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Soft tissue sarcoma

Malignant (cancerous) tumors that develop in soft tissue are called sarcomas, a term that comes from a Greek word meaning "fleshy growth." more...

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In this context, the term soft tissue refers to tissues that connect, support, or surround other structures and organs of the body. Soft tissue includes muscles, tendons (bands of fiber that connect muscles to bones), fibrous tissues, fat, blood vessels, nerves, and synovial tissues (tissues around joints).

There are many different kinds of soft tissue sarcomas. They are grouped together because they share certain microscopic characteristics, produce similar symptoms, and are generally treated in similar ways. (Bone tumors, also known as osteosarcomas, are also called sarcomas, but are in a separate category because they have different clinical and microscopic characteristics and are treated differently.)

Sarcomas can invade surrounding tissue and can metastasize (spread) to other organs of the body, forming secondary tumors. The cells of secondary tumors are similar to those of the primary (original) cancer. Secondary tumors are referred to as "metastatic soft tissue sarcoma" because they are part of the same cancer and are not a new disease.

Some tumors of the soft tissue are benign (noncancerous). These tumors do not spread and are rarely life-threatening. However, benign tumors can crowd nearby organs and cause symptoms or interfere with normal body functions.

What are the possible causes of soft tissue sarcomas?

Scientists do not fully understand why some people develop sarcomas while the vast majority do not. However, by identifying common characteristics in groups with unusually high occurrence rates, researchers have been able to single out some factors that may play a role in causing soft tissue sarcomas.

Studies suggest that workers who are exposed to phenoxyacetic acid in herbicides and chlorophenols in wood preservatives may have an increased risk of developing soft tissue sarcomas. An unusual percentage of patients with a rare blood vessel tumor, angiosarcoma of the liver, have been exposed to vinyl chloride in their work. This substance is used in the manufacture of certain plastics.

In the early 1900s, when scientists were just discovering the potential uses of radiation to treat disease, little was known about safe dosage levels and precise methods of delivery. At that time, radiation was used to treat a variety of noncancerous medical problems, including enlargement of the tonsils, adenoids, and thymus gland. Later, researchers found that high doses of radiation caused soft tissue sarcomas in some patients. Because of this risk, radiation treatment for cancer is now planned to ensure that the maximum dosage of radiation is delivered to diseased tissue while surrounding healthy tissue is protected as much as possible.

Researchers believe that a retrovirus plays an indirect role in the development of Kaposi's sarcoma, a rare cancer of the cells that line blood vessels in the skin and mucus membranes. Kaposi's sarcoma often occurs in patients with AIDS (acquired immune deficiency syndrome). AIDS-related Kaposi's sarcoma, however, has different characteristics and is treated differently than typical soft tissue sarcomas.


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Classification of positive margins after resection of soft-tissue sarcoma of the limb predicts the risk of local recurrence
From Journal of Bone and Joint Surgery, 11/1/01 by Gerrand, C H

We considered whether a positive margin occurring after resection of a soft-tissue sarcoma

of a limb would affect the incidence of local recurrence. Patients with low-grade liposarcomas were expected to be a low-risk group as were those who had positive margins planned before surgery to preserve critical structures. Two groups, however, were expected to be at a higher risk, namely, patients who had undergone unplanned excision elsewhere with a positive margin on re-excision and those with unplanned positive margins occurring during primary resection.

Of 566 patients in a prospective database, 87 with positive margins after limb-sparing surgery and adjuvant radiotherapy were grouped according to the clinical scenario by an observer blinded to the outcome. The rate of local recurrence differed significantly between the two low- (4.2% and 3.6%) and the two high-risk groups (31.6% and 37.5%). This classification therefore provides useful information about the incidence of local recurrence after positive-margin resection.

J Bone Joint Surg [Br] 2001;83-B: 1149-55.

Received 9 January 2001; Accepted after revision after revision 14 May 2001

After resection of a soft-tissue sarcoma the status of the surgical margin predicts the risk of local recurrence.1-6 Enneking et al6 described the margin as intralesional when resection was carried out within the (pseudo) capsule of the tumour, marginal when the tumour was shelled out within the surrounding reactive zone, wide when the resection passed through normal tissue outside the reactive zone but within the anatomical compartment which was involved, and radical when the entire compartment was resected. The rate of local recurrence was 50% after marginal, 25% after wide and 4% after radical excision.

Rydholm and Rooser7 considered an intact muscle to be a distinct anatomical compartment and subclassified wide margins as wide-S (subcutaneous) when a subcutaneous tumour was excised with a cuff of subcutaneous tissue and deep fascia, wide-F (fascia) when a deep tumour was excised with an intact envelope of uninvolved fascia and wide-AM (areolar tissue and muscle) when a deep tumour was excised with a wide margin, some or all of which comprised muscle or areolar tissue. The five-year rate of local recurrence was 10% with wide-S and wide-F margins and 30% with a wide-AM margin.

Kawaguchi, Matumoto and Manabe8 suggested a classification which abandoned the use of compartmental anatomy to describe the resection. Margins were classified as curative, adequate or inadequate depending on the width and quality of the tissue comprising the margin. Inadequate wide margins did not ensure local control even with adjuvant radiotherapy in high-grade sarcomas, but were sufficient for low-grade tumours.

Since the development of management which combines limb-sparing surgery and adjuvant treatment, the description of surgical margins as simply positive or negative has become more common.1-5,9-11 A positive surgical margin in which there is tumour at the resection margin, implies that there is residual disease and is associated with an increased risk of local recurrence.1-5 In this situation, the volume and biological activity of residual disease are presumably critical to the risk of recurrence. While recognising that a positive surgical margin may occur under different circumstances, we have examined how these may influence the risk of recurrence.

Patients and Methods

We agreed a classification of four mutually exclusive clinical groups representing the clinical scenario in which a positive surgical margin may occur after limb-sparing surgery for sarcoma of a limb. A positive margin was defined as the presence of tumour at the margin of resection or intraoperative exposure of the tumour, even if the margin was subsequently revised to 'negative'. We defined margins as grossly positive when the surgeon or the pathologist could identify tumour at the margin of resection. A microscopic positive margin occurred when inspection of the margin did not reveal tumour, which was identified at histological examination.

Low-grade liposarcomas (group 1). The first group included all patients with a low-grade, well-differentiated liposarcoma. In our experience, and that of others, lowgrade liposarcoma arising in the limb seldom recurs locally after treatment and rarely metastasises.12,13 These lesions are often extensive at the time of presentation and adjacent to critical structures such as nerves, vessels or bones. In this situation we frequently accept microscopically positive margins after resection to preserve critical structures. A positive margin in this situation reflects this treatment philosophy of deliberate marginal excision (Fig. 1).

Planned positive margins against critical structures (group 2). This group included patients who had positive surgical margins against one or more critical structures (nerve, vessel or bone) which had been planned preoperatively as part of a primary resection. The decision to accept a positive margin was made in advance at a multidisciplinary team conference and confirmed at the time of resection by the surgeon and pathologist (Fig. 2).

Positive margin during re-excision after prior unplanned excision (group 3). Patients in this group had undergone unplanned excision of a sarcoma at another institution before referral, and subsequent re-excision at our centre with a positive surgical margin. An unplanned excision was defined as an excisional biopsy or resection carried out without adequate preoperative staging or consideration of the need to remove normal tissue around the tumour.14 The extent and adequacy of the unplanned excision were assessed in discussion with the original surgeon and by review of the initial pathology report, the initial operative note, and imaging studies undertaken before re-excision in our centre. Further excision was done if there was gross residual tumour on clinical examination or imaging, or if the resection had been inadequate.

Unplanned positive margins (group 4). In this group, during primary resection in our centre, a positive margin occurred which had not been planned (Fig. 3). This usually followed an error in assessing the extent of the primary lesion despite review of the imaging of the local site. If the positive margin was recognised during or immediately after surgery, further tissue was excised if this did not compromise critical structures. If the positive margin was recognised after definitive histological evaluation, a further wide excision was always considered. No patients had grossly evident tumour left in the wound at the completion of surgery.

It was considered that groups I and 2 would be at low risk of local recurrence and that groups 3 and 4 would be at higher risk. To test this hypothesis, a prospectively collected database containing all patients undergoing surgery for softtissue sarcoma in our centre was used to identify suitable patients. The inclusion criteria were: 1) a diagnosis of sarcoma other than dermatofibrosarcoma protruberans; 2) location in a limb; 3) the undertaking of limb-sparing surgery with curative intent; 4) a positive surgical margin; and 5) the administration of neoadjuvant radiotherapy. All patients underwent surgery between January 1986 and April 1997 to allow a minimum follow-up period of three years.

Patients who received chemotherapy because of histological type or metastatic disease were excluded. Our standard protocol of adjuvant external-beam radiotherapy comprises either 50 Gy preoperatively, with a postoperative boost of 16 Gy if there is a positive margin, or 66 Gy postoperatively by a reducing-field technique.

The following data were extracted from the prospective database and verified against the clinical records: age at surgery, gender, presentation with a primary tumour or local recurrence, open or needle biopsy, histological type, grade, anatomical location (deep or superficial, extra- or intracompartmental), maximum diameter of the tumour, the presence of lung metastases at presentation (all patients were staged by chest CT) and grossly or microscopically positive margins. The further management of positive margins was assessed from the clinical records. A pathologist with expertise in sarcoma determined the histological type and graded the tumours as 1, 2 or 3.(15)

A reviewer (CHG), blinded to the clinical outcome, assigned each case to one of the four groups. All low-grade liposarcomas were assigned to group 1 and all patients who had had an unplanned excision before referral were assigned to group 3, regardless of further management. After the initial classification, the surgeons who undertook the operations reviewed the classification of each tumour to ensure a consensus. The number and timing of local recurrences were reviewed. Local recurrence was defined as the reappearance of the tumour, proven by biopsy, adjacent to or within the previously treated field at any time after treatment in our centre.

Statistical analysis. We consider that low-grade liposarcomas (group 1) differ in their biological behaviour and management from tumours of other histological types and therefore they were analysed separately. The remainder (groups 2 to 4) were compared for differences in the local recurrence-free rate and the disease-specific survival as well as variables which may account for differences in these outcomes.

Continuous variables were compared using one-way analysis of variance (ANOVA) and the Tukey post-hoc test. Differences in proportions were compared using the chisquared test. Curves for the local recurrence-free rate and disease-specific survival were constructed using the method of Kaplan and Meier and compared using the log-rank statistic. A p value of 0.05 or below was considered to be significant. Data were analysed using the SPSS version 10.0.5 (SPSS Inc, Chicago, Illinois).


Between January 1986 and April 1997, 566 patients had been entered on the database, 112 of whom had positive surgical margins. We excluded 25 patients as follows: 12 who did not receive standard radiotherapy, seven who received chemotherapy, four with advanced metastatic disease who underwent palliative procedures, one with a positive margin after primary amputation and one who had exploration of an extensive sarcoma in the foot and was secondarily treated by amputation.

The remaining 87 patients, 42 men and 45 women, had a mean age of 60 years (21 to 95). A total of 24 patients died from metastatic disease at a mean of 1.8 years (0.3 to 6.6), and eight from unrelated causes at a mean of 2.1 years (0.2 to 7.7). The mean follow-up of the 55 surviving patients was 5.4 years (3.0 to 9.5).

The 24 patients with low-grade liposarcomas were placed in group 1. None had grossly positive margins. There was one local recurrence (4.2%, 95% CI 0 to 12.2) at four months, which was re-excised. All patients were alive and free from disease at a mean follow-up of 5.1 years (3.2 to 9.3).

Of the remaining patients, 28 were placed in group 2, 19 in group 3 and 16 in group 4 (Table I). When these groups were compared, group-3 tumours were significantly smaller than group-4 (p = 0.04), and group-4 tumours were smaller than group-2 (p = 0.02). There were more tumours in the proximal limb in group 2 than in group 3 (79% v 42%, p = 0.01) and group 4 (44%, p = 0.02). Groups 2, 3 and 4 did not differ significantly in regard to age, gender, local recurrence at presentation, grade and length of follow-up. There was no difference in the distribution of histological types across those groups, and no significant difference between the groups when deep and superficial, intra- and extracompartmental, and upper- and lower-limb tumours were compared.

In group 2, one of 28 patients developed a local recurrence (3.6%, 95% CI 0 to 10.4) at two months. This case was one of the 25 with microscopically positive margins. There were no local recurrences in the three patients with grossly positive margins. Twelve patients were alive at a mean of 5.2 years (3.0 to 7.4), 11 died from metastatic disease at a mean of 1.6 years (0.3 to 2.8) and five from other causes at a mean of 1.6 years (0.2 to 4.7).

In group 3, there were six local recurrences (31.6%, 95% CI 10.7 to 52.5). The mean time to local recurrence was 34.5 months (2.7 to 82.0). Clinical examination or imaging before re-excision identified 11 patients with a residual tumour mass. In five of these the positive margins were planned against critical structures adjacent to the residual mass and one had a further local recurrence. In comparison, an unplanned positive margin occurred during resection of the other six of the 11 patients with a residual tumour mass, and three of these had a local recurrence. In the eight patients without a residual tumour there were two local recurrences. Of all 19 patients, two had grossly positive margins and both had local recurrences, compared with four local recurrences in 17 patients with microscopically positive margins. In four patients, the positive margin was recognised intraoperatively, and the margin revised; two of these had a local recurrence. In two patients, the positive margin was recognised intraoperatively, but the margin could not be revised with acceptable morbidity. Neither of these developed a local recurrence. In 13 patients, the positive margin was recognised after histological examination; four of these developed a local recurrence. Of all 19 patients, ten were alive at a mean of 6.3 years (3.5 to 9.4), six died from metastatic disease at a mean of 1.7 years (0.7 to 3.2) and three died from other causes at a mean of 3.1 years (0.7 to 7.7).

In group 4, there were six local recurrences in 16 patients (37.5%, 95% CI 13.8 to 61.2). The mean time to the development of local recurrence was 24.9 months (5.9 to 68.1). One of four patients with grossly positive margins and five of 12 with microscopically positive margins developed a local recurrence. In nine patients, the positive margin was recognised intraoperatively, and the margin revised. Four of these developed a local recurrence. In three patients the positive margin was recognised intraoperatively, but the margin could not be revised with acceptable morbidity and none developed a local recurrence. In four patients, the positive margin was recognised after histological examination; three of these had no further surgery but two developed a local recurrence. In the fourth case, a second wide excision was carried out and there has not been local recurrence. Of the 16 patients in group 4, nine were alive at a mean of 5.6 years (3.0 to 8.9) and seven died from metastatic disease at a mean of 2.0 years (0.3 to 6.6).

The crude local recurrence rate in group 2 was significantly lower than that in group 3 (p = 0.03) and group 4 (p = 0.01), but that of group 3 and group 4 was not significantly different. The local recurrence-free survival was significantly different between groups 2 and 3 (p = 0.01) and groups 2 and 4 (p = 0.02), but not between groups 3 and 4 (p = 0.64; Fig. 4). The disease-specific survival in groups 2, 3 and 4 did not differ significantly (p = 0.74; Fig. 5).


Our study shows that the significance of a positive surgical margin after resection of a soft-tissue sarcoma in a limb is determined by the clinical scenario, and that classifying patients into groups may predict the risk of the development of local recurrence. Low-grade liposarcomas are biologically different, with a low risk of local recurrence despite marginal excision. Planned positive margins during primary resection (with adjuvant radiotherapy) are associated with a low risk of local recurrence. Positive margins following unplanned excision before referral as well as unplanned positive margins are associated with a higher risk of local recurrence.

Positive margins are more likely after limb-sparing procedures, although amputation does not guarantee negative margins.1-9 Trovik et al16 reported that positive margins were more common in patients over 50 years of age, with either low-grade tumours, tumours the diameter of which was more than 7 cm, deep tumours or tumours involving the trunk. After excision of soft-tissue sarcomas of the trunk or limb the reported rates of positive margins vary from 1%(17) to 26%(3). In a review of patients treated by an experienced multidisciplinary sarcoma group in Toronto, Wilson et al18 reported nine positive margins in 62 patients, a rate of 14.5%. The higher rate of positive margins after resection of low-grade liposarcomas in our database (27 of 49 patients, 55%) reflects a management philosophy which accepts deliberate marginal excision in many patients. Our study confirms that this approach, when combined with adjuvant radiotherapy, is associated with a low rate of local recurrence at the medium-term follow-up. Our rate of positive margins for other histological types (85 of 518 patients, 16%) is within the range which has previously been described.

When a soft-tissue sarcoma is adjacent to critical structures, the multidisciplinary team has to weigh the benefits of wider excision against the morbidity. The low rate of local recurrence after a planned positive margin in this situation demonstrates that this is a safe approach for many tumours. The experience of the multidisciplinary team is critical in making the decision to approach treatment in this way and may contribute to better outcomes in specialised centres.

It is our practice to offer re-excision to all patients who have undergone an unplanned excision unless the margins can be reliably assessed as adequate.19 If after unplanned excision there is a residual mass which lies adjacent to critical anatomical structures, a positive margin may be planned. If there is no residual mass, the extent of contamination by tumour cannot be accurately defined and reexcision has to be planned based on an estimate of the area at risk and the associated morbidity. A positive margin under these circumstances not only means that there is residual tumour, which may lead to local recurrence, but that the area involved with tumour has been underestimated.14

The exposure of tumour during primary resection because of surgical error is associated with a high risk of local recurrence.20 There was one local recurrence in four such cases in group 4. Of 16 patients in whom an unplanned positive margin occurred, 12 had microscopically positive margins and five developed local recurrence, suggesting that microscopically positive margins are also associated with a high risk of local failure.

Our study was not designed to assess the effect of revision of a positive margin. In patients who were not able to undergo revision of the positive margin because of local anatomical constraints, there were no local recurrences. It may be that a positive margin against a structure such as muscle, which is readily revised, is associated with more residual disease than a positive margin against a critical structure such as bone, nerve or vessel, which may not readily be resected and which may be more resistant to invasion by tumour.

The experience which we have gained while treating this group of patients was used to generate hypotheses tested on the same group and this study thus remains exploratory. A prospective study on a different group of patients is required to confirm the value of this classification. Classifying patients who have a positive resection margin in this way may provide useful information with regard to the development of local recurrence.

Mr Gerrand's Fellowship was supported by the Wishbone Trust, Ethicon, Depuy UK and Stryker Howmedica. Dr Davis is supported by a Health Career Award from the Canadian Institutes of Health Research, SSHRC/ NHRDP.

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.


1. Bell RS, O'Sullivan B, Liu FF, et al. The surgical margin in softtissue sarcoma. J Bone Joint Surg [Am] 1989:71:370-5.

2. Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF. Analysis of prognostic factors in 1041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 1996;14:1679-89.

3. Tanabe KK, Pollock RE, Ellis LM, et al. Influence of surgical margins on outcome in patients with preoperatively irradiated extremity soft tissue sarcomas. Cancer 1994;73:1652-9.

4. Singer S, Corson JM, Gonin R, Labow B, Eberlein TJ. Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma. Ann Surg 1994;219:165-73.

5. Sadoski C, Suit HD, Rosenberg A, Mankin H, Efird J. Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues. J Surg Oncol 1993:52:223-30.

6. Enneking WF, Spanier SS, Malawer MM. The effect of the anatomic setting on the results of surgical procedures for soft parts sarcoma of the thigh. Cancer 1981;47:1005-22.

7. Rydholm A, Rooser B. Surgical margins for soft-tissue sarcoma. J Bone Joint Surg [Am] 1987;69:1074-8.

8. Kawaguchi N, Matumoto S, Manabe J. New method of evaluating the surgical margin and safety margin for musculoskeletal sarcoma, analysed on the basis of 457 surgical cases. J Cancer Res Clin Oncol 1995; 121:555-63.

9. Heslin MJ, Woodruff J, Brennan MF Prognostic significance of a positive microscopic margin in high-risk extremity soft tissue sarcoma: implications for management. J Clin Oncol 1996;14:473-8.

10. Lewis JJ, Leung D, Casper ES, et al. Multifactorial analysis of longterm follow-up (more than 5 years) of primary extremity sarcoma. Arch Surg 1999;134:190-4.

It. Hajdu SI, Shiu MH, Brennan MFThe role of the pathologist in the management of soft tissue sarcomas. World J Surg 1988;12:326-31. 12. Zagars GK, Goswitz MS, Pollack A. Liposarcoma: outcome and

prognostic factors following conservation surgery and radiation therapy. Int J Radiat Oncol Biol Phys 1996;36:311-9.

13. Gustafson P. Soft tissue sarcoma: epidemiology and prognosis in 508 patients. Acta Orthop Scand Suppl 1994;259:1-31:1-31.

14. Davis AM, Kandel RA, Wunder JS, et al. The impact of residual disease on local recurrence in patients treated by initial unplanned resection for soft tissue sarcoma of the extremity. J Surg Oncol 1997;66:81-7.

15. Kandel RA, Bell RS, Wunder JS, et al. Comparison between a 2and 3-grade system in predicting metastatic-free survival in extremity soft-tissue sarcoma. J Surg Oncol 1999;72:77-82.

16. Trovik CS, Bauer HC, Alvegard TA, et al. Surgical margins, local recurrence and metastasis in soft tissue sarcomas: 559 surgically-- treated patients from the Scandinavian Sarcoma Group Register. Eur J Cancer 2000;36:710-6.

17. Flugstad DL, Wilke CP, McNutt NA, et al. Importance of surgical resection in the successful management of soft tissue sarcoma. Arch Surg 1999;134:856-61.

18. Wilson AN, Davis A, Bell RS, et al. Local control of soft tissue sarcoma of the extremity: the experience of a multidisciplinary sarcoma group with definitive surgery and radiotherapy. Eur J Cancer 1994;30-A:746-51.

19. Noria S, Davis A, Kandel R, et al. Residual disease following unplanned excision of soft-tissue sarcoma of an extremity. J Bone Joint Surg [Am] 1996;78-A:650-5.

20. Enneking WF, Meale GE. The effect of inadvertent tumor contamination of wounds during the surgical resection of musculoskeletal neoplasms. Cancer 1988;62:1251-6.

C. H. Gerrand, J. S. Wunder, R. A. Kandel, B. O'Sullivan,

C. N. Catton, R. S. Bell, A. M. Griffin, A. M. Davis

From Mount Sinai Hospital and Princess Margaret Hospital, Toronto, Canada

C. H. Gerrand, FRCS Ed (Trauma & Orth), Clinical Fellow

J. S. Wunder, FRCS C, Orthopaedic Surgeon

R. S. Bell, FRCS C, Director

A. M. Griffin, BSc, Research Assistant Suite 476

R. A. Kandel, FRCP C, Pathologist Department of Pathology, 6th Floor

Mount Sinai Hospital, 600 University Avenue, Toronto, Canada MSG 1X5.

A. M. Davis, PhD, Scientist

Room 1119, Toronto Rehabilitation Institute, 500 University Avenue, Toronto, Canada MSG 2A2.

B. O'Sullivan, FRCP C, Radiation Oncologist

C. N. Carton, FRCP, Radiation Oncologist

Department of Radiation Oncology, Princess Margaret Hospital, the University Health Network, 5th floor, 610 University Avenue, Toronto, Canada M56 2M9.

Correspondence should be sent to Dr A. M. Davis.

Copyright British Editorial Society of Bone & Joint Surgery Nov 2001
Provided by ProQuest Information and Learning Company. All rights Reserved

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