Authors: Kebria, M et al.
Title: Primary retroperitoneal LAM in a postmenopausal woman.
Journal: Internal Gynecology Cancer 2007, vol 17:pp 528-32.

The authors describe one patient, a 59 year old woman who had post-menopausal bleeding and no pulmonary complaints. A CT-scan of the abdomen revealed a mass at the back of her abdominal wall as well as enlarged abdominal lymph glands. Cancer was suspected, but a biopsy revealed LAM. This case is atypical because of the unusual presentation.

Authors: Taveira-DaSilva, AM, Steagall, WK and Moss, J.
Title: Lymphangioleiomyomatosis
Journal: Cancer Control 2007; vol 13: pp 276-85.

This is a summary article by the NIH group outlining the various features of LAM including presentation, frequency, pathology, clinical features, how to make the diagnosis and treatment options.

*This is a good article for health care professionals.

Authors: Garzon, JC et al
Title: Video-assisted thoracic surgery for pneumothorax in LAM
Journal: Heart Lung Circulation 2007: vol 7

The authors describe the management of pneumothorax in LAM by describing the treatment of a woman who had a pneumothorax in both lungs. The surgeons were able to take a biopsy and re-inflate the woman's lung by removing some of the larger cysts and by instilling talc for a pleurodesis. All this was done by a small incision guided by a camera. The authors also discuss why the management of pneumothorax in LAM is different than from other causes of pneumothorax.

Authors: Chen, F et al.
Title: Recurrent LAM after living-donor lobar lung transplantation.
Journal: Transplant Proceedings: vol 38, 2006 pp 3151-3.

Lung transplantation from living donors is possible - but very difficult. Two donors are needed, each giving a lobe of lung to the recipient. That means there are more rejection issues to deal with because there are two donors. As well, there is major surgery for three people; the two donors and the recipient. Chen et al describe a case in Japan where a 24 year old woman with LAM received a living donor transplant. One year later, she had shadows in her chest x-ray and a collapsed lung. These resolved on their own. From a CT-scan, the physicians also found some cysts at the bottom of the left lung. A biopsy of the cysts revealed LAM. This is probably the first report of recurrence of LAM in the transplanted lung of a living LAM patient. The woman continues to do well.

Authors: Ho, TB et al.
Title: An 86-year old female with LAM
Journal: European Journal of Respirology vol, 28: 2006 pp 1065.

This brief report describes the finding of LAM in a woman who is 86 years old. This is the oldest LAM patient recorded in the literature.

Authors: Juvet, Stephen, Hwang, D., Downey, G.
Title: Rare Lung Diseases I: Lymphangioleiomyomatosis
Journal: Canadian Respiratory Journal 2006;13:375-80

The article begins with a case presentation of a young woman with a chylothorax, then describes the clinical features of LAM and TSC-LAM with photographs of chest x-rays, and CT-scans of the lung. The molecular basis and pathology of LAM are discussed. Management and treatment are included as well as a section on management of pneumothorax. The article closes with a mention of the MILES trial. This article is shorter than the others but still a good synopsis of the relevant issues around diagnosing and treating LAM.

Author: McCormack, Frank
Title: Lymphangioleiomyomatosis
Journal: Medscape General Medicine 2006; 8:1-13.

This article is an overview for clinicians about LAM. Dr. McCormack begins with a history of LAM, followed by a summary of the genetics of LAM and its relationship to tuberous sclerosis (TSC).

He next outlines the main symptoms of LAM: shortness of breath, pneumothorax and that LAM is often misdiagnosed as other lung ailments such as asthma or emphysema. The recommended laboratory tests to make the diagnosis of LAM are explained (e.g. pulmonary function tests, CT-scan of the lungs, ultrasound of the kidneys to look for angiolipomas (AML)). Some useful diagrams and photographs of x-rays and CT-scans are provided to help clinicians make the diagnosis. The article includes management and treatment of LAM noting that there are no proven treatments for LAM.

Author: Johnson, Simon
Title: Rare interstitial lung diseases: Lymphangioleiomyomatosis
Journal: European Respiratory Journal 2006; 27:1056-65.

Dr. Johnson has written several articles on LAM in the past and this one updates current state of knowledge about LAM. It focuses more on the clinical aspects of LAM beginning with the clinical features and symptoms. These include shortness of breath (dyspnea), pneumothorax, chylothorax and less commonly cough, coughing up blood, and coughing up chyle (lymph fluid). About 2/3 of LAM patients will have had a pneumothorax. Manifestations of LAM outside of the lung include AMLs, chyle in the abdomen, lymphangioleiomyomas (cystic masses in the abdomen or elsewhere), and enlarged lymph nodes. LAM patients typically see their physician because of shortness of breath or collapsed lung. LAM should be suspected in any young woman with shortness of breath, non-smoker or pneumothorax.

Dr. Johnson then outlines the investigations that should be undertaken including pulmonary function tests and CT-scans. The treatment of LAM complications, such as pneumothorax is discussed as well as hormonal therapy (not currently shown to be useful). Removal of the ovaries is not recommended. The role of pregnancy in LAM is discussed as well as air travel.

Authors: Avila,Nilo, Dwyer, A., Rabel,A , DeCastron, R., Moss.J
Title: CT of pleural abnormalities in LAM and comparison of pleural findings after different types of pleurodesis.
Journal: American Journal of Radiology 2006: 186: 1007-12.

This article included 258 LAM women seen during an ongoing study of LAM at the National Institutes of Health in Bethesda Maryland. Among the women, 133 had at least one pleurodesis for treatment of a pneumothorax.

The authors examined the CT-scans from the 258 patients to examine the frequency of pleural abnormalities in LAM women with and without a pleurodesis. The pleura is the lining of the lung. A pleurodesis is an operation that uses various methods to adhere the lung to the chest wall after a lung collapse. The authors found that 148 of the 258 women had a pleural abnormality on CT-scan. Women with pleurodesis were more likely to have an abnormality. These abnormalities included pleural thickening, pleural effusion (fluid in between the lung and the chest wall), calcification, and masses (areas of tissue growth). These are probably the result of fibrous tissue formation after the procedure. There was no change in the size of the abnormalities over time. The importance of this paper is for clinicians to know that women with LAM will have abnormalities on their CT-scans especially if they have had a pleurodesis and that no further investigations are required.

Authors: Steagall,W. , Taveira-DaSilva, A., Moss,J.
Title: Clinical and Molecular Insights into Lymphangioleiomyomatosis
Journal: Sarcoidosis Vasculitis and Diffuse Lung Diseases 2005;22:S49-66.

This in-depth article is a summary of the latest scientific and clinical knowledge about LAM written by Dr. Moss and colleagues, based on the NIH study and is the most comprehensive LAM review. The article begins with the prevalence of LAM which is estimated to be 2 per million women.

The article next describes the pathology of LAM with photographs of lung tissue under the microscope and discusses how the lungs are damaged in LAM. Next, the molecular basis of LAM is described, namely the TSC1 and TSC2 genes and how smooth muscle cell growth (i.e. LAM cells) is affected in LAM. A long description of what is now known about the molecular pathways is included in the article. The paper next moves to the clinical features of LAM. Symptoms are described: progressive shortness of breath, pneumothorax (collapsed lung), pleural effusion (fluid between the lungs and the chest wall). The presence of benign tumours in the kidney (AML) helps to make the diagnosis of LAM. Physical examination of patients is usually normal.

This article also discusses some other problems seen in LAM patients. First, meningiomas (benign brain tumours) have been found in some patients with LAM but might be related to the use of progesterone. Bone density is often low in LAM patients and treatment is recommended.

Other items discussed in the paper include lung function tests, CT-scan of the abdomen and exercise in LAM. The article points out that contrary to earlier notions, LAM is a chronic disease spanning decades. Even when severe, the disease may remain stable with minimal progression. Also, unlike many other lung diseases, LAM patients are usually comfortable at rest. In their study of 402 LAM patients, 85% are alive without lung transplantation.

Authors: Kpondonu, J., Massad, M., Chae, R., Caines, A., Evans,A., Snow,N., and Geha,A..
Title: The US experience with lung transplantation for pulmonary LAM
Journal: Journal Heart Lung Transplant 2005:24; 1247-53.

The authors review the records of 79 women who had undergone a transplant for LAM between 1987 and 2002. Women were on average 41 years old (range 24 to 65 years of age). Thirty four women received a single lung transplant and 45 women had a double lung transplant. Six women died within 30 days. There were 20 deaths after 1 month; the main causes of death were organ failure, pulmonary complications, and fungal infection. As well, 4 women died from organ rejection. Four women were re-transplanted. In total, 55 women (70%) were alive with an average follow-up of 37 months (range 0-128 months). The survival at 1 year was 86%, 3 year survival was 76% and 5 year survival was 65%. Transplantation in LAM confers survival rates that are equivalent or better than those of patients receiving a lung transplant for other lung diseases.

Authors:Avila, N, Dwyer, A, Murphy-Johnson, D, Brooks, P, Moss, J.
Title: Sonography of Lymphangioleiomyoma in Lymphangioleiomyomatosis: Demonstration of Diurnal Variation in Lesion Size.
Journal: American Journal of Respirology 2005; 184: 459-464. www.atsjournals.org

In LAM, abdominal and pelvic masses (identified by CT scan or by sonography (ultrasound)) are often misdiagnosed as lymphoma or ovarian cancer. However, biopsies reveal that these masses are not malignancies.

This study's aim was to use sonography to define the features of abdominal and pelvic masses in LAM and to decide how useful it is in seeing the changes that take place in these masses during the day.

Patients had sonography done in the morning and the afternoon. An increase in the volume of the masses was observed in all cases.

These changes in size/volume act in the same way as LAM symptoms (i.e. bloating, abdominal discomfort or pain, incontinence, edema) do. They become worse as the day progresses, being most marked in the evening. Malignant abdominal and pelvic masses do not change in this way.

The findings of this study, from case histories and same day repeat sonography, would prevent un-necessary biopsies in LAM patients.

Authors: Taveira-DaSilva A, Stylianou M, Hedin C, Hathaway O, Moss J.
Title: Bone Mineral Density in Lymphangioleiomyomatosis.
Journal: Am Journal of Respiratory Critical Care Medicine, 2005: 171: 61-67. www.atsjournals.org

The bone mineral density (BMD) study had three aims: to find out the occurrence and factors associated with BMD in women with LAM; to find out if progesterone treatment accelerates BMD; and to find out whether treatment with bisphosphonates (drugs to help prevent bone loss) is linked with lower rates of BMD.

There was a high frequency of abnormal BMD in 70% of the 211 women studied, related to severity of the disease and to age. Because of the believed negative impact of estrogen on LAM, none of the post-menopausal patients were using hormone replacement therapy, and all the pre-menopausal patients stopped use of oral contraceptives once the LAM diagnosis was made.

Under certain situations, progesterone may have a positive influence on BMD, but in general, progesterone therapy was not linked with changes in BMD.

The study recommended that LAM patients receive early treatment of BMD with bisphosphonates because taking them was connected with lower rates of bone loss.

Authors: Taveira-DaSilva A, Stylianou M, Hedin C, Hathaway O, Moss J.
Title: Decline in Lung Function in Patients with Lymphangioleiomyomatosis Treated with or without Progesterone.
Journal: Chest 2004; 126: 1867-1874. www.chestjournal.org

Since LAM occurs mostly in women, the thought has been that estrogen plays a role. Hormonal therapy with progesterone has been used as a potential therapy for LAM. This study set out to decide whether the use of progesterone, either orally or by injection, slowed the decline in lung function that is typical in LAM.

The rate of decline in lung function in 275 patients with LAM was followed for about 4 years. Some used progesterone while others did not. The pulmonary function tests used to measure decline were FEV1 (forced expiration volume per second) and DLCO (diffusion capacity of the lung for carbon monoxide). There was no difference found in the rate of change in FEV1 or DLCO between those taking progesterone and those not taking progesterone.

The study concluded that there is no benefit of progesterone in decreasing the rate of decline in lung function.

Authors: Crooks DM, Pacheco-Rodriguez, DeCastro RM, McCoy P, Want J, Kumaki F, Darling T, Moss J.
Title: Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis.
Journal: Proceedings of the National Academy of Sciences 101: 2004, 17462-7. www.pnas.org

LAM is a multi-system disorder in women characterized by benign LAM cells appearing in the lungs, kidneys and lymph system. LAM cells are thought to travel from site to site.

Because of this, the scientists attempted to isolate LAM cells from bodily fluids. They were able to find LAM cells in the blood of 55% of 60 LAM patients, in the urine of 79% of 14 patients who had kidney tumours (angiomyolipomas), and from the chylous fluid of one of three patients.

The ability to find LAM cells in the various fluids was not related to the severity of the lung disease or other clinical manifestations of LAM. LAM cells were also found in one patient who had a double lung transplant.