Editorial   |    
Editorial - Biopsy: Complicated and Risky
Dempsey S. Springfield, M.D.; Andrew Rosenberg, M.D.
J Bone Joint Surg Am, 1996 May 01;78(5):639-43
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Tumors of the musculoskeletal system, especially malignant tumors, are rare. The practicing orthopaedic surgeon will see fewer than one primary malignant tumor of the musculoskeletal system every three years. This means that only orthopaedic oncologists will have much experience in the treatment of sarcomas, and there can be little, if any, argument that a patient who has a sarcoma should be referred to a medical center at which there are physicians who have expertise in the treatment of musculoskeletal neoplasia. We suspect that this happens when the referring surgeon knows that the lesion is malignant. All too often, however, the referring surgeon either does not think that the patient has a malignant tumor or finds the temptation to perform a biopsy too strong to resist. When the possibility of malignancy is not even considered, the lesion usually is excised inadequately. An inadequately excised or poorly biopsied sarcoma makes a difficult situation worse. The biopsy of musculoskeletal tumors is not easy and requires careful thought and planning. This issue of The Journal contains three articles that address this topic.
Skrzynski et al. compare the diagnostic accuracy and monetary cost of open biopsy performed in an operating room with those of needle biopsy done in an outpatient clinic and report that, for selected patients who have a musculoskeletal tumor, the latter procedure is just as accurate and is less expensive than the former. Noria et al. examine the problem of residual tumor in patients who have had an unplanned excision and report that macroscopic or microscopic tumor often is present even when the referring surgeon thinks that the entire tumor has been removed and when no tumor is seen on postoperative cross-sectional computerized tomographic or magnetic resonance imaging studies. Mankin et al. revisit the issue of complications associated with biopsy and report that the same problems that they described at the time of their original study2 still were present at the time of their later study3. It seems that nothing had changed in the eleven years between the two study periods. These three reports remind us that a biopsy is an important aspect of the evaluation of musculoskeletal tumors and that it needs to be given more attention than it has been given in the past.
Skrzynski et al. report that, in selected patients, a needle biopsy can be done with local anesthesia and without having to admit the patient to the hospital. (Although it is not stated, most of their patients probably were evaluated with computerized tomography or magnetic resonance imaging before the biopsy was performed.) This saves more than $6000 per patient compared with the cost of an open biopsy performed in an operating room. The diagnostic accuracy of the closed needle biopsy was 84 per cent (fifty-two of sixty-two lesions were diagnosed correctly), and that of the open biopsy was 96 per cent (forty-eight of fifty lesions were diagnosed correctly). Only ten of sixty-two lesions were not diagnosed correctly on the basis of closed needle biopsy. All ten were soft-tissue tumors, and the sample that was obtained from eight of the ten did not include diagnostic tissue. Those authors suggest that it is safe, reasonable, and cost-effective for an experienced orthopaedic oncologist (or musculoskeletal tumor surgeon) to perform needle biopsies in the outpatient setting for patients who have certain tumors. We add the additional caveat that such procedures should be performed only after an adequate evaluation. Although $6000 will not be a substantial percentage of the eventual medical bills of most of these patients, and we do not know what costs were not accounted for in the analysis, it is likely that these data provide a basis for the recommendation of outpatient needle biopsies for properly selected patients. The most important aspect of the selection of the patients for outpatient needle biopsy was that it was performed carefully by an experienced orthopaedic oncologist. We suspect that the average surgeon would have considerable difficulty matching the high rate of diagnostic accuracy for core biopsy reported by Skrzynski et al. as selection of patients and correct interpretation of the imaging studies are critical. Another issue is that the tumors selected for an outpatient needle biopsy were the easy ones. What about a small soft-tissue tumor deep in the thigh, a tumor in the true pelvis, or a lesion in the body of a lumbar vertebra? That is where we have real trouble.
We have found that the selection criteria for patients who are to have a closed needle biopsy can be broadened substantially if the biopsy is performed under the guidance of computerized tomography. Generally, three cores of tumor-bearing tissue are required for an appropriate workup. One core should be used for frozen-section analysis to confirm the presence of tumor and to allow for the appropriate triage of tissue for special studies, if necessary. This core should be kept frozen for immunohistochemical analysis (certain antigens are best preserved in frozen tissue) and molecular genetic studies. A piece of the second core can be used for electron microscopy. The rest of the second core and the entire third core should be processed routinely in paraffin so that a hematoxylin and eosin-stained slide can be produced. The tissue in the block also can be used for immunohistochemical analysis and flow cytometry.
Noria et al. studied a situation that is encountered too often in the treatment of musculoskeletal tumors: the presence of residual tumor after an unplanned excision. Those authors reviewed the records of a group of patients who had been referred to their orthopaedic oncology center after having had an excision of a soft-tissue sarcoma and selected those in whom the excision had been inadequate. They further selected only those who had no evidence of residual tumor on the basis of a review of the operative report and the diagnostic cross-sectional computerized tomographic scans or magnetic resonance images that had been made at their institution after the excision. A re-excision then was performed by one of the authors, and residual tumor was found in twenty-three (35 per cent) of the sixty-five specimens. This result is not surprising, however, because many important pathological and clinical features at the site of the initial excision—for example, the anatomical depth as well as the margins of the tumor (well circumscribed or infiltrative), the presence of vascular or neural invasion, and the proximity of the tumor to major neurovascular and skeletal structures—were not evaluated. Furthermore, the pathological examination of the specimens obtained at the time of the re-excision, which is of prime importance to this study, should have been more comprehensive. The specimens were sectioned serially only at 1.2-centimeter mean intervals, and the number of sections actually taken from the operative site was not mentioned. Consequently, most of the tissue was not examined histologically, and this may explain why residual tumor was not found in 65 per cent (forty-two) of the specimens. We think that the entire operative site should have been examined histologically. Residual microscopic disease is the source of local recurrence, and postoperative irradiation will not control all local recurrences. Another disturbing aspect of the study by Noria et al. is that approximately one-quarter of the new patients referred to their clinic were referred after the excision of a sarcoma. Most of these patients had had limited or no evaluation before the excision. The principle of "first do no harm" was violated for these patients. Our experience has been similar to that of Noria et al. Almost all of the patients referred to us after an inadequate excision had had a small (less than five-centimeter-diameter), often subcutaneous, mass in the extremity at the time of the examination by the initial surgeon, and these lesions had been excised after only a cursory physical examination.
Mankin et al. and the members of the Musculoskeletal Tumor Society decided to perform a study3 similar to that published in The Journal in 19822 because they thought that, although orthopaedists were referring more patients without first performing a biopsy, too many biopsies still were being carried out without an adequate evaluation. The current report is based on the results of a questionnaire that was completed by twenty-five members of the Musculoskeletal Tumor Society and includes objective and subjective data on almost 600 bone and soft-tissue tumors. The objective data reveal that only 315 (52.8 per cent) of the 597 biopsies were done by a member of the Musculoskeletal Tumor Society, that 153 (54 per cent) of the 282 biopsies done by referring physicians were performed by an orthopaedist, and that eighty-one (14 per cent) of the 597 biopsies led to a major error in diagnosis. A major error was twice as likely to occur if the biopsy had been done by a referring physician rather than by a member of the Musculoskeletal Tumor Society. Twenty of the eighty-five needle or fine-needle biopsies led to an error in diagnosis, and an additional fourteen were inadequate; thus, 40 per cent (thirty-four) of all needle biopsies failed to provide the correct diagnosis. This finding probably does not contradict the data of Skrzynski et al., as the needle biopsies in that study were done in carefully selected patients. The results of open biopsies were significantly better; only 122 (24 per cent) of 512 such biopsies provided an incorrect diagnosis or were inadequate for the purpose of diagnosis (p < 0.01). The subjective responses of the participants indicated that the biopsy had altered the management of 115 (19.3 per cent) of the 597 patients; such alterations were more common when the biopsy had been performed by a referring physician rather than by the treating physician. The disturbing aspect of this report is that little changed in the eleven years between the study periods. The rate of complications associated with biopsy remains high, especially when the procedure is done by a less experienced surgeon or a non-surgeon. Has anyone been listening?
The summary of these three articles is that the biopsy of musculoskeletal tumors is difficult. It is possible and cost-effective to do the biopsy as an outpatient procedure, but the patient must be evaluated carefully and only certain patients are appropriate candidates for a needle biopsy. Inadvertent excision of a soft-tissue sarcoma rarely if ever is adequate treatment, and many (probably most) patients have residual tumor. An unplanned excision makes care of the patient more difficult. Finally, not much has changed since the data of the Musculoskeletal Tumor Society were first reported in 1982. The medical community needs to do better with regard to the initial evaluation of these life-threatening tumors.
Are any of these findings surprising? They should not be. As early as 1949, Bradley Coley wrote in his text Neoplasms of Bone and Related Conditions that a biopsy "is part of the management of a case of osteogenic sarcoma which should be the responsibility of the surgeon who is prepared to carry out later treatment. Ill-advised and improperly performed biopsy may, and frequently does, reduce the patient's chance of cure to zero." Nothing has changed since Dr. Coley wrote these words. Unfortunately, that includes the frequency with which ill advised and improperly performed biopsies are done. Dr. Coley also stated that "the advantages [of aspiration biopsy] we may mention are: the simplicity of the technic of obtaining the material for study; the fact that it can be carried out in the outpatient or examining department with little inconvenience to the patient; that it permits of immediate operation or radiation therapy without the lapse of time necessary for wound healing as is the case when a formal biopsy is performed; and finally, that it obviates hospitalization and consequent expense to the patient." Coley gave this advice forty-seven years ago.
Why are these articles worth publishing more than four decades after the publication of a textbook that made the same recommendations that would be derived from the articles? There has been no controversy regarding the statements by Coley. It generally is agreed that a patient who has a malignant tumor is best managed at a medical center by a multidisciplinary team of specialists. It is unlikely that any surgeon has not heard the admonition: "Do not biopsy what you are not going to treat." Most, if not all, recognize the importance of pre-biopsy studies. And yet, biopsies of sarcomas still are performed by surgeons, radiologists, and internists without an adequate preceding evaluation. Many patients have had no evaluation other than palpation before the biopsy.
Why? We cannot blame this problem on managed care, although it may increase with managed care. It probably is due to a combination of factors. The first is the belief that the initial physician should establish a specific histological diagnosis before referring the patient to a specialist. As medical students, we were taught that diagnosis is critical. Therefore, we focus mainly on the diagnosis, without considering what we will do with this information, and afterward we consider the treatment options. This is not the best approach for the treatment of musculoskeletal tumors. Second, the patient usually has to travel out of town or even out of state to see the orthopaedic oncologist, and the referring physician does not want the patient to do this unnecessarily. However, a few unnecessary trips are more than adequately compensated for by the one necessary trip that results in the proper treatment of a sarcoma. Third, even when the initial physician considers the possibility of a sarcoma, he or she may hope that the tumor is not malignant (unless the tumor is very large or the patient is systemically ill) and may elect not to go to the trouble of performing the required tests when the mass simply can be excised and all questions can be answered. Usually, the physician and patient are lucky and the tumor is benign, but when the tumor is malignant the situation is made worse. Finally, as physicians, we are taught to believe that we can handle all problems related to our specialty, and it is difficult to tell a patient that another physician would be able to provide better care.
It is especially frustrating that orthopaedic surgeons continue to perform biopsies of musculoskeletal tumors without an adequate evaluation and instead of referring the patient to a medical center with expertise in musculoskeletal oncology. An extensive effort has been made in the orthopaedic residency programs and by the Musculoskeletal Tumor Society to educate practicing orthopaedists with regard to the hazards associated with the biopsy of musculoskeletal tumors. The consequences of a poorly done biopsy are increasingly serious as we have learned that almost all patients can be managed with a limb-salvage operation. Currently, an ill planned biopsy is one of the most common reasons—if not the most common reason—for an amputation. Complications may occur even when the biopsy is done by a specialist, but at least those complications were introduced by the specialist and were not added to an already complicated situation by someone else.
What is the best thing to do when confronted with a patient who has a musculoskeletal tumor? Most bone tumors can be diagnosed on the basis of plain radiographs. On occasion, computerized tomographic scanning or magnetic resonance imaging will help the physician to make a specific diagnosis. If the suspected diagnosis or diagnoses include only those lesions that the physician is comfortable treating, then he or she should do the biopsy. If not, then the patient should be referred. It is not just the skills of the physician that must be considered. The physician will need the assistance of a pathologist and should discuss the case with the pathologist before performing a biopsy. Although the physician may be able to perform the biopsy, the patient may need two operations instead of one if the pathologist cannot make the diagnosis.
Soft-tissue tumors are particularly difficult. Plain radiographs usually are not of much help in establishing a differential diagnosis. A deep lipoma may be suspected if a plain radiograph shows a low-density mass in the extremity, and a computerized tomographic scan or a magnetic resonance image should confirm the diagnosis. Myositis ossificans can be suspected on the basis of a plain radiograph and confirmed with a computerized tomographic scan, but mistakes have been made. As a general rule, all other deep lesions (those deep to the superficial fascia) should be considered malignant until proved otherwise. Unless the physician wants to treat a soft-tissue sarcoma, he or she should refer a patient in whom such a lesion is suspected to a surgeon who will manage the patient regardless of the diagnosis. If the physician elects to perform the biopsy, he or she should perform a complete evaluation and plan the biopsy carefully.
Subcutaneous masses are the most frustrating. These common lesions almost always are benign and need either no treatment or a limited excision. Unfortunately, malignant fibrous histiocytoma and leiomyosarcoma occur in the subcutaneous tissue and can have the characteristics of a benign tumor. We suggest that subcutaneous lesions that feel like fat and that have been present for more than a year without changing or causing pain should be followed without additional evaluation. All other lesions should be evaluated with a computerized tomographic scan or a magnetic resonance image and either incisionally biopsied or widely excised. If a wide excision is done, it is important that the pathologist examine the specimen carefully to determine the status of the margins of the excision.
If the physician thinks that a biopsy is necessary before referral or is going to perform the biopsy, he or she should follow a few important guidelines to reduce the risk that the biopsy will add to the patient's problems. The first is to obtain all of the information needed to treat the tumor before doing the biopsy. This information is valuable not only because it helps the physician decide exactly how to do the biopsy but also because the biopsy alters the appearance of the tumor and the surrounding tissues so that subsequent studies are less accurate than those done before the biopsy. The next step is to decide what kind of biopsy should be done. The options are fine-needle aspiration biopsy, trocar needle biopsy, open incisional biopsy, and excisional biopsy. In general, tumors that have been recognized on the basis of their clinical presentation and radiographic characteristics and for which the histological diagnosis is easy can be evaluated safely with either a fine-needle aspiration or trocar needle biopsy. The physician should ask the pathologist which method he or she prefers. A fine-needle aspiration or trocar needle biopsy also can be performed for a patient who has a lesion in an anatomical site that is not easily accessible, such as the spine or deep in the pelvis. These lesions usually can be biopsied with less contamination by the radiologist with the aid of a computerized tomographic scanner. The physician should remember that the radiologist has no understanding of operative excisions and needs advice concerning the placement of the needle.
An open incisional biopsy is necessary when the list of differential diagnoses is long and varied. In most cases, the pathologist will have an easier time making the diagnosis if he or she has a block of tissue rather than a cytological smear or a small needle core. Excisional biopsies are for only the brave of heart. When performing an excisional biopsy, the surgeon should be sure that the excision achieves the definite operative margin needed to control the tumor. At least a wide margin is needed for malignant tumors of the musculoskeletal system. An intralesional or marginal margin is adequate if the physician is positive that the tumor is a benign inactive lesion, but if he or she is wrong and the lesion needs a wider margin the situation is made worse.
Before doing any biopsy, the physician should consult with the pathologist who is to evaluate the biopsy material. In all likelihood, the pathologist is not accustomed to analyzing tumors of the musculoskeletal system, and giving him or her advance warning helps. The pathologist may even suggest that the biopsy be done elsewhere so that another pathologist can prepare the fresh tissue as he or she prefers. When the biopsy is done, the pathologist must handle the tissue properly to ensure an accurate diagnosis.
The final step before performing the biopsy is planning the exact path that will be used to obtain the tissue. The path of the needle and all tissue that is exposed at the time of an incisional or inadequate excisional biopsy subsequently must be excised if a definitive operative excision is needed. The placement of the needle or incision can substantially alter subsequent operative treatment. If a radiologist does the biopsy, he or she should be advised of the pathway of choice and should not be allowed to place the needle outside of this pathway. The incision for the biopsy should be longitudinal and in the plane of an incision that could be used for an excision. The path should be through muscle, not between muscles. Neurovascular structures should not be exposed, and no flaps should be made. At least a 0.5-square-centimeter piece of the tumor should be removed, and this tissue must be handled carefully and not be crushed. A frozen section should be examined. This at least will show that diagnostic tumor tissue has been obtained. Holes in the cortex of the bone can be filled with polymethylmethacrylate or Gelfoam. If a drain is used, it must exit the skin in line with the incision. Hemostasis must be obtained carefully. The bone should be protected if it is at risk for a pathological fracture.
A biopsy is a difficult operation not because of the technical aspects (although the technical aspects are important) but because planning is difficult and frequently is neglected. Each tumor presents its own special problems, and good judgment is needed to know when and how to perform a biopsy of a tumor of the musculoskeletal system. A biopsy that is done correctly provides sufficient material for a correct diagnosis and does not alter the operative management or outcome of the patient. A biopsy that is done poorly may not provide sufficient tissue for a diagnosis, and it may alter the extent of the tumor so that a patient who could have had a limb-salvage operation is forced to have an amputation. Before doing a biopsy, think.
Dempsey S. Springfield
Andrew Rosenberg
Coley, B. L.: Neoplasms of Bone and Related Conditions; Their Etiology, Pathogenesis, Diagnosis, and Treatment, pp. 28-36. New York, Paul B. Hoeber, 1949. 
Mankin, H. J.; Lange, T. A.; and |and |Spanier, S. S.: The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J. Bone and Joint Surg.,64-A: 1121-1127, Oct. 1982.64-A1121  1982 
Mankin, H. J.; Mankin, C. J.; and |and |Simon, M. A.: The hazards of the biopsy, revisited. For the members of the Musculoskeletal Tumor Society. J. Bone and Joint Surg.,78-A: 656-663, May 1996.78-A656  1996 
Noria, S.; Davis, A.; Kandel, R.; Levesque, J.; O'Sullivan, B.; Wunder, J.; and |and |Bell, R.: Residual disease following unplanned excision of a soft-tissue sarcoma of an extremity. J. Bone and Joint Surg.,78-A: 650-655, May 1996.78-A650  1996 
Skrzynski, M. C.; Biermann, J. S.; Montag, A.; and |and |Simon, M. A.: Diagnostic accuracy and charge-savings of outpatient core needle biopsy compared with open biopsy of musculoskeletal tumors. J. Bone and Joint Surg.,78-A: 644-649, May 1996.78-A644  1996 

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Coley, B. L.: Neoplasms of Bone and Related Conditions; Their Etiology, Pathogenesis, Diagnosis, and Treatment, pp. 28-36. New York, Paul B. Hoeber, 1949. 
Mankin, H. J.; Lange, T. A.; and |and |Spanier, S. S.: The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J. Bone and Joint Surg.,64-A: 1121-1127, Oct. 1982.64-A1121  1982 
Mankin, H. J.; Mankin, C. J.; and |and |Simon, M. A.: The hazards of the biopsy, revisited. For the members of the Musculoskeletal Tumor Society. J. Bone and Joint Surg.,78-A: 656-663, May 1996.78-A656  1996 
Noria, S.; Davis, A.; Kandel, R.; Levesque, J.; O'Sullivan, B.; Wunder, J.; and |and |Bell, R.: Residual disease following unplanned excision of a soft-tissue sarcoma of an extremity. J. Bone and Joint Surg.,78-A: 650-655, May 1996.78-A650  1996 
Skrzynski, M. C.; Biermann, J. S.; Montag, A.; and |and |Simon, M. A.: Diagnostic accuracy and charge-savings of outpatient core needle biopsy compared with open biopsy of musculoskeletal tumors. J. Bone and Joint Surg.,78-A: 644-649, May 1996.78-A644  1996 
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