The benign, non-invasive lesions of tuberous sclerosis can appear in any organ like the brain, heart, skin, eyes, kidney, lung, and liver. Therefore, TS has a wide clinical spectrum. The diagnosis of definitive TS is based on specific clinical features and requires the presence of two major criteria, or one major and two minor [3]. Pulmonary lymphangioleiomyomatosis, renal angiomyolipoma and facial angiofibroma are some of the major clinical features.
The most frequent cause of death in patients with TS is renal complication [3, 5]. Multifocal, bilateral angiomyolipomas are found in about 70-90% of adult patients [3], and the prevalence increases with age, being less frequent in children [3, 4]. These lesions are more often prevalent in women, suggesting a hormonal component to the tumor growth [6]. The angiomyolipomas are composed of varying amounts of mature adipose tissue, smooth muscle, and abnormal blood vessels [3, 6]. The demonstration of intratumoral fat with negative attenuation values at CT is virtually pathognomonic of angiomyolipoma. Thin-section unenhanced CT is essential to visualize the fat content of angiomyolipomas [7]. Progressive enlargement of tumors and hemorrhage into the lesion can result in flank pain, a palpable tender mass and gross or microscopic hematuria, and interfere with renal function [6]. Tumors larger than 4 cm in diameter have a greater risk of spontaneous or traumatic rupture resulting in hemorrhagic complications [6], which is the most common cause of death in patients with TS [8]. Some patients with TS carry a contiguous germline deletion that affects both the TSC2 gene and the adjacent gene, polycystic kidney disease type 1 (PKD1), resulting in a polycystic kidney phenotype that leads to early renal insufficiency [3, 4]. In our patient, the family history indicates that she inherited a germline mutation in the TSC2 gene. Renal cell carcinoma can occur in approximately 2-3% of adults with TS [3].
Pulmonary LAM is a rare progressive disease that predominantly affects women of childbearing age. Estrogen is thought to play a role in disease progression since it does not present prior to menarche and only rarely after menopause [9], and is exceptionally rare in men [1, 3, 8]. LAM probably affects 1-3% of patients with tuberous sclerosis [3, 5]. Although some articles report the occurrence of LAM in 1 to 3% of the patients with TS [3, 5], it seems that this incidence is much higher. Recent articles [10]-[12] report an incidence ranging from 26 to 34%. It is characterized by alveolar smooth-muscle proliferation leading to air trapping, pulmonary hemorrhage and lymphatic extravasation, and cystic destruction of the normal lung parenchyma [3]. Some of the manifestations are shortness of breath, coughing, chest pain, pneumothorax, chylous pleural effusions, hemoptysis, and eventually respiratory failure, but asymptomatic cases may occur [1, 3, 4]. Pulmonary function tests can show an obstructive or restrictive pattern [1]. Classical CT findings (diffuse, homogeneous, small thin-walled cysts) and compatible clinical history can be highly suggestive of LAM [5]. It is extremely difficult to treat, and the long-term prognosis is poor with the average duration of survival from the time of diagnosis near to 10 years [1]. Treatment consists of supportive management; hormonal therapy has been tried but without consistent success [1, 9]. Sirolimus (rapamycin) is being explored as another potential treatment, but additional trials will be needed to assess efficacy and potential side effects [11, 13].
Renal angiomyolipomas are present in 93% of patients with tuberous-sclerosis-associated pulmonary lymphangiomyomatosis [3]. It is important to recognize LAM before renal surgery for angiomyolipoma because of the risk of spontaneous pneumothorax or other perioperative pulmonary complication [5, 8]. Pneumothoraces ultimately occur in approximately 60 to 70% of patients with LAM, and the rate of recurrence is >70%, the highest among all chronic lung diseases [11].
Finally, it is very important to understand that a patient with TS requires a multidisciplinary clinical staff to receive a complete evaluation of the multisystem complications. In patients with lymphangiomyomatosis, annual pulmonary-function testing may be useful to monitor lung function and provide a measure of disease progression [4]. The monitoring of angiomyolipomas growth, by ultrasonography, CT, or magnetic resonance, is an essential issue in the management of TS [4].