What is LAM?

What is LAM?

Women with Lymphangioleiomyomatosis (LAM) often look completely healthy, but our lungs are full of holes and slowly being destroyed.

LAM is a lung disease that affects women. The main symptoms are shortness of breath with exertion, fatigue, cough and chest pain.

About 2/3 of women with LAM have had at least one lung collapse and some women have had many episodes of collapsed lung(s). Having a lung collapse means hospital admission, painful treatment and sometimes difficult lung surgery. About half the women with LAM also have kidney tumours called angiomyolipoma (AML). Some women have abdominal LAM and others have been diagnosed after bleeding kidney tumours. LAM is progressive, with no treatment or cure. LAM is diagnosed only in women and hits us in the prime of our lives, in some cases as young as age 17.

Continuous supplemental oxygen is often needed and the last option is a single- or double- lung transplant. So far, these options allow for extending our lives only but it is eventually fatal shortening the life span and the quality of life for virtually every woman who develops the disease. Nevertheless, quality of life can be improved with supplemental oxygen, pulmonary rehabilitation and other measures. For many women, just understanding why they are so tired all the time can be a relief.

In the past, LAM was often misdiagnosed as asthma or emphysema, but now LAM can be diagnosed more easily from a lung biopsy or a CT-Scan. Yet, even today, women with LAM are still frequently misdiagnosed because many physicians continue to be unaware of this disease. It is important to obtain a correct diagnosis both because of the dangers of inappropriate treatments being applied and because of the steps that can be taken to make life more comfortable for women with LAM.

What causes LAM?
There are two types of LAM: sporadic LAM and LAM associated with another condition called tuberous sclerosis complex (TSC)

The cause of LAM is unknown. But recent research has found that LAM is associated with mutations in the TSC1 and TSC2 genes, the same genes that are associated with tuberous sclerosis. What is known is that LAM cells (an unusual type of smooth muscle cell) invades lung tissue, destroys air sacs and obstructs the airways leading to increasing respiratory impairment.

LAM: is it cancer?
LAM may be a mild form of cancer.

What is the thinking behind this statement? According to Dr. Frank McCormack (LAM researcher and Medical Director of the LAM Foundation) and Dr. Lisa Henske (LAM researcher), each type of disease that we think of as cancer is different; the term “cancer” defines a spectrum of diseases. These diseases have four elements in common: 1) genetic mutations, 2) loss of control of cellular growth and cell survival, 3) movement of abnormal cells to new sites (metastasis) and, 4) tissue destruction. All of these elements are present in LAM:

Genetic mutations: Current research in cancer has shown that in cancer, genetic mutations develop in cells. These mutations allow the cell to have the ability to multiply, move to other locations in the body (metastasis) and resist dying (apotosis). In cancer cells, there are multiple genetic mutations. In LAM there is a single mutation. This mutation in the TSC1 or TSC2 gene is involved in a single but critical pathway that controls cell growth, movement, and survival.

Loss of growth control: Tuberous sclerosis genes (TSC1 or TSC2) control cell growth; when the mutation occurs, the cells lose their ability to stop growing when conditions are such that normal cells would not grow, for example when nutrients are limited.

Metastasis: LAM cells have been shown to move to other sites in the body and to recur in the donor lung of LAM patients who have undergone lung transplantation. Sporadic LAM involves mainly two organ systems, the kidney and the lung, and appears to spread via the lymphatics, which frequently become enlarged in the abdomen and chest. Lymph fluid build up (effusions) occur in many patients with LAM.

Tissue destruction: LAM cells infiltrate and cause cysts in the lung leading to decreased respiratory function. LAM is very slowly progressive, resulting in the slow loss of lung function.

Determining the secrets of cancer is complex due to the multiple genetic mutations involved. In LAM there is only one gene mutation, thereby simplifying the study of how cells grow, metastasize and resist cell death. These are crucial areas of study in the study of cancer. This new way of thinking about LAM has led prominent cancer researchers into thinking about participating in LAM research. This new interest in LAM as a mild form of cancer should bring more researchers into the LAM field.