J54Orthop Sci (1999) 4:54–65 Y.

Iwamoto: Management of soft tissue tumors

Diagnosis and treatment of soft tissue tumors*

Yukihide Iwamoto
Department of Orthopaedic Surgery, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

Abstract: In the management of soft-tissue tumors, accurate Introduction

diagnosis, using a combination of clinical, radiographic, and
histological data, is critical in optimizing outcome. Radio- The term “soft tissues” refers to the extraskeletal con-
graphic diagnoses can be useful, but they cannot accurately nective tissues of the body that connect, support, and
predict histology or whether a lesion is benign or malignant. surround other discrete anatomic structures. Soft-tissue
Therefore, all soft lumps that persist or grow should be
tumors are malignant or benign tumors that arise in the
biopsied if possible. Fine-needle aspiration biopsy is useful in
soft tissues anywhere in the body, and are grouped to-
differentiating benign from malignant lesions. Core-needle
biopsies can yield a histological diagnosis when the sample is gether because of similarities in pathological appear-
sufficiently large. When open biopsy is required, the skin inci- ance, clinical presentation, and behavior. Malignant
sion must be carefully placed so that the biopsy site can be tumors arising from soft tissues are known as sarcomas,
completely excised if the lesion is subsequently found to be while those arising from epithelial tissues are carcino-
malignant. Excisional biopsy should be used only for small mas. Approximately 40% of soft tissue sarcomas occur
lesions or when the surgeon is confident that the lesion is in the lower extremity and 20% in the upper extremity:
benign. If, following excision, the lesion is found to be malig- the head and neck region accounts for 10% of these
nant or desmoid, additional surgery with an adequate excision tumors, and the trunk accounts for 30%.3
margin should be performed. In the resection of high-grade In the management of soft-tissue tumors, accurate
sarcomas treated by surgery alone or resistant to preoperative
diagnosis, using a combination of clinical, radiographic,
adjuvant therapies, a “curative (wide) margin” must be
and histological data, is critical for optimizing outcome.
achieved. We occasionally use preoperative radiation with or
without hyperthermia for malignant lesions in the vicinity of The purpose of this review is to discuss the classifica-
neurovascular structures where adequate surgical margins are tion, clinical findings, radiographic features, staging,
unlikely to be achieved. The use of chemotherapy is justified and consistent use of strategies for the evaluation,
only in small-cell sarcomas in which metastasis occurs fre- biopsy, and treatment of both benign and malignant
quently and chemotherapy is known to be effective. For high- tumors.
grade spindle-cell or pleomorphic sarcomas, the value of
adjuvant chemotherapy remains controversial and needs
investigation. Classification

Key words: soft tissue tumors, diagnosis, treatment Y. Soft-tissue tumors are commonly classified according to
Iwamoto: Management of soft tissue tumors
the direction of cellular differentiation. Benign lesions
are more frequent than sarcomas, and the National
Cancer Survey in the United States indicated that soft-
tissue sarcomas occur approximately 2.4 times as often
as bone sarcomas.6 The registry of soft-tissue tumors
maintained for 20 years at the Second Department
Offprint requests to: Y. Iwamoto of Pathology, Kyushu University, contains 17 832
* Instructional Course Lecture, presented at the 71st benign lesions and 1073 malignant lesions.16 The
Annual Meeting of the Japanese Orthopaedic Associa- most frequent benign lesion was lipoma, followed by
tion in Tokushima on April 19, 1998 hemangioma, schwannoma, inflammatory granuloma,
Received for publication on June 9, 1998 fibroma, neurofibroma, dermatofibrohistiocytoma, leio-
Y. Iwamoto: Management of soft tissue tumors 55

myoma, mucous cyst, and lymphangioma. The most (17%), rhabdomyosarcomas (12%), epithelioid sarco-
frequent malignant lesion was malignant fibrous mas (20%), and clear cell sarcomas, and the prognosis is
histiocytoma (MFH), followed by liposarcoma, rhab- poor with lymph node involvement.3 Therefore, routine
domyosarcoma, leiomyosarcoma, synovial sarcoma, examination of regional or other lymph node sites
fibrosarcoma, malignant peripheral nerve sheath (inguinal, axillary, cervical, and supraclavicular) is im-
tumor, neuroblastoma, angiosarcoma and extra-skeletal portant at the initial examination.
chondrosarcoma.
The histologic classification of soft-tissue tumors pro-
posed by the World Health Orgarisation (WHO) in Radiographic features
1994 is shown in Table 1.27 In this new classification,
there are several changes from the traditional WHO Radiographic evaluation of the patient with soft-tissue
classification12: (1) Angiomatoid MFH, which differs tumors includes soft-tissue radiographs, computed
in morphology and biological behavior from the radiographs, echosonograms, computed tomography
storiform-pleomorphic or myxoid type of MFH, was (CT) scans, MRI, and arteriography. Soft-tissue radio-
named angiomatoid fibrous histiocytoma and was ex- graphs, CT, and MRI are the most commonly used.
cluded from the MFH group. (2) Synovial sarcoma was Soft-tissue radiographs in two planes are routinely
excluded from the group of synovial tumors and was obtained at the initial visit after a thorough history and
reclassified in the group of miscellaneous tumors. (3) examination. In the diagnosis of bone tumors, plain
Clear cell sarcoma and granular cell tumor were ex- radiography is the most useful radiographic procedure,
cluded from the category of uncertain histogenesis but only soft-tissue tumors that contain fat, or mineral-
and classified under neural tumors. (4) Malignant ized tumors, can be visualized using this procedure.
schwannoma was named malignant peripheral nerve Lipomas can sometimes be diagnosed on plain radiog-
sheath tumor. raphy, where they appear as a round or oval radiolucent
shadow similar in radiographic density to the subcuta-
neous fat (Fig. 1A). Mineralization occurs in several
Clinical findings benign lesions, including myositis ossificans, lipoma,
extraskeletal chondroma, and hemangioma, as well as
Soft-tissue tumors usually present as asymptomatic soft- in some malignant lesions, including synovial sarcoma,
tissue masses. Symptoms are few until the lesions are liposarcoma, extraskeletal chondrosarcoma, and
quite large, since they arise in compressible tissues, of- extraskeletal osteosarcoma. However, CT is more sensi-
ten far from vital organs. Eighty-five percent of benign tive for detecting mineralization, and can sometimes
lesions and 70% of malignant lesions are asymptomatic. demonstrate it even when plain radiographs fail to do so
There are no reliable physical signs to differentiate be- (Fig. 1B). In myositis ossificans, mineralization appears
nign from malignant soft-tissue tumors. However, care- primarily at the periphery of the lesion, while the center
ful physical examination is important, since several does not mineralize (“zoning phenomenon”; Fig. 1C).
findings do suggest malignant lesions. Small intralesional phleboliths occasionally seen in
Most soft-tissue sarcomas are large (greater than hemangiomas are helpful in the diagnosis of this lesion.
5 cm), firm, and situated in the deeper planes of the A useful physical sign in the diagnosis of hemangioma is
musculoaponeurotic structures. In contrast, small, su- a change from soft to hard consistency after occlusion of
perficial, and soft lesions are more likely to be benign. the extremity proximal to the lesion with a rubber band-
Deep-seated lesions in the buttock or medial side of the age. Plain radiographs and CT can sometimes demon-
proximal thigh are difficult to palpate since they are strate erosion or destruction of underlying bone by
covered by a thick layer of muscle. Magnetic resonance these tumors.
imaging (MRI) or echosonography is recommended to MRI has become the radiographic procedure of
confirm the presence of the lesion. choice for the diagnosis of soft-tissue tumors. T1- and
Lesions in neurofibromatosis patients that have in- T2-weighted sequences are essential to characterize
creased rapidly in size may represent change to a malig- soft-tissue lesions. Most of the lesions reveal low inten-
nant peripheral nerve sheath tumor. Physicians should sity on T1- and high intensity on T-2-weighted images.
bear in mind that malignant soft-tisssue sarcomas may Although MRI is very useful for delineating the extent
also arise at the site of lymphedema or previously irra- of the tumor and its relationship to neurovascular struc-
diated soft tissues. tures, it cannot accurately predict the histology or
The most common site for metastatic disease from a whether a lesion is benign or malignant. However, there
soft-tissue sarcoma is the lung, and only 5% of patients are several exceptions to this general rule. Lipogenic
develop lymph node metastases. The incidence of tumors, including lipomas and well-differentiated
lymph node metastasis is higher in synovial sarcomas liposarcomas, have an increased signal intensity on both
56 Y. Iwamoto: Management of soft tissue tumors

Table 1. Histologic classification of soft-tissue tumors (WHO, 199427)

1. Fibrous tissue tumors Well differentiated liposarcoma
Benign Lipoma-like
Fibroma Sclerosing
Keloid Inflammatory
Nodular fasciitis Myxoid liposarcoma (poorly differentiated myxoid)
Proliferative fasciitis/Proliferative myositis liposarcoma
Elastofibroma Pleomorphic liposarcoma
Fibrous hamartoma of infancy Dedifferentiated liposarcoma
Myofibromatosis, solitary and multicentric
4. Smooth muscle tumors
Fibromatosis colli
Benign
Calcifying aponeurotic fibroma
Leiomyoma
Hyalin fibromatosis
Angiomyoma
Fibromatosis
Epithelioid leiomyoma
Superficial fibromatosis
Leiomyomatosis peritonealis disseminata
Palmar and plantar fibromatosis
Malignant
Infantile digital fibromatosis (digital fibroma)
Leiomyosarcoma
Deep fibromatosis
Epithelioid leiomyosarcoma
Abdominal fibromatosis (desmoid tumor)
Extra-abdominal fibromatosis (desmoid tumor) 5. Skeletal muscle tumors
Intra-abdominal and mesenteric fibromatosis Benign
Infantile fibromatosis Rhabdomyoma
Malignant Adult
Fibrosarcoma Genital
Adult fibrosarcoma Fetal
Congenital or infantile fibrosarcoma Malignant
Rhabdomyosarcoma
2. Fibrohistiocytic tumors
Embryonal rhabdomyosarcoma
Benign
Botryoid rhabdomyosarcoma
Fibrous histiocytoma
Spindle cell rhabdomyosarcoma
Cutaneous histiocytoma (dermatofibroma)
Alveolar rhabdomyosarcoma
Deep histiocytoma
Pleomorphic rhabdomyosarcoma
Juvenile xanthogranuloma
Rhabdomyosarcoma with ganglionic differentiation
Reticulohistiocytoma
(“ectomesenchymoma”)
Xanthoma
Intermediate 6. Endothelial tumors of blood and lymph vessels
Atypical fibroxanthoma Benign
Dermatofibrosarcoma protuberans Papillary endothelial hyperplasia
Pigmented dermatofibrosarcoma protuberans Hemangioma
(Bednar tumor) Capillary hemangioma
Giant cell fibroblastoma Cavernous hemangioma
Plexiform fibrohistiocytic tumor Venous
Angiomatoid fibrous histiocytoma Epithelioid hemangioma (angiolymphoid
Malignant hyperplasia, histiocytoid hemangioma)
Malignant fibrous histiocytoma Pyogenic granuloma (granulation tissue type
Storiform-pleomorphic hemangioma)
Myxoid Acquired tufted hemangioma
Giant cell Lymphangioma
Xanthomatous (inflammatory) Lymphangiomyoma and lymphangiomyomatosis
Angiomatosis and lymphangiomatosis
3. Lipomatous tumors
Intermediate (hemangioendothelioma)
Benign
Spindle cell hemangioendothelioma
Lipoma
Endovascular papillary angioendothelioma (Dabska
Lipoblastoma (fetal lipoma)
tumor)
Lipomatosis
Epithelioid hemangioendothelioma
Angiolipoma
Malignant
Spindle cell lipoma/Pleomorphic lipoma
Angiosarcoma (lymphangiosarcoma)
Angiomyolipoma
Kaposi sarcoma
Myelolipoma
Hibernoma 7. Perivascular tumors
Atypical lipoma Benign
Malignant Benign hemangiopericytoma
Y. Iwamoto: Management of soft tissue tumors 57

Table 1. (Continued)
Glomus tumor Malignant granular cell tumor
Malignant Clear cell sarcoma (malignant melanoma of soft
Malignant hemangiopericytoma parts)
Malignant glomus tumor Malignant melanotic schwannoma
Neuroblastoma
8. Synovial tumors
Ganglioneuroblastoma
Benign
Neuroepithelioma (peripheral neuroectodermal
Tenosynovial giant cell tumor
tumor, peripheral neuroblastoma)
Localized
Diffuse (extra-articular pigmented villonodular 11. Paraganglionic tumors
synovitis) Benign
Malignant Paraganglioma
Malignant tenosynovial giant cell tumor Malignant
Malignant paraganglioma
9. Mesothelial tumors
Benign 12. Cartilage and bone tumors
Solitary fibrous tumor of pleura and peritoneum Benign
(localized fibrous mesothelioma) Panniculitis ossificans
Multicystic mesothelioma Myositis ossificans
Adenomatoid tumor Fibrodysplasia (myositis) ossificans progressiva
Well differentiated papillary mesothelioma Extraskeletal chondroma
Malignant Extraskeletal osteochondroma
Malignant solitary fibrous tumor of pleura and Extraskeletal osteoma
peritoneaum (malignant localized fibrous Malignant
mesothelioma) Extraskeletal chondrosarcoma
Diffuse mesothelioma Well differentiated chondrosarcoma
Epithelial Myxoid chondrosarcoma
Spindled (sarcomatoid) Mesenchymal chondrosarcoma
Biphasic Dedifferentiated chondrosarcoma
Extraskeletal osteosarcoma
10. Neural tumors
Benign 13. Pluripotential mesenchmal tumors
Traumatic neuroma Benign
Morton neuroma Mesenchymoma
Neuromuscular hamartoma Malignant
Nerve sheath ganglion Malignant mesenchymoma
Schwannoma (neurilemoma)
14. Miscellaneous tumors
Plexiform schwannoma
Benign
Cellular schwannoma
Congenital granular cell tumor
Degenerated (ancient) schwannoma
Tumoral calcinosis
Neurofibroma
Myxoma
Diffuse
Cutaneous
Plexiform
Intramuscular
Pacinian
Angiomyxoma
Epithelioid
Amyloid tumor
Granular cell tumor
Parachordoma
Melanocytic schwannoma
Ossifying fibromyxoid tumor
Neurothekeoma (nerve sheath myxoma)
Juvenile angiofibroma
Ectopic meningioma
Inflammatory myofibroblastic tumor (inflmmatory
Ectopic ependymoma
fibrosarcoma)
Ganglioneuroma
Malignant
Pigmented neuroectodermal tumor of infancy (retinal
Alveolar soft part sarcoma
anlage tumor, melanotic progonoma)
Epithelioid sarcoma
Malignant
Extraskeletal Ewing sarcoma
Malignant peripheral nerve sheath tumor (MPNST),
“Synovial” sarcoma, monophasic fibrous type
(malignant schwannoma, neurofibrosarcoma)
Malignant (extrarenal) rhabdoid tumor
MPNST with rhabdomyosarcoma (malignant Triton
Desmoplastic small cell tumor in children and young
tumor)
adults
MPNST with glandular differentiation
Epithelioid MPNST 15. Unclassified tumors
WHO, World Health Organisation
58 Y. Iwamoto: Management of soft tissue tumors

T1- and T2- images, and the intensity of the signal on T1 these reasons, angiography is not now routinely per-
is higher than that on T2, as with normal subcutaneous formed for the evaluation of soft-tissue tumors.
fat. However, myxoid liposarcomas have a low signal on
T1- and a high signal on T2- images. The signal intensity
pattern of this lesion is similar to that in cystic and Biopsy
cartilaginous lesions, since all these lesions contain a
large amount of water. Alveolar soft-part sarcomas also All soft-tissue lumps that persist or grow should be
have a high signal on both T1- and T2- weighted images biopsied, as (i) there are no reliable physical or radio-
(Fig. 1D,E).17 However, the intensity of the signal on T1 graphic features to differentiate benign from malignant
is lower than that on T2, and it is this finding which lesions, and (ii), to make an accurate histological diag-
allows differentiatiation of alveolar soft part sarcomas nosis. Soft-tissue lumps should be observed without bi-
from lipogenic tumors. Extra-abdominal desmoids and opsy only if they have been present and unchanged for
pigmented villonodular synovitis show mixed low and many years before being brought to the attention of
high signals on T2 within the same lesion, since collagen the physician. There are three types of biopsy: needle
fibers in the former and hemosiderin in the latter lesion biopsy (fine-needle aspiration or core-needle biopsy),
generate the low signal on the T2 image. Myositis open incisional biopsy, and open excisional biopsy.
ossificans has considerable extension of the perifocal Fine-needle aspiration biopsy or core-needle biopsy has
reactive high signal area on T2, and it is this finding the following advantages: (i) it can be performed with-
which differentiates this lesion from osseous soft-tissue out skin incision under local anesthesia in the outpatient
tumors. Malignant lesions are more likely to have a clinic and (ii) it does not contaminate the compartment
reactive zone which appears as a fuzzy area between the containing the tumor.
tumor and the normal tissues on T1 images. However, At our institution, fine-needle aspiration biopsy is
margination of the lesion is clearer than in extra- performed using a Sure-cut biopsy needle (Tochigi-
abdominal desmoids, myositis ossificans, hematoma, Seiko, Tochigi, Japan). The stopper of this needle is
or abscess. designed not to aspirate more than the volume of the
Arteriography is useful for delineating the position needle itself (Fig. 2B). Therefore, aspiration of material
and status of major vessels and the local extent of dis- into the syringe is avoided. Cytology using material col-
ease, and it is particularly useful for determining the lected by aspiration biopsy is useful, since it can reliably
relation of tumor to major arteries if displacement or differentiate benign and malignant lesions with more
encasement is present. However, this procedure is inva- than 90% sensitivity, and a definite diagnosis can be
sive, and vascular structures can also be evaluated by obtained in about 30 min. However, histological diagno-
MRI. Although malignant lesions usually show highly sis of the tumor is rarely achieved with this technique,
vascularized features, this is not always the case. For since the connective tissues surrounding the tumor cells,

Fig. 1A–E. Radiographic findings of soft

tissue tumors. A Soft-tissue radiograph;
radiolucent oval shadow of lipoma. B
Computed tomography (CT); mineraliza-
tion of synovial sarcoma (arrow), not
demonstrated on plain radiographs. C
CT; “zoning phenomenon” of myositis
ossificans (arrow); D,E magnetic reso-
nance imaging (MRI); alveolar soft part
sarcomas show high signal on both T1-(D)
and T2-weighted images (E)
Y. Iwamoto: Management of soft tissue tumors 59

neurovascular bundles nor intermuscular planes should

be exposed. If only the periphery of the lesion is sam-
pled, adequate diagnostic material may not be obtained,
as the specimen may contain only reactive or edematous
normal tissue. Many malignant tumors tend to bleed
excessively, and meticulous attention should therefore
be paid to hemostasis. This will minimize hematoma
formation and avoid subsequent dissection of soft-tissue
planes with the accompanying risk of tumor contamina-
tion. Muscle should be closed tightly and sutures to
close the skin should be placed close to the incision.
Excisional biopsy refers to the removal of the entire
lesion. This method is not recommended in most in-
stances, since a large wound is created and excision of
the entire biopsy tract if the lesion is found to be malig-
nant will be difficult. Excisional biopsy should therefore
be used only when the surgeon is sure that the lesion is
benign, or for lesions under 3 cm in diameter. If, follow-
ing excision, the lesion is found to be malignant, addi-
tional surgery with an adequate surgical margin should
be performed as early as possible.15

Staging
Fig. 2. Biopsy needles. A, B Sure-cut needle (Tochigi-Seiko,
Tochigi, Japan) for fine-needle aspiration biopsy. A Top of the
double-barreled needle. B The stopper (arrow) is designed Factors thought to be of prognostic importance in pa-
not to aspirate a sample size that is more than the volume of tients with soft-tissue sarcomas are histologic grade,22,5
the needle. C Tru-cut needle (Baxter Healthcare, Deerfield, site of tumor (proximal vs distal; extremity vs trunk),26
IL, USA) for core-needle biopsy. Accurate histological diag- size,25 and presence or absence of metastasis to regional
nosis can be expected, since tumor cells with surrounding
connective tissues are retrieved. Left Insertion of double- lymph nodes or distant organs. The histologic grade of
barreled needle into the tumor. Middle The inner barrel is the primary lesion is the most important prognostic fac-
pushed forward. Note the gutter of the inner barrel. Right The tor in soft-tissue sarcomas. Myhre-Jensen et al.22 and
outer barrel is pushed forward and the tumor tissue is con- Costa et al.5 employed a three-grade system using a
tained in the gutter combination of cellularity, pleomorphism, mitotic rate
and necrosis, and concluded that the grade correlated
well with survival. The site of the tumor often influences
which are important in the histological diagnosis, are its resectability and local control. Lesions on the trunk
rarely retrieved by aspiration. Core-needle biopsy is are usually large and frequently involve vital structures
performed with the Tru-cut biopsy needle (Baxter before they become clinically apparent. Therefore, local
Healthcare, Deerfield, IL, USA) (Fig. 2C). Both tumor control using any approach is less likely to be achieved
cells and connective tissues are retrieved using this tech- for these tumors than for tumors in the extremity. In the
nique, so a histological diagnosis can be achieved when extremities, proximal lesions are less frequently curable
sufficient material is obtained. However, in most in- than distal lesions.26 Size is also an important factor in
stances the amount of tumor tissue obtained with a determining whether local treatment will be sufficient
needle biopsy is small, and not all pathologists are com- and in determining the likelihood of distant metastasis,
fortable interpreting such small tissue samples. Gener- the former becoming less and the latter more likely as
ous quantities of tumor tissue are required to study tumor size increases.
lesions with special stains or electron microscopy, Several staging systems provide a valuable guide to
and for these reasons, open incisional biopsy is often therapy and prognosis. Table 2 shows the surgical stag-
required. ing system developed by the Musculoskeletal Tumor
Several principles should be closely followed when Society based on the grade of the lesion, local extent
open incisional biopsies are performed. The skin inci- (intracompartmental or extracompartmental), and the
sion must be longitudinal and carefully placed so that presence or absence of metastases.10 This system can be
the biopsy site can be completely excised if the applied for benign and malignant tumors of both bone
lesion is subsequently found to be malignant. Neither and soft tissues. In this system, benign lesions are
60 Y. Iwamoto: Management of soft tissue tumors

Table 2. Surgical staging of musculoskeletal neoplasms with a layer of healthy tissue at all parts of its border;
Stage Grade Site Metastasis skip metastases may remain. (iv) Radical; dissection is
extracompartmental, and the tumor is removed en bloc
1 (Latent) G0 T0 M0 with the entire compartment containing it. In the longi-
2 (Active) G0 T0 M0
tudinal direction, the surgical dissection passes through
3 (Aggressive) G0 T1–2 M0–1a
IA G1 T1 M0 or beyond the proximal and distal joint of the bone
IB G1 T2 M0 affected, and the proximal and distal muscular inser-
IIA G2 T1 M0 tions of the muscles affected. In the transverse direc-
IIB G2 T2 M0 tion, dissection goes beyond the fascial planes bordering
IIIA G1–2 T1 M1
the compartment, and in bone tumors, beyond the
IIIB G1–2 T2 M1
periosteum; there are no residual local tumor foci. Re-
G0, Benign; G1, low-grade malignant; G2, high-grade malignant; section with a radical margin may provide oncological
M0, no evidence of regional or distant metastasis; M1, regional or
distant metastasis. T0, intracapsular; T1, intracompartmental; T2, results similar to those of an amputation. This evalua-
extracompartmental tion system has been widely adopted internationally. In
a
Giant cell tumor of bone occasionally metastasized to the lung 1989, the Japanese Orthopaedic Association Musculo-
Modified from Enneking10
skeletal Committee modified this classification and
proposed new criteria (Evaluation method of surgical
categorized as stage 1 (latent), stage 2 (active), or stage margin for musculoskeletal sarcoma).18,19 In this classifi-
3 (aggressive), and malignant lesions as stage I (low- cation, surgical margins are divided into four categories:
grade, no metastasis), stage II (high-grade, no metasta- curative (wide) margin, wide margin, marginal margin,
sis), or stage III (either grade with regional or distant and intralesional margin. The newly proposed “curative
metastasis). The grade combines histological, radio- (wide)” margin, replacing Enneking’s “radical” margin,
graphic, and clinical assessments; grade G0 tumors are is a surgical margin which passes through the region
benign, G1 tumors are low-grade malignant, and G2 outside the tissue at a distance of more than 5 cm from
high-grade malignant. Tumors are designated “A” if the tumor-reactive zone. According to these modified
they are contained within an anatomic compartment criteria, surgical procedures are classified as curative,
and “B” if they extend across fascial planes. According wide, marginal, or intralesional, irrespective of limb sal-
to Enneking’s experience with 397 soft-tissue sarcomas, vage and ablative surgery. For high-grade sarcomas
the probability of 5-year survival in patients with stage treated by surgery alone or those that are resistant
IA, IB, IIA, IIB, and III lesions was 0.97, 0.89, 0.73, 0.45, to preoperative adjuvant therapy, a curative margin
and 0.08, respectively.11 should be achieved to avoid local recurrence. For high-
grade sarcomas responding to preoperative chemo-
therapy, or for low-grade sarcomas, a wide margin
Surgical planning should be achieved.
In curative (wide) or wide margin resections, surgical
Most benign lesions, such as those of fibrous and adi- tools must not touch the tumor, and the surgeon must
pose tissue origin, are completely treated by simple ex- not be able to visualize it. If a high-grade sarcoma origi-
cision and do not recur. However, in malignant lesions, nates in or is adherent to a nerve trunk, the nerve must
the local recurrence rate following this simple proce- be resected (Fig. 3A,B), and if necessary, substituted
dure is 60%–80% because of local spread and the infil- with a graft. If a high-grade sarcoma adheres to bone
trative nature of these lesions. A major advance in the cortex, the bone should be resected and substituted by
past was the use of radical procedures to reduce the prosthesis or bone grafts (Fig. 3C,D). Likewise, if a
local recurrence rate. Nowadays, however, limb-saving high-grade sarcoma is adherent to major vessels, the
procedures are regarded as acceptable alternatives to vessels should be resected and substituted by prosthesis
amputation in the management of malignant lesions. In or vascular grafts. The decision to adopt either a limb-
order to understand the surgical procedures used in saving procedure or amputation is a difficult one, but of
extremity sarcomas, Simon and Enneking have classi- vital importance, as the survival of the patient may
fied them according to the surgical margins achieved.26 depend on it. When a truly wide or curative (wide)
They describe four types of excision: (i) intralesional; resection for a high-grade sarcoma is not possible, am-
the dissection penetrates the tumor. (ii) Marginal; the putation should be performed.
tumor is removed whole, incising along the capsule
or pseudocapsule; tumor islands may remain in Surgery after inadquate resection
the pseudocapsule (satellite) or further away in the
same compartment (skip). (iii) Wide; dissection is Inadequate resection of soft-tissue sarcomas occurs
intracompartmental, but the tumor is removed en bloc more frequently than in bone sarcomas. Even surgeons
Y. Iwamoto: Management of soft tissue tumors 61

Fig. 3A–D. Surgical specimens of malignant soft-tissue using orthotics. C MR image of malignant fibrous histio-
tumors after limb-saving procedures. A MRI shows malignant cytoma adhering to the femur. D The bone was resected to
peripheral nerve sheath tumor originating in the sciatic nerve. achieve an adequate surgical margin and substituted by an
B Sciatic nerve (arrow) was resected to achieve an adequate allogeneic bone graft
surgical margin. The patient was able to walk after surgery,

who do not have any specialist knowledge of sarcomas form further surgery with a wide or curative margin
are usually alerted to the aggressive nature and extent as soon as possible. Even if no residual tumor is de-
of bone sarcomas by preoperative radiography and by tected on MRI, scars resulting from the initial surgery
the difficulty experienced in operative resection and that are detected on MRI, and which may be contami-
reconstruction. Patients with bone sarcomas are there- nated by tumor cells, are also resected with a curative
fore usually referred to specialists before any form of or wide margin. This additional surgery may be more
treatment has been started. In contrast, patients with important in preventing local recurrence than radio-
soft-tissue sarcomas often have excisions performed therapy, since most soft-tissue sarcomas are not very
with an inadequate surgical margin (marginal or radiosensitive.
intralesional margin) with local anesthesia on their ini- We have experienced a patient with DFSP (low-
tial presentation to the outpatient clinic, as marginal grade sarcoma) who was referred to our institution
resection of soft-tissue tumors is considered a simple only after recurrences that followed three separate
procedure, especially with superficially located tumors. marginal resections. Pathological examination after
Physicians should bear in mind that malignant soft- wide resection at our institution revealed transforma-
tissue tumors such as myxoid MFH, leiomyosarcomas, tion into fibrosarcoma, a high-grade sarcoma, and the
and dermatofibrosarcoma protuberans (DFSP) may patient subsequently died of pulmonary metastases.
occur superficially, although most sarcomas are Recurrence and metastasis in this patient may have
deep-seated. been prevented if additional surgery with a wide margin
After a patient has been referred to us with a tumor had been performed immediately after the initial
shown to be malignant on histology, we routinely per- surgery.
62 Y. Iwamoto: Management of soft tissue tumors

Fig. 4A–D. Myxoid liposarcoma of the

thigh treated by radiation plus hyper-
thermia. Low-dose irradiation (30 Gy)
and hyperthermia were performed preo-
peratively, since the tumor was adherent
to popliteal vessels and the sciatic nerve.
A,B T2-weighted MR images A before
and B after radiation plus hyperthermia
(arrows; sciatic nerve). Thereafter, resec-
tion with marginal margin was performed.
C Histology of the biopsy specimen;
viable cells of myxoid liposarcoma. (HE
3300) D Histology of the surgical speci-
men in the vicinity of the sciatic nerve;
necrosis (HE 3120)

Radiotherapy wound, contracture of the joint, and (rarely) radiation-

induced sarcoma. When radiation must be used in
Radiation therapy in combination with surgery leads to young patients, we occasionally use hyperthermia in
a much lower amputation rate, allows for better preser- combination with a moderate dose of irradiation
vation of limb function, and, at the same time, provides (30 Gy), with the aim of minimizing the risk of
acceptable local control of the disease. Irradiation radiation-induced sarcoma (Fig. 4). Hyperthermia has
can be delivered using a high-energy external beam, a synergistic effect when given with radiation,
brachytherapy,2 or intraoperative electron therapy. Ex- since maligant tumor cells in the S phase of the cell cycle
ternal beam techniques (50–60 Gy) are the most widely are sensitive to the former but resistant to the latter.28
available and most commonly used. Although radiation reduces the risk of local recur-
Preoperative radiation followed by surgery has sev- rence in patients in whom there has been an inadequate
eral advantages compared with postoperative radiation: resection margin, the incidence of recurrence in patients
(i) the treatment volume is smaller than for postopera- managed in this way is still significantly higher than that
tive radiation since the latter requires irradiation of all in patients in whom there has been adequate surgical
tissues manipulated during surgery. (ii) Seeding of vi- resection without radiation.20 Surgeons should therefore
able tumor cells into vascular beds may be reduced with not rely on radiation, but try, as far as possible, to resect
effective radiation therapy. (iii) Surgical resection may all tumors with an adequate surgical margin.
be easier if the tumor regresses with radiotherapy. We
use preoperative radiation in patients with soft-tissue
sarcomas near neurovascular structures where adequate Chemotherapy
surgical margins will not be achieved.
Postoperative radiation has the following advantages: Despite adequate local treatment, many patients
(i) There is no delay in surgery. (ii) The entire specimen with high-grade soft tissue sarcomas develop metastatic
is available for histopathological grading. We occasion- disease, most frequently in the lungs. This has led to
ally use this approach in patients with soft-tissue sarco- intensive efforts to develop adjuvant chemotherapy
mas in which the surgical margin has been found regimens that may able to prevent metastatic spread.
inadequate postoperatively after examination of the However, the use of chemotherapy is justified only
surgical specimen. in small-cell sarcomas, including Ewing sarcoma,
Radiation therapy is not without potential complica- primitive neuroectodermal tumor (PNET), and rhabdo-
tions, including necrosis and dehiscence of the surgical myosarcoma, in which metastasis occurs frequently and
Y. Iwamoto: Management of soft tissue tumors 63

rapidly.13 In these tumors, neoadjuvant chemotherapy has not been confirmed in other studies.9,1 A study at
given both pre- and postoperatively has become part of the National Cancer Institute, US of 67 patients with
the initial therapeutic protocol in combination with sur- extremity lesions showed a significant overall survival
gery and/or radiation, and in rhabdomyosarcomas has benefit at 5-year follow-up, but, because of some late
been shown to increase the percentage of patients with deaths, the difference was not significant after a median
long-term disease-free survival.21 Although extrask- follow-up of 9 years.4 The different outcomes in these
eletal Ewing sarcomas and PNETs are also sensitive to studies may be due to the heterogeneity of histological
chemotherapy, there have not yet been sufficient num- diagnoses and grading, the generally low response rate,
bers of patients treated to prove the efficacy or other- and the relatively low frequency of soft-tissue tumors.
wise of adjuvant chemotherapy. At our institution, At our institution, chemotherapy has not been routinely
regimens of VACA (vincristine, adriamycin, cyclopho- given for high-grade spindle-cell or pleomorphic sarco-
sphamide, and actinomycin-D)8 or VAIA (vincristine, mas and low-grade sarcomas. However, some patients
adriamycin, ifosphamide, and actinomycin-D)8 have with these sarcomas have developed metastases even
been used for extraskeletal Ewing sarcoma, PNET, and when local recurrences have not been found. Overt
rhabdomyosarcoma. For extraskeletal osteosarcoma, a clinical metastases have been difficult to eradicate with
combination of high-dose methotrexate, adriamycin, chemotherapy, other than in a patient with synovial
and cisplatin has been used. Although adriamycin is sarcoma (Fig. 5). Therefore, in the future, high-grade
likely to be of value in the treatment of these tumors, its spindle-cell or pleomorphic sarcomas are likely to be
cardiotoxicity is a significant problem. It has been re- treated with chemotherapy only when an effective
ported that approximately 15% of patients develop chemotherapeutic regimen has been developed and the
congestive heart failure with regimens containing survival of patients has been demonstrated to be signifi-
adriamycin, and 50% of asymptomatic patients given cantly improved.
maximal doses (550 mg/m2) of adriamycin have evi-
dence of decreased left ventricular ejection fraction
measured by electrocardiogram gated radionucleotide Follow-up and prognosis
angiography.7
The value of adjuvant chemotherapy in the treatment Patients should be monitored carefully at 3-month in-
of patients with high-grade spindle cell sarcomas or tervals for 2 years, as this is the period in which local
pleomorphic sarcomas remains controversial and needs recurrence and pulmonary metastases are most likely to
investigation. Several studies in patients with sarcomas, occur. Local recurrence can be detected most efficiently
including spindle-cell and pleomorphic sarcomas, have through careful physical examination, and pulmonary
reported significant improvement in survival rates for metastases should be sought with chest radiographs or
patients who received with chemotherapy,24,14 but this CT scans.22 At our institution, patients with high-grade

Fig. 5A,B. Eradication of synovial sar-

coma metastasis by chemotherapy. A
Multiple metastases (arrows) were found
1 year after surgery. B Metastatic tumors
resolved after combination chemotherapy
with cisplatin and adriamycin. The
patient is alive without any evidence of
the disease 4 years after the end of
chemotherapy
64 Y. Iwamoto: Management of soft tissue tumors

sarcomas are monitored at 2-month intervals for 2 4. Chang AE, Kinsella T, Glatstein E, et al. Adjuvant therapy
for patients with high-grade soft-tissue sarcomas of the extremi-
years. Thereafter, patients are monitored at 6-month
ties. J Clin Oncol 1988;6:1491–500.
intervals over the next 5 years. 5. Costa J, Wesley RA, Glatstein E, et al. The grading of soft tissue
The author has operated on 55 patients with soft-tissue sarcomas. results of a clinicopathologic correlation in a series of
sarcomas in the past 10 years. One patient with MFH and 163 cases. Cancer 1984;53:530–41.
6. Cutler SJ, Young IL. Third National Cancer Survey. Incidence
two patients with alveolar soft part sarcomas had clinical data. NCI Monogr 1975;41:1–9.
metastases prior to surgery. The histological diagnoses in 7. Dresdale A, Bonow RO, Wesley R, et al. Prospective evaluation
the 52 patients without metastasis were: liposarcoma (n of doxorubicin-induced cardiomyopathy resulting from post-
5 16) , MFH (n 5 10), leiomyosarcoma (n 5 6), synovial surgical adjuvant treatment of patients with soft tissue sarcomas.
Cancer 1983;52:51–60.
sarcoma (n 5 5), fibrosarcoma and Ewing sarcoma (n 5 3 8. Dunst J, Burgers JM, Hawliczek R, et al. Radiation therapy as
each), chondrosarcoma and osteosarcoma (n 5 2 each), local treatment in Ewing’s sarcoma. Results of the cooperative
and single cases of alveolar soft part sarcoma, Ewing’s sarcoma studies CESS81 and CESS86. Cancer 1991;28:
rhabdomyosarcoma, angiomatoid fibrous histiocytoma, 2818–25.
9. Edmonson JH. Role of adjuvant chemotherapy in the manage-
malignant peripheral nerve sheath tumor, and epithe- ment of patients with soft tissue sarcomas. Cancer Treat Rep
lioid sarcoma. Limb-saving procedures were performed 1984;68:1063–66.
in 50 patients and amputation was performed in two 10. Enneking WF. A system of staging musculoskeletal neoplasms.
patients, one with Ewing sarcoma of the thigh and one Clin Orthop 1986;204:9–24.
11. Enneking WF, Spanier SS, Goodman MA. A surgical staging of
with myxoid liposarcoma of the thigh. All patients have musculoskeletal sarcomas. J Bone Joint Surg Am 1980;62:1027–
been followed postoperatively for at least 2 years. Only 30.
two patients developed local recurrence after limb- 12. Enzinger FM, Lattes R, Torloni R. Histological typing of
soft tissue tumours. International histological classification of
saving procedures — a 55-year-old man with recurrent
tumours. No.3. Geneva: World Health Organisation, 1969.
synovial sarcoma in the groin and an 82-year-old woman 13. Fukuma H, Beppu Y, Yokoyama R, et al. Treatment of
with recurrent dedifferentiated liposarcoma in the groin; soft tissue tumors. J Jpn Orthop Assoc 1993;67:298–309 (in
both died of tumor growth and metastasis. The groin is a Japanese).
14. Gherlinzoni F, Bacci G, Picci P, et al. A randomized trial for the
particularly common site for recurrences of sarcomas.26 treatment of high-grade sarcomas of the extremities: Preliminary
Local control was achieved in 50 of the 52 patients observations. J Clin Oncol 1986;4:552–8.
(96%), and 41 patients (82%) had disease-free survival 15. Hosokawa A, Iwamoto Y, Chuman H, et al. Additional
of more than 2 years. Nine patients died of distant wide resection for the patients with malignant soft part tumors.
J West-Pacific Assoc Orthop Traumatol 1991;40:527–9 (in
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liposarcoma, rhabdomyosarcoma, leiomyosarcoma, do, 1989:14–7 (in Japanese).
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imaging in the diagnosis of alveolar soft part sarcoma: A report of
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patients had high-grade sarcomas and all died of mittee: Evaluation method of surgical margin for musculoskeletal
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19. Kawaguchi N, Matsumoto S, Manabe J, et al. New method
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Acknowledgments. This work was supported in part by musculoskeletal sarcoma, analyzed on the basis of 457 surgical
Grants-in-Aid for Scientific Research (Nos. 09557124 cases. J Cancer Res Clin Oncol 1995;121:555–63.
20. Lindberg RD, Martin RG. Conservative surgery and postopera-
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tive radiotherapy in 300 adults with soft-tissue sarcomas. Cancer
and Culture of Japan, and a Grant-in Aid for Cancer 1981;47:2391–97.
Research from the Ministry of Health and Welfare, 21. Maurer H, Beltangady M, Gehan E, et al. The intergroup
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