Epithelioid haemangioendothelioma is a rare pulmonary neoplasm with less than 40 cases described world wide. We describe the only case to have presented with hypertrophic pulmonary osteoarthropathy who has been treated with azathioprine and has remained alive and well with no deterioration in pulmonary function since being diagnosed 16 years ago. The progression of the chest radiograph and spiral CT appearances of this rare neoplasm are described, and current views regarding the cellular origin of the neoplasm, its cytological appearance, clinical presentation and prognosis are discussed.
- epithelioid haemangioendothelioma
- intravascular sclerosing bronchioalveolar tumour
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Epithelioid haemangioendothelioma (EHE) (formerly known as intravascular sclerosing bronchioalveolar tumour, IVBAT) is a rare pulmonary neoplasm with less than 40 cases described world wide. We have described the first reported case presenting with hypertrophic pulmonary osteoarthropathy.1 We now report the progress of this patient who is unique in that she has been treated with azathioprine and has remained alive and well with no deterioration in pulmonary function since being diagnosed 16 years ago.
In April 1981 a 24 year old woman presented to our unit with a six month history of pain and swelling in her ankles and a six week history of mild exertional dyspnoea. On examination her fingers and toes were grossly clubbed and her wrists and ankles were swollen and tender. Inspiratory crackles were audible at the left base posteriorly. Her chest radiograph, which had been normal six years earlier, showed multiple irregular, unequal, bilateral, uniformly distributed, non-calcified nodular shadowing. Radiographs of her wrists and ankles showed changes of hypertrophic pulmonary osteoarthropathy. Full blood count, urea and electrolytes, liver function tests, calcium, and serum immunoglobulins were all normal. Autoantibodies including rheumatoid factor and antinuclear factor were negative, as was a Mantoux test. The erythrocyte sedimentation rate was 46 mm in the first hour. Pulmonary function tests revealed a mild restrictive ventilatory defect with lung volumes 70% predicted. Gas transfer was normal. No endobronchial lesions were found at fibreoptic bronchoscopy and a transbronchial lung biopsy specimen was unhelpful. The patient therefore underwent an open lung biopsy via a left thoracotomy. At operation multiple nodules up to 15 mm in diameter were found throughout the lung. Two wedge biopsies were taken from the lingula. All nodules had similar histological appearances which were considered typical of EHE.
As the majority of her symptoms were due the hypertrophic pulmonary osteoarthropathy indomethacin was commenced with good effect. Azathioprine was also started and the patient returned to work. The patient has been reviewed yearly for the past 16 years and her symptoms have remained unchanged. Increasing calcification of the nodules was seen radiologically by 1989, and by 1996 (fig 1) the overall number of nodules remained unchanged but their size had decreased to a maximum of 12 mm. A thoracic spiral intravenously enhanced CT scan was performed in 1997 (fig 2) showing innumerable 12 mm calcified nodules in all areas but more concentrated at the lung bases and subpleurally. This CT scan also revealed about 20 low attenuation, non-enhancing, asymmetrically calcified liver lesions. In October 1995 azathioprine was discontinued. Her pulmonary function tests have not deteriorated over the past 16 years.
EHE is a rare pulmonary neoplasm with fewer than 40 cases reported in the literature. The tumour was initially described in 1975 by Dail and Liebow and was named intravascular sclerosing bronchioalveolar tumour (IVBAT)2 3 because of the proposed bronchioalveolar origin of the neoplasm. Corrinet al 4 postulated that the tumour arose from precursor cells capable of differentiation along endothelial cell lines. Weldon-Linne et al,5 using electron microscopy, determined endothelial characteristics of the cells and thought they were derived from multipotential mesenchymal reserve cells. Using applied immunochemistry, Bhagavan et al 6 described diffuse cytoplasmic staining of tumour cells with factor VIII related antigen which binds to a storage product of endothelial cells.
Microscopically the initial change is an interstitial alveolar infiltrate with lymphocytes, followed by protrusion of the alveolar wall in a polypoidal manner into the alveolar lumen. This protrusion is covered with hypertrophied alveolar epithelial cells and its core consists at first of a mixoid type of connective tissue which stains positively with PAS and Congo Red. As the stroma matures it is converted into hyaline fibrous tissue. Embedded in this hyaline fibrous tissue are large malignant-appearing cells with large round to oval grainy nuclei, often prominent nucleoli, and abundant homogeneous cytoplasm. Eventually the whole alveolus is obliterated. The same tissue that obliterates the alveoli may spread into and along the small bronchi and bronchioles and also fills small branches of the pulmonary arteries and veins.7 Thus multiple non-encapsulated parenchymal nodules are seen exhibiting a zonal architecture. There have been reports of nodules with calcification, chondrification, or even ossification, but this occurs in less than 10% of cases.3
Weiss et al 8 first used the term EHE. It is now well recognised that the IVBAT is an EHE occurring in the lung which may also occur in the soft tissues, bone, and liver.
Three quarters of patients with EHE of the lung are women. The age range at presentation is wide (12–61 years), and 40% of patients are below the age of 30. Half the patients are asymptomatic and are discovered on incidental chest radiography. Symptoms are uncommon and are usually mild and include shortness of breath, mild pleuritic chest pain, and non-productive cough, although haemoptysis has been reported. However, hypertrophic pulmonary osteoarthropathy has not been previously reported. The chest radiograph usually reveals multiple bilateral pulmonary nodules and pleural effusions are rarely seen.9 Distant metastases are seen in less than a quarter of cases, the sites involved including the liver, lymph nodes, bowel, retroperitoneal soft tissues, and skin. In most cases the disease has a slowly progressive course and patients die 2–24 years after diagnosis of restrictive lung disease. The shortest survival is eight weeks in a patient who succumbed to gross haemoptysis.10 The longest survivor was treated surgically, undergoing 11 separate resections over 24 years, finally succumbing to pneumonia superimposed on a decreasing respiratory function.11 Other treatments tried have been chemotherapy and radiotherapy with limited success in symptomatic patients near death. Our patient refused the empirical use of oral corticosteroids in an attempt to control potential fibrosis. She was therefore commenced on azathioprine following diagnosis and so far has had no deterioration in pulmonary function. However, at the patient’s request azathioprine was discontinued in October 1995. The patient is now the second longest survivor with this condition. She continues to have mild symptoms from her hypertrophic pulmonary osteoarthropathy but is asymptomatic from the pulmonary point of view and is still able to work as a paediatric nurse.
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