[3][4][5][6] 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.

The typical disease course displays progressive dyspnea on exertion, spaced by recurrent pneumothoraces and in some patients, chylous pleural effusions or ascites.

[17][18] A variable percentage of cells within the LAM lesion contain mutational inactivation of the tuberous sclerosis complex (TSC1 or TSC2) tumor suppressor genes.

[70] VEGF-D levels correlate with the severity of LAM, evaluated as a measure of CT grade (the abundance of chylous effusions and lymphatic involvement).

[71] VEGF-D is a secreted homodimeric glycoprotein and a member of the VEGF family of growth factors, is known for its role in cancer lymphangiogenesis and metastasis.

Progressive dyspnea on exertion without the exacerbations and remissions that are characteristic of asthma or COPD sometimes prompt a chest CT. A review of the CT by an expert familiar with LAM may increase diagnostic accuracy.

In some cases, a LAM diagnosis can be made with confidence on clinical grounds (without biopsy) in patients with typical cystic changes on high resolution CT scanning of the lung and findings of tuberous sclerosis, angiomyolipoma, lymphangioleiomyoma, chylothorax or serum VEGF-D > 800 pg/ml.

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.

[3][5][6][87] The typical CT shows diffuse round, bilateral, thin-walled cysts of varying sizes ranging from 1 to 45 mm in diameter.

"[citation needed] LAM and AML lesions do not typically exhibit increased uptake of 18F-fluorodeoxyglucose on positron emission tomography (PET) scanning.

[11] Central nervous system abnormalities, such as cortical or subependymal tubers and astrocytomas, are common in patients with TSC, including those with TSC-LAM, but are not found in women with S-LAM.

Quality-controlled lung function data were collected prospectively by the NHLBI Registry, a five-year study of patients with LAM in centers around the United States.

[101] 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.

[104] Grossly, LAM lungs are enlarged and diffusely cystic, with dilated air spaces as large as several centimeters in diameter.

LAM lesions often contain an abundance of lymphatic channels, forming an anastomosing meshwork of slit-like spaces lined by endothelial cells.

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.

[113][114] Unlike the dilated airspaces in emphysema, the cystic spaces found in LAM may be partially lined with hyperplastic type II cells.

[118] Renal angiomyolipomas (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.

[120] Nephrectomy 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.

[citation needed] Potential side effects from mTOR inhibitors include swelling in the ankles, acne, oral ulcers, dyspepsia, diarrhea, elevation of cholesterol and triglycerides, hypertension and headache.

[citation needed] Treatment with another mTOR inhibitor, everolimus, was reported in a small, open-label trial to be associated with improvement in FEV1 and six-minute walking distance.

Adverse events were generally consistent with those known to be associated with mTOR inhibitors, although some were serious and included peripheral edema, pneumonia, cardiac failure and Pneumocystis jirovecii infection.

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.

[citation needed] 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.

[127] The average annual rate of decline in FEV1 and DLCO in 275 patients studied in a single pulmonary function laboratory at the NHLBI was 75 ± 9 mL, and 0.69 ± 0.07 mL/min/mm Hg, respectively.

[35] 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.

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.

[137] It occurs in more than 30% of women with tuberous sclerosis complex (TSC-LAM), a heritable syndrome that is associated with seizures, cognitive impairment and benign tumors in multiple tissues.

[9][138][139][79] Most LAM patients who present for medical evaluation have the sporadic form of the disease (S-LAM), however, which is not associated with other manifestations of tuberous sclerosis complex.

In "Lucky Thirteen", the fifth episode of the fifth season of House, Spencer (Angela Gots) was diagnosed with LAM, though later it was found to be a case of Sjögren's syndrome.