A Case Report and Review of the Literature

Pulmonary capillary hemangiomatosis (PCH) was first described by Wagenvoort et al. in 1978.' Subsequently, a total of 18 cases have been described in the literature.'-'* This condition is characterized by proliferating sheets of thin-walled capillary channels that infiltrate the walls of pulmonary blood vessels inducing a secondary pulmonary venoocclusive disease. The interlobular septa, pulmonary parenchyma, bronchioles, and pleura may also be involved. We have described an additional case of PCH associated with thrombocytopenia in a child, and it was diagnosed during life by an open lung biopsy.


INTRODUCTION
Pulmonary capillary hemangiomatosis (PCH) was first described by Wagenvoort et al. in 1978.' Subsequently, a total of 18 cases have been described in the literature.'-'* This condition is characterized by proliferating sheets of thin-walled capillary channels that infiltrate the walls of pulmonary blood vessels inducing a secondary pulmonary venoocclusive disease. The interlobular septa, pulmonary parenchyma, bronchioles, and pleura may also be involved. We have described an additional case of PCH associated with thrombocytopenia in a child, and it was diagnosed during life by an open lung biopsy.

CASE REPORT
A 12-year-old Syrian girl was perfectly well until 2 months prior to her referral to our hospital when she complained of cough and shortness of breath. The cough was productive of whitish sputum, but there was no hemoptysis. She was initially treated with erythromycin with suspicion of mycoplasma pneumonia because of lung infiltrates on a chest X-ray. However, she remained symptomatic and had anorexia and weight loss. There was no history of cosanguinity or similar illness in the family. On examination she did not have clubbed fingers, and the only abnormality was mild respiratory distress and few scattered crepitations bilaterally.

Investigations
Her arterial blood gases at rest were normal. Her CBC revealed an Hb of 12.2 g/dL, the platelet count was 94 X lo9 L-', and the differential WBC was normal. Her erythrocyte sedimentation rate (ESR) was 7 m d h r and her reticulocyte count was 0.6%. In the peripheral blood smear there were some giant platelets. Her coagulation profile was normal, including platelet aggregation study. Her direct and indirect Coomb's tests were negative. Her hepatic, renal profile, blood sugar, LDH, and urinalysis were normal. Her qualitative immunoglobulins revealed an IgG of 1.8 g/dL, an IgA of 0.33 g/dL, and an IgM of 0.25 g/dL. T and B lymphocyte functions and number were normal. Serology for hepatitis B surface antigen and antihepatitis C antibody tests were negative. Mantoux skin tests with 5 and 10 units of PPD were nonreactive. Multiple sputum samples were negative on smear for acid-fast bacilli and TB cultures were also negative. Bone marrow aspiration and biopsy revealed normal cellularity and adequate number of megakaryocytes. There was no evidence of infiltration of the bone marrow with foreign cells. Pulmonary function tests revealed a mild obstructive pattern with an increased residual volume. Her chest X-ray revealed mediastinal widening, prominent interstitial infiltrates with well-defined Kerley's lines on the peripheral aspect of both lung fields (Fig. 1). CT scan of the chest and mediastinum showed widening of the mediastinum with a diffuse increase in mediastinal density. The vascular structures and trachea were not displaced or compressed. A small lymph node was noted at the right azygoesophageal recess. The lung fields showed diffusely distended lymphatics. No effusion was seen, but there was pleural thickening in the left paravertebral region (Fig. 2). A ventilation/perfusion scan showed mismatching, especially on the left side. Cardiac catheterization and echocardiogram revealed normal pulmonary blood flow and pressures.
In order to reach a diagnosis, a left minithoracotomy was performed. The whole left lung was very stiff and  studded with numerous subpleural hemorrhagic nodules. The mediastinum was extensively infiltrated with multiple hemorrhagic masses, pink and black in color. Three biopsies were taken, two from the lung and the third from the mediastinum. The lung biopsy specimens were two fresh spongy pieces of tissue each measuring 12.5 mm long (lingula and left lower lobe). The mediastinal specimen was a piece of dark red fatty tissue 15 mm long. The tissues were fixed in 10% neutral buffered formalin, processed, embedded, and cut in the usual fashion. Sections were stained with hematoxylin-eosin (H&E), Masson's trichrome, and Verhoeff's Elastic Van Gieson stains.

Pathology
Histologically the lung parenchyma was infiltrated by sheets of proliferating thin-walled vascular channels, for most part of the size of capillaries (Fig. 3a). There was widening of the interstitium to variable degrees, creating small nodules or sheets of back-to-back capillary vessels. The vascular channels are lined by flattened inactive endothelial cells (Fig. 3b). The proliferating vessels invaded the subpleural region and the interlobular septa. In a few locations there was invasion of the walls of small pulmonary veins with associated intimal fibrosis. The venous lumen was not completely occluded by the in-traluminal proliferation and venous thrombi were not seen. The pulmonary arterial and bronchial walls were also surrounded by the proliferating vascular channels, but their walls were not invaded.
The alveolar spaces contained hemosiderin laden macrophages and red blood cells. The alveolar septa were mildly thickened at the margins of the vascular tumor. In some regions the dilated lymphatic channels were prominent within the lung parenchyma. Focal interstitial lymphocytic infiltrates of the alveolar walls and bronchi were present. The mediastinal biopsy showed similar proliferation of capillary size:d vascular channels in the pleura and stroma which invaded the pulmonary venous walls. The identification of these striking features led to the diagnosis of pulmonary capillary hemangiomatosis.

DISCUSSION
Pulmonary capillary hemangiomatosis is characterized by the proliferation of small vessels within the peribronchial, perivascular, septal, or pleural connective tissues. '- 12 The infiltration and compression of pulmonary veins can result in a secondary pulmonary venoocclusive disease. Within the lung, the vascular proliferation can involve the pleura, interlobular septa, bronchioles, and parenchyma. The involvement of airways probably leads to hemoptysis. In mast cases, the proliferating vessels were capillary but in others they were of venule ~i z e .~,~ There may also be extrapulmonary involvement of such structures as the mediastinum, pericar- dium, thymus, and spleen.'-" In our patient the pathologic features of PCH were noted in the lung parenchyma, pleura, and interlobular septa with early pulmonary venous involvement. Extrapulmonary involvement was seen only in the mediastinum on both histopathology and CT scanning.
The natural history of the previously reported cases of PCH is one of progressive unrelenting dyspnea as summarized in Table 1. The ages at diagnosis of the earlier cases ranged from 12 to 71 year^,^^',^^^^ but the disease onset can be as early as 6 years of age.' The disease has been observed in male and female patients, and a familial association has been reported.' In most cases death ensues within 1 to 4 years of symptomatic presentation as the result of progressive pulmonary hypertension, cor pulmonale, pulmonary hemorrhage, or both.
The diagnosis of PCH in the living patient requires a high index of suspicion and an aggressive approach. Most patients are not recognized until signs of marked pulmonary hypertension have developed.8311*12 The early presentation can be indistinguishable from that of interstitial lung d i~e a s e .~ In addition to radiographic evidence of interstitial infiltrations, thickened fissures, interlobular septa, or pleura can be seen separately or in combination. 8,11,12 Although the changes seen on lung perfusion scan are not specific, they can suggest pulmonary hypertension of any cause and direct the physician to do early catheterization and pulmonary angiography to exclude pulmonary venoocclusive disease. l 3 To confirm the diagnosis by histopathology, open lung biopsy is helpful but often misinterpreted. Transbronchial biopsy is contraindicated to avoid massive bleeding.
Although the exact cause of PCH is not known, an uncontrolled angiogenesis in the lung appears to be the pathogenetic basis of this disease. The outcome of the disease in most of the previously reported cases is shown in Table 1. Twelve out of 19 cases died. Cases treated surgically by pneumonectomy or heart-lung transplantat i~n * '~ survived, and one case was treated with interferon Although, the finding of thrombocytopenia has been reported previ~usly'~ in some cases of pulmonary hemangiomatosis, it was not a frequently recognized feature of PCH. However, in our case, the thrombocytopenia was very mild and with no evidence of consumption coagulopathy, and/or bleeding tendency.