Suzanne S. Spanier

A system for the surgical staging of musculoskeletal sarcoma

A surgical staging system for musculoskeletal sarcomas stratifies bone and soft-tissue lesions of any histogenesis by the grade of biologic aggressiveness, by the anatomic setting, and by the presence of metastasis. The three stages: I--low grade; II--high grade; and III--presence of metastases, are subdivided by (a) whether the lesion is anatomically confined within well-delineated surgical compartments, or (b) beyond such compartments in ill-defined fascial planes and spaces. Operative margins are defined as intralesional, marginal, wide, and radical, and relate the surgical margin to the lesions, its reactive zone, and anatomic compartment. The system defines prognostically significant progressive stages of risk which also have surgical implications. When the system is linked to clearly defined surgical procedures, it permits appropriate evaluation and comparison of the new treatment protocols designed to replace standard surgical treatment.

The effect of the anatomic setting on the results of surgical procedures for soft parts sarcoma of the thigh

The results of surgical treatment in 40 patients with a soft tissue sarcoma of the thigh were analyzed to determine the influence of the anatomic setting on the effectiveness of the procedure. The anatomic setting, based on functional anatomic compartments, was defined as either intra‐ or extracompartmental. The lesions were graded for aggressiveness as either high or low. The lesions were staged by biologic aggressiveness, anatomic setting, and metastases. The procedures, whether amputations or local resections, were classified by the relationship of the surgical margin to the pseudocapsule and reactive zone about the lesion as marginal, wide, or radical.

The influence of skeletal implants on incidence of infection: experiments in a canine model

We have performed experiments in 187 dogs in order to evaluate the effect of commonly used implant materials on rate of infection. We opened the femoral canal with a hand drill and awl, instilled a suspension of bacteria, and then inserted one of the implants. The implants--stainless-steel and cobalt-chromium alloys, high-density polyethylene, prepolymerized polymethylmethacrylate, and polymethylmethacrylate polymerized in vivo--were compared with no implant (control). The effect of the different implants on the incidence of infection with Staphylococcus epidermidis, Staphylococcus aureus, and Escherichia coli was compared by determining the number of bacteria required to produce infection in 50 per cent of the femora. All of the implants were significantly more likely than the controls to be associated with infection with Staphylococcus aureus. Polymethylmethacrylate polymerized in vivo was found to be significantly more likely than all other implants to be associated with infection with Escherichia coli and Staphylococcus epidermidis. In addition to evaluating all specimens bacteriologically, we carried out a histological evaluation, and found that infection was highly correlated with an increased inflammatory response for all three bacteria. However, even with this highly statistically significant correlation, the correlation was not absolute; when only limited portions of randomly selected specimens of tissue were examined, the correlation was reduced.

Cytogenetic findings in 73 osteosarcoma specimens and a review of the literature

Tumor-specific chromosomal abnormalities have been identified in several histologic subtypes of sarcomas. Characterization of recurrent chromosomal abnormalities has provided direction for molecular investigations of pathogenetically important genes. Cytogenetic reports of osteosarcoma, the most common primary malignant bone tumor, are relatively rare. In this study, 73 osteosarcoma specimens from 51 patients were cytogenetically analyzed following short-term culture. Clonal chromosomal abnormalities were detected in 47 and included one haploid specimen, 18 near-diploid specimens, 17 near-triploid, 8 near-tetraploid, 1 near-hexaploid, and 2 specimens with multiple clones of different ploidy levels. Examination of the present data and previously published data (111 clonally abnormal osteosarcoma specimens) reveals that chromosomal bands or regions 1p11-13, 1q10-12, 1q21-22, 11p15, 12p13, 17p12-13, 19q13, and 22q11-13 are most frequently rearranged and the most common numerical abnormalities are +1, -9, -10, -13, and -17. Partial or complete loss of the long arm of chromosome 6 also was seen in all cases of the present study and all previously published cases describing structural abnormalities of 6q. Parosteal osteosarcoma, a prognostically favorable osteosarcoma subtype, was characterized by the presence of a ring chromosome accompanied by no or few other abnormalities. Complex karyotypes were seen nearly exclusively in the high-grade lesions. These findings indicate that specific chromosomal bands and/or regions are nonrandomly involved in osteosarcoma and may provide useful clinical information.

Trisomies 8 and 20 Characterize a Subgroup of Benign Fibrous Lesions Arising in Both Soft Tissue and Bone

Trisomy 8 and trisomy 20 are nonrandom aberrations in desmoid tumors. The presence of these trisomies in related benign fibrous lesions of bone has not been previously addressed. In this study, 22 specimens from 19 patients diagnosed with desmoid tumor, desmoplastic fibroma, periosteal desmoid tumor, osteofibrous dysplasia, or fibrous dysplasia were examined by cytogenetic analysis of short-term cultures and bi-color fluorescence in situ hybridization of cytological touch preparations or paraffin-embedded tissue with centromeric probes for chromosomes 8 and 20. Trisomy 8 and trisomy 20 were detected by molecular cytogenetic methodologies in 15 specimens, including 10 primary bone lesions. Traditional cytogenetic analysis revealed trisomy 8 in two cases of osteofibrous dysplasia. Our findings demonstrate that trisomy 8 and trisomy 20 are also nonrandom aberrations in histologically similar, but clinically distinct, benign fibrous lesions of bone.

Surgical treatment for osteosarcoma.

Fifty-three patients who had a high-grade osteosarcoma had either a limb-salvage resection or an amputation. They all received adjuvant therapy that consisted of administration of Adriamycin (doxorubicin) and whole-lung irradiation. At the time of follow-up, the surgical margin was assessed by examination of the surgical specimen. Each patient was followed for at least three years or until death. The data suggested that a wide surgical margin is adequate to control a primary osteosarcoma. When a wide surgical margin can be used and a functional limb can be salvaged, an amputation probably is not required.

Flow cytometric analysis of DNA in bone and soft‐tissue tumors using nuclear suspensions

Ninety‐four bone and soft tissue tumors were analyzed for their DNA content using flow cytometry (FCM). A simple, rapid method for preparing isolated nuclear suspensions was used. Tissues, minced in a hypotonic solution containing detergent and propidium iodide as a fluorescent probe for DNA, provided in most instances high nuclear yields from only 0.02 to 0.03 g of solid tumor. Whereas all nonneoplastic samples had a diploid DNA content, various degrees of abnormal DNA distributions were detected in 90% of the neoplastic samples and were present in benign as well as malignant tumors. Our findings demonstrate that FCM DNA analysis is practical in most musculoskeletal tumors and support the observations of others that abnormal DNA content may serve as a general neoplastic marker in these tumors.

Multifocal osteosarcoma. A case report with review of the literature

Multifocal osteosarcoma with unique patho‐biological features in a 23‐year‐old white male is reported. The natural history and classification of multiple osteosarcomas are reviewed. A proposal is presented for evaluation of the multicentric origin in future cases.

Osteosarcoma of the pelvis. A clinical and histopathological study of twenty-five patients.

Twenty-five patients who had an osteosarcoma of the pelvis were treated at the University of Florida between 1967 and 1990. Two of these patients had underlying Paget disease, and five had received previous radiation therapy to the pelvis. Common problems in this series of patients included delays and errors in establishment of the diagnosis, underestimation of the extent of the tumor on the radiographic staging studies, histopathological findings of local extension next to and into pelvic structures, widespread invasion into major pelvic veins, and microscopic foci of tumor in otherwise normal tissue. These problems led to difficulty in gaining local control of the tumor with any type of operative procedure. Of the eighteen patients who had a resection, only four had a contamination-free wide margin, and a local recurrence developed in thirteen. Only one patient, who had no evidence of disease eleven years after treatment, was alive at the time of writing. Because of the tendency for venous invasion, the radiographic staging studies should include a thorough evaluation of the blood vessels adjacent to the tumor.

The effect of local extent of the tumor on prognosis in osteosarcoma

The effect of local extent of the tumor on disease-free survival was studied in fifty-one patients who had an osteosarcoma, all of whom were treated according to the same protocol. Disease-free survival was defined as the interval between entry into the protocol and local recurrence, metastasis, or death (whichever occurred first). All patients had a Stage-IIB intramedullary osteosarcoma--that is, a high-grade malignant tumor (Stage II) with cortical penetration (B). The tumors were subdivided on the basis of the amount of local extension: E1--the tumor touches but does not elevate or penetrate the periosteum; E2--the tumor elevates but does not penetrate the periosteum; E3--the tumor penetrates into, but not through, the periosteum; E4--there is minimum extraperiosteal extension without invasion of another structure, such as a muscle, tendon, or ligament; E5--the tumor invades one additional structure (a muscle, ligament, or tendon); and E6--the tumor invades two or more structures adjacent to the bone. When the tumor had invaded two or more adjacent structures (E6), the instantaneous risk of failure was estimated to be 5.9 times greater than when the tumor had a lesser extent (E1 through E5). The relative prognostic importance of the amount of local extension, the size of the tumor, and the sex and age of the patient was compared with forward step-wise Cox multivariate analysis. Only the amount of local extension had a significant effect on disease-free survival. The estimated cumulative probabilities of disease-free survival at five years, according to the Kaplan-Meier method, were 49.1 +/- 8.5 per cent for patients who had a Stage-IIB tumor, 79.8 +/- 9.3 per cent for those who had a Stage-IIB but not E6 tumor, and 17.6 +/- 11.3 per cent for those who had a Stage-IIB E6 tumor. These data suggest that, with respect to prognosis, there are two distinct subgroups of Stage-IIB osteosarcomas that can be objectively defined by the amount of local extension.