Malignant transformation of chondroblastoma.
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Biomedical subjects
Publications and source records attributed to G Delling.
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207 osteosarcomas were examined morphologically after neoadjuvant chemotherapy according to the COSS-86 protocol using representative slides of one whole tumor plane. The rate of responders 63%. In relapse-free patients both the whole tumors and the vital areas there of were smaller than in patients with relapse during a follow-up period of 5 years. Within the subgroup of osteoblastic osteosarcomas, metastases were observed following smaller tumors than in chondroblastic osteosarcomas. Therefore, in addition to degree of regression, histological subtype and tumor size should be considered in the prognostic evaluation of osteosarcomas.
DNA cytometric investigations of intraosseous cystic lesions and osteoblastic tumors may be helpful in morphological diagnosis. The detection of a DNA-aneuploid stemline supports the diagnosis of a high-grade malignant bone neoplasm, even in small biopsies. Solitary and aneurysmal bone cysts have DNA-diploid cell populations. Low-grade central osteosarcomas may show single-cell aneuploidies of varying extent as well as a DNA-diploid stemline. Their presence may be a sign of genetic instability within the population of neoplastic cells before a DNA-aneuploid stemline is established and should prompt careful postoperative observation.
To evaluate the natural history of bone mineral density after successful renal transplantation (TPL) modulated by therapeutic strategies in pediatric patients we have studied peripheral and partially proximal quantitative computed radius tomography (XCT) differentiating between trabecular (TBD), cortical (CBD) and total bone density (BD) cross-sectionally in a group of 24 subjects (mean age 17.1 +/- 7.0 y, mean Scr 1.66 +/- 0.89), 66.1 months (5-260) post transplant and compared the results with 12 controls. After TPL median TBD was elevated (182.5 vs. 155.5 mg/cm3) whereas the opposite was true for CBD (361.8 vs. 437.8 mg/cm3). The physiologic age dependency of BD had got lost after TPL but could be reassumed by the measurement of proximal CBD. TBD correlated with the cumulative calcitriol dosage (r = 0.60, p < 0.05), bone alkaline phosphatase (r = 0.55, p < 0.01), the Ca x P product (r = 0.43, p < 0.05) and inversely with the time after TPL (r = -0.45, p < 0.05), but no significant correlation could be detected with the cumulative steroid dose. It was found to be higher in calcitriol treated than in vitamin D3 treated patients. Proximal CBD was inversely correlated with bone alkaline phosphatase (r = -0.71, p < 0.01) and intact PTH (r = -0.59, p < 0.05). In conclusion CBD in kidney grafted pediatric patients seems to be more or less reduced by secondary hyperparathyroidism whereas the increase of TBD appears to be induced by anticipated calcitriol treatment under dialysis regimen and gradually normalizes after TPL.
Microcallus formations are demonstrable in nearly all spongy bone by means of suitable preparation techniques. Histologically, these structures are immature fibrous bone. Their genesis, frequency, and importance are largely unknown. To address these issues, 26 normal human spines, 11 osteoporotic spines, and different parts of the skeleton (femur head, iliac crest) were investigated for microcallus using a new preparation technique--allowing a combined 2- and 3-dimensional analysis. According to our analysis, microcallus formation occurs frequently in persons older than 45 years of age. These formations are mainly localized in the lower thoracic and lumbar spine and are obviously more frequent in females than in males. In individuals with a trabecular bone volume (BV/TV) in the spine below 11%, microcallus formations occur regularly. But the number of microcallus formations depends more on the microarchitecture of the cancellous bone (trabecular bone pattern factor, TBPf), than on individual trabecular parameters (trabecular number, TbN; trabecular bone volume, BV/TV; and trabecular thickness, TbTh). In about 33% of cases microfractures are demonstrable in the center of the microcallus formation. It is unclear whether microcallus may be the result of a nontraumatic process. In therapy studies the bone mass could be misrepresented due to the amount of microcallus. Although it indicates instability of the bone structure, microcallus formation is not only a negative mechanism, but stabilizes and regenerates the bone tissue. Furthermore, complete new trabeculae can be formed due to bridges of microcallus between the remnant trabeculae. Osteoporosis is not the result of an inability to form microcallus formations.
The case histories of all patients with osteosarcoma of the trunk entered into the consecutive studies COSS 80 through COSS 86 of the Cooperative German/Austrian Osteosarcoma Study Group (COSS) were analyzed in order to evaluate their clinical characteristics and the impact of modern neoadjuvant therapy on prognosis. They were compared to those of all patients with extremity osteosarcoma treated according to the same protocols. While tumors of the trunk comprised only 32 (4.8%) of 665 primary classical osteosarcomas, secondary osteosarcomas were much more likely to be located in bones of the axial skeleton (6 of 18, 33%). Patients with primary osteosarcoma of the axial skeleton were older (mean: 20.8 vs. 15.2 years, P < 0.01) and were more likely to present with metastases at diagnosis (34% vs 12%, P < 0.001) than those with primary extremity osteosarcoma. In contrast to extremity tumors, local surgical treatment failure was very common in osteosarcomas of the trunk. Complete tumor removal was achieved in less than half of all evaluable cases. The prognosis of eight patients with localized primary axial osteosarcoma and effective surgical local control was not inferior to that of 483 equally evaluable patients with extremity tumors. In conclusion, while secondary systemic spread of axial osteosarcoma may be avoided in patients treated with multiagent chemotherapy, successful treatment is often barred by primary metastatic disease and inability to control the local tumor site.
Fourteen solitary bone cysts (SBC) with large areas of calcification (7 in the femur, 4 in the humerus, and 1 each in the pelvis, the tibia and the scapula) and 402 SBC from the Hamburg Bone Tumour Registry were reviewed in a retrospective study. The analysis was done with emphasis on the clinical, radiological and histological appearances. SBC are well known lesions, but calcifying SBC (CSBC) or extensive extragnathic cement-like bone productions are rare. The clinical and radiological differential diagnosis includes fibrous dysplasia, chondroma, low-grade chondrosarcoma and osteosarcoma. Bits of this cement-like matrix are detectable within the wall of approximately 70% (278 of 402) of SBC from the registry. CSBC are changed SBC. The intraoperative confirmation of the diagnosis on a frozen section by the bone pathologist leads to curettage which is currently the most common therapy in this benign lesion.
To evaluate the effects of increased parathyroid hormone (PTH)-secretion on trabecular bone structure in patients with primary hyperparathyroidism (PHPT) we have analysed iliac crest biopsies from 84 patients (38 male, 46 female, age 20-85 years) with surgically proven PHPT by using quantitative histomorphometry. As there might be an influence of age or sex, subjects were divided into 4 subgroups according to age (younger than 50 years, older than 50 years) and sex. Eighty four age and sex matched autopsy cases of accidental death served as controls. When compared with age matched controls, trabecular bone volume (BV/TV) and trabecular diameter in PHPT were increased. Trabecular density in PHPT was elevated significantly in the older age-groups. These results suggest a preservation of intertrabecular connectivity, which we were able to confirm by measurement of the number of intertrabecular nodes and trabecular bone pattern factor (TBPf). No differences were demonstrated between male and female subjects. Furthermore, no variations according to the histological type (with or without endosteal fibrosis) could be demonstrated in our material. We conclude that increased trabecular bone volume in PHPT is the result not only of thicker trabecula but also of a reduction of the age-dependent loss of complete trabecular plates due to perforations. Thus PHPT leads to a substantial preservation of intertrabecular connectivity.
The composition of collagen was analyzed and the degree of lysyl hydroxylation of individual collagen chains was determined in four osteosarcomas and two osteofibrous dysplasias. In addition, the tumor proliferation (number of mitoses, proliferating-nuclear-antigen-positive cells, MIB) as well as the response to chemotherapy (morphological regression grade) were checked. All tumors contained a high proportion of collagen III and, in all but one osteosarcoma, pepsin-extracted collagens I and III were overmodified. Furthermore, the proportion of diglycosides in collagen I was about four times higher than in controls. The collagen composition and modification resembled those of bones at early stages of human development. One osteosarcoma and both osteofibrous dysplasias were in the normal range of lysyl hydroxylation. There was no correlation between the collagen properties and the histopathological marker of tumor proliferation.
The combined histological and microcomputed analysis of human iliac crest biopsies leads to major advances in our understanding of three-dimensional bone architecture. Microcomputed tomography avoids the time-consuming reconstruction and artifacts of serial sections. Furthermore, its high resolution allows the recording of structural differences as low as 10 microns. Thus, three-dimensional analysis in combination with histological evaluation of cellular dynamics facilitates earlier and easier recording of changes of cancellous bone.
The vertebral bodies of the complete spine (C-3-L-5) were removed in 26 autopsy cases without evidence for primary or secondary bone disease (13 males aged 19-79 years and 13 females aged 17-90 years). A sagittal segment through the center of all vertebral bodies was embedded undecalcified in hydroxyethylmethacrylate and processed to so-called surface stained block grindings. Histomorphometric analysis of the complete segment was performed using a computer-assisted image analysis system (IBAS 2000). The structural parameters investigated were bone volume (BV/TV) and trabecular interconnection quantificated by trabecular bone pattern factor (TBPf). A close correlation of BV/TV and TBPf was found in all vertebral bodies irrespective of vertebral region (r = 0.8, p < 0.001). This indicates that the age-related decrease of trabecular bone mass is primarily the consequence of the transformation from plates to rods and the loss of whole trabecular structures. This basic principle is valid throughout the complete spine. However, the systematic analysis of vertebral trabecular bone from C-3 to L-5 revealed a significant intervertebral variation of trabecular microarchitecture. The density of trabecular structure of cervical vertebrae is much higher than that of thoracic and lumbar vertebrae (p < 0.001). The extent of age-related loss of trabecular bone mass and structure showed a decrease within the spine from the caudal to the cranial region (p < 0.05). The loss of bone volume in individuals between the ages of 30 and 80 years in the lumbar spine was 53%, whereas in the thoracic spine the decrease was 41%, and in the cervical spine only 24%.(ABSTRACT TRUNCATED AT 250 WORDS)
Fractures of the odontoid process are potentially serious injuries; Type II and III fractures, as described by Anderson and D'Alonzo, are seen in the emergency room especially in young adolescents and individuals over 60 years of age. The etiology of these fractures is still controversial. Malunion and nonunion in both types of fractures are presumed to be due to insufficient external or internal fixation, but this theory has not been fully explained. To examine these issues, the authors expanded their prior studies of the anatomy of the axis. For histomorphometric analysis of cancellous and cortical bone, the axis was removed in 37 autopsies (26 normal and 11 osteoporotic cases) and sectioned in the sagittal plane to a thickness of 1 mm using a surface-stained block-grinding technique. The base of the dens is the region of least resistance for fractures because of its reduced trabecular bone volume, a poorer trabecular interconnection, and a cortical thickness one-third that of the axis. In all cases, trabeculae were disconnected from the trabecular lattice, and in 30%, microcallus formations were demonstrated in the base of the dens. A special filigree type of trabeculae in the base of the dens is often seen in patients with osteoporosis; microarchitectural differences of cancellous bone between the base of the dens and the other regions of the axis are also markedly increased. The authors infer from the data that the bone structure of the axis is responsible for the location, distribution, and frequency of fractures of the odontoid process in normal healthy bone and this frequency is greatly increased in individuals with osteoporosis. The deficiency of bone mass within the base also suggests a new explanation for the occurrence of nonunions, even after treatment of fractures of the base of the dens.
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Histoplasma infections in Europe are rare, and acute disseminated histoplasmosis has only been observed in immunocompromised persons. We describe a case of acute disseminated histoplasmosis in a young, nonimmunocompromised European woman. The probable source of infection was Sri Lanka or the Maldives. At presentation she was severely ill with fever, lymphadenopathy, anemia, thrombocytopenia, hepatosplenomegaly, and polyserositis. Histologically, myelofibrosis and osteosclerosis were observed with extramedullary hematopoiesis. Histoplasma capsulatum yeasts were detected in bone marrow trephine biopsy by methenamine silver staining. Treatment with conventional and liposomal amphotericin B and subsequent itraconazole led to rapid and complete recovery.
The peculiarities within the microarchitecture of the base of the dens have to be assumed as one of the underlying causes for type II and III fractures of the dens according to Anderson and D'Alonzo. As can be demonstrated in a section of the dens of a patient after primary osteosynthesis using two small fragment AO cancellous screws this leads to multiple local trabecular fractures and destruction of the cancellous microarchitecture. Further more compression by the screws results in a higher density of the bone mass in the region of fracture. Apart from the fact that two AO screws guarantee rotational stability, this type of osteosynthesis seems to favour intracorporal bony fusion by increased trabecular bone volume and induction of microcallus within the base of the dens. In a patient with a small intracortical transverse diameter of the dens the available space is completely filled by the screws threads. Partial penetration of the threads through the cortical bone seems to be of no clinical and biomechanical relevance and can be avoided using screws of smaller diameter.
Characteristic skeletal changes occur in patients with chronic renal insufficiency. The aim of this study was comprehensively to record bone volume changes in the spine, from C2 to L5, after a long history of hemodialysis. The spinal columns of nine autopsy cases who had undergone 4 to 15 years of dialysis were thoroughly examined. The age-related control group consisted of 26 autopsy cases with intact skeletons. A iliac crest biopsy facilitated a direct comparison of the diagnostic biopsy location and the spinal column. A newly developed preparation technique enables a combined two- and three-dimensional analysis to be made, so that in addition to the histologic image, the directly underlying three-dimensional structure can be analyzed. The spine deformity index (SDI), the bone volume (BV/TV), and the trabecular interconnection (TBPf) was quantitatively evaluated. The SDI shows vertebral fractures in renal osteodystrophy (ROD) types I and II in spite of a trabecular bone volume within normal limits. The trabecular bone volume shows a distribution throughout the spinal column familiar from the skeletally intact control group. The plateau-like curve line, decreasing from the cervical spine to the lumbar spine is, however, 5% lower in ROD. BV/TV values of 51.2% and 74.1% in the 2nd lumbar vertebra are clearly lower than in the corresponding iliac crest biopsy. Cases with a longer history of hemodialysis show higher BV/TV values irrespective of age and sex. Normal BV/TV does not mean physiological linking. Three-dimensional analysis in ROD shows, in comparison to the controls, a much stronger restructuring of the architecture than can be assumed from the two-dimensional histological sections.(ABSTRACT TRUNCATED AT 250 WORDS)
Microcallus formations are demonstrable in nearly all cancellous bones by means of suitable preparation techniques. Histologically, these structures are immature fibrous bone formed in local overloaded parts of the trabeculae. Using a preparation technique that allows combined two- and three-dimensional analysis, 26 normal human spines and 11 osteoporotic spines were investigated for microcallus. Microcallus formations occur frequently in people over 45 years of age. They are mainly localized in the lower thoracic and lumbar spine and occur significantly more frequent in females than in males. The number of microcallus formations depends more on the microarchitecture of the cancellous bone than on individual trabecular parameters. In about 33% of cases microfractures are demonstrable in the centre of the microcallus formation. In non-invasive studies the bone mass could be misinterpreted due to microcallus. Although it indicates instability of the bone structure, microcallus formation is not a purely negative mechanism. It stabilizes and regenerates the bone tissue. Furthermore, complete new trabeculae can be formed due to bridges of microcallus between residual trabeculae. Osteoporosis is not the result of an inability to form microcallus.