Introduction

Proper diagnosis is essential for the adequate management of musculoskeletal (MSK) tumors and biopsy is an important step to establish a definitive diagnosis of bone and soft tissue tumors.

The objective of biopsy is to obtain diagnostic tissue, minimizing morbidity by limiting potential tumor spread and avoiding interference with future treatments [1].

Percutaneous image-guided musculoskeletal biopsies are a cost-effective, rapid, and accurate method in the diagnosis of malignant and benign musculoskeletal lesions.

A multidisciplinary team, including a surgical oncologist, oncologist, and musculoskeletal pathologist is essential [2].

The purpose of this article is to review the literature in imaging-guided musculoskeletal biopsies.

Indications and ContraIndications

Indications

The major indications for bone or soft tissue biopsy are the evaluation of neoplasm or infection. Both treatment planning and pre-treatment (neoadjuvant therapy) of a neoplastic lesion depend on the tissue type while infections often appear aggressive on imaging, and discrimination from malignancy can be difficult [3].

The biopsy also allows isolating microorganisms in a musculoskeletal infection especially in patients who are unresponsive to conventional antibiotic treatment, leading to adequate targeted antimicrobial therapy [2].

Contraindications

The expected benefits of biopsy results should be significant when compared to their risks. Limitations and/or contraindications for musculoskeletal biopsy are bleeding diatheses, soft tissue infection, and inaccessible sites. [4, 5]

Before undergoing a biopsy, coagulation disorders must be corrected. The administration of fresh-frozen plasma, immediately prior the procedure temporarily corrects the international normalized ratio (INR), activated partial thromboplastin time and prothrombin time.

Inaccessible sites include sclerotic lesions next to major arteries and C1 and the odontoid process of C2 lesions [4, 5]. Tumor lesions that indistinctly involve neurovascular bundles, nerve plexus, and intestinal loops walls are a challenge to biopsy, especially when the method to be used does not define the correct differentiation of the planes, bringing potential undesirable complications such as intestinal fistulas, the formation of pseudoaneurysms, arteriovenous fistulas, and nerve lesions. At this point, methods that use contrast media may benefit this approach.

High bleeding risk procedures, such as biopsies of hypervascular lesions or lesions with blood content, must be carefully analyzed, considering the surrounding structures that can be potentially affected by the bleeding. Potentially bleeding lesions that occupy part of or erode the cortical of the spinal canal, at any level of the spine, can determine immediate complications of the biopsy, including hemorrhage and meningeal irritation.

The indications and contraindications for performing an osseous or soft tissue biopsy are similar and are outlined in Table 1.

Table 1 Indications and Contraindications for musculoskeletal biopsies
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Percutaneous Needle Biopsies Versus Open Surgery Biopsies

Complications of percutaneous needle biopsies are rare (1,1%), whereas open biopsy has a complication rate of up to 16% [6, 7].

Open biopsy has the advantage of non-exposure of the patient and/or the team to ionizing radiation, different from CT or fluoroscopic-guided biopsy, besides the possibility to confirm if the obtained material is adequate, in case of associating with frozen section analysis, or even the excision of confirmed benign lesions [1, 3, 8, 9••].

An open biopsy is preferred when a core biopsy gets the inadequate material, or when large specimens are needed to an accurate histological study, in order to lead to adequate preoperative radiotherapy or chemotherapy [1].

The disadvantages of open biopsies include the increased procedure time, complications of wound healing, and increased costs related to the operation room, hospital stay, and anesthesia [3, 10].

The advantages of percutaneous biopsy include a minor morbidity, besides a minor cost and less time procedure [3].

The main disadvantage of percutaneous biopsy is the accuracies large range varying from 74 up to 97% [3, 8, 10,11,12,13,14].

Sung et al. made a review of 309 cases, showing that for the diagnosis of homogeneous soft tissue tumors, core needle biopsy was particularly effective [15].

Generally, accuracy is low for primary bone tumors and high for metastatic disease [16]. Determining the exact grade and histologic type of the lesion from a sample can remain a difficult process, even in series in which biopsy had a great accuracy in differentiating benign and malignant process [3, 6].

The main advantages and disadvantages of percutaneous needle biopsies are outlined in Table 2.

Table 2 The main advantages and disadvantages of percutaneous needle biopsies compered to open biopsy
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Imaging Modalities

Various imaging modalities can be used to guide musculoskeletal biopsies, including CT, US, fluoroscopy, or MRI. Only 8–10% of the procedures are non-diagnostic when proper techniques are used [17, 18].

Ultrasound-Guided Biopsies

US guidance is useful to acquire samples from a variety of soft tissue processes and tumors as well as from lesions near a bone surface or bone lesion with an extra-osseous component. The high resolution of US allows easier visualization of some lesions, specially the small ones that are difficult to visualize on non-enhanced CT [2].

Kim and Chung showed that US-guided core needle biopsy of musculoskeletal soft tissue lesions is effective for diagnosis and decision making, even in lesions measuring 2 cm or smaller. However, when a lesion is 1 cm or smaller, US-guided core needle biopsy is more frequently insufficient for histopathologic diagnosis [19]. Figure 1 shows a small hypoechogenic lesion (2.6 × 1.6 cm) on the deep layer of the subcutaneous tissue in the right iliac fossa, which proved to be an endometrioma.

Fig. 1
figure 1

40-Year-old female with a painful nodule in the deep layer of the subcutaneous tissue in the right iliac fossa. a, b B-mode (a) and color doppler ultrasonography (b) shows hypoechogenic lesion without significant vascular flow. c Biopsy performed with tru-cut coaxial needle. Histologic examination confirmed it to be an endometrioma

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Furthermore, the US is a dynamic method and enables the monitoring of the needle tip throughout the procedure, avoiding vital structures and providing a satisfactory and safe biopsy [2, 20].

When bone lesions are associated with cortical destruction, US-guided biopsy can be performed using it as a window for the entrance of the needle into the medullary cavity [21].

Few studies demonstrated that US-guided MSK biopsies are reliable in distinguish malignant and benign lesions, with sensitivity of 95–96% and specificity of 100%. Accuracy for identifying the exact tissue type has been reported in 83–98% of cases [2, 22].

Computed Tomography-Guided Biopsies

Blastic or lytic bone lesions with or without soft tissue component can be visualized using CT scanning. It provides excellent confidence with its great spatial localization of the lesion, which allows determining the needle path, avoiding important structures, such as neurovascular bundles that are not involved by the lesion [2].

False-negative findings are rare in CT, as well false-positive are not common. One study with 176 core biopsies (accuracy of 93%) and 45 fine needle aspiration (accuracy of 80%), showed only 8% of non-diagnostic or insufficient biopsies [23, 24].

In another study, Trieu et al. observed an accuracy of 80.8% for bone tumors with diagnostic errors of 7.1% and undiagnostic rates of 12.1% and accuracy of 83.2% for soft tissue tumors with diagnostic errors of 10.5% and undiagnostic rates of 6.3%. They also showed that biopsy of benign tumors was more accurate than malignant tumors with a low overall procedural complication rate (0.7%) [25•].

Preprocedural Steps

Initially, a medical appointment is scheduled with the patient and his relatives, when all the available laboratory and imaging exams are evaluated, and with the requesting doctor, the real need for the procedure and the best planning is established, about the imaging method for procedure guidance, the material to be used and the path.

At this moment, we evaluate the blood coagulation and possible treatments with anticoagulant and antiplatelet drugs.

Platelet counts greater than 50,000/mm3 and INR between 1 and 1.2 are considered safe. There is no consensus regarding prothrombin time [20].

Oral anticoagulant drugs should be previously changed by low molecular weight heparin, which must be suspended 12–24 h before the procedure.

The suspension of antiplatelet agents and other anticoagulants, such as acetylsalicylic acid, warfarin, and clopidogrel, should be decided together with the assistant physician and in cases of punctures with fine needles, whose caliber not exceeding 20 gauge, the suspension of these drugs can be avoided.

In procedures with thicker needles and involving more complexity, either by the access route or by the number of fragments and expected time of manipulation, it is imperative their suspension 7-10 days before the procedure and perform a new coagulogram.

In high bleeding risk procedures (e.g., tumor radiofrequency), even with fine needles, the suspension of the treatment is recommended 7–10 days before the intervention [20].

The evaluation of all available imaging studies is mandatory. MRI helps in the characterization of soft tissue masses or soft tissue component of primary bone lesions and its relation to neurovascular structures, and CT is useful for detecting foci of internal mineralization and assessing cortical integrity. Whole-body scintigraphy is helpful for detecting metastatic disease or may reveal another lesion that could be easier or safer to biopsy than the original lesion.

If there is more than one candidate lesion for biopsy, the preferred lesion is usually the bigger or the more superficial one. When the lesions have heterogeneous imaging findings, the choice of the location of the biopsy within the lesion is crucial, because obtaining a sample that does not represent the main disease process could result in an incorrect diagnosis [3, 9, 26].

Enhancing areas or more vascular areas in post-contrast imaging are also more likely to provide diagnostic tissue, than non-enhancement areas, that could represent cystic or necrotic areas (Fig. 2).

Fig. 2
figure 2

81-Year-old male with peritrochanteric soft tissue mass suspicious of metastasis of squamous cell carcinoma. a–c Axial T1-weighted (a), T2-weighted fat-suppressed (b) and T1-weighted fat-suppressed gadolinium-enhanced (c) MR images and CT (d) showing central necrotic area (asterisk in a–c), corresponding to hypoattenuating area on CT (double asterisk in d). e Ultrasound-guided biopsy with a cutting core needle at the periphery of the lesion

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Planning the Biopsy Route

If there is suspicion for metastasis, surgical resection is usually not indicated, then the percutaneous biopsy can be performed by the safest and easier path, meanwhile, solitary bone or soft tissue lesion must be considered for primary sarcoma with possibility of surgical resection. When there is the possibility of a primary sarcoma, the radiologist should select the biopsy pathway in collaboration with the surgeon to ensure that the surgical resection includes the potentially contaminated tissue by needle track with the same margins of the primary lesion. Besides, knowledge of anatomic compartments of extremities is important, as the needle must not traverse an unaffected compartment or a neurovascular bundle, what would require a major surgical resection or a lager irradiation field to minimize the chance of local recurrence and could increase the morbidity or functional deficit [3, 9••, 27••, 28].

Pathway

Flat bones (scapula, sternum, ribs, and skull) are accessed through an oblique approach with angle of 30°–60° (Fig. 3).

Fig. 3
figure 3

Third costal arch lytic lesion biopsied with Jamshidi® 11G needle. Axial CT with MIP reconstruction (a) and axial CT image (b) show the tangential path of the needle. The lesion was related to multiple myeloma

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For clavicle lesions, the location of the lesion within the bone determines the route taken to obtain a diagnostic sample. Medial or proximal third clavicle lesions can be biopsied from a medial-to-lateral approach traveling along the long-axis of the clavicle; middle third clavicle lesions can be accessed with a direct anterior oblique approach and lateral or distal third clavicle lesions can be accessed from a lateral-to-medial approach [29].

For lesions on the pelvic girdle, the posterior way is the preferred, avoiding the nervous structures and the sacral canal (Fig. 4).

Fig. 4
figure 4

A 72-year-old male with history of prostate neoplasia presenting with suspicious acetabular lesion. CT (a) shows mixed lesion without cortical rupture with focal area of increased FDG uptake on PET (b) (white arrow in a, b). c CT image with oblique reconstruction showing the posterior path of the biopsy needle, avoiding the sciatic nerve and adjacent vascular bundle. Histopathology confirmed that it was prostate metastasis

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For peripheral long bone, orthogonal route to the bone cortex minimizes slippage with the needle tip, keeping in mind that the shortest path reduces tissue damage, however without forgetting that the approach must avoid vascular, nervous, visceral and tendinous structures, multicompartmental path and sometimes, muscular and joint structures (Fig. 5).

Fig. 5
figure 5

35-Year-old female presenting with a sclerotic medullar lesion in the medial aspect of the right distal femur. a CT-guided biopsy with core needle passing through the posteromedial portion of the vastus medialis muscle. b Post-procedure CT showing the needle path

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Different routes can do the access to the lesions of vertebral bodies: thoracic level can be accessed through transpedicular, posterolateral (Fig. 6), or transcostovertebral route (Fig. 7) and lumbar level biopsy can be performed by posterolateral or transpedicular route (Fig. 8) [20, 30].

Fig. 6
figure 6

69-Year-old male with suspected spondylodiscitis at T12-L1. CT oblique axial image (a) and oblique sagittal image (b) reconstructions showing posterolateral path of the core needle

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Fig. 7
figure 7

Transcostovertebral pathway for biopsy of mixed lesion in the vertebral body of T10 related to breast metastasis

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Fig. 8
figure 8

Lytic lesion biopsy in the vertebral body of L4 related to multiple myeloma. Transpedicular route with Jamshidi® 11G needle

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Comparing the effectiveness of biopsying the paravertebral soft tissue with biopsying the disk or vertebral endplate, Chang et al. concluded that paravertebral soft tissue changes, when present, might be considered a viable target for biopsy in cases of diskitis–osteomyelitis, even in the absence of a paravertebral abscess [31].

Technique

There are two types of percutaneous biopsies: core needle biopsies (CNB) and fine needle aspirations (FNA).

In FNA, fine needles (20–25G) are used to obtain a cellular aspirate for cytologic analysis. Its main advantage is to be less invasive, and its main limitation is not to give structural information [20].

However, Kaur et al. showed that FNA and CNB can alleviate the need for an open biopsy in many cases of musculoskeletal neoplasms, reporting a high accuracy with FNA (correct diagnosis in 72.2% cases) and with CNB, which was able to identify the accurate grade in 84.6% of the cases when compared with final excision. The specificity of both the techniques, FNA and CNB was 100% [32].

For infections or metastatic disease, fine needle aspiration usually provides adequate diagnostic samples. For additional information about the cell type, lesion’s architecture, and histologic grade, which are important for diagnosis of a primary bone or soft tissue malignancy, core needle biopsies are preferred [3].

CNB can be performed by direct needle insertion or by coaxial technique.

Coaxial technique consists of a method that allows multiple biopsies to be performed with a single puncture, reducing the potential for complications and the patient’s exposition. By means of this technique, a needle of the appropriate size is placed so that another finer one passes through its interior and can be able to realize multiple passages.

In the setting of bone lesions with cortical destruction, biopsies of the soft tissue component of the tumor should be preferred, as it is the most active or aggressive component (Fig. 9).

Fig. 9
figure 9

a–d Axial T1-weighted (a) T2- weighted fat-suppressed (b) and T1-weighted fat-suppressed gadolinium-enhanced (c) MRI images and axial CT image (d) show multiple lesions in the medullary of the iliac and sacrum, the largest in the left iliac demonstrates extensive soft-tissue component (white arrows in a–c) and lytic appearance on CT (asterisk in d). e Ultrasound-guided biopsy of the soft tissue component in the left iliac with tru-cut 16G core needle by coaxial method

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In soft tissue tumors, it is recommended obtaining up to five samples, for better diagnostic accuracy, with cylinders of 10 mm in length. The most active zone of the tumor (vascularized, solid, greater PET activity, soft tissue component of a bone lesion) must be the target of the biopsy [20].

It is possible to differentiate malignant or benign lesions in more than 90% of the cases [9••].

When there is no soft tissue component of the bone lesion, should be used specific needles to penetrate the bone, such as Ostycut®, Bonopty®, or Jamshidi®.

Type of Needle

The choice of the type of needle for bone biopsy depends on the location (bone or soft tissue), consistency, and depth of the lesion as well as the integrity of the cortical bone in cases of bone lesion.

For bone biopsies:

If the lesion is intramedullary and covered by intact bone cortex, a biopsy needle system with a drill tip will provide the easiest and quickest access.

Trephine Needles: These large-gauge needles have a serrated or saw-toothed cutting edge, including Ostycut® (C.R. Bard) and Jamshidi® (CareFusion Corp., San Diego, Calif.):

The Ostycut® (C.R. Bard) needle has a threaded cutting cannula with a trocar point stylet.

Jamshidi® is a cylindrical needle with a tapered cutting tip, which reduces the potential of crush artifact. It can be used in cases of mild ossification or a small cortex surrounding the lesion.

Bonopty®: The RADI Bonopty coaxial drill and biopsy needle system (RADI Medical Systems, Uppsala, Sweden), with a 14-gauge sheath and eccentrically cutting 15-gauge drill tip, is one of the most effective in penetrating intact cortical bone [7]. In cases of dense ossification or dense cortical bone surrounding the lesion can be used a 14-gauge Bonopty penetration set.

Spring-loaded core biopsy needles are not sufficiently strong for bone biopsies. The fragile trocar can be damaged in hard lesions or soft lesions surrounded by intact or sclerotic bone. [28].

For soft tissue biopsies:

Coaxial True-cut 14- to 16-gauge needles are used (Temno; Allegiance Sante S.A., Maurepas, France).

The Procedure

Patient should be informed again, in the day of the procedure, about the technique and eventual risks, and so, a written consent term is obtained.

Computed Tomography-Guided Biopsies

Material

Sterile drapes, tampons

20 or 22-gauge Chiba needle

Surgical hammer (may be required)

Iodine, 1% lidocaine

Naropin (bupivacaine) 1% in a 50% ou 25% dilution

Scalpel

Biopsy needle:

Bone tumor: trephine needle

Soft tissue tumor: 14 or 16-gauge coaxial tru-cut needle

Opsite®

First, a CT scan is performed to localize the lesion precisely and to plan the needle pathway, avoiding neurovascular and visceral structures.

The procedure must be performed in accordance with the principles of asepsis in relation to the puncture site and to the material employed.

Bone biopsies may be done under local anesthesia alone or under local anesthesia associated with general anesthesia, depending on the integrity of the cortical bone and the presence of soft tissue component. When there is clear rupture of the cortical and soft parts component, we performed the biopsy under isolated local anesthesia.

For local anesthesia, the track is infiltrated with lidocaine 1%, using a 22-Gauge Chiba needle, including skin, subcutaneous tissue, muscles, and periosteum. Using the same needle, it is injected naropin 1% in a 50% dilution.

Then, the bone biopsy needle usually Jamshidi® is inserted. It can be necessary using a surgical hammer for perforation of the cortical bone, when it is preserved. A new CT imaging, for checking the needle position, is then performed (Fig. 8) and so the samples are acquired, usually one or two fragments using the 8 or 11 Gauge bone biopsy needle are enough, although Wu et al. [14] suggested a greater diagnostic yield when obtaining a minimum of three specimens in bone lesions and four specimens in soft tissue lesions during CNB with thinner needles (15 Gauge).

The specimens are fixed in 10% formalin for histopathologic examination. Some specimens are not fixed, and sent for culture if bacteriological studies are necessary.

CT can also guide soft tissue biopsies. In these cases, local anesthesia with or without general anesthesia and specific needle use may be done (Fig. 10), similar to the ultrasound-guided procedure.

Fig. 10
figure 10

a, b Axial unenhanced CT images with soft-tissue (a) and bone (b) windows showing paravertebral soft tissue mass (asterisk in a, b) with bone changes at T10 level. c Axial unenhanced CT image with patient prone during percutaneous biopsy shows spring-loaded soft-tissue biopsy needle (Tru-cut 16 G) (arrow) with tray open. The mass proved to be large cell B non-Hodgkin lymphoma

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Ultrasound-Guided Biopsies

Material

Sterile drapes, tampons

20 or 22-gauge Chiba needle

Surgical hammer (may be required)

Iodine, 1% lidocaine

Naropin (bupivacaine) 1% in a 50% or 25% dilution

Scalpel

Biopsy needle

High-resolution linear transducers are the ideal for MSK interventions. However, in some cases, such as deep lesions or obese patient, it may be necessary to use lower frequency convex probes with the drawback of loss of spatial resolution and greater difficulty in visualizing the needle [2, 33].

For identifying any neighboring vascular structures or vascularization within the lesion, color Doppler is routinely used. Vascular and solid regions of the lesion should be sampled [2].

The procedure is performed under local anesthetic, and rarely using sedation. The biopsy site is then prepared in a sterile manner. A sterile bag with a small amount of sterile gel (used as a coupling agent) covers the ultrasound probe.

The choice of the biopsy needle depends on the operator preference and the type of lesion.

We often use 14, 16, or 18 gauge core biopsy-cutting needle. The length of the needle and the length of the throw depend on the lesion and its location. Typically, a 20-mm throw is sufficient.

Using ultrasound guidance, local anesthetic is injected into the skin and along the needle path. Then the biopsy needle is inserted in the same longitudinal plane as the ultrasound transducer, in order to allow the visualization of the needle (Fig. 1).

To facilitate the entry of the biopsy needle, it is made a 5-mm longitudinal skin incision, which also serves as a marker of the biopsy site, for the surgeon.

Using the same path of the anesthetic needle, the biopsy needle is inserted.

In the case of cystic lesions, solid parts or regions with more vascularity shown on Doppler should be targeted. These areas are more effective in providing histological diagnosis. Otherwise, the wall of the lesion should be targeted [2].

After performing the biopsy, ultrasound of the site must look for complications, mainly hematomas. An adhesive film, such as OPSITE®, is used to close the skin lesion. Observation for at least 120 min before discharging the patient is necessary, in uncomplicated cases.

Additional home care includes relative rest for 24–48 h with little ambulation and no physical effort.

The use of ice pack for 20 min at 4/4 h intervals during the first 12–24 h is mandatory for helping controlling pain, bruise, and local swelling.

The initial occlusive curative should be kept for 24 h and then removed. The site should be kept clean, dry, and uncovered from this moment onwards.

The use of antibiotics and analgesics is generally not necessary and is restricted to cases of prolonged manipulation, difficult access, and immunosuppressed patients.

Non-hormonal anti-inflammatory drugs or corticosteroids should be avoided which would facilitate local bleeding. Preference is given to common analgesics such as acetaminophen.

Complications

Complications of percutaneous image-guided musculoskeletal biopsies are rare.

Potential complications include bleeding, infection, or neuropraxia [2].

One of the most worrying complications is the septic osteitis. Strict sterile technique limits the risk of infection.

Seeding malignant cells in the needle path in cases of sarcoma is another possible complication. The adequate needle path is crucial for limb-salvage procedures [7].

Other rare possible complications are reflex sympathetic dystrophy and pneumothorax [30].

Conclusion

Percutaneous image-guided MSK biopsies are a minimally invasive, safe, and cost-effective method that provides high diagnostic results with lower risks when compared to open biopsies. The knowledge of the best techniques, indications, and contraindications for percutaneous image-guided MSK biopsies is mandatory as they have an important role in patient management.