Diffuse pulmonary haemorrhage accompanied by haemothorax as a rare presentation of primary lung angiosarcoma

Abstract

Primary pulmonary angiosarcoma is an extremely rare disease. Chest computed tomography demonstrates solitary or multifocal lesions, sometimes associated with ground-glass opacities or pleural effusion. Diagnosis is based on histological examination that reveals spindle-shaped epithelioid cells with positive staining for endothelial markers (factor VIII, CD 31, CD34, Fli-1, Ulex europaeus agglutinin 1, vimentin). The prognosis is poor and effective treatment is still being researched. This is a report of a 65-year-old patient with a four-month history of haemoptysis, cough, and dyspnoea. The primary radiological findings suggested interstitial lung disease. After one month the clinical presentation evolved into diffuse pulmonary haemorrhage with concomitant haemothorax. The diagnosis of primary lung angiosarcoma was based on histological and immunohistochemical examination of the lung and pleural biopsy obtained by videothoracoscopy.

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Kardiochirurgia i Torakochirurgia Polska 2015; 12 (4) 367
Address for correspondence: Katarzyna Modrzewska, MD, III Department of Lung Diseases, Institute of Tuberculosis and Lung Diseases,
26 Płocka St., 01-138 Warsaw, Poland, phone: +48 506 131 729, e-mail: k.modrzewska@hotmail.com
Streszczenie
Pierwotny płucny naczyniakomięsak (angiosarcoma) jest nie-
zwykle rzadką chorobą. Badanie tomograi komputerowej płuc
demonstruje najczęściej pojedyncze guzy lub mnogie guzki,
czasami z towarzyszącymi zmianami o typie matowej szyby lub
płynu opłucnowego. Rozpoznanie ustala się na podstawie oceny
histologicznej, która uwidacznia wrzecionowate komórki epite-
lioidalne wybarwiające się w kierunku markerów śródbłonko-
wych (czynnik VIII, CD 31, CD34, Fli-1, Ulex europaeus agglutinin 1,
vimentina). Rokowanie jest bardzo złe, nadal poszukiwane są
skuteczne metody leczenia. W pracy zaprezentowano przypa-
dek 65-letniej pacjentki z 4-miesięcznym wywiadem krwio-
plucia, kaszlu i duszności. Początkowe badania radiologiczne
sugerowały śródmiąższową chorobę płuc. Po miesiącu obraz
kliniczny ewoluował w kierunku rozsianego krwawienia płuc-
nego z towarzyszącym krwiakiem opłucnej. Rozpoznanie pier-
wotnej płucnej angiosarcomy zostało ustalone na podstawie
oceny histologicznej i immunohistochemicznej bioptatów płuc
i opłucnej pobranych drogą wideotorakoskopii.
Słowa kluczowe: naczyniakomięsak, rozlany krwotok płucny,
krwiak opłucnej.
CASE REPORTS
Abstract
Primary pulmonary angiosarcoma is an extremely rare disease.
Chest computed tomography demonstrates solitary or multifo-
cal lesions, sometimes associated with ground-glass opacities
or pleural eusion. Diagnosis is based on histological exami-
nation that reveals spindle-shaped epithelioid cells with posi-
tive staining for endothelial markers (factor VIII, CD 31, CD34,
Fli-1, Ulex europaeus agglutinin 1, vimentin). The prognosis is
poor and eective treatment is still being researched. This is
a report of a 65-year-old patient with a four-month history of
haemoptysis, cough, and dyspnoea. The primary radiological
ndings suggested interstitial lung disease. After one month the
clinical presentation evolved into diuse pulmonary haemor -
rhage with concomitant haemothorax. The diagnosis of pri-
mary lung angiosarcoma was based on histological and immu-
nohistochemical examination of the lung and pleural biopsy
obtained by videothoracoscopy.
Key words: angiosarcoma, diuse pulmonary haemorrhage,
haemothorax.
Diuse pulmonary haemorrhage accompanied
by haemothorax as a rare presentation of primary lung
angiosarcoma
Katarzyna Modrzewska1, Elżbieta Radzikowska1, Małgorzata Szołkowska2, Karina Oniszh3,
Magdalena Szczęsna4, Kazimierz Roszkowski-Śliż1
1III Department of Lung Diseases, Institute of Tuberculosis and Lung Diseases in Warsaw, Poland
2Department of Pathology, Institute of Tuberculosis and Lung Diseases in Warsaw, Poland
3Department of Radiology, Institute of Tuberculosis and Lung Diseases in Warsaw, Poland
4Department Thoracic Surgery, Institute of Tuberculosis and Lung Diseases in Warsaw, Poland
Kardiochirurgia i Torakochirurgia Polska 2015; 12 (4): 367-371
DOI: 10.5114/kitp.2015.56792
Introduction
Primary pulmonary angiosarcoma (PPA) is a rare neo-
plasm originating from endothelial cells of small vessels of
the lung [1]. The highest incidence of the disease occurs in
the fth and sixth decade of life. Chest computed tomog-
raphy (CT) demonstrates solitary or multifocal lesions occa-
sionally accompanied by ground-glass opacities or pleural
eusion [2-4]. Diuse alveolar haemorrhage with concomi-
tant haemothorax is an extremely rare manifestation of
primary angiosarcoma of the lung. There has been only
one other report published with a similar presentation [5].
The diagnosis is based on histological ndings comple-
mented by immunohistochemical stainings typical for en-
dothelial markers. Due to high malignancy, patients with
angiosarcoma have a low rate of survival. An eective
therapeutic regimen is still being researched. We present
a case of rapid progression of PPA manifested as bilateral
pulmonary opacities and haemothorax.

Kardiochirurgia i Torakochirurgia Polska 2015; 12 (4)368
Diuse pulmonary haemorrhage accompanied by haemothorax as a rare presentation of primary lung angiosarcoma
Case report
A 65-year-old smoking woman presented a four-month
history of haemoptysis, cough, and dyspnoea. The patient’s
medical history was signicant for chronic obstructive pul-
monary disease (COPD), permanent atrial brillation (AF)
under continuous anticoagulation treatment, hypertension,
and diabetes. Due to severe haemoptysis, she reduced the
dose of anticoagulant by 50% without medical consultation.
Chest CT performed one month prior to hospitalisation re-
vealed bilateral interstitial opacities with air bronchogram
and ground-glass attenuations. The radiological ndings
suggested interstitial lung disease, and the patient was
referred to our Department. On admission the general con-
dition of the patient was severe. She presented dyspnoea
in rest and massive haemoptysis. Physical examination
showed obesity (BMI 47.5), tachypnoea (30 per minute),
tachycardia (105 per minute), and oedema of the ankles. On
auscultation, the respiratory sounds over the lower right
lobe were diminished, and crackles over the middle right
lobe and the whole left lung were detected. The patient
had respiratory insuciency (PaO2 – 50 mmHg, PaCO2 –
33 mmHg, pH 7.48). Laboratory tests revealed an elevated
level of C-reactive protein (26.5 mg/dl), D-dimer (3991 ng/
ml) and anaemia (haemoglobin 9 g/dl, haematocrit 29.7%).
Chest X-ray demonstrated right-sided opacity correspond-
ing to pleural uid, scattered pulmonary lesions, and mod-
erately enlarged hila (Fig. 1). Computed tomography scans
of the chest showed progression of bilateral ground-glass
opacities of dierent shape and size with peripheral pre-
dilection, small nodules (including one peripheral left lung
nodule with slight cavitation), right-sided pleural eusion,
and enlargement of the heart (Fig. 2 and 3). There were no
radiological signs of pulmonary embolism in large branches
of pulmonary arteries, but a suggestion that small vessels
could have been lled with thrombotic material was made.
Echocardiography showed enlargement of the right ventri-
cle and both atria, and elevated pulmonary artery pressure
at 42 mmHg. The values of tumour markers (cancer antigen
CA 15-3, CA 19-9, CA 125, carcinoembryonic antigen), anti-
neutrophil cytoplasmic antibody (ANCA), and anti-nuclear
antibody (ANA) were in normal range. Ultrasonography
of the abdomen did not reveal any pathological masses.
Bronchoscopy revealed a bronchi eld with a signicant
amount of fresh blood without any visible point of origin.
The bacterial and fungal cultures of bronchial washing
were negative. Due to severe dyspnoea, two pleurocente-
ses were performed. The drainage was close to 1000 ml of
bloody uid. The haematocrit of the eusion was 19.8%
and it was higher than 50% of the haematocrit of periph-
eral blood, which met the criteria of true haemothorax.
The cytological examination of bronchial washing and pleu-
ral uid was negative for neoplasmatic cells. On suspicion
of immunologically-induced intra-alveolar haemorrhage,
80 mg of prednisone was administrated. After a brief sta-
bilisation, videothoracoscopic pleural and lung biopsy was
performed. Intra-operative biopsy for frozen section exami-
nation did not reveal any neoplasmatic cells. During the
next two days after the surgery the condition of the patient
was critical and she died a few days after.
Microscopic examination of pleural samples revealed
that the areas of slit spaces were lled with erythrocytes and
surrounded by epithelioid cells. Immunohistochemical re-
actions showed diuse reactivity with anti-CD31 (LC70, Cell
Marque) antibody (Fig. 4) and focal anti-CD34 (QBEnd/10,
Cell Marque) staining. Reactions with cytokeratins (AE1AE3,
Roche) and calretinin (SP65, Roche) were negative. In the
lung specimen, cohesive and ill-dened lesions were found.
On microscopic examination, the lesions were composed
of groups of loosely packed epithelioid cells mixed with -
brin and erythrocytes. Adjacent alveolar spaces were lled
with red blood cells and haemosiderin-laden macrophages
(Fig. 5). A diagnosis of epithelioid angiosarcoma was estab-
lished.
Discussion
Primary epithelioid angiosarcoma of the lung is an ex-
tremely rare disease. Typically, angiosarcomas occur as skin
and subcutaneous tissue neoplasms of the head, neck, and
lower and upper extremities, or involve the heart and ex-
trathoracic organs [3, 4]. Pulmonary manifestation must be
rst of all dierentiated with metastasis from other organs.
There are no typical factors associated with development
of these tumours. Some reports suggest a correlation be-
tween radiotherapy, chemotherapy, past surgical interven-
tions, environmental carcinogens, or chronic tuberculosis
pyothorax [1, 3, 6, 7].
Primary pulmonary angiosarcoma patients complain
of haemoptysis, dyspnoea, cough, weight loss, fatigue,
pleuritic chest pain, and sometimes fever [3, 8]. Our pa-
tient presented most of these symptoms. Nevertheless,
due to nonspecic complaints, continuous anticoagulant
Fig. 1. Chest radiograph shows right-sided opacity corresponding
to pleural uid; diuse pulmonary lesions focally conuent, for-
ming bigger opacities within left lung; hila moderately enlarged

Kardiochirurgia i Torakochirurgia Polska 2015; 12 (4) 369
CASE REPORTS
therapy, history of heart disease, misleading radiological
features, and rapid progression, the diagnosis was made in
a very advanced and metastatic stadium. In the presented
case, the clinical condition was also complicated by mas-
sive right-sided pleural eusion. The haematocrit of the
uid was higher than 50% of the haematocrit of peripheral
blood, which met the criteria of true haemothorax [9].
There are no dierences between PPA and metastatic
angiosarcoma of the lung in radiological manifestation.
In both cases CT demonstrates solitary or multifocal le-
sions, sometimes associated with ground-glass opacities
or pleural eusion. Usually at the time of diagnosis, the
neoplasm presents extensive local and metastatic invasion
[1-4]. The rst lung CT scan of our patient was confusing.
It showed abnormalities suggesting interstitial pneumonia.
There were no signs of typical tumour. Radiological chang-
es evolved with the progression of the disease. Images ob-
tained on admission revealed bilateral pulmonary opacities
with ground-glass attenuations, a small number of nodules,
and pleural eusion. There is only one case reported with
this rare presentation of PPA [5].
The histological examination of epithelioid angiosar-
comas reveals single or multifocal tumours composed of
sheets of atypical epithelioid cells, focal vasoformative
areas, and necrosis. Haematoxylin-eosin stained sections
show irregularly anastomosing vessels, cells with nuclear
atypia, and often a high mitotic count [4, 6]. The diagnosis
needs to be conrmed by immunohistochemical reactions.
Factor VIII, CD 31, CD34, Fli-1, Ulex europaeus agglutinin 1,
and vimentin are typical endothelial markers [4, 7, 8]. The
biopsy specimen of our patient showed positive reaction
for CD 31 and CD 34. The other stains, including cytokeratin
(AE1/AE3) for epithelial and calretinin for mesothelial pro-
liferations, were negative. It is suggested that at least two
markers should be present in order to conrm the endothe-
lial origin [8].
Fig. 2. Computed tomography scan shows a large right pleural eusion

Kardiochirurgia i Torakochirurgia Polska 2015; 12 (4)370
Diuse pulmonary haemorrhage accompanied by haemothorax as a rare presentation of primary lung angiosarcoma
Fig. 3. High-resolution computed tomography (HRCT) scans: multiple ground-glass opacities, predominantly subpleural; some small
nodules bilaterally
Fig. 5. Epithelioid angiosarcoma. Low- and medium-power magni-
cation of a pulmonary lesion composed of epithelioid cells, haemor-
rhages, and brin deposits surrounded by hyperaemic lung pa-
renchyma with aggregations of haemosiderin-laden macrophages
(HE staining, magnication 200×)
Fig. 4. Epithelioid angiosarcoma, pleural lesion. Epithelioid cells
revealed diuse reactivity with anti-CD31 antibody (CD31, magni-
cation 200×)

Kardiochirurgia i Torakochirurgia Polska 2015; 12 (4) 371
CASE REPORTS
Unfortunately, the survival rate in primary pulmonary
manifestation is less than 39 months [8]. There have been
reports summarising poor prognostic factors for angiosar-
comas, such as age (> 70 years), tumour size (> 5 cm), me-
tastases at presentation, grade, and mitotic count, but they
are still under debate [7, 10].
The presented case is a rare manifestation of primary
pulmonary angiosarcoma with diuse pulmonary haemor-
rhage and haemothorax. Non-distinctive clinical and radio-
logical symptoms and a rapidly progressive course make
this type of neoplasm a considerable challenge for clini-
cians. Our case is a reminder of the necessity to include
PPA in dierential diagnosis of diuse alveolar haemor-
rhage and haemothorax.
Disclosure
Authors report no conict of interest.
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