Herbert Rosenthal

Oncogenic osteomalacia: exact tumor localization by co-registration of positron emission and computed tomography.

In oncogenic osteomalacia, the causative tumor is almost always difficult to find. A novel diagnostic approach is presented that facilitates a precise and rapid localization of the associated lesion by PET‐CT co‐registration using the radiotracer 68Ga‐DOTANOC.

Efficacy of antibiotic therapy for SAPHO syndrome is lost after its discontinuation: an interventional study

IntroductionThe acronym SAPHO was introduced in 1987 to unify the various descriptions of a seronegative arthritis associated with skin manifestations and to show synovitis, acne, pustulosis, hyperostosis, and osteitis with and without sterile multifocal osteomyelitis. The etiology of SAPHO syndrome is unknown, but an association with infection by semipathogenic bacteria like Propionibacterium acnes has been suggested. We conducted an interventional study of SAPHO patients receiving antibiotics.MethodsThirty-seven patients met the clinical criteria of SAPHO syndrome, 21 of them underwent a needle biopsy of the osteitis lesion, and 14 of them showed positive bacteriological cultures for P. acnes. Thirty patients (14 bacteriological positive and 16 without biopsy) were treated with antibiotics for 16 weeks. The activity of skin disease and osteitis were assessed by a physician using a scoring model (from 0 to 6). In addition, patients completed a Health Assessment Score (HAS, from 0 to 6). The erythrocyte sedimentation rate was determined and a MRI (of the osteitis lesion, radiologic activity score from 0 to 2) was performed in week 1 (W1), week 16 (W16), and week 28 (W28, 12 weeks after antibiotics).ResultsTwenty-seven patients continued the medication (azithromycin, n = 25, 500 mg twice a week; clindamycin, n = 1, 300 mg daily; or doxycycline, n = 1, 100 mg daily) for 16 weeks. After W16 the scores for MRI (1.5 to 1.1, P = 0.01), skin activity (3.2 to 1.2, P = 0.01), osteitis activity (4.0 to 2.1, P = 0.02), and HAS (3.3 to 2.1, P = 0.01) decreased significantly. However, this was followed by increasing values for MRI scores (1.2 to 1.4, P = 0.08), skin activity (1.2 to 1.7, P = 0.11), osteitis activity (1.9 to 2.7, P = 0.01), and HAS (2.2 to 3.3, P = 0.02) from W16 to W28. The comparison of the scores in W1 and W28 in these 12 patients showed no significant differences.ConclusionsFor the period of application, the antibiotic therapy seems to have controlled the disease. After antibiotic discontinuation, however, disease relapse was observed. SAPHO syndrome thus groups with other chronic inflammatory arthropathies with a need for permanent therapy.

Diagnostic management of patients with SAPHO syndrome: use of MR imaging to guide bone biopsy at CT for microbiological and histological work-up

Propionibacterium acnes (P. acnes) is suspected to be involved in the pathophysiology of SAPHO syndrome, since it has been isolated repeatedly through open surgical bone biopsy. This study demonstrates the role of MRI in identifying inflamed bone areas in patients with SAPHO syndrome and the role of CT-guided bone biopsies in obtaining samples from these areas for microbiological and histopathological investigations, thus obviating open surgery. Fourteen consecutive patients with SAPHO syndrome were investigated by MRI to identify acute inflammatory changes in hyperostotic periarticular bone. The CT-guided biopsies for microbiological investigations were taken from the areas identified. Patients positive for P. acnes were started on long-term antibiotic therapy according to antibiotic susceptibility. On MRI the inflammatory changes appeared as hyperintense areas on fat-saturated T2 fast-spin-echo (FSE) images and showed signal increase on fat-saturated T1 SE images after Gd-DTPA. With MR localization CT-guided bone biopsies yielded P. acnes in 8 patients. No bacteria could be isolated from the remaining 6 patients. Acute inflammatory bone changes in SAPHO syndrome are well localized by MRI. With MR localization, CT-guided bone biopsies offer a minimally invasive alternative to open surgery in the detection of. P. acnes leading to the institution of a specific antibiotic therapy.

Improvement of Erdheim–Chester disease in two patients by sequential treatment with vinblastine and mycophenolate mofetil

Erdheim–Chester disease (ECD) is a rare non-Langerhans’ form of histiocytosis with a plethora of different clinical manifestations owing to multiple organ involvement. We report two patients who presented initially with different clinical symptoms. The presenting complaint of the first patient was bone pain, predominantly in the legs, whereas in the other patient the initial symptoms were related to obstruction of both ureters, as in idiopathic retroperitoneal fibrosis. Ultimately, ECD was diagnosed in both patients by the occurrence of both pathognomonic manifestations, the histologic presence of non-Langerhans’ histiocytes in bone biopsies, and osteosclerotic lesions of the long bones. Because the extraosseous manifestations progressed and a single application of corticosteroids was ineffective, sequential treatment with vinblastine and mycophenolate mofetil, together with prednisolone, was started. At follow-up respectively 15 and 16 months after the start of treatment a beneficial effect was noted in both patients. These cases illustrate the clinical spectrum of ECD, detail the pathognomonic manifestations of this rare disease, emphasize the need to consider ECD as an uncommon but important differential diagnosis in patients with arthralgias or systemic fibrosis, and give the first evidence for a new treatment option.

68 Ga-DOTANOC PET/CT for the detection of a mesenchymal tumor causing oncogenic osteomalacia

A 54-year-old female patient had presented with clinical features of hyperphosphaturia, hypophosphatemia and osteomalacia. These findings were suggestive of oncogenic osteomalacia, a rare paraneoplastic disorder that is usually associated with a phosphaturic mesenchymal tumor [1]. Conventional morphologic imaging including whole-body computed tomography (CT) failed to localise the primary tumor. The patient underwent additional positron emission tomography (PET)/CT using Ga-DOTANOC, a highly sensitive and specific tracer for imaging of somatostatin receptor overexpression, which has recently proven potential in oncogenic osteomalacia [2, 3]. Abnormal focal tracer uptake was seen in the right distal femur (A). Using image fusion and three-dimensional volume-rendering techniques, the localisation of the suspected primary tumor was clearly visualised (B). Notably, no morphologic correlative was observed in the corresponding low-dose CT (C). Based on the PET/CT findings, the patient underwent segmental resection and compound osteosynthesis of the distal femur. The hematoxylin and eosin-stained section (D) demonstrated randomly organised spindle cells with slight cellular and nuclear atypia and a sparse intercellular matrix. Immunohistochemistry was negative for myogenic, neural, vascular and epithelial markers. These histopathologic findings were consistent with the diagnosis of a benign phosphaturic, mesenchymal tumor.

Initiation and perpetuation of rat adjuvant arthritis is inhibited by the anti-CD2 monoclonal antibody (mAb) OX34

OBJECTIVE The purpose of this study was to investigate the therapeutic potential of the anti-CD2 mAb OX34 first with regard to bone protection in established rat adjuvant arthritis (AA) and secondly with regard to prevention of AA induction. METHODS Established AA was treated with dexamethasone (1 mg/kg body weight) for two days plus OX34 mAb or control mAb over three days (2 mg and then 1 mg) starting at different time points of the disease. For prevention studies animals were injected as above with mAb before induction of AA. Arthritis score (AS), hindpaw thickness, and body weight were blindly measured three times per week. Flow cytometry and hindpaw radiography were performed at the end of the study (day 29). RESULTS Treatment of early AA with OX34 mAb combined with dexamethasone but not dexamethasone plus control mAb dramatically suppressed established AA as assessed by AS and hind paw thickness (>65% and >80% reduction, respectively; p < 0.05). Most importantly, early treatment in the course of AA almost completely prevented bone destruction in established AA. When given before AA induction OX34 alone prevented the initiation of arthritis compared with controls (AS reduction 83-95%, p < 0.05). In addition, OX34 plus dexamethasone treatment resulted in depletion of CD4+ T cells but not CD8+ T cells. IL2R+ and CD45RC-(‘memory’) T cells were significantly reduced. CONCLUSIONS Anti-CD2 mAb treatment prevents AA induction confirming the role of CD4+ T cells in the induction phase of AA. In addition, early OX34 plus dexamethasone treatment resulted in pronounced clinical improvement and joint protection. OX34 treatment therefore inhibits the initiation and the perpetuation of rat AA.

Coccydynia due to a benign notochordal cell tumor.

Study Design. Case report. Objective. To present a rare case of a notochordal cell tumor. Summary of Background Data. We report on a 27-year-old female patient with pain at the lower back and muscle cramps in the area of the right hip. Image studies demonstrated a cystic lesion of the coccyx. Methods. As clinical symptoms became chronic and were resistant to conservative treatment, a resection of the coccyx was performed. Results. Histology revealed an intraosseous benign notochordal cell tumor. This tumor represents a recently described notochordal cell proliferation biologically distinct from chordomas. Conclusions. Overdiagnosis of these notochordal cell proliferations as chordomas may occur if clinicians and pathologists are unfamiliar with the spectrum of notochordal proliferations.

Radiofrequency Ablation of a Rare Case of an Intraosseous Hibernoma Causing Therapy-refractory Pain

and the smaller-diameter stents would have been more likely to cause obstruction and would have been more difficult to exchange in the future (1). A three-staged combined procedure (2) involving placement of an antegrade nephrostomy catheter/nephroureterostomy catheter, conversion to a retrograde nephroureteral catheter, and, finally, transileal exchange of the retrograde nephroureteral stent and removal of the antegrade nephrostomy tube was also not considered appropriate despite a success rate greater than 90% because, again, this would involve positioning the patient prone to initially insert the antegrade nephrostomy. In most cases of ileal conduit obstruction and urosepsis, we would advocate percutaneous nephrostomy to decompress the system and antibiotic treatment with retrograde exchange of ureteroileal stents via the ileal conduit at a later date. However, in the present case, positioning the patient prone to perform nephrostomy insertion was considered more difficult as a result of recent laparotomy and large parastomal hernia. A retrograde transileal approach reduced the risk associated with the performance of percutaneous nephrostomy and

Whole-body diffusion-weighted MRI in a case of Rosai–Dorfman disease with exclusive multifocal skeletal involvement

Rosai–Dorfman disease (RDD) is a rare disorder and usually presents with painless bilateral cervical lymphadenopathy. About 43% of RDD patients show extranodal involvement, including bones (8%). As RDD is a systemic disease, which can involve lymph nodes, bones, skin, kidneys, respiratory tract, parotid gland, orbital cavity and the central nervous system, whole-body imaging may be useful for the assessment of extent, distribution and follow-up of disease. Whole-body diffusion-weighted MRI is able to demonstrate lesions and to assess therapy response without the need for radiation or intravenous contrast agent. Here, we report a case of a 15-year-old boy with primary skeletal RDD without lymphadenopathy, who was staged and followed by whole-body diffusion-weighted MRI.

Avid uptake of [18F]-FDG in fibrous dysplasia can mimic skeletal involvement in Hodgkin’s disease

Fibrous dysplasia is a common benign skeletal disorder that is assumed to result from a development failure during the bone maturization process. It can be either mono- or polyostotic. Most patients present before the age of 30 years [1]. To date, only a few descriptions of the appearance of fibrous dysplasia on [ 18 F]-fluorodeoxyglucose–positron emission tomography (FDG PET) images have been reported in the literature [2, 3]. We present here the case of monostotic fibrous dysplasia which was detected through the avid uptake of [ 18 F]-FDG. A 12-year-old boy was diagnosed with Hodgkin’s disease. The initial [ 18 F]-FDG PET images showed cervical lymphadenopathy and an avid tracer uptake in the right proximal femur. This finding was interpreted as skeletal involvement of lymphoma, thus defining clinical stage IV disease. After four courses of chemotherapy, a second [ 18 F]-FDG PET (a) was performed for response evaluation. At this time, pathologic tracer uptake was only seen in the right proximal femur (a, arrow), and we therefore considered residual lymphoma in the differential diagnosis. The corresponding radiograph (b) revealed an ill-defined area of ground-glass opacity and a cortical thickening (b, arrowhead). Magnetic resonance imaging showed the lesion to be hypointense in T1weighted sequences and hyperintense in T2-weighted sequences, and demonstrated a strong uptake of contrast medium (c). Due to the significant implications of possible residual lymphoma, open biopsy was performed. The hematoxylin and eosin-stained section (d) showed typical features of fibrous dysplasia with randomly organized trabeculae of woven bone surrounded by immature fibrous tissue.