Lymphangioleiomyomatosis (leiomyomatosis): causes, symptoms, diagnosis, treatment

Lymphangioleiomyomatosis (leiomyomatosis) is a benign proliferation of smooth muscle cells in all parts of the lung, including pulmonary blood and lymph vessels, as well as the pleura. Disease lymphangioleiomyomatosis (leiomyomatosis) - rare, occurs exclusively in young women. The reason is unknown. It manifests as shortness of breath, cough, pain in the chest and hemoptysis; spontaneous pneumothorax often develops.

Suspicion of the presence of the disease is established when analyzing the clinical manifestations and results of chest radiography and is confirmed with high-resolution CT. The prognosis is not established, but the disease is slowly progressing, and over a number of years often leads to respiratory failure and death. Radical treatment of lymphangioleiomyomatosis - lung transplantation.

Lymphangioliomiomatosis (leiomyomatosis) is a pathological process characterized by tumor-like proliferation of smooth muscle fibers along the course of small bronchi, bronchioles, walls of blood and lymphatic vessels of the lungs followed by small-cystic transformation of lung tissue. The disease affects only women aged 18-50 years.

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What causes lymphangioleiomyomatosis?

Lymphangioleiomiomatosis is a lung disease that affects only women, mainly between the ages of 20 and 40 years. Representatives of the white race are in the most risky group. Lymphangioleiomiomatosis occurs with a frequency of less than 1 case per million people and is characterized by benign proliferation of atypical smooth muscle cells in the chest, including lung parenchyma, blood and lymph vessels and pleura, resulting in a change in lung structure, cystic emphysema and a progressive decrease in lung function. The description of this disease is included in the current chapter, since patients with lymphangioleiomyomatosis are sometimes mistakenly diagnosed with IBLARB.

The cause of lymphangioleomyomatosis is unknown. An attractive hypothesis that female sex hormones play a role in the pathogenesis of the disease remains unproven. Lymphangioleiomyomatosis usually arises spontaneously and in many ways is similar to tuberous sclerosis. Lymphangioleiomyomatosis is also found in some patients with TS; Therefore, it was suggested that it is a special form of the TS. Mutations of the Tuberous Sclerosis-2 gene complex (TSC-2) have been described in cells of lymphangioleiomyomatosis and in angiomyolipomes. These data indicate the presence of one of two possibilities:

1. The somatic mosaicity of TSC-2 mutations in the lungs and kidneys leads to the appearance of foci of the disease among the normal cells of these tissues (while the appearance of individual parts of the disease can be expected);
2. Lymphangioleiomyomatosis is the spreading of angiomyolipoma tissue into the lung, similar to that seen with benign metastatic lesion syndrome.

The following pathomorphological signs of the disease are characteristic:

• considerable density of the lungs, many small nodules 0.3-0.7 cm in diameter, whitish, filled with fluid, they are located subpleural;
• the presence in some parts of the lungs of large air cavities;
• hyperplasia of lymph nodes;
• diffuse proliferation of smooth muscle fibers in the interstitium of the lungs (interalveolar, perivascular, peribronchial, subpleural, along the lymphatic vessels);
• destructive changes in the walls of the blood and lymph vessels, the walls of the bronchi, alveoli;
• formation of microcystic "cellular" lung;
• the development of pneumochemohylotrox in connection with the destruction of the walls of the blood and lymph vessels of the lungs and the rupture of subpleural cysts.

These pathomorphological manifestations are characteristic of the diffuse form of the disease.

The focal form (leiomyomatosis) is characterized by the development in the lung parenchyma of tumorous formations - leiomyoma.

Symptoms of lymphangioleiomyomatosis

The initial manifestations of the disease are shortness of breath and, more rarely, coughing, chest pain and hemoptysis. In general, manifestations are usually meager, but some patients may have wet and dry rales. Spontaneous pneumothorax often develops. There are also manifestations of lymphatic duct obstruction, including chylothorax, chylous ascites and hiluria. Deterioration is thought to occur during pregnancy and, possibly, during air travel; the latter are particularly contraindicated in the appearance or aggravation of manifestations on the part of the respiratory system; presence in the anamnesis of pneumothorax or hemoptysis and signs of extensive subpleural bullous or cystic changes revealed in HRCT. Angiomyolipoma of the kidneys (hamartomas consisting of smooth muscles, blood vessels and adipose tissue) are found in 50% of patients and, although usually asymptomatic, can cause bleeding, which, with progression, usually manifests as hematuria or pain in the flank region.

For a long time the disease is asymptomatic. In the expanded stage, the characteristic symptoms of lymphangioleiomyomatosis are:

• shortness of breath, at first she worries only with physical exertion, then becomes permanent;
• pains in the chest, worse with breathing;
• hemoptysis (unstable symptom);
• recurrent spontaneous pneumothorax - observed in 1 / 3-1 / 2 patients, manifested by sudden intense pain in the chest, shortness of breath, lack of vesicular breathing and tympanic hue of percussion sound on the side of the lesion;
• chylothorax - a cluster of chyleic fluid in the pleural cavity (on one or both sides). With the development of chilothorax, shortness of breath increases, an intense blunt sound appears during percussion over the area of effusion, there is no breathing in this place; Chilious liquid accumulates again after its removal. It is characteristic that the development of pnevo- and chylothorax coincides with menstruation;
• Chylopericarditis and chylous ascites develop as the disease progresses and their appearance also coincides with menstruation;
• development of the chronic pulmonary heart (for symptomatology see "Pulmonary hypertension").

The focal form of the disease is asymptomatic and is detected radiographically. In some cases, the disease takes a systemic character - leiomyomas develop in the abdominal cavity, retroperitoneal space, uterus, intestine, kidneys.

The activation of the disease contributes to pregnancy, childbirth, the reception of contraceptives.

Diagnosis of lymphangioliomyomatosis

Suspicion of the presence of lymphangiomyomiomatosis occurs in young women complaining of shortness of breath, with interstitial changes in normal or enlarged lung volume according to chest radiographs, spontaneous pneumothorax, and / or chyle efflux. Verification of the diagnosis is possible during a biopsy, but first in all cases the HRCT should be performed. The detection of multiple small diffusely distributed cysts is pathognomonic for lymphangioleiomyomatosis.
 
Biopsy is performed only if there are doubts about the results of HRCT. Detection of pathological proliferation of smooth muscle cells (lymphangioleiomyomatosis cells) associated with cystic changes in histological examination is evidence of the presence of the disease.

The results of lung function tests also support the diagnosis and are particularly useful in monitoring the dynamics of the process. Typical changes consist in the appearance of obstructive or mixed (obstructive and restrictive) type of disorders. Lungs are usually hyper-airy, with an increase in total lung capacity (OEL) and chest airiness. Usually there is an air delay (increase in residual volume (TOE) and OO / OEL ratio). Also, PaO ₂ and the diffusibility of carbon monoxide are usually reduced . The majority of patients also show a decrease in working capacity.

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Laboratory diagnosis of lymphangioleiomiomatosis

1. The general or common analysis of a blood - essential changes are not present. Some patients have eosinophilia, often with increased ESR, especially with the development of pneumo- chylothorax.
2. General urine analysis - there may be a slight proteinuria (symptom non-specific and unstable);
3. Biochemical blood test - sometimes hypercholesterolemia is observed, an increase in the level of alpha2 and gamma globulins, aminotransferases, total lactate dehydrogenase, and angiotensin-converting enzyme is possible.
4. Investigation of the pleural fluid. Chilothorax is extremely characteristic for lymphangioleiomyomatosis. Pleural fluid has the following characteristic features:
   • color milky white;
   • the turbidity of the liquid is retained after centrifugation;
   • the content of triglycerides is more than 110 mg%;
   • contains chylomicra, which are detected by electrophoresis of lipoproteins in a polyacrylamide gel.

Instrumental diagnosis of lymphangioleiomyomatosis

1. X-ray examination of the lungs. In the diffuse form of the disease, characteristic x-ray signs are intensification of the pulmonary pattern due to the development of interstitial fibrosis and diffuse multiple fine-focal (miliary) obscurations. Later, in connection with the formation of many small cysts, a picture of the "cellular lung" appears.

The focal shape is characterized by foci of darkening from 0.5 to 1.5 cm in diameter with clear boundaries.

With the development of pneumothorax, the collapsed air-compressed lung is determined, with the development of chylothorax, an intensive homogeneous shadow (due to effusion) with an oblique upper border.

2. Computer tomography of the lungs reveals the same changes, but much earlier, including cystic and bullous formations.
3. Investigation of the ventilation capacity of the lungs. Characteristic increase in the residual volume of the lungs due to the formation of a number of cysts. Most patients also have an obstructive type of respiratory failure (decrease in FEV1). As the disease progresses, restrictive respiratory failure is also associated (decreased GEL).
4. Investigation of blood gases. As the development of respiratory failure arises arterial hypoxemia, the partial tension of oxygen decreases, especially after physical exertion.
5. ECG. As the disease progresses, signs of myocardial hypertrophy of the right atrium and right ventricle are revealed (see "Pulmonary hypertension").
6. Lung biopsy. A study of the lung tissue biopsy is performed to verify the diagnosis. Only an open lung biopsy is informative. The biopsy reveals the diffuse proliferation of smooth muscle fibers in the interstitium of the lungs.

The examination program for lymphangioleiomyomatosis

1. Common blood tests, urine tests.
2. Biochemical blood test - determination of cholesterol, triglycerides, total protein, protein fractions, bilirubin, transaminases.
3. X-ray examination of the lungs.
4. Investigation of pleural fluid - assessment of color, transparency, density, cytology, biochemical analysis (determination of cholesterol, triglycerides, glucose).
5. ECG.
6. Ultrasound of the abdominal cavity and kidneys.
7. Open lung biopsy followed by histological examination of biopsy specimens.

Treatment of lymphangioleiomyomatosis

The standard treatment of lymphangiomyomiomatosis is lung transplantation, but the disease can recur in the transplant. Alternative therapies, in particular hormone therapy with progestins, tamoxifen and ovariectomy, are in most cases ineffective. Pneumothorax can also be a problem, as it can often recur, be bilateral and insensitive to standard therapy. Repeated pneumothorax requires decortication of the lung, pleurodesis (talc or other substances) or pleurrectomy. In the US, patients can receive psychological support in the Lymphangioleiomyomatosis Foundation.

What prognosis does lymphangioleiomyomatosis have?

Lymphangioleiomyomatosis has not a clear prognosis, in view of the extreme rarity of the disease and the considerable variability of the clinical state of patients with lymphangioleiomyomatosis. In general, the disease is slowly progressing, leading ultimately to respiratory failure and death, but life expectancy varies widely according to various sources. Patients should be aware that the progression of the disease can accelerate during pregnancy. The median survival is approximately 8 years from the date of diagnosis.