Per-Ulf Tunn (Ed.), Treatment of Bone and Soft Tissue Sarcomas. Recent Results in Cancer Research 179, 3DOI: 10.1007/978-3-540-77960-5, © Springer-Verlag Berlin Heidelberg 2009

Abstract Although the diagnostic algorithm of a suspected bone or soft tissue tumour, as well as the biopsy itself, are well defined, avoidable errors still happen. Major flaws might lead to unnecessary tissue contamination resulting in amputations or recurrences. In the current review we will focus in particular on biopsy guidelines and possible biopsy-related problems such as haematomas, sampling errors, and postoperative fractures. Finally, we will provide ten simple rules for a successful biopsy.

1.1 Introduction

In suspicion of a bone or soft tissue sarcoma, biopsy is the key procedure in a well-defined diag-nostic algorithm. Although the primary goal of a biopsy (from old Greek: bíos , “life”, and ópsis , “look/appearance”) is to provide enough and rep-resentative tumour tissue for a histological diagnosis,

the performing surgeons should remember that avoidable errors could compromise subsequent surgery. Major flaws might lead to unnecessary tis-sue contamination possibly resulting in amputa-tions or recurrences (Mankin et al. 1982, 1996).

Some people may regard biopsies as the sim-plest procedures that could easily be handed over to the youngest and most inexperienced sur-geons. These people are partly right in that biop-sies are technically easy to perform, considering national or international guidelines (Bickels et al. 1999; Leithner and Windhager 2007a, b; Mankin et al. 1996). However, simple mistakes can lead to an increased morbidity rate (Bhangu et al. 2004; Mankin et al. 1982; Mankin et al. 1996; Zacherl et al. 2006). In the 1982 study by Mankin et al., biopsy-related problems occurred three to five times more frequently when the biopsy was performed at a referring rather than in a specialised centre (Mankin et al. 1982).

1.2 Diagnostic Algorithm

Jaffe stated in a book published in 1958 that a biopsy should be regarded as the final diagnostic procedure, not as a mere shortcut to diagnosis

Biopsy of Bone and Soft Tissue Tumours:Hints and Hazards

Andreas Leithner , Werner Maurer-Ertl , and Reinhard Windhager

1

Andreas Leithner (�)Univ. Clinic of Orthopaedic SurgeryMedical University of GrazAuenbruggerplatz 58036 GrazAustriaE-mail: andreas.leithner@meduni-graz.at

4 A. Leithner et al.

1(Jaffe 1958). Therefore, biopsies should always be preceded by primary diagnostics such as medical history, clinical examination, primary imaging studies such as X-rays and simple blood tests, and special diagnostic studies such as magnetic resonance imaging (MRI) and case-dependent computed tomography (CT), whole body bone scintigraphy, positron emission tom-ography (PET) and angiography (for a simpli-fied diagram see Fig. 1. 1 ).

A useful medical history should include start, kind, and duration of symptoms. A possi-

ble familial predisposition should be questioned (e.g. in hereditary osteochondromatosis or neu-rofibromatosis). Clinical examination consists of inspection and palpation to get an idea of the extent and the consistency of the swelling (solid/elastic/bony/...) and its relation to neighbouring structures. The size of the palpable mass should be documented in centimetres or millimetres and not in terms with great variability such as fruits, fists or children’s heads (Gray et al. 2003). If the swelling is located near a joint, its function and a possible intraarticular effusion should be noted. Sensomotoric deficiencies have to be docu-mented in detail in order to facilitate the early diagnosis of changes. In addition, the patient should be inspected undressed as, for example, café-au-lait spots would help to lead to the diag-nosis of neurofibromatosis.

Primary imaging studies of a suspected bone tumour comprise X-rays of the affected region in two planes. Nearly all bone tumours have their characteristic radiological features (Lodwick et al. 1980). Even for suspected soft tissue tumours X-rays might be useful, as calcifications might be shown. Unfortunately there are no reliable blood screening tests for musculoskeletal tumours avail-able. Some general blood parameters, however, could be helpful in determining local bone resorp-tion and signs of infection (e.g. red and white blood cell count, C-reactive protein (CRP), cal-cium, alkaline phosphatase, etc.).

When these primary diagnostic procedures still leave the suspicion of a musculoskeletal tumour, secondary or special diagnostic proce-dures are indicated. Especially the importance of MRI for bone and soft tissue tumours is unchallenged. Prior to definitive surgery a con-trast-enhanced MRI of the affected region and its neighbouring compartments is mandatory to detect possible skip lesions or regional metas-tases. The advantage of CT, in contrast to MRI, lies in the better visualisation of bony structures, for example in order to detect cortical destruc-tion. Knowing its limitations (sometimes false-negative for chondromatous tumours),

Fig. 1.1 Diagram of the simplified diagnostic algorithm recommended. (Translated from Leithner et al. 2007)

1 Biopsy of Bone and Soft Tissue Tumours: Hints and Hazards 5

whole body bone scintigraphy demonstrates the biological activity of a bone process and might detect a systemic spread (e.g. bone metastases) or a multifocal disease (e.g. enchondromatosis). Sensitivity, specificity, and accuracy of PET for the detection of sarcomas are still considered controversial (Bastiaannet et al. 2004).

1.3 Biopsy

After undertaking the diagnostic tasks men-tioned above, one has to decide whether or not a biopsy is indicated. If the tumour is clinically and radiologically unmistakably identified as a benign lesion one could omit a biopsy (Windhager et al. 2006). For example, some benign tumours could be observed (e.g. non-ossifying fibroma) or treated without prior biopsy (e.g. osteoid osteoma). When a bone metastasis is suspected in a case of a known systemic spread of a primary disease a biopsy is indicated only as an excep-tion. However, one should be aware that patho-

logical fractures in older patients are not always due to osteoporosis or metastatic disease—if the cause of the fracture or the imaging of the area are unclear, a biopsy should be performed to exclude a primary malignant tumour like a chondrosarcoma.

Again, when it is still not possible to exclude a primary malignant tumour as a potential dif-ferential diagnosis after all the previous steps of the diagnostic algorithm are complete, one has to perform a biopsy. The goal of a biopsy is to acquire enough representative tissue for histo-logical examination and contaminate as little as possible of the neighbouring tissue with the biopsy tract. If the presence of a malign tumour is confirmed, one has to excise the tumour including the biopsy tract with, in most instances, a surrounding cuff of normal tissue (Fig. 1. 2 ; Enneking et al. 1980). If the biopsy tract is not resected, local recurrences might occur (Schwartz and Spengler 1997). If an inad-equate biopsy led to the contamination of a joint and/or main neurovascular structures even an amputation might be indicated in some cases (Mankin et al. 1982, 1996). It is internationally

a b

Fig. 1.2 a Photograph after an inadequate intralesional resection (“whoops procedure”) of a fibromyxoid sarcoma G1 of the right axilla of a 49-year-old man. Note the two distant drainage exits resulting in an even larger re-resection b and the need for reconstruction with a musculocutaneous flap

6 A. Leithner et al.

1accepted that primary malignant musculoskel-etal tumours have to be resected with wide or radical margins according to the Enneking classification, while intralesional or marginal resections are associated with higher recur-rence/mortality rates and are therefore indicated only in exceptional circumstances (Enneking et al. 1980).

To perform a representative and technically adequate biopsy, the following preconditions are necessary:

1. Exact preoperative imaging. “Whoops pro-cedures” (e.g. when a so-called ganglion intraoperatively turns out to be a highly malignant soft tissue sarcoma) are in most instances the result of no or inadequate preop-erative imaging and are therefore avoidable (Davies et al. 2004). X-rays in two planes, an MRI (and sometimes a CT), a whole body bone scintigraphy or a PET should help to preoperatively define one main suspected entity and two to three potential differential diagnoses. Preoperative imaging studies should not be older than 4 weeks.

2. Preoperative planning. The shortest/simplest way to a tumour is not always the wisest. Before performing a biopsy one should think about how to resect the tumour when it would turn out to be malignant. According to these resection lines the biopsy has to be planned, as the biopsy tract is assumed to be contami-nated with tumour cells and has therefore to be resected with wide margins, as with the primary tumour itself. This implies that the surgeon doing the biopsy should be well acquainted with how the definitive surgery will proceed. For these reasons it is required that even the biopsy should be performed by an orthopaedic oncologist, or at least after consultation with one and following his rec-ommendations. Springfield and Rosenberg put all this in a simple “take home message”: “Do not biopsy what you are not going to treat” (Springfield and Rosenberg 1996).

1.3.1 Biopsy Technique

Generally, two types of biopsies exist—closed biopsies (e.g. core needle biopsies) and open biopsies (excisional or incisional biopsies).

1. Core needle biopsies (CNB), using a 14-gauge needle, and fine needle aspiration biopsies (FNAB), using 22- to 25-gauge needles, have been shown to be reliable techniques for bone and soft tissue tumours (Kilpatrick et al. 2001; Mitsuyoshi et al. 2006). Especially when the tumour is homogeneous, diagnostic accuracy is high. Even cytogenetic analyses have been shown to be possible in FNAB specimens from bone and soft tissue sarcomas (Kilpatrick et al. 2006). Both techniques are faster, simpler and cheaper compared to open biopsies and present less of infection and haematoma that can delay or compromise further treatment. Although sensitivity and specificity have been reported to be similar to open biopsy (Kilpatrick et al. 2001; Mitsuyoshi et al. 2006), other authors reported high rates of diagnostic errors for closed biopsies (den Heeten et al. 1985; Mankin et al. 1996). We are of the opinion that one should individually decide whether to perform a closed or an open biopsy based on individual patient factors, including location, suspected tumour type and homogeneity of the tumour, and according to the pathologist’s need. Guidance by fluoro-scope or CT for bony lesions or MRI in soft tissue cases is recommended to ensure that the area most suspicious of malignancy is chosen. With a closed biopsy one should never forget to exactly document and/or mark the biopsy canal entry point, as in case of malignancy this biopsy tract has to be resected and it is sometimes hard to detect the skin perforation after healing. For the same reason, if the closed biopsy is performed by a radio-logist, the orthopaedic oncologist has to define the path of the needle/trocar.

1 Biopsy of Bone and Soft Tissue Tumours: Hints and Hazards 7

2. With an incisional biopsy a representative tumour specimen is taken at the extremities through the smallest possible longitudinal incision. This technique is preferably chosen when a closed biopsy is impossible or the result of a closed biopsy was inconclusive or did not correlate with the clinical presentation and/or radiological finding. Other advantages are associated with the large amount of tumour tissue available for sometimes neces-sary additional pathological studies. When at the end of the diagnostic algorithm the diag-nosis of a benign tumour is evident, an excisional biopsy may be performed. In these cases the whole tumour is resected—e.g. an osteochondroma or an insuspect subcutane-ous tumour of less than 5 cm in diameter.

1.4 Hints

We propose ten rules for a successful biopsy:

1. Do not hurry 2. Do not contaminate nerves, vessels or joints 3. Do not operate without adequate preopera-

tive imaging 4. Send the biopsy specimen to a bone-/soft

tissue pathologist 5. Take the shortest way through one compart-

ment only 6. Plan your biopsy according to later resections 7. Gain enough and representative tissue 8. Operate as atraumatically as possible 9. Avoid a postoperative haematoma by all

possible means 10. Insert a drain, and lead it out through your

biopsy tract

An intraoperative frozen section is necessary when it is not certain if only the reactive zone or tumour itself was hit. In highly malignant tumours it is sometimes hard to macroscopically divide between vital tumour tissue and the pre-

dominantly present necrotic tissue. Here again an instant frozen section should be waited for.

If a potential differential diagnosis is a bacte-rial infection, an intraoperative swab should be gained prior to the administration of a perioper-ative antibiotic prophylaxis.

When performing an open biopsy of a bony lesion, the shape of the cortical window should be oblong with rounded ends, as it has been shown to provide greater residual strength when compared to rectangular holes with round or square corners (Clark et al. 1977).

1.5 Hazards

With some surgical procedures haematomas are regarded as unwelcome but acceptable side products. A haematoma at biopsy, however, could lead to an amputation (Mankin et al. 1982; Mankin et al. 1996). Especially with open biop-sies it is therefore mandatory to insert a drain and lead it out through the biopsy tract or in proximity and continuation with the skin inci-sion, as the drain path is considered contami-nated. Using a tourniquet during biopsy may be helpful in highly vascularised lesions; it should be opened, however, before wound closure to ensure exact haemostasis. In case of an iatrogenic cortical window and massive bleeding through it, one could close the hole using polymethylmeth-acrylate. If a haematoma already exists before biopsy one should photograph it to document its existence and its extent to enable an adequate resection of the tumour and the area that con-tained the haematoma (Fig. 1. 3 ).

The risk of having a “sampling error” is min-imised by sticking to the guidelines described above, but unfortunately such an error can never be totally excluded. As presented in Fig. 1. 4 , the malignant part of a heterogeneous and other-wise benign tumour is missed by 1 mm only.

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Therefore, multiple samples from different parts of the tumour should be obtained.

Especially incisional and excisional biopsies should keep incorrect histological diagnoses to

a minimum. In a retrospective analysis of 602 patients that had been operated on due to a soft tissue tumour at our institution, histological diagnoses of referring centres were reviewed as

a b

Fig. 1.3 a Perioperative photograph of the left proximal arm of a 59-year-old male patient with a suspected soft tissue sarcoma; note the existing haematoma. b The drain leaves directly through the biopsy canal

Fig. 1.4 “Sampling error”: cross-section of a 6 × 5 × 11-cm large sclerosing epithelioid fibrosarcoma G3 of a 69-year-old female patient. Although the biopsy tract (red area left) is 3 cm deep, it did not reach the highly malignant (violet) central part. Therefore the histological diagnosis of a (benign) desmoplastic fibroblastoma was given

1 Biopsy of Bone and Soft Tissue Tumours: Hints and Hazards 9

well as diagnoses based on open biopsies at our own institution. The histological diagnoses made by referring pathologists had to be cor-rected by the specialised pathologist in 41 of 187 cases (22%), and the histological change was of therapeutic relevance (e.g. benign to malign) in 17 cases (9%). At our centre the his-tological diagnosis at biopsy had to be changed after obtaining the whole specimen at defini-tive surgery in 16 of 249 cases (6%). Thirteen changes were of therapeutic relevance (5%) (Leithner et al. 2007). These results are slightly better compared to two other reports (Mankin et al. 1982, 1996; Table 1.1 ). The improvement may be attributed to a higher awareness of pos-sible flaws due to articles such as Mankin’s. The histological diagnosis of a soft tissue tumour should therefore always be made or at least controlled by a specialised pathologist at a tumour centre. Both surgeon and pathologist are responsible for a correct diagnosis.

Using local anaesthesia in tumour biopsy is sometimes risky as the area could be easily con-taminated with tumour cells.

Post-biopsy, care with mobilisation is recom-mended. Immobilisation and local compression should minimise the risk of a postoperative hae-matoma. Due to the same dangers after inci-

sional or excisional biopsies, drains should be left for at least 2 days. Especially after a bone biopsy at an extremity, the limb should be mobilised without load to reduce the risk of a postoperative fracture.

To the best of our knowledge it has not been sufficiently proved that a initial, technically poor biopsy decreases a patient’s chance of survival. However, it has been shown exten-sively that mistakes at biopsy might lead to higher morbidity due to unnecessarily large resections, re-resections, extensive reconstruc-tions, postoperative radiation and eventually amputations.

1.6 Definitive Diagnosis

The final diagnosis of a musculoskeletal tumour should never be based on histological findings alone. Only the synopsis drawn from all f indings—imaging studies, histology, age, loca-tion and medical history—will lead to a reliable diagnosis. A tight co-operation between all specialists of a multidisciplinary team is there-fore mandatory.

Table 1.1 Incorrect histological diagnosisa

Histological errors

Study Centre performing biopsy Total Majorb

Mankin et al. 1982 Referring centre (n=143)Specialised centre (n=186)

56 (39%)26 (14%)

43 (30%)17 (9%)

Mankin et al. 1996 Referring centre (n=282)Specialised centre (n=315)

--

52 (18%)29 (9%)

A. Leithner, W. Maurer-Ertl, Referring centre (n=187) 41 (22%) 17 (9%)

R. Windhager, unpublished Specialised centre (n=249) 16 (6%) 13 (5%)

a N umber of patients, with percentages in parenthesesb “Major“ means of therapeutic relevance

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