1
Bone and Soft-tissue Sarcomas:
Epidemiology, Radiology,
Pathology and Fundamentals of
Surgical Treatment
Barry Shmookler, Jacob Bickels, James Jelinek, Paul
Sugarbaker and Martin M. Malawer
OVERVIEW
An understanding of the basic biology and pathology of bone and soft-tissue tumors is essential for appropriate
planning of their treatment. This chapter reviews the unique biological behavior of soft-tissue and bone sarcomas,
which underlies the basis for their staging, resection, and the use of appropriate adjuvant treatment modalities.
A detailed description of the clinical, radiographic, and pathological characteristics for the most common
sarcomas is presented.
Malawer Chapter 01 21/02/2001 14:56 Page 3
BIOLOGY AND NATURAL HISTORY OF BONE
AND SOFT-TISSUE TUMORS
Soft-tissue and bone sarcomas are a rare and hetero-
geneous group of tumors. Although soft tissues and
bone comprise 75% of the average body weight, these
neoplasms represent less than 1% of all adult and 15%
of pediatric malignancies. The annual incidence in the
United States, which remains relatively constant, is
approximately 6000–7000 soft-tissue and 2500 bone
sarcomas. Because these lesions are so rare, few pathol-
ogists have sufficient experience to deal comfortably
with their diagnosis. This is further compounded by
the steady evolution in the classification of soft-tissue
and bone tumors, which is based on their biological
behavior, ultrastructure, and results of immunohisto-
chemical and cytogenetic studies.
Risk factors for soft-tissue and bone sarcomas include
previous radiation therapy, exposure to chemicals (e.g.,
vinyl chloride, arsenic), immunodeficiency, prior injury
(scars, burns), chronic tissue irritation (foreign-body
implants, lymphedema), neurofibromatosis, Paget’s
disease, bone infarcts, and genetic cancer syndromes
(hereditary retinoblastoma, Li–Fraumeni syndrome,
Gardner’s syndrome). In most patients, however, no
specific etiology can be identified.
Sarcomas originate primarily from elements of the
mesodermal embryonic layer. Soft-tissue sarcomas are
classified according to the adult tissue that they resem-
ble. Similarly, bone sarcomas are usually classified
according to the type of matrix production: osteoid-
producing sarcomas are classified as osteosarcomas,
and chondroid-producing sarcomas are classified as
chondrosarcomas. The three most common soft-tissue
sarcomas are malignant fibrous histiocytoma (MFH),
liposarcoma, and leiomyosarcoma. These tumors are
anatomic site-dependent; in the extremities the
common subtypes are MFH and liposarcoma, whereas
liposarcomas and leiomyosarcoma are the common
subtypes in the retroperitoneum and the abdominal
cavity. The most common bone sarcomas are osteo-
sarcoma, chondrosarcoma, and Ewing’s sarcoma.
Although soft-tissue sarcomas can arise anywhere in
the body, the lower extremities are the most common
site. Incidence is as follows: lower extremities – 46%;
trunk – 19%; upper extremities – 13%; retroperitoneum
– 12%; head and neck – 9%; other locations – 1%. The
presenting symptoms and signs of soft-tissue sarcomas
are nonspecific; they commonly present as a painless,
slow-growing mass. Diagnosis of sarcomas involving
the abdominal and pelvic cavity is subtle; these tumors
may progress for long periods without causing overt
symptoms. Their location deep within the body
precludes palpation of the tumor mass early in the
course of the disease; consequently, these tumors often
reach tremendous size prior to diagnosis.
In the past two decades, survival and the quality of
life of patients with soft-tissue and bone sarcomas have
dramatically improved as a result of the multimodality
treatment approach. Surgery, used in combination with
chemotherapy and radiation therapy, can achieve cure
in the majority of patients with soft-tissue and bone
sarcomas and resection is performed in lieu of
amputation in more than 90% of all patients. Principles
of chemotherapy and radiation therapy in the
treatment of soft-tissue and bone sarcomas are
discussed in Chapters 3, 4, and 5.
Biological Behavior
Tumors arising in bone and soft tissues have charac-
teristic patterns of biological behavior because of their
common mesenchymal origin and anatomical environ-
ment. Those unique patterns form the basis of the staging
system and current treatment strategies. Histologically,
sarcomas are graded as low, intermediate, or high
grade. The grade is based on tumor morphology, extent
of pleomorphism, atypia, mitosis, and necrosis. It
represents its biological aggressiveness and correlates
with the likelihood of metastases.
Sarcomas form a solid mass that grows centrifugally
with the periphery of the lesion being the least mature.
In contradistinction to the true capsule that surrounds
benign lesions, which is composed of compressed
normal cells, sarcomas are generally enclosed by a
reactive zone, or pseudocapsule. This consists of
compressed tumor cells and a fibrovascular zone of
reactive tissue with a variable inflammatory
component that interacts with the surrounding normal
tissues. The thickness of the reactive zone varies with
the histogenic type and grade of malignancy. High-
grade sarcomas have a poorly defined reactive zone
that may be locally invaded by the tumor (Figure 1.1).
Musculoskeletal Cancer Surgery4
Figure 1.1 A pseudocapsule of a high-grade soft-tissue sar-
coma (arrows). It is composed of compressed tumor cells
and a fibrovascular zone of reactive inflammatory response.
Malawer Chapter 01 21/02/2001 14:56 Page 4
In addition, they may break through the pseudo-
capsule to form metastases, termed “skip metastases”,
within the same anatomic compartment in which the
lesion is located. By definition, these are locoregional
micrometastases that have not passed through the
circulation (Figure 1.2). This phenomenon may be
responsible for local recurrences that develop in spite of
apparently negative margins after a resection.
Although low-grade sarcomas regularly interdigitate
into the reactive zone, they rarely form tumor skip
nodules beyond that area.
Sarcomas respect anatomical borders. Local anatomy
influences tumor growth by setting natural barriers to
extension. In general, sarcomas take the path of least
resistance and initially grow within the anatomical
compartment in which they arose. In a later stage the
walls of that compartment are violated (either the
cortex of a bone or aponeurosis of a muscle), and the
tumor breaks into a surrounding compartment (Figure
1.3). Most bone sarcomas are bicompartmental at the
time of presentation; they destroy the overlying cortex
and extend directly into the adjacent soft tissues
(Figures 1.4, 1.5). Soft-tissue sarcomas may arise
between compartments (extracompartmental) or in an
anatomical site that is not walled off by anatomical
barriers such as the intermuscular or subcutaneous
planes. In the latter case they remain extracompart-
mental and only in a later stage break into the adjacent
compartment. Carcinomas, on the other hand, directly
invade the surrounding tissues, irrespective of
compartmental borders (Figure 1.6).
Bone and Soft-tissue Sarcomas 5
Figure 1.2 High-grade sarcomas may break through the pseudocapsule to form “skip” metastases within the same anatomical
compartment. They are occasionally found with low-grade sarcomas. Skip nodules are tumor foci not in continuity with the
main tumor mass that form outside the pseudocapsule. “Satellite"” nodules, by contrast, form within the pseudocapsule. (A)
Multiple satellite nodules (arrows) associated with a high-grade MFH. Note the normal intervening tissue. (B) “Skip” metastases
(arrows) from an osteosarcoma of the distal femur. This finding is preoperatively documented in less than 5% of patients.
A
B
Malawer Chapter 01 21/02/2001 14:56 Page 5
Musculoskeletal Cancer Surgery6
A B
Figure 1.3 (A) Sagittal section of a high-grade osteosar-
coma of the distal femur. The growth plate, although not
invaded by the tumor in this case, is not considered an
anatomical barrier to tumor extension. This is probably
because of the numerous vascular channels that pass
through the growth plate to the epiphysis. However, the
articular cartilage is an anatomical barrier to tumor
extension and very rarely is directly violated by a tumor. (B)
Coronal section of a high-grade osteosarcoma of the distal
femur. Although gross involvement of the epiphysis and
medial cortical breakthrough and soft-tissue extension are
evident, the articular cartilage is intact. This phenomenon
allows intra-articular resection of high-grade sarcomas of the
distal femur in most cases. Thick fascial planes are barriers to
tumor extension. (C) axial MRI, showing a high-grade
leiomyosarcoma of the vastus lateralis and vastus inter-
medius muscles. The tumor does not penetrate (clockwise)
the lateral intermuscular septum, adductor compartment,
and the aponeuroses of the sartorius and rectus femoris
muscles.
C
Malawer Chapter 01 21/02/2001 14:56 Page 6
Joint Involvement
Direct tumor extension through the articular cartilage is
rare and usually occurs as the result of a pathological
fracture with seeding of the joint cavity or by peri-
capsular extension (Figure 1.7). Occasionally, structures
that pass through the joint (e.g., the cruciate ligaments)
act as a conduit for tumor growth (Figures 1.8, 1.9).
Transcapsular skip nodules are demonstrated in 1% of
all osteosarcomas.
Metastatic Pattern
Unlike carcinomas, bone and soft-tissue sarcomas
disseminate almost exclusively through the blood.
Hematogenous spread of extremity sarcomas is mani-
fested by pulmonary involvement in the early stages
and by bony involvement in later stages (Figure 1.10).
Abdominal and pelvic soft-tissue sarcomas, on the
other hand, typically metastasize to the liver and lungs.
Low-grade soft-tissue sarcomas have a low (< 15%)
rate of subsequent metastasis while high-grade lesions
have a significantly higher (> 15%) rate of metastasis.
Metastases from sarcomas to regional lymph nodes are
infrequent; the condition is observed in only 13% of
patients with soft-tissue sarcomas and 7% of bone
sarcomas at initial presentation. The prognosis
associated with such an event is similar to that of
distant metastasis.
Most patients with high-grade primary bone
sarcomas, unlike soft-tissue sarcomas, have distant
micrometastases at presentation; an estimated 80% of
patients with osteosarcomas have micrometastatic lung
disease at the time of diagnosis. For that reason, in most
Bone and Soft-tissue Sarcomas 7
A B
Figure 1.4 (A) Ewing’s sarcoma of the distal two-thirds of the femur, and (B) osteosarcoma of the proximal tibia. Note the
extraosseous component of the tumor. Most high-grade bone sarcomas are bicompartmental at the time of presentation (i.e., they
involve the bone of origin as well as the adjacent soft tissues). Tumors at that extent are staged as IIB tumors (see staging of
malignant bone tumors: Enneking’s classification).
Malawer Chapter 01 21/02/2001 14:56 Page 7
cases, cure of a high-grade primary bone sarcoma can
be achieved only with systemic chemotherapy and
surgery. As mentioned, high-grade soft-tissue sarcomas
have a smaller metastatic potential. Because of that
difference in metastatic capability the role of chemo-
therapy in the treatment of soft-tissue sarcomas and its
impact on survival are still a matter of controversy.
STAGING OF MUSCULOSKELETAL TUMORS
Staging is the process of classifying a tumor, especially
a malignant tumor, with respect to its degree of
differentiation, as well its local and distant extent, in
order to plan the treatment and estimate the prognosis.
Staging allows the surgeon to determine the type and
the extent of the operation that is necessary for a
specific type of tumor in a particular anatomic location,
as well as the indication for neoadjuvant treatment
modalities. Staging of a musculoskeletal tumor is based
on the findings of the physical examination and the
results of imaging studies. Biopsy and histopathological
evaluation is an essential component of staging, but
should always be the final step. The concept and
practice of biopsy of musculoskeletal tumors is
discussed in Chapter 2.
Plain radiographs remain the key imaging modality
in the evaluation of bone tumors. Based on medical
history, physical examination, and plain radiographs,
accurate diagnosis of bone tumors can be made in more
than 80% of cases. Because of the fine trabecular detail
revealed by plain radiographs, bone lesions of the
extremities can be detected at a very early stage; lesions
of the spine and pelvis, by contrast, are not diagnosed
until a large volume of bone has been destroyed. Once
a bone lesion is found, computerized tomography (CT)
is the imaging modality of choice to evaluate the extent
of bone destruction. Magnetic resonance imaging
(MRI) has been proven to be superior to CT in the
evaluation of the intramedullary and extraosseous,
soft-tissue extent of bone tumors (Figure 1.11).
In their early stages, soft-tissue tumors are hard to
detect due to the lack of bone involvement.
Occasionally, distortion of fat planes in plain radio-
graphs implies the presence of a soft-tissue mass.
CT should be performed on a helical scanner that
enables improved two-dimensional images and three-
dimensional reconstruction capability. The field of view
should be small enough to allow adequate resolution,
particularly of the lesion and the adjacent neuro-
vascular bundle and muscle groups. The slice thickness
should be designed in order to allow at least 10–15
slices through the tumor. Intravenous contrast dye
should be employed in the evaluation of soft-tissue
tumors unless a clear contraindication for its use exists.
On the other hand, contrast dye is of little value in the
evaluation of bone tumors.
MRI is a valuable tool in the evaluation of soft-tissue
tumors and of the medullary and soft-tissue com-
ponents of bone tumors. The signal intensity of a tumor
is assessed by comparing it with that of the adjacent
soft tissues, specifically skeletal muscle and subcu-
taneous fat. MRI also enables one to view a lesion in all
three planes (axial, sagittal, and coronal). Contrast-
Musculoskeletal Cancer Surgery8
Figure 1.5 Biologic behavior of bone and soft-tissue
sarcomas. Unique features are formation of reactive zone,
intracompartmental growth, and, rarely, the presence of
skip metastases.
Malawer Chapter 01 21/02/2001 14:56 Page 8
enhanced MRI is useful in evaluating the relationship
of a tumor to the adjacent blood vessels and in charac-
terizing cystic lesions. The presence of orthopedic
hardware or surgical clips is not a contraindication to
the performance of MRI; however, if a lesion is
immediately adjacent to the location of the hardware,
the local field may be distorted.
Although the purpose of MRI is to evaluate the
anatomical extent of a lesion, it also can accurately diag-
nose a variety of soft-tissue tumors, including lipomas,
liposarcomas, synovial cysts, pigmented villonodular
synovitis, hemangiomas, and fibromatoses.
Hematomas frequently have a characteristic appear-
ance in MRI; however, high-grade sarcomas that have
undergone significant intratumoral hemorrhage may
resemble hematomas. For this reason the diagnosis of a
simple hematoma should be made cautiously and, once
it is made, close clinical monitoring must be made until
the condition has been resolved. The general guidelines
regarding narrowing of the field and recommended
number of slices per tumor are similar to those of CT.
Bone scintigraphy was traditionally used to assess
the medullary extension of a primary bone sarcoma. As
a rule the bone was cut approximately 6 cm proximal to
the margin of the increased uptake. MRI allows more
accurate determination of the medullary tumor extent;
as a result, safer resections in narrower margins can be
performed. Bone scan is currently used to determine
the presence of metastatic and polystotic bone disease
and the involvement of a bone by an adjacent soft-
tissue sarcoma. In addition, the appearance of a bone
lesion in the flow and pool phases of a three-phase
bone scan reflects its biological activity and may be
helpful in its diagnosis. It is also used as an indirect
means of evaluating tumor response to chemotherapy.
Angiography is essential prior to surgery because
vascular displacement is common in tumors that have a
large extraosseous component. Blood vessels are likely
Bone and Soft-tissue Sarcomas 9
Figure 1.6 (A) Axial MRI, showing metastatic bladder carcinoma to the posterior thigh. (B) Plain radiograph of the proximal
femur revealed direct invasion through the cortical bone with a pathological fracture of the lesser trochanter (arrows). (C) In
surgery, exploration of the sciatic nerve revealed direct tumor involvement with extension under the epineural sheath.
A B
C
Malawer Chapter 01 21/02/2001 14:56 Page 9
to be distorted or, less commonly, directly incorporated
to the tumor mass. Angiography provides information
that helps the surgeon plan the anatomical approach
and gauge the likelihood that a major blood vessel has
to be resected en-bloc with the tumor. It can also detect
vascular anomalies (Figure 1.12) and establish patency
of collateral vessels. Proximal femur resection, for
example, frequently necessitates ligation of the profun-
dus femoral artery (PFA). A patent superficial femoral
artery (SFA) must be documented by angiography prior
to surgery, otherwise the extremity will suffer severe
ischemia following ligation of the PFA. Preoperative
embolization may be useful in preparation for resection
of metastatic vascular carcinomas if an intralesional
procedure is anticipated. Metastatic hypernephroma is
an extreme example of a vascular lesion that may bleed
extensively and cause exsanguination upon the execu-
tion of an intralesional procedure without prior
embolization.
Intra-arterial administration of chemotherapy allows
the use of another type of information that can
obtained from angiographs; reduction in tumor
vascularity. As revealed by serial angiographs, such
reduction was shown to be indicative of good response
to preoperative chemotherapy. Figure 1.13 summarizes
the use of the various imaging modalities in the staging
process of a primary bone sarcoma.
There is no single universally accepted staging system
for soft-tissue and bone sarcomas. Some systems are
valuable in the determination of the operative strategy,
whereas others may be more useful in the estimation of
the prognosis. An important variable in any staging
system for musculoskeletal tumors, unlike a staging
Musculoskeletal Cancer Surgery10
Figure 1.7 Pericapsular extension of an osteosarcoma of the
proximal humerus (arrows).
Figure 1.8 Extension of an osteosarcoma of the distal
femur to the knee joint along the cruciate ligaments (arrow
points to tumor); the articular cartilage is intact. Knee joint
extension of a high-grade sarcoma of the distal femur is a
rare event, necessitating extra-articular resection (i.e., en-
bloc resection of the distal femur, knee joint, and a
component of the proximal tibia), as shown in this figure.
Figure 1.9 The five major mechanisms of joint involve-
ment by a bone sarcoma. The most common mechanisms
are pathologic fracture and pericapsular extension.
Malawer Chapter 01 21/02/2001 14:56 Page 10
system for carcinomas, is the grade of the tumor. The
system that is most commonly used for the staging of
soft-tissue sarcomas is that of the American Joint
Committee on Cancer (Table 1.1).1 It is based primarily
on the Memorial–Sloan Kettering staging system and
does not apply to rhabdomyosarcoma. Critics of this
system point out that it is based largely on single-
institution studies that were not subjected to multi-
institutional tests of validity. The Musculoskeletal
Tumor Society adopted staging systems that were
originally