MINISTRY OF PUBLIC HEALTH OF UKRAINE
KHARKOV NATINAL MEDICAL UNIVERSITY
МИНИСТЕРСТВО ЗДРАВООХРАНЕНИЯ УКРАИНЫ
ХАРЬКОВСКИЙ НАЦИОНАЛЬНЫЙ МЕДИЦИНСКИЙ
Soft tissue tumours
Опухоли м’яких тканей
ученым советом ХНМУ
Протокол № 6 от 19.3.2008 г.
Kharov KNMU- 2008
Харьков ХНМУ – 2008
Опухоли мягких тканей: Метод. указ. к практ. занятиям для студентов
V-VI курсов медицинских вузов, обучающихся на английском языке /
Сост. В.И. Стариков, А.Н. Белый.– Харьков: ХНМУ, 2008.– 16 с.
Soft tissue tumours are approved by the Scientific Committee of the
Kharkov state medical university and is recommended for V-th, VI-th year
students of medical faculty / Authors: V.I. Starikov, A.N. Bely.– Kharkov:
KNMU.2008. – 16 p.
Authors: Starikov V.I.
Present achievements in the field of soft tissue tumor,s are the result of advances in
molecular biology, oncogenetics, imaging techniques, immunochemistry, diagnosis by fine-
needle aspiration, surgical reconstruction, radiation therapy, and tissue banking. Benign soft
tissue tumors are fairly common and are treated with surgery alone. Prior to the 1970s, surgery
was the primary therapy for malignant soft tissue tumors, and most patients with high-grade
tumors had a poor prognosis and a significant mortality rate. Since the mid-1970s, radiation
therapy, chemotherapy, and advanced surgical techniques have helped increase long-term
survival and decrease the need for ablative surgery. Future advances in molecular oncology
may further improve diagnostic, prognostic, and treatment protocols for patients with soft
Soft tissue is defined as the supportive tissue of various organs and the nonepithelial,
extraskeletal structures exclusive of lymphohematopoietic tissues. It includes fibrous
connective tissue, adipose tissue, skeletal muscle, blood/lymph vessels, and the peripheral
nervous system. Embryologically, most of it is derived from mesoderm, with a
neuroectodermal contribution in the case of peripheral nerves.
Soft tissue tumors are a large and heterogeneous group of neoplasms. Traditionally,
tumors have been classified according to histogenetic features. (Fibrosarcoma, for example, is
categorized as a tumor arising from fibroblasts.) However, histomorphologic,
immunohistochemical, and experimental data suggest that most, if not all, sarcomas arise from
primitive, multipotential mesenchymal cells, which in the course of neoplastic transformation
differentiate along one or more lines. A liposarcoma appears to arise from a lipoblast but may
actually develop through lipoblastic differentiation of a precursor multipotent mesenchymal
cell. At the clinical level, soft tissue tumors are classified according to various parameters,
including location, growth pattern, likelihood of recurrence, presence and distribution of
metastases, patient age, and prognosis.
Although most soft tissue tumors of various histogenetic types are classified as either
benign or malignant, many are of an intermediate nature, which typically implies aggressive
local behavior with a low to moderate propensity to metastasize.
In general, benign soft tissue tumors occur at least 10 times more frequently than
malignant ones, although the true incidence of soft tissue tumors is not well documented.
However, some insight regarding the incidence of soft tissue sarcomas can be derived
from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)
Program, which, between 1973 and 1983, accumulated data on 6883 such tumors.
Overall, age-adjusted annual incidence of soft tissue sarcomas ranges from 15-35 per
1 million population. The rate increases steadily with age and is slightly higher in men than in
Malignant soft tissue tumors occur twice as often as primary bone sarcomas.
Approximately 45% of sarcomas occur in the lower extremities, 15% in the upper
extremities, 10% in the head-and-neck region, 15% in the retroperitoneum, and the remaining
15% in the abdominal and chest wall. Visceral sarcomas, arising from the connective tissue
stroma in parenchymal organs, are not common.
The different types of soft tissue tumors have distinct age distributions.
o Rhabdomyosarcoma is seen more frequently in children and young adults.
o Synovial sarcoma arises in young adults.
o Malignant fibrous histiocytoma and liposarcoma generally occur in older adults.
Benign deep masses in adults usually are due to intramuscular lipoma.
In general, the prognosis in older patients with a diagnosis of high-grade sarcoma is
The incidence of soft tissue tumors is slightly higher in males than in females.
Good evidence exists suggesting that certain genetic disorders and gene mutations are
predisposing factors for some benign and malignant soft tissue tumors. The NF1 gene in
neurofibromatosis is a classic example, predisposing patients to multiple neurofibromas with a
proclivity for malignant transformation. Many tumor suppressor genes, oncogenes, and
cytogenetic defects are now associated with various soft tissue sarcomas. Other clinical risk
factors account for a small proportion of soft tissue malignancies.
Cytogenetic abnormalities have a significant role in diagnosis, and, in the future, some
of these abnormalities may become therapeutically significant. Specific translocations
involving selected genes have been observed. One of these, the t(X;18) translocation in
synovial sarcoma, results in fusion of the SYT gene from chromosome 18 to either of 2 highly
homologous genes at Xp11, SSX1 or SSX2. SYT-SSX fusion transcript may be detected by
reverse transcriptase-polymerase chain reaction assay, using a cytologic specimen from fine-
needle aspiration biopsy (FNAB), histologic material from paraffin block, or frozen material.
Similar to postirradiation bone tumors, postirradiation fibrosarcomas have been
described. The pathogenetic mechanism is the emergence of radiation-induced genetic
mutations that encourage neoplastic transformation.
As observed in patients with late-stage breast carcinoma, chronic lymphedema may
predispose individuals to the development of lymphangiosarcoma.
An association between exposure to various carcinogens and an increased incidence of
soft tissue tumors has been reported. The occurrence of hepatic angiosarcoma, for example, has
been linked to arsenic, thorium dioxide, and vinyl chloride exposure.
A classic example of an infection-induced soft tissue tumor is Kaposi sarcoma resulting
from human herpesvirus type 8 in patients with human immunodeficiency virus (HIV).
Infection with Epstein-Barr virus in an immunocompromised host also increases the likelihood
of soft tissue tumor development.
The relationship between trauma and soft tissue tumors appears to be coincidental.
Trauma probably draws medical attention to a pre-existing lesion.
Generally, soft tissue tumors grow centripetally, although some benign tumors, such as
fibrous lesions, may grow longitudinally along tissue planes. Most soft tissue tumors respect
fascial boundaries, remaining confined to the compartment of origin until the later stages of
development. Once the tumor reaches the anatomic limits of the compartment, the tumor is
more likely to breach compartmental boundaries. Major neurovascular structures usually are
displaced as opposed to being enveloped or invaded by tumor. Tumors arising in
extracompartmental locations, such as the popliteal fossa, may expand more quickly because of
a lack of fascial boundaries; they are also more likely to involve neurovascular structures.
The peripheral portion of the tumor compresses surrounding, normal soft tissue because
of centripetal expansile growth. This results in the formation of a relatively well-defined zone
of compressed fibrous tissue potentially containing scattered tumor cells. This zone may also
consist of inflammatory cells and demonstrate neovascularity. A thin layer of tissue called the
reactive zone surrounds the compression zone, especially in higher-grade tumors. Together, the
compression and reactive zones form a pseudocapsule that encloses the tumor and is useful in
defining the extent of surgical resection.
Some extremely aggressive lesions with infiltrative growth patterns, such as childhood
rhabdomyosarcoma, may not respect anatomic compartmental boundaries and frequently will
invade fascial planes.
Soft tissue sarcomas have the propensity to recur locally. Because recurrences are more
difficult to treat than the primary lesion is, complete resection and appropriate use of radiation
therapy are critical during the initial treatment. The pseudocapsule provides surgeons with a
more or less obvious plane of dissection; however, such an excision can leave behind
microscopic or occasionally gross tumor. This may lead to local recurrences in up to 80% of
patients. The addition of postoperative radiation therapy decreases the risk of recurrence
associated with a marginal resection.
Technical ease of resectability (and, thus, the likelihood of local control) may be
affected by the location of a soft tissue sarcoma. For example, lesions of the head and neck are
more likely to involve or abut vital structures; consequently, they often are more difficult to
resect than are lesions of the extremities. Even in an extremity, the tumor site may have
prognostic implications. For proximal tumors, local control is more difficult to achieve than in
tumors located more distally. Retroperitoneal sarcomas, which typically have a poor prognosis,
have a higher proclivity for local recurrence and for intra-abdominal dissemination.
The pattern of recurrence generally is predictable, and most tumors destined to recur do
so within the first 2-3 years. Adjuvant radiation therapy clearly minimizes local recurrence, but
its ability to increase overall chances of survival, although likely, is not certain. Adjuvant
chemotherapy may decrease the risk of local recurrence of high-grade tumors, presumably
because of a reduction in the size of the tumor and an increase in the reactive zone, but this
notion is very controversial.
Regional lymph node involvement is rare in soft tissue sarcomas; fewer than 4% of
cases have nodal metastases at presentation. Lymph node involvement is more frequent in
epithelioid sarcoma, rhabdomyosarcoma, synovial sarcoma, and clear cell sarcoma. Carcinoma
and melanoma should be included in the differential diagnosis for any mass presenting with
lymph node metastases.
Many patients with high-grade soft tissue sarcomas, as well as a few with the low-grade
type, progress to metastatic disease, even following adequate local control of the primary
tumor. The lung is by far the most common site of metastasis, which occurs in up to 52% of
patients with high-grade lesions. Although, at the time of presentation, most patients do not
have clinically evident metastases, they may have occult micrometastases that eventually
manifest clinically. This would appear to be an impetus for the development of
chemotherapeutic methods of systemic disease control. At present, however, this is a
controversial area of investigation, and it is uncertain whether systemic chemotherapy can
improve long-term survival rates for patients with high-grade sarcomas.
A mass is the most common sign of a soft tissue tumor. It usually is painless and does
not cause limb dysfunction. However, depending on the anatomic location of the tumor, it may
cause pain or neurologic symptoms by compressing or stretching nerves, by irritating overlying
bursae, or by expanding sensitive structures. A rapid rate of increase in the size of a mass
should arouse suspicion that the lesion is malignant.
Physical examination can be used to determine the location and size of a mass and to
exclude other, more common causes of pain. Whether the mass is deep or subcutaneous,
transilluminates (cysts), and adheres to underlying structures also can be gleaned from physical
examination. Regional lymph nodes should be examined as well. Neurovascular examination is
useful for the detection of either primary or secondary tumor involvement.
Extremity masses larger than 5-7 cm and deeper than subcutaneous tissue favor a
diagnosis of a malignant soft tissue tumor. However, up to 30% of soft tissue sarcomas occur in
subcutaneous tissue and exhibit relatively less aggressive behavior. 6
Other than histologic and cytogenetic analysis, no specific laboratory tests exist for
diagnosing soft tissue tumors. However, ancillary studies may be indicated as part of the
general workup in patients with other systemic conditions.
In the past 2 decades, imaging studies have contributed greatly to the management of
soft tissue tumors. Although these studies cannot themselves yield a specific diagnosis (except
for a few conditions, such as lipoma or liposarcoma), they are extremely useful for defining
anatomic location, tumor extent, and involvement of vital structures.
Imaging studies should be obtained before biopsy to ensure that a biopsy of a
potentially malignant lesion is taken in a manner that will not preclude limb-salvage surgery.
Imaging should also be performed before biopsy, to prevent the biopsy tract from adversely
affecting the capture of anatomic detail by magnetic resonance imaging (MRI). The
relationship of the tumor and surrounding normal structures to the planned biopsy site should
be evaluated, as should the functional status of the involved limb, signs of lymph node
involvement, and any other factors that could compromise optimal surgical or radiation
Because prognosis is primarily dependent on the disease stage rather than the
histologic tumor type, evaluation of local and distant extent is pivotal in the ultimate
management of soft tissue sarcoma. Imaging methods commonly used for such evaluation
include plain radiographs, computed tomography (CT) scanning, MRI, and bone scintigraphy
(bone scan). Positron emission tomography (PET) scanning is being used more frequently to
assess the metabolic activity and, presumably, the biologic aggressiveness of a lesion.
Angiography to evaluate any vascular involvement by soft tissue tumors has essentially been
replaced by MRI.
o CT scanning
Check for presence and number of pulmonary metastases.
Consider performing a CT scan of the liver in cases of intra-abdominal or
In contrast to CT scanning, MRI is not limited to the transverse (axial) plane. Coronal,
sagittal, and oblique planes may be imaged.
MRI best defines the relationship between a tumor and adjacent anatomic structures,
such as compartment boundaries, nerves, vessels, and muscle.
Although for most patients MRI alone suffices, the information obtained from CT
scanning and MRI of the primary tumor occasionally may be complementary. Bony
involvement may be better assessed with a CT scan, as may the boundary between normal
muscle and fibrous lesions.
Biopsy usually is indicated for a soft tissue mass arising in a patient without a history
of trauma or for a mass that persists for more than 6 weeks following local trauma. All soft
tissue masses larger than 5 cm, as well as any enlarging or symptomatic lesions, also should be
biopsied. Small, subcutaneous lesions that persist unchanged for years may be considered for
observation rather than biopsy. A high level of suspicion is necessary to ensure early treatment.
Early tissue diagnosis is the most important component of multimodality treatment for
soft tissue tumor. Proper and timely biopsy is critical. An inadequately performed biopsy may
complicate patient care and result in loss of limb or life. Several biopsy techniques are
available, including FNAB, core needle biopsy, incisional biopsy, and excisional biopsy. The
choice of biopsy is based on the size and location of the mass and the experience of the
surgeon. Excisional biopsy is indicated only for small, superficial masses (<3-5 cm in greatest
dimension), in which the probability of malignancy is low. Effective reexcision is more likely
for smaller malignant lesions that initially are unintentionally treated as benign.
o Fine-needle aspiration biopsy
This is a cytologic technique involving the use of a fine-gauge (usually 21- to 25-
gauge) needle to aspirate individual tumor cells and microfragments from the mass. The
aspirated material can be examined as a cytology smear, with immediate evaluation of
specimen adequacy. Depending on the initial cytomorphologic features observed during the
onsite adequacy evaluation, additional passes may be performed at the same time to obtain
more material for cell-block preparation (for histomorphology and immunocytochemical
evaluation), cytogenetic analysis, or examination using electron microscopy or microbiology
cultures. With the help of relevant ancillary techniques, diagnostic accuracy with FNAB is very
high, and soft tissue tumors can be graded. This method is minimally invasive and relatively
Published literature highlights the rarity of needle-track seeding with FNAB. Core
biopsy, on the other hand, has a higher rate of needle-track seeding.
o Core needle biopsy
This technique retrieves a thin core of tissue (approximately 1×10 mm). The
procedure may be performed using various needles (most commonly a Tru-Cut needle ). The
core may not be representative of the entire tumor, so nonrepresentative grading is possible.
FNAB samples a larger area of the tumor than does core needle biopsy.
Concern has been expressed about possible dissemination of tumor cells beyond the
confines of the primary site; however, this appears to be uncommon. Both core needle and
open biopsies can result in histologic diagnosis and grading of a sarcoma in more than 90% of
cases. Similar to FNAB, a biopsy may be taken of deeper lesions under image guidance (eg,
CT scanning, ultrasound scanning, MRI).
o Incisional biopsy
Open incisional biopsy is used for most soft tissue masses. A generous wedge of
tissue is removed, with minimal manipulation of tissue. Several important technical factors
must be considered while performing an incisional biopsy. In the case of extremity lesions, the
incision should be oriented along the long axis. Any biopsy incision and tract should be
oriented so that they can be resected during definitive surgery for the soft tissue mass.
The sample obtained may be evaluated for adequacy by using intraoperative cytology
or a frozen section at the time of biopsy. Meticulous hemostasis minimizes local dissemination
of tumor cells.
o Excisional biopsy
With this method, the entire lesion is removed surgically. Many sarcomas appear to
be well demarcated grossly. Microscopically, however, the demarcation usually is seen to exist
along a pseudocapsule with foci of infiltrating tumor. Removal of the tumor along this apparent
plane may leave gross or microscopic sarcoma behind.
Excisional biopsy may be safely performed for small, superficial tumors (<
approximately 5 cm in diameter) or for those known to be benign.
o Frozen section and intraoperative cytology
Frozen section and intraoperative cytology are extremely helpful tools for the
management of soft tissue tumors.13,14 Proper communication with a musculoskeletal
oncopathologist preoperatively and intraoperatively is essential for evaluation. Frozen section
can guide retrieval of adequate diagnostic material and, depending on the initial evaluation, can
be an important triage mechanism to direct further pathologic workup.
If support is available, FNAB offers most of the advantages for diagnostic biopsy that
frozen sectioning does. However, open biopsy—with the help of frozen-sectioning support—
may be indicated when the FNAB result is equivocal or for other clinical reasons.
Fatty lesions are not suitable for frozen-section evaluation, because of a loss of
diagnostic material during frozen sectioning and other technical difficulties. In addition,
freezing compromises the final interpretation on permanent sections.
The outline below comprises the histologic classification of soft tissue tumors. The
histopathologic evaluation of these lesions, with categorization into one of the groups listed
below, is performed on permanent sections. Such classification may require data from various
sources, including immunochemical, cytogenetic, electron microscopic, and molecular studies.
Sarcomas usually are assigned a histologic grade. Low-grade lesions rarely metastasize
but can be locally aggressive; high-grade sarcomas pose a significant threat of metastasis and
carry a greater risk of local recurrence. Although assigning a pathologic grade to an individual
tumor is a subjective and difficult task, the grade's clinical importance in determining a
treatment strategy cannot be overemphasized. An ideal biopsy, with proper sampling of the
lesion, should allow a confident grade assignment.
Many grading systems exist; they generally are based on evaluation of
histomorphologic features, including cellularity, cellular pleomorphism, mitotic activity, and
necrosis, as well as histologic category. A 3-grade system (grades 1, 2, 3) may be simplified
further by lumping the sarcomas into low-grade (grade 1) and high-grade (grade 2) categories.
Other markers have been investigated as potential indicators of proliferation activity of
soft tissue tumors. They include Ki-67, argyrophilic stain for nucleolar organizer regions
(AgNOR), mast cell counts, and DNA flow cytometry.
As part of this 2002 WHO classification, soft tissue tumors are divided into the
following 4 categories.
Benign - These usually do not recur locally, and if they do, the recurrence is
nondestructive and almost always readily curable by complete local excision. Morphologically
benign lesions, which are extremely rare, may give rise to distant metastases, which cannot be
predicted on the basis of routine, contemporary histologic evaluation. This is best documented
in rare, cutaneous benign fibrous histiocytoma.
Intermediate (locally aggressive) - These tumors show an infiltrative and locally
destructive growth pattern. However, although they may recur locally, they do not metastasize.
They usually require excision with a wide margin of normal tissue for better local control. The
example in this category is desmoid (fibromatosis).
Intermediate (rarely metastasizing) - These tumors are often locally aggressive, but in
some cases, they also have a tendency to produce distant metastases (usually in a lymph node
or lung). This risk is low (<2%), but histomorphologically, it is not reproducibly predictable.
The classic examples in this group are plexiform fibrohistiocytic tumor and angiomatoid
Malignant - Soft tissue sarcomas are locally destructive with the potential to recur.
The risk of distant metastasis is significant. (Depending on histologic type and grade, the
potential ranges from 20% to almost 100%). Histologically low-grade sarcomas have a lower
chance of metastasis (only 2-10%). However, the recurrences of such tumors may advance in
grade and attain a higher risk of metastatic potential similar to that associated with
myxofibrosarcoma and leiomyosarcoma.
This terminology should not be confused with the grading system mentioned above, in
which grade 2 may be regarded as intermediate.
Histologic grading is an important prognostic factor in sarcomas. Therefore, the usual
tumor, node, metastases (TNM) classification scheme is modified into a grading, tumor, node,
metastases (GTNM) staging system for soft tissue tumors. This system, which is clinically very
useful, stratifies patients into groups with distinct prognostic patterns.
Size of the tumor also is of prognostic significance. The risk of metastasis and death is
higher with larger primary sarcomas. According to the current American Joint Commission on
Cancer (AJCC) system, tumors of 5 cm or less in greatest dimension are designated as T1, and
those exceeding 5 cm are categorized as T2. Although they are not a part of the AJCC system,
tumors larger than 10 cm have a worse prognosis than do those larger than 5 cm.
Site is another important prognostic factor. Superficially located tumors (those situated
entirely superficial to the deep or muscular fascia) have a relatively better prognosis than that
characterizing deeper sarcomas. Alternative staging systems incorporate site into their
GTNM staging system definitions are as follows:
G - Tumor grade
o G1 - Well differentiated
o G2 - Moderately differentiated
o G3 - Poorly differentiated
T - Primary tumor
o T1 - Tumor less than 5 cm in greatest diameter
o T2 - Tumor more than 5 cm in greatest diameter
N - Regional lymph node involvement
o N0 - No known metastasis to lymph nodes
o N1 - Verified metastasis to lymph nodes
M - Distant metastasis
o M0 - No known distant metastasis
o M1 - Known distant metastasis
Table. AJCC GTNM Classification and Stage Grouping of Soft Tissue Sarcomas
Stage Groupings Tumor Grade Primary Tumor Regional Lymph Distant
Stage IA G1 T1 N0 M0
Stage IB G1 T2 N0 M0
Stage II A G2 T1 N0 M0
Stage IIB G2 T2 N0 M0
Stage IIIA G3 T1 N0 M0
Stage IIIB G3 T2 N0 M0
Stage IVA Any G Any T N1 M0
Stage IVB Any G Any T Any N M1
High-grade soft tissue sarcomas often are treated with ifosfamide- and doxorubicin-
based chemotherapy. This is controversial, as no definitive studies exist proving that adjuvant
chemotherapy contributes to prolonged overall survival. 20,21
Complete local excision is adequate treatment for benign soft tissue tumors. However, a
variety of treatment options, including surgery alone or combined with radiation therapy or
chemotherapy, may be considered for treatment of localized primary and recurrent sarcomas.
Extremity sarcomas may be treated surgically, with or without radiation therapy and
Surgery is the most important component of any treatment plan for a clinically localized
primary or recurrent soft tissue sarcoma. On the basis of the achievable margin, 4 types of
excisions may be performed.
Intracapsular excisions and amputation - The excision or amputation passes within the
tumor itself. The tumor inside the pseudocapsule is removed (often piecemeal). Incidence of
local recurrence with these types of excisions is virtually 100%; these procedures are
performed only in unusual circumstances.
Marginal excisions and amputation - The excision is performed through the
pseudocapsule surrounding the tumor. Shelling-out procedures and most excisional biopsies
belong to this category. The chance of local recurrence is 20-75%, depending on the nature of
the tumor and whether or not radiotherapy is used.
Wide excisions and amputation - The tumor is excised with a wide margin of
surrounding normal tissue but within the muscular compartment. Without adjuvant therapy, the
incidence of local recurrence following wide excision varies but may reach 30%; the rate of
recurrence depends on the selection criteria used and the adequacy of the histologically
assessed surgical margin. A wide amputation is performed through the normal tissue proximal
to the reactive zone around the tumor but remains within the involved compartment. Limb-
sparing procedures belong to this category.
Radical excisions and amputation - These are en bloc excisions of the tumor along
with the entire muscle compartment. Amputation with disarticulation of the joint proximal to
the involved compartment is called radical amputation. The risk of local recurrence is lowest
with this procedure.
Small, superficial, or low-grade tumors treated with only a wide, local excision have a
very low risk of local recurrence.12 For better local control, many patients undergoing surgical
excision receive radiation therapy. In patients who refuse or cannot tolerate surgery, radiation
alone can be an effective treatment for certain extremity sarcomas.
Postoperative radiation therapy - Following wide surgical excision, radiation therapy
enhances local control for primary extremity sarcomas. The concept of limb-sparing surgery
with postoperative radiation has been validated by randomized trials of amputation versus wide
local excision. Usually, a total dose of about 60 grays (Gy) is adequate.
Brachytherapy - Postoperative radiation can also be delivered to the tumor bed by
means of brachytherapy (in which radioactive sources are implanted in the patient). The
advantage of this approach is that it requires a much shorter time for initiation and completion
of therapy than does external radiation. External beam radiation is used for 6 weeks beginning
a month or more following surgery; brachytherapy usually is started within a week of surgery
and completed in 4 or 5 days. Because of its technical complexity, brachytherapy requires an
experienced radiation oncologist during the operating procedure. Brachytherapy and external
beam radiation appear to be equally effective when properly administered.
Preoperative radiation therapy - The employment of preoperative radiation therapy
may allow less radical forms of surgery to be used, specifically on large tumors that otherwise
may compromise limb-sparing procedures. Radiation-induced tumor shrinkage decreases the
magnitude of resection needed and reduces the risk of seeding by viable tumor cells. Local
fibrosis may make the resection more challenging.
Even after achieving local control in patients with intermediate- and high-grade soft
tissue sarcomas, the risk of metastatic disease following multimodality treatments without
amputation is as high as 50%. The risk is even greater if stage IIIB tumors are included. Thus,
effective systemic, adjuvant chemotherapy is desirable following definitive treatment of local
disease. However, conclusive evidence that adjuvant chemotherapy for extremity sarcomas
increases overall survival rates is lacking. Randomized trials have not demonstrated that higher
overall survival rates occur with surgery and adjuvant doxorubicin therapy than with surgery
In randomized clinical trials, multiagent chemotherapy with doxorubicin,
cyclophosphamide, and methotrexate following surgery improved disease-free survival rates
for patients with high-grade extremity sarcomas (except when the lesions were associated with
the trunk or retroperitoneum). However, the toxicity associated with this regimen was
Preoperative chemotherapy, also called neoadjuvant chemotherapy, is an option for
most patients with osteosarcomas of the extremity. However, it has not been established that
this treatment is superior to conventional chemotherapy for soft tissue tumors. Preoperative
chemotherapy may be used alone or with preoperative or postoperative radiation therapy.
A significant hypothetical advantage of neoadjuvant chemotherapy is that it allows
treatment effectiveness to be monitored through evaluation of the degree of necrosis in the
resected primary tumor. However, no evidence exists that this results in improved clinical
As with sarcomas of extremities, options for therapeutic management of nonextremity
sarcomas include surgery, radiation, and chemotherapy. Sarcomas arising in the head and neck,
thoracic or abdominal wall, mediastinum, or retroperitoneum are difficult to treat. Most of
these tumors develop in areas where surrounding normal tissue limits the maximum dosage of
radiation that can safely be delivered to the tumor bed. In general, the risk of local recurrence is
high. For retroperitoneal tumors, the patient usually succumbs as a result of local
complications, before metastases are evident.
Recurrent and metastatic disease
As many as 35% of patients develop local recurrence or distant metastases following a
combination of surgical resection and adjuvant therapy. Eighty percent of local recurrences and
disseminated metastases were observed within 5 years. 5
Although removal of normal lymph nodes generally has no role in the treatment of soft
tissue sarcomas, dissection of biopsy-proven tumor-positive lymph nodes is recommended in
the absence of metastatic disease elsewhere. Radical lymphadenectomy in patients who have
nodal involvement without pulmonary metastases may yield better 5-year survival rates.
Whenever it is technically amenable, surgical removal of pulmonary metastases is
recommended following thorough evaluation for extrapulmonary tumor. In 1 study, resection
of isolated pulmonary metastases achieved an actuarial 3-year survival rate of 38%. The
presence of fewer than 3 or 4 metastatic nodules, as observed with preoperative CT scanning, is
a favorable prognostic factor.
Because some clinical response has been achieved with neoadjuvant chemotherapy in
soft tissue sarcomas, studies to evaluate the use of high-dose therapy with autologous stem cell
transplantation have been conducted. These studies have been pursued for patients with a high
risk of metastatic disease at the time of diagnosis and as salvage therapy at the time of disease
relapse. Most of this research has been conducted in children with small blue cell tumors
(Ewing sarcomas, PNETs).27 The results of these studies have been mixed. Randomized trials
have not been reported. Some studies showed better survival rates for patients treated with the
newer technique than for control patients treated with conventional therapy. Other research has
failed to show any improvement in outcomes. Thus, the use of high-dose therapy in sarcomas
remains controversial. This approach should be investigated further in well-designed,
randomized clinical trials.
Compressive bandages and suction drains should be used to minimize seroma formation
that can delay administration of chemotherapy or radiation therapy. Physical therapy and
rehabilitation support may be required.
General follow-up care includes surveillance studies to evaluate local recurrence and
distant metastasis of malignant and intermediate tumors. The precise interval between and the
duration of various follow-up studies are not well defined. In general, vigorous surveillance
continues for 3-5 years after treatment. Benign tumors generally do not require such
Complications can be divided into those that occur before therapy is completed and
those that develop after its completion.
Before completion of therapy
Related to the tumor: Depending on histopathologic category and anatomic site, the
tumor may cause complications such as skin ulceration, thrombocytopenia, hemorrhage, and
Related to operative procedures: Infection and wound dehiscence are possible.
After completion of therapy
Related to the tumor: Complications include local recurrence and distant metastasis.
Related to chemotherapy and radiation therapy: Infections may result from
immunosuppression. Postirradiation sarcomas can occur, usually 10 years or longer after
Outcome and Prognosis
Outcome and prognosis depend on several, often interrelated factors.
Tumor size - As with tumors of other tissues, a direct relationship exists between the
size of soft tissue sarcomas and outcome. The larger tumors confer a worse prognosis.
Depth of tumor - Superficially located tumors (dermis and subcutaneous tissue) have
a relatively better prognosis than do deep-seated lesions (intermuscular/intramuscular,
retroperitoneal) of similar histologic type. This difference probably results from the fact that
superficial lesions are considerably smaller at the time of excision.
Histologic type - With few exceptions, most sarcomas of the same stage and grade
behave the same regardless of histologic subtype. Some soft tissue tumors (eg, atypical
lipomatous tumors) are low-grade, without any ability to metastasize. Others, such as
pleomorphic liposarcoma, are highly aggressive, with a tendency for distant metastases.
Surgical margins - Adequacy of surgical margins is directly related to local relapse.
However, development of distant metastases may not be related to the development of local
Histologic grade - A relationship exists between various microscopic grading systems
Clinical stage - Clinical stage is the most important predictor of clinical outcome.
DNA ploidy - DNA ploidy can be evaluated by flow-cytometric studies performed on
formalin-fixed, paraffin-embedded tissue sections or by image analysis using cytology smears.
Aneuploidy is observed in tumors that have a higher microscopic grade and a greater rate of
cell proliferation. However, its role as an independent prognostic factor has not been
Cell proliferation - The number of mitotic figures stratifies the tumors into benign,
intermediate, and malignant categories and is incorporated into most grading systems.
Proliferation markers, including Ki-67 and p105, are useful for evaluation of proliferative
activity and its relationship to prognosis. However, similar to ploidy, proliferation markers
remain to be established as independent prognostic factors.
Oncogene mutations - Mutations of TP53, overexpression of MDM2, and altered
expression of the retinoblastoma gene have reportedly been associated with a worse prognosis.
Future and Controversies
Management of soft tissue tumors may evolve as a result of the advent of molecular
diagnostics and antitumor therapies. It is problematic, however, that despite the existence of
many histologic subtypes of soft tissue tumors, only a small number of them are seen at any
one institution. More multi-institutional studies are necessary.
Soft tissue sarcomas are challenging lesions that demand a multidisciplinary and
multimodality approach for proper clinical evaluation and treatment. Although, in the past,
high-grade extremity sarcomas were treated with amputation, limb-sparing therapies for these
tumors are well established today. The successful management of such lesions requires a
multidisciplinary team of surgeons, radiologists, pathologists, medical oncologists, radiation
oncologists, oncology nurses, rehabilitation therapists, and social workers.
Because of the comparative rarity of soft tissue sarcomas and a general lack of related
medical expertise, patients with these tumors should be considered for referral, preferably
during the initial evaluation phase, to medical centers experienced in sarcoma management.