Original ArticleDifferent sizes of centrilobular ground-glass opacities in chest high-resolution computed tomography of patients with pulmonary veno-occlusive disease and patients with pulmonary capillary hemangiomatosis
Introduction
Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare diseases that are classified as a subgroup of pulmonary arterial hypertension (PAH) [1], [2], [3]. PVOD is histologically characterized by intimal fibrosis that narrows and occludes pulmonary veins and it accounts for 5–10% of cases initially thought to be idiopathic PAH (IPAH) [4]. PVOD occurs in a wide range of ages. Among adult patients, the incidence in men is about twice that in women. PCH is histologically characterized by localized capillary proliferation within the lung in which capillaries invade the pulmonary interstitium, vessels and, less commonly, airways [5]. PCH has been reported to be much less frequent than PVOD [6]. PCH and PVOD have similar clinical presentations with poor prognosis.
In recent years, PAH-targeted drugs including epoprostenol have improved the survival of patients with IPAH [3], [7], [8], but no medical treatment to improve the survival of patients with PVOD or PCH has been established. Several investigators have reported the possible efficacy of cautious application of epoprostenol [9], [10], but incautious administration of vasodilators including epoprostenol sometimes causes massive pulmonary edema and can be fatal in these patients. Therefore, the establishment of methods for medical treatment in these patients is required. To that end, accurate diagnosis of PVOD and PCH is also needed.
Histological proof is required for a definitive diagnosis of PVOD and PCH. Since surgical lung biopsy is too invasive and is a high risk for patients with PVOD or PCH, a noninvasive approach is preferable. High-resolution computed tomography (HRCT) of the chest is one of the diagnostic tools for PVOD and PCH. Centrilobular ground-glass opacities (GGOs), septal lines and mediastinal lymph node enlargement are characteristic findings in chest HRCT of patients with PVOD or PCH [6], [11], [12]. However, clinical differential diagnosis of these diseases has not been established.
We previously reported success in visualization of the 3-dimensional structures of pulmonary capillary vessels in patients with PAH, PVOD and PCH using scanning electron microscopy of blood vascular casts [13]. Study of blood vascular casts revealed differences in the three diseases. PAH was characterized by a deficient capillary network, PVOD was characterized by swollen capillary vessels and PCH was characterized by tumor-like outgrowth of capillaries. These differences in capillaries might reflect differences in the sizes of GGOs in chest HRCT since centrilobular GGOs reflect thickening of interstitial tissues, local fluid accumulation in airspaces, local alveoli collapse and increased capillary blood volume [14], [15]. Thus, we compared the sizes of centrilobular GGO in chest HRCT and the sizes of capillary assemblies in pulmonary vascular casts in patients diagnosed pathologically with PVOD and patients diagnosed pathologically with PCH in order to clarify their differences.
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Subjects
We obtained lung tissues from 27 patients clinically diagnosed with PAH by living-donor lobar lung transplantation (LDLLT), cadaveric lung transplantation (CLT) or autopsy between 1999 and 2011 in our institution. Twenty patients were diagnosed with pulmonary arteriopathy, four patients were diagnosed with PVOD and three patients were diagnosed with PCH by pathological examination. We could obtain findings of chest HRCT from four patients with idiopathic PAH (IPAH), three patients with PVOD and
Patient characteristics at chest CT examination
Patient characteristics at HRCT of the chest are shown in Table 1. Patients with IPAH included two males and two females with a mean age of 18.3±6.2 years at HRCT of the chest (No. 1–4). Three patients underwent LDLLT or CLT and one patient was an autopsy case (No. 2). Three patients were treated with a prostaglandin I2 (PGI2) analog or intravenous PGI2 and the other patient was not treated with a PAH-specific drug (endothelin receptor antagonist or phosphodiesterase 5 inhibitor) at HRCT of the
Discussion
PVOD and PCH have been diagnosed pathologically, making it difficult to examine the hemodynamics, reactivity to PAH-specific treatment and survival prospectively. Therefore, clinical diagnosis is important for clinicians to understand these diseases. Results of a pulmonary function test and HRCT findings can suggest a diagnosis of PVOD or PCH. Septal lines, lymph node enlargements, pulmonary artery dilatation, pericardial effusion and pleural effusion are observed in HRCT images of patients
Acknowledgments
The authors thank Kaoru Akazawa, Masayo Ohmori, and Miyuki Fujiwara for their excellent technical assistance.
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This study was supported by the Research Grant for Cardiovascular Diseases (H19-9) from the Ministry of Health, Labour and Welfare, Japan, and in part by a grant to the Respiratory Failure Research Group (H23-24) from the Ministry of Health, Labour and Welfare, Japan.