Michael A. Simon

The Hazards of the Biopsy, Revisited. For the Members of the Musculoskeletal Tumor Society*

In 1982, members of the Musculoskeletal Tumor Society, representing sixteen centers for the treatment of bone and soft-tissue cancer, compiled data regarding the hazards associated with 329 biopsies of primary malignant musculoskeletal sarcomas. The investigation showed troubling rates of errors in diagnosis and technique, which resulted in complications and also adversely affected the care of the patients. These data were quite different when the biopsy had been carried out in a treatment center rather than in a referring institution. On the basis of these observations, the Society made a series of recommendations about the technical aspects of the biopsy and stated that, whenever possible, the procedure should be done in a treatment center rather than in a referring institution. In 1992, the Musculoskeletal Tumor Society decided to perform a similar study to determine whether the rates of complications, errors, and deleterious effects related to biopsy had changed. Twenty-five surgeons from twenty-one institutions submitted the cases of 597 patients. The results were essentially the same as those in the earlier study. The rate of diagnostic error for the total series (in which cases from referring institutions and treatment centers were combined) was 17.8 per cent. There was no significant difference in the rate of patients for whom a problem with the biopsy forced the surgeon to carry out a different and often more complex operation or to use adjunctive irradiation or chemotherapy (19.3 per cent in the current study, compared with 18 per cent in the previous one). There was also no significant difference in the percentage of patients who had a change in the outcome, such as the need for a more complex resection that resulted in disability, loss of function, local recurrence, or death, attributable to problems related to the biopsy (10.1 per cent in the current study, compared with 8.5 per cent in the 1982 study). Eighteen patients in the current study had an unnecessary amputation as a result of the biopsy, compared with fifteen in the previous study. Errors, complications, and changes in the course and outcome were two to twelve times greater (p < 0.001) when the biopsy was done in a referring institution instead of in a treatment center.

Limb salvage compared with amputation for osteosarcoma of the distal end of the femur. A long-term oncological, functional, and quality-of-life study.

The outcome of treatment of nonmetastatic high-grade osteosarcoma in the distal part of the femur was studied in 227 patients from twenty-six institutions. Eight of the seventy-three patients who had had a limb-salvage procedure and nine of the 115 patients who had had an above-the-knee amputation had a local recurrence, but there was no local recurrence in the thirty-nine patients who had had a disarticulation at the hip. There were no significant differences in the rate of survival or in the duration of the postoperative disease-free period between the three groups. One hundred and nine patients (48 per cent) were alive at an average of eleven years after the operation, and ninety patients (40 per cent) remained continuously disease-free. An additional operation on the limb was necessary more often for patients who had had a limb-salvage procedure than for those who had had an amputation. Function in seventy-eight living patients was assessed with the system of the Musculoskeletal Tumor Society for evaluation of function and by the functional assessment portion of the 1989 scoring system of the Knee Society; the scores were higher for the patients who had had a limb-salvage procedure than for the two groups of patients who had had an amputation. No difference was identified between the groups with regard to the patients acceptance of the postoperative state, the ability to walk, or the amount of pain. The quality of life was evaluated for twenty-nine patients with a series of complex questionnaires.(ABSTRACT TRUNCATED AT 250 WORDS)

The malignant potential of enchondromatosis.

In a tri-institutional, retrospective study with long-term follow-up, forty-four patients who had multiple enchondromas were identified. Thirty-seven patients did not have hemangiomas (Ollier disease) and seven did (Maffucci syndrome). Of the thirty-seven patients who had Ollier disease, a low-grade chondrosarcoma developed in four; an astrocytoma, in one; and a granulosa-cell ovarian tumor, in one. In four of the seven patients who had Maffucci syndrome, there were six low-grade chondrosarcomas, one high-grade osteosarcoma, one pancreatic adenocarcinoma, one biliary adenocarcinoma, and one astrocytoma. None of the patients in either group died of the skeletal sarcoma, but four of five patients who had a non-skeletal malignant lesion died. From life-table analyses of these patients, we estimated that the incidence of secondary chondrosarcoma in patients who have Ollier disease is about 25 per cent at the age of forty years, and that malignant degeneration is almost a certainty in patients who have Maffucci syndrome. We concluded that periodic surveillance of the brain and abdomen for occult malignant lesions is indicated in patients who have enchondromatosis.

Diagnostic Accuracy and Charge-Savings of Outpatient Core Needle Biopsy Compared with Open Biopsy of Musculoskeletal Tumors*

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

Skeletal metastases of unknown origin. A prospective study of a diagnostic strategy.

1106, compared with

Biopsy of bone and soft-tissue lesions.

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.

Cytoplasmic and/or nuclear accumulation of the β‐catenin protein is a frequent event in human osteosarcoma

We carried out a prospective study of the effectiveness of a diagnostic strategy in forty consecutively seen patients who had skeletal metastases of unknown origin. The diagnostic strategy consisted of the recording of a medical history; physical examination; routine laboratory analysis; plain radiography of the involved bone and the chest; whole-body technetium-99m-phosphonate bone scintigraphy; and computed tomography of the chest, abdomen, and pelvis. After this evaluation, a biopsy of the most accessible osseous lesion was done. The laboratory values were non-specific in all patients. The history and physical examination revealed the occult primary site of the malignant tumor in three patients (8 per cent): one patient who had carcinoma of the breast; one, of the kidney; and one, of the bladder. Plain radiographs of the chest established the diagnosis of carcinoma of the lung in seventeen patients (43 per cent). Computed tomography of the chest identified an additional six primary carcinomas of the lung (15 per cent). Computed tomography of the abdomen and pelvis established the diagnosis in five patients (13 per cent): three patients who had carcinoma of the kidney; one, carcinoma of the liver; and one, carcinoma of the colon. Examination of the biopsy tissue established the diagnosis in only three additional patients (8 per cent) and confirmed it in eleven others. On the basis of the biopsy alone, we were unable to identify the primary site of the malignant tumor in twenty-six (65 per cent) of the patients. In thirty-four (85 per cent) of the forty patients, the primary site was identified with the use of the diagnostic strategy described here, and only two additional occult malignant tumors were found on follow-up studies. Our diagnostic strategy was simple and highly successful for the identification of the site of an occult malignant tumor before biopsy in patients who had skeletal metastases of unknown origin.

Conservative surgery and adjuvant radiation therapy in the management of adult soft tissue sarcoma of the extremities: Clinical and radiobiological results

The biopsy of a soft-tissue mass or of a radiographically apparent bone lesion is usually essential before one embarks on a treatment plan. Whereas biopsy frequently demands relatively few technical skills, the decisions related to the performance of the biopsy require considerable thought and experience20. Without appropriate planning or execution, biopsies frequently lead to adverse effects on patient prognosis and on treatment options’4. Poorly performed biopsies, poorly placed mcisions, and biopsy complications can considerably compromise the subsequent local management of bone and soft-tissue tumors’4. In order to carry out the biopsy appropriately, the surgeon must first ensure that adequate diagnostic and staging studies were performed92”. These studies include clinical, laboratory, and radiographic assessments to provide the surgeon with knowledge of the extent of the tumor. The surgeon can then develop a differential diagnosis that facilitates decision-making regarding the optimum location of the biopsy site, the performance of closed or open biopsy or an incisional or excisional biopsy, and the processing of the biopsy specimen. The biopsy has potential prognostic and therapeutic consequences and, therefore, should be undertaken by the surgeon who plans to carry out the definitive treatment of the patient. Lesions that are highly likely to be malignant should be referred promptly to a musculoskeletal oncologist for biopsy or additional staging studies. These lesions include large or deep soft-tissue masses as well as bone lesions that are suspected, on the basis of their radiographic appearance. of being primary malignancies.

An AOA critical issue. Future physician workforce requirements: implications for orthopaedic surgery education.

The molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of β‐catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of β‐catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for β‐catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the β‐catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of β‐catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating β‐catenin signaling in osteosarcoma. In our survival analysis, β‐catenin deregulation conferred a hazard ratio of 1.05, indicating that β‐catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, β‐catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of β‐catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.

Aneurysmal bone cyst of the extremities. Factors related to local recurrence after curettage with a high-speed burr.

PURPOSE The outcome of adult patients with soft tissue sarcoma of the extremities treated with conservative surgery and adjuvant irradiation was evaluated to (a) determine the appropriate treatment volume and radiation dosage in the postoperative setting, and (b) correlate in vitro radiobiological parameters obtained prior to therapy with clinical outcome. METHODS AND MATERIALS Sixty-four consecutive adult patients with soft tissue sarcoma of the extremities (40 lower, 24 upper) who underwent conservative surgery and adjuvant irradiation 7 preoperative, 50 postoperative, 7 perioperative) between 1978 and 1991 were reviewed. The initial radiation field margin surrounding the tumor bed/scar was retrospectively analyzed in all postoperative patients. Initial field margins were < 5 cm in 12 patients, 5-9.9 cm in 32 and > or = 10 cm in 6. Patients with negative pathological margins were initially treated with traditional postoperative doses (64-66 Gy); however, in later years the postoperative dose was reduced to 60 Gy. Thirteen cell lines were established prior to definite therapy, and radiobiological parameters (multitarget and linear-quadratic) were obtained and correlated with outcome. RESULTS Postoperative patients treated with an initial field margin of < 5 cm had a 5-year local control of 30.4% vs. 93.2% in patients treated with an initial margin of > or = 5 cm (p = 0.0003). Five-year local control rates were similar in patients treated with initial field margins of 5-9.9 cm (91.6%) compared with those treated with > or = 10 cm margins (100%) (p = 0.49). While postoperative patients receiving < 60 Gy had a worse local control than those receiving > or = 60 Gy (p = 0.08), no difference was seen in local control between patients receiving less than traditional postoperative doses (60-63.9 Gy) (74.4% vs. those receiving 64-66 Gy (87.0%) (p = 0.5). The local control of patients treated in the later years of the study, with strict attention to surgical and radiotherapeutic technique, was 87.6%. Severe late sequelae were more frequent in patients treated with doses > or = 63 Gy compared to patients treated with lower doses (23.1% vs. 0%) (p < 0.05). Mean values for Do, alpha, beta, D, n and SF2 obtained from the 13 cell lines were 115.7, 0.66, 0.029, 2.15, 0.262, respectively. Four of the 13 cell lines established prior to therapy ultimately failed locally. The radiobiological parameters of these cell lines were similar to the other nine cell lines in terms of radiosensitivity. CONCLUSIONS Our data confirm the importance of maintaining an initial field margin of at least 5 cm around the tumor bed/scar in the postoperative setting. No benefit was seen with the use of margins > or = 10 cm. In addition, patients undergoing wide local excision with negative margins can be treated with lower than traditional postoperative doses (60 Gy) without compromising local control and with fewer chronic sequelae. Finally, it does not appear that inherent tumor cell sensitivity is a major determinant of local failure following radiation therapy and conservative surgery in soft tissue sarcoma.