Pulmonary Vascular Abnormalities and Spontaneous Pneumothorax in Loeys‐Dietz Syndrome

Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disorder whose clinical phenotype overlaps with that of Marfan syndrome (MFS) and vascular Ehlers-Danlos syndrome (vEDS), including aortic and/or arterial aneurysms, skeletal abnormalities, and spontaneous pneumothorax. Although the pathological features of MFS- and vEDS-associated pulmonary lesions have been described, the pulmonary pathology of LDS remains virtually unknown. Herein, we report the detailed histopathological features of LDS-associated pulmonary vascular abnormalities and pneumothorax. A 32-year-old Japanese woman underwent pulmonary surgery for spontaneous pneumothorax. She had undergone aortic valve surgery 7 years earlier, and genetic testing identified a heterozygous germline missense variant in TGFBR2 (c.1150 A > C, p.Asn384His). Histologically, the resected lung showed a ruptured bulla/bleb. Localized distal acinar emphysema was present in continuity with the bullous lesion. In the remaining parenchyma, the alveolar septa exhibited a distinctive proliferation of irregularly dilated and tortuous capillaries, reminiscent of pulmonary capillary hemangiomatosis. Hemosiderin-laden macrophages were conspicuous in some air spaces. In addition, several pulmonary muscular arteries and veins showed irregular dilatation and tortuosity, with elastic fibers that were fragmented and disorganized. Aberrant TGF-β signaling, together with deranged matrix formation, may underlie both the dilated, tortuous vasculature and the emphysematous/bullous changes leading to pneumothorax in the LDS lung.