Surgical Science, 2011, 2, 130-133
doi:10.4236/ss.2011.23026 Published Online May 2011 (
Copyright © 2011 SciRes. SS
Metastatic Primary Pulmonary Angiosarcoma
Brendan F. Judy1, Jarrod D. Predina1, Jay Mittal1, Charuhas Deshpande2, Sunil Singhal1
1Division of Thoracic Surgery, Department of Surgery,
University of Penn syl va ni a School of Medici ne, Philadelphia, USA
2Department of Pathology and Laboratory Medicine,
University of Penn syl va ni a School of Medici ne, Philadelphia, USA
Received January 18, 2011; revised March 20, 201 1; accepted April 2, 2011
Angiosarcoma is an extremely aggressive tumor with a high rate of mortality. It can arise in any tissue of the
body and is most commonly found in the skin and soft tissue [1]. Pulmonary angiosarcoma is usually secon-
dary to a primary location of the body and presents as both solitary and multiple nodules. Primary pulmonary
angiosarcoma is a rare disease with less than 20 cases reported in the English literature. In our report we
present a case of metastatic primary pulmonary angiosarcoma involving the most (>100) pulmonary nodules
known to date. Novel treatment strategy using an anti-angiogenic inhibitor was used to treat this disease for
the first time to our knowledge; however, it was unsuccessful in controlling disease progression. This report
reviews the literature of this rare and devastating disease.
Keywords: Angiosarcoma; Pulmonary; Tumor; Surgery
1. Introduction
Angiosarcoma of the lung is a rare tumor that most often
presents as metastatic disease [2 ,3]. Rarer still is primary
pulmonary angiosarcoma, with less than 20 cases re-
ported in the literature. Patients have been treated with
steroids, radiotherapy, surgical resection, immunotherapy
and chemotherapy [3]. All except three cases fall into a
survival range of 1 - 9 months. The two survivors in the
literature are a 25-year-old male who received radio-
therapy and immunotherapy with recombinant inter-
leukin-2 (rIL-2) [4], and a 65-year-old male who under-
went surgery for tumor removal, a complete pneu-
monectomy, and chemotherapy using ifosfamide-
doxorubicin combination [5]. In this report we describe a
patient with innumerable primary pulmonary angiosar-
coma nodules who presented with dramatic weight loss
and hemoptysis.
2. Case Report
A 45-year-old-male nurse was referred to our hospital
with 40 lb weight loss over four months, anorexia,
hemoptysis, and fatigue. The patient had smoked one
pack-per-day for 20 years and recently quit. The patient
was otherwise healthy and had no preceding medical
Figure 1. (a) Posterior - anterior chest x-ray demonstrating
multiple bilateral nodular opacities and vascular crowding.
(b) A contrast enhanced computed tomography examina-
tion of the chest revealing over 100 bilateral pulmonary
B. F. JUDY ET AL.131
Two years prior to presentation, th e patient had a chest
x-ray that revealed no abnormalities. On admission, a
posterior-anterior chest radiograph demonstrated multi-
ple pulmonary nodular opacities with vascular crowding
(Figure 1(a)). A chest computed tomography (CT) scan
showed innumerable bilateral nodules (>100) varying in
size from a few mm to 18 mm with scattered areas of
groundglass opacities (Figure 1(b)). A pericardial effu-
sion was noted and measured 35 Hounsfield units. De-
generative changes were seen in the thoracic spine but
the great vessels, heart, and airways were all normal in
appearance. Imaging of the head, abdomen and pelvis
were unremarkable. The patient underwent a muscle
sparing limited thoracotomy on the right side with multi-
ple pulmonary wedge resections and a pericardial win-
dow for drainage of a bloody pericardial effusion. His
postoperative course was uneventful and he was dis-
charged from the hospital on postoperative day four.
Pathological examination revealed multiple nodules of
proliferating and pleomorphic spindle cells suggestive of
vascular neoplasm (Figure 2). The tumor cells showed
intravascular “hobnailing” and occasional intracytoplas-
mic lumina (Figure 3(a)). The tumor specimen under-
went immunohistochemical staining and was positive for
vimentin, CD31, CD34 (Figures 3(b) and (c)). The tu-
mor cells were negative for pancytokeratin (Figure 3(d)),
AE1/AE3, CK7, CAM 5.2, TTF-1, p63, thyroglobulin,
S100, SALL 4, HMB45, calcitonin, synaptophysin, EMA,
and HHV-8. The histology and immunohistochemistry of
the tumor were consistent with angiosarcoma [2,3,6]. The
pericardial effusion was negative for malignant cells .
The patient was started on bevacizumab, a vascular
endothelial growth factor A inhibitor, and paclitaxel. He
received three courses of paclitaxel and underwent repeat
imaging, four months after surgery, which revealed pro-
gression of his pulmonary disease, liver metastases
Normal Lung
Figure 2. Multiple pulmonary nodules re vealed dur ing open
surgical biopsy. When palpated, these nodules were soft,
non-mobile and non-blanching.
(a) (b)
(c) (d)
Figure 3. (a) Hematoxylin and eosin (H&E) staining dem-
onstrates poor cell differentiation, hobnailing, and intracy-
toplasmic lumina, 40x. (b) Malignant cells immunoreactive
to CD31, 40x. (c) Malignant cells immunoreactive to CD34,
40x. (d) Malignant cells not immunoreactive to pancy-
tokeratin, 40x.
and solitary brain metastasis. Paclitaxel was stopped and
dexamethasone was started for two months and tapered
off. The patient received whole brain external beam irra-
diation (3000 rads) and was started on sorafenib, a small
molecular inhibitor of several tyrosine protein kinases
and Raf. Despite this approach, the pulmonary disease
progressed and the patient expired five months following
diagnosis from respiratory failure.
3. Discussion
Angiosarcoma is a rare tumor that accounts for approxi-
mately 1% of all soft tissue sarcomas [7]. The cause of
the pulmonary angiosarcoma is unknown however mas-
tectomy, radiation treatment [8], and exposure to poly-
vinyl chloride, Thorotrast [2], and copper mining dusts
[9] have all been suggested as associated to the disease
[7]. Pulmonary sarcomas are most often the result of
metastasis from a primary site such as skin, bone, liver,
breast, or heart [2-4]. Males are more often affected than
females by a 3:1 ratio [10]. There are no symptoms spe-
cific to pulmonary angiosarcoma as the presentation is
similar to presenting symptoms found in all lu ng cancers,
such as hemoptysis, weakness, dyspnea, and chest pain
[7,11]. It has been speculated that up to 20% of all cases
are asymptomatic and diagnosis only occurs post-au-
topsy [2,10,12]. Primary pulmonary angiosarcoma pre-
sents as both solitary and multiple nodules. Although
multiple nodules have been noted before [1,7,13,14],
there have been no reports of innumerable (>100) nod-
Copyright © 2011 SciRes. SS
ules as we present in our case. A literature search for
“primary pulmonary angiosarcoma” yielded 15 articles,
which indicates the lack of literature on the topic.
In order to properly diagnose primary pulmonary
angiosarcoma it is critical to exclude primary tumors
elsewhere in the body [11]. Diagnosis requires a CT scan
or magnetic resonance imaging of the body. The CT scan
of pulmonary angiosarcoma has a distinctive appearance
of soft tissue attenuation surrounded by groundglass at-
tenuation which is also known as the halo sign [7]. The
halo is thought to represent the hemorrhage in the sur-
rounding lung du e to the nodule [7]. Fur thermore, biopsy
is necessary in order to confirm the histological and im-
munohistochemical characteristics of the cancer. Angio-
sarcoma is positive for endothelial cell markers (CD31,
CD34, factor VIII related antigen, and Ulex europaeus
agglutin-1 [UEA-1]), epithelial cell markers (cy-
tokeratins, EMA), and vimentin [2,3,12]. Staining of
epithelial markers (keratins and EMA) is variable [3] and
in our case is negative.
Currently, the therapeutic options for primary pul-
monary angiosarcoma include but are not limited to ster-
oids, radiotherapy, surgical resection, immunotherapy
and chemotherapy [3]. There is no standard regimen, yet
surgery has been the mainstay for locally confined dis-
ease [3]. Due to the rarity and aggressive nature of pri-
mary pulmonary angiosarcoma, early detection is un-
common and prognosis is poor. The cancer is usually
inoperable at the time of diagnosis, as in this case. Only
two survival cases have been reported in the literature,
yet one survivor was significantly younger (25 years old)
than other reported cases [4,5]. The 25-year-old survivor
received radiotherapy and immunotherapy with recom-
binant interleukin-2 intratumoral injection. Previous
studies have shown that angiosarcoma is responsive to
radiotherapy [15,16]. Systemic administration of high
dose recombinant interleukin-2 (rIL-2) has been shown
to inhibit pulmonary metastasis of angiosarcoma of the
skin [17]. The mechanism of rIL-2 is thought to involve
direct inhibition of tumor cells and activation of natural
killer cells and lymphokine-activated killer cells [4, 18].
Two chemotherapeutic combinations have demonstrated
partial and full effects: doxorubicin/ifofsamide and do-
cetaxel/gemcitabine. Doxorubicin and ifofsamide were
used in one of the reported cases of primary pulmonary
angiosarcoma survival [5]. Docetaxel and gemcitabine
have proved effective in a variety of other malignancies
such as esophageal cancer, non-small cell lung cancer,
and breast cancer [3,19,20]. This combination continues
to be explored in a number of clinical trials. The syner-
gism is purportedly due to docetaxel’s effect on metabo-
lism and repair, which results in increased integration of
gemcitabine into the DNA [3,21,22].
4. Conclusions
Primary pulmonary angiosarcoma is a devastating dis-
ease with almost a 100% mortality rate. The diagnosis of
this tumor and histological findings were presented. The
gold standard for diagnosing this disease is full body
imaging in order to rule out other primary tumors and
immunohistochemical confirmation. Attempts at novel
therapies such as targeted biological agents such as in
this patient were unsuccessful. Intuition would suggest
that an anti-vascular inhibitor such as bevacizumab
would permit some disease regression; however, this was
not seen. In addition, a tyrosine kinase inhibitor was also
unsuccessful in stabilizing disease progression. Future
efforts at biological agents are reasonable, but alternative
strategies should be considered.
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