Venous and venular lesions (Pulmonary veno-occlusive disease and pulmonary hemangiomatosis) 
A clear-cut differentiation between pre-and post-capillary pulmonary vascular lesions is sometimes difficult to make: lesions frequently concern veins and arteries in lungs of patients with PVOD, and vice-versa veins may be strongly involved in some subgroups of PAH. This is not contradictory because the clinical approach to ‘difficult-to-treat’ PAH-groups may be similar to clinical management of PVOD and PVOD-patients are frequently treated – under great precaution – with pulmonary arterial dilators, e.g. prostanoids. Recent reports, for example, indicate that CTD associated PAH, classically being considered as pre-capillary PH, simultaneously displays a PVOD-like pattern in histology [178,179]. Like in PVOD, the observed post-capillary lesions concern septal veins and pre-septal venules and usually consist of a loose and pauci-cellular and cushion-like intimal fibrosis that may totally occlude the lumen. A muscularization of both, septal veins and pre-septal venules may be observed (Figure 3A, B). Importantly, occult pulmonary hemorrhage regularly occurs in patients displaying PVOD. This particularity, which is certainly due to the post-capillary bloc, is of diagnostic importance, as bronchio-alveolar lavage can reveal an occult hemorrhage. The degree of hemorrhage can be evaluated semi-quantitatively and qualitatively using the Golde Score, which takes number and Perls-Prussian-Blue staining-degree of intra-alveolar siderophages into consideration (Figure 3C) [180]. Pulmonary capillary hemangiomatosis has been historically described as an aggressive capillary proliferation with patchy distribution within the pulmonary parenchyma: alveolar septa are thickened by 3 to 4 capillary layers, and infiltration of venous and bronchiolar structures with secondary occlusion may be present (Figure 3D). It is thought, that a clinically relevant post-capillary bloc is owed to this angiomatoid expansion. Occult hemorrhage or hemosiderosis, therefore, is frequently found [181]. However, Lantuejoul and co-workers have shown in a remarkable retrospective histological analysis, that capillary hemangiomatosis-pattern is virtually always present in PVOD, and vein-remodelling is constantly observed in case with a primary diagnosis of PCH [54]. The authors suggest the possibility, that PVOD and PCH might be the same disease, with a vein- or a capillary-predominating pattern. We fully support this view, and in our experience from the French National PH Reference Center, no clinical distinction is made between both conditions.
Figure 3  Pulmonary veins with obstructive venopathy in lungs of patients with PVOD and a case of pulmonary capillary hemangiomatosis. A Longitudinally dissected septal vein with asymmetric intimal and partially occlusive fibrosis. Note the intra-alveolar hemorrhage due to the post-capillary block on the upper half of the photograph. Magnification × 100, EvG. B Pre-septal venule with occlusive intimal fibrosis. Magnification × 100, EvG. C Bronchio-alveolar lavage in a PVOD-patient. Perls-Prussian-Blue staining. Note the siderophages displaying gradually different color-shades (see text). Magnification × 400. D Excessively proliferating alveolar capillaries in a patient with pulmonary capillary hemangiomatosis. Note protrusion of ectatic lumina into the alveoli. Magnification × 200, anti-CD31 staining.

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