Abstract
We performed a prospective study of sixty-two patients who were managed with a closed core needle biopsy in an outpatient clinic for a soft-tissue mass or a bone tumor with soft-tissue extension between August 1, 1992, and June 1, 1994. Eight (13 per cent) of the closed core needle biopsies yielded no neoplastic tissue. Two needle biopsies (3 per cent), which were of myxomatous masses, did not allow distinction between a benign and a malignant neoplasm; both masses were extraskeletal myxoid chondrosarcomas. Additionally, the histological grade of four resected specimens (6 per cent) differed from that determined with the closed needle biopsy.The diagnostic accuracy of the closed needle biopsies was 84 per cent (fifty-two of sixty-two). All ten diagnostic errors involved soft-tissue tumors. A retrospective study of a similar cohort of patients, who had open biopsy in an outpatient operating room by the same surgeon in a contemporary period in the same institution and with analysis by the same pathologist, revealed a diagnostic accuracy of 96 per cent (forty-eight of fifty).The hospital charges for the closed core needle biopsy were $1106, compared with $7234 for the open biopsy.We concluded that core needle biopsy can be performed in an outpatient clinic with use of local anesthesia and that it is substantially less expensive and more convenient than open biopsy. This technique has an acceptable but definitely lower rate of accuracy compared with open biopsy, especially for soft-tissue tumors, and it should be used only in a small subset of patients (those who have a large soft-tissue mass or a bone tumor with palpable soft-tissue extension). However, given the small size of the tissue sample, the clinician must recognize possible disadvantages, including a non-diagnostic biopsy, an indeterminate biopsy, or a potential error in the histological grade. These problems are much more likely to occur after core needle biopsy of soft-tissue masses. Because of the potential for errors in diagnosis when core needle biopsy is used, the musculoskeletal oncologist must rely on his or her clinical acumen. When a diagnostic is in reasonable doubt, there is no radiographic confirmation, the biopsy shows no tumor cells, or there is a combination of these findings, operative decisions should be made as if no biopsy had been performed. The management of patients who, after core needle biopsy, have a diagnosis of a bone or soft-tissue tumor, is best carried out by an experienced musculoskeletal oncologist working in close collaboration with an experienced musculoskeletal pathologist.
In an era in which limb-salvage procedures are increasingly common in the treatment of malignant soft-tissue and bone tumors of an extremity, biopsy has emerged as a conceptually complex and critical step in the staging process6,14,15. Open biopsy has been the conventional procedure for obtaining adequate and representative samples of tissue for diagnosis7,11-14. Disadvantages associated with this procedure have included spillage of tumor cells and wound complications10,14. The biopsy should provide adequate tissue for histopathological determination of whether a tumor is benign or malignant and of the grade, with minimum trauma to the tissue and at a reasonable charge.
Closed needle biopsy has become increasingly popular12-14; however, previous studies of this technique have been retrospective2,8,17 or have lacked clear-cut criteria for the selection of patients2,12. The procedure has usually been performed in a radiology suite2,5,9,12,17, and occasionally general anesthesia has been used2,17. To our knowledge, there has been no study in which the accuracies of closed and open biopsy, performed in a single institution by the same surgeon and pathologist, have been compared, and we know of only one study in which the charge-savings of closed and open biopsy were compared17. Therefore, we performed a prospective study to evaluate the diagnostic accuracy of core needle biopsy of soft-tissue tumors and bone tumors with soft-tissue extension. All procedures were performed in an outpatient clinic with use of local anesthesia and without fluoroscopic aid. We compared the accuracy with that of open biopsy in a matched patient population at our institution. We also compared the charge for core needle biopsy with that for open biopsy for the two groups of patients.
*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.
†Section of Orthopaedic Surgery and Rehabilitation Medicine, Mail Code 3079 (M. C. S. and M. A. S.), and Department of Pathology, Mail Code 6101 (A.M.). The University of Chicago Hospitals and Clinics, 5841 South Maryland Avenue, Chicago, Illinois 60637.
‡University of Michigan Medical Center, TC-2912, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0324.
Five hundred and seventy-three new patients were seen in our musculoskeletal oncology outpatient clinic between August 1, 1992, and June 1, 1994. Sixty-two of these patients, who had a soft-tissue mass larger than four centimeters in diameter, a malignant-appearing bone lesion with a palpable soft-tissue extension, or a suspected recurrence of a soft-tissue tumor, were included in the current prospective study. Patients were excluded from the study if they had had a recent biopsy, were less than thirteen years old, had an inaccessible soft-tissue mass, had a bone lesion without a soft-tissue mass, had a soft-tissue mass with characteristics of a lipoma on magnetic resonance imaging, or declined the procedure.
All sixty-two patients had a needle biopsy, performed in the outpatient clinic by an orthopaedic oncology surgical fellow according to the specifications of the manufacturer of the needle-biopsy system (Tru-cut; Baxter Health Care, Valencia, California). The skin was prepared with sterile technique, a local anesthetic was injected, and a stab wound was made with a number-11 blade. Three to six passes were then made through the mass, and cores of tissue were obtained. The site of the biopsy was marked permanently with India ink in the event of later resection. The core specimens were immediately fixed in formalin. Each specimen was reviewed by one of us (A.M.), a musculoskeletal pathologist, and additional studies such as immunohistochemical analysis were carried out at his discretion. When an open biopsy or a resection of the tumor was subsequently performed, the histological diagnosis was compared for accuracy with the diagnosis based on the needle biopsy.
Fifty consecutive patients who had had an open biopsy were identified with use of the just described criteria for inclusion in the study. In an attempt to eliminate selection bias, we retrospectively studied patients who had been managed just before the implementation of core needle biopsy at our institution—that is, from November 1989 to August 1991 (one year before the prospective study was begun). All open biopsies were performed with use of a regional or general anesthetic in the operating room on an outpatient basis under the supervision of the senior one of us (M. A. S.), and the specimens were reviewed by the same musculoskeletal pathologist (A.M.). We routinely prepared an intraoperative frozen section to ascertain that a representative sample of tissue was obtained; we also made permanent sections and performed additional studies as determined by the pathologist. As was done for the patients who had a core needle biopsy, when a subsequent resection of the tumor was performed the histological diagnosis was compared with the diagnosis based on the open biopsy. The diagnostic accuracy of the open biopsies was then compared with that of the core needle biopsies.
We prospectively recorded complications after the core needle biopsies, and we retrospectively reviewed the office notes of the senior one of us to evaluate the complications after the open biopsies.
We also assessed the average charges for the needle and open biopsies. On the basis of the computerized hospital charge-code system, the standard facility, professional, laboratory, pathology, and equipment fees were determined for these two groups of patients. Each patient was initially evaluated in the musculoskeletal oncology clinic. One group of patients then had a needle biopsy in the outpatient clinic, and the other group had an open biopsy with use of regional or general anesthesia in the operating room on an outpatient basis. The charges for the patients who had an open biopsy included the basic preoperative laboratory evaluation, one to two hours of operating-room time, professional and equipment fees, and a one to two-hour interval in the recovery room before they returned home. The processing and professional fees for the pathological evaluation were tabulated for both groups of patients.
The final histological diagnoses for the two biopsy groups were distributed similarly between benign and malignant bone and soft-tissue tumors (Table I and Table II). The diagnoses were based on all available pathological material and on follow-up studies for each patient.
Core Needle Biopsy
Sixty-two patients had a closed core needle biopsy, and forty-three had a subsequent resection. On the basis of the specimens obtained during the resection, there were twenty-six primary malignant tumors (nineteen soft-tissue and seven bone), eleven benign tumors (nine soft-tissue and two bone), two metastatic tumors, one recurrent lymphoma, and three non-tumorous lesions. Of the forty-three tumors, four were recurrent. The nineteen remaining patients were managed nonoperatively (seventeen) or were operated on elsewhere (two). However, an accurate diagnosis was obtained with needle biopsy for eighteen of the nineteen patients. (Four had a metastatic tumor; five, a lymphoma; three, a soft-tissue sarcoma; three, a benign soft-tissue tumor; one, multiple myeloma; and two, a primary bone sarcoma.)
The over-all diagnostic accuracy of the core needle biopsies was 84 per cent (fifty-two of sixty-two). The diagnostic accuracy was 100 per cent for recurrent lesions, metastatic disease, lymphoma, and myeloma.
There were eight non-diagnostic core needle biopsies (no neoplastic cells were found). The patients who had these biopsies were managed by the senior one of us (M. A. S.), an experienced musculoskeletal oncologist, as if no biopsy had been performed. Three of the eight patients subsequently had an open biopsy, and each biopsy was diagnostic for a malignant tumor. Another patient, who had known neurofibromatosis, was managed with observation for a stable mass in the groin. Two patients had a wide resection of a large, deep mass without an open biopsy; one was found to have a soft-tissue sarcoma and the other, a benign myxoma. We consider the latter patient to have had a somewhat adverse outcome because a wide excision was performed for a benign tumor. However, this was the treatment chosen by the senior one of us; the choice was not related to the non-diagnostic biopsy. Two patients had a marginal excision of a small, deep mass; one mass was a myositis ossificans and the other, a fibroma of the biceps tendon.
In two additional patients, the core needle biopsy was considered to reveal a myxomatous lesion; a low-grade malignant tumor could not be ruled out. Both lesions proved to be a low-grade extraskeletal myxoid chondrosarcoma after a primary wide excision.
Four of the fifty-two so-called diagnostic core needle biopsies indicated a histological grade that differed from that of the resected soft-tissue sarcoma. Thus, for soft-tissue tumors, the diagnostic accuracy of the core needle biopsies was only 78 per cent (thirty-five of forty-five). All eight non-diagnostic biopsies and both ambiguous diagnostic biopsies were of soft-tissue tumors.
One patient had a delayed infection of a core needle-biopsy track, which necessitated a decrease in the dose of preoperative radiation. An early operation was performed without any apparent adverse impact on the outcome.
Open Biopsy
Fifty consecutive patients had an open biopsy, and thirty-nine of them subsequently had a resection. In this group of thirty-nine patients, the diagnoses included twenty-eight primary malignant tumors (fourteen soft-tissue and fourteen bone), nine benign tumors (seven soft-tissue and two bone), and two inflammatory lesions. Nine patients were managed non-operatively; the diagnoses included lymphoma in three and desmoid tumor, abscess, metastatic soft-tissue chondrosarcoma, metastatic carcinoma, neuroblastoma, and undifferentiated blue-cell tumor in one each. The two remaining patients, who had a leiomyosarcoma and a neurilemmoma, sought treatment elsewhere.
The over-all diagnostic accuracy of the open biopsies was 96 per cent (forty-eight of fifty). The tumors included an unusual small-cell osteosarcoma of the ilium, which was thought to be a high-grade malignant hemangiopericytoma on open biopsy and was widely resected, and a large Triton tumor of the calf, which was interpreted as a hyalinized fibrotic mass on the basis of the open biopsy and was marginally excised. Only one open biopsy revealed a histological grade that was different than that of the specimen (a bone sarcoma) obtained during resection.
Three patients had complications after the open biopsy. One of these patients had a large hematoma after an open biopsy of an osteosarcoma of the tibia. Although this caused concern for the senior one of us, a limb-salvage procedure was subsequently performed, after preoperative chemotherapy had been administered, and the patient was alive with no evidence of local recurrence at the time of long-term follow-up. Another patient, who had synovial chondromatosis of the interphalangeal joint of the great toe, had a delay in wound-healing, without any apparent adverse effect on the outcome. The third patient had a wound dehiscence after an open biopsy of a very large synovial sarcoma of the groin. Tumor grew from the site of this wound, and we performed a hemipelvectomy. We do not know if the chemotherapy that we had intended to administer preoperatively (but that could not be given until after the operation) would have made a difference in the outcome. However, we certainly had to change the sequence of the therapeutic strategy because of the complication.
Charges
The hospital charges, including those for the initial office visit, hospital facility, equipment, and professional and pathology fees, were $1106 for the core needle biopsy, compared with $7234 for the open biopsy (Table III).
The best study comparing the results of closed needle biopsy with those of open biopsy would be a prospective, randomized trial in which the only variable is the type of biopsy performed. In the current study, the results of needle biopsy were examined prospectively, while those of open biopsy were evaluated retrospectively. Nevertheless, the two groups of patients were comparable because the same criteria had been used for inclusion, the two types of biopsy were performed in a contemporary period by the same senior surgeon at the same institution, and the results were reviewed by the same pathologist. Although the design of the study has flaws, to our knowledge it has two characteristics not found in any previous study on biopsy. First, the patients who had a core needle biopsy were studied prospectively, with specific data sheets and criteria for inclusion in the study. Second, there was a meaningful, albeit retrospective, contemporary control group of patients who had had an open biopsy. Although the specific diagnoses differed somewhat between the two cohorts, the over-all percentages of patients who had benign, malignant, metastatic, and inflammatory tumors were remarkably similar.
Only a few patients who had a closed biopsy had a benign bone tumor because few benign bone tumors have soft-tissue extension. For these patients, either an open biopsy or a closed biopsy with use of a trocar and radiographic control is necessary. All of the biopsies of metastases, in both groups, were in patients who did not have a known history of cancer; thus, the results could not be considered confirmatory. No patient who had a history of multiple myeloma had a biopsy.
As far as we know, all studies of closed biopsy have revealed higher rates of accuracy for bone tumors than for soft-tissue tumors because the diagnosis is often reasonably certain from the radiographic appearance of a bone tumor. Therefore, the biopsy is often confirmatory for bone tumors. Our study confirms this bias.
The current study also demonstrates that complications of biopsy, although rare, can occur after both open and closed biopsy but are somewhat more likely after an open procedure.
Although there are no clear-cut indications for closed as opposed to open biopsy for musculoskeletal tumors, the risks and benefits of each can be analyzed. Closed core needle biopsy can be performed with use of local anesthesia in an office setting or a radiology suite. The rate of complications has been less than 1 per cent in most series3,4,8,17. When a needle biopsy is non-diagnostic, it can easily be repeated, or an open biopsy can be performed without major morbidity to the patient.
For soft-tissue tumors and bone tumors with soft-tissue extension, there are basically two types of closed biopsy: fine needle aspiration and core needle biopsy. Fine needle aspiration has proved reliable for metastatic tumors9, recurrent sarcomas4,12, and osteosarcomas (when coupled with radiographic studies)16. However, fine needle aspiration relies on cytological interpretation, and obtaining adequate and representative tissue can be a problem. Fine needle aspiration has had variable (64 to 96 per cent) diagnostic accuracy for soft-tissue tumors1,4, and the rate has been as low as 54 per cent for primary malignant tumors of bone5,9. In a core needle biopsy, a core of tissue is extracted with use of a trocar-cannula system and the architecture of the tissue is preserved, thus theoretically aiding in the histological diagnosis and the grading of the tumor. Core needle biopsy can also provide adequate tissue for immunohistochemical analysis that cytological specimens cannot supply1,4,14. Core needle biopsy has a reported rate of accuracy of 76 to 96 per cent4,12.
Compared with open incisional biopsy, core needle biopsy has a few disadvantages, including the relatively small size of the sample, the possibility of a non-diagnostic biopsy, and the potential for errors in diagnosis. In the current study, there were two indeterminate diagnoses in which a subsequently widely resected extraskeletal myxoid chondrosarcoma was deemed a myxoid tumor on needle biopsy. In both instances, the pathologist was unable to differentiate between a benign and a malignant tumor. We recommend special caution in the interpretation of the results of a biopsy of a myxomatous tumor. In four of forty-nine patients, the histological grade of the specimen obtained during resection differed from that of the specimen obtained by needle biopsy. These errors obviously could influence strategies for preoperative treatment, including the use of adjuvant radiation or chemotherapy3,4,8,12. Because of the small size of the specimens obtained with needle biopsy, careful allotment of tissue is clearly necessary and should be decided on in collaboration with the pathologist. In addition, an accurate histological diagnosis requires an expert musculoskeletal pathologist3,8,12.
Eight (13 per cent) of the sixty-two patients had a non-diagnostic needle biopsy, perhaps as a result of sampling error, central tumor necrosis, or a geographic miss. Seven of these eight patients had a second operative procedure to establish the diagnosis. Other authors have reported similar rates of non-diagnostic core needle biopsies3,12,17. The problem could be partially alleviated by familiarity with the technique and by submission of at least three cores of tissue, depending on the tolerance of the patient. Unfortunately, given the clinical circumstances under which closed needle biopsy is carried out, frozen sections are not obtained. Open biopsy, in contrast, allows frozen sections to be obtained, thus providing intraoperative assurance that there will be adequate specimens of tissue for diagnosis.
For determination of the charges, we decided to use an ideal model rather than actual charges, for two main reasons. First, although the two cohorts were managed in fairly contemporary periods, we would have had to take into account inflation and other unknown confounding factors that would have affected hospital and professional charges. Second, just a few operative complications or adverse events in either cohort could have drastically changed the average charge for this relatively small group of patients. Therefore, use of the actual charges could have markedly changed the average charge17. For the three patients who had both a closed and an open biopsy, the charges were increased by more than $1000 compared with those for open biopsy alone.
Over-all, our 84 per cent rate of accuracy for core needle biopsy approaches, but does not equal, that of open biopsy performed in referral centers (91 per cent in the multi-institutional study of Mankin et al. and 96 per cent at our institution). Core needle biopsy is especially useful for recurrent neoplasms or relatively homogeneous tumors. It should be noted that, when the eight non-diagnostic core needle biopsies are disregarded, our rate of accuracy improves remarkably to 96 per cent, the same as or better than that of open biopsy. However, we considered it more appropriate to classify a non-diagnostic biopsy as an inaccurate biopsy. These eight patients were managed as if no biopsy had been performed. Another disadvantage of closed biopsy, irrespective of the accuracy, is that the small amount of tissue available often precludes additional studies, such as immunohistochemical analysis and cytogenetic evaluation, which are frequently necessary for more accurate diagnosis, evaluation, staging, and clinical and basic research. The diagnostic accuracy of closed biopsies for bone tumors is higher than that for soft-tissue tumors. In the evaluation of bone tumors, unlike that of soft-tissue tumors, diagnostic radiographs are often available so that the results of the biopsy are confirmatory. In addition, patients who have a soft-tissue tumor have much more variable diagnoses and often have much more tumor necrosis. It should also be noted that the only real missed diagnosis in the patients who had an open biopsy was that of a soft-tissue tumor. Thus, closed and open biopsies of soft-tissue tumors have more potential for missed diagnosis, inaccurate diagnosis, or non-diagnostic tissue than do those of bone tumors. Our study confirms this observation because all eight non-diagnostic closed biopsies and both of the diagnostically ambiguous ones were of soft-tissue masses.
Because of the potential for diagnostic errors when core needle biopsy is used, the musculoskeletal oncologist must rely on his or her clinical acumen. When a diagnosis is in reasonable doubt, there are no associated radiographic findings, the specimen obtained at biopsy shows no tumor cells, or there is a combination of these findings, the surgeon should perform an open biopsy and should manage the patient as if no biopsy had been performed before making operative decisions. However, closed needle biopsy in the outpatient setting should be considered as a primary diagnostic aid for all large soft-tissue masses or for bone tumors with palpable soft-tissue extension.
In addition, with the current impetus toward cost containment, core needle biopsy offers major savings compared with open biopsy3,4,8,12,17. The main difference lies in the charges for use of the hospital facility, the professional charges for anesthesia, and the charges for the time in the operating and recovery rooms.
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