Effect of recombinant human bone morphogenetic protein-2 on a novel lung cancer spine metastasis model in rodents.

Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30-90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability. While some research suggests that BMP-2 may possess tumorigenic effects, other studies show possible inhibition of cancer growth. Thirty-six athymic rats underwent intraosseous injection of lung adenocarcinoma cells into the L5 vertebral body. Cells were pre-treated with vehicle control (Group A) or rhBMP-2 (Group B) prior to implantation. At 4 weeks post-implantation, in vivo bioluminescent imaging (BLI) was performed to confirm presence of tumor and quantify signal. Plain radiographs and microComputed Tomography (microCT) were employed to establish and quantitate osteolysis. Histological analysis characterized pathologic changes in the vertebral body. At 4 weeks post-implantation, BLI showed focal signal in the L5 vertebral body in 93% of Group A animals and 89% of Group B animals. Average tumor burden by BLI radiance was 7.43 × 10(3) p/s/cm(2) /sr (Group A) and 1.11 × 10(4) p/s/cm(2) /sr (Group B). Radiographs and microCT demonstrated osteolysis in 100% of animals showing focal BLI signal. MicroCT demonstrated significant bone loss in both groups compared to age-matched controls but no difference between study groups. Histological analysis confirmed tumor invasion in the L5 vertebral body. These findings provide a reliable in vivo model to study isolated spinal metastases from lung cancer. Statement of Clinical Significance: The data support the notion that exposure to rhBMP-2 does not promote the growth of A549 lung cancer spine lesions. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1274-1281, 2016.

Two cases of Kawasaki disease with hidden neuroblastoma.

Neuroblastoma is the third most common pediatric cancer and can mimic many other diseases. However, clinicians need to be aware about the possibility of neuroblastoma, when other more obvious clinical conditions such as the Kawasaki disease (KD) are present. KD is an acute febrile vasculitis of childhood with coronary complications. There were a few reports for autopsy of KD patients with neuroblastoma. A 2-y-old girl was admitted for definite KD with five clinical signs. Her fever did not respond to retreatment with intravenous high dose immunoglobulin. Later a chest computerized tomography scan revealed a mass lesion in the right lower lung field, and ultimately diagnosed as neuroblastoma on the paravertebral area of thoracic spine levels T4 to T10. The second patient was a 3-y-old boy who was diagnosed as incomplete KD with left coronary ectasia. His fever also did not respond to retreatment with immunoglobulin, and the abdominal computerized tomography scan with biopsy confirmed neuroblastoma of the right adrenal gland. We report two patients with KD who were additionally diagnosed as having neuroblastoma.

Could an osteoinductor result in degeneration of a neurofibroma in NF1?

We report a case of fatal evolution of neurofibromatosis in a young boy. A laminectomy was performed when he was 9 years old. A secondary hyperkyphosis led to many surgeries resulting in recurrent malunions. When he was 23 years old, a breakage of his rods was treated by a new instrumentation and a T12-L1 interbody cage fitted with rh-BMP. Five months later, he developed a huge posterior tumour on his back. The biopsy diagnosed a neurofibrosarcoma. The growth of the tumour was extremely rapid. He died after several months from a septic shock. NF1 is characterised by neurofibromas that have a possibility of malign degeneration and conversion to a sarcoma. However, the chronology, rapidity of evolution and the exceptional volume of the tumour made us wonder whether the BMP had a part of responsibility as osteoinductor in the malignant degeneration, in this particular case, of neurofibromatosis. It seemed important to point out this case to the medical community.

Plasmablastic lymphoma presenting as a paravertebral mass in a patient with Crohn's disease after immunosuppressive therapy.

The case of a 32-year-old man with a paravertebral mass and skin nodules, occurring against a background of immunosuppressive therapy for Crohn's disease, is presented. The tumours showed morphological and immunophenotypical features of plasmablastic lymphoma. To our knowledge, this is the first reported case of plasmablastic lymphoma presenting in this location, and also after immunosuppression with infliximab treatment for Crohn's disease.

True histiocytic lymphoma following therapy for lymphoblastic neoplasms.

True histiocytic lymphomas (THLs) are rare tumors in which the malignant cells show morphologic and immunophenotypic evidence of histiocytic differentiation. We describe THLs that arose after therapy for one case of T-lineage lymphoblastic lymphoma (LyL) and two cases of acute lymphoblastic leukemia (ALL) (both CD10+, one pre-B phenotype). The lymphoblastic neoplasms were not unusual in any way, and responded well to standard therapy. The THLs arose 10 to 20 months after complete remission was achieved for the lymphoblastic neoplasms, at which time there was still no clinical or pathologic evidence of the lymphoblastic neoplasms. All three THLs exhibited clinical and morphologic features of malignancy. Neoplastic cells in the THLs had abundant eosinophilic vacuolated cytoplasm and pleomorphic nuclei, and expressed histiocytic antigens in the absence of lymphocyte-specific lineage markers. Because THLs are rare neoplasms, their occurrence after otherwise successful therapy for lymphoblastic neoplasms in these three cases may constitute a distinct clinicopathologic entity.

Epidural hibernoma as a complication of corticosteroid treatment. Case report.

Centripetal fat deposition is a well-recognized consequence of excessive use of corticosteroids, either endogenous or exogenous. Recently, several patients receiving large doses of corticosteroids have suffered compressive myelopathies due to excessive epidural fat collections, labeled "epidural lipomatosis." Two of these have been children, and a third child is reported here. This child was receiving chronic steroids for juvenile rheumatoid arthritis when he presented with such a myelopathy, which was confirmed by metrizamide computerized tomography myelography as well as by surgical exploration. Histological examination revealed that the epidural tissue was a brown-fat tumor or "hibernoma." An epidural hibernoma has not been described previously. The histological and endocrine features of fat in Cushing's syndrome are discussed, and the literature concerning hibernoma and epidural lipomatosis is reviewed.

Spinal cord compression by epidural lipomatosis in juvenile rheumatoid arthritis.

Two cases of spinal cord compression secondary to steroid-induced epidural lipomatosis in systemic juvenile rheumatoid arthritis (JRA) patients are reported. This complication of prolonged corticosteroid therapy has not been described previously in children with JRA. Epidural lipomatosis should be considered in the differential diagnosis of JRA patients receiving high-dose and/or prolonged corticosteroid therapy who present with neurologic signs and symptoms referable to the spinal cord.

Epidural lipomatosis and renal transplantation.

A 34-year-old man presented with progressive myelopathy 4 months after cadaveric renal transplant for endstage renal disease. Radiographic evaluation gave findings consistent with epidural lipomatosis and compression of the thoracic thecal sac. Decompressive laminectomy resulted in dramatic improvement of his neurologic deficit. This case is unusual in the brevity of steroid treatment prior to onset of the myelopathy, as well as the relatively small dose. The 10 previous cases of epidural lipomatosis are also reviewed.

Lymphomatous meningitis and steroid-induced epidural lipomatosis: CT evaluation.

A case of spinal cord compression secondary to steroid-induced epidural lipomatosis is reported. The epidural lipomatosis developed in a setting of spinal lymphomatous leptomeningitis secondary to adult T-cell leukemia/lymphoma, an unusual type of non-Hodgkin lymphoma with a high frequency of leptomeningeal involvement. Computed tomography was invaluable in diagnosing epidural lipomatosis, despite the concomitant spinal lymphomatous leptomeningitis. To our knowledge this is the first case of epidural lipomatosis following chemotherapy for a malignancy.

Spinal epidural lipomatosis: a complication of glucocorticoid therapy.

A 21-year-old woman receiving prolonged high dosage glucocorticoids developed spinal cord compression due to excessive accumulation of epidural fat. Computerized tomographic scanning confirmed the diagnosis and revealed a peculiar pattern of spinal cord displacement which we believe to be unique to compression by fat. Laminectomy did not afford relief, possibly because of prolonged neural compression or because of compression at a higher spinal level. Although an unusual complication of Cushing's syndrome, epidural lipomatosis should be considered when such a patient develops symptoms of spinal cord or cauda equina compression.

Influence of five different postnatal lifelong treatments on the transplacental carcinogenicity of ethylnitrosourea in Sprague-Dawley rats.

Sprague-Dawley rats received in 10 mg/kg body weight (group I) or 30 mg/kg body weight (group II) ethylnitrosourea (ENU) orally on the 19th day of pregnancy. Their offspring were treated with Bacille Calmette-Guerin, human albumin, hydrocortisone, cyclophosphamide or nicotine starting on the 6th day of life. The ENU treatment significantly reduced the life expectancy of all offspring. Treatment of the offspring did not influence tumor frequency, induction time or localization of neurogenic malignant tumors. Cyclophosphamide treatment of group II offspring increased the number of females bearing mammary carcinomas.

Induction of malignant bone tumors in rats by 1-(2-hydroxyethyl)-1-nitrosourea.

Forty male MRC-W rats were treated chronically with 1-(2-hydroxyethyl)-1-nitrosourea in drinking water (total dose, 330 mg/rat). Fifteen rats (38%) developed osteogenic osteosarcomas or chondrosarcomas of the lower vertebrae. This was the first time that an orally administered organic compound induced a high incidence of these tumors.