(Radiographics. 2002;22:S185-S198.)
© RSNA, 2002
Lymphangioleiomyomatosis: Pulmonary and Abdominal Findings with Pathologic Correlation1
Esther Pallisa, MD,
Pilar Sanz, MD,
Antonio Roman, MD,
Joaquim Majó, MD,
Jordi Andreu, MD and
José Cáceres, MD
1 From the Departments of Radiology (E.P., P.S., J.A., J.C.), Respiratory Medicine (A.R.), and Pathology (J.M.), Hospital General Universitari Vall d’Hebron, Passeig Vall d’Hebron 119–129, 08035 Barcelona, Spain. Presented as an education exhibit at the 2001 RSNA scientific assembly. Received February 8, 2002; revision requested March 18; final revision received June 19; accepted July 2. Address correspondence to E.P. (e-mail: 26787epn@comb.es).
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Abstract
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Lymphangioleiomyomatosis (LAM) is a rare disease characterized by pulmonary cysts at computed tomography (CT) and proliferation of abnormal smooth muscle cells at lung biopsy. Almost all patients are female, and all have pulmonary cysts at high-resolution CT. Although the presence of cysts may be suggested at conventional CT or chest radiography, high-resolution CT is superior for cyst detection and is essential for diagnosis. The cysts are typically round; in most cases, the cyst wall is barely seen at thin-section CT. They are typically diffusely distributed throughout the central and peripheral lung parenchyma. The lung bases are affected in all patients. Some patients also have increased lung attenuation or a reticular pattern. Expiratory CT shows no air trapping between the cysts, and most of the cysts decrease in size. Pneumothorax, pleural effusion, and chylothorax are complications of LAM. Certain abdominal findings may provide additional corroborative evidence of the diagnosis. Renal angiomyolipomas, the most frequent abdominal lesions, usually manifest as asymptomatic, small, bilateral tumors of fat attenuation in the renal cortex. Lymphangiomas are cystic retroperitoneal masses that occur in up to 20% of patients. Other CT findings are hypo- or hyperattenuating lymph nodes, a dilated thoracic duct, and ascites.
© RSNA, 2002
Index Terms: Lung, cysts, 60.3129 • Lung, diseases, 60.799 • Lymphangiomyomatosis, 60.799, 99.829
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Introduction
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Lymphangioleiomyomatosis (LAM) is a rare, idiopathic disorder that predominantly affects the lung parenchyma of women of childbearing age (1). It is characterized by pulmonary cysts at computed tomography (CT). In addition, certain abdominal findings have been seen in more than 50% of patients (1) and may reinforce the diagnosis suspected on the basis of the pulmonary features. The radiologist is often the first to suggest the diagnosis of LAM. However, misdiagnosis is common and may result in inappropriate therapeutic procedures that can further complicate treatment.
There is no known familial tendency, although the pathologic findings in LAM are identical to those seen when tuberous sclerosis complex, an autosomal dominant inherited disorder, affects the lung. Two gene mutations cause tuberous sclerosis complex: TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13. Recent evidence suggests that the proliferative and invasive nature of LAM cells may be due, in part, to somatic mutations in the TSC2 gene. Somatic mutations in the TSC2 gene occur in the angiomyolipomas and the abnormal pulmonary smooth muscle cells of patients with LAM (2).
The most common presenting symptoms of LAM are dyspnea on exertion and pneumothorax, leading to progressive loss of lung function (3,4). The basic radiologic manifestations are a coarse reticulonodular pattern predominantly in the lung bases, increased lung volume, recurrent pneumothorax, and pleural effusion. These conventional radiographic findings are nonspecific. However, high-resolution CT and abdominal CT reveal very characteristic abnormalities, which may so strongly suggest the diagnosis of LAM that lung biopsy could be obviated. For this reason, a comprehensive review of this entity can be useful.
In this article, we review the clinical symptoms and the pulmonary and abdominal CT findings of LAM. We also present the pathologic correlation of the pulmonary findings and the differential diagnosis of the pulmonary manifestations.
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Clinical Features
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LAM occurs almost exclusively in women. The average age at onset of symptoms is approximately 34 years (5–7). The first symptoms of the disease can occur before an abnormality is detectable with chest plain radiographs or pulmonary function tests; even when such abnormalities exist, the disease may be initially misdiagnosed. There is often a delay between the onset of symptoms and correct diagnosis.
LAM commonly manifests as exertional dyspnea and recurrent pneumothorax. During the course of the illness, there may be nonproductive cough, hemoptysis, chylous pleural effusion, or chylous ascites (3,5). Obstruction of pulmonary venules causes vascular congestion and hemoptysis, and lymphatic obstruction leads to chylothorax and chylous ascites.
The clinical course of patients with LAM shows considerable variation. The disease is believed to be slowly progressive, leading to respiratory failure and death. The 10-year survival from the start of symptoms in a study at our institution was 49% (7), although reported figures range from an 8.5-year survival probability of 38% to a 10-year survival of 79% (8). Differences in survival rates may be due to improvements in diagnosis, particularly regarding the contribution of high-resolution CT, and do not mean that the progression of the disease has changed substantially. Diagnosis of mild asymptomatic forms may also have contributed to the longer survival rates (4).
Spirometry studies in LAM patients demonstrate chronic airway obstruction with increased lung volume and decreased CO2 diffusion. The radiologic finding of an interstitial pattern with these spirometric results in a young woman narrows the differential diagnosis to some forms of emphysema, Langerhans cell histiocytosis, and sarcoidosis. The information provided by HRCT is essential for differentiating LAM from these conditions.
Numerous therapeutic strategies have been described to treat LAM (4). In light of the reports of clinical worsening of the disease during pregnancy and with use of exogenous estrogens, many clinicians have applied therapeutic hormone manipulation. Antiestrogen therapy, first used in the early 1980s, consists of surgical castration by oophorectomy or administration of tamoxifen, progesterone, and gonadotropin-releasing hormone agonist or luteinizing hormone–releasing hormone (3,5). Several studies have reported beneficial effects of antiestrogen hormone therapies for LAM, but careful scrutiny of some of these studies reveals that the treatment improved the chylothorax or chylous ascites, whereas pulmonary involvement seemed to remain stationary or to progress. Since lung transplantation has become available for patients with poor response to therapies, certain treatments must be used with caution. In fact, castration does not clearly demonstrate a beneficial effect on the course of the disease, and the long-term effects of castration, particularly in the postoperative period of lung transplantation, can increase bone complications.
In most cases, chylothorax should be managed conservatively. Chylothorax usually appears early in the course of the disease, when the patient’s functional status is good. Early application of surgical techniques such as pleural abrasion, pleurodesis, or pleurectomy must be avoided because these treatments might limit future lung transplantation. Medical treatment includes tamoxifen, progesterone, and, in some cases, a low-fat diet (4,5).
When the patient’s functional status declines, bilateral lung transplantation is the best therapeutic option. The guidelines indicating transplantation include progression despite medical treatment, forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of less than 50%, total lung capacity of greater than 130%, and FEV1 of less than 30%. In the largest published series of lung transplantations in LAM patients, the average FEV1 at the time of evaluation for the procedure was 24%.
Common postoperative complications of lung transplantation are bacterial, viral, and fungal infections; acute rejection episodes; and chronic rejection. Complications specific to LAM are pneumothorax of the native lung after single-lung transplantation, chylothorax, recurrence of LAM, and abdominal complications (4,9).
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Pulmonary Findings
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Pulmonary Cysts
Cyst is a nonspecific term for a thin-walled (usually <3 mm), well-defined and circumscribed, air- or fluid-containing lesion 1 cm or more in diameter. At high-resolution CT, the term usually refers to an air-containing lesion. Air-filled cysts are commonly seen in patients with Langerhans cell histiocytosis and LAM. This term is not usually used to refer to the focal lucencies associated with emphysema. The presence of multiple cysts in a basal subpleural location can result in a honeycomb appearance similar to that of idiopathic pulmonary fibrosis. In idiopathic pulmonary fibrosis, the cystic lung disease is associated with decreased lung volumes, whereas in Langerhans cell histiocytosis or LAM the lung volumes are increased.
Cysts have been seen in 100% of patients with LAM reported to date. They are characteristically round and thin-walled (Fig 1); nevertheless, some do not have walls and others have an irregular configuration (10,11). The appearance, size, and contour of lung cysts vary considerably in LAM (Figs 2, 3).
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Figure 1. Typical lung cysts in a 52-year-old woman with LAM. High-resolution CT scan shows well-defined thin-walled bilateral lung cysts (arrow), which are randomly distributed throughout the lungs. The lung parenchyma between the cysts is normal. Note the scarring due to open lung biopsy in the lingula.
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Figure 2. Irregular cysts in a 36-year-old woman with LAM. High-resolution CT scan obtained at the level of the aortic arch shows irregular cysts of different sizes. Some cyst walls are barely seen (white arrow). There are also small nodules (black arrow) in the lung parenchyma.
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Figure 3. Atypical lung cysts in a 34-year-old woman with severe dyspnea. High-resolution CT scan obtained at the lung apices shows lung cysts with an anterior distribution in the upper lobes. There is also a left pleural effusion. The diagnosis of LAM was confirmed at analysis of the explanted lungs.
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The cysts are generally symmetrically (Fig 3) and uniformly distributed throughout the lungs, affecting the upper and lower and the central and peripheral lung parenchyma (12). The profusion of cysts and the quantitative CT scores clearly correlate with impairment on functional tests and clinical conditions (12,13).
Air trapping at expiratory CT is uncommon in patients with LAM (Fig 4) except in patients who have almost the whole lung replaced with cystic spaces, and normal parenchyma cannot be identified. The size of the cysts decreases on expiratory images (Fig 4b), indicating a communication with the airway. Air trapping was found in only one of 11 women in a previous series (14). To explain the parenchymal destruction and the absence of air trapping, Sobonya et al (23) have suggested that LAM cells destroy interstitial collagen, generating a loss of alveolar support (10,13). Some authors have speculated that small airway disease may be the origin of cyst formation in LAM and describe the presence of air trapping (14,15); however, the mechanism of cyst formation in LAM and the relation of the cysts to small airway disease and the presence of air trapping is still controversial.
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Figure 4a. Inspiratory and expiratory findings at the lung bases in a 43-year-old woman with biopsy-proved LAM. (a) Inspiratory high-resolution CT scan shows well-defined lung cysts and normal lung tissue between them. Note the surgical biopsy scar in the left lower lobe. (b) Expiratory high-resolution CT scan shows normal-appearing increased attenuation of the normal lung tissue.
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Figure 4b. Inspiratory and expiratory findings at the lung bases in a 43-year-old woman with biopsy-proved LAM. (a) Inspiratory high-resolution CT scan shows well-defined lung cysts and normal lung tissue between them. Note the surgical biopsy scar in the left lower lobe. (b) Expiratory high-resolution CT scan shows normal-appearing increased attenuation of the normal lung tissue.
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The lung parenchyma between the cysts is typically normal, but in highly cellular forms with significant smooth cell proliferation, small nodules, reticulation, or ground-glass attenuation may appear (6,16).
Pneumothorax
LAM manifests with dyspnea due to pneumothorax in 40% of patients (1,3). Chemical or surgical pleurodesis has been advocated to prevent recurrent pneumothorax, but the resulting adhesions can make future lung transplantation more complicated. For this reason, one should take a conservative stance when recommending abrasion procedures in a young woman with pneumothorax.
Reticular Opacities
Reticular opacities and increased lung volume are the most common abnormalities on chest radiographs. The reticular interstitial pattern shown on chest radiographs results from summation of numerous cysts. The basal predominance reported for this pattern may be due to a summation effect (Fig 5), as apical sparing by the disease has not been described (12).
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Figure 5a. Reticular pattern in a 38-year-old woman with severe dyspnea and a 3-year history of LAM. (a) Chest radiograph shows a bilateral reticular pattern in the lung bases and bilateral pleural effusions. (b) High-resolution CT scan shows that the reticular pattern is due to multiple cysts.
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Figure 5b. Reticular pattern in a 38-year-old woman with severe dyspnea and a 3-year history of LAM. (a) Chest radiograph shows a bilateral reticular pattern in the lung bases and bilateral pleural effusions. (b) High-resolution CT scan shows that the reticular pattern is due to multiple cysts.
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Septal lines and interstitial lymphatic edema may be seen in addition to pleural effusion. Both are an expression of interstitial edema caused by obstruction of the lymphatic vessels (4,16).
Increased Attenuation
Ill-defined areas of increased attenuation may result from hemorrhage or edema (16), as both are known complications of LAM.
Pulmonary hemorrhage occurs in 8%–14% of women with LAM (Fig 6). Involvement of the venules may result in total occlusion of the vessels, causing pulmonary venous hypertension and hemoptysis (1,3,16).
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Figure 6. Pulmonary hemorrhage in a 46-year-old woman 10 months after unilateral left lung transplantation for LAM. CT scan shows increased attenuation in the native right lung and a small right pleural effusion. Bronchoalveolar lavage of the right lung showed hemosiderin-laden macrophages in the alveoli. The transplanted left lung was partially collapsed due to hypoventilation and shift of the mediastinum.
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Foci of hemosiderin-laden macrophages may be present in the air spaces and interstitium as remnants of past hemorrhage. In such circumstances, the clinical sign is recurrent hemoptysis without evolution to severe alveolar hemorrhage syndrome. These cases may be misdiagnosed as primary hemosiderosis.
Occasionally, ground-glass attenuation may be due to proliferation of smooth cells in the alveolar walls (Fig 7). Tiny centrilobular nodules (Fig 2), corresponding to bronchioles surrounded by accumulated smooth muscle cells, have also been described.
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Figure 7a. Increased lung attenuation in a 34-year-old woman with highly cellular LAM. (a) Inspiratory high-resolution CT scan obtained at the level of the lung bases shows bilateral ground-glass attenuation and intralobular and septal lines. The cysts are elongated and have a subpleural (arrow) and peribronchovascular distribution. (b) High-resolution CT scan of the explanted lung (sagittal view) shows the irregular cystic spaces in the left lower lobe along the bronchovascular bundles (arrow). Note the basal distribution of the cysts and the diffuse increased attenuation of the lung.
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Figure 7b. Increased lung attenuation in a 34-year-old woman with highly cellular LAM. (a) Inspiratory high-resolution CT scan obtained at the level of the lung bases shows bilateral ground-glass attenuation and intralobular and septal lines. The cysts are elongated and have a subpleural (arrow) and peribronchovascular distribution. (b) High-resolution CT scan of the explanted lung (sagittal view) shows the irregular cystic spaces in the left lower lobe along the bronchovascular bundles (arrow). Note the basal distribution of the cysts and the diffuse increased attenuation of the lung.
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Chylous Pleural Effusion
Unilateral or bilateral chylothorax is typically large and recurrent (Fig 8) and usually appears during the course of the disease (3). The CT attenuation of chylous pleural effusion is usually indistinguishable from that of other effusions because it is protein rich.
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Figure 8. Chylothorax. Contrast material-enhanced CT scan (7-mm collimation) obtained at the level of the lung bases shows bilateral pleural effusions, which turned out to be chylous.
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Drainage of chylous pleural fluid collections can lead to protein loss. Aggressive measures aimed at decreasing the production of chylous pleural fluid, such as ligation or irradiation of the thoracic duct, are no longer recommended.
Thoracic Duct and Mediastinal Ganglia
Mediastinal ganglia increased in size (>1 cm) and dilatation of the thoracic duct are known thoracic manifestations of LAM. Various series report no mediastinal or hilar lymphadenopathy (5,14). Chu et al (6) report that retrocrural adenopathy was seen in nine of 35 patients (26%) in their study.
Complications of Lung Transplantation
Lung transplantation has particular complications in patients with LAM. In addition to infection, rejection, airway anastomotic complications, and lymphoproliferative disease, patients undergoing lung transplantation for LAM are also susceptible to complications related to their underlying disease (8) (Figs 6, 9). Excessive bleeding from pleural adhesions during surgery, pneumothorax of the native lung, chylothorax, hemorrhage, and recurrence of the disease in the transplanted lung have been described (9). Abdominal complications such as bleeding of renal angiomyolipomas and chylous ascites may also complicate the postoperative management.
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Figure 9. Pneumothorax involving the native lung in a 46-year-old woman 3 months after left lung transplantation for LAM. CT scan shows multiple cysts in the native right lung and a large right-sided hydropneumothorax that displaces the mediastinum, compromising the function of the transplanted lung.
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Pathologic Findings
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Light microscopy findings in LAM are characterized by diffuse interstitial proliferation of bundles of "immature" smooth muscle cells. These lesions are frequently located in the wall of enlarged air cavities and, to a larger or lesser degree, make up part of the wall (Fig 10).
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Figure 10a. (a) Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows an enlarged air space with a thick wall due to myomatosis (arrow). The surrounding parenchyma has a normal appearance. (b) Photomicrograph (original magnification, x250; Gomori trichrome stain) shows a myomatous bundle in the wall of the lesion. Arrow indicates the myomatous cells.
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Figure 10b. (a) Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows an enlarged air space with a thick wall due to myomatosis (arrow). The surrounding parenchyma has a normal appearance. (b) Photomicrograph (original magnification, x250; Gomori trichrome stain) shows a myomatous bundle in the wall of the lesion. Arrow indicates the myomatous cells.
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The proliferating cells have a benign appearance, and immunohistochemistry shows smooth muscle actin and melanoma-associated (HMB-45) antigens. The HMB-45 antigens are useful for diagnosis of LAM because LAM is the unique smooth muscle cell proliferation in the lung that expresses such antigen (Fig 11).
The air-enlarged cavities appear as large spaces because of dilatation rather than destruction (Fig 12). They are randomly localized in the secondary lobule (Fig 13). In addition, the distribution in the lung is homogeneous without lobar differences, as seen in the transplantation cases (Fig 14).
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Figure 12. Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows enlargement of a small air space (*) between a respiratory bronchiole (solid arrow) and a larger and more distal LAM lesion without myomatosis (open arrow).
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Figure 13. Photomicrograph (Gomori trichrome stain) shows a lung biopsy specimen with typical features of LAM. Note that the enlarged air spaces differ in size and location within the secondary lobule. The thickness of the walls of the enlarged air spaces also differs. There is a small lesion in the centrilobular area (arrow) and a medium-sized lesion at the periphery of the lobule (arrowhead) with a subpleural location; in comparison, there is a medium-sized lesion in the middle lobular area with a thicker myomatous wall (*).
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Hemosiderin deposition in the interstitium and within the alveolar macrophages is another typical finding. The degree of this deposition is associated with the degree of myomatosis.
The small airway disease is quite heterogeneous within the same lung and among patients. The entire spectrum from normal appearance to considerable fibrotic stenosis may be seen.
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Abdominal Manifestations
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Renal Angiomyolipomas
Abdominal findings may be present in more than 70% of patients with LAM (17), and the most common abdominal finding is renal angiomyolipoma. Angiomyolipomas are often small (<1 cm), multiple, bilateral, and asymptomatic (Fig 15) and occur in 20%–54% of patients with LAM (17,18). Angiomyolipomas are characterized by the presence of mature fat, smooth muscle, and blood vessels. The muscle and fat vary in relative amounts from one tumor to another.
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Figure 15. Renal angiomyolipomas in a 45-year-old woman with LAM. Unenhanced abdominal CT scan shows multiple bilateral small nodules (arrows). Analysis of CT numbers revealed fat attenuation in the left renal cortex, a finding diagnostic of renal angiomyolipomas.
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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. In a patient with a history of LAM, the absence of fat in a renal lesion should not preclude the diagnosis of angiomyolipoma (19), as fat is not detectable in up to 5% of these tumors (Fig 16). The signal intensity of the lesion at magnetic resonance imaging and the echogenicity at ultrasonography (US) also vary with the degree of fat content within the tumor. If fat is not detected, close follow-up of these lesions with US, unenhanced CT, or image-guided biopsy is recommended (19).
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Figure 16a. Hyperattenuating angiomyolipoma in a young woman with LAM. Abdominal CT scans obtained before (a) and after (b) administration of contrast material show a slightly hyperattenuating renal tumor (arrows) in the left upper pole. Unenhanced CT could not demonstrate tissue of fat attenuation. CT-guided biopsy was performed to confirm the diagnosis.
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Figure 16b. Hyperattenuating angiomyolipoma in a young woman with LAM. Abdominal CT scans obtained before (a) and after (b) administration of contrast material show a slightly hyperattenuating renal tumor (arrows) in the left upper pole. Unenhanced CT could not demonstrate tissue of fat attenuation. CT-guided biopsy was performed to confirm the diagnosis.
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The clinical manifestations and management of these tumors depend on their size. Abdominal pain and hematuria may occur. Hemorrhage, a major complication of renal angiomyolipoma, is related to the size of the tumor. The majority of masses that undergo spontaneous hemorrhage are more than 3.0 cm in diameter (1,4,6).
Lymphangioleiomyoma
Proliferation of smooth muscle cells in the lymph vessels may produce cystic masses consistent with dilatations of the abdominal lymph vessels due to lymphatic obstruction; these are known as lymphangioleiomyomas (Fig 17). These low-attenuation retroperitoneal masses occur in up to 20% of patients (20). They may be thick- or thin-walled and can vary in size depending on diet or gravitational factors (Fig 18) (21).
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Figure 17. Lymphangioleiomyomas in a young woman with pulmonary cysts. Contrast-enhanced abdominal CT scan (10-mm collimation) shows low-attenuation retroperitoneal cystic masses (arrows), which are consistent with dilatation of the abdominal lymph vessels.
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Figure 18a. Thick-walled lymphangioleiomyoma in a 39-year-old woman with LAM and multiple retroperitoneal low-attenuation masses. (a) Contrast-enhanced CT scan obtained during the arterial phase shows a hypoattenuating pelvic mass (arrow). (b) Contrast-enhanced CT scan obtained 10 minutes later shows increased attenuation of the mass (right arrow). There is also a small hypoattenuating lesion on the right side (left arrow).
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Figure 18b. Thick-walled lymphangioleiomyoma in a 39-year-old woman with LAM and multiple retroperitoneal low-attenuation masses. (a) Contrast-enhanced CT scan obtained during the arterial phase shows a hypoattenuating pelvic mass (arrow). (b) Contrast-enhanced CT scan obtained 10 minutes later shows increased attenuation of the mass (right arrow). There is also a small hypoattenuating lesion on the right side (left arrow).
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Lymphangiomas are endothelium-lined lymphatic spaces that have no smooth muscle–LAM cells in their walls. The difference is thus microscopic. In LAM patients, retroperitoneal cystic masses are assumed to be lymphangioleiomyomas unless there are clinical indications of abscess or tumor (17,20).
Lymphadenopathy
Enlarged lymph nodes are described in up to 40% of cases. Lymph nodes can measure up to 4 cm in diameter. Some lymph nodes contain low-attenuation areas, which indicate the presence of chylous lymph collections, or hamartomatous hyperattenuating areas that enhance after contrast material administration (1,17) (Fig 19).
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Figure 19. Retroperitoneal lymphadenopathy. Contrast-enhanced abdominal CT scan obtained at the level of the kidneys shows a hyperattenuating enlarged paraaortic lymph node (left arrow). Nodular enhancement within the area of adenopathy (right arrow) occurs in patients with replacement of the normal lymph nodes by smooth muscle cells.
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Chylous Ascites
Overdistention of lymphatic cysts may result in intraperitoneal rupture and chylous ascites. This is an unusual abdominal complication of LAM that can occur in the absence of pleural effusion (Fig 20). Chylous ascites may be more frequent after transplantation (1,3,4,9,17). Conservative management includes restriction of oral fat intake. Some patients may require a peritoneal shunt.
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Figure 20. Chylous ascites in a patient who had undergone bilateral lung transplantation. Contrast-enhanced abdominal CT scan shows abundant abdominal fluid. Paracentesis demonstrated that it was chylous ascites.
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Differential Diagnosis
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Tuberous Sclerosis
Tuberous sclerosis complex is an autosomal dominant disease caused by gene mutations that affect the migration and differentiation of neural crest cells in many organs and tissues. Some published studies have established the relationship with the germ line mutations in the two genes that cause tuberous sclerosis: TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13 (2). Tuberous sclerosis affects men and women equally and is classically characterized by the triad of mental retardation, epilepsy, and adenoma sebaceum (Fig 21). Pulmonary LAM can occur as part of the tuberous sclerosis complex. Some investigators claim that isolated pulmonary LAM and LAM associated with renal angiomyolipomas are a forme fruste of tuberous sclerosis. Pulmonary involvement in tuberous sclerosis is very uncommon, occurring in only 0.1%–1% of cases. The prevalence of LAM in women with asymptomatic tuberous sclerosis may be as high as 34%. LAM has been rarely described in males with tuberous sclerosis (1,3,4,21).
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Figure 21a. Tuberous sclerosis in a young woman with seizures. (a) Contrast-enhanced CT scan of the brain shows the typical subependymal calcifications and an astrocytoma (arrow). (b) High-resolution CT scan shows bilateral lung cysts indistinguishable from those seen in LAM.
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Figure 21b. Tuberous sclerosis in a young woman with seizures. (a) Contrast-enhanced CT scan of the brain shows the typical subependymal calcifications and an astrocytoma (arrow). (b) High-resolution CT scan shows bilateral lung cysts indistinguishable from those seen in LAM.
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Langerhans Cell Histiocytosis
Langerhans cell histiocytosis (histiocytosis X) is characterized by an abnormal infiltration of mononuclear cells centered on the walls of the bronchioles, producing diffuse pulmonary cysts on chest radiographs. Langerhans cell histiocytosis is associated with cigarette smoking in 90% of cases, and up to 97% of patients have been regular smokers at some time. Nodules, cavitating nodules, and thick-walled cysts are common findings in Langerhans cell histiocytosis but are very unusual in LAM (22).
The disease in Langerhans cell histiocytosis is more marked in the upper lobes, with relative sparing of the lung bases (10,22). The cysts are frequently bizarre (Fig 22) when developed and may mimic bronchiectasis in early stages. Despite the characteristics mentioned earlier, when pulmonary cysts are found in a young female smoker, it may be impossible to differentiate between Langerhans cell histiocytosis and LAM on the basis of high-resolution CT features alone.
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Figure 22a. Langerhans cell histiocytosis in a young male smoker. (a) High-resolution CT scan shows cystic spaces predominating in both lung apices. The cysts are irregular and have well-defined walls. (b) High-resolution CT scan obtained at the costophrenic angles shows that the lung bases are less affected by small cysts (arrows).
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Figure 22b. Langerhans cell histiocytosis in a young male smoker. (a) High-resolution CT scan shows cystic spaces predominating in both lung apices. The cysts are irregular and have well-defined walls. (b) High-resolution CT scan obtained at the costophrenic angles shows that the lung bases are less affected by small cysts (arrows).
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Pulmonary Fibrosis
Honeycomb cysts due to idiopathic pulmonary fibrosis, collagen-vascular diseases, and asbestosis tend to occur in subpleural clusters and commonly involve the costophrenic angles. In contrast to LAM and histiocytosis, these diseases are predominantly subpleural and basal and have associated lung volume loss (Fig 23) (22).
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Figure 23. Pulmonary fibrosis. High-resolution CT scan shows rounded, well-defined cysts in the right lung (black arrow) in a patient with traction bronchiectasis (white arrow) and bilateral basal subpleural honeycombing (arrowheads).
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Emphysema
Emphysema is a permanent, abnormal enlargement of air spaces distal to the terminal bronchioles accompanied by destruction of their walls. Some fibrosis is not uncommon. High-resolution CT shows areas of low attenuation with or without visible walls (Fig 24). Centrilobular emphysema affects the respiratory bronchioles. It is commonly seen affecting the upper lobes in smokers (22).
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Figure 24. Emphysema in a 40-year-old smoker. High-resolution CT scan of the right lower and middle lobes obtained at the lung bases shows ill-defined hypoattenuating areas of lung destruction (arrow) that lack recognizable walls.
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Pneumatocele
A pneumatocele is a thin-walled, gas-filled cystic space within the lung, usually associated with acute pneumonia and almost invariably transient. Pneumatoceles have an appearance similar to that of lung cysts or bullae at high-resolution CT, but the clinical presentation makes the diagnosis clear.
Pneumatoceles are reported in up to 30% of patients with Pneumocystis carinii pneumonia. Innumerable cysts are superimposed on a background of diffuse air-space consolidation. Following therapy, these lesions eventually regress, resulting in either complete disappearance or residual nodules.
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Conclusions
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LAM is a serious progressive disease that predominantly affects women of childbearing age and leads to chronic incapacitating respiratory insufficiency.
Clinical suspicion arises when an interstitial disease occurs with pneumothorax and obstructive spirometric findings in a young female. The radiologist is often the first to suggest the diagnosis of LAM on the basis of the high-resolution CT findings alone.
High-resolution CT findings of LAM are very characteristic and can be considered diagnostic, particularly when typical abdominal lesions are also present.
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Footnotes
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Abbreviation: LAM = lymphangioleiomyomatosis
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References
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Abstract
Introduction
