A detailed histologic analysis of pulmonary arteriovenous malformations in children with cyanotic congenital heart disease Brian W. Duncan, MDa, James.

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A detailed histologic analysis of pulmonary arteriovenous malformations in children with cyanotic congenital heart disease Brian W. Duncan, MDa, James M. Kneebone, MSa, Emil Y. Chi, MDb, Viktor Hraska, MDc, F.Frank Isik, MDd, Geoffrey L. Rosenthal, MD, PhDe, Thomas K. Jones, MDe, Sandra L. Starnes, MDa, Flavian M. Lupinetti, MDa The Journal of Thoracic and Cardiovascular Surgery Volume 117, Issue 5, Pages 931-938 (May 1999) DOI: 10.1016/S0022-5223(99)70374-0 Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 1 Selective injection of the right lower lobe pulmonary artery of the first patient, demonstrating diffuse pulmonary AV malformations. Rapid filling of the pulmonary vein (arrow) is seen in the capillary phase of injection. The Journal of Thoracic and Cardiovascular Surgery 1999 117, 931-938DOI: (10.1016/S0022-5223(99)70374-0) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 2 Micrographs of a lung biopsy specimen from the first patient with pulmonary AV malformations. A, Slight hypertrophy of the muscle of pulmonary arteriole (BV) with distended, irregular, thin-walled vessel arising from arteriole (arrows) (“lake” type of pulmonary AV malformations). Edema (ED) of the pulmonary parenchyma is evident in a perivascular location. (Hematoxylin and eosin stain, 200x). B, Airway (AW) surrounded by numerous, small, thin-walled blood vessels (BV and *) (“chain” type of pulmonary AV malformations). Cross-sectioned vessels demonstrate their irregular shape (arrows). (Hematoxylin and eosin, 200×.) C, Origin of pulmonary AV malformation “lake” branching from pulmonary arteriole (BV) stained for elastin, demonstrating fibrous and elastin intimal thinning of pulmonary AV malformations (arrows). (Movat's pentachrome, 200×.) D, Pulmonary AV malformation “chains” (BV and *) surrounding an airway (AW) with thin walls demonstrating incomplete elastin staining (arrows) (Movat's pentachrome, 200×.) The Journal of Thoracic and Cardiovascular Surgery 1999 117, 931-938DOI: (10.1016/S0022-5223(99)70374-0) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 3 Microvessel densities of patients with pulmonary AV malformations (PAVM) versus age-matched controls. Microvessel density was determined for 10 high-power (200×) fields from histologic sections stained with Movat's pentachrome for both the patients with pulmonary AV malformations and the age-matched controls and are expressed as the mean ± the standard deviation. The Journal of Thoracic and Cardiovascular Surgery 1999 117, 931-938DOI: (10.1016/S0022-5223(99)70374-0) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 4 Immunohistochemical staining for PCNA for patients with pulmonary AV malformations (A) and positive control (intestinal epithelium, B). Note frequent nuclear staining in the positive control (arrowheads) that is absent in pulmonary AV malformation tissue (methyl green counterstain, 450×). Immunohistochemical staining for CD31 demonstrating minimal (solid arrow) or no (hollow arrow) staining for pulmonary AV malformations vessels (C) compared with dense staining of endothelium in blood vessels of controls (arrowheads) (D) (methyl green counterstain, 450×). The Journal of Thoracic and Cardiovascular Surgery 1999 117, 931-938DOI: (10.1016/S0022-5223(99)70374-0) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 5 Electron micrographs of lung biopsy tissue from patient with pulmonary AV malformations. A, Wall of pulmonary AV malformations demonstrates the lumen (L) and an endothelial cell (E) attached to an abnormal basement membrane (BM). The basement membrane appears to be irregular, thickened, and multilayered in places (arrows). The endothelial cell contains stress fiber bundles (arrowheads). Also demonstrated are elastin fibers (EL), collagen fibers (C), and smooth muscle (SM). B, Abnormal appearance of endothelium (E) of pulmonary AV malformation endothelium, demonstrating thickening and irregularity (arrowheads). Collagen fibers (arrows) are demonstrated in the thickened basement membrane (BM). Smooth muscle (SM), elastin fibers (EL), and collagen bundles (C) are also seen beneath the basement membrane. L, Lumen. C, An area of basement membrane (BM) thickening (arrows) demonstrating many collagen fibrils (arrowheads) loosely attached to the endothelium (E). SM, Smooth muscle; C, collagen fibers below basement membrane. The Journal of Thoracic and Cardiovascular Surgery 1999 117, 931-938DOI: (10.1016/S0022-5223(99)70374-0) Copyright © 1999 Mosby, Inc. Terms and Conditions