Lymphangioleiomyomatosis

date : 05.11.2014

Emil Vachev
Galina Kirova
Natalia Stoeva
Cvetan Minchev

Department of medical imaging, Tokuda Hospital Sofia, Sofia, 51B N.Vaptzarov blvd, 1000

d-r_vachev@dir.bg

Keywords: lympangioleiomyomatosis, computed tomography, pulmonary cyst, pneumothorax, chylothorax

Clinical history: We present a 35-year-old woman with complaints from weakness, dyspnea and pain in the left hemithorax. The physical examination showed lack of pulmonary sound. A conventional X-ray was made. A partial pneumothorax was found. Neither X-ray nor video assisted thoracoscopy found bullae. During the next two months the woman was readmitted at the hospital with clinical and radiological features of re-occurring pneumothorax. Atypical lung resection on the right was done. Several CT follow-ups were assigned.

Imaging findings:

In the acute phases conventional X-rays of the chest proved the re-occurring pneumothorax. The follow-up conventional X-rays (CXR) showed lack of pneumothorax, with areas of reticular opacities. From the lung CT numerous, primarily small, thin walled air filled cysts were found evenly spread throughout both lungs. The surrounding lung parenchyma is with a normal appearance or with small and undefined areas of consolidation. The spontaneous pneumothorax is well defined. As a result of the numerously performed scarifications and pleural drainages due to receding pneumothorax, pleural adhesions were formed.A well-circumscribed, oval zone with a higher density in comparison to the renal parenchyma was also found protruding out of the left kidney's cortex.There was no sign of pleural effusion and/or ascites. Normal sized mediastinal lymph nodes.

Final diagnosis: Lymphangioleiomyomatosis. After an atypical resection of the right lung, the histology showed dilated vessels, emphysematous alveoli, acute and chronic hemorrhages with the presents of siderophages.

Discussion:

Lymphangioleiomyomatosis is a rare, slow progressing neoplasm, with a frequency of 1:400 000 in women. This is due to the TSC1 (hamartin) and TSC2 (tuberin) gene mutation, which are also responsible for the development of the tuberous sclerosis group of diseases. As a result of this mutation the uncontrollable proliferation of immature smooth muscle cells and lymph endothelial cells begins. Through the lymph and venous blood flow these cells end up in the walls of the venous vessels and the lymph ducts, as well as in the walls of the lung's bronchiole therefore leading to the stenosis and obstruction of these structures, with lymph and venous stasis and the formation of air filed cysts in the lungs. The fully developed clinical picture is almost always presented in women of childbearing age, even though the mentioned above mutations can be found in men with cystic changes in the lungs with or without the presence of tuberous sclerosis. The disease can manifest with a cough with or without haemoptoë. A common first sign is one of the following complications – a spontaneous and/or reoccurring pneumothorax, hilous pleural effusion, pericarditis and a respiratory insufficiency in the late stage. The disease is associated with tuberous sclerosis in about 2.5% of the cases. Renal angiomyolipomes are also commonly found. Macroscopically, rarely a lipid component is found in them, in comparison to the sporadic angiomyolipomes. Lymphangioleiomyomatosis can manifest with enlarged lymph nodes, hilous ascites, uterine fibroids, and splenic cysts. In the neck cystic hygromes can develop, and destructive zones in the bones may also be found. In the early stages of the disease a normal chest X-ray appearance is noted. However on a later stage diffused reticulonodular pattern on the plain X-ray film may be seen. The presence of pleural effusion and pneumothorax are signs of complications. Computed Tomography is the diagnostic method of choice. It shows numerous (more than 10) thin walled air filled cysts, spread out evenly in the lungs. The cysts are usually small, with a measurement of 3-5 mm, but can reach a maximum of 30 mm. The surrounding lung parenchyma is unchanged. Occasionally septal thickening and consolidating zones are seen, due to intracystic hemorrhage. CT easily confirms plural effusions and pneumothorax. Other spotted findings from the chest CT are dilated lymphatic ducts, pericardial effusion, and enlarged lymph nodes. The final method of diagnosis is open lung biopsy. In the case of the inability to perform a lung biopsy, this disease can be suspected on the basis of CT findings – the presence of hilous plural effusion or hilous ascites, angiomyolipoma on the kidneys or an abdominal lymphangioleiomioma. For this reason in the case of suspected lymphangioleyomiomatosis a targeted CT examination of the abdomen and lower pelvis must be performed. A MRI examination of the head is recommended, for excluding tuberous sclerosis and/or meningioma.

Differential diagnosis:

The primary differential diagnosis that comes in place is Langerhan's histyocytosis (Histocytosis X), where the cystic appearance is presented at a later stage. The cysts have an irregular form, and are predominantly located in the upper and middle lobes of the lungs.The centrilobular emphysema and the lymphoid pneumonia are the other two diseases with which differential diagnosis should also be made. Centirlobular emphysema is strongly associated with tobacco smoking. The changes are unevenly spread out and are prominent in the upper lobes. The subpleural parenchyma is preserved. The centrilobular artery in the emphysematous bullae is intact.In the case of lymphoid pneumonia cysts may be observed. These cysts have well defined walls. They may be diffused, but are predominantly located in the lower lobes and in the subpleural zones. The surrounding parenchyma shows a ground-glass opacity pattern. The bronchovascular bundles are widened and perilymphatic thickening can be seen.Poor fatty tissue renal angiomyolipoma needs to be differentiated from renal cell carcinoma, complicated cyst and oncocytoma.

Take home messages:

Lymphangioleiomyomatosis is a rare disease, which should come to mind in female patients with spontaneous pneumothorax and/or multiple lung cysts. In patients with tuberous sclerosis and/or angiomyolipoma we always need to remember to look for lymphangioleiomyomatosis.

Bibliography:

1. Elizabeth P. Henske, Francis X. McCormack; Lymphangioleiomyomatosis — a wolf in sheep’s clothing; J Clin Invest. 2012;122(11):3807–3816 2. S. Harari, O. Torre and J. Moss; Lymphangioleiomyomatosis: what do we know and what are we looking for? J Clin Invest., 2011;20:034-044 3. Johnson SR, Cordier JF, Lazor R, et al. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur Respir J 2010;35:14-264. Bissler JJ, McCormack FX, Young LR, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 2008;358:140-515. Juvet SC, McCormack FX, Kwiatkowski DJ, et al. Molecular pathogenesis of lymphangioleiomyomatosis: lessons learned from orphans. Am J Respir Cell Mol Biol 2007;36:398-4086. Maria Mavroudi, Paul Zarogoulidis, Nikolaos Katsikogiannis et al. Lymphangioleiomyomatosis: current and future. J Thorac Dis. Feb 2013; 5(1): 74–79.7. M. C. Castoldi, A. Verrioli, E. De Juli, A. Vanzul

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