Pathology and genetics of tumors of soft tissue and bone

The need for a standardized system of end result reporting of various surgical alternatives after limb salvaging and ablative procedures for musculoskeletal tumors was clearly recognized during the first International Symposium on Limb Salvage (ISOLS) in 1981. During the ensuing four biannual symposia, there has been an ongoing developmental experience with a system extensively field tested in 1989 by the Musculoskeletal Tumor Society (MSTS). This system of functional evaluation has been adopted by the MSTS and ISOLS for their joint studies and program presentation. In brief, the system assigns numerical values (0-5) for each of six categories: pain, and function and emotional acceptance in upper and lower extremities; supports, and walking and gait in the lower extremity; and hand positioning, and dexterity and lifting ability in the upper extremity. Demographic information and a patient satisfaction component is included. A numerical score and percent rating is calculated to allow for comparison of results. The system has been field tested in 220 patients with low (+/-) interobserver variability. It was well accepted by the participants, and its usage is recommended by the MSTS to facilitate valid comparative end result studies of musculoskeletal tumor reconstructions.

A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system.

Historically, an adequate surgical procedure has been the most effective means of treating the majority of primary musculoskeletal sarcomas, and amputation has figured prominently in the surgical armamentarium. 4, 7, 9, 19, 21, 29, 41 The recent evidence that certain chemotherapeutic agents may have significant anti-sarcoma activity 2, 15, 17, 38 and coincident technical advances in irradiation therapy, radiographic localization, and reconstructive surgery have fostered enthusiastic interest in extremity-saving treatments. Almost all such treatments emphasize limb salvage as an alternative to amputation and are usually performed under a protective cloak of adjunctive chemotherapy, irradiation or immunoactive agents. 20, 23, 24, 30, 37, 39 Since neither chemotherapy nor irradiation therapy alone has been shown to assure long-term local control of bulk disease, surgical intervention remains an essential step in the overall management of musculoskeletal sarcomas. 3, 9, 17, 18, 29 Questions concerning the magnitude and timing of the surgical procedure are as unanswered as those relating to the most appropriate use of the adjuncts themselves. Increasingly, the surgeon and his patient are confronted with a bewildering array of therapeutic options, the long-term outcomes of which are unknown. These relatively rare sarcomas increasingly are distributed among a variety of treatment protocols in which multiple parameters differ. This trend necessitates interinstitutional cooperation if sufficient numbers of patients are to be available for the timely evaluation of treatments in clinical use. Such cooperation and even effective interinstitutional communication are seriously hampered by the lack of uniform language, so that meaningful comparison of treatments is currently impossible. Prime factors include the lack of a consistent definition of the surgery performed and a serviceable surgical staging system encompassing bone and soft tissue. Standard terminology will assure that like and unlike treatments are appropriately compared. Although an effective staging system should serve all members of the multidisciplinary team, the biologic behavior of musculoskeletal sarcomas suggests that the most useful staging system will articulate with the surgical procedure.

A system for the surgical staging of musculoskeletal sarcoma.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines

Autograft is considered ideal for grafting procedures, providing osteoinductive growth factors, osteogenic cells, and an osteoconductive scaffold. Limitations, however, exist regarding donor site morbidity and graft availability. Allograft on the other hand, posses the risk of disease transmission. Synthetic graft substitutes lack osteoinductive or osteogenic properties. Composite grafts combine scaffolding properties with biological elements to stimulate cell proliferation and differentiation and eventually osteogenesis. We present here an overview of bone grafts and graft substitutes available for clinical applications.

Bone substitutes: an update.

A system for staging benign and malignant musculoskeletal lesions is presented. This system, first devised at the University of Florida in 1977, was based on data assembled from 1968 through 1976. It was field tested by the Musculoskeletal Tumor Society and published in Clinical Orthopaedics and Related Research in 1980. In the ensuing five years, the system has undergone refinement. It has recently been adapted by the American Joint Committee Task Force on Bone Tumors and proposed by them to the International Union Against Cancer (IUCC) for international usage. Based upon histologic grade (G), anatomic site (T), and presence or absence of metastases (M), it describes the progressive stages, irrespective of histogenesis, that assess the progressive degrees of risk to which the patient is subject. This system articulates well with current radiologic techniques of staging and serves as a useful guide in the selection of an appropriate definitive surgical procedure. Its usage permits comparative end result studies on the effect of surgical and nonsurgical methods of management.

A system of staging musculoskeletal neoplasms.

Fibrous dysplasia is a common benign skeletal lesion that may involve one bone (monostotic) or multiple bones (polyostotic) and occurs throughout the skeleton with a predilection for the long bones, ribs, and craniofacial bones. The etiology of fibrous dysplasia has been linked to an activating mutation in the gene that encodes the alpha subunit of stimulatory G protein (G(s)alpha) located at 20q13.2-13.3. Most lesions are monostotic, asymptomatic, and identified incidentally and can be treated with clinical observation and patient education. Bisphosphonate therapy may help to improve function, decrease pain, and lower fracture risk in appropriately selected patients with fibrous dysplasia. Surgery is indicated for confirmatory biopsy, correction of deformity, prevention of pathologic fracture, and/or eradication of symptomatic lesions. The use of cortical grafts is preferred over cancellous grafts or bone-graft substitutes because of the superior physical qualities of remodeled cortical bone.

Fibrous dysplasia. Pathophysiology, evaluation, and treatment.

Background: We studied seventy-three massive preserved human allografts, retrieved from two to 156 months after implantation, to provide insight into the mechanisms of their repair.

Methods: The specimens were studied with radiographic and histological techniques that permitted time-related quantitative analysis of the reparative mechanisms of union, cortical repair, soft-tissue attachment, fracture, and characteristics of the allograft-cement interface and the articular cartilage.

Results: Union at cortical-cortical junctions occurred slowly (approximately twelve months) by host-derived external callus that bridged the junction and filled the gap between abutting cortices. The bone in the gap did not undergo stress-oriented remodeling even after many years, and, when the union was intentionally disrupted, failure occurred at the cement line that marked the allograft-host junction. Repair of the necrotic graft matrix was both external and internal. External repair consisted of the apposition of a thin seam of host bone on the outer surface of the graft, coating about 40% of the surface at one year and 80% at two years. Internal repair was confined to the ends and the periphery of the cortices and penetrated so slowly that only 15% to 20% of the graft was repaired by five years, after which deeper repair seldom occurred. Graft fractures in specimens retrieved soon after fracture showed only necrotic bone adjacent to the fracture site, whereas those retrieved after fracture-healing showed a marked increase in internal repair of the bone about the fracture site. When bone cement had been used to fix a prosthesis, there was no evidence of bone resorption or loosening of the device.

The osteoarticular specimens showed no survival of chondrocytes in the articular cartilage. However, the architecture of the acellular cartilage was well preserved after two to three years and occasionally after as many as five years. Late degenerative changes in the articular cartilage coincided with subchondral revascularization and fragmentation, and the articulating surfaces became covered by a pannus of fibrovascular reparative tissue. Degenerative changes in articular cartilage occurred earlier and were more advanced in specimens retrieved from patients with an unstable joint than in those retrieved from patients with a stable joint.

Conclusions: Repair of massive human allografts is an indolent process that follows a fairly predictable course during the first few years and is influenced by other biological activities, such as fracture repair, supplementary autografting, and tumor recurrence.

Clinical Relevance: These observations provide a clear, detailed picture of the extent, timing, and deficiencies in the incorporation and repair of large human allografts preserved by conventional banking techniques. As such, they provide a basis for comparative studies of the efficacy of the recently developed osteoinductive substances currently under investigation.

William F. Enneking

Papers

A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system.

A system for the surgical staging of musculoskeletal sarcoma.

A system of staging musculoskeletal neoplasms.

Fibrous dysplasia. Pathophysiology, evaluation, and treatment.

Retrieved human allografts : a clinicopathological study.