Case report 714. Postirradiation osteosarcoma after radiation of metastatic skeletal lesion.

Two cases of postirradiation osteosarcoma are presented--one in a 76-year-old woman with breast carcinoma and subsequent osteosarcoma after radiation therapy for a metastatic lesion in the right tibia, and the other in a 16-year-old girl with hepatocellular carcinoma metastatic to the left tibia and osteosarcoma after radiation therapy to that bone. Microscopically, both cases were high-grade spindle cell lesions with osteoid production. Both patients fared poorly. This is a rare complication of radiation therapy.

Calcifying pseudoneoplasms of the neural axis.

An unusual fibrocalcifying lesion of the neural axis was identified in 14 cases. The radiographic appearance was that of a mass, which in some instances was calcified. The surrounding structures were compressed and the adjacent bone was involved. Histologically, the process was basically a granulomatous one. The granulomas were either nodular or confluent, producing a large mass with peripheral lobular configuration. Epithelioid cells and giant cells bordered the granulomas. Most of the granulomas were composed of fibrochondrocalcifying material. The lesion was particularly dangerous when located in a strategic site, such as the foramen magnum or the base of the skull. Two of the 14 patients with this pseudotumor died, and the other 12 have done well. Complete ablation, marginal or even intralesional, assures control of the lesion. The lesion is probably reactive rather than neoplastic.

Osteosarcoma: pathology and classification.

Osteosarcoma encompasses many different clinical, roentgenographic, and pathologic entities. Some of the tumors, but not all, have prognostic implications that have to be considered during the evaluation of the results of new treatment regimens.

Cancer after exposure to metronidazole.

We assessed the risk of occurrence of cancer associated with exposure to metronidazole in the 771 female residents of Rochester, Minnesota, who were treated with metronidazole for vaginal trichomoniasis during the period 1960 through 1969 and were followed up for a total of 12,628 person-years. Standardized morbidity and mortality ratios were determined by using an expected number calculated by applying age-specific incidence rates from Rochester studies and Cancer Surveillance, Epidemiology, and End-Results Reporting (SEER) data to the person-years of follow-up. The overall standardized morbidity ratios for cancer at all sites were 1.4 (Rochester, 1978 through 1983), 1.5 (SEER data for Iowa, 1978 through 1981), and 1.2 (SEER data for Connecticut, 1978 through 1981). By site of the cancers, the standardized morbidity ratios greater than unity were those for malignant lesions of the lung, breast, thyroid, bladder, brain, kidney, nasopharynx, and oral cavity, as well as for multiple myeloma and malignant melanoma; however, the only significantly elevated standardized morbidity ratio was that for bronchogenic carcinoma. After adjustment for smoking status, the standardized morbidity ratio for bronchogenic cancer was 2.5 (95% confidence interval of 1.3 to 4.4). The standardized mortality ratio for cancer at all sites was 1.4 (95% confidence interval of 0.9 to 2.2). The analysis of these data suggests no significant increase in cancer-related morbidity or mortality for women exposed to metronidazole for treatment of vaginal trichomoniasis.

Chondroblastoma of the skull and facial bones.

A series of 30 chondroblastomas was reviewed: 21 had occurred in the lateral part of the temporal bone, 6 in the mandible, 1 in the parietal bone, and 2 in the region that included the temporal bone and mandible. Of the 30 patients in the series, 20 were males and 9 were females; the sex of 1 patient was not stated. The ages of 29 patients ranged from 2 years 11 months to 70 years (mean, 43.5 years). Radiologic findings were not suggestive of a specific diagnosis, although the lesions appeared to be benign. Histologically, most tumors were classic chondroblastomas. However, some showed aneurysmal bone cyst-like areas and nodules of epithelioid cells without chondroid differentiation. Conservative reexcisions were usually curative. Approximately half of the patients had recurrence after curettage.

Giant-cell-bearing lesions of bone of the hands.

Giant cell tumors, giant-cell reparative granulomas, and aneurysmal bone cysts may produce rarefying defects in the bones of the hand. The radiologic features of the three lesions overlap so much that the distinction must be made on the basis of pathologic study. Experience at the Mayo Clinic and reports in the literature suggest that, when small bones are involved, giant cell tumors are more likely to be multicentric and to recur; two thirds of the giant cell tumors of small bones, 39 per cent of the giant cell reparative granulomas, and 33 per cent of the aneurysmal bone cysts recurred. This difference in recurrence makes it seem important to distinguish these three benign lesions.

Cartilage- and bone-forming tumors of the soft tissues.

Benign and malignant cartilage- and bone-forming tumors arising in soft tissues are unusual. Hyaline cartilage tumors may easily be mistaken as malignant if the histologic criteria of intraosseous lesions are applied directly. Other chondroid- and bone-forming tumors also may be difficult to recognize. The correct pathologic diagnosis within this group of neoplasms requires close clinical correlation, as well as familiarity and careful interpretation of a broad histologic spectrum.

Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients.

Twenty-six patients who had a malignant giant-cell tumor of bone--a sarcoma either juxtaposed to a zone of typical benign giant-cell tumor or occurring at the site of a previously documented benign giant-cell tumor--have been seen at the Mayo Clinic. Of the twenty-six tumors, nineteen were secondary to a previous attempt at local control of a benign giant-cell tumor. All but one of these nineteen patients with a secondary tumor had received therapeutic irradiation four to thirty-nine years earlier. The nature and duration of the symptoms and the sites of predilection of the malignant giant-cell tumors were the same as for benign giant-cell tumor. Fibrosarcoma occurred three times as frequently as osteosarcoma. The best results of treatment of the secondary sarcoma were obtained with early ablation.

Giant cell reaction (giant cell reparative granuloma) of the small bones of the hands and feet.

Giant cell reactions (giant cell reparative granulomas) are uncommon lesions that predominantly involve the small bones of the hands and feet. In 1980, only 13 cases of this entity had been described. Three patients with similar giant cell reactions were identified from the Mayo Clinic files, and an additional 27 patients were collected from the consultation files of one of the authors. Clinical information and follow-up data for these 30 patients suggest that the biologic behavior and, therefore, treatment of giant cell reactions differ from those of true giant cell tumors in the small bones of the hands and feet.

Mesenchymal chondrosarcoma of bone and soft tissue. A review of 111 cases.

A series of 111 mesenchymal chondrosarcomas was reviewed. The ages of the patients ranged from 5 to 74 years, and approximately 60% of them were in the second and third decades of life. There was no significant sex predilection. Seventy-two tumors, including 5 that involved multiple skeletal sites, arose in bone. Thirty-eight tumors were found in extraskeletal sites. At initial diagnosis, multifocal involvement, both in bone and in soft tissue, was observed in one case. Roentgenographically, the lesions in bone frequently resembled ordinary chondrosarcomas, showing osteolytic and destructive appearances with stippled calcification. Tumors in extraskeletal sites were almost always identified as calcified masses. Histologically, a combination of cellular zones composed of undifferentiated small cells and chondroid zones typically presented a bimorphic appearance that was virtually pathognomonic in most cases. Ablative surgical treatment seemed to be the procedure of choice. The value of irradiation or chemotherapy (or both) was difficult to assess in the current study. Prognosis for patients with mesenchymal chondrosarcoma is usually poor, and long-term follow-up is necessary. In a group of 23 patients from the Mayo Clinic, the 5-year survival rate was 54.6% and the 10-year survival rate was 27.3%.

Osteosarcoma of the spine.

Primary osteosarcoma of bone has originated in the spine in only a few patients. This report concerns twenty-seven of thirty patients who had the original diagnosis made and surgical treatment, if any, performed at the Mayo Clinic. The patients' ages ranged from eleven to eighty years. Pain in the area of involvement was the first symptom in all patients. In addition, nineteen patients (70 per cent) had neurological symptoms and signs when they were first seen. All patients had a surgical biopsy of the lesion, often combined with decompressive laminectomy. Twenty-one of the twenty-seven patients received postoperative radiation therapy in various dosages. Only five patients received adjunctive chemotherapy. All but one patient died of the disease, with a median length of survival of ten months (range, one to thirty-eight months). Although rare, osteosarcoma of the spine can usually be suspected on roentgenograms, and then the most aggressive therapy is justified.

Giant-cell tumor of bone.

Our experience involving 221 consecutive patients with giant-cell tumor who were treated from 1960 to 1982 is reported. Of one group of 146 patients, twenty-seven who were initially treated by wide resection and 112 who had thorough curettage had a recurrence rate of 23 per cent after an average length of follow-up of seven years. All thirty-three recurrences were noted less than six years after operation, and twenty-seven were noted within the first three years postoperatively. Over-all, the type of surgical removal was the most significant factor in recurrence. The recurrence rate was 34 per cent in the patients who had curettage of the lesion and 7 per cent in those who had a wide resection. In a second group of seventy-five patients, initially treated by us for a recurrent tumor, there were fifteen subsequent recurrences, after an average length of follow-up of seven years. Curettage and bone-grafting, with preservation of function of the joint, is the preferred treatment for most patients.

Caldwell Lecture. Giant cell tumor of bone: highlights of 407 cases.

This retrospective study of 407 cases of giant cell tumor indicated that most tumors were in the expected locations, usually in the end of a major tubular bone. Female patients accounted for a definite, but slight, majority. Five patients had metaphyseal tumors, and three patients had multifocal tumors. Only one tumor occurred in a lesion of Paget disease. Local soft-tissue implantation, ordinarily with the implant having a mineralized shell, was observed in 10 of the cases. Eight patients had tumors that produced benign metastatic lesions, and two of them have died. Histologically, malignant change developed in 28 of the cases; in 21 of these, radiation had been included in the treatment of the primary lesion.

Trends and variability in survival among patients with osteosarcoma: a 7-year update.

This report is an update of a 1978 article on osteosarcoma in Mayo Clinic patients. It includes additional follow-up on previously reported cases and incorporates new cases treated since the time of that original study. From 1963 through 1981, 336 patients with classic, previously untreated osteosarcoma received their first definitive treatment at our institution. Survival of these patients was studied in detail. The most significant result was that survival in the 1960s was much worse than that in the 1970s. The first evidence of improvement in survival was noted in 1969; subsequently, further improvement occurred but was not consistent. This finding prevailed with respect to duration of survival to death, survival to detection of metastasis, and survival from occurrence of metastasis to death. On the basis of detailed regression analysis, several variables had independent prognostic value. From these findings, a prognostic score was developed, which was based on the number of the following unfavorable characteristics: age younger than 10 years, male sex, tumor diameter more than 15 cm, cell type osteoblastic or chondroblastic, duration of symptoms 2 months or less, and involvement of the femur or humerus. Patients with five or six of these unfavorable characteristics had a very poor survival; in contrast, patients with only one or two characteristics had a good outcome. Even when these scores were fairly constant, however, the calendar period had a strong influence on survival. Likewise, when treatment was considered and adjustments by score were made, no significant differences could be found between those patients treated by amputation only and those treated by amputation supplemented with chemotherapy or radiotherapy.

Osteosarcoma resembling osteoblastoma.

A series of 17 patients with osteosarcomas that histologically resembled osteoblastomas was studied. The ages of the 9 male and 8 female patients ranged from 11 to 58 years. The roentgenographic appearance was suggestive of malignancy in most cases. Two histologic features seemed most important in differentiating osteosarcoma from osteoblastoma. In the former, there is permeation of surrounding tissues and lack of "maturation" toward the edges, whereas osteoblastoma tends to show maturation peripherally and is circumscribed. Osteoblastoma-like osteosarcoma should be considered to be a malignant tumor because 7 of the 17 patients died of their disease. The authors believe that malignant osteoblastoma and aggressive osteoblastoma are really osteosarcomas that resemble osteoblastomas.

Giant cell tumor: ossification in soft-tissue implants.

Benign giant cell tumor of bone may be implanted into the surrounding soft tissues at the time of surgery or pathologic fracture. These soft-tissue implants may produce ossification that is radiographically visible. A review of the available radiographs of 400 cases of giant cell tumor from the Mayo Clinic and 700 cases seen in consultation yielded 17 examples of this phenomenon. In all but one case, the ossification was found at the periphery of the implant. The radiographic appearance of these implants is characteristic. Recognition of this appearance is necessary so that the tumor may be totally eradicated.

Genotoxicity studies with paracetamol.

Paracetamol and its major ultimate reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI) were studied for their genotoxic potential. Neither paracetamol nor NAPQI were found to cause mutations in Salmonella typhimurium, whereas NAPQI was severely cytotoxic to the bacteria. Radiolabelled paracetamol was found to bind covalently to DNA added to mouse-liver microsomal incubations at a rate of 2.6 pmoles/mg DNA/min. Paracetamol also bound covalently to hepatic DNA at a level of 15 pmoles/mg DNA after a hepatotoxic dose of paracetamol to mice. NAPQI caused extensive DNA single-strand breaks as evidenced by alkaline elution of DNA from treated Reuber hepatoma cells. This effect occurred at concentrations which later resulted in cytotoxicity. Paracetamol was shown to induce increased DNA-repair synthesis in isolated mouse-liver cells in monolayer culture, at concentrations where also cytotoxicity was evident. Increased DNA-repair synthesis occurred at lower paracetamol concentrations in cells isolated from mice pretreated with phenobarbital. Taken together, these data show that paracetamol can cause DNA interaction leading to damage at levels which are cytotoxic.