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Orthopedic Surgery > NEOPLASMS
Benign and Malignant Soft Tissue Tumors
Article Last Updated: Dec 12, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Vinod B Shidham, MD, FRCPath, FIAC, Associate Professor, Director of FNAB Service, Director of Cytopathology Fellowship Training Program, Coeditor-in-chief of CytoJournal, Department of Pathology, Medical College of Wisconsin
Vinod B Shidham is a member of the following medical societies: American Association for Cancer Research, American Society of Cytopathology, College of American Pathologists, International Academy of Cytology, Royal College of Pathologists, and United States and Canadian Academy of Pathology
Coauthor(s):
Scott M Acker, MD, Associate Professor, Director of Dermatopathology, Departments of Dermatology and Pathology, University of Alabama at Birmingham;
David H Vesole, MD, PhD, FACP, Attending Physician, St Vincent's Comprehensive Cancer Center;
Donald Hackbarth, MD, FACS, Director of Musculoskeletal Oncology, Associate Professor, Department of Orthopaedic Surgery, Medical College of Wisconsin
Editors: Howard A Chansky, MD, Associate Professor, Department of Orthopedics and Sports Medicine, University of Washington Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Sean P Scully, MD, PhD, Professor, Department of Orthopedics, University of Miami; Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital; Harris Gellman, MD, Consulting Surgeon, Broward Hand Center, Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine
Author and Editor Disclosure
Synonyms and related keywords:
sarcoma, fibrosarcoma, liposarcoma, lipoma, head-and-neck cancer, retroperitoneal cancer, visceral sarcoma, neurofibromatosis, neurofibroma, synovial sarcoma, Kaposi sarcoma, Kaposi's sarcoma, rhabdomyosarcoma, malignant fibrous histiocytoma, liposarcoma, intramuscular lipoma, Ewing sarcoma, primitive neuroectodermal tumors
History of the Procedure
Present achievements in the field of soft tissue tumors 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 tissue sarcomas.
Problem
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.
Frequency
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 women.
- 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.
- Rhabdomyosarcoma is seen more frequently in children and young adults.
- Synovial sarcoma arises in young adults.
- 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 poor.
- The incidence of soft tissue tumors is slightly higher in males than in females.
Etiology
Genetic conditions 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. A partial list of reported cytogenetic abnormalities is shown in Table 1. They have a significant role in diagnosis, and in the future, some of these abnormalities may be 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. Radiation 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. Chronic lymphedema As observed in patients with late-stage breast carcinoma, chronic lymphedema may predispose individuals to the development of lymphangiosarcoma. Environmental carcinogens 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. Infection 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. Trauma The relationship between trauma and soft tissue tumors appears to be coincidental. Trauma probably draws medical attention to a pre-existing lesion.
Pathophysiology
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. Local recurrence 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 (Enneking, 1984). 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. Distant metastasis 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 (Potter et al, 1985). 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.
Clinical
A mass is the most common symptom 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 (Gustafson, 1994).
See Treatment, Surgical therapy.
Lab Studies
- 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.
Imaging Studies
- 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 therapy.
- 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.
- CT scanning
- Check for presence and number of pulmonary metastases.
- Consider performing a CT scan of the liver in cases of intra-abdominal or retroperitoneal tumors.
- MRI
- 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.
Diagnostic Procedures
- 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.
- Fine-needle aspiration biopsy
- Core needle biopsy
- This technique retrieves a thin core of tissue (approximately 1X10 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).
- 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.
- Excisional biopsy
- With this method, the entire lesion is surgically removed. 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.
- Frozen section and intraoperative cytology
- Frozen section and intraoperative cytology are extremely helpful tools for the management of soft tissue tumors. 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.
Histologic Findings
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 further simplified 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. WHO (2002) Classification of Soft Tissue Tumors
- Adipocytic tumors
- Benign
- Lipoma
- Lipomatosis
- Lipomatosis of nerve
- Lipoblastoma/lipoblastomatosis
- Angiolipoma
- Myolipoma
- Chondroid lipoma
- Extrarenal angiomyolipoma
- Extra-adrenal myelolipoma
- Spindle cell/pleomorphic lipoma
- Hibernoma
- Intermediate (locally aggressive)
- Atypical lipomatous tumor/well-differentiated liposarcoma
- Malignant
- Dedifferentiated liposarcoma
- Myxoid liposarcoma
- Round cell liposarcoma
- Pleomorphic liposarcoma
- Mixed-type liposarcoma
- Liposarcoma, not otherwise specified
- Fibroblastic/myofibroblastic tumors
- Benign
- Nodular fasciitis
- Proliferative fasciitis
- Proliferative myositis
- Myositis ossificans
- Fibro-osseous pseudotumor of digits
- Ischemic fasciitis
- Elastofibroma
- Fibrous hamartoma of infancy
- Myofibroma/myofibromatosis
- Fibromatosis colli
- Juvenile hyaline fibromatosis
- Inclusion body fibromatosis
- Fibroma of tendon sheath
- Desmoplastic fibroblastoma
- Mammary-type myofibroblastoma
- Calcifying aponeurotic fibroma
- Angiomyofibroblastoma
- Cellular angiofibroma
- Nuchal-type fibroma
- Gardner fibroma
- Calcifying fibrous tumor
- Giant cell angiofibroma
- Intermediate (locally aggressive)
- Superficial fibromatoses - Palmar/plantar
- Desmoid-type fibromatoses
- Lipofibromatosis
- Intermediate (rarely metastasizing)
- Solitary fibrous tumor and hemangiopericytoma - Including lipomatous hemangiopericytoma
- Inflammatory myofibroblastic tumor
- Low-grade myofibroblastic sarcoma
- Myxoinflammatory fibroblastic sarcoma
- Infantile fibrosarcoma
- Malignant
- Adult fibrosarcoma
- Myxofibrosarcoma
- Low-grade fibromyxoid sarcoma
- Hyalinizing spindle cell tumor
- Sclerosing epithelioid fibrosarcoma
- So-called fibrohistiocytic tumors
- Benign
- Giant cell tumor of tendon sheath
- Diffuse-type giant cell tumor
- Deep benign fibrous histiocytoma
- Intermediate (rarely metastasizing)
- Plexiform fibrohistiocytic tumor
- Giant cell tumor of soft tissues
- Malignant
- Pleomorphic 'MFH'/undifferentiated pleomorphic sarcoma
- Giant cell 'MFH'/undifferentiated pleomorphic sarcoma with giant cells
- Inflammatory 'MFH'/undifferentiated pleomorphic sarcoma with prominent inflammation
- Smooth muscle tumors
- Angioleiomyoma
- Deep leiomyoma
- Genital leiomyoma
- Leiomyosarcoma - Excluding skin
- Pericytic (perivascular) tumors
- Glomus tumor (and variants)
- Myopericytoma
- Skeletal muscle tumors
- Benign
- Malignant
- Embryonal rhabdomyosarcoma - Including spindle cell, botryoid, anaplastic
- Alveolar rhabdomyosarcoma - Including solid and anaplastic
- Pleomorphic rhabdomyosarcoma
- Vascular tumors
- Benign
- Hemangiomas of subcutaneous and deep soft tissue
- Capillary
- Cavernous
- Arteriovenous
- Venous
- Intramuscular
- Synovial
- Epithelioid hemangioma
- Angiomatosis
- Lymphangioma
- Intermediate (locally aggressive)
- Kaposiform hemangioendothelioma
- Intermediate (rarely metastasizing)
- Retiform hemangioendothelioma
- Papillary intralymphatic angioendothelioma
- Composite hemangioendothelioma
- Kaposi sarcoma
- Malignant
- Epithelioid hemangioendothelioma
- Angiosarcoma of soft tissue
- Chondro-osseous tumors
- Benign
- Malignant
- Mesenchymal chondrosarcoma
- Extraskeletal osteosarcoma
- Tumors of uncertain differentiation
- Benign
- Intramuscular myxoma - Including cellular variant
- Juxta-articular myxoma
- Deep ("aggressive") angiomyxoma
- Pleomorphic hyalinizing angiectatic tumor
- Ectopic hamartomatous thymoma
- Intermediate (rarely metastasizing)
- Angiomatoid fibrous histiocytoma
- Ossifying fibromyxoid tumor - Including atypical/malignant
- Mixed tumor
- Myoepithelioma/parachordoma
- Malignant
- Synovial sarcoma
- Epithelioid sarcoma
- Alveolar soft-part sarcoma
- Clear cell sarcoma of soft tissue
- Extraskeletal myxoid chondrosarcoma - "Chordoid" type
- Primitive neuroectodermal tumor (PNET)/extraskeletal Ewing tumor
- Peripheral PNET
- Extraskeletal Ewing tumor
- Desmoplastic small round cell tumor
- Extra-renal rhabdoid tumor
- Malignant mesenchymoma
- Neoplasms with perivascular epithelioid cell differentiation (PEComa)
- Clear cell myomelanocytic tumor
- Intimal sarcoma
As part of this 2002 WHO classification, the 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 fibrous histiocytoma.
- 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%) (Wunder, 2000). 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.
Staging
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 (see Table 2, below). 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 (Suit et al, 1988). 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 classification strategy. GTNM staging system definitions are as follows:
- G - Tumor grade
- G1 - Well differentiated
- G2 - Moderately differentiated
- G3 - Poorly differentiated
- T - Primary tumor
- T1 - Tumor less than 5 cm in greatest diameter
- T2 - Tumor more than 5 cm in greatest diameter
- N - Regional lymph node involvement
- N0 - No known metastasis to lymph nodes
- N1 - Verified metastasis to lymph nodes
- M - Distant metastasis
- M0 - No known distant metastasis
- M1 - Known distant metastasis
Table 2. AJCC GTNM Classification and Stage Grouping of Soft Tissue Sarcomas
Stage Groupings | Tumor Grade | Primary Tumor | Regional Lymph Node Involvement | Distant Metastasis | 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 |
Medical therapy
High-grade soft tissue sarcomas are often treated with ifosfamide- and doxorubicin-based chemotherapy. This is controversial, as no definitive studies exist proving that adjuvant chemotherapy contributes to prolonged overall survival.
Surgical therapy
Localized tumors
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 sarcoma
Extremity sarcomas may be treated surgically, with or without radiation therapy and adjuvant chemotherapy.
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. 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 alone.
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 substantial.
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 prognosis.
Nonextremity sarcoma
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 (Potter et al).
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 one study, resection of isolated pulmonary metastases achieved an actuarial 3-year survival rate of 38% (Potter). 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). 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.
Postoperative details
Compressive bandages and suction drains should be used to minimize seroma formation that can result in delayed administration of chemotherapy or radiation therapy. Physical therapy and rehabilitation support may be required.
Follow-up
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 surveillance.
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 fracture.
- 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 radiation therapy.
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 recurrence.
- Histologic grade - A relationship exists between various microscopic grading systems and outcome.
- Clinical stage - Clinical stage is the most important predictor of clinical outcome. The GTNM staging system, which incorporates microscopic grading, is described in Table 2.
- 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 established.
- 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 an independent prognostic factor.
- Oncogene mutations - Mutations of TP53, overexpression of MDM2, and altered expression of the retinoblastoma gene have reportedly been associated with a worse prognosis.
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.
| Media file 1:
A computed-tomography (CT)–guided needle biopsy of a high-grade soft tissue sarcoma arising in the left hemipelvis. The CT artifact from the needle can be seen in the upper right corner of the image as the needle enters the lesion just anterior and medial to the dome of the left hip joint. Courtesy of Howard A. Chansky, MD |
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Media type: CT
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| Media file 2:
Magnetic resonance imaging (MRI) is used to demonstrate involvement of critical structures by tumor. This recurrent, high-grade soft tissue sarcoma in the posterior calf abuts the tibial nerve and posterior tibial vessels. An extensive reactive zone surrounds the structures. This patient was treated with below-knee amputation. Courtesy of Howard A. Chansky, MD |
 | View Full Size Image | |
Media type: MRI
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- Agarwal V, Greenebaum E, Wersto R. DNA ploidy of spindle cell soft-tissue tumors and its relationship to histology and clinical outcome. Arch Pathol Lab Med. Jun 1991;115(6):558-62. [Medline].
- Association of Directors of Anatomic and Surgical Pathology. Recommendations for the reporting of soft tissue sarcomas. Mod Pathol. Dec 1998;11(12):1257-61. [Medline].
- Ball AB, Fisher C, Pittam M. Diagnosis of soft tissue tumours by Tru-Cut biopsy. Br J Surg. Jul 1990;77(7):756-8. [Medline].
- Barth RJ, Merino MJ, Solomon D. A prospective study of the value of core needle biopsy and fine needle aspiration in the diagnosis of soft tissue masses. Surgery. Sep 1992;112(3):536-43. [Medline].
- Bell RS, O''Sullivan B, Liu FF, et al. The surgical margin in soft-tissue sarcoma. J Bone Joint Surg Am. Mar 1989;71(3):370-5. [Medline].
- Bennert KW, Abdul-Karim FW. Fine needle aspiration cytology vs. needle core biopsy of soft tissue tumors. A comparison. Acta Cytol. May-Jun 1994;38(3):381-4. [Medline].
- Bland KI, McCoy DM, Kinard RE. Application of magnetic resonance imaging and computerized tomography as an adjunct to the surgical management of soft tissue sarcomas. Ann Surg. May 1987;205(5):473-81. [Medline].
- Boddaert A, Trojani M, Contesso G, et al. Soft tissue sarcomas of adults: study of pathological variables and definition of a histopathological grading system. In: van Oosterom AT, van Unnik JAM, eds. Management of Soft Tissue and Bone Sarcomas. New York, NY: Raven Press;1986.
- Cance WG, Brennan MF, Dudas ME. Altered expression of the retinoblastoma gene product in human sarcomas. N Engl J Med. Nov 22 1990;323(21):1457-62. [Medline].
- Cantin J, McNeer GP, Chu FC. The problem of local recurrence after treatment of soft tissue sarcoma. Ann Surg. Jul 1968;168(1):47-53. [Medline].
- Casper ES, Gaynor JJ, Harrison LB. Preoperative and postoperative adjuvant combination chemotherapy for adults with high grade soft tissue sarcoma. Cancer. Mar 15 1994;73(6):1644-51. [Medline].
- Chang AE, Kinsella T, Glatstein E. Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity. J Clin Oncol. Sep 1988;6(9):1491-500. [Medline].
- Chang AE, Matory YL, Dwyer AJ. Magnetic resonance imaging versus computed tomography in the evaluation of soft tissue tumors of the extremities. Ann Surg. Apr 1987;205(4):340-8. [Medline].
- Coindre JM, Nguyen BB, Bonichon F. Histopathologic grading in spindle cell soft tissue sarcomas. Cancer. Jun 1 1988;61(11):2305-9. [Medline].
- Conrad EU, Bradford L, Chansky HA. Pediatric soft-tissue sarcomas. Orthop Clin North Am. Jul 1996;27(3):655-64. [Medline].
- Costa J, Wesley RA, Glatstein E. The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases. Cancer. Feb 1 1984;53(3):530-41. [Medline].
- Costa MJ, Campman SC, Davis RL. Fine-needle aspiration cytology of sarcoma: retrospective review of diagnostic utility and specificity. Diagn Cytopathol. Jul 1996;15(1):23-32. [Medline].
- Dal Cin P. Soft tissue tumors: an overview. Atlas Genet Cytogenet Oncol Haematol. January 2003;[Full Text].
- Drobnjak M, Latres E, Pollack D. Prognostic implications of p53 nuclear overexpression and high proliferation index of Ki-67 in adult soft-tissue sarcomas. J Natl Cancer Inst. Apr 6 1994;86(7):549-54. [Medline].
- Elias AD, Antman KH. Adjuvant chemotherapy for soft-tissue sarcoma: a critical appraisal. Semin Surg Oncol. 1988;4(1):59-65. [Medline].
- Enneking WF. Staging of musculoskeletal neoplasms. In: Uhthoff HK, ed. Current Concepts of Diagnosis and Treatment of Bone and Soft Tissue Tumors. Heidelberg:. Springer-Verlag;1984.
- Enneking WF, McAuliffe JA. Adjunctive preoperative radiation therapy in treatment of soft tissue sarcomas: a preliminary report. Cancer Treat Symp. 1985;3:37.
- Enneking WF, Maale GE. The effect of inadvertent tumor contamination of wounds during the surgical resection of musculoskeletal neoplasms. Cancer. Oct 1 1988;62(7):1251-6. [Medline].
- Enzinger FM, Weiss SW. Soft Tissue Tumors. 3rd ed. St. Louis, Mo:. Mosby;1995.
- Epstein HD. Fine-needle aspiration of soft tissue lesions. Pathology (Phila). 1996;4(2):463-92. [Medline].
- Fong Y, Coit DG, Woodruff JM. Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. Ann Surg. Jan 1993;217(1):72-7. [Medline].
- Geer RJ, Woodruff J, Casper ES. Management of small soft-tissue sarcoma of the extremity in adults. Arch Surg. Nov 1992;127(11):1285-9. [Medline].
- Giuliano AE, Eilber FR. The rationale for planned reoperation after unplanned total excision of soft-tissue sarcomas. J Clin Oncol. Oct 1985;3(10):1344-8. [Medline].
- Greenberg DB. Psychological aspects of patient management. In: Simon MA, Springfield D, eds. Surgery for Bone and Soft-Tissue Tumors. Philadelphia, Pa:. Lippincott-Raven;1998:67-75.
- Gustafson P, Rooser B, Rydholm A. Is local recurrence of minor importance for metastases in soft tissue sarcoma?. Cancer. Apr 15 1991;67(8):2083-6. [Medline].
- Gustafson P. Soft tissue sarcoma. Epidemiology and prognosis in 508 patients. Acta Orthop Scand Suppl. Jun 1994;259:1-31. [Medline].
- Hashimoto H, Daimaru Y, Takeshita S. Prognostic significance of histologic parameters of soft tissue sarcomas. Cancer. Dec 15 1992;70(12):2816-22. [Medline].
- Herbert SH, Corn BW, Solin LJ. Limb-preserving treatment for soft tissue sarcomas of the extremities. The significance of surgical margins. Cancer. Aug 15 1993;72(4):1230-8. [Medline].
- Huth JF, Eilber FR. Patterns of metastatic spread following resection of extremity soft- tissue sarcomas and strategies for treatment. Semin Surg Oncol. 1988;4(1):20-6. [Medline].
- Jensen OM, Hogh J, Ostgaard SE. Histopathological grading of soft tissue tumours. Prognostic significance in a prospective study of 278 consecutive cases. J Pathol. Jan 1991;163(1):19-24. [Medline].
- Kawai A, Noguchi M, Beppu Y. Nuclear immunoreaction of p53 protein in soft tissue sarcomas. A possible prognostic factor. Cancer. May 15 1994;73(10):2499-505. [Medline].
- Kroese MC, Rutgers DH, Wils IS. The relevance of the DNA index and proliferation rate in the grading of benign and malignant soft tissue tumors. Cancer. Apr 15 1990;65(8):1782-8. [Medline].
- Kushner BH, Meyers PA. How effective is dose-intensive/myeloablative therapy against Ewing''s sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review. J Clin Oncol. Feb 1 2001;19(3):870-80. [Medline].
- Lawrence W, Donegan WL, Natarajan N. Adult soft tissue sarcomas. A pattern of care survey of the American College of Surgeons. Ann Surg. Apr 1987;205(4):349-59. [Medline].
- Mankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited. Members of the Musculoskeletal Tumor Society. J Bone Joint Surg Am. May 1996;78(5):656-63. [Medline].
- Marcus SG, Merino MJ, Glatstein E. Long-term outcome in 87 patients with low-grade soft-tissue sarcoma. Arch Surg. Dec 1993;128(12):1336-43. [Medline].
- Markhede G, Angervall L, Stener B. A multivariate analysis of the prognosis after surgical treatment of malignant soft-tissue tumors. Cancer. Apr 15 1982;49(8):1721-33. [Medline].
- Meyers PA, Heller G, Healey J. Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience. J Clin Oncol. Jan 1992;10(1):5-15. [Medline].
- Montag A. Management of surgical specimen. In: Simon MA, Springfield D, eds. Surgery for Bone and Soft-Tissue Tumors. Philadelphia, Pa:. Lippincott-Raven;1998:67-75.
- Myhre-Jensen O, Kaae S, Madsen EH. Histopathological grading in soft-tissue tumours. Relation to survival in 261 surgically treated patients. Acta Pathol Microbiol Immunol Scand [A]. Mar 1983;91(2):145-50. [Medline].
- Pezzi CM, Pollock RE, Evans HL. Preoperative chemotherapy for soft-tissue sarcomas of the extremities. Ann Surg. Apr 1990;211(4):476-81. [Medline].
- Pinkerton CR, Groot LJ, Barrett A. Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas. Br J Cancer. 1991;64:381-385. [Medline].
- Potter DA, Glenn J, Kinsella T. Patterns of recurrence in patients with high-grade soft-tissue sarcomas. J Clin Oncol. Mar 1985;3(3):353-66. [Medline].
- Praemer A, Furner S, Rice DP. Neoplasms of bone and connective tissue. In: Musculoskeletal conditions in the United States. Park Ridge, Ill:. American Academy of Orthopaedic Surgeons;1992:55.
- Rooser B, Attewell R, Berg NO. Prognostication in soft tissue sarcoma. A model with four risk factors. Cancer. Feb 15 1988;61(4):817-23. [Medline].
- Rosenberg SA, Tepper J, Glatstein E. Prospective randomized evaluation of adjuvant chemotherapy in adults with soft tissue sarcomas of the extremities. Cancer. Aug 1 1983;52(3):424-34. [Medline].
- Rosenberg SA, Tepper J, Glatstein E. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg. Sep 1982;196(3):305-15. [Medline].
- Roth JA Jr, Roth JA. Resection of sarcomatous pulmonary metastases. Surg Oncol Clin N Am. 1993;2:673.
- Rydholm A, Gustafson P, Rooser B. Limb-sparing surgery without radiotherapy based on anatomic location of soft tissue sarcoma. J Clin Oncol. Oct 1991;9(10):1757-65. [Medline].
- Shidham V, Gupta D, Galindo LM. Intraoperative scrape cytology: comparison with frozen sections, using receiver operating characteristic (ROC) curve. Diagn Cytopathol. Aug 2000;23(2):134-9. [Medline].
- Shidham VB, Dravid NV, Grover S. Role of scrape cytology in rapid intraoperative diagnosis. Value and limitations. Acta Cytol. Jul-Aug 1984;28(4):477-82. [Medline].
- Stotter AT, A''Hern RP, Fisher C. The influence of local recurrence of extremity soft tissue sarcoma on metastasis and survival. Cancer. Mar 1 1990;65(5):1119-29. [Medline].
- Suit HD, Mankin HJ, Wood WC. Treatment of the patient with stage M0 soft tissue sarcoma. J Clin Oncol. May 1988;6(5):854-62. [Medline].
- Swanson SA, Brooks JJ. Proliferation markers Ki-67 and p105 in soft-tissue lesions. Correlation with DNA flow cytometric characteristics. Am J Pathol. Dec 1990;137(6):1491-500. [Medline].
- Tanabe KK, Pollock RE, Ellis LM. Influence of surgical margins on outcome in patients with preoperatively irradiated extremity soft tissue sarcomas. Cancer. Mar 15 1994;73(6):1652-9. [Medline].
- Tepper JE, Suit HD. Radiation therapy of soft tissue sarcomas. Cancer. May 1 1985;55(9 Suppl):2273-7. [Medline].
- Trojani M, Contesso G, Coindre JM. Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer. Jan 15 1984;33(1):37-42. [Medline].
- Tsujimoto M, Aozasa K, Ueda T. Multivariate analysis for histologic prognostic factors in soft tissue sarcomas. Cancer. Sep 1 1988;62(5):994-8. [Medline].
- Ueda T, Aozasa K, Tsujimoto M. Prognostic significance of Ki-67 reactivity in soft tissue sarcomas. Cancer. Apr 15 1989;63(8):1607-11. [Medline].
- Willén H, Akerman M, Carlén B. Fine needle aspiration (FNA) in the diagnosis of soft tissue tumours; a review of 22 years experience. Cytopathology. Aug 1995;6(4):236-47. [Medline].
- Wunder JS, Healey JH, Davis AM. A comparison of staging systems for localized extremity soft tissue sarcoma. Cancer. Jun 15 2000;88(12):2721-30. [Medline].
- Zalupski MM, Ryan JR, Hussein ME, et al. Systemic adjuvant chemotherapy for soft tissue sarcomas of the extremities. Surg Oncol Clin N Am. 1993;2:621.
Benign and Malignant Soft Tissue Tumors excerpt Article Last Updated: Dec 12, 2006
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