Alan L. Schiller

Clinical and pathologic review of 48 cases of chordoma

The results of treatment of 48 patients with the diagnosis of chordoma during the period 1931 to 1981 at the Massachusetts General Hospital were reviewed. Fourteen patients were treated with surgery alone: eight patients with primary tumors in the sacrococcygeal region were treated with radical surgery and four are alive with no evidence of disease (NED) with follow‐up of 8 to 20 years. Recurrent tumors in six patients were treated with surgery alone resulting in long palliation (3–25 years). The actuarial survival rate at 5 years for all patients treated with surgery was 76%. Radiation therapy was used in patients after either a biopsy (15), partial excision (17), or before radical excision in 2 patients. To achieve a worthwhile level of palliation, doses greater than 4000 cGy were required. High‐dose levels (>6500 cGy) were achieved in nine cases by a combination of photon and 160 MeV proton beams. The results to date of this approach for lesions of the base of skull and cervical vertebral body are encouraging: high local control and low morbidity. The 5‐year actuarial survival rate of all patients treated with radiation was 50%.

Desmoplastic fibroma of bone. A report of eight cases and review of the literature.

Desmoplastic fibroma of bone is a rare benign tumor consisting of thin, wavy fibroblasts set in an abundant matrix of collagen fibers. At times it is difficult to distinguish desmoplastic fibroma from other fibrous lesions, especially low-grade fibrosarcomas. Fewer than eight cases have been previously reported. We have reviewed the diagnostic and therapeutic findings of eighty additional cases. Six patients had the lesions located in an extremity and two had an axial lesion. The average age of the patients was twenty-five years (range, twelve to fifty-six years) and all of the patients had more than two years of follow-up (range, two to seventeen years). The radiographic findings in all but one patient were of a purely lytic, honeycombed lesion that often widened the bone, and was metaphyseal in long bones. The tumor replaced the medullary cavity with a grayish-white, rubbery to firm tissue that was often, but not always, contained by a rim of periosteal reactive bone. Histologically, the features were: (1) prominent loose bundles of fibrous tissue composed of slim, spindle-shaped fibroblasts with wavy, elongated nuclei; (2) variable amounts of bands of collagen fibers; and (3) absence of mitoses or atypical cells. Areas of metaplastic bone were found only around sites, of pathological fractures. The biology of desmoplastic fibroma is different from that of other benign fibrous lesions in that the lesion is very destructive locally and often recurs after incomplete excision. It is also distinguished from low-grade malignant lesions (for example, fibrosarcoma) in that metastases have never been reported. In our series an intralesional excision was initially performed in six of the eight patients and a marginal resection, in two. There were four recurrences, treated by a marginal resection in two patients and repeat curettage in one. The recurrence in the fourth patient required an amputation above the knee after two additional intralesional procedures had been unsuccessful. Wide or marginal resection appears to be the treatment of choice when the lesion is located in a site that can be resected without significant loss of function. In other areas, an attempt at curettage, instillation of phenol, and bone-grafting seems to be warranted, resorting to more radical procedures only if this fails to control local disease.

Histological studies of the glenoid labrum from fetal life to old age.

To help to resolve the controversy regarding the composition of the glenoid labrum, thirty-eight shoulders from cadavera were examined grossly and histologically. We used specimens for individuals of different ages so that we could determine what changes occur as a result of aging. In children and adults, the labrum appeared to be fibrocartilaginous tissue. The labrum was a separate anatomical structure that could be distinguished from the fibrous capsule of the shoulder. Neonatal labra were composed of primitive mesenchymal tissue containing only few chondrocytes that modulated into fibrocartilage in the first few years of life. Neonatal labra contained no elastin, whereas specimens from adults had rare elastin fibers. The labrum was sparsely vascularized throughout its substance, with no particular pattern of distribution. Vascularity decreased with increasing age of the individual.

Primary lymphoma of bone the relationship of morphologic diversity to clinical behavior

Since primary lymphoma of bone (PLB) exhibits morphologic diversity and variability in individual survival, we analyzed the relationship between histopathologic features and biological behavior in 33 patients treated at the Massachusetts General Hospital. Three major histologic subgroups were identified, based on a variety of criteria, the most important of which were the predominance of cells with or without nuclear clefts and the degree of pleomorphism. The probability of NED survival at five years was 64% for patients with tumor predominantly composed of cleaved cells, 13% for those with tumors classified in the noncleaved cell tumor group, and 0% (no survivors) for the pleomorphic subgroup. When tumors were subclassified according to the size of the predominant cell (small versus large), this parameter was found to be of no value in predicting NED survival. Factors that could have potentially influenced the results were analyzed. Since this is a retrospective review, the questions addressed in this study should be further studied in a prospective way.

Multicentric giant-cell tumor of bone.

Five patients with primary multicentric giant-cell tumor of bone (eighteen lesions) were followed for four to fourteen and one-half years from the time of the original diagnosis. Only fifteen such cases (fifty-two lesions) have been reported previously. In our series the course of each lesion was similar to that expected of the monostotic tumor. There was a high incidence of lesions in the small bones of the hand (eleven of the eighteen). The histological features were generally typical, but some lesions had a stroma composed mostly of spindle cells. All of the lesions were excised and there was a recurrence in four patients. Of eight lesions treated by curettage with or without autogenous bone-grafting, six recurred. All lesions in the hand that were treated by curettage recurred. There was only one recurrence of the lesions treated by amputation or en bloc resection. Infection occurred in one patient. There were no metastases.

The histologic response of soft tissue sarcoma to radiation therapy

Twenty‐seven patients with soft tissue sarcoma had preoperative radiotherapy, limb‐sparing marginal surgical resection and whole‐mount tumor histologic analysis. Incisional biopsy specimens before radiotherapy were reviewed for tumor type, grade, and extent of necrosis. Preoperative radiotherapy was given in either of two regimens: 13 patients received a mean total dose of 5250 cGy in one daily 180 to 200 cGy fractions and 14 patients a mean total dose of 4770 cGy in two daily fractions of 180 to 200 cGy separated by 4 hours. Twenty‐one specimens had at least 80% necrosis or severely altered cells, a 3+ to 4+ response. Grade and size of the tumor appeared to be indicators of response to treatment rather than histologic type. Three of five patients (60%) with Grade 1, eight of 11 patients (73%) with Grade 2 lesions, and ten of 11 patients (91%) with Grade 3 tumors had 80% or greater necrosis or severely altered cells. For tumors 10 cm or less in greatest diameter, the 3+ to 4+ histologic response was seen in 12 of 14 patients (86%) whereas for lesions greater than 10 cm, this response was observed in nine of 13 patients (69%). For patients with Grade 2 or 3 soft tissue sarcoma, 13 of 14 patients (93%) treated with two fractions per day and two of four patients (50%) receiving one fraction per day exhibited significant response. All six patients treated twice daily for lesions greater than 10 cm had 3+ to 4+ histologic response compared to three of seven (43%) patients treated once per day. Therefore, grade and size of soft tissue sarcoma are important predictors of response to radiotherapy and preoperative twice daily radiotherapy may more likely permit the conservative surgical excision of sarcomas of borderline resectability.

Grading of bone tumors by analysis of nuclear DNA content using flow cytometry.

We studied 217 consecutive tumors of bone by flow cytometric analysis of nuclear DNA concentration after staining with propidium iodide. A diagnosis and histological grade (benign, low-grade, or high-grade sarcoma) were assigned to each tumor on the basis of staging data (with the exception of the forty-six giant-cell tumors, which, although indistinguishable histologically, were divided according to the flow cytometric pattern into two distinct groups), and we quantitatively studied the flow cytometry data to assess the percentages of cells in diploidy, tetraploidy, or aneuploidy. When compared, the mean values for the flow cytometric data for the three grades showed significant differences. Criteria were established for the three classes of tumors: for benign tumors, less than 11 per cent tetraploidy and no aneuploidy; for low-grade sarcomas, more than 11 per cent and less than 17 per cent tetraploidy, and no aneuploidy; and for high-grade tumors, either more than 17 per cent tetraploidy or aneuploidy. Tests for compliance for all groups of tumors (excluding the forty-six giant-cell tumors)--benign, low grade, or high grade--were significant for most of the benign lesions (with the exception of chondroblastoma and fibrous dysplasia) and for the high-grade sarcomas (with the exception of round-cell tumors). The low-grade sarcomas did far less well, based principally on the failure of the low-grade chondrosarcomas, chordomas, and adamantinomas to comply with the criteria. An attempt to assess the value of the system as a predictor of metastases showed that a low percentage of diploid cells (less than 75 per cent) and the presence of an aneuploid peak correlated statistically with the development of metastatic disease, but the usefulness of this observation could not be fully assessed because of multiple variables, associated principally with treatment.

Characterization of cells from human giant cell tumors of bone.

In vitro cell culture techniques were used to identify and characterize the individual cell types present in human giant cell tumors of bone. Three major cell types were identified based on morphologic characteristics, patterns of specific cell surface antigens, presence of receptors for hormones, and cell products. One population consisted of mononuclear cells that expressed monocyte-macrophage markers. These cells lacked receptors for skeletal hormones and did not persist in culture. Distinct from these cells was a population of mononuclear cells that proliferated in culture and most likely represented the neoplastic element of the tumor. These cells phenotypically resembled connective tissue stromal cells, i. e., they did not express macrophage surface antigens and they produced collagens (Types I and III). They also possessed receptors for parathyroid hormone. The final population of tumor cells consisted of multinucleated giant cells. These cells lacked monocyte-macrophage surface antigens and possessed receptors for calcitonin, a phenotypic marker for osteoclasts. These studies illustrate that in vitro cell culture techniques can be employed to identify and characterize the cell populations of tumors of skeletal tissues, and demonstrate the usefulness of these cell culture models for investigating the biology of bone tumors.

Vascular events associated with the appearance of the secondary center of ossification in the murine distal femoral epiphysis.

Although the formation of a secondary center of ossification is often compared with that of the primary center, there are striking differences between these processes. In the formation of the primary center, vascular invasion is always associated with the maturation of chondrocytes, whereas vascularization of the epiphysis can proceed in two different ways. In some species, the epiphysis is vascularized by cartilage canals before the appearance of the secondary center. However, in the mouse, the distal femoral epiphysis is vascularized by peripheral vascular invasion without pre-existing cartilage canals. Histological study of serial sections and studies of vascularization by injection with India ink demonstrated the relationship between hypertrophic chondrocyte formation, vascular invasion, and the formation of the secondary center of ossification in the murine distal femoral epiphysis.

Chondrosarcoma of the temporal bone: Diagnosis and treatment of 13 cases and review of the literature

Chondrosarcoma of the temporal bone is a rare lesion. Clinically it has been confused with multiple sclerosis, glomus jugulare tumors, meningioma, and chordomas. The cranial nerve palsies frequently observed with the tumors are related to the anatomic locations of the tumors. Thirteen patients with this entity are presented and the eleven other cases in the literature are reviewed. Histologically the tumors are low grade and exhibit myxoid features. The myxoid features must be differentiated from chordoma and chondroid chordoma. The tumor locations preclude surgical excision and conventional radiation therapy can cause unacceptable neurologic sequelae. Proton beam therapy has been effective in short‐term results and appears capable of avoiding serious neurologic side effects.