2004PNAS..10117462C 2374:(50): 17462–17467. 2150:1971PNAS...68..820K 2039:2000PNAS...97.6085C 1769:10.1272/jnms.67.311 745:anaerobic threshold 634:Computed tomography 311:interstitial spaces 8000:Pyogenic granuloma 7867:Hemangiopericytoma 7711:External resources 5059:(Suppl 1): S81-5. 3122:10.1242/jcs.051011 1101:Sjögren's syndrome 1085:In popular culture 613: 570: 562: 508:Sjögren's syndrome 493:metalloproteinases 379:germline mutations 292:low blood pressure 209:Signs and symptoms 8101: 8100: 8068:Lymphangiomatosis 8027:lymphangiosarcoma 7889:African cutaneous 7759: 7758: 7551:(12): 1313–1322. 7471:Am Rev Respir Dis 6933:Am Rev Respir Dis 6841:(17): 5173–5177. 6594:(9869): 817–824. 6396:(10): 1354–1359. 6139:(25): 1461–1465. 5856:(12): 1427–1431. 5815:Am Rev Respir Dis 5655:(15): 1879–1881. 5197:10.1159/000328602 5113:10.1159/000325340 5018:(10): 1521–1526. 4463:Lancet Respir Med 4072:(10): 1356–1366. 3757:10.1002/gcc.10252 3554:(10): 3436–3443. 3456:(12): 2484–2498. 3208:(14): 1296–1302. 3161:(11): 1122–1128. 3018:(18): 1865–1870. 2714:(17): 1595–1606. 2433:(11): 1410–1418. 2033:(11): 6085–6090. 1943:(5327): 805–808. 1847:(13): 1345–1356. 1723:(10): 1242–1248. 1408:(12): 1052–1057. 1257:(18): 1254–1260. 992:Bone densitometry 685:Abdominal imaging 520:lymphangiogenesis 336:Most people have 327:pleural effusions 240:Coughing up blood 188: 187: 132:Medical condition 130: 129: 122: 104: 16:(Redirected from 8131: 7916:Hemangioblastoma 7884:Kaposi's sarcoma 7786: 7779: 7772: 7763: 7604: 7585: 7584: 7577: 7571: 7570: 7560: 7536: 7530: 7529: 7501: 7495: 7494: 7466: 7460: 7459: 7439: 7433: 7432: 7412: 7406: 7405: 7369: 7363: 7362: 7333: 7327: 7326: 7315:10.4065/75.6.591 7298: 7292: 7291: 7263: 7257: 7256: 7246: 7214: 7208: 7207: 7179: 7170: 7169: 7159: 7135: 7129: 7128: 7099: 7088: 7087: 7059: 7050: 7049: 7039: 7007: 7001: 7000: 6963: 6957: 6956: 6927: 6921: 6920: 6884: 6878: 6877: 6857: 6851: 6850: 6830: 6824: 6823: 6787: 6778: 6777: 6749: 6743: 6742: 6740: 6739: 6733: 6727:. Archived from 6703:(4): 1114–1123. 6694: 6685: 6679: 6678: 6660: 6650: 6626: 6620: 6619: 6582: 6576: 6575: 6565: 6541: 6535: 6534: 6516: 6492: 6486: 6485: 6457: 6451: 6450: 6433:(9): 1404–1405. 6422: 6416: 6415: 6405: 6381: 6375: 6374: 6346: 6340: 6339: 6319: 6313: 6312: 6276: 6270: 6269: 6246:Am J Clin Pathol 6241: 6235: 6234: 6198: 6192: 6191: 6168:Am J Surg Pathol 6163: 6157: 6156: 6128: 6122: 6121: 6101: 6095: 6094: 6066: 6055: 6054: 6048: 6040: 6012: 6006: 6005: 5995: 5971: 5962: 5961: 5944:(9): 1167–1170. 5932: 5926: 5925: 5915: 5898:(5): 1573–1578. 5883: 5874: 5873: 5845: 5839: 5838: 5810: 5804: 5803: 5767: 5761: 5760: 5743:(6): 1072–1076. 5731: 5722: 5721: 5684: 5675: 5674: 5664: 5640: 5634: 5633: 5621: 5612: 5611: 5601: 5569: 5563: 5562: 5552: 5535:(6): 1748–1756. 5520: 5514: 5513: 5503: 5471: 5465: 5464: 5454: 5422: 5416: 5415: 5379: 5373: 5372: 5349:Am J Surg Pathol 5344: 5338: 5337: 5301: 5295: 5294: 5258: 5252: 5251: 5223: 5217: 5216: 5191:(6): 1081–1084. 5180: 5174: 5173: 5163: 5139: 5133: 5132: 5095: 5089: 5088: 5078: 5068: 5044: 5038: 5037: 5027: 5003: 4997: 4996: 4978: 4968: 4944: 4938: 4937: 4919: 4910:(4): 1196–1199. 4894: 4888: 4887: 4877: 4853: 4840: 4839: 4829: 4812:(6): 2441–2449. 4797: 4791: 4790: 4772: 4748: 4742: 4741: 4731: 4699: 4693: 4692: 4655: 4649: 4648: 4612: 4601: 4600: 4590: 4565: 4556: 4555: 4545: 4535: 4503: 4497: 4496: 4486: 4453: 4444: 4443: 4433: 4401: 4392: 4391: 4368:Lymphat Res Biol 4362: 4356: 4355: 4345: 4305: 4299: 4298: 4288: 4265:Lymphat Res Biol 4256: 4250: 4249: 4239: 4222:(125): 196–206. 4207: 4201: 4200: 4190: 4158: 4147: 4146: 4136: 4104: 4098: 4097: 4066:Am J Surg Pathol 4060: 4049: 4048: 4038: 4015:Br. J. Pharmacol 4006: 4000: 3999: 3989: 3957: 3951: 3950: 3940: 3916: 3910: 3909: 3873: 3867: 3866: 3837: 3831: 3830: 3820: 3809:10.1172/JCI58709 3788: 3777: 3776: 3740: 3734: 3733: 3723: 3713: 3681: 3675: 3674: 3664: 3632: 3626: 3625: 3592:proliferation". 3588: 3582: 3581: 3563: 3539: 3533: 3532: 3522: 3490: 3484: 3483: 3473: 3441: 3435: 3434: 3424: 3392: 3383: 3382: 3372: 3355:(6): 1171–1182. 3340: 3334: 3333: 3323: 3291: 3285: 3284: 3274: 3242: 3236: 3235: 3217: 3193: 3187: 3186: 3150: 3144: 3143: 3133: 3101: 3095: 3094: 3076: 3052: 3046: 3045: 3027: 3003: 2997: 2996: 2978: 2954: 2948: 2947: 2929: 2905: 2899: 2898: 2880: 2856: 2850: 2849: 2839: 2815: 2809: 2808: 2798: 2766: 2760: 2759: 2749: 2741: 2731: 2698: 2685: 2684: 2674: 2650: 2644: 2643: 2625: 2601: 2595: 2594: 2584: 2552: 2546: 2545: 2527: 2503: 2497: 2496: 2467: 2461: 2460: 2450: 2418: 2412: 2411: 2401: 2391: 2359: 2353: 2352: 2342: 2310: 2301: 2300: 2283:(8): 1537–1540. 2272: 2266: 2265: 2255: 2231: 2225: 2224: 2205:10.1038/35101031 2188: 2182: 2181: 2171: 2161: 2129: 2123: 2122: 2112: 2080: 2071: 2070: 2060: 2050: 2018: 1999: 1998: 1970: 1961: 1960: 1931: 1925: 1924: 1914: 1882: 1873: 1872: 1836: 1827: 1826: 1816: 1788: 1782: 1781: 1771: 1747: 1741: 1740: 1708: 1699: 1698: 1670: 1664: 1663: 1653: 1621: 1615: 1614: 1586: 1575: 1574: 1564: 1531: 1520: 1519: 1490: 1479: 1478: 1461:(5): 1274–1281. 1449: 1436: 1435: 1425: 1393: 1382: 1381: 1352: 1325: 1324: 1307:(4): 1041–1052. 1296: 1277: 1276: 1266: 1242: 1229: 1228: 1200: 1183: 1182: 1180: 1178: 1164: 1158: 1157: 1129: 971:Other management 925:peripheral edema 622:chest radiograph 616:Chest radiograph 262:Chylopericardium 242:(rarely massive) 184: 183: 155: 135: 125: 118: 114: 111: 105: 103: 62: 38: 30: 21: 8139: 8138: 8134: 8133: 8132: 8130: 8129: 8128: 8104: 8103: 8102: 8097: 8072: 8009: 7899:AIDS-associated 7809:Hemangiosarcoma 7795: 7790: 7760: 7755: 7754: 7706: 7705: 7615: 7594: 7589: 7588: 7579: 7578: 7574: 7538: 7537: 7533: 7503: 7502: 7498: 7468: 7467: 7463: 7441: 7440: 7436: 7414: 7413: 7409: 7371: 7370: 7366: 7335: 7334: 7330: 7300: 7299: 7295: 7265: 7264: 7260: 7216: 7215: 7211: 7181: 7180: 7173: 7150:(11): 971–979. 7137: 7136: 7132: 7101: 7100: 7091: 7061: 7060: 7053: 7009: 7008: 7004: 6965: 6964: 6960: 6929: 6928: 6924: 6886: 6885: 6881: 6859: 6858: 6854: 6832: 6831: 6827: 6789: 6788: 6781: 6751: 6750: 6746: 6737: 6735: 6731: 6692: 6687: 6686: 6682: 6628: 6627: 6623: 6584: 6583: 6579: 6543: 6542: 6538: 6494: 6493: 6489: 6459: 6458: 6454: 6424: 6423: 6419: 6383: 6382: 6378: 6348: 6347: 6343: 6321: 6320: 6316: 6278: 6277: 6273: 6243: 6242: 6238: 6200: 6199: 6195: 6165: 6164: 6160: 6130: 6129: 6125: 6103: 6102: 6098: 6068: 6067: 6058: 6041: 6014: 6013: 6009: 5973: 5972: 5965: 5934: 5933: 5929: 5885: 5884: 5877: 5847: 5846: 5842: 5812: 5811: 5807: 5769: 5768: 5764: 5733: 5732: 5725: 5686: 5685: 5678: 5642: 5641: 5637: 5623: 5622: 5615: 5571: 5570: 5566: 5522: 5521: 5517: 5473: 5472: 5468: 5437:(12): 1354–66. 5424: 5423: 5419: 5381: 5380: 5376: 5346: 5345: 5341: 5303: 5302: 5298: 5260: 5259: 5255: 5225: 5224: 5220: 5182: 5181: 5177: 5148:Ann Thorac Surg 5141: 5140: 5136: 5097: 5096: 5092: 5046: 5045: 5041: 5005: 5004: 5000: 4946: 4945: 4941: 4896: 4895: 4891: 4855: 4854: 4843: 4799: 4798: 4794: 4750: 4749: 4745: 4701: 4700: 4696: 4657: 4656: 4652: 4629:10.1038/nrc3677 4614: 4613: 4604: 4567: 4566: 4559: 4505: 4504: 4500: 4455: 4454: 4447: 4403: 4402: 4395: 4364: 4363: 4359: 4307: 4306: 4302: 4258: 4257: 4253: 4209: 4208: 4204: 4173:(12): 797–805. 4160: 4159: 4150: 4106: 4105: 4101: 4062: 4061: 4052: 4008: 4007: 4003: 3959: 3958: 3954: 3918: 3917: 3913: 3884:(3): L393–400. 3875: 3874: 3870: 3839: 3838: 3834: 3803:(11): 3807–16. 3797:J. Clin. Invest 3790: 3789: 3780: 3742: 3741: 3737: 3683: 3682: 3678: 3634: 3633: 3629: 3590: 3589: 3585: 3541: 3540: 3536: 3492: 3491: 3487: 3443: 3442: 3438: 3394: 3393: 3386: 3342: 3341: 3337: 3293: 3292: 3288: 3263:10.1038/nrm3025 3244: 3243: 3239: 3195: 3194: 3190: 3167:10.1038/ncb1183 3152: 3151: 3147: 3103: 3102: 3098: 3054: 3053: 3049: 3005: 3004: 3000: 2969:(10): 797–806. 2956: 2955: 2951: 2907: 2906: 2902: 2858: 2857: 2853: 2817: 2816: 2812: 2768: 2767: 2763: 2742: 2700: 2699: 2688: 2652: 2651: 2647: 2603: 2602: 2598: 2554: 2553: 2549: 2505: 2504: 2500: 2469: 2468: 2464: 2420: 2419: 2415: 2361: 2360: 2356: 2312: 2311: 2304: 2274: 2273: 2269: 2233: 2232: 2228: 2190: 2189: 2185: 2131: 2130: 2126: 2082: 2081: 2074: 2020: 2019: 2002: 1972: 1971: 1964: 1933: 1932: 1928: 1884: 1883: 1876: 1838: 1837: 1830: 1790: 1789: 1785: 1749: 1748: 1744: 1710: 1709: 1702: 1672: 1671: 1667: 1623: 1622: 1618: 1588: 1587: 1578: 1533: 1532: 1523: 1492: 1491: 1482: 1451: 1450: 1439: 1395: 1394: 1385: 1354: 1353: 1328: 1298: 1297: 1280: 1244: 1243: 1232: 1202: 1201: 1186: 1176: 1174: 1166: 1165: 1161: 1131: 1130: 1126: 1121: 1109: 1087: 1078: 1069: 1033: 1017: 980:bronchodilators 973: 889: 880: 856:angiomyolipomas 852: 835: 822: 814:Lung transplant 802: 775:retroperitoneal 762: 740: 724: 704: 687: 675: 659: 644:lymphadenopathy 636: 618: 548: 437: 435:Pathophysiology 418:angiomyolipomas 369:(9q34) and the 346: 288:Angiomyolipomas 257:Chylous ascites 211: 178: 133: 126: 115: 109: 106: 63: 61: 55: 51:primary sources 39: 28: 23: 22: 15: 12: 11: 5: 8137: 8135: 8127: 8126: 8121: 8119:Lung disorders 8116: 8106: 8105: 8099: 8098: 8096: 8095: 8090: 8080: 8078: 8074: 8073: 8071: 8070: 8065: 8060: 8058:Cystic hygroma 8055: 8054: 8053: 8041: 8040: 8039: 8034: 8019: 8017: 8011: 8010: 8008: 8007: 8002: 7997: 7996: 7995: 7990: 7980: 7977: 7976: 7975: 7970: 7965: 7960: 7950: 7949: 7948: 7943: 7938: 7933: 7928: 7918: 7913: 7912: 7911: 7906: 7901: 7896: 7891: 7881: 7876: 7875: 7874: 7864: 7859: 7858: 7857: 7852: 7846: 7841: 7836: 7831: 7826: 7816: 7811: 7805: 7803: 7797: 7796: 7791: 7789: 7788: 7781: 7774: 7766: 7757: 7756: 7753: 7752: 7741: 7730: 7715: 7714: 7712: 7708: 7707: 7704: 7703: 7692: 7681: 7670: 7662: 7647: 7632: 7616: 7611: 7610: 7608: 7607:Classification 7601: 7600: 7593: 7592:External links 7590: 7587: 7586: 7572: 7531: 7512:(5): 440–444. 7496: 7461: 7434: 7407: 7380:(7): 465–468. 7364: 7345:(4): 669–671. 7328: 7309:(6): 591–594. 7303:Mayo Clin Proc 7293: 7258: 7229:(9): 910–914. 7209: 7190:(7): 625–628. 7171: 7130: 7089: 7070:(2): 749–754. 7051: 7022:(9): 800–803. 7002: 6958: 6939:(1): 174–176. 6922: 6879: 6852: 6825: 6779: 6760:(5): 782–785. 6744: 6680: 6641:(3): 783–794. 6621: 6577: 6556:(3): 924–934. 6536: 6507:(3): 215–218. 6487: 6468:(2): 623–627. 6452: 6417: 6376: 6357:(11): 1642–8. 6341: 6314: 6271: 6252:(5): 609–614. 6236: 6209:(4): 495–503. 6193: 6174:(9): 803–807. 6158: 6123: 6112:(7): 732–734. 6096: 6077:(3): 327–336. 6056: 6007: 5963: 5927: 5875: 5840: 5805: 5778:(5): 643–648. 5762: 5723: 5696:(4): 523–530. 5676: 5649:J Am Med Assoc 5635: 5613: 5584:(3): 926–933. 5564: 5515: 5466: 5417: 5390:(3): 263–265. 5384:Histopathology 5374: 5355:(4): 465–472. 5339: 5312:(6): 570–575. 5306:Histopathology 5296: 5269:(4): 347–354. 5263:Histopathology 5253: 5234:(2): 335–339. 5218: 5175: 5134: 5107:(4): 402–409. 5090: 5039: 4998: 4939: 4889: 4868:(2): 578–585. 4841: 4792: 4743: 4694: 4661:Growth Factors 4650: 4623:(3): 159–172. 4617:Nat Rev Cancer 4602: 4581:(2): 181–195. 4557: 4518:(2): 548–553. 4498: 4445: 4416:(3): 674–681. 4393: 4374:(3): 143–152. 4357: 4300: 4251: 4216:Eur Respir Rev 4202: 4167:Ann Intern Med 4148: 4099: 4050: 4001: 3952: 3931:(5): 1625–33. 3911: 3868: 3832: 3778: 3751:(4): 376–381. 3735: 3676: 3641:Mol. Pharmacol 3627: 3594:Mol. Pharmacol 3583: 3534: 3485: 3436: 3384: 3335: 3286: 3237: 3188: 3145: 3096: 3067:(1): 125–137. 3047: 2998: 2949: 2920:(2): 163–175. 2900: 2871:(2): 177–189. 2851: 2810: 2781:(2): 140–151. 2761: 2686: 2665:(5): 525–534. 2645: 2596: 2573:10.1086/316951 2561:Am J Hum Genet 2547: 2498: 2479:(7): 976–982. 2462: 2413: 2354: 2331:10.1086/301804 2325:(4): 810–815. 2319:Am J Hum Genet 2302: 2267: 2246:(2): 400–406. 2240:Am J Hum Genet 2226: 2199:(2): 157–162. 2193:Nat Rev Cancer 2183: 2144:(4): 820–823. 2124: 2095:(6): 663–665. 2072: 2000: 1981:(1): 253–258. 1962: 1926: 1897:(12): 1210–2. 1874: 1828: 1799:(4): 276–285. 1793:Cancer Control 1783: 1762:(1): 311–329. 1742: 1700: 1681:(1): 147–153. 1665: 1636:(1): 277–285. 1616: 1597:(2): 415–421. 1576: 1547:(1): 105–111. 1521: 1502:(4): 661–668. 1480: 1437: 1383: 1364:(5): 321–337. 1326: 1278: 1230: 1211:(2): 527–533. 1184: 1159: 1123: 1122: 1120: 1117: 1116: 1115: 1108: 1105: 1091:Lucky Thirteen 1086: 1083: 1077: 1074: 1068: 1065: 1032: 1029: 1016: 1013: 984:bronchodilator 972: 969: 888: 885: 879: 876: 851: 848: 834: 831: 821: 818: 801: 798: 761: 758: 738: 723: 720: 703: 700: 686: 683: 674: 671: 658: 655: 635: 632: 617: 614: 590:angiomyolipoma 547: 544: 461:phosphorylates 436: 433: 414:heterozygosity 381:in either the 345: 342: 299: 298: 295: 285: 284: 283: 282:Chyle in stool 280: 274: 269: 264: 259: 254: 246: 243: 237: 234: 210: 207: 186: 185: 172: 166: 165: 157: 156: 148: 147: 144: 140: 139: 131: 128: 127: 42: 40: 33: 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 8136: 8125: 8124:Rare diseases 8122: 8120: 8117: 8115: 8112: 8111: 8109: 8094: 8091: 8089: 8085: 8082: 8081: 8079: 8075: 8069: 8066: 8064: 8061: 8059: 8056: 8052: 8049: 8048: 8047: 8046: 8042: 8038: 8035: 8033: 8030: 8029: 8028: 8024: 8021: 8020: 8018: 8016: 8012: 8006: 8003: 8001: 7998: 7994: 7991: 7989: 7986: 7985: 7984: 7983:Angiokeratoma 7981: 7978: 7974: 7971: 7969: 7966: 7964: 7961: 7959: 7956: 7955: 7954: 7951: 7947: 7944: 7942: 7939: 7937: 7934: 7932: 7929: 7927: 7924: 7923: 7922: 7919: 7917: 7914: 7910: 7907: 7905: 7902: 7900: 7897: 7895: 7892: 7890: 7887: 7886: 7885: 7882: 7880: 7877: 7873: 7870: 7869: 7868: 7865: 7863: 7860: 7856: 7853: 7850: 7847: 7845: 7842: 7840: 7837: 7835: 7832: 7830: 7827: 7825: 7822: 7821: 7820: 7817: 7815: 7812: 7810: 7807: 7806: 7804: 7802: 7798: 7794: 7787: 7782: 7780: 7775: 7773: 7768: 7767: 7764: 7751: 7747: 7746: 7742: 7740: 7736: 7735: 7731: 7729: 7726: 7722: 7721: 7717: 7716: 7713: 7709: 7702: 7698: 7697: 7693: 7691: 7687: 7686: 7682: 7680: 7676: 7675: 7671: 7668: 7667: 7663: 7661: 7657: 7656: 7652: 7648: 7646: 7642: 7641: 7637: 7633: 7631: 7627: 7626: 7622: 7618: 7617: 7614: 7609: 7605: 7599: 7596: 7595: 7591: 7582: 7576: 7573: 7568: 7564: 7559: 7554: 7550: 7546: 7542: 7535: 7532: 7527: 7523: 7519: 7515: 7511: 7507: 7500: 7497: 7492: 7488: 7484: 7480: 7476: 7472: 7465: 7462: 7457: 7453: 7449: 7445: 7438: 7435: 7430: 7426: 7422: 7418: 7411: 7408: 7403: 7399: 7395: 7391: 7387: 7383: 7379: 7375: 7368: 7365: 7360: 7356: 7352: 7348: 7344: 7340: 7332: 7329: 7324: 7320: 7316: 7312: 7308: 7304: 7297: 7294: 7289: 7285: 7281: 7277: 7273: 7269: 7262: 7259: 7254: 7250: 7245: 7240: 7236: 7232: 7228: 7224: 7220: 7213: 7210: 7205: 7201: 7197: 7193: 7189: 7185: 7178: 7176: 7172: 7167: 7163: 7158: 7153: 7149: 7145: 7141: 7134: 7131: 7126: 7122: 7118: 7114: 7110: 7106: 7098: 7096: 7094: 7090: 7085: 7081: 7077: 7073: 7069: 7065: 7058: 7056: 7052: 7047: 7043: 7038: 7033: 7029: 7025: 7021: 7017: 7013: 7006: 7003: 6998: 6994: 6990: 6986: 6982: 6978: 6974: 6970: 6962: 6959: 6954: 6950: 6946: 6942: 6938: 6934: 6926: 6923: 6918: 6914: 6910: 6906: 6902: 6898: 6894: 6890: 6883: 6880: 6875: 6871: 6867: 6863: 6856: 6853: 6848: 6844: 6840: 6836: 6829: 6826: 6821: 6817: 6813: 6809: 6805: 6801: 6797: 6793: 6786: 6784: 6780: 6775: 6771: 6767: 6763: 6759: 6755: 6748: 6745: 6734:on 2020-04-26 6730: 6726: 6722: 6718: 6714: 6710: 6706: 6702: 6698: 6691: 6684: 6681: 6676: 6672: 6668: 6664: 6659: 6654: 6649: 6644: 6640: 6636: 6632: 6625: 6622: 6617: 6613: 6609: 6605: 6601: 6597: 6593: 6589: 6581: 6578: 6573: 6569: 6564: 6559: 6555: 6551: 6547: 6540: 6537: 6532: 6528: 6524: 6520: 6515: 6510: 6506: 6502: 6498: 6491: 6488: 6483: 6479: 6475: 6471: 6467: 6463: 6456: 6453: 6448: 6444: 6440: 6436: 6432: 6428: 6421: 6418: 6413: 6409: 6404: 6399: 6395: 6391: 6387: 6380: 6377: 6372: 6368: 6364: 6360: 6356: 6352: 6345: 6342: 6337: 6333: 6329: 6325: 6318: 6315: 6310: 6306: 6302: 6298: 6294: 6290: 6286: 6282: 6275: 6272: 6267: 6263: 6259: 6255: 6251: 6247: 6240: 6237: 6232: 6228: 6224: 6220: 6216: 6212: 6208: 6204: 6203:Virchows Arch 6197: 6194: 6189: 6185: 6181: 6177: 6173: 6169: 6162: 6159: 6154: 6150: 6146: 6142: 6138: 6134: 6127: 6124: 6119: 6115: 6111: 6107: 6100: 6097: 6092: 6088: 6084: 6080: 6076: 6072: 6065: 6063: 6061: 6057: 6052: 6046: 6038: 6034: 6030: 6026: 6023:(6): 977–95. 6022: 6018: 6011: 6008: 6003: 5999: 5994: 5989: 5986:(2): 348–82. 5985: 5981: 5980:Am. J. Pathol 5977: 5970: 5968: 5964: 5959: 5955: 5951: 5947: 5943: 5939: 5931: 5928: 5923: 5919: 5914: 5909: 5905: 5901: 5897: 5893: 5889: 5882: 5880: 5876: 5871: 5867: 5863: 5859: 5855: 5851: 5844: 5841: 5836: 5832: 5828: 5824: 5820: 5816: 5809: 5806: 5801: 5797: 5793: 5789: 5785: 5781: 5777: 5773: 5766: 5763: 5758: 5754: 5750: 5746: 5742: 5738: 5730: 5728: 5724: 5719: 5715: 5711: 5707: 5703: 5699: 5695: 5691: 5683: 5681: 5677: 5672: 5668: 5663: 5658: 5654: 5650: 5646: 5639: 5636: 5631: 5627: 5620: 5618: 5614: 5609: 5605: 5600: 5595: 5591: 5587: 5583: 5579: 5575: 5568: 5565: 5560: 5556: 5551: 5546: 5542: 5538: 5534: 5530: 5526: 5519: 5516: 5511: 5507: 5502: 5497: 5493: 5489: 5485: 5481: 5477: 5470: 5467: 5462: 5458: 5453: 5448: 5444: 5440: 5436: 5432: 5428: 5421: 5418: 5413: 5409: 5405: 5401: 5397: 5393: 5389: 5385: 5378: 5375: 5370: 5366: 5362: 5358: 5354: 5350: 5343: 5340: 5335: 5331: 5327: 5323: 5319: 5315: 5311: 5307: 5300: 5297: 5292: 5288: 5284: 5280: 5276: 5272: 5268: 5264: 5257: 5254: 5249: 5245: 5241: 5237: 5233: 5229: 5222: 5219: 5214: 5210: 5206: 5202: 5198: 5194: 5190: 5186: 5179: 5176: 5171: 5167: 5162: 5157: 5153: 5149: 5145: 5138: 5135: 5130: 5126: 5122: 5118: 5114: 5110: 5106: 5102: 5094: 5091: 5086: 5082: 5077: 5072: 5067: 5062: 5058: 5054: 5050: 5043: 5040: 5035: 5031: 5026: 5021: 5017: 5013: 5009: 5002: 4999: 4994: 4990: 4986: 4982: 4977: 4972: 4967: 4962: 4958: 4954: 4950: 4943: 4940: 4935: 4931: 4927: 4923: 4918: 4913: 4909: 4905: 4901: 4893: 4890: 4885: 4881: 4876: 4871: 4867: 4863: 4859: 4852: 4850: 4848: 4846: 4842: 4837: 4833: 4828: 4823: 4819: 4815: 4811: 4807: 4806:Mol Cell Biol 4803: 4796: 4793: 4788: 4784: 4780: 4776: 4771: 4766: 4762: 4758: 4754: 4747: 4744: 4739: 4735: 4730: 4725: 4721: 4717: 4714:(8): 580–90. 4713: 4709: 4705: 4698: 4695: 4690: 4686: 4682: 4678: 4674: 4670: 4667:(2): 99–107. 4666: 4662: 4654: 4651: 4646: 4642: 4638: 4634: 4630: 4626: 4622: 4618: 4611: 4609: 4607: 4603: 4598: 4594: 4589: 4584: 4580: 4576: 4572: 4564: 4562: 4558: 4553: 4549: 4544: 4539: 4534: 4529: 4525: 4521: 4517: 4513: 4509: 4502: 4499: 4494: 4490: 4485: 4480: 4476: 4472: 4469:(6): 445–52. 4468: 4464: 4460: 4452: 4450: 4446: 4441: 4437: 4432: 4427: 4423: 4419: 4415: 4411: 4407: 4400: 4398: 4394: 4389: 4385: 4381: 4377: 4373: 4369: 4361: 4358: 4353: 4349: 4344: 4339: 4335: 4331: 4327: 4323: 4320:(1): 206–14. 4319: 4315: 4311: 4304: 4301: 4296: 4292: 4287: 4282: 4278: 4274: 4270: 4266: 4262: 4255: 4252: 4247: 4243: 4238: 4233: 4229: 4225: 4221: 4217: 4213: 4206: 4203: 4198: 4194: 4189: 4184: 4180: 4176: 4172: 4168: 4164: 4157: 4155: 4153: 4149: 4144: 4140: 4135: 4130: 4126: 4122: 4118: 4114: 4113:Am. J. Pathol 4110: 4103: 4100: 4095: 4091: 4087: 4083: 4079: 4075: 4071: 4067: 4059: 4057: 4055: 4051: 4046: 4042: 4037: 4032: 4028: 4024: 4020: 4016: 4012: 4005: 4002: 3997: 3993: 3988: 3983: 3979: 3975: 3972:(2): 227–34. 3971: 3967: 3963: 3956: 3953: 3948: 3944: 3939: 3934: 3930: 3926: 3922: 3915: 3912: 3907: 3903: 3899: 3895: 3891: 3887: 3883: 3879: 3872: 3869: 3864: 3860: 3856: 3852: 3849:(4): 504–11. 3848: 3844: 3836: 3833: 3828: 3824: 3819: 3814: 3810: 3806: 3802: 3798: 3794: 3787: 3785: 3783: 3779: 3774: 3770: 3766: 3762: 3758: 3754: 3750: 3746: 3739: 3736: 3731: 3727: 3722: 3717: 3712: 3707: 3703: 3699: 3695: 3691: 3687: 3680: 3677: 3672: 3668: 3663: 3658: 3654: 3650: 3647:(4): 766–77. 3646: 3642: 3638: 3631: 3628: 3623: 3619: 3615: 3611: 3607: 3603: 3600:(3): 778–88. 3599: 3595: 3587: 3584: 3579: 3575: 3571: 3567: 3562: 3557: 3553: 3549: 3545: 3538: 3535: 3530: 3526: 3521: 3516: 3512: 3508: 3505:(3): 227–30. 3504: 3500: 3496: 3489: 3486: 3481: 3477: 3472: 3467: 3463: 3459: 3455: 3451: 3450:Mol Cell Biol 3447: 3440: 3437: 3432: 3428: 3423: 3418: 3414: 3410: 3407:(4): 473–80. 3406: 3402: 3398: 3391: 3389: 3385: 3380: 3376: 3371: 3366: 3362: 3358: 3354: 3350: 3346: 3339: 3336: 3331: 3327: 3322: 3317: 3313: 3309: 3305: 3301: 3297: 3290: 3287: 3282: 3278: 3273: 3268: 3264: 3260: 3256: 3252: 3248: 3241: 3238: 3233: 3229: 3225: 3221: 3216: 3211: 3207: 3203: 3199: 3192: 3189: 3184: 3180: 3176: 3172: 3168: 3164: 3160: 3156: 3155:Nat Cell Biol 3149: 3146: 3141: 3137: 3132: 3127: 3123: 3119: 3115: 3111: 3107: 3100: 3097: 3092: 3088: 3084: 3080: 3075: 3070: 3066: 3062: 3058: 3051: 3048: 3043: 3039: 3035: 3031: 3026: 3021: 3017: 3013: 3009: 3002: 2999: 2994: 2990: 2986: 2982: 2977: 2972: 2968: 2964: 2960: 2953: 2950: 2945: 2941: 2937: 2933: 2928: 2923: 2919: 2915: 2911: 2904: 2901: 2896: 2892: 2888: 2884: 2879: 2874: 2870: 2866: 2862: 2855: 2852: 2847: 2843: 2838: 2833: 2829: 2825: 2821: 2814: 2811: 2806: 2802: 2797: 2792: 2788: 2784: 2780: 2776: 2772: 2765: 2762: 2757: 2753: 2747: 2739: 2735: 2730: 2725: 2721: 2717: 2713: 2709: 2705: 2697: 2695: 2693: 2691: 2687: 2682: 2678: 2673: 2668: 2664: 2660: 2659:Hum Mol Genet 2656: 2649: 2646: 2641: 2637: 2633: 2629: 2624: 2619: 2615: 2611: 2607: 2600: 2597: 2592: 2588: 2583: 2578: 2574: 2570: 2566: 2562: 2558: 2551: 2548: 2543: 2539: 2535: 2531: 2526: 2521: 2517: 2513: 2509: 2502: 2499: 2494: 2490: 2486: 2482: 2478: 2474: 2466: 2463: 2458: 2454: 2449: 2444: 2440: 2436: 2432: 2428: 2424: 2417: 2414: 2409: 2405: 2400: 2395: 2390: 2385: 2381: 2377: 2373: 2369: 2365: 2358: 2355: 2350: 2346: 2341: 2336: 2332: 2328: 2324: 2320: 2316: 2309: 2307: 2303: 2298: 2294: 2290: 2286: 2282: 2278: 2271: 2268: 2263: 2259: 2254: 2249: 2245: 2241: 2237: 2230: 2227: 2222: 2218: 2214: 2210: 2206: 2202: 2198: 2194: 2187: 2184: 2179: 2175: 2170: 2165: 2160: 2155: 2151: 2147: 2143: 2139: 2135: 2128: 2125: 2120: 2116: 2111: 2106: 2102: 2098: 2094: 2090: 2086: 2079: 2077: 2073: 2068: 2064: 2059: 2054: 2049: 2044: 2040: 2036: 2032: 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1341: 1339: 1337: 1335: 1333: 1331: 1327: 1322: 1318: 1314: 1310: 1306: 1302: 1295: 1293: 1291: 1289: 1287: 1285: 1283: 1279: 1274: 1270: 1265: 1260: 1256: 1252: 1248: 1241: 1239: 1237: 1235: 1231: 1226: 1222: 1218: 1214: 1210: 1206: 1199: 1197: 1195: 1193: 1191: 1189: 1185: 1173: 1169: 1163: 1160: 1155: 1151: 1147: 1143: 1140:(2): 507–16. 1139: 1135: 1128: 1125: 1118: 1114: 1111: 1110: 1106: 1104: 1102: 1098: 1097: 1092: 1084: 1082: 1075: 1073: 1066: 1064: 1060: 1058: 1054: 1053:benign tumors 1050: 1046: 1041: 1037: 1030: 1028: 1025: 1021: 1014: 1012: 1009: 1005: 1001: 997: 993: 989: 988:oxyhemoglobin 985: 981: 977: 970: 968: 964: 962: 958: 954: 950: 946: 945:GnRH agonists 942: 937: 934: 932: 931: 926: 922: 918: 913: 911: 906: 902: 901:triglycerides 898: 893: 886: 884: 877: 875: 873: 869: 865: 861: 857: 849: 847: 845: 844:thoracic duct 841: 832: 830: 828: 819: 817: 815: 811: 807: 799: 797: 795: 791: 787: 782: 780: 776: 772: 768: 759: 757: 754: 749: 746: 742: 733: 730: 721: 719: 717: 713: 709: 701: 699: 696: 695:pathognomonic 692: 684: 682: 680: 672: 670: 668: 667:heterogeneity 664: 661:In one study 656: 654: 652: 649: 645: 641: 633: 631: 628: 625:effusion and 623: 615: 608: 604: 601: 597: 595: 591: 587: 582: 580: 576: 566: 560: 559:H&E stain 556: 552: 545: 543: 541: 537: 533: 529: 525: 521: 517: 513: 509: 506:, emphysema, 505: 501: 496: 494: 489: 484: 481: 478: 474: 470: 466: 462: 458: 454: 449: 447: 443: 434: 432: 430: 426: 421: 419: 415: 411: 407: 403: 398: 395: 390: 388: 384: 380: 376: 375:chromosome 16 372: 368: 364: 360: 356: 352: 343: 341: 339: 334: 332: 328: 324: 320: 316: 312: 308: 304: 296: 293: 289: 286: 281: 278: 275: 273: 270: 268: 265: 263: 260: 258: 255: 253: 250: 249: 247: 244: 241: 238: 235: 232: 231: 230: 228: 224: 220: 215: 208: 206: 204: 200: 196: 192: 182: 176: 173: 171: 167: 163: 158: 154: 149: 145: 141: 136: 124: 121: 113: 102: 99: 95: 92: 88: 85: 81: 78: 74: 71: – 70: 66: 65:Find sources: 59: 53: 52: 48: 43:This article 41: 37: 32: 31: 19: 8093:Angiofibroma 8088:angiosarcoma 8050: 8043: 8023:Lymphangioma 7941:Microvenular 7855:Spindle cell 7801:Blood vessel 7743: 7732: 7718: 7694: 7683: 7672: 7664: 7649: 7634: 7619: 7575: 7548: 7544: 7534: 7509: 7505: 7499: 7474: 7470: 7464: 7447: 7443: 7437: 7423:(7): 553–7. 7420: 7417:J Reprod Med 7416: 7410: 7377: 7373: 7367: 7342: 7338: 7331: 7306: 7302: 7296: 7274:(1): 81–85. 7271: 7267: 7261: 7226: 7222: 7212: 7187: 7183: 7147: 7143: 7133: 7111:(1): 96–98. 7108: 7104: 7067: 7063: 7019: 7015: 7005: 6975:(1): 39–50. 6972: 6968: 6961: 6936: 6932: 6925: 6895:(1): 28–34. 6892: 6888: 6882: 6868:(6): 377–8. 6865: 6861: 6855: 6838: 6834: 6828: 6798:(1): 35–42. 6795: 6791: 6757: 6753: 6747: 6736:. 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Pathol 5772:Respirology 5690:Respirology 5529:Am J Pathol 5154:(6): e7-8. 5076:2434/712668 4976:2434/749090 4757:J Biol Chem 4575:Cancer Cell 3349:J Cell Biol 2830:(1): 9–22. 2824:Cancer Cell 2610:J Biol Chem 2512:J Hum Genet 961:Doxycycline 949:leuprorelin 921:collagen IV 910:skin cancer 864:Nephrectomy 840:lymph nodes 827:pleurodesis 771:endothelial 651:hyperplasia 594:chylothorax 579:Chylothorax 267:Chyloptysis 252:Chylothorax 199:cystic lung 175:Pulmonology 143:Other names 8108:Categories 7988:of Mibelli 7921:Hemangioma 7839:Kaposiform 7696:DiseasesDB 7545:Hum Pathol 6835:Cancer Res 6738:2019-09-02 6550:Kidney Int 6390:Respir Med 5185:Acta Cytol 5101:Acta Cytol 5053:Respir Med 5012:Respir Med 3548:Cancer Res 3110:J Cell Sci 1814:2042/44594 1717:Hum Pathol 1119:References 917:everolimus 887:Medication 868:Everolimus 808:inhibitor 729:Spirometry 716:meningioma 648:pneumocyte 555:Micrograph 536:podoplanin 532:hyaluronan 524:metastasis 488:metastatic 402:bi-allelic 315:hemoptysis 307:lymphatics 303:neoplastic 245:Chest pain 80:newspapers 47:references 8015:Lymphatic 7931:Cavernous 7926:Capillary 7844:Infantile 7824:Composite 7728:radio/415 7720:eMedicine 6862:Eur J Med 5228:Radiology 3202:Curr Biol 3012:Curr Biol 2963:Curr Biol 1675:Radiology 1630:Radiology 1591:Radiology 1067:Pregnancy 1015:Prognosis 1008:influenza 1000:menopause 957:tamoxifen 953:goserelin 897:dyspepsia 842:into the 810:sirolimus 800:Treatment 760:Pathology 546:Diagnosis 446:sirolimus 442:rapamycin 170:Specialty 7849:Retiform 7745:Orphanet 7725:med/1348 7669:: 9174/1 7444:Kans Med 7402:22501227 7394:19419980 7359:11520735 7323:10852420 7288:12639372 7204:21459371 7166:21764810 7125:17431222 7084:10934115 7046:15333859 6997:44865113 6989:18069418 6917:18536568 6909:15514113 6847:14500340 6820:32978654 6812:23007140 6725:20074278 6717:24311763 6667:26113676 6616:25667463 6608:23312829 6572:15327383 6531:24365886 6523:10233482 6482:12576391 6447:25150902 6412:26321137 6371:11079017 6309:32090320 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6188:2764227 6153:7432404 6118:8024410 6002:1146965 5993:1912658 5913:2946895 5835:2024811 5632:: A807. 5599:3198490 5550:2408433 5501:5447298 5452:5442966 5412:7284904 5369:9537475 5326:9205862 5283:2071093 5248:2326457 5213:3374041 5129:3353292 4993:8775139 4827:1061605 4729:3724387 4645:6976027 4552:9435229 4520:Bibcode 4484:3804556 4431:2940071 4343:3392168 4322:Bibcode 4286:2883505 4237:4241262 4188:3176735 4134:2843492 4036:3171862 3987:2822984 3818:3484429 3721:3145704 3698:Bibcode 3662:2769052 3520:2715313 3471:3133430 3422:2644208 3370:2172598 3321:3750737 3272:3390257 3232:4658268 3131:2758797 3042:8239162 2944:4656930 2895:6438316 2796:3398441 2729:3118601 2582:1234935 2448:3029931 2376:Bibcode 2349:9529362 2340:1377043 2262:8755927 2253:1914733 2178:5279523 2146:Bibcode 2110:3733437 2035:Bibcode 1957:9242607 1937:Science 1912:3622443 1869:3579356 1651:2940246 1562:2662978 1423:1745654 1273:2215609 1225:7842216 1076:Society 967:cases. 947:(e.g., 860:Nephron 611:surgery 463:p70 S6 385:or the 353:in the 338:dyspnea 331:ascites 323:dyspnea 233:Fatigue 94:scholar 8077:Either 8045:PEComa 7973:Tufted 7968:Spider 7958:Cherry 7679:606690 7645:J84.81 7565: 7524: 7489: 7454: 7427: 7400: 7392: 7357: 7321: 7286: 7251: 7244:475191 7241: 7223:Thorax 7202: 7164: 7123: 7082: 7044: 7034: 7016:Thorax 6995: 6987: 6951: 6915: 6907: 6872: 6845: 6818: 6810: 6772: 6723: 6715: 6673: 6665: 6614: 6606: 6588:Lancet 6570: 6529: 6521: 6480: 6445: 6410: 6369: 6334: 6307: 6299: 6264: 6229: 6221: 6186: 6151: 6116: 6089: 6037:931190 6035: 6000: 5990: 5956: 5920: 5910: 5868: 5833: 5798: 5790: 5755: 5716: 5708: 5669: 5606: 5596: 5557: 5547: 5508: 5498: 5459: 5449: 5410: 5402: 5367: 5332: 5324: 5289: 5281: 5246: 5211: 5203: 5168: 5127: 5119: 5083: 5032: 4991: 4983: 4932: 4924: 4882: 4834: 4824: 4785: 4777: 4736: 4726: 4687: 4679: 4643: 4635: 4595: 4550: 4540: 4491: 4481: 4438: 4428: 4386: 4350: 4340: 4293: 4283: 4244: 4234: 4195: 4185: 4141: 4131: 4092: 4084: 4043: 4033: 3994: 3984: 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5796:S2CID 5714:S2CID 5578:Chest 5408:S2CID 5330:S2CID 5287:S2CID 5209:S2CID 5125:S2CID 4989:S2CID 4930:S2CID 4862:Chest 4783:S2CID 4685:S2CID 4641:S2CID 4543:18457 4410:Chest 4090:S2CID 3902:S2CID 3769:S2CID 3618:S2CID 3574:S2CID 3228:S2CID 3179:S2CID 3087:S2CID 3038:S2CID 2989:S2CID 2940:S2CID 2891:S2CID 2636:S2CID 2538:S2CID 2217:S2CID 2058:18562 1865:S2CID 1455:Chest 1301:Chest 1134:Chest 1096:House 786:actin 779:lumen 691:renal 528:VEGFR 510:, or 477:actin 277:Chyle 236:Cough 101:JSTOR 87:books 7734:NORD 7685:MeSH 7674:OMIM 7655:9-CM 7630:CB07 7563:PMID 7522:PMID 7487:PMID 7452:PMID 7425:PMID 7390:PMID 7355:PMID 7319:PMID 7284:PMID 7249:PMID 7200:PMID 7162:PMID 7121:PMID 7080:PMID 7042:PMID 6985:PMID 6949:PMID 6905:PMID 6870:PMID 6843:PMID 6808:PMID 6792:Lung 6770:PMID 6713:PMID 6663:PMID 6604:PMID 6568:PMID 6519:PMID 6478:PMID 6443:PMID 6408:PMID 6367:PMID 6332:PMID 6297:PMID 6262:PMID 6219:PMID 6184:PMID 6149:PMID 6114:PMID 6087:PMID 6051:link 6033:PMID 5998:PMID 5954:PMID 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