Biopsy of bone and soft tissue sarcoma: pitfalls



1. Bone and Soft Tissue Sarcoma Service, Royal Prince Alfred Hospital, New South Wales.
2. Royal Prince Alfred Hospital, New South Wales.


The biopsy of bone and soft tissue sarcoma is an integral part in the management of patients with these disorders and inadequate, inappropriate or inaccurate non-representative biopsies do lead to poorer outcomes for patients in terms of survivorship and limb salvage. We have conducted a review by comparing results of an audit conducted in 2002 with a repeat audit in 2009 of all biopsies performed in our department and biopsies performed on patients prior to referral for treatment. The results of that review clearly show that the method of biopsy is important in establishing a correct diagnosis and that inadequate or poorly performed biopsies compromise patient outcomes. It is clear that there is a significantly higher incidence of the need to change treatment to a more radical procedure than would originally have been necessary or to convert to palliative rather than curative intent on patients biopsied outside a specialist unit. Patients biopsied elsewhere were more likely to have an incomplete excision requiring re-excision, more likely to require amputation and more likely to require adjuvant radiotherapy. Sarcoma patients are best served by early referral to a specialist centre where staging investigations including biopsy can be performed with minimal morbidity.

Bone and soft tissue sarcomas are rare tumours accounting for 0.7% of all new cancer notifications in NSW per annum (soft tissue sarcoma 0.5%, bone sarcoma 0.2%). Within this group of tumours are a large number of diagnoses and it is necessary to have adequate tissue samples to establish not only cytology, but tumour structure to enable accurate diagnosis.1 Adequate specimens must be available for immunohistochemistry, cytogenetics, flow cytometry and progressively more complex molecular biological assessment. Careful planning of the biopsy is essential. An adequate volume of representative tissue must be obtained while avoiding contamination of adjacent tissue.2-4 The location of the biopsy tract must be noted to allow accurate excision at the time of the definitive surgery.

Furthermore, the specimen should be examined by a pathologist with experience in the area.2,3,7 It was first noted in 1982 by Mankin et al, that biopsy-related problems occurred up to five times more frequently if the biopsy was not performed by a specialist sarcoma surgeon.2,3 It was also recommended that if the surgeon or institution was not equipped to investigate the patient appropriately, perform definitive surgery and administer adjuvant therapy, then the patient should be referred to a treatment centre before biopsy. There are numerous papers that concur with this advice.8,9-12

Despite this extensive literature, it is apparent from our audit that inappropriate and inaccurate biopsies are performed by non-specialist practitioners, resulting in poorer outcomes.2-6 In the case of malignant tumours, the most destructive of biopsies in our audit involved an open biopsy performed inaccurately with contamination of the surgical field, resulting in the need for extensive re-excision or more mutilating surgery than otherwise would have been necessary. As a result there was a demonstrable reduction in five year survivorship.2,3,8,13-18

Data acquisition

An audit was performed initially, in 2002, at Royal Prince Alfred Hospital of all patients referred to the Bone and Soft Tissue Sarcoma Service. We excluded patients with metastatic lesions from unknown primary tumours at the time of presentation, infection or non-tumourous conditions. Patients staged elsewhere and referred purely for a second opinion, rather than ongoing management, were also excluded. Only those patients who had biopsy either prior to referral to our service, or after referral, and then subsequent definitive treatment were included. Staging investigations were completed as recommended by the Musculoskeletal Tumour Society.1 We recorded who performed the biopsy, the type of biopsy, the choice of biopsy site, whether or not adequate material was obtained and whether or not a poorly performed biopsy compromised or altered the definitive treatment. All histological diagnoses were recorded with the site of the tumour and stage. All referring surgical biopsies performed externally were examined by our own pathologists to confirm the diagnosis.

The most important part of the review was to make a comparison between the results of biopsy and the final resected specimen to confirm the accuracy of diagnosis. Complications of inappropriate or inaccurate biopsy were also recorded.

Following this initial audit being published and the information widely disseminated within the orthopaedic community in NSW, a similar audit was performed in 2009, to establish if there had been any general change in practice over the subsequent seven years.


In the initial audit, 142 patients satisfied inclusion criteria, 72 men and 70 women, with a mean age of 40 years (6-88 years). Eighty-three tumours arose primarily in bone, of which 48 (58%) were malignant. Fifty nine tumours arose in soft tissue sites, of which 29 (49%) were malignant. Overall there were 77 primary malignant tumours and 65 benign tumours, of which 14 were benign-aggressive. The distribution of the histological tumour types is shown in table 1.

The referring surgeon performed biopsies in 29 cases, of which 20 were malignant. The senior author (PDS) biopsied the remaining 113 cases, of which 57 were malignant. The diagnostic distribution of types of biopsy performed between these two groups is shown in table 2. Adequate diagnostic material was obtained in 21/29 (72%) of patients biopsied elsewhere, compared to 110/113 (97%) in the service at RPA (P<0.0001). The biopsy site was suboptimal and hindered definitive treatment in 11/29 (38%) performed externally, compared to 2/113 (1.8%) performed internally.

Table 1: The distribution of histological types in 142 patients with musculoskeletal tumours - 2002 Table 2: Distribution of types of biopsy performed by referring surgeons compared to the senior author in 2002

Fine needle aspiration had been performed in 7/29 patients biopsied elsewhere, with the important observation that only two of these patients were able to generate significant diagnostic material to plan further management.

Of the malignant lesions alone, 8/20 (40%) of patients biopsied by the referring surgeon required re-excision of an incompletely excised tumour, compared to 2/57 (3.5%) of patients biopsied by the senior author (P<0.0001). Adjuvant radiotherapy was required 4/20 (20%) compared to 3/57 (5.3%) (P<0.05). The amputation rate was 5/20 (25%) for external patients and of these, three were thought to have been unnecessary had the biopsy been performed differently. The amputation rate in those patients treated in the specialist service was 4/57 (7%) (P<0.03).

Table 3: The distribution of histological types in 144 patients with musculoskeletal tumours - 2009

Errors relating to biopsy had significantly altered the definitive management of 11/29 (38%) patients. An example of this is a 72 year-old woman who presented with a two month history of a rapidly enlarging and painful mass in the calf. The attending surgeon diagnosed an abscess and performed an ‘incision and drainage’ of the lesion without prior imaging.

Histological examination revealed a malignant fibrous histiocytoma. Staging investigations revealed a stage IIb tumour that would have been resectable with good margins. However, due to the extensive soft tissue and skin contamination, a below knee amputation was the sole alternative treatment.

These results were published in Australian literature19 and widely disseminated among the orthopaedic community. We have subsequently performed a further audit using the same criteria as in 2002 in an attempt to ascertain whether there has been any change in practice and therefore in outcome for patients with bone and soft tissue sarcoma.

The second audit was performed in 2009. Of the 144 patients, there were 81 males and 62 females with a mean age of 43 years (8-83 years). Sixty nine tumours arose primarily in bone, of which 45 (31%) were malignant. Seventy four tumours arose in the soft tissues, of which 33 (23%) were malignant. The distribution of histological tumour types is shown in table 3. One hundred and ten tumours were located in the extremities; 14 were in the pelvis, 14 in the trunk and five spinal.

The referring surgeon performed biopsies in eight cases, of which six were malignant. The senior author biopsied the remaining 138 cases, of which 72 were malignant. The distribution of the types of biopsy performed in both groups is shown in table 4. There were five fine needle aspirations within the group where the biopsy was performed by an external referring surgeon, all of which were non-diagnostic to a necessary level to determine appropriate treatment of the patient. The one excisional biopsy was incomplete and resulted in wide spread subcutaneous contamination, which ultimately could not be salvaged and the patient died.

There were no fine needle aspirations performed by the senior author. All biopsies, but one, were correct when compared to the final resected specimen. The one incorrect diagnosis was of an angiosarcoma overlying the sacrum. Multiple surgeries were necessary until the diagnosis became apparent. Even after repeat review of previous resected specimens, the histopathological diagnosis could not be made retrospectively.

Table 4: Distribution of types of biopsy performed by referring surgeons compared to the senior author in 2009

Interpretation and recommendations

It would appear that there has been a reduction in the number of biopsies performed externally to the Bone and Soft Tissue Sarcoma Service. We presume that this is due to wide-spread dissemination of the concepts to referring surgeons that poor biopsy leads to poor results. Stratification of which surgeons have performed those biopsies clearly shows that orthopaedic surgeons are much more likely to refer a patient for biopsy than other specialties. As the method of biopsy appears to have a significant impact on patient survivorship and morbidity, it seems incumbent on those specialising in the area to draw up guidelines for biopsy algorithms to improve patient outcome.

In the initial audit of 2002, 38% of patients’ definitive treatment was hindered by a poorly performed external biopsy. In 25% of patients, definitive treatment had to be changed to a more radical procedure or led to a palliative rather than curative procedure than would have been originally possible.8,13,17,20 It is also important to note that in the first audit, patients biopsied elsewhere had a much higher incidence of fine needle aspiration biopsy and non-diagnostic biopsy than those done in a specialist centre. In the subsequent audit, in 2009, there was a significant drop in the number of inappropriate biopsies being performed, however, numbers and examples of poor results still plague us.

One such example, perhaps, can be mentioned as it illustrates clearly the multiple steps required in the biopsy and treatment of a tumour in a young woman that needed to be addressed for appropriate management. A 17 year-old girl presented to a non-specialist sarcoma surgeon with a five x three centimetre mass in the subcutaneous tissue over the spinous processes in the mid-thoracic spine. An ultrasound examination was performed that demonstrated a “solid tumour”. Without further imaging and with a clinical provisional diagnosis of an epidermoid cyst, having been made, an excisional procedure was performed in a marginal fashion. The treating surgeon stated that during the procedure it was clear that the lesion was a solid tumour and not an epidermoid cyst, and yet a marginal excision was performed. The result was a cavity with contaminated margins from an infiltrating pleomorphic sarcoma, with considerable haemorrhage in the subcutaneous tissues five to seven centimeters in most directions.

The patient was then accurately staged and although initially without metastatic disease, resulted in both local recurrence and ultimately fatal metastatic disease, despite wide excision of the primary bed with over five centimetres margins radially.

This case demonstrates several inappropriate actions.

  1. The performance only of an ultrasound examination of an unusual tumour in an unusual location is inadequate pre-operative imaging before biopsy. Had a magnetic resonance image (MRI) scan been performed, it is highly likely that the misdiagnosis provisionally of an epidermoid cyst could have been avoided and a core biopsy performed to allow a diagnosis without contamination.
  2. Upon encountering a mass different to what was expected and having made the decision to proceed to excision of the lesion, the courageous decision would have been to stop at that point and not proceed. A formal incisional biopsy or frozen section could have been made, which would have allowed for the diagnosis of a pleomorphic sarcoma and hence the need for a different and appropriate plan of management.
  3. The worst option was that of marginal excision, leaving circumferentially positive margins, haemorrhage and an ultimate inability to obtain a safe excision.

While the literature unambiguously stresses the need for correct, adequate and careful biopsy by someone skilled in this process, there will still be occasions when an incorrect course of action is embarked upon. Any treatment algorithms should acknowledge this and allow salvage of the situation as safely as possible.

The following suggestions are made:

Any mass of sufficient size, where the diagnosis is in doubt and histology will be sought, requires adequate imaging prior to biopsy. This imaging almost always will involve MRI scanning. Ultrasound imaging is historically inaccurate in terms of the demands of biopsy for soft tissue sarcomas and should not be relied upon. It can accurately demonstrate the presence of a lesion and some of its characteristics, but cannot describe to the biopsying surgeon variability within the lesion and thus the location for biopsy for the most representative samples to be obtained. It is important in sarcoma biopsy to avoid necrotic areas and obtain viable material and the MRI scan is very helpful in this aspect. Failure to perform an MRI investigation on the patients in this audit and to rely on ultrasound was the single largest group of patients who have had inappropriate or inadequate biopsy.

An adequate volume of tissue must be obtained representatively from the tumour without contamination of the surrounding surgical field. Fine needle aspiration simply does not deliver adequate material in most cases for confident and accurate diagnosis and should be avoided.21,22 Core biopsy should remain the minimum standard of volume of tissue for histological analysis. Where an open biopsy is performed, it should be direct on to the tumour and through the pathway that would subsequently be used by a treating surgeon attempting limb salvage or excision of the tumour. There must be a frozen section performed at this stage to confirm the diagnosis prior to proceeding to either marginal or wide excision. In our audit, the performance of an inadequate marginal excision as the biopsy, without frozen section, has resulted in a large percentage of poor outcomes. If frozen section at this stage is not available, then the procedure should be abandoned and converted to a two-stage process allowing for laboratory analysis of the biopsy before definitive surgery.

The rareness of musculoskeletal sarcoma means that most treating surgeons will see few in a practice lifetime. The temptation for marginal excision is there, but should be resisted. In our audit, the most common point of re-referral to the Bone and Soft Tissue Sarcoma Service was when the treating surgeon was informed of positive margins on the resected specimen. Re-excision after positive margins is necessarily a more radical and mutilating process than a primary wide excision.

It is clearly shown that local recurrence is more likely and that five year survival is reduced despite wide re-excision. Thus, avoidance of inadequate primary resection is of paramount importance in the appropriate management of these rare tumours. Fine needle aspiration for sarcoma surgery has many disadvantages: it does not deliver the volume of specimen the pathologist often needs for the diagnosis of sarcomas; and the tract produced is often unidentifiable at the time of definitive surgery and may therefore be difficult to be excised. For these reasons, fine needle aspiration is not encouraged.

CT guided biopsy is widely used for tumours, particularly in difficult locations. For example, in the pelvis, the biopsy of a mass through an open procedure may be counterproductive as it would mean a huge exposure. There are always exceptions to the rule and particularly in locations such as the pelvis, a CT guided core biopsy is likely to produce less contamination than would an open procedure and is therefore appropriate practice. It is, however, recommended that the radiologist performing the procedure should discuss with the treating surgeon the best approach in an attempt to minimise contaminated biopsy tracts.

Recommendations from the Bone and Soft Tissue Sarcoma Service are that biopsy of tumours that could be sarcoma require the following:

  • appropriate pre-biopsy imaging
  • adequate and accurate biopsy by an experienced surgeon
    – if the above is not available, then communication with a skilled surgeon to discuss the biopsy prior to it being performed 
  • adequate volume of representative tissue must be obtained while avoiding contamination of adjacent tissue, with the specimen examined by a pathologist with experience in the area
  • if intra-operative frozen section of an adequate standard is not available after an open biopsy then definitive surgery should be delayed to a second procedure

The most commonly made mistakes remain the:

  •  inadvertent marginal excision of a primary malignant soft tissue sarcoma
  •  inappropriate biopsy of primary bone sarcomas.


1. Enneking WF. A system of staging musculoskeletal neoplasms. Clin. Orthop. 1986;204:9-24.
2. Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft-tissue tumours. J. Bone Joint Surg. 1982;64(A):1121-7.
3. Mankin HJ, Mankin CJ, Simon MA. The hazards of biopsy revisted. J. Bone Joint Surg. 1996;78(A):656-63.
4. Springfield DS, Rosenberg A. Biopsy: complicated and risky. J. Bone Joint Surg. 1996;78(A):639-43.
5. Markel DC, Neumann KU, Steinau HU. Appropriate techniques for musculoskeletal tumor biopsy. Orthop. Rev. 1994;23:176-80.
6. Bickels J, Jelinek JS, Shmookler BM, Neff RS, Malawer MM. Biopsy of musculoskeletal tumors. Current concepts. Clin. Orthop. 1999;368:212- 19.
7. Heslin MJ, Lewis JJ, Woodruff JM, Brennan MF. Core needle biopsy for diagnosis of extremity soft tissue sarcoma. Ann. Surg. Oncol. 1997;4:425- 31.
8. Siebenrock KA, Hertel R, Ganz R. Unexpected resection of soft-tissue sarcoma. More mutilating surgery, higher local recurrence rates, and obscure prognosis as consequences of improper surgery. Arch. Orthop. Trauma Surg. 2000;120:65-9.
9. Simon MA, Finn HA. Diagnostic strategy for bone and soft-tissue tumours. J. Bone Joint Surg. 1993;75(A):622-31.
10. Gustafson P, Dreinhofer KE, Rydholm A. Soft tissue sarcoma should be treated at a tumor centre. A comparison of quality of surgery in 375 patients. Acta Orthop. Scand. 1994;65:47-50.
11. Trovik CS, Gustafson P, Bauer HC et al. Consequences of local recurrence of soft tissue sarcoma: 205 patients from the Scandinavian Sarcoma Group Register. Acta Orthop. Scand. 2000;71:488-95.
12. Yao L, Nelson SD, Seeger LL, Eckardt JJ, Eilber FR. Primary musculoskeletal neoplasms: effectiveness of core-needle biopsy. Radiology. 1999;212:682- 6.
13. Noria S, Davis A, Kandel R et al. Residual disease following unplanned excision of a soft tissue sarcoma of an extremity. J. Bone Joint Surg. 1996;78(A):650-5.
14. Davis AM, Kandel RA, Wunder JS, Unger R, Meer J, O’Sullivan B 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. Stojadinivic A, Leung DH, Hoos A, Jaques DP, Lewis JJ, Brennan MF. Analysis of the prognostic significance of microscopic margins in 2084 localized primary adult soft tissue sarcomas. Ann. Surg. 2002;235:424-34.
16. Emrich LJ, Ruka W, Driscoll DL, Karakousis CP. The effect of local recurrence on survival time in adult high-grade soft tissue sarcomas. J. Clin. Epidemiol. 1989;42:105-10.
17. Zornig C, Peiper M, Schroder S. Re-excision of soft tissue sarcoma after inadequate initial operation. Br. J. Surg. 1995;82:278-9.
18. Bell RS, O’Sullivan B, Liu FF et al. The surgical margin in soft-tissue sarcoma. J. Bone Joint Surg. 1989;71:A370-5.
19. Pollock RC, Stalley PD. Biopsy of musculoskeletal tumours – beware. ANZ J. Surg. 2004;74(7):516-9.
20. Gerrand CH, Wunder JS, Kandel RA et al. Classification of positive margins after resection of soft-tissue sarcoma of the limb predicts the risk of local recurrence. J. Bone Joint Surg. 2001;83(B):1149-55.
21. Ward WG, Kilpatrick S. Fine needle aspiration biopsy of primary bone tumours. Clin. Orthop. 2000;373:80-7.
22. Kilpatrick SE, Cappellari JO, Bos GD, Gold SH, Ward WG. Is fine-needle aspiration biopsy a practical alternative to open biopsy for the primary diagnosis of sarcoma? Experience with 140 patients. Am. J. Clin. Pathol. 2001;115:59-68.

Be the first to know when a new issue is online. Subscribe today.