Chordoma is the second most common primary malignant tumor of the spine. These tumors rarely metastasize but are considered malignant and, when present in younger individuals, can be aggressive. In the setting of unresectable primary, recurrent, or metastatic tumors the current armamentarium of adjuvant therapy for this condition is very limited. Recent research, however, has identified potential targets for immunotherapy, including the tumor associate antigens High Molecular Weight Melanoma Associated Antigen (HMW-MAA) and B7H3. The goal of this investigation was to correlate expression of B7H3 and HMW-MAA in chordoma tumors with disease severity and clinical outcome. Tissue MicroArrays (TMA) were constructed using an automated arrayer to include 70 conventional chordoma tumors obtained from archives at our institution. Triplicate cores (0.6 mm in diameter) from each sample were created and two sets of cores were created for each chordoma specimen. One triplicate sample was incubated in a closed humid chamber with a pool of HMW-MAA-specific mAb, while the other was incubated with mAb specific for B7H3. Samples were washed in PBS and incubated with a secondary antibody for one hour. Staining was evaluated independently by two researchers and scored using validated systems. A retrospective chart review was performed for each chordoma specimen to determine demographic data, disease course, disease status at final follow-up and mortality. Clinical outcomes were then correlated to the expression of HMW-MAA and B7H3 within the chordoma lesions. Kaplan-Meier curves and Cox proportional hazard regression analysis were utilized to facilitate comparisons. Chordoma tumors from 70 patients were included in this study. Average age at the time of presentation was 57.4 years (31–88 years). Average follow-up was 5.5 years (3.6 months-21 years). Forty-three patients developed recurrences and 10 had metastatic disease. Twenty-three patients (33%) had died of disease at the time of final follow-up. Ninety-seven percent of chordoma tumors stained positive for B7H3 while 44% stained positive for HMW-MAA. No correlation could be drawn between clinical course, recurrence rate, or mortality and tumor expression of B7H3 and HMW-MAA. Kaplan-Meier analysis did demonstrate a shorter survival time for patients whose tumors stained positive for HMW-MAA compared to those whose tumors were negative for the antigen. The goal of this investigation was to correlate expression of B7H3 and HMW-MAA in chordoma tumorswith disease severity and clinical outcome. Results indicate that expression of HMW-MAA may be predictive of more aggressive disease and shorter survival. HMW-MAA and especially B7H3, in light of its near universal expression in the chordoma tumors studied here, may serve as potential targets for adjuvant immunotherapy.
A relatively common complication of Gaucher disease, the so-called crisis, frequently is difficult to differentiate from acute osteomyelitis. We reviewed the cases of forty-nine patients with Gaucher disease who were treated at the Massachusetts General Hospital and found that eleven patients had required admission to the hospital for an acute symptom complex that represented either a crisis or an infection. Five of the patients proved to have acute hematogenous osteomyelitis. The delayed diagnosis of the infection in three of the patients with osteomyelitis led to an unsatisfactory outcome.
The radiographic and CT appearance of 20 cases of chondrosarcoma were correlated with histological grade and type of matrix. Features which were useful in predicting histological grade included (a) margins between bone and tumor (radiograph), (b) morphology of calcification (radiograph, CT), (c) distribution of calcification within the lesion (radiograph, CT), (d) pattern of tumor growth within soft tissues (CT), and (e) presence of necrosis (CT). Tumor/soft-tissue margins were usually well defined on the CT scan regardless of grade.
A new association between multicentric fibromatosis and a bone dysplasia is reported. Three patients are described, each of whom had multicentric fibromatosis of the lower extremity and a skeletal dysplasia. One of the patients had dysplastic changes restricted to the involved extremity. The other two had dysplastic changes of all the long bones. The dysplasia consisted predominantly of undertubulation reminiscent of the findings seen in Pyle disease. No clinical or radiographic abnormalities of the marrow were found in any of these patients. It is believed that this association represents mesenchyme that is predisposed to develop both dysplastic bone changes and tumor.
Magnetic resonance imaging was used to study the skeletal involvement in a series of twenty-four patients with Gaucher disease. Many sites in the marrow of these patients were characterized by an abnormally low signal intensity that reflected shortened T1 and markedly shortened T2 values in the replaced marrow. The abnormality was non-homogeneous in distribution. In the lower extremity, the proximal (femoral) areas were more frequently affected than the distal (tibial) sites. The epiphyses were generally spared unless the involvement of bone was extensive. Lack of epiphyseal involvement on the magnetic resonance images generally precluded any suspicion of osteonecrosis. The extent of involvement, as suggested by the magnetic resonance data, appeared to correlate well with the occurrence of musculoskeletal complications. Magnetic resonance imaging is more sensitive than computerized tomography in demonstrating the extent of abnormalities in patients with Gaucher disease, and it may have prognostic value.
