[Osteogenic tumors of bone]. / Osteogene Tumoren.

BACKGROUND: Osteogenic tumors include malignant and benign tumors that produce tumor osteoid and/or bone tissue. Osteosarcoma is the most common malignant bone tumor, especially in children and young adults. OBJECTIVES: The entities with their characteristic morphological features are described to enable the reader to come to a diagnosis and differential diagnosis on the basis of patient age, history and predominant location of the tumor. METHODS: For this review we selectively used mainly large published patient cohorts. Our own and externally published data on widely accepted tumor criteria were also compared. RESULTS: Detection is the initial diagnostic step for an osseous lesion, and is determined by the sensitivity of the method applied. Plain X­ray films in two planes and CT are the basics in the radiological toolkit for osteogenic tumors. For evaluation of local tumor extension and biopsy planning MRI or scintigraphy should be combined. MRI as a stand-alone diagnostic tool is insufficient. For malignant bone tumors staging should be performed, applying a variable combination of thoracic CT, MRI, scintigraphy, and positron emission tomography (PET). Osteosarcoma, along with Ewing sarcoma and chondrosarcoma, are the most common malignant bone tumors; all sub-entities are significantly rarer. Among benign bone tumors, osteoid osteomas have the highest incidence, presenting with typical pain, location, and age predilection. CONCLUSIONS: Diagnostics and treatment of malignant bone tumors should preferably be performed in specialized centers because of significant therapeutic implications for patients. In uncertain cases, a second opinion should always be obtained.

Prognostic relevance of the mitotic count and the amount of viable tumour after neoadjuvant chemotherapy for primary, localised, high-grade soft tissue sarcoma.

BACKGROUND: We sought to examine whether mitotic count (MC) and the amount of viable tumour (VT) following neoadjuvant systemic chemotherapy (SC) for primary, localised, high-grade soft tissue sarcoma (STS) correlate with prognosis. METHODS: Retrospective analysis of 57 patients who underwent SC involving a combination of an anthracycline and an alkylating agent, followed by surgical resection between 2001 and 2011. RESULTS: The amount of VT after chemotherapy was significantly associated with disease-specific survival (DSS) and event-free survival (EFS). Patients with <10% VT had a DSS of 94% at 5 years, compared with 61% for patients with ⩾10% VT (P=0.033); EFS was 75%, compared with 48% (P=0.030). Patients with an MC of ⩾20/10 high power fields (HPF) after chemotherapy had a significantly lower DSS (33% vs 84% at 5 years, P<0.001) and EFS (40% vs 63% at 5 years, P=0.019) than patients with an MC of <20/10 HPF. CONCLUSIONS: The MC and the amount of VT after neoadjuvant therapy for primary, localised, high-grade STS appear to correlate with prognosis. If these results are validated prospectively, then they could provide a rational for the design of neoadjuvant treatment modification/escalation studies, analogue to the EURAMOS-1 trial for bone sarcomas.

Teriparatide in bisphosphonate-resistant osteoporosis: microarchitectural changes and clinical results after 6 and 18 months.

A number of osteoporotic patients under bisphosphonate treatment present persistent fragility fractures and bone loss despite good compliance. The objective of this 18-month prospective study was to investigate the effect of teriparatide [rhPTH(1-34)] in 25 female osteoporotics who were inadequate responders to oral bisphosphonates and to correlate microarchitectural changes in three consecutive iliac crest biopsies measured by micro-computed tomography (µCT) with bone mineral density (BMD) and bone serum markers. Scanned biopsies at baseline (M0), 6 months (M6), and 18 months (M18) demonstrated early significant (P < 0.01) increases in bone volume per tissue volume (+34%) and trabecular number (+14%) at M6 with only moderate changes in most µCT structural parameters between M6 and M18. µCT-measured bone tissue density was significantly decreased at M18, expressing an overall lower degree of tissue mineralization characteristic for new bone formation despite unchanged trabecular thickness due to increased intratrabecular tunneling at M18. µCT results were consistent with serum bone turnover markers, reaching maximal levels of bone alkaline phosphatase and serum ß-crosslaps at M6, with subsequent decline until M18. BMD assessed by DXA demonstrated persistent increases at the lumbar spine until M12, whereas no significant change was observed at the hip. Type (alendronate/risedronate) and duration (3.5 ± 4 years) of prior bisphosphonate treatment did not influence outcome on µCT, BMD, or bone marker results. The overall results indicate a positive ceiling effect of teriparatide on bone microarchitecture and bone markers after 6 and 12 months for lumbar spine BMD, with no additional gain until M18 in bisphosphonate nonresponders.

Effects of strontium ranelate administration on bisphosphonate-altered hydroxyapatite: Matrix incorporation of strontium is accompanied by changes in mineralization and microstructure.

Strontium ranelate (SR) is one therapeutic option for reducing risk of fracture in osteoporosis. The effects of SR treatment on hydroxyapatite (HA) previously altered by bisphosphonate (BP) administration remain to be established. Patients who have received long-term BP treatment and present with persistent high fracture risk are of particular interest. Paired iliac crest biopsies from 15 patients post-BP therapy were subjected to a baseline biopsy and a follow-up biopsy after treatment with 2g SR day⁻¹ after either 6 months (n=5) or 12 months (n=10). Dual energy X-ray absorptiometry scans, serum parameters and biochemical markers were obtained. Quantitative backscattered electron imaging and energy-dispersive X-ray analyses combined with micro-X-ray fluorescence determinations were performed to observe any mineralization changes. Static 2-D histomorphometry was carried out to evaluate cellular and structural indices. After 6 months of SR treatment, increases in osteoid surface and strontium content were observed, but no other indices showed significant change. After 12 months of SR treatment, there was a significant increase in bone volume and trabecular thickness, and further increases in strontium content and backscattered signal intensity. These structural changes were accompanied by increased numbers of osteoblasts and increased osteoid surface and volume. Additionally, low bone resorption, as measured by beta-cross-laps, and a low number of osteoclasts were observed. SR treatment led to increased strontium content within the BP-HA nanocomposites and to increased osteoid indices and bone volume, which is indicative of newly formed bone, while osteoclasts were still suppressed. These data points suggest that SR might be considered as a therapeutic option for patients following long-term BP treatment.

Protracted disseminated skeletal metastases from angiosarcoma of the spleen.

Angiosarcomas are high-grade vascular tumors associated with poor prognosis due to their aggressive nature. Occasional skeletal manifestations present commonly as osteolytic destruction. The 55-years-old patient presented in this case report had a disease-free 4 years interval between splenectomy after primary angiosarcoma of the spleen and an unusual skeletal metastatic pattern mimicking benign angiomatosis. Despite lacking radiographic evidence for a highly aggressive osseous process, the histopathological resemblance of the bone biopsy with the primary tumor manifestation and the fulminant course of disease after onset of disseminated osseous spread confirmed the malignant character of the vascular tumor. The case demonstrates the highly variable radiographic pattern and particular pathobiological behavior of vascular malignancies.

Allocation of nonbirefringent wear debris: darkfield illumination associated with PIXE microanalysis reveals cobalt deposition in mineralized bone matrix adjacent to CoCr implants.

Abrasive joint replacement material that accumulates in the tissue induces reciprocal effects between prosthesis material and organism. Since the limitations of brightfield and polarized light microscopy for foreign body analysis are well known, a method was applied that ensures the detailed histological assessment of nonbirefringent particles in periprosthetic soft and hard tissue. Cemented and cementless interface regions of five selected autopsy hip implant cases (2 x Endo-Modell Mark III, LINK, 1 x St. Georg Mark II, LINK, Germany; 2 x Spongiosa Metal II, ESKA, Germany) were viewed under darkfield illumination and subsequently analyzed with proton-induced X-ray emission (PIXE). Eight autopsy cases without implants served as controls. Using darkfield illumination technique, metallic particles became visible as luminous points under the microscope. The majority of particles in the samples from the cemented cases were degradation products of radiopaque bone cement. There was minimal evidence of metallic alloy particles in the soft tissues. However, a considerable quantity of heavy metal cobalt (Co) was found in the periprosthetic mineralized bone tissue, which was not observed in the controls. The periprosthetic concentration of cobalt ranged from 38 to 413 ppm. The findings demonstrate a correlation between cobalt concentration, time since implantation, and distance from the implant. Darkfield microscopy associated with PIXE enables a detailed histological assessment of metal particles in the tissue. In an effort to optimize biomechanics, implant design and implantation techniques, the contamination of soft and hard tissue with heavy metal degradation products deserves similar attention in terms of alloy assortment.

Assessment of trabecular bone structure comparing magnetic resonance imaging at 3 Tesla with high-resolution peripheral quantitative computed tomography ex vivo and in vivo.

UNLABELLED: In vivo high-resolution peripheral quantitative micro-CT (HR-pQCT) is a new modality for imaging peripheral sites like the distal tibia and the distal radius, providing structural bone parameters. Comparing HR-pQCT with MRI, we found that both modalities are capable of offering meaningful information on trabecular structure. BACKGROUND: Magnetic resonance imaging (MRI) has emerged as the leading in vivo method for measuring trabecular bone micro-architecture and providing structural information. Recently, an in vivo HR-pQCT modality was introduced for imaging peripheral sites like the distal tibia and the distal radius, providing structural bone parameters. The goal of this work was to compare and evaluate the performances and in vivo capabilities of HR-pQCT in comparison with MRI at 3 Tesla. METHODS: To this end images of 8 human specimens (5 tibiae and 3 radii) and 11 participants (6 tibia and 5 radii) were acquired with both modalities. Additionally, the radius specimens were scanned with micro-CT (muCT), which was used as a standard of reference. Structural parameters calculated from MRI were compared with results from HR-pQCT images and additionally muCT for the radii specimens. RESULTS: High correlations (r > 0.7) were found for trabecular number and trabecular spacing between the two modalities in vivo and ex vivo. 2D and 3D analysis revealed high correlations (r > 0.8) in structural bone parameters for all measurements. Using micro-CT as standard of reference both results from QCT and MRI correlated well. CONCLUSION: Both imaging modalities were found to perform equally well regarding trabecular bone measurements.

[Fluorosis--a forgotten entity. Case report of a woman with coxarthrosis and newly diagnosed fluorosis]. / Fluoridosteopathie--eine vergessene Entität. Gleichzeitiges Auftreten von Coxarthrose und bis dahin unbekannter Fluoridosteopathie bei einer 73-jährigen Patientin.

The clinical manifestation of fluorosis has become rare over the past years. Although the use of fluoride medication in osteoporosis therapy remains controversial, past study results have led to a reduction in fluoride prescriptions. Several studies have shown minor biomechanical properties of newly built woven bone compared to original bone. Despite new prescription protocols, fluoride therapy should not be disregarded in the anamnesis of osteoporosis patients. In addition to conventional diagnostics in fluorosis, new techniques such as microanalysis and micro-CT-analysis show a diagnostic benefit. In this case, the edx-microanalysis results show an F concentration of over 1.0 wt% in bone. The ratio of bone to tissue volume, evaluated by micro-CT, is clearly elevated at 46% BV/TV. The histopathological preparation of the femoral head has made the possible effects of fluoride medication on bone visible and quantifiable. A direct causal relationship between coxarthrosis and fluoride medication, found both in our patient as well as in the literature, has not been demonstrated. In order to better understand the broad effects of fluoride medication in combination with coxarthrosis more studies are needed.

[Cartilage tumors. Classification, conditions for biopsy and histologic characteristics]. / Knorpelbildende Tumoren Klassifikation, Voraussetzungen für die Biopsie und histologische Charakteristika.

Primary cartilage-forming tumors of the bone are a large group among the rare bone tumors. The clinical and radiographic findings of the different entities show similar findings. Bone biopsy is still the most relevant examination in the final diagnosis of the lesion. The requirements for a correct biopsy and the main features of the macroscopic and histologic findings of cartilage tumors are presented from the viewpoint of the pathologist. Differentiation between benign enchondroma and grade I chondrosarcoma requires close interdisciplinary cooperation to avoid over-treatment and relapse. Rare low-grade malignant cartilage tumors such as clear-cell chondrosarcoma need to be diagnosed in specialized centres to arrive at the correct therapy. The morphologic features of mesenchymal chondrosarcoma, clear-cell chondrosarcoma and secondary chondrosarcoma in osteochondroma are demonstrated. The aim is to correlate the morphologic and radiographic features. The same applies to benign entities such as osteochondroma, chondroblastoma and chondromyxoid fibroma.