Lymphangioma are uncommon benign vascular tumours, thought to originate from congenital malformation and aberrant proliferation of lymphatic vessels. They involve the skin and subcutaneous tissues and commonly present in the head and neck region, trunk and extremities in children. Only 10% of lymphangioma involve internal organs such as lungs, liver or spleen.1
Diffuse lymphangiomatosis, a generalised abnormality of the lymphatic system, resembles lymphangioma but is characterised by a more diffuse proliferation of lymphatic vessels at multiple sites. The increased number of complex anastomosing lymph vessels with secondary dilatation helps to differentiate this disorder from primary lymphangiectasia.2,3
Diffuse lymphangiomatosis is particularly difficult to treat and no consensus has been reached on the most appropriate treatment.
In the English literature only around 300 cases of diffuse lymphangiomatosis have been reported worldwide. Disease manifestation in bone and surrounding soft tissue is called Gorham’s disease or vanishing bone disease.4–6
Other localisations are liver, spleen and mediastinum.7–14
Lung or pleura involvement has been described and is associated with a poor prognosis.12
Pericardial involvement is rare. To our knowledge only 16 cases, including the present case, have been reported in the past 35 years and 12 of these are children (). The male/female ratio seems equal. Seven patients died because of complications of lymphangiomatosis or treatment.
Cases of lymphangiomatosis with pericardial involvement
Chylopericardium often results from an infectious problem, malignancy or a traumatic lesion. Also disorders of the lymphatic system, such as mechanical obstruction of the thoracic duct, reflux of lymph or lymphangiomatosis, as in our patient, can cause chylopericardium.
To visualise such lymphatic abnormalities lymphangiography in combination with computerised tomography has been used several times and has been proven to be suitable for establishing the diagnosis of diffuse lymphangiomatosis.15–20
Therefore it should be kept in mind as a useful diagnostic option.
In our patient a diagnostic pulmonary biopsy caused serious and life-threatening complications due to massive chyle loss. Since this problem has been reported before13,21,22
non-invasive methods for diagnosis should be considered, especially in asymptomatic patients.
In our patient it would have been appropriate to perform lymphangiography combined with computerised tomography before open lung biopsy, especially since pericardiocentesis had already raised the suspicion of a lymphatic origin of his pulmonary disease. This might have led to the correct diagnosis and would have probably prevented his dramatic clinical course.
Another option would have been the measurement of vascular endothelial growth factor (VEGF) by PCR or ELISA, which has been reported to be abnormally raised in a patient with lymphangiomatosis.7
There are different therapeutic options for the treatment of diffuse lymphangiomatosis. Surgical interventions, such as excision of a localised lesion, pleurodesis, pleurosclerosis, pleuroperitoneal shunting, chest wall resection or thoracic duct ligation in the case of thoracal involvement have been applied with differing results.14,21,23–27
Systemic treatment with corticosteroids, immunomodulating agents and chemotherapy have shown varying results.2,9,12,24,26,27
Interferon α, a cytokine with antiangiogenic activity, appears to be beneficial and has been used for the treatment of lymphangiomatosis for almost 20 years. Clinical improvement has been reported in the majority of cases, although the optimal treatment duration remains unclear and ranges from 3 weeks to several years.7,21,24,26,27
Radiation therapy has mainly been used for patients with cutaneous or abdominal involvement,28
but has also proven successful in patients with thoracic lymphangiomatosis.29–31
Acute adverse effects such as radiation pneumonitis have been described23,32
but seldom occur with fractional doses of 20 Gy or less.33
Chronic complications such as secondary malignancies and restrictive lung disease are rare.34
The exact mechanism of radiation therapy is not known, but is possibly a result of radiation induced lymphatic endothelial oedema and proliferation leading to obstruction of the abnormal lymphatic channels.28,35
In our patient radiotherapy seems to have been an effective intervention for the acute management of chyle loss, although its simultaneous use with interferon α and steroids makes it difficult to determine what its effect would have been had it been used alone.
Still we believe radiotherapy might have had an important additional effect to the use of interferon α and steroids and should be considered as a treatment option in lymphangiomatosis when surgery or systemic treatment alone fail, especially since side effects such as radiation pneumonitis or pulmonary fibrosis are infrequent when correct radiation doses are used.
- Diffuse lymphangiomatosis is a rare disorder, with only a few hundred cases described in the literature. Involvement of the pericardium is uncommon. All patients with primary idiopathic chylopericardium should undergo further investigations to determine whether malformations of the lymphatic system are present.
- When lymphangiomatosis is suspected diagnostic tests should, as far as possible, be non-invasive, to prevent serious complications, such as massive chyle loss, as seen in our patient.
- Less invasive diagnostic options include measurement of vascular endothelial growth factor (VEGF) or a combination of lymphangiograpy with computed tomography. Biopsy of skeletal lesions usually does not lead to serious complications.
- Radiation therapy should be kept in mind as an additional therapeutic option in diffuse lymphangiomatosis not responding to thoracic duct ligation and/or medical treatment.