Lymphangioleiomyomatosis D48.1

Lymphangioleiomyomatosis (LAM) is a very rare, progressively progressive disease of the lung, characterized by a proliferation of abnormal epithelioid smooth muscle-like cells (LAM cells) of the lung, which leads to displacement and destruction of the normal lung parenchyma and to repiratory insufficiency.

Lymphangioleiomyomatosis almost exclusively affects women of childbearing age. On average, it begins in middle age at about 35 years. However, the final diagnosis is often made later.

Two different forms of lymphangioleiomyomatosis are distinguished:

• Sporadic form: In sporadic LAM, patients have a spontaneously acquired genetic defect. This form of LAM cannot be inherited.
• LAM in the context of tuberous sclerosis (TSC): LAM can also develop as a consequence of tuberous sclerosis. This is a hereditary disease caused by a mutation in the TSC gene. It results in benign cell growths in various organs of the body. The skin and brain as well as the kidneys are particularly affected. About 30 to 40 percent of TSC patients develop LAM of the lungs. The numerous mutations identified are summarized in the Tuberous Sclerosis Complex Variation Database for TSC1 and for TSC2. However, in 10-15% of patients no mutations (no mutation identified) can be detected (NMI patients).

The inherited LAM form is about four times more common than sporadic LAM (sLAM). Nevertheless, most women treated for lymphangioleiomyomatosis of the lung have the sporadic form.

The average age at the time of diagnosis is 41 years (18 - 76 years).

The macroscopic findings resemble a severe emphysema with widened alveolar septum. This makes breathing increasingly difficult for patients with LAM, and they are physically less able to cope with stress. LAM is associated with (sometimes aggressively growing) angiomyolipomas of the kidneys (Cooper A et al. 2018) or fibrosis of the abdominal cavity in some patients. Angiomyolipomas of the kidneys are associated with tuberous sclerosis in about 80% of patients (Cai Y et al. 2018). In 50% of all patients with LAM, severe symptoms such as pneumothorax occur during the course of the disease and in about 15% of patients with LAM, chylothorax is present.

Most of the proliferating cells are HMB-45 positive and show reactivity for estrogen receptors (ER), progesterone receptors, the epidermal growth factor receptor (EGFR) and podoplanin (Grzegorek I et al. 2015).

Computer tomography: multiple cyst-like lesions in the lungs. CT-guided lung biopsy is a complementary and diagnostic tool.

The current therapy with Medroxy-Progesterone seems to be effective in only a part of the patients. In 2011, a larger study showed that Sirolimus (Rapamycin) stabilizes lung function, reduces symptoms and improves quality of life.

Ultima ratio in advanced stages of the disease is lung transplantation. The prognosis after a lung transplantation is good. Recurrences have not yet been described.

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