AJR 2003; 180:1671-1674
© American Roentgen Ray Society
Metastatic Angiosarcoma of the Lung: Spectrum of CT Findings
Ukihide Tateishi1,
Tadashi Hasegawa2,
Masahiko Kusumoto1,
Naoya Yamazaki3,
Gen Iinuma1,
Yukio Muramatsu1 and
Noriyuki Moriyama1
1 Department of Diagnostic Radiology, National Cancer Center Hospital, 5-1-1,
Tsukiji, Chuo-Ku, Tokyo 104-0045, Japan.
2 Department of Pathology, National Cancer Center Hospital, Tokyo 104-0045,
Japan.
3 Department of Dermatology, National Cancer Center Hospital, Tokyo 104-0045,
Japan.
Received August 5, 2002;
accepted after revision November 22, 2002.
Address correspondence to U. Tateishi.
Supported in part by grants from Scientific Research Expenses for Health
and Welfare Programs, The Foundation for the Promotion of Cancer Research, and
Second-Term Comprehensive 10-Year Strategy for Cancer Control.
Abstract
OBJECTIVE. The purpose of our study was to summarize the CT features
of pulmonary metastases in angiosarcoma in 24 patients.
CONCLUSION. A variety of CT features were associated with metastatic
angiosarcoma of the lung. The common CT manifestations of metastatic
angiosarcoma were multiple solid nodular lesions and multiple thin-walled
cysts that were often accompanied by hemorrhagic change.
Introduction
Angiosarcoma is a rare malignant neoplasm of the vascular or lymphatic
endothelium that accounts for 2% of all soft-tissue sarcomas
[1,
2]. Angiosarcoma seems to have
a predilection for the skin in either the head or the neck. However, the tumor
less commonly originates from the deep soft tissue. Angiosarcomas, regardless
of their sites of origin, are particularly likely to metastasize to the lung.
Other frequent sites for metastatic spread include the bone, liver, and lymph
nodes [1,
2,
3].
Metastatic pulmonary angiosarcoma exhibits a variety of radiographic
appearances. Chest radiography shows bilateral peripheral solid nodules that
are often accompanied by infiltrates, pneumothorax, and pleural effusions
[4,
5,
6,
7,
8,
9]. However, the CT findings of
metastatic angiosarcoma have been described only in case reports or small
series [10,
11,
12]. The purpose of this study
was to summarize the CT findings of lung metastasis in a larger group of
patients with angiosarcoma.
Materials and Methods
We retrospectively reviewed the records of patients with pathologically
proven angiosarcoma seen at our institution between 1984 and 2001 in whom
pulmonary metastases were identified. Patients were identified by means of
computerized searches of pathology reports in the pathology information system
and patient files. Twenty-four patients, comprising 12 males and 12 females,
were included only if a definitive diagnosis could be made for the lung nodule
by means of histologic examination or clinical course. At the time of CT
diagnosis, patients were 16–86 years old (mean age, 60 years). Ten of
the 24 patients had respiratory symptoms leading to CT, including dyspnea
(n = 10), cough (n = 8), hemoptysis (n = 4), and
chest pain (n = 2). Fourteen patients had no respiratory complaints
at the time CT was performed. The primary sites of angiosarcoma included the
scalp (n = 12), cutaneous tissue other than the scalp (n =
4), and deep soft tissue (n = 8). The diagnosis of metastatic
angiosarcoma to the lung was made antemortem in six of 24 patients, either by
lung biopsy specimen (n = 2), biopsy evidence of metastatic disease
elsewhere with abnormal chest radiographic findings (n = 4), or a
compatible clinical picture in patients with previously documented
angiosarcoma arising in an extrapulmonary site (n = 12). In nine
patients, definitive diagnosis was determined by autopsy sampling of the
involved lung. All histopathologic specimens were reviewed by an experienced
pathologist to confirm the diagnosis.
CT scans were obtained in all patients. CT was performed on two
single-slice helical CT scanners (X-Vigor or 900S, Toshiba Medical Systems,
Tokyo, Japan) with 10-mm collimation, a pitch ratio of 1, a 10-mm
reconstruction interval, and standard and lung reconstruction algorithms. All
images were obtained with standard mediastinal and lung window settings. IV
iodinated contrast material was administered in 19 patients. Follow-up CT was
performed within a mean interval of 61 days. In four patients, thin-section CT
images were obtained using a section thickness of 2 mm at 5-mm intervals,
reconstructed using a high-spatial-frequency algorithm, and printed with
window settings appropriate for viewing the lungs (window width,
1500–2000 H; window level, –600 H). The duration between CT and
histologic diagnosis was less than 31 days (median, 8 days) in 15 patients.
Two radiologists simultaneously reviewed all CT images; findings were recorded
by consensus. The CT scans were assessed for the presence of solid nodular
lesions and thin-walled cysts. The presence and extent of associated findings
such as ground-glass attenuation, linear opacity, air–fluid level,
pneumothorax or hemothorax, pleural effusion, and lymph node enlargement were
also assessed. Solid nodular lesions were defined as parenchymal nodules with
soft-tissue attenuation of less than 30 mm in diameter. Thin-walled cysts were
defined as cystic areas of air density with a wall thickness of less than 2
mm. Ground-glass attenuation was defined as a hazy increase in lung opacity in
which the bronchi and vessels remained visible.
Results
Multiple solid nodular lesions were identified in 15 patients (63%). The
size of these nodules ranged from 6 to 30 mm (mean, 15 mm). Linear opacity
distributed in the periphery of the solid nodule was seen in two patients
(8%). Ground-glass attenuation (Figs.
1A,
1B) surrounding solid nodules
was seen in six patients (25%), which corresponded to alveolar hemorrhage on
microscopic observation. Of 15 patients with multiple solid nodular lesions,
one patient (4%) showed miliary spread. Solitary solid nodular lesions (Figs.
2A,
2B) were identified in two
patients (8%). The mean size of these nodules was 26 mm; the nodules were also
associated with punctate calcification (Figs.
2A,
2B). Tumors showed
inhomogeneous enhancement in 71% of solitary or multiple solid nodular lesions
on enhanced CT; homogeneous enhancement was found in 29%. Obstructive
pneumonia was identified in one patient with a solitary solid nodular lesion.
Interlobular septal thickening was associated in one patient with multiple
solid nodular lesions, which was consistent with the lymphangitic spread of
tumor by histopathologic observation (Fig.
3). One patient in whom a miliary pattern of spread was seen died
of respiratory failure 1 week after CT examination.
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Fig. 1A. —Metastatic angiosarcoma of lung in 32-year-old woman. Chest
CT scan (lung window setting) shows solid nodular lesion with surrounding
ground-glass attenuation (arrow) in left lower lobe. Note small
nodular lesions in adjacent lung parenchyma.
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Fig. 1B. —Metastatic angiosarcoma of lung in 32-year-old woman.
Photomicrograph of histopathologic specimen taken at autopsy shows atypical
endothelial cells involving lung parenchyma mixed with marked hemorrhage. (H
and E, x200)
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Fig. 2B. —Metastatic angiosarcoma of lung in 61-year-old woman.
Contrast-enhanced CT scan (mediastinal window setting) shows slightly
inhomogeneous enhancement. Note punctate calcification (arrow) in
periphery of lesion.
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Fig. 3. —Metastatic angiosarcoma of lung in 48-year-old woman. Chest
CT scan shows multiple solid nodular lesions and ground-glass attenuation.
Note septal thickening (arrows) throughout lung, suggesting
lymphangitic spread of tumor cells. Poorly demarcated solid nodular lesions
(arrowheads) accompanied by ground-glass attenuation are seen in
periphery of both lungs.
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Multiple thin-walled cysts were identified in five patients (21%). The size
of these lesions ranged from 8 to 71 mm (mean, 46 mm). Air–fluid levels
in thin-walled cysts were seen in three patients (13%). Ground-glass
attenuation surrounding thin-walled cystic lesions was seen in four patients
(17%). Multiple thin-walled cysts were enlarged and the walls of the cysts
thickened on subsequent examinations in five patients (Figs.
4A,
4B). Pneumothoraces or
hemothoraces, suggesting rupture of cysts distributed in the subpleura, were
observed in all patients with multiple thin-walled cysts (Figs.
5A,
5B). Five patients had CT
findings suggesting small to moderate-sized pleural effusions.
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Fig. 4A. —Metastatic angiosarcoma of lung in 78-year-old man. Chest CT
scan (lung window setting) shows multiple thin-walled cysts (arrows)
with ground-glass attenuation (arrowheads). Air–fluid levels
are seen in several cysts.
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Fig. 5A. —Metastatic angiosarcoma of lung in 60-year-old woman with
history of mastectomy of left breast for cancer approximately 10 years
previously. Chest CT scan (lung window setting) shows thin-walled cyst
(arrow) in left upper lobe. Irregular nodule (arrowhead) is
also seen in right lower lobe.
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Fig. 5B. —Metastatic angiosarcoma of lung in 60-year-old woman with
history of mastectomy of left breast for cancer approximately 10 years
previously. Chest CT scan 10 months later exhibits right hemothorax and
enlargement of cyst. Areas of ground-glass attenuation have enlarged diffusely
in both lungs. Thickened cyst wall and surrounding hemorrhage
(arrows) is noted. Irregular nodule (arrowhead) in right
lower lobe has enlarged.
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Mixed-pattern tumors (i.e., multiple solid nodular lesions and thin-walled
cysts) were identified in two patients (8%). One patient with a mixed pattern
developed a hemothorax during the course of the disease. Hilar node adenopathy
was seen in three patients (13%), in two of whom it was associated with
multiple solid nodular lesions.
All patients underwent chemotherapy and were clinically followed up for a
median of 18 months (range, 0–39 months). All patients who had
pneumothoraces or hemothoraces underwent chest drainage. The clinical course
was dismal, with 20 (83%) of 24 patients dying an average of 18 months (range,
0–39 months) after the initial diagnosis of the primary lesion.
Discussion
The most common CT finding of lung metastasis by angiosarcoma in our series
was multiple solid nodular lesions, which were seen in 15 patients (63%).
Patel and Ryu [7] reported that
multiple nodules were seen in 11 patients on chest radiographs, and one of
three patients who underwent chest CT showed a 2-cm mass in the area of a
nodular apical infiltrate. Bilateral nodules were uncalcified and
indistinguishable from those seen in other metastatic malignant neoplasms on
chest radiographs. Punctate calcification in solid nodular lesions was
identified on CT in two of our patients, which might be difficult to identify
on chest radiographs. Because of the hemorrhagic nature of metastatic
angiosarcoma, we believe that punctate calcification may have been caused by
hemorrhagic necrosis, which is often seen in soft-tissue angiosarcoma
[2].
Lung metastases of soft-tissue sarcomas commonly take the form of solid
nodules. However, the mere appearance of cystic or bullous lung changes on CT
scans in patients with known sarcoma has been proposed as a sign heralding
metastatic disease. The distinctive appearance of some angiosarcomatous
pulmonary metastases as thin-walled cysts has also been reported in
association with spontaneous hemopneumothorax
[8,
9]. Miller et al.
[10] reported a 57-year-old
man with metastatic angiosarcoma confirmed by CT-guided needle biopsy in whom
CT revealed multiple delicate, thin-walled, annular lesions in both lung
fields. With this patient, a scalp lesion was discovered on a subsequent
physical examination and proved to be angiosarcoma.
In our study, multiple thin-walled cysts, seen in five (21%) of 24
patients, was the second most common CT finding of metastatic angiosarcoma.
All these patients had enlargement of the cystic lesions during the course of
the disease and developed pneumothoraces or hemothoraces. This appearance of
cystic metastasis was similar to the description by Miller et al.
[10]. The presence of an
air–fluid level in a cystic nodular lesion may suggest hemorrhage and
will indicate abrupt enlargement of the lesion. If these lesions are
distributed in the subpleura, the incidence of pneumothorax or hemothorax will
increase.
Four possible mechanisms exist for the development of thin-walled cysts.
First, excavation of a solid nodular lesion through the discharge of necrotic
material in a tumor can cause cyst formation. Thirteen of 15 cases exhibiting
solid masses or nodules on CT contained hemorrhagic necrosis in pathologic
specimens. Pathologically, excavation was not identified in any case; however,
the possibility exists of thin-walled cysts being formed because of the
necrotic nature of the tumor tissue. Second, the infiltration of tumor cells
into the walls of preexisting bullous lung tissue may be similar to cyst
formation. Third, the circumferential growth of a tumor around small
bronchioles often results in bronchiole obstruction when the tumor penetrates
the wall of the structures through the ball-valve effect of the tumor.
Finally, tumor cells may proliferate to form some blood-filled cystic spaces
anastomosing the network of sinusoids, which is a characteristic microscopic
finding of angiosarcoma [1,
2,
3].
Involvement of the first mechanism in our study might be ruled out because
no solid nodular lesions changed into cavitary lesions on CT during the
follow-up period. However, most solid nodular lesions in our patients
exhibited hemorrhagic necrosis on microscopic observation. The second
mechanism was also unlikely, because the consistent increase in the number of
pulmonary cysts could hardly be explained by a progressive emphysematous
change in the lungs. The likelihood of the third mechanism is strengthened by
the evidence of enlargement of thin-walled cysts identified on CT. These
lesions are considered to be a later stage in the development of macroscopic
thin-walled cysts. The final mechanism might be explained by microscopic
observation. Most angiosarcomas form distinct vascular channels, albeit of
irregular size and shape [1,
2,
3]. Moreover, the vascular
channels of the tumor often communicate with each other, anastomosing the
network of sinusoids [1,
2,
3]. These vascular channels are
also immature and easily dissecting
[1,
2,
3]. Most of the metastases in
our patients exhibited vascular channels on macroscopic observation, which
might suggest that dissection of vascular channels in the tumors formed cystic
spaces mixed with hemorrhage.
Confusion exists and concepts overlap concerning excavating, cavitary, and
cystic pulmonary metastatic tumors. Excavating pulmonary metastasis may be
defined by the mechanism of its formation; it is initially a solid mass and
its air-filled cavity is formed after discharge of the necrotic material
inside. Such lesions usually have a thick irregular wall and are seen with
other lesions at various stages of excavation. A cystic pulmonary metastasis
is a thin-walled, bullalike lesion with or without accompanying nodular
lesions.
Hemorrhagic change in association with metastatic lesions was depicted on
CT images. Ground-glass attenuation was seen in 32% of our patients
surrounding both solid nodular lesions and thin-walled cysts. Solid nodular
lesions with hemorrhage showed central softtissue attenuation with surrounding
ground-glass attenuation, termed the CT "halo sign." This evidence
was consistent in part with a previous study
[12]. However, CT scans
exhibited various hemorrhagic findings for metastatic angiosarcoma
[11]. Adem et al.
[12] described seven patients
with metastatic angiosarcoma presenting with diffuse pulmonary hemorrhage. In
four of those patients, chest radiographs showed diffuse pulmonary infiltrates
in both lungs. In the same four patients, the histologic findings of four
lesions were ill-defined nodules admixed with a distinctly lymphangitic
pattern in distribution involving bronchovascular bundles, interlobular septa,
and visceral pleura. In all patients, a background of acute and chronic
pulmonary hemorrhage was a prominent feature. Air–fluid levels in
thin-walled cysts, seen in 13% of our patients on CT, also suggest the
presence of hemorrhage. Hemorrhagic change is considered to be a
characteristic finding in metastatic angiosarcoma and may be caused by the
fragility of the neovascular tissue, which predisposes vessels to thrombosis
and rupture.
In summary, the common CT manifestations of metastatic angiosarcoma in our
series were multiple solid nodular lesions and multiple thin-walled cysts,
often admixed with hemorrhagic change.
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Abstract
Introduction
