Sebastian Blasius

Chondrosarcoma of the pelvis

Thirty-one patients with chondrosarcoma of the pelvis were reviewed. The median followup period of the surviving patients was 66 months. Thirteen of 23 tumors after surgery with inadequate margins (57%) and 1 of 8 after surgery with adequate margins (13%) relapsed locally. Four of 10 patients had local recurrence, 2 of 2 patients had metastasis, and 4 of 4 patients who had local recurrence and metastasis died. A cumulative 10-year overall survival of patients with pelvic chondrosarcoma was 54%. Patients who had primary or high grade chondrosarcoma had a poor prognosis. Multivariate analysis (Cox proportional hazard model) showed that tumor type was the most important prognostic factor. Eight patients underwent hindquarter amputation, 6 patients had resection alone, and 17 patients had resection and reconstruction as follows: 3 interpubic arthrodeses, 2 iliosacral arthrodeses, 3 ischiofemoral arthrodeses, 8 hip prostheses (3 prostheses alone and 5 prostheses with allograft), and 1 hip transposition. Failure of reconstruction was attributed to infection in 5 patients, local recurrence of tumor in 5, and local recurrence and fracture of implant in 1 patient.

Analysis of mutant P53 protein in osteosarcomas and other malignant and benign lesions of bone

SummaryAlterations of tumour suppressor genes are considered crucial steps in the development of human cancers. Expressions of p53 protein, a product of the tumour suppressor gene altered most commonly in human cancers examined so far, were investigated immunohistochemically in 18 osteosarcomas and 40 other malignant and benign lesions of bone. A monoclonal antibody clone PAb240, which recognizes a common conformational epitope of mutant p53 proteins, stained nuclei of tumour cells in 12 of 18 osteosarcomas (67%). Six tumours (33%) particularly showed positive immunoreactions in more than half of the tumour cells. PAb240 also stained tumour cells in a small number of other malignant bone tumours, such as malignant fibrous histiocytoma, chondrosarcoma, and Ewings sarcomas. Furthermore, a small number of cells of giant-cell tumours were positively stained. In contrast, PAb240 was completely negative in 21 benign bone tumours and reactive lesions examined. Another monoclonal antibody clone PAb1801, which reacts with both wild- and mutant-type p53 protein, reacted in nuclei of tumour cells of 7 osteosarcomas (39%). Most of those also reacted with PAb240. PAb1801 was expressed much more frequently in other malignant bone tumours and giant-cell tumours. In addition, PAb1801 showed intranuclear positive reactions in tumour cells of a benign chondroblastoma, and reactive cells such as actively proliferating preosteoblasts in a myositis ossificans and osteoclast-like giant cells in a giantcell tumour. The immunoelectron-microscopic observation that p53 protein was localized in euchromatic areas of nuclei of osteosarcoma cells supported the specificity of immunoreaction for p53 protein, indicating an active role of p53 protein in the regulation of DNA synthesis and transcription. These findings suggest that point mutation of the p53 gene is frequently involved in the development of osteosarcomas. PAb240 may be a useful tool not only in screening point mutations of the p53 gene in osteosarcomas but also in the differential diagnosis between osteosarcomas and reactive bone-forming lesions. Expressions of mutant p53 protein were not correlated with any clinical or pathological factors examined, although the results should be confirmed in studies of a large number of osteosarcomas.

Diagnostic value of the molecular genetic detection of the t(11;22) translocation in Ewing's tumours

One consistent feature of the Ewings tumour family is the presence of a balanced translocation involving band q12 and band q24 of chromosome 22 and chromosome 11. Recent cloning of the chromosome breakpoint regions of t(11;22)(q24;q12) Ewings sarcoma translocation has revealed that the breakpoints were localized within the Ewings sarcoma gene (EWS gene) on chromosome 22 and the Fli-1 gene on chromosome 11. Molecular genetic techniques can thus be applied to the detection of the t(11;22) translocation in Ewings tumours. By reverse transcription and polymerase chain reaction technique (RT-PCR) 11 Ewings tumour derived cell lines, 12 primary Ewings tumours, and 11 tumours after treatment were analysed for the occurence of the t(11;22) translocation. Furthermore, blood and bone marrow samples from 5 patients were available for RT-PCR. In 78% of the cell lines and 91% of the primary Ewings tumours the t(11;22) translocation was detectable by RT-PCR. In bone marrow samples from a Ewings sarcoma patient presenting in relapse tumour cells were detected by molecular genetic analysis. Our results indicate that molecular genetic detection of the t(11;22) translocation is valuable in the differential diagnosis of small round cell tumours and will provide important information for the staging and prognosis of Ewings tumour.

Chondroblastoma of bone : a clinical, radiological, light and immunohistochemical study

This is a retrospective study of 70 patients with chondroblastoma treated between 1973 to 2000. Of these 70 patients, 53 had their primary procedure performed at our unit in the form of an intralesional curettage. The purpose of this study was to determine the rates of recurrence and the functional outcomes following this technique. Factors associated with aggressive tumour behaviour were also analysed. The patients were followed up for at least 22 months, up to a maximum of 27 years. 6 out of these 53 cases (11. 3%) had a histologically proven local recurrence. Three patients underwent a second intralesional curettage procedure and had no further recurrences. Two patients had endoprosthetic replacement of the proximal humerus and one patient underwent a below knee amputation following aggressive local recurrences. One patient had the rare malignant metastatic chondroblastoma and died eventually. The mean MSTS score was 94. 1%. We conclude that meticulous primary intralesional curettage without any additional procedure can achieve low rates of local recurrence and excellent long-term functional results.The clinical and morphological findings of 53 chondroblastomas in the files of the Bone Tumour Registry of Westphalia are presented. The mean age of all patients was 19.2 years. The male-to-female ratio was 1.5∶1. Forty-two of the tumours (79.8%) were located in the long tubular bones and short tubular bones of the hands and were closely related to the growth plate. Six cases (11.3%) were found in the flat bones, 4 cases (7.5%) in the tarsal bones and 1 case (1.9%) in the craniofacial bones. The characteristic radiological feature of 44 investigated lesions was a mostly eccentric radiolucency with a geographic pattern of bone destruction and matrix calcifications. Periosteal reaction was evident in 9% of the cases. Most tumours demonstrate the typical morphological features of chondroblastoma, but 3 cases resembled a giant cell tumour. In 2 cases a haemangio-pericytomalike growth pattern was observed. Nine of the tumours had an aneurysmal bone cyst-like component. Vascular invasion was seen in 1 case. Immunohistochemically most cells in 30 of the cases and fetal chondroblasts in 3 cases were strongly positive with vimentin and S-100 protein. Collagen type II was positive in the chondroid matrix of the tumours and in fetal cartilage tissue; collagen type VI was present focally around individual tumour cells and was always seen in the chondroid matrix of the lesions and in fetal cartilage. These findings support the cartilaginous nature of these tumours. In paraffin sections, 46.6% of the cases revealed a distinct positive reaction of some tumour cells with the monoclonal cytokeratin antibody KL1 (molecular weight 55–57 kDa). Only 4 of them demonstrated a coexpression with the other monoclonal cytokeratin anti-body CK (clone MNF 116, molecular weight 45–56.5 kDa). In paraffin sections all fetal chondroblasts were negative with both cytokeratin antibodies. Frozen sections of 3 tumours showed a strong positive reaction with both cytokeratin antibodies in many chondroblasts, indicating an “aberrant” cytokeratin expression. Osteoclast-like giant cells stained positive with leucocyte-common antigen (LCA) and with the macrophage-associated antibody KP1, but were negative with the other macrophage-associated antibody MAC 387. Recurrence rate was 10.7%. The clinical course of all tumours was benign.The clinical and morphological findings of 53 chondroblastomas in the files of the Bone Tumour Registry of Westphalia are presented. The mean age of all patients was 19.2 years. The male-to-female ratio was 1.5∶1. Forty-two of the tumours (79.8%) were located in the long tubular bones and short tubular bones of the hands and were closely related to the growth plate. Six cases (11.3%) were found in the flat bones, 4 cases (7.5%) in the tarsal bones and 1 case (1.9%) in the craniofacial bones. The characteristic radiological feature of 44 investigated lesions was a mostly eccentric radiolucency with a geographic pattern of bone destruction and matrix calcifications. Periosteal reaction was evident in 9% of the cases. Most tumours demonstrate the typical morphological features of chondroblastoma, but 3 cases resembled a giant cell tumour. In 2 cases a haemangio-pericytomalike growth pattern was observed. Nine of the tumours had an aneurysmal bone cyst-like component. Vascular invasion was seen in 1 case. Immunohistochemically most cells in 30 of the cases and fetal chondroblasts in 3 cases were strongly positive with vimentin and S-100 protein. Collagen type II was positive in the chondroid matrix of the tumours and in fetal cartilage tissue; collagen type VI was present focally around individual tumour cells and was always seen in the chondroid matrix of the lesions and in fetal cartilage. These findings support the cartilaginous nature of these tumours. In paraffin sections, 46.6% of the cases revealed a distinct positive reaction of some tumour cells with the monoclonal cytokeratin antibody KL1 (molecular weight 55–57 kDa). Only 4 of them demonstrated a coexpression with the other monoclonal cytokeratin anti-body CK (clone MNF 116, molecular weight 45–56.5 kDa). In paraffin sections all fetal chondroblasts were negative with both cytokeratin antibodies. Frozen sections of 3 tumours showed a strong positive reaction with both cytokeratin antibodies in many chondroblasts, indicating an “aberrant” cytokeratin expression. Osteoclast-like giant cells stained positive with leucocyte-common antigen (LCA) and with the macrophage-associated antibody KP1, but were negative with the other macrophage-associated antibody MAC 387. Recurrence rate was 10.7%. The clinical course of all tumours was benign.

Periosteal chondroma: MR characteristics.

Purpose The purpose of this study was to describe the MR characteristics of periosteal chondroma. Method MR images of 12 proven cases of periosteal chondroma were analyzed with reference to tumor morphology and size. MR features were correlated with radiographic and pathologic findings. Results Tumor size ranged from 1 to 7 cm in maximum diameter with a mean value of 2.6 cm. On MR images, a soft tissue mass at the bone surface with pressure erosion of adjacent cortical bone could be identified in all cases. All lesions were bordered by a hypointense rim (100%) and frequently showed a lobulated configuration (75%). Edema of medullary bone or soft tissues was not observed in any of the cases. Signal intensity of cartilaginous tumor tissue was typically hypo-or isointense relative to muscle on T1-weighted (100%) and hyperintense relative to fat on T2-weighted (92%) and T2*-weighted (100%) MR images. Radiographically significant calcifications of the tumor matrix, present in half of the cases, caused focal signal loss on MR images of all pulse sequences. Contrast enhancement was observed predominantly at the periphery of the lesions (100%), which on pathologic examinations typically contained fibrovascular bundles, surrounding the cartilage lobules. Conclusion Periosteal chondroma appears to have a relatively typical MR appearance, which reflects the histologic composition of the lesion. In addition to radiography, MRI therefore can substantially aid in the preoperative diagnosis of this rare bone lesion.

Monitoring radiation-induced changes in bone marrow histopathology with ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI.

The purpose of this study was to monitor radiation‐induced alterations of the blood‐bone marrow barrier (BMB) and the reticuloendothelial system (RES) with AMI‐227‐enhanced magnetic resonance imaging (MRI). Twenty New Zealand white rabbits (n = 10 following total body irradiation and n = 10 controls) underwent AMI‐227‐enhanced MRI. Pulse sequences included dynamic fast low‐angle shot (FLASH; TR/TE 50/4 msec, flip angle 60°) MRI and static T1‐ and T2‐weighted spin‐echo (SE) and turbo‐SE sequences of the lumbar spine and sacrum. Bone marrow enhancement was quantified as Δ signal intensity (SI) (%) = |[(SIpost ‐ SIpre)/SIpre] × 100%| and compared with histopathology, including iron stains and electron microscopy. Dynamic bone marrow ΔSI (%) data steadily increased up to 10–15 minutes after AMI‐227 administration, while blood ΔSI (%) data stayed nearly constant, histologically corresponding to iron oxide leakage into the bone marrow interstitium. This bone marrow contrast enhancement increased significantly following irradiation, corresponding to alterations of the endothelial lining of the bone marrow sinusoids. Late postcontrast images exhibited a significant positive T1 enhancement and negative T2 enhancement of the normal bone marrow, which further increased with irradiation due to increased RES activity. Irradiation‐induced changes in bone marrow physiology could be reliably assessed with AMI‐227‐enhanced MRI. J. Magn. Reson. Imaging 1999;9:643–652, 1999.

Metastasis of chondrosarcoma

This study was undertaken to analyse metastases of patients with intermediate- or high-grade chondrosarcomas. Out of 24 intermediate-grade tumours, 5 (21%) developed metastases, as did 6 of 10 high-grade tumours (60%) (P=0.04). Four patients developed pulmonary metastasis only, 5 developed both pulmonary metastases and metastases of the other sites. Two patients showed a rare metastatic pattern: bone metastases only. The metastasis rate in the primary chondrosarcoma (42%) was higher than that in the secondary chondrosarcomas (0%) (P=0.03). The metastasis rate was higher in patients with local recurrence (86%) than in those without local recurrence (19%) (P=0.01). In 5 of 6 patients who had a local relapse and metastasis, the interval between the two relapses was a few months.

Malignant fibrous histiocytoma of bone: conventional X-ray and MR imaging features

Abstract Objective. To evaluate the conventional X-ray and MR imaging features of malignant fibrous histiocytoma (MFH) of bone. Design. MRI examinations and conventional radiographs were reviewed in 39 patients with biopsy-proven MFH. Imaging characteristics were analyzed and the differential diagnoses assessed in a masked fashion by two experienced radiologists. Results. Typical X-ray features included aggressive, destructive tumor growth centrally located in the metaphysis of long bones. Periosteal reactions and expansive growth were rarely seen. On MR images extraosseous tumor spread was frequently noted. On T2-weighted images and contrast-enhanced T1-weighted images most of the tumors displayed an inhomogeneous, nodular signal pattern with peripheral Gd-DTPA enhancement. Conclusions. Although several MR imaging criteria were typical for MFH none of them was specific. X-ray diagnosis of MFH may also prove difficult, with the main differential diagnosis being metastasis in the older and osteosarcoma in the younger population.

Prognostic implication of immunodetection of P glycoprotein in Ewing's sarcoma

Increased expression of P glycoprotein is associated with multidrug resistance in many cell lines. P glycoprotein has been detected in different human tumors. To assess the implication of multidrug resistance in the prognosis of Ewings sarcoma the expression of P glycoprotein was studied immunohistochemically in pre- and post-therapeutic tumor tissues of 21 cases treated according to the CESS 81 or 86 protocol. The response to chemotherapy was evaluated histologically. Formalin-fixed, paraffin-embedded and fresh frozen sections were immunostained with a monoclonal antibody to P glycoprotein, clone JSB 1, using the double APAAP method. P glycoprotein was detected in 12 cases of 21 (57%) in either pre- or postchemotherapy tumor tissues. From the 21 cases 8 revealed a good morphological response to chemotherapy (33%); 10 of the 13 non-responders were positive for P glycoprotein (77%), but only 2 of the 8 responders (25%). The difference was statistically significant (P<0.05). Comparing P glycoprotein expression with the clinical outcome, we found that 7 of 12 positive cases had died (58%). From the negative cases only 3 of 9 had died (33%). However, judged by the the Kaplan Meyer life tables, these data were not significant. In conclusion our results suggest that the immunodetection of P glycoprotein indicates a poor response to chemotherapy and probably a bad clinical outcome for Ewings sarcoma patients.

Dedifferentiated chondrosarcoma in Albright syndrome. A case report and review of the literature.

Fibrous dysplasia is a developmental condition in which the skeleton fails to mature normally. Albright syndrome, which was first reported in 1937 by McCune and Bruch23 and by Albright1, is characterized by polyostotic fibrous dysplasia, endocrine disorders, and brown patches on the skin ( cafe-au-lait spots)3,17,25. It is seen more often in female than in male patients35. Malignant transformation in fibrous dysplasia was noted, in 1945, by Coley and Stewart5, and since then it has been reported in more than 100 patients12,19,33,43. The most common secondary malignant lesion in fibrous dysplasia is osteosarcoma, followed by fibrosarcoma and chondrosarcoma6,9,15,18,33,42. The prevalence of malignant transformation in fibrous dysplasia is only 0.4 per cent (six of 1517 patients)36. However, the prevalence of malignant transformation in Albright syndrome is 4 per cent (four of 100 patients36), which is higher than that in other forms of fibrous dysplasia36. To our knowledge, we are the first to report the case of a patient who had a dedifferentiated chondrosarcoma secondary to Albright syndrome. A fifty-two-year-old man who had had polyostotic fibrous dysplasia and many cafe-au-lait spots since he was an infant was seen at our hospital because of mild pain and increased swelling of the left knee. There was no family history of bone tumors, skin pigmentation, or precocious puberty. During childhood, he had sustained multiple fractures of the long bones of the lower limbs. When he was five years old, acne, growth of pubic hair, and an increase in the size of the penis and testes were observed. During adolescence and adulthood, more fractures of the lower limbs occurred. …