William G. Ward

Osteosarcoma, Chondrosarcoma, and Ewing's Sarcoma: National Cancer Data Base Report

We summarize descriptive epidemiologic and survival data from the National Cancer Data Base of the American College of Surgeons for 26,437 cases of osteosarcoma (n = 11,961), chondrosarcoma (n = 9606), and Ewings sarcoma (n = 4870) from 1985 to 2003. Survival data are reported on cases with a minimum 5-year followup from 1985 to 1998 (8,104 osteosarcomas, 6,476 chondrosarcomas, and 3,225 Ewings sarcomas). The relative 5-year survival rate was 53.9% for osteosarcoma, 75.2% for chondrosarcoma, and 50.6% for Ewings sarcoma. Survival rates did not change notably over the collection period. Within osteosarcomas, the relative 5-year survival rates were 52.6% for high grade, 85.9% for parosteal, and 17.8% for Pagets subtypes. For osteosarcoma patients, the relative 5-year survival rate was 60% for those younger than 30 years, 50% for those aged 30 to 49 years, and 30% for those aged 50 years or older. Within chondrosarcomas, the relative 5-year survival rate was 76% for conventional, 71% for myxoid, 87% for juxtacortical, and 52% for mesenchymal. While the National Cancer Data Base has limitations, the survival data and demographics for bone sarcomas are unprecedented in numbers and duration. Our report supports continued efforts to refine data collection and stimulate further data analysis.Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Is fine-needle aspiration biopsy a practical alternative to open biopsy for the primary diagnosis of sarcoma? Experience with 140 patients.

We reviewed the clinicopathologic features of 145 consecutive fine-needle aspiration biopsy (FNAB) specimens from 140 patients without a previous diagnosis of sarcoma. Among 138 adequate specimens, 42 bone sarcomas and 80 soft tissue sarcomas were recognized as sarcomas; histologic subtyping was easier in bone than in soft tissue sarcomas and in pediatric than in adult cases. There was no correlation in accuracy of subtyping in low- vs high-grade sarcomas. FNAB was most accurate for subtyping of skeletal osteosarcoma, pediatric small round cell bone/soft tissue sarcomas, synovial sarcoma, skeletal chondrosarcoma, and adult myxoid soft tissue sarcomas. Although almost always recognized as sarcoma, subtyping of adult pleomorphic soft tissue sarcomas generally was not possible but did not influence therapy; all were considered high-grade sarcomas for treatment purposes. There were 4 misinterpretations of subtype in soft tissue sarcomas; none resulted in a change in therapy. Cytogenetic analysis on aspirated material confirmed t(11;22) in 2 Ewing and t(X;18) in 3 synovial sarcomas. No procedure-related complications occurred. Among bone and soft tissue sarcomas, FNAB was sufficient for initiation of definitive therapy in 87% and 83% of patients, respectively. Most FNAB specimens from bone and soft tissue sarcomas are recognized easily as sarcoma, but subtyping seems more accurate in bone sarcomas. Although histologic subtyping of adult soft tissue sarcomas is often impossible, no influence on initial therapy is usually observed. In contrast, subtyping of pediatric sarcomas by FNAB seems highly accurate and is necessary for appropriate therapy.

Expandable endoprosthesis reconstruction in skeletally immature patients with tumors.

Between September 1984 and January 1996, 32 expandable endoprostheses were used for limb reconstruction after resection of malignant bone tumors in patients who were skeletally immature. The 20 boys and 12 girls ranged in age from 3 to 15 years (mean, 9.7 years). One patient had a Stage IIA tumor, 22 patients had Stage IIB tumors, and seven patients had Stage III tumors according to the classification of the Musculoskeletal Tumor Society. There also were two patients with parosteal osteosarcomas. The histologic diagnosis was osteosarcoma in 23 patients and Ewings sarcoma in nine. All patients except the patients with parosteal osteosarcoma received standard neoadjuvant therapy. Twenty-two Lewis Expandable Adjustable Prostheses, four modular Wright Medical prostheses, four modular Howmedica prostheses, and two Techmedica expandable prostheses were used. Thirteen patients died, two have no evidence of disease, and 17 are continuously disease free. Sixteen of 32 patients (50%) have not had an expansion procedure because of early death in 10 and early amputation in three. Three patients are waiting to undergo an expansion procedure. Sixteen of the 32 patients (50%) have undergone 32 expansion procedures, to a maximum of 9 cm, without any infection. To maintain range of motion before the expansion procedure, a complete resection of the pseudocapsule was done routinely. Fourteen of the 32 patients did not have complications. Eighteen of the 32 patients had 27 complications. All Lewis Expandable Adjustable Prosthesis endoprostheses and the two nonmodular Techmedica prostheses were associated with a large amount of titanium debris. The childrens functional results were similar to the results reported for adults with an average Musculoskeletal Tumor Society rating of good to excellent at the knee, fair to good at the hip, and fair about the shoulder. Rehabilitation of the knee in very young patients (5-8 years) remains problematic and careful selection of patient and family is necessary. The Lewis Expandable Adjustable Prosthesis probably should be reserved for very young patients (5-8 years) and modular systems should be used for large preadolescent and adolescent children.

Metastatic Disease of the Femur: Surgical Treatment

The senior author’s 12-year consecutive series of surgery for metastatic disease of the femur was reviewed. Treatment of 97 impending pathologic fractures yielded better results than treatment of 85 completed pathologic fractures with less average blood loss (438 cc versus 636 cc), shorter hospital stay (7 days versus 11 days), greater likelihood of discharge to home as opposed to an extended care facility (79% versus 56%) and greater likelihood of resuming support-free ambulation (35% versus 12%). Internal stabilization with a reconstruction-type intramedullary nail provided satisfactory pain relief and functional preservation for most patients with impending pathologic femur fractures (69 of 97, 71%), although alternate forms of internal fixation (21 of 97, 22%) or cemented arthroplasty (seven of 97, 7%) were used successfully. Completed pathologic fractures were more likely to require some form of arthroplasty (47 of 85, 55%), although reconstruction-type nails (20 of 85, 24%), and other internal fixation techniques (18 of 85, 21%) also were used. Modular oncology-type arthroplasty systems offered a viable salvage option in both groups. In the absence of conflicting goals or contraindications, internal stabilization of impending pathologic fractures before the completion of the fracture seems to be reasonable and appropriate.

Customized treatment algorithm for giant cell tumor of bone: report of a series.

Between 1991 and 2000, 30 patients with 31 resections of giant cell tumors of bone were treated (average followup, 4.9 years; range, 1–9.6 years). Intralesional resection with curettes and a high-speed burr and reconstruction with polymethylmethacrylate cementation or bone grafting was used for salvageable, nonexpendable bones. Wide resection and allograft reconstruction was done in nonexpendable bones that were too destroyed for salvage. Adjuvant treatments were used for all intralesional procedures and when wide resection with a close margin was obtained. Adjuvant treatments included hydrogen peroxide instillation in 30 patients, electrocautery in 27 patients, phenol irrigation in 26 patients, sterile water irrigation in 15 patients, and polymethylmethacrylate cementation in 15 patients. There have been only two (6.4%) local recurrences, one in bone and one in soft tissue. Both patients had intralesional resections initially and both had salvage procedures with wide resections of the recurrent tumors. The 5-year recurrence-free survivorship was 93%. A delayed ray amputation for failed bone graft of the little finger was the only amputation. In all other patients, a functional limb was preserved. Wide resection only is required when bone salvageability is impractical. Intralesional curettage and high-speed burr resection, when supplemented with the adjuvant therapies as described, is adequate for the majority of patients with giant cell tumor of bone. A proposed treatment algorithm is presented.

Atypical and malignant variants of ossifying fibromyxoid tumor. Clinicopathologic analysis of six cases.

Ossifying sibromyxoid tumor (OFMT) of soft parts is a recently defined fibro-osseous neoplasm. the biologic behavior of which is generally regarded as benign. We report six variant cases of OFMT with histologic features of malignancy, two of which behaved aggressively. All these tumors arose in the extremities of adults (aged 36–76 years), and five of the six were subcutaneous. Four patients were men. Macroscopically, all the tumors were well circumscribed and somewhat lobulated. Cardinal morphologic features included lobulates of round to spinded cells within a fibromyxoid matrix and randomly distributed, often centrally located osteoid within which were plump neoplastic cells. In contrast to typical OFMT, a hypocellular, cytologically benign, lamellar bony shell was observed only focally: cellularity was increased (four cases), and mitotic activity was frequent, exceeding two mitotic figures per 10 high-power fields (three cases). One case associated with metastases was morphologically bland. Immunohistochemically, positivity for S-100 protein was observed in the primary tumors of three cases and in the pulmonary metastasis of a fourth. Desmin was positive in one case. Ultrastructural features in three cases were very similar to usual OFMT. Clinical follow-up revealed local recurrence in two cases: one patient has developed recurrent pulmonary metastases. We believe these findings support the view that some atypical cases of OFMT exhibit morphologic patterns that might predict more aggressive behavior.

Endoprosthetic reconstruction for malignant upper extremity tumors

Between December 1980 and December 1992, 59 patients underwent 60 reconstructions with endoprostheses after resection of malignant tumors in the upper extremity. There were 32 male patients and 27 female patients, with a mean age of 33 years (range, 3-83 years). The type of reconstruction was based on the location of the primary tumor site. The histologic diagnoses included osteosarcoma, chondrosarcoma, Ewings sarcoma, malignant fibrous histiocytoma, soft tissue sarcoma, and fibrosarcoma of bone. Most of the patients had Stage IIB disease (N = 38), as established by the Musculoskeletal Tumor Society classification. An additional six patients had metastatic tumors to the upper extremity. Twenty-seven of 59 patients died of disease progression. Two patients died of other causes (chronic leukemia, human immunodeficiency virus infection). The 30 survivors had a mean followup of 90 months (range, 60-170 months). The Musculoskeletal Tumor Society functional analysis for the patients with a minimum 2-year followup (N = 41) averaged 74%. Sixteen of the 59 (27%) patients had local complications. Problems related to mechanical failure and infection were managed successfully with second operation. Amputation was rare, occurring in three of 60 (5%) patients and was related only to local recurrence. Endoprosthetic reconstructions of the upper extremity after tumor resections have proven to be successful.

Osteoid osteoma diagnosis and management with low morbidity.

Wide excision, a recommended treatment for osteoid osteoma, creates needless resection of surrounding bone and causes difficult intraoperative nidus identification. Less bone resection is required by successively burring through the reactive bone to identify the nidus, which is then removed with curettes and burrs. This burr-down technique requires precise preoperative anatomic localization by thin section (1-1.5 mm) computed tomography (CT) scans. In a consecutive series of 19 osteoid osteomas, 18 were accurately diagnosed before operation, using a combination of clinical findings, plain roentgenograms, and CT scans. The burr-down technique was successfully used in 15 cases, and four were treated with wide excision. There have been no local recurrences. The follow-up period for all 19 patients was at least six months. No bone grafts were required in the burr-down group in nonspinal locations; there have been no fractures despite early return to unrestricted activity. The burr-down technique was associated with less postoperative immobilization, a shorter duration of protected weight bearing, and an earlier return to activity. The burr-down technique is recommended for accessible osteoid osteoma lesions.

Clinicopathologic analysis of HER-2/neu immunoexpression among various histologic subtypes and grades of osteosarcoma.

Overexpression of the HER-2/neu oncogene appears to have prognostic significance in breast cancer. Recently, some have reported a relationship between increased immunohistochemical expression in osteosarcoma and poor clinical outcome. Despite limited data, a pilot trial of Herceptin, which targets the oncogene product, has been initiated for the therapy of some metastatic osteosarcomas (CCG-P9852). Archival formalin-fixed, paraffin-embedded tissue obtained from 41 patients diagnosed with osteosarcoma was examined immunohistochemically by 2 antibodies against the HER-2/neu oncogene product: CB-11 (monoclonal, 1/100) and Oncor (polyclonal, 1/200). All but one tumor (case of recurrent dedifferentiated parosteal osteosarcoma) represented primary tumor samples; when applicable, only prechemotherapy biopsies were analyzed. The study sample included the full spectrum of histologic subtypes and grades of osteosarcoma (25 conventional high grade; 3 telangiectatic; 1 small cell; 6 parosteal; 1 periosteal; and 5 low-grade intramedullary). A case of metastatic breast cancer with known overexpression of the HER-2/neu oncogene served as the positive control. Complete membranous positivity, considered prognostically significant in breast cancer, was not seen in any of our osteosarcoma cases. At least focal cytoplasmic positivity was documented in 40 (98%) tumors using the CB11 antibody and in 34 (83%) using the Oncor antibody. The intensity of the cytoplasmic staining (0, 1–3+) did not correlate with histologic subtype/grade, response to chemotherapy (<90% versus ≥90% necrosis), metastasis, or survival. Immunohistochemical overexpression of the HER-2/neu oncogene, defined as complete membranous positivity, is not present in our series of osteosarcomas. Cytoplasmic positivity is observed in most osteosarcomas, irrespective of histologic subtype/grade, and is not associated with response to preoperative chemotherapy or disease progression.

Endoprosthetic replacement for stage IIB osteosarcoma

Over an eight-year period, 100 patients with IIB osteosarcoma have been managed. Eighty-one were treated with limb-salvage procedures, 78 of which involved reconstruction utilizing endoprostheses. Only 19 patients received amputation as the primary treatment for local control. Since 1984, all patients received preoperative and post-operative adjuvant chemotherapy. Those patients who received chemotherapy had a statistically significant improvement in five-year survival over those who did not (57% and 32%, respectively, p = 0.014). The functional results were good overall, with excellent results seen in distal femoral reconstruction. Twenty-eight of the 78 patients treated with endoprosthetic reconstruction experienced 30 complications (36%). Mechanical failure was the most common complication (10%) but was generally correctable. The local recurrence rate was 5% and the infection rate was 3%. Local complications were manageable. A statistical analysis revealed that the relative risk of patient death was 2.5 times higher than prosthesis failure for the 78 patients with endoprosthetic reconstruction. The intermediate-term results, with a median follow-up period of 43 months, remains encouraging.