Identification of chromosomal aberrations associated with disease progression and a novel 3q13.31 deletion involving LSAMP gene in osteosarcoma.

Five osteosarcoma (OS) cell lines, 37 OS tumors and 9 corresponding non-neoplastic samples were genotyped by Affymetrix 10 K 2.0 SNP array. Regions of high level amplification and homozygous deletion were identified and validated by quantitative PCR and FISH. Certain recurrent cytogenetic alterations were more frequent in recurrent/metastatic than in primary OS. These included deletion of 6q14.1, 6q16.2-q22.31, and 8p23.2-p12, amplification of 8q21.12, 8q22.3-q24.3 and 17p12, and loss of heterozygosity (LOH) at 2q24.3-q31.2, 5q11.2, 6p21.31-p21.1, 6q14.1-q16.2, 8p22-p12, 9q22.1, 10q21.1-q22.1, 10q23.31-q24.1, 12q15-q21.1 and 21q21.2-q21.3. Most of the LOH calls were associated with deletion, but a subset of them was associated with normal or increased copy number (CN). A consensus 3q13.31 deletion localized to a region within the limbic system-associated membrane protein (LSAMP) gene was also identified. The FISH evaluations demonstrated highly-localized homozygous or heterozygous LSAMP deletions in 6 of 11 primary OS. qRT-PCR evaluations of the two major alternative LSAMP transcripts demonstrated reduced expression of 1b isoform transcript in each of three OS with LSAMP exon 1b deletion. Further, the 1a isoform transcripts in these same OS had either reduced expression or a premature termination codon in LSAMP exon 2. This SNP genotyping study identified chromosomal aberrations associated with disease progression in OS and disclosed LSAMP as a novel tumor suppressor gene in OS. The study also demonstrated that CN and LOH analyses were able to detect distinct subsets of genetic abnormalities in OS.

Malignant ganglioneuroma arising from mediastinal mixed germ cell tumor.

Mixed germ cell tumors with non-germ cell malignant components rarely occur in the anterior mediastinum. We report a case of a 34-year-old man who presented with an anterior mediastinum mass. Mixed germ cell tumor was initially diagnosed based on the pathologic findings of germinoma on thoracoscopic biopsy and clinical findings of elevated serum alpha-fetoprotein and beta-human chorionic gonadotropin. The patient received preoperative chemotherapy and subsequent complete resection of the residual tumor. Pathologic examination of the excised specimen showed predominantly malignant ganglioneuroma and small residual foci of teratoma. To our knowledge, this is the first reported case of a malignant ganglioneuroma arising from mediastinal mixed germ cell tumor.

Comparison between F-18-FDG positron emission tomography and histology for the assessment of tumor necrosis rates in primary osteosarcoma.

BACKGROUND: The purpose of this prospective study was to identify if F-18-fluorodeoxy-D-glucose positron emission tomography (F-18-FDG PET) was a reliable noninvasive surrogate of histologic response in determining the efficacy of neoadjuvant chemotherapy before surgical resection in primary osteosarcoma. METHODS: Between January 2003 and December 2003, 10 patients with primary osteosarcomas were examined using F-18-FDG PET before neoadjuvant chemotherapy and surgery. The mean age at the time of first intervention was 19 years (range, 4-47 years). Positive prognostic significance was defined as more than 90% tumor necrosis response following neoadjuvant chemotherapy. The parameters of FDG uptake were correlated with histologic findings. The intraclass correlation coefficient was used to validate the tumor necrosis rates determined by PET and histology. RESULTS: The tumor necrosis rate determined by PET was comparable with that determined histologically. The mean standardized uptake value before and following neoadjuvant chemotherapy were 8.2 and 4.4, respectively. The average tumor necrosis rate determined by PET was 22%. However, the mean tumor necrosis rate determined histologically was 54.5%. According to the intraclass correlation coefficient models, the intraclass correlation coefficient equaled O. The relationship of tumor necrosis rates determined by F-18-FDG PET and histology seems to be statistically insignificant. CONCLUSION: In this preliminary study, FDG PET did not seem to be a promising tool for evaluating the response of primary osteosarcoma to neoadjuvant chemotherapy.

Extraosseous osteogenic sarcoma.

Extraosseous osteogenic sarcoma is a very rare malignant neoplasm. Out of the more than 400 cases of soft tissue sarcomas on file in our hospital, only 2 were extraosseous osteogenic sarcomas. Both were situated in the thigh. The first case was initially diagnosed as a hematoma and treated by marginal excision. The diagnosis of high-grade osteosarcoma primarily arising in soft tissue was made from histopathologic examination. Radiotherapy of 60 Gy in 30 fractions was given postoperatively. The second patient, primarily diagnosed as having a soft tissue sarcoma, was treated by wide excision. The final pathologic report was high-grade extraosseous osteogenic sarcoma. Adjuvant chemotherapy was given postoperatively. Both patients are alive without local recurrence and distant metastasis at postoperative 90-month and 107-month follow-up, respectively.

Retroperitoneal venous hemangioma.

Venous hemangioma is an extremely uncommon tumor. We report a 61-year-old woman with a surgically proven venous hemangioma in the retroperitoneum. Image studies, including sonography, computed tomography and angiography, revealed a heterogeneous mass lesion with firm adherence to the adjacent organs and engulfing the major vessels. Only subtotal resection of the tumor was done due to technical difficulty. Follow-up magnetic resonance imaging 7 months after surgery showed reduction in size and much delayed enhancement of the residual tumor. In conclusion, firm attachment to adjacent organs and much delayed enhancement are clues for the diagnosis of a venous hemangioma.

Allograft arthrodesis of the knee in high-grade osteosarcoma.

BACKGROUND: A retrospective cohort study was conducted to evaluate the outcomes of massive allograft arthrodesis in the management of high-grade osteosarcoma around the knee. METHODS: The results of 19 patients with high-grade osteosarcoma around the knee, which was treated by wide resection and reconstruction using allograft arthrodesis, were evaluated for a mean length of 7.3 years (range, 3-13 years). The mean age at the time of surgery was 13.3 years (range, 6-27 years). According to the Musculoskeletal Tumor Society staging system, 17 patients were stage IIB and 2 were stage IIIB at presentation. Evaluations were based on the oncologic results, non-oncologic results and complications. Functional evaluation was performed with the Enneking functional evaluation form. RESULTS: Four patients (21.1%) died of their disease; 3 (15.8%) are alive with disease; and 12 (63.2%) are free of disease. Four patients (21.1%) had local recurrence of their tumor at a mean of 23 months postoperatively (range, 9-44 months). The mean time to union of the metaphyseal junction was 24.7 weeks (range, 16-30 weeks) and the diaphyseal junction was 47 weeks (range, 24-78 weeks). The overall complication rate was 31.6%, including 2 (10.5%) infections, 3 (15.8%) allograft fractures, and 1 (5.3%) nonunion. Our mean final functional result was 65%. CONCLUSION: Due to the high rate of complications in this study, we conclude that allograft arthrodesis should be left as a salvage or "back-up" reconstructive procedure after resection of osteosarcoma around the knee, unless there are special indications for this procedure. We found allograft fracture to be the most common complication.

Accumulation of mitochondrial DNA with 4977-bp deletion in knee cartilage--an association with idiopathic osteoarthritis.

OBJECTIVE: Since mitochondrial DNA (mtDNA) mutations have been established to associate with the aging process and some degenerative diseases, we investigated the correlation between idiopathic osteoarthritis (OA) and the 4977-bp mtDNA deletion. DESIGN: Cartilage were collected from six sites in knee joints removed from 18 aged patients with idiopathic OA, 10 aged non-OA cadavers, 3 young cadavers (YC), and lateral femoral condyle of 9 young patients. Histopathologic changes were examined and the common 4977-bp mtDNA deletions were analyzed in young and elderly cartilages obtained from different sites in the knee joint. The association of the 4977-bp deletion of mtDNA with idiopathic OA and aging was evaluated. RESULTS: The 4977-bp mtDNA deletion was detected in 17 of the 18 OA patients, 9 of the 10 aged non-OA cadavers, and 1 of the 3 YC. None of the nine specimens collected from the lateral femoral condyle of young patients had a detectable deletion of mtDNA. The 4977-bp mtDNA deletion was not significantly correlated with the severity of OA graded by the Mankin score. The frequencies of occurrence of the 4977-bp mtDNA deletion were significantly different between the OA group and the aged non-OA control group (P=0.004) and between the aged non-OA group and the young control group (P=0.002). CONCLUSIONS: The results suggest that accumulation of the 4977-bp deletion of mtDNA in knee cartilage increases with age and may play a role in the development of idiopathic OA in the knee joint.

Orbital metastatic osteosarcoma.

A 15-year-old girl with right tibial osteosarcoma, diagnosed 22 months previously, developed right orbital and skull base metastases, with symptoms including painful protrusion of the right eyeball and severe visual impairment. She underwent embolization of the metastatic tumor, local irradiation, and chemotherapy followed by intralesional resection of the mass because extensive involvement of the skull base precluded complete surgical resection. The best corrected visual acuity in her right eye initially decreased to 20/200, then dropped to no light perception after embolization, and then improved to counting fingers at 50 cm after radiotherapy. The symptoms of pain and proptosis subsided completely. After 24 months of follow-up from the presentation of orbital metastasis, the patient's right-eye vision remained unchanged. The surgical specimen revealed a necrotic tumor similar to osteosarcoma. In conclusion, orbital metastasis of osteosarcoma is rare, but may lead to severe visual impairment. Combined radiotherapy, chemotherapy and surgery can partially relieve symptoms, but cannot completely eradicate the tumors.

Angiofibroma of the hypopharynx.

Primary extranasopharyngeal angiofibroma is very rare. To date, approximately 60 cases have been reported in the English literature. Only 1 case was confined to the posterior wall of hypopharynx. In August 2000, a 68-year-old man presented with a 6-month history of progressive foreign-body sensation in the throat and intermittent inspiratory stridor. Endoscopic examination of the larynx and pharynx revealed a nonpulsatile, pink-grayish, polypoid mass arising from the posterior pharyngeal wall of the left hypopharynx. Under general anesthesia, this tumor mass was subsequently removed by the endoscopic CO2 laser. The histologic diagnosis was an angiofibroma. Three-year follow-up found no evidence of tumor recurrence or post-operative complications.

Huge aneurysmal bone cyst of iliac bone in a mid-aged female.

Aneurysmal bone cyst is a rare nonneoplastic expansile osteolytic bone lesion of unknown etiology. It usually occurs in the first 2 decades of life. The most common sites are the metaphysio-epiphyseal areas of long bones or vertebrae with eccentric expansion. We present a 42-year-old female with a huge aneurysmal bone cyst of the pelvis with dumbbell-shaped expansion on the both side of the iliac bone, which grew rapidly in 6 months. We also review the literature and discuss its prevalence, clinicopathologic characteristics, differential diagnostic problems, optimal treatment, and the potential of recurrence.

Treatment of focal cerebral ischemia with liposomal nerve growth factor.

Liposomal nerve growth factor (NGF) was used for the treatment of focal cerebral ischemia in a rat model. Positive charge inducing agents of sphingosine (SP) and stearylamine (S) were formulated in the liposomal NGF. Dose-response of intraventricular injection of liposomal NGF showed significant reduction in infarct volume at the dose of 5 and 10 microg/rat of NGF. The liposomal NGF formulated with SP or S demonstrated similar results in the reduction of total infarct volume in rats. When we increased the molar ratio of SP and S from 0.15 to 0.3, the infarct volume from rats showed a similar value as that of the control treated with NGF solution. Liposomal NGF was given prior to the development of ischemia. We found that NGF was effective in prevention of neuronal death. The NGF concentrations in brain for liposomal NGF were maintained in a level significantly higher than those for NGF solution. This was attributed to the positively charged liposomal NGF bound effectively in brain ventricle and caused longer retention time than free NGF for localization in brain. Therefore, the effect of liposomal NGF on reduction of infarct volume was significant. We assumed that the transportation of NGF might go through the cerebrospinal fluid pathway throughout the ventricular system and subarachnoid system to cerebral cortex to produce a therapeutic effect on ischemia.

Localized amyloidosis of the cornea secondary to trichiasis: clinical course and pathogenesis.

PURPOSE: To present four cases of localized corneal amyloidosis secondary to trichiasis and to discuss its pathogenesis. METHODS: Medical and pathologic records of four patients with corneal amyloidosis secondary to trichiasis were reviewed retrospectively. Two patients underwent trichiasis surgery and then lamellar keratectomy. One patient underwent trichiasis surgery only, and one patient received keratectomy only. The excised specimens were examined by light and electron microscopy. In two cases, they were stained with antibodies against kappa and lambda immunoglobulin light chains. All patients were followed for evidence of progression or recurrence of the lesions. RESULTS: Three cases presented with blurring of vision and a progressively enlarging vascularized unilateral corneal mass. One case had normal vision and a smaller, nonvascularized mass. All four cases had a history of trichiasis. After trichiasis surgery but before corneal surgery, two patients were followed for 24 and 18 months, respectively, and showed no progression of the corneal lesions. The patient who did not undergo trichiasis surgery had a recurrence of the corneal lesion after lamellar keratectomy. Pathologic examination confirmed amyloid deposition in all three excised specimens with almost no inflammatory cells. Immunohistochemical stains were negative. CONCLUSION: The close correlation between trichiasis surgery and the clinical course of corneal amyloidosis provides further evidence for their association. The pathologic findings in this study do not confirm that the amyloid deposits are light chain proteins (AL).