Regional Sparing in an Oligemic Lung Segment Supports Hematogenous Spread as a Pathogenic Mechanism in Lymphangioleiomyomatosis

To the Editor:

A 44-year-old white female with prior history of tuberous sclerosis (TSC) was seen in our clinic for evaluation of dyspnea on exertion. A high-resolution computed tomography (HRCT) scan of the chest showed diffuse, bilateral, thin-walled cysts (Figure 1A) consistent with a diagnosis of lymphangioleiomyomatosis (LAM). The posterior basilar segment of the left lower lobe was hyperlucent and oligemic (Figure 1B, arrow), with markedly attenuated pulmonary arterial branches, consistent with a possible diagnosis of focal obliterative (Swyer-James) bronchiolitis due to remote infection. Air trapping of the affected region was apparent on expiratory views (Figure 1C, arrow), despite a patent central airway. This area was relatively spared of the cystic changes seen in other lung fields (Figures 1B and 1C, arrow). Ventilation perfusion scanning revealed a subtle, triangular, matched defect in the distribution of the posterior basal segment (not shown).

Figure 1.

High-resolution computed tomography (CT) chest findings in our patient. (A) Chest CT showing diffuse involvement of the pulmonary parenchyma by thin-walled cysts consistent with a diagnosis of lymphangioleiomyomatosis. (B) Chest CT showing a hyperlucent and oligemic posterior basilar segment of the left lower lobe (arrow), consistent with focal obliterative (Swyer-James) bronchiolitis. (C) Expiratory views showing air trapping in the posterior basilar segment of left lower lobe despite a patent central airway (arrow). Note that the posterior basilar segment of the left lower lobe is devoid of the cystic changes seen in other lung fields.

Over the next few months, the patient experienced rapid disease progression requiring up to 8 liters of supplemental oxygen at rest. The Multicenter International LAM Efficacy of Sirolimus trial, which demonstrated that sirolimus stabilizes lung function in LAM, was published just before the listing of the patient for transplant (1), and she was started on therapy. Treatment with sirolimus resulted in remarkable clinical improvement. The patient’s supplemental oxygen requirement resolved completely over the course of 5 months, and she was taken off the transplant list. Currently, 4 years later, the patient is taking 2 mg sirolimus daily with stabilization of her pulmonary function tests and not requiring supplemental oxygen.

LAM is a progressive, diffuse cystic lung disease caused by mutations in the TSC gene, leading to constitutive activation of the mechanistic target of rapamycin pathway (2). LAM is characterized by infiltration of the pulmonary parenchyma with abnormal smooth muscle cells (LAM cells). The origin of LAM cells is unknown, but they are believed to originate from an extrapulmonary source and metastasize to lungs. The primary evidence supporting a metastatic mechanism for LAM derives from cases of recurrence of LAM lesions in donor allografts of patients with LAM after transplantation (3–5), with genetic analyses supporting a recipient source (6, 7), and from autopsy findings of extensive infiltration of the thoracic duct and lymphatic channels with LAM cells (8, 9), including the presence of LAM cell tumor emboli (LAM cell clusters) in the lumen (9–11). In addition, identification of matching TSC mutations in the angiomyolipomas, lymph nodes, and lungs within individuals suggest seeding of the lung from a common extrapulmonary source (12, 13). Collectively, these data indicate that LAM is a low-grade, destructive, metastasizing neoplasm (14).

There are certain limitations to our proposed hypothesis. Our diagnosis of Swyer-James bronchiolitis is based on expert review of the lung images. The differential diagnosis of unilateral, segmental, hyperlucent lung includes other conditions, such as congenital lobar emphysema, congenital cystic airway malformation, bronchial atresia, et cetera (15). Another limitation is that emphysematous lung may be less susceptible to cyst formation because of the relative paucity of lung tissue.

In conclusion, we believe that relative sparing of the oligemic lung field in this case provides further circumstantial evidence of hematogenous spread as the primary mechanism for pulmonary involvement in LAM.