Biopsies

The need for a biopsy in the workup of oncologic disease 
It has become the norm that a biopsy is performed prior to surgical procedures involving malignancy.

At its most basic, the biopsy is a procedure designed to make a diagnosis of a lesion so that any further treatment can be indicated. In the case of tumors where the treatment is pharmaceutical (say lymphomas) it is only necessary to get a small amount of tissue to avoid the morbidity from a bigger procedure.

In the vast majority of solid tumors however because surgery is the norm, morbidity from a bigger operation can become necessary to establish a diagnosis before proceeding with the surgery.

3 scenarios of biopsy sequences can be described:

1. An incisional biopsy
In these sorts of procedures a small cut is made in a larger tumor. This can be done with a specialized cutting needle (Tru-cut biopsies). If it turns out that the tumor should be removed with a margin of tissue this can result in damage to surrounding structures. By knowing the diagnosis ahead of time however, both the surgeon and the patient will understand that this damage is required in order to control the tumor. Therefore in instances where the expected damage to surrounding structures is likely to be severe it is usually a good idea to get a biopsy beforehand (Figure 1).

Figure 1. An obvious reason for biopsy before surgery would be a case like this. Here a boy of 12 presented with pain in the left knee (a). The diagnosis was osteosarcoma, which meant the boy, would lose the distal half of his thigh bone (b) with a specialized joint replacement device (c). In this case I was able to save his tibia growing zone (d). He also required to undergo chemotherapy prior to surgery. All of these factors necessitate a biopsy to be done beforehand.

The problem with an incisional biopsy is contamination or risk of spread. In some areas this risk can be higher and can damage surrounding structures causing a salvageable limb to become unsalvageable or crippled (Figure 2). For example if a tumor is around a joint or next to an artery or nerve or other vital structure some thought should be given to removing a tumor immediately without an incisional biopsy. A variation on this theme is to do a frozen section biopsy on the table and then proceed in the same sitting to the actual excision. This approach is very dependent on acute diagnosis by a pathologist which can be wrong in as high as 20% of cases. Because of this it is often worth discussing an excisional biopsy as an option.


Figure 2. This boy had a Ewing’s sarcoma of the proximal tibia (a). Unfortunately he had been biopsied in a previous institution laterally which injured his common peroneal nerve (arrow, b). The tumor was resected after chemotherapy (c). A bone transplant was successfully performed (d). Nevertheless the nerve could not be saved and the boy had to undergo tendon transfers to correct his foot paralysis.


2. An excisional biopsy with minimal risk
In this procedure, the tumor is removed immediately without a biopsy. In principle this is done when removal poses minimal risk or morbidity to the outcome. Therefore if a patient presents with a small tumour (less than 3cm) it makes sense to just remove it immediately. It would be odd to biopsy it first because by the time a biopsy is done its already almost removed. Damage to surrounding tissue would also be minimal.

The same applies when the lesion is at the end of an expendable bone or structure like the rib, proximal fibula, distal ulna or distal phalanx. Especially in the proximal fibula a biopsy can result in leakage and contamination of the common peroneal nerve, which may have to be sacrificed thereafter (Figure 3).

Figure 3. This patient had a tumor in the proximal fibula (a). We approached the tumor laterally (b). Exposing the tumor showed the nerve in close proximity (arrowed, c). Obviously a biopsy here is ill-advised due to contamination of the nerve.


The spine is a special area for consideration. Often by doing a biopsy in the spine, it can become unstable and therefore one may be forced to do the biopsy and the main surgical procedure at the same time. For this reason a needle biopsy with a CT scan guide may be a better option but this can result in negative yield and therefore committing one to an open biopsy anyway.

It should be noted that an excisional biopsy is the most accurate modality of diagnosis compared to all other forms of biopsies.


3. An excisional biopsy with significant risk
These scenarios are the most difficult to manage. In such instances the biopsy itself may be a dangerous procedure and compel the excision of the tumor without a biopsy beforehand. Special categories of this include cartilaginous tumors, neural tumors and fat tumors. Careful understanding of the ramifications of the tumor needs to be understood.


Fatty tumors exist in three forms or grades namely, low, intermediate and high grade. The intermediate and high-grade tumors are usually sufficiently characteristic on MRI that a biopsy may be performed and a discussion of surgery and morbidity necessarily facilitated (as in 1 above). It may also qualify the need for preoperative adjuvant therapy (radiation and chemotherapy) if such is the practice. Low-grade tumors however look exactly like fat. They are very difficult to diagnose on biopsy due to sampling error – the tendency to biopsy a location in a tumor that looks benign. Because of this such a tumor may best be removed in toto as a malignant lesion (Figure 4) accepting the morbidity from loss of surrounding structures within reasonable limits (more or less muscle and minor nerves and vessels but perhaps not bone and major neurovascular structures).

 Figure 4. This tumor appeared to be fatty on MRI(a). It was seen to surround the sciatic nerve and femoral artery (circled). A biopsy was ill-advised as the tumor was close to these vital structures, had to be taken out anyway and if biopsied would have been subject to sampling error (b). In the specimen (b), we found three different tumor types from low-grade (well-differentiated) to intermediate grade. If the biopsy had sampled the low-grade area, the tumor would have been read as a benign tumor and either left alone or resected with less radical intent. Either approach could have been deleterious for the patient.


A similar problem is posed by cartilaginous tumors that again exist in low, intermediate and high-grade forms. The high-grade tumors are readily diagnosed but the intermediate and low-grade forms can be subject to sampling error and sometimes may look completely benign and later turn out to be malignant. The musculoskeletal oncologist must therefore be able to plan around the possibility that these low and intermediate tumors could be malignant even if seemingly benign. This usually takes the form of curettage with cryosurgery and a policy of close surveillance (Figure 5).

Figure 5. This boy had a fall and fracture of the left femur (a). We saw abnormal tissue at the fracture site and sent it for biopsy. This was read as a benign cartilaginous tumor (b). The fracture was stabilized and the patient followed closely. At 2 years he developed increasing pain (c). This was confirmed on CT scan to be a recurrence (d). The tumor was resected (e) and the limb salvaged with a massive prosthetic reconstruction (f).


Neural tumors inevitably result in nerve damage when subjected to biopsy or excision. This can result in paresis. Careful consideration is needed in this group of tumors (Figure 6). We have developed techniques of intraneural resection and repair of the nerve bearing the tumor that would minimize contamination and be compatible with limb salvage surgery (Figure 7). Typical tumors in this category are the nerve sheathe tumors (benign: Neurilemmoma or Schwannoma, malignant: Malignant Schwannoma), mixed nerve and sheathe tumors (neurofibroma and neurofibrosarcoma) and the PNET group of tumors (peripheral neuroepithelioma).


Figure 6. This patient presented with a tumor in the buttocks. Preoperatively, the scans did not show any sign of malignancy. Nerve biopsies can cause paralysis. In this case we biopsied the tumor and it was read as normal. Two biopsy procedures proved unhelpful. An open excisional biopsy showed it to be malignant and the tumor was then resected en bloc with all contaminated tissue.


Figure 7 (video). The case is a soft tissue sarcoma of the thigh. This presented as a tumor in the sciatic nerve which was resected intraneurally using a microscope because the clinical impression was of a nerve sheathe tumor. The patient did not have any neurological deficit and a well-centralised spot of sarcoma was found surrounded by benign tissue.


Conclusions
One should not take the biopsy lightly as a benign procedure as it can compromise successful limb salvage surgery. A careful consideration of all factors individualized to the specific patient is a necessary step in successful management of such cases.