Axillary and perianal leiomyosarcoma: report of two cases.

Abstract

Soft tissue leiomyosarcoma is a relatively rare malignant tumor. It may be difficult to be distinguished from gastrointestinal stromal tumors and Schwann cell neoplasms. To make a correct identification of soft tissue leiomyosarcoma, immunostaining with several smooth muscle differentiation markers (actin, calponin and desmin), and negative staining results with S100 (to rule out Schwann cell neoplasm), c-kit and CD34 (to rule out gastrointestinal stromal tumors) is needed. Prompt diagnosis and referral are desirable, since the size of the tumor at presentation is a continuous variable for the risk of local recurrence and metastatic disease. Chemosensitivity varies according to the tumor subtype, and the tumor grade, the patient's age, performance status, and the timing of metastatic disease further influence the likelihood of a response and survival. Chemotherapy is palliative for most patients with unresectable or metastatic disease. Ifosfamide and doxorubicin are routinely used in this setting; doxorubicin as a single agent is considered the drug of choice.

Full text

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Romanian Journal of Morphology and Embryology 2010, 51(2):379–385

C CA AS SE E R RE EP PO OR RT TS S
Axillary and perianal leiomyosarcoma:
report of two cases
C. MEŞINĂ1), I. VASILE1), I. D. VÎLCEA1), C. C. VERE2),
CLAUDIA VALENTINA GEORGESCU3), MIRELA GHILUŞI3),
M. PAŞALEGA1), H. PÂRVĂNESCU4), F. CALOTĂ1), S. S. MOGOANTĂ1)
1)Department of Surgery
2)Department of Gastroenterology
3)Laboratory of Pathology
4)Department of Reconstructive Surgery
Emergency County Hospital, Craiova
University of Medicine and Pharmacy of Craiova
Abstract
Soft tissue leiomyosarcoma is a relatively rare malignant tumor. It may be difficult to be distinguished from gastrointestinal stromal tumors
and Schwann cell neoplasms. To make a correct identification of soft tissue leiomyosarcoma, immunostaining with several smooth muscle
differentiation markers (actin, calponin and desmin), and negative staining results with S100 (to rule out Schwann cell neoplasm), c-kit and
CD34 (to rule out gastrointestinal stromal tumors) is needed. Prompt diagnosis and referral are desirable, since the size of the tumor at
presentation is a continuous variable for the risk of local recurrence and metastatic disease. Chemosensitivity varies according to the
tumor subtype, and the tumor grade, the patient’s age, performance status, and the timing of metastatic disease further influence the
likelihood of a response and survival. Chemotherapy is palliative for most patients with unresectable or metastatic disease. Ifosfamide and
doxorubicin are routinely used in this setting; doxorubicin as a single agent is considered the drug of choice.
Keywords: soft tissue leiomyosarcoma, immunostaining, S100.
? Introduction
Leiomyosarcoma is an aggressive soft tissue
sarcoma derived from smooth muscle cells typically of
uterine, gastrointestinal or soft tissue origin. Sarcomas
are malignant tumors arising from mesenchymal cell
lines. They comprise a heterogeneous group of cancers,
each with unique clinical, histological, and radiographic
characteristics. Soft tissue sarcomas account for 0.7% of
malignancies. Sarcomas are generally classified accor-
ding to the normal cell line that they most closely
resemble. Of all soft tissue sarcomas, approximately
5–10% are leiomyosarcomas [1]. Leiomyosarcoma of
soft tissue is thought to arise from the smooth muscle
cells lining small blood vessels. Leiomyosarcoma can
also arise directly from the viscera, including the
gastrointestinal tract and uterus. Leiomyosarcoma of
soft tissue is discussed in this article, while the
companion article addresses the uterine form of this
disease. Gastrointestinal lesions are not included in this
discussion. Primary leiomyosarcoma of bone is a
distinct entity, which is quite rare. While histologically
similar, soft tissue leiomyosarcoma has classically been
subdivided into three groups for prognostic and
treatment purposes: leiomyosarcoma of somatic soft
tissue, cutaneous leiomyosarcoma and leiomyosarcoma
of vascular origin [2]. A group of patients with
leiomyosarcoma in the setting of immune dysfunction
is also being discovered [3]. Leiomyosarcomas are
aggressive tumors that are often difficult to treat. The
prognosis is poor, with survival rates among the lowest
of all soft tissue sarcomas [4].
? Patients and Methods
We will describe two cases of patients with leiomyo-
sarcoma of soft tissue with localization in right axilla
and left ischiorectal fossa.
The patient, C.V., 77-year-old man, OF 57213 from
03.11.2008, with a mass of the right axilla, functional
impotence of the right upper limb, paresthesia of the
right arm. From antecedents results that the patient was
surgical treated for right axillary tumor in one year ago,
the histological diagnosis was liposarcoma.
The physical examination showed the right axillary
mass, measuring 8×12 cm, ovallary shape, unmoved
consistency, irregular surface, mobilization on the deep
plans, adherent on the superficial plans (Figure 1). The
pulse was present of the right radial artery. The labora-
tory data on admission: Hb 12.3 g/dL, L 7800/mm3,
glycemia 86 mg%, urea 42 mg%, Quick T. 100%,
ASAT 15 iu, ALAT 18 iu, ECG normal, Rx chest: right
pronounced broncho-vascular design hilio-basal.
On 04.11.2008, we perform the surgical treatment
through axillary abord and we constate axillary-mass,
round-ovalary shape, 10×8 cm adherent on the axillary
fascia, but with mobility on the axillary vein and artery
and on the brachial plexus.

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Postoperative evolution was favorable. It was dis-
charge in a good condition.
On light microscopy examination, the tumor mass
was composed of spindle cell tumor composed of eosi-
nophyl mesenchymal cells forming fascicles inter-
secting at right angles with pushing margins. Tumor
cells possessed hyperchromatic cigar-shape nuclei,
prominent nucleoli and typical and atypical figures,
epitheloid cells with round eosinophylic cytoplasm.
Immunohistochemical
(CKAE–1AE3), epithelial membrane antigen (EMA),
S100-protein, CD117 ended with negative results.
Tumor cells showed strong positivity for vimentin,
desmin and smooth muscle actin (SMA) antisera. Ki-67
proliferation marker showed positivity in 30% of tumor
cells.
The patient, R.M., 72-year-old female, admitted and
operated in Surgical Clinic of Emergency County Hos-
pital of Craiova for tumor of ischiorectal fossa. Post-
operative evolution was favorable. The patient was dis-
charge in a good condition after seven days. Immuno-
histochemical examinations showed: strong positivity
for vimentin, desmin and smooth muscle α-actin (SMA)
antisera. CD117-negative results in the tumor cells,
CD34-negative results in the tumor, positive in vessels;
p53-protein negative results in the tumor; S100-protein
negative results; glial fibrillary acid protein (GFAP)
slow focal positive results in the tumor; Ki-67 prolifera-
tion marker showed positivity in 10% of tumor cells.
The patient was treated with six cures of chemothe-
rapy with methotrexate, antifolan, ifosfamide, cisplatin.
Evolution was favorable so far six months ago when the
patient remarked the reappearance of the tumor to
ischiorectal fossa.

examinations cytokeratin
The patient was admitted in the Second Surgical
Clinic of Emergency County Hospital of Craiova with
tumor recidivated of left ischiorectal fossa. Physical
examination showed recidivated tumor of left ischio-
rectal fossa, measuring 3×4 cm, adherent of the super-
ficial plans of anal canal (Figure 2). Rectal examination:
anal canal and rectal ampulla normal aspect. Vaginal
examination: vagina walls normal aspect.
The laboratory data: Hb 12.7 g/dL, L 8800/mm3,
glycemia 96 mg/dL, urea 32 mg%, Quick T. 100%,
ASAT 13 iu, ALAT 17 iu. ECG: sinusal rhythm, QRS
axe 600, subdenivelated of ST segment in V1, V2, V5,
V6. Rx chest: right pronounced broncho-vasculary
design hilio-basal.
Computerized tomography (CT): Liver with normal
dimension and hemangioma in the VIIth segment,
20 mm in diameter. Pancreas, spleen, kidney, urinary
bladder normal aspect. Normal aspect of ischiorectal
fossa and normal density of internal obturatorius muscle
and levator ani muscle.
MRI pelvis: corpus uteri measuring 4.7/2.5 cm, with
tumoral mass 5 mm in diameter, in the body zone of
corpus uteri, fibromatous aspect. Ovalary-shape tumor,
measuring 20/13 mm, left perianal localization, hypo-
signal on T1 – weighted images and greater signal inten-
sity on T2 – weighted images, without pelvic adeno-
pathy and without peritoneal fluid. Urinary bladder had
a normal aspect (Figure 3).
On 15.01.2009, we performed the surgical treatment
and we noticed a tumoral mass measuring 2.5/3 cm
situated left side of anal canal, oval shape unmoved
consistency, irregular surface. We removed this tumor
upon healthy tissue. Postoperative evolution was
favorable. It was discharged in a good condition.

Figure 1 – Right axillary mass,
measuring 8×12 cm, ovalary-
shape, unmoved consistency, ire-
gular surface, mobilization on the
deep plans, adherent on the super-
ficial plans.
Figure 2 – Recidivated tumor of
left ischiorectal fossa, measuring
3×4 cm, adherent of the superfici-
al plans of anal canal.
Figure 3 – Ovalary-shape tumor,
measuring 20/13 mm, left peri-
anal localization, hypo-signal on
T1 – weighted images and greater
signal intensity on T2 – weighted
images.

? Results
Primary cutaneous leiomyosarcoma are uncommon
soft tissue tumors with more than 100 cases reported in
literature. Leiomyosarcoma are divided into two
subtypes depending on the location. The superficial
dermal form of leiomyosarcoma is thought to arise from
the arrector pili muscles whereas the deep subcutaneous
type is though to arise from the smooth muscle of
the vascular wall. Histologically, the tumor is composed
of highly cellular fascicles of spindle-shaped cells.
The fascicles are arranged in irregular interlacing bund-
les, often intersecting at right angles (Figure 4).
The cells have nuclei that are elongated and blunt-
ended giving a “cigar” appearance. The degree of differ-
entiation may vary within a single tumor. In some well-

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381
differentiated areas, the cells resemble the typical
smooth muscle cells of leyomiomas. Other areas may be
poorly differentiated, with extensive cellular atypia and
prominent nuclei and nucleoli. Mitotic figures are seen
throughout the lesion. Criteria for malignancy remain
controversial. Generally accepted, features of malignan-
cy, include the presence of mitosis of the least one per
10-high-power fields, high cellularity, significant nuclear
atypia and tumor giant cells (Figure 5).
Therefore, careful scrutinize of cytological details
in multiple sections, clinicopathological correlation
an immunohistochemistry are mandatory for definition

diagnosis. Unusual morphologic variants of cutaneous
leiomyosarcoma have been described that can introduce
difficulties for diagnosis including epitheloid, granular
cell, desmoplastic, inflammatory and myxoid leiomyo-
sarcoma. If the lesion is poorly differentiated, immuno-
histochemical studies can differentiate the muscular
origin of the lesion. Classical immunophenotyping of
leiomyosarcoma comprises positive vimentin, desmin
and smooth muscle actin (SMA) staining. Our results
confirm vimentin and SMA staining in both cases
(Figures 6 and 7).
Figure 4 – The tumor is composed of highly cellular
fascicles of spindle-shaped cells. The fascicles are
arranged in irregular interlacing bundles, often
intersecting at right angles (HE stain, ×100).
Figure 5 – Tumor cells possessed hyperchromatic cigar
shaped nuclei, prominent nucleoli and numerous
typical and atypical mitotic figures (HE stain, ×100).

Figure 6 – Smooth muscle alpha actin, marker for
differentiate smooth muscle, positive intracytoplas-
matic in tumoral cells. Tumor cells showed strong
positivity for smooth muscle actin antiserum (×100).
Figure 7 – Vimentin, mesenchymal marker, positive
intracytoplasmatic in tumoral cells, ×100.

SMA seems to be more sensitive than desmin for
smooth muscle tumors, although the antibody is not
always specific. Desmin staining is sensitive and
specific for both normal and affected muscle tissue, but
it does not differentiate between leiomyosarcoma and
rabdomyosarcoma. In our cases, both cases showed
positive immunostaining with desmin. Some authors
emphasize the polymorphism of the immunophenotype
expression and the importance of using several
antibodies. Pan-muscle actin HH35 is sometimes
present focally. Like desmin, this marker is not specific
because it can stain myofibroblasts and striated muscle.
Several benign or malignant tumor lesions are difficult
to distinguish from leiomyosarcoma namely desmo-
plastic malignant melanoma (value of PS100 and
HMB45 staining), spindle-cell angiosarcoma, spindle-
cell synovial sarcoma, malignant striform pleomorphic
histiocytofibroma, schwannoma or plexiform neurofi-
broma and atypical fibroxanthoma.
Immunohistochemistry is a valuable diagnostic tool
in these difficult cases. Electron microscopy can reveal
intracytoplasmatic myofilaments in cases, which are
difficult to diagnose.
CD117 is a 145–160-kD cell membrane protein

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382
encoded by the c-kit proto-oncogene (chromosome
4q11–12). The protein is a type III tyrosine kinase
growth factor receptor for stem cell factor, also know as
mast cell growth factor. CD117 is required for
development and growth a large number of cells
expressing this protein. CD117 is expressed in mast
cells, melanocytes and interstitial cells of Cajal.
S100 protein is a 21-kD highly acidic and water-
soluble protein first isolated from brain but later shown
to be produced by a wide variety of normal and neo-
plastic cells of mesodermal, neuroectodermal and epi-
thelial origin. S100 protein may be found in the cell
membranes, cytoplasm and nuclei. S100 protein is pre-
sent in glial cells, Schwann cells and satellite cells (but
not perineurial cells), melanocytes, myoepithelial cells,
some glandular epithelia (breast, kidney), skeletal and
heart muscle cells, fat cells, chondrocytes and follicular
dendritic cells. In both cases, in our study S100 protein

was negative (is positive in liposarcoma) (Figure 8).
Leiomyosarcomas demonstrate a moderate degree of
heterogeneity, not only at a conventional histological
level but also in immunophenotypic terms. Classically,
these tumors are potentially encountered in the soft
tissues, as well as several viscera and selected bones.
They are composed of interweaving fascicles of
relatively uniform spindle cells, showing blunt-ended
nuclei and fibrillar eosinophilic cytoplasm. However,
myxoid, epitheloid and pleomorphic variants of
leiomyosarcomas have been well documented, and these
often represent challenging differential diagnosis
problems. From an immunohistochemical perspective,
the most frequent antigenic profile seen in smooth
muscle sarcomas is that of positivity for vimentin, actin,
desmin and collagen type IV or laminin with non-
reactivity for keratin, EMA, S100 protein, myoglobin,
HMB45, CD31, CD34 and CD57 (Figure 9).
Figure 8 – S100-protein negative in tumoral cells (is
positive in liposarcoma), ×100.
Figure 9 – CD31 endothelial marker showed intra-
tumoral neovessels, ×100.

However, leiomyosarcomas that arise in the uterine
myometrium, urinary bladder, and pelvic soft tissues
often express keratin in an “aberrant” fashion, as proven
with immunoblotting studies done on fresh tumor tissue.
S100 protein may conversely be observed in
superficial smooth muscles tumors – perhaps because of
analogies with arrectores pilorum of the skin – and
CD57 reactivity is apparent in roughly 50% of deep
leiomyosarcomas with a “vascular” appearance.
Miettinen (1988) has drawn attention to the fact that
cytoplasmic staining for EMA is also evident in some
smooth muscle tumors. However, this pattern is essent-
ially meaningless, with only plasmalemmal labeling for
EMA representing an epithelial lineage-specific profile
of staining. Another phenotypic peculiarity of leiomyo-
sarcomas is their tendency to express the Mic-2 protein,
recognized by the monoclonal antibodies HBA71.
Nevertheless, we have found it useful diagnostically in
selected circumstances where aberrant keratin expre-
ssion makes the interpretation of leiomyosarcomas
somewhat tenuous, because sarcomas (which are
routinely keratin-positive and may show “divergent”
myogenic differentiation) have not been labeled for
Mic-2.
A point of some importance is considering the immu-
nophenotype of leiomyosarcomas is the coexpression of
“muscle-specific” (MSA) or “smooth muscle” actin
(SMA) isoforms with desmin. A common practice in
some centers is to rely exclusively on one of these
markers to recognize all examples of leiomyoma and
leiomyosarcoma. This is a flawed approach, in our opi-
nion, because myogenic determinants are not necessa-
rily synthesized by neoplastic smooth muscle cells in a
syntonic fashion. In other words, SMA has now been
reported in a considerable number of other lesions, in-
cluding many with a myofibroblastic nature (Figure 10).

Figure 10 – Ki-67 proliferation marker showed posi-
tivity in 30% of the tumor cells, ×200.

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383
? Discussion
There are no specific clinical features diagnostic of
leiomyosarcoma of soft tissue that distinguish these
tumors from other soft tissue sarcomas. Women are
affected more than men (2:1), with the disease typically
occurring in the 5th and 6th decades of life. This gender
distribution may reflect the proliferation of smooth
muscle that can occur in response to estrogen. The most
common site of involvement of leiomyosarcoma is the
retroperitoneum, accounting for approximately 50% of
occurrences [5]. Leiomyosarcoma of somatic soft
tissues, like other soft tissue sarcomas, often present as
an enlarging, painless mass. Although these tumors are
generally associated with small blood vessels, they
usually do not present with signs or symptoms of
vascular compression. However, when leiomyosarcoma
arises from a major blood vessel, symptoms of vascular
compromise or leg edema may be present, as well as
neurological symptoms such as numbness from
compression of an adjacent nerve. Soft tissue
leiomyosarcoma typically affects adults, however it can
present in childhood [3]. Most soft tissue sarcomas have
no clearly defined etiology, although multiple
associated or predisposing factors have been identified.
Typically, once a lesion suspicious for a sarcoma has
been discovered, diagnosis and staging studies are
performed simultaneously. Initial imaging should
include plain radiographs of the affected area, an MRI
of the lesion, and a chest CT-scan. As Angiography may
be a useful modality in cases involving a major blood
vessel. CT scanning of the chest is useful to evaluate for
the presence of metastatic disease in the lungs. The role
of PET-scanning has not been studied in particular
reference to leiomyosarcoma, but has been studied in
other soft tissue sarcomas with early promising results.
Biopsy is necessary to establish a specific diagnosis of
leiomyosarcoma, and is often accomplished using a CT-
guided core needle biopsy. This technique can be
performed in most cases with less morbidity than an
open incisional biopsy. Histologically, soft tissue
leiomyosarcomas that arise in different anatomic
locations are similar. However, based on the location of
the tumor, prognosis and possible treatments differ. For
this reason, leiomyosarcoma of soft tissues is divided
into four groups: leiomyosarcoma of soft tissue retro-
peritoneal somatic soft tissue, leiomyosarcoma of cuta-
neous origin, leiomyosarcoma of vascular origin (large
vessel), leiomyosarcoma in the immunocompromised
host. Furthermore, there are sporadic case reports of
primary leiomyosarcoma of bone, a clinically distinct
entity.
Immunohistochemical analysis suggests that the cell
line of origin of leiomyosarcoma is the smooth muscle
cell. The most common site of leiomyosarcoma of soft
tissue is the retroperitoneum, accounting for 50% of all
cases [5]. Smooth muscle sarcomas arising from the
abdominal viscera or uterus are considered to be distinct
disease entities. Other sites of involvement include the
deep soft tissues of the extremities and are referred to as
leiomyosarcoma of somatic soft tissue [2]. Soft tissue
leiomyosarcoma was at one time believed to arise from
leiomyomas, however, this is now thought to be an
extremely rare occurrence. Most malignant leiomyo-
sarcomas arise independently, and are not associated
with benign tumors. Histological studies of somatic soft
tissue leiomyosarcomas have shown that many, if not
all, of these tumors arise directly from the smooth
muscle cells lining small blood vessels. When the retro-
peritoneum is involved, presenting symptoms are
usually vague abdominal discomfort, an abdominal
mass and weight loss. Retroperitoneal leiomyosarcoma
is an aggressive disease that is often not amenable to
complete surgical resection. Leiomyosarcoma can arise
within the dermis. When this occurs, it is referred to as
cutaneous leiomyosarcoma. Unlike other forms of leio-
myosarcoma, men are affected more than women at a
ratio of 2:1 [6]. These lesions are typically small when
first diagnosed (1–2 cm), and prognosis is generally
good [7]. When leiomyosarcoma develops within the
dermis itself, it is thought to be derived from the pillar
arrecti [8]. Tumors that develop within subcutaneous
tissue arise from small or microscopic vessels and
should be considered leiomyosarcoma of somatic soft
tissue. The behavior of these tumors is more consistent
with that of deeper tumors than intradermal tumors.
When the lesion is confined to the dermis, metastasis
typically does not occur [6]. Deeper lesions can meta-
stasize in up to 30–40% of cases, usually hematoge-
nously to the lungs [7]. Treatment consists of wide
resection, and is often curative when the lesion is initially
confined to the dermis, regardless of histological grade.
The annual new cases in the U.S. are over 6000.
The five-year survival rate after diagnosis is about 50%.
What kind of biopsy is appropriate in the diagnostic
process and treatment of a patient with a soft tissue
mass? After taking medical history and performing
physical examination, the tumor is first locally staged
with MRI- or CT-scan before any biopsy [9]. Positron
emission tomography might allow differentiation
between a benign and malignant tumor [10]. The diag-
nostic accuracy of a CNB in referral centers is equi-
valent to incisional biopsies, although it may be difficult
to differentiate a low-grade malignancy from a benign
tumor mass [11]. The histological subtype and grade of
the STS can be determined for the vast majority of core
needle biopsies, and pathologists experienced in exami-
ning STS have a reproducible diagnostic accuracy
approaching 95% to 99% when comparing core needle
with incisional biopsy diagnostic approaches [11].
Incisional biopsy is the diagnostic procedure of choice if
needle biopsy is not feasible; it provides sufficient
tissues for histological diagnosis as well as other
laboratory studies that may be occasionally useful, such
as immunohistochemical or chromosomal analyses.
Sarcomas are still diagnosed after an unplanned
excision, the so-called ‘whoops approach’. The patholo-
gy report will describe an R1 (microscopically involved
margin) or R2 (macroscopically involved margin)
resection requiring further therapy. If further surgery
may render a patient disease-free (R0 resection) or an
R2 might become an R1 resection, re-resection is
essential. If this aggressive surgical policy is applied,
these patients are not apparently at risk for a worse

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outcome as compared with patients primarily referred to
a multidisciplinary sarcoma unit.
Combining functional imaging with anatomic detail
may aid in the diagnostic effectiveness of both types of
imaging techniques. For example, positron emission
tomography (PET) scanning combined with MRI [12]
can increase the utility of these techniques in certain
specific situations. Magnetic resonance spectroscopy
may be useful in some circumstances, such as assessing
patient responses to neoadjuvant chemotherapy when
resection has not yet been performed [13].
Soft tissue leiomyosarcoma was classified based on
salient gene expression characteristics. Three types of
leiomyosarcoma were proposed: (1) “simplification” of
gene expression in leiomyosarcoma, characterized by
dramatic down regulation of large number of genes;
(2) “inflammation related” gene expression, characteri-
zed by the prominent presence of lymphocyte specific
genes in the analysis; and (3) “neural” gene expression,
characterized by neuronal gene expression. Cytologic
analysis of fine-needle aspirates alone can be used to
diagnose recurrent tumor [14] or nodal metastases.
Regardless of how biopsy material is obtained, the
specimen is best evaluated by a pathologist specializing
in soft-tissue diseases.
Histological subtype should also be specified and
may occasionally require immunohistochemical analysis,
cytogenetics, or even electron microscopy. However,
there is a high degree of discordance (2% to 40%) [15]
even among expert sarcoma pathologists regarding STS
histological subtyping and grade assignment, empha-
sizing the usefulness of histological peer (and even
expert) review, as well as the importance of developing
objective and standardized methods for sarcoma
histopathological typing and grading.
Although the presence of regional lymph node
involvement is considered stage IV disease, recent
studies [16] suggest that nodal status may not confer as
ominous a prognostic impact as distant metastatic
disease. These contemporary analyses suggest that
isolated lymph node metastases may more closely
resemble an AJCC stage III rather than stage IV
survival pattern. This possibility raises the question
about appropriate management of lymphatic metastasis-
prone STS histological subtypes, such as epithelioid
sarcoma or synovial sarcoma, including the specific
issue of whether such individuals should be offered
sentinel node evaluation as part of their treatment
program, perhaps under the aegis of a prospective
clinical trial [17].
Local recurrent tumor, positive surgical margins,
>50-year-old, >20 mitoses per high power field are
adversely associated with survival.
Chemosensitivity varies according to the tumor
subtype, and the likelihood of a response and survival is
further influenced by the tumor grade, the patient’s age,
performance status, and the timing of metastatic disease
[18]. Leiomyosarcoma, for example, responds variably
to conventional chemotherapy, depending on the site
and grade of the tumor. Uterine leiomyosarcoma is
particularly aggressive, but it may respond to high-dose
gemcitabine with docetaxel. Facial and scalp angio-
sarcoma may respond to paclitaxel [19], and taxanes
may have broader utility against angiosarcomas at other
sites. A pegylated liposomal formulation of doxorubicin
(with reduced toxicity) [20] has also been reported to be
active against angiosarcomas [21].
Chemotherapy is palliative for most patients with
unresectable or metastatic disease. Ifosfamide and doxo-
rubicin are routinely used in this setting; doxorubicin as
a single agent is considered the drug of choice. Recent
studies have reevaluated ifosfamide dosing, [22] high-
dose ifosfamide with doxorubicin is commonly used
for younger patients with aggressive tumors; response
rates of approximately 50 to 60% have been reported.
It remains unclear whether this approach improves
survival, which is about 12 months in this situation [18].
Trabectidin (Yondelis, PharmaMar), a natural product
from the marine tunicate Ecteinascidia turbinata that
selectively inhibits DNA-transcription, [23] is a new
agent that has shown some activity in advanced disease
refractory to conventional cytotoxic drugs. It appears to
induce a low rate of objective remission (4%) but a high
rate of disease stabilization (a 24% rate of progression-
free survival at six months), though it is moderately
toxic [24].
? Conclusions
Surgery is the mainstay of treatment for soft-tissue
sarcomas. Neoadjuvant or adjuvant radiation therapy is
appropriate in some circumstances where local control
is an issue. Radiotherapy is useful in selected cases.
Chemotherapy is employed for the treatment of
systemic disease. Conventional chemotherapy has little
effect on the outcome of most tumors, but the
availability of novel targeted agents may drastically
improve the prognosis of some soft-tissue sarcomas, as
has been demonstrated with imatinib in the case of
gastrointestinal stromal tumors. Prompt diagnosis and
referral are desirable, since the size of the tumor at
presentation is a continuous variable for the risk of local
recurrence and metastatic disease.
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Corresponding author
Cristian Meşină, Assistant Professor, MD, PhD, Department of Surgery, University of Medicine and Pharmacy
of Craiova, 2–4 Petru Rareş Street, 200349 Craiova, Romania; Phone: +40724–513 221, e-mail:
mesina.cristian@doctor.com






Received: November 10th, 2009
Accepted: April 5th, 2010