Pathology and genetics of tumors of soft tissue and bone

In the past 50 years considerable progress has been made in orthopedics and traumatology. One of the principal reasons for these advances has undoubtedly been the separation of these specialties from general surgery. Alongside this development the number of those devoted to the study and treatment of locomotor disabilities, who could formerly be counted on the fingers of one hand-at least in our country-has multiplied by thousands and even more have subspecialized. This accelerated growth has encouraged the sharpen ing of diagnostic skills, technical improvement, and the application of advances in other fields of medicine to orthopedics. However, paradoxically enough, one of the most important aspects of orthopedics, bone pathology, has not attracted enough specialists worldwide to handle the complex problems, encountered daily, that only an expert and experienced pathologist is capable of resolving. Within the modern milieu, the personality and accomplishments of Professor Fritz Schajowicz stand out distinctly. Dr. Schajowicz, of Austrian origin, studied with Pro fessor J. Erdheim of Vienna. Having afterwards been granted a fellowship to extend his knowledge of bone pathology at the Rizzoli Orthopedic Institute of Bologna under the direction of Professor Vittorio Putti, he complemented this work with the study of clinical orthopedics at that prestigious institution. In 1938, Professor Jose Valls visited the Rizzoli Institute and, recognizing the outstanding training of Professor Schajowicz, invited him to move to Argentina where we were in need of an expert pathologist."

Tumors and Tumorlike Lesions of Bone and Joints

collected in the literature. Most of the descriptions of sarcomas in fibrous dysplasia that are in the literature are single case reports or reports of a few case^.^-'^ The largest series, which includes 15 cases, is that from Memorial Sloan-Kettering Cancer Center, New York.2,20 In 1988, Yabut and coworkers' reported a new case and found 83 cases in a careful review of the literature. The most common of the malignancies was osteosarcoma, followed by fibrosarcoma and chondrosarcoma. The possibility of sarcomatous change in fibrous dysplasia without prior irradiation seems well established, as verified by several reports of documented case~.~~~~'' The role of radiation therapy in the occurrence of sarcoma in fibrous dysplasia is still c~ntroversial.'~~~~' In Huvos' series," only 1 of 15 patients with sarcomas in fibrous dysplasia had received radiation therapy. In the review of the literature by Yabut and coworker^,^ 23 patients had received radiation therapy, 46 had not had prior irradiation, and 14 did not have information available. The purpose of the current study was to review and report our experience with malignancies in fibrous dysplasia. Materials and Methods

Malignancies in fibrous dysplasia.

Sixty-six patients with well-documented osteogenic sarcomas arising in bones and soft tissues after exposure to x-rays, which represent approximately 5.5 percent of all osteogenic sarcomas registered since 1921 at this institution, were studied. These secondary sarcomas occurred in equal proportion in both sexes, with the sixth decade of life being the most common age. In 42 patients, the bone had been normal at the time of irradiation, whereas in 24, the radiation was directed against an osseous tumor or tumor-like lesion. The median latent period was 10.5 years in both groups, ranging from 3.5 to 33 years. The radiation varied from diagnostic quality to 1 MeV x-rays. The dose was variable, but none was less than 2000 rads. Postradiation osteogenic sarcomas most commonly arose in the bones of the pelvic and shoulder regions. Histologically, the sarcomas were mostly of the fibrous type (46%) and radiographically showed a destructive bone lesion with or without signs of radiation osteitis. The cumulative disease-free survival rate at 5 years was 17%, with a median survival estimate of 1 year.

Postradiation osteogenic sarcoma of bone and soft tissues. A clinicopathologic study of 66 patients.

From the records of Memorial Hospital of the past 50 years, 47 cases with an established diagnosis of radiation-induced sarcoma were identified and divided into two groups: the first included 20 cases of soft-tissue sarcoma arising from irradiated tissues, and the second comprised 27 cases of bone sarcoma arising from normal bones in the irradiated field. Medians for the latent periods from irradiation to diagnosis of bone and soft-tissue sarcoma were 11 and 12, years, respectively. In bone sarcomas, the latent period was longer after larger radiation doses and children appeared to be more susceptible to cancer induction than adults. Criteria for establishing the diagnosis of radiation-induced sarcoma and the magnitude of the risk of bone sarcoma are discussed.

Radiation-induced soft-tissue and bone sarcoma.

During the period 1931 to 1970, 50 cases of radiation-induced osteogenic sarcoma were seen at the Memorial and James Ewing Hospitals. Twenty-two of these cases had previously been described; the present paper adds an additional 28 cases to the existing series and reviews those factors related to the development of neoplastic changes. In 35 patients, there was evidence of preexisting bone pathology in the form of benign osseous growths. Fifteen patients had soft-part and visceral neoplasms, such as retinoblastoma, seminoma, and breast carcinoma, the involved bone lying in the pathway of the radiation beam. Symptoms ranged from a palpable tender mass in the involved bone to intestinal obstruction secondary to metastatic radiation-induced osteogenic sarcoma. Essentially all bones in the skeletal system appear to have been vulnerable. The radiation dosages ranged from 1,200 rads given in a few weeks to 24,000 rads given in 2 years. Induction time covered a period of 4 through 30 years with a mean of 9 years. Thirty-two of the patients developing this neoplasm have since died of their disease.

Radiation‐induced sarcoma of bone

One hundred thirty patients with histologically verified primary fibrosarcoma of bone, unassociated with any pre-existent benign bone condition, were treated at Memorial Sloan-Kettering Cancer Center between 1918 and 1973. This series of cases represents approximately 5% of primary malignant bone tumors treated in our institution. Eighty-nine of the lesions were medullary or central in location, and 41 were periosteal or peripheral. There was a nearly equal sex distribution, and a mean age of 38 years ranging from 4 to 83 years. This lesion exhibited a strong predilection for long bones, with the most common location being the femur (43 cases), humerus (16 cases), and tibia (12 cases). In 19 instances, bones of the head and neck area were the primary sites. The roentgenographic differential diagnoses included osteolytic osteogenic sarcoma, malignant giant cell tumor, metastatic carcinoma, or solitary plasma cell myeloma. Major ablative surgery was the primary method of therapy. Amputation was performed, yielding the best curative results in high-grade tumors, while radical local excision sufficed for most low-grade periosteal fibrosarcomas. Thirty-four percent of the patients survived 5 years (27% medullary and 52% periosteal), while 28% were alive after 10 years (20% medullary and 48% periosteal). These survival rates provide further evidence that fibrosarcoma of bone is a distinct clinicopathologic entity and not a variant of osteosarcoma, which carries a much poorer 5-year survival rate of approximately 17%.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197503%2935%3A3%3C837%3A%3AAID-CNCR2820350341%3E3.0.CO%3B2-U

Norman L. Higinbotham

Papers

Radiation‐induced sarcoma of bone

Primary fibrosarcoma of bone. A clinicopathologic study of 130 patients.